Teresa M. MacDonald

Shining light in dark corners: Diagnosis and management of late-onset fetal growth restriction

Fetal growth restriction (FGR) is the single biggest risk factor for stillbirth. In the absence of any effective treatment for fetal growth restriction, the mainstay of management is close surveillance and timely delivery. While such statements are almost self‐evident, the daily clinical challenge of late‐onset fetal growth restriction remains; the competing priorities of minimising stillbirth risk, while avoiding excessive obstetric intervention and the neonatal sequelae of iatrogenic preterm birth. This dilemma is made harder because the tools for late‐onset FGR diagnosis and surveillance compare poorly to those used in early‐onset FGR; screening tests in early pregnancy have limited predictive value; most cases escape clinical detection, a phenomenon set to worsen given the obesity epidemic; there is a failure of consensus on the definition of small for gestational age, and ancillary tools, such as umbilical artery Doppler – of value in identification of preterm FGR – are less useful in the late‐preterm period and at term. Most importantly, the problem is common; 96% of all births occur after 32 weeks. This means a poor noise/signal ratio of any test or management algorithm will inevitably have large clinical consequences. Into such a dark corner, we cast some light; a summary on diagnostic criteria, new developments to improve the diagnosis of late‐onset FGR and a suggested approach to management.

OC24.04: The association between the cerebral-placental-uterine ratio and fetal growth restriction: a prospective cohort study

Objectives: Umbilical artery (UA) Doppler Pulsatility Index, Resistance Index and Systolic/Diastolic Ratio are measured in clinical practice to assess fetal wellbeing. Different normal values are used for decision-making and there is a need for uniform UA Doppler criteria. Methods: Prospective study of healthy women with singleton pregnancies, recruited <14 weeks’ gestational age (GA), from study sites in Brazil, Kenya, Pakistan and the UK between 2012-2015. Women were included if they met the INTERGROWTH-21st Fetal Growth Longitudinal Study criteria. UA measurements were serially taken at 5±1 week intervals, according to a standardised protocol by dedicated research staff, using identical equipment. The UA measures were modelled as functions of GA in a multilevel framework, following established methodology. Results: A total of 539 women contributed 1563 Doppler measures; 75% of women had ≥3 measures. Low rates of adverse events confirmed the low-risk status of the population: preterm birth (6.5%), pre-eclampsia (0.8%), neonatal mortality (0.6%), and birthweight for GA z-score of 0.1. From 24-40 weeks GA, there were between 21 and 134 individual observations per week. All three Doppler indices decreased with advancing GA (p<0.001). The figure below presents the individual values for the three Doppler indices and the corresponding 5th, 50th and 95th smoothed centile curves. Conclusions: These normative data should help to standardise the evaluation of the UA circulation worldwide.

The cerebral-placental-uterine ratio as a novel predictor of late fetal growth restriction: a prospective cohort study: CPUR prediction of FGR

Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third‐trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small‐for‐gestational age and FGR.

OP01.05: Reduced third trimester growth velocity in appropriate‐for‐gestational‐age fetuses is associated with multiple indicators of placental insufficiency

76% by developmental anomalies, especially hyper-ramification and villous immaturity in 100% of the cases, indicating late placental oxidative stress. sFlt-1/PlGF ratio correlates with vascular lesions on the placental maternal side, typical of the severe IUGR group. Conclusions: Placental histology and angiogenic markers correlate with the severity of placental damage and with the different clinical fetoplacental phenotypes of IUGR, supporting investigations about their pathogenesis.

Prospective longitudinal assessment of the fetal left modified Myocardial Performance Index

