Pregnancy Outcomes With Exposure to Second-Generation Antipsychotics During the First Trimester.

Objective: To investigate the risk of major congenital malformations associated with exposure to second-generation antipsychotics (SGAs) in the first trimester.Methods: Pregnant women who received consultation on drug exposure from the Japan Drug Information Institute in Pregnancy from October 2005 to December 2016 were asked to complete a questionnaire at 1 month after the expected delivery date. The questionnaire included items on pregnancy outcome, date of delivery, gestational age at delivery, malformations in the infant that were confirmed by the pediatrician's report, and the following parameters at birth: height, weight, head circumference, and chest circumference. Odds ratios (ORs) for major congenital malformations among live-born children of pregnant women with SGA exposure during the first trimester (SGA group) relative to children of women not exposed to SGAs and medications known to be teratogenic (comparison group) were estimated using an inverse probability of treatment weighting approach.Results: Of 404 women with SGA exposure during the first trimester, there were 351 live births, 3 stillbirths, 34 spontaneous abortions, and 16 elective abortions. The rate of major congenital malformations among live-born children was 0.9% (3/351) in the SGA group and 1.8% (70/3,899) in the comparison group. No statistically significant differences were observed in the adjusted OR for major congenital malformations (adjusted OR = 0.44; 95% CI, 0.12-1.48; P = .179).Conclusions: SGA exposure during the first trimester is not associated with an increased risk of major congenital malformations. These findings might be reassuring for pregnant women who require SGAs.

The advances in dealing with the safety of medicated drugs in pregnancy.

The Japan Drug Information Institute in Pregnancy (JDIIP) was established with the aims of providing information on drug safety to women who are worried about drug use during pregnancy and creating evidence through epidemiological studies based on counseling cases. Since being established, JDIIP has made many contributions to the wellness of mothers and children by promoting the proper use of drugs during pregnancy. A network consisting of Core hospitals in 47 prefectures plays an important role in providing information for women living anywhere in Japan. Because cases of exposure to drugs whose safety we want to analyze are usually rare, networks of domestic and foreign teratology information services are necessary in order to produce high-quality evidence. JDIIP has been contributing to the education of pharmacists and doctors and to the creation of clinical practice guidelines in various medical societies by using keywords such as "pregnancy" and "medication". Future issues include creating an environment that is easily accessible for those seeking consultation, building a mechanism that makes it easy to create a basis for safety, and aiming for the continuing development of the organization.

Safety of Amlodipine in Early Pregnancy.

Background Amlodipine is used for the treatment of hypertension, but reports on its use in early pregnancy are limited. Methods and Results In the present study, we recruited 231 women with chronic hypertension, including those who received amlodipine or other antihypertensives during early pregnancy, and investigated frequencies of morphologic abnormalities in their 231 offspring. Specifically, we evaluated 48 neonates exposed to amlodipine in the first trimester (amlodipine group, Group A), 54 neonates exposed to antihypertensives other than amlodipine (other antihypertensive group, Group O), and 129 neonates not exposed to antihypertensives (no-antihypertensive group, Group N). The number of morphologic abnormalities of offspring in each group were 2 in Group A (4.2%; 95% CI, 0.51-14.25); 3 in Group O (5.6%; 95% CI, 1.16-15.39) and 6 in Group N (4.7%; 95% CI, 1.73-9.85). The odds ratio of the primary outcome comparing Group A and Group O was 0.74 (95% CI: 0.118-4.621) and Group A and Group N was 0.89 (95% CI: 0.174-4.575). Conclusions The odds of birth defects in Group A in the first trimester were not significantly different from those with or without other antihypertensives.

Perception of pregnant Japanese women regarding the teratogenic risk of medication exposure during pregnancy and the effect of counseling through the Japan drug information institute in pregnancy.

OBJECTIVE: To confirm the current state of Japanese women's perception of the teratogenic risk of medication exposure during pregnancy, and to assess the effect of counseling by　Japan Drug Information Institute in Pregnancy. METHODS: We used VAS to monitor the sentiments of pregnant women, before and after face-to-face counseling, about their own teratogenic risk perception, and their intention to continue pregnancy. Pregnancy outcomes were investigated by mailed questionnaires. RESULTS: Among 681 pregnant women, the median estimation of the risk of having a baby with a birth defect was 33.0% (interquartile range 16.0-50.0%) prior to counseling and 5.0% after counseling (2.0-11.0%). The median intention to continue pregnancy increased from 86.0% to 100.0% after counseling. The actual outcome survey revealed that almost all participants (97.1%) continued their pregnancies. CONCLUSIONS: Pregnant women tend to overestimate the fetal risks of medication exposure during pregnancy. Counseling would prevent unnecessary termination.

