Maternal environmental and lifestyle factors in adverse birth outcomes: a case-control study

The Generation Gemelli study, as part of the “Valutazione dell’esposoma nei primi 1000 giorni in coorti di nati in aree ad elevata antropizzazione e attuazione di interventi per la riduzione del rischio” project, investigates the exposome in late intrauterine growth restriction (IUGR) and spontaneous preterm birth (PTB), also exploring early neurodevelopment and mitochondrial DNA (mtDNA) variability. A nested case–control study within a Rome birth cohort (2022–2025) with 24-month follow-up included singleton pregnancies with late IUGR (≥32 weeks) or spontaneous PTB (<32 weeks) and uncomplicated term controls. Maternal exposures were assessed by questionnaire; child development at follow-up. Blood samples underwent exploratory mtDNA analyses. Associations were estimated by regression models adjusted for maternal age, pre-pregnancy BMI, and parity. 158 mother–newborn dyads were included (63 cases, 95 controls). Gym-based activity was associated with lower odds of case status across all trimesters (1st: aOR 0.27, 95% CI 0.08–0.88; 2nd: aOR 0.20, 95% CI 0.05–0.71; 3rd: aOR 0.16, 95% CI 0.03–0.76). Walking in the third trimester showed a similar pattern (aOR 0.49, 95% CI 0.23–1.03). Higher pre-pregnancy BMI was associated with increased odds (aOR 1.12, 95% CI 1.03–1.22), while multiparity was associated with lower odds (aOR 0.32, 95% CI 0.16–0.65). Household mold exposure showed a suggestive association with higher odds (aOR 1.26, 95% CI 0.64–2.47). In a subgroup (49/158), exploratory analyses suggested associations between maternal mold exposure and the child’s motor domain (p = 0.023), poor maternal diet and mtDNA variability (p = 0.034), and cord blood heteroplasmy and cognitive scores (p = 0.032). Selected environmental and lifestyle exposures were associated with adverse birth outcomes, suggesting a role for modifiable factors but requiring confirmation in larger studies. Project carried out with the technical and financial support of the Italian Ministry of Health–PNC.

Key messages

• Maternal environmental and lifestyle exposures may influence adverse birth outcomes and could represent actionable targets for public health prevention.

• Integrating exposome-based approaches into maternal health policies may strengthen early-life prevention and help reduce long-term health inequalities.