Relation between Stillbirth and Specific Chlorination By-Products in Public Water Supplies.During water treatment, chlorine reacts with naturally occurring organic matter in surface water to produce a number of by-products. Of the by-products formed, trihalomethanes (THMs) are among the highest in concentration. We conducted a retrospective cohort study A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design. In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute to evaluate the relationship between the level of total THM and specific THMs in public water supplies and risk for stillbirth Stillbirth Definition A stillbirth is defined as the death of a fetus at any time after the twentieth week of pregnancy. Stillbirth is also referred to as intrauterine fetal death (IUFD). . The cohort was assembled from a population-based perinatal perinatal /peri·na·tal/ (-na´t'l) relating to the period shortly before and after birth; from the twentieth to twenty-ninth week of gestation to one to four weeks after birth. per·i·na·tal adj. database in the Canadian province Noun 1. Canadian province - Canada is divided into 12 provinces for administrative purposes province, state - the territory occupied by one of the constituent administrative districts of a nation; "his state is in the deep south" of Nova Scotia Nova Scotia (nō`və skō`shə) [Lat.,=new Scotland], province (2001 pop. 908,007), 21,425 sq mi (55,491 sq km), E Canada. Geography and consisted of almost 50,000 singleton sin·gle·ton n. An offspring born alone. singleton Medtalk One baby. Cf Triplet, Twin. deliveries between 1988 and 1995. Individual exposures were assigned by linking mother's residence at the time of delivery to the levels of specific THMs monitored in public water supplies. Analysis was conducted for all stillbirths and for cause-of-death categories based on the physiologic process responsible for the fetal death. Total THMs and the specific THMs were each associated with increased stillbirth risk. The strongest association was observed for bromodichloromethane exposure, where risk doubled for those exposed to a level of [is greater than or equal to] 20 [micro]g/L compared to those exposed to a level [is less than] 5 [micro]g/L (relative risk = 1.98, 95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. , 1.23-3.49). Relative risk estimates associated with THM exposures were larger for asphyxia-related deaths than for unexplained deaths or for stillbirths overall. These findings suggest a need to consider specific chlorination chlorination Public health Addition of chlorinated compounds to drinking water as disinfectants. Cf Ozonation. by-products in relation to stillbirth risk, in particular bromodichloromethane and other by-product by·prod·uct or by-prod·uct n. 1. Something produced in the making of something else. 2. A secondary result; a side effect. by-product Noun 1. correlates. The finding of a stronger effect for asphyxia asphyxia (ăsfĭk`sēə), deficiency of oxygen and excess of carbon dioxide in the blood and body tissues. Asphyxia, often referred to as suffocation, usually results from an interruption of breathing due to mechanical blockage of the deaths requires confirmation and research into possible mechanisms. Key words: chlorination by-products, epidemiology, public water supplies, stillbirth, trihalomethanes. Environ Health Perspect 108:883-886 (2000). [Online 2 August 2000] http://ehpnet1.niehs.nih.gov/docs/2000/108p883-886king/abstract.html In Canada, stillbirths occur at a rate of approximately 6 per 1,000 births (1). Despite the obvious importance of stillbirths as a health event, little is known about the risk factors that contribute to this event. In a recent study examining the relationship between chlorination by-products and several adverse birth outcomes, we reported an increase in stillbirth risk with high exposure to total trihalomethanes (THMs) (2). Several other studies have also implicated im·pli·cate tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates 1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot. 2. water chlorination by-products as a potential cause of spontaneous abortion spon·ta·ne·ous abortion n. A naturally occurring termination of a pregnancy. Also called miscarriage. spontaneous abortion and stillbirth (3-5), but this relationship requires confirmation. During the water treatment process, natural organic substances can react with chlorine to produce a number of halogenated halogenated pertaining to a substance to which a halogen is added. halogenated salicylanilides see rafoxanide, clioxanide. hydrocarbon compounds. By-products formed include THMs, halogenated acetic acids acetic acid (əsē`tĭk), CH3CO2H, colorless liquid that has a characteristic pungent odor, boils at 118°C;, and is miscible with water in all proportions; it is a weak organic carboxylic acid (see carboxyl group). , halogenated acetonitriles, chlorinated chlorinated /chlo·ri·nat·ed/ (klor´i-nat?ed) treated or charged with chlorine. chlorinated charged with chlorine. chlorinated acids some, e.g. ketones Ketones Poisonous acidic chemicals produced by the body when fat instead of glucose is burned for energy. Breakdown of fat occurs when not enough insulin is present to channel glucose into body cells. Mentioned in: Diabetic Ketoacidosis, Urinalysis , and halogenated phenols phenols (fēˑ·n  lz),n. (6). Quantitatively, the