Risk Of Birth Defects Research Articles

Methotrexate use among men—association with fertility and the perinatal health of their children: a Swedish nationwide register study

To study the effect of methotrexate on male fertility and subsequent effects on their children, for which data are scarce and contradictory. Nationwide multiregister cohort study. Not applicable. All children born alive in Sweden between 2006 and 2014 and their fathers. Three cohorts were defined: children to fathers with periconceptional methotrexate exposure (exposed cohort), children whose fathers stopped methotrexate intake ≥2 years before conception (previously exposed cohort), and children to fathers with no methotrexate exposure (control cohort). The father having at least one dispensed methotrexate prescription from pharmacies 0-3 months before conception, along with at least one more dispensed methotrexate prescription 0-12 months before conception (periconceptional exposure). Previously exposed cohort: the father having no dispensed methotrexate prescriptions in the 2 years before conception, but having at least two dispensed prescriptions before that. Congenital anomalies (major and any; primary outcomes), preterm birth (PTB) and being small for gestational age (SGA; secondary outcomes), as well as need of intracytoplasmic sperm injection (ICSI) to achieve pregnancy (primary outcome in exposed cohort vs. controls, exploratory outcome in previously exposed cohort vs. controls). Outcomes were analyzed using logistic regression. A total of 223 children to fathers with periconceptional methotrexate exposure were identified, along with 356 children whose fathers stopped methotrexate intake ≥2 years before conception and 809,706 not methotrexate-treated controls. In children with fathers periconceptionally exposed to methotrexate, the adjusted and unadjusted odds ratios (95% confidence intervals) for major congenital anomalies were 1.1 (0.4-2.6) and 1.1 (0.4-2.4), any congenital anomalies 1.3 (0.7-2.4) and 1.4 (0.7-2.3), PTB 1.0 (0.5-1.8) and 1.0 (0.5-1.8), SGA 1.1 (0.4-2.6) and 1.0 (0.4-2.2), and conception by use of ICSI 3.9 (2.2-7.1) and 4.6 (2.5-7.7). Use of ICSI was not increased among fathers who stopped methotrexate intake ≥2 years before conception, having adjusted and unadjusted odds ratios 0.9 (0.4-1.9) and 1.5 (0.6-2.9). This study suggests that paternal periconceptional methotrexate use does not increase risk of congenital anomalies, PTB, or SGA in the offspring but may temporarily reduce fertility.

Pregnancy-associated Cancer and Chemotherapy during Pregnancy

The diagnosis of pregnancy-associated cancer, although rare, is a condition of great human and social significance and difficult clinical management. A pregnancy-associated neoplasm is defined as a cancer diagnosis made during pregnancy or within 12 months after delivery/abortion. The most common cancers in pregnancy occur most frequently in women of reproductive age with an incidence overall like that observed in non-pregnant women of the same age. This incidence is likely to increase in view of both the expected increase in certain malignancies among young women (particularly breast cancer and melanoma) and the increasing frequency of pregnancies undertaken later in life (fourth and fifth decades of life) that is characterizing modern society. Chemotherapy is generally contraindicated before 12 weeks of pregnancy due to the increased risk of congenital anomalies while exposure in the second and third trimester of pregnancy to chemotherapy has been associated with more growth restriction and preterm delivery. Clinical decisions about the optimal management should consider maternal and fetal characteristics with the involvement of a multidisciplinary team.

