Birth Defects Research Articles

A Comprehensive Review on Rubella Virus

Rubella, colloquially known as German measles, is an exceptionally contagious viral illness that primarily affects children and non-immune young adults. While the infection is typically mild and self-limiting in most cases, rubella virus infection during early pregnancy can have devastating consequences, leading to a range of severe birth defects collectively termed congenital rubella syndrome (CRS). The etiological agent, Rubella virus (RV), is an enveloped, positive-sense single-stranded RNA virus and the sole member of the genus Rubivirus within the Matonaviridae family. Despite the availability of an effective and safe rubella vaccine, the disease continues to pose a significant global health threat, with an estimated 100,000 cases of CRS occurring annually worldwide, predominantly in regions with suboptimal vaccination coverage. This comprehensive review delves into the intricate details of rubella virus, encompassing its epidemiological patterns, modes of transmission, and the complex pathogenic mechanisms underlying congenital rubella syndrome

Deep postnatal phenotyping of a new mouse model of nonketotic hyperglycinemia.

Nonketotic hyperglycinemia due to deficient glycine cleavage enzyme activity causes a severe neonatal epileptic encephalopathy. Current therapies based on mitigating glycine excess have only limited impact. An animal model with postnatal phenotyping is needed to explore new therapeutic approaches. We developed a Gldc p.Ala394Val mutant model and bred it to congenic status in two colonies on C57Bl/6J (B6) and J129X1/SvJ (J129) backgrounds. Mutant mice had reduced P-protein and enzyme activity indicating a hypomorphic mutant. Glycine levels were increased in blood and brain regions, exacerbated by dietary glycine, with higher levels in female than male J129 mice. Birth defects were more prevalent in mutant B6 than J129 mice, and hydrocephalus was more frequent in B6 (40%) compared to J129 (none). The hydrocephalus rate was increased by postnatal glycine challenge in B6 mice, more so when delivered from the first neonatal week than from the fourth. Mutant mice had reduced weight gain following weaning until the eighth postnatal week, which was exacerbated by glycine loading. The electrographic spike rate was increased in mutant mice following glycine loading, but no seizures were observed. The alpha/delta band intensity ratio was decreased in the left cortex in female J129 mice, which were less active in an open field test and explored less in a Y-maze, suggesting an encephalopathic effect. Mutant mice showed no evidence of memory dysfunction. This partial recapitulation of human symptoms and biochemistry will facilitate the evaluation of new therapeutic approaches with an early postnatal time window likely most effective.

Tracking the Global Burden of Neural Tube Defects and Assessing Disparities Across World Health Organization Regions: A Scoping Literature Review.

Neural tube defects (NTDs) are an important cause of global morbidity worldwide. Well-planned global neurosurgery and public health efforts can aid vulnerable communities, but there is a need to elucidate the global burden of NTDs and identify regions without available data to better target interventions. A scoping review to quantify worldwide NTD prevalence using the PubMed/Medline and birth defects surveillance registries was conducted. Data published after January 1, 1990, encompassing prevalence values of at least the 2 most prevalent NTDs-spina bifida and encephalocele-were abstracted. Average NTD prevalence rates were aggregated by World Health Organization (WHO) region and World Bank classification, and differences were determined using the analysis of variance test. Differences in availability of nationally representative data by WHO region and World Bank classification were determined using χ2 tests. This review captured 140 studies from a total of 93 of 194 WHO member countries. The percentage of countries within a geographic region with available NTD prevalence data was highest in the Eastern Mediterranean (EMR) (85.7%) and lowest in Africa (AFR) (31.3%). The NTD prevalence range was 0.9-269.6 per 10 000 births. Statistically significant differences in reported NTD prevalence rates existed by WHO Region (P = .00027) and World Bank income level of study country (P = .00193). Forty countries (43%) had conducted national-level studies assessing NTD prevalence. There was a statistically significant difference in the availability of nationally representative prevalence data depending on the WHO region (P = .0081) and World Bank classification of study country (P = .0017). There is a gap in availability of NTD prevalence data worldwide, with many WHO member states lacking national-level NTD prevalence estimates. These findings highlight the need for greater NTD surveillance efforts to identify the countries with the greatest need for targeted global intervention.

