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Maternal Exposure (maternal + exposure)

Distribution by Scientific Domains

Medical Sciences	42%
Life Sciences	42%

Selected Abstracts

Maternal exposure to first-trimester sunshine is associated with increased birth weight in human infants

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2004
Karen Tustin
Abstract Two alternative hypotheses have been generated to account for seasonal variation in the birth weight of human infants born in industrialized countries. First, it has been hypothesized that low ambient temperature during the second trimester of gestation decreases birth weight. Second, it has been hypothesized that exposure to bright sunshine during the first trimester increases birth weight. We tested these two hypotheses to determine which, if either, accounted for seasonal variation in birth weight of full-term infants. Birth weight data, collected over a 5-year period, were analyzed as a function of peak and trough sunshine and ambient temperature. Although there was no effect of ambient temperature during any trimester on birth weight, infants whose mothers were exposed to peak sunshine during their first trimester were born significantly heavier than infants whose mothers experienced trough levels of sunshine during the same trimester. Furthermore, infants whose mothers were exposed to trough levels of sunshine during their second and third trimesters were born significantly heavier than infants whose mothers were exposed to peak levels of sunshine during the same trimesters. We hypothesize that high levels of sunshine during early gestation may increase the level of insulin-like growth factor (IGF)-1, facilitating prenatal growth. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 45: 221,230, 2004. [source]

Relationships between air pollution and preterm birth in California

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2006
Mary Huynh
Summary Air pollution from vehicular emissions and other combustion sources is related to cardiovascular and respiratory outcomes. However, few studies have investigated the relationship between air pollution and preterm birth, a primary cause of infant mortality and morbidity. This analysis examined the effect of fine particulate matter (PM2.5) and carbon monoxide (CO) on preterm birth in a matched case,control study. PM2.5 and CO monitoring data from the California Air Resources Board were linked to California birth certificate data for singletons born in 1999,2000. Each birth was mapped to the closest PM monitor within 5 miles of the home address. County-level CO measures were utilised to increase sample size and maintain a representative population. After exclusion of implausible birthweight,gestation combinations, preterm birth was defined as birth occurring between 24 and 36 weeks' gestation. Each of the 10 673 preterm cases was matched to three controls of term (39,44 weeks) gestation with a similar date of last menstrual period. Based on the case's gestational age, CO and PM2.5 exposures were calculated for total pregnancy, first month of pregnancy, and last 2 weeks of pregnancy. Exposures were divided into quartiles; the lowest quartile was the reference. Because of the matched design, conditional logistic regression was used to adjust for maternal race/ethnicity, age, parity, marital status and education. High total pregnancy PM2.5 exposure was associated with a small effect on preterm birth, after adjustment for maternal factors (adjusted odds ratio [AOR] = 1.15, [95% CI 1.07, 1.24]). The odds ratio did not change after adjustment for CO. Results were similar for PM2.5 exposure during the first month of pregnancy (AOR = 1.21, 95% CI [1.12, 1.30]) and the last 2 weeks of pregnancy (AOR = 1.17, 95% CI [1.09, 1.27]). Conversely, CO exposure at any time during pregnancy was not associated with preterm birth (AORs from 0.95 to 1.00). Maternal exposure to PM2.5, but not CO, is associated with preterm birth. This analysis did not show differences by timing of exposure, although more detailed examination may be needed. [source]

Parental exposure to lead and small for gestational age births

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 6 2006
Pau-Chung Chen MD
Abstract 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 µg/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. Am. J. Ind. Med. 2006. © 2006 Wiley-Liss, Inc. [source]

Altered localization of gene expression in both ectoderm and mesoderm is associated with a murine strain difference in retinoic acid,induced forelimb ectrodactyly,

