Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are peptide analogues that are used to treat type 2 diabetes mellitus (T2DM) and obesity. The first medication in this class, Exenatide, was approved in 2005, and these medications, specifically Semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there is currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to GLP-1RAs in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by T2DM and compared outcomes from periconceptional exposure to GLP-1RAs and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking GLP-1RAs, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of GLP-1RAs during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking GLP-1RAs.

OBJECTIVE: What are the maternal and neonatal outcomes of second delivery in women who underwent uterine artery embolization (UAE) during their first delivery?
CONCLUSIONS: Women who underwent UAE during their first delivery exhibited higher risks of placental problems, preterm births, and postpartum hemorrhage (PPH) in second delivery and the second offspring also showed increased risk of major congenital malformations, admission to the neonatal intensive care units (NICU), necrotizing enterocolitis, intraventricular hemorrhage, and bronchopulmonary dysplasia.
BACKGROUND: UAE is a minimally invasive procedure used as an alternative to hysterectomy for managing severe PPH. However, recent studies have raised concerns about potential obstetric complications, including recurrent PPH, placenta accreta spectrum (PAS), and fetal growth restriction in subsequent delivery following UAE.
UNASSIGNED: This was a nationwide retrospective cohort study using the Korean National Health Insurance Service (K-NHIS) database, covering 50 million individuals from 2004 to 2020. The cohort included 3 616 923 women with live births between 1 January 2005 and 31 December 2019 with follow-up data extending to 31 December 2020.
METHODS: The study included women who had their first live birth between 2005 and 2019, excluding those who underwent hysterectomy (without UAE = 3 612 389, UAE = 4534). Among them, we selected women who had single gestation secondary delivery (without UAE = 1 694 600, UAE = 1146). Propensity score matching was used to control for confounding factors, resulting in 11 184 women without UAE and 1119 women with UAE for subsequent analysis.
RESULTS: Women in the UAE group had significantly higher risks of PAS (odds ratio (OR) = 38.91, 95% CI = 18.61-81.34), placenta previa (OR = 6.98, 95% CI = 5.57-8.75), and preterm birth (OR = 2.23, 95% CI = 1.71-2.90) during their second delivery. The risk of recurrent PPH was also significantly higher (OR = 8.94, 95% CI = 7.19-11.12). Their second offspring were more likely to have major congenital malformations (OR = 1.62, 95% CI = 1.25-2.11) and adverse neonatal outcomes, including NICU admissions (OR = 1.83, 95% CI = 1.48-2.25). Long-term outcomes showed a higher risk of attention-deficit/hyperactivity disorder (hazard ratio = 1.64, 95% CI = 1.03-2.63) but were otherwise comparable to those in the without UAE group.
CONCLUSIONS: Retrospective nature of the study may have introduced exposure and outcome misclassifications, despite the reliability of the K-NHIS database. Unmeasured confounders and selection bias due to only including live births could also have influenced the results.
CONCLUSIONS: Women with a history of UAE require meticulous prenatal care and close monitoring during subsequent deliveries due to increased risks of complications. Counseling and referral to high-risk medical centers may improve outcomes. Further research is needed to understand the mechanisms of complications in both mothers and offspring at sequential delivery, as well as to refine UAE procedures.
BACKGROUND: This study supported by Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea (HC21C0123). This study was funded by S.-Y.O. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.
BACKGROUND: N/A.