MicroR-1199-5p targeting SRD5A2 promotes the biological behavior and EMT of hypospadias cells.

Hypospadias, an oft-occurring penis anomaly, ranks among neonatal's foremost birth defects. The SRD5A2 can affect male reproductive system development and is abnormally expressed in its epithelial cells. This study exploration aimed at understanding the role of SRD5A2 in the development of hypospadias from a molecular perspective. SRD5A2 levels in hypospadias primary cells were analyzed by Western blot, while targeted interaction with miR-1199-5p was ascertained by dual-luciferase gene reporter assay. In vitro biological experiments were used to confirm the biological function of SRD5A2 in hypospadias. SRD5A2 expression was significantly upregulated, and miR-1199-5p expression was significantly downregulated in hypospadias primary cells. Intervention of SRD5A2 expression can affect cell proliferation, migration, invasion, EMT, and the expression of cell cycle-related proteins. Additionally, we found that SRD5A2 is regulated by upstream miR-1199-5p and can enhance the effect of SRD5A2 on hypospadias cells. Conclusions Silencing SRD5A2 promotes cell proliferation, invasion, and migration blocks the cell cycle at the G1 phase, and simultaneously promotes EMT, cell cycle, and cell proliferation-related protein expression. The biological function of SRD5A2 in hypospadias cells is regulated by miR-1199-5p. SRD5A2 may be an effective therapeutic target for hypospadias.

Valproate Use During Spermatogenesis and Risk to Offspring

Concerns exist about teratogenic and long-term neurodevelopmental outcomes of paternal use of valproate during spermatogenesis. To evaluate the association between paternal use of valproate during spermatogenesis and offspring risk of congenital malformations and neurodevelopmental disorders. This nationwide cohort study included 1 235 353 singletons born in Denmark between January 1, 1997, and December 31, 2017, identified in the Medical Birth Register; 1336 children had fathers who had filled prescriptions for valproate during spermatogenesis. Congenital malformations were identified in the first year of life and neurodevelopmental disorders were identified from 1 year of age until December 31, 2018. Statistical analysis was performed March 2024. Paternal valproate exposure was defined as fathers who filled 1 or more prescriptions for valproate immediately before or during the time of spermatogenesis (ie, 3 months prior to conception). Children with major congenital malformations in the first year of life and with neurodevelopmental disorders before death or end of follow-up were identified in Danish health registers. Log-binomial regression was used to estimate adjusted relative risks (ARRs) of congenital malformations, and Cox proportional hazards regression was used to estimate adjusted hazards ratios (AHRs) of neurodevelopmental disorders, adjusted for relevant confounders. Among 1 235 353 live births (634 415 boys [51.4%] and 600 938 girls [48.6%]), 1336 children (0.1%) had fathers who filled prescriptions for valproate during spermatogenesis. The median follow-up was 10.1 years (IQR, 5.1-14.8 years) for valproate-exposed children and 10.3 years (IQR, 5.2-15.6 years) for valproate-unexposed children. A total of 43 903 children (3.6%) received a diagnosis of major congenital malformations in the first year of life, and 51 633 children (4.2%) received a diagnosis of neurodevelopmental disorders during follow-up. When comparing the risk among valproate-exposed children with that among unexposed children, the ARR of major congenital malformations was 0.89 (95% CI, 0.67-1.18), the AHR of neurodevelopmental disorders was 1.10 (95% CI, 0.88-1.37), and the AHR of autism spectrum disorder was 0.92 (95% CI, 0.65-1.30). In analyses addressing the robustness of the findings (ie, dose-response analyses, sibling analyses, analyses restricted to children of fathers with epilepsy, analyses that used children with paternal lamotrigine exposure as active comparator, and analyses that used children with paternal exposure to valproate only before spermatogenesis as a negative control exposure), there still was no increased risk of any of the included end points. In all analyses based on this large Danish cohort study, results suggest that exposure to valproate during spermatogenesis was not associated with offspring risk of congenital malformations or neurodevelopmental disorders, including autism spectrum disorder.

