Spontaneous abortion and maternal work in greenhouses

BACKGROUND: A positive association between maternal occupational exposure to pesticide and spontaneous abortion has been reported in some studies. Work in greenhouses may imply exposure of pregnant women to pesticides continuously and at elevated level. METHODS: A total of 717 women working in greenhouses provided information on 973 pregnancies, including 110 spontaneous abortions. These pregnancies were classified as exposed or not exposed according to maternal occupation, re-entry activities and application of pesticides in greenhouses during at least 1 month in the first trimester of pregnancy. The ORs for spontaneous abortion were estimated through a generalised estimate equations model for all orders of pregnancy together, and through a logistic regression model limited to first pregnancies. RESULTS: Increased risks of spontaneous abortion were found for maternal re-entry activities within 24 hr after pesticides were applied (all orders of pregnancy: OR 3.2, 95% CI 1.3-7.7; first pregnancies: OR 3.8, 95% CI 1.0-13.9) and for those who applied pesticides (all orders of pregnancy: OR 2.6, 95% CI 1.0-6.6; first pregnancies: OR 3.7, 95% CI 0.7-20,6) CONCLUSIONS: The observed results support the hypothesis of an association between maternal work in greenhouses and spontaneous abortion. The main limitations of the study are lack of information on the specific chemicals used and the small number of pregnancies heavily exposed to pesticides.     

Occupational exposure to organic solvents and pregnancy. Review of current epidemiologic knowledge

The findings and methodological issues of recent epidemiological studies (1989-1999) on adverse developmental effects of maternal occupational exposure to organic solvents are reviewed. Several studies suggest the possibility of a moderate increase in the risk of spontaneous abortion and congenital malformations, especially facial clefts, associated with maternal exposure to solvents. A common methodological weakness of these studies is the inaccuracy of data on exposures. Positive findings encourage further epidemiological studies of high-quality design and use of protective measures to minimize exposure to these agents from the preconceptional period to the end of pregnancy.     

Risk of spontaneous abortion in women occupationally exposed to anaesthetic gases: a meta-analysis.

OBJECTIVES: To determine the association between maternal occupational exposure to anaesthetic gases and risk of spontaneous abortion. METHODS: A meta-analysis was performed of published epidemiological studies identified from literature reviews, unsystematic perusal of reference lists of relevant publications, and two Medline searches (1984-92, keywords: anaesthetic gases; anaesthetics; anaesthetics, local; operating rooms; operating room nursing; pregnancy; abortion; 1985-92, keywords: anaesthetics; adverse effects; occupational exposure; anaesthesia, inhalation; operating room nursing; pregnancy; abortion). All peer reviewed studies were retained. Student theses were excluded, as were conference abstracts, unpublished material, and two studies in which data on paternal and maternal occupational exposures were pooled. The relative risk of spontaneous abortion was estimated. RESULTS: One study found no increase in risk of abortion when gases were scavenged or when the exposure to unscavenged gases was low. None of the studies included ambient gas sampling. 24 comparisons between exposed and unexposed women, obtained from 19 reports, were included. The overall relative risk was 1.48 (95% confidence interval (95% CI), 1.4 to 1.58). To test whether this result was influenced by the quality of the studies, the validity of the reviewed papers was rated on the basis of three criteria: appropriateness of the unexposed comparison group, control for non-occupational confounding variables, and response rate. The estimate of risk increased to 1.9 (95% CI, 1.72 to 2.09) when analysis was restricted to the six comparisons which were rated the most rigorous. CONCLUSIONS: Epidemiological studies based on data obtained in the prescavenging era indicate an increased risk of spontaneous abortion. The estimated increased risk was not diminished but rather increased by exclusion of the more methodologically flawed studies.     

Effects of parental occupational exposures on spontaneous abortion and congenital malformation

Human reproduction is a complex process and can be disturbed in many phases by both host and environmental factors. Therefore, it has been difficult to distinguish the occupational causes of spontaneous abortion and congenital malformations from other factors related to the parents' characteristics and their living environment. The extrapolation of results of animal studies to humans is often complicated because there are structural and functional differences between the species and the mechanisms of harmful effects are seldom known. There is also a lack of conclusive epidemiologic studies on the topic. At present knowledge on the potential reproductive toxicity of even rather common occupational exposures is limited and in many cases only suggestive. Paternal exposure to organic solvents before conception and maternal exposure during pregnancy may have adverse effects on the pregnancy and offspring. Heavy physical work during pregnancy may increase the risk of spontaneous abortion.     

