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PubMed1990

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.

Abnormalities, Drug-Induced↗
PubMed2004

Pesticide exposure in male farmers and survival of in vitro fertilized pregnancies.

BACKGROUND: Male-mediated spontaneous abortion is well described among animals, but less well documented in humans. Studies that include early pregnancy experience are expensive to conduct, but IVF provides new opportunities. MATERIALS AND METHODS: The Danish IVF register covers all IVF treatments performed after 1993. We mailed a questionnaire to 5879 women (response rate 68.2%). A subgroup of exposed male partners received a questionnaire on specific exposure to pesticides and growth retardants (n = 128 men, response rate 81.3%). Information on outcome was collected from national health registers. Survival of the first HCG-positive pregnancy was analysed using Cox regression. RESULTS: The proportion of pregnancies terminated by spontaneous abortion before 28 gestational weeks was 19.7% (n = 66 pregnancies), 19.7% (n = 61), 21.3% (n = 47) and 22.2% (n = 18) in pregnancies with paternal exposure to herbicides, fungicides, pesticides and growth retardants. respectively. In the reference group of 2925 pregnancies, the abortion rate was 28.4%. The differences in survival were not statistically significant. CONCLUSIONS: We found no increased risk of spontaneous abortion in IVF-treated women attributable to paternal agricultural application of pesticides and growth retardants. Exposure to potentially harmful pesticides in Denmark is relatively low, and the findings are restricted to countries with similar standards of protection.

Abortion, Spontaneous↗
PubMed1993

Transplacental transfer of genotoxins and transplacental carcinogenesis.

A number of chemical compounds induce cancer in the offspring of animals treated with these compounds. The fetus is sensitive to the toxic and teratogenic effects of chemicals in the early embryonic stages, whereas it is sensitive to carcinogenic effects during late fetal stages. Carcinogens may be direct acting or may require metabolic oxidation such as those in tobacco smoke. Activation can occur in utero. Animal experiments indicate that tumors can be initiated in utero, commonly by activation of cellular proto-oncogenes, and that promotion can occur after birth by postnatal treatment with tumor promoters. This may have important implications for humans. The initial peak of cancer incidence during the first 5 years of life may be due to prenatal exposure of either parent to mutagens, but the role of paternal exposure in relation to childhood cancer is controversial. There is an increased risk of cancer in children whose fathers work in heavy industry or whose mothers work in medical or dental services. The exact etiological agents have not been unequivocally identified. Information on human transplacental exposure to carcinogens and genotoxins is limited and based on measurement of maternal plasma concentrations or analysis of cord blood. Transplacental transfer of carcinogens in smoke and smoke-related damage to fetal tissue have been demonstrated. The mycotoxin aflatoxin B1 or its metabolites have been detected in cord blood, as have metabolites of pesticides and polychlorinated biphenyls. New biomarkers may provide important information on the transplacental transfer of genotoxic compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Anesthetic practice and pregnancy. Controlled survey of male anaesthetists in the United Kingdom.

7949 male doctors in the U.K. were surveyed to determine whether there was a relation between operating-theatre work (exposure) and abnormalities in the obstetric history of their marriages. Paternal exposure did not appear to influence the overall abortion-rate or the frequency of major congenital abnormality and involuntary infertility. The frequency of minor congenital abnormality in the children of exposed fathers was 3.09% compared with 2.35% (non-exposed). Maternal exposure was associated with a 15.5% frequency of abortion. Matching of exposed and non-exposed pregnancies with respect to birth order, maternal age, and smoking-habits suggests that the risk of abortion may increase by 158% to 271% with maternal exposure.

Abnormalities, Drug-Induced↗
PubMed1998

Does paternal occupational lead exposure increase the risks of low birth weight or prematurity?

The relation between paternal occupational lead exposure and low birth weight/prematurity was examined in a retrospective cohort study. Birth weight and gestational age (1981-1992), obtained from New York State birth certificates, were compared between lead-exposed and nonexposed workers. The exposed group (n = 4,256) consisted of births to male workers of reproductive age reported to the New York State Heavy Metals Registry. The control group (n = 2,318) consisted of the offspring of a random sample of male bus drivers, frequency matched by age and residence. There were no statistically significant differences in birth weight or gestational age between the exposed and the control groups. However, workers who had elevated blood lead levels for more than 5 years had a higher risk of fathering a child with low birth weight (risk ratio = 3.85, 95% confidence interval 1.5-9.88) or prematurity (risk ratio = 2.45, 95% confidence interval 1.03-5.84) than did controls after adjustment for paternal age, low maternal education, race, residence, gravidity, maternal spontaneous abortion history, perinatal complications, adequacy of prenatal care, and infant gender. The risks of low birth weight and prematurity increased with the duration of exposure to lead. Our results were limited by the inability to control for some potential confounders, such as pregravid underweight and maternal nutrition status.