OBJECTIVE: This review aims to summarize existing evidence on the adverse pregnancy outcomes and seizure control effects of using lamotrigine (LTG) monotherapy in pregnancy women with epilepsy (WWE) during pregnancy.
METHODS: A comprehensive search was conducted in various databases including Cochrane, Web of Science, CBM, PubMed, Embase, CNKI, and Pregnancy Registration Center databases to identify relevant studies. The search was concluded up to January 2024. Studies comparing LTG with other antiseizure medications (ASMs) for treating epilepsy in pregnant women were included, with no language or regional restrictions.
RESULTS: A total of 19 studies were included for analysis, with 16 studies reporting adverse pregnancy outcomes and 6 studies reporting seizure control outcomes. Meta-analysis showed that compared to monotherapy with carbamazepine (CBZ), sodium valproate (VPA), and levetiracetam (LEV), LTG monotherapy had a slightly weaker ability to control seizures during pregnancy, with ORs and 95 %CIs of 0.65 (0.57-0.75; CBZ), 0.50 (0.32-0.79; VPA), and 0.55 (0.36-0.84; LEV). Regarding adverse pregnancy outcomes, the occurrence rate of LTG monotherapy was significantly lower than that of CBZ, VPA, phenytoin (PHT), and phenobarbital (PHB), with ORs and 95 %CIs ranging from 0.30 (0.25-0.35; VPA) to 0.68 (0.56-0.81; CBZ).
CONCLUSIONS: Based on meta-analysis, LTG and LEV appear to be preferred medications for controlling seizures during pregnancy. This review provides further support for the use of LTG monotherapy in pregnant WWE, building upon existing evidence for clinical practitioners.

OBJECTIVE: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).
METHODS: This population-based cohort study utilised Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within one year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes, and corticosteroids). Modified Poisson regression models with robust variance estimated risk ratios and 95% confidence intervals (RR 95%CI).
RESULTS: We included 1,007 births (453 exposed) and 2,500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed, and unexposed groups were 3.6%, 3.7%, and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6%, and 4.3%, respectively. The adjusted RRs (95%CI) were 1.29 (0.65-2.56) in the SLE cohort, 1.32 (0.56-3.13) in the RA cohort, and 1.30 (0.76-2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings.
CONCLUSIONS: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ\'s benefits may outweigh the risks in managing SLE or RA during pregnancy.

Objective: To evaluate pregnancy and infant outcomes among persons immunized with a cell-based quadrivalent inactivated influenza vaccine (IIV4c) during routine pregnancy care. Design: Prospective observational cohort. Setting: US-based obstetrics/gynecology clinics. Population: Pregnant persons. This US-based, prospective observational cohort study evaluated the safety of quadrivalent inactivated influenza vaccine (IIV4c; Flucelvax® Quad) in pregnant persons immunized over 3 influenza seasons between 2017 and 2020. Pregnant persons were immunized with IIV4c as part of routine care, after which their health care provides HCPs with all observational data to a single coordinating center. Follow-up data were collected at the end of the second trimester and/or at the time of pregnancy outcome. A scientific advisory committee reviewed the data. Prevalence point estimates were reported with 95% confidence intervals (CIs). Pregnancy outcomes included: live birth, stillbirth, spontaneous abortion, elective termination, and maternal death. Infant outcomes included: preterm birth (<37 weeks gestational age), low birth weight (<2500 g), or major congenital malformations (MCMs). Of the 665 evaluable participants, 659 (99.1%) had a live birth. No stillbirths (0% [95% CI 0.0−0.6]), 4 spontaneous abortions (1.9% [0.5−4.8]), and 1 elective termination (0.5% [0.0−2.6]) were reported. Among 673 infants, 9.2% (upper 95% CI 11.5%) were born prematurely, 5.8% (upper 95% CI 7.6%) had low birth weight, and 1.9% (upper 95% CI 3.1%) were reported to have an MCM. No maternal deaths were reported. Of the 2 infants who died shortly after birth, one was adjudicated as not related to the vaccine; the other’s cause could not be determined due to maternal loss to follow-up. The prevalence of adverse pregnancy outcomes or preterm birth, low birth weight, or MCMs in newborns was similar in persons vaccinated with IIV4c compared to the rates observed in US surveillance systems. The safety profile of IIV4c in pregnant persons is consistent with previously studied influenza vaccines.