THMs are among the highest in concentration of the chlorination by-products and are the most consistently measured in treated water. THMs comprise four compounds: chloroform chloroform (klôr`əfôrm) or trichloromethane (trī'klôrōmĕth`ān), CHCl3 , bromodichloromethane, chlorodibromomethane, and bromoform. THM compounds as well as other by-products may occur in different concentrations in water supplies with a similar total THM level. Five studies, including our own, have examined either stillbirth or spontaneous abortion in relation to chlorination by-products (2-5,7). Exposure in three of these was based on total THM level, and in another study, exposure was based on a chlorinated versus chloraminated water source. Only Waller et al. (3) examined risk in relation to specific THMs. They found a stronger association with bromodichloromethane than with THM compounds per se, which points to the need to examine risk in relation to specific THMs. The etiology of stillbirths is multifactorial multifactorial /mul·ti·fac·to·ri·al/ (mul?te-fak-tor´e-al) 1. of or pertaining to, or arising through the action of many factors. 2. and likely differs depending on the specific pathophysiologic process responsible for the fetal death. Therefore, this study evaluated the relationship between specific THM compounds and stillbirth according to according to prep. 1. As stated or indicated by; on the authority of: according to historians. 2. In keeping with: according to instructions. 3. cause-of-death categories based on the physiologic process responsible for the fetal death. Methods The cohort consisted of singleton births with known gestational age ges·ta·tion·al age n. See estimated gestational age. Gestational age The estimated age of a fetus expressed in weeks, calculated from the first day of the last normal menstrual period. in the Canadian province of Nova Scotia between 1988 and 1995. It was assembled from a population-based perinatal database that contains mother and infant information for all live born and stillborn infants with birth weights [is greater than or equal to] 500 g. Data were collected prenatally, during labor, delivery, and postpartum postpartum /post·par·tum/ (post-pahr´tum) occurring after childbirth, with reference to the mother. post·par·tum adj. Of or occurring in the period shortly after childbirth. and included demographic and risk factor information. A detailed description of this retrospective cohort study has been previously published (2). Information on cause of death of the stillbirths was not included in the previous study and was added to the original cohort. Exposure information came from the Nova Scotia Department of the Environment, which provided results of monitoring for public water facilities throughout Nova Scotia during the relevant time period. Each facility measured total THM, chloroform, bromodichloromethane, bromoform, and chlorodibromomethane on an average of four samples per year. Although bromoform and chlorodibromomethane are measured in Nova Scotia, they occur at very low concentrations and were not included in this analysis. To provide estimates for each water facility for each month, we performed a least-squares regression on chlorination by-product values for year, month, and facility and predicted values were obtained. The mother's residence at the time of delivery was assumed to be her residence during the entire pregnancy. We estimated individual exposures by linking mother's residence to the geographic area served by each water facility. The study area was restricted to those municipalities where [is greater than] 90% of households were served by the public water facility, reducing the probability that subjects in a particular area did not use the public water supply. The data set was also restricted to those served by a surface water source as chlorination by-products are essentially nonexistent non·ex·is·tence n. 1. The condition of not existing. 2. Something that does not exist. non in groundwater sources. We averaged predicted values of by-product level for the months covering the duration of the mother's pregnancy to provide an exposure measure during pregnancy. We excluded women if gestational age was unknown. We examined risk for the by-product factors in continuous and categorical That which is unqualified or unconditional. A categorical imperative is a rule, command, or moral obligation that is absolutely and universally binding. Categorical is also used to describe programs limited to or designed for certain classes of people. representations. Identical groupings were used for total THM and chloroform because exposures were of similar range and magnitude for these factors. The referent ref·er·ent n. A person or thing to which a linguistic expression refers. Noun 1. referent - something referred to; the object of a reference group for total THM and chloroform exposures were those with average pregnancy exposure of [is less than] 50 [micro]g/L. The majority ([is greater than] 95%) of women in the referent category had an average exposure in the range 25-49 [micro]g/L. Categorical groupings for bromodichloromethane reflected the lower magnitude and narrower range of values for this by-product. To provide consistent increments of exposure level for the continuous representation of THM compounds, increments of 10 [micro]g/L were used