Adult↗
PubMed1992

Paternal occupational lead exposure and congenital malformations.

STUDY OBJECTIVE: The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. DESIGN: The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. SUBJECTS: Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. MEASUREMENTS AND MAIN RESULTS: Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. CONCLUSIONS: Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.

Abnormalities, Drug-Induced↗
PubMed1989

A case-control study of risk factors for hepatoblastoma. A report from the Childrens Cancer Study Group.

Parents of 75 children with hepatoblastoma, registered with the Childrens Cancer Study Group, and 75 age-matched controls, who had been identified through random digit dialing were interviewed. No evidence was found to support the primary study hypotheses relating to hepatitis infection, maternal estrogen exposure, alcohol consumption, smoking, or potential sources of nitrosamines. Case mothers were more likely to report occupational exposure to metals (odds ratio [OR] = 8.0, P = 0.01), petroleum products (OR = 3.7, P = 0.03), and paints or pigments (OR = 3.7, P = 0.05). Metal exposures were commonly to welding or soldering fumes, and most occurred daily, before and during the index pregnancy. Petroleum product exposures were predominantly to lubricating oils or protective greases. The only significant paternal exposure was to metals (OR = 3.0, P = 0.01) and the risk with exposure to petroleum products was marginally significant (OR = 1.9, P = 0.06). These findings provide further evidence that occupational exposures may increase the risk of cancer in offspring.

Adult↗
PubMed1991

Paternal occupational lead exposure and spontaneous abortion.

A case-referent study was conducted on whether occupational exposure of men to inorganic lead is related to spontaneous abortion in their wives. The men were biologically monitored for lead exposure. The cases (213 spontaneous abortions) and referents (300 births) were identified from medical registers. Lead exposure was assessed with blood lead (PbB) measurements and data obtained from a questionnaire. The results did not show a statistically significant relationship between spontaneous abortion and paternal lead exposure among all the study subjects. A significant increase was observed in the risk of those women whose husbands had been monitored (PbB greater than or equal to 1.5 mumol/l) during or close to the time of spermatogenesis. The association between lead exposure and spontaneous abortion was modified also by the age of the wife and paternal alcohol use. The findings suggest that there may be an association between paternal lead exposure and the risk of spontaneous abortion.

Abortion, Spontaneous↗
PubMed2004

Neurobehavioral effects in rat pups whose sires were exposed to alcohol.

Developmental neurobehavioral effects associated with maternal exposure to alcohol during pregnancy are well described, but little is known about the effects of paternal exposure prior to conception. Using a quasi-experimental, within-subjects design, neurobehavioral outcomes (reflex acquisition, activity, gait) and cerebral cortical layer thickness were assessed in Sprague-Dawley rat pups from breeding pairs where the sires were exposed to alcohol. Comparisons were made on the basis of the timing of conception relative to alcohol exposure: phase 1 (controls), prior to initiation of alcohol exposure; phase 2, during the period of treatment with 20% alcohol; and phase 3, following cessation of alcohol exposure. Phase 2 and 3 pups were noted to attain negative geotaxis and reflex suspension benchmarks earlier than control pups and to have more difficulty with balance. Phase 3 pups were noted to attain righting reflex earlier than controls. In addition, phase 3 pups demonstrated increased levels of reverse maze activity and a shorter and narrower gait. Brain morphometry revealed thickening of cortical sections I-IV and V-VI resulting in overall cortical enlargement in both phase 2 and 3 pups. Further analysis of phase 2 and 3 subphases based on the presumed stages of the spermatogenic cycle during which sires were exposed to alcohol revealed significant differences in maze activity, reflex acquisition, and gait length. These findings suggest pre-conception male exposure to alcohol may have an effect on the offspring and the extent of the effects may vary with the timing of alcohol exposure relative to conception.

Alcohol Drinking↗
PubMed2003

Parental occupational exposure to pesticides and childhood brain cancer.

The authors examined the risk of childhood brain cancer in relation to parental exposure to classes of pesticides among 154 children diagnosed with astrocytoma and 158 children diagnosed with primitive neuroectodermal tumors (PNET) in the United States and Canada between 1986 and 1989. Controls were selected by random digit dialing and were individually matched to cases by race, age, and geographic area. Each job in the fathers' work history and the usual occupation of mothers were assigned a probability, intensity, and frequency of exposure to insecticides, herbicides, and agricultural and nonagricultural fungicides. Elevated risks of astrocytoma were found for paternal exposure (ever vs. never) to all four classes of pesticides (odds ratio (OR) = 1.4-1.6). An increased risk of PNET was observed for only herbicides (OR = 1.5). For mothers, odds ratios for astrocytoma were elevated for insecticides, herbicides, and nonagricultural fungicides (OR = 1.3-1.6) but not agricultural fungicides (OR = 1.0). No indication was found of an increased risk for PNET. There was little indication for an association with cumulative and average parental exposure. Most risk estimates were around unity, and exposure-response patterns were absent. Overall, it seems unlikely that parental exposure to pesticides plays an important role in the etiology of childhood brain cancer.

