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PubMed1989

Maternal thyroid disease and risk of birth defects in offspring: a population-based case-control study.

We investigated the relationship between maternal thyroid disease and the risk of birth defects in offspring using data from a large population-based, case-control study. Cases included 4904 stillborn and liveborn infants with major anomalies diagnosed in the first year of life and born to residents of metropolitan Atlanta between 1968 and 1980. Controls included 3027 normal babies, frequency-matched to cases by race, hospital of birth and quarter of birth. We compared mothers of cases and controls regarding history of physician-diagnosed hypothyroidism and hyperthyroidism before the infant's birth, age at diagnosis of thyroid condition, duration of illness, and intake of thyroid medications before and during pregnancy. Information obtained from maternal interviews was evaluated for concordance with hospital records. We adjusted for potentially confounding factors using conditional logistic regression analysis. Overall, there was no relationship between the risk of total birth defects and history of maternal hypothyroidism (odds ratio (OR) = 1.05, 95% C.I. 0.84-1.31), maternal hyperthyroidism (OR = 1.00, 95% C.I. 0.66-1.53), and intake of thyroid hormone and antithyroid drugs before and during pregnancy. In an analysis of 66 specific birth defects and defect groups, we found two statistically significant associations with hypothyroidism and three with hyperthyroidism which may reflect chance findings. In an evaluation of babies with multiple anomalies, we observed a two-fold increased risk with hypothyroidism but no discernible pattern of defects. The absolute risk of major birth defects in offspring of women with history of hypothyroidism can be estimated as 2.1%, a finding at odds with the 10-20% risk cited in the literature.

Abnormalities, Drug-Induced↗

PubMed1983

Induction of T cell hyporesponsiveness to Bebaru in mice, and abnormalities in the immune responses of progeny of hyporesponsive males.

Non-specific hyporesponsiveness of cytotoxic T cells to alphaviruses and alloantigens was induced in male mice by multiple, large injections, starting at birth, of gamma-inactivated alphavirus, stock-grown in outbred mouse brains. Offspring of matings between 2 out of 17 treated males and normal females also exhibited significant non-specific hyporesponsiveness (in comparison with normal control mice), without prior exposure to gamma-inactivated alphavirus stock.

Alphavirus↗

PubMedDate not supplied

Parotid gland enlargement and female reproductive performance in a Papua New Guinea highland population.

Swelling of the parotid salivary glands is commonly observed among males and females of highland Papua New Guinea. Evidence suggests that the condition is related to the highlanders' high starch consumption in the form of sweet potato. In this paper we regard parotid enlargement as an indicator of high energy intake and test its association with two measures of reproductive performance, the number of live births and living offspring, in a sample of 274 women from Lufa in the Eastern Highlands District of Papua New Guinea. Multiple regression analysis including maternal age showed that parotid enlargement is positively correlated with both measures of reproductive performance. Given that parotid gland enlargement in this population is due to persistent starch consumption, and that the condition represents above average energy intake, these results suggest that increases in energy intake relate to increases in reproductive performance in this sample of highland females.

Adult↗

PubMed1984

Parental determinants of birth weight.

As part of a study on causes of variation in birth weight, questionnaire data on parental measures were related to offspring birth weights recorded in the Medical Birth Registry of Norway. A genetic analysis of parent-offspring covariances in birth weight indicated that about 60% of the variance in birth weight could be explained by effects of fetal genes, while no effects of maternal genes were detectable. Multiple regression analysis showed that height and weight of both parents and maternal smoking status were associated with variation in birth weight. Socioeconomic status, educational attainment and paternal smoking habit had no independent effects. The adult, parental variables could only explain 10% of the variation in mean offspring birth weight.

Birth Weight↗

PubMed2005

Teratogenicity of depleted uranium aerosols: a review from an epidemiological perspective.