for total THM, chloroform, and bromodichloromethane. In Nova Scotia, all stillbirths and neonatal deaths are reviewed by hospital perinatal committees and further reviewed by clinicians with obstetrical obstetrical, obstetric pertaining to or emanating from obstetrics. obstetrical anesthesia an anesthetic procedure designed especially for patients undergoing cesarean operation or intrauterine manipulation of the fetus. and neonatal expertise from the Reproductive Care Program of Nova Scotia. A primary cause of death was assigned according to guidelines prepared by the Reproductive Care Program of Nova Scotia, and these guidelines were used consistently throughout the province. During the study period, autopsies were performed in 75% of the stillbirth cases. The categories for the underlying causes of death were adopted from methods proposed previously (8,9). These categories included intrauterine intrauterine /in·tra·uter·ine/ (-u´ter-in) within the uterus. in·tra·u·ter·ine adj. Within the uterus. Intrauterine Situated or occuring in the uterus. asphyxia, congenital anomalies congenital anomaly n. See birth defect. , deaths related to immaturity, other specified deaths, and unexplained deaths. Asphyxia deaths included placental placental pertaining to or emanating from placenta. placental barrier the placental separation of maternal and fetal blood which varies in its structure and permeability between the species. causes, umbilical cord umbilical cord (ŭmbĭl`ĭkəl), cordlike structure about 22 in. (56 cm) long in the pregnant human female, extending from the abdominal wall of the fetus to the placenta. causes, and labor and delivery causes. If two or more conditions were present, the condition that was most likely to have caused the fetal death was coded. We estimated relative risks (RRs) and 95% confidence intervals (CIs) adjusted for potential confounders using Poisson regression In statistics, the Poisson regression model attributes to a response variable Y a Poisson distribution whose expected value depends on a predictor variable x, typically in the following way: We determined potentially important confounders on the basis of the confounder--outcome relationship. A backward regression approach with factors eliminated at a significance [is greater than] 0.15 was used to identify the subset of factors with the potential to confound con·found tr.v. con·found·ed, con·found·ing, con·founds 1. To cause to become confused or perplexed. See Synonyms at puzzle. 2. the relationship of interest. Factors were maternal age maternal age, n the age of the mother at the period of conception. , parity, smoking during pregnancy, infant's sex, and neighborhood family income. With the exception of family income, this information was obtained from the perinatal database. Maternal age was represented in three categories, [is less than] 25, 25-34, and [is greater than or equal to] 35 years. Parity and smoking were dichotomous di·chot·o·mous adj. 1. Divided or dividing into two parts or classifications. 2. Characterized by dichotomy. di·chot variables. Neighborhood family income, with adjustment for family size, was calculated based on 1991 census information for the enumeration 1. (mathematics) enumeration - A bijection with the natural numbers; a counted set. Compare well-ordered. 2. (programming) enumeration - enumerated type. area of the mother's residence. Enumeration area is the smallest standard geographic area for which Canadian census data are available. In 1991 the average population size of enumeration areas in Nova Scotia was 680. Results The cohort consisted of 49,756 singleton deliveries between 1988 and 1995, where mothers were resident in an area with municipal surface water service. Among the 214 stillbirths in the cohort, the largest subgroup included those with an unexplained cause (Table 1). Asphyxia-related causes accounted for 34% of stillbirths, with 63% of asphyxia deaths classified as abruptio placentae ab·rup·ti·o pla·cen·tae n. The premature detachment of a normally situated placenta. abruptio placentae Ablatio placentae, abruptio, premature separation of placenta Obstetrics The premature separation of the placenta . The analyses to determine the relationship between total THM and individual THM compounds and cause-of-death categories were restricted to unexplained deaths and asphyxia-related deaths because the number in the other categories was too small to permit a meaningful analysis. Table 1. Description of stillbirths by cause-of-death category Stillbirths Number Percent Unexplained 84 39 Asphyxia 72 34 Other specified 21 10 Immaturity 20 9 Congenital anomaly 15 7 Infection 2 1 Total 214 100 Table 2 presents the mean exposure value and correlation between by-product compounds. On average, 90% of the total THM value (mean 71 [micro]g/L) was accounted for by chloroform levels (mean 64 [micro]g/L), and exposure values for these factors were highly correlated. The mean value for bromodichloromethane was 6.9 [micro]g/L, which correlated moderately with total THM (Pearson correlation coefficient Correlation Coefficient A measure that determines the degree to which two variable's movements are associated. The correlation coefficient is calculated as: , r = 0.44), but less so with chloroform (r = 0.26). Table 2. Correlation between exposures to total THM, chloroform, and bromodichloromethane.
