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Happy New Year 2013


Online Submission

IJCP Group of Publications Dr Sanjiv Chopra Prof. of Medicine and Faculty Dean Harvard Medical School Group Consultant Editor

Asian Journal of

Paediatric Practice

Volume 16, No. 2, 2012

Dr Deepak Chopra Chief Editorial Advisor

Padma Shri and Dr BC Roy National Awardee

Dr KK Aggarwal

Group Editor-in-Chief

Dr Veena Aggarwal

FROM THE DESK OF EDITOR 5

Swati Y Bhave

MD, Group Executive Editor Anand Gopal Bhatnagar Editorial Anchor

AJPP Speciality Board Chief Editor Dr Swati Y Bhave Editorial Board National Dr Alagiriswamy Parthasarathy Dr Ajay Kalra Dr K Nedunchelian Dr Yagnesh Popat Dr Chhaya Prasad Dr Atul Agarwal Dr Anoop Verma Dr Vijay Zawar Dr J S Tuteja Dr Surekha Joshi Editorial Board International Dr Professor Antonio An Tung Chuh Dr Jay E Berkelhamer Dr Neil Wigg Professor Andreas Konstantopoulos Ahmaduddin Maarij Professor Leyla Namazova-Baranova Dr Angelo Neeneo Dr Yoshikatsu Eto Dr Peter Cooper

FROM THE DESK OF GROUP EDITOR-IN-CHIEF 6

review article

IJCP Editorial Board Obstetrics and Gynaecology Dr Alka Kriplani Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra Dr SK Parashar Paediatrics Dr Swati Y Bhave Diabetology Dr CR Anand Moses, Dr Sidhartha Das Dr A Ramachandran, Dr Samith A Shetty ENT Dr Jasveer Singh Dentistry Dr KMK Masthan Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Neurology Dr V Nagarajan Journal of Applied Medicine and Surgery Dr SM Rajendran, Dr Jayakar Thomas Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

KK Aggarwal

7

Tdap Vaccine: The Current Status

AJ Chitkara

10 Mental Health in Children: An Overview

Krishan Kumar, Rajeev Dogra, Brij Lata Kotia


Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

Clinical study 23 Effect of Rag Neelambari on Certain Physiological and Behavioral Parameters of Preterm Infants

Printed at SR Offset Art Printers, Chennai

P Bharathi, R Sobana, K Jaiganesh, S Parthasarathy, S Vadivel

Š Copyright 2012 IJCP Publications Ltd. All rights reserved. The copyright for all the editorial material contained in this journal, in the form of layout, content including images and design, is held by IJCP Publications Ltd. No part of this publication may be published in any form whatsoever without the prior written permission of the publisher.

Editorial Policies

27 The Role of Clinical Signs in the Diagnosis of Late-onset Neonatal Sepsis and Formulation of Clinical Score

The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

Subhranshu Sekhar Kar, Rajani Dube, Samarendra Mahapatro, Sitanshu Sekhar Kar

News and Views 32

Journal Scan

Note: Asian Journal of Paediatric Practice does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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from the desk of editor

Dr Swati Y Bhave

Chief Editor Executive Director AACCI, (Association of Adolescent and Child Care in India) Senior Visiting Consultant, Indraprastha Apollo Hospitals, New Delhi

Dear Readers I wish you all a very happy and prosperous new year 2013. This issue has interesting articles on a variety of topics. It is now well-known that the childhood vaccine immunity can wane at an older age unless booster doses are given in adolescent age group. There are a high number of cases in diphtheria and pertussis in adolescent and adult cases in many countries in the world. TDap is one vaccine that will protect adolescent and adults against diphtheria, pertussis and tetanus. A good review article has been written by Dr Chitkara who is an immunization expert. Krishan Kumar et al have given a good overview on mental health in children. Music therapy is well-known to be effective in many medical conditions, world over mothers sing lullaby to their children to soothe them or put them to sleep. This issue has an interesting article of “Effect of Rag Neelambari on Certain Physiological and Behavioral Parameters of Preterm Infants”, by Dr Bharathi and Dr Parthasarathy, et al. Neonatal sepsis is a challenging area that affects the outcome in a NICU. Subhranshu Sekhar Kar has given “The Role of Clinical Signs in the Diagnosis of Late-onset Neonatal Sepsis and Formulation of Clinical Score.” Abstracts from various journals on Zinc in health make interesting reading in the news and event section.

Address for correspondence IJCP Group of Publications E - 219, Greater Kailash, Part - 1, New Delhi - 110 048

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from the desk of group editor-in-chief

Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS National Vice President, Elect IMA Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Wishing all our readers a very Happy and Healthy New Year! Although we love our children, it is also a sad fact that child abuse is very rampant the world over. Child maltreatment is an intentional harm or threat of harm to a child by a parent or a person who is acting as a caregiver. Healthcare providers who care for children have a professional, and legal, obligation to identify and protect children who may be victims of abuse and neglect. Physicians are mandated to report suspected child abuse and neglect. The parents of the child (ren) should be informed that the child abuse report is being made. In cases of suspected child abuse or neglect, the medical record should provide as much detail about the circumstances of the event as possible, including direct quotations from caretakers and sketches or photographs of the injuries. Photography with parental consent is useful for documentation of external injuries. Photographs must depict the injuries accurately. They must be of high quality, taken in good light and preferably by an experienced photographer. There should be photographic evidence of a victim of child abuse, and each of the images must be labeled with the name of the child, age, date of birth, date and time of photograph, hospital number, name of photographer and the name of physician. The differential diagnosis include: ÂÂ

Undiagnosed bleeding disorders, salicylate ingestion, vasculitis and mongolian spots

ÂÂ

Burn like lesions may arise from phytophotodermatitis, impetigo or various complementary and alternative medicine therapies.

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Cupping, coining, spooning, moxibustion, caida de mollera and salting. These practices produce skin lesions that are characteristic and may be confused with inflicted injury.

Let us, as health care provider, do our best to recognise and prevent child abuse whenever we can Happy reading!

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review article

Tdap Vaccine: The Current Status AJ Chitkara

Abstract Following the use of DPT and antenatal vaccinations, tetanus has virtually disappeared and diphtheria as a childhood disease remains fairly well-controlled. Pertussis on the other hand has shown a resurgence in highly immunized population. This indicates that current immunization schedules are inadequate to protect against the disease due to waning immunity irrespective of the vaccine used. Tdap vaccine holds promise by its appropriate use in various situations to provide a protective immunity against all the three disease and a positive impact on the transmission dynamics of diphtheria and pertussis to protect the susceptible. Keywords: DPT vaccine, pertussis, Tdap vaccine, resurgence

T

he widespread use of diphtheria, pertussis and tetanus (DPT) vaccines starting 1940 onwards with the developed countries and subsequently through Expanded Program on Immunization (EPI) in 1978, in the developing countries has had a tremendous impact on morbidity and mortality because of DPT. While tetanus has virtually disappeared following infant DPT and antenatal tetanus vaccination, diphtheria as a childhood disease remains fairly well-controlled with some evidence of an epidemiological shift affecting adolescents and adults. Pertussis on the other hand has become an enigma with resurgence in highly immunized population. Though failure to vaccinate is responsible for much of the disease, questions are being raised on the failure of vaccine too. Burden of disease According to World Health Organization (WHO) global estimates, there are 16 million pertussis cases occurring annually. However, only 129, 265 cases were reported in 2010 clearly indicating a gross underreporting. The lack of awareness, nonavailability of laboratory support for confirmation of the disease, atypical pertussis that occurs in infants, adolescents and adults, notification not mandatory (in some developing countries) and lack of an effective vaccine preventive disease (VPD) surveillance are some of the reasons for under-reporting. The maximum morbidity and Head, Dept. of Pediatrics Max Super Specialty Hospital Shalimar Bagh, New Delhi E-mail: drajchitkara@gmail.com

mortality occurs amongst infants who are partially or unimmunized. The adolescents and adults on the other hand act as reservoir of infection in the community and transmit the disease to vulnerable infants. Waning Immunity and the Need for Boosting The general resurgence of reported pertussis, especially among the adolescent and adult populations in countries with high vaccine coverage, indicates that current immunization schedules are inadequate to protect against the disease due to waning immunity irrespective of the vaccine used whether whole cell or acellular. The lack of natural boosting because of cessation of wild organism circulation in high vaccine coverage areas results in a sizeable susceptible population. The protective immunity is invariably 6-12 years after vaccination but recent studies have indicated that it may be as low as 1-3 years in certain populations and responsible for recent pertussis outbreaks in USA, Australia and UK. Even natural infection by Bordetella pertussis does not confer life long immunity; it wanes off in 12-15 years. Following primary vaccination, antidiphtheria antibodies also wane in the absence of boosting either by natural exposure or through administration of booster vaccination. Waning of antibodies in adults has been documented in various studies in Australia, New Zealand, Germany and Poland. The importance of maintaining adequate population immunity against diphtheria was highlighted when epidemic diphtheria re-emerged in several eastern European countries in the 1990s, with a high proportion of adult cases.

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review article Cases of diphtheria are being not infrequently reported in developing countries where vaccination coverage is suboptimal. The occurrence of cases among adolescents and adults in these endemic regions does however point towards a shifting epidemiology. The definite evidence for the waning immunity postvaccination or natural infection, a shift in epidemiology of both diphtheria and pertussis, which is now being reported frequently among older children and adults, has necessitated that immunity against these diseases be maintained at all ages. This can only be achieved by periodic boosters. The issue remains of immense importance especially for adult pertussis, which is directly responsible for infant pertussis with a high morbidity and mortality. The high reactogenecity of pertussis vaccines beyond 5-6 years of age had precluded boosting for pertussis till a decade back but the availability of low-dose tetanus, diphtheria and pertussis (Tdap) has now provided various options for boosting among all ages. The real impetus has been provided by The Global Pertussis Initiative since year 2000. The recommendations for Tdap vary from 5th year booster (Germany), universal adolescent immunization, cocoon immunization (USA, Australia and many other developed countries) to decennial booster (Europe). However, the implementation remains suboptimal. The optimum duration of protection that was considered to be about ten years till now has become a subject of debate in view of the recent outbreaks across many developed countries.

Reduced Antigen Diphtheria-Tetanus-Acellular Pertussis Vaccine Tdap has a reduced content of diphtheria toxoid (onetenth), acellular pertussis components (one-third) and about half tetanus toxoid. It has been extensively tested in adults and adolescents and found to be immunogenic, safe and effective. Use of Tdap for the 6th dose at 5-6 years of age has also shown to be as immunogenic as a whole cell or acellular pertussis vaccine, but much less reactogenic (Thailand, Germany, India). The persistence of antibodies however varies from one to seven years in different populations for reasons not understandable.

Tdap: Indications Based on the Worldwide Recommendations (USA-ACIP, Europe-COPE, India-IAPCOI) ÂÂ

Adolescent vaccination „„

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Ten years and above for boosting against tetanus, pertussis and diphtheria.

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

Regardless of time of administration of Td, such adolescents should receive Tdap to protect against pertussis. Children 7-10 years of age having missed or age appropriate incomplete DTwP/DTaP vaccination. If totally unimmunized, Tdap dose followed by two additional doses of Td at 2 and 6 months after the first dose of Tdap to provide effective protection against all three diseases. However, such children should not receive the proposed Tdap at 10-12 years but 10 years later. Adult immunization: Though, it is desirable to maintain immunity lifelong and recommendations do exist for a decennial Tdap (Europe) vaccination but is seldom implemented. The vaccine is licensed for use between 19-64 years of age by US FDA. However, in USA only one dose in a lifetime is recommended till date but decennial Td is in place. Tdap as second booster at 4-6 years of age: Germany is the only country to have implemented this in the UMV. More data is needed before it can be suggested. Also Tdap as a second booster can be used only if the primary and the first booster of DTwP/DTaP have very high coverage in a population, which is at present unthinkable in developing countries.

„„

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Use of Tdap to prevent infant pertussis: ÂÂ Postpartum Tdap immunization has been recommended to protect the newborn and infant from pertussis transmitted from mother. The program has had varying success in the developed countries and recently Tdap has been permitted for use in pregnancy after the 20th week of gestation. The safety has been established but the surveillance however continues (USA). ÂÂ Cocoon vaccination: It is an attempt to immunize all family contacts including siblings, grand parents and other family members who are likely to be in contact with an infant below 12 months of age in the family. The vaccination must be done at least two weeks prior to the contact. The aim is to prevent their acquisition of disease and the likelihood of transmission to the unimmunized or incompletely immunized infant. It is easier said than done and in the best of centers has been only 40%. However, the strategy does have its merits but implementation remains difficult due to the varied age groups involved. ÂÂ Healthcare workers: All healthcare providers and day-care workers should receive one dose of Tdap at any age if they have not received any Tdap previously.


review article ÂÂ

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Wound prophylaxis: For wound management at 10 years and above if there is no history of having received Tdap vaccine earlier, it is recommended to use Tdap instead of TT or Td. However, if the person is totally unimmunized, one dose of Tdap followed by two doses of Td or TT are given at one month and six months after the Tdap vaccine to complete the immunization. Tdap is also recommended for wound prophylaxis in pregnant women if five years have elapsed since the previous tetanus containing vaccine and >10 years of Tdap. Care must be taken to give Tdap after 20 weeks of gestation.

previous vaccine, it’s reasonable to postpone Tdap till 10 years after the previous dose. However, in practice this is rarely seen. Breastfeeding, stable neurological disorder, cerebral palsy, controlled seizures and immunosuppression are neither a precaution nor contraindication to Tdap administration.