BIRTH DEFECTS RESEARCH, Issue 6 2007
Hirohito Shimizu
Abstract BACKGROUND: Defects in digit number or fusion as a teratogenic response are well documented in humans and intensively studied in various mouse models. Maternal exposure to excess levels of all- trans -retinoic acid (RA) at gestational day 9.5 induces postaxial ectrodactyly (digit loss) in the murine C57BL/6N strain but not in the SWV/Fnn strain. METHODS: Whole-mount in situ hybridization was used to examine the differential expression of limb patterning genes at the transcriptional level between the two mouse strains following the maternal exposure to a teratogenic level of RA. The detection of a gene with altered expression was followed by either the evaluation of other genes that were synexpressed or with an assessment of downstream genes. RESULTS: In the C57BL/6N limb bud following maternal RA administration, gene-specific perturbations were observed within hours of the RA injection in the posterior pre-AER (apical ectodermal ridge) (Fgf8, Dlx3, Bmp4, Sp8, but not Dlx2 or p63), whereas these genes were normally expressed in the SWV/Fnn limb bud. Furthermore, although RA caused comparable reductions of Shh expression between the strains in the 12 h after administration, some Shh downstream genes were differentially expressed (e.g., Gli1, Ptc, and Hoxd13), whereas others were not (e.g., Fgf4, Bmp4, and Gremlin). CONCLUSIONS: It is proposed that altered gene expression in both pre-AER and mesoderm is involved in the pathogenesis of postaxial digit loss, and that because the alterations in the pre-AER occur relatively early in the temporal sequence of events, those changes are candidates for an initiating factor in the malformation. Birth Defects Research (Part A) 2007. © 2007 Wiley-Liss, Inc. [source]

In utero exposure to female hormones and germ cell tumors in children,

CANCER, Issue 5 2006
M.P.H., Sadhna Shankar M.D.
Abstract BACKGROUND Maternal exposure to exogenous female hormones during pregnancy has been implicated as a risk factor for malignant germ cell tumors (GCTs) in the offspring in some epidemiologic studies of testicular and ovarian carcinoma in adults. METHODS From 1996 to 2002, 278 children younger than 15 years of age with malignant GCTs and 423 healthy controls, frequency-matched for geographic location, age, and sex were enrolled in a case,control study to investigate whether in utero exposure to female hormones is associated with the risk of malignant GCT in children. Cases were recruited from 84 institutions in the U.S. and controls were enrolled through random digit dialing. Information was obtained through telephone interview with the biological mothers of the subjects and through blinded review of the mothers' medical records. RESULTS Neither self-reported (odds ratio [OR] = 1.15; 95% confidence interval [CI], 0.63, 2.12) nor medical chart based (OR = 1.14; 95% CI, 0.75, 1.73) maternal exposure to exogenous female hormones was related to malignant GCT risk. Pregnancy-related conditions that may have altered serum levels of circulating female hormones were also unrelated to the risk of GCT in the offspring. CONCLUSION This study failed to provide strong evidence to support the hypothesis that maternal exposure to exogenous female hormones during pregnancy increases the risk of GCT in the offspring. Cancer 2006. © 2006 American Cancer Society. [source]

Antiandrogenic effects of dibutyl phthalate and its metabolite, monobutyl phthalate, in rats

CONGENITAL ANOMALIES, Issue 4 2002
Makoto Ema
ABSTRACT, Developmental toxicity following administration of dibutyl phthalate (DBF) and its major metabolite, monobutyl phthalate (MBuP), by gavage was determined in Wistar rats. DBF on days 0,8 of pregnancy induced an increase in the incidence of preimplantation loss at 1250 mg/kg and higher and postimplantation loss at 750 mg/kg and higher. MBuP on days 0,8 of pregnancy produced an increase in the incidence of pre-and postimplantation loss at 1000 mg/kg. DBF on days 7,15 of pregnancy caused an increase in the incidence of fetuses with malformations at 750 mg/kg. MBuP on days 7,15 of pregnancy produced an increased incidence of fetuses with malformations at 500 mg/kg and higher. DBF on days 15,17 of pregnancy resulted in a decrease in the anogenital distance (AGD) of male fetuses and increase in the incidence of fetuses with undescended testes at 500 mg/kg and higher. MBuP on days 15,17 of pregnancy caused a decreased male AGD and increased incidence of fetuses with undescended testes at 250 mg/kg and higher. No effect of DBF and MBuP on the AGD was found in female offspring. The spectrum of fetal malformations, dependence of gestational days of treatment on the manifestation of teratogenicity, and alterations in development of the male reproductive system observed after administration of DBF were in good agreement with those observed after administration of MBuP. These findings suggest that MBuP may be responsible for the induction of developmental toxic effects of DBP. The doses that produced a decrease in the AGD and undescended testes in male offspring were lower than those producing maternal toxicity, fetal malformations after administration during major organogenesis, and embryonic loss. The male reproductive system may be more susceptible than other organ systems to DBP and MBuP toxicity after maternal exposure. [source]

