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Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study
Role of Doppler ultrasound at time of diagnosis of late-onset fetal growth restriction in predicting adverse perinatal outcome: prospective cohort study
REVIEWED BY | Ling Lee ASA SIG: Obstetrics
REFERENCE | Authors: G Rizzo, I Mappa, V Bitsadze, M Słodki, J Khizroeva, A MakatsariyA and F D’Antoni Journal: Ultrasound Obstet Gynecol 2020; 55:793–798. DOI: 10.1002/uog.20406
WHY THE STUDY WAS PERFORMED
There are numerous research studies conducted on early-onset fetal growth restriction (FGR); however, the diagnosis of late-onset FGR is equally important due to the increased risk of short-term and long-term morbidities when compared to normally grown fetuses. Late-onset growth restriction is defined as growth restriction diagnosed after gestational age of 32 weeks (K32). It is challenging to diagnose late-onset FGR as the tools we rely upon are fetal growth scan with Doppler assessments, which often include fetal umbilical artery (UA) Doppler, fetal middle cerebral artery (MCA) pulsatility index (PI), cerebroplacental ratio (CPR), umbilical vein (UV) Doppler, maternal uterine arteries Doppler, etc., as well as amniotic fluid assessment. Unlike early-onset FGR whereby fetal UA Doppler is useful in diagnosing, fetal UA Doppler is usually normal in late-onset FGR. Thus the study suggested the importance of utilising other Doppler indices to aid in the diagnosis of late-onset FGR.
There are two main aims for this study, with the primary aim of exploring the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, including their predictive accuracy. The secondary aim was to evaluate whether a multiparametric diagnostic model improved the diagnostic ability of Doppler ultrasound in detecting adverse perinatal outcomes in pregnancies affected by lateonset FGR.
HOW THE STUDY WAS PERFORMED
This is a prospective study conducted at Cristo Re Hospital in Rome, Italy, in the Division of Maternal Fetal Medicine over a period of one year and three months (October 2017 – December 2018).
The study population consists of singleton pregnancies complicated by late-onset FGR, with a definition of ultrasound estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd percentile using local population charts, or EFW or AC < 10th percentile with UA-PI > 95th percentile or CPR < 5th percentile. The exclusion criteria are pregnancies with FGR diagnosed before K32, as well as pregnancies complicated by congenital infections, chromosomal anomalies or structural anomalies.
The ultrasound scans were conducted by two experienced sonographers, whereby EFW and amniotic fluid (deepest vertical pocket without fetal parts or umbilical cords) were recorded, as well as the following Doppler indices measured:
• Fetal UA Doppler PI (free floating loop)
• Fetal MCA Doppler (at the origin from the circle of Willis in the axial plane)
• Fetal UV blood flow (UVBF) Doppler (from the intra-abdominal portion using automated trace of at least three consecutive waveforms or 10s for UVBF)
• Mean PI of both maternal uterine arteries (measured at the crossover with the external iliac artery).
Additional Doppler index such as umbilical vein blood flow normalised for fetal abdominal circumference (UVBF/AC) was also included. UVBF/AC is the absolute value of UV blood flow corrected for fetal size.
Since fetal Doppler indices change with gestational age (GA), the study transformed the obtained Doppler indices into Z-scores (calculated using the formula: observed value – expected value for GA/standard deviation for GA).
The purpose of the ultrasound examination is to detect the occurrence of adverse perinatal outcomes in pregnancies affected by late onset FGR and its accuracy, which is called composite adverse perinatal outcome (CAPO), including at least one of the following:
• Emergency caesarean section for fetal distress
• 5 minutes Apgar score < 7
• Umbilical artery pH < 7.10
• Neonatal admission to special care unit.
Pregnancies that were diagnosed with late onset FGR were managed by obstetricians who were blinded from the Doppler data obtained by the research study, except UA-PI. These pregnancies were managed according to local protocol, such as weekly or fortnightly clinical evaluation, fortnightly fetal growth assessment, etc. In the case of pregnancies complicated by maternal medical conditions (pre-eclampsia, gestational hypertension), reduced amniotic fluid, reduced fetal movement, further decline in fetal growth and pregnancies beyond gestational age of 39 weeks, induction of labour was warranted immediately.
WHAT THE STUDY FOUND
The study has a total of 261 pregnancies complicated by late-onset FGR; 18 cases were excluded with incomplete data, and the remaining 243 pregnancies were analysed, whereby CAPO happened in 32.5% of cases. The highest occurrence CAPO was emergency caesarean sections for fetal distress (74.5%). Mean GA at delivery and birth weight were found to be lower in the pregnancies complicated by CAPO.
The result focused on comparing the Z-scores of the Doppler indices between pregnancies complicated by CAPO and those without. Z-scores of mean MCA-PI, CPR and UVBF/AC were lower for pregnancies with CAPO, except for Z-scores of mean maternal uterine artery PI, which was higher. No significant difference between the two groups in fetal EFW, amniotic fluid and UA-PI. Z-scores of mean maternal uterine artery PI, CPR and UVBF/AC were associated independently of CAPO but GA at delivery and birth weight were not.
For the secondary aim of the study, the study went on to analyse the performance of the various Doppler indices in predicting CAPO in pregnancies affected by late-onset FGR. The area under receiver operating characteristic curve (AUC) of Doppler parameters was generated. Using these parameters, the study found that UVBF/AC Z-score had an AUC of 0.723, which had better accuracy compared to mean maternal uterine artery PI Z-score and CPR Z-score (whereby both were poor in predicting). When combining all three Z-scores, the AUC was 0.745, which showed better accuracy.
STRENGTHS AND LIMITATIONS OF THE STUDY
The strength of the study was its large sample size, conducting in a prospective approach, inclusion of cases only affected by late-onset FGR, and the attending obstetricians were blinded to the Doppler findings (except UA Doppler).
The limitation of the study was the ultrasound Doppler assessment was only conducted once at the time of diagnosis without continuous documentation of the Doppler changes in the affected pregnancies from the time of diagnosis to delivery.
RELEVANCE TO CLINICAL PRACTICE
At the beginning, the study had stated the difficulty in detecting and diagnosing pregnancies affected by late-onset FGR. From previous studies, the readers were informed that UA-PI was usually normal in fetuses with late-onset FGR and therefore unreliable in detecting the condition.
The readers were also informed that low PI in MCA or CPR was known to be associated with abnormal acid-base status (which could cause fetal hypoxemia and acidemia) and admission to the neonatal unit, while increased resistance in maternal uterine arteries was associated with caesarean sections for fetal distress.
This study highlighted the potential of using the umbilical vein blood flow, more precisely the UVBF/AC, to improve the detection of late-onset FGR and the prediction of pregnancies affected by adverse perinatal outcomes, defined as CAPO by the authors. The study also achieved its secondary aim by suggesting that a multiparametric diagnosis model (UVBF/ AC Z-score, mean uterine artery PI Z-score and CPR Z-score) offered a higher accuracy in predicting CAPO.
The authors concluded with future studies to further evaluate the usefulness of UVBF/AC as a standalone predictor for CAPO by acknowledging the difficulty in obtaining accurate UVBF. Furthermore, the authors suggested more studies are required to build a multiparametric model by including the assessment of UVBF, maternal uterine arteries and other pregnancy characteristics to predict CAPO.