Analysis of Fetal Chromosome Abnormalities by Karyotpye

Prenatal screening is a crucial method employed during the fetal stage to detect and intervene early, thereby ensuring the health of newborn babies. This approach serves to enhance the overall quality of the population and mitigate the severe consequences associated with birth defects. Prenatal screening encompasses various techniques, including epidemiological investigations, fetal imaging ultrasound, maternal blood screening, and amniotic fluid screening by karotype technique. The process involves extracting fetal chromosomes from cells present in the amniotic fluid, followed by cell culture and hypotonic treatment. Subsequently, these chromosomes are stained with G-band and examined under a microscope. The results obtained from prenatal screening in a sample of 121 patients, with an average age of 32 ± 6.69, indicated that 21% of pregnant women had experienced a miscarriage, 23.1% had previously given birth to a malformed baby, 8.3% of families had a genetic disease, and 5% of parents exhibited chromosomal abnormalities. Among the 51 patients screened using the Double test, 26.45% of fetuses exhibited a high risk of birth defects, whereas the Tripple test identified a high risk in 9.09% of the 19 cases. Chromosome analysis of the 121 cases revealed that 15.7% of the fetuses exhibited chromosomal abnormalities, with Edwards syndrome accounting for 5.78%, Down syndrome accounting for 4.96%, chromosomal abnormalities accounting for 3.30%, Patau syndrome accounting for 0.83%, and Turner syndrome accounting for 0.83%. Age over 35 years (r = 0.08 and OR = 0.63), history of miscarriage (r = 0.05 and OR = 1.38), family history of hereditary disease (r = 0.04 and OR = 1.38), and parental chromosomal mutations (r = 0.01 and OR = 1.08) were all found to have a strong positive correlation with fetal abnormalities. Additionally, positive correlations were observed between the results of ultrasound screening (r = 0.22 and OR = 5.48) and blood screening (r = 0.14 and OR = 1.22).
 Prenatal screening, Amniocentesis, Karyotype, Chromosome, fetal chromosome.
 
 

P-736 Balanced cryptic chromosomal rearrangement carriers detection by optical genome mapping (OGM)

Abstract Study question To evaluate diagnosis value of optical genome mapping (OGM) for potential preimplantation genetic testing in chromosomal structural rearrangement (PGT-SR) patients with cryptic chromosomal rearrangement. Summary answer OGM is an efficient method for cryptic chromosomal rearrangement detection. However, SVs near telomere and centromere regions could hardly be reported with this method. What is known already About 5∼10% infertility or sterility people carry balanced chromosomal structural variations (SVs) with high risks of miscarriage and birth defects resulting from imbalanced gametes when producing fetus. However, some balanced cryptic SVs with specific location or small fragments cannot be detected by traditional cytogenetic techniques like G-banding testing or CNV-seq. Currently, several optimized techniques are able to detect typically cryptic structural abnormality. OGM, the molecular genetic detection technique relying on new principle in recent years, have overcome the shortcomings of former techniques and are potentially capable to detect both routine and cryptic SVs well. Study design, size, duration From 2019 to 2022, 12 couples in The First Affiliated Hospital of Sun Yat-sen University and The First People’s Hospital of Yunnan Province with history of offspring birth defect, recurrent unexplained recurrent miscarriage or unexpected copy number variation in embryos from previous PGT cycles were included for diagnosis or re-analysis. Participants/materials, setting, methods Peripheral blood lymphocytes from these patients were collected and detected by OGM or traditional karyotype analysis(G-400 banding), FISH, CNV-seq, third generation sequencing(Nanopore). The results of traditional genetic test and OGM were compared to evaluate the accuracy of OGM detection of chromosomal structure vatiation. Main results and the role of chance In the 11 couples bearing adverse pregnancy or childbirth defect with normal karyotype by G-banding, OGM discovered novel chromosome translocations or inversion in 9 couples (81.81%). In 1 couple with t(4:17)(q12;p13) diagnosed by G-banding, OGM detect an additional chromosomal translocation of t(17;19)(q12;p13), which produced the repeated CNVs in chromosome19 observed in embryos from two previous PGT cycles. For small fragment translocation, terminal translocation and inversion, OGM is able to detected balanced structure abnormal of 500kbs. The OGM diagnosis were confirmed by FISH or third generation sequencing (Nanopore) or embryo mutation. The breaking position reported by OGM and Nanopore were comparable. In sum, OGM reported further information of balanced SVs in 83.33% (10/12) potential patients with duplication and depletion in embryos or abortus. Limitations, reasons for caution Due to the limitation of principle, the structural abnormalities of some special locations (centromere, secondary constriction, etc.) cannot be detected. OGM has high sensitivity and many mutations, which requires examiners to have strong ability to analyze results and genetic counseling. The price of OGM also limits the promotion and application. Wider implications of the findings OGM can provide more precious result for SVs, and PGT-SR can definitely improve the outcome of certain population with cryptic chromosomal rearrangements. The shortcoming of OGM has not been overcame yet, so it is suggested as auxiliary method beside conventional G-binding in certain circumstances in ART population. Trial registration number Not applicable

P-788 Embryo vitrification affects the epigenome of preimplantation embryos and the effects are inherited by the female offsprings.

