Congenital Vascular and Lymphatic Diseases.

Over the past several centuries, the integration of contemporary medical techniques and innovative technologies, like genetic sequencing, have played a pivotal role in enhancing our comprehension of congenital vascular and lymphatic disorders. Nonetheless, the uncommon and complex characteristics of these disorders, especially considering their formation during the intrauterine stage, present significant obstacles in diagnosis and treatment. Here, we review the intricacies of these congenital abnormalities, offering an in-depth examination of key diagnostic approaches, genetic factors, and therapeutic methods.

Pediatric cancer incidence among individuals with overgrowth syndromes and overgrowth features: A population-based assessment in seven million children.

BACKGROUND: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. METHODS: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. RESULTS: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). CONCLUSIONS: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.

4D formation of human embryonic forelimb musculature.

The size, shape and insertion sites of muscles enable them to carry out their precise functions in moving and supporting the skeleton. Although forelimb anatomy is well described, much less is known about the embryonic events that ensure individual muscles reach their mature form. A description of human forelimb muscle development is needed to understand the events that control normal muscle formation and to identify what events are disrupted in congenital abnormalities in which muscles fail to form normally. We provide a new, 4D anatomical characterisation of the developing human upper limb muscles between Carnegie stages 18 and 22 using optical projection tomography. We show that muscles develop in a progressive wave, from proximal to distal and from superficial to deep. We show that some muscle bundles undergo splitting events to form individual muscles, whereas others translocate to reach their correct position within the forelimb. Finally, we show that palmaris longus fails to form from early in development. Our study reveals the timings of, and suggests mechanisms for, crucial events that enable nascent muscle bundles to reach their mature form and position within the human forelimb.

An ESHG-ESHRE survey on the current practice of expanded carrier screening in medically assisted reproduction.

