Spontaneous fetal behavior after maternal exposure to ethanol

Acute and chronic intubations of ethanol to pregnant rats produced changes in spontaneous fetal behavior four hours later. Fetuses from mothers in intermediate alcohol groups (4 and 6 g/kg) were substantially less active than controls (0 g/kg), but fetuses from low (2 g/kg) and high (8 g/kg) alcohol groups showed little indication of behavioral suppression. Circulating levels of alcohol in maternal blood, fetal homogenate and amniotic fluid at the time fetuses were observed confirmed that fetuses were exposed to alcohol in utero, but the measured concentrations of alcohol were not predictive of fetal activity. We suggest that some of the developmental consequences of Fetal Alcohol Syndrome may be the consequence of fetal inactivity induced by alcohol in utero.     

Pregnancy outcome after exposure to injectable ribavirin during embryogenesis

We describe normal pregnancy outcome in a case of first trimester exposure to injectable ribavirin in a 36-year-old pregnant woman who received three intramuscular injections of ribavirin for suspected SARS. She delivered at 40 weeks of gestation a healthy baby girl. In pediatric follow up at 8 month of age, physical examination and neurodevelopmental milestones were normal.     

Pregnancy outcome after paternal exposure to azathioprine/6-mercaptopurine

There are only few studies with conflicting results on pregnancy outcome after paternal exposure to azathioprine or 6-mercaptopurine. In our study, pregnancy outcome of 115 prospectively followed pregnancies after paternal exposure to azathioprine or 6-mercaptopurine is compared to a control group of 341 pregnancies. The rate of major malformations was not increased (3.0% in exposed versus 2.2% in the control group). There was no specific pattern of birth defects and no indication for chromosomal aberrations in the exposed group. We observed a higher rate of elective terminations of pregnancy in the exposed group and a non-significant increase of spontaneous abortions (cumulative incidence 19% versus 13%, respectively). Further prospective studies are required to address the question of a possibly increased risk for spontaneous abortion.     

Pregnancy outcome after exposure to oral contraceptives during the periconceptional period

To evaluate whether periconceptional exposure to oral contraceptives (OCs) increased adverse pregnancy outcomes, 136 pregnant women taking OCs within the periconceptional period were identified at the Korean Motherisk Program. Of them, 120 pregnant women accepted to participate in their study and were followed up until completion of the pregnancy. A control group of 240 age- and gravidity-matched pregnant women exposed to non-teratogen drugs for at least 1 month before pregnancy was also included. The median gestational age at delivery was 39.1 (27.0-41.0) weeks in the exposed group and 39.3 (27.4-42.0) weeks in the control group (P = 0.19). In the exposed group, 7.1% of babies were born with low birth weight versus 2.6% in the control group (P = 0.068). The number of preterm deliveries or babies born large for gestational age did not differ between the two groups. In the exposed group, the rate of birth defects was 3.2% (n = 3/99) versus 3.6% (n = 7/193) in the control group (P = 1.0). There were 15 women who took high doses of progesterone (emergency contraception) and no adverse fetal outcomes were observed. In conclusion, periconceptional exposure to OCs does not appear to increase the risk for adverse pregnancy outcomes.     

Pregnancy outcomes following exposure to serotonin reuptake inhibitors: a meta-analysis of clinical trials

Serotonin reuptake inhibitors (SRIs) are extensively used in management of clinical depression. Reports vary about the risk of these drugs during pregnancy. To determine the risk of exposure to SRIs, we pooled data from multiple clinical studies that investigated obstetrical outcomes in women exposed to this group of drugs during pregnancy. Studies were identified by search of PUBMED, OVID, and SCOPUS databases and the data were derived from 1990 to 2005 (August). Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. The criteria for inclusion of studies in this meta-analysis were exposure of women to any therapeutic dosage of SRI (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) during pregnancy.

Our results find that SRIs do not increase the risk of major, cardiovascular and minor malformations but do increase the risk of spontaneous abortion significantly.     

Pregnancy outcomes following pre- and post-implantation exposure of Sprague-Dawley rats to benzyl isothiocyanate.

The present investigation examines the outcomes of rats' pregnancy following pre- and post-implantation maternal exposure (orally) to benzyl isothiocyanate (BITC; 12.5, 25 and 50 mg/kg body weight). Three maternal deaths were recorded in the group of rats treated with 50 mg/kg BITC. Obvious signs of toxicity characterized by hypo-activity, perinasal staining, piloerection, hunched posture and decrease in body weights were observed in BITC-treated rats during the treatment periods. Dose-dependent increase in early fetal resorptions was seen in rats treated with BITC prior to implantation, but was not statistically significant. There were no significant differences in the number of implantation sites in treatment groups compared with the control. Similarly, there were no significant differences in the number of fetal resorptions, relative weights of maternal liver, kidney and spleen of rats in post-implantation treatment groups compared with the control. The differences in the number of viable fetuses in treatment groups compared with the control were also not significant. However, fetal weights in rats treated with 25 and 50 mg/kg BITC and placental weights in all the treatment groups were significantly lower than the control. In conclusion, at 12.5-50 mg/kg, BITC did not cause significant pre- and post-implantation fetal loss in pregnant rats. BITC-induced low fetal and placental weights could be of obstetrical importance, but at levels/doses that would provoke maternal toxicity.     