Pearson correlation
coefficient
Mean
Exposure ([micro]g/L) Total THM Chloroform
Total THM 71.3 1.00 0.98
Chloroform 64.1 0.98 1.00
Bromodichloromethane 6.9 0.44 0.26
Pearson correlation
coefficient
Exposure Bromodichloromethane
Total THM 0.44
Chloroform 0.26
Bromodichloromethane 1.00
Table 3 presents crude and adjusted RRs for stillbirth according to the by-product exposures. Relative risks were adjusted for smoking and maternal age, and adjustment resulted in only small changes to the risk estimates. Five percent of the total cohort and 7% of those with a stillbirth are not included in this analysis due to missing information on smoking. Relative risks associated with total THM rose with increasing levels of exposure to 1.7 for exposure to an average total THM level of 100 [micro]g/L relative to exposures [is less than] 50 [micro]g/L. The continuous representation showed a 5% increase in risk with each 10 [micro]g/L total THM. Results were similar according to chloroform exposure. A dose-response pattern was also observed according to levels of bromodichloromethane exposure, with a doubling of risk associated with the highest exposure category. The continuous representation displayed a 29% increase in risk with each 10 [micro]g/L of bromodichloromethane. Because the range of exposures is much lower for bromodichloromethane, increments of 10 [micro]g/L represent a larger proportion of the total range than for chloroform. Table 3. RRs and 95% CIs for the relationship between stillbirth and total THM, chloroform, and bromodichloromethane.
No.
Exposure stillbirths Rate (%)
Total THM ([micro]g/L)
< 50 43 0.33
50-74 79 0.42
75-99 31 0.42
[is greater than or equal to] 100 44 0.56
per 10 [micro]g/L -- --
Chloroform ([micro]g/L)
< 50 68 0.35
50-74 63 0.42
75-99 29 0.46
[is greater than or equal to] 100 37 0.56
per 10 [micro]g/L -- --
Bromodichloromethane ([micro]g/L)
< 5 96 0.37
5-9 57 0.40
10-19 23 0.54
[is greater than or equal to] 20 21 0.74
per 10 [micro]g/L -- --
Exposure RR (95% CI)
Total THM ([micro]g/L)
< 50 1.00
50-74 1.26 (0.87-1.83)
75-99 1.26 (0.80-2.00)
[is greater than or equal to] 100 1.69 (1.11-2.58)
per 10 [micro]g/L 1.05 (1.01-1.09)
Chloroform ([micro]g/L)
< 50 1.00
50-74 1.19 (0.84-1.67)
75-99 1.35 (0.87-2.07)
[is greater than or equal to] 100 1.59 (1.06-2.37)
per 10 [micro]g/L 1.05 (1.00-1.09)
Bromodichloromethane ([micro]g/L)
< 5 1.00
5-9 1.08 (0.77-1.50)
10-19 1.45 (0.91-2.28)
[is greater than or equal to] 20 1.99 (1.24-3.20)
per 10 [micro]g/L 1.30 (1.10-1.53)
Adjusted RR
Exposure (95% CI)(a)
Total THM ([micro]g/L)
< 50 1.00
50-74 1.27 (0.88-1.85)
75-99 1.28 (0.81-2.03)
[is greater than or equal to] 100 1.66 (1.09-2.54)
per 10 [micro]g/L 1.05 (1.01-1.09)
Chloroform ([micro]g/L)
< 50
50-74 1.20 (0.85-1.68)
75-99 1.35 (0.87-2.08)
[is greater than or equal to] 100 1.56 (1.04-2.34)
per 10 [micro]g/L 1.04 (1.00-1.09)
Bromodichloromethane ([micro]g/L)
< 5
5-9 1.07 (0.77-3.19)
10-19 1.44 (0.90-2.27)
[is greater than or equal to] 20 1.98 (1.23-3.49)
per 10 [micro]g/L 1.29 (1.10-1.53)
(a) RRs adjusted for smoking and maternal age. In an attempt to determine the independent effects of THM by-products, the continuous representations of chloroform and bromodichloromethane were entered simultaneously into a model (data not shown). Relative risk estimates in this analysis represent the effect of each by-product adjusted for the other by-product, maternal smoking, and maternal age. Chloroform was not associated with increased risk in this model (RR = 1.03 per 10 [micro]g/L; CI, 0.98-1.07), whereas bromodichloromethane was associated with a 26% increase in risk per 10 [micro]g/L (RR = 1.26; CI, 1.05-1.49). The data were analyzed by the stillbirth cause-of-death classifications of unexplained and asphyxia-related deaths (Table 4). For unexplained stillbirths, the risk estimates were lower than those for all stillbirths combined, and CIs consistently overlapped the null value A value in a field or variable that indicates nothing was ever derived and stored in it. For example, in a decimal-based amount field, a null value might be all binary 0s (null characters), but not a decimal 0. . In the analysis of asphyxia cases and total THM exposure, relative risks increased with increasing levels of exposure, to 5.0 for total THM [is greater than or equal to] 100 [micro]g/L. The continuous representation showed a 13% increase in asphyxia stillbirth risk with each 10 [micro]g/L total THM. Results were similar for chloroform, with an RR estimate of 3.6 for those exposed to chloroform levels [is greater than or equal to] 100 [micro]g/L. Elevated relative risks were also observed for bromodichloromethane exposure. The continuous representation showed a 32% increase in risk with each 10 [micro]g/L bromodichloromethane. Table 4. RRs and 95% CIs for the relationship between unexplained and asphyxia-related stillbirth and total THM, chloroform, and bromodichloromethane.