STUDY QUESTION: What is the current practice and views on (expanded) carrier screening ((E)CS) among healthcare professionals in medically assisted reproductive (MAR) practices in Europe? SUMMARY ANSWER: The findings show a limited support for ECS with less than half of the respondents affiliated to centres offering ECS, and substantial variation in practice between centres in Europe. WHAT IS KNOWN ALREADY: The availability of next-generation sequencing, which enables testing for large groups of genes simultaneously, has facilitated the introduction and expansion of ECS strategies, currently offered particularly in the private sector in the context of assisted reproduction. STUDY DESIGN, SIZE, DURATION: A cross-sectional survey evaluating practice and current views among professionals working in MAR practice in different European countries was designed using the online SurveyMonkey tool. The web-based questionnaire included questions on general information regarding the current practice of (E)CS in MAR and questions on what is offered, to whom the test is offered, and how it is offered. It consisted mostly of multiple-choice questions with comment boxes, but also included open questions on the respondents' attitudes/concerns relevant to (E)CS practice, and room to upload requested files (e.g. guidelines and gene panels). In total, 338 responses were collected from 8 February 2022 to 11 April 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: The online survey was launched with an invitation email from the ESHRE central office (n = 4889 emails delivered) and the European Society of Human Genetics (ESHG) central office (n = 1790 emails delivered) sent to the ESHRE and ESHG members, and by social media posts. The survey was addressed to European MAR centres or gamete banks and to centres located in non-European countries participating in the European IVF-monitoring Consortium. Two reminder emails were sent. After exclusion of 39 incomplete responses received (e.g. only background information), 299 respondents from 40 different countries were included for analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 42.5% (127/299) of respondents were affiliated to centres offering ECS. The perceived responsibility to enable prospective parents to make informed reproductive decisions and preventing suffering/burden for parents were the main reasons to offer ECS. A single ECS panel is offered by nearly 45% (39/87 received answers) of the centres offering ECS, 25.3% (22/87) of those centres offer a selection of ECS panels, and 29.9% (26/87) offer whole exome sequencing and a large in silico panel. Different ranges of panel sizes and conditions were included in the ECS panel(s) offered. Most of the respondents (81.8%; 72/88 received answers) indicated that the panels they offer are universal and target the entire population. Pathogenic variants (89.7%; 70/78 received answers), and to a lesser extent, likely pathogenic variants (64.1%%; 50/78 received answers), were included in the ECS report for individuals and couples undergoing MAR with their own gametes. According to 87.9% (80/91 received answers) of the respondents, patients have to pay to undergo an ECS test. Most respondents (76.2%; 61/80 received answers) reported that counselling is provided before and after the ECS test. Preimplantation genetic testing, the use of donor gametes, and prenatal diagnostic testing were the three main reproductive options discussed with identified carrier couples. The main reason, according to the respondents, for not offering ECS in their centre, was the lack of professional recommendations supporting ECS (52.5%; 73/139 received answers) and the high cost for couples or reimbursement not being available (49.6%; 69/139). The challenges and moral dilemmas encountered by the respondents revolved mainly around the content of the offer, including the variants classification and the heterogeneity of the panels, the counselling, and the cost of the test. LIMITATIONS, REASONS FOR CAUTION: Although the total number of respondents was acceptable, the completion rate of the survey was suboptimal. In addition, the heterogeneity of answers to open-ended questions and the ambiguity of some of the answers, along with incomplete responses, posed a challenge in interpreting survey results. It is also plausible that some questions were not easily understood by the respondents. For this reason, response and non-response bias are acknowledged as further limitations of the survey. WIDER IMPLICATIONS OF THE FINDINGS: The results of this survey could aid in identifying potential challenges or areas for improvement in the current practice of ECS in the MAR field and contribute to the discussion on how to address them. The results underline the need to stimulate a more knowledge-based debate on the complexity and the pros and cons of a possible implementation of ECS in MAR. STUDY FUNDING/COMPETING INTEREST(S): All costs relating to the development process were covered from European Society of Human Reproduction and Embryology and European Society of Human Genetics funds. There was no external funding of the development process or manuscript production. A.C. is full-time employee of Juno Genetics. L.H. declared receiving a research grant during the past 36 months from the Netherlands Organisation for Health Research and Development. She has also participated in a Health Council report of the Netherlands on preconception carrier screening and collaborated with the VSOP Dutch Genetic Alliance (patient umbrella organization on rare and genetic disorders). L.H. and C.v.E. are affiliated with Amsterdam University Medical Centre, a hospital that offers ECS in a non-commercial setting. R.V. received honoraria for presentations from Merck Academy and is unpaid board member of the executive committee of the Spanish Fertility Society. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Classification of isolated versus multiple birth defects: An automated process for population-based registries.

Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co-occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999-2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies.

Very young and advanced maternal age strongly elevates the occurrence of nonchromosomal congenital anomalies: a systematic review and meta-analysis of population-based studies.

BACKGROUND: Nonchromosomal congenital anomalies (NCAs) are the most common cause of infant mortality and morbidity. The role of maternal age is well known, although the specifics are not thoroughly elucidated in the literature. OBJECTIVE: To evaluate the role of maternal age in the incidence of NCAs and to pinpoint age groups at higher risk to refine screening protocols. STUDY DESIGN: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines and Cochrane Handbook. Searches were performed on October 19, 2021, across MEDLINE (via PubMed), Cochrane Library (CENTRAL), and Embase. Population-based studies assessing the impact of maternal age on the incidence of NCAs in pregnant women were included, without restrictions on age range, country, or comorbidities. A random-effects model was used for pooling effect sizes, considering the heterogeneity across studies. RESULTS: From 15,547 studies, 72 were synthesized. Maternal age >35 showed an increased NCA risk (risk ratio [RR]: 1.31, confidence interval [CI]: 1.07 -1.61), rising notably after>40 (RR: 1.44, CI: 1.25 -1.66). The latter changes to 1.25 (CI: 1.08 -1.46) if the co-occurrence of chromosomal aberrations is excluded. Specific anomalies like cleft lip/palate (>40, RR: 1.57, CI: 1.11 -2.20) and circulatory system defects (>40, RR: 1.94, CI: 1.28 -2.93) were significantly associated with advanced maternal age. Conversely, gastroschisis was linked to mothers <20 (RR: 3.08, CI: 2.74 -3.47). CONCLUSION: The study confirms that both very young and advanced maternal ages significantly increase the risk of NCAs. There is a pressing need for age-specific prenatal screening protocols to better detect these anomalies, especially considering the current trend of delayed childbearing. Further research is required to fully understand the impact of maternal age on the prevalence of rarer NCAs.

