Musculoskeletal Malformations Research Articles

Updates on the Care of Cloacal Exstrophy.

Cloacal exstrophy is the most severe congenital anomaly of the exstrophy-epispadias complex and is characterized by gastrointestinal, genitourinary, neurospinal, and musculoskeletal malformations. Individualized surgical reconstruction by a multidisciplinary team is required for these complex patients. Not infrequently, patients need staged surgical procedures throughout childhood and adolescence. Following significant improvements in medical care and surgical reconstructive techniques, nearly all patients with cloacal exstrophy now survive, leading to an increased emphasis on quality of life. Increased attention is given to gender identity and the implications of reconstructive decisions. Long-term sequelae of cloacal exstrophy, including functional continence and sexual dysfunction, are recognized, and many patients require ongoing complex care into adulthood.

Risk factors of developmental dysplasia of the hip in infants: A meta-analysis based on cohort studies

IntroductionDevelopmental dysplasia of the hip (DDH) is a prevalent condition in children. Currently, the exact etiology of DDH remains uncertain. The objective of this study was to conduct a meta-analysis to investigate the risk factors associated with DDH in infants. The findings would provide a theoretical foundation for targeted early screening and diagnosis. HypothesisSeveral indicators, such as gender, intrauterine position, family history of DDH, gestational age, delivery mode, amniotic fluid levels, swaddling, parity, fetus number, combined musculoskeletal deformities, birth weight, and physical examination results, may serve as risk factors for DDH. Materials and methodsCohort studies investigating the risk factors of DDH in infants through logistic regression analysis were searched in the Wanfang, VIP citation, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, Excerpta Medica Database (Embase), PubMed, and Cochrane Library databases up to May 2023. After extracting the data from eligible literature and assessing them using the Newcastle-Ottawa Scale (NOS), articles were selected based on pre-established inclusion and exclusion criteria. ResultsA total of eleven literature reports covering 979,757 infants were included in this meta-analysis. The publication bias did not significantly influence the results. The incidence rate of DDH was 47.99‰ among infants with risk factors compared to 3.21‰ in the general population. Risk factors for DDH included being female (OR=6.97, 95% CI: 5.18–9.39, p<0.001), breech delivery (OR=4.14, 95% CI: 3.09–5.54, p<0.001), positive family history (OR=4.07, 95% CI: 2.20–7.52, p<0.001), cesarean section (OR=1.11, 95% CI: 1.01–1.21, p=0.032), oligohydramnios (OR=3.93, 95% CI: 1.29–12.01, p=0.016), swaddling (OR=6.74, 95% CI: 1.25–36.31, p=0.026), firstborn status (OR=1.84, 95% CI: 1.49–2.53, p<0.001), combined musculoskeletal malformations (OR=2.27, 95% CI: 1.58–3.27, p<0.001), and physical signs of DDH (OR=8.71, 95% CI: 2.44–31.07, p=0.001). Premature delivery (OR=0.91, 95% CI: 0.88–0.95, p<0.001) was a protective factor for DDH. The relationship between multiple pregnancies (OR=0.58, 95% CI: 0.33–1.02, p=0.060) and low birth weight (OR=0.62, 95% CI: 0.14–2.76, p=0.529) in relation to DDH remained uncertain. DiscussionThis meta-analysis shows that female, breech delivery, positive family history, cesarean section, firstborn status, oligohydramnios, swaddling and combined musculoskeletal malformations are associated with DDH. Premature delivery appeared to be a protective factor against DDH. Nevertheless, the other factors need more research to reach more conclusive results. Level of evidenceIII; meta-analysis.