尿道下裂危险因素的病例对照研究

目的 探讨尿道下裂病因。方法 采用以医院为基础的1:2配比的病例对照研究方法,以统一的调查表及调查方式对107倒尿道下裂及214例对照进行面对面问卷调查,应用SAS 6.12软件对所有调查因素进行单因素及多因素logistic回归分析。结果 胎儿尿道下裂的发生与母亲孕前自然流产史(OR=3.87,95％CI:1.60～9.39)、孕期发生先兆流产(OR=3.57,95％CI:1.31～9.64)、孕早期感冒伴发热(OR=7.63,95％CI:2.50～23.24)、孕中期用抗感染和/或解热止痛药(OR=16.46,95％CI;3.46～78.21)、父亲职业性接触农药(OR=3.70,95％CI:1.49～9.16)及胎儿低出生体重(OR=12.62,95％CI:2.97～53.67)呈正相关,与母亲孕早期增加蛋白质类营养(OR=0.33,95％CI:O.15～0.74)呈负相关。结论 母亲孕前自然流产史、孕期发生先兆流产、孕早期感冒伴发热、孕中期用抗感染和/或解热止痛药、父亲职业性接触农药、胎儿低出生体重等可能增加胎儿发生尿道下裂的危险,而母亲孕早期增加蛋白质类营养可能降低胎儿发生尿道下裂的危险。     

Employment status as a confounder when assessing occupational exposures and spontaneous abortion

Studies of occupational exposure and spontaneous abortion may use pregnancies during which the mother was unemployed as part or all of the unexposed comparison group. Any type of maternal employment, however, may be a risk factor for spontaneous abortion, and potential confounder in occupational reproductive studies. This study evaluates the effect of employment in a cohort of pregnancies of 1535 women. Employed pregnancies had a significantly higher rate of spontaneous abortion (14.5%) than unemployed pregnancies (11.7%) (RR = 1.23, 95% CI = 1.02, 1.49). Gravidity acted as an effect modifier, as the employment effect was seen only in multigravidous pregnancies (RR = 1.38, 95% CI = 1.11, 1.72) and not primigravidous pregnancies (RR = 0.96). The effect persisted when an independent sample of one randomly selected pregnancy per woman was used for the analysis (RR = 1.27, 95% CI = 0.90, 1.79). The data were examined for confounding by other factors which could explain the excess in spontaneous abortion among employed pregnancies. The employment effect persisted with adjustment for other risk factors including maternal age, education, income, maternal diabetes, race, alcohol usage and smoking, and prior pregnancy ending in induced abortion. Stratifying by prior pregnancy loss eliminated the employment effect among those with prior loss (RR = 1.03) but enhanced the effect among those multigravidous without the risk factor (RR = 1.50, 95% CI = 1.15, 1.97). Selection bias, also, was explored as a possible explanation of this employment effect, but could not be substantiated. Assessment of a true exposure effect requires consideration of a potential employment effect either in the design or analysis.     

Video display terminal use during pregnancy and reproductive outcome--a meta-analysis.

STUDY OBJECTIVE--The aim was to obtain quantitative information from published data on the potential association between video display terminal (VDT) use during pregnancy and the outcome. DESIGN--Results of nine published case-control studies (or cohort studies analysed as case-control) on the relation between VDT exposure during pregnancy and the outcome were sought by reviewing reference lists in relevant reports and by conducting manual and computer searches of the reports published in English. MEASUREMENTS AND MAIN RESULTS--The nine reviewed reports included information on about 9000 cases of spontaneous miscarriages, 1500 of low birth weight, 2000 of congenital malformation, and 50,000 controls. The results of these studies on each outcome of pregnancy examined were reduced to a single 2 x 2 table (cases/controls--exposed/unexposed). Pooled odds ratio (OR) estimates were computed separately for miscarriage, low birth weight, and congenital malformation. Seven studies analysed the relation between VDT exposure in pregnancy and the risk of miscarriage: the estimates' crude OR of spontaneous abortion ranged from 0.9-1.2 and the pooled OR was 1.0 (95% confidence interval (CI) 0.9, 1.0). No consistent evidence of increasing risk with duration of exposure to VDT was found. Two studies analysed the relation between VDT use and risk of having a low birth weight infant: the OR estimates in the individual studies were 1.0 and 1.1. Likewise, no relation emerged from the five studies providing information on congenital malformations and VDT use: the pooled OR was 1.0 (95% CI 0.9, 1.2). No specific malformation pattern emerged. CONCLUSIONS--This meta-analysis provides reassuring evidence on the absence of any major risk of adverse pregnancy outcome as a result of exposure to a VDT. With the number of cases reviewed, it was possible to exclude excess risk of 20% for spontaneous abortion, low birth weight, and congenital malformations.     