Investigation of Potentially Toxic Elements (PTEs) Concentrations in Natural and Synthetic Product Cosmetics Used in Lagos, Nigeria

The use of cosmetics in their various forms has been historical and still trending. Potentially toxic elements (PTEs) have been found to be critical constituents of these cosmetics, though as either functional ingredients or as impurities. This has raised health concerns such as; in kidney failures, heart diseases and birth defects. This study investigate the presence and levels of certain indexed PTEs in both natural and synthetic cosmetics and their associated health implications on users in Lagos State, Nigeria. Three natural product cosmetics namely; palm kernel oil (PKO), shear butter and ‘tiro’ labelled as NC1, NC2 and NC3 respectively, and five brands of synthetic product cosmetics (SPCs) labelled as SC1, SC2, SC3, SC4 and SC5 were selected for analysis based on questionnaire response to cosmetic use among Badagry women. The metal analysis done using ICPOES showed that NC3 is PTEs laden; Mn (38.132 + 8.195) ppm, Ni (42.04 + 2.331) ppm, Pb (65.341 + 3.064) and Zn (92.89 + 6.62) ppm. Mn concentration is the highest amongst all the SPCs, ranging from 17.56 + 2.09 ppm to 29.04 + 0.012 ppm. Ni concentration ranged from 0.506 + 0.073 ppm to 9.88 + 1.43 ppm. The presence of these PTEs could be attributed to unintended contamination from raw material or product processing, or deliberately added as part of the required ingredients as in the case of some synthetic cosmetics. The level of PTEs in the synthetic cosmetics were below the permissible limits set by WHO. However, the risk of bioaccumulation exists due to continuous use over time.

A rare case of polysplenia syndrome associated with atrioventricular canal defect and type four ileal atresia in a preterm neonate: A case report and literature review

Antenatal diagnosis of heterotaxy syndrome is only the tip of the iceberg. These neonates can have a myriad of multi-system anomalies, each of which requires anticipation and an individualized management plan. The spectrum of heterotaxy syndrome ranges from incidentally detected innocuous anomalies to major life-threatening congenital malformations such as atrioventricular canal defects and bowel atresia. Neonatal sepsis tends to be more fulminant and catastrophic in these neonates with complex anomalies and poor outcomes that necessitates better-informed antenatal counseling regarding the termination of such pregnancies.

Identification of RESP18 Gene Mutations Linked to Hereditary Non-Syndromic Cleft Lip and Palate in a Southern Chinese Family.

BACKGROUND Non-syndromic cleft lip with cleft palate (NSCLP) is one of the most common congenital birth defects worldwide; it causes lifelong problems and imposes burdens on patients and their families. This study aimed to describe the genomic analysis and identification of de novo regulated endocrine-specific protein 18 (RESP18) rs2385404 and rs2385405 gene polymorphisms associated with NSCLP in a southern Chinese family and to improve prevention, treatment, and prognosis of NSCLP. MATERIAL AND METHODS We performed a genome-wide association study (GWAS) to investigate the association of NSCLP phenotype with gene mutation. We investigated a 5-persons NSCLP family to screen the genetic variation of Han nationality in southern Chinese. Whole-genome sequencing (WGS) was used to detect all candidate genetic variants, and whole-exome sequencing (WES) was implemented to further verify mutations. The Clinical Variation Data Base (ClinVar) was employed for screening gene mutations. Finally, Sanger sequencing was applied to verify gene variations. RESULTS The combined analysis of WGS, WES, and ClinVar showed that a total of 9 variation positions overlapped among the 3 study cohorts. Sanger sequencing verified Glu amino acid variation in 2 mutation sites (rs2385404, rs2385405) from the RESP18 gene, which caused abnormal RESP18 function and was associated with hereditary NSCLP. CONCLUSIONS The combined genomic results showed that 2 mutations (rs2385404 and rs2385405) of the RESP18 gene were related to NSCLP in the family. The RESP18 gene may play an important role in the etiology and pathogenesis of cleft lip and palate.