Maternal anesthesia via isoflurane or ether differentially affects pre-and postnatal behavior in rat offspring

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 7 2007
April E. Ronca
Abstract Our understanding of prenatal behavior has been significantly advanced by techniques for direct observation and manipulation of unanesthetized, behaving rodent fetuses with intact umbilical connections to the mother. These techniques involve brief administration of an inhalant anesthesic, enabling spinal transection of the rat or mouse dam, after which procedures can continue with unanesthetized dams and fetuses. Because anesthetics administered to the mother can cross the placental barrier, it is possible that fetuses are anesthetized to varying degrees. We compared in perinatal rats the effects of prenatal maternal exposure to two inhalant anesthetics: ether and isoflurane. Fewer spontaneous fetal movements and first postpartum nipple attachments were observed following maternal exposure to ether as compared to isoflurane. Neonatal breathing frequencies and oxygenation did not account for group differences in nipple attachment. Our results provide evidence that the particular inhalant anesthetic employed in prenatal manipulation studies determines frequencies of perinatal behavior. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 675,684, 2007. [source]

Postnatal stress in mice: Does "stressing" the mother have the same effect as "stressing" the pups?

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2004
A. Moles
Abstract Short- and long-term effects of brief maternal separation, maternal exposure to novel male odor, and standard rearing were compared in NMRI mice. The first condition consisted of 15 min of daily exposure of pups to clean bedding (CB), and the second condition consisted of 15 min of mothers' exposure to the odor of strange males (SM), for 14 days after birth starting from postnatal Day 1. Thus, both conditions entailed the same period of maternal separation. A control mother,offspring group was left undisturbed (nonhandled, N-H). Corticosterone levels of mothers and pups were measured at the end of the last manipulation session. Corticosterone levels were higher in SM mothers, differing from both those of CB and of control dams; CB pups showed the highest corticosterone levels in comparison with the pups belonging to the other groups. Maternal behavior observed as furthest as possible from the daily separation session did not differ among the three groups. The behavioral response to 0.5 mg/kg of apomorphine in 15-day-old pups was enhanced in both CB and SM animals, which suggests an alteration of dopaminergic functioning. Finally, adult CB and SM male mice showed an increase in the percentage of time and entries into the open arms of the plus-maze in comparison to nonhandled males. This study indicates that exposure to ecologically relevant stimuli elicited a stress response in lactating dams. This "social stress" brings about short- and long-term effects in the offspring, even in the absence of any direct manipulation of the pups. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 44: 230,237, 2004. [source]

Perinatal exposure to bisphenol-A changes N -methyl- D -aspartate receptor expression in the hippocampus of male rat offspring

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010
Xiao-Hong Xu
Abstract Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters with mixed estrogen agonist/antagonist properties. The toxicity of BPA has been extensively evaluated in a variety of tests in rodents, including developmental and reproductive toxicity, and carcinogenicity. The objective of the present study is to evaluate whether or not perinatal maternal exposure to BPA at 0.05, 0.5, 5, 50, and 200 mg/kg/d affects N -methyl- D -aspartate (NMDA) receptor (NMDAR) subunits NR1, NR2A, 2B, estrogen receptor beta (ER,), and aromatase cytochrome P450 (P450arom) protein expressions of hippocampus in male rat offspring during postnatal development. Western-blotting analyses showed that perinatal exposure to BPA significantly affected the expression of NMDAR subunits. At the lower doses of 0.05 to 50 mg/kg/d, BPA concentration dependently inhibited the expression of NMDAR subunits. However, at the higher dose (200 mg/kg/d), the effects of BPA on these subunits were different, with a stronger inhibition of NR1 expression and a slighter inhibition of NR2A, 2B expression when compared with those at the lower dosage of BPA. In addition, perinatal exposure to BPA inhibited the expression of ER, protein, but increased P450arom protein expression in a concentration-dependent manner, especially during the early postnatal period (the first 1,3 postnatal weeks). No significant influence of BPA on P450arom was observed at postnatal week 8. These data suggest that environmental BPA exposure may affect the development of the brain, enhancing the local biosynthesis of estrogen in the brain, inhibiting ER, and NMDAR expressions. Environ. Toxicol. Chem. 2010;29:176,181. © 2009 SETAC [source]

