Maternal arsenic exposure and nonsyndromic orofacial clefts

Birth Defects Res. 2018 Nov 15;110(19):1455-1467. doi: 10.1002/bdr2.1386. Epub 2018 Oct 27.


Background: Arsenic is widely distributed in the environment in both inorganic and organic forms. Evidence from animal studies suggests that maternal inorganic arsenic may lead to the development of orofacial clefts (OFC)s in offspring. This evidence, together with the limited epidemiologic data available, supports the need for a comprehensive examination of major sources of arsenic exposure and OFCs in humans.

Methods: Using interview data collected in the National Birth Defects Prevention Study, public and well water arsenic sampling data, and dietary arsenic estimates, we compared expert-rater assessed occupational arsenic exposure, individual-level exposure to arsenic through drinking water, and dietary arsenic exposure between mothers of OFC cases (N = 435) and unaffected controls (N = 1267). Associations for each source of exposure were estimated for cleft lip ± palate (CL/P) and cleft palate (CP) using unconditional logistic regression analyses.

Results: Associations for maternal drinking water arsenic exposure and CL/P were near or below unity, whereas those for dietary arsenic exposure tended to be positive. For CP, positive associations were observed for maternal occupational arsenic and inorganic arsenic exposures, with confidence intervals that excluded the null value, whereas those for drinking water or dietary arsenic exposures tended to be near or below unity.

Conclusions: Positive associations were observed for maternal occupational arsenic exposure and CP and for maternal dietary arsenic exposure and CL/P; the remainder of associations estimated tended to be near or below unity. Given the exploratory nature of our study, the results should be interpreted cautiously, and continued research using improved exposure assessment methodologies is recommended.

Keywords: Arsenic; Cleft Lip; Cleft Palate; Metal; Pregnancy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Arsenic / adverse effects*
  • Arsenic Poisoning / complications
  • Brain / abnormalities*
  • Case-Control Studies
  • Cleft Lip / etiology*
  • Cleft Palate / etiology*
  • Female
  • Humans
  • Infant, Newborn
  • Logistic Models
  • Male
  • Maternal Exposure
  • Mothers
  • Odds Ratio
  • Population Surveillance / methods*
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects / chemically induced
  • Risk Factors
  • Self Report


  • Arsenic

Supplementary concepts

  • Orofacial Cleft 1