1. Shanna H. Swan, Kirsten Waller, Barbara Hopkins, Gerald DeLorenze, Gayle Windham, Laura Fenster, Catherine Schaefer, Raymond Neutra Environmental Health Investigations Branch California Department of Health Services Division of Research Kaiser Permanente Medical Care Program Water Consumption in Early Pregnancy and Risk of Spontaneous Abortion: Trihalomethanes and Other Factors

2. Why was the Pregnancy Outcome Study Conducted? To examine this association in: A prospective study Santa Clara and two additional areas of California (Walnut Creek and Fontana) More recent pregnancies Also conducted analysis of chlorination by-products.

3. How was this Study Conducted? Study participants were members of Kaiser Permanente HMO Pregnant women were recruited in 1990-1991 when scheduling prenatal care Phone interview in first trimester of pregnancy Pregnancy outcome from medical records

4. Study Population N Women contacted7,881 Women eligible/willing (78%)6,179 Interviews completed (86%)5,342 Pregnancy outcome determined (99%)5,289 Final study population * 5,144 *Excludes ectopics, molar pregnancies and therapeutic abortions

5. Exposure Assessment: Type and Amount of Water Consumed? “How many glasses did you drink per day of... cold tap water (and drinks made from cold tap water) at home?” heated tap water (and drinks made from heated tap water) at home?” bottled (noncarbonated) water consumed anywhere?” carbonated water consumed anywhere?”

6. Exposure Assessment: When in pregnancy? Women were asked to estimate: glasses consumed in the week beginning with the last menstrual period glasses consumed in the week ending with the interview when amount changed (if different) Exposure at 8 weeks gestation used in analysis

7. Other Water Exposure Variables Name of water utility (confirmed by address) How tap water was consumed: – Straight from the tap – Let stand before drinking – Stored in refrigerator – Filtered (type of filter) Brand of bottled water Frequency and duration of showering (and swimming)

8. Study Population—All Study Areas Age: less than 3589% Interviewed by 8 weeks gestation64% Pregnancy history: Nulliparous26% Multiparous:0 or 1 prior SAB69% at least 2 prior SABs5% Race: White66% Hispanic18% Employed during pregnancy79% At least some college education68% Any smoking in week before interview10%

9. Tap Water Use—All Areas Consumption of cold tap water at home None37% 0.5 - 553% 6 or more10% Filter use (among tap water drinkers) None80% Usual method of drinking tap water Straight from the tap58% Refrigerate/let stand42%

10. Analysis (Swan et al) “High” consumption defined as >5 glasses/day Analyses stratified by study area Covariates considered initially: –Age, parity, prior SAB, body weight, race, smoking, alcohol, caffeine, education, marital status, gestational age at interview –Water-related variables Variables included in multivariate models: –Age, prior SAB, body weight, race, gestational age, showering

11. SAB Rates by Water Consumption and Study Area—Santa Clara % SAB Glasses Tap Bottled

12. Results: Santa Clara County (Swan et al) SAB rate among women drinking >1glass/day: tap water only:12.8% bottled water only:8.3% Adjusted Odds Ratio =1.7 (95% CI 1.1, 2.6) SAB rate among women drinking >5 glasses/day: tap water only:17.9% bottled water only:6.5% Adjusted Odds Ratio = 4.6 (95% CI 2.0, 10.6)

13. SAB Rates by Water Consumption and Study Area—Walnut Creek and Fontana % SAB Glasses Tap Bottled

14. Conclusions (Swan et al) Confirms increased risk of SAB in tap water drinkers in Santa Clara Results cannot be explained by recall bias or confounding Association not seen in two new study areas Future studies should compare: – tap water between utilities – bottled water between brands

15. Disinfection By-Products Formed in water that is chlorinated and contains organic matter Trihalomethanes (THM) are most prevalent by- products and include 4 compounds Some evidence of mutagenicity and reproductive toxicity in animals, so USEPA regulates maximum contaminant levels New studies find association with LBW

16. Exposure Assessment for THM Levels (Waller et al) Identified 85 drinking water utilities that served women’s residences Obtained quarterly trihalomethane (THM) measurements from utilities Estimated THM levels by averaging measurements throughout the utility during first trimester

17. SAB Rate by Estimated Total THM Level in Home Tap Water During First Trimester a a a 0 2 4 6 8 10 12 14 16 0 non-detectable 1-1415-2930-4445-5960-7475-8990-104105-119>120 Total THM Level (µg/L) % SAB

18. SAB Rate by Estimated Total THM Level and Amount of Cold Tap Water Consumed a a a 0 2 4 6 8 10 12 14 16 TTHM >75 µg/L >5 glasses/day TTHM > 75 µg/L <5glasses/day TTHM <75 µg/L <5 glasses/day TTHM <75 µg/L >5 glasses/day Total THM Level and Amount of Water Consumed % SAB

19. SAB Rate by Region and Personal Total THM Exposure aa a Region and Personal Total THM Exposure Low personal exposure — Drinking >5 glasses/day of cold tap water containing an estimated total THM level > 75 µg/L High personal exposure — Drinking <5 glasses/day of cold tap water OR an estimated total THM level <75 µg/L Santa Clara Low Santa Clara High Walnut Creek Low Walnut Creek High Fontana Low Fontana High 0 5 10 15 20 25 % SAB

20. SAB Rate by Estimated BDCM Level and Amount of Cold Tap Water Consumed a a a 0 2 4 6 8 10 12 14 16 18 BDCM Level and Amount of Water Consumed BDCM >18 µg/L >5 glasses/day BDCM >18 µg/L <5 glasses/day BDCM <18 µg/L <5 glasses/day BDCM <18 µg/L >5 glasses/day

21. Study Strengths Interviews in early pregnancy Nearly complete follow-up of all pregnancies Detailed information on water consumption THM measurements specific to first trimester Diverse study population with range of water sources and trihalomethane levels

22. Study Weaknesses About 25% of SABs missed Other sources of water not ascertained Insufficient power to look at specific utilities, bottled water brands, filters, letting water stand Some misclassification of THM likely THM may be markers for other chlorination by-products

23. Regulatory Standards Maximum Contaminant Level (MCL) Based on utility-wide average over 4 quarters Current total THM = 100µg/L New total THM = 80µg/L No MCLs for individual trihalomethanes

24. Conclusions (Waller et al) One of the first studies to find association between total THMs and SAB Bromodichloromethane most strongly associated Results not explained by recall bias or confounding Results stronger among women not employed outside the home Repeat study in other areas and obtain more precise THM assessment