Rate Of Birth Defects Research Articles

Building Healthy Babies: A Mixed-Methods Needs Assessment for a Pre-Conception Program in Ontario

ObjectivesThe objective of this study was to gather Ontario clinicians’ and public members’ views on the design of a pre-conception patient education program. MethodsIn this mixed-methods study, online surveys comprised of rank order, multiple choice, and short answer questions were completed by clinicians and public members. Semi-structured focus groups consisting of 2–6 participants each were then held via videoconference. Demographic variables and survey responses were analyzed quantitatively using descriptive and summary statistics. Descriptive thematic qualitative analysis using the constant comparative method of grounded theory was completed on each transcript to generate themes. ResultsA total of 168 public members and 43 clinicians in Ontario completed surveys, while 11 clinicians and 11 public members participated in the focus groups. A pre-conception program in Ontario was felt to be important. An individual appointment with a primary care provider was the favoured program format per survey responses, whereas a virtual format with an interactive component was preferred among focus group participants. Important topics to include were pre-conception health (infertility, genetic screening, folic acid), prenatal and postpartum counselling (diet, activity, substance use, prenatal care, postpartum course), and medical optimization in pregnancy (high-risk medical conditions, medications, mental health). Both groups emphasized the need to consider accommodations for marginalized populations and various cultures and languages. ConclusionA standardized pre-conception patient education program is felt to be of high value by Ontario clinicians and public members. A pre-conception program may help improve obstetrical outcomes and decrease rates of major congenital anomalies in Ontario.

Transient ischemic attack and pregnancy, delivery and neonatal outcomes-An evaluation of a population database.

Transient ischemic attack (TIA) is rare in women of reproductive age. We aimed to compare perinatal outcomes between women who suffered from a TIA to those who did not. A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS). All women who delivered or had a maternal death in the US (2004-2014) were included in the study. Pregnancy, delivery, and neonatal outcomes were compared between women with an ICD-9 diagnosis of a TIA to those without. Overall, 9 096 788 women met the inclusion criteria. Of these, 203 women (2.2/100000) had a TIA (either before or during pregnancy). Women with TIA, compared to those without, were more likely to be older than 35 years of age, white, in the highest income quartile, be insured by private insurance and suffer from obesity and chronic hypertension. Patients in the TIA group, compared to those without, had a higher rate of pregnancy-induced hypertension (aOR 2.5, 95% CI: 1.55-4.05, P < 0.001), pre-eclampsia (aOR 3.77, 95% CI: 2.15-6.62, P < 0.001), eclampsia (aOR 28.05, 95% CI: 6.91-113.95, P < 0.001), preterm delivery (aOR 1.78, 95% CI: 1.03-3.07, P = 0.039), and maternal complications such as deep vein thrombosis (aOR 33.3, 95% CI: 8.07-137.42, P < 0.001). Regarding neonatal outcomes, patients with a TIA, compared to those without, had a higher rate of congenital anomalies (aOR 7.04, 95% CI: 2.86-17.32, P < 0.001). Women with a TIA diagnosis before or during pregnancy had a higher rate of maternal complications, including hypertensive disorders of pregnancy and venous thromboembolism, as well as an increased risk of congenital anomalies.

The congenital birth defects burden in children younger than 14 years of age, 1990 - 2019: An age-period-cohort analysis of the global burden of disease study.

This study aims to delineate the burden of congenital birth defects (CBDs) in children under 14 years of age from 1990 to 2019, using an age-period-cohort framework to analyse data from the Global Burden of Disease Study (GBD). Data on prevalence cases, age-standardised prevalence rates (ASPRs), death cases, and age-standardised death rates (ASDRs) of congenital birth defects (CBDs) from 1990 to 2019 were obtained from GBD 2019. Using this data set, we conducted an age-period-cohort (APC) analysis to examine patterns and trends in mortality, prevalence, and disability-adjusted life years (DALYs) associated with CBDs, while exploring correlations with age, time periods, and generational birth cohorts. Furthermore, to quantify the temporal trends, we calculated the estimated annual percentage changes (EAPCs) for these parameters. The global prevalence of CBDs decreased from 1404.22 to 1301.66 per 100 000 with an EAPC of -0.18% from 1990 to 2019. CBD mortality decreased by 42.52% between 1990 and 2019, with the global age-standardised death rate declining from 49.72 to 25.58 per 100 000. The age-standardised DALY rate decreased from 4529.16 to 2393.61 per 100 000. Prevalence declined most notably among older children. The risk of CBDs reached its lowest during adolescence (10-14 years) across all regions. The most recent period (2015-2019) showed a reduced risk of prevalence compared to 2000-2004. Earlier birth cohorts displayed declining tendencies followed by slight increases in risk. This study demonstrates encouraging global reductions in the burden of CBDs among children over the past three decades. Prevalence, mortality, and DALYs attributable to CBDs have exhibited downward trajectories, although regional disparities remain. APC analysis provides valuable insights to inform prevention and management strategies for pediatric CBDs.

