Congenital Anomalies In Offspring Research Articles

Association of maternal cancer with congenital anomalies in offspring.

Congenital anomalies are common, but the possibility that maternal cancer increases the chance of having a child with a birth defect is not fully understood. To examine the association between maternal cancer before or during pregnancy and the risk of birth defects in offspring. We conducted a retrospective cohort study of live births in Quebec, Canada, between 1989 and 2022 using hospital data. The main exposure measure was maternal cancer before or during pregnancy. The outcome included birth defects detected in offspring during gestation or at birth. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of maternal cancer with birth defects using log-binomial regression models adjusted for potential confounders. In this study of 2,568,120 newborns, birth defects were present in 6.0% and 6.7% of infants whose mothers had cancer before or during pregnancy, respectively, compared with 5.7% of infants whose mothers never had cancer. Cancer during pregnancy was associated with heart (RR 1.58, 95% CI 1.03, 2.44), nervous system (RR 4.05, 95% CI 2.20, 7.46) and urinary defects (RR 1.72, 95% CI 1.01, 2.95). Among specific types of malignancies during pregnancy, breast cancer was the most prominent risk factor for birth defects (RR 1.55, 95% CI 1.02, 2.37). Cancer before pregnancy was not associated with any type of birth defect or with defects overall (RR 1.01, 95% CI 0.92, 1.11). Moreover, no specific type of cancer before pregnancy was associated with an increased risk of birth defects. Maternal cancer during pregnancy is associated with the risk of congenital anomalies in offspring, however, cancer before pregnancy is not associated with this outcome.

Pregabalin alters reproductive performance in male mice and causes congenital anomalies in offspring.

Pregabalin is an anticonvulsant drug with analgesic activity for the treatment of neuropathic pain. To valuate the toxicity of pregabalin in reproductive parameters, spermatogenesis, and teratogenicity in the offspring of mice. Twenty male mice were randomly distributed into two groups: PGB group and group C (n =10 per group). The animals in the PGB group received, via gavage, 200mg/kg of pregabalin diluted in distilled water daily, for a period of 45days. Group C received distilled water under the same experimental design. In the paternal parameters of the PGB group, there was a significant increase in the size of the testicles, morphological alterations in the spermatozoa, a decrease in the Johnsen score, an increase in the Leydig cells, and a decrease in the serum level of testosterone. In the intrauterine development parameters of females mated with males from the PGB group, a significant decrease in placental weight, weight and length of fetuses, and fetal viability rate was observed. There was a significant increase in the number of resorptions and post-implantation losses. The significant anomalies observed in the offspring were alteration in the size of the kidneys, absent metacarpals and phalanges, alteration in the sternum, and supernumerary thoracic vertebrae. Results suggest that pregabalin had toxic effects on the reproductive function of male mice and teratogenic potential. The findings of this study may provide new hypotheses, taking into account the risk-benefit ratio for male reproduction and offspring health.

The influence of harmful occupational physical factors on the male workers’ reproductive health (analytical review)

This paper provides a review of the literature for the analysis and assessment of the occupational risk of reproductive health disorders of male workers under the influence of harmful physical factors of production.
 To assess the risk of exposure to harmful industrial physical factors on the reproductive health of male workers, the authors have applied the method of analytical review of the data obtained.
 Literature data show that the work of men in conditions of both high and low temperatures can lead to a violation of reproductive function. In the bakery, ceramic, steel, welding and other industries, working conditions are characterized by the presence of hyperthermia. Researchers have identified a violation of reproductive function in male workers, along with changes in the physiological parameters of the body's homeostasis.
 There are few studies on the effects of noise and vibration on the reproductive health of working men, and there are few studies on the effects of ultra- and infrasound. The consequences of such exposure are disorders of hormonal status, spermatogenesis, leading to further changes in reproductive function, impotence and infertility. Scientists confirm these data with experimental studies on animals and volunteers.
 Exposure to ionizing radiation is a proven factor of reproductive dysfunction, which leads to changes in the quantity and quality of sperm, reproductive hormones. The consequence of exposure to ionizing radiation are chromosomal abnormalities, leading to congenital anomalies in offspring.
 It has been shown that the biological effect of electromagnetic fields of various frequency ranges (cell phones, microwave ovens, laptops, devices with Wi-Fi, as well as other types of non–ionizing radiation — low-frequency electromagnetic fields and extremely high-frequency) on reproductive organs can manifest itself in changes in spermatogenesis indicators, DNA damage, genomic instability, hormonal regulation and work disorders protein kinases, hormones, antioxidant enzymes, leading to disorders of sexual behavior, decreased fertility, up to infertility.
 The presented data show that harmful occupational physical factors can lead to violations of the reproductive health of male workers. Currently, there is no systematic approach to solving the problem. In this regard, it is necessary to develop a scientifically sound system for assessing occupational risk and making managerial decisions to preserve reproductive health, since a decrease in the fertility of male workers potentially affects the well-being of the family and society as a whole.

