Perinatal outcomes after selective third-trimester ultrasound screening for small-for-gestational age: prospective cohort study nested within DESiGN randomized controlled trial.

Objective: In screening for small-for-gestational age (SGA) using third-trimester antenatal ultrasound, there are concerns about the low detection rates and potential for harm caused by both false-negative and false-positive screening results. Using a selective third-trimester ultrasound screening program, this study aimed to investigate the incidence of adverse perinatal outcomes among cases with (i) false-negative compared with true-positive SGA diagnosis and (ii) false-positive compared with true-negative SGA diagnosis.

Methods: This prospective cohort study was nested within the UK-based DESiGN trial, a prospective multicenter cohort study of singleton pregnancies without antenatally detected fetal anomalies, born at > 24 + 0 to < 43 + 0 weeks' gestation. We included women recruited to the baseline period, or control arm, of the trial who were not exposed to the Growth Assessment Protocol intervention and whose birth outcomes were known. Stillbirth and major neonatal morbidity were the two primary outcomes. Minor neonatal morbidity was considered a secondary outcome. Suspected SGA was defined as an estimated fetal weight (EFW) < 10^th percentile, based on the Hadlock formula and fetal growth charts. Similarly, SGA at birth was defined as birth weight (BW) < 10^th percentile, based on UK population references. Maternal and pregnancy characteristics and perinatal outcomes were reported according to whether SGA was suspected antenatally or not. Unadjusted and adjusted logistic regression models were used to quantify the differences in adverse perinatal outcomes between the screening results (false negative vs true positive and false positive vs true negative).

Results: In total, 165 321 pregnancies were included in the analysis. Fetuses with a false-negative SGA screening result, compared to those with a true-positive result, were at a significantly higher risk of stillbirth (adjusted odds ratio (aOR), 1.18 (95% CI, 1.07-1.31)), but at lower risk of major (aOR, 0.87 (95% CI, 0.83-0.91)) and minor (aOR, 0.56, (95% CI, 0.54-0.59)) neonatal morbidity. Compared with a true-negative screening result, a false-positive result was associated with a lower BW percentile (median, 18.1 (interquartile range (IQR), 13.3-26.9) vs 49.9 (IQR, 30.3-71.7)). A false-positive result was also associated with a significantly increased risk of stillbirth (aOR, 2.24 (95% CI, 1.88-2.68)) and minor neonatal morbidity (aOR, 1.60 (95% CI, 1.51-1.71)), but not major neonatal morbidity (aOR, 1.04 (95% CI, 0.98-1.09)).

Conclusions: In selective third-trimester ultrasound screening for SGA, both false-negative and false-positive results were associated with a significantly higher risk of stillbirth, when compared with true-positive and true-negative results, respectively. Improved SGA detection is needed to address false-negative results. It should be acknowledged that cases with a false-positive SGA screening result also constitute a high-risk population of small fetuses that warrant surveillance and timely birth. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.