Trends and socioeconomic inequality of the burden of congenital abnormalities of the kidney and urinary tract among children and adolescents.

BACKGROUND: Although congenital abnormalities of the kidney and urinary tract (CAKUT) is the leading cause of childhood onset chronic kidney disease (CKD) and kidney failure, comprehensive information on the disease burden among children and adolescents globally is lacking. We aim to report the trends and socioeconomic inequality of CAKUT burden for people aged 0-24 years from 1990 to 2019·. METHODS: We reported the prevalence, mortality and disability-adjusted life-years (DALYs) for CAKUT based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, quantified the association of disease burden and socio-demographic index (SDI), calculated the slope index of inequality (SII) the relative index of inequality (RII) and concentration index. RESULTS: In 2019, the global prevalence, mortality, and DALYs of CAKUT among individuals aged 0-24 years were 167.11 (95%Confident Interval 166.97, 167.25), 0.30 (0.29, 0.30), and 32.22 (32.16, 32.29) per 100 000 population. The greatest prevalence, mortality and DALYs were recorded in the 0-4 year age group. The greatest mortality and DALYs were recorded in low SDI countries and territories. During 1990 to 2019, the prevalence, mortality and DALYs decreased globally, while in low and low-middle countries and territories the reduction was much less slower. India, Nigeria and Pakistan had the highest DALYs. Saudi Arabia and China exhibited a markedly decrease of CAKUT burden. Globally for every 0.1 increase in SDI, there was a 20.53% reduction in mortality, a 16.31% decrease in DALYs, but a 0.38% rise in prevalence. CONCLUSIONS: Inequality for disease burden of varying SDI was increasing globally. Thus, specific preventive and health service measures are needed to reduce the global burden from CAKUT.

Bronchoscopy findings in children with congenital lung and lower airway abnormalities.

Congenital lung and lower airway abnormalities are rare, but they are an important differential diagnosis in children with respiratory diseases, especially if the disease is recurrent or does not resolve. The factors determining the time of presentation of congenital airway pathologies include the severity of narrowing, association with other lesions and the presence or absence of congenital heart disease (CHD). Bronchoscopy is required in these cases to assess the airway early after birth or when intubation and ventilation are difficult or not possible. Many of these conditions have associated abnormalities that must be diagnosed early, as this determines surgical interventions. It may be necessary to combine imaging and bronchoscopy findings in these children to determine the correct diagnosis as well as in operative management. Endoscopic interventional procedures may be needed in many of these conditions, ranging from intubation to balloon dilatations and aortopexy. This review will describe the bronchoscopic findings in children with congenital lung and lower airway abnormalities, illustrate how bronchoscopy can be used for diagnosis and highlight the role of interventional bronchoscopy in the management of these conditions.

Neonatal outcomes and follow-up of children born to women with pregnancy-associated cancer: a prospective observational study.

BACKGROUND: During the last decade, there has been a growing number of cases of children born from pregnancy-associated cancer (PAC), however there are currently insufficient data on the follow up to be observed in this category of newborns. Objective of the study was to evaluate the neonatal outcomes of infants born to mother with PAC, the potential adverse effect of chemotherapy during pregnancy and the risk of metastasis to the fetus. METHODS: Maternal clinical data and neonatal outcomes of child born to mothers diagnosed with PAC were collected; infants were divided into those were and were not exposed to chemotherapy during fetal life and their outcomes were compered. RESULTS: A total of 37 newborn infants from 36 women with PAC were analyzed. Preterm delivery occurred in 83.8% of the cases. No significant differences in neonatal outcomes were found between infants who were and were not exposed to chemotherapy during pregnancy. The median follow-up period was 12 months. CONCLUSIONS: PAC treatment during the second or third trimester does not seem to be dangerous for the fetus, however infants born from PAC must be carefully evaluated for to rule out the consequences of chemotherapy and exclude the presence of metastasis. Long-term follow-up, especially in children exposed to chemotherapy, should be encouraged to obtain relevant data on long-term toxicity.

