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

Abstract

Objective The aims of this study are to examine the potential association between grandmaternal BMI and grandchild’s birth weight (BW) and whether maternal BW and BMI mediate this association. Methods Data of 209 grandmother‐mother pairs and 355 grandchildren from the Isle of Wight birth cohort in the UK were analyzed using path analysis. Results An indirect effect of grandmaternal BMI on increasing grandchild’s BW was mediated by maternal BW and BMI at age 18 years (indirect effects: β = 2.3 g/unit increase in grandmaternal BMI via maternal BW and β = 4.4 g via maternal BMI; P = 0.04). These two mediating effects of maternal BW and BMI confounded one another. Grandmaternal smoking during pregnancy had an indirect effect on decreasing grandchild’s BW, dependent on maternal smoking during pregnancy and BW (indirect effects: β = −36.1 g compared with nonsmoking grandmothers via maternal smoking during pregnancy and β = −27.2 g via maternal BW; P = 0.005). Neither direct effect between grandmaternal BMI and grandchild’s BW nor that between grandmaternal smoking during pregnancy and grandchild’s BW was statistically significant. Conclusions Larger grandmaternal BMI indirectly increased grandchild’s BW via maternal BW and BMI. Grandmaternal smoking during pregnancy indirectly reduced grandchild’s BW via maternal smoking during pregnancy and BW.

Transgenerational Studies: How Do We Investigate Multigenerational Effects?

“…In this issue of Obesity , Shen and colleagues estimate the transgenerational (although the children in the study were directly exposed to grandmaternal risk factors, as their mother’s reproductive cells were exposed in utero ) causal effects of smoking and BMI in the maternal line using mediation analysis, which they argue is a better statistical method than previous analyses that controlled for generation 2 factors. If the goal is numerical estimates of direct and indirect effects, mediation analysis is appropriate, although the authors’ conclusions of no direct association are in fact consistent with previous studies’ conclusions of no effect after control for generation 2: the crude association seen between generation 1 and generation 3 is diluted by the generation 2 and, thus, grandmaternal BMI is associated with child birth weight only through its effect on maternal factors.…”

“…In addition to the complex hypothesized causal pathways, multigenerational studies suffer from technical limitations that affect interpretation. Information on the father’s genotype and phenotype, as well as on shared environmental factors across generations, is often absent . Some births may remain unidentified because of loss to follow‐up or may not occur because of subfertility, which in turn could be related to smoking or extremes of BMI, and other analytic techniques may be needed to account for these missing outcomes.…”

Exploring the evidence for epigenetic regulation of environmental influences on child health across generations

“…This association was dependent on the grandmother's birth cohort: infants whose grandmothers were born between 1929 and 1945 experienced this effect, but infants whose grandmothers were born between 1904 and 1928 did not. Other studies have also shown that the relation between grandmothers' smoking and children's birthweight is mediated by maternal smoking 217,219,220 . However, the pattern of the results of these studies is not consistent.…”

“…BMI and smoking history across generations have also been examined for their relations to grandchildren's birth weight, but studies have largely failed to find direct associations. Some data suggest that associations between grandparents' BMI and grandchildren's birthweight are mediated by maternal BMI 216,217 . There is evidence that smoking may have intergenerational effects on birthweight.…”

Decreased Fatty Acid Transporter FABP1 and Increased Isoprostanes and Neuroprostanes in the Human Term Placenta: Implications for Inflammation and Birth Weight in Maternal Pre-Gestational Obesity

“…Obesity in Brazil [2] and worldwide [3] has reached epidemic proportions, in adults and in children. Therefore, the rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society [4][5][6][7] and highlighting the necessity of determining the mechanisms involved.…”