Summary of epidemiological studies on chlorinated disinfection byproducts and adverse reproductive outcomes
| Author (year) | Study details (location, time, sample size) | Cases | Exposure assessment | Other risk factors included | Main positive findings OR (95% CI) |
| Kramer et al 48(1992) | Iowa, US 151 Towns with a single water source 1989–90 Sample population: 4028 | 588 (Total) 159 Low birth weight 342 Preterm delivery 187 Intrauterine growth retardation, small for gestational age | Based on maternal residential address and one municipal water survey to estimate individual THM concentrations (2 or 3 exposure categories) | Maternal age Parity Marital status Education Smoking Prenatal care |
Chloroform, No
vmedium (1–9 μg/l) v high (⩾10 μg/l): Low birth weight Chloroform, 1 v 1.1 (0.7–1.6)v 1.3 (0.8–2.2) Intrauterine growth retardation Chloroform, 1 v 1.3 (0.9–1.8)v 1.8 (1.1–2.9) Intrauterine growth retardation Dichlorobromomethane, 1 v 1.2 (0.8–1.7)v 1.7 (0.9–2.9) |
| Aschengrau et al 45 (1993) | Massachusetts, USA 2 Hospitals 1977–80 Sample population: 2348 | 1171 (total) 1039 Major congenital malformations Urinary tract defects Respiratory tract defects 77 Stillbirths 55 Neonatal deaths | Based on maternal residential address to ascertain type of water supply, chlorination v chloramination, and ground or mixed water v surface water. | Maternal age Pregnancy history Alcohol Ethnicity Hospital payment Other water contaminants |
Chlorinated
vchloraminated: Stillbirth 2.6 (0.9 to 7.5) Neonatal deaths 1.1 (95% CI not provided) Congenital malformations Major malformations 1.5 (0.7 to 2.1) Respiratory defects 3.2 (1.1 to 9.5) Urinary tract defects 4.1 (1.2 to 14.1) |
| Bove et al 49 (1995) | New Jersey, USA 75 Towns with a public water supply 1985–88 Sample population: 81602 | 29268 (Total) Live births: 1853 Low birth weight 905 Very low birth weight 4082 Small for gestational age 7167 Preterm 594 Foetal deaths All births: defects: 669 Surveillance 118 Central nervous system defects 83 Oral cleft 56 Neural tube 108 Major cardiac | Based on maternal residential address and municipal water surveys to estimate monthly TTHM concentrations (5 or 6 exposure categories) | Maternal age Ethnicity Sex of baby Primipara Prenatal care Education Previous still or miscarriage Other contaminants |
TTHM concentrations >100 μg/l
v ⩽20 μg/l: Low birth weight 1.4 (50% CI 1.2 to 1.7) Intrauterine growth retardation or small for gestational age 1.5 (90% CI 1.2 to 1.9) TTHM concentrations >80 μg/l v ⩽20 μg/l: Surveillance Register defects 1.6 (90% CI 1.2 to 2.0) CNS system defects 2.6 (90% CI 1.5 to 4.3) Neural tube defects 3.0 (90% CI 1.3 to 6.6) Major cardiac defects 1.8 (90% CI 1.0 to 3.3) TTHM concentrations >100 μg/l v ⩽20 μg/l: Oral cleft defects 3.2 (90% CI 1.2 to 7.3) |
| Savitz et al 52 (1995) | Carolina, USA 6 Hospitals 1988–91 Sample population: 1003 | 548 (Total) 126 Spontaneous abortion 244 Preterm 178 Low birth weight | Based on maternal residential address and quarterly municipal water surveys to estimate average TTHM concentrations. Analysis of: (a) Surface vground water source, (b) TTHM concentrations, (3 exposure categories) (c) Consumption during pregnancy (d) Water source × amount (e) TTHM dose (concentration × amount) | Maternal age Ethnicity Hospital Education Marital status Poverty level Smoking Alcohol consumption Employment Nausea |
40.8–59.9
v81.1–168.8 μg/l TTHM: Spontaneous abortion 1.2 (0.6 to 2.4) 40.8–63.3 v 82.8–168.8 μg/l TTHM: Low birth weight 1.3 (0.8 to 2.1) Per 50 μg/l TTHM increment change: Spontaneous abortion 1.7 (1.1 to 2.7) |
| Kanitz et al 46(1996) | Liguria, Italy 2 Hospitals 1988–1989 Sample population: 676 | 548 Live births in exposed area 50 Preterm 141 Caesarean section 133 Neonatal jaundice 20 Low birth weight 288 Small body length 370 Small cranial circumference | Based on maternal residential address to ascertain type of water source (chlorine dioxide or hypochloritev not treated) | Maternal age Education Smoking Alcohol Sex of child |
