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The term fetal alcohol spectrum disorder includes a group of diseases caused by fetal alcohol exposure (FAE). Patients with fetal alcohol spectrum disorder display heterogeneous socioemotional and cognitive deficits, particularly in the domain of executive function, that share symptoms with other neuropsychiatric disorders. Despite the availability of several preclinical models, the developmental brain defects causally linked to behavioral deficits induced by FAE remain poorly understood. Here, we first review the effects of FAE on corticostriatal development and its impact on both corticostriatal pathway function and cognitive abilities. We propose three non–mutually exclusive circuit models of corticostriatal dysfunctions to account for some of the FAE-induced cognitive deficits. One model posits that associative-sensorimotor imbalance causes hyper goal-directed behavior, and a second model implies that alteration of prefrontal-striatal behavioral suppression circuits results in loss of behavioral inhibition. A third model suggests that local striatal circuit deficits affect striatal neuronal ensemble function to impair action selection and performance. Finally, we discuss how preclinical approaches applied to these circuit models could offer potential rescue strategies for executive function deficits in patients with fetal alcohol spectrum disorder.

Profound physiological changes in the maternal cardiovascular system occur shortly after conception. These changes may impact upon the investigation of healthy and complicated pregnancies. Additionally, concerns regarding fetal exposure to ionising radiation are important considerations in maternal testing. This manuscript reviews the important physiological changes pertinent to the investigation of maternal cardiovascular disease in pregnancy.

International audience; OBJECTIVE: To evaluate the effects of ionizing radiation exposure during the first trimester of pregnancy in usual clinical situations.STUDY DESIGN: We conducted a prospective observational cohort study using data collected between 1987 and 2014. This database was authorized by the French "Commission Nationale de l'Informatique et des Libertés". The exposed group consisted of 319 pregnant women exposed to sub diaphragmatic ionizing radiations for diagnostic purposes, during the first trimester of pregnancy, and the control group consisted of 319 pregnant women without any exposure or exposed to non-teratogenic agents. Data on maternal history and radiations exposure were collected on first contact, and pregnancy outcomes were documented at follow-up. An univariate analysis was performed to compare both groups for the main outcomes.RESULTS: Exposure to sub diaphragmatic ionizing radiation for diagnosis purpose (median fetal dose of 3.1 mGy [0.2-130.0]) during the first trimester of pregnancy was not significantly associated with an increased risk of malformations (1.5% vs 1.8%, p = 1.00), miscarriage (7.8% vs 7.2%, p = 0.88), in utero fetal death (0.3% vs 0%, p = 1.00) or fetal growth restriction (5.4% vs 3.5%, p = 0.62).CONCLUSION: Pregnant women exposed to irradiant diagnostic procedures do not present a higher risk of malformations, miscarriage, in utero fetal death or fetal growth restriction and should be reassured, even if the examination focused on the pelvis.

Although the incidence of gastroschisis is increasing, risk factors are not clearly identified.Using the Linked Birth Database from the California Office of Statewide Health Planning and Development from 1995 to 2012, patients with gastroschisis were identified by ICD-9 diagnosis/procedure code or birth certificate designation. Logistic regressions examined demographics, birth factors, and maternal exposures on risk of gastroschisis.The prevalence of gastroschisis was 2.7 cases per 10,000 live births. Patients with gastroschisis had no difference in fetal exposure to alcohol (p = 0.609), narcotics (p = 0.072), hallucinogenics (p = 0.239), or cocaine (p = 0.777), but had higher exposure to unspecified/other noxious substances (OR 3.27, p = 0.040; OR 2.02, p = 0.002). Gastroschisis was associated with low/very low birthweight (OR 5.08-16.21, p 0.001) and preterm birth (OR 3.26-10.0, p 0.001). Multivariable analysis showed lower risk in black (OR 0.44, p 0.001), Asian/Pacific Islander (OR 0.76, p = 0.003), and Hispanic patients (OR 0.72, p 0.001) compared to white patients. Risk was higher in rural areas (OR 1.24-1.76, p = 0.001). Compared to women age 20, risk decreased with advancing maternal age (OR 0.49-OR 0.03, p 0.001). Patients with gastroschisis had increased total charges ($336,270 vs. $9012, p 0.001) and length of stay (38.1 vs. 2.9 days, p 0.001). Mortality was 4.6%.This is the largest population-based study summarizing current epidemiology of gastroschisis in California.Retrospective comparative cohort study.III.