Hao-Fountain syndrome: 32 novel patients reveal new insights into the clinical spectrum.

Hao-Fountain syndrome (HAFOUS, OMIM: #616863) is a neurodevelopmental disorder caused by pathogenic variants in the gene USP7 coding for USP7, a protein involved in several crucial cellular homeostatic mechanisms and the recently described MUST complex. The phenotype of HAFOUS is insufficiently understood, yet there is a great need to better understand the spectrum of disease, genotype-phenotype correlations, and disease trajectories. We now present a larger cohort of 32 additional individuals and provide further clinical information about six previously reported individuals. A questionnaire-based study was performed to characterize the phenotype of Hao-Fountain syndrome more clearly, to highlight new traits, and to better distinguish the disease from related neurodevelopmental disorders. In addition to confirming previously described features, we report hyperphagia and increased body weight in a subset of individuals. HAFOUS patients present an increased rate of birth complications, congenital anomalies, and abnormal pain thresholds. Speech impairment emerges as a potential hallmark of Hao-Fountain syndrome. Cognitive testing reports reveal borderline intellectual functioning on average, although some individuals score in the range of intellectual disability. Finally, we created a syndrome-specific severity score. This score neither indicates a sex- nor age-specific difference of clinical severity, yet highlights a more severe outcome when amino acid changes colocalize to the catalytic domain of the USP7 protein.

Pregnant women’s experiences of extreme exposure to bushfire associated smoke: a qualitative study

In 2019/2020, multiple bushfires burned across south-east Australia converging into unprecedented megafires that burned 5.8 million hectares. From October 2019–February 2020, 80% of Australians were affected by smoke from these fires, exposing them to dramatic increases of PM2.5 in the air at an average level of ∼70 μg m3 per day, well above the World Health Organisation recommendation of ∼10 μg m3. Maternal exposure to PM2.5 has been associated with negative birth outcomes and an increased rate of birth defects, yet there is a dearth of literature regarding how pregnant women deal with exposure to bushfire smoke. The aim of this study was thus to investigate how pregnant and postpartum women experienced severe bushfire smoke associated with the 2019–2020 bushfires in south-east Australia and the strategies they used to mitigate exposure to smoke for themselves and their unborn or newborn children. Forty-three women who were exposed to fire and/or smoke from the 2019–2020 bushfires participated in one-on-one semi-structured interviews via phone or videoconference. These women were selected purposively from a larger group of women who had elected to be interviewed. After interview, data were transcribed and thematically analysed using the four phases of disaster response (prevention, preparedness, response, recovery) as a frame. Overall, our results indicated that public health advice failed to meet the unique needs of this group. While many protected their properties appropriately and were reasonably well prepared for evacuation, they were unprepared for the disruption to vital services including power and communications. Women exposed to smoke inundation were unprepared for this outcome and self-initiated a variety of strategies. The support of community was also key to recovery. There is a clear need for specific recognition of the needs of pregnant women across all phases of disaster response, incorporating public health messaging, peer support, and access to resources.

Antiepileptic treatment with levetiracetam during the first trimester and pregnancy outcome: An observational study.