Classifications of anterior segment structure of congenital corneal opacity in infants and toddlers by ultrasound biomicroscopy and slit-lamp microscopic photographs: an observational study.

BACKGROUND: The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity. METHODS: Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed. RESULTS: Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003). CONCLUSIONS: This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.

Pregnancies in patients with systemic lupus erythematosus during 2000-2018 in Finland: a case-control study.

OBJECTIVES: The aim was to investigate, how pregnancies proceed in patients with systemic lupus erythematosus (SLE) compared to their individually matched population controls. MATERIAL AND METHODS: Adult incident SLE patients were identified from the register of new special reimbursement decisions for SLE drugs in 2000-2014. For each patient, 1-3 randomly selected controls from the Population Register Centre were matched. Data regarding pregnancies were obtained from the Finnish Medical Birth Register, Care Register and Register of Congenital Malformations until 2018. The study utilized data from the Drug Purchase Register and educational information from Statistic Finland. RESULTS: A total of 163 deliveries for 103 mothers with SLE and 580 deliveries for 371 population controls were identified. The duration of pregnancies in SLE women was significantly shorter compared to controls (38.9 versus 39.6 weeks). There were more urgent Caesarean Sections. (15% versus 9%) and need for care at neonatal intensive care unit (NICU) (21% versus 11%) among deliveries in SLE mothers. No statistical difference was observed between SLE and control groups in the occurrence of preeclampsia or major congenital malformations. Gestational age was 2.5 weeks shorter when the mother experienced pre-eclampsia. Hydroxychloroquine was purchased by 30% of SLE mothers during pregnancy. CONCLUSION: The course of pregnancies in Finnish SLE patients seems to be quite moderate compared to controls, and no new safety issues were detected. The low utilization of hydroxychloroquine indicates that the benefits of the drug to pregnancy and disease course are not optimally recognized by specialists treating SLE mothers.

Multivariate logistic regression analysis of risk factors for birth defects: a study from population-based surveillance data.