Prenatal exposure to toxic substances is an important public health problem. Many biological specimens obtained from the fetus or mother are used for biomonitoring. Each material reflects exposure in a specific time period and has different advantages and disadvantages in terms of accuracy, time window of detection and cost/benefit ratio. Recently, meconium has become the matrix of choice in toxicology screening for detecting exposure to xenobiotics. Alcohol metabolites and illicit drugs, pharmaceuticals, nicotine, heavy metals, persistent organic pollutants and their metabolites have been detected in meconium samples. Meconium testing is non-invasive, highly accurate and able to detect prior exposure in utero from 12 to 13 weeks of gestation. This paper reviews current studies focused on meconium analysis for the assessment of fetus exposure to xenobiotics. Analytical procedures for the determination of these compounds and their metabolites and the possibilities and limitations of their use in clinical toxicology are also presented and discussed.

Appendix A. Supplementary material: Supplementary data to this article can be found online at https://doi. org/10.1016/j.envint.2021.106904. Copyright © 2021 The Authors. Background: Prenatal exposure to endocrine-disrupting compounds (EDCs) may contribute to endocrine-related diseases and disorders later in life. Nevertheless, data on in utero exposure to these compounds are still scarce. Objectives: We investigated a wide range of known and novel nonpolar EDCs in full-term human amniotic fluid (AF), a representative matrix of direct fetal exposure. Methods: Gas chromatography high-resolution mass spectrometry (GC-HRMS) was used for the targeted and non-targeted analysis of chemicals present in nonpolar AF fractions with dioxin-like, (anti-)androgenic, and (anti-)estrogenic activity. The contribution of detected EDCs to the observed activity was determined based on their relative potencies. The multitude of features detected by non-targeted analysis was tentatively identified through spectra matching and data filtering, and further investigated using curated and freely available sources to predict endocrine activity. Prioritized suspects were purchased and their presence in AF was chemically and biologically confirmed with GC-HRMS and bioassay analysis. Results: Targeted analysis revealed 42 known EDCs in AF including dioxins and furans, polybrominated diphenyl ethers, pesticides, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. Only 30% of dioxin activity and

Recent studies suggest universal fetal exposure to Bisphenol A (BPA) and its association with the adverse birth outcomes. Estimation of the fetal plasma BPA concentration from the maternal plasma BPA would be highly useful to predict its associated risk to this specific population. The objective of current work is to develop a pregnancy-physiologically based pharmacokinetic (P-PBPK) model to predict the toxicokinetic profile of BPA in the fetus during gestational growth, and to evaluate the developed model using biomonitoring data obtained from different pregnancy cohort studies. To achieve this objective, first, the adult PBPK model was developed and validated with the human BPA toxicokinetic data. This validated human PBPK model was extended to develop a P-PBPK model, which included the physiological changes during pregnancy and the fetus sub-model. The developed model would be able to predict the BPA pharmacokinetics (PKs) in both mother and fetus. Transplacental BPA kinetics parameters for this study were taken from the previous pregnant mice study. Both oral and dermal exposure routes were included into the model to simulate total BPA internal exposure. The impact of conjugation and deconjugation of the BPA and its metabolites on fetal PKs was investigated. The developed P-PBPK model was evaluated against the observed BPA concentrations in cord blood, fetus liver and amniotic fluid considering maternal blood concentration as an exposure source. A range of maternal exposure dose for the oral and dermal routes was estimated, so that simulation concentration matched the observed highest and lowest mother plasma concentration in different cohorts' studies. The developed model could be used to address the concerns regarding possible adverse health effects in the fetus being exposed to BPA and might be useful in identifying critical windows of exposure during pregnancy.