A rare case report of Gorlin-Goltz’s syndrome: a multisystemic disorder of otolaryngological domain

BackgroundGorlin-Goltz’s syndrome (GGS) is an extremely rare autosomal dominant disorder showing a high penetrance and variable expressivity. Gorlin-Goltz’s syndrome is an infrequent multisystemic disease, which is usually characterized by numerous basal cell carcinomas, odontogenic keratocysts (OKCs), and musculoskeletal malformations along with neurological, ophthalmic, endocrine, and genital manifestations. There are also multiple manifestations in the domain of ENT and patient may primarily present to an ENT clinician with one of the diverse clinical involvements.Case presentationWe report one such infrequent case of a 24-year-old male patient who presented with an oroantral fistula at our tertiary health care center and was diagnosed to have Gorlin-Goltz’s syndrome. The diagnosis was made in our patient by the presence of 4 major and 2 minor criteria.ConclusionEarly diagnosis and management of GGS helps to prevent long-term sequelae including malignancy and oro-maxillofacial deformation. The constellation of symptoms of such rare disorders should be promptly recognized and a high index of suspicion should be maintained. This case report is an appraisal of the diagnosis and management of GGS from an otolaryngological perspective and is being reported here for extreme rarity and clinical interest.

Gorlin-Goltz Syndrome: An Incidental Finding of a Rare Entity.

Gorlin-Goltz syndrome (GGS) is a rare hereditary disease characterized by multiple basal cell carcinomas, odontogenic keratocyst (OKCs) and musculoskeletal malformations. Pathogenesis of the syndrome is attributed to abnormalities in the long arm of chromosome 9 (q22.3-q31) and mutations in the human patched gene (PTCH1 gene). Here, we report a rare case of an incidental finding of GGS in an 18-year-old male patient presenting multiple OKCs, calcification of the falx cerebri, and bifid rib.

Hexavalent chromium inhibits myogenic differentiation and induces myotube atrophy

Hexavalent chromium [Cr(VI)] is extensively used in many industrial processes. Previous studies reported that Cr(VI) exposures during early embryonic development reduced body weight with musculoskeletal malformations in rodents while exposures in adult mice increased serum creatine kinase activity, a marker of muscle damage. However, the impacts of Cr(VI) on muscle differentiation remain largely unknown. Here, we report that acute exposures to Cr(VI) in mouse C2C12 myoblasts inhibit myogenic differentiation in a dose-dependent manner. Exposure to 2 μM of Cr(VI) resulted in delayed myotube formation, as evidenced by a significant decrease in myotube formation and expression of muscle-specific markers, such as muscle creatine kinase (Mck), Myocyte enhancer factor 2 (Mef2), Myomaker (Mymk) and Myomixer (Mymx). Interestingly, exposure to 5 μM of Cr(VI) completely abolished myotube formation in differentiating C2C12 cells. Moreover, the expression of key myogenic regulatory factors (MRFs) including myoblast determination protein 1 (MyoD), myogenin (MyoG), myogenic factor 5 (Myf5), and myogenic factor 6 (Myf6) were significantly altered in Cr(VI)-treated cells. The inhibitory effect of Cr(VI) on myogenic differentiation was further confirmed in freshly isolated mouse satellite cells, a stem cell population essential for adult skeletal muscle regeneration. Furthermore, Cr(VI) exposure to fully differentiated C2C12 myotubes resulted in a decrease in myotube diameter, which was exacerbated upon co-treatment with dexamethasone. Together, our results demonstrate that Cr(VI) inhibits myogenic differentiation and induces myotube atrophy in vitro.

Bladder Agenesis: A Systematic Review.