BACKGROUND: Depleted uranium is being used increasingly often as a component of munitions in military conflicts. Military personnel, civilians and the DU munitions producers are being exposed to the DU aerosols that are generated. METHODS: We reviewed toxicological data on both natural and depleted uranium. We included peer reviewed studies and gray literature on birth malformations due to natural and depleted uranium. Our approach was to assess the "weight of evidence" with respect to teratogenicity of depleted uranium. RESULTS: Animal studies firmly support the possibility that DU is a teratogen. While the detailed pathways by which environmental DU can be internalized and reach reproductive cells are not yet fully elucidated, again, the evidence supports plausibility. To date, human epidemiological data include case examples, disease registry records, a case-control study and prospective longitudinal studies. DISCUSSION: The two most significant challenges to establishing a causal pathway between (human) parental DU exposure and the birth of offspring with defects are: i) distinguishing the role of DU from that of exposure to other potential teratogens; ii) documentation on the individual level of extent of parental DU exposure. Studies that use biomarkers, none yet reported, can help address the latter challenge. Thoughtful triangulation of the results of multiple studies (epidemiological and other) of DU teratogenicity contributes to disentangling the roles of various potentially teratogenic parental exposures. This paper is just such an endeavor. CONCLUSION: In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU.

Abnormalities, Radiation-Induced↗

PubMed1984

Prenatal exposure to carbon monoxide: learning and memory deficits.

Exposing pregnant rats to carbon monoxide (150 parts per million) produced only minor reductions in the birth weights of the pups and gave no evidence of overt teratogenesis. However, behavioral evaluation of learning and memory processes in a two-way avoidance task suggested a functional deficit in the central nervous system of the exposed offspring. Multiple dependent measures and specific control groups confirmed that this deficit was independent of nonassociative or motivational alterations.

Animals↗

PubMed1994

Sex ratios of the offspring of patients with multiple sclerosis.

The sex ratios (proportions male) of the offspring of both male and female MS patients produced before disease onset are similar, and closely approximate Caucasian live birth sex ratios. The sex ratio of the offspring of male patients sired after disease onset is significantly lower than these values. In contrast, the sex ratio of the offspring born to female patients after disease onset is non-significantly higher. In short, MS patients produce unusual offspring sex ratios only after disease onset. It is suggested here that they do so as a consequence of a stress-induced reduction in testosterone levels in male patients, and possibly a stress-induced increase in testosterone in female patients. In any case, the data suggest that the sex ratios are a consequence of the disease and not a key to its cause(s).

Adult↗

PubMed1992

[Reproductive and developmental toxicity study of suplatast tosilate (IPD-1151T) (4)--Perinatal and postnatal study in rats by oral administration].

In order to assess the effect of suplatast tosilate (IPD-1151T) on pregnancy of the rat, and the post natal development to maturity of the F1 generation, daily doses of 0 (control), 200, 600 and 1800 mg/kg/day were administered orally to female Wistar rats from day 17 of pregnancy to day 21 after delivery. All females were allowed to give birth and rear their young to weaning. F0 dams showed no treatment-related changes in general conditions including the state of delivery or nursing, gestation period, birth rate, or autopsy findings. The dams at 1800 mg/kg/day showed a tendency to reduction in body weight gain and a decrease in food consumption. F1 offspring showed no treatment-related changes in clinical signs on the birth day or during the nursing period, external examination on the birth day, general condition, physical or reflex development, open-field test, water multiple T-maze test, autopsy findings, organ weights, skeletal examination, reproductive ability, or histopathological examination on the reproductive organs of the animals of both sexes that failed to produce pregnancy. The offspring at 1800 mg/kg/day showed a reduction or its tendency in body weight gain. There were no treatment-related changes in any of reproductive parameters of F1 dams including external examination of F2 fetuses. The results suggest that the non-effective dose level of IPD-1151T is 600 and 1800 mg/kg/day for F0 dams in general toxicity and reproductive ability, respectively, and 600 mg/kg/day for F1 offspring in post natal development under the conditions of this study.

Abnormalities, Drug-Induced↗

PubMed2003

Obstetric complications correlate with neurobehavioral and brain structural alterations in young relatives at risk for schizophrenia.

As complications of pregnancy and birth may be important risk factors for the development of schizophrenia, studying the "roots" of schizophrenia in high-risk offspring may better elucidate the interface between biology, environment, and susceptibility to illness. Using magnetic resonance imaging (MRI), neurobehavioral assessments and obstetric histories, we found several significant correlations between these multiple factors, suggesting that birth complications may be a nonspecific etiopathogenic risk factor for psychopathology in young relatives at risk for schizophrenia.

