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ObjectivesGlucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy.DesignThis multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022.SettingData were collected from the databases of six Teratology Information Services.ParticipantsThis study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women.ResultsExposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses.ConclusionsThis study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.

As pregnant women are at high risk of severe SARS-CoV-2 infection and COVID-19 vaccines are available in Switzerland, this study aimed to assess the willingness of Swiss pregnant and breastfeeding women to become vaccinated. Through a cross-sectional online study conducted after the first pandemic wave, vaccination practices and willingness to become vaccinated against SARS-CoV-2 if a vaccine was available were evaluated through binary, multi-choice, and open-ended questions. Factors associated with vaccine willingness were evaluated through univariable and multivariable analysis. A total of 1551 women responded to questions related to the primary outcome. Only 29.7% (153/515) of pregnant and 38.6% (400/1036) of breastfeeding women were willing to get vaccinated against SARS-CoV-2 if a vaccine had been available during the first wave. Positive predictors associated with SARS-CoV-2 vaccine acceptance were an age older than 40 years, a higher educational level, history of influenza vaccination within the previous year, having an obstetrician as the primary healthcare practitioner, and being in their third trimester of pregnancy. After the first pandemic wave, Switzerland had a low SARS-CoV-2 vaccination acceptance rate, emphasizing the need to identify and reduce barriers for immunization in pregnant and breastfeeding women, particularly among the youngest and those with a lower educational level.

Little is known about the long-term neurological development of children diagnosed with congenital Zika infection at birth. Here, we report the imaging and clinical outcomes up to three years of life of a cohort of 129 children exposed to Zika virus in utero. Eighteen of them (14%) had a laboratory confirmed congenital Zika infection at birth. Infected neonates have a higher risk of adverse neonatal and early infantile outcomes (death, structural brain anomalies or neurologic symptoms) than those who tested negative: 8/18 (44%) vs 4/111 (4%), aRR 10.1 [3.5–29.0]. Neurological impairment, neurosensory alterations or delays in motor acquisition are more common in infants with a congenital Zika infection at birth: 6/15 (40%) vs 5/96 (5%), aRR 6.7 [2.2–20.0]. Finally, infected children also have an increased risk of subspecialty referral for suspected neurodevelopmental delay by three years of life: 7/11 (64%) vs 7/51 (14%), aRR 4.4 [1.9–10.1]. Infected infants without structural brain anomalies also appear to have an increased risk, although to a lesser extent, of neurological abnormalities. It seems paramount to offer systematic testing for congenital ZIKV infection in cases of in utero exposure and adapt counseling based on these results. Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.

Zika virus (ZIKV), a neurotropic single-stranded RNA flavivirus, remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in populations where ZIKV has adapted to a nexus involving the Aedes mosquitoes and humans. To date, outbreaks of ZIKV have occurred in Africa, Southeast Asia, the Pacific islands, the Americas, and the Caribbean. Emerging evidence, however, suggests that the virus also has the potential to cause infections in Europe, where autochtonous transmission of the virus has been identified. This review focuses on evolving ZIKV epidemiology, modes of transmission and host-virus interactions. The clinical manifestations, diagnostic issues relating to cross-reactivity to the dengue flavivirus and concerns surrounding ZIKV infection in pregnancy are discussed. In the last section, current challenges in treatment and prevention are outlined.

Tobacco smoking is associated with adverse health outcomes for both pregnant women and their offspring. Smoking cessation counseling is an effective method to help women quit smoking. Developing a targeted smoking cessation intervention could benefit those who struggle to quit tobacco and potentially reduce the harm due to any co-occurring tobacco use. Assessing the prevalence of tobacco, electronic nicotine delivery systems (ENDS), nicotine replacement therapy (NRT), and cannabinoid use in pregnancy is key to developing such interventions. Thus, we aimed to assess the prevalence and patterns of tobacco, ENDS, NRT, and cannabinoid use in pregnancy. We further aimed to assess the prevalence of smoking cessation counseling intervention. We conducted a cross-sectional survey among pregnant women attending regular clinical visits at Spitalzentrum Biel between February and May 2023 (n = 262). Frequency and proportion along with 95% confidence intervals (CI) were reported for tobacco, ENDS, NRT, and cannabinoid use in pregnancy. Tobacco use was reported among 7.6% (20/262, 95% CI: 4.2%-11.1%) of the included pregnant women. Tobacco cigarettes (conventional or roll-on) were used by 7.3% (19/262, 95% CI: 3.8%-10.7%) of the surveyed pregnant women, with 0.8% (2/262, 95% CI: 0.0%-3.4%) of them reporting use of cigarettes along with ENDS and 0.4% (1/262, 95% CI: 0.0%-3.8%) reporting use of the cigarettes with NRT. Cannabinoid use was reported by 3.8% (10/262, 95% CI: 1.1%-7.0%) of pregnant women and all of them used products with Cannabidiol (CBD) only. Additionally, only 25% (5/20, 95% CI: 10.0%-48.3%) of tobacco users had received smoking cessation counseling intervention. The estimated prevalence of tobacco, ENDS, NRT, and cannabinoid use among the pregnant women in this survey was 7.6%, 0.8%, 0.4%, and 3.8% respectively. However, among tobacco users, only one-fourth received smoking cessation counseling intervention.