Levetiracetam is increasingly used in pregnant women with epilepsy. Although teratogenic effects have not been observed so far, data on the risks of spontaneous abortion and major birth defects are still limited, especially for the frequently used dual therapy of levetiracetam and lamotrigine. Our primary aim was to analyze rates of major birth defects and spontaneous abortion after maternal levetiracetam treatment. This was a cohort study based on pregnancies recorded by the Embryotox Center from 2000 to 2017. Outcomes of prospectively ascertained pregnancies with first trimester levetiracetam monotherapy (n = 221) were compared to pregnancies with lamotrigine monotherapy for epilepsy (n = 469). In addition, all pregnancies with levetiracetam (n = 364) exposure during the first trimester were analyzed in comparison to a nonexposed cohort (n = 729). Pregnancies with the most frequently used combination therapy comprising levetiracetam and lamotrigine (n = 80) were evaluated separately. There was no significantly increased risk of major birth defects or of spontaneous abortions after first trimester exposure to levetiracetam. Birth weight of male neonates was significantly lower after levetiracetam monotherapy compared to lamotrigine monotherapy. Dual therapy with levetiracetam and lamotrigine resulted in a significantly increased risk of spontaneous abortion (adjusted hazard ratio = 3.01, 95% confidence interval [CI] = 1.43-6.33) and a nonsignificant effect estimate for major birth defects (7.7%, n = 5/65, adjusted odds ratio = 1.47, 95% CI = .48-4.47) compared to a nonexposed cohort. Our study confirms the use of levetiracetam as a suitable antiepileptic drug in pregnancy. The lower birth weight of male neonates after maternal levetiracetam monotherapy and the unexpectedly high risk of spontaneous abortion and birth defects after dual therapy with levetiracetam and lamotrigine require further investigation.

Perinatal deaths from birth defects in Hunan Province, China, 2010-2020.

To describe the perinatal mortality rate (PMR) of birth defects and to define the relationship between birth defects (including a broad range of specific defects) and a broad range of factors. Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2010-2020. The prevalence rate (PR) of birth defects is the number of birth defects per 1000 fetuses (births and deaths at 28 weeks of gestation and beyond). PMR is the number of perinatal deaths per 100 fetuses. PR and PMR with 95% confidence intervals (CI) were calculated using the log-binomial method. Chi-square trend tests (χ2trend) were used to determine trends in PR and PMR by year, maternal age, income, education level, parity, and gestational age of termination. Crude odds ratios (ORs) were calculated to examine the association of each maternal characteristic with perinatal deaths attributable to birth defects. Our study included 1,619,376 fetuses, a total of 30,596 birth defects, and 18,212 perinatal deaths (including 16,561 stillbirths and 1651 early neonatal deaths) were identified. The PR of birth defects was 18.89‰ (95%CI: 18.68-19.11), and the total PMR was 1.12%(95%CI: 1.11-1.14). Birth defects accounted for 42.0% (7657 cases) of perinatal deaths, and the PMR of birth defects was 25.03%. From 2010 to 2020, the PMR of birth defects decreased from 37.03% to 2010 to 21.00% in 2020, showing a downward trend (χ2trend = 373.65, P < 0.01). Congenital heart defects caused the most perinatal deaths (2264 cases); the PMR was 23.15%. PMR is highest for encephalocele (86.79%). Birth defects accounted for 45.01% (7454 cases) of stillbirths, and 96.16% (7168 cases) were selective termination of pregnancy. Perinatal deaths attributable to birth defects were more common in rural than urban areas (31.65% vs. 18.60%, OR = 2.03, 95% CI: 1.92-2.14) and in females than males (27.92% vs. 22.68%, OR = 1.32, 95% CI: 1.25-1.39). PMR of birth defects showed downward trends with rising maternal age (χ2trend = 200.86, P < 0.01), income (χ2trend = 54.39, P < 0.01), maternal education level (χ2trend = 405.66, P < 0.01), parity (χ2trend = 85.11, P < 0.01) and gestational age of termination (χ2trend = 15297.28, P < 0.01). In summary, birth defects are an important cause of perinatal deaths. Rural areas, female fetuses, mothers with low maternal age, low income, low education level, low parity, and low gestational age of termination were risk factors for perinatal deaths attributable to birth defects. Future studies should examine the mechanisms. Our study is helpful for intervention programs to reduce the PMR of birth defects.

Risk of birth defects in pregnant persons with sleep-disordered breathing during pregnancy.

As many as one in four pregnant women may experience sleep-disordered breathing (SDB) during pregnancy. The same sequelae of SDB, such as insulin resistance and inflammation, have been implicated in the development of certain birth defects. This is a secondary analysis of the SDB substudy of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be study, which included 2106 participants who had a sufficiency sleep study at two visits at different time points in pregnancy. SDB was based on a self-administered home sleep apnea test with data scored by trained, blinded research polysomnologists. SDB was defined as an apnea-hypopnea index (AHI) ≥5. The primary outcome of this analysis was any of the 45 non-chromosomal birth defects included in the National Birth Defects Prevention Network Annual Report. In this cohort, the overall rate of birth defects was 3.1%. The prevalence was similar between those without SDB (3.0%) and those with only mid-pregnancy SDB (3.4%), but was higher in those with early-pregnancy SDB (6.7%). After adjusting for maternal age, chronic hypertension, pregestational diabetes, and body mass index (BMI), there were no statistically significant differences in the risk of birth defects by subject SDB status. Further studies to evaluate the effect of prepregnancy and early-pregnancy SDB on the fetus, as well as the risk of specific birth defects and neonatal outcomes in those with an objectively measured diagnosis of SDB, are still needed.