Indian Academy of Pediatrics (IAPCOI) recommends an adolescent booster at 10 years replacing the TT vaccine as mentioned in the UMV program. The cost incurred on this expensive vaccine merits individual discussion. Tdap is also endorsed for wound prophylaxis at ages above 10 with no previous history of receiving pertussis vaccine and especially if the patient merits a TT booster in view of the elapsed 5-10 years after the previous tetanus vaccine and depending on the injury sustained.

Suggested Reading

Safety issues: Local and systemic adverse events after administration of Tdap in adolescents and adults are mild comprising mainly local swelling or soreness, mild fever and headache and are comparable to Td administration. The only absolute contraindication is an immediate anaphylactic reaction after an earlier DTP vaccine. History of Guillain-Barré syndrome within six weeks of a tetanus containing vaccine is a precaution. In cases of severe arthus hypersensitivity reaction occurring after a tetanus containing vaccine within 10 years of

To summarize, the Tdap vaccine holds promise by its appropriate use in various situations to provide a seamless protective immunity against all the three disease tetanus, diphtheria and pertussis and a positive impact on the transmission dynamics of diphtheria and pertussis to protect the susceptible.

1. Plotkin S. The global pertussis initiative: process overview. Pediatr Infect Dis J 2005;24(5 Suppl):S7-9. 2. Redbook Online 2012, American Academy of Pediatrics. 3. Zepp F, Heininger U, Mertsola J, Bernatowska E, Guiso N, Roord J, et al. Rationale for pertussis booster vaccination throughout life in Europe. Lancet Infect Dis 2011;11(7): 557-70. 4. Centers for Disease Control and Prevention (CDC). Pertussis epidemic - Washington, 2012. MMWR Morb Mortal Wkly Rep 2012;61(28):517-22. 5. Guidebook of Immunization, Indian Academy of Pediatrics (IAPCOI) 2011. 6. Chitkara AJ, Kukreja S, Shah RC. Pertussis and diphtheria immunization. Indian Pediatr 2008;45(9):723-7. 7. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine from the Advisory Committee on Immunization Practices, 2010. MMWR Morb Mortal Wkly Rep 2011;60(1):13-5. 8. http://apps.who.int/immunization_monitoring/en/ globalsummary/countryprofileselect.cfm

Relationships between Serum Free Fatty Acids and Zinc, and Attention Deficit Hyperactivity Disorder: A Research Note The purpose of this study is to evaluate the relationships between serum free fatty acids (FFA) and zinc, and attention deficit hyperactivity disorder (ADHD). Forty-eight children with ADHD (33 boys, 15 girls) were included in the patient group and 45 healthy volunteer children (30 boys, 15 girls) constituted the control group. The mean serum FFA level in the patient group was 0.176 ± 0.102 mEq/l and in control group, 0.562 ± 0.225 mEq/l (p < 0.001). The mean serum zinc level of patient group was 60.6 ± 9.9 mg/dl and that of the control

group, 105.8 ± 13.2 mg/dl (p < 0.001). A statistically significant correlation was found between zinc and FFA levels in the ADHD group. These findings indicate that zinc deficiency may play a role in etiopathogenesis of ADHD. Although we observed decreased FFA levels in ADHD cases, it is necessary to determine whether this condition is a principal cause of ADHD or is secondary to zinc deficiency. Bekaroğlu M, Aslan Y, Gedik Y, et al. J Child Psychol Psychiatry 1996;37(2):225-7.

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review article

Mental Health in Children: An Overview Krishan Kumar*, Rajeev Dogra**, Brij Lata Kotia†

Abstract Definitions and concepts of mental health or disorder in adults cannot be always generalized to childhood population. Many factors should be considered before diagnosing a mental disorder in children. Childhood mental health and disorders appear to be different in many aspects of diagnosis, management and outcome, from their adult counterparts. Keywords: Cognitive developmental, disorganized family environment, child abuse

T

raditionally, psychiatry has always assumed that mental health could be defined as the autonym of mental disorder. In other words, mental health was thought to be the absence of psychopathology. Because, mental illness was easier to define, the concept of positive health was ignored. But, mental health is “not the absence of negatives but the presence of positives” (Vaillant, 2005).

Every model has advantages and limitations. Thus, mental health was described by Freud as ‘an ideal fiction’ and described by Aubrey Lewis as ‘an invincibly obscure concept.’

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They are in touch with own identity and feelings.

In modern psychiatry, there are different empirical approaches to the concept of mental health: ÂÂ Mental health as above normal or above average mental state that is objectively desirable. ÂÂ Mental health as positive psychology - as epitomized by presence of multiple human strengths. ÂÂ Mental health as developmental maturity. ÂÂ Mental health as socioemotional intelligence. ÂÂ Mental health as subjective well-being, a mental state subjectively experienced as happy, contented and desired. ÂÂ Mental health as resilience, as the capacity for successful adaptation and homeostasis in the face of adversity.

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They are oriented towards the future and over time, they should remain fruitfully invested in life.

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They should develop resistance to stress.

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They should possess autonomy and should recognize what suits their needs.

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They should perceive reality without distortion and yet possess empathy.

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They should be masters of their environment able to work/play/love and be efficient in problem solving.

*Clinical Psychologist Dept. of Computational Neuroscience National Brain Research Centre, Manesar, Haryana **Associate Professor Dept. of Clinical Psychology Post Graduate Institute and Medical Sciences, Rohtak, Haryana †Professor and Head, Dept. of Psychology University of Rajasthan, Jaipur Address for correspondence Dr Krishan Kumar Clinical Psychologist (Computational Neuroscience) Flat No. 104-B National Brain Research Centre, NH-8, Near NSG Campus Manesar, Haryana E-mail: keshusony@rediffmail.com

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Characteristics of mentally healthy people (Jahoda, 1958):

However, definitions and concepts of mental health/ disorder in adults cannot be always generalized to childhood population. Following factors should be considered before diagnosing mental disorder in children: ÂÂ

The child is continually changing and growing. Sound knowledge is therefore required of normal development and its limits. Because mental processes and behaviors change as a child develops, it is also not clear whether same diagnosis can be applied across the age range e.g., repetitive rituals may be normal in 5-year-old but abnormal in 8-year-old. Once identified as abnormal, it is again helpful to decide if abnormalities are due to delay or due to deviance from usual pattern of development.

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Secondly, majority of childhood cases arise from an excess of behavior exhibited by normal young


review article people e.g., aggression. They are seldom due to qualitatively distinct phenomena more often seen in adult conditions (e.g. hearing voices). Consequently, choosing a cut-off point to make a diagnosis is inevitably an arbitrary process. ÂÂ

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Thirdly, children’s difficulty often arises in the context of relationships within the family. Some or all of the problems may be in structure and functioning of the family, rather than in the individual child. Fourthly, information is gathered typically from multiple informants - child/parents/teachers, etc. This may be noncorroborative leading to diagnostic bias and confusion, since the weight given to a particular informant may vary according to clinical condition e.g., if parent says that child has conduct disorder features but child denies this, parent is more likely to be right. However, if the parent says that child is not depressed but examination of child reveals otherwise, it is the parent who may be ignorant of the child’s true state. Fifthly, comorbidity is rule rather the exception in childhood disorders, further confusing clinical diagnosis. True comorbidity may arise by: „„ Shared risk factors (e.g., early deprivation may lead to both oppositional defiant disorder [ODD] and attachment disorder). „„ Overlap between risk factors (e.g., depressed mother may genetically contribute to depression in child and provide inconstant discipline predisposing to conduct disorder [CD]). „„ One disorder creating increased risk for the other (CD leading to addiction) „„ Comorbid pattern itself constitutes a meaningful syndrome (e.g., depressive CD).

Epidemiology The classic Isle of Wight study by Rutter (1970) was a landmark two phase survey for determining prevalence of mental disorder in a sample of total 2,193 school attending children, using multiple informants (parents/ teachers) (screening followed by in depth assessment of selected subsample). The one year prevalence rate of psychiatric disorder was 7% and M:F ratio was 2:1. A subsequent study using similar design found rates of all types of disorders as twice than Isle of Wight, in an inner London borough (Rutter, 1975). One year follow-up of Isle of Wight study (Rutter et al. 1976) revealed one year prevalence of 20% in adolescents.

In a recent review of 52 separate communities-based studies, mean prevalence was noted as 15.8% (Robert et al., 1998).

Selected Correlates ÂÂ

Age: Prevalence increases with age e.g., prevalence of - 10% for preschoolers and 16.5 for adolescents (Roberts et al., 1998).

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Sex: In preadolescents, mental illness is more prevalent in boys due to higher occurrence of behavior problems. In adolescence, girls have higher rates than boys because of the higher rates of emotional problems, especially depression.

Higher rates were also correlated with: ÂÂ

Chronic health problems and disability (Cadman et al., 1,987)

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Organic brain disorders like epilepsy (Rutter, 1985)

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Low IQ and learning disorders (Hinshaw, 1992)

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Difficult temperament (Hirschfield et al., 1992)

In a review of 55 Indian epidemiological studies in community and school settings, Bhola and Kapur (2003) found persistently lower rates of prevalence in Indian children (range; 0.48-17.2%), which may be due to methodological limitations or true cross-cultural differences. Higher rates of conversion disorders and mild mental retardation (MR) have been reported in India (Srinath and Girimaji, 1999). Interesting epidemiological trends over time has been reported in both positive and negative directions. Performance in IQ tests has risen substantially around the world at all ages, a phenomenon known as the Flynn effect (Flynn, 1987). Average increase of 3 IQ points per decade has been found from 1952 to 1992 (Flynn, 1999). Obviously, such massive shifts can not be explained by hereditary changes within one generation. Environmental factors implicated are: ÂÂ

Improved nutrition

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Increased urbanization

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Better quality primary education

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Exposure to media, especially television

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More cognitively demanding jobs.

On the other hand, Ryan et al (1992), reported secular increase in childhood affective disorder, especially depression over time. Achenbach and Howell (1993), using Child Behavior Check List (CBCL) (Parent’s version) over a 13-year-old period, found significantly increased scores in problem items in 1,989 compared to

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review article 1,976. Eighteen of 1,989 subjects were in clinical range versus 10% of 1976 subjects. While this may reflect true environmental influences, as above, methodological artifacts can also be responsible: ÂÂ

More refined diagnostic criteria/techniques

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Recall bias.

as

However, by the 19th century, children were viewed as having unique psychological, physical and educational needs. Charles Darwin did much to generate interest in evolution and development of all sorts including that of children. Sigmund Freud startled the entire world when he theorized that adult abnormalities are rooted in early childhood experiences. John Watson propagated the concept of behaviorism, which emphasized the role of environment in shaping childhood behavior. Other influential theorists in this field were Maudsley, Emminghaus, Kanner, Bowlby and Piaget while pioneers in clinical research include Cantwell and Rutter. Diagnostic and Statistical Manual Mental Disorders (DSM) I did not have separate category for childhood disorders, which first appeared in DSM II as ‘behavior disorders of childhood and adolescence’ with six diagnostic categories while DSM III first introduced multiaxial framework and operationalized diagnostic criteria. In India, the earliest record of child development is found in the Ayurveda. It was considered that feeding practices, especially breastfeeding, formed the major influence on personality development (Kapur, 1995). As a result of rapid advances cited above, the field of developmental psychology came into forefront. It is the study of how human behavior changes throughout the life span and especially during the childhood years. Developmental psychopathology is an emerging discipline, which studies how abnormal behavior can be understood in terms of processes underpinning human development. It forms a Iiason between abnormal psychology and developmental psychology and focuses on psychopathology as developmental deviations. This discipline was defined by Stroufe and Rutter (1984) as “The study of origins and cause of individual pattern of behavioral maladaptation, whatever the age of onset, whatever the causes, whatever the transformations in

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Various developmental theorists have given models explaining developmental underpinning of childhood mental health and disorders.

Psychodynamic Developmental Theories

Historical Perspective Historically, children were viewed merely underdeveloped adults on the fringe of society.

behavioral manifestations and however complex the developmental pattern may be”:

Freud’s psychosexual theory: Over the course of childhood (birth to adolescence), sexual impulses shift their focus from oral to anal to genital regions of the body. He emphasized that how parents manage their child’s sexual and aggressive drives in the first few years of life is crucial for healthy personality development. Too much or too little gratification of the child’s drives can cause his/her psychic energies to be fixated or arrested at a particular stage. Erikson’s psychosocial theory: Erikson expanded Freud’s theory emphasizing the psychosocial outcomes of development. A basic psychosocial conflict, which resolved along a continuum from positive to negative, determines healthy or maladaptive outcomes at each stage. Also, he did not regard important developmental tasks as limited to early childhood but to occur throughout the life span, thereby adding three adult stages to Freud’s model.