Voriconazole and fluconazole increase the exposure to oral diazepam

Objective We assessed the effect of voriconazole and fluconazole on the pharmacokinetics and pharmacodynamics of diazepam. Methods Twelve healthy volunteers took 5 mg of oral diazepam in a randomised order on three study sessions: without pretreatment, after oral voriconazole 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after oral fluconazole 400 mg on the first day and 200 mg on the second day. Plasma concentrations of diazepam and N-desmethyldiazepam were determined for up to 48 h. Pharmacodynamic variables were measured for 12 h. Results In the voriconazole phase, the area under the plasma concentration time curve of diazepam was increased (geometric mean ratio) 2.2-fold (p < 0.05; 90% confidence interval [CI] 1.56 to 2.82). This was associated with the prolongation of the mean elimination half-life (t_1/2) from 31 h to 61 h (p < 0.01) after voriconazole. In the fluconazole phase, the of diazepam was increased 2.5-fold (p < 0.01; 90% CI 1.94 to 3.40), and the t_1/2 was prolonged from 31 h to 73 h (p < 0.001). The peak plasma concentration of diazepam was practically unchanged by voriconazole and fluconazole. The pharmacodynamics of diazepam were changed only modestly. Conclusion Both voriconazole and fluconazole considerably increase the exposure to diazepam. Recurrent administration of diazepam increases the risk of clinically significant interactions during voriconazole or fluconazole treatment, because the elimination of diazepam is impaired significantly.     

Pregnancy outcome after exposure to antidepressants and the role of maternal depression: results from the Norwegian Mother and Child Cohort Study

Results of previous studies on the safety of antidepressants during pregnancy have been conflicting. The primary objective of this study was to investigate whether first-trimester exposure to antidepressants, specifically selective serotonin reuptake inhibitors (SSRIs), was associated with increased risk of congenital malformations. The secondary objective was to examine the effects of exposure to antidepressants during pregnancy on birth weight and gestational age.We included 63,395 women from the Norwegian Mother and Child Cohort Study. The women had completed 2 self-administered questionnaires at gestational weeks 17 and 30 on medication use and medical, sociodemographic, and psychological factors. Data on pregnancy outcome were retrieved from the Medical Birth Registry of Norway.Of the 63,395 women, 699 (1.1%) reported using antidepressants during pregnancy, most frequently SSRIs (0.9%). Exposure to SSRIs during the first trimester was not associated with increased risk of congenital malformations in general (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.81-1.84) or cardiovascular malformations (adjusted OR, 1.51; 95% CI, 0.67-3.43). Exposure to antidepressants during pregnancy was not associated with increased risk of preterm birth (adjusted OR, 1.21; 95% CI, 0.87-1.69) or low birth weight (adjusted OR, 0.62; 95% CI, 0.33-1.16).This study does not suggest a strongly increased risk of malformations, preterm birth, or low birth weight following prenatal exposure to antidepressants. Without adjustments for level of maternal depression and various sociodemographic and lifestyle factors, antidepressant use during pregnancy would wrongly have been associated with an increased risk of preterm birth.     

妊娠早期服用米非司酮和前列腺素对继续妊娠的安全讨论

目的 系统评价妊娠早期服用米非司酮对继续妊娠是否有不良影响。方法 计算机检索中国知网、万方数据库、维普数据库、Web of Science、Pubmed等数据库,检索时限从数据库建立时到2017年,纳入服用米非司酮后继续妊娠试验-对照研究以及病案报道。对纳入的文献进行质量评价,用RevMan 5.3软件进行统计分析,计算纳入试验-对照研究的合并比值比（OR）及其95% CI。结果 纳入4个试验-对照研究,Meta分析结果显示,口服紧急避孕药继续妊娠者产生不良反应的可能性是非口服紧急避孕者的6.09倍,6.72倍;米非司酮紧急避孕失败者如果选择继续妊娠,新生儿窒息发生率高于正常人群,合并计算的OR值7.65,95% CI为3.13~18.69;妊娠期服用米非司酮和同时服用米非司酮、前列腺素对继续妊娠造成新生儿畸形的发生率并无太大差异,合并计算的OR值0.45,95% CI为0.12~1.73。结论 表明妊娠早期服用米非司酮可能会对继续妊娠产生不良影响,如选择继续妊娠则要积极预防。但由于纳入的文献研究数量较少,上述结论尚需开展更多高质量研究进一步加以证明。     

Arsenicals in maternal and fetal mouse tissues after gestational exposure to arsenite

Exposure of pregnant C3H/HeNCR mice to 42.5- or 85-ppm of arsenic as sodium arsenite in drinking water between days 8 and 18 of gestation markedly increases tumor incidence in their offspring. In the work reported here, distribution of inorganic arsenic and its metabolites, methyl arsenic and dimethyl arsenic, were determined in maternal and fetal tissues collected on gestational day 18 of these exposure regimens. Tissues were collected from three females and from associated fetuses exposed to each dosage level. Concentrations of total speciated arsenic (sum of inorganic, methyl, and dimethyl arsenic) were higher in maternal tissues than in placenta and fetal tissues; total speciated arsenic concentration in placenta exceeded those in fetal tissues. Significant dosage-dependent (42.5 ppm versus 85 ppm of arsenite in drinking water) differences were found in total speciated arsenic concentrations in maternal lung (p<0.01) and liver (p<0.001). Total speciated arsenic concentrations did not differ significantly between dosage levels for maternal blood or for fetal lung, liver, and blood, or for placenta. Percentages of inorganic, methyl, or dimethyl arsenic in maternal or fetal tissues were not dosage-dependent. Over the range of total speciated arsenic concentrations in most maternal and fetal tissues, dimethyl arsenic was the most abundant arsenical. However, in maternal liver at the highest total speciated arsenic concentration, inorganic arsenic was the most abundant arsenical, suggesting that a high tissue burden of arsenic affected formation or retention of methylated species in this organ. Tissue concentration-dependent processes could affect kinetics of transfer of inorganic arsenic or its metabolites from mother to fetus.