title: Women exposure during pregnancy to haloacetaldehydes and haloacetonitriles in drinking water and risk of small-for-gestational-age neonate.
abstract: BACKGROUND
  Past studies have examined the effects of maternal exposure to water chlorination disinfection by-products (DBPs), such as trihalomethanes (THMs) and haloacetic acids (HAAs) during pregnancy. However, no human-based study has yet evaluated the effect of emerging DBPs, such as haloacetaldehydes (HAs) and haloacetonitriles (HANs) on small-for-gestational-age (SGA) status in newborns.
  
  
  OBJECTIVE
  This study aims to assess the association between maternal multiroute exposure to HAs and HANs during the third trimester of pregnancy and SGA status at birth, among neonates delivered by women residing in the Quebec City area (Province of Quebec, Canada). We also evaluated the interaction between exposure to these emerging unregulated by-products and regulated DBPs also found in drinking water (THMs and HAAs), for which a positive association with adverse reproductive outcomes has been suggested in previous studies.
  
  
  METHODS
  We conducted a population-based case-control study in the Quebec City area. SGA newborns (n=330) were compared to 1100 controls, with matching based on calendar week of birth. HA and HAN concentrations in drinking water at participant's tap were estimated using spatio-temporal strategy based on bimonthly measurements carried out at several locations in the participant's distribution system. A computer-assisted telephone interview was completed to collect information on individual habits of water consumption and water related activities in order to determine individual multiroute exposure. This enabled us to estimate the dose of HAs and HANs absorbed daily by each participant. Associations between total HA, HAN concentrations in drinking water and SGA were analyzed. Associations between the daily-absorbed doses of these emerging DBPs and SGA were also analyzed. Odds ratios (ORs) comparing the 4th quartile of exposure to the reference group (the first three quartiles) were obtained by means of conditional logistic regression, and controlling for potential confounders.
  
  
  RESULTS
  Globally, no evidence of increased risk of SGA was found with total HA and HAN concentrations in tap water when participants in the 4th quartile of exposure were compared to the first three quartiles (OR=1.0; 95% CI [0.7-1.5] and OR=0.8; 95% CI [0.6-1.2], respectively). Similarly, no association was found with the daily-absorbed doses of total HAs or HANs (OR=0.9; 95% CI [0.6-1.3] and OR=1.1; 95% CI [0.7-1.6], respectively). However, a small non statistically significant association was found between the dose of brominated HA and SGA (OR=1.4; 95% CI [0.9-2.1]). Also, in spite of the lack of interaction between other DBP classes, an unexpected negative interaction was observed between concentration of chloral hydrate (CH) (which represents the main HA species), and regulated DBPs (P=0.006).
  
  
  CONCLUSIONS
  In this population, exposure to low levels of HAs and HANs during the third trimester of pregnancy through drinking water was not associated to SGA status in newborns. Nonetheless, more research is needed to clarify possible effect of brominated compounds and interaction between different DBPs.
authors.affiliation: Département de médecine sociale et préventive, Faculté de médecine, Université Laval, 1050 Avenue de la Médecine, Québec Québec, Canada G1V 0A6; Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, 2705 Boulevard Laurier, Québec Québec, Canada G1V 2L9.
authors.forename: Samuel
authors.initials: S
authors.lastname: Ileka-Priouzeau
authors.affiliation: Direction de la santé environnementale et de la toxicologie, Institut national de santé publique du Québec, 945 Avenue Wolfe, Québec Québec, Canada G1V 5B3.
authors.forename: Céline
authors.initials: C
authors.lastname: Campagna
authors.affiliation: Chaire de recherche en eau potable, École supérieure d'aménagement du territoire et de développement régional, Université Laval, Pavillon Félix-Antoine-Savard, 2325 rue des Bibliothèques, Québec Québec, Canada G1V 0A6.
authors.forename: Christelle
authors.initials: C
authors.lastname: Legay
authors.affiliation: Interdisciplinary School of Public Health, University of Ottawa, Thompson Hall, 25 University Private, Ottawa Ontario, Canada K1N 6X1.
authors.forename: Raywat
authors.initials: R
authors.lastname: Deonandan
authors.affiliation: Chaire de recherche en eau potable, École supérieure d'aménagement du territoire et de développement régional, Université Laval, Pavillon Félix-Antoine-Savard, 2325 rue des Bibliothèques, Québec Québec, Canada G1V 0A6.
authors.forename: Manuel J
authors.initials: MJ
authors.lastname: Rodriguez
authors.affiliation: Département de médecine sociale et préventive, Faculté de médecine, Université Laval, 1050 Avenue de la Médecine, Québec Québec, Canada G1V 0A6; Axe santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, 2705 Boulevard Laurier, Québec Québec, Canada G1V 2L9; Direction de la santé environnementale et de la toxicologie, Institut national de santé publique du Québec, 945 Avenue Wolfe, Québec Québec, Canada G1V 5B3. Electronic address: patrick.levallois@msp.ulaval.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Levallois
mesh_terms: D000097:Acetonitriles / Q000633:toxicity*; D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000633:toxicity*; D016022:Case-Control Studies; D004202:Disinfectants / Q000633:toxicity*; D060766:Drinking Water / Q000032:analysis*; D005260:Female; D054879:Halogenation; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*; D011792:Quebec / Q000453:epidemiology; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000097:Acetonitriles; D000447:Aldehydes; D004202:Disinfectants; D060766:Drinking Water
keywords: Drinking water; Intra-uterine growth retardation; Non-regulated chlorination by-products; Pregnancy outcome; Small for gestational age