Risk Of Malformations Research Articles

Cryopreservation of human spermatozoa or testicular tissue for fertility preservation

Loss of reproductive capacity due to treatments for malignant or non-malignant diseases or even as aresult of diseases themselves significantly impacts patients' quality of life. Cryopreservation of sperm from ejaculate is awell-established procedure for preserving the fertility of these patients and thus improving their quality of life in the long term. If cryopreservation of sperm from ejaculate is not possible, either because ejaculation cannot occur or no sperm can be found in the ejaculate, the preferred treatment option is (microsurgical) testicular sperm extraction (mTESE). Testicular sperm and ejaculated spermatozoa can be cryopreserved and later used for intracytoplasmic sperm injection (ICSI) treatment. The use of cryopreserved sperm for fertility treatment does not carry an increased risk of malformations in the offspring. If gonadotoxic therapy is necessary in pre- or early pubertal boys, the only option to preserve fertility in the long term is to cryopreserve spermatogonial stem cells from testicular tissue as part of the Androprotect© network. This is an experimental approach which has been available since 2012 acrossGermany and which is accompanied by intensive scientific work ( www.androprotect.de ).

Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study

ObjectiveTo evaluate the association between paternal metformin use and risk of congenital malformations in offspring.DesignPopulation based, cross national cohort study.SettingNorway and Taiwan.Participants619 389 offspring with paternal data during the period...

Maternal periconception hyperglycemia, preconception diabetes, and risk of major congenital malformations in offspring.

What are the roles of maternal preconception diabetes and related periconceptional hyperglycemia on the risk of major congenital malformations (MCMs) in offspring? Maternal periconceptional glycated hemoglobin (HbA1c) levels over 5.6% were associated with an increased risk of congenital heart defects (CHD) in the offspring, and maternal preconception diabetes was associated with an increased risk of CHD, including when HbA1c levels were within euglycemic ranges. Maternal preconception diabetes has been linked with MCMs in the offspring. However, evidence concerning associations with specific periconception serum measures of hyperglycemia, and susceptibility of different organ systems, is inconsistent. Moreover, limited evidence exists concerning the effectiveness of antidiabetic medications in mitigating diabetes-related teratogenic risks. A large Israeli birth cohort of 46534 children born in 2001-2020. Maternal HbA1c test results were obtained from 90 days before conception to mid-pregnancy. Maternal diabetes, other cardiometabolic conditions, and MCMs in newborns were ascertained based on clinical diagnoses, medication dispensing records, and laboratory test results using previously validated algorithms. Associations were modeled using generalized additive logistic regression models with thin plate penalized splines. Maternal periconceptional HbA1c value was associated with CHD in newborns, with the risk starting to increase at HbA1c values exceeding 5.6%. The association between HbA1c and CHD was stronger among mothers with type 2 diabetes mellitus (T2DM) compared to the other diabetes groups. Maternal pre-existing T2DM was associated with CHD even after accounting for HbA1C levels and other cardiometabolic comorbidities (odds ratio (OR)=1.89, 95% CI 1.18, 3.03); and the OR was materially unchanged when only mothers with pre-existing T2DM who had high adherence to antidiabetic medications and normal HbA1c levels were considered. The rarity of some specific malformation groups limited the ability to conduct more granular analyses. The use of HbA1c as a time-aggregated measure of glycemic control may miss transient glycemic dysregulation that could be clinically meaningful for teratogenic risks. The observed association between pre-existing diabetes and the risk of malformations within HbA1c levels suggests underlying causal pathways that are partly independent of maternal glucose control. Therefore, treatments for hyperglycemia might not completely mitigate the teratogenic risk associated with maternal preconception diabetes. The work was supported by NIH grants K99ES035433, R01HD097778, and P30ES000002. None of the authors reports competing interests. N/A.

Chromosome 8p Syndromes Clinical Presentation and Management Guidelines.

Rearrangements of the p-arm of Chromosome 8 can result in a spectrum of neurodevelopmental challenges, along with increased risk of epilepsy, structural brain and cardiac malformations, persisting developmental delays, and other health challenges. The majority of patients reported on in this sample are characterized by an inverted-duplication deletion rearrangement, but deletions, duplications, and mosaic ring changes in 8p result in similar phenotype. In this report, we add to the phenotypic and functional description of these patients according to their specific chromosomal rearrangement, share neuro-psychometric values, and propose surveillance care guidelines for caregivers and medical providers of patients with Chromosome 8p Syndromes. Observations from clinical experience with 24 patients seen at our 8p-dedicated Multi-Disciplinary Neurogenetics program are shared.