A new perspective on isotretinoin in pregnancy: Pregnancy outcomes, evaluation of complex phenotypes, and importance of teratological counselling

ObjectivesTeratogens are responsible for 5% of all known causes of congenital anomalies. Isotretinoin, a retinoic acid–derived agent, leads to congenital anomalies in 21–52% of cases when exposure occurs during pregnancy according to studies conducted before 2006. However, rates of congenital anomalies were much lower in later studies. The purpose of this study was to investigate the rates of congenital anomalies in isotretinoin exposure during pregnancy, isotretinoin exposure before pregnancy, and a control group unexposed to any teratogenic agents. Study DesignIn this cohort study, we divided pregnant women admitted to our center between 2009 and 2020 into two groups: isotretinoin exposure before and during the pregnancy (n = 77) and isotretinoin exposure before the pregnancy (n = 75). We selected the control group from among the non-teratogen exposed pregnant women with a simple random sampling method. Obstetricians calculated the ages of all pregnancies via ultrasound (USG) (crown-rump diameter for the first trimester; biparietal diameter and femur length for the second trimester). After birth, a pediatric genetics specialist examined all babies. Whole-exome sequencing (WES) was conducted on the babies who displayed complex phenotypes. ResultsAmong the isotretinoin exposure before and during the pregnancy, isotretinoin exposure before the pregnancy, and the control groups, there were statistically significant differences in live births (respectively, 64.3 %, 88 %, 93.3 %), congenital anomalies (respectively, 28.6 %, 6.1 %, 1.4 %), miscarriages (respectively, 13 %, 2.7 %, 4 %), terminations (respectively, 32.5 %, 9.3 %, 2.7 %), and premature births (11.9 %, 16.7 %, 2.9 %) (respectively, p < 0.001, p < 0.001, p = 0.014, p < 0.001). We detected novel phenotypical features in five patients. ConclusionsOur study demonstrated that study design, long-term follow-up, teratological counseling, and implementation of advanced molecular analysis in complex phenotypes with novel phenotypical features are beneficial for understanding the association of congenital anomalies with isotretinoin exposure. While evaluating congenital anomalies, we detected statistically significant differences between isotretinoin exposure before and during the pregnancy vs control, but we did not detect any statistically significant differences between isotretinoin exposure before the pregnancy and controls. Another finding of the study is that WES might be an efficient way to evaluate complex phenotypes in isotretinoin-exposed babies; however, further research is required.

Pregnancy, delivery and neonatal outcomes among women with hypoparathyroidism-A population-based study.

Data are inconclusive regarding pregnancy complications associated with maternal chronic hypoparathyroidism. Therefore, we aimed to compare pregnancy, delivery and neonatal outcomes in patients affected by chronic hypoparathyroidism to those without chronic hypoparathyroidism. A retrospective population-based study utilising data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) database over 11 years from 2004 to 2014 inclusively. Multivariate logistic regression was used to control for confounders. Patients with chronic hypoparathyroidism compared with those without. Obstetric and neonatal outcomes. We identified 204 pregnancies in mothers with chronic hypoparathyroidism and 9,096,584 pregnancies without chronic hypoparathyroidism. After adjusting for age, insurance plan type, obesity, chronic hypertension, thyroid disease, pregestational diabetes mellitus, and previous caesarean section, patients in the hypoparathyroidism group, compared with those without hypoparathyroidism, were found to have an increased rate of preterm birth (<37 weeks) (19.1% vs. 7.2%, aOR: 2.49, 95% confidence interval [CI]: 1.74-3.54, p < 0.0001, respectively); and blood transfusions (4.9% vs. 1.0%, aOR: 4.07, 95% CI: 2.15-7.73, p < -0.0001). Neonates to mothers with chronic hypoparathyroidism had a higher rate of congenital anomalies (4.4% vs. 0.4%, aOR: 6.50, 95% CI: 3.31-12.75, p < 0.0001), with comparable rates of small-for-gestational-age neonates and intrauterine foetal death. This is the largest study of chronic hypoparathyroidism in pregnancy to date. We found significant increases in the rates of preterm birth, blood transfusions and congenital anomalies in chronic hypoparathyroidism. Our findings highlight the importance of identifying chronic hypoparathyroidism as a risk factor for pregnancy and neonatal complications, although it remains unknown if maintaining calcium in the target range will mitigate these risks.