Adolescent↗

PubMed1996

Birth weight and cardiovascular risk factors in an epidemiological study.

Low birth weight has been proposed as a risk factor for development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease in the adult. To ascertain the extent to which birth weight was associated with cardiovascular risk factors, we examined 620 subjects (median age 48 years) in a cross-sectional study. Of these 317 were offspring of diabetic patients and 303 were offspring of non-diabetic control subjects. Known risk factors for development of cardiovascular disease were correlated to birth weight and examined as dependent variables by multiple linear regression. Age, body mass index (BMI), subjects gender along with parental gender, diabetes status of the parents, and birth weight were independent variables. The variance of the risk factors as dependent variables explained by age, gender, and BMI as independent variables was examined and birth weight was added as an independent variable. We found birth weight was inconsistently correlated to the different risk factors in the different groups of subjects. When adjusted for age, BMI, subject's gender, parental gender, and the diabetes status of the parents, birth weight was negatively correlated to fasting blood glucose. In offspring of diabetic patients the explained variance of risk factors did not change as we added birth weight to the model. In offspring of non-diabetic subjects we found that the explained variance of diastolic blood pressure, fasting blood glucose, HbA1c, and cholesterol increased 1-3% as birth weight was added to the model. We conclude that birth weight may not be a major risk factor for development of hypertension and cardiovascular disease in our population.

Adult↗

PubMed2004

Responsiveness of expectant male cotton-top tamarins, Saguinus oedipus, to mate's pregnancy.

In the cotton-top tamarin, a primate where paternal care is critical to the survival of the offspring, we found that expectant fathers experienced multiple hormonal changes during their mate's pregnancy. Fathers that had experienced several previous births showed significant changes in urinary estrogens, androgens, prolactin and cortisol in the last 2 months before birth, whereas less-experienced fathers (LEF) did not. The female's midpregnancy rise in glucocorticoids was followed within 1-2 weeks by a peak of cortisol and corticosterone in her paired male in 70% of all males and 100% of all experienced males. Examination of behavioral interactions between the pairs did not reveal changes in rates of interactions between the experienced pairs over pregnancy. However, the less-experienced pairs had significantly higher levels of affiliative and sexual interactions. Therefore, behavioral communication between the pair did not appear to account for the hormonal changes occurring within the experienced fathers (EF). The midpregnancy rise of glucocorticoids in females may stimulate a glucocorticoid response in male tamarins and thereby activate other hormonal changes in males to prepare them for their parenting role.

Androgens↗

PubMed2001

Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study.

We assessed the relation between febrile illness during pregnancy and cardiac defects in the offspring in a population-based case-control study in metropolitan Atlanta. Case infants (905) with cardiac defects were actively ascertained from multiple sources. Control infants (3,029) were infants without birth defects who were selected from birth certificates by stratified random sampling. We compared those whose mothers reported febrile illness from 1 month before pregnancy through the third month of pregnancy with those whose mothers reported no illness during the same period. Febrile illness was positively associated with the occurrence of heart defects in the offspring (odds ratio [OR] = 1.8; 95% confidence interval = 1.4-2.4). When influenzalike illness was the reported febrile illness, the OR was 2.1 (95% confidence interval = 0.8-5.5). The association with febrile illness was strongest for tricuspid atresia (OR = 5.2), left obstructive defects (OR = 2.7), transposition of the great arteries (OR = 1.9), and ventricular septal defects (OR = 1.8). These ORs were generally lower among mothers who used multivitamins during the periconceptional period.

Adolescent↗

PubMedDate not supplied

Aging unmasks adverse effects of gestational exposure to methylmercury in rats.