Maternal migraine and risk of pediatric cancers.

Maternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been speculated that this may be due to the use of medications in pregnancy, but lifestyle, genetic, hormonal, and neurochemical factors could also play a role. There is evidence for varying cancer incidences among adults with migraine. Here, we utilized data from national registries in Denmark to examine associations between maternal diagnoses of migraine and risk for cancer in offspring. We linked several national registries in Denmark to identify cases from the Cancer Registry among children less than 20years (diagnoses 1996-2016) and controls from the Central Population Register, matched to cases by birth year and sex (25:1 matching rate). Migraine diagnoses were identified from the National Patient Register using International Classification of Diseases, versions 8 and 10 codes and migraine-specific acute or prophylactic treatment recorded in the National Pharmaceutical Register. We used logistic regression to estimate the risk of childhood cancers associated with maternal migraine. Maternal migraine was positively associated with risk for non-Hodgkin lymphoma (odds ratio [OR]=1.70, 95% confidence interval [CI]: 1.01-2.86), central nervous system tumors ([OR=1.31, 95% CI: 1.02-1.68], particularly glioma [OR=1.64, 95% CI: 1.12-2.40]), neuroblastoma (OR=1.75, 95% CI: 1.00-3.08), and osteosarcoma (OR=2.60, 95% CI: 1.18-5.76). Associations with maternal migraine were observed for several childhood cancers, including neuronal tumors. Our findings raise questions about the role of lifestyle factors, sex hormones, genetic, and neurochemical factors in the relationship between migraine and childhood cancers.

Maternal exposure to particulate matter early in pregnancy and congenital anomalies in offspring: Analysis of concentration-response relationships in a population-based cohort with follow-up throughout childhood

Studies have suggested an association between particulate matter (PM) air pollution and certain congenital anomalies (CAs). However, most studies assumed a linear concentration-response relation and were based on anomalies that were ascertained at birth or up to 1 year of age. We investigated associations between exposures to PM during the first trimester of pregnancy and CAs in 9 organ systems using birth and childhood follow-up data from a leading health care provider in Israel. We conducted a retrospective population-based cohort study among 396,334 births, 2004–2015. Daily PM data at a 1 × 1 km spatial grid were obtained from a satellite-derived prediction models and were linked to the mothers' residential addresses at birth. Adjusted odds ratios (ORs) were estimated with logistic regression models using exposure levels as either continuous or categorical variables. We captured 57,638 isolated CAs with estimated prevalence of 96 and 136 anomalies per 1000 births in the first year of life and by age 6 years, respectively. Analysis of continuous PM with diameter < 2.5 μm (PM2.5) indicated a supra-linear relation with anomalies in the circulatory, respiratory, digestive, genital and integument systems (79 % of CAs). The slope of the concentration-response function was positive and steepest for PM2.5 lower than the median concentration (21.5 μg/m3) and had a less steep or negative slope at higher levels. Similar trends were observed for PM2.5 quartiles. For example, for cardiac anomalies, the ORs were 1.09 (95 % confidence interval: 1.02, 1.15), 1.04 (0.98, 1.10) and 1.00 (0.94, 1.07) for births in the second, third and fourth quartiles, respectively, when compared to the first quartile. In sum, this study adds new evidence for adverse effects of air pollution on neonatal health even with low-level air pollution. Information on late diagnosis of children with anomalies is important in evaluating the burden of disease.

Association of Maternal History of Preterm Birth With Congenital Anomalies in Offspring

Association of Maternal History of Preterm Birth With Congenital Anomalies in Offspring

Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births.

Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs.

Impact of Maternal and Neonatal Vitamin D Status on the Development of Congenital Anomalies in Egyptian Model