OBJECTIVE: To explore risk factors for birth defects (including a broad range of specific defects). METHODS: Data were derived from the Population-based Birth Defects Surveillance System in Hunan Province, China, 2014-2020. The surveillance population included all live births, stillbirths, infant deaths, and legal termination of pregnancy between 28 weeks gestation and 42 days postpartum. The prevalence of birth defects (number of birth defects per 1000 infants) and its 95% confidence interval (CI) were calculated. Multivariate logistic regression analysis (method: Forward, Wald, α = 0.05) and adjusted odds ratios (ORs) were used to identify risk factors for birth defects. We used the presence or absence of birth defects (or specific defects) as the dependent variable, and eight variables (sex, residence, number of births, paternal age, maternal age, number of pregnancies, parity, and maternal household registration) were entered as independent variables in multivariate logistic regression analysis. RESULTS: Our study included 143,118 infants, and 2984 birth defects were identified, with a prevalence of 20.85% (95%CI: 20.10-21.60). Multivariate logistic regression analyses showed that seven variables (except for parity) were associated with birth defects (or specific defects). There were five factors associated with the overall birth defects. The risk factors included males (OR = 1.49, 95%CI: 1.39-1.61), multiple births (OR = 1.44, 95%CI: 1.18-1.76), paternal age < 20 (OR = 2.20, 95%CI: 1.19-4.09) or 20-24 (OR = 1.66, 95%CI: 1.42-1.94), maternal age 30-34 (OR = 1.16, 95%CI: 1.04-1.29) or > = 35 (OR = 1.56, 95%CI: 1.33-1.81), and maternal non-local household registration (OR = 2.96, 95%CI: 2.39-3.67). Some factors were associated with the specific defects. Males were risk factors for congenital metabolic disorders (OR = 3.86, 95%CI: 3.15-4.72), congenital limb defects (OR = 1.34, 95%CI: 1.14-1.58), and congenital kidney and urinary defects (OR = 2.35, 95%CI: 1.65-3.34). Rural areas were risk factors for congenital metabolic disorders (OR = 1.21, 95%CI: 1.01-1.44). Multiple births were risk factors for congenital heart defects (OR = 2.09, 95%CI: 1.55-2.82), congenital kidney and urinary defects (OR = 2.14, 95%CI: 1.05-4.37), and cleft lip and/or palate (OR = 2.85, 95%CI: 1.32-6.15). Paternal age < 20 was the risk factor for congenital limb defects (OR = 3.27, 95%CI: 1.10-9.71), 20-24 was the risk factor for congenital heart defects (OR = 1.64, 95%CI: 1.24-2.17), congenital metabolic disorders (OR = 1.56, 95%CI: 1.11-2.21), congenital limb defects (OR = 1.61, 95%CI: 1.14-2.29), and congenital ear defects (OR = 2.13, 95%CI: 1.17-3.89). Maternal age < 20 was the risk factor for cleft lip and/or palate (OR = 3.14, 95%CI: 1.24-7.95), 30-34 was the risk factor for congenital limb defects (OR = 1.37, 95%CI: 1.09-1.73), >=35 was the risk factor for congenital heart defects (OR = 1.51, 95%CI: 1.14-1.99), congenital limb defects (OR = 1.98, 95%CI: 1.41-2.78), and congenital ear defects (OR = 1.82, 95%CI: 1.06-3.10). Number of pregnancies = 2 was the risk factor for congenital nervous system defects (OR = 2.27, 95%CI: 1.19-4.32), >=4 was the risk factor for chromosomal abnormalities (OR = 2.03, 95%CI: 1.06-3.88) and congenital nervous system defects (OR = 3.03, 95%CI: 1.23-7.47). Maternal non-local household registration was the risk factor for congenital heart defects (OR = 3.57, 95%CI: 2.54-5.03), congenital metabolic disorders (OR = 1.89, 95%CI: 1.06-3.37), congenital limb defects (OR = 2.94, 95%CI: 1.86-4.66), and congenital ear defects (OR = 3.26, 95%CI: 1.60-6.65). CONCLUSION: In summary, several risk factors were associated with birth defects (including a broad range of specific defects). One risk factor may be associated with several defects, and one defect may be associated with several risk factors. Future studies should examine the mechanisms. Our findings have significant public health implications as some factors are modifiable or avoidable, such as promoting childbirths at the appropriate age, improving the medical and socio-economic conditions of non-local household registration residents, and devoting more resources to some specific defects in high-risk groups, which may help reducing birth defects in China.

Barriers to healthcare access for children with congenital heart disease in eight Latin American countries.

BACKGROUND: Mortality from congenital heart disease has decreased considerably in the last two decades due to improvements in overall health care. However, there are barriers to access to healthcare in Latin America for this population, which could be related to factors such as healthcare system, policies, resources, geographic, cultural, educational, and psychological factors. Understanding the barriers to access to care is of paramount importance for the design and implementation of policies and facilitate the provision of care. AIM: The aim of the study was to investigate the perception of barriers to access to health care on parents/guardians of children with congenital heart disease in selected Latin American countries. METHODS: A descriptive, cross-sectional study, in which parents/guardians or primary caregivers of children with congenital heart disease was recruited to participate and surveyed. Once the informed consent process had been completed, a set of paper-based scales was used to collect data, namely socioeconomic and demographic information, the Barriers to Care for Children with Special Health Care Needs Questionnaire, and the General Health Questionnaire. RESULTS: In total, 286 participants completed the surveys, with an average age of 34.81 years and 73.4% being female. Mean score of overall barriers was 54.45 (minimum score 39, maximum score 195, higher scores show greater perception of barriers). In Mexico, the parents/guardians of children perceived fewer barriers to access (46.69), while Peru is the country where the most barriers were perceived (69.91). Nonpoor participants showed higher overall barrier perception scores (57.34) than poor participants (52.58). The regression analysis demonstrated the overall perception of barriers was positively associated with individual and social factors, such as educational level, contract status, household monthly income, and psychological well-being and with the country of the participants. CONCLUSIONS: Multiple factors are associated with the perception of barriers to accessing health care for children with congenital heart disease, including socioeconomic status, expectations, psychological well-being, and structural factors.