Association between maternal occupational exposure to organic solvents and congenital heart defects, National Birth Defects Prevention Study, 1997-2002

Objective To examine the relation between congenital heart defects (CHDs) in offspring and estimated maternal occupational exposure to chlorinated solvents, aromatic solvents and Stoddard solvent during the period from 1 month before conception through the first trimester. Methods The study population included mothers of infants with simple isolated CHDs and mothers of control infants who delivered from 1997 through 2002 and participated in the National Birth Defects Prevention Study. Two methods to assess occupational solvent exposure were employed: an expert consensus-based approach and a literature-based approach. Multiple logistic regression was used to calculate adjusted ORs and 95% CIs for the association between solvent classes and CHDs. Results 2951 control mothers and 2047 CHD case mothers were included. Using the consensus-based approach, associations were observed for exposure to any solvent and any chlorinated solvent with perimembranous ventricular septal defects (OR 1.6, 95% CI 1.0 to 2.6 and OR 1.7, 95% CI 1.0 to 2.8, respectively). Using the literature-based approach, associations were observed for: any solvent exposure with aortic stenosis (OR 2.1, 95% CI 1.1 to 4.1) and Stoddard solvent exposure with d-transposition of the great arteries (OR 2.0, 95% CI 1.0 to 4.2), right ventricular outflow tract obstruction defects (OR 1.9, 95% CI 1.1 to 3.3) and pulmonary valve stenosis (OR 2.1, 95% CI 1.1 to 3.8). Conclusions The authors found evidence of associations between occupational exposure to solvents and several types of CHDs. These results should be interpreted in light of the potential for misclassification of exposure.     

低浓度芳香烃溶剂暴露对自然流产影响的基因多态性研究

目的 探讨女工芳香烃溶剂暴露和细胞色素P450氧化酶MSP1基因和谷胱甘肽S转移酶GSTM1基因的多态性对自然流产的影响。方法 采用回顾性流行病学调查方法。使用统一调查表，由经过培训的调查员在北京燕山地区调查了276个女工，其中有自然流产史者58人，无自然流产史者218人。结果 单因素分析发现；GSTM1缺失基因型可致女工自然流产的危险度显著增加[OR=2.07(95%CI:1.15-3.71)]，但未观察到MSP1基因及芳香烃溶剂暴露对女工自然流产的影响，采用多元Logistic回归模型。经文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素调整后，可见GSTM1缺失基因型能显著致女工自然流产危险度增加[OR=2.15(95%CI;1.17-3.98)]。以GSTM1存在基因型和MSP1野生基因型为参照组。采用多元Logistic回归模型。并将文化程度，年龄，倒班，体重指数，被动吸烟，职业紧张混杂因素放入回归模型进行调整，在调整混杂因素前后，与参照组比较，均可见MSP1杂合子/突变基因型合并GSTM1缺失基因型使女工自然流失基因型与MSP1突变纯合子/杂合子基因型之间对自然流产的影响存在相加的联合作用。     

Maternal occupational exposure and congenital malformations.

A case-referent study was conducted to assess the risk of congenital malformations in relation to maternal occupational exposure before and during pregnancy. Three hundred and twenty-five cases of major malformations and 325 normal (at birth) referents identified in 15 maternity hospitals were included in the study. The occupational history obtained from an interview of the mother was blindly reviewed by an industrial hygienist who assessed the presence of chemical exposure and the probability of exposure. The results suggested that mothers of the case children with oral clefts were more often exposed to solvents during pregnancy [odds ratio (OR) 7.9, 90% confidence interval (90% CI) 1.8-44.9] and worked more often as cleaners (four cases, no referents). Digestive anomalies (OR 11.9, 90% CI 2.0-149) and multiple anomalies (OR 4.5, 90% CI 1.4-16.9) were also associated with occupational exposure to solvents at work. These results were not modified when differences in maternal age, area of residence, and socioeconomic status were taken into account.     