Background: Vitamin D (VD) is a remarkable problem during pregnancy. VD plays a crucial role in cellular growth and differentiation during embryogenesis. VD deficiency in pregnancy is associated with various maternal and neonatal comorbidities. &#x0D; Aim: In this study, we aimed to evaluate the potential association between maternal and neonatal vitamin D status and the subsequent development of congenital anomalies.&#x0D; Patients and methods: A case-control study involving 30 mothers and their neonates born with gross structural congenital anomalies as cases and 30 mothers and their healthy neonates as controls recruited from Ain Shams University Children Hospital. Maternal and Neonatal blood samples were obtained to determine serum 25-hydroxyvitamin D. The 25-hydroxyvitamin D concentration was stratified into a severe deficient&lt;10ng/ml, deficient &lt;20ng/ml, insufficient 20-29ng/ml and sufficient &gt;30ng/ml. Status above 150ng/ml presents high risk of toxicity. &#x0D; Results: There were statistically significant differences between the two groups regarding maternal and neonatal vitamin D serum level within 29 days postpartum. Mean maternal vitamin D level in cases was 23.8ng/ml versus 42.13ng/ml in controls (P = 0,000). Mean neonatal vitamin D level in cases was 15.97ng/ml versus 28.9ng/ml in controls (P = 0,000).There was significant positive correlation between both maternal and neonatal vitamin D level with birth weight.&#x0D; Conclusion: A compromised maternal vitamin D status is associated with an increased prevalence of congenital anomalies in offspring. Therefore, improvement of the periconceptional maternal vitamin D status is recommended.

Maternal cigarette smoking before or during pregnancy increases the risk of birth congenital anomalies: a population-based retrospective cohort study of 12 million mother-infant pairs

BackgroundThe associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA.MethodsWe used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking.ResultsAmong the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05).ConclusionsMaternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births

Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births

Risks of specific congenital anomalies in offspring of diabetic mothers: a systematic review and meta-analysis of population-based studies of more than 80 million births

Risks of specific congenital anomalies in offspring of diabetic mothers: a systematic review and meta-analysis of population-based studies of more than 80 million births

Association between Maternal and Neonatal Vitamin D status and the Development of Congenital Anomalies

Abstract Background Vitamin D (VD) is a remarkable problem during pregnancy. VD plays a crucial role in cellular growth and differentiation during embryogenesis. VD deficiency in pregnancy is associated with various maternal and neonatal comorbidities. In this study, we aimed to evaluate the potential association between maternal and neonatal vitamin D status and the subsequent development of congenital anomalies. Patients and methods A case-control study involving 30 mothers and their neonates born with gross structural congenital anomalies as cases and 30 mothers and their healthy neonates as controls recruited from Ain Shams University Children Hospital. Maternal and Neonatal blood samples were obtained to determine serum 25hydroxyvitamin D. The 25-hydroxyvitamin D concentration was stratified into a severe deficient&amp;lt;10ng/ml, deficient &amp;lt;20ng/ml, insufficient 20-29ng/ml and sufficient &amp;gt;30ng/ml. Status above 150ng/ml presents high risk of toxicity. Results There were statistically significant differences between the two groups regarding maternal and neonatal vitamin D serum level within 29 days postpartum. Mean maternal vitamin D level in cases was 23.8ng/ml versus 42.13ng/ml in controls (P = 0,000). Mean neonatal vitamin D level in cases was 15.97ng/ml versus 28.9ng/ml in controls (P = 0,000).There was significant positive correlation between both maternal and neonatal vitamin D level with birth weight. Conclusion A compromised maternal vitamin D status is associated with an increased prevalence of congenital anomalies in offspring. Therefore, improvement of the periconceptional maternal vitamin D status is recommended.

Meta-analyses of maternal exposure to atmospheric particulate matter and risk of congenital anomalies in offspring.

Congenital anomalies are the main causes of infant death and disability. Previous studies have suggested that maternal exposure to particulate matter is related to congenital malformation. However, the conclusions of this study remain controversial. Hence, meta-analyses were performed to assess the relationship between maternal exposure to particulate matter and the risk of congenital anomalies. The Medline, Embase, and Web of Science databases were systemically searched from inception until August 2020 to find articles related to birth defects and particulate matter. The pooled risk estimated for the combination of pollution outcomes was calculated for each study by performing fixed effects or random effects models. The existence of heterogeneity and publication bias in relevant studies was also examined. Thirty studies were included in the analysis. A statistically increased summary risk valuation was found. PM10 exposure was associated with an increased risk of congenital heart disease, neural tube defects, and cleft lip with or without cleft palate (OR per 10 μg/m3 = 1.05, 95% CI, 1.03-1.07; OR per 10 μg/m3 = 1.04, 95% CI, 1.01-1.06; OR per 10 μg/m3 = 1.03, 95% CI, 1.01-1.06). Maternal exposure to particulate matter might be associated with an increased risk of congenital anomalies. Our results indicate the dangers of particulate matter exposure on fetal development and the importance of protection against exposure to such particles during pregnancy. The schematic representation of the association between maternal exposure to PM2.5/PM10 and congenital anomalies in offspring, and geographic distribution of the included reports in the meta-analyses.