Analyzing the Expectant Management of Redefined Active Phase of Labor (WHO 2018 Guidelines) in Nulliparous Women: A Randomized Control Trial

BACKGROUND:The World Health Organization (WHO) in their 2018 guidelines favored a noninterventional approach toward the labor process. The active phase of labor will be initiated when the cervix is 5 cm dilated and during obsoleted use of a 1 cm/hour cervical dilation rate as a diagnostic test for abnormal birth outcomes.OBJECTIVES:The aim of the study is to compare an active interventional labor management approach to a noninterventional labor management approach in nulliparous parturient women in terms of need of intervention, mode of birth, and maternofetal outcome.METHODOLOGY:This randomized control study was conducted at a rural tertiary care hospital for a period of 1.5 years. Nulliparous low-risk pregnant women presenting in latent labor were randomly allocated into two groups on the basis of cervical dilation and labor intervention. WHO 2014 guidelines with partograph were followed in group 1, and 2018 WHO guidelines with labor care guide were followed in group 2.RESULT:Both the groups were comparable with age, parity, and Bishop score at the time of admission. The incidence rates of intervention in the active first stage of labor in group 1 and group 2 were 31% and 10% with an odds ratio of 0.192 (95% confidence interval [CI] [0.079, 0.466]), and the rates of lower segment cesarean section in both the groups were 17.6% and 5.8%, respectively. The odds ratio with 95% CI for postpartum hemorrhage and neonatal intensive care unit admission in group 1 compared with group 2 was 0.313 [0.061, 1.610] and 1.057 [0.143, 7.832], respectively.CONCLUSION:This study showed that the shifting of the active first-stage threshold by 1 cm and letting labor progress at its natural pace significantly reduced the need for intervention and affected the fetal and maternal outcome positively.

Zika Virus Infection Knowledge and Communication Preferences Among Women of Reproductive Age in Central Brooklyn, New York: A Thematic Analysis.

The 2016 outbreak of Zika virus (ZIKV) infected millions and resulted in thousands of infants born with malformations. Though the clusters of severe birth defects resulting from this outbreak have subsided, ZIKV continues to be a concern throughout much of Latin America and the Caribbean. Travel and sexual intercourse remain the dominant transmission risk factors for women of reproductive age and their partners. This is particularly true for communities in Brooklyn, New York, that comprise large immigrant and foreign-born populations. Practitioners of public health understand little about how women at risk for ZIKV are most likely to receive information about the virus or who they trust most to provide that information. In the context of five focus group discussions, this study explored the knowledge and communication preferences of 20 women of reproductive age in Central Brooklyn. Results derived from a thematic analysis suggest that while most women are familiar with mosquitos as ZIKV vectors, knowledge of sexual transmission is considerably lower. Many respondents believe that only women who are pregnant or trying to become pregnant are at risk, and public health agencies, such as the U.S. Centers for Disease Control and Prevention, remain the most trusted sources of information. These findings can support more effective communication about the risks of ZIKV infection and other vector-borne diseases to women in New York City and similar urban communities.

Meaning and Clinical Interest of Minor Malformations and Normal Variants in Neonatology.