Adult↗
PubMed1995

Parental exposure to hydrocarbons in Prader-Willi syndrome.

The purpose of this study was to ascertain whether parental age and parental pre-conceptional exposure to various agents differentiated children with Prader-Willi syndrome (PWS) from obese children without PWS. Two groups of patients under 25 years of age were studied, 15 persons with PWS, and 13 with PWS-like symptoms. In the PWS group deletions were detected on chromosome 15q11-q13 and parents were older. The parents' occupational and recreational exposure to environmental toxins was recorded and correlated to the clinical diagnosis, genetics and behaviour characteristics. Paternal exposure to gasoline/petrol was significantly higher in the PWS group and is suggested as a possible important factor in the aetiology of PWS.

Adolescent↗
PubMed2006

Parental exposure to lead and small for gestational age births.

BACKGROUND: Previous studies about the effect of lead exposure on adverse birth outcomes are still inconsistent and few studies estimate the relationship between parental lead exposure and small for gestational age (SGA) infants. An occupational cohort study to assess whether parental lead exposure would be related to decreased birth weight and shortened gestational ages of their offspring was conducted. Whether higher lead exposure doses would increase risks of low birth weight (LBW), preterm delivery, and SGA births was also investigated. METHODS: A Program to Reduce Exposure by Surveillance System-Blood Lead Levels (Press-BLLS) was established in Taiwan in July 1993. The names of workers exposed to lead was collected from this occupational blood-lead notification database. The birth outcomes of their offspring were determined by linking to the Taiwan birth registration database from 1993 to 1997. Only singleton births whose parental blood-lead concentrations were tested during pregnancy or prior to conception, or within a 1-year span before these two periods were included. RESULTS: Among 1,611 eligible births, 72 births were LBW, 74 were preterm deliveries, and 135 were SGA. Maternal blood-lead concentrations (PbBs) equal to or more than 20 microg/dl had a higher risk of mothering a SGA child (risk ratio (RR) = 2.15; 95% confidence interval (CI), 1.15-3.83). CONCLUSIONS: Additional evidence of the effects of lead on adverse birth outcomes, especially for SGA births is reported. Maternal exposure to lead plays a more important role in the adverse effect on birth outcome than does paternal exposure.

Adult↗
PubMed1995

An exploratory analysis of risk factors for childhood malignant germ-cell tumors: report from the Childrens Cancer Group (Canada, United States).

A study of 105 patients with childhood malignant germ-cell tumors (MGCT) and 639 community controls was conducted utilizing a large epidemiologic database collected by the Childrens Cancer Group from 25 member institutions in the United States and Canada. This study was designed to explore the risk factors of this malignancy whose etiology remains poorly understood. A structured, self-administered questionnaire was used to collect exposure information, and data were analyzed using an unconditional logistic regression model with adjustment for relevant confounders. Consistent with the findings from studies of adult MGCT, gestational age was associated inversely with risk of MGCT, with a 70 to 75 percent reduction in risk for children born at term compared with those born pre-term. Parental, particularly maternal, self-reported exposure to chemicals or solvents (odds ratio [OR] = 4.6, 95 percent confidence interval [CI] = 1.9-11.3) and OR = 2.2, CI = 1.1-4.7 for maternal and paternal exposure, respectively) and plastic or resin fumes (OR = 12.0, CI = 1.9-75.0 [maternal] and OR = 2.5, CI = 1.0-6.5 [paternal]) were associated with elevated risk of MGCT. New findings, not reported previously, include a positive relationship of MGCT risk with birthweight and prolonged breastfeeding, an inverse association between MGCT risk and number of cigarettes smoked by the mother during pregnancy, and a 3.1-fold increased risk (CI = 1.5-6.6) associated with maternal urinary infections during index pregnancy. Although these findings need confirmation from future studies, they suggest a potential influence of in utero exposure to maternal endogenous hormones, parental environmental exposures, and maternal diseases during pregnancy in the development of childhood MGCT.

Adolescent↗
PubMed2025

Short-term diet intervention comprising of olive oil, vitamin D, and omega-3 fatty acids alters the small non-coding RNA (sncRNA) landscape of human sperm.

