Disentangling the relationship between intrauterine exposures and offspring growth in mid-childhood.

backgroundConventional epidemiological studies have suggested that lower birthweight and adverse pregnancy events are associated with later life obesity and cardiometabolic disorders, suggesting that intrauterine factors may play an important role in the offspring's later life health. Nevertheless, it remains unclear whether the link between intrauterine factors and childhood anthropometry is causal or driven by confounding or genetic factors.

methodsWe performed two-sample Mendelian randomization (MR) to assess whether adverse pregnancy-related conditions (gestational diabetes, gestational hypertension and pre-eclampsia) and birth outcomes (birthweight, gestational duration and placental weight) have a causal effect on mid-childhood (age 8-10) body mass index (BMI) and height. We selected independent genetic variants from the largest publicly available genome-wide association studies that were associated (P < 5 × 10

resultsWe found evidence for a causal effect of birthweight on mid-childhood height (β

conclusionsOur study suggests that intrauterine exposures acting through gestational diabetes, gestational hypertension, preeclampsia, birthweight, gestational duration and placental weight are unlikely to be key drivers of offspring mid-childhood BMI or height. The causal relationship identified between birthweight and mid-childhood height but not with mid-childhood BMI suggests that the intrauterine environmental and genetic factors impacting birthweight may be predominantly related to skeletal growth.