Bladder agenesis is a rare congenital deformity characterized by the absence of the bladder. It is primarily observed in postmortem dissections of stillbirths rather than live births. The condition is often associated with other congenital anomalies, leading to the hypothesis that most affected fetuses do not survive to term. However, the exact cause and specific associated anomalies remain unclear and poorly described in the literature. The limited mention of bladder agenesis in textbooks and literature underscores the importance of creating a comprehensive source for future research in this field. Therefore, our objective is to collect and analyze data on bladder agenesis, focusing on associated anomalies and potential causes, to enhance our understanding of the condition. We conducted a thorough review of reports collected from three databases, Google Scholar, PubMed, and Science Direct, last searched on July 30, 2023, starting with 327 reports. Excluding duplicates and records written in languages other than English, veterinary studies, irrelevant reports, or stillbirths. Inclusion criteria were the following: cases must have proven bladder agenesis, not hypoplasia, and must have most of the information, including the age of diagnosis, presenting symptoms, gender, associated anomalies, and management or outcome of the patient. A quality assessment was conducted according to the Joanna Briggs Institute checklist for case reports. A total of 65 case reports from 56 articles were included in the review. Through our manual analysis, we documented a wild array of malformations associated with bladder agenesis. Among the reports reviewed, 93% exhibited urinary system malformations beside bladder agenesis, 77% were found to have reproductive malformations, 44% had gastrointestinal anomalies, 38% showed musculoskeletal malformations, 28% had cardiac malformations, and another 28% had vascular anomalies. The overall mortality rate was 38%, with a higher rate of 74% for males compared to 20% for females. By collating and analyzing those case reports, we aim to contribute to a better understanding of bladder agenesis and its associated anomalies, facilitating further investigations and advancements in the field.

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.

Beyond the diaphragm and the lung: a multisystem approach to understanding congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a birth defect characterized by the incomplete closure of the diaphragm and herniation of abdominal organs into the chest during gestation. This invariably leads to an impairment in fetal lung development (pulmonary hypoplasia) that involves the pulmonary vessels (vascular remodeling) leading to postnatal pulmonary hypertension. Moreover, approximately 60% of CDH survivors have long-term comorbidities, including critical cardiac anomalies, neurodevelopmental impairment, gastroesophageal reflux, and musculoskeletal malformations. While the pathophysiology of the diaphragmatic defect and pulmonary hypoplasia have been studied in detail over the decades, less is known about the other organs affected in CDH. In this review, we searched the literature for reports on other organs beyond the lung and diaphragm in human and experimental models of CDH. We found studies reporting gross morphometric changes and alterations to biological pathways in the heart, brain, liver, kidney, gastrointestinal tract, and musculoskeletal system. Given the paucity of literature and the importance that these comorbidities play in the life of patients with CDH, further studies are needed to comprehensively uncover the pathophysiology of the changes observed in these other organs.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Clinical characteristics and offspring developmental malformation of 126 patients with septate uterus.

Gorlin-Goltz Syndrome: Case Report and Literature Review

Gorlin-Goltz syndrome, also known as basal cell nevus syndrome, is an uncommon, autosomal dominant inherited disorder, which is characterized by numerous basal cell carcinomas, maxillary keratocysts and musculoskeletal malformations. In this article a case of Gorlin-Goltz syndrome has been reported in 28 -year-old male patient with illustration and review of literature.

CDK13-related disorder: a deep characterization of speech and language abilities and addition of 33 novel cases.

Speech and language impairments are central features of CDK13-related disorder. While pathogenic CDK13 variants have been associated with childhood apraxia of speech (CAS), a systematic characterisation of communication has not been conducted. Here we examined speech, language, non-verbal communication skills, social behaviour and health and development in 41 individuals with CDK13-related disorder from 10 countries (male = 22, median-age 7 years 1 month, range 1-25 years; 33 novel). Most participants used augmentative and alternative communication (AAC) in early childhood (24/41). CAS was common (14/22). Performance varied widely across intellectual ability, social behaviour and expressive language skills, with participants ranging from within average through to the severely impaired range. Receptive language was significantly stronger than expressive language ability. Social motivation was a relative strength. In terms of abroader healthphenotype, a quarter had one or more of: renal, urogenital, musculoskeletal, and cardiac malformations, vision impairment, ear infections and/or sleep disturbance. All had gross and fine motor impairments (41/41). Other conditions included mild-moderate intellectual disability (16/22) and autism (7/41). No genotype-phenotype correlations were found. Recognition of CAS, a rare speech disorder, is required to ensure appropriately targeted therapy. The high prevalence of speech and language impairment underscores the importance of tailored speech therapy, particularly early access to AAC supports.

