Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study

Caitlin G Howe; Birgit Claus Henn; Shohreh F Farzan; Rima Habre; Sandrah P Eckel; Brendan H Grubbs; Thomas A Chavez; Dema Faham; Laila Al-Marayati; Deborah Lerner; Alyssa Quimby; Sara Twogood; Michael J Richards; John D Meeker; Theresa M Bastain; Carrie V Breton

doi:10.1016/j.envres.2020.110388

Prenatal metal mixtures and fetal size in mid-pregnancy in the MADRES study

Environ Res. 2021 May:196:110388. doi: 10.1016/j.envres.2020.110388. Epub 2020 Oct 28.

Authors

Caitlin G Howe¹, Birgit Claus Henn², Shohreh F Farzan³, Rima Habre³, Sandrah P Eckel³, Brendan H Grubbs⁴, Thomas A Chavez³, Dema Faham³, Laila Al-Marayati⁵, Deborah Lerner⁶, Alyssa Quimby⁷, Sara Twogood⁷, Michael J Richards⁸, John D Meeker⁹, Theresa M Bastain³, Carrie V Breton³

Affiliations

¹ Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: caitlin.g.howe@dartmouth.edu.
² Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
³ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁵ Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Eisner Health, Los Angeles, CA, USA.
⁶ Eisner Health, Los Angeles, CA, USA.
⁷ Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁸ NSF International, Ann Arbor, MI, USA.
⁹ Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Abstract

Background: Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles.

Methods: For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW).

Results: BKMR identified Mo and Ba as the mixture components that contributed most to associations with EFW. Linear associations were observed for both metals. An increase in Mo from the 25th to 75th percentile was associated with a 0.114 (95% credible interval (CI): 0.019, 0.247) SD higher EFW, equivalent to a 7.4 g difference. Similar associations were observed between Mo and the other fetal measures evaluated. In contrast, an increase in Ba from the 25th to 75th percentile was associated with a -0.076 (95% CI: 0.217, 0.066) SD lower EFW, equivalent to a 4.9 g difference. Similar inverse associations were observed for Ba in relation to abdominal circumference and biparietal diameter. BKMR also identified a possible interaction between Ba and Mo in relation to head circumference, suggesting that the positive associations between Mo and this outcome may be attenuated at high levels of Ba, which was consistent with findings from linear regression (P_interaction = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW.

Conclusions: Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.

Keywords: Essential elements; Fetal biometry; Fetal growth; Mixtures; Pregnancy; Toxic metals.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Bayes Theorem
Birth Weight
Female
Fetal Development*
Fetal Weight*
Humans
Los Angeles
Pregnancy
Ultrasonography, Prenatal

Abstract

Publication types

MeSH terms

Grants and funding