No.
Cause of death/exposure stillbirths Rate (%)
Unexplained
Total THM ([micro]g/L)
< 50 19 0.15
50-74 32 0.17
75-99 14 0.19
[is greater than or equal to] 100 12 0.15
per 10 [micro]g/L -- --
Chloroform ([micro]g/L)
< 50 28 0.14
50-74 28 0.19
75-99 13 0.21
[is greater than or equal to] 100 8 0.12
per 10 [micro]g/L -- --
Bromodichloromethane ([micro]g/L)
< 5 42 0.16
5-9 20 0.14
10-19 9 0.21
[is greater than or equal to] 20 6 0.21
per 10 [micro]g/L -- --
Asphyxia
Total THM ([micro]g/L)
< 50 7 0.05
50-74 27 0.14
75-99 10 0.13
[is greater than or equal to] 100 21 0.27
per 10 [micro]g/L -- --
Chloroform ([micro]g/L)
< 50 17 0.09
50-74 18 0.12
75-99 10 0.16
[is greater than or equal to] 100 20 0.30
per 10 [micro]g/L -- --
Bromodichloromethane ([micro]g/L)
< 5 29 0.11
5-9 18 0.13
10-19 12 0.28
[is greater than or equal to] 20 6 0.21
per 10 [micro]g/L -- --
Cause of death/exposure RR (95% CI)
Unexplained
Total THM ([micro]g/L)
< 50 1.00
50-74 1.05 (0.51-2.16)
75-99 1.29 (0.65-2.57)
[is greater than or equal to] 100 1.16 (0.66-2.04)
per 10 [micro]g/L 1.00 (0.94-1.08)
Chloroform ([micro]g/L)
< 50 1.00
50-74 1.28 (0.76-2.17)
75-99 1.47 (0.76-2.83)
[is greater than or equal to] 100 0.84 (0.38-1.83)
per 10 [micro]g/L 1.00 (0.93-1.07)
Bromodichloromethane ([micro]g/L)
< 5 1.00
5-9 1.00 (0.61-1.64)
10-19 1.38 (0.69-2.74)
[is greater than or equal to] 20 1.26 (0.54-2.96)
per 10 [micro]g/L 1.13 (0.83-1.53)
Asphyxia
Total THM ([micro]g/L)
< 50 1.00
50-74 2.65 (1.15-6.09)
75-99 2.50 (0.95-6.57)
[is greater than or equal to] 100 4.96 (2.11-11.67)
per 10 [micro]g/L 1.13 (1.06-1.19)
Chloroform ([micro]g/L)
< 50 1.00
50-74 1.36 (0.70-2.64)
75-99 1.86 (0.85-4.06)
[is greater than or equal to] 100 3.43 (1.80-6.56)
per 10 [micro]g/L 1.13 (1.06-1.21)
Bromodichloromethane ([micro]g/L)
< 5 1.00
5-9 1.13 (0.63-2.03)
10-19 2.50 (1.27-4.89)
[is greater than or equal to] 20 1.89 (0.78-4.55)
per 10 [micro]g/L 1.36 (1.04-1.78)
Adjusted
Cause of death/exposure RR (95% CI)(a)
Unexplained
Total THM ([micro]g/L)
< 50 1.00
50-74 1.16 (0.66-2.04)
75-99 1.31 (0.66-2.62)
[is greater than or equal to] 100 1.07 (0.52-2.22)
per 10 [micro]g/L 1.01 (0.94-1.08)
Chloroform ([micro]g/L)
< 50 1.00
50-74 1.29 (0.77-2.19)
75-99 1.49 (0.77-2.87)
[is greater than or equal to] 100 0.86 (0.39-1.89)
per 10 [micro]g/L 1.00 (0.93-1.08)
Bromodichloromethane ([micro]g/L)
< 5 1.00
5-9 0.87 (0.51-1.49)
10-19 1.34 (0.65-2.75)
[is greater than or equal to] 20 1.35 (0.57-3.19)
per 10 [micro]g/L 1.15 (0.85-1.55)
Asphyxia
Total THM ([micro]g/L)
< 50 1.00
50-74 2.67 (1.16-6.14)
75-99 2.49 (0.95-6.54)
[is greater than or equal to] 100 4.57 (1.93-10.77)
per 10 [micro]g/L 1.12 (1.05-1.18)
Chloroform ([micro]g/L)
< 50 1.00
50-74 1.36 (0.70-2.63)
75-99 1.82 (0.83-3.97)
[is greater than or equal to] 100 3.15 (1.64-6.03)
per 10 [micro]g/L 1.12 (1.05-1.20)
Bromodichloromethane ([micro]g/L)
< 5 1.00
5-9 1.09 (0.61-1.97)
10-19 2.32 (1.18-4.55)
[is greater than or equal to] 20 1.75 (0.72-4.22)
per 10 [micro]g/L 1.32 (1.00-1.74)
(a) RRs adjusted for smoking and maternal age. Discussion When all stillbirths combined were considered, the level of total THM and the specific THMs in public water supplies were each associated with increased risk. Chloroform accounts for a large proportion of total THM, and exposure measures for these two factors were highly correlated. Accordingly, results for chloroform were similar to those reported for total THM in a previous paper (2). High exposure to bromodichloromethane was associated with a doubling of risk compared to low exposure. Simultaneous modeling of the two specific THMs suggested that bromodichloromethane was the stronger independent predictor of risk. Two previous studies examined the relationship between stillbirths and water chlorination (5,7). Aschengrau et al. (5) reported an increased risk (odds ratio = 2.6) related to the use of chlorinated versus chloraminated surface water, whereas Bore et al. (7) found no association between stillbirth and total THM level. Previous studies of spontaneous abortion are also relevant to this discussion, as they may have a similar biologic response with respect to the toxicity of chlorination by-products. Waller et al. (3) examined total THM and the four individual THMs. Their finding