Fetal and Neonatal Adverse Drug Reactions Associated with Biologics Taken During Pregnancy by Women with Autoimmune Diseases: Insights from an Analysis of the World Health Organization Pharmacovigilance Database (VigiBase®).

Published data on the safety of biologics other than tumor necrosis factor (TNF) inhibitors during pregnancy are limited. The aim was to detect pharmacovigilance signals for fetal and neonatal adverse drug reactions (ADRs) to biologics taken by pregnant women with autoimmune diseases. We performed a disproportionality analysis of the World Health Organization's VigiBase® pharmacovigilance database from 1968 to June 1, 2021. Data were collected in June 2021. By using terms for different hierarchical levels of the Medical Dictionary for Regulatory Activities, we selected the following fetal or neonatal ADRs: stillbirth, premature birth, low birth weight, small for gestational age, and congenital malformations. The frequency of all identified ADRs for biologics of interest (adalimumab, infliximab, golimumab, certolizumab, etanercept, anakinra, canakinumab, tocilizumab, sarilumab, ustekinumab, guselkumab, secukinumab, ixekizumab, belimumab, abatacept, and rituximab) was compared with that of all other reports for all other drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval]. Reports with known concomitant use of teratogenic drugs were excluded from the main analysis. Other analyses included ROR stratifications by therapeutic indication in the periods 1968-2021 and 2001-2021, and an analysis after excluding reports with steroids. In the main analysis, the RORs were particularly high for musculoskeletal malformations with anakinra (7.18 [3.50-14.73]), canakinumab (19.54 [12.82-29.79]), and abatacept (5.09 [2.77-9.33]), and for immune system disorders with canakinumab (347.88 [217.9-555.50]) and rituximab (9.27 [2.95-29.15]). After the exclusion of reports with steroids, the ROR was significant for neonatal infections with belimumab (28.49 [5.75-141.25]). We identified possible associations with some adverse fetal and neonatal outcomes, suggesting that vigilance is required when prescribing certain biologics during pregnancy.

The Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO): Comparisons between Quebec, Manitoba, Saskatchewan, and Alberta.

BackgroundGiven that pregnant women taking medications are excluded from clinical trials, real-world evidence is essential. We aimed to build a Canadian Mother-Child Cohort Active Surveillance Initiative (CAMCCO) and compare frequency of prematurity, low-birth-weight (LBW), major malformations, multiplicity, and gestational medication use across four provinces.MethodsCAMCCO is a collaborative research infrastructure that uses real-world data from large provincial health care databases in Canada; developed with standardized methods to similarly construct population-based pregnancy/child cohorts with longitudinal follow-up by linking administrative/hospital/birth databases. CAMCCO also includes a common repository to i) share algorithms and case definitions based on diagnostic and procedural codes for research/training purpose, and ii) download aggregate data relevant to primary care providers, researchers, and decision makers. For this study, data from Quebec (1998–2015), Manitoba (1995–2019), Saskatchewan (1996–2020), and Alberta (2005–2018) are compared (Chi-square tests, p-values), and trends are calculated using Cochran-Armitage trend tests.ResultsAlmost two-thirds (61%) of women took medications during pregnancy, mostly antibiotics (26%), asthma drugs (8%), and antidepressants (4%). Differences in the prevalence of prematurity (5.9–6.8%), LBW (4.0–5.2%), and multiplicity (1.0–2.5%) were statistically significant between provinces (p<0.001). Frequency of major malformations increased over time in Quebec (7–11%; p<0.001), Saskatchewan (5–11%; p<0.001), and Alberta (from 7–8%; p<0.001), and decreased in Manitoba (5–3%; p<0.001). Cardiovascular and musculoskeletal malformations were the most prevalent.InterpretationMedications are often used among Canadian pregnancies but adverse pregnancy outcomes vary across provinces. Digitized health data may help researchers and care providers understand the risk-benefit ratios related to gestational medication use, as well as province-specific trends.