Abstract Study question How does embryo vitrification regulates the transcriptome of preimplantation embryos through epigenetic regulation and how are the effects transmitted to the female offsprings? Summary answer Embryo vitrification changed the DNA methylation level of preimplantation embryo and disturbed glycolipid metabolism of female offsprings in mice. What is known already Vitrification is a type of embryo cryopreservation increasingly frequently used clinically. The effect of embryo freezing on the health of offspring has been widely concerned. Some clinical studies have shown that offspring obtained from frozen embryo transplantation has higher birth weight and may be at higher risk of certain birth defects, increased risk of type 1 diabetes and cancer. But not all studies agree. The offspring safety of vitrification needs further follow-up research. Mouse model is a helpful tool for us to carry up follow-up study and explore mechanism. Study design, size, duration After superovulation and mating of ICR mice, we obtained 8-Cell embryos. In Vitrify Group, the 8-Cell embryos underwent vitrification and thawing and culture in vitro till blastocysts. In InVitro Group, the 8-Cell embryos were directly cultured in vitro till blastocysts. We transplanted these blastocysts into surrogate mice to get offspring of InVitro and Vitrify. Along with offspring of natural conception (NC), we observed their growth and development and glycolipid metabolism until 18 weeks old. Participants/materials, setting, methods Single embryo RNA-seq and Whole Genome Bisulfite Sequencing (WGBS) were performed to get transcriptome and DNA methylation atlas. Immunofluorescence of blastocysts was performed to test level of 5mC/5hmC and Tet2. Glucose and insulin tolerance test (GTT/ITT), serum lipid level test were performed on offspring to examine the glycolipid metabolism status. Liver transmission electron microscope photographs were take to observe ultramicrostructure. Liver RNA-seq and WGBS were performed to verify the variation on pathways concerning glycolipid metabolism. Main results and the role of chance Pseudo-time analysis from RNA-seq of 16-Cell, morula and blastocyst showed a relative developmental time lag in Vitrify. Differentially expressed genes (DEGs) of vitrify group at the blastocyst stage are mainly enriched in lipid metabolism, insulin signal, TOR signal regulation, gamete production related DNA methylation pathways. GSEA analysis revealed down-regulation of insulin response pathway genes. WGBS showed a trend of genome-wide methylation increase in vitrify group. Immunofluorescence confirmed this observation as the fluorescence intensity ratio of 5mC/5hmC was increased. RNA-seq, qPCR and western-blot showed a lower expression level of Tet2. These results suggested that the demethylation was insufficient in vitrify group. Blastocyst differentially methylated genes (DMRs) from WGBS were enriched in insulin response pathways. In offspring, birth weight of Vitrify offspring is higher than InVitro. GTT and ITT showed an elevated level of AUC in Vitrify 10-week-female, indicating an impaired glucose tolerance. And the fasting serum cholesterol level was elevated in Vitrify 10-week-female, indicating an impaired lipid metabolism. Under transmission electron microscope, we saw swollen mitochondria in liver of Vitrify 10-week-female. We extracted RNA from 10-week-female for RNA-seq, DEGs were enriched in cholesterol biosynthesis pathway. We extracted DNA from 10-week-female for WGBS, DEGs were enriched in cAMP and AMPK signaling pathway. Limitations, reasons for caution We have not confirm the precise molecular site affected by vitrification, clarify the mechanism and conduct the rescue test yet, which we are currently working on. This study is just the first step in this direction, and more efforts are needed. Wider implications of the findings Although more clinical trials and basic science studies are required, our findings provide valuable information for preventive and clinical decisions, as ‘freeze-all’ strategy springs up in many centers. Embryo vitrification needs more cautious consideration. Optimizing embryo vitrification protocols are needed according to the mechanism to minimize unwanted effects. Trial registration number 2021YFC2700601

P-774 Congenital Heart Disease in Children Born after Assisted Reproductive Technology: A Nordic Cohort Study.