Introduction Exposure to potentially teratogenic medications during pregnancy is underinvestigated in Switzerland. We aimed to assess exposure to potential teratogens preconceptionally, during the first trimester, and in women of childbearing age, and specifically explore the effectiveness of the valproate pregnancy prevention program (2018). Material and Methods Retrospective study using the Swiss Helsana claims database. In a pregnancy cohort (2015–2021) and a cohort of women of childbearing age (2021 and 2018), we defined three 90‐day time periods: (1) first trimester, (2) preconceptional period (days 180–90 before pregnancy), and (3) January 01, 2021, and March 31, 2021 (women of childbearing age). During all periods, we quantified the exposure prevalence to at least one dispensed weak, proven, and unequivocally potent teratogen overall and by age strata. We quantified the exposure prevalence to each individual teratogen, and to valproate during pregnancy by calendar year to compare its use before and after the introduction of a pregnancy prevention program (2018). We investigated the use of systemic retinoids particularly isotretinoin in women of childbearing age. Results Of 34 584 pregnant women, 1.4% were exposed to potential teratogens during the first trimester (weak: 1.3%, proven: 0.06%, unequivocally potent: 0.04%). During the preconceptional period, 2.9% were exposed to any teratogen compared to 4.7% of women of childbearing age (Ntotal = 95 059). Systemic glucocorticoids were the most prevalent weak teratogens during all time periods (75% of all claimed teratogens during the first trimester). In the first trimester, the antibiotic cotrimoxazole and the thyreostatic thiamazole (weak teratogens), ranked second and third, followed by the antiseizure medications carbamazepine and topiramate (proven teratogens). Among women of childbearing age, exposure to weak and proven teratogens increased with age, whereas exposure to unequivocally potent teratogens decreased with age. This was due to 2.3% of women <26 years who claimed systemic isotretinoin. Valproate use during pregnancy decreased after the introduction of a pregnancy prevention program (2.39/10 000 pregnancies [2015–2018] vs. 0.93/10 000 pregnancies [2019–2021]). Conclusions Most medications with potential teratogenic effects dispensed to women of childbearing age and pregnant women were in the group of weak teratogenicity level, and many women discontinued treatment before pregnancy. Preliminary evidence suggests the valproate pregnancy prevention program in Switzerland may be beneficial. In Switzerland, most dispensed medications with teratogenic effect debated or proven were in the group of weak teratogenicity level. Reassuringly, many women discontinue treatment with potential teratogens before pregnancy.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal-fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus-infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January-July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9-57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0-15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9-5.5]).

Janus kinase inhibitors (JAKIs) are immunomodulatory drugs used for autoimmune and inflammatory conditions. Their potential impact on pregnancy and fetal development remains a concern due to placental transfer and potential disruption of cytokine and growth factor signaling, with limited human data. This study analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to assess signals of disproportionate reporting (SDRs) for pregnancy‐related adverse drug reactions (ADRs) reported with systemic JAKIs, including abrocitinib, baricitinib, deucravacitinib, fedratinib, filgotinib, itacitinib, momelotinib, pacritinib, peficitinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. As of May 26, 2024, 163 ICSRs met inclusion criteria, mainly from North America (41.7%) and Europe (39.3%). The most frequently reported JAKIs were tofacitinib (44.8%) and upadacitinib (34.4%), primarily indicated for rheumatoid arthritis (29.4%). Among 213 pregnancy‐related ADRs, spontaneous abortion was the most frequently reported event (47.9%) without representing an SDR compared with other drugs in the database (reporting odds ratio [ROR] 0.37, 95% confidence interval [CI] 0.30–0.46). Congenital anomalies were reported in 16.0% of ICSRs (43 events), but no specific organ‐related patterns were identified. Prematurity occurred in 9.2% of ICSRs, without SDR compared to the full database (ROR 0.07, 95% CI 0.04–0.11). Current pharmacovigilance data from VigiBase do not indicate SDRs for spontaneous abortion or prematurity following JAKI exposure during pregnancy. Findings should be interpreted cautiously given the limitations of spontaneous reporting systems and the exploratory nature of the analysis. Further studies are needed to better characterize the JAKI safety in pregnancy.