Pregnancy is one of the defining characteristics of placental mammals. Key in the growth and development of the fetus during pregnancy are the dynamics of glucocorticoids (GCs) and their binding protein,corticosteroid-binding globulin (CBG), which determines how much of the GCs are free and biologically active. Out of more than 5000 species of placental mammals in 19 different orders, our understanding of the dynamics of maternal GCs and CBG during pregnancy is largely limited to the detailed study of 3 groups - sheep, laboratory rodents, and humans. The assumption is often made that what we see in these few species applies to the rest. To examine this generality, we compared patterns of maternal GCs over pregnancy from all placental mammals where data is available: in the blood of 13 species from 5 different orders and in metabolites in excreta in an additional 20 species from 9 orders. We found that maternal free GCs increase by late pregnancy in most taxa. This increase is achieved by either an increase in total GC secretion or a decrease in CBG. A major exception is found in the even-toed ungulates (sheep, cows, etc.) where maternal GCs and CBG remain stable, but where the fetal adrenals mature in late pregnancy and produce the majority of their own GCs. We conclude that patterns of change in maternal GCs and CBG during pregnancy are species-specific but are alternative means to the same end: increased fetal exposure to GCs in late pregnancy, which is essential for development.

Background and purpose Use of valproate (VPA) in women of childbearing age is restricted due to dose-dependent risk of teratogenicity. The purpose of this study was to characterise pharmacokinetic variability of VPA in pregnancy, and discuss use of therapeutic drug monitoring (TDM) as guidance to exposure in women. Method Measurements of trough total and unbound VPA concentrations before, during and after pregnancy, at assumed steady-state were collected from the TDM-database (2006–2016) at the National Center for Epilepsy in Norway. Additional clinical data were obtained from the Oppland county Perinatal Database (1994–2011). Results Data from 51 pregnancies in 33 women aged 19–40 years were included. Each woman underwent 1–4 pregnancies, and 1–7 measurements per pregnancy were performed. The variability in total concentration/dose (C/D)-ratios between women was 13-fold, and intra-patient variability extensive. Total C/D-ratios were reduced by 46% from before pregnancy to third trimester (0.48–0.29 μmol/L/mg). Unbound concentrations of VPA were only requested in 10% of the pregnancies. Repeated measurements from two pregnancies in one women revealed increased unbound concentration of VPA during pregnancy. There were 19 with idiopathic generalized epilepsy and two focal based on clinical data from 21 women and 38 pregnancies; 1 major congenital malformation was noted. Conclusion There is pronounced pharmacokinetic variability of VPA during pregnancy. Unbound concentrations are rarely requested. TDM should be used by measurements of both total and unbound concentrations since total concentrations may be misleading for efficacy and fetal exposure of VPA.

Misoprostol is often used for termination of pregnancy in France and others countries. However, some pregnancies are continued after taking the drug and congenital malformations are known to be the consequence of fetal exposure to misoprostol, among then hydrocephalus. The type of hydrocephalus in case of misoprostol exposure is not known. We report the first case in the literature of an obstructive hydrocephalus due to an aqueduct of Sylvius stenosis diagnosed during the pregnancy after misoprostol intake. The possible physiopathological implications of the drug are discussed regarding the genesis of this malformation.

The number of nuclear medicine examinations performed worldwide has been steadily increasing over the last few years. By consequence, an ever increasing number of pregnant women are likely to be exposed to radioisotopes. The range of doses encountered in nuclear medicine practice is well below the threshold for deterministic effects, such as embryonic death, birth defects or mental retardation. According to the linear no-threshold hypothesis, however, stochastic effects (e.g. an increased risk of cancer) remain possible even at this dose range. This purely hypothetical radiation risk to the fetus should however be put in perspective with the risk of having a scan of low diagnostic quality for a life-threatening medical condition. In recent years there has been a push to reduce as much as possible the dose from radiological imaging, for example by using acquisition protocols specific to pregnant women and by injecting lower activities. These approaches, in our opinion, overweigh the radiation risk and actually may put the life of both the mother and the fetus in danger. Since imaging protocols already seek to use the lowest possible dose compatible with a quality scan for all patients, pregnant women should be imaged using the protocols applied to any other patient. Encouraging bladder voiding by natural means after injection will significantly reduce fetal exposure without compromising image quality.

The Distilbène® story is a dramatic episode which belongs to the history of medicine. It provided several useful lessons such as the importance of evidence-based medicine and the hazard to develop treatments during pregnancy without careful animal verifications. However, this experience has also provided unexpected progress by suggesting new pathophysiological concepts: fetal programming of adult diseases and/or transgenerational transmission of environmental effects through epigenetic modifications.