Abstract Study question Do children conceived after assisted reproductive technology (ART) have a higher risk of Congenital Heart Disease (CHD) in comparison with children born after spontaneous conception? Summary answer Children born after ART have a higher risk of a major CHD compared with children born after spontaneous conception. What is known already It is well-known that children born after ART have higher risk of birth defects compared to children born after spontaneous conception. Congenital heart disease (CHD) is the most common birth defect, accounting for almost 50% of all major birth defects. Several cohort studies and systematic reviews have also found an increased risk of CHD in children born after ART, a recent review included 41 studies and 25 856 ART children covering CHDs in ART children. Conflicting results have been reported for specific CHDs. Study design, size, duration This Nordic registry-based cohort study from CoNARTaS (Committee of Nordic ART and Safety) included 171 774 live births born after use of ART and 7 772 474 live births born after spontaneous conception during a study period of up to three decades (Denmark 1994-2014, Finland 1990-2014, Norway 1984-2015, and Sweden 1985-2015). National data from ART registries, medical birth registries, malformation registries, patient registries, cause of death registries, and population registries were crosslinked. Participants/materials, setting, methods International Classification of Diseases (ICD) versions 8, 9, 10 were used for CHD codes at birth and up to one year of age. Major CHDs were defined according to European Concerted Action on Congenital Anomalies and Twins (EUROCAT). According to EUROCAT, 26 of the major CHDs were considered as severe. All major CHDs were further classified into six different groups in a hierarchical order. Minor CHDs as well as stillbirths and pregnancy terminations were excluded. Main results and the role of chance Data from Sweden included a total of 3 228 526 singletons and multiples; 62 243 children conceived after use of ART and 3 166 283 children after spontaneous conception. Among ART children, 2.27% (n = 1411) were diagnosed with any major non-chromosomal CHD during their first year of life, corresponding figures for children born after spontaneous conception was 1.43% (n = 45 310) (Odds Ratio [OR] 1.60; 95% Confidence Interval (CI) 1.51 to 1.69, p < 0.0001). Severe CHD occurred in 0.40% (n = 249) in the ART group and 0.31% (n = 9 795) in the spontaneous conception group (OR 1.29; 95% CI 1.14 to 1.47, p < 0.0001). Ventricular septal defect was the most common CHD, 0.97% (n = 603) in the ART vs 0.64% (n = 20 343) in the spontaneous conception group (OR 1.51; 95% CI 1.39 to 1.64, p < 0.0001), followed by atrial septal defect; 0.84% (n = 525) in the ART and 0.42% (n = 13 363) in the spontaneous conception group (OR 2.00; 95% CI 1.83 to 2.19, p < 0.0001). Limitations, reasons for caution This analysis included only non-adjusted Swedish data. Further analysis will include Danish, Finnish, and Norwegian data with adjustments, and subgroup analysis on singletons and multiples. No data are available on prenatal diagnosis, or pregnancies not ending to a live birth. A skewed distribution in these outcomes might introduce a bias. Wider implications of the findings Pregnancies conceived after use of ART may benefit from screening with fetal echocardiography. Although most children with CHD reach adulthood, the mortality rate is still high for this group during the first years of life. Early detection with antenatal diagnosis and pre/postnatal intervention may be beneficial and improve the outcome. Trial registration number Not applicable

The Impact of Environmental Pollution on Congenital Anomalies of New Birth in Kirkuk City – Iraq

