Antiepileptic Medication During Pregnancy: Does Fetal Genotype Affect Outcome?

Atkinson, Diane E.; Brice-Bennett, Sophie; D'Souza, S W

doi:10.1203/pdr.0b013e3180a02e50

Cited by 52 publications

(36 citation statements)

References 80 publications

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“…T his may be especially important for VPA since VPA exposure increases the frequency of congenital malformations more than other AEDs (ref. 41 ). At least one prospective observational study suggested that higher doses of VPA may significantly increase the risk of major malformations 42 .…”

Section: Discussionmentioning

confidence: 99%

Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight

Kacířová¹,

Grundmann²,

Brozmanová³

2015

BIOMED PAP

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Aims. The data on the valproic acid transplacental transfer and risk to the fetus of exposure, remain sparse and only a limited number of studies have reported umbilical cord blood levels. Materials and Methods. Maternal and umbilical cord serum levels were analyzed at delivery in a cohort of 58 women, between the years 1991 -2013. The request forms for routine therapeutic drug monitoring were used as the data source. Maternal levels and dosing information were used for estimating the maternal apparent oral clearance and the paired umbilical cord and maternal levels for estimation of umbilical cord/maternal level ratios. Results. The levels varied from 5.3 -59.5 mg/L in maternal and 5.4 -72.1 mg/L in umbilical cord serum. The umbilical cord/maternal level ratios ranged from 0.64 -2.49. Significant correlation was found between maternal and umbilical cord levels. Significant inverse correlations were found between birth length, and both maternal and umbilical cord levels in monotherapy.Conclusions. There were large individual variations in umbilical cord/maternal level ratios of valproic acid. Neonatal length and weight were inversely related to maternal and umbilical cord levels, but not to dose. Therefore, therapeutic drug monitoring in mothers is more useful than the given dose for the estimation of fetal exposure and minimization of the risk of fetal effects.

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Section: Discussionmentioning

confidence: 99%

Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight

Kacířová¹,

Grundmann²,

Brozmanová³

2015

BIOMED PAP

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“…Recent studies have also revealed that intrauterine exposure of CBZ is associated with spina bifida [114] and neuro developmental problems [115] of human embryo when gravidas were exposed to CBZ monotherapy. Atkinson et al [116] also reported higher fetal losses and congenital malformation rates among women who were prescribed carbamazepine during pregnancy. Because the residue of CBZ in drinking water may provide a pathway to embryo and infant via intrauterine exposure or breast-feeding, the presence of CBZ in groundwater, and drinking water remains a significant concern warranting further systematic risk assessment studies.…”

Section: Toxicological Effectsmentioning

confidence: 96%

Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

Hai

Yang

Asif

et al. 2018

Water

147

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Carbamazepine (CBZ), a pharmaceutical compound, has been proposed as an anthropogenic marker to assess water quality due to its persistence in conventional treatment plants and widespread presence in water bodies. This paper presents a comprehensive literature review on sources and occurrences of CBZ in water bodies, as well as toxicological effects and regulations of the drug. Given the documented side effects of CBZ on the human body when taken medicinally, its careful monitoring in water is recommended. CBZ residues in drinking water may provide a pathway to embryos and infants via intrauterine exposure or breast-feeding, which may cause congenital malformations and/or neurodevelopmental problems over long term exposure. An in-depth technical assessment of the conventional and advanced treatment technologies revealed the inadequacy of the standalone technologies. Compared to conventional activated sludge and membrane bioreactor processes, effective removal of CBZ can be achieved by nanofiltration and reverse osmosis membranes. However, recent studies have revealed that harsh chemical cleaning, as required to mitigate membrane fouling, can often reduce the long-term removal efficiency. Furthermore, despite the efficient performance of activated carbon adsorption and advanced oxidation processes, a few challenges such as cost of chemicals and regeneration of activated carbon need to be carefully considered. The limitations of the individual technologies point to the advantages of combined and hybrid systems, namely, membrane bioreactor coupled with nanofiltration, adsorption or advanced oxidation process.

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“…The placenta is obviously considered the crucial organ responsible for successful ontogeny. Evidence strongly suggests that the placenta expresses a range of transporters which are capable of controlling the transplacental dispositions of many toxicant agents, thereby playing a crucial role in fetal protection against maternal toxins (Myllynen et al, 2005Ceckova et al, 2006;Atkinson et al, 2007;Behravan and Piquette-Miller, 2007;Myren et al, 2007;Vahakangas and Myllynen, 2009;Prouillac and Lecoeur, 2010;Ni and Mao, 2011;Iqbal et al, 2012). Of main interest are the ATPbinding cassette (ABC) transporters, particularly the P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP), which are most intensively studied currently.…”

Section: Introductionmentioning

confidence: 99%

Associations Between ABCG2 Gene Polymorphisms and Isolated Septal Defects in a Han Chinese Population

Wang

Xie

et al. 2014

DNA and Cell Biology

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Breast cancer resistance protein (BCRP) in the placenta, encoded by the ABCG2 gene in humans, plays an essential role in regulating fetal exposure to toxicants and the maintenance of cellular folic acid homeostasis. This study aimed at exploring the associations between 421C > A and 34G > A polymorphisms within the ABCG2 gene of the children and isolated septal defects in a Han Chinese population. An age-and gendermatched case-control study involving 210 pairs was conducted. Genotyping of the ABCG2 gene polymorphisms was performed by sequencing. Forty-six placental tissues and umbilical cords from healthy Han Chinese mothers with uncomplicated pregnancy were collected to investigate the impact of these two polymorphisms on the transcription and translation activities of the ABCG2 gene. The results showed that there were no differences in the genotype distributions and allele frequencies of 421C > A polymorphism. For the 34G > A polymorphism, more cases were carriers of the GA/AA genotypes (adjusted odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.0-2.3). The ABCG2 mRNA and protein expression did not differ among the three genotypes of 421C > A polymorphism. For the 34G > A polymorphism, the ABCG2 mRNA and protein expression of the GG genotype was significantly higher than that of the AA genotype. In conclusion, 34G > A polymorphism in the ABCG2 gene of the children is associated with isolated septal defects in a Han Chinese population, presumably through regulation of BCRP expression in the placenta.

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Antiepileptic Medication During Pregnancy: Does Fetal Genotype Affect Outcome?

Cited by 52 publications

References 80 publications

Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight

Serum levels of valproic acid during delivery in mothers and in umbilical cord - correlation with birth length and weight

Carbamazepine as a Possible Anthropogenic Marker in Water: Occurrences, Toxicological Effects, Regulations and Removal by Wastewater Treatment Technologies

Associations Between ABCG2 Gene Polymorphisms and Isolated Septal Defects in a Han Chinese Population

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