Maternal fetal programming of birthweight among Australian Aboriginal infants: a population-based data linkage study

Abstract

Summary: Background: Low birthweight, which is common among Australian Aboriginal infants, has been found to persist across generations because of shared genetic and environmental factors and possibly fetal programming. Fetal programming refers to the response of a fetus to hostile uterine conditions with lifelong effects and possibly, in turn, providing a poorer uterine environment for future offspring. Fetal programming might have a greater effect in populations that have undergone rapid lifestyle transitions—for example, Indigenous populations. Disentangling causal effects is difficult, but family-based approaches could provide insights. We explored whether poor maternal fetal growth caused low birthweight in Aboriginal infants. Methods: In this data linkage study, we used linked administrative health records of 12 865 singleton Aboriginal infants born in Western Australia between 1980 and 2010 and their relatives (including siblings born in 2011). Electronic birth records included all births since 1980 with at least 20 weeks completed gestation or a birthweight of 400 g. We compared parental–offspring birthweight associations using three approaches—a regression analysis of the complete sample, adjusting for confounding variables; a comparison of the maternal–offspring and paternal–offspring associations; and a within-cousin group comparison. We used binary and continuous measures of birthweight. We categorised infants and their parents as small for gestational age (SGA) if their birthweight was below the first decile of birthweights for all singleton livebirths of the same sex and gestational age in Australia between 1998 and 2007. Findings: The relative risk (RR) of SGA birth was higher for infants with SGA mothers than for those with non-SGA mothers (RR 1·65, 95% CI 1·49 to 1·83), after adjusting for grandmaternal parity. After additional adjustment for maternal height, the risk remained higher for those with non-SGA mothers (RR 1·51, 1·36 to 1·68). The maternal birthweight Z score coefficient was 0·17 (95% CI 0·14 to 0·20), compared with 0·13 (0·10 to 0·16) for paternal birthweight, a difference of 0·03 (−0·01 to 0·08). In the cousin analysis, the maternal–offspring association was fully attenuated (0·00, 95% CI −0·05 to 0·06). Conditions in the current pregnancy were strongly associated with offspring birthweight Z score. Smoking was associated with a mean decrease of 0·39 (95% CI −0·45 to −0·34) in offspring birthweight Z score, drug misuse with a decrease of 0·31 (−0·43 to −0·20), and diabetes with an increase of 0·58 (0·39 to 0·77). Interpretation: We found little support for maternal fetal programming causing low offspring birthweight. The similar maternal and paternal influence on birthweight and our cousin analysis suggested transmission of genetic and environmental factors could explain much of the maternal–offspring birthweight association. Compared with other risk factors in the current pregnancy, fetal programming appears to have little or no role in the high numbers of infants with low birthweight among Aboriginal populations. Funding: National Health and Medical Research Council of Australia and Bellberry Ltd.