Javier Caradeux

Diagnosis and surveillance of late-onset fetal growth restriction

&NA; By consensus, late fetal growth restriction is that diagnosed >32 weeks. This condition is mildly associated with a higher risk of perinatal hypoxic events and suboptimal neurodevelopment. Histologically, it is characterized by the presence of uteroplacental vascular lesions (especially infarcts), although the incidence of such lesions is lower than in preterm fetal growth restriction. Screening procedures for fetal growth restriction need to identify small babies and then differentiate between those who are healthy and those who are pathologically small. First‐ or second‐trimester screening strategies provide detection rates for late smallness for gestational age <50% for 10% of false positives. Compared to clinically indicated ultrasonography in the third trimester, universal screening triples the detection rate of late smallness for gestational age. As opposed to early third‐trimester ultrasound, scanning late in pregnancy (around 37 weeks) increases the detection rate for birthweight <3rd centile. Contrary to early fetal growth restriction, umbilical artery Doppler velocimetry alone does not provide good differentiation between late smallness for gestational age and fetal growth restriction. A combination of biometric parameters (with severe smallness usually defined as estimated fetal weight or abdominal circumference <3rd centile) with Doppler criteria of placental insufficiency (either in the maternal [uterine Doppler] or fetal [cerebroplacental ratio] compartments) offers a classification tool that correlates with the risk for adverse perinatal outcome. There is no evidence that induction of late fetal growth restriction at term improves perinatal outcomes nor is it a cost‐effective strategy, and it may increase neonatal admission when performed <38 weeks.

Longitudinal growth assessment for the prediction of adverse perinatal outcome in SGA-suspected fetuses

Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small‐for‐gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA‐suspected fetuses.

Second- to Third-Trimester Longitudinal Growth Assessment for the Prediction of Largeness for Gestational Age and Macrosomia in an Unselected Population

Background: Prenatal detection of excessive growth remains inaccurate. Most strategies rely on a single cross-sectional evaluation of fetal size during the third trimester. Objectives: To compare second- to third-trimester longitudinal growth assessment with cross-sectional evaluation at the third trimester in the prediction of largeness for gestational age (LGA) and macrosomia. Methods: A cohort of 2,696 unselected singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks was created. Abdominal circumference (AC) measurements were transformed to z values according to the INTERGROWTH-21st standards. Longitudinal growth assessment was performed by calculation of z velocity and conditional growth. Both methods were compared to cross-sectional assessment at 32 ± 2 weeks. Predictive performance for LGA and macrosomia was determined by receiver operating characteristic curve analysis. Result: A total of 188 (7%) newborns qualified for LGA and 182 (6.8%) for macrosomia. The areas under the curve (AUCs) for 32-week AC z score, AC z velocity, and conditional AC were 0.78, 0.61, and 0.55, respectively, for the prediction of LGA, and 0.75, 0.61, and 0.55, respectively, for the prediction of macrosomia. Both AUCs of AC z velocity and conditional AC were significantly lower (p < 0.001) than the AUC of cross-sectional AC z scores. Conclusions: In the general population, second- to third-trimester longitudinal assessment of fetal growth is inferior to third-trimester cross-sectional evaluation of size in the prediction of LGA and macrosomia.

Longitudinal growth assessment for prediction of adverse perinatal outcome in fetuses suspected to be small‐for‐gestational age

Fetal growth restriction (FGR) is associated with an increased risk of adverse perinatal outcome. However, distinguishing this condition from small‐for‐gestational age (SGA) remains elusive. A set of criteria has been proposed recently for such a purpose, including the degree of smallness, Doppler parameters and growth velocity. The aim of this study was to establish whether the use of growth velocity adds value to Doppler assessment in predicting adverse perinatal outcome among SGA‐suspected fetuses.

Second‐ to third‐trimester longitudinal growth assessment for prediction of small‐for‐gestational age and late fetal growth restriction

Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross‐sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second‐ to third‐trimester longitudinal growth assessment to cross‐sectional evaluation in the third trimester for the prediction of small‐for‐gestational age (SGA) and late FGR in low‐risk singleton pregnancy.This article is protected by copyright. All rights reserved. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/uog.17471 A cc ep te d A rti cl e Background: Detection of fetal growth restriction (FGR) remains poor. Most screening strategies rely on a cross-sectional evaluation of fetal size at one point during the third trimester. A longitudinal and individualized approach may allow a more appropriate evaluation. Objectives: To compare second to third trimester longitudinal growth assessment with cross-sectional evaluation at third trimester in the prediction of SGA and late FGR. Methods: A cohort of 2696 unselected singletons pregnancies scanned at 21±2 and 32±2 weeks was created. Abdominal circumference (AC) measurements were transformed to zvalues according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by the calculation of z-velocity and second to third trimester conditional growth centile. Longitudinal assessment was compared to cross-sectional assessment at 32 weeks. Predictive performance for SGA and late FGR was determined by receiver operating characteristic (ROC) curve analysis. Result: A total of 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. None of the longitudinal measures (AC z-velocity and conditional AC growth) relevantly improved the association to SGA or late FGR provided by the cross-sectional evaluation of AC z-score at 32 weeks. Both areas under the curve (AUC) of AC z-velocity and conditional AC growth were significantly lower than that of cross-sectional AC z-scores (p<0.001). AC zvelocity performed significantly better than conditional AC growth (p<0.001). Conclusions: Longitudinal assessment of fetal growth from second to third-trimester has a low predictive capacity for SGA and late FGR in the general population.

Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis

Objective The objective of the study was to establish the risk of fetal death in early‐onset growth‐restricted fetuses with absent or reversed end‐diastolic velocities in the umbilical artery or ductus venosus. Data Sources A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. Study Eligibility Criteria The study criteria included observational cohort studies and randomized controlled trials of early‐onset growth‐restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end‐diastolic velocities in the umbilical artery and/or ductus venosus. Study Appraisal and Synthesis Methods For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle‐Ottawa Scale for observational studies and the Cochrane Collaboration’s tool for randomized trials. For the meta‐analysis, odds ratio for both fixed and random‐effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau2, χ2 (Cochrane Q), and I2 statistics. Publication bias was assessed by a funnel plot for meta‐analyses and quantified by the Egger method. Results A total of 31 studies were included in this meta‐analysis. The odds ratios for fetal death (random‐effects models) were 3.59 (95% confidence interval, 2.3–5.6), 7.27 (95% confidence interval, 4.6–11.4), and 11.6 (95% confidence interval, 6.3–19.7) for growth‐restricted fetuses with umbilical artery absent end‐diastolic velocities, umbilical artery reversed end‐diastolic velocities, and ductus venosus absent or reversed end‐diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. Conclusion Early‐onset growth‐restricted fetuses with either umbilical artery or ductus venosus absent or reserved end‐diastolic velocities are at a substantially increased risk for fetal death.

Can previous preterm birth classification influence treatment of short cervix in a subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary

To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound.

Added value of cerebro-placental ratio and uterine artery Doppler at routine third trimester screening as a predictor of SGA and FGR in non-selected pregnancies

Abstract Objectives: The objective of this study is to determine the added value of cerebroplacental ratio (CPR) and uterine Doppler velocimetry at third trimester scan in an unselected obstetric population to predict smallness and growth restriction. Methods: We constructed a prospective cohort study of women with singleton pregnancies attended for routine third trimester screening (32+0–34+6 weeks). Fetal biometry and fetal–maternal Doppler ultrasound examinations were performed by certified sonographers. The CPR was calculated as a ratio of the middle cerebral artery to the umbilical artery pulsatility indices. Both attending professionals and patients were blinded to the results, except in cases of estimated fetal weight < p10. The association between third trimester Doppler parameters and small for gestational age (SGA) (birth weight <10th centile) and fetal growth restriction (FGR) (birth weight below the third centile) was assessed by logistic regression, where the basal comparison was a model comprising maternal characteristics and estimated fetal weight (EFW). Results: A total of 1030 pregnancies were included. The mean gestational age at scan was 33 weeks (SD 0.6). The addition of CPR and uterine Doppler to maternal characteristics plus EFW improved the explained uncertainty of the predicting models for SGA (15 versus 10%, p < .001) and FGR (12 versus 8%, p = .03). However, the addition of CPR and uterine Doppler to maternal characteristics plus EFW only marginally improved the detection rates for SGA (38 versus 34% for a 10% of false positives) and did not change the predictive performance for FGR. Conclusions: The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Longitudinal Assessment of Abdominal Circumference versus Estimated Fetal Weight in the Detection of Late Fetal Growth Restriction

Objectives: To perform a longitudinal assessment comparison between estimated fetal weight (EFW) and abdominal circumference (AC) in the prediction of late fetal growth restriction (FGR) as opposed to small for gestational age (SGA). Patients and Methods: A cohort of unselected singleton pregnancies scanned at 32±2 and 37±1 weeks was created. Longitudinal growth assessment by calculating the conditional AC and conditional EFW was performed, and both parameters were compared for their prediction capacity for late FGR and SGA. Conditional standards set an expected size (EFW or AC) given a first measurement performed earlier. A declining growth was defined as a conditional growth of <10th centile. Results: A total of 938 pregnancies were included. As expected, declining growth between 32±2 and 37±1 weeks was associated with late FGR and SGA, but the predictive capacity of both conditional AC and conditional EFW was comparably poor, with detection rates of 28% at a 10% rate of false positives for late FGR. Conclusions: Longitudinal assessment of fetal growth during the third trimester has a low predictive capacity for late FGR, with no differences between conditional AC and conditional EFW.

Third-trimester conditional reference values for longitudinal fetal growth assessment

Objectives: The aim of this study was to derive longitudinal reference values of fetal growth (estimated fetal weight [EFW] and abdominal circumference [AC]) during the third trimester and to develop coefficients for conditional growth assessment. Patients and Methods: A prospective cohort study was conducted involving consecutive singleton pregnancies in a low-risk population for a routine third-trimester scan at 30+0-34+6 weeks and follow-up at 37+0-38+6 weeks for an additional ultrasound. Statistical analysis was based on multilevel modeling using MLwiN software. Unconditional centiles were calculated from z-values at each gestational age, and conditional centiles were calculated from z-values at a given measurement (30-34 weeks) and the expected measurement (37-38 weeks). Results: At 30-34 weeks, 8 and 9.3% of the fetuses had an unconditional EFW below the 10th and above the 90th centile, respectively. At 37-38 weeks, these figures were 10.3 and 9.3%, respectively. Regarding the unconditional AC, at the first scan, 8.9 and 9.6% had values below the 10th and above the 90th centile, while at the second scan 10.5 and 10.5% had values below the 10th and above the 90th centile, respectively. The proportion with a conditional EFW below the 10th and above the 90th centile was 10.2 and 9.4% at the second scan, respectively. For conditional AC, these figures were 10.7 and 10.3%, respectively. Conclusion: We have produced reference centiles for EFW and AC growth during the third trimester as a useful tool for quantifying growth.