Recurrent miscarriage is a distressing condition with limited therapeutic options. Chronic histiocytic intervillositis of unknown etiology (CIUE) is a rare inflammatory placental disorder characterized by maternal immune cell infiltration of the intervillous space, fibrin deposition, and ischemic tissue damage, leading to pregnancy loss. The condition likely reflects an immune response against paternal alloantigens, with histopathological features resembling antibody-mediated rejection in solid organ transplantation. We investigated two women with recurrent CIUE-related pregnancy losses. Detailed immunological profiling included anti-human leukocyte antigen (HLA) antibody characterization, compatibility testing, and histopathological examination of previous placentas, as well as screening for other causes of recurrent pregnancy losses. Based on evidence of antibody-mediated alloimmune injury, we implemented a targeted immunosuppressive regimen derived from transplantation medicine, combining intravenous immunoglobulins (IVIG), tacrolimus, corticosteroids, and hydroxychloroquine, with close pregnancy monitoring. The first patient, after six consecutive CIUE-related pregnancy losses, underwent preconception desensitization and continued treatment throughout pregnancy. Early signs of placental dysfunction prompted therapy intensification, leading to delivery of a viable infant at 33 + 2 weeks. Placental histology showed only minor residual CIUE lesions. The second patient, with two pregnancy losses and a fetal demise from CIUE, began treatment at 6 weeks’ gestation and delivered a healthy infant at 36 weeks. In both cases, therapy was generally well tolerated, with gestational diabetes as the main complication, and no major maternal or neonatal adverse events. These cases support the concept that CIUE represents a breakdown of maternal immune tolerance toward paternal antigens, mediated by fetal-specific anti-HLA antibodies—akin to solid organ graft rejection. An immunosuppressive protocol adapted from transplantation medicine achieved two successful live births after multiple CIUE-related pregnancy losses. Targeting antibody-mediated alloimmunity may represent a promising therapeutic strategy for selected patients with recurrent miscarriages due to CIUE. Further studies are warranted to define optimal regimens and identify predictors of response.

Metformin is considered as first-line treatment for type 2 diabetes and an effective treatment for polycystic ovary syndrome (PCOS). However, evidence regarding its safety in pregnancy is limited. We conducted a systematic review and meta-analysis of major congenital malformations (MCMs) risk after first-trimester exposure to metformin in women with PCOS and pregestational diabetes mellitus (PGDM). Randomized controlled trials (RCTs) and observational cohort studies with a control group investigating risk of MCM after first-trimester pregnancy exposure to metformin were searched until December 2021. ORs and 95% CIs were calculated separately according to indications and study type using Mantel-Haenszel method; outcome data were combined using random-effects model. Eleven studies (two RCTs; nine observational cohorts) met the inclusion criteria: four included pregnant women with PCOS, four included those with PGDM and three evaluated both indications separately and were considered in both indication groups. In PCOS group, there were two RCTs (57 exposed, 52 control infants) and five observational studies (472 exposed, 1892 control infants); point estimates for MCM rates in RCTs and observational studies were OR 0.93 (95% CI 0.09 to 9.21) (I2=0%; Q test=0.31; p value=0.58) and OR 1.35 (95% CI 0.37 to 4.90) (I2=65%; Q test=9.43; p value=0.05), respectively. In PGDM group, all seven studies were observational (1122 exposed, 1851 control infants); the point estimate for MCM rates was OR 1.05 (95% CI 0.50 to 2.18) (I2=59%; Q test=16.34; p value=0.01). Metformin use in first-trimester pregnancy in women with PCOS or PGDM do not meaningfully increase the MCM risk overall. However, further studies are needed to characterize residual safety concerns.