The 2012 meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG) focused on the development and ethics of biomarkers for fetal alcohol exposure. This one-day international conference brought students and trainees together with clinicians and researchers to discuss the latest research on FASD. One keynote speaker discussed the value of profiling epigenetic modifications in readily available fetal tissues to diagnose fetal exposure to environmental agents, while the second speaker discussed the ethics of biomarker development within the context of core principles of justice, autonomy, beneficence and non-maleficence. Three sessions of short data talks informed the audience of research advances with particular emphasis on the diagnosis of FASD. Other activities included updates on FASD-related activities by representatives of government agencies, a report on the implementation FASD-related diagnostic criteria in the fifth edition of the Diagnostic and Statistical Manual (DSM-5) of the American Psychiatric Association and a networking lunch, and the presentation of the “Merit Award” to Dr. Nathan Muraski for his work on behavioural outcomes of fetal alcohol exposure. The capstone of the meeting was the presentation of the “Henri Rosett” award to Dr. Denis Viljoen, in recognition of his role in raising awareness about the incidence of FASD in South Africa and in promoting FASD prevention and treatment programs as chairperson and chief executive officer of the Foundation for Alcohol Related Research (FARR).

Background Prefeeding cues are oral-motor neurobehaviors that communicate feeding readiness, and the ability to self-comfort and regulate behavioral state. Intrapartum and newborn procedures have been associated with altered frequency and emergence of prefeeding cues soon after birth. Intrapartum synthetic oxytocin is commonly used for labor induction/augmentation in the US, yet there is little research on potential effects on infant neurobehavioral cues. Aims To explore whether fetal exposure to synthetic oxytocin was associated with the infant's level of prefeeding organization shortly after birth. Study design Cohort. Subjects A convenience sample of 47 healthy full-term infants (36 exposed and 11 unexposed to intrapartum synthetic oxytocin) was studied. Exclusion criteria Fetal distress, vacuum/forceps, cesarean, and low Apgar. Outcome measures Videotapes of infants (45–50min postbirth) were coded for frequency of eight prefeeding cues, and analyzed by level of prefeeding organization. Results In general, fewer prefeeding cues were observed in infants exposed versus unexposed to synOT and differences were significant for brief and sustained hand to mouth cues [incidence rate ratio (95% CI)=0.6 (0.4, 0.9) and 0.5 (0.2, 0.9), respectively]. Forty-four percent of exposed infants demonstrated a low level of prefeeding organization, compared to 0% from the unexposed group. In contrast, 25% of exposed versus 64% of unexposed infants demonstrated high prefeeding organization. After adjusting for covariates, exposed infants were at 11.5 times (95% CI=1.8–73.3) the odds of demonstrating low/medium versus high levels of prefeeding organization compared to unexposed infants. Conclusions Newborn neurobehavioral cues may be sensitive to intrapartum synthetic oxytocin.

Bisphenol A (BPA) is an estrogenic compound widely used in polycarbonate plastics. The placental enzyme β-glucuronidase may deconjugate BPA into its "free" active form. We sought to quantify levels of conjugated and free BPA in second and third trimester amniotic fluid. Liquid chromatography coupled with mass spectrometry was used to measure BPA concentrations in 20 second trimester and 20 third trimester amniotic fluid specimens. Total BPA was detected in 16/20 second trimester samples; levels ranged from non-detectable to 0.75ng/mL (median 0.47ng/mL). Free BPA was detected in 9/20 second trimester samples; levels ranged from 0.31 to 0.43ng/mL (median 0.38ng/mL). Total BPA was detected in 2/20 third trimester samples. Free BPA was detected in 1/20 (0.42ng/mL). When detected, free BPA comprised 83% and 91% of total BPA in second and third trimester amniotic fluid, respectively. Placental β-glucuronidase may deconjugate BPA, increasing fetal exposure to free BPA.

Background Previous studies have suggested that fetal smoke exposure is associated with increased risks of wheezing during childhood. The underlying pathways are unknown. We examined the associations of parental smoking during pregnancy with wheezing in preschool children and whether these associations are explained by postnatal smoke exposure or small for gestational age at birth. Methods This study was embedded in a population-based prospective cohort study. Parental smoking was prospectively assessed by questionnaires. Wheezing was reported at 1 to 4 years. Small for gestational age at birth was available from registries. The analyses were based on 4,574 subjects. Results Maternal smoking during the first trimester only was not associated with wheezing. Continued maternal smoking in pregnancy was associated with the risk of wheezing at 1 to 4 years (P for trends Conclusions Fetal exposure to continued maternal smoking is associated with increased risks of wheezing in preschool children. Further research is needed to explore the effects of paternal smoking. Diminishing maternal smoking before conception or in early pregnancy is likely to have the greatest impact on reducing childhood wheezing.

