American Journal of Epidemiology ª The Author 2011. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail:
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Vol. 175, No. 4 DOI: 10.1093/aje/kwr419 Advance Access publication: December 7, 2011
Original Contribution Environmental and Urinary Markers of Prenatal Exposure to Drinking Water Disinfection By-Products, Fetal Growth, and Duration of Gestation in the PELAGIE Birth Cohort (Brittany, France, 2002–2006)
Nathalie Costet*, Ronan Garlante´zec, Christine Monfort, Florence Rouget, Bertrand Gagnie`re, Ce´cile Chevrier, and Sylvaine Cordier * Correspondence to Nathalie Costet, INSERM U1085, Institut de Recherches sur la Sante´, l’Environnement et le Travail, University of Rennes 1, Institut Fe´de´ratif de Recherches 140, Avenue du Ge´ne´ral Leclerc, F-35042 Rennes, France (e-mail:
[email protected]).
Initially submitted March 2, 2011; accepted for publication August 30, 2011.
Although prenatal exposure to water disinfection by-products does not appear to affect the duration of gestation, its impact on fetal growth remains an open question. The authors studied the associations between prenatal exposure to disinfection by-products and fetal growth restriction (FGR) and preterm birth in the PELAGIE cohort, a French birth cohort comprising 3,421 pregnant women recruited between 2002 and 2006. Exposure was assessed by estimating levels of trihalomethanes (THMs) in tap water during pregnancy and maternal water use and by measuring maternal urinary levels of trichloroacetic acid (TCAA) during early pregnancy in a nested case-control design that compared 174 FGR cases, 114 preterm births, and 399 controls. Higher uptake of THMs (especially brominated THMs) was associated with a higher risk of FGR. Women with TCAA detected in their urine (>0.01 mg/L) had a higher risk of FGR than those with TCAA levels below the detection limit (adjusted odds ratio ¼ 1.8, 95% confidence interval: 0.9, 3.7) and had an odds ratio for preterm birth below 1 (adjusted odds ratio ¼ 0.8, 95% confidence interval: 0.3, 2.6). Results from this prospective study, the first to use a biomarker of disinfection by-product exposure, suggest that prenatal exposure affects fetal growth, but the causal agent or agents remain to be identified. biological markers; fetal development; maternal exposure; pregnancy; premature birth; trichloroacetic acid; trihalomethanes; water purification
Abbreviations: BDCM, bromodichloromethane; CI, confidence interval; DBCM, dibromochloromethane; DBP(s), disinfection by-products(s); FGR, fetal growth restriction; OR, odds ratio; PELAGIE, Perturbateurs endocriniens: E´tude Longitudinale sur les Anomalies de la Grossesse, l’Infertilite´, et l’Enfance; SISE-Eaux, Syste`me d’Information en Sante´-Environnement sur les Eaux; TCAA, trichloroacetic acid; THM(s), trihalomethane(s).
Editor’s note: An invited commentary on this article appears on page 276.
treatment process (3–5). The presence of these chemicals in drinking water has shifted health concerns from bacteriologic risks to chemical risks, since several identified DBPs are recognized carcinogens or fetotoxic compounds in animals (6–9). Since 1982, more than 20 reports (10–31) have investigated the possible impact of prenatal exposure to DBPs on the duration of gestation and fetal growth. These investigations have differed in the sophistication of their methods for assessing DBP exposure, which have ranged from crude classifications of water sources to better measures such as ad hoc
Adequate control of bacterial contamination of drinking water by disinfectants, mainly chlorinated disinfectants, inevitably leads to production of disinfection by-products (DBPs). Several hundred of these by-products have been identified, the most frequent being trihalomethanes (THMs) and haloacetic acids (1–3). Chemical types and levels of DBPs depend on the characteristics of the raw water and on the disinfection 263
Am J Epidemiol. 2012;175(4):263–275
Cohort Members (n 5 3,223) No.
%
Mean (SD)
Controls (n 5 399) Range
No.
%
Mean (SD)
Fetal Growth Restriction Cases (n 5 174) Range
No.
%
Mean (SD)
Range
Preterm Birth Cases (n 5 114) No.
%
Mean (SD)
Range
Maternal characteristics Year of inclusion 2002–2003
1,568
48.6
149
37.3
85
48.9
59
51.8
2004
1,166
36.2
189
47.4
58
33.3
41
36.0
489
15.2
61
15.3
31
17.8
14
12.3
2005–2006 District of residence Ille et Vilaine
2,010
62.4
238
59.6
106
60.9
72
63.2
Coˆtes d’Armor
904
28.0
132
33.1
55
31.6
28
24.6
Finiste`re and Morbihan
309
9.6
29
7.3
13
7.5
14
12.3
Age, years
30.0 (4.3)
16–44
30.0 (4.2)
19–41
30.0 (4.4)
19–42
30.0 (4.2)
360
11.2
45
11.3
25
14.4
16
14.0
25–
