Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case-Control Study in the Danish National Birth Cohort

Zeyan Liew; Jiajun Luo; Ellen A Nohr; Bodil Hammer Bech; Rossana Bossi; Onyebuchi A Arah; Jørn Olsen

doi:10.1289/EHP6202

Lifestyle and Environment Environmental Exposures

Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case-Control Study in the Danish National Birth Cohort

Liew Z, Luo J, Nohr EA, Bech BH, Bossi R, Arah OA, Olsen J

Published April 2020 Environmental health perspectives, 128(4), 47007

DOI 10.1289/EHP6202 PMID 32319790 PMC PMC7228130

RRM Academy Synopsis

Higher PFOA and PFHpS levels in early pregnancy track with miscarriage

Higher PFOA and PFHpS levels in early pregnancy were linked to higher miscarriage odds in a Danish nested case-control study of 220 miscarriages at weeks 12 to 22 and 218 live births. Women in the highest PFOA quartile had 2.2 times the odds of miscarriage of women in the lowest quartile.

Key Findings

A doubling of PFOA went with 40% higher odds of miscarriage (odds ratio 1.4, 95% CI: 1.0, 1.9).
Comparing the top quartile with the bottom, the odds ratio was 2.2 for PFOA (95% CI: 1.2, 3.9) and 1.8 for PFHpS (95% CI: 1.0, 3.2).
A summary index combining seven PFAS carried 64% higher miscarriage odds per interquartile range increase (95% CI: 1.15, 2.34).
PFOA contributed 60% of that index, PFHpS 17% and PFDA 11%.
Associations were more consistent in women who had given birth before, although interaction p-values exceeded 0.10. Among women with no prior births, no linear dose-response association appeared for any PFAS.

Interpretation

The study is a case-control design nested in the Danish National Birth Cohort. Researchers measured seven PFAS in plasma drawn at about gestational week 8. They compared women who miscarried during weeks 12 to 22 with women who had live births. Enrollment ran from 1996 to 2002. The authors note that stronger findings in women with prior births raise concern about residual confounding from reproductive history, and they call for larger studies of women with no prior births.

RRM Context

PFAS belong to the endocrine disruptors, chemicals that interfere with hormone action. The authors write that the cause of most miscarriages is unexplained and that more modifiable causes need to be found. Restorative reproductive medicine treats such losses as undiagnosed and asks what drives them. Environmental exposures fit naturally into a cause-based review.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied.

Methods

Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted.

Results

We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women.

Conclusion

Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.

Topics

Lifestyle and Environment › Environmental Exposures › Persistent Organic Pollutants · Pregnancy › Pregnancy Complications › Premature Rupture of Membranes · Birth and Delivery › Birth Outcomes › Maternal Morbidity

Zeyan Liew, Jiajun Luo, Ellen A Nohr, Bodil Hammer Bech, Rossana Bossi, Onyebuchi A Arah, Jørn Olsen

Z Liew, J Luo, E Nohr, B Bech, R Bossi, O Arah, J Olsen

PMID 32319790 32319790 DOI 10.1289/EHP6202 10.1289/EHP6202 Liew et al. 2020, Liew 2020

Maternal Plasma Perfluoroalkyl Substances and Miscarriage: A Nested Case-Control Study in the Danish National Birth Cohort

Higher PFOA and PFHpS levels in early pregnancy track with miscarriage

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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