Screening for fetal growth restriction using ultrasound and the sFLT1/PlGF ratio in nulliparous women: a prospective cohort study

Published on Aug 1, 2018in The Lancet Child & Adolescent Health8.543
· DOI :10.1016/S2352-4642(18)30129-9
Francesca Gaccioli25
Estimated H-index: 25
(University of Cambridge),
Ulla Sovio65
Estimated H-index: 65
(University of Cambridge)
+ 3 AuthorsGordon C. S. Smith67
Estimated H-index: 67
(University of Cambridge)
Sources
Abstract
Summary Background Fetal growth restriction is a major determinant of perinatal morbidity and mortality. This condition has no gold standard definition, but a widely used proxy is delivery of a small for gestational age infant ( Methods In this prospective cohort study, using serial antenatal blood sampling and blinded ultrasound scans, we investigated the association between the combination of an elevated sFLT1/PlGF ratio (>85th percentile) and ultrasonically suspected small for gestational age ( Findings Between Jan 14, 2008, and July 31, 2012, we recruited 4512 nulliparous women. 4098 women (91%) had a sFLT1/PlGF ratio measurement and estimated fetal weight at 28 or 36 weeks of gestational age, and outcome data available. 3981 women were analysed for 28 weeks of gestational age measurements and 3747 women were analysed for 36 weeks of gestational age measurements. At 28 weeks, 47 (1%) of 3981 women had the combination of ultrasonic small for gestational age and an elevated sFLT1/PlGF ratio. The positive likelihood ratio for preterm delivery of a small for gestational age infant associated with this combination was 41·1 (95% CI 23·0–73·6), the sensitivity was 38·5% (21·1–59·3), the specificity was 99·1% (98·7–99·3), and the positive predictive value was 21·3% (11·6–35·8). At 36 weeks, 102 (3%) of 3747 women had the combination of ultrasonic small for gestational age and an elevated sFLT1/PlGF ratio. The positive likelihood ratio for delivery of a small for gestational age infant associated with maternal pre-eclampsia or perinatal morbidity or mortality was 17·5 (95% CI 11·8–25·9), the sensitivity was 37·9% (26·1–51·4), the specificity was 97·8% (97·3–98·3), and the positive predictive value was 21·6% (14·5–30·8). The positive likelihood ratios at both gestational ages were higher than previously described definitions of suspected fetal growth restriction using purely ultrasonic assessment. Interpretation The combination of ultrasonically suspected small for gestational age plus an elevated sFLT1/PlGF ratio in unselected nulliparous women identified a relatively small proportion of women who have high absolute risks of clinically important adverse outcomes. Screening and intervention based on this approach could result in net benefit and this could be an appropriate subject for a randomised controlled trial. Funding NIHR Cambridge Comprehensive Biomedical Research Centre, Medical Research Council, and Stillbirth and neonatal death society (Sands).
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Fetal growth restriction is a major determinant of perinatal morbidity and mortality. Screening for fetal growth restriction is a key element of prenatal care but it is recognized to be problematic. Screening using clinical risk assessment and targeting ultrasound to high-risk women is the standard of care in the United States and United Kingdom, but the approach is known to have low sensitivity. Systematic reviews of randomized controlled trials do not demonstrate any benefit from universal ult...
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