Risks of Specific Congenital Anomalies in Offspring of Diabetic Mothers: A Systematic Review and Meta-Analysis of Population-Based Studies of More than 76 Million Births

Background: Pregestational diabetes (PGDM) has been known to be a risk factor for congenital heart defects (CHD) for decades. However, the associations between maternal PGDM and gestational diabetes (GDM) and risk of specific types of CHD and other systems congenital anomalies (CAs) remains under debate. We investigated type-specific CAs in offspring of diabetic mothers and examined the extent to which different types of maternal diabetes increase CAs risks in offspring. Methods: For this systematic review and meta-analysis, we searched PubMed and Embase from inception to December 27, 2020, for population-based studies reporting on type-specific CAs in offspring of diabetic mothers. We assessed methodological quality using the Cochrane Risk of Bias Tool for Non-randomised Studies of Interventions. We calculated summary estimates for meta-analysis using random effects models. The primary outcomes were overall CAs and specific types of CHD. Findings: 56 studies (76,860,298 participants) were included. The meta-analyses showed increased risks of overall CAs/CHD, in offspring born to mothers with PGDM (for overall CAs, relative risks [RR] 1.99, 95% CI 1.82 to 2.17 and for CHD, 3.42, 95% CI 2.73 to 4.28) or GDM (for overall CAs, 1.18, 95% CI 1.13 to 1.23 and for CHD, 1.50, 95% CI 1.38 to 1.64). Results of meta-regression analyses showed significant differences in RRs of CAs/CHD in PGDM versus GDM (all P ˂ 0.001). Of 23 type-specific CAs of other systems in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories, while maternal GDM had a small but significant increase in risk of CAs in 9 categories. Interpretation: The findings suggest that timely screening for diabetes in women who are pregnant or planning to be pregnant provides a window of opportunity to prevent congenital anomalies in offspring. Registration Information: This systematic review is registered with PROSPERO, number CRD42021229217. Funding Information: None. Declaration of Interests: We declare no competing interests.

Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring.

A father's lifestyle impacts offspring health; yet, the underlying molecular mechanisms remain elusive. We hypothesized that a diet that changes methyl donor availability will alter the sperm and embryo epigenomes to impact embryonic gene expression and development. Here, we demonstrate that a folate-deficient (FD) dietalters histone H3 lysine 4 trimethylation (H3K4me3) in sperm at developmental genes and putative enhancers. A subset of H3K4me3 alterations in sperm are retained in the pre-implantation embryo and associated with deregulated embryonic gene expression. Using a genetic mouse model in which sires have pre-existing altered H3K4me2/3 in sperm, we show that a FD diet exacerbates alterations in sperm H3K4me3 and embryonic gene expression, leading to an increase in developmental defect severity. These findings imply that paternal H3K4me3 is transmitted to the embryo and influences gene expression and development. It further suggests that epigenetic errors can accumulate in sperm to worsen offspring developmental outcomes.

Ранние и поздние эффекты материнского ожирения в диаде «мать–дитя»

Obesity in pregnancy poses health risks to both the woman herself and the developing fetus, newborn, child, and adult offspring. High maternal body weight in early pregnancy is associated with an increased risk of neonatal mortality. Inflammatory factors secreted by maternal adipose tissue enhance the differentiation of stem cells into adipocytes, thereby accelerating the development of fetal adipose tissue, which is transformed into obesity in offspring. Leptin resistance in offspring at an early age is a direct consequence of maternal obesity. Children born to obese mothers are more likely to develop leukemia in early childhood. High maternal BMI during pregnancy is associated with higher BMI, blood pressure, insulin and triglyceride levels, abdominal obesity, and lower levels of «protective» lipids in offspring. Increased maternal body weight during pregnancy, especially in the early stages, correlates with cardiovascular diseases in offspring in adulthood. Data on the influence of changes in the intestinal microbiome in the form of high concentrations of Bacteroides spp. and Staphylococcus on the development of maternal obesity during pregnancy and on fetal health are presented, which is associated with increased assimilation of energy sources, increased pro-inflammatory processes, and reduced synthesis of several essential factors, particularly folic acid, which may explain the growth of congenital anomalies in offspring. A number of genetic polymorphisms that are relevant to the development of childhood obesity, especially the genes PPAR, MC4R, TMEM18, GNPDA2, NEGR1, KCTD15, ETV5, and among others FTO, are considered. Key words: inflammation, genetic polymorphisms, FTO gene, children, gut microbiome, maternal obesity, pregnancy pathology

In utero exposure to Azathioprine in autoimmune disease. Where do we stand?

Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES.