Effect of maternal exposure to tributyltin on reproduction of the pearl oyster (Pinctada fucata martensii)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2004
Suguru Inoue
Abstract We examined the effect of tributyltin (TBT) on reproduction of the pearl oyster (Pinctada fucata martensii). In a maternal exposure test, five female pearl oysters were exposed to TBT at measured concentrations of 0 (control), 0.092, or 0.191 ,g/L at 25°C for one week, and the embryo developmental success (the ratio of normal D-larvae to all larvae) was measured. The embryo developmental success was significantly decreased in the 0.191-,g/L treatment group (65.5%) compared to that in the control group (82.5%; p = 0.031). Concentrations of TBT in the ovary reached 0.088 ,g/g in the 0.191-,g/L treatment group. In a waterborne exposure test, inseminated eggs were exposed to TBT at measured concentrations of 0 (control), 0.020, 0.045, 0.091, 0.192, or 0.374 ,g/L for 24 h. The embryo developmental success also was significantly decreased in the 0.192-,g/L treatment group (78.3%; p = 0.020) and no development at all was observed in the 0.374-,g/L treatment group compared with that in the control group (95.4%). These results clearly demonstrate that TBT accumulating in the bodies of bivalves has the potential to inhibit reproduction. [source]

Alterations of postsynaptic density proteins in the hippocampus of rat offspring from the morphine-addicted mother: Beneficial effect of dextromethorphan

HIPPOCAMPUS, Issue 6 2006
San Nan Yang
Abstract Infants passively exposed to morphine or heroin through their addicted mothers usually develop characteristic withdrawal syndrome of morphine after birth. In such early life, the central nervous system exhibits significant plasticity and can be altered by various prenatal influences, including prenatal morphine exposure. Here we studied the effects of prenatal morphine exposure on postsynaptic density protein 95 (PSD-95), an important cytoskeletal specialization involved in the anchoring of the NMDAR and neuronal nitric oxide synthase (nNOS), of the hippocampal CA1 subregion from young offspring at postnatal day 14 (P14). We also evaluated the therapeutic efficacy of dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic effects on NMDARs, for such offspring. The results revealed that prenatal morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed by an age-dependent improvement. In addition, prenatal morphine exposure reduced not only the expression of nNOS and the phosphorylation of cAMP responsive element-binding protein at serine 133 (CREBSerine-133), but also the magnitude of long-term depression (LTD) at P14. Subsequently, the morphine-treated offspring exhibited impaired performance in long-term learning and memory at later ages (P28,29). Prenatal coadministration of dextromethorphan with morphine during pregnancy and throughout lactation could significantly attenuate the adverse effects as described above. Collectively, the study demonstrates that maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the phosphorylation of CREBSerine-133, and LTD expression in hippocampal CA1 subregion of young offspring (e.g., P14). Such alterations within the developing brain may play a role for subsequent neurological impairments (e.g., impaired performance of long-term learning and memory). The results raise a possibility that postsynaptic density proteins could serve an important role, at least in part, for the neurobiological pathogenesis in offspring from the morphine-addicted mother and provide tentative therapeutic strategy. © 2006 Wiley-Liss, Inc. [source]

Kisspeptin/GPR54 system as potential target for endocrine disruption of reproductive development and function

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010
M. Tena-Sempere
Summary Kisspeptins, the products of Kiss1 gene acting via G protein-coupled receptor 54 (also termed Kiss1R), have recently emerged as essential gatekeepers of puberty onset and fertility. Compelling evidence has now documented that expression and function of hypothalamic Kiss1 system is sensitive not only to the activational effects but also to the organizing actions of sex steroids during critical stages of development. Thus, studies in rodents have demonstrated that early exposures to androgens and oestrogens are crucial for proper sexual differentiation of the patterns of Kiss1 mRNA expression, whereas the actions of oestrogen along puberty are essential for the rise of hypothalamic kisspeptins during this period. This physiological substrate provides the basis for potential endocrine disruption of reproductive maturation and function by xeno-steroids acting on the kisspeptin system. Indeed, inappropriate exposures to synthetic oestrogenic compounds during early critical periods in rodents persistently decreased hypothalamic Kiss1 mRNA levels and kisspeptin fibre density in discrete hypothalamic nuclei, along with altered gonadotropin secretion and/or gonadotropin-releasing hormone neuronal activation. The functional relevance of this phenomenon is stressed by the fact that exogenous kisspeptin was able to rescue defective gonadotropin secretion in oestrogenized animals. Furthermore, early exposures to the environmentally-relevant oestrogen, bisphenol-A, altered the hypothalamic expression of Kiss1/kisspeptin in rats and mice. Likewise, maternal exposure to a complex cocktail of endocrine disruptors has been recently shown to disturb foetal hypothalamic Kiss1 mRNA expression in sheep. As a whole, these data document the sensitivity of Kiss1 system to changes in sex steroid milieu during critical periods of sexual maturation, and strongly suggest that alterations of endogenous kisspeptin tone induced by inappropriate (early) exposures to environmental compounds with sex steroid activity might be mechanistically relevant for disruption of puberty onset and gonadotropin secretion later in life. The potential interaction of xeno-hormones with other environmental modulators (e.g., nutritional state) of the Kiss1 system warrants further investigation. [source]