Abstract Introduction: The fetal left modified Myocardial Performance Index (Mod-myocardial performance index (MPI)) is a measure of systolic versus diastolic time intervals obtained from a single cardiac cycle with ultrasound. It is a measure of global ventricular function and has been investigated for potential utility in fetal conditions associated with cardiac dysfunction. Objectives: The objective of this study is to compare values from a precisely replicated fetal left Mod-MPI technique to published reference ranges. Methods: Three hundred and sixty-five nulliparae prospectively underwent fetal left Mod-MPI measurement at 27+0–29+0 and 35+0–37+0 weeks’ gestation. Measurements from pregnancies complicated by gestational diabetes mellitus, preeclampsia, or a small-for-gestational-age (<10th centile) infant were excluded. Mod-MPI values were compared with three published references created using similar measurement techniques. Results: Compared with one selected reference, at 29+0 and 35+0–37+0 weeks’ gestation, 90–100% of our values fell within the 5th–95th percentile range as expected. Thus, this reference range was validated for our population in late pregnancy. However, the expected level of concordance was not seen at 27+0–28+6 weeks’. The other two references to which we compared our Mod-MPI values demonstrated poor concordance, especially at 27+0–29+0 weeks’. Pearson interobserver correlation was also improved at 35+0–37+0 weeks’ at 0.434, compared with 0.083 at 27+0–29+0 weeks’ gestation. Conclusions: Concordance and interobserver variability between our cohort and similar populations were both improved at 35+0–37+0 weeks’ compared with 27+0–29+0 weeks’ gestation. Overall, variable Mod-MPI reproducibility across gestations limits clinical application, especially earlier in pregnancy. Manual Mod-MPI measurement should be considered most reliable in late pregnancy until automated MPI measurement is possible.

Variable effect of maternal oral glucose load on circulating cell-free placental mRNAs

Abstract Background: It is not known whether fasting affects levels of circulating placenta-specific transcripts. Objective: To assess whether a glucose load affects circulating placenta-specific transcripts. Method: RNA was extracted from paired blood samples (fasting and 1-h post 75 g oral glucose) from 22 women. Placenta-specific genes were measured by RT-qPCR. Results: There was no change in ADM, CSH1, PAPPA2, PSG1 or TAC3 expression between fasting and post-glucose states. However, HTRA1 decreased after glucose load. Conclusion: Maternal fasting state does not influence expression of the majority of placenta-specific genes but may need to be accounted for when validating biomarkers of placental disease.

Re. Shining light in dark corners: Diagnosis and management of late‐onset fetal growth restriction. ANZJOG 2015; 55(1):3–10. Author response (II)

gestation, infant gender, maternal characteristics (height, weight, parity and ethnicity) and pathological variables] with ultrasound (Hadlock) and gender customisation alone. In our National Women’s Health cohort of births (n = 25,976), full customisation identified SGA babies with higher odds of perinatal death (OR 5.6, 95% CI 3.6– 8.7) compared with ultrasound and gender alone (OR 2.1, 95% CI 1.4–3.3). Our data therefore support the use of a full customised model for defining babies who are SGA and at the risk of severe adverse outcomes. In New Zealand 4 and elsewhere women of South Asian ethnicity have higher perinatal mortality. McDonald et al. express concern that adjusting for ethnicity in customised centiles may wrongly classify babies as appropriately grown, that a population standard would classify as SGA, potentially missing perinatal deaths. This issue has been specifically addressed, using data from a large database in the West Midlands, UK (n = 10,405 mothers of South Asian origin). Again, comparisons were made between SGA infants by Hadlock criteria alone and those SGA by full customisation. Hadlock criteria classified twice as many South Asian babies as SGA (n = 1554, 14.9%) compared with full customisation (n = 706, 6.8%). The risk of perinatal death was lower among babies SGA by Hadlock (RR 3.7, 95% CI 2.1–6.4) compared with SGA by full customisation (RR 5.7, 95% CI 3.2–10.4). Perinatal mortality among the 864 babies identified as SGA by Hadlock criteria alone was the same as the appropriate for gestational age group (RR 1.2, 95% CI 0.5–3.0). These data suggest that full customisation correctly identifies South Asian pregnancies at highest risk of perinatal mortality, at least in a UK setting. We commend the flow chart for the management of late-onset SGA pregnancies, a useful aid for clinicians, which is similar to that published in 2014 by the New Zealand Maternal Fetal Medicine Network. Lesley MCCOWAN, Ngaire ANDERSON and Lynn SADLER University of Auckland Obstetrics & Gynaecology, University of Auckland, Auckland 1003, New Zealand Waitemata District Heath Board, Private Bag 93503, Takapuna, North Shore City 0740, New Zealand Auckland District Health Board, National Women’s Hospital, Auckland, New Zealand E-mail: l.mccowan@auckland.ac.nz