495 Mutations in different domains of bullous pemphigoid antigen-1 (BPGA1) encoded by DST result in either epidermolysis bullosa simplex or musculoskeletal and neuronal deformities-associated HSAN-VI

DST encodes bullous pemphigoid antigen-1 (BPAG1), a protein with eight tissue-specific isoforms expressed in the skin, muscle, brain, and nerves. Accordingly, mutations in this gene cause different phenotypes, including epidermolysis bullosa simplex (EBS) and hereditary sensory and autonomic neuropathy type VI (HSAN-VI). The genotype-phenotype correlation is attested to by 19 distinct mutations but not well established for both disorders. In this study, we performed next-generation sequencing (NGS) on two families with different phenotypic presentations, one fetus (P1) with musculoskeletal and neurological malformations established by prenatal ultrasound and family history, and a 15-year-old female (P2) with skin blistering. P1 had a novel homozygous nonsense mutation, DST: NM_001144769, c.3805C>T, p.R1269* within a region of homozygosity (ROH). This mutation, within the plakin domain, ablates all BPGA1 isoforms leading to novel extracutaneous phenotypes in P1. P2 has a recurrent homozygous mutation DST: NM_001723.7, c.3370C>T, p.Gln1124* that presented with giant, trauma-induced skin blisters without extracutaneous involvement. This mutation is located within the coiled-coil domain present on the skin isoform of DST, BPGA1-e, associated with EBS. In summary, we report two Iranian families with DST variants, expanding the genotypic and phenotypic spectrum of DST.

Screening for musculoskeletal system malformations and birth injuries in newborns: Results of a screening program in two hospitals in Shenzen, China.

ABSTRACTImportanceThere are a variety of musculoskeletal malformations and injuries that can occur in newborns. These can be a significant cause of perinatal death or a reason for miscarriage and can lead to long‐term functional issues if not managed appropriately. There is no systematic and well‐established screening program for neonatal musculoskeletal malformations and injuries in China now.ObjectiveTo report the incidence and types of congenital musculoskeletal malformations in two hospitals in Shenzhen City, to explore and discuss the details of the screening procedure and improve future prevention and treatment.MethodsFrom October 2013 to May 2014, 2564 one‐day‐old newborns were screened by a pediatric orthopedic physical examination, in combination with ultrasonography when required, and the incidence and variety of diseases were recorded statistically.ResultsAmong 2564 screened newborns, the following musculoskeletal conditions were identified: congenital muscular torticollis (CMT) (seven cases, 0.27%), hip subluxation (four cases, 0.16%), hip dysplasia (47 cases, 1.83%), congenital talipes equinovarus (CTEV) (two cases, 0.08%), congenital talipes calcaneovalgus (15 cases, 0.58%), polydactyly (nine cases, 0.35%), syndactyly (one case, 0.04%), and spinal hemivertebra (one case, 0.04%). Additionally, there were five (0.19%) neonates with birth injuries.InterpretationIt is feasible to carry out neonatal screening and identification of musculoskeletal malformations and birth injuries in China. This is helpful as timely detection and early intervention for many of these conditions can avoid permanent functional impairment in these children.

Hip Prognosis in Patients With Congenital Diastasis of the Pubic Symphysis.