Behavioral/Learning Theories Traditional behaviorism: Pioneers like Watson or Skinner rejected psychoanalytic perspectives of inner drives and concluded that environment is the supreme force in child development. Adults, thus, could mold future behavior of child by carefully controlling reinforcements and punishments. Social learning theory: Expanding behavioral theories, Bandura and colleagues demonstrated that modeling, also known as imitation or observational learning, is the basis for wide variety of childhood behaviors. Children acquire many favorable and unfavorable responses in the absence of direct rewards and punishments, simply by watching or listening to others around them.

Theories of Cognitive Development Jean Piagets’ cognitive developmental theory: According to Piaget, children actively construct knowledge as they manipulate and explore their world. Children move through four broad stages of development, each of which is characterized by qualitatively distinct ways of thinking. In the sensorimotor stage, cognitive development begins with the use of senses and


review article movements to explore the world. These action patterns evolve into the symbolic but illogical thinking of the preschooler in the preoperational stage. Then cognition is transformed into more organized reasoning of the school age child in the concrete operational stage. Finally, in the formal operational stage, thought becomes the complex, abstract reasoning system of the adolescent and the adult.

of mood; they found that temperament is a major factor in increasing the risk that a child will develop psychological problems or alternatively be protected from stress. Three types of children were noted: „„

Easy child: Quickly establishes regular routines, is generally cheerful, adapts readily to new experiences

Vygotsky’s sociocultural theory: Lev Vygotsky focused on how culture- the values, belief customs and skills of a social group is transmitted to the next generation; social interaction, especially cooperative dialogues between children and more knowledgeable members of the society, is necessary for acquisition of knowledge. As adults and more expert peers help children master culturally meaningful activities, the communication between them becomes part of children’s thinking.

„„

Difficult child: Irregular daily routines, tends to react negatively and intensely to new experiences

„„

Slow to warm-up child: Inactive, shows mild, low key reactions to environmental stimuli, adjusts slowly to new experience.

Information processing theories: In these theories, human mind is perceived as a complex, system, through which information flows. Like Piaget, this model regards children as active beings who modify their own thinking in response to environmental demands. But unlike Piaget, there are no discrete stages; rather, the thought processes (e.g., perception, attention, planning) are assumed to be similar in all ages but present to a lesser extent in children. Thus, development occurs by continuous increase rather than abrupt, stage-wise changes.

Theories of Socioemotional Development ÂÂ

Attachment theories John Bowlby in his ethological theory of attachment took a view of how infants build emotional bonding with caregiver. This begins with a set of innate signals by the infant that call the adult to the baby’s side. Attachment develops in four stages: „„ Preattachment phase (birth to 6 weeks) „„ Attachment in the making phase (6 weeks to 6 months) „„ Phase of clear cut attachment (6 months to 2 years) „„ Formation of a reciprocal relationship (2 years onward).

Temperament theories Temperament consists of stable individual differences in quality and intensity of emotional reaction. Chess and Thomas studied different dimensions of temperament- activity level, rhythm city, distractibility, persistence, intensity of reaction, threshold of responsiveness and quality ÂÂ

Theories of Language Development This involves development of both semantics and pragmatics ÂÂ

Semantics: Component of language concerned with understanding the meaning of word and word combinations.

ÂÂ

Pragmatics: Component of language concerned with how to engage in socially effective and appropriate communication with others.

Learning Theories According to Skinner, language, just like any other behavior, is learned as adults apply the principles of operant conditioning to their children’s verbalizations. As the baby makes sounds, parents reinforce those that are most like words with rewards like hugs or smiles. Classical conditioning also proposed to be involved in children’s ability to respond appropriately to the language they hear. Imitation also explains partly how children rapidly pick up complex verbal behaviors, such as whole phrases and sentences. Nativist Theories According to linguist Noam Chomsky, rather than being influenced fully by environment, language is a biologically based, innate, uniquely human accomplishment. Human are born with a language acquisition device, which is an inborn system for picking up language that needs only to be triggered by verbal inputs from the environment.

Theories of Moral Development ÂÂ

Piaget’s theory - identified two broad stages of moral understanding.

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review article

ÂÂ

Heteronomous morality or moral realism: (5-10 years) - children view rules as handed down by authorities (e.g. God/parents, teachers), as having a permanent existence, as unchangeable and requiring strict obedience.

ÂÂ

Axis III: Intellectual level

ÂÂ

Axis IV: Associated medical conditions

ÂÂ

Axis V: condition

Autonomous morality or morality of cooperation (10 years or above) through cognitive development, children become aware that people can have different perspectives about moral action and that intentions, not objective consequences, should serve as the basis for judging behavior.

ÂÂ

Axis VI: Global social functioning.

Kohlberg’s Theory ÂÂ

He organized his six stages of moral development into three general levels. He regarded the stages as invariant and universal - a sequence through, which all people everywhere pass in a fixed order, albeit not in same pace or extent. „„

The preconventional level: Morality is externally controlled, children blindly accept rules of authority figures, and actions are judged by their consequences.

„„

Conventional level: Individuals continue to confirm to social rules, but not for reasons of self-interest. They believe that actively maintaining the current social system is important for ensuring positive human relationships and societal order.

„„

Post conventional/principled level: Individuals move beyond unquestioning support for own societal rules, they define morality in terms of abstract principles and values that apply to all situations and societies.

Classification Classification systems may be categorical or dimensional. They may follow uniaxial or multiaxial frameworks. A simple diagnostic classification: ÂÂ Emotional disorders e.g., anxiety/phobia/ depression. ÂÂ Disruptive disorders e.g., CD/ADHD (attentiondeficit/hyperactivity disorder). ÂÂ Developmental disorders e.g., MR, autism spectrum, language disorders. International Classification of Disease ICD-10: has special multiaxial framework for psychiatric disorders in childhood and adolescence: ÂÂ

Axis I: Clinical psychiatric syndromes

ÂÂ

Axis II: Specific disorders of development.

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Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

Associated

abnormal

psychosocial

DSM IV: Uses a similar multiaxial (5 axis) format for both adult/childhood disorders. Rutter (1975) has also developed a multiaxial framework from the developmental perspective: ÂÂ

Diagnostic category

ÂÂ

Developmental delays

ÂÂ

Level of intellectual functioning

ÂÂ

Medical condition likely to have influenced the symptoms

ÂÂ

Psychosocial stressors (coded into 16 categories).

A new diagnostic framework “Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood” has been introduced for 0-3 years old (DC: 0-3) taking into account of unique developmental issues of very young children. „„

Primary Diagnosis

„„

Relationship disorder

„„

Medical and developmental diagnosis

„„

Psychosocial stressors

„„

Functional: Emotional developmental level (Greenspan and Wieder, 2003).

In contrast to the above categorical systems, Achenbach and Edelbrock (1978) has given a dimensional system based on scores obtained on CBCL. The two major dimensions factorially derived were: ÂÂ

Internalizing disorders: Includes emotional disorders (anxiety/depression/summarization).

ÂÂ

Externalizing disorders: Includes conduct and hyperkinetic disorders.

Factors Influencing Mental Health in Children These factors may be risk factors or protective factors. Again, risk factors may be predisposing, precipitating and perpetuating/maintaining. ÂÂ

Predisposing factor: Increases vulnerability of children to developing psychological problems.

ÂÂ

Precipitating factor: Triggers the onset exacerbation of psychological problems.

or


review article ÂÂ

Perpetuating factor: Maintains psychological problems and prevent their resolution, once they have developed.

ÂÂ

Protective factor: Prevents further deterioration and have implications for prognosis and response to treatment. Any causally related factors may again be: „„

Personal: Referring to individual biological or psychological characteristics of the child e.g., family history and temperament.

„„

Contextual: Referring to features of child’s psychosocial environments e.g., school/peer group influences.

Risk Factors

Biological Genetic factors: Recent population-based twin and adoption studies demonstrate that development of various discrete disorders as well as predisposition/ vulnerability characteristics like intelligence or temperament is greatly influenced by genetic factors. Size of this genetic influence has been estimated to account for 30-60% of overall variation within a population (Rutter, 1991). Mechanism is usually nonmendelian and polygenic. Direct or strong genetic influences have been identified for limited disorders like Tourrette disorder/ autism/juvenile bipolar disorder, while otherwise genetic influences are mediated indirectly via broader characteristics like temperament (Plomin, 1991). ÂÂ

Prenatal/Perinatal complications: Intrauterine environment may entail hazards, which compromise healthy development of fetus (Rutter, 1991). This is influenced by antenatal factors like:

formed skull vault. Perinatal damage is most commonly associated with developmental delays/hyperactivity (Hinshaw, 1993). ÂÂ

Physical injuries/diseases: Organic brain disorders especially head trauma/epilepsy are one of the strongest predictors of later psychological problems (Rutter, 1976).

Childhood injury may result in cognitive impairment, disinhibition and behavioral problems. Extent of sequelae is related to severity of damage but not closely to the site/location. Progress is also related to the social context in which recovery occurs (Hawkins et al., 1998)

Head trauma sequelae in children differ from adult in following ways:

ÂÂ

Capacity to compensate: Immature brain is more able than adult brain to compensate for localized damage e.g., hemispherectomy in early childhood may be followed by normal language development.

ÂÂ

Delayed effects: Early damage may not become manifest as a disorder until late stage of development.

Often, subtle damage insufficient to cause definite neurological signs or structural changes can cause behavioral problem later on - this concept known was known as ‘Minimal brain dysfunction.’ Childhood epilepsy especially temporal lobe epilepsy, often contributes to psychiatric disorder in following ways: ÂÂ

The brain lesion causing epilepsy may cause psychiatric disorder

ÂÂ

Psychosocial consequences of seizures may be contributory

ÂÂ

Antiepileptic drugs may contribute through side effects (e.g., phenobarbitone and hyperactivity).

„„

Advanced maternal age

„„

Blood group incompatibility

„„

Maternal malnutrition

„„

Smoking

Other disorders associated with increased risk:

„„

Alcohol and drug use

ÂÂ

Meningitis/Encephalitis

„„

Maternal infections like rubella/syphilis/AIDS

ÂÂ

„„

Prematurity and intrauterine growth retardation (IUGR) leading to low birth weight [LBW] «2000 g).

Hypoxia resulting electrocution

ÂÂ

Childhood human immunodeficiency virus (HIV) infection

ÂÂ

Chronic lead poisoning (-low IQ and hyperactivity) (Taylor, 1991)

ÂÂ

Chronic medical illness, not involving central nervous system (CNS), like asthma/diabetes/renal failure/cancer (Eiser, 1990).

Perinatal/Birth complications are commonly associated with forceps delivery, breech delivery and prolonged or obstructed labor, leading to fetal distress/injury during birth canal passage. Premature infants are particularly susceptible to brain injury during birth due to poorly

from

near

drowning/

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15


review article Psychological Individual psychological characteristics of child may be contributory:  Temperament: In a 26-year-old longitudinal follow-up study, Chess and Thomas, (1984) studied outcome of three types of temperament. Initially, an easy temperament was found in 40%, difficult temperament in 10% and slows to warm-up temperament in 15 %, of children. Easy temperament was a protective factor, while difficult temperament predicted future psychological difficulties,- these children experienced more conflict and negative reactions from caregivers/peers/teachers. Prognosis for ‘slow-to-warm up’ children was intermediate.  Intelligence: Low IQ and MR are associated with increased psychiatric disorder upto 2-3 times (Hinshaw, 1992). This dual diagnosis entails major additional handicap and impairment of adaptive behavior.  Immature/Neurotic defense mechanisms: when excessively used, allow child to regulate anxiety in short-term but entail long-term difficulties (Conte and Plutchik, 1995).  Coping strategies: These may be problem focused or emotion focused and is used consciously in crises. Use of dysfunctional coping strategies like avoidance of a problem/alcohol or drug use, maintain or exacerbate long-term difficulties (Zeidner and Endler, 1996).  Other cognitive distortions in children that contribute to future risk: „„ External locus of control (Rotter, 1966) „„ Low self esteem (Rolf, 1990) „„ Deficient self-regulatory beliefs e.g., depressive attribution style and school-based learned helplessness.

ÂÂ

Parental separation and loss: Psychiatric morbidity has been found to be persistently higher in bereaved children than controls, at both short-term and long-term follow-up depression and anxiety disorders occur most commonly but alcohol and drug use in males is particularly high (Kranzler et al, 1990). However, bereaved children may show resilience in presence of various protective factors. Risk factors in children are: „„ Young age (especially before 11 years) „„ Female sex „„ No preparation for death „„ Sudden or catastrophic death „„ Witnessing the death „„ Death of mother „„ Prior ambivalent relationship „„ Previous psychiatric disorder „„ Previous and subsequent losses „„ Poor social support „„ Inability to mourn, no involvement in death rituals „„ Lack of bereavement counseling.

