Multigenerational Cardiometabolic Risk as a Predictor of Birth Outcomes: The Bogalusa Heart Study

Abstract

Objective To examine the relationship between generation 1 (grandmaternal) cardiometabolic risk factors and generation 3 (grandchild’s) birthweight and gestational age Study design Mother-daughter pairs in the Bogalusa Heart Study (1973-present) were linked to their children’s birth certificates; women were also interviewed about their reproductive histories, creating a three-generation linkage including 177 generation 1 (grandmothers), 210 generation 2 (mothers), and 424 generation 3 children. Pre-pregnancy cardiometabolic risk factors (BMI, lipids, glucose) for generation 1 (mean age 16.2) and 2 (mean age 11.1) were examined as predictors of generation 3 birthweight and gestational age using linear and logistic regression with adjustment for age, race, parity, and other confounders. Results Generation 2 higher BMI was associated with higher birthweight (28 g per 1 unit, 95% CI 12–44) and gestational age (0.08 weeks, 95% CI 0.02–0.14) in generation 3, and generation 1 higher BMI was associated with higher birthweight (52 g, 95% CI 34–70)) in the generation 2. Generation 1’s higher glucose levels were associated with higher birthweight in generation 3 (adjusted beta 111 g, 95% CI 33–189), and triglycerides (adjusted beta −21, 95% CI −43-0) and LDL (adjusted beta −24, 95% CI −48-0) were associated with lower birthweight. Conclusions These results suggest the possibility of multigenerational developmental programming of birth outcomes, although mechanisms (whether biological or environmental) are undetermined.

Maternal Birth Weight and BMI Mediate the Transgenerational Effect of Grandmaternal BMI on Grandchild’s Birth Weight

“…This may be due to the methodological limitation of not using path analytical models. Another possible reason may be that grandmaternal BMI in the study by Harville et al was measured during adolescence (at a mean age of 16.2) , which may result in an underestimation of the grandmaternal BMI effect.…”

“…Most studies, assessing the association of transgenerational risk factors with grandchild's BW, have included maternal BW and/or BMI as covariates (13,(15)(16)(17)(18)(19)(20). So far, only two studies examined the potential mediating effect of maternal BW (12) or maternal prepregnancy overweight (23) on the association between grandmaternal risk factors and grandchild's BW.…”

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring

“…16 With theories about the propagation of obesity across generations as the subject of influential commentaries 3 and the evolution of associated theories, the epidemiological literature on the transgenerational influence of pregnancy-related exposures on weight-related outcomes in humans is growing. Several birth cohorts either currently have grandparental, parental, and offspring data [17][18][19][20][21][22][23] or are being extended to include three generations of data. [24][25][26] Many of these cohorts contain only birth data for the offspring and cross-sectional data collected by self-report for the mothers and grandparents at the time of birth of the offspring.…”

“…Transgenerational studies in humans that are focused on children's birthweight 19 and weight status [29][30][31][32][33][34][35][36] have examined the influence of grandparental obesity, [30][31][32] diabetes, 29,36 smoking, [33][34][35] and elevated cardiometabolic risk. 19 The available evidence, however, is limited by small sample sizes, 19,30,36 self-report of information, [29][30][31][32][33] the inability to adjust for all relevant confounders, 31 and improper adjustment for mediators. 19,29,[34][35][36] Thus, the need to clarify these transgenerational associations remains.…”

“…19 The available evidence, however, is limited by small sample sizes, 19,30,36 self-report of information, [29][30][31][32][33] the inability to adjust for all relevant confounders, 31 and improper adjustment for mediators. 19,29,[34][35][36] Thus, the need to clarify these transgenerational associations remains.…”