Real-world prevalence, time of diagnosis, and co-occurrence patterns of birth defects in live-born infants, 2014-2020: A health administrative database study in Japan.

A study evaluating the real-world prevalence of birth defects (BDs), including co-occurrence patterns, will provide the information required to estimate Japan's true BD prevalence and monitor it. Information such as when infants are diagnosed with BDs is crucial for defining the study population and data collection period in future administrative database studies. This study utilized the DeSC database, a large claims database comprising multiple health insurance schemes. The prevalence of major BDs, including structural congenital malformations (CMs) and chromosomal abnormalities, was determined in infants born between 2014 and 2020 and continuously insured for ≥1 year. The time of the first BD diagnosis and multiple BD patterns were also evaluated. Among 43,147 infants, 3050 (7.07%) were diagnosed with major BDs, and 3002 (6.96%) with major CMs. The circulatory system (2.95%) was the most frequent organ system affected by CMs, followed by CMs and deformations of the musculoskeletal system (1.94%). The cumulative diagnostic rates of BDs and CMs at month 6 were 85.9% and 85.6%, respectively. The EUROCAT BD subgroups diagnosed in more than 1.0% of the infants were atrial septal defects (1.47%) and patent ductus arteriosus (1.07%). Among the 2997 infants with EUROCAT BDs, 241 (8.04%) were classified as having multiple BDs. A large claims database is a valuable resource for evaluating and monitoring the prevalence of BDs, including multiple patterns. At least 1 year since birth should be considered in future administrative database studies evaluating BDs as outcomes.

Association between usage of household cooking fuel and congenital birth defects-18 months multi-centric cohort study in Nepal

Background- An estimated 240,000 newborns die worldwide within 28 days of birth every year due to congenital birth defect. Exposure to poor indoor environment contributes to poor health outcomes. In this research, we aim to evaluate the association between the usage of different type household cooking fuel and congenital birth defects in Nepal, as well as investigate whether air ventilation usage had a modifying effect on the possible association.Methods- This is a secondary analysis of multi-centric prospective cohort study evaluating Quality Improvement Project in 12 public referral hospitals of Nepal from 2017 to 2018. The study sample was 66,713 women with a newborn, whose information was available in hospital records and exit interviews. The association between cooking fuel type usage and congenital birth defects was investigated with adjusted multivariable logistic regression. To investigate the air ventilation usage, a stratified multivariable logistic regression analysis was performed.Results-In the study population (N = 66,713), 60.0% used polluting fuels for cooking and 89.6% did not have proper air ventilation. The prevalence rate of congenital birth defect was higher among the families who used polluting fuels for cooking than those who used cleaner fuels (5.5/1000 vs. 3.5/1000, p < 0.001). Families using polluting fuels had higher odds (aOR 1.49; 95% CI; 1.16, 1.91) of having a child with a congenital birth defect compared to mothers using cleaner fuels adjusted with all available co-variates. Families not using ventilation while cooking had even higher but statistically insignificant odds of having a child with congenital birth defects (aOR 1.34; 95% CI; 0.86, 2.07) adjusted with all other variates.Conclusion- The usage of polluted fuels for cooking has an increased odds of congenital birth defects with no significant association with ventilation. This study adds to the increasing knowledge on the adverse effect of polluting fuels for cooking and the need for action to reduce this exposure.