Polybrominated diphenyl ethers (PBDEs) have been used extensively in electrical and electronic products, but little is known about the exposure level in the electrical appliance factories workers and nearby local residents. In this study, we assessed body burdens of PBDEs in 194 Chinese injection workers from electrical appliance factories and also measured 205 blood samples from catering workers, leather factory workers, umbilical cord and infertile men for comparison. Twelve PBDE congeners in serum samples were measured by GC–MS. The highest concentration for total PBDEs was found in injection workers, which is positively correlated to employment duration. BDE-209 was the most dominant congener followed by BDE-47, 28 and 99. We also found the presence of all twelve PBDEs in cord blood, suggesting an evidence of fetal exposure. Concentration of BDE-47 was particularly higher in serum samples from infertile men in comparison with that of catering workers and leather factory workers.

In this paper we estimate long-run effects of fetal exposure to the 1918/19 influenza pandemic for a European country. Using data from the 1970 Swiss census, we find that the male 1919 cohort that had a strongly increased likelihood of fetal exposure to the pandemic performs significantly worse in terms of educational attainment and has a lower chance of marriage than the surrounding cohorts. Further, we find similar results when we in addition use regional differences in influenza severity to test for the impact of influenza on later-life outcomes. A set of robustness tests confirm our findings.

The principles of clinical pharmacology also apply to neonates, but their characteristics warrant a tailored approach. We focus on aspects of both developmental pharmacokinetics (concentration/time relationship) and developmental pharmacodynamics (concentration/effect relationship) in neonates. We hereby aimed to link concepts used in clinical pharmacology with compound-specific observations (anti-epileptics, analgosedatives) in the field of neonatal neurology. Although in part anecdotal, we subsequently illustrate the relevance of developmental pharmacology in the field of neonatal neurology by a specific intervention (e.g. whole body cooling), specific clinical presentations (e.g. short and long term outcome following fetal exposure to antidepressive agents, the development of new biomarkers for fetal alcohol syndrome) and specific clinical needs (e.g. analgosedation in neonates, excitocytosis versus neuro-apoptosis/impaired synaptogenesis).

Resume La responsabilite des perturbateurs endocriniens environnementaux (PEE) comme facteurs de risque dans la physiopathologie des cancers hormonodependants s’appuie a la fois sur : (1) l’exposition in utero au distilbene, un modele experimental humain involontaire ayant entraine chez la jeune fille, un cancer rare, le cancer du vagin, et chez la femme de plus de 40 ans, un risque majore de cancer du sein, le plus frequent des cancers feminins ; (2) de nombreuses etudes epidemiologiques cas/controles qui, bien que d’interpretation difficile et soumises a de nombreux biais, mettent en evidence une relation avec les taux de PEE dans le sang, le tissu graisseux ou la tumeur (cancer du sein et biphenyls polychlores [PCB], hydrocarbures polyaromatiques (PAH), dioxine ou organochlores ; cancer de la prostate et chlordecone ; cancer du testicule et PCB, hexachlorobenzene [HCB] ou chlordane) ; (3) des modeles experimentaux, permettant ainsi chez les rongeurs apres exposition fœtale ou perinatale au diethylstilbestrol (DES), au bisphenol A, ou a l’atrazine de reproduire chez l’animal adulte des lesions precancereuses mammaires ou prostatiques ; (4) la possibilite d’interferer in vitro sur la croissance de lignees de cellules malignes humaines avec le bisphenol A neutralisant l’efficacite de la chimiotherapie (sein) ou stimulant la proliferation cellulaire (prostate, testicule). Bien que de nombreuses interrogations persistent, ces differents elements orientent vers une nouvelle evaluation de la responsabilite carcinogenique des PEE, prenant en compte les faibles doses, dans des fenetres d’exposition critiques surtout fœtale, la synergie entre les molecules et l’induction de modifications epigenetiques stables ne touchant pas la structure du genome mais etant susceptibles de participer a la transformation maligne et/ou a la promotion tumorale.

