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PubMed1999

Stillbirths among offspring of male radiation workers at Sellafield nuclear reprocessing plant.

BACKGROUND: Ionising radiation is a known mutagen, but few studies have examined transgenerational effects of paternal exposure in human beings. The workforce at the Sellafield nuclear reprocessing plant in the county of Cumbria, UK, is the most highly exposed workforce in western Europe and North America. This study, which is part of a larger programme of work investigating the health of the children of the Sellafield workforce, set out to find whether there was evidence of an association between stillbirth risk and paternal exposure to ionising radiation. METHODS: We collected details from birth registration documents for all singleton 248,097 livebirths and 3715 stillbirths in the county of Cumbria 1950-89. Within this cohort the 130 stillbirths and 9078 livebirths to partners of male radiation workers employed at Sellafield were identified. Logistic regression was used to analyse the relation between stillbirth risk and father's preconceptional radiation exposure, with adjustment for social class, year of birth, father's age, and birth order. FINDINGS: A significant positive association was found between the risk of a baby being stillborn and the father's total exposure to external ionising radiation before conception (adjusted odds ratio per 100 mSv 1.24 [95% CI 1.04-1.45], p=0.009). The risk was higher for stillbirths with congenital anomaly and was highest for the nine stillbirths with neural-tube defects. The statistical models predicted that, were the association to be interpreted as causal, between 0 and 31.9 of the 130 stillbirths to the workforce may be attributable to father's radiation exposure. INTERPRETATION: The findings of an increased risk of stillbirth with increasing paternal occupational exposure to external radiation are qualitatively consistent with those from animal models, though the risk estimate is higher. Although we cannot exclude the possibility of an unmeasured risk factor for stillbirth, confounded with paternal preconceptional irradiation, extensive checks confirmed that the statistical models were a good fit to the data and there was not statistical evidence of unmeasured factors.

Adult↗

PubMed2001

Parental occupational exposures to chemicals and incidence of neuroblastoma in offspring.

To evaluate the effects of parental occupational chemical exposures on incidence of neuroblastoma in offspring, the authors conducted a multicenter case-control study, using detailed exposure information that allowed examination of specific chemicals. Cases were 538 children aged 19 years who were newly diagnosed with confirmed neuroblastoma in 1992-1994 and were registered at any of 139 participating hospitals in the United States and Canada. One age-matched control for each of 504 cases was selected through random digit dialing. Self-reported exposures were reviewed by an industrial hygienist, and improbable exposures were reclassified. Effect estimates were calculated using unconditional logistic regression, adjusting for child's age and maternal demographic factors. Maternal exposures to most chemicals were not associated with neuroblastoma. Paternal exposures to hydrocarbons such as diesel fuel (odds ratio (OR) = 1.5; 95% confidence interval (CI): 0.8, 2.6), lacquer thinner (OR = 3.5; 95% CI: 1.6, 7.8), and turpentine (OR = 10.4; 95% CI: 2.4, 44.8) were associated with an increased incidence of neuroblastoma, as were exposures to wood dust (OR = 1.5; 95% CI: 0.8, 2.8) and solders (OR = 2.6; 95% CI: 0.9, 7.1). The detailed exposure information available in this study has provided additional clues about the role of parental occupation as a risk factor for neuroblastoma.

Adolescent↗

PubMed1996

Maternal exposure to paternal HLA does not explain the postpartum increase in rheumatoid arthritis.

The postpartum period, particularly after the first pregnancy, represents a time of increased risk for the development of rheumatoid arthritis (RA). The present study was undertaken to investigate whether this increase in risk may be due to maternal exposure to fetally inherited paternal HLA-DR antigens that were either 1) similar to their own or 2) had an increased likelihood of being one of the two specific types, HLA-DR1 and DR4, implicated in the etiology of RA. We recruited 94 families where the mother had developed RA within 12 months of a pregnancy, and HLA typed the mother, father, and relevant child of each family. Mothers were not more likely to share HLA-DR genes with their partners than would be expected, and children whose parents shared one HLA-DR gene were not more likely to inherit the shared gene from their father as opposed to the non-shared gene. Further, those children whose fathers were heterozygous for HLA-DR1 or DR4 were not more likely to inherit these genes as opposed to the non-DR1/DR4 gene. In conclusion, maternal exposure during pregnancy to either fetally inherited paternal HLA-DR1 and DR4 genes or to paternal DR genes similar to their own does not appear to contribute to postpartum maternal susceptibility of RA.