ÂÂ

Parental psychiatric/medical illness: Besides contributing to genetic transmission, parental illness also adversely affects children via environmental mechanisms like insecure attachment, chaotic family environment, marital disharmony and economic difficulties. „„ Parental depression is associated with 3-fold increased risk of depression in offspring, as well as increased rates of phobias/panic disorder/alcohol-dependence and conduct disorder (Weissman et al., 1997). „„ Parental substance use and personality disorders contribute to conduct disorders and substance abuse (Merikangas et al., 1998). „„ Parental chronic physical illness like cancer/ AIDS/heart disease cause increased risk for anxiety/low self-esteem and poor social skills (Grant and Compas, 1995)

ÂÂ

Parenting style: Four types of parenting styles have been described with different developmental outcomes of the child: „„ Authoritative style: is a protective factor with maximum benefit to child (Darling and Steinberg, 1993). „„ Authoritarian style: Results in shy/anxious child. „„ Permissive style: Results in poor impulse control

Socioenvironmental ÂÂ

ÂÂ

Parental and familial factors „„ Attachment/bonding: Mary Ainsworth et al (1978) first described patterns of mother infant interaction following brief episode of experimentally contrived separation denoted as ‘strange situation’. Three types of attachment were: Secure attachment „„ Anxious attachment „„ Resistant attachment „„

Lack of secure attachment predicts future psychological problem (Fonagy et al. 1994).

16

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review article „„ ÂÂ

Neglecting style: Results in conduct problem.

Parental marital status/relationship: Parental divorce is associated with psychological/behavioral problems, specially in short-term with boys, with particular risk for conduct problems and academic failure (Cherlin et al., 1991) „„ More than the divorce itself, marital discord/ conflict preceding divorce especially increase risk of conduct problems. Single parent and step-parent/reconstituted families show higher mean levels of emotional problems and educational underachievement (Dunn et al., 1998). „„

ÂÂ

ÂÂ

Dysfunctional/Disorganized family environment: Apart from above family related factors, increased risk for both externalizing/internalizing disorders in children are associated with: „„ Inconsistent/Unclear rules „„ Ineffective monitoring and supervision „„ Lack of intellectual stimulation. „„ Over punitive/harsh discipline „„ Excessive use of corporal punishment „„ Younger maternal ages (especially teenage mothers) „„ Large family size „„ Abnormal parent child interactions like hostility/lacking of warmth/disengagement overprotection/inadvertent reinforcement of undesirable behaviors. Child abuse and maltreatment: „„ Child abuse includes physical abuse/sexual abuse/emotional abuse and neglect. „„ Physical abuse (nonaccidental physical injury) results in ‘battered child syndrome’ and results. In physical abuse (nonaccidental physical injury) results in ‘battered child syndrome’ and results in physical sequelae as well as behavioral problems like poor social skills, chronic oppositional and aggressive behavior and academic failure (Cichetti and Toth, 1995). „„ Sexual abuse: This can lead to wide range of psychological sequelae: (Kendall-Tackett et al, 1993). „„ Affective symptoms: Phobia/PTSD/Depression „„ Behavior problems: Conduct disorder, hyperactivity, sexualized behavior, selfdestructiveness. „„ Cognitive functioning: Educational/Language difficulties.

However, ultimate risk is tempered by effects of both quality of family environment and nature of subsequent life events. ÂÂ

Neglect: (Physical, emotional, medical care and educational) results in failure to thrive (psychosocial dwarfism), developmental delays, attachment disorders and conduct problems.

ÂÂ

Peer-related factors: Beyond family, relationships with peers provide unique and essential contribution to social, emotional and cognitive development. Increased risk may be caused by (Hawkins, 1992): „„ Rejection/Isolation by peers: Results in low self-esteem and poor social skills. „„ Affiliation with behaviorally deviant peers: predispose to conduct problems.

ÂÂ

School-related factors: School life brings its own particular demands and challenges. Adverse influences include (Rutter, 1985): „„ Frequent change of school „„ Chaotic school environment „„ Absence of consistent discipline/rules „„ Corporal punishment „„ Bullying in school

ÂÂ

Community related factors: Poverty and social disadvantage: Lower socioeconomic class and persistent financial difficulties are strongly associated with difficulties in cognitive skills and educational achievements (Carlson et al., 2000). „„ Urban inner city residential area: Risk of disorders were doubled in some studies (Rutter, 1975). „„ Increased community violence, criminality and unemployment. „„ Lack of supportive community and social network „„ Increased prevalence of alcohol and substance use. „„

Protective Factors ÂÂ

Biological factors (Rutter, 1995) „„ Good physical health „„ Absence of genetic vulnerabilities „„ No history of serious illness or injuries „„ Uncomplicated birth „„ Adequate nutrition „„ Female gender before puberty and male gender thereafter

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review article ÂÂ

ÂÂ

Psychological factors (Carlson, 2000) „„ Easy temperament „„ High level of intellectual ability „„ High self-esteem „„ Use of mature defenses and functional coping Familial factors (Darling and Steinberg, 1993) Secure attachment „„ Authoritative parenting style „„ Parental marital harmony „„ Involvement of father in child rearing „„ Explicit/consistent family rules „„ Clear and direct communication „„

ÂÂ

Educational factors (Rutter, 1985) „„ High quality day-care „„ Preschool early intervention educational program „„ Favorable school environment with firm authoritative leadership „„ Involvement with peer group

Assessment Dramatic advance has occurred in concept of psychiatric assessment of children in recent years, as follows: ÂÂ The identification of child as key informant ÂÂ The re-emergence of descriptive psychopathology instead of psychodynamic formulations ÂÂ The emergence of more highly specified diagnostic criteria for child and adolescent disorders ÂÂ The development of structured diagnostic interviews for children, parents and teachers ÂÂ Increasing awareness that diagnostic comorbidity is the norm ÂÂ Importance of identifying both strengths and weaknesses in a particular child. Assessment will include ÂÂ Detailed history ÂÂ Physical examination of child ÂÂ Psychiatric examination of child ÂÂ Examination of family and environment ÂÂ Psychological testing and assessment History should cover ÂÂ Presenting complaints ÂÂ Obstetric history ÂÂ Developmental history ÂÂ Family and past history ÂÂ School and play history

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Psychiatric Examination of Child Establishing rapport is of crucial importance. The examiner should not only focus on presenting symptom but also use a judicious mixture of appropriate techniques of play, drawing, painting, storytelling, etc. Verbal, nonverbal gestures and behaviors should be picked up by examiner. ÂÂ

General appearance: Stature, nutrition, congenital defects, injury suggestive of abuse, attitude towards examiner.

ÂÂ

Motor function: Activity compulsions.

ÂÂ

Speech: Articulation, vocabulary, fluency, abnormal speech, stammering, receptive or expressive language deficits.

ÂÂ

Content of talk and thought: Logical stream, abnormal use of words, delusions, obsessions, suicidal ideas.

ÂÂ

Perception: Illusions, hallucinations.

ÂÂ

Intellectual function: Attention, general information, abstraction (age and background appropriate)

ÂÂ

Emotional state: Affective display, attitude to family and school, separation responses

ÂÂ

Inquiry about fantasy life: Three wishes, worse or best things, dreams and ambitions.

ÂÂ

Indicators of social adjustment; peer relationship, hobbies, interests, games, (follower/leader, bully/ bullied).

level,

coordination,

Physical Examination of Child Including detailed neurological exam, and search for signs of abuse and neglect. Examination of Family ÂÂ

ÂÂ

Family structure „„

Parents - age, occupation, current physical/ emotional states, history of psychiatric disorders

„„

Siblings - ages, presence of problems

„„

Home circumstances, sleeping arrangements

Family function „„

Quality of parental relationship - mutual affection, capacity to communicate, sharing of attitudes

„„

Quality of parent child relationship - positive interaction, mutual enjoyment, criticism, hostility, rejection

„„

Sibling relationship


review article „„

support was found for the following interventions in high-risk children (Hill, 2000): „„ Home visits by nurses „„ Compensatory preschool education „„ Social skills and problem solving training.

Overall pattern of family dynamics - alliance, communication, exclusion, scapegoating, intergenerational confusion.

Psychological assessment: Should focus on the following areas: ÂÂ

Cognition (Intelligence, language and number skills, achievement, aptitude)

ÂÂ

Personality (temperament, adjustment)

ÂÂ

Perception of environment (attitude toward parents, peers)

ÂÂ

Self-concept

ÂÂ

Social behavior

ÂÂ

Sensory motor skills/brain damage

ÂÂ

Physical attributes

ÂÂ

Environment

Treatment Issues Important differences between management issues between children and adolescents: ÂÂ

Referral issues: Child is usually brought to clinic because someone else (parent, teacher) is concerned of annoyed by child’s behavior. Thus patient may be passive, if not reluctant, participant in treatment.

ÂÂ

Ethical issues: „„ Of prescription drugs marketed, 80% are not approved by Food and Drug Administration (FDA) for pediatric use. Thus, psychiatrists face the dilemma of either depriving children of potentially beneficial medical treatment or prescribing such medication ‘off label’ (Jensen et al., 1999). „„ Confidentiality is a key issue with the dilemma being how much disclosure to be made to parents, especially in case of adolescents.

ÂÂ

Pharmacokinetic issues: There are a number of pharmacokinetic differences which frequently lead to need for higher doses in children on milligram per kilogram basis to achieve similar drug concentration as in adults on the usually effective adult doses (Leeder and Kearns, 1997). „„ Activity of most drug metabolizing enzymes (CYP/glucuronidation) is absent in fetus but rapidly increase after birth and greatly exceed adult levels over first years of life; usual adult levels are achieved only after puberty. „„ Renal clearance is more rapid in children than in adults (Thus higher dose of lithium is required in children).

ÂÂ

Effectiveness issues: Many drugs proved effective in adults are not well-established in pediatric patients. Trycyclic antidepressants (TCAs) with proved efficacy in adults were mostly found to be equally effective to placebo in children and adolescents in controlled trials. Only two trials have proven modest benefit over placebo (Preskorn et al., 1987) while typically high placebo response rates (upto 68%) have been reported (Puig-Antich et al., 1987). This lower efficacy and higher placebo response has been attributed to following factors (Birmaher et al., 1996).

Prevention Prevention aims to reduce quantity and burden of psychiatric disorder in a population and may act on primary, secondary and tertiary levels. Primary prevention may involve 2 approaches (Kellam, 1993) ÂÂ

Targeted interventions: Aimed at selected highrisk group of children and families e.g., child care training for single mothers in lower social class.

ÂÂ

Universal interventions: Aimed at benefit for entire populations e.g., primary education for everyone. To be effective, intervention measures should have following features: „„ Must be active and persistent „„ Must start at an early age „„ Must be rooted in developmental processes „„ Must address the needs of child’s individual environment.

Health promotion may be done in school, home and community settings setting up any preventive program includes the following steps: ÂÂ

Identification of a problem/disorder

ÂÂ

Identification of risk and protective factors

ÂÂ

Carrying out pilot efficacy studies

ÂÂ

Launching and evaluating large scale effectiveness trails

ÂÂ

Dissemination of the program in variety of community settings. Prevention approaches to conduct disorder has been most established and successful. Evidence in

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

19


review article

ÂÂ

ÂÂ

20

„„

Greater importance of psychosocial variables in childhood depression (e.g. more hospitalization/ removal from home environment resulting in response even to placebo).

„„

Depression in children being heterogeneous entity with high comorbidity, predicting poorer drug response.

„„

Inclusion of mild/moderate depression, lower prevalence of melancholic depression in children.

„„

Insufficient dosage/duration in pediatric drug trials.

„„

Mostly tertiary amine TCA used in trials (e.g. imipramine) having major effect on noradrenergic system, which is fully developed only after puberty.

„„

More efficient hepatic deamination in children resulting in decreased TCA efficacy.

„„

Pubertal hormonal changes (e.g. increased gonadal steroids) inhibiting neurotransmitter function.

Tolerability issues: Side effects may be particularly deleterious in children with possible long-term effects on growth and development, due to prolonged cumulative exposure. Of particular concern in this population are (Janicak et al. 2001): „„

Stimulants and growth retardation

„„

Selective serotonin reuptake inhibitors (SSRls) and suicidal intentions

„„

TCAs and cardiotoxicity

„„

Neuroleptics and tardive dyskinesia

Psychotherapeutic issues: Nonsomatic treatments may be more acceptable in child populations due to lesser risk of iatrogenic side effects. However, psychotherapy has to be flexibly and intelligently adjusted to be effective, including the following factors: „„

Therapist has to deal not only with child but also with environmental and familial dynamics.

Close collaboration is needed with child and parents as well as school, legal officers, social welfare agencies and community leaders at times.

„„

Therapist must be aware of the individual child’s physical, emotional and cognitive development to understand symptoms and set treatment goals.

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„„

The child is less proficient~ in abstract language use and therapist has to involve nonverbal indirect techniques like play, art, writing and fantasy.

Course and Outcome in Child Psychiatry Childhood psychiatric disorders are generally associated with poorer outcome and graver prognosis than their adult counterparts (Rutter, 1995). Individual disorders have been shown to have significant continuity into adulthood either in a diagnosis-specific manner or in terms of nonspecific psychosocial impairments. Important questions addressed in outcome studies in children are: (Rutter, 1995) ÂÂ

What happens to the children diagnosed to have psychiatric disorders?

ÂÂ

What is natural course of the disorder?

ÂÂ

Do these children continue to suffer from the same or some other psychiatric disorder?

ÂÂ

Does any specific intervention alter the course of the disorders favorably and to what extent?