Congenital malformations can be found in all organ systems of a newborn. Almost two-thirds of congenital malformations have an unknown cause. There are minor (mM) and major (MM) congenital malformations. Searching for minor malformations has its vital place in everyday neonatology practice. Minor malformations are defined as physical variants that have no medical consequences and are mostly located on the face and distal parts of the extremities and are easily noticed. Minor malformations occur in approximately 15% of newborns. Minor congenital malformations are of great importance because they can be an indicator of the existence of major congenital malformations and syndromes. In a one-year retrospective study that analyzed the occurrence of 38 minor malformations through the year 2023 at the University Clinical Hospital of Mostar, there was an incidence of 10.59% of minor malformations. The most frequently recorded minor malformation was deep a sacral dimple at 44.72%, then poorly modeled ears at 15.08%, and moderate rectal diastasis at 14.58%. Three or more minor congenital malformations indicate one or more major congenital malformations. Major congenital malformations are severe structural defects of tissues and organs that endanger life, create serious functional disturbances and hinder the development of the child. In our country, there is currently a recorded incidence of 8.04%. The search for minor malformations in the newborn period is of great importance to children and the whole family, and the search must not be neglected.

Specific Birth Defects Following Antiseizure Medications Used By Pregnant Women With Epilepsy.

Previous research has been limited in the comprehensive study of associations between the use of individual antiseizure medications (ASMs) in pregnancy and specific groups of birth defects, and systematic reviews and meta-analyses on the topic are limited by pooled samples and study designs. This study investigated birth defects related to ASM use in pregnancy in children born to women with epilepsy in Sweden over 20 years. We used data from Swedish national registers to follow a cohort of 17,996 children born to women diagnosed with epilepsy any time before conception in Sweden from 1996 to 2016, following them through 2017. We examined maternal-reported use of the 4 most commonly reported ASMs: lamotrigine (n = 2,148, 11.9%), carbamazepine (n = 1,940, 10.8%), valproic acid (n = 1,043, 5.80%), and levetiracetam (n = 587, 3.26%). We identified birth defects using diagnoses recorded at the time of discharge from the hospital and inpatient and outpatient diagnoses recorded in the first year of life. Models were estimated in a stepped fashion: unadjusted, adjusted for covariates, among a subcohort born to women diagnosed 10 years before conception (n = 14,586), and restricted to monotherapy. Valproic acid use in pregnancy had the strongest and most widespread associations with birth defects in children, with carbamazepine also having links to several birth defects, including respiratory system and genital organ defects. Lamotrigine use in pregnancy was associated with cleft lip/palate and chromosomal abnormalities. Levetiracetam was most often used with other ASMs and preliminarily associated with many birth defects. Our findings support avoidance of valproic acid use in pregnancy whenever possible. Lamotrigine and carbamazepine may be safer alternatives. However, these medications were also associated with certain birth defects, including some not reported previously. We are among the first to examine the possible effects of levetiracetam use in pregnancy, though more research is needed to investigate this further.

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Natural mineral spring water (hora) and surrounding soils in southwestern Ethiopia: farmers’ feeding practices and their perception about its nutritional roles on animal performance

Natural mineral water (termed hora in Afan Oromo) and surrounding soils are the most important source of mineral supplement traditionally used for livestock in many parts of Ethiopia. However, limited information exists on feeding practices and the impact of hora on animal performance. Thus, the present study aimed to assess farmers' feeding practices and perceptions about the role of hora and surrounding soils on animal performance. Data were collected from 385 households in four districts (Bedele, Dabo, Gechi and Boracha) through face-to-face interviews using a semi-structured questionnaire with the help of the KoboCollect application. Data were analyzed using SPSS version 26. The majority (72.3 %) of respondents reported hora as an important source of mineral supplement for livestock. About 78.1 % of respondents in Boracha routinely supplement their animals compared with farmers from other districts. Large ruminants were given first priority in supplementation with hora compared to other livestock. Interviewed farmers trekked their animals a distance of 6.5 ± 0.2 km to access hora twice a year during the dry season. The majority of the farmers (68.1 %) believed that hora supplementation improved animal performance, while 35.1 % noted negative impacts such as abortions, birth defects, delayed puberty, decreased conception rates and paralysis due to excessive consumption. This study underscores the perceived importance of hora as a natural source of mineral supplementation for livestock health and productivity. It emphasizes the need for improved management and conservation practices to ensure sustainable utilisation and mitigate negative impacts associated with excessive consumption. Moreover, to validate local farmers' perceptions regarding the importance of hora mineral water in animal nutrition and health, further research is needed to determine mineral composition of hora and livestock responses under controlled feeding trials.