Risk of Congenital Malformation in Newborns of Mothers with Kidney Diseases: A Retrospective Cohort Study Using National Health Insurance Service Data

Risk of Congenital Malformation in Newborns of Mothers with Kidney Diseases: A Retrospective Cohort Study Using National Health Insurance Service Data

Clinical features, hemorrhage risk and epilepsy outcomes of familial cerebral cavernous malformation: A 20-year observational pragmatic single-center study

IntroductionFamilial Cerebral Cavernous Malformations (fCCMs) are rare, hereditary conditions characterized by multiple central nervous system lesions. Despite their rarity, CCMs can cause significant clinical challenges when symptomatic, manifesting as seizure and symptomatic hemorrhage (CASH). Guidelines suggest neurosurgical intervention for symptomatic or previously symptomatic lesions, while conservative management is recommended for new-onset epilepsy. However, the natural history and optimal management remain unclear, necessitating further research. ObjectiveThis study aims to provide a comprehensive analysis of the clinical features, hemorrhage risk, and epilepsy outcomes in fCCM patients over an extended follow-up period, offering a more precise estimate of CASH and epilepsy rates in this population. MethodsThis retrospective longitudinal cohort study included fCCM patients enrolled from 2001 to May 2024. Data collected included demographic information, new neurological symptoms, symptomatic hemorrhages, seizures, and modified Rankin Scale (mRS) scores. Incidence rates of first symptomatic events and Kaplan-Meier survival curves were calculated, with logistic and Cox-proportional hazard regression models used to evaluate outcomes. ResultsA total of 47 patients were included in this study, with a mean age at diagnosis of 37.51 years. At diagnosis, 68 % were symptomatic, with 30 % having CASH and 36 % experiencing seizures without CASH. During a median follow-up of 126.0 months (interquartile range, 110.5 months), 17 % had a new CASH event, 20 % had seizures without CASH, and 60 % remained asymptomatic. The bleeding rate was 1.02 % per patient-year, with new focal neurological symptoms at 2.045 per 1000 patient-years and new CASH at 10.225 per 1000 patient-years. Most patients maintained minimal or no disability (mRS 0 or 1). Presenting with epilepsy at baseline significantly increased the odds of future seizures (OR 18.13, p = 0.001). ConclusionThis study highlights the complex presentation and progression of fCCMs, emphasizing the necessity for long-term monitoring. Baseline epilepsy is a significant predictor of future seizures, underscoring the need for individualized management strategies. Future research with larger cohorts and standardized criteria is essential to refine the understanding and management of fCCMs.

Cool mama: Temperature regulation during high-intensity interval running in pregnant elite and recreational athletes

BackgroundRegular exercise during pregnancy is beneficial, but athletes often exceed the recommended 150 min of moderate-intensity activity, incorporate high-intensity exercises. The upper limit for exercise intensity and duration on fetal and maternal safety remains uncertain. A concern is a maternal core body temperature of >39.0 °C, potentially increase the risk of heat-related fetal malformations and complications during pregnancy. Blood flow redirection for thermoregulation could compromise fetal cardiovascular function, increasing the risk of miscarriage and preterm labor. This study evaluated whether pregnant women (gestational weeks 25–35) were at risk of exceeding a core body temperature of 39.0 °C during high-intensity running. We also investigated effects on skin temperature, fluid loss, and thermal sensation, comparing pregnant athletes to non-pregnant controls. MethodsIn this comparative cross-sectional study, 30 elite and recreational athletes (pregnant n = 15) completed up to five high-intensity treadmill-intervals. Core and skin temperature were continuously measured. Body weight was utilized to calculate the amount of fluid loss. ResultsHighest core body temperature were 38.76 °C and 39.56 °C in one pregnant and non-pregnant participant, respectively. Pregnant participants had lower core body temperatures (mean difference −0.47 °C, p ≤ 0.001) initially and a smaller increase (0.10 °C, p ≤ 0.003) during later intervals compared with the non-pregnant controls. Pregnant participants also showed a greater increase in skin temperature (4.08 ± 0.72 °C vs. 3.25 ± 0.86 °C, p = 0.008) and fluid loss (0.81 ± 0.19 L vs. 0.50 ± 0.12 L, p˂0.001). ConclusionPhysiological changes in pregnancy may enhance thermoregulation, indicating that high-intensity interval runs are unlikely to pose a risk of exceeding a core body temperature of 39 °C for pregnant athletes.