Evaluating the Prevalence of Congenital Anomalies in Neonatal Live Births in Rafsanjan

Introduction: Congenital anomalies are one of the important causes of disability and infant mortality. These abnormalities occur during egg fertilization or embryonic development, which can be detected by laboratory methods. The aim of this study is to investigate the prevalence of congenital anomalies in Rafsanjan City.&#x0D; Methods: This cross-sectional study was performed on 4868 infants born in Rafsanjan city in 2018. Data collection tool was a questionnaire including information about mothers and infants. The questionnaire was completed using health records available in health centers of Rafsanjan city. Data were analyzed using SPSS 20 and independent t-test and Chi-square.&#x0D; Results: The results showed that the overall prevalence of congenital anomalies in Rafsanjan was 5/38 per 1000 live births. Out of 4868 pregnant women, 474 (9/7%), had abortions or stillbirths before the second trimester, and 12 (0/2%) had therapeutic abortions. After analyzing these anomalies, three cases of Down syndrome (trisomy 21), three cases of Edward syndrome (trisomy 18), one case of aneuploidy, and two cases of microcephaly were found, and the rest had one of the structural abnormalities..&#x0D; Conclusion: The results of this study indicated a high rate of congenital anomalies in Rafsanjan. Therefore, further studies are recommended to better understand the causes and prevent these anomalies.

Application of Chromosome Microarray in Diagnosis of Amniotic Fluid in Older Pregnant Women

Background: To improve the detection rate of chromosome abnormalities in fetuses and to reduce the birth defects rate in elderly pregnant women using chromosome karyotype analysis combined with the chromosome microarray analysis (CMA) technique. Methods: Overall, 210 elderly pregnant women with singleton pregnancies aged between 16 and 30 weeks (mean gestational age, 19.19 weeks) and 35 and 47 years (mean age, 38.08 years) were selected from January 1, 2020 to June 1, 2021 in the Eugenics Genetics Department of Yulin Maternal and Child Health Hospital. Chromosome G banding karyotype analysis and CMA detection were performed simultaneously. Results: Among the 210 elderly pregnant women with singleton pregnancies, 26 (12.38%) and 52 (24.76%) cases were detected as abnormal using chromosome karyotype analysis and CMA technology, respectively. The abnormal CMA chromosomes’ total detection rate was 12.38% higher than that using chromosome karyotype analysis (p &lt; 0.001). CMA detected 22 pathogenic copy number variants (CNVs), 1 probable CNV, and 7 CNVs of unknown clinical significance in patients with normal karyotype analysis. Among the patients with abnormal karyotype analysis, CMA missed detection in 5 cases. Overall, 57 abnormal cases were detected when the two methods were combined, with a detection rate of 27.14% (57/210) higher than that of CMA or karyotype analysis alone. Conclusions: For the prenatal diagnosis of fetal amniotic fluid in elderly pregnant women, the combined application of chromosome karyotype analysis and CMA detection technology can further improve the detection rate of abnormal chromosomes and reduce missed diagnosis rates.

The Risks and Benefits of Monoclonal Antibody Therapy During Pregnancy and Postpartum: Maternal, Obstetric, and Neonatal Considerations.

Autoimmune and rheumatologic conditions can lead to multiple adverse maternal, obstetric, and neonatal outcomes, especially if they flare during pregnancy. Although many medications to control these conditions exist, concerns regarding their safety often unnecessarily limit their use. We aim to review the current evidence available describing the use of monoclonal antibody (mAb) therapeutics in pregnancy and postpartum and understand the impact of their use on the developing fetus and neonate. Original research articles, review articles, case series and case reports, and pregnancy guidelines were reviewed. Multiple retrospective (including 1924 patients) and prospective studies (including 899 patients) of anti-tumor necrosis factor (TNF) agent use in pregnancy found no significant increase in rates of miscarriage, preterm birth, or congenital anomalies compared with controls. Most societies, including American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine, recommend initiation or continuation of TNF-α inhibitors during pregnancy for patients with autoimmune diseases. An increased risk of mild infections in newborns has been reported, although infections requiring hospitalizations are rare. Data suggest that breastfeeding while taking anti-TNF agents is safe for neonates. Less data exist for the use of other mAbs including anticytokine, anti-integrin, and anti-B-cell agents during pregnancy and postpartum. Current evidence suggests that the use of mAbs, particularly anti-TNF agents, is safe in pregnancy and postpartum, without significant adverse effects on the pregnant patient or infant. The benefits of ongoing disease control in pregnant patients result in favorable maternal and neonatal outcomes.

Adverse maternal and neonatal outcomes of preimplantation genetic testing with trophectoderm biopsy: a retrospective cohort study of 3373 intracytoplasmic sperm injection single frozen-thawed blastocyst transfer cycles.

