Lightning Talk and Poster Presentation GENEMAPPERS 2024

Disentangling the relationship between intrauterine exposures and offspring growth in childhood (#17)

Kym-Mai Nguyen 1 , Roya Karimi 2 , Marc Vaudel 2 , Stefan Johansson 2 , David Evans 1 3 4 , Nicole Warrington 1 3
  1. Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
  2. Mohn Center for Diabetes Precision Medicine, University of Bergen, Bergen, Norwary
  3. Frazer Institute, University of Queensland, Brisbane, Australia
  4. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom

Childhood obesity is a large healthcare burden that has seen no substantial improvements in its prevalence globally. Hence, there is urgent need for evidence-based strategies to curb this growing problem. The prenatal period is a timepoint of interest for early prevention of obesity. However, it remains unclear whether observational associations between intrauterine exposures and offspring childhood growth outcomes are due to true causal effects, genetic pleiotropy or confounding factors. Investigating this relationship is further complicated by the correlation between maternal and offspring genotypes. To overcome this issue, we performed two-sample Mendelian randomization (MR) using mother-offspring pairs (N=26,243) from one Norwegian and two British birth cohorts. We assessed whether maternal intrauterine factors (gestational diabetes, gestational hypertension and preeclampsia) and birth outcomes (birth length, birthweight, gestational duration, placental weight and ponderal index) have causal effects on body mass index (BMI) and height in mid-childhood (age 8-10). Maternal gestational diabetes, gestational hypertension and preeclampsia were found to have no significant causal effect on either offspring BMI (βgestational diabetes-BMI=0.03, 95% confidence interval (CI)=-0.02–0.07; βgestational hypertension-BMI=-0.03, 95%CI=-0.12–0.05; βpreeclampsia-BMI=-0.05, 95%CI=-0.14–0.04) or height (βgestational diabetes-height=0.04, 95%CI=-0.0004–0.09; βgestational hypertension-BMI=-0.04, 95%CI=-0.12–0.03; βpreeclampsia-BMI=0.01, 95%CI=-0.07–0.09). Additionally, maternal genetic scores for birthweight, gestational duration, placental weight and preterm birth were not associated with the offspring outcomes. Conversely, an offspring’s effect on their birth length and birthweight showed suggestive causal effects on their mid-childhood BMI (βbirth length-BMI=0.29, 95%CI=0.09–0.49; βbirthweight-BMI=0.30, 95%CI=0.21–0.40) and height (βbirth length-height=0.63, 95%CI=0.27–1.00; βbirthweight-height=0.45, 95%CI=0.33–0.57). Effect sizes represent change in one standard deviation (SD) of outcome per SD change of exposure. Overall, we found little evidence that the intrauterine environment is having causal impact on offspring BMI and height in mid-childhood. Therefore, intervention strategies targeting these intrauterine exposures are unlikely beneficial in reducing childhood obesity and its associated poor health outcomes.