Perinatal outcomes with a copper intrauterine device in situ after 28 gestational weeks: A retrospective study of sole center in southeast China.

The purpose of this study was to investigate the pregnancy outcomes with a copper intrauterine device (IUD) in situ after 28 gestational weeks and the association between pregnancy with copper IUDs and neonatal congenital malformations. This retrospective study had compared the singleton pregnancies with the copper IUDs in situ and without after 28 gestational weeks in 1 delivery center of southeast China. The main exposure was a copper IUD in uterine cavity with pregnancy. The pregnant outcomes as preterm birth, premature rupture of membranes, infections were observed and compared. We had also compared neonatal congenital malformations in 2 groups. The statistical analysis was carried out using R (version 4.0.4; R Development Core Team) statistical software. Association between IUD use or duration of IUD use and adverse pregnancy outcomes were estimated using logistic model. Two-tailed P value < .05 was deemed statistically significant. A total of 148 pregnant women were included in our study, 74 with copper IUDs in situ were categorized into case group and 74 without IUDs during pregnancy into control group. No significant difference of maternal age, BMI, birth weight and gender were observed between 2 groups. In case group, the rates of preterm premature rupture of membranes (37.8%) and spontaneous preterm birth (23.0%) were significantly high compared to control group. Odds ratios of premature rupture of membranes and spontaneous preterm birth were 2.86 and 5.22 respectively. Women of elder age (≥35 years) in case group were more likely to experience premature rupture of membranes. The rates of neonatal congenital malformation were 10.8% (8/74) in case group and 1.4% (1/74) in control group respectively. We had found that pregnancy with copper IUD in situ increased the risk of premature rupture of membranes and spontaneous preterm birth after 28 gestation weeks, the risk of spontaneous preterm birth increased 5.22 times. Pregnancy with IUD in situ may be at increased risk of infection and neonatal malformation.

Cognitive outcomes after fetal exposure to carbamazepine, lamotrigine, valproate or levetiracetam monotherapy: Data from the EURAP neurocognitive extension protocol

PurposePrenatal exposure to antiseizure medications (ASMs) has been associated with an increased risk of major malformations and neurodevelopmental disorders, with the latter being mainly associated with valproate (VPA). Our aim was to compare neurocognitive outcome at age 6–7 years in children exposed prenatally to lamotrigine (LTG), carbamazepine (CBZ), valproate (VPA) or levetiracetam (LEV) monotherapy. MethodsEligible mother–child pairs were identified from the observational prospective multinational EURAP cohort study. Assessor-blinded testing was conducted at age 6–7 years using WISC-III and NEPSY-II. Verbal IQ (VIQ), performance IQ (PIQ), full scale IQ (FSIQ) and performance in neuropsychological tasks were compared across ASM groups by ANOVA. Scores were adjusted for maternal IQ, paternal education, maternal epilepsy type and child sex. ResultsOf 169 children enrolled in the study, 162 (LTG n = 80, CBZ n = 37, VPA n = 27, LEV n = 18) had sufficient data from WISC-III, NEPSY-II or both, and were included in the analyses. Observed (unadjusted) PIQ and FSIQ did not differ across exposure groups, but a difference was identified for VIQ (P<0.05), with children exposed to VPA having lower scores than children exposed to LEV (P<0.05) and children from all groups combined (P<0.01). Adjusted VIQ, PIQ and FSIQ scores did not differ significantly across groups, but VPA-exposed children had borderline significantly lower adjusted VIQ scores than children from all groups combined (P=0.051). VPA-exposed children had lower scores in comprehension of instructions before and after adjustment for confounding variables than children exposed to LTG (P<0.001), LEV (P<0.01) or children from all groups combined (p < 0.001). The VPA-exposed group also had lower scores in immediate and delayed memory for faces compared to children exposed to CBZ (P<0.05 and P<0.001, respectively) and LTG (P<0.05 and P<0.02, respectively), and children from all groups combined (P<0.02 and P<0.001, respectively). LEV-exposed children had lower scores in delayed memory for names than children exposed to LTG (P<0.001), CBZ (P<0.001), VPA (P<0.05) and children from all groups combined (P<0.001). ConclusionsConsistent with previous reports, our results provide evidence for an adverse effect of prenatal exposure to valproate on verbal development. Our finding of relatively weaker performance of VPA-exposed children compared to other ASM exposures in both comprehension of instructions and face memory also suggest that children of mothers treated with VPA are at increased risk for compromised memory functions or altered processing of socially relevant information.