Pregnancy outcomes after exposure to tocilizumab: A retrospective analysis of 61 patients in Japan.

OBJECTIVES: To assess the effects of tocilizumab on pregnancy outcomes in Japanese patients with rheumatic disease. METHODS: Data from Chugai's tocilizumab safety database (April 2005 to October 2014) were retrospectively analyzed to identify pregnancy outcomes in patients exposed to tocilizumab. RESULTS: Data were available for 61 pregnancies exposed to tocilizumab, and outcomes were reported for 50 of those pregnancies. In 36 births, no congenital anomalies were identified; however, six neonatal abnormalities were reported: five cases of low birth weight (<2500 g) and one case of neonatal asphyxia. Of 36 births, tocilizumab was resumed during lactation in two patients, with no subsequent adverse events reported in newborns. The spontaneous abortion rate was 18.0% (9 of 50 pregnancies), which is comparable to the rate in the general population. The five terminated pregnancies included one case of caudal regression syndrome. CONCLUSIONS: The present retrospective study of 61 pregnancies exposed to tocilizumab at conception indicated no increased rates of spontaneous abortion or congenital abnormalities in patients with rheumatic disease. However, further study is necessary to confirm the benefit-risk profile of tocilizumab treatment during pregnancy.

[Current evaluation of teratogenic and fetotoxic effects of psychotropic drugs].

Psychiatric disorders are equally common among pregnant and non-pregnant women, and many of these conditions are treated with psychotropic medications. The use of psychotropic medicines during pregnancy, especially antidepressants, became increasingly prevalent in the early 2000's, although many physicians prefer not to prescribe drugs for pregnant women due to concerns about teratogenicity. Current data on the risks of in utero exposure to psychotropic medications are limited, leaving women and physicians to make difficult decisions regarding the initiation or maintenance of treatment during pregnancy without a complete knowledge of the risks. Of all the psychotropics, antidepressant use in pregnancy has been relatively well studied. However, available studies have not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health-related behaviors such as smoking and alcohol use during pregnancy. This review focuses on the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, the antidepressants most commonly used to treat depression. In the evaluation of medication during pregnancy, teratogenicity and fetotoxicity must be considered. Most studies on the use of SSRIs during the first trimester of pregnancy have not shown an increase in the overall risk of major malformations, although several studies have suggested that SSRIs may be associated with a small increased risk of cardiovascular malformations, mainly involving ventricular and atrial septal defects. In addition to structural malformations, drugs were also observed to induce other adverse effects. Since SSRIs readily cross the placenta, concern has been raised about the short- or long-term effects of prenatal exposure to SSRIs on the developing offspring. Epidemiological studies have documented that 10-30% of neonates exposed to SSRIs near term had poor neonatal adaptation syndrome (PNAS). Some studies reported that persistent pulmonary hypertension of the newborn (PPHN) is weakly associated with in utero antidepressant exposure, while no association has been reported in other studies. Recent studies have raised questions about possible associations with antidepressant use during pregnancy and long-term effects on neurobehavioral development. Some individual studies have suggested associations between prenatal exposure to antidepressants and autism spectrum disorder; however, other studies identified no associations. On the other hand, depressive symptoms during pregnancy are also associated with increased risks of preterm delivery, fetal growth retardation, and postpartum depression. Therefore, the effects of untreated maternal depression on both maternal and child outcomes must be taken into consideration when making treatment decisions. Future research needs to focus on large prospective studies with adequate adjustments for key potential confounding factors, including maternal mental illness, other exposures, and an adequate length of follow-up, in order to obtain accurate child developmental outcomes.

Expression of Fas ligand and bcl-2 in cervical carcinoma and their prognostic significance.

Apoptosis-related factors are known to influence survival with many malignant tumors. We performed immunohistochemical analysis of Fas ligand (FasL) and bcl-2 in invasive cervical cancer to determine the association with prognosis. In 125 patients with cervical cancer, 93 cases (74.4%) were positive for FasL, and 94 cases (75.2%) were positive for bcl-2. When 101 cases, clinical stages I through IV, were analyzed by univariate analysis, negative bcl-2 (P = .035) and combined positive FasL and negative bcl-2 (PFNB; P = .0025) were associated with significantly decreased disease-free survival. Positive FasL (P = .042), negative bcl-2 (P = .0004), and PFNB (P < .0001) were associated with a significantly worse prognosis in overall survival. In clinical stages II through IV, positive FasL (P = .04), negative bcl-2 (P = .002), and PFNB (P < .0001) had significant associations with shorter disease-free survival and positive FasL (P = .049), negative bcl-2 (P < .0001), and PFNB (P < .0001) with worse overall survival.