Preconceptional paternal antiepileptic drugs use and risk of congenital anomalies in offspring: a nationwide cohort study.

Recent studies have shown that certain pharmacological agents used by fathers before conception may increase the risk of adverse neonatal outcomes in offspring. However, little is known about the effect of paternal use of antiepileptic drugs (AEDs) on congenital anomalies in children. Based on Danish national registers, we conducted a cohort study of 733, 282 singletons born from 1997 to 2008, with follow-up throughout 2013. The children whose fathers used AEDs during the 3months before conception were categorized as the exposed. Logistic regression model was used to examine association between paternal AEDs use before conception and the risk of congenital anomalies in offspring. Compared with unexposed children, the exposed had a 23% increased risk of congenital anomalies (odds ratios (OR) 1.23, 95% confidence interval [CI] 1.10-1.37) after adjusting for potential confounders. When extending the exposure window to 1year before conception to the end of pregnancy, except for those using AEDs during 3months before conception (the susceptible period of exposure), the increased risks were also observed in children whose fathers were former users (i.e., those using AEDs only from 1year to 3months before conception) (OR 1.29, 95%CI 1.03-1.61) and later users (i.e., those using AEDs only during pregnancy) (OR 1.35, 95%CI 1.12-1.65). This study suggested that the mildly increased risk of congenital anomalies in the offspring associated with paternal AEDs use before conception may be attributable to the underlying indications related to AEDs use.

Maternal obstructive sleep apnea and neonatal birth outcomes in a population based sample

ObjectiveEvaluate the association of OSA with birth outcomes including the risk of congenital anomalies and the need for a higher level of clinical care at delivery. MethodsPopulation-based study that linked newborn records with maternal records. Data from 95 perinatal centers across all geographic census divisions of the U.S. of women with a delivery diagnosis from 2010 to 2014 whose records could be linked to the corresponding newborn record. An International Classification of Diseases, ninth Revision (ICD-9) code for sleep apnea was used to identify exposure and outcome variables. Univariate and multivariate logistic regression analyses were performed with a model that included substance use, obesity, diabetes, maternal co-morbidities, and pregnancy complications. ResultsIn this study, 1,423,099 maternal records were linked to live newborn records. OSA was associated with a higher risk for congenital anomalies in offspring (aOR 1.26, 1.11 to 1.43), with the highest risk being that of musculoskeletal anomalies (aOR 1.89, 1.16 to 3.07) after adjusting for comorbidities and potential teratogens. Neonates born to mothers with OSA were more likely to be admitted to the intensive care unit (25.3% vs. 8.1%, p < 0.001), require resuscitation (aOR 2.76, 1.35 to 5.64) and have a longer hospital stay (aOR 2.25, 1.85 to 2.65). ConclusionsAlthough our study does not establish causation, it is the first to demonstrate a higher risk of congenital anomalies and resuscitation at birth in neonates of mothers with OSA, emphasizing the importance of identifying OSA in pregnant women and women of reproductive age.

A randomized, double‐blind, placebo‐ and risperidone‐controlled study on valnoctamide for acute mania

Mood stabilizers administered for bipolar disorder during pregnancy, such as valproic acid, can increase the risk of congenital anomalies in offspring. Valnoctamide is a valproic acid derivative associated with a decreased risk for congenital abnormalities in animals. The present study evaluated the efficacy and safety of valnoctamide monotherapy, compared to placebo, in the treatment of patients in an acute manic episode. A 3-week, double-blind, randomized, placebo- and risperidone-controlled, parallel group trial was conducted on 173 patients in an acute manic episode. Patients were randomized to receive valnoctamide 1500mg/d (n=71), risperidone 6mg/d (n=32), or matching placebo (n=70). The primary outcome measure was the change in Young Mania Rating Scale (YMRS) scores. Valnoctamide did not differ significantly from placebo on any of the study endpoints (YMRS, Positive and Negative Syndrome Scale, and the Clinical Global Impression Scale for Bipolar Disorder [CGI-BP] scales; all P>.60). Mixed models for repeated measures showed that risperidone produced significantly more improvement than placebo in the overall bipolar disorder CGI-BP severity scale (P=.036), and the CGI-BP severity scale for mania (P=.021). The Kaplan-Meier survival curve revealed higher all-cause discontinuation rates (mainly due to lack of efficacy) in the valnoctamide group compared to the other study groups (P=.026). Patients with higher valnoctamide plasma levels had a numerically higher YMRS response, but this was not statistically significant. Valnoctamide was well tolerated at 1500mg/d but lacked efficacy in the treatment of symptoms in patients with acute mania. Possible differences between the biological mechanisms of action of valproic acid and valnoctamide are discussed.