Exposure to GLP-1 receptor agonists in early pregnancy did not increase the risk of congenital malformations.

Exposure to GLP-1 receptor agonists in early pregnancy did not increase the risk of congenital malformations.

Genetic Insights Into Perinatal Outcomes of Maternal Antihypertensive Therapy During Pregnancy

Limited information exists regarding the impact of pharmacotherapy in pregnancy due to ethical concerns of unintended fetal harm. Yet, maternal prescriptive drug use for chronic conditions such as hypertension is common. To investigate potential causal relationships between perturbing maternal genetic variants influencing antihypertensive drug targets and perinatal outcomes among offspring using mendelian randomization (MR). This 2-sample MR study used individual-level single-nucleotide variation (SNV) outcome data from mother-father-offspring trios with complete genetic and phenotypic information from the Norwegian Mother, Father and Child Cohort Study (MoBa) and summary-level SNV exposure data from UK Biobank participants sourced from the Integrative Epidemiology Unit OpenGWAS project. Pregnant individuals were recruited across Norway during their routine ultrasonography examination at 18 weeks' gestation between June 1999 and December 2008, and mothers, fathers, and offspring were followed up after birth. Novel genetic instruments for maternal antihypertensive drug targets that act via systolic blood pressure (SBP) were derived from individual-level data analyzed in January 2018. Two-sample multivariable MR analysis of these maternal drug targets and offspring outcomes were performed between January 2023 and April 2024. Maternal genetic variants associated with drug targets for treatments of hypertension, as specified in the National Health Service dictionary of medicines and devices. Offspring outcomes were Apgar score at 1 minute and 5 minutes, offspring developmental score at 6 months, birth length, birth weight z score, gestational age, head circumference, and congenital malformation. Maternal hypertensive disorders of pregnancy were a positive control. The MoBa sample contained 29 849 family trios, with a mean (SD) maternal age of 30.2 (18.6) years and a mean (SD) paternal age of 32.8 (13.1) years; 51.1% of offspring were male. Seven independent SNVs were identified as influencing maternal SBP via the antihypertensive drug target instruments. For higher levels of maternal SBP acting through the CACNB2 calcium channel blocker target, the estimated change in gestational age was 3.99 days (95% CI, 0.02-7.96 days) per 10-mm Hg decrease in SBP. There was no evidence of differential risk for measured perinatal outcomes from maternal SBP acting through drug targets for multiple hypertensive subclasses, such as between the ADRB1 β-adrenoceptor-blocking target and risk of congenital malformation (estimated odds ratio, 0.28 [95% CI, 0.02-4.71] per 10-mm Hg decrease in SBP). Maternal and paternal SBP acting through the EDNRA vasodilator antihypertensive target did not have a potential causal effect on birth weight z score, with respective β estimates of 0.71 (95% CI, -0.09 to 1.51) and 0.72 (95% CI, -0.08 to 1.53) per 10-mm Hg decrease in SBP. The findings provided little evidence to indicate that perturbation of maternal genetic variants for SBP that influence antihypertensive drug targets had potential causal relationships with measures of perinatal development and health within this study. These findings may be triangulated with existing literature to guide physicians and mothers in decisions about antihypertensive use during pregnancy.

The Association of Adverse Pregnancy Outcomes With Overactive Bladder Anticholinergics.