that only high bromodichloromethane exposure was associated with spontaneous abortion both alone and after adjustment for the other THMs is consistent with our results. Savitz et al. (4) reported increased risk of spontaneous abortion only in the highest sextile sex·tile adj. Of or relating to the position of two celestial bodies when they are 60° apart. [Latin sext of THM concentration. Analysis of stillbirth groups defined by cause-of-death categories was conducted with the intent of focusing on stillbirths with etiologic similarities. Two subgroups were defined with sufficient numbers to allow meaningful analysis. A stronger relationship with the THM factors was observed for asphyxia-related deaths than unexplained deaths. The observation of a stronger relationship with asphyxia-related deaths indicates that this subgroup merits specific consideration in future investigations. In this cohort, 63% of the asphyxia-related deaths were due to abruptio placentae. Research into the mechanisms responsible for abruptio placentae suggest that folate deficiency folate deficiency Folic acid deficiency Hematology A condition caused by a decrease in dietary folic acid, resulting in megaloblastic anermia, GI tract complaints–eg, glossitis, stomatitis, malabsorption, infertility, neural tube defects, and possibly also and defects within the methionine-homocysteine metabolic pathway increase the risk of placental vascular disease, including abruptio placentae (11). A possible biologic mechanism to explain the increased risks found for abruptio placentae and exposure to chlorination by-products may be the effect on folate folate /fo·late/ (fo´lat) 1. the anionic form of folic acid. 2. more generally, any of a group of substances containing a form of pteroic acid conjugated with l-glutamic acid and having a variety of substitutions. or methioinine-homocysteine metabolism. Methionine methionine (mĕthī`ənēn), organic compound, one of the 20 amino acids commonly found in animal proteins. Only the L-stereoisomer appears in mammalian protein. biosynthesis Biosynthesis The synthesis of more complex molecules from simpler ones in cells by a series of reactions mediated by enzymes. The overall economy and survival of the cell is governed by the interplay between the energy gained from the breakdown of compounds has been shown to be inhibited by chloroform and related compounds in cell culture (12). The primary methodologic limitation of this study is potential misclassification of individual exposure to THMs. Individual exposure assessment was based on a measure of specific THMs for the water distribution system serving the area of the mother's residence at the time of delivery. This measure does not take into account variations in by-product concentrations within a treatment distribution system and individual behaviors that may influence exposure. The role of mobility in this study was addressed in a previous study in which we estimated that the change in municipality MUNICIPALITY. The body of officers, taken collectively, belonging to a city, who are appointed to manage its affairs and defend its interests. of residence would likely affect [is less than] 10% of study subjects (2). This study was limited to fetal deaths [is greater than or equal to] 500 g, as information on earlier fetal deaths (e.g., spontaneous abortions) is not available in the perinatal database. We were unable to examine other THMs (e.g., bromoform and chlorodibromomethane) because these by-products occurred in low concentrations in the water supplies examined. In this cohort, only 3% of mothers had average bromoform exposure [is greater than] 1 [micro]g/L, and only 2% had average chlorodibromomethane exposure [is greater than] 1 [micro]g/L. In contrast, 18% of the population studied by Waller et al. (3) were exposed to bromoform concentrations [is greater than] 16 [micro]g/L, and 16% were exposed to chlorodibromomethane of [is greater than] 31 [micro]g/L (3). A relationship between total THM and stillbirth was suggested in our previous publication of total THM exposure and several adverse birth outcomes (2). The findings presented here focus on specific chlorination by-products and categories of stillbirth in an attempt to better understand