Association between congenital heart disease and cancer: A meta-analysis of 30 million patients.

10568 Background: Birth defects have been associated with increased cancer risk; however, the association between congenital heart disease (CHD) and cancer risk has not been well established with limited and conflicting literature till date. Children afflicted with CHD possess multiple risk factors for oncogenesis, such as chromosomal and genetic abnormalities, ionising radiation exposure during cardiac imaging and interventions, chronic hypoxia and debility. We sought to evaluate the relationship between CHD and cancer risk and its various subtypes. Methods: We performed a systematic literature search on PubMed, EMBASE, and Scopus for relevant articles from inception until February 4th, 2023. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effects model, and a p-value of <0.05 was considered statistically significant. Results: A total of 5 studies with 30,437,431 patients (CHD group=213,229, and non-CHD group = 30,224,202) were involved in the analysis. Mean age of patients with CHD and non CHD was 48.4 and 51.3 years. The pooled analysis revealed that patients with CHD had a higher risk of skin cancer (OR, 1.16(95%CI: 1.10-1.24), p<0.00001), and thyroid cancer (OR, 1.47(95%CI: 1.20-1.80), p<0.001) compared with non-CHD patients. However, leukemia (OR, 0.74(95%CI: 0.22-2.48), p=0.62), gastrointestinal cancer (OR, 1.50(95%CI: 0.79-2.87), p=0.22), central nervous systems tumor (OR, 1.18(95%CI: 0.74-1.88), p=0.48), respiratory system cancer (OR, 0.94(95%CI: 0.67-1.30), p=0.69), breast cancer (OR, 95%CI: 0.96-1.48), p=0.87, genitourinary system cancer (OR, 1.06(95%CI: 0.73-1.54), p=0.76), and musculoskeletal cancer (OR, 1.40(95%CI: 0.92-2.41), p=0.12) was comparable between CHD and non-CHD groups of patients. Conclusions: Our findings indicate that CHD patients are at higher risk of thyroid and skin cancer compared with non-CHD patients; however, no such association with other cancers was observed. The implications of these results extend to the delineation of subsequent research, and the results underscore the necessity for further exploration into the underlying pathophysiological mechanisms. Potential implications include the establishment of enhanced surveillance and screening protocols to protect this vulnerable patient group. [Table: see text]

Thalassemia Genotypes and HbA2 levels of Children in Wuzhou, Guangxi

To analyze thalassemia genotypes and distribution of children in Wuzhou Guangxi, and evaluate the diagnostic value of HbA2 in children's thalassemia screening, so as to provide scientific evidence for the prevention and control strategies of thalassemia. Four hundred and fifty-eight children suspected with thalassemia in Wuzhou were enrolled from March 2017 to June 2022. The level of HbA2 was detected using Bio-Rad VARIANT II Hb analysis system. The deletion of α-thalassemia was measured with gap-PCR assay, and the point mutation of α- and β-thalassemia was tested with DNA reverse dot blot hybridization assay. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of HbA2 for children's thalassemia. A total of 304 thalassemia carriers were detected in 458 children, accounting for 66.38%. One hundred and seventy-five cases were defined to be α-thalassemia, with the main type of --SEA/αα (54.86%). Thirty-six cases were defined to be intermediate α-thalassemia, with the main type of -α3.7/--SEA (9.72%). In 108 cases with β-thalassemia, βCD41-42/βN was the main type, accounting for 49.07%, followed by βIVS-Ⅱ-654 /βN (14.81%). Seven cases were moderate/severe β-thalassemia (predominantly β-28/β-28 and βCD41-42/βCD17/). Twenty-one genotypes of α- and β-thalassemia were found in the children. There was significant difference of HbA2 level between the children with different types of thalassemia and healthy controls (all P < 0.001). ROC curve analysis showed that the sensitivities of HbA2 for α-thalassemia, β-thalassemia and αβ-thalassemia were 74.3%, 82.4% and 85.7%, with the optimal cut-off values of 2.60%, 3.60% and 3.70%, respectively, the specificities were 64.3%, 96.1% and 96.8%, and the area under the curve were 0.690, 0.887 and 0.916, respectively. The thalassemia genotypes of children in Wuzhou are diverse. It is necessary to further strengthen the prevention and control measure of thalassemia to reduce birth defects and improve birth quality.