Maternal pre-eclampsia/eclampsia and the risk of sudden infant death syndrome in offspring

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 2 2000
De-Kun Li
To determine whether maternal exposure to pre-eclampsia/eclampsia during pregnancy increases the risk of sudden infant death syndrome (SIDS) in offspring, we conducted a population-based case,control study using the California linked birth and death certificate data. All infants who died of SIDS (ICD-9 code 798.0) during 1989,91 were identified as cases. More than 96% of the identified SIDS cases were diagnosed through autopsy. Ten controls who did not die from SIDS were randomly selected for each case from the birth certificate matched to the case on the year of birth. Among 2029 cases and 21 037 controls included in the final analysis, mothers of 49 cases (2.4%) and 406 controls (1.9%) had a diagnosis of either pre-eclampsia or eclampsia noted on the birth certificate. After adjustment for maternal age, prenatal smoking, race/ethnicity, parity, maternal education, gestational age at the initial visit for prenatal care, infant year of birth and infant sex, maternal pre-eclampsia/eclampsia during pregnancy was associated with a 50% increased risk of SIDS in the offspring (odds ratio = 1.5, 95% confidence interval 1.1, 2.0). Potential under-reporting of pre-eclampsia/eclampsia on the birth certificates was likely to be non-differential and is unlikely to explain the finding. Fetal hypoxia resulting from pre-eclampsia/eclampsia or immunological aetiology affecting the risk of both pre-eclampsia/eclampsia and SIDS may explain the finding. [source]

Maternal nickel exposure and congenital musculoskeletal defects

AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 11 2008
Vaktskjold Arild DrScient
Abstract Objective To investigate whether women occupationally exposed to nickel in early pregnancy are at elevated risk of delivering a newborn with a malformation or deformation of the musculoskeletal system (ICD-10: Q65-Q79). Methods Data about the newborn, maternal occupation and workplace were obtained using the Kola Birth Register (KBR). Each record in the KBR was assigned a categorical nickel (Ni) exposure rating according to the occupation the delivering woman had at the time of becoming pregnant. This was achieved by using as a guideline the water-soluble Ni subfraction of the inhalable aerosol fraction obtained by personal monitoring for nickel- and copper-refinery workers or/and measured urinary-Ni concentrations. The reference population was delivering women from the source population with background exposure level. In total, the study population consisted of 22,965 births. Results Three hundred and four infants (13.3/1,000 births; 95% confidence interval (CI): 11.9,14.7) were diagnosed with isolated musculoskeletal defect(s) at birth. The adjusted odds ratio for the association between the maternal exposure to Ni and this outcome was 0.96 (95% CI: 0.76,1.21) per unit increase in exposure category. Conclusion The incidence of defects in the musculoskeletal system at birth was high, especially for feet deformities, but we found no effect of maternal exposure to water-soluble Ni on the risk of delivering a newborn with a defect. However, the incidence among women working in the copper refinery was higher than in the other employment groups. Am. J. Ind. Med. 51:825-833, 2008. © 2008 Wiley-Liss, Inc. [source]

Oral cleft defects and maternal exposure to ambient air pollutants in New Jersey,