this potentially important relationship. These results suggest a need to consider specific chlorination by-products in relation to stillbirth risk, in particular bromodichloromethane and other by-products that correlate with this THM. In addition, stronger associations and a dose-response relationship The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a stressor (usually a chemical). This may apply to individuals (eg: a small amount has no observable effect, a large amount is fatal), or to populations were evident with stillbirths due to asphyxia-related causes of death, a result that requires confirmation and research into possible mechanisms. REFERENCES AND NOTES (1.) Health Statistics Division. Births and Deaths, 1995. Ottawa, Ontario, Canada:Statistics Canada, 1997. (2.) Dodds L, King W, Woolcott C, Pole J. Trihalomethanes in public water supplies and adverse pregnancy outcomes. Epidemiology 10(3):233-237 (1999). (3.) Waller K, Swan SH, DeLorenze G, Hopkins B. Trihalomethanes in drinking water drinking water supply of water available to animals for drinking supplied via nipples, in troughs, dams, ponds and larger natural water sources; an insufficient supply leads to dehydration; it can be the source of infection, e.g. leptospirosis, salmonellosis, or of poisoning, e.g. and spontaneous abortion. Epidemiology 9:134-140 (1998). (4.) Savitz DA, Andrews KW, Pastore LM. Drinking water and pregnancy outcome in central North Carolina North Carolina, state in the SE United States. It is bordered by the Atlantic Ocean (E), South Carolina and Georgia (S), Tennessee (W), and Virginia (N). Facts and Figures Area, 52,586 sq mi (136,198 sq km). Pop. : source, amount, and trihalomethane tri·hal·o·meth·ane n. A chemical compound containing three halogen atoms substituted for the three hydrogen atoms normally present in a methane molecule. levels. Environ Health Perspect 103:592-596 (1995). (5.) Aschengrau A, Zierler S, Cohen cohen or kohen (Hebrew: “priest”) Jewish priest descended from Zadok (a descendant of Aaron), priest at the First Temple of Jerusalem. The biblical priesthood was hereditary and male. A. Quality of community drinking water and the occurrence of late adverse pregnancy outcomes. Arch Environ Health 48:105-113 (1993). (6.) Stevens AA, Moore LA, Slocum CJ, Smith BL, Seeger DR, Ireland JC. By-products of water chlorination at ten operating utilities. In: Water Chlorination: Chemistry, Environmental Impact and Health Effects, Vol 6: Proceedings of the Sixth Conference on Water Chlorination--Environmental impact and Health Effects (Jolley R, Condie L, Johnson JD, Katz S Katz , Bernard 1911-2003. German-born British physiologist. He shared a 1970 Nobel Prize for the study of nerve impulse transmission. , Minear RA, Mattice JS, Jacobs VA, eds). Chelsea, MI:Lewis Publishers, Inc, 1990;579-604. (7.) Bove FJ, Fulcomer MC, Klotz JB, Esmart J, Dufficy EM, Savrin JE. Public drinking water contamination and birth outcomes. Am J Epidemiol 141(9):850-862 (1995). (8.) Cole S, Hartford RB, Bergsjo P, McCarthy B. International collaborative effort (ICE) on birth weight, plurality The opinion of an appellate court in which more justices join than in any concurring opinion. The excess of votes cast for one candidate over those votes cast for any other candidate. Appellate panels are made up of three or more justices. , perinatal, and infant mortality (hardware) infant mortality - It is common lore among hackers (and in the electronics industry at large) that the chances of sudden hardware failure drop off exponentially with a machine's time since first use (that is, until the relatively distant time at which enough mechanical III: a method of grouping underlying causes of infant death Noun 1. infant death - sudden and unexpected death of an apparently healthy infant during sleep cot death, crib death, SIDS, sudden infant death syndrome to aid international comparisons. Acta Obstet Gynecol Scand 68:113-117 (1989). (9.) Alberman E, Blatchley N, Botting B, Schuman J, Dunn A. Medical causes on stillbirth certificates in England and Wales England and Wales are both constituent countries of the United Kingdom, that together share a single legal system: English law. Legislatively, England and Wales