This US-based, prospective observational cohort study evaluated the safety of a quadrivalent inactivated influenza vaccine (IIV4; Afluria Quadrivalent) in pregnant persons immunized over four influenza seasons between 2017 and 2021. Pregnancy outcomes included live birth, stillbirth, spontaneous abortion, and elective termination. Infant events of interest were major congenital malformations (MCMs), preterm birth (<37 weeks gestational age), and low birth weight (LBW). Data were descriptive; prevalence point estimates were reported with 95% confidence intervals (CI). A total of 483 pregnant persons were given IIV4 and evaluated; 477 (98.8%) reported a live birth, and there were 2 stillbirths, 4 spontaneous abortions, and no elective terminations or maternal deaths. The prevalence rates of infant events were as follows: preterm birth, 7.2% (upper 95% CI, 9.6%); LBW, 5.4% (upper 95% CI, 7.4%); and MCMs, 0.8% (upper 95% CI, 1.9%). Point estimates and upper 95% CIs of the observed prevalence rates were lower than or similar to background prevalence in the general US population. Our findings suggest no evidence of a safety concern with vaccinating this group at high risk of influenza complications and are consistent with published data from databases and surveillance systems that monitor the safety of influenza vaccines in pregnant persons.

Sex and gender differences in epilepsy are important influencing factors in epilepsy care. In epilepsy, the hormonal differences between the sexes are important as they impact specific treatment considerations for patients at various life stages particularly during early adulthood with establishment of the menstrual cycle, pregnancy, perimenopause and menopause. Choice of antiseizure medication may have direct consequences on hormonal cycles, hormonal contraception, pregnancy and fetal risk of major congenital malformation. Conversely hormones whether intrinsic or extrinsically administered may have direct impact on antiseizure medications and seizure control. This chapter explores these important influences on the management of persons with epilepsy.

The therapeutic management of women with epilepsy (WWE) of childbearing age can be complicated by the need to balance maternal/fetal risks related to seizure occurrence during gestation with the potential teratogenic risks related to the use of anti-seizure medications (ASMs).
The authors review clinical evidence on seizure-related and ASM-related risks during pregnancy. Current regulatory indications are discussed, evaluating their impact on clinical practice, and ethical implications of pharmacological decisions are debated.
If properly informed about the maternal/fetal risks carried by different pharmacological choices, WWE can become the final decision makers regarding their care in every phase of their life. Over the coming years, analysis of aggregated pregnancy registry data on the structural impact, on the fetus, of low doses of valproate and of newer ASMs, together with analysis of the main population study data on functional (cognitive and behavioral) outcomes, could lead to huge advances, making choosing an ASM a less complex process for the clinician and a less painful decision for the woman. Future objectives should include identification of the potential role of the pharmacogenomic profile of WWE in determining the risk of fetal malformations.

OBJECTIVE: To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM).
METHODS: A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models.
RESULTS: Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results.
CONCLUSIONS: Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.

OBJECTIVE: To compare the antiepileptic drug (AED) treatment patterns, seizure control, and folic acid supplementation between planned and unplanned pregnancy in women with epilepsy (WWE) and to investigate the effects of planned pregnancy on fetal outcomes.
METHODS: A prospectively collected database including WWE with pregnancy from Feb 2010 to Dec 2018 was retrospectively analyzed. Planned pregnancy was defined as WWE being regularly supervised by epileptologists from the time of intended pregnancy until delivery. Clinical characteristics and fetal outcomes were compared between the planned and unplanned pregnancy groups. Logistic regression was used to identify modifiable factors associated with adverse fetal outcomes.
RESULTS: A total of 188 planned pregnancies and 289 unplanned pregnancies were enrolled in our study. Among planned pregnancies, 66.0 % took AED monotherapy, and 32.4 % received polytherapy. Among unplanned pregnancies, 58.1 % didn\'t take AEDs, 28.0 % took monotherapy, and 12.8 % received polytherapy. The planned pregnancies had less generalized tonic-clonic seizures (P = 0.002) and higher proportion of being seizure-free (41.0 % vs. 22.8 %; P <0.001). All planned pregnancies took folic acid while 39.8 % of unplanned pregnancies never took it (P <0.001). The planned pregnancies had less rates of induced abortions (2.7 % vs. 13.5 %; P <0.001), preterm births (3.3 % vs. 20.4 %; P <0.001), and major congenital malformations (1.6 % vs. 7.5 %; P = 0.016). Pregnancy planning was independently associated with adverse fetal outcomes (adjusted OR, 0.14; 95 % CI, 0.08-0.27; P <0.001).
CONCLUSIONS: Planned pregnancy in WWE contributes to more optimized AED pattern, better seizure control, more appropriate folic acid supplementation, and less adverse fetal outcomes.