Review of epidemiologic studies of paternal occupational exposure and spontaneous abortion

The question of whether paternal exposures influence risk of spontaneous abortion is of great public interest, with the possibility supported by laboratory investigations. Thirty-nine studies of male occupational exposure and risk of spontaneous abortion were examined, with the methods and results tabulated. Many of those reports were limited by exposure data based on maternal report of the father's job title or by potentially inaccurate paternal reports of spontaneous abortion, though the quality of more recent studies is markedly enhanced. Mercury has been implicated most strongly based on recent studies that included quantitative exposure estimates; a number of studies showing associations for exposure to anesthetic gases. Suggestive associations have also been found inconsistently for exposure to lead, rubber manufacturing, selected solvents, and some pesticides. Further study is encouraged, but with more intensive effort to measure accurately both spontaneous abortion and occupational exposures. © 1994 Wiley-Liss, Inc.     

Spontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents

A case-referent study nested in a cohort monitored biologically for exposure to six organic solvents (styrene, toluene, xylene, tetrachloroethylene, trichloroethylene, and 1,1,1-trichloroethane) was conducted to investigate the effects of paternal exposure on pregnancy outcome. The pregnancies were identified from medical registers. The exposures of the men during the spermatogenesis preceding the pregnancies and of the women during the first trimester of the pregnancies were obtained with questionnaires, and the available biological monitoring measurements were used in the exposure assessment. Factors which significantly increased the odds ratio of spontaneous abortion were paternal exposure to organic solvents in general, high/frequent exposure to toluene or miscellaneous organic solvents (including thinners), and maternal heavy lifting. No significant association between paternal or maternal exposure and congenital malformations was found, but because of the few cases no firm conclusions can be drawn.     

Exposure to organic solvents and adverse pregnancy outcome

In a large case-control study (n = 1,926) of spontaneous abortion (SAB), exposure to solvents was ascertained by a telephone interview that asked about occupational use of 18 specific solvents or products, as well as an open-ended "other" solvent category. The adjusted odds ratio for use of any solvent was 1.1 (0.8, 1.5). Solvents for which at least a doubled crude risk of SAB was found included perchlorethylene (OR = 4.7, 95% CI = 1.1, 21.1), trichloroethylene (OR = 3.1, CI = 0.9, 10.4), and paint thinners (OR = 2.3, CI = 1.0, 5.1). Comparing exposure greater than 10 hours per week versus less did not show consistent dose-response effects. By solvent class, an association was seen with aliphatic solvents (adjusted OR = 1.8, 95% CI = 1.1, 3.0), but there was no dose-response effect by hours of use. Household use of solvent-containing products was generally not strongly associated with SAB, nor did it appear to confound the association seen with occupational use. From this and other studies, occupational exposure to at least some solvents appears associated with SAB. The associations of solvent exposure and fetal growth among liveborn offspring of controls was also examined.     

Paternal laboratory work and congenital malformations

Animal studies indicate male-mediated teratogenicity for certain carcinogens/mutagens. Nevertheless, paternal occupational determinants of malformations in humans have been sparsely investigated. Data on male employees at Swedish universities from 1970 to 1989 were linked to the Medical Birth Register. The relationship between major malformations and exposure to laboratory work and to specific laboratory agents/techniques before the third trimester were analyzed using logistic regression. For major malformations, "laboratory work in general" (n = 3237) gave an adjusted odds ratio (OR) of 1.3 (95% CI = 0.8-2.1) and carcinogenic solvent use (n = 2489) of 2.0 (95% CI = 0.8-4.9) around the time of conception. For carcinogenic solvents and neural crest malformations, OR was 4.9 (95% CI =1.5-15.8). In conclusion, the prevalence of congenital malformations was not increased in offspring of males with laboratory work in general (1970-1989). Paternal work with agents such as carcinogens could, however, be of concern.     

