Determinants of externally visible birth defects among perinatal deaths at Adama Comprehensive Specialized Hospital: a case-control study.

BACKGROUND: Birth defects (BDs) are the major causes of infant morbidity and mortality in both developed and developing countries. Regardless of their clinical importance, few studies on predisposing factors have been conducted in Ethiopia. However, due to a lack of advanced diagnostic materials, we only considered the externally visible BDs. OBJECTIVE: To assess the determinants of externally visible birth defects among perinatal deaths at Adama Comprehensive Specialized Hospital. METHODS: A retrospective unmatched case-control study design was conducted from November 01 to 30, 2021. The sample size was determined by Epi Info version 7 software considering sample size calculation for an unmatched case-control study. A total of 315 participants (63 cases, and 252 controls) were selected by simple random sampling. Data were collected by an open data kit (ODK) and transported to a statical package for social sciences (SPSS) version 26 software for analysis. The bivariate followed by multivariable logistic regression analyses were done to determine the factors associated with the BD. RESULTS: This study showed that drinking alcohol during pregnancy (AOR = 6.575; 95% CI: 3.102,13.937), lack of antenatal care (ANC) follow-up during pregnancy (AOR = 2.794; 95% CI: 1.333, 5.859), having a history of stillbirth in a previous pregnancy (AOR = 3.967; 95% CI: 1.772, 8.881), exposure to pesticides during pregnancy (AOR = 4.840; 95% CI: 1.375, 17.034), having a history of BDs in a previous pregnancy (AOR = 4.853; 95% CI: 1.492, 15.788), and lack of folic acid supplementation during early pregnancy (AOR = 4.324; 95% CI: 2.062, 9.067) were significant determinants of externally visible BDs among perinatal deaths. CONCLUSION: In this study, alcohol use, exposure to pesticides, and lack of folic acid supplementation during pregnancy were identified as the major determinants of externally visible BDs among perinatal deaths. Thus, health education regarding the associated factors of BDs and their preventive strategies should be given to pregnant mothers.

Multidisciplinary spina bifida clinic: the Chicago experience.

Open spina bifida (open SB) is the most complex congenital abnormality of the central nervous system compatible with long-term survival. Multidisciplinary care is required to address the effect of this disease on the neurological, musculoskeletal, genitourinary, and gastrointestinal systems, as well as the complex psychosocial impact on the developing child. Individuals with SB benefit from the involvement of neurosurgeons, orthopedic surgeons, urologists, physical medicine and rehabilitation specialists, pediatricians, psychologists, physical/occupational/speech therapists, social workers, nurse coordinators, and other personnel. Multidisciplinary clinics are the gold standard for coordinated, optimal medical and surgical care. Ann and Robert H. Lurie Children's Hospital, formerly known as Children's Memorial Hospital, was one of the first hospitals in the USA to manage patients with this complex disease in a multidisciplinary manner. We describe the longitudinal experience of the multidisciplinary Spina Bifida Center at our institution and highlight the advances that have arisen from this care model over time. This clinic serves as an exemplar of organized, effective, and patient-centered approach to the comprehensive care of people living with open SB.

Effect of maternal dietary niacin intake on congenital anomalies: a systematic review and meta-