Individual disorder specific findings are: ÂÂ Depressive disorders are resistant, chronic and recurrent, with higher risk of bipolarity, than adults (Birmaher et al., 2002). ÂÂ Bipolar disorders show increased frequency of mixed episodes and rapid cycling with poorer rate of recovery (Carlson et al., 2000). ÂÂ About 50% of ADHD patients will have persistent symptoms in adulthood with higher risk of antisocial behavior, substance abuse and socio-occupational dysfunction (Mannuzza and Klein., 2000). ÂÂ Twenty-five percent of children with ODD develop CD while 10% progress to antisocial personality disorder (ASPD) while 40% of children with CD will ultimately develop ASPD in future (Steiner et al., 1990) ÂÂ Obsessive-compulsive disorders (OCD) has a chronic and relapsing course, with poorer response to medications (Leonard, 1993). ÂÂ In childhood autism, only upto 15% had good outcome while upto 75% had poor! Very poor outcome. ÂÂ In almost all disorders, any comorbidity predicted poorer outcome (Mannuzza et al., 1991) Conclusion It is evident that mere extrapolation of research data from adults to childhood populations is undesirable


review article and untenable. Childhood mental health and disorder appears to be different in many aspects of diagnosis, management and outcome, from their adult counterparts. There is an unfortunate dearth of research in fields of pediatric epidemiology, clinical assessment, pharmacological and psychosocial management, which needs to be addressed systematically in future. Suggested Reading 1. Achenbach TM, Edelbrock CS. The classification of child psychopathology: a review and analysis of empirical efforts. Psychol Bull 1978;85(6):1275-301. 2. Birmaher B, Arbelaez C, Brent D. Course and outcome of child and adolescent major depressive disorder. Child Adolesc Psychiatr Clin N Am 2002;11(3):619-37, x. 3. Cadman D, Boyle M, Szatmari P, Offord DR. Chronic illness, disability, and mental and social well-being: findings of the Ontario Child Health Study. Pediatrics 1987;79(5):805-13. 4. Carlson GA, Bromet EJ, Sievers S. Phenomenology and outcome of subjects with early- and adult-onset psychotic mania. Am J Psychiatry 2000;157(2):213-9. 5. Chess S, Thomas A. Origins and evolutions of behaviour disorders. Brunner/Maze: New York, 1984. 6. Cicchetti D, Toth SL. A developmental psychopathology perspective on child abuse and neglect. J Am Acad Child Adolesc Psychiatry 1995;34(5):541-65. 7. Conte H, Plutchik R. Ego Defenses: Theory and Measurement. Wiley: New York, 1995. 8. Darling N, Steinberg L. Parenting style and context: An integrative model. Psychol Bull 1993;113(3): 487-96. 9. Dunn J, Deater-Deckard K, Pickering K, Oâ&#x20AC;&#x2122;Connor TG, Golding J. Childrenâ&#x20AC;&#x2122;s adjustment and prosocial behaviour in step-, single-parent, and non-stepfamily settings: findings from a community study. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. J Child Psychol Psychiatry 1998;39(8):1083-95. 10. Eiser C. Psychological effects of chronic disease. J Child Psychol Psychiatry 1990;31(1):85-98. 11. Flynn J. Massive IQ gains in 14 nations. Psychol Bull 1987:101(4):171-91. 12. Flynn JR. Searching for justice: the discovery of IQ gains over time. Am Psychol 1999; 54(1): 5-20. 13. Fonagy P, Steele M, Steele H, Higgitt A, Target M. The Emanuel Miller Memorial Lecture 1992. The theory and practice of resilience. J Child Psychol Psychiatry 1994;35(2):231-57. 14. Greenspan SI, Wieder S. Diagnostic classification in infancy and early childhood. In: Psychiatry. 2nd edition, Vol. II, Tasman A, Kay J, Lieberman J (Eds.), John Wiley & Sons: Chichester, 2003. 15. Hawkins JD, Catalano RF, Miller JY. Risk and protective factors for alcohol and other drug problems in adolescence and early adulthood: implications for substance abuse prevention. Psychol Bull 1992;112(1):64-105.

16. Hill P. Prevention of mental disorder in childhood. In: New Oxford Textbook of Psychiatry. Gelder M, LopezIbor J, Andreasen NC (Eds.), Oxford University Press Oxford 2000:p.1705-11. 17. Hinshaw S, Lahey B, Hart E. Issues of taxonomy and comorbidity in the development of conduct disorder. Development and Psychopathology Special Issue: Toward a Developmental Perspective on Conduct Disorder 1993;5:310-49. 18. Hinshaw SP. Externalizing behavior problems and academic underachievement in childhood and adolescence: causal relationships and underlying mechanisms. Psychol Bull 1992;111(1):127-55. 19. Hirshfeld DR, Rosenbaum JF, Biederman J, Bolduc EA, Faraone SV, Snidman N, et al. Stable behavioral inhibition and its association with anxiety disorder. J Am Acad Child Adolesc Psychiatry 1992;31(1):103-11. 20. Jahoda M. Current concepts of positive mental health. Basic Books: New York, 1958. 21. Janicak PG, Davis JM, Preskorn SH, et al. Principles and Practice of Psychopharmacotherapy. 3rd edition, Lippincott Williams & Wilkins: Philadelphia, 2001. 22. Jensen PS, Bhatara VS, Vitiello B, Hoagwood K, Feil M, Burke LB. Psychoactive medication prescribing practices for U.S. children: gaps between research and clinical practice. J Am Acad Child Adolesc Psychiatry 1999;38(5):557-65. 23. Kellam SG. Concluding remarks at the 5th Indo-US Symposium on Child Mental Health. NIMHANS, Bangalore, 1989. 24. Kendall-Tackett KA, Williams LM, Finkelhor D. Impact of sexual abuse on children: a review and synthesis of recent empirical studies. Psychol Bull 1993;113(1):164-80. 25. Kranzler EM, Shaffer D, Wasserman G, Davies M. Early childhood bereavement. J Am Acad Child Adolesc Psychiatry 1990;29(4):513-20. 26. Leeder JS, Kearns GL. Pharmacogenetics in pediatrics. Implications for practice. Pediatr Clin North Am 1997;44(1):55-77. 27. Leonard HL, Swedo SE, Lenane MC, Rettew DC, Hamburger SD, Bartko JJ, et al. A 2- to 7-year followup study of 54 obsessive-compulsive children and adolescents. Arch Gen Psychiatry 1993;50(6):429-39. 28. Mannuzza S, Klein RG. Long-term prognosis in attentiondeficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 2000;9(3):711-26. 29. Mannuzza S, Klein RG, Bonagura N, Malloy P, Giampino TL, Addalli KA. Hyperactive boys almost grown up. V. Replication of psychiatric status. Arch Gen Psychiatry 1991;48(1):77-83. 30. Ainsworth M, Bhetra PS, Vitiello VS, et al. Early childhood bereavement. Am Acad Child Adolescent Psychiatr 1978;31:513-20. 31. Merikangas KR, Dierker LC, Szatmari P. Psychopathology among offspring of parents with substance abuse and/ or anxiety disorders: a high-risk study. J Child Psychol Psychiatry 1998;39(5):711-20.

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review article 32. Plomin R. Genetic risk and psychosocial disorders. In: Biological Risk Factors for Psychosocial Disorders. Rutter M, Caeser D. (Eds.), Cambridge University Press: Cambridge 1991:p.101-38.

Schedule for Children Version 2.3 (DISC-2.3): description, acceptability, prevalence rates, and performance in the MECA Study. Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. J Am Acad Child Adolesc Psychiatry 1996;35(7): 865-77.

33. Preskorn SH, Weller EB, Hughes CW, Weller RA, Bolte K. Depression in prepubertal children: dexamethasone nonsuppression predicts differential response to imipramine vs. placebo. Psychopharmacol Bull 1987;23(1):128-33.

46. Srinath S, Girimaji S. Epidemiology of child and adolescent mental health problems and mental retardation. NIMHANS J 1999;17:355-66.

34. Puig-Antich J, Perel JM, Lupatkin W, Chambers WJ, Tabrizi MA, et al. Imipramine in prepubertal major depressive disorders. Arch Gen Psychiatry 1987;44(1):81-9.

47. Steiner H, Cauffman E, Duxbury E. Personality traits in juvenile delinquents: relation to criminal behavior and recidivism. J Am Acad Child Adolesc Psychiatry 1999;38(3):256-62.

35. Roberts RE, Attkisson CC, Rosenblatt A. Prevalence of psychopathology among children and adolescents. Am J Psychiatry 1998;155(6):715-25.

48. Sroufe LA, Rutter M. The domain of developmental psychopathology. Child Dev 1984;55(1):17-29.

36. Rolf J, Masten A, Cichetti D, et al. Risk and protective factors in the development of psychopathology. Cambridge University Press: New York, 1990.

49. Taylor DC. The concept of mental health in children. Eur Child Adolesc Psychiatry 2003;12(3):107-13. 50. Taylor E. Developmental neuropsychiatry. J Child Psychol Psychiatry 1991;32(1):3-47.

37. Rotter JB. Generalized expectancies for internal versus external control of reinforcement. Psychological Monographs 1966;80(1):1-28.

51. Loeber R. The prevention of serious delinquency and violence. In: Sourcebook on Serious, Violent and Chronic Juvenile Offenders. Howell JC, Krisberg B, Hawkins JD. et al. (Eds.), Thousand Oaks, CA, Sage, 1995.

38. Rutter M. A childrenâ&#x20AC;&#x2122;s behaviour questionnaire for completion by teachers: preliminary findings. J Child Psychol Psychiatry 1967;8(1):1-11.

52. Loeber R. Epidemiology of Juvenile Violence. In: Child and Adolescent Psychiatric Clinics of North America. Lewis DO, Yeager CA (Eds.) 2000;9:733-48.

39. Rutter M. Brain damage syndrome in childhood: concepts and findings. J Child Psychol Psychiatr 1977;18(1):1-21. 40. Rutter M. Family and school influences on behavioural development. J Child Psychol Psychiatry 1985;26(3):349-68.

53. Vaillant GE, Vaillant CO. Normality and Mental Health. In: Comprehensive Textbook of Psychiatry. 8th edition, Vol. I, Sadock BJ, Sadock VA (Eds.), Williams & Wilkins: Philadelphia, Lipincott, 2000.

41. Rutter M. Nature, nurture and psychopathology: a new look at on old topic. Develop Psychopathol 1991;3(2): 125-36.

54. Vogel JM, Vemberg EM. Childrenâ&#x20AC;&#x2122;s psychological responses to disasters. J Clin Child Psychol 1993;22: 464-84.

42. Rutter M. Relationships between mental disorders in childhood and adulthood. Acta Psychiatr Scand 1995;91(2):73-85.

55. Wallerstein JS, Kelly JB. Surviving the Breakup: How Children and their Parents Cope with Divorce. Basic Books: New York, 1980.

43. Rutter M, Tizard J, Yule W, et al. (1976). Isle of Wight Studies 1964-1974. Psychological Medicine, 6, 313-332. Ryan, N.D., Williamson, D.E., Iyenger, S. et al. (1992). Journal of American Academy of Child and Adolescent Psychiatry, 31, 4,600-605.

56. Wallerstein JS, Carbin SB. The child and vicissitudes of divorce. In: Child and Adolescent Psychiatry. Lewis M (Ed). Williams & Wilkins: Philadelphia, Lippincott 2004: p.1275-84.

44. Scott, S. Developmental psychopathology and classification in childhood & adolescence. In: New Oxford Textbook of Psychiatry Gelder M, Lopez-Ibor J, Andreasen, NC (Eds.), Oxford University Press: Oxford. 2000:p.1705-711, 1685-690.

57. Weissman MM, Warner V, Wickramaratne P, Moreau D, Olfson M. Offspring of depressed parents. 10 Years later. Arch Gen Psychiatry. 1997;54(10):932-40.