Arthritis, Rheumatoid↗

PubMed1989

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.

Abnormalities, Drug-Induced↗

PubMed2004

[A case-control study on the risk factors of central nervous system congenital malformations].

OBJECTIVE: To determine the risk factors in the development of central nervous system (CNS) congenital malformations. METHODS: A hospital-based 1:2 matched case-control study was conducted. Each case was matched with two normal controls on sex and residential area, date of birth, within half a year. By means of simple and multivariable conditional logistic regression, 48 factors were analyzed. RESULTS: Maternal exposure to pesticide or having cold with fever, family history of positive congenital malformations, preference eating pickled vegetables, negative life events, large consumption of meat, eggs, beans and milk during pregnancy and paternal exposure to poisonous chemicals were significantly associated with CNS congenital malformations, with odds ratios 16.471, 12.621, 10.246, 7.274, 3.730, 0.229, 5.616, respectively. CONCLUSIONS: Maternal exposure to pesticides, cold with fever, positive congenital malformations family history, preference of eating pickled vegetables, negative life events during pregnancy, and paternal exposure to poisonous chemicals were the key risk factors contributing to CNS congenital malformations, while maternal exposure to big consumption of meat, eggs, beans and milk during pregnancy was protective factors that reducing CNS congenital malformations.

Adult↗

PubMedDate not supplied

Parental exposure to organic solvents and reduced birth weight.

The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.

Adult↗

PubMed1984

Fetal loss and work in a waste water treatment plant.

We investigated pregnancy outcomes in 101 wives of workers employed in a waste water treatment plant (WWTP), and verified fetal losses by hospital records. Paternal work histories were compiled and each of the 210 pregnancies was assigned a paternal exposure category. The relative risk of fetal loss was increased when paternal exposure to the WWTP occurred around the time of conception.

Abortion, Spontaneous↗

PubMed1995

Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand.

We studied whether paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) during the Vietnam War is related to adverse reproductive outcomes after service in Southeast Asia. The index cohort comprises conceptions and children of veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam from 1962 to 1971. The comparison cohort comprises conceptions and children of Air Force veterans who served in Southeast Asia during the same period but who were not involved with spraying herbicides. We found no meaningful elevation in risk for spontaneous abortion or stillbirth. In analyses of birth defects, we found elevations in risk in some organ system categories, which, after review of the clinical descriptions, were found to be not biologically meaningful. There was an increase in nervous system defects in Ranch Hand children with increased paternal dioxin, but it was based on sparse data. We found no indication of increased birth defect severity, delays in development, or hyperkinetic syndrome with paternal dioxin. These data provide little or no support for the theory that paternal exposure to Agent Orange and its dioxin contaminant is associated with adverse reproductive outcomes.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMed2005

Environmental exposure to residential pesticides, chemicals, dusts, fumes, and metals, and risk of childhood germ cell tumors.

We examined relationships between exposure to residential pesticides, chemicals, dusts, fumes, and metals, and childhood germ cell tumors (GCTs) in the largest case-control study to date on the topic. We recruited 272 children under 15 years old who had GCT diagnosed between January 1, 1993 and December 31, 2001. Controls were selected by random-digit dialing and were frequency matched to cases by sex, age, and geographic area. Telephone interviews and self-administered questionnaires of parents were used to collect exposure information. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). Maternal and paternal exposure from 6 months before pregnancy to during breastfeeding and children's postnatal exposure to residential pesticides were generally unrelated to risk of childhood GCT. Elevated OR were observed for mothers' exposure to hair dyes 1 month before pregnancy for boys (OR = 1.7, 95% CI = 1.0-2.8) and during breastfeeding for boys and girls combined, and for girls (OR = 1.5, 95% CI = 1.0-2.2 and OR = 1.7, 95% CI = 1.1-2.6, respectively). Among boys, OR for paternal exposure to insecticides more often than four times or exposure to indoor insecticides more often than three times were 0.5 (95% CI = 0.2-0.9, trend test p = 0.05) and 0.3 (95% CI = 0.2-0.8, trend test p = 0.02) during the index pregnancy. Overall this study produced no strong evidence linking parental and child residential exposure to pesticides, certain chemicals, dusts, fumes, and metals to increased risk of childhood GCT. Statistically significant associations need to be confirmed in future studies.

