BMI modifies the effect of pregnancy complications on risk of small- or large-for-gestational-age newborns

Maternal physical condition (reflected by maternal body mass index (BMI) at delivery) and pregnancy complications influence neonatal health outcomes. High BMI during pregnancy increases various health problems' risks, but studies about the synthesized effect of these factors on fetal growth, are scarce.

The retrospective cohort study was conducted in Zhejiang Province, China from 1 January 2019 to 31 December 2021. The associations between complications and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) were measured by the Fine-Gray model and subgroup analysis. Effect modification and interaction analyses were conducted to explore BMI's modification effect and complications' interaction.

Several complications increased the risk for SGA and LGA, some significance varied in different subgroups. There was a positive effect modification of gestational diabetes mellitus (GDM) across BMI strata on LGA (relative excess risk due to interaction (RERI) [95% CI] = 0.57 [0.09,1.04]). Several pairwise complications' interactions were synergistic (e.g., pregestational diabetes and intraamniotic infection for SGA (ratio of ORs [95% CI] = 8.50 [1.74,41.37]), pregestational diabetes and assisted reproductive technology (ART) for LGA (ratio of ORs [95% CI] = 2.71 [1.11,6.62])), one was antagonistic (placental problems and ART for LGA (ratio of ORs [95% CI] = 0.58 [0.35,0.96])).

High-BMI positively modified the risk of GDM on LGA. Many interactions existed when two specific pregnancy complications occurred simultaneously.

This is the largest retrospective study covering more than 10 pregnancy complications to date in this aspect. High-BMI (BMI > 28 kg/m²) positively modifies the risk of GDM on LGA. Many pregnancy complications influence the risk of SGA and LGA, with several interactions that may create a "syndrome" effect. Pregnant women with different BMIs should consider the additional risks caused by pregnancy complications for their heterogeneous effects on abnormal fetal growth. Measures should be taken to prevent the occurrence of other exposure factors in the "syndrome". This study may aid in developing a new strategy for improving neonatal outcomes.