TY - JOUR
T1 - Perinatal outcomes after selective third-trimester ultrasound screening for small-for-gestational age
T2 - prospective cohort study nested within DESiGN randomized controlled trial
AU - Winsloe, C.
AU - Elhindi, J.
AU - Vieira, M. C.
AU - Relph, S.
AU - Arcus, C. G.
AU - Coxon, K.
AU - Briley, A.
AU - Johnson, M.
AU - Page, L. M.
AU - Shennan, A.
AU - Marlow, N.
AU - Lees, C.
AU - Lawlor, D. A.
AU - Khalil, A.
AU - Sandall, J.
AU - Copas, A.
AU - Pasupathy, D.
AU - on behalf of the DESiGN Trial Team
AU - Peebles, Donald
AU - Thilaganathan, Baskaran
AU - Alagna, Alessandro
AU - Healey, Andrew
AU - McCowan, Lesley
AU - Muruet-Gutierrez, Walter
AU - Elstad, Maria
AU - Coker, Bolaji
PY - 2025/1
Y1 - 2025/1
N2 - 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.
AB - 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.
KW - antenatal diagnosis
KW - cerebral intraventricular hemorrhage
KW - fetal death
KW - fetal growth restriction
KW - fetal weight
KW - hypoxia–ischemia, brain
KW - missed diagnosis
KW - perinatal mortality
KW - pregnancy complications
KW - prenatal ultrasonography
UR - http://www.scopus.com/inward/record.url?scp=85210449004&partnerID=8YFLogxK
U2 - 10.1002/uog.29130
DO - 10.1002/uog.29130
M3 - Article
AN - SCOPUS:85210449004
SN - 0960-7692
VL - 65
SP - 30
EP - 38
JO - Ultrasound in Obstetrics and Gynecology
JF - Ultrasound in Obstetrics and Gynecology
IS - 1
ER -