Adolescent↗

PubMedDate not supplied

Chromosomal analysis and health status of children conceived to men during or following dibromochloropropane-induced spermatogenic suppression.

Although the mutagenic effect of Dibromochloropropane (DBCP) on experimental mammal systems has been described, its possible effect on the human genome has not yet been investigated. The present study describes the results of chromosomal analysis and health evaluation of offspring conceived to families during and after paternal exposure to DBCP. Ten children conceived during or following severe exposure and four who were conceived prior to DBCP exposure were evaluated. The chromosomal constitution of peripheral lymphocytes was normal in all cases. The mode of delivery, birth weight, physical examination and growth pattern were normal. No congenital malformations were detected. One spontaneous abortion out of 23 pregnancies was recorded. These results suggest that paternal exposure to DBCP, severe enough to cause azoospermia or oligozoospermia did not alter the paternal sperm genome or the chromosomal constitution of offspring conceived during or after exposure. This is further supported by the excellent health and lack of malformations among the children, along with the low rate of spontaneous abortions in the families studied.

Adolescent↗

PubMed1995

Dibromochloropropane (DBCP): a 17-year reassessment of testicular function and reproductive performance.

The current study summarizes a 17-year reevaluation of testicular function and reproductive performance of 15 production workers with dibromochloropropane (DBCP)-induced testicular dysfunction. Sperm count recovery was evident within 36 to 45 months in three of the nine azoospermic and in three of the six oligozoospermic men with no improvement thereafter. A significant increase in plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and a nonsignificant decrease in testosterone level were detected in the severely affected individuals. There was no increase in the rate of spontaneous abortions and congenital malformations among pregnancies conceived during or after exposure. A low prevalence of male infants conceived during paternal exposure was found as compared with the preexposure period (16.6% versus 52.9%; P<.025). Restoration of fertility was followed by a gradual increase of this value to 41.4%.

Adult↗

PubMed2000

Occupational and environmental exposure correlates of adverse live-birth outcomes among 1032 US Navy women.

The integration of women into non-traditional military occupations raises questions concerning the impact of such jobs on women's reproductive health. This study examines the extent to which US Navy women in their reproductive years report exposures to potential occupational and environmental hazards, and the degree to which such exposures are associated with self-reported adverse live-birth outcomes. Data from a survey of pregnant Navy women provided both maternal and paternal exposure information on more than 1000 active-duty women. Self-reported exposures to heavy metals, pesticides, petroleum products, and other chemicals were associated with adverse live-birth outcomes at the bivariate level. Only a father's exposure to pesticides at work predicted an adverse live-birth outcome (preterm delivery) in multivariate models. Maternal occupational exposures may exert their influence through maternal health and/or pregnancy complications and may act as mediators of health-reproductive outcome relationships.

Adolescent↗

PubMed2005

Parental occupational exposure to pesticides and childhood germ-cell tumors.

In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring.

Adolescent↗

PubMed2003

Parental occupation at periconception: findings from the United Kingdom Childhood Cancer Study.

AIMS: To study the risk of childhood cancer in relation to parental occupation and related exposures. METHODS: Self reported occupational data from mothers and fathers of 3838 children with cancer and 7629 control children were analysed. Odds ratios were calculated for 31 "occupational groups" by parent, diagnostic group (leukaemia, acute lymphoblastic leukaemia (ALL), central nervous system tumours, and other cancers) and time of exposure (periconception, birth, and diagnosis). RESULTS: Findings did not support the hypothesis that occupational exposure of fathers to ionising radiation increases the risk of childhood cancer in their offspring. Specific examination of periconceptual chemical exposures showed small but statistically significant increased risks for leukaemia and ALL among children whose fathers were exposed to exhaust fumes, driving, and/or inhaled particulate hydrocarbons. In the remaining analyses, a fourfold increase in the risk of other cancers was observed among the children of fathers working with leather but based on small numbers. Both maternal and paternal exposure to textile dust was related to an increased risk of other cancers. CONCLUSION: Results failed to produce any strong evidence to link parental occupational exposures with an increased risk of childhood cancer. No relation was found for paternal periconceptual exposure to ionising radiation. The consistency of the associations observed between childhood leukaemia and paternal occupational exposure to exhaust fumes, driving, and/or inhaled particulate hydrocarbons at periconception suggest a small risk for vehicle related exhaust. However, other explanations cannot be excluded and further research into the nature of the associations is required.