45. Shaffer D, Fisher P, Dulcan MK, Davies M, Piacentini J, Schwab-Stone ME, et al. The NIMH Diagnostic Interview

n

22

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58. Zeidner M, Endler N. Handbook of coping: Theory, Research, Applications. Wiley: New York, 1996.

n

n


Clinical Study

Effect of Rag Neelambari on Certain Physiological and Behavioral Parameters of Preterm Infants P Bharathi*, R Sobana**, K Jaiganesh†, S Parthasarathy**, S VadiveL†

Abstract It has been established by several authors that premature babies benefit immensely from lullaby-style music exposure. Most lullabies in South India are sung in the melodic mode known as Neelambari, and it is widely accepted traditionally for its sleep-promoting effects. The present study was designed to elicit the effects of Neelambari on heart rate, respiratory rate, O2 saturation and behavioral score of medically healthy premature infants admitted in neonatal intensive care unit (NICU). Thirteen stable infants received the pre-recorded music at 70 dB through free field delivery for 30 minutes for three consecutive days. All the physiological and behavioral parameters were recorded every five minutes, before, during and after therapy, allowing 30 minutes for each interval. It was found that Neelambari has a beneficial effect on all the above physiological parameters. Behavioral score demonstrated decreased arousal and a state of progression towards deep sleep about 20 minutes after exposure to this rag. These findings refute those of an earlier study conducted in Puducherry, which concluded that the anecdotal references to the sleep-promoting effects of Neelambari reflect a conditioned response. Several authors have stated that it is difficult to elicit conditioned responses in premature infants, due to cortical immaturity. Since, all the infants demonstrated decreased arousal, drowsiness and a state of deep sleep following Neelambari exposure, we can infer that Neelambari does possess sleep-inducing qualities. Keywords: Preterm neonates, music therapy, Neelambari

P

remature infants (born before 37 weeks gestation) are the ones who have not yet reached the level of development that allows life outside the womb. Specific risks for the preterm neonates include respiratory problems like infant respiratory distress syndrome (IRDS), defective sleep patterns and inadequate development of brain structure. A majority of them are subjected to costly and invasive treatment measures. Katz1 and Segall2 were the pioneers who exposed premature babies to music stimulation, and observed that they benefited well from such exposures. Later, several researchers established that premature infants in the neonatal intensive care unit (NICU) show improvements in physiological parameters such as

*Professor and Head Dept. of Music Therapy **Assistant Professor †Associate Professor Dept. of Physiology Mahatma Gandhi Medical College and Research Institute, Puducherry ‡Professor, Dept. of Physiology Karpaga Vinayaga Institute of Medical Sciences, Madhuranthagam, Chennai Address for correspondence Dr S Parthasarathy, Assistant Professor Mahatma Gandhi Medical College and Research Institute Puduchery, South India E-mail: painfreepartha@yahoo.com

heart rate, blood pressure, oxygen(O2) saturation and respiratory rate, when exposed to music stimulation.3,4 Standley5 has stated that playing a music lullaby can have a noticeable therapeutic effect on premature babies in NICU. Malloy6 studied infants who received a recorded instrumental Brahms’ lullaby, and found that these infants were about 10 days younger at discharge than those in the routine care group. Coleman7 et al reported increased caloric intake and weight gain in premature infants exposed to recorded instrumental music. A raga is one of the melodic modes used in Indian Classical Music: A series of five or more musical notes upon which a melody is made. Rag Neelambari belongs to the Indian Carnatic system of music and is widely believed to induce sleep, and possess some sleep promoting qualities.8 Most lullabies in South India are sung in Neelambari. The present study was designed to elicit the effects of the Indian Rag Neelambari on physiological parameters like heart rate, respiratory rate, O2 saturation and behavioral score of premature infants admitted in NICU. Aims ÂÂ

To study the changes in physiological parameters like heart rate, respiratory rate and O2 saturation

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23


clinical study levels, and behavioral ratings after exposing medically healthy preterm infants to recorded, instrumental music composed in Rag Neelambari. ÂÂ

To determine whether Rag Neelambari possesses inherent sleep-promoting qualities.

Methods The study was carried out in a Multispeciality Hospital situated in South Chennai. The study protocol was approved by the hospital Ethical Committee, and a written informed consent was obtained from all the concerned parents. Inclusion criteria were: a) Gestational age at birth of 31-33 weeks; b) birth weight, height and head circumference appropriate for gestational age (10th to 90th percentile); c) hearing confirmed by audiometry and d) no acute illness. Exclusion criteria were: a) Use of dopamine, hydrocortisone or phenobarbital; b) anomalies associated with neurological problems; c) congenital or acquired infections (HIV, sepsis) and d) major maternal illness, or chronic medication (insulin, steroids). Thirteen premature infants who satisfied the inclusion criteria were exposed to a recorded instrumental music composed in Rag Neelambari, for a duration of 30 minutes/day for three consecutive days, commencing an hour after the infants were fed. All the infants were placed in the supine position. The music chosen for administration was a pre-recorded purely instrumental lullaby-style melody, soothing, slow, repetitive and rhythmic, composed in Rag Neelambari and was delivered by free field (sound transferred to the ear via sound waves). The decibel (dB) level of the music was controlled at the 70 dB range, two speakers were placed about 1 m from the infant’s bed, exposing 3-4 infants at a time to the music. The door of the NICU was closed to prevent external disturbances, and it was ensured that the background noise did not exceed 45 dB, by using a Sound Analyzer incorporated with a decibel-A scale filter. The music exposures were carried out for a duration of 30 minutes for three consecutive days, at 11 am in the morning, an hour after the babies completed their feeding. Data collection was performed by the same trained nurses every day, for all the three

days of music exposure, every 5 minutes: a) At the 30-minute interval before music exposure; b) during the 30-minute of music exposure and c) during the 30-minute interval following music exposure. Respiratory rate, O2 saturation, heart rate and the behavioral state of the infants devised by Als9 were noted and recorded every five minutes before, during and after 30 minutes of music exposure, each interval consisting of a duration of 30 minutes. The behavioral state of the infant was scored as follows: deep sleep = 1; light sleep = 2; drowsy = 3; quite awake or alert = 4; actively awake and aroused = 5; highly aroused, upset or crying = 6; prolonged respiratory pause >8 seconds = 7. The pattern, effort and rate of breathing per minute were counted by observing the abdominal movements. Heart rate and oxygen saturation (SpO2) were monitored with respective monitors. As the study involves such open intervention it is difficult to do any blinding. The statistics include simple description and paired student ‘t’ tests. Results The observed variables are shown in Table 1. The significant change in the physiological variables is depicted in a bar diagram (Fig. 1). We can infer from the table and chart that the respiratory rate, heart rate improved significantly with initiation and completion of music therapy. Even though the O2 saturation decreased initially, the overall improvement was significant. At the 30-minute interval after music exposure, there was a significant reduction in behavioral score (p < 0.001), with the lowest score being recorded at the 29th minute following the cessation of music administration, indicating a state of deep sleep experienced by the infants at this time. Discussion Our study was performed using recorded instrumental lullaby-style music, which had a slow, rhythmic and repetitive pattern played in a simple and soothing way. The melody was played step-wise, within a limited

Table 1. Showing Effect of Rag Neelambari on Physiological and Behavioral Parameters in Preterm Infants during Study Therapies (n = 13) Test parameter Heart rate (BPM) Respiratory rate (per min) O2 saturation Behavioral score

24

Before therapy 147 ± 2.7 44 ± 3.27 93 ± 1.3 3.3 ± 0.28

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

During therapy 140 ± 2 48 ± 1.5 90 ± 1.14 2.6 ± 0.29

After therapy 124 ± 2.12 38 ± 1.36 96 ± 0.85 1.6 ± 0.28


clinical study 160

147

140

140 124

120 100

93

90

Before

During

96

80 60

44

48

Before

During

38

40 20 0 Before

During

After

Heart rate (p < 0.001; t = 25.02);

(p <0.001; t = 5.09);

After

Resp. rate

After

O2 saturation

(p <0.001; t = 9.859)

Figure 1. Effect of Rag Neelambari on the heart rate, respiratory rate and O2 saturation of infants before, during and after exposure for 30 minutes.

range of octave, and notes in the major scale. Classical music is known to improve the physiologic and psychological well-being of newborns.10 Fassbender states that the infantsâ&#x20AC;&#x2122; capacity for perceiving both tonal and rhythmic information is far more sensitive than that of adults.11 It can easily be inferred from our findings that musical melody based on Rag Neelambari has a beneficial effect on physiological parameters like heart rate, respiratory rate and O2 saturation levels of preterm infants. Behavioral score based on the level of alertness and drowsiness clearly demonstrates decreased arousal, and a state of progression towards deep sleep about 20-30 minutes after exposure to the rag. Though a previous study has stated that the references to the sleep-promoting effects of Neelambari probably reflect a conditioned response,12 our study on premature infants in whom it is difficult to demonstrate conditioned responses,13 reveals that Neelambari does have the capacity to induce sleep. Danuta and Marvin14 argue that premature infants show less rapid habituation, due to cortical immaturity. Another study performed in Canada studied the preterm infantsâ&#x20AC;&#x2122; behavioral and cardiac responses to repeated auditory stimuli, and concluded that preterms were unable to habituate to repeated presentations of auditory stimuli.15 Since, all the 13 infants exposed to Neelambari demonstrated a gradual shift from the aroused state towards drowsiness, followed by light sleep, finally progressing towards deep sleep, we can arrive at the conclusion that Neelambari has inherent sleep-promoting qualities. We found our results to

be better. We theorize that it is necessary that the rag should not be rendered fast, in a complex manner or in the wrong key for the young listeners. The melody should be simple, repetitive and step-wise, with a slow and soft rhythm to get the necessary results. The limitations of this study were a small sample size, absence of control group without music of the same gestational age and maturity. We suggest that controlled studies with larger samples are essential to confirm our initial findings. Conclusion Exposure to recorded instrumental music based on Rag Neelambari for 30 minutes/day for three consecutive days is beneficial to preterm infants. It is associated with a reduced heart rate, respiratory rate, increased O2 saturation and a deeper sleep in stable preterm infants at 30 minutes after exposure. Further research with other ragas used in lullabies is needed to confirm the sleep-inducing properties of Indian ragas like Neelambari. References 1. Katz V. Auditory stimulation and developmental behavior of the premature infant. Nurs Res 1971;20(3):196-201. 2. Segall M. The relationship between auditory stimulation and heart rate response of the premature infant. Nurs Res Conf 1971;7:119-29. 3. Cassidy JW, Standley JM. The effect of music listening on physiological responses of premature infants in the NICU. J Music Ther 1995;46(3):180-90.

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25


clinical study 4. Chou LL, Wang RH, Chen SJ, Pai L. Effects of music therapy on oxygen saturation in premature infants receiving endotracheal suctioning. J Nurs Res 2003;11(3):209-16.

care unit and developmental outcome. Pediatrics 1986;78(6):1123-32.

5. Standley JM. A meta-analysis of the efficacy of music therapy for premature infants. J Pediatr Nurs 2002;17(2):107-13.

10. Shoemark H, Wolfe R, Calabro J. The effects of recorded sedative music on the physiology and behaviour of premature infants with a respiratory disorder. Aust J Music Ther 2003;14:3-19.

6. Malloy GB. The relationship between maternal and musical auditory stimulation and the developmental behavior of premature infants. Birth Defects Orig Artic Ser 1979;15(7):81-98.

11. Fassbender C. Infants’ auditory sensitivity towards acoustic parameters of speech and music. In: Musical Beginnings. Deliege I, Sloboda J (Eds.), Oxford University Press: Oxford 1996:p.56-87.

7. Coleman JM, Pratt RR, Stoddard RA, Gerstmann DR, Abel HH. The effects of the male and female singing and speaking voices on selected physiological and behavioral measures of premature infants in the intensive care unit. Int J Arts Med 1997;5(2):4-11.

12. Gitanjali B. Effect of the Karnatic music raga “Neelambari” on sleep architecture. Indian J Physiol Pharmacol 1998;42(1):119-22.

8. Bagyalakshmi K. Ragas in Carnatic music. 2nd edition, Carnatic Music Book Centre, Mylapore, Chennai. 2009. 9. Als H, Lawhon G, Brown E, Gibes R, Duffy FH, McAnulty G, et al. Individualized behavioral and environmental care for the very low birth weight preterm infant at high risk for bronchopulmonary dysplasia: neonatal intensive

13. Sameroff, Arnold J. Can conditioned responses be established in the newborn infant: 1971? Developmental Psychology 1971;5(1):1-12. 14. Bukatko D, Daehler MW. In: Child Development: A Thematic Approach. 5th edition, University of Massachusetts, Amherst, 1982. 15. Marie Boyle R. Learned Responses in Preterm infants. A Thesis Submitted to the National Library of Canada, Ontario, University of Alberta, 1991.

Double-blind, Placebo-controlled Study of Zinc Sulfate in the Treatment of Attention Deficit Hyperactivity Disorder Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the etiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. Methods: Patients with a primary DSM-IV diagnosis of ADHD (n = 400; 72 girls, 328 boys, mean age = 9.61 ± 1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n = 202) (150 mg/ day) or placebo (n = 198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values.

26

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high body mass index (BMI) score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well-tolerated and associated with a low rate of side effect. Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels. Bilici M, Yildirim F, Kandil S, et al. Prog Neuropsychopharmacol Biol Psychiatry 2004;28(1):181-90.


Clinical Study

The Role of Clinical Signs in the Diagnosis of Late-onset Neonatal Sepsis and Formulation of Clinical Score Subhranshu Sekhar Kar*, Rajani Dube**, Samarendra Mahapatro*, Sitanshu Sekhar Karâ&#x20AC;

Abstract Neonatal sepsis is the most important cause of morbidity and mortality in developing countries. The low birth weight and preterm babies are more vulnerable to it. It is diagnosed when generalized systemic features are associated with pure growth of bacteria from one or more sites. However, the signs of sepsis are nonspecific and the outcome of a neonate with sepsis depends on its early identification. So, this study is done to evaluate the role of various clinical signs in diagnosing late-onset sepsis, their statistical analysis and to develop a scoring system-based purely on clinical signs for early diagnosis and prompt institution of treatment. Keywords: Sepsis, late-onset, clinical score

I

nfection, as either prime pathology or a complication of other illness, is a major cause of neonatal mortality and morbidity throughout the world.1,2 In developing countries, sepsis accounts for 30-50% of five million total deaths each year.3,4 It is estimated that almost 20% of all neonates develop infection and approximately 1% die of the serious systematic infection.4 The incidence of neonatal sepsis according to the data from National Neonatal Perinatal Database (NNPD, 2002-03) is 30 per 1,000 live births.5 The microorganisms most commonly associated with sepsis include Group B Streptococcus (GBS), Escherichia coli, coagulase-negative Staphylococcus (CoNS), Haemophilus influenzae and Listeria monocytogenes.6,7

paucity of data regarding the scoring purely based on clinical signs for the prediction of neonatal sepsis (late-onset) and hence the intention of the study is to develop a scoring system for risk predictability and early management. Aims and Objectives To evaluate the role of various clinical signs in the diagnosis of late-onset neonatal sepsis, their statistical analysis and formulation of clinical score. Material and Methods

As the clinical signs of sepsis are mostly nonspecific, hence the outcome of a neonate with sepsis depends on its early identification.8

The present prospective study was undertaken in the neonatal intensive care unit (NICU) and special care neonatal unit (SCNU), Hi-Tech Medical College, Bhubaneswar during the year 2007-2010.

