Associations Of Gestational Diabetes Mellitus And Excessive Gestational Weight Gain With Offspring Obesity Risk

Gestational diabetes mellitus(GDM)is defined as any degree of glucose intolerance that is onset or first discovered during pregnancy.Gestational weight gain(GWG)is an important indicator to measure the nutritional status of pregnant women during pregnancy.GDM and GWG are known risk factors that affect the development and long-term health of children.Although many studies have explored the relationships of GDM and excessive GWG with children’s birth weight,development,and obesity,the results were inconsistent and some problems remained unresolved.Firstly,most of the previous studies were conducted in the developed countries.With the rapid increase in the incidence of GDM and excessive GWG in China,it is particularly important to explore the relationships between these two risk factors and the health of children in China.Some studies conducted in China had a small sample size and only focused on birth outcomes.Therefore,it is very necessary to explore the impact of GDM and excessive GWG on the long-term health of children.Secondly,because GDM and excessive GWG are mutually influential,but previous studies only focused on the influence of GDM or excessive GWG as a single factor,and research exploring the interaction between the two in the growth of children was very limited.In addition,few studies adjusted GWG/GDM when exploring GDM/GWG.Thirdly,more and more animal and epidemiological studies have pointed out that gender has a certain influence on the relationships between the mother’s intrauterine environment and the development process of children.But current research on this aspect either only focused on the birth outcomes or only focused on a single factor between GDM and GWG.Therefore,it is very important to explore the role of gender in the relationships between these two risk factors and the long-term health of children.Based on a large-scale and prospective cohort study in China,the present study aimed to explore the relationships of GDM and excessive GWG with children’s physical development,growth trajectory,and risk of obesity.Moreover,the interaction analysis was used to explore the interaction effect between these two risk factors and the gender stratification analysis was used to examine whether the interaction effect differed by children’s sex.Part 1.Associations of GDM and excessive GWG with newborn birth outcomesObjectives: The purpose of this study was to investigate the associations of GDM and excessive GWG with newborn birth outcomes.Methods: This study was based on a prospective birth cohort of 7,949 mother-child pairs,recruited in Wuhan from 2012 to 2015.Maternal sociodemographic information and life habit information,including occupation,drinking,and smoking,was obtained by face-to-face questionnaires.Other information,such as fetal birth weight and birth length,was obtained through the hospital electronic medical record system.GDM was diagnosed according to the results of oral glucose tolerance test(OGTTs).Maternal GWG was categorized as inadequate GWG,adequate GWG,and excessive GWG.The general linear model was used to estimate the relationships of GDM and excessive GWG with weight-for-age Z scores(ZWAZ),height-for-age Z scores(ZHAZ),BMI-for-age Z scores(ZBMI),birth weight,birth height,and ponderal index(PI).In addition,the modified Poisson regression model was used to estimate the links of GDM and excessive GWG with the risks of macrosomia,small for gestational age(SGA),large for gestational age(LGA),and low birth weight(LBW).We further analyzed the interactive effect of these two risk factors with the risk of macrosomia.Results: After adjusting for confounding factors including GDM and GWG,GDM and excessive GWG were positively associated with ZWAZ,ZBMI,birth weight,and PI.Both GDM and excessive GWG were associated with an increased risk of macrosomia(Risk ratio(RR)and 95% confidence intervals(CI)were 1.91(1.52,2.38)and 3.05(2.40,3.87),respectively).Besides,GDM was positively associated with an increased risk of LGA(RR(95%CI)=1.60(1.42,1.81)).Excessive GWG was associated with an increased risk of LGA(RR(95%CI)=2.00(1.77,2.27)),and decreased risks of SGA(RR(95%CI)=0.60(0.51,0.70))and LBW(RR(95%CI)=0.72(0.52,0.99)).In addition,these two risk factors had a significant synergistic effect on macrosomia at birth.Conclusions: Both GDM and excessive GWG were positively associated with newborn anthropometry index and birth weight.Both of them were correlated with higher risks of macrosomia and LGA,and co-presence of them had the interactive effect on the risk of macrosomia.Part 2: Associations of GDM and excessive GWG with offspring growth trajectories and risks of obesityObjectives: The purpose of this study was to evaluate the independent and interactive effect of the status of GDM and excessive GWG on offspring growth trajectories and risk of overweight/obesity from birth to 24 months of age.Methods: 7949 mother-child pairs were recruited from 2012 to 2015 in Wuhan.We acquired children anthropometry data during the follow-up years when they reached 6,12 and 24 months of age.The linear mixed model and the general linear model was used to estimate the relationships of GDM and excessive GWG with children average ZWAZ,ZHAZ and ZBMI,and anthropometry data at the follow-up time points,respectively.The group-based trajectory modeling(GBTM)was used to conduct offspring growth trajectories from birth to 24 months of age,and the multinomial logistic regression model was used to assess the associations of GDM and excessive GWG with each growth trajectory pattern from GBTM.The modified Poisson regression model was used to estimate relationships of GDM and excessive GWG with risks of overweight/obesity at 6,12 and 24 months of age.The additive interaction analysis was used to explore the interaction between GDM and excessive GWG,and the sex-stratified analysis was further conducted to examine whether children’s sex would change the relationship between exposure and outcomes.Results: GDM was not associated with children anthropometry data and risks of overweight/obesity at 6,12 and 24 months of age.In contrast,excessive GWG not only was associated with children anthropometry data,but also increased the risks of overweight/obesity in the first 24 months of age(RRs(95%CI)for 6,12 and 24 months of age were 1.16(1.03,1.31),1.34(1.19,1.52)and 1.36(1.20,1.53)).Excessive GWG was also associated with increased odds ratio(OR)of 1.18(1.07,1.31)and 1.80(1.42,2.27)for the relatively stable high ZBMI trajectory pattern and the stable high ZBMI trajectory pattern,respectively.Besides,excessive GWG was associated with lower ORs for the stable low ZBMI trajectory pattern and the catch up ZBMI trajectory pattern(ORs(95%CIs)were 0.56(0.46,0.67)and 0.58(0.48,0.69),respectively).In addition,the interactive effect between these two risk factors was only significant in boys during the follow-up years in the sex-stratified analyses.Conclusions: Excessive GWG was a more pronounced predictor than GDM with relation to ZBMI and risks of offspring overweight/obesity in early childhood.Besides,the interactive effect of them on offspring overweight/obesity was only obvious in boys.