Congenital diastasis of the pubic symphysis (CDPS) is a rare musculoskeletal malformation in the exstrophy-epispadias complex that is potentially associated with the development of hip dysplasia. The purpose of this study was to investigate the incidence and prognostic factors of hip dysplasia in patients with CDPS. Fifty-four hips in 27 patients with CDPS initially evaluated between 1983 and 2016 were retrospectively reviewed. The mean age at the first visit was 2.3 (0 to 8) years. The mean follow-up duration was 10.5 (1 to 36) years. Patient characteristics at the first visit, the clinical course at the most recent follow-up, and radiologic parameters on pubic malformation and hip dysplasia during at least 2 time points (first visit or age 1, and either the most recent visit or before hip surgery) were evaluated. Prognostic factors associated with the development of hip dysplasia were analyzed using univariate/multivariate analysis. The Kaplan-Meier survival curves were generated and compared based on these factors. Nine of 27 patients (33%) and 13 of 54 hip joints (24%) with CDPS developed hip dysplasia. Paraplegia (odds ratio, 10.0; 95% confidence interval, 1.7-76.6) and center-edge angle of <5 degrees at the first visit or age 1 (P<0.001) were independent predictors of the development of hip dysplasia. Patients with CDPS and either paraplegia or center-edge angle <5 degrees at the first visit or age 1 were significantly more likely to develop hip dysplasia than other patients (hazard ratio, 29.3; 95% confidence interval, 3.4-250). Approximately one third of patients with CDPS develop hip dysplasia. Paraplegia and center-edge angle of <5 degrees at the first visit are independent risk factors. Level III.

Evaluation of the Toxicity of Bisphenol A in Reproduction and Its Effect on Fertility and Embryonic Development in the Zebrafish (Danio rerio).

Bisphenol A (BPA) is a chemical substance commonly used in the manufacture of plastic products. Its inhalation or ingestion from particles in suspension, water, and/or polluted foods can trigger toxic effects related to endocrine disruption, resulting in hormonal, reproduction, and immunological alterations in humans and animals. The zebrafish (Danio rerio) is an ideal experimental model frequently used in toxicity studies. In order to assess the toxic effects of BPA on reproduction and embryonic development in one generation after parental exposure to it, a total of 80 zebrafish, males and females, divided into four groups in duplicate (n = 20) were exposed to BPA concentrations of 500, 50, and 5 µg L−1, along with a control group. The fish were kept in reproduction aquariums for 21 days. The embryos obtained in the crosses were incubated in a BPA-free medium and observed for signs of embryotoxicity. A histopathological study (under optical and electron microscopes) was performed of adult fish gonads. The embryos of reproducers exposed to BPA were those most frequently presenting signs of embryotoxicity, such as mortality and cardiac and musculoskeletal malformations. In the histopathological studies of adult individuals, alterations were found in ovocyte maturation and in spermatazoid formation in the groups exposed to the chemical. Those alterations were directly related to BPA action, affecting fertility in both sexes, as well as the viability of their offspring, proportionally to the BPA levels to which they were exposed, so that our results provide more information by associating toxic effects on the offspring and on the next generation.

Congenital anomalies in Santa Catarina: case distribution and trends in 2010-2018.

Objective:To evaluate the distribution of cases of congenital anomalies in the state of Santa Catarina by health macro-region, to determine the frequency according to maternal and neonatal variables, to estimate the related mortality, and the trends in the period 2010–2018.Methods:An ecological time-series study with secondary data on congenital anomalies and the sociodemographic and health variables of mothers and newborns living in Santa Catarina, from 2010 to 2018. For temporal trend analysis, generalized linear regression was performed using the Prais-Winsten method with robust variance.Results:The average prevalence of congenital anomalies in the period was 8.9 cases per 1,000 live births, being 9.4 cases by 1,000 live births in 2010 and, in 2018, 8.2/1,000. The trend remained stable in the analyzed period. The major malformations were musculoskeletal, hip, and foot malformations, with a proportion ≥30%. There was a higher prevalence of congenital anomalies in low birthweight, preterm, male livebirths with Apgar≤7, born by cesarean section, mothers of older age (≥40 years), and less educated (less than eight years of study). Infant mortality due to congenital malformations was 2.6 deaths/1,000 live births, representing about 25.8% of the total infant deaths in the period.Conclusions:The frequency of congenital anomalies and the mortality with anomalies was stable in the studied period in Santa Catarina. The presence of anomalies was associated with low birth weight, prematurity, and low Apgar score. The highest proportion of congenital anomalies was in the musculoskeletal system.