are treated as a single unit (see State (law)) for the conflict of laws. : distribution and results of hierarchical classifications tested by the Office for National Statistics. Br J Obstet Gynaecol 104:1043-1049 (1997). (10.) Hertz-Picciotto I. Environmental epidemiology. In: Modern Epidemiology (Rothman KJ, Greenland S, eds), 2nd ed. Philadelphia, PA:Lippencott-Raven Publishers, 1998;555-583. (11.) Ray JG, Laskin CA. Folic acid folic acid: see coenzyme; vitamin. folic acid or folate Organic compound essential to animal growth and health and needed by bacteria as a growth factor. and homocyst(e)ine metabolic defects and the risk of placental abruption Placental Abruption Definition Placental abruption occurs when the placenta separates from the wall of the uterus prior to the birth of the baby. This can result in severe, uncontrollable bleeding (hemorrhage). , preeclampsia preeclampsia /pre·eclamp·sia/ (pre?e-klamp´se-ah) a toxemia of late pregnancy, characterized by hypertension, proteinuria, and edema. pre·e·clamp·si·a n. and spontaneous pregnancy loss: a systematic review. Placenta placenta (pləsĕn`tə) or afterbirth, organ that develops in the uterus during pregnancy. It is a unique characteristic of the higher (or placental) mammals. In humans it is a thick mass, about 7 in. 20:519-529 (1999). (12.) Alston TA. Inhibition of vitamin B vitamin B n. 1. Vitamin B complex. 2. A member of the vitamin B complex, especially thiamine. vitamin B, vitamin B complex a group of water-soluble substances described separately. 12-dependent methionine biosynthesis by chloroform and carbon tetrachloride carbon tetrachloride (tĕ'trəklôr`īd) or tetrachloromethane (tĕ'trəklôr'əmĕth`ān), CCl4, colorless, poisonous, liquid organic compound that boils at 76. . Biochem Pharmacol 42:R25-R28 (1991). Will D. King,(1) Linda Dodds,(2,3) and Alexander C. Allen(2,3) (1) Department of Community Health and Epidemiology, Queen's University Queen's University, at Kingston, Ont., Canada; nondenominational; coeducational; founded 1841 as Queen's College. It achieved university status in 1912. It has faculties of arts and sciences, education, law, medicine, and applied science, as well as schools of , Kingston, Canada; (2) Perinatal Epidemiology Research Unit, IWK IWK Indah Water Konsortium Sdn Bhd (Malaysia) IWK I Was Kidding Grace Health Centre, Halifax, Nova Scotia For other uses, see Halifax. Halifax, Nova Scotia may refer to any of the following:
Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system. and Pediatrics, Dalhousie University Dalhousie University (dălhou`zē), at Halifax, N.S., Canada; nonsectarian; coeducational; founded 1818 by the 9th earl of Dalhousie. Except for a few years between 1838 and 1845, Dalhousie did not function as a university until 1863. , Halifax, Nova Scotia, Canada Address correspondence to W.D. King, Department of Community Health and Epidemiology, Abramsky Hall, Queen's University, Kingston, Ontario Kingston, Ontario, is a Canadian city located at the eastern end of Lake Ontario, where the lake runs into the St. Lawrence River and the Thousand Islands begin. Kingston is the county seat of Frontenac County. K7L 3N6 Canada. Telephone: (613) 533-6000, ext. 74735. Fax: (613) 533 6686. E-mail: kingw@post.queensu.ca We thank C. Woolcott and J. Pole for computing support and J. Scott and D. Briggins for their helpful discussions. This research was supported by the Prince Edward Island Prince Edward Island, province (2001 pop. 135,294), 2,184 sq mi (5,657 sq km), E Canada, off N.B. and N.S. Geography One of the Maritime Provinces, Prince Edward Island lies in the Gulf of St. Reproductive Care Program through Health Canada Health Canada (French: Santé Canada) is the department of the government of Canada with responsibility for national public health. Health Canada's goal is to improve Canadian life by improving Canadian longevity, lifestyle and use of public healthcare. Green Plan funds. The perinatal data were provided by the Nova Scotia Reproductive Care Program, and the chlorination by-product data were provided by the Nova Scotia Department of the Environment. Received 21 January 2000; accepted 17 May 2000. |
|
||||||||||||||
Printer friendly
Cite/link
Email
Feedback
Reader Opinion