Maternal exposure to ambient temperature and the risk of preterm birth and stillbirth in Brisbane, Australia

Almost 10% of all births are preterm and 2.2% are stillbirths globally. Recent research has suggested that environmental factors may be a contributory cause to these adverse birth outcomes. The authors examined the relationship between ambient temperature and preterm birth and stillbirth in Brisbane, Australia between 2005 and 2009 (n = 101,870). They used a Cox proportional hazard model with live birth and stillbirth as competing risks. They also examined if there were periods of the pregnancy where exposure to high temperatures had a greater effect. Exposure to higher ambient temperatures during pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12 °C relative to the reference temperature at 21 °C. The temperature effect was greatest for fetuses of less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for live birth was 0.96 at 15 °C and 1.02 at 25 °C. This effect was greatest at later gestational ages. The results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestations.

Maternal exposure to heatwave and preterm birth in Brisbane, Australia

Objective To quantify the short-term effects of maternal exposure to heatwave on preterm birth. Design An ecological study. Setting: A population-based study in Brisbane, Australia. Population All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000–2010 were studied. Methods Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Main outcome measure Spontaneous preterm births. Results The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03–1.24) to 2.00 (95% CI 1.37–2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Conclusions Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses.

Assessment of the effects of maternal exposure to heatwave on birth outcomes in Brisbane, Australia

Even though heatwave events have become more frequent and intense in most regions around the world, little is known about the impact of heatwave on birth outcomes. This thesis uses a population-based study design to investigate the relationship between maternal heatwave exposure and adverse birth outcomes in Brisbane, Australia. This study found that heatwave exposure at any stage of pregnancy can be harmful to fetal growth, and further increase the risk of adverse birth outcomes. Both short- and long-term effects of heatwave on adverse birth outcomes were found. The findings in this thesis may have significant public health implications.

Maternal exposure to aqueous extract of Jacaranda decurrens: Effects on reproductive system in male rats

Context: Jacaranda decurrens subsp. symmetrifoliolata Farias & Proenca (Bignoniaceae) is a species widely used for their medicinal properties. At least to our known, no study has been conducted concerning its toxicological profile after gestational and lactational exposure.Objective: The present study was carried out to evaluate the effects of J. decurrens on development of the reproductive system in male rats.Materials and methods: Pregnant rats were treated daily (gavage) with 250 or 500 mg/kg/day of aqueous extract of J. decurrens or vehicle, from day 12 of pregnancy to day 21 of lactation.Results and Discussion: Both doses of J. decurrens significantly anticipated (p < 0.05) the age of testicular descent to the scrotum, a parameter indicative of puberty initiation. Furthermore, at puberty, there was a significant reduction (p < 0.05) in testicular and epididymis weights in the offspring exposed to the higher dose of extract, without effect on sperm production and the histology of reproductive organs. on the other hand, at adulthood, the reproductive parameters analyzed did not differ among groups.Conclusions: J. decurrens, in this experimental model, interfered with the initial development of the reproductive system, but without lasting effects on sperm production in adulthood.

Effects of maternal exposure to an aromatase inhibitor on sexual behaviour and neurochemical and endocrine aspects of adult male rat

The present study examined the effects of letrozole exposure during brain sexual differentiation on endocrine, behavioural and neurochemical parameters in male rat descendants. Pregnant female rats received 1 mg kg(-1) day(-1) letrozole or vehicle by oral gavage on gestational Days 21 and 22. Exposure to letrozole reduced anogenital distance in males on postnatal Day (PND) 22. At adulthood (PND 75), plasma testosterone levels and hypothalamic dopaminergic activity were increased, but sexual competence was impaired, because fewer successful sexual behaviours (mount, intromission and principally ejaculation) were observed. The impairment of reproductive function by prenatal exposure to an aromatase inhibitor reinforces the importance of adequate oestrogenic activity during perinatal sexual differentiation for complete masculinisation of the hypothalamus.

Effects of maternal exposure to the galactagogue Sulpiride on reproductive parameters in female rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Safety assessment of after maternal exposure on male reproductive parameters in rats

Context: Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. Objective: This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Materials and methods: Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Results and discussion: Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. Conclusion: These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.

Maternal exposure to picrotoxin modifies the response of the GABA(A) receptor during sexual behavior of adult male rat offspring

This study investigated whether perinatal exposure to picrotoxin, a GABA(A) antagonist, modifies the effect of muscimol, a GABA(A) agonist, on the sexual behavior of adult male rats. Two hours after birth and then once daily during the next 9 days of lactation, dams received picrotoxin (0.75 mg/kg subcutaneously) or saline (1 ml/kg subcutaneously). The adult male offspring from the picrotoxin and saline groups received saline (1 ml/kg intraperitoneally) or muscimol (1 mg/kg intraperitoneally), and 15 min later, their sexual behavior was assessed. Muscimol treatment in the saline-exposed group increased the mount and intromission latencies. However, these effects were absent in the picrotoxin-exposed groups. The latencies to first ejaculation, postejaculatory mount, and intromission were decreased in both picrotoxin-exposed groups relative to the saline-exposed groups. The picrotoxin + muscimol-treated rats required more intromissions to ejaculate and the picrotoxin-exposed groups made more ejaculations than the saline-exposed groups. Thus, muscimol treatment did not increase the mount and intromission latencies following picrotoxin exposure, but increased the ejaculation frequency, which did not differ between the picrotoxin + muscimol and the picrotoxin + saline groups. These data indicate that perinatal picrotoxin treatment interfered with GABA(A) receptor development Behavioural Pharmacology 23:703-709 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Maternal exposure to hazardous air pollutants and oral clefts among offspring: Texas, 1999-2008

