The influence of pre-pregnancy weight and weight changes on pregnancy complications and child growth and development

Background and aims: Pre-pregnancy obesity (body mass index [BMI] ≥ 30 kg/m2) and pregnancy complications such as gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are major and increasing global public health concerns because of a number of consequences to women and their babies. While the associations of pre-pregnancy obesity and GDM and HDP are well established, little is known about the relationship between pre-pregnancy weight change and GDM and HDP risk. Growing evidence also implicates pre-pregnancy obesity and pregnancy complications with offspring childhood growth and development, although the findings are inconclusive, and associations of preconception BMI trajectory and child outcomes have been rarely investigated. This thesis examines the associations between pre-pregnancy weight characteristics, GDM and HDP and offspring childhood growth and development. Methods: Several data sources and analysis approaches were employed across the papers included in the thesis. First, literature searches were performed in CINAHL, EMBASE, PSYCINFO, PUBMED and SCOPUS for systematic reviews on 1) the association of pre-pregnancy obesity and offspring childhood physical and cognitive development, and 2) the association of diabetes during pregnancy and childhood cognitive development. Second, self-reported data from the 1973-78 cohort (aged 18-23 years at the first survey in 1996) of the Australian Longitudinal Study on Women’s Health (ALSWH) were used to examine the associations between adult pre-pregnancy weight change and GDM (n = 5,242) and HDP (n = 4,813) risk. Third, data from the 1973-78 cohort of the ALSWH, Mothers and their Children’s Health (MatCH) study and linked data from the Australian Early Development Census (AEDC) were used to evaluate the associations of 1) preconception BMI trajectories, GDM and HDP and offspring childhood physical and cognitive development (n = 771), and 2) preconception BMI trajectories and offspring childhood BMI (n = 2,733), and 3) to quantify the mediation role of offspring’s birthweight between the association of pre-pregnancy BMI and childhood anthropometrics (BMI-for-age, height-for-age, weight-for-age and weight-for-height) (n = 1,618). In addition to descriptive statistics, multinomial logistic regression, generalised estimating equations, g-computation and latent class growth modelling were used for analyses. Results: A total of 17 articles were eligible for the systematic review on pre-pregnancy obesity and offspring childhood physical and cognitive development. A large proportion of studies supported the adverse association between pre-pregnancy obesity and childhood cognitive development. A few studies also demonstrated a negative association between pre-pregnancy obesity and the gross motor function of the offspring but not with the fine motor function. The evidence was based on a limited number of studies with heterogeneous measurement scales and obesity definition. For the systematic review on diabetes during pregnancy and offspring childhood cognitive development, we found a small number of geographically limited studies, the majority of which were small and did not adjust for key confounders. Of 14 eligible studies included in the systematic review, 10 investigated the associations between pre-existing diabetes or both pre-existing diabetes and GDM and cognitive development in offspring. Of these, six found at least one negative association. Four studies exclusively examined the relationships between GDM and offspring’s cognitive development; two of them found negative, one positive and one null associations. In the ALSWH, annual pre-pregnancy weight change from early adulthood (mean age 20 years, 1996) to the index pregnancy (between 2003 and 2012) was significantly associated with risk of development of GDM and HDP. Women with considerable weight gain (>2.5% body weight /year) were more likely to develop GDM (RR = 2.94, 95% CI: 2.16, 4.01) and HDP (RR = 2.31, 95% CI: 1.77, 3.03) compared to women with stable weight (loss or gain of up to 1.5%). We also found that children (mean age 5 years) born to women with a chronically obese BMI trajectory were more likely to be classified as developmentally vulnerable/at-risk on the AEDC domains of gross and fine motor skills (RR = 1.64, 95% CI: 1.04, 2.61) and communication skills and general knowledge (RR = 1.71, 95% CI: 1.09, 2.68) compared with children born to women with a normative BMI trajectory. They also had an elevated risk of suspected gross motor delay (RR = 2.62, 95% CI: 1.26, 5.44) at the average age of 3.5 years, and being overweight (RR = 2.48, 95% CI: 1.65, 3.73) and obese (RR = 6.65, 95% CI: 3.40, 13.01) at the average age of 7.7 years. Diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Our mediation analysis further demonstrated that pre-pregnancy obesity had only significant natural direct (β = 0.75, 95% CI: 0.55, 0.95) and total causal effects (β = 0.79, 95% CI: 0.59, 0.99) on children’s BMI at the average age of 8.6 years. Conclusions: Although there are relatively few data available, the current evidence from the literature suggests that pre-pregnancy obesity and diabetes in pregnancy are associated with offspring’s childhood cognitive development, but evidence of the association between pre-pregnancy obesity and physical development of children is too scarce to offer a conclusion. Evidence from our population-based prospective cohort study demonstrated that women with considerable annual pre-pregnancy weight gain were significantly more likely to develop GDM and HDP. Our study further demonstrated that children born to chronically overweight and chronically obese women were significantly more likely to be overweight and obese themselves and to have poorer physical and cognitive development. Most of the effect of pre-pregnancy obesity on child anthropometrics appears to be via a direct effect, not mediated through offspring’s birthweight. Further studies are warranted to unravel the mechanisms linking preconception BMI trajectory and child outcomes and to examine the impact of preconception weight loss intervention to improve offspring childhood outcomes