Nitrosodimethylamine (NDMA) is a carcinogenic compound present in tobacco smoke and food such as cured meat, smoked fish and beer. The O(6)-methylguanine formed in human cord blood in mothers highly exposed to such products implicates NDMA exposure of the fetus. Dual recirculating human placental perfusion was used to get direct evidence of the transplacental transfer of NDMA and DNA adduct formation in perfused human placenta. Eleven placentas from normal full-term pregnancies were collected immediately after delivery and an isolated lobule was perfused with 1 or 5 microM of (14)C-NDMA with a reference substance, antipyrine (0.1mg/ml) added to the maternal circulation. Perfusate samples were collected from both maternal and fetal circulations every half an hour for the first two hours and once per hour from thereon. NDMA was analyzed by scintillation counting and antipyrine by high performance liquid chromatography. The transfer of NDMA was comparable to that of antipyrine and probably occurred through passive diffusion, with the concentrations in maternal and fetal sides equilibrating in 2-3h. No indication of any effect by efflux transporters on NDMA kinetics was noticed in the experiments utilizing Caco-2 or MDCK- MDCKII-MDR1 cell culture monolayer in a transwell system, either. Furthermore, no NDMA-DNA-adducts were found after the perfusions and no DNA-binding of NDMA was seen in in vitro incubations with human placental microsomes from 8 additional placentas. Thus, our study demonstrates that the human fetus can be exposed to NDMA from the maternal circulation. According to this study and the literature, NDMA is not metabolized in full-term human placenta from healthy non-smoking, non-drinking mothers. It remains to be studied whether NDMA concentrations high enough to evoke fetal toxicity can be obtained from dietary sources. We appreciate the collaboration with all members in Dan Segerbäck's group, partner of the Network of Excellence ECNIS. Finally, the authors thank Dr. Ewen MacDonald for his comments on English language in the paper. The project was financially supported by EU network NewGeneris (FOOD-CT-2005 016320).

Most drugs can penetrate the placenta but there are only a few studies on placental transfer of environmental toxic compounds. In this study, we used dual recirculating human placental perfusion to determine the transfer rate through the placenta of a neurotoxic and carcinogenic compound found in food, acrylamide and its genotoxic metabolite glycidamide. Putative acrylamide metabolism into glycidamide during the 4-h perfusions and acrylamide-derived DNA adducts in placental DNA after perfusions were also analyzed. Placentas were collected immediately after delivery and kept physiologically functional as confirmed by antipyrine kinetics, glucose consumption and leak from fetal to maternal circulation. Acrylamide (5 or 10 microg/ml) or glycidamide (5 microg/ml), both with antipyrine (100 microg/ml), was added to maternal circulation. Acrylamide and glycidamide were analyzed in the perfusion medium by liquid chromatography/mass spectrometry. Acrylamide and glycidamide crossed the placenta from maternal to fetal circulation with similar kinetics to antipyrine, suggesting fetal exposure if the mother is exposed. The concentrations in maternal and fetal circulations equilibrated within 2h for both studied compounds and with both concentrations. Acrylamide metabolism into glycidamide was not detected during the 4-h perfusions. Moreover, DNA adducts were undetectable in the placentas after perfusions. However, fetuses may be exposed to glycidamide after maternal metabolism. Although not found in placental tissue after 4h of perfusion, it is possible that glycidamide adducts are formed in fetal DNA. Finally, we appreciate the collaboration with all members in Dan Segerbäck’s group, partner of the Network of Excellence ECNIS. This project was financially supported by EU networks NewGeneris (FOOD-CT-2005 016320) and ReProTect (LSHB-CT-2004-503257).