BIRTH DEFECTS RESEARCH, Issue 4 2010
Elizabeth G. Marshall
BACKGROUND Evidence links exposure to ambient air pollution during pregnancy, particularly gaseous pollutants and particulate matter, to an increased risk of adverse reproductive outcomes though the results for birth defects have been inconsistent. METHODS We compared estimated exposure to ambient air pollutants during early pregnancy among mothers of children with oral cleft defects (cases) to that among mothers of controls, adjusting for available risk factors from birth certificates. We obtained ambient air pollutant data from air monitoring sites in New Jersey for carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), particulate matter <10 ,m in aerodynamic diameter (PM10) and particulate matter <2.5 ,m in aerodynamic diameter (PM2.5). We used values from the nearest monitor (within 40 km of the residence at birth) for controls, cleft lip with or without cleft palate (CLP) and cleft palate only (CPO). RESULTS Based on logistic regression analyses for each contaminant and all contaminants together, there were no consistent elevated associations between selected air pollutants and cleft malformations. Quartile of CO concentration showed a consistent protective association with CPO (p < 0.01). For other contaminants, confidence intervals (95%) of the odds ratios for some quartiles excluded one. CLP showed limited evidence of an association with increasing SO2 exposure while CPO showed weak associations with increasing O3 exposure. CONCLUSION There was little consistent evidence associating cleft malformations with maternal exposure to ambient air pollutants. Evaluating particular pollutants or disease subgroups would require more detailed measurement of exposure and classification of cleft defects. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc. [source]

Fetal alcohol syndrome (FAS) in C57BL/6 mice detected through proteomics screening of the amniotic fluid,

BIRTH DEFECTS RESEARCH, Issue 4 2008
Susmita Datta
Abstract BACKGROUND: Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol-induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high-risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low-risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS-positive and FAS-negative pregnancies. METHODS: B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix-assisted laser desorption,time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods. RESULTS: We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS-positive litters was confirmed by area under the receiver operating characteristic curve. CONCLUSIONS: These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage. Birth Defects Research (Part A), 2008. © 2008 Wiley-Liss, Inc. [source]

Altered localization of gene expression in both ectoderm and mesoderm is associated with a murine strain difference in retinoic acid,induced forelimb ectrodactyly,

First trimester exposure to corticosteroids and oral clefts

BIRTH DEFECTS RESEARCH, Issue 12 2003
Pierre Pradat
BACKGROUND The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database. METHODS The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy. RESULTS After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18,5.67). CONCLUSIONS If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc. [source]

Septo-optic dysplasia as a manifestation of valproic acid embryopathy

BIRTH DEFECTS RESEARCH, Issue 2 2001
Carrie L. McMahon
Background The use of valproic acid during pregnancy has been associated with adverse fetal outcomes, including major and minor congenital malformations, intrauterine growth retardation (IUGR), hyperbilirubinemia, hepatotoxicity, transient hyperglycemia, and fetal and neonatal distress. In addition, intrauterine exposure to valproic acid has been associated with an increased risk of central nervous system abnormalities, primarily neural tube defects. Optic nerve hypoplasia has been reported in association with other prenatal anticonvulsant exposures, but the occurrence of septo-optic dysplasia as a manifestation of valproic acid embryopathy has not been reported previously. Results We report on a woman who received Depakote (valproic acid) throughout her pregnancy for the treatment of a seizure disorder. The patient presented with features typical of valproic acid embryopathy, including bitemporal narrowing, hypertelorism, short palpebral fissures, epicanthal folds, microphthalmia, a flat broad nasal bridge, small mouth, hypoplastic nails, mild clinodactyly, and camptodactyly. MRI showed hypoplasia of the optic chiasm and absence of the septum pellucidum. Conclusions We report the first case of septo-optic dysplasia associated with maternal exposure to valproic acid throughout pregnancy. This case expands the clinical phenotype of valproate embryopathy. Teratology 64:83,86, 2001. © 2001 Wiley-Liss, Inc. [source]