The Birth abnormalities or congenital malformations can emerge during the fetal development stage or from a parent's genetic composition. The main contributors to neonatal and childhood disease and impairment are congenital abnormalities. Increase the observation of congenital anomaly (CA) in Mama Village that belong to Kirkuk city has been made with information about frequency and nature of these abnormalities. This study was conducted to estimate the prevalence of congenital anomaly in Mama Village that belong to Kirkuk city. A Cross sectional study that includes 60 couples who are living in Mama Village for the duration from March 2020 to March 2022 to investigate the risk of congenital anomaly that increases in frequency in 2019. The data was collected by direct interview of the participants and took a full history of the performing ultrasonography. The highest prevalence of CA that reach 55%, 96.7% of participant were cousin. Nearly two third of participant had single anomaly. Central nervous system anomaly was the most prevalent anomaly in the current study, and hydrocephalous was presented in 18.3% of them. Young age group mother, cousin marriage and history of infant death were a risk factor for CA. It is concluded that a higher prevalence of congenital anomaly in the current study especially when compared with the number of area population. The central nervous system was more probable which shown to be substantially correlated with maternal history of prior previous child death, paternal consanguinity, and age. Higher prevalence of central nervous system could be related to the environment effect which is (weapon-related) occur in the studied area previously. Key words: Congenital anomaly, cousin marriage, weapon explosion.

Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Perinatal Outcome Following Assisted Reproductive Technology Treatment at A Tertiary Fertility Center In Nepal.

Introduction: Globally, an increasing number of babies have been born with the help of Assisted Reproductive Technology (ART) treatment. While most births after ART are uncomplicated, sometimes it is associated with adverse perinatal outcomes such as preterm birth, low birth weight and increased risk of congenital anomalies. Therefore, the objective of this study was to assess the perinatal outcomes in children born after assisted reproductive technologies at a tertiary fertility center in Nepal.
 Methodology: This was a descriptive study which analyzed retrospective data collected from the medical record of a tertiary fertility center at Lalitpur, Nepal. Perinatal outcomes of total 201 births that resulted from various ART treatment that was conducted in the center from November 2015 till April 2021 have been included in this study. Univariate analysis was done in SPSS version 20.
 Results: Altogether, there were 201 total births out of which 199 were live births and 2 were stillbirths. Among the live births around two-third (69.7%) were singleton deliveries and remaining one- third (30.4%) were multiple deliveries. More than 90% of study population had undergone Lower Segment Caesarean Section (LSCS). There were 263 live born babies resulting from 199 live births. More than half of the babies were born prematurely (50.19%). Low birth weight (LBW) and very low birth weight (VLBW) was seen among 36.50% and 7.22% babies respectively. Congenital abnormality was identified in 13 babies (4.94%) Four stillborn babies and eight neonatal deaths were reported. More adverse perinatal outcomes were seen among twins and triplets than singleton babies.
 Conclusion: While most births were uncomplicated, certain extent of adverse perinatal outcomes among the ART conceived babies cannot be ignored. Vigilant monitoring of pregnancy conceived by ART treatment helps in improving the perinatal outcome.

0909 Pitolisant Pregnancy Registry: An Observational Study of the Safety of Pitolisant Exposure in Pregnant Women and Their Offspring

Abstract Introduction WAKIX (pitolisant) is a potent and highly selective histamine 3 receptor antagonist/inverse agonist approved for the treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy. The safety of pitolisant in pregnant women has not been established. Available case reports from clinical trials and postmarketing experience have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The registry is a prospective, observational cohort study designed to evaluate the association between pitolisant exposure during pregnancy and subsequent maternal, fetal, and infant outcomes. Methods The primary study population consists of 3 cohorts: pregnant women with a diagnosis of narcolepsy who are exposed to pitolisant during pregnancy, pregnant women with narcolepsy who are unexposed to pitolisant but exposed to comparator products during pregnancy, and pregnant women with narcolepsy who are neither exposed to pitolisant nor comparator products. Comparator products include modafinil, armodafinil, sodium oxybate, oxybate mixed salts, solriamfetol, methylphenidate, and amphetamines. Outcomes of interest include major congenital malformation (primary outcome), minor congenital malformation, pre-eclampsia, eclampsia, spontaneous abortion, stillbirth, elective termination, small for gestational age, preterm birth, postnatal growth deficiency, and infant developmental deficiency. Data are collected from enrolled pregnant women and healthcare providers involved in their care or the care of their infants, if applicable. Only data that are routinely documented in patients' medical records during usual care are collected. Participation in the registry is voluntary and participants may withdraw their consent to participate at any time. The registry design follows current FDA guidance for designing and implementing pregnancy exposure registries. Results The registry was initiated in May 2021. Presently, data are insufficient to assess an association between pitolisant exposure and any endpoint of interest. Study completion is planned in 2030. Conclusion Healthcare providers are encouraged to discuss this voluntary pregnancy registry with their eligible patients and assist women who are interested in enrolling. The study is registered on Clinicaltrials.gov (ID# NCT05536011). Support (if any) This study is sponsored by Harmony Biosciences LLC.