To investigate whether trophectoderm biopsy increases the risk of adverse maternal and neonatal outcomes in intracytoplasmic sperm injection (ICSI) single frozen-thawed blastocyst transfer cycles. This respective cohort study enrolled 3373 ICSI single frozen-thawed blastocyst transfer cycles with and without trophectoderm biopsy. Statistical methods including univariate logistic regression analysis, multivariate logistic regression analysis, and stratified analyses were performed to explore the impact of trophectoderm biopsy on adverse maternal and neonatal outcomes. The rates of adverse maternal and neonatal outcomes were comparable between the two groups. Univariate analysis showed that the live birth rate (45.15% vs. 40.75%; P = 0.010) in the biopsied group was statistically higher than that in the unbiopsied group, and the rates of miscarriage (15.40% vs. 20.00%; P = 0.011) and birth defects (0.58% vs. 2.16%; P = 0.007) were statistically lower in the biopsied group. After adjusting for confounding factors, the rates of miscarriage (aOR = 0.74; 95% CI = 0.57-0.96; P = 0.022) and birth defects (aOR = 0.24, 95% CI = 0.08-0.70, P = 0.009) in the biopsied group were significantly lower than those in the unbiopsied group. Stratified analyses showed that the birth defects rate after biopsy was significantly reduced in the subgroups of age < 35years old, BMI ≥ 24kg/m2, artificial cycle with downregulation, poor-quality blastocysts, and Day 5 poor-quality blastocysts. Preimplantation genetic testing (PGT) with trophectoderm biopsy does not increase the risk of adverse maternal and neonatal outcomes in ICSI single frozen-thawed blastocyst transfer cycles, and PGT can effectively reduce the rates of miscarriage and birth defects.

Frequency of Ultrasonographically Detectable Fetal Anomalies in Known Oligohydramnios Pregnancies

Background: The amniotic fluid protects and cushions the developing baby. Reduced amniotic fluid, or oligohydramnios, is linked to a higher rate of birth defects. Objective: To find out the frequency of ultrasonographically detectable fetal anomalies in pregnancies complicated by oligohydramnios. Study Design: Cross sectional study. Settings: Department of Diagnostic Radiology, University of Child Health Sciences (UCHS), Children Hospital, Lahore Pakistan. Duration: 6th October 2020 to 5th April 2021. Methods: A total of 173 women 19 to 40 years old having oligohydramnios during their second or third trimester of pregnancy were included. Patients with multiple gestation and intrauterine fetal death were excluded. They were scanned in detail with ultrasound machine having a convex 3.5 MHz probe for the severity of Amniotic Fluid Index (AFI) and for congenital fetal anomalies. Patients’ demographics and clinical characteristics were recorded. Results: Age range in this study was from 19 to 40 years with mean age of 27.8±5.1 years. Majority of the patients 144(83.23%) were between 25 to 35 years of age. Among pregnancies complicated by oligohydramnios, 39(22.54%) were reported to have ultrasonographically identifiable foetal abnormalities. Among the females, 58 (33.52%) had a vaginal delivery, while 115(66.47%) underwent a cesarean delivery. Still births observed in 7(4.04%), fetal renal tract anomalies 17(9.82%), fetal distress 13(7.51%), musculoskeletal anomalies 11(6.35%), cardiac anomalies 5(2.89%), central nervous system anomalies 6(3.46%), gastrointestinal anomalies 13(7.51%) hydronephrosis 6(3.46%), hydrocephalus 4(2.31%), meningocele 3(1.73%), diaphragmatic anomalies 5(2.89%) and hernias was noted in 8(4.62%) females. Lastly, multiple congenital anomalies were identified in 17(9.82%) cases. Conclusion: This study concluded that frequency of ultrasonographically detectable fetal anomalies in pregnancies complicated by oligohydramnios is quite high.

Whole exome sequencing reveal 83 novel Mendelian disorders carrier P/LP variants in Chinese adult patients.

Carrier screening can identify people at risk of conceiving pregnancies affected with inherited genetic disorders or who have a genetic disorder with late or variable onset. Carrier screening based on whole exome sequencing (WES) data can offer more comprehensive assessment than on-target carrier screening tests. A total of 224 Chinese adult patients WES data was analyzed, except positive variants associated with the patients' major complaint, 378 pathogenic (P) and "likely pathogenic" (LP) variants from 175 adult patients were identified. Whole exome-wide frequency of carriers for Mendelian disorders in Chinese adult patients was about 78.13% in this study, which was lower than the previously reported carrier frequency in healthy population. Contrary to expectations, the number of P or LP variants did not increase with larger chromosome size or decrease with smaller chromosome size. Totally 83 novel P or LP variants were identified which could further expand the carrier variants spectrum of the Chinese population. GJB2: NM_004004.6:c.299_300delAT:p.His100fs*14 and C6:NM_000065.4:c.654T>A:p.Cys218* were found in two or more patients, which might be two underestimated carrier variants in Chinese population. We also found 9 late-onset or atypical symptoms autosomal/X-linked dominant Mendelian disorders causative genes, which were easily overlooked during pathogenicity analysis. These results can provide a strong basis for preventing and avoiding the prevalence rates of birth defects and reducing social and family burdens. By comparing with three different expanded carrier screening gene panels, we further confirmed carrier screening based on WES could offer more comprehensive assessment and WES was applicable for carrier screening.