In utero exposure to female hormones and germ cell tumors in children,

Testicular dysgenesis syndrome: foetal origin of adult reproductive problems

CLINICAL ENDOCRINOLOGY, Issue 4 2009
Christine Wohlfahrt-Veje
Summary The evidence for the existence of testicular dysgenesis syndrome (TDS) is presented in this review. Several epidemiological studies have shown that conditions like cryptorchidism, impaired spermatogenesis, hypospadias and testicular cancer can be associated as risk factors for each other. Thus, the risk of testis cancer is significantly increased in men with cryptorchidism and/or infertility. Several recent studies point towards early dysgenesis of the foetal testis as the biological link between these disorders. Dysgenesis has been demonstrated in biopsies of the contralateral testis of men with testis cancer and in infertile men. The histological evidence includes immature seminiferous tubules with undifferentiated Sertoli cells, microliths and Sertoli-cell only tubules. Dysgenetic testes often have an irregular ultrasound pattern, where microliths may also be visible. Our current hypothesis is that maternal exposure to endocrine disrupting chemicals may contribute to the pathogenesis of TDS. Animal experiments have shown that all TDS symptoms, except testicular cancer, can be induced by foetal exposure to anti-androgenic chemicals. However, the cause of TDS in humans remains to be determined. [source]

Epidemiology underpinning research in the aetiology of orofacial clefts,

ORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 3 2007
Peter Mossey
Structured Abstract Author,,, Mossey P Introduction,,, Epidemiological information gathered through birth defects surveillance is an important adjunct to carrying out clinical and aetiological research. Information on the incidence in the population, causative risk factors and providing baseline data prior to intervention are all important elements. Under the auspices of the World Health Organisation, it was agreed that a global registry and database on craniofacial anomalies should be created and this, the International Database on Craniofacial Anomalies (ICDFA) was designed to gather information on craniofacial abnormalities from existing birth defects registries and databases around the world to become a resource underpinning research. There are currently 62 registries covering 2 million births per year contributing to a database along with information on the size and type of studies used to collect the information, any variation in ascertainment and on the inclusion of syndromes and associated abnormalities. Generation of hypotheses,,, From the epidemiological data collected it is possible to carry out meta-analysis and to search for trends and consistencies in the data that enable hypothesis to be generated. Issues such as geographical distribution, ethnicity, gender, associated abnormalities and clefts in stillbirths can all be examined in a meta-analytical approach. Collection of information on risk factors such as maternal illnesses, medications, lifestyle factors, nutrition and perhaps occupational exposures enables investigation into environmental contribution to causality and genetic predisposition. A range of techniques are currently being used to identify new candidate genes and ultimately it will be necessary to test genetic and environmental hypothesis in the context of human population studies. Conclusions,,, It is only by consistency of association between different populations with different gene pools and maternal exposures, lifestyles, nutrition etc that conclusive evidence regarding causality will be found. It is therefore essential, and a major objective of the WHO that international multicentre collaborative studies are setup to gather the appropriate evidence and improve knowledge and the cause of birth defects in general and orofacial clefts in particular, with the ultimate humanitarian and scientific objective of the WHO being primary prevention. Clinical utility and implications,,, This IDCFA project fulfils three basic objectives namely to enable global surveillance of CFA; to create online access to those who wish to contribute to the IDCFA, and to develop an online directory of resources on craniofacial anomalies for the support of research and improving quality of care. The next sttif for IPDTOC are to expand the number of participating registries and to actively collect data on other craniofacial birth defects. [source]

Hypospadias and maternal exposures to cigarette smoke

PAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 6 2005
Suzan L. Carmichael
Summary The few previous studies of hypospadias and smoking have suggested either no association or a reduced risk. This study, which uses data from the National Birth Defects Prevention Study, a multi-state, population-based case,control study, includes data on males born with severe hypospadias (i.e. the urethra opens at the penile shaft, scrotum or perineum) from 1997 to 2000. Non-malformed, liveborn male controls were selected randomly from birth certificates or from birth hospitals. Maternal interviews were completed by telephone with 453 case mothers and 1267 control mothers. Maternal smoking was not associated with hypospadias risk. For example, during the third month of pregnancy, smoking < 0.5 pack/day had an odds ratio (OR) of 1.1 [95% CI 0.6, 1.9]; 0.5 pack/day, 0.6 [0.4, 1.1]; and ,,1 pack/day, 0.8 [0.4, 1.6]. Exposure to any secondhand smoke at home during the third month of pregnancy showed an OR of 0.6 [95% CI 0.4, 1.0], and exposure at work or school, an OR of 0.7 [0.5, 1.1]. Similar risks were observed for other months during the periconceptional period, and adjustment for several potential confounders did not substantially alter results. This analysis does not confirm a recent report suggesting that maternal smoking is associated with a reduced risk of having offspring with hypospadias. [source]

