# Mediating role of preterm birth in the relationship between maternal disease and infant development

## TL;DR

The study shows that preterm birth can link maternal diseases to poor infant growth and development outcomes.

## Contribution

This study is among the first to demonstrate preterm birth as a mediator between maternal diseases and infant developmental outcomes.

## Key findings

- Preterm birth mediates the link between pregnancy-induced hypertension and neonatal neurological assessment scores.
- Preterm birth also mediates the association between gestational diabetes and infant body mass index.

## Abstract

Preterm birth is a major adverse perinatal outcome and may act as a mediator linking maternal disease to impaired infant growth and neurodevelopment. However, the mediating role of preterm birth has not been well explored in relation to maternal diseases. This study aimed to investigate whether preterm birth mediates the association between maternal diseases and infant outcomes including Body Mass Index, the Neonatal Behavioral Neurological Assessment, and the Gesell Development Schedule.

This study recruited a total of 2000 mother-child pairs from the Pediatric Healthcare Centre at the Third Xiangya Hospital. Maternal diseases, including gestational diabetes mellitus, pregnancy-induced hypertension, anaemia, hypothyroidism, hyperthyroidism, and thrombocytopenia, were assessed through hospital records and parental questionnaires verified against medical records. Infant outcomes were evaluated by trained pediatric nurses blinded to maternal conditions, using anthropometric measurements (Body Mass Index) and standardized neurodevelopmental tools (Neonatal Behavioral Neurological Assessment and Gesell Development Schedule). Mediation analysis with 1,000-sample bootstrapping was applied to quantify the indirect effects of preterm birth.

Preterm birth significantly mediated the association between Pregnancy-Induced Hypertension and Neonatal Behavioral Neurological Assessment (Indirect effect = -0.653, 95% CI: -0.98 – -0.36, p < 0.001). Preterm birth also significantly mediated the relationship between Gestational Diabetes Mellitus and Body Mass Index (Indirect effect = − 0.046, 95% CI: -0.08 – -0.01, p = 0.01).

Preterm birth may act as a mediator between maternal diseases and infant growth and neurodevelopmental outcomes. The results support the feasibility and value of using mediation analysis in maternal–infant research. Findings highlight the importance of early prenatal screening, prevention, and management of preterm birth in pregnancies complicated by maternal disease. Future research is warranted to employ longitudinal neurodevelopmental monitoring in affected infants.

The online version contains supplementary material available at 10.1186/s12884-025-08268-7.