The pregnancy safety and teratogenicity of overactive bladder (OAB) anticholinergic medications in humans are unknown. The aim of this study was to determine if the use of OAB anticholinergics during pregnancy was associated with adverse pregnancy outcomes or congenital malformation. Using routinely collected health care data from Ontario, Canada, we conducted a retrospective cohort study and identified women aged 18-45 years who gave birth between 2004 and 2022 and were eligible for provincial drug benefits. We used gestational age and birth dates to approximate conception dates. The primary exposure was filling a prescription for an OAB anticholinergic during pregnancy (compared with nonusers). The coprimary outcomes were pregnancy complication (which included preterm birth or low birth weight) and congenital malformation. Poisson regression models with generalized estimating equations and inverse probability of treatment weighting were used to estimate risk ratios (RRs). We identified 138,271 births, of which 479 (0.3%) had exposure to an OAB anticholinergic, for a median of 60 (interquartile range, 30-120) days. The most common OAB anticholinergic was oxybutynin (84%). In the weighted cohort, the risk of a pregnancy complication was significantly elevated (RR, 1.65; 95% confidence interval [CI], 1.40-1.95; P < 0.01; absolute risk difference + 9.9% [95% CI, +5.9, +13.9]), with a dose-response relationship close to statistical significance (P = 0.07). The risk of congenital malformations with OAB anticholinergic use was not significant (RR, 1.24; 95% CI, 0.85-1.80; P = 0.26). Pregnant women who take OAB anticholinergic medications have a higher risk of pregnancy complications, but not congenital malformations, compared with non-OAB anticholinergic users. This information can be used when counseling women of child-bearing age about these medications.

The Methodological Quality of Observational Studies Examining the Risk of Pregnancy Drug Use on Congenital Malformations Needs Substantial Improvement: A Cross-Sectional Survey.

An increasing number of observational studies have investigated the risk of using drugs during pregnancy on congenital malformations. However, the credibility of the causal relationships drawn from these studies remains uncertain. This study aims to evaluate the potential methodological issues in existing observational studies. We used a stepwise approach to investigate this issue. First, we identified observational studies published in 2020 that examined the risk of congenital malformations associated with medication use during pregnancy. We assessed the methodological characteristics for establishing causality, including study design, confounding control, and sensitivity analysis, and compared them between "core clinical journals" and "general journals." For studies reporting an increased risk of congenital malformations in core clinical journals, we searched for subsequent studies addressing the same research question published between January 2021 and May 2023 to assess the consistency of the literature. A total of 40 eligible studies were published in 2020, primarily focused on the safety of vitamin B12 and folic acid (n=4), antidepressants (n=4), and others (n=32). Our findings suggest that only two (5.00%) studies used causal models to guide the identification of confounding, and only eight (20.00%) studies assessed the potential dose-response relationship. In all, 15 (37.50%) studies used propensity score analysis strategy to achieve "mimic-randomization." In addition, 22 studies (55.00%) performed sensitivity analyses, while 10 (45.45%) showed inconsistency with the primary outcome. Furthermore, 5 studies reported positive outcomes, whereas only 1 out of 11 studies demonstrated a positive correlation between drug usage during pregnancy and major malformations in subsequent studies. A significant portion of the studies has failed to sufficiently consider the essential methodological characteristics required to improve the credibility of causal inferences. The increased risk of congenital malformations documented in core clinical journal was not adequately replicated in subsequent studies.

Exposures to non-therapeutic chemicals before, during and after pregnancy: data from the Swiss Teratogen Information Service (STIS).

Limited knowledge exists regarding exposures to non-therapeutic chemicals by women planning to conceive, or during pregnancy or breastfeeding. The Swiss Teratogen Information Service (STIS) provides information to healthcare professionals about medications and other exposures during pregnancy or breastfeeding. This study aimed to describe the queries on non-therapeutic chemicals addressed to the STIS over the past two decades. Using data from the STIS for the years 2000 to 2019, we conducted a descriptive analysis of all queries related to women's exposures to non-therapeutic chemicals during pregnancy planning, pregnancy or breastfeeding. Over two decades, the STIS database recorded 320 exposures to chemicals. Workplace settings accounted for over 60% of queries, followed by exposures at home (20%). In almost half (48%) of the queries, more than one chemical was mentioned, totalling 885 chemicals across these 320 queries. Commonly mentioned chemicals included isopropanol, acetone and lead. Solvents were the leading category of products (16%), followed by cleaning products (10%), paints (8%) and insecticides (5%). The follow-up data showed five diverse cases of congenital malformations, accounting for 4.0% (5 out of 125) of the sample, a figure in line with the background risk of malformations in the general population. This study emphasises the importance of conducting research that comprehensively captures the highly heterogeneous exposures to non-therapeutic chemicals during pregnancy and suggests that attention should be given not only to professional settings, but also to domestic contexts.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

Epilepsy, Antiepileptic Drugs, and Adverse Pregnancy Outcomes, 2: Major Congenital Malformations With Antiepileptic Drug Monotherapy.