The consequences of developmental exposure to methylmercury on behavior in aged animals were investigated. Methylmercury exposure was arranged by placing 0, 0.5 or 6.4 ppm Hg in the drinking water of female rats at least 4 weeks before mating and continuing until post-natal (PN) day 16. Brain Hg concentrations in cohorts of low- and high-dose offspring were 0.5 and 9.1 ppm at birth and 0.04 and 0. 52 ppm at weaning (described in another report). Lever pressing of female offspring was maintained under a Multiple Differential Reinforcement of High Rate 9:4 Extinction schedule of food reinforcement (Mult DRH 9:4 EXT). Under the DRH 9:4 schedule, a food reinforcer was delivered when nine responses occurred within 4 s. Under the Extinction schedule, responding had no programmed consequences. No exposure-related differences in reinforcement rate under the DRH schedule or discrimination between the DRH and extinction components were apparent initially. At 950 days of age, the overall response rates of controls had shown a gradual decline over the previous 500 days to about 80% of their beginning levels, but, otherwise, most controls were healthy. A gradual decline in the reinforcement rate began to appear in low- and high-dose rats at about 500 and 800 days of age, respectively. Microanalyses of the nine-response burst maintained by the DRH schedule revealed that the lever-press duration increased, the inter-response time (IRT) was unaffected, and the time between response bursts increased. Overall, the nine-response burst remained intact as a coherent response unit. The increased time between response bursts caused the decline in reinforcement rate. All rats displayed these effects as they aged, but the mercury-exposed rats did so sooner.

Aging↗

PubMed1997

Transplacental effects of 3'-azido-2',3'-dideoxythymidine (AZT): tumorigenicity in mice and genotoxicity in mice and monkeys.

BACKGROUND: When given during pregnancy, the drug 3'-azido-2',3'-dideoxythymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed the transplacental tumorigenic and genotoxic effects of AZT in the offspring of CD-1 mice and Erythrocebus patas monkeys given AZT orally during pregnancy. METHODS: Pregnant mice were given daily doses of either 12.5 or 25.0 mg AZT on days 12 through 18 of gestation (last 37% of gestation period). Pregnant monkeys were given a daily dose of 10.0 mg AZT 5 days a week for the last 9.5-10 weeks of gestation (final 41%-43% of gestation period). AZT incorporation into nuclear and mitochondrial DNA and the length of chromosomal end (telomere) DNA were examined in multiple tissues of newborn mice and fetal monkeys. Additional mice were followed from birth and received no further treatment until subjected to necropsy and complete pathologic examination at 1 year of age. An anti-AZT radioimmunoassay was used to monitor AZT incorporation into DNA. RESULTS: At 1 year of age, the offspring of AZT-treated mice exhibited statistically significant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice and monkeys. Shorter chromosomal telomeres were detected in liver and brain tissues from most AZT-exposed newborn mice but not in tissues from fetal monkeys. CONCLUSIONS: AZT is genotoxic in fetal mice and monkeys and is a moderately strong transplacental carcinogen in mice examined at 1 year of age. Careful long-term follow-up of AZT-exposed children would seem to be appropriate.

Animals↗

PubMed1997

Teratologic evaluation of 178 infants born to mothers who attempted suicide by drugs during pregnancy.

OBJECTIVE: To identify the teratogenic risk of large doses of various drugs taken by women in attempting suicide. METHODS: This population-based, prospective, epidemiologic study involved 559 women with pregnancy verified by a serum pregnancy test who were admitted to the toxicologic inpatient clinic in Budapest responsible for providing health services to chemically poisoned individuals from a population of 3 million. Each self-poisoned woman was matched for age and gestational age with a control selected from among participants in periconceptional care. RESULTS: Two of 559 self-poisoned pregnant women died. One hundred seventy-eight infants born to mothers who poisoned themselves during pregnancy either were examined personally or had appropriate medical data available. After excluding eight infants with fetal alcohol syndrome born to heavy-drinking mothers, the rate of congenital abnormalities in study infants (9.0%) did not significantly exceed the rate of control infants (6.1%). Thus, no teratogenic effect of drugs used for self-poisoning could be identified, even though large doses of drugs were used in 27 cases between the 3rd and 8th weeks of fetal development. This sample was not large enough to evaluate single drugs separately. CONCLUSION: Drugs taken by women in attempting suicide do not seem to pose a risk for structural birth defects in the offspring.

Abnormalities, Drug-Induced↗

PubMed2006

Parental investment, late reproduction, and increased reserve capacity are associated with longevity in humans.