Adolescent↗

PubMedDate not supplied

Dibromochloropropane-induced reduction of the sex-ratio in man.

The present study evaluated the effect of paternal exposure to Dibromochloropropane (DBCP) during its production, on the sex ratio of offsprings conceived during the exposure period. The study population consisted of 30 families of which 13 fathers became azoospermic, 8 oligozoospermic and 9 normozoospermic. Of the 89 pregnancies recorded, 68 culminated in the birth of live infants. The prevalence of male infants conceived during the pre-exposure period was 52.9% , in contrast to 35.2% for boys conceived during exposure. For the combined azoospermic and oligozoospermic groups, a significantly low prevalence of male infants of 16.6% (p less than 0.025) was found. It is concluded that paternal exposure to DBCP during its production process is associated with a significant decrease in the sex ratio of offsprings conceived during the exposure period. This drop in the sex ratio might be a reflection of the early effect of DBCP on male reproductive performance before a state of severe testicular dysfunction and infertility is reached.

Antinematodal Agents↗

PubMedDate not supplied

Paternal alcohol exposure and hyperactivity in rat offspring: effects of amphetamine.

Locomotor activity of rat offspring sired by fathers treated with 0, 2 or 3 g/kg of alcohol twice daily was assessed at 21, 42 and 90 days of age. Fathers treated with the two lower doses were pair-fed to those treated with the highest dose. Offspring of nontreated ad-lib fed fathers were also evaluated to determine the possible role of paternal stress associated with intubation and pair-feeding. The behavioral response to amphetamine was also examined in 90-day-old male offspring. Paternal alcohol treatment resulted in increased activity at each age for 3 g/kg offspring compared to pair-fed controls. Ad-lib offspring did not differ from 0 g/kg controls at 21 and 42 days of age. The significant effect of paternal alcohol treatment on offspring activity at 90 days, including a significant linear paternal effect, occurred when all amphetamine-treated groups were pooled. The alcohol x amphetamine interaction was not significant, but a significant linear paternal alcohol x linear amphetamine interaction indicated that the paternal alcohol effect on activity was differentially responsive to amphetamine. Subsequent analysis of this interaction indicated a significant linear paternal alcohol trend only at the high dose of amphetamine. These results corroborate a previous report of increased activity on the part of offspring sired by fathers treated with alcohol. The presence of a differential effect of amphetamine suggests that the paternal effect on activity may be mediated by catecholaminergic activity. The absence of significant differences between ad lib and 0 g/kg pair-fed controls indicates that paternal stress/undernutrition does not significantly affect offspring activity.

Aging↗

PubMed1994

Acute paternal alcohol exposure impairs fertility and fetal outcome.

An acute injection of an intoxicating dose of alcohol to male rats 24 hours prior to breeding with drug-naive females produced no discernible effect on copulatory activity, as reflected in vaginal plugs, but resulted in markedly (> 50%) reduced pregnancy rates. Fetal outcome was also markedly affected in offspring sired by alcohol-treated males: litter sizes were appreciably smaller (30%) and fetal mortality was more than 2 times higher than in controls. These results suggest that paternal alcohol use, like maternal alcohol abuse, may adversely affect fertility and fetal outcome.

Alcoholic Intoxication↗

PubMed1988

Paternal alcohol exposure affects offspring behavior but not body or organ weights in mice.

Male mice consumed liquid alcohol diets containing 20, 10, or 0% ethanol-derived calories (EDC) for 56-61 days. Animals fed the 10 and 0% EDC diets were pair-fed to 20% EDC animals. A nontreated ad libitum group was included to assess the effects of pair-feeding. After treatment, males were bred to nontreated females. Litter size, birthweight, bodyweight at 21 or 55 days of age, and organ weights except for thymus were not affected by paternal alcohol ingestion. There was a dose-related decrease in activity at 20 and 24 days of age in an activity chamber and a dose-related decrease in serum testosterone levels at 55 days of age in male offspring sired by alcohol-consuming males. Offspring sired by males consuming the 20% EDC diet also required fewer trials to learn a passive avoidance task and had longer latencies to reach the choice point in a T maze.

Alcohol Drinking↗