Unraveling DREAM-PL: A Case Report on Challenges and Management

An uncommon autosomal recessive condition called DREAM-PL syndrome is typified by dysmorphic facial features, renal agenesis, male ambiguous genitalia, microcephaly, polydactyly, and lissencephaly. The CTU2 gene, which is in charge of tRNA post-transcriptional modification, is mutated in the syndrome. This alteration is necessary for the correct translation of genes, and its disruption can result in several aberrant embryonic processes. The severity of DREAM-PL syndrome can vary from moderate to severe, and the clinical characteristics can be diverse. While some patients may exhibit only some of the distinguishing features, others may have all of them. The most common characteristics include ambiguous genitalia, dysmorphic facies, and microcephaly. Diagnosis of DREAM-PL syndrome is typically based on clinical signs and confirmed through genetic testing, which can identify mutations in the CTU2 gene. Material and methodology: In the case being referred to as a study, a 37-week-old male neonate was delivered by lower segment cesarean section. The baby's birth weight was 2.760 Kg, and a heterozygous CMP mutation of the CTU2 gene was confirmed through whole-exome sequencing (WES). Unfortunately, there is currently no known cure for DREAM-PL syndrome. Result: Treatment focuses on managing the symptoms and providing supportive care. In some cases, surgical correction of birth defects may be beneficial.

AXIN1 mutations in nonsyndromic craniosynostosis.

Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown. The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands. The authors also utilized the GeneMatcher platform and the Gabriella Miller Kids First genome sequencing project to identify additional CS patients with AXIN1 mutations. The authors describe 11 patients with nonsyndromic CS harboring rare, damaging mutations in AXIN1, an inhibitor of Wnt signaling. AXIN1 regulates signaling upstream of key mediators of osteoblast differentiation. Three of the 6 mutations identified in trios occurred de novo in the proband, while 3 were transmitted from unaffected parents. Patients with nonsyndromic CS were highly enriched for mutations in AXIN1 compared to both expectation (p = 0.0008) and exome sequencing data from > 76,000 healthy controls (p = 2.3 × 10-6), surpassing the thresholds for genome-wide significance. These findings describe the first phenotype associated with mutations in AXIN1, with mutations identified in approximately 1% of nonsyndromic CS cases. The results strengthen the existing link between Wnt signaling and maintenance of cranial suture patency and have implications for genetic testing in families with CS.

Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

World health assembly resolution for preventing micronutrient deficiencies and associated neural tube defects-A case study of global partnerships for a successful resolution adoption.

On May 29, 2023, the 76th World Health Assembly (WHA) unanimously adopted the resolution entitled, "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification."The Society for Birth Defects Research and Prevention published their resolution in 2015 supporting mandatory fortification of staple foods with folic acid and recommendations aiming to achieve global total prevention of folate-sensitive spina bifida and anencephaly, setting a goal to achieve by the year 2024.The WHA resolution provides another global push for the cause, with recommendations to member nations for food fortification to be achieved by the year 2030. This short communication documents the steps, from inception up to the passage, of the 76th WHA resolution on food fortification, with a narrative on the nature of strategic advocacy efforts by multiple governmental and nongovernmental organizations. WHA resolutions can take many years to be introduced and passed by the assembly; however, this is a case study of the swiftness of the process enabled by powerful global partnership. The documentation of this process serves as an example for developing and processing future WHA resolutions aiming to improve global maternal and child health.