A case of a blind-ending right ureter first identified intraoperatively during total laparoscopic hysterectomy for uterine adenomyosis and fibroids in a woman with severe ipsilateral kidney hypoplasia.

Detecting ureteral injury-a serious intraoperative and postoperative complication of hysterectomy-is a high level of difficulty if ureteral malformations are not identified preoperatively. A 39-year-old Japanese woman underwent total laparoscopic hysterectomy for uterine adenomyosis. During surgery, ureteral peristalsis was absent on the right side, whereas the left ureter was visible under the peritoneum. Transabdominal ultrasonography failed to locate the right kidney, with cystoscopy showing no flow from the right ureteral orifice. The ureteral tunnel was identified by tracing the vascular path of the internal iliac and uterine arteries, confirming that the corded tissue was the right ureter. Postoperative contrast-enhanced CT revealed severe right kidney atrophy with no contrast effect or connected ureter. Based on intraoperative laparoscopy and postoperative examination, a diagnosis of a unilateral ureteral scar with a proximal blind end and ipsilateral renal dysgenesis was established, marking the first reported instance of endoscopic visualization of this anomaly. In addition to normal pelvic anatomy, surgeons must consider embryological abnormalities to prevent intraoperative complications.

Risk of teratogenicity in continued pregnancy after gestational exposure to mifepristone and/or misoprostol: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aimed to comprehensively assess the teratogenic risk to offspring associated with continuing pregnancy after administering mifepristone and/or misoprostol during gestation. METHODS: We conducted a systematic search of multiple databases, including PubMed, Web of Science, Embase, Cochrane, CNKI, and CBM, from their inception to February 2024, with no language restrictions. We included cohort and case-control studies that analyzed the teratogenic effects of mifepristone and/or misoprostol on fetuses and newborns. Quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The odds ratios (OR) from individual studies were combined using meta-analysis. Sensitivity testing and heterogeneity analysis were conducted. RESULTS: A total of 13 studies were eligible for inclusion, comprising 5193 cases of congenital malformations and 12,232 controls. CONCLUSION: Our findings indicated that the use of misoprostol during early pregnancy increased the risk of congenital abnormalities in offspring (OR = 2.69; 95% CI: 1.57-4.62). However, the potential teratogenic effect of mifepristone during pregnancy cannot be ruled out. Additionally, the use of mifepristone and/or misoprostol has been linked to a higher risk of certain congenital anomalies, such as hydrocephalus (OR = 3.41; 95% CI: 1.17-9.97), Möbius syndrome (OR = 26.48; 95% CI: 11.30-62.01), and terminal transverse limb defects (OR = 10.75; 95% CI: 3.93-29.41). (PROSPERO, CRD42024522093, 03182024).

Fibrates and risk of congenital malformations: a nationwide cohort study in South Korea.

PURPOSE: To examine the association between maternal prescriptions for fibrates and congenital malformations in live births. METHODS: Nationwide retrospective cohort study was conducted using the data sourced from the Korean National Health Insurance database. A cohort of 756,877 completed pregnancies linked to live-born infants in 215,600 women with dyslipidemia between 2012 and 2021. The study compared data on congenital anomalies between pregnancies who were exposed to fibrates and those who were not exposed to fibrates in the first trimester. Odds ratios (OR) were calculated by a multivariable analyses using logistic regression models to adjust for potential confounders. RESULTS: 260 pregnancies (0.12%) were exposed to fibrates during the first trimester. The prevalence of malformations in exposed offspirng was 10.77%, not significantly different compared with 9.68% in offspring of women who were not prescribed fibrates during pregnancy in patients with dyslipidemia (OR 1.13; 95% CI 0.75-1.70). CONCLUSION: This study implies that the use of fibrates during pregnancy may be safe, as it did not show any association with congenital anomalies. However, caution is warranted due to an elevated risk associated with prolonged exposure.

Extending the new era of genomic testing into pregnancy management: A proposed model for Australian prenatal services.

BACKGROUND: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. AIMS: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. MATERIALS AND METHODS: Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. RESULTS: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. CONCLUSIONS: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.

Efforts to improve outcomes among neonates with complex intestinal atresia: a single-center low-income country experience.

