Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study

Objectives: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. Methods: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10 ^th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3 ^rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. Results: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. Conclusions: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements.