Long-term weight development in offspring exposed to obesity in pregnancy

Gomes, Delphina (2023): Long-term weight development in offspring exposed to obesity in pregnancy. Dissertation, LMU München: Medizinische Fakultät

Abstract

The prevalence of childhood overweight has increased drastically, and weight development in preschool years is linked to future obesity. A greater risk of overweight at preschool age is conferred by a higher maternal preconception body mass index (BMI), an urgent public health issue, since overweight or obesity occurs in up to two-thirds of child-bearing women today, frequently developing metabolic complications. In fact, our research group previously found that women with obesity may develop dysglycemia towards the end of pregnancy, despite a negative test for gestational diabetes (GDM). Therefore, we hypothesized that late-pregnancy dysglycemia could also contribute to adverse longitudinal BMI development in their offspring. For prevention, such offspring should be identified at a time prior to the first upper divergence in BMI gain in the trajectory towards overweight manifestation. However, prediction of early deviations in weight gain has not been achieved on an individual level as a prerequisite for implementation in the public health setting, because data on weight trajectories in children who had exposure to gestational overnutrition and the contribution of “obesogenic influences” are lacking. Using comprehensive and longitudinal data from different gestational and postnatal phases of the large Programming of Enhanced Adiposity Risk in CHildhood - Early Screening (PEACHES) cohort study of women with obesity and their children (n = 1,707), we performed linear mixed-effects models and mediation analysis to evaluate the long-term (from age 2 to 4 years) effect and contribution of obesity-related dysglycemia at the end of gestation (women’s HbA1c [glycated hemoglobin] at delivery ≥5.7%) on preschool BMI (at 4 years of age), respectively. We also identified specific patterns of BMI growth from birth until 5 years of age following exposure to obesity in pregnancy, assessed various BMI outcomes, and evaluated their underlying contributors in offspring using k-means cluster analysis and a series of multivariable regression models. Subsequently, a serial approach of individual risk score assessment, prediction, and re-assessments was developed using penalized logistic regressions. Data from an independent mother-child cohort (PErinatal Prevention of Obesity [PEPO], n = 11,730) were available for data validation. In the analysis of children exposed to gestational obesity, a diagnosis of GDM did not influence offspring BMI at age 4 years. However, within the group of mothers with obesity who tested negative for GDM towards the end of the second trimester, dysglycemia in late pregnancy was associated with high BMI gains between ages 2 and 4 years in offspring (mean annual increment Δ 0.18, 95% confidence interval [CI] 0.06–0.30). Overall, it accounted for almost one-quarter of the contribution of gestational obesity on offspring BMI z-score at age 4 years. In these mothers, the presence of late-pregnancy dysglycemia was related to a risk of prediabetes or type 2 diabetes (T2D) a few years later that was four times higher than in mothers with normal HbA1c at delivery (relative risk [RR] 4.01, 95% CI 1.97–8.17). Excessive third-trimester weight gain was related to a mean increase in the risk of dysglycemia in late pregnancy by 72% (RR 1.72, 95% CI 1.12–2.65) in mothers with obesity who had a negative GDM test. Next, we focused on a “pre-symptomatic” offspring BMI outcome and identified a “high-risk” subgroup of children (21%) likely to undergo early upper divergence from a healthy BMI growth track after exposure to gestational overnutrition. Belonging to this upper BMI cluster was associated with a high risk of preschool overweight/obesity (odds ratio [OR] 16.13; 95% CI 9.98–26.05). Underlying pre- and perinatal influences such as high maternal weight gain (OR 2.08, 95% CI 1.25–3.45) and smoking in pregnancy (OR 1.94, 95% CI 1.27–2.95) were essential to predict a subsequent “higher-than-normal BMI growth” pattern in the 3-month-old, 1-year-old, and 2-year-old offspring. Sequential prediction models showed adequate predictive performances (area under the receiver operating characteristic [AUROC] 0.69–0.79, specificity 64.7–78.1%, sensitivity 70.7–76.0%), and findings were confirmed in the cohort PEPO. In conclusion, in order to achieve healthy weight development at the beginning of life, efforts should be made to optimize maternal weight gain and glucose metabolism as well as fetal growth also in the 3rd trimester of pregnancy, particularly if the mother with obesity had a prior GDM-negative test result. After birth, children of women with obesity should be closely sequentially assessed for risk quantification and individual detection of an increased risk of “higher-than-normal” BMI growth at the established well-child care visits for intensified prevention measures. A “continuum” of targeted management strategies in the very early stages of life could help reduce intergenerational transmission of obesity.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Maternal obesity, childhood obesity, childhood growth
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 13. Juli 2023
• 1. Bericht­erstatter:in: Ensenauer, Regina