PURPOSE: Intestinal obstruction caused by intestinal atresia is a surgical emergency in newborns. Outcomes for the jejunal ileal atresia (JIA), the most common subtype of atresia in low-income countries (LIC), are poor. We sought to assess the impact of utilizing the Bishop-Koop (BK) approach to JIA in improving outcomes. METHODS: A retrospective cohort study was performed on children with complex JIA (Type 2-4) treated at our national referral hospital from 1/2018 to 12/2022. BK was regularly used starting 1/1/2021, and outcomes between 1/2021 and 12/2022 were compared to those between 1/2018 and 12/2020. Statistical significance was set at p < 0.05. RESULTS: A total of 122 neonates presented with JIA in 1/2018-12/2022, 83 of whom were treated for complex JIA. A significant decrease (p = 0.03) was noted in patient mortality in 2021 and 2022 (n = 33, 45.5% mortality) compared to 2018-2020 (n = 35, 71.4% mortality). This translated to a risk reduction of 0.64 (95% CI 0.41-0.98) with the increased use of BK. CONCLUSION: Increased use of BK anastomoses with early enteral nutrition and decreased use of primary anastomosis improves outcomes for neonates with severe JIA in LIC settings. Implementing this surgical approach in LICs may help address the disparities in outcomes for children with JIA.

Hidden blood loss and bleeding characteristics in children with congenital scoliosis undergoing spinal osteotomies.

PURPOSE: Spinal osteotomies are often essential in the treatment of congenital scoliosis. Risk factors for bleeding in these patients needing extracavitatory approaches, especially hidden blood loss, are sparsely investigated. We aimed to investigate the bleeding characteristics and hidden blood loss in paediatric patients undergoing spinal osteotomies for congenital scoliosis. METHODS: A retrospective analysis identified all patients with congenital scoliosis were retrospectively identified from the prospectively collected spine register from 2010 to 2022. Operative technique, perioperative laboratory results and imaging studies were extracted. The primary outcome was total blood loss including intraoperative, drain output and hidden blood loss. RESULTS: Fifty-seven children (32 boys) with a mean age of 8.3 years underwent spinal osteotomy for congenital scoliosis. Posterolateral hemivertebrectomy was sufficient in 34 (59%) patients, while vertebral column resection (VCR) was required in 23 patients. Total bleeding averaged 792 (523) ml accounting for 42% of the estimated blood volume. Hidden blood loss accounted for 40% of total bleeding and 21% of estimated blood volume with a mean of 317 (256) ml. VCR was associated with greater intraoperative and total bleeding than hemivertebrectomies (p = 0.001 and 0.007, respectively). After adjusting for patient weight and fusion levels, hidden blood loss was larger in hemivertebrectomies (4.18 vs. 1.77 ml/kg/fused level, p = 0.049). In multivariable analysis, intraoperative blood loss was inversely correlated with preoperative erythrocyte levels. Younger age was associated with significantly greater drain, hidden and total blood loss. CONCLUSION: Hidden blood loss constitutes a significant portion (40%) of total bleeding in congenital scoliosis surgery. Younger age is a risk factor for bleeding and the hidden blood loss should be taken into consideration in their perioperative management.

[Contemporary diagnosis and management of congenital microtia and aural atresia : Part 2: Overview of therapeutic approaches]. / Aktuelle Diagnostik und Therapie bei Ohrmuscheldysplasien und Gehörgangsfehlbildungen : Teil 2: Übersicht der verschiedenen Therapieansätze.

Congenital malformations of the pinna and aural atresia can result in major aesthetic and functional deficits. Knowledge about embryologic developments and established classification systems is an essential requirement when dealing with affected patients. Early detection of deficiencies and introduction of appropriate diagnostic measures is vital to initiate adequate therapies and prevent long-term disabilities. Treatment for malformations of the pinna-if requested-is mostly surgical, infrequently an epithesis is applied. As in other surgical fields, tissue engineering will likely play a crucial role in the future. Treatment of aural stenosis and atresia aims at improvement of hearing levels and prevention of secondary complications like cholesteatoma and chronic otorrhea. Auditory rehabilitation comprises a spectrum from conventional hearing aids to invasive hearing implants, the latter being favored in recent years.