Analysis for trends in disease burden of congenital birth defects among children under 5 years old in China.

Congenital birth defects are the main source of disease burden among children under 5 years old in China. This study aims to compare the trends in disease burden of different congenital birth defects among Chinese children under 5 years old from 1990 to 2019, and to provide a scientific basis for strengthening the comprehensive prevention and control of birth defects. Based on data from the Global Burden Disease (GBD) in 2019, the incidence mortality rate, and disability-adjusted life years (DALYs) rate of congenital birth defects among Chinese children under 5 years old from 1990 to 2019 were selected as evaluation indicators. The Joinpoint regression model was used to analyze the trends in disease burden of different types with congenital birth defects over three decades. The study also compared the differences in disease burden of congenital birth defects among children under 5 years old by gender. Compared to 1990, the DALYs rates of congenital heart anomalies (1 931.91/100 000), digestive congenital anomalies (364.63/100 000), neural tube defects (277.20/100 000), congenital musculoskeletal and limb anomalies (133.33/100 000), and Down syndrome (128.22/100 000) in children under 5 years old in China in 2019 were decreased 70.78%, 71.61%, 86.21%, 36.84% and 73.65%, respectively. From 1990 to 2019, the mortality rates and DALYs rates of different congenital birth defects showed an overall downward trend, but the incidence of digestive congenital anomalies and Down syndrome showed an upward trend after 2005 and 2001, respectively. Except for congenital musculoskeletal and limb anomalies, incidence of the remaining categories of birth defects were higher in boys than that in girls. The disease burden of congenital birth defects in children under 5 years old in China is decreased substantially from 1990 to 2019, but the burden of congenital heart anomalies is still serious and the incidence of some birth defect diseases is on the rise, and it is still crucial to strengthen the prevention and treatment for birth defects in children and propose targeted measures according to their gender characteristics.

Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site.

Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics. Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study. The odds ratio (OR) and 95% confidence interval (CI) of GCTs according to birth defects status were estimated by using unconditional logistic regression. All defects were considered collectively and by genetic and chromosomal syndromes and nonsyndromic defects. Stratification was by sex, tumor histology (yolk sac tumor, teratoma, germinoma, and mixed/other), and location (gonadal, extragonadal, and intracranial). Birth defects and syndromic defects were more common among GCT cases than controls (6.9% vs. 4.0% and 2.7% vs. 0.2%, respectively; both p < .001). In multivariable models, GCT risk was increased among children with birth defects (OR, 1.7; 95% CI, 1.3-2.4) and syndromic defects (OR, 10.4; 95% CI, 4.9-22.1). When stratified by tumor characteristics, birth defects were associated with yolk sac tumors (OR, 2.7; 95% CI, 1.3-5.0) and mixed/other histologies (OR, 2.1; 95% CI, 1.2-3.5) and both gonadal tumors (OR, 1.7; 95% CI, 1.0-2.7) and extragonadal tumors (OR, 3.8; 95% CI, 2.1-6.5). Nonsyndromic defects specifically were not associated with GCTs. In sex-stratified analyses, associations were observed among males but not females. These data suggest that males with syndromic birth defects are at an increased risk of pediatric GCTs, whereasmales with nonsyndromic defects and females are not at an increased risk. We investigated whether birth defects (such as congenital heart disease or Down syndrome) are linked to childhood germ cell tumors (GCTs), cancers that mainly develop in the ovaries or testes. We studied different types of birth defects (defects that were caused by chromosome changes such as Down syndrome or Klinefelter syndrome and defects that were not) and different types of GCTs. Only chromosome changes such as Down syndrome or Klinefelter syndrome were linked to GCTs. Our study suggests that most children with birth defects are not at an increased risk of GCTs because most birth defects are not caused by chromosome changes.