REVIEW ARTICLE: Maternal Transmission of Asthma Risk

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2009
Robert H. Lim
Maternal asthma significantly increases the risk of asthma in offspring, but the mechanisms remain poorly defined. We review animal models used to study the maternal effect, focusing on a murine model developed in our laboratory. Mother mice rendered allergic to ovalbumin produce offspring that are more susceptible to allergic sensitization, seen as airway hyperresponsiveness and allergic airway inflammation after a sensitization protocol, which has minimal effects on newborns from normal mothers. Mechanistic analyses identify a role for interleukin-4 (based on pre-mating injection of neutralizing antibodies), dendritic cells and allergen-specific T cells (based on adoptive transfer experiments). Other maternal exposures (e.g. pollutant exposure and non-pulmonary allergy) can increase asthma susceptibility in offspring. This observation implies that the maternal transmission of asthma represents a final common pathway to various types of inflammatory stimuli. Identification of the shared molecular mechanisms in these models may allow better prevention and therapy. Current knowledge, gaps in knowledge and future directions are discussed. [source]

The effect of fever, febrile illnesses, and heat exposures on the risk of neural tube defects in a Texas-Mexico border population

BIRTH DEFECTS RESEARCH, Issue 10 2004
Lucina Suarez
Abstract BACKGROUND Hyperthermia produces neural tube defects (NTDs) in a variety of animal species. Elevated maternal body temperatures may also place the developing human embryo at risk. We examined the relation between maternal hyperthermia and the development of NTDs in a high-risk Mexican-American population. METHODS Case-women were Mexican-American women with NTD-affected pregnancies who resided and delivered in any of the 14 Texas counties bordering Mexico, during 1995,2000. Control-women were randomly selected from study area residents delivering normal live births, frequency-matched to cases by hospital and year. Information on maternal fevers, febrile illnesses, exposures to heat generated from external sources, and hyperthermia-inducing activities was gathered through in-person interviews, conducted about six weeks postpartum. RESULTS The risk effect (OR) associated with maternal fever in the first trimester, compared to no fever, was 2.9 (95% CI, 1.5,5.7). Women taking fever-reducing medications showed a lower risk effect (OR, 2.4; 95% CI, 1.0,5.6) than those who did not (OR, 3.8; 95% CI, 1.4,10.9). First-trimester maternal exposures to heat devices such as hot tubs, saunas, or electric blankets were associated with an OR of 3.6 (95% CI, 1.1,15.9). Small insignificant effects were observed for activities such as cooking in a hot kitchen (OR, 1.6; 95% CI, 1.0,2.6) and working or exercising in the sun (OR, 1.4; 95% CI, 0.9,2.2). CONCLUSIONS Maternal hyperthermia increases the risk for NTD-affected offspring. Women intending to become pregnant should avoid intense heat exposures, carefully monitor and manage their febrile illnesses, and routinely consume folic acid supplements. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source]

Are influences during pregnancy associated with wheezing phenotypes during the first decade of life?

ACTA PAEDIATRICA, Issue 5 2005
Ramesh J Kurukulaaratchy
Abstract Aim: Recently, attention has focused on possible early life origins for asthma. We sought to identify whether factors present during pregnancy were associated with development of childhood wheezing phenotypes. Methods: A whole population birth cohort (n=1456) on the Isle of Wight, UK, was followed through to age 10 y. Where possible, information regarding environmental exposures and events during pregnancy was obtained from the maternity records (n=1238). Children were seen at ages 1, 2, 4 and 10 y, and wheezing symptoms were used to define wheezing phenotypes in the first decade (n=1034). Results: Risk of early-onsetpersistent wheeze (onset in the first 4 y, still present at age 10) was increased by environmental tobacco smoke exposure in pregnancy (OR=2.44; 95% CI: 1.37,4.34) plus maternal asthma (3.57; 1.84,6.94), but reduced by cat ownership (0.30; 0.13,0.62). Early transient wheeze (onset in the first 4 y, but not present at age 10) was increased by environmental tobacco smoke exposure (1.58; 1.02,2.45), male gender (1.68; 1.09,2.60) and low birthweight (3.65; 1.27,10.52). No environmental factors in pregnancy were associated with late-onset persistent wheeze (onset after age 4 y, still present at 10 y). Conclusion: In addition to genetics, maternal exposures during pregnancy show association with childhood and especially early-life wheezing phenotypes. [source]