Adverse birth outcomes among offspring born to women diagnosed with cancer: a population-based cohort study

With increasing cancer incidence and survival rates, the prevalence of maternal cancer and its effect on adverse birth outcomes are important for prenatal care and oncology management. However, the effects of different types of cancer at different gestational stages have not been widely reported. To describe the epidemiological characteristics of pregnancy-associated cancers (during and one year after pregnancy) and evaluate the association between adverse birth outcomes and maternal cancers. Of 983,162 children, a history of maternal cancer, including pregestational cancer, pregnancy-associated cancer and subsequent cancer, was identified in 16,475 cases using a health information network. The incidence and 95% confidence interval (CI) of pregnancy-associated cancer were calculated with the Poisson distribution. The adjusted risk ratio (RRadj) with 95%CI of the association between adverse birth outcomes and maternal cancer were estimated using the multilevel log binomial model. A total of 38,295 offspring were born to mothers with a cancer history. Of these, 2,583 (6.75%) were exposed to pregnancy-associated cancer, 30,706 (80.18%) had a subsequent cancer diagnosis, and 5006 (13.07%) were exposed to pregestational cancer. The incidence of pregnancy-associated cancer was 2.63/1000 pregnancies (95%CI: 2.53-2.73‰), with cancer of the thyroid (1.15‰), breast (0.25‰), and female reproductive organs (0.23‰) being the most common cancer types. The increased risks of preterm birth and low birth weight were significantly associated with cancer diagnosed during the second and third trimester of pregnancy, while increased risks of birth defects (RRadj=1.48, 95%CI: 1.08-2.04) were associated with cancer diagnosed in the first trimester. An increased risk of preterm birth (RRadj=1.16, 95%CI: 1.02-1.32), low birth weight (RRadj=1.24, 95%CI: 1.07-1.44), and birth defects (RRadj=1.22, 95%CI: 1.10-1.35) was observed in thyroid cancer survivors. Careful monitoring of fetal growth should be implemented for women diagnosed with cancer in the second and third trimester, to ensure timely delivery and balance the benefits of neonatal health and cancer treatment. The higher incidence of thyroid cancer and increased risk of adverse birth outcomes among thyroid cancer survivors suggested that the regular thyroid function monitoring and regulation of thyroid hormone levels are important in maintaining pregnancy and promoting foetal development among thyroid cancer survivors before and during pregnancy.

A systematic review of in utero cannabis exposure and risk for structural birth defects.

Cannabis use among pregnant women has increased over time. Therefore, there is a great public health need to understand the consequences of in utero cannabis exposure. While several meta-analyses and reviews have summarized the evidence of in utero cannabis exposure on adverse obstetric outcomes (e.g., low birth weight and preterm birth) and long-term offspring development, there has not been a focus on in utero cannabis exposure and risk for structural birth defects. We conducted a systematic review using PRISMA guidelines to evaluate the association between in utero cannabis exposure and structural birth defects. We identified 20 articles to include in our review and focused on interpreting findings from the 12 that adjusted for potential confounders. We report findings by seven organ systems. Within the 12 articles, four reported on cardiac malformations, three reported on central nervous system malformations, one reported on eye malformations, three reported on gastrointestinal malformations, one reported on genitourinary malformations, one reported on musculoskeletal malformations, and two reported on orofacial malformations. Findings on associations between in utero cannabis exposure and birth defects reported in more than two articles were mixed (i.e., findings for cardiac, gastrointestinal, central nervous system malformations). Findings for associations between in utero cannabis exposure and birth defects reported in two articles (i.e., orofacial malformations) or in a single article (eye, genitourinary, and musculoskeletal) suggested that cannabis exposure was not associated with these types of malformations, but strong conclusions cannot be drawn from such sparce research. We review the limitations and gaps in the existing literature and call for more research to rigorously evaluate associations between in utero cannabis exposure and structural birth defects. identifier CRD42022308130.

