Maternal body burden of cadmium: impacts on gestational diabetes and fetal growth

Abstract

<bold>Introduction:<bold/> Cadmium (Cd) exposure has been associated with increased risk of diabetes mellitus, hypertension, and osteoporosis. However, the effect of Cd on gestational diabetes mellitus (GDM) has not been investigated, and the influence of Cd on infant size at birth has not been fully elucidated. Interpretation of studies examining potentially infant sex-specific effects of Cd on fetal growth has been hindered by limited description of sex-specific fetal growth determinants. <bold>Methods:<bold/> The study population consisted of pregnant women and singletons from the Omega Study, a large prospective cohort study examining risk factors for pregnancy complications based in Seattle and Tacoma, Washington (1996-2008). Data were gathered by interviewer-administered questionnaires, medical record abstraction, and semi-quantitative food frequency questionnaires. Creatinine-corrected Cd in early pregnancy urine samples was quantified by inductively coupled plasma mass spectrometry. Multivariable unconditional logistic regression was used to analyze the association of urinary Cd with GDM. Infant sex-stratified multivariable linear regression was used to assess potential demographic, obstetric, medical, nutritional, and lifestyle factors influencing birth anthropometric measurements (birthweight, ponderal index, birth length, and head circumference), and to analyze the association of maternal urinary Cd with size at birth. <bold>Results:<bold/> Controlling for potential confounders, there was a trend of increased risk of GDM with increasing urinary Cd (p-trend=0.015). Multiparity was associated with a greater increase in birthweight among females, whereas among males maternal pre-pregnancy obese or underweight status were associated with greater increases and decreases in birthweight, respectively. For males maternal hypertensive conditions were associated with decreased birthweight and ponderal index. Female infants had reduced birth length with greater tertile of maternal urinary Cd, whereas males had a marginal increase in birth length (females: p-trend=0.11; males; p-trend=0.06; p for interaction=0.03). <bold>Conclusion:<bold/> Greater Cd is associated with greater risk of GDM. Careful consideration must be given to parity, pre-pregnancy body mass index, and hypertension disorders when assessing factors influencing size at birth due to observed differences in these associations for male and female infants. Finally, our findings suggest a possible infant sex-specific reversal of effects for Cd on birth length; however, replication in other populations and investigation of the underlying mechanisms are warranted.