Birth defects are a leading cause of infant mortality in the United States. About one in 33 births in the United States is diagnosed with birth defects. Common birth defects include neural tube defects, Down syndrome and oral clefts. The present study focused on oral clefts. ^ Oral clefts refer to the malformation of lip, mouth or both. Birth prevalence of oral clefts in Texas is about 11 per 10,000 births. Etiologically, oral clefts have been classified into two groups, cleft lip with or without cleft palate (CL±P) and isolated cleft palate (CP). In spite of their high prevalence and clinical significance, the etiology of oral clefts in humans has not been well understood. Though a number of risk factors have been identified in epidemiological studies, most of them do not explain the majority of the cases. The need to identify novel risk factors associated with oral clefts provided the motivation for this study. The present study focused on maternal exposure to several hazardous air pollutants. A common subgroup of hazardous air pollutants is the volatile organic compounds found in petroleum derivatives. Four important hydrocarbons in this group are benzene, toluene, ethyl benzene and xylenes (BTEX). ^ The specific aim of this study was to evaluate the association between maternal exposure to environmental levels of BTEX and oral clefts among offspring in Texas for the period 1999-2008. ^ A case-control study design was used to assess if maternal exposure to BTEX increased the risk of oral clefts. The Texas Birth Defects Registry provided data on cases of non-syndromic oral clefts delivered in Texas during the period 1999-2008. Census tract level maternal exposure to BTEX concentrations were obtained from the Hazardous Air Pollutant Exposure Model (HAPEM) developed by the U.S. Environmental Protection Agency. Unconditional logistic regression was used to assess the relationship between maternal exposure to BTEX levels and risk of oral clefts in offspring. ^ In the selected population, mothers who had high estimated exposure to any of the BTEX compounds were not more likely to deliver an offspring with oral clefts. Future research efforts will focus on additional birth defects and thorough assessment of additional potential confounders.^

Peri-conceptional changes in maternal exposure to sewage sludge chemicals disturbs fetal thyroid gland development in sheep

Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chronic effects of water-borne PFOS exposure on growth, survival and hepatotoxicity in zebrafish: A partial life-cycle test

Perfluorooctane sulfonate (PFOS) is widely distributed and persistent in the environment and wildlife. The main aim of this study was to investigate the impact of long-term exposure to low concentrations of PFOS in zebrafish. Zebrafish fry (F-0, 14d post-fertilization, dpf) were exposed via the water for 70d to 0 (control), 10, 50 and 250 mu g L-1 PFOS, followed by a further 30d to assess recovery in clean water. The effects on survival and growth parameters and liver histopathology were assessed. Although growth suppression (weight and length) was observed in fish treated with high concentrations PFOS during the exposure period, no mortality was observed throughout the 70d experiment. Embryos and larvae (F-1) derived from maternal exposure suffered malformation and mortality. Exposure to 50 and 250 mu g L-1 PFOS could inhibit the growth of the gonads (GSI) in the female zebrafish. Histopathological alterations, primary with lipid droplets accumulation, were most prominently seen in the liver of males and the changes were not reversible, even after the fish were allowed to recover for 30d in clean water. The triiodothyronine (T-3)) levels were not significantly changed in any of the exposure groups. Hepatic vitellogenin (VTG) gene expression was significantly up-regulated in both male and female zebrafish, but the sex ratio was not altered. The overall results suggested that lower concentrations of PFOS in maternal exposure could result in offspring deformation and mortality. (c) 2008 Elsevier Ltd. All rights reserved.

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia

BACKGROUND: Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.

METHODS: We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip.

RESULTS: AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate < 0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-related genes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified.

CONCLUSIONS: This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development.

Maternal Western Style Diet Increases Susceptibility to Chemically-Induced Mammary Carcinogenesis in Female Rats Offspring

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The exposure to Trichilia catigua (catuaba) crude extract impairs fertility of adult female rats but does not cause reproductive damage to male offspring

Ethnopharmacological relevance: Trichilia catigua is broadly used in folk medicine due to its mental and physical tonic activities and stimulant effects. In animal models, its antidepressant-like effects have been associated with the dopaminergic (DA) system modulation, which has an important role on maternal behavior and male offspring reproductive development.Aim of the study: Since little is known about the adverse effects of the exposure to T. catigua crude extract (CAT) in rats, specially regarding maternal homeostasis and offspring development, the aim of the present study was to evaluate whether CAT exposure may influence maternal toxicity parameters and behavior or disrupt male offspring physical and reproductive development.Material and methods: Dams were treated daily (by gavage) with 400 mg/kg of CAT or vehicle (control=CTR) throughout pregnancy and lactation. Fertility and maternal behavior tests were conducted in dams. Male offspring reproductive and behavioral parameters were analyzed.Results: Dams exposed to CAT showed increased pre- and post-implantation losses rates when compared to CTR group. No significant changes regarding maternal behavior or male offspring parameters were observed.Conclusion: In conclusion, maternal exposure to CAT interfered with implantation during the initial phases of pregnancy but did not induce changes on maternal behavior or male offspring reproductive and behavioral parameters.

Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.