Association between air pollutants and birth defects in Xiamen, China.

To explore the relationship between common air pollution and common birth defects, and to provide reference for the prevention of birth defects. We conducted a case-control study in Xiamen, a city in southeastern China from 2019 to 2020. Logistics regression was used to analyze the relationship between sulfur dioxide(SO2), fine particulate matter 2.5(PM2.5), nitrogen dioxide(NO2), ozone(O3), carbon monoxide(CO) and the occurrence of common birth defects such as congenital heart disease, facial cleft, and finger deformity. SO2 significantly increased the risk of birth defects such as congenital heart disease, cleft lip and/or cleft palate, and ear deformity in the first and second months of pregnancy. Exposure to common air pollutants increases the risk of birth defects, and SO2 significantly affects the occurrence of birth defects in the first two months of pregnancy.

Comparison of the safety between propylthiouracil and methimazole with hyperthyroidism in pregnancy: A systematic review and meta-analysis.

The purpose of this meta-analysis was to assess the safety of the anti-thyroid drugs (ATDs) propylthiouracil (PTU) and methimazole (MMI) in the treatment of hyperthyroidism during pregnancy. From inception until June 2, 2022, all available studies were searched in PubMed, Web of Science, Cochrane, EBSCO, Embase, Scopus, and CNKI. Thirteen articles satisfying the inclusion criteria were examined. Our meta-analysis indicated that pregnant women treated with MMI had a higher risk of congenital anomalies than those treated with PTU (OR 0.80, 95%CI 0.69-0.92, P = 0.002, I2 = 41.9%). Shifting between MMI and PTU during pregnancy did not reduce the risk of birth defects compared to PTU alone (OR 1.18, CI 1.00 to 1.40, P = 0.061, I2 = 0.0%). There were no statistically significant differences in hepatotoxicity (OR 1.54, 95%CI 0.77-3.09, P = 0.221, I2 = 0.0%) or miscarriage (OR 0.89, 95%CI 0.72-1.11, P = 0.310, I2 = 0.0%) between PTU and MMI exposure. The study confirmed propylthiouracil is a safer alternative to methimazole for treating hyperthyroidism in pregnant women, and it is appropriate to treat maternal thyroid disease with PTU during the first trimester of pregnancy. However, it is not clear whether switching between propylthiouracil and methimazole is a better option than treating PTU alone during pregnancy. Further studies on this matter may be needed to develop new evidence-based guidelines for the treatment of pregnant women with hyperthyroidism.

Paternal age, risk of congenital anomalies, and birth outcomes: a population-based cohort study.

The objective of the study was to explore the impact of paternal age on the risk of congenital anomalies and birth outcomes in infants born in the USA between 2016 and 2021. This retrospective cohort study used data from the National Vital Statistics System (NVSS) database, a data set containing information on live birth in the USA between 2016 and 2021. Newborns were divided into four groups based on their paternal age (< 25, 25-34, 35-44, and > 44years) and using the 25-34 age group as a reference. The primary outcomes were congenital anomalies involving structural anomalies and chromosome anomalies. Secondary outcomes were preterm birth, low birth weight, severe neonatal perinatal asphyxia, and admission to neonatal intensive care units (NICU). A multivariable logistic regression model was used to analyze the association between paternal age and outcomes. Overall, 17,764,695 live births were included in the final analyses. After adjusting confounding factors, advanced paternal age > 44years was associated with increased odds of congenital anomalies (adjusted odds ratio (aOR) = 1.17, 95%CI 1.12-1.21) compared with the 25-34 age group, mainly for the chromosomal anomalies (aOR = 1.59, 95%CI 1.40-1.78) but not the structure anomalies (aOR = 1.03, 95%CI 0.97-1.09). The risk of preterm delivery, low birth weight, and NICU hospitalization in their infants was increased by advanced parental age as well. Conclusion: Advanced paternal age increases the risk of congenital anomalies, especially chromosomal anomalies in their offspring, implying prenatal genetic counseling is required. What is Known: • There's a rising trend of advanced paternal age, which is associated with an increased likelihood of premature birth and low birth weight in their offspring. However, the exploration between paternal age and congenital abnormalities in offspring was limitedand contradictory. What is New: • Infants with a paternal age > 44 years were more likely to be born with congenital anomalies, especially chromosomal anomalies.