Offspring health outcomes are often linked with epigenetic alterations triggered by maternal nutrition and intrauterine environment. Strong experimental data also link paternal preconception nutrition with pathophysiology in the offspring, but the mechanism(s) routing effects of paternal exposures remain elusive. Animal experimental models have highlighted small non-coding RNAs (sncRNAs) as potential regulators of paternal effects. Here, we characterised the baseline sncRNA landscape of human sperm and the effect of a 6-week dietary intervention on their expression profile. This study involves sncRNAseq profiling, that was performed on a subset (n = 17) of the participants enrolled in the PREPARE trial: 9 from the control group and 8 from the intervention group. 5'tRFs, miRNAs and piRNAs were the most abundant sncRNA subtypes identified; their expression was associated with age, BMI, and sperm quality. Nutritional intervention with olive oil, vitamin D and omega-3 fatty acids altered expression of 3 tRFs, 15 miRNAs and 112 piRNAs, targeting genes involved in fatty acid metabolism and transposable elements in the sperm genome. PREPARE Trial registration number: ISRCTN50956936, Trial registration date: 10/02/2014.

Humans↗
PubMed1981

Power considerations in studies of reproductive effects of vinyl chloride and some structural analogs.

We review the evidence examining the relation of reproductive function and exposure to vinyl chloride and selected structural analogs. Investigation of these compounds for possible reproductive effects has focused on paternal exposure, a much less well studied route than maternal exposure. Drawing on animal models, we discuss what is known about the possible reproductive consequences of exposure to the father as well as to the mother. In evaluating the studies of reproductive outcome in relation to vinyl chloride or analogs, we consider what biologic model may have been tested and whether there was statistical power to detect moderate increases in risk. Parameters influencing statistical power are reviewed, and recommended sample sizes are set out which would insure sufficient power, in future studies, to detect adverse effects.

Abnormalities, Drug-Induced↗
PubMed1990

Ionising radiations from nuclear establishments and childhood leukaemias--an enigma.

The Gardner report, recently published in the UK, showing a correlation between incidence of childhood leukaemia and paternal exposure to ionising radiations (amongst fathers working in nuclear power plants) has added a new element to debates about both the risk factors in nuclear power plants and the relationships between ionising radiations and leukaemogenesis. The epidemiologic and genetic evidence concerning leukaemias is reviewed here and it is concluded that the leukaemogenic agent, whose existence is indicated in the Gardner report, is unlikely to be paternal radiation dose per se but rather exposure to another factor that is correlated with parternal radiation dose received.

Child↗
PubMed2000

The evidence that lead increases the risk for spontaneous abortion.

BACKGROUND: Reports from a period spanning more than a century, and covering occupationally exposed women in several countries, support an increase in pregnancy loss from high maternal lead exposures. Nevertheless, most studies conducted among populations with low/moderate exposures have provided little evidence of an association with pregnancy loss, or in particular, spontaneous abortions. METHODS: A critique of these low/moderate level studies reveals small sample sizes, problems in definition or ascertainment of outcome, lack of control for confounding, and/or deficiencies in the exposure assessment. For estimating exposure, either an ecologic measure was used, or individual biologic specimens were taken but attention was not paid to the timing of measurement of lead levels in these samples. A prospective study that overcame most of the deficiencies of previous studies enrolled pregnant women in Mexico City with low-to-moderate-level lead exposures, collected blood specimens during their first trimester, and ascertained spontaneous abortions by week 20. A key design element of this study was the use of incidence-density-matched controls in order to achieve comparable opportunity for the outcome and comparable timing of exposure measurements. The latter is especially important because blood lead levels are altered by pregnancy. RESULTS: In the prospective Mexico City Study, a striking dose-response relation between blood lead and risk of spontaneous abortion was found: the odds ratio for spontaneous abortion was 1.8 (95% confidence interval = 1.1-3.1) for every 5 microg/dL increase in blood lead. CONCLUSIONS: Low-to-moderate lead exposures may increase the risk for spontaneous abortion at exposures comparable to U.S. general population levels during the 1970s and to many populations worldwide today; these are far lower than exposures encountered in some occupations. Further research is needed to confirm the association, to delineate the role of maternal vs. paternal exposures, and to assess increases in menstrual variability as an explanation for this finding.

Abortion, Spontaneous↗
PubMed1986

Health effects of phenoxy herbicides. A review.

A review of epidemiological studies on the health effects of exposure to phenoxy herbicides suggests that exposure may be associated with an increased incidence of cancer and unfavorable outcomes of pregnancy. Studies on cancer have found increased risks of 5.3, 6.8 and 3.96 for soft-tissue sarcoma, 7.7 and 6.0 for stomach cancer, 2.05 for lung cancer, 4.8 for lymphoma, 2.3 for all cancers combined, and 5.2 for liver cancer after exposure to 2,4,5-T or dioxin contaminants. Several studies have suggested a possible increase in birth defects after paternal exposure. An increased risk of hydatidiform mole is suggested by Vietnamese studies on the effects of maternal exposure.

Carcinogens↗