Through there are various scoring systems on perinatal risk factors and hematological parameters, there is

Selection of Cases

*Associate Professor Dept. of Pediatrics **Associate Professor Dept. of Obstetrics and Gynecology Hi-Tech Medical College, Bhubaneswar â&#x20AC; Assistant Professor Dept. of Community Medicine, JIPMER, Puducherry Address for correspondence Dr Subhranshu Sekhar Kar Associate Professor, Dept. of Pediatrics Plot No.: 1, Lane-12, Aryabarta Colony Jagannathnagar, Rasulgarh, Bhubaneswar - 751 010, Odisha E-mail: drsskar@gmail.com

The newborns having clinical signs of sepsis after three days of life were included in this study. Those having major congenital malformations were excluded.

Data Collection In all cases detail maternal and neonatal history with respect to symptoms, signs, complications and other relevant data were recorded in a pre-prepared proforma. All admitted neonates were monitored for clinical signs till 28 days of life or till discharge from hospital whichever is earlier. Babies showing any of the

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

27


clinical study clinical signs were evaluated for sepsis. Repeat sepsis screen and cultures were done only if there was a fresh clinical sign after 72 hours of first blood culture.

ÂÂ

Categories

Clinical signs studied:

The neonates were grouped into three categories:

l

Sick looking

l Apnea

l

Refusal to feed

l

Increased prefeed aspirate

l

Lethargy

l

Chest retraction

l

Seizure

l Grunting

ÂÂ

Definite sepsis: Presence of clinical signs „„ Isolation of bacterial infective agent from either blood or cerebrospinal fluid (CSF). Probable sepsis: „„ Presence of clinical signs „„ Two screening parameters positive „„ Blood/CSF culture sterile „„

ÂÂ

Table 1. Day of Occurrence of Symptomatic Events (n = 210) Onset (days)

Frequency of occurrence (events)

Percentage (%)

4-7

90

42.8

8-14

66

31.4

15-21

30

14.3

22-28

24

11.5

Total

210

100%

No sepsis: „„ Presence of clinical signs „„ Sepsis screen and cultures - negative

l

Sclerema l

Abdominal distension increase abdominal girth by 2 cm

l

Central cyanosis l Increased respiratory rate >60/min

l

Hypothermia (axillary temperature <360 C).

l

Fever (axillary temperature >37.50 C)

l

Bradycardia - Heart rate <100/min

l

Tachycardia - Heart rate >160/min

Sepsis screening parameters ● CRP ● ANC

● ●

mESR Band cell count

● TLC

● I/T (Immature to total neutrophil) ratio ● Platelets

The mean of onset (days) = 10.7 ± 6.8

Table 2. Presenting Clinical Signs Presenting feature

Frequency of occurrence (Events) (n = 210)

Percentage (%)

Sepsis

No sepsis

Sick looking

38

18.1

20

18

Refusal to feed

24

11.4

6

18

Lethargy

76

36.1

40

36

Apnea

102

48.6

46

56

Increased prefeed aspirates

24

11.4

10

14

Chest retraction

12

5.7

6

6

Grunting

8

3.8

6

2

Abdominal distension

28

13.3

16

12

Increased respiratory rate

34

16.2

16

18

Bradycardia

0

0

0

0

Tachycardia

46

22

20

26

Hypothermia

8

3.8

4

4

Fever

36

17.1

20

16

Seizure

0

0

0

0

Sclerema

0

0

0

0

Central cyanosis

0

0

0

0

28

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012


clinical study Table 3. Relationship of Sepsis with Occurrence of Events Events (n = 210)

Table 4. Bacteriological Profile in Definite Sepsis Bacteria

Sepsis

No. of events (n = 60)

Percentage (%)

Definite

Probable

Gram-positive bacteria

26

43.3

8 (40%)

12 (60%)

Staphylococcus aureus

18

30

Refusal to feed (n = 6)

2 (33.3%)

4 (66.7%)

Enterococcus faecalis

6

10

Lethargy (n = 40)

24 (60%)

16 (40%)

28 (60.8%)

18 (39.2%)

Coagulase-negative staphylococcus (CoNS)

2

3.3

8 (80%)

2 (20%)

Gram-negative bacteria

34

56.7

Chest retraction (n = 6)

4 (66.7%)

2 (33.3%)

Klebsiella pneumoniae

12

20

Grunting (n = 6)

4 (66.7%)

2 (33.3%)

Alkaligenes faecalis

8

13.3

Abdominal distension (n = 16)

12 (75%)

4 (25%)

Escherichia coli

6

10

Enterobacter spp.

4

6.7

Increased respiratory rate (n = 16)

12 (75%)

4 (25%)

Acinetobacter

4

6.7

Bradycardia (n = 0)

0

0

Tachycardia (n = 20)

18 (90%)

2 (10%)

OBSERVATIONS

Hypothermia (n = 4)

2 (50%)

2 (50%)

Fever (n = 20)

12 (60%)

8 (90%)

Seizure (n = 0)

0

0

The study cohort included 160 neonates with 210 symptomatic events (i.e., the occurrence of one or more clinical signs in each event).

Sclerema (n = 0)

0

0

Central cyanosis (n = 0)

0

0

Sick looking (n = 20)

Apnea (n = 46) Increased prefeed aspirates (n = 10)

Out of 160 cases - male to female ratio is - male (118): Female (42) = 2.8:1 and majority 91% (=146) babies were preterms with mean gestational age Âą SD = 31.4 Âą 3.4

Table 5. Statistical Analysis of Clinical Signs in Definite Sepsis Signs

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

LR+

LR-

Apnea (n = 102)

47

51

28

70

0.95

1.08

Lethargy (n = 76)

40

65

32

73

1.14

0.92

Tachycardia (n = 46)

30

81

39

74

1.57

0.86

Sick looking (n = 38)

13

80

21

70

0.65

1.08

Fever (n = 36)

20

84

33

73

1.25

0.95

Increased respiratory rate (n = 34)

10

81

18

69

0.5

1.1

Abdominal distension (n = 28)

20

89

43

74

1.8

0.89

Refusal to feed (n= 24)

3

85

83

69

0.22

1.13

Increased prefeed aspirate (n = 24)

17

91

41

73

1.6

0.93

Chest retraction (n = 12)

7

95

33

72

1.22

0.99

Grunting (n = 8)

7

97

50

72

2.33

0.96

Hypothermia (n = 8)

3

96

25

71

0.07

0.95

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

29


clinical study value (PPV) ranges from 8.3 to 50%. Grunting is the only sign having LR+ of >2.

Table 6. Clinical Score Clinical sign

Score

Lethargy

1

Tachycardia

1

Fever

1

Abdominal distension

1

Increased prefeed aspirate

1

Chest retraction

1

Grunting

2

The clinical signs showing LR+ >1 were considered for clinical score, score-1 was given for signs with LR+ between 1 & 2 and score 2 for signs with LR+ >2.

DISCUSSION

Table 7. Statistical Analysis of Clinical Score Score Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

LR+

45

78

2

2

47

77

3

13

92

40

73

1.6

4

3

99

100

72

3

weeks. 150 (93%) were low birth weight (LBW) babies and 10 (6.2%) weighed >2.5 kg at birth with mean birth weight (mean ± SD) = 1,378 ± 507 g. The frequency of occurrence of apnea is maximum followed by lethargy and tachycardia. However, tachycardia, increased prefeed aspirates, increased respiratory rate and abdominal distension were more common in definite sepsis, whereas, refusal to feed, sick looking and hypothermia were more common in probable sepsis. But in no sepsis group, refusal to feed, increased prefeed aspirate and tachycardia predominated. In this study, central cyanosis, sclerema, seizures and bradycardia were not present in any group (Tables 2 and 3). It is found that, with respect to the symptomatic events (n = 210), two clinical signs were present in 94 events (44.8%), followed by one sign in 62 events (29.5%), three clinical signs in 34 events (16.2%) and ≥4 signs in 20 (9.5%) events, respectively. And out of 210 symptomatic events; in 60 (28.5%) events, blood culture was positive (definite Sepsis), in 34 (16%) events, sepsis screen was positive only (probable sepsis) and in 116 (55.5%) events, no sepsis was found. The sensitivity of clinical signs varied from 3 to 47% and specificity from 51 to 97%. The positive predictive

30

It showed that the combined clinical score of 2 and 3 had PPV of 45 and 40%, respectively. However, a clinical score of 4 gave a maximum PPV of 100% and LR+ of 3. So, this predictive ability is significantly more than any of the clinical signs in isolation.

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

Infections are the single largest cause of neonatal deaths globally. Klebsiella pneumoniae and Staphylococcus aureus were the two most common organisms isolated. Based on the onset, neonatal sepsis is classified into two major categories: Early-onset sepsis, which usually presents with respiratory distress and pneumonia within 72 hours of age and late-onset sepsis that usually presents with septicemia and pneumonia after 72 hours of age. Clinical features of sepsis are nonspecific in neonates and a high index of suspicion is required for timely diagnosis. Although blood culture is the gold standard for the diagnosis of sepsis, culture reports would be available only after 48-72 hours. In our study, there is male preponderance, which is due to the prevalent custom of taking male babies preferentially to healthcare institutions and also because female babies are immunologically more competent9,10 Gerdes et al11 reported that male infants are four times vulnerable to sepsis than females. Also majority of this study group are preterms, which may be attributed to the occurrence of more number of premature deliveries in our institution hence they are more prone for sepsis.2 It is found that the mean age of onset of symptomatic events is 10.7 ± 6.8 days. Majority occurred between 4-7 days of life. This is in accordance with other studies.13 Also apnea, lethargy and tachycardia were the common clinical signs present in babies at enrollment for evaluation of sepsis which is similar to the study by Fanaroff et al.14 Any illness in neonates is bound to present with a constellation of clinical signs, hence, majority of symptomatic events presented with two clinical signs per event. Sixty (28.5%) events belong to the culture-positive group hence classified under definite sepsis category, which correlates with the report by Singh et al.15 Gram-negative sepsis predominates in our study (Table 4) with Klebsiella being the most frequent gramnegative isolate and S. aureus the gram-positive one. Kuruvilla et al16 reported similar isolates in his study in 1998. However, the incidence of CoNS is low in our


clinical study set up. It is seen from Table 4 that the sensitivity of clinical signs is low (3-47%). It is because of the variable presentation of clinical signs at one time or other. Also, the PPV is low as these signs may be present in multiple other causes apart from sepsis.14

of sepsis on neonatal mortality: field trial in rural India. Lancet 1999;354(9194):1955-61. 4. Stoll BJ. The global impact of neonatal infection. Clin Perinatol 1997;24(1):1-21. 5. Report of the National Neonatal Perinatal Database (National Neonatology Forum), 2002-2003.

This study tries to find out a scoring system based on individual clinical signs, hence signs with LR+ >1 are included in the score (Table 6). The diagnostic value of combined clinical score was depicted in Table 7. A clinical score of 4 and maximum PPV of 100% with a positive LR of three meaning, when the clinical score is 4 then there is 3 times higher chance that the clinical signs are due to sepsis and there is 100% probability of presence of disease among test positives.

6. Klinger G, Levy I, Sirota L, Boyko V, Reichman B, LernerGeva L; Israel Neonatal Network. Epidemiology and risk factors for early onset sepsis among very-low-birth weight infants. Am J Obstet Gynecol 2009;201(1):38.e1-6. 7. van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, Fleer A, Krediet TG. Long-term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of causative agents. Neonatology 2010;97(1):22-8. 8. Gotoff SP, Behrman RE. Neonatal septicemia. J Pediatr 1970;76(1):142-53.

Scores for diagnosis of early-onset sepsis basing on clinical, laboratory and perinatal risk factors have been developed by many workers.17,18 But in India, where ready access to laboratory tests is meagre, the score based on clinical signs can significantly contribute to the diagnosis of late-onset septicemia and its early management.

9. Singh M. Care of Newborn. 5th edition, 1999:p.211. 10. Klein JO, Marey SM. Bacterial Sepsis and Meningitis Infectious D. of the Fetus & Newborn, 3rd edition, 1990: p.601-50. 11. Gerdes JS, Polin RA. Sepsis screen in neonates with evaluation of plasma fibronectin. Pediatr Infect Dis J 1987;6(5):443-6.

KEY MESSAGE ÂÂ

The early diagnosis and timely treatment of neonatal sepsis is rather difficult due to the nonspecific clinical presenting signs.

