Prenatal exposure to extreme temperatures alters offspring growth trajectories: evidence from birth cohort and animal experiment

Prenatal exposure to extreme temperatures may affect fetal development and childhood growth, yet longitudinal evidence and causal support remain limited. We analyzed 2,217 mother-child pairs from a prospective birth cohort in Guangzhou, China, with repeated anthropometric measurements from birth to 6 years. Growth trajectories for weight-for-age, length/height-for-age, and BMI-for-age z-scores were identified using group-based trajectory modeling. Prenatal temperature was classified by percentile thresholds: below the 25 th , 15 th , 10 th , and 5 th percentiles for cold exposure and above the 75 th , 85 th , 90 th , and 95 th percentiles for heat exposure. Multinomial logistic regression estimated associations with growth trajectories, and difference-method mediation analyses evaluated the mediating roles of adverse birth outcomes. Pregnant Wistar rats were exposed to high (38 ± 1 °C) or low (5 ± 1 °C) temperatures during gestational days 7-13. Offspring body weight and weight gain were monitored from birth to postnatal day 42. In the cohort, prenatal extreme cold and heat were associated with severe growth restriction and catch-up growth trajectories, particularly for weight-for-age and length/height-for-age. For weight-for-age trajectories, exposure above the 95th percentile and below the 5th percentile was associated with catch-up growth, with odds ratios of 3.44 (95% CI: 1.37, 8.61) and 7.60 (95% CI: 3.64, 15.83), respectively. Preterm birth mediated 38.35%-81.73% of these associations. In rats, offspring prenatally exposed to heat or cold had lower birth weight followed by accelerated postnatal growth. These findings suggest that prenatal temperature extremes may increase risks of offspring growth restriction and catch-up growth, partly through adverse birth outcomes.