Women with epilepsy (WWE) are usually advised antiepileptic drug (AED) treatment even during pregnancy. It is therefore important to know what the major congenital malformation (MCM) risks might be with untreated epilepsy, and with first-trimester exposure to different AEDs in monotherapy. This article reviews recent findings from a large multinational registry, a large multinational population based study, and a large meta-analysis. In summary, data from the meta-analysis suggest that the MCM rate is 2%-3% in women without epilepsy and about 3% in WWE who were unexposed to AEDs during pregnancy. Data from the meta analysis also suggest that the MCM rate is approximately population level at 2.6%-3.5% with levetiracetam and lamotrigine and that it is about 4%-5% with carbamazepine, 2.8%-4.8% with oxcarbazepine, about 4% with topiramate, about 5%-7% with phenytoin, about 6%-9% with phenobarbital, and nearly 10% with valproate. The MCM risk with valproate is significantly higher than that with other AEDs (including topiramate and phenobarbital) that significantly increase the risk. Data from the registry suggest that risks are dose-dependent with valproate, phenobarbital, and carbamazepine and that the risk with valproate may be as high as 25% at doses >1,450 mg/d. Valproate is also associated with a wide range of MCMs. Data from the population-based study were generally confirmatory. Strengths and limitations of the studies are considered. The findings of these studies encourage the consideration of levetiracetam or lamotrigine monotherapy for WWE who are pregnant and strongly discourage the consideration of the older AEDs, especially phenytoin and phenobarbitone, and most especially valproate. These considerations also apply to all WWE of childbearing age because it may not be easy to change AEDs when pregnancy is planned and because pregnancy is often unplanned.

Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan

Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations. We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process. The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons. The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making. National Science and Technology Council.

Summary for Patients: Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations.

Summary for Patients: Metformin Use in the First Trimester of Pregnancy and Risk for Nonlive Birth and Congenital Malformations.

The most common teratogens as factors of mutability: A literature review

Introduction: The teratogenic agents during the embryonic period can result in disorders in organ differentiation. Concerns regarding medication use during pregnancy heightened after the thalidomide case in the 1960s, underscoring the need for a balance between caution and effective treatment, given the lack of clear information on risks. The aim of the research was to understand teratogens as factors that increase mutability and highlight the relevance of preventive strategies to ensure fetal and maternal health. Methods: Literature review using the PubMed database, Scopus and Web of Science was conducted. Forty-four articles, documents, clinical trials, and systematic reviews published in English were included. Teratogens and their effects, as well as preventive strategies for teratogenic congenital defects, were explored. Results: Risks associated with specific substances were examined, highlighting their effects on the fetus and providing epidemiological data. Preventive measures such as vaccination, folic acid supplementation, and control of metabolic diseases were addressed. Conclusions: During pregnancy, it is crucial to avoid exposure to chemicals, drugs, and medications that may harm the fetus. Caution should be exercised with the use of medications, and alcohol, tobacco, and illicit drugs should be avoided. Preventive strategies such as vaccination and folic acid supplementation reduce the risk of congenital malformations and promote a healthy pregnancy.

Zika virus infection: sexual transmission and implications for prevention

Zika virus infection, most oft n responsible for a benign arboviral disease or an asymptomatic infection, rarely Guillain-Barré syndrome, can become problematic in pregnant women, due to a risk of fetal malformations, in particular microcephaly linked to its neurotropism. The most recent large-scale epidemic was observed throughout Latin America between 2015 and 2017, causing several hundred thousand cases. Transmission is predominantly vector-borne, but sexual transmission has been described, mainly among travelers, although it undoubtedly accounts for a significant proportion of transmission in epidemic areas. The aim of this review is to describe this sexual transmission, mainly through examples linked to this large-scale epidemic in Latin America, to describe the link with prolonged excretion of infectious viral particles in genital secretions, especially semen but also vaginal secretions, and to highlight possible preventive measures apart from vector transmission, in particular the need for pregnant women or women wishing to become pregnant to avoid visiting countries where circulation of Zika virus is described.