ÂÂ

Also, in India ready access to laboratory tests is meager and cost-prohibitive.

ÂÂ

So, on the basis of the clinical score, i.e., a score ≥4, which has 100% positive predictive value, early diagnosis and prompt institution of therapy can be started without waiting for other laboratory parameters. The clinical score may be very useful in resource-poor settings.

12. Gotoff SP. Nelson TB of Pediatrics. 16th edition, WB Saunders: Philadelphia 2000:p.541. 13. Sepsis and Septic Shock. Drug Ther Perspect 2001;17(6): 8-13. 14. Fanaroff AA, Korones SB, Wright LL, Verter J, Poland RL, Bauer CR, et al. Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants. The National Institute of Child Health and Human Development Neonatal Research Network. Pediatr Infect Dis J 1998;17(7):593-8. 15. Singh M, Narang A, Bhakoo ON. Evaluation of a sepsis screen in the diagnosis of neonatal sepsis. Indian Pediatr 1987;24(1):39-43. 16. Kuruvilla KA, Pillai S, Jesudason M, Jana AK. Bacterial profile of sepsis in a neonatal unit in south India. Indian Pediatr 1998;35(9):851-8.

References 1. Rennie Janet M, Roberton NRC. TB of Neonatology. 3rd edition, 1999:p.1109.

17. Takkar VP, Bhakoo ON, Narang A. Scoring system for the prediction of early neonatal infections. Indian Pediatr 1974;11(9):597-600.

2. Khatua SP, Das AK, Chatterjee BD, Khatua S, Ghose B, Saha A. Neonatal septicemia. Indian J Pediatr 1986; 53(4):509-14.

18. Bergqvist G, Eriksson M, Zetterström R. Neonatal septicemia and perinatal risk factors. Acta Paediatr Scand 1979;68(3):337-9.

3. Bang AT, Bang RA, Baitule SB, Reddy MH, Deshmukh MD. Effect of home-based neonatal care and management

n

n

n

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

31


news and views

Journal Scan Long-term Treatment with Montelukast and Levocetirizine Combination in Persistent Allergic Rhinitis: Review of Recent Evidence Allergic rhinitis is the most prevalent of the atopic disorders, affecting 25-35% of persons, depending on the population studied. Considered by nonsufferers to be a trivial disease, allergic rhinitis delivers a significant personal impact on quality-of-life. Antihistamines have been successfully used for years in the treatment of seasonal/persistent allergic rhinitis. The new generation antihistaminics are all safe, with

negligible sedative effects, excellent tolerability and have no influence on cardiac parameters. Montelukast when used as monotherapy is efficacious and improves quality-of-life. Combination therapy (montelukast plus levocetirizine) is a more effective strategy than monotherapy in the treatment of persistent allergic rhinitis. Adsule SM, Misra D. J Indian Med Assoc 2010;108(6):381-2.

Formulation and Evaluation of Bilayered Tablets of Montelukast and Levocetirizine Dihydrochloride Using Natural and Synthetic Polymers The objective of present work was to formulate and evaluate bilayered tablets of levocetirizine and montelukast for treating allergic rhinitis effectively. Anti-allergic medicines (e.g., some antihistamines) can cause adverse events such as somnolence and sedation. The combining montelukast with levocetirizine gives additional benefits in comparison with either drug alone and could be considered for patients whose quality-of-life is impaired by persistent allergic rhinitis. Montelukast sodium is alkaline stable (bioavailability 64%), most of drug being absorbed from the intestine while levocetirizine dihydrochloride is acid stable. When tablets of the combination of these are prepared, they tend to become unstable during the shelf life of the formulation. Hence it is recommended to prepare a bilayer tablet, by formulating montelukast in sustained release layer and levocetirizine as immediate release layer as it improves and increases the stability by reducing the acid base interactions of both the drugs in combination there by increasing the bioavailability. Taking this into account different formulations were prepared by wet granulation method using natural Tamarind Seed Polysaccharide and synthetic HPMCK100, K15M and K4M release rate controlling hydrophilic

polymers. The formulations were evaluated for hardness, weight variation, friability, swelling index and drug content uniformity. The in vitro release of drug from the formulations was studied in pH 1.2 acidic buffer and pH 7.4 phosphate buffer, and it was found that the prepared tablets were able to sustain the release of the drug upto 12 hours. The release of montelukast and levocetirizine of both layers from the tablets was found to be diffusion controlled and the release mechanism was nonFickian based on the n value of Korsmeyer-peppas plot. The FTIR studies were performed on three optimized formulations (F4, F12, F16) and the plain drug controls (levocetirizine, montelukast). From the observed peaks it is evident that the polymers used and the drugs were found to be mutually compatible chemically. The Pharmacokinetic studies were performed in two groups of male wistar rats. One group was administered with the optimized formulation containing tamarind Seed Polysaccharide (F12) while plain montelukast oral suspension acted as control in the second group. The results indicate that the formulation optimized with 1:4 (drug:TSP) was able to sustain the release of montelukast upto 12 hours. Increase in Tmax and AUC(0-Îą) also were also observed in the studies indicating efficient sustained

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

33


News and Views action and improved bioavailability of the drug. The formulated bilayered tablets using natural polymers provided immediate release of levocetirizine and

sustained release of montelukast and therefore hold promise as an alternative dosage form in the treatment of allergic rhinitis and bronchial asthma.

Mohammed M, Srinivas PM, Sadanandam M. Int J Drug 2011;3(4):597-618.

Role of Zinc in Pediatric Diarrhea Zinc supplementation is a critical new intervention for treating diarrheal episodes in children. Recent studies suggest that administration of zinc along with new low osmolarity oral rehydration solutions/ salts (ORS), can reduce the duration and severity of diarrheal episodes for upto three months. The World Health Organization (WHO) and UNICEF recommend daily 20 mg zinc supplements for 10-14 days for children with acute diarrhea, and 10 mg/day

for infants under six months old, to curtail the severity of the episode and prevent further occurrences in the ensuing: 2-3 months, thereby decreasing the morbidity considerably. This article reviews the available evidence on the efficacy and safety of zinc supplementation in pediatric diarrhea and convincingly concludes that zinc supplementation has a beneficial impact on the disease outcome. Brajait C, Thawani V. Int J Pharmacol 2011;43(3):232-5.

The Curious Case of Zinc for Diarrhea: Unavailable, Unprescribed and Unused Diarrhea kills nearly 650 children below the age of five years each day in India. Oral rehydration solution (ORS) and oral zinc have been recommended for the treatment of acute diarrhea in children by the Indian Academy of Paediatrics (IAP) National task force for use of ORS and zinc in the year 2003 and later endorsed in 2006. Zinc was included in the National Programme for the treatment of Diarrhea in 2007. The Integrated Management of Neonatal and Childhood Illness (IMNCI) advocates the use of these two drugs in the treatment of acute diarrhea. The evidence for the use of ORS and zinc as first-line treatment in children in resource limited countries is overwhelming. If given early on during an episode of diarrhea it would help save 50% of children who would otherwise die. The treatment is effective, safe, cheap and easily tolerated by children. More

importantly, there are no other alternatives to this treatment. Recognizing the importance of this, the National Rural Health Mission (NRHM) has included ORS and zinc in the list of medicines to be available at the subcenters. Yet, unfortunately, it is hardly available in the public and private health facilities in India. Only 34.2% of children with diarrhea in India receive ORS and a minuscule 1% are prescribed zinc during an episode of diarrhea. The lack of availability in public health facilities points to the fact that zinc was probably not procured at all, or if procured it was not done in sufficient quantities. Why does this state of affairs persist? We explore some of the regulatory and other issues which prevent access to zinc in India. Gitanjali B, Weerasuriya K. J Pharmacol Pharmacother 2011;2(4):225-9.

Unraveling the Role of Zinc in Memory Dietary zinc deficiency has been associated with memory impairment but the mechanisms underlying this effect remain unclear. The divalent cation zinc is one of the most abundant trace elements in the body

34

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

and plays myriad functional roles. Although the vast majority of zinc is tightly bound to proteins, a pool of zinc in the mammalian forebrain is selectively stored in and released from glutamatergic neurons. This


News and Views chelatable zinc is sequestered in synaptic vesicles and coreleased with glutamate during neuronal activity. Synaptically released zinc has the potential to interact with and modulate many different synaptic targets, including glutamate receptors and voltage-gated channels. Zinc can also modulate synaptic plasticity. The ability of zinc to modulate both ion channels and synaptic plasticity predicts that it plays a key role in learning and memory. Recent studies using (ZnT3 KO mice) mice in which the zinc transporter-3 (ZnT3) had been genetically deleted has revealed that they exhibit impaired fear memory as well as accelerated aging related decline of spatial memory. In a study, Sindreu et al focused on the Erk signaling pathway of the MAPK family which has a role in the regulation of synaptic plasticity, learning and memory. They found that the phosphorylated form of Erk (pErk) was selectively reduced in synaptic membranes from hippocampal mossy fibers (MFs) of ZnT3 KO mice. This shows that endogenous zinc (and ZnT3) is necessary for Erk activation and extracellular release of zinc is necessary for modulation of pErk. One possible indirect mechanism through which zinc could enhance pErk is by inhibiting its dephosphorylation by protein tyrosine phosphatases (PTPs). PTPs

terminate Erk activity by dephosphorylation, and it is well-established that zinc inhibits the activity of these PTPs . Endogenous zinc enhances Erk activation by inhibiting tyrosine phosphatases. In ZnT3 KO mice, the lack of zinc disinhibits these tyrosine phosphatases, thereby suppressing Erk activity. The Erk signaling pathway plays a crucial role in the regulation of activity-dependent changes in the strength of synaptic transmission. Erk signaling modulates synaptic plasticity through a variety of post- and presynaptic mechanisms. Stimulation of Erk in presynaptic terminals regulates synaptic plasticity through a mechanism involving phosphorylation of synapsin I. Furthermore, in behavioral studies Erk is necessary for the development of several forms of memory, including fear conditioning and spatial memory. Given that Erk-dependent synaptic plasticity is essential for cognitive processes, the ability of zinc and ZnT3 to regulate Erk activation predicts cognitive deficits in ZnT3 KO mice. Zinc regulates a number of postsynaptic targets, including NMDA and kainate receptors Perhaps inhibition of postsynaptic NMDA or kainate receptors by zinc regulates other forms of learning. Additionally, results in this study indicate that the effects of zinc on Erk signaling are specific for the MF pathway. Mott DD, Dingledine R. Proc Natl Acad Sci USA 2011;108(8):3103-4.

Effect of Iron and Zinc Deficiency on Short-term Memory in Children Objective: To evaluate the effect of iron and zinc deficiency on short-term memory of children in the age group of 6-11 years and to assess the response to supplementation therapy. Design: Interventional study. Setting: 100 children in the age group of 6-11 years (subdivided into 6-8 year and 9-11 year groups) from an urban corporation school. Methods: After collection of demographic data, the study children underwent hematological assessment which included serum iron, serum zinc and hemoglobin estimation. Based on the results, they were divided into Iron deficient, Zinc deficient and Combined deficiency groups. Verbal and nonverbal memory assessment was done in all the children. Intervention: Iron (2 mg/kg body weight in two divided doses) and

zinc (5 mg once-a-day) supplementation for a period of three months for children in the deficient group. Results: All children with iron and zinc deficiency in both the age groups had memory deficits. Combined efficiency in 9-11 years group showed severe degree of affectation in verbal (p < 0.01) and nonverbal memory (p < 0.01), and improved after supplementation (p = 0.05 and p < 0.01, respectively). In 6-8 years group, only nonverbal form of memory (p = 0.02) was affected, which improved after supplementation. Conclusion: Iron and zinc deficiency is associated with memory deficits in children. There is a marked improvement in memory after supplementation. Post supplementation IQ scores do not show significant improvement in deficient groups in 6-8 years old. Umamaheswari K, et al. Indian Pediatrics 2011;48(4):289-93.

Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

35


Asian Journal of

Paediatric Practice Information for Authors Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Asian Journal of Paediatric Practice strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper.

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References These should conform to the Vancouver style. References should be numbered in the order in which they appear in the texts and these numbers should be inserted above the lines on each occasion the author is cited (Sinha12 confirmed other reports13,14...). References cited only in tables or in legends to figures should be numbered in the text of the particular table or illustration. Include among the references papers accepted but not yet published; designate the journal and add ‘in press’ (in parentheses). Information from manuscripts submitted but not yet accepted should be cited in the text as ‘unpublished observations’ (in parentheses). At the end of the article the full list of references should include the names of all authors if there are fewer than seven or if there are more, the first six followed by et al., the full title of the journal article or book chapters; the title of journals abbreviated according to the style of the Index Medicus and the first and final page numbers of the article or chapter. The authors should check that the references are accurate. If they are not this may result in the rejection of an otherwise adequate contribution. Examples of common forms of references are:

Articles

Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

Books

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Articles in Books

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

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Asian Journal of Paediatric Practice, Vol. 16, No. 2, 2012

For Editorial Correspondence: Dr KK Aggarwal Group Editor-in-Chief

Asian Journal of Paediatric Practice E- 219, Greater Kailash, Part - 1, New Delhi - 110 048, Tel: 40587513 E-mail: editorial@ijcp.com Website: www.ijcpgroup.com


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