ABSTRACT
OBJECTIVES: First, to evaluate the predictive performance for preterm growth-related neonatal morbidity of high soluble fms-like tyrosine kinase-1 (sFLT-1) / placental growth factor (PlGF) ratio or low PlGF at mid-gestation, and second, to compare the performance of the high sFLT-1/PlGF ratio or low PlGF with that of the competing risks model for small for gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI). METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 to 24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFLT-1. The primary outcome was delivery <32 and <37 weeks' gestation of SGA neonate with birth weight <10th or <3rd percentile for gestational age, combined with neonatal unit (NNU) admission for ≥48 hours or a composite of major neonatal morbidity. The detection rates in screening by either PlGF <10th percentile, sFLT-1/PlGF ratio >90th percentile and the competing risks model for SGA were estimated and they were compared using McNemar's test. RESULTS: In the study population of 40241 women prediction of preterm growth-related neonatal morbidity provided by the competing risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio. For example, at screen positive rate (SPR) of 10.0%, as defined by the sFLT-1/ PlGF ratio >90th percentile, the competing risks model predicted 70.1% (95% CI 61.0 - 79.2) of SGA <10th percentile and 76.9% (67.6-86.3) of SGA <3rd percentile with NNU admission for ≥48 hours delivered <32 weeks gestation and these were significantly higher than the respective values of 35.0% (25.6-44.6) and 35.9% (25.3 - 46.5), achieved by the application of the sFLT-1/ PlGF ratio >90th percentile (p<0.0001 for both). The respective values for SGA with major neonatal morbidity were 73.8% (64.4-83.2), 77.9% (68.0-87.8), 38.1% (27.7-48.5) and 39.7% (28.1-51.3) (Both p<0.0001). CONCLUSION: At mid-gestation, the prediction of growth-related neonatal morbidity by the competing risks model for SGA is superior to that of high sFlt-1/PlGF ratio or low PlGF. This article is protected by copyright. All rights reserved.
ABSTRACT
OBJECTIVES: First, to investigate the association between adverse neonatal outcomes and birth weight and gestational age at delivery. Second, to describe the distribution of adverse neonatal outcomes within different risk strata derived by a population stratification scheme based on the midgestation risk assessment for small-for-gestational-age (SGA) neonates using a competing-risks model. METHODS: This was a prospective observational cohort study in women with a singleton pregnancy attending a routine hospital visit at 19 + 0 to 23 + 6 weeks' gestation. The incidence of neonatal unit (NNU) admission for ≥ 48 h was evaluated within different birth-weight-percentile subgroups. The pregnancy-specific risk of delivery with SGA < 10th percentile at < 37 weeks was estimated by the competing-risks model for SGA, combining maternal factors and the likelihood functions of Z-score of sonographically estimated fetal weight and uterine artery pulsatility index multiples of the median. The population was stratified into six risk categories: > 1 in 4, > 1 in 10 to ≤ 1 in 4, > 1 in 30 to ≤ 1 in 10, > 1 in 50 to ≤ 1 in 30, > 1 in 100 to ≤ 1 in 50 and ≤ 1 in 100. The outcome measures were admission to the NNU for a minimum of 48 h, perinatal death and major neonatal morbidity. The incidence of each adverse outcome was estimated in each risk stratum. RESULTS: In the study population of 40 241 women, 0.8%, 2.5%, 10.8%, 10.2%, 19.0% and 56.7% were in the risk strata > 1 in 4, > 1 in 10 to ≤ 1 in 4, > 1 in 30 to ≤ 1 in 10, > 1 in 50 to ≤ 1 in 30, > 1 in 100 to ≤ 1 in 50 and ≤ 1 in 100, respectively. Women in higher-risk strata were more likely to deliver a baby that suffered an adverse outcome. The incidence of NNU admission for ≥ 48 h was highest in the > 1 in 4 risk stratum (31.9% (95% CI, 26.9-36.9%)) and it gradually decreased until the ≤ 1 in 100 risk stratum (5.6% (95% CI, 5.3-5.9%)). The mean gestational age at delivery in SGA cases with NNU admission for ≥ 48 h was 32.9 (95% CI, 32.2-33.7) weeks for risk stratum > 1 in 4 and progressively increased to 37.5 (95% CI, 36.8-38.2) weeks for risk stratum ≤ 1 in 100. The incidence of NNU admission for ≥ 48 h was highest for neonates with birth weight below the 1st percentile (25.7% (95% CI, 23.0-28.5%)) and decreased progressively until the 25th to < 75th percentile interval (5.4% (95% CI, 5.1-5.7%)). Preterm SGA neonates < 10th percentile had significantly higher incidence of NNU admission for ≥ 48 h compared with preterm non-SGA neonates (48.7% (95% CI, 45.0-52.4%) vs 40.9% (95% CI, 38.5-43.3%); P < 0.001). Similarly, term SGA neonates < 10th percentile had significantly higher incidence of NNU admission for ≥ 48 h compared with term non-SGA neonates (5.8% (95% CI, 5.1-6.5%) vs 4.2% (95% CI, 4.0-4.4%); P < 0.001). CONCLUSIONS: Birth weight has a continuous association with the incidence of adverse neonatal outcomes, which is affected by gestational age. Pregnancies at high risk of SGA, estimated at midgestation, are also at increased risk for adverse neonatal outcomes. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