Paternal organic solvent exposure and adverse pregnancy outcomes: a meta-analysis

BACKGROUND: Organic solvents are widely used, but conflicting reports exist concerning paternal exposure and adverse pregnancy outcomes. We conducted a meta-analysis to assess the risks of spontaneous abortions (SAs) and major malformations (MMs) after paternal exposure to organic solvents. METHODS: Medline, Toxline, Reprotox, and Embase from 1966 to 2003 were searched. Two independent reviewers searched for cohort and case-control studies in any language on adult human males exposed chronically to any organic solvent. Two non-blinded independent extractors used a standardized form for data extraction; disagreements were resolved through consensus discussion. RESULTS: Forty-seven studies were identified; 32 exclusions left 14 useable studies. Overall random effects odds ratios and 95% confidence intervals (CI95%) were 1.30 (CI95%: 0.81-2.11, N=1,248) for SA, 1.47 (CI95%: 1.18-1.83, N=384,762) for MMs, 1.86 (CI95%: 1.40-2.46, N=180,242) for any neural tube defect, 2.18 (CI95%: 1.52-3.11, N=107,761) for anencephaly, and 1.59 (CI95%: 0.99-2.56, N=96,517; power=56.3%) for spina bifida. CONCLUSIONS: Paternal exposure to organic solvents is associated with an increased risk for neural tube defects but not SAs.     

Multiple malformations and maternal smoking

The Swedish health registries were used to investigate a possible effect of maternal smoking on the incidence of multiple malformations. Among 1413811 infants born in 1983-96 and with known smoking exposure in early pregnancy, 26619 with isolated malformations and 1409 with two or more malformations were selected. After controlling for year of birth, maternal age, parity and educational level, a statistically significant association between maternal smoking and multiple malformations was found (OR 1.15; 95% CI 1.02, 1.29). Among isolated malformations, the estimated OR for maternal smoking was close to unity (OR 1.02; 95% CI 0.99, 1.05), but a strong heterogeneity of the magnitude of the association between maternal smoking and the different malformations was found. Among multimalformed, no such heterogeneity was indicated. The ORs for maternal smoking were calculated for all possible pairwise combinations of 44 selected malformations, but no association between maternal smoking and any specific combination could be detected. The ORs for maternal smoking among probable cases of VATER, CHARGE or OEIS non-random associations, respectively, were estimated, but no association was indicated between maternal smoking and any of the malformation complexes. The results of the present study indicate that maternal smoking is associated with a non-specific increased risk of multiple malformations, but further research is needed before such an inference can be made.     

Adverse pregnancy outcomes in relation to water contamination, Santa Clara County, California, 1980-1981

An epidemiologic study was conducted to investigate a suspected cluster of adverse outcomes of pregnancies conceived in 1980-1981 among women who resided in a census tract in Santa Clara County, California that was thought to be exposed to drinking water from a well contaminated by an organic solvent, trichloroethane. A comparison census tract that received water from a different source was selected on the basis of demographic comparability. The cluster was confirmed; the odds ratio for spontaneous abortion was 2.3 (95% confidence interval (Cl) 1.3-4.2) after adjustment by multiple logistic regression for maternal risk factors, including maternal age, alcohol consumption, smoking, and prior fetal loss. The relative risk for congenital malformations was 3.1 (95% Cl 1.1-10.4). Because of the lack of precise information on the timing and extent of contamination, the pattern of spontaneous abortion rates throughout the study period cannot be used to either support or refute a causal inference.     

A prospective-controlled study of pregnant veterinary staff exposed to inhaled anesthetics and x-rays

Most veterinary staff are women of reproductive age. They are exposed to "waste" anesthetic gas and ionizing radiation in their workplace, which may endanger fetal safety. Presently, exposure of female veterinary staff to these health hazards has not been adequately addressed in the medical literature. Our primary objective was to investigate the incidence of major malformations associated with occupational exposure to inhaled anesthetics and/or radiation among pregnant veterinary staff. The secondary objective was to determine the rates of other adverse outcomes. We prospectively collected data on and followed-up women occupationally exposed to inhaled anesthetics and/or radiation in veterinary practices in Ontario, and compared them to controls matched for maternal age and gestational age at the time of call to the Motherisk Program. A total of 95 women were prospectively enrolled and followed-up. Among the participants there were 87 (93.5%) and 88 (92.8%) livebirths in the study and control groups, respectively. There were 4 (4.8%) major birth defects in the study group and 3 (3.4%) in the control group. The rates of spontaneous abortion were also similar, 6 (6.4%) cases in the study group and 7 (7.4%) cases in the control group. These results suggest that Ontario female veterinary staff exposed to inhaled anesthetics and/or radiation do not seem to be at an increased risk for major malformations above baseline risk.