Sodium hypochlorite treated (8–16 μg/l TTHMs)
v non treated water: Neonatal jaundice 1.1 (0.7 to 2.8) Low birth weight 6.0 (0.6 to 12.6) Small body length 2.3 (1.3 to 4.2) Small cranial circumference 3.5 (2.1 to 8.5) |
| Waller et al 53 (1998) | California, USA 3 Regions of surface, ground, and mixed drinking water 1989–1991 Sample population: 5144 pregnancies | 499 Spontaneous abortions | Based on maternal residential address and quarterly municipal water surveys to estimate average TTHM and individual THM concentrations. Analysis based on: (a) THM concentrations (3 or 10 exposure categories) (b) consumption during first trimester from interview (2 exposure categories) | Maternal age Gestational age Smoking History of pregnancy loss Ethnicity Employment |
High TTHM dose (⩾5 glasses/day + ⩾75 μg/l)
v low dose (<5 glasses/day + <75 μg/l): Spontaneous abortion 1.8 (1.1 to 3.0). High BDCM dose (⩾5 glasses/day + ⩾18 μg/l) v low dose (<5 glasses/day + <18 μg/l): Spontaneous abortion 3.0 (1.4 to 6.6) |
| Gallagher et al 50 (1998) | Colorado, USA 28 Census blocks in 2 water districts 1990–1993 Sample population: 1244 live births | 72 Low birth weight 29 Term low birth weight 68 Preterm delivery | Based on maternal residential address and municipal water surveys. Estimate of household TTHM concentration during last trimester based on hydraulic modelling (4 exposure categories) | Maternal age Smoking Marital status Parity Education Employment Prenatal care |
High TTHM concentration (⩾ 61 μg/l)
v lowest (⩽20 μg/l): Low birth weight 2.1 (1.0 to 4.8) Term low birth weight 5.9 (2.0 to 17.0) |
| Dodds et al 51 (1999) | Nova Scotia, Canada 1988–95 Sample population: 49842 births | 4673 Small for gestational age 2393 Low birth weight 342 Very low birth weight 2689 Preterm delivery 77 Neural tube 82 Cleft defect 430 Major cardiac defects 197 Stillbirth 96 Chromosomal abnormalities | Based on maternal residential address and TTHM concentrations for public water facilities (3 sampling locations) modelled with linear regression on the basis of observations by year, month, and facility (4 exposure categories) | Maternal age Parity Maternal smoking Attendance prenatal classes Neighbourhood family income Sex Pregnancy and predelivery weight |
0–49 μg/l
v >100 μg/l TTHMs Still birth 1.66 (1.09 to 2.52) Chromosomal abnormalities 1.38 (0.73 to 2.59) Small for gestation age 1.08 (0.99 to 1.18) Neural tube defects 1.18 (0.67 to 2.10) |
| Klotz and Pyrch56 (1999) | New Jersey, US 1993–4 Sample population: All births, of which 112 cases and 248 controls were selected | 112 Neural tube defects | Based on residential address and public water facility TTHM data, and tap water sampling for TTHMs, HANs, and HAAs (3–5 exposure categories) | Sociodemographics Pregnancy and medical history Parental occupational Use of vitamins |
TTHMs public monitoring data, Known residence and isolated cases <5 μg/l
v>40 μg/l Neural tube defects 2.1 (1.1 to 4.0) |
| Magnuset al 47 (1999) | Norway Sample population: 141077 | 2608 All birth defects 62 Neural tube defects 250 Major cardiac defects 91 Respiratory defects 122 Urinary defects 143 Oral cleft | Chlorination yesv no Colour highv low (in chlorinated water average TTHMs = 9.4 μg/l, average HAAs = 14.6 μg/l) | Maternal age Parity Geographical placement Population density Industry profile |
No chlorination low colour
v chlorination high colour All birth defects 1.14 (0.99 to 1.31) Urinary tract defects 1.99 (1.10 to 3.57) Neural tube defects 1.26 (0.61 to 2.62) Major cardiac defects 1.05 (0.76 to 1.46) Respiratory tract defects 1.07 (0.52 to 2.19) |