Throughout the living world trade-offs between reproductive success and longevity have been observed. In general, two extremes of life history patterning are reported, r- and K-selected species. The latter tend toward larger body sizes, few offspring from any one pregnancy, few offspring over the female reproductive span, longer life spans, and greater parental investment (PI: all efforts and expenses associated with the production, gestation, post-natal care, feeding, and protection of young) (e.g., whales, elephants, hominids). r-selected species tend toward smaller body size, multiple births/litters per pregnancy, female production of many gametes and offspring over the life span, and low levels of PI (e.g., most plants, insects, mice). These differences have significant influences on physiological variation among human populations. Across human samples, reproductive success (RS: the number of offspring successfully birthed and reared to reproductive age) has been reported to vary positively, negatively, and not at all with longevity of women. This complexity may be in part due to the fact that both early-life and late-life fecundity are associated with longevity in women, while total parity seems a poor gauge of female longevity in humankind. Large variations in associations of RS with longevity in women suggest that multiple factors may confound this association. One confounding factor is that among women, RS is largely determined not by fecundity, but by the quality of PI available to offspring. Among modern humans, PI is more complex, longer lasting (both relatively and absolutely), and extensive than for any other mammal. This suggests that modern human life history is a reflection of the co-evolution of longevity and extensive PI as part of our species' biocultural evolution. The need for long-term PI has greatly shaped human physiological variation and patterns of longevity.

Adolescent↗

PubMed2006

No association between periconceptional multivitamin supplementation and risk of multiple congenital abnormalities: a population-based case-control study.

Two previous Hungarian intervention trials showed that periconceptional folic acid-containing multivitamin supplementation did not change the total (birth + fetal) prevalence of cases with multiple congenital abnormalities (MCAs). However, two US observational studies found an elevated risk for MCAs in the offspring of women who reported periconceptional use of multivitamins containing folic acid. These conflicting results stimulated us to evaluate the data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities and to check the possible association between the use of periconceptional multivitamin supplementations and the total prevalence of cases with MCAs. Of 1,349 cases with MCA, 69 (5.1%) had mothers who used multivitamins during the second and third month of pregnancy. Of 2,405 matched controls without any defect, 126 (5.2%) had mothers who used multivitamin supplementation in early pregnancy. Of 21,494 malformed controls with isolated congenital abnormalities, 1,052 (4.9%) mothers received supplementation with multivitamins during the critical period of CAs including MCAs. There was no difference in the use of multivitamins among the study groups either in the total data set or at the evaluation of only prospective medically recorded data. Medically recorded folic acid use without any multivitamins in the second and third gestational month showed some protective effect for MCAs. In conclusion, our observational case-control study did not detect a folic acid containing multivitamins during the early pregnancy as a risk factor for MCAs.

Abnormalities, Multiple↗

PubMed2006

Coeliac disease in the father and risk of adverse pregnancy outcome: a population-based cohort study.

OBJECTIVE: The risk of adverse foetal outcomes was investigated in offspring to men with coeliac disease (CD) diagnosed prior to infant birth and in offspring to men who did not receive a diagnosis of CD until after the delivery. MATERIAL AND METHODS: A cohort study was based on national registry data restricted to women aged 15-44 years with singleton live-born infants, with linkage between the Swedish national birth registry (1973-2001) and the national inpatient registry (1964-2001). A total of 1059 offspring to men who had received a diagnosis of CD were included: 554 offspring to men diagnosed prior to birth and 505 offspring to men diagnosed after infant birth. RESULTS: Undiagnosed CD in the father was associated with an increased risk of caesarean section (adjusted odds ratio (AOR)=1.83; 95% confidence interval (CI) for AOR=1.13-2.95; p=0.014) but was otherwise not linked to adverse pregnancy outcome: (intrauterine growth retardation (OR=1.37; 95% CI=0.91-2.07), low birth-weight (OR=1.41; 95% CI=0.93-2.12), very low birth-weight (OR=1.21; 95% CI=0.39-3.77), preterm birth (OR=1.10; 95% CI=0.74-1.62), and very preterm (OR=0.62; 95% CI=0.09-4.40)). A paternal diagnosis of CD made before infant birth was not associated with adverse foetal outcome. CONCLUSIONS: CD in the father is not a risk factor for unfavourable foetal outcome. The increased risk for caesarean section in offspring to men with undiagnosed CD in this study may be due to multiple comparisons.

Adolescent↗