DYNAMICS OF FREQUENCY AND PECULIARITIES OF THE STRUCTURE OF CONGENITAL MALFORMATIONS IN SOUTH UKRAINE (MONITORING STUDY)

Background. In Ukraine, the unfavorable demographic situation makes monitoring of the birth rate of children with congenital malformations urgent issue to identify regional features of epidemiology and develop methods for prenatal diagnosis and prognosis. &#x0D; Objective. Objective of this study is to characterize the frequency dynamics, to identify structural features of congenital malformations of newborns in Kherson region over a 20-year period (2000-2019) and to compare the prevalence of various nosological forms of malformations in the region, in Ukraine and in European countries.&#x0D; Methods. Research methods: epidemiological, medical-statistical. &#x0D; Results. In Kherson region, the average frequency of congenital malformations over the past 20 years is: for newborns – 31.57±1.25‰; for live births – 31.38±1.11‰; for stillborns – 197.7±0.65 per 10,000. In the structure of defects, cardiovascular malformations are leading (31.77%), musculoskeletal malformations (25.14%), genital malformations (17.5%). Increased prevalence of developmental anomalies in the region is mainly associated with an increase in the frequency of model malformations recorded by EUROCAT (r=0.69, p&lt;0.05). The increase in the total frequency of congenital malformations is caused by increased number of births of children with cardiovascular defects (by 4.67‰), genital defects (by 1.21‰), other congenital malformations (by 1.55‰), multiple malformations (by 0.37‰).&#x0D; Conclusion. Monitoring results showed an increase in congenital malformations incidence in Kherson region over a 20-year period by 7.94‰ possibly caused by population decline due to negative natural and mechanical growth. The prevalence of hereditary defects is at the same level. The frequency of some nosological forms significantly exceeds in the region compare to that in Ukraine and Europe: cardiovascular defects – in 1.5 times, genital malformations – in nearly 3 times, musculoskeletal defects – almost twice.

Major Congenital Malformations Associated With Exposure to Second-Generation Antipsychotic Drugs During Pregnancy.

Major congenital malformations (MCMs) are gestational outcomes that are seen in about 2%-3% of pregnancies in the general population. In this context, many studies have examined the MCM risk associated with gestational antipsychotic exposure. These articles were summarized in a recent meta-analysis. The present article examines the findings of the meta-analysis as well as the findings of 2 recent observational studies that were not included in the meta-analysis; an outcome of specific interest was the risk of MCMs after first-trimester gestational exposure to second-generation antipsychotic (SGA) drugs. In brief, meta-analysis of data from 6 observational studies found that exposure to antipsychotic drugs during pregnancy was not associated with a significantly increased risk of MCMs; this finding was also true of early pregnancy exposure and of SGA exposure alone. A large, retrospective, population-based cohort study from Finland found that first-trimester gestational exposure to SGAs was not associated with a significantly increased MCM risk relative to either no exposure or exposure to first-generation antipsychotics; however, in exploratory analyses, olanzapine was associated with increased risk relative to unexposed pregnancies, and specifically so for musculoskeletal malformations. Prospective data from a US pregnancy registry also found no increase in risk associated with first trimester gestational exposure to SGAs in a cohort of women with psychiatric disorders. In smaller studies that used data from the same registry, neither quetiapine nor aripiprazole were associated with increased MCM risk after first trimester use. It is possible that where risk was identified, such as in unadjusted or exploratory analyses, the significant findings were false positives arising from multiple hypothesis testing, or findings driven by residual confounding. The substantial benefits associated with use of antipsychotics, when indicated, must therefore be weighed against the unsubstantiated risks of MCMs in a shared decision-making process.