Children are exposed to Hg from mothers (via placenta and lactation), environment (food), and in many parts of the world by thimerosal-containing vaccines (TCV) during immunization. Neurodevelopment studies based on infant hair-Hg (HHg) have been designed without explicit attention to the factors associated with changes in infant physiology and Hg sources of exposure. A longitudinal study of changes in HHg concentrations from birth to 5 years was done in a sample of children from Porto Velho (Rondonia), Brazilian Amazonia. The study extracted information from the asymmetry associated with maternal and infant HHg changes at specified sampling: birth (fetal exposure), 6 months of exclusive breastfeeding, 36 months (weaning) and 60 months (pre-school). The distribution of HHg in breastfed infants followed a pattern different from their mothers. While mothers had the highest HHg concentrations at childbirth, infants showed the highest HHg values at 6 months after the recommended full schedule (six shots) of immunization with TCV; after that, the downward trend in HHg shown by children coincided with both weaning and less frequent vaccination period (5 years). Extended lactation (up to 36 months) was not significantly associated with HHg of infants or mothers; however, significant association (Spearman’s r ) between maternal and infant HHg concentration was seen at birth ( r = 0.3534; P = 0.001), 6 months ( r = 0.4793; P r = 0.0122; P = 0.012) and 5 years ( r = 0.0357; P = 0.005). Maternal postpartum metabolic changes, infant development and transitional diets and possibly Hg from TCV contribute to the asymmetry of HHg changes between mothers and children.

Whole-body autoradiography (WBA) allows the determination of sites of accumulation and differential distribution of radiolabeled compounds within organs. WBA is routinely conducted in pregnant rats to evaluate placental transfer and fetal distribution of potential developmental toxins. This technique has recently been adapted to evaluate tissue distribution in the pregnant rabbit, which may be a more appropriate model for some pharmaceutical candidates. A preliminary WBA study was conducted on New Zealand white (NZW) rabbits at gestation day 18, 1 h following a single oral dose of 14C-glucose. The purpose of this study was to validate the use of WBA techniques in assessing the placental transfer of compounds in pregnant rabbits. Antiviral compound LY217896 sodium demonstrated developmental toxicity in the pregnant NZW rabbit following multiple oral doses of 10 mg/kg on gestation days 6 through 18. WBA techniques were used to determine the distribution of radiocarbon 30 minutes following a single oral 10-mg/kg dose of 14C-LY217896 sodium in pregnant NZW rabbits on gestation day 18.

bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicol Ind Health 1999;15:12 27. Thigpen JE, Setchell KD, Goelz MF, Forsythe DB. The phytoestrogen content of rodent diets (letter). Environ Health Perspect 1999;107:A182 28. Boettger-Tong H, Murthy L, Chiappetta C, et al. A case of a laboratory animal feed with high estrogenic activity and its impact on in vivo responses to exogenously administered estrogens. Environ Health Perspect 1998;106:369 29. Newbold RR, Hanson RB, Jefferson WN, et al. Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol. Carcinogenesis 1998;19:1655 30. North K, Golding J. A maternal vegetarian diet in pregnancy is associated with hypospadias. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. BJU Int 2000;85:107

This article reviews the general approach for assessing teratogenic risks related to fetal exposure, concentrating on the specific patterns associated with anticonvulsant usage and maternal epilepsy. Major anomalies that might be detected prenatally are presented, as well as the patterns of minor anomalies (syndromes) that might be detected at birth or later. Each of the specific drugs used in the treatment of epilepsy is reviewed in detail. In addition, recent information concerning genetically determined variations in the metabolism of antiepileptic drugs is discussed in light of how genetic factors might relate to teratogenicity.

This case describes the treatment of a group O RH 17-positive baby affected by high titre maternal anti-RH17. Fetal treatment was 2 Rh null and 2 -D-/-D- (one ABO-mismatched and CMV-seropositive), RH17-negative intrauterine transfusions. Intravenous immunoglobulin was given prophylactically to the fetus because of maternal CMV-seronegativity. Postnatally, 3 RH 17-negative transfusions and folic acid were administered. Rh null intrauterine transfusions gave poor results but overall treatment was successful. The baby was well at 6 months of age. Fetal exposure to A antigen caused neither tolerisation nor premature alloimmunisation.

Article Title and Bibliographic Information Fetal exposure to oral pathogens and subsequent risk of neonatal intensive care admission. Jared H, Boggess KA, Moss K, Bose C, Auten R, Beck J, et al. J Periodontal 2009;80:878-83. Reviewer Paul I. Eke, PhD, MPH Purpose/Question Is fetal exposure to oral pathogens associated with increased risk for infant admissions to neonatal intensive care unit (NICU)? Source of Funding Government: National Institutes of Health Grant (R01DE01245) Type of Study/Design Prospective cohort study Level of Evidence Level 2: limited-quality, patient-oriented evidence Strength of Recommendation Grade Not applicable