The effect of China’s birth policy changes on birth defects—A large hospital-based cross-sectional study

ABSTRACT A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25–40 years increased significantly (AAPC<20=-5.58; AAPC20–24=-6.38; AAPC25–29 = 5.15; AAPC30–35 = 7.07; AAPC35–40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother’s age on the risk of BDs.

Management of heterotopic pregnancy: clinical analysis of sixty-five cases from a single institution.

This retrospective study aims to analyze the influence of different treatment modalities on viable intrauterine pregnancy and to summarize the clinical features of heterotopic pregnancy (HP) patients. All patients diagnosed with HP between January 2012 and December 2022 in Tianjin Central Obstetrics and Gynecology Hospital were reviewed retrospectively. This study diagnosed 65 patients using transvaginal ultrasound (TVS), including two cases of natural pregnancy, seven cases of ovulation induction pregnancy, and 56 cases after in vitro fertilization and embryo transfer (IVF-ET). The gestational age was 50.2 ± 13.0 days at the time of diagnosis. The most frequent manifestations were abdominal pain (61.5%) and vaginal bleeding (55.4%), while 11 patients (16.9%) had no symptoms before the diagnosis. The primary treatment was expectant and surgical management, including laparotomy and laparoscopic surgery. In the expectant management group, four patients were transferred to surgery due to rupture of ectopic pregnancy or ectopic pregnancy mass gradually enlarged. In the surgical management group, 53 patients underwent laparoscopic surgery, and six underwent laparotomy. The laparoscopic group's mean operation time was 51.3 ± 14.2 min (range: 15-140 min), and the median intraoperative blood loss was 20 mL (range 5-200 mL). In contrast, the laparotomy group's mean operation time was 80.0 ± 25.3 min (range 50-120 min), and the median intraoperative blood loss was 22.5 mL (range 20-50 mL). Four patients had postoperative abortions. Sixty-one newborns had no birth abnormalities, and no developmental malformations were discovered after a median follow-up of 32 months. Expectant treatment has a high failure rate in HP, and laparoscopic surgery is a safe and effective treatment for removing ectopic pregnancy without increasing the risk of abortion or newborn birth defects.

Effect of extremely low-frequency electromagnetic radiation on pregnancy outcome: A meta-analysis.

Extremely low-frequency electromagnetic radiation (ELF-EMF) are generated by electrical devices and power systems (1 to 300 Hz). Although several studies have demonstrated that ELF-EMF may beassociated with an increased risk of adverse pregnancy outcomes, other studies have shown no evidence of associations. This meta-analysis was conducted to assess the effect of extremely low frequency electromagnetic radiation on pregnancy outcomes. The following electronic bibliographic databases were searched to identify relevant studies: PubMed, Web Of Science, Cochrane library, Embase, EBSCO. In addition, the manual retrieval of relevant references was conducted as a supplement. Select all eligible studies published from Database construction library to March 10, 2021. Search type for queue research on influence of electromagnetic field radiation on pregnancy results. Data were screened and extracted independently by two researchers. Review Manager 5.3 software was used for the meta-analysis. There was no significant increase in the risk of miscarriage, stillbirth, birth defects and preterm delivery in the pregnant women who lived near the electromagnetic fields compared with the control group. Conclusions: No correlation has been found between maternal ELF-EMF exposure and miscarriage, stillbirth, neonatal birth defects and preterm delivery, while the effects on small gestational age and low birth weight are still uncertain. Related research with high-quality large samples and different regions are still needed for further verification.

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

Unsubstantiated use of Selective serotonin reuptake inhibitors as an alternative for the treatment of depression

Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry (P9-3.003)

Diroximel Fumarate Pregnancy Outcomes in EVOLVE-MS-1 and Study Design of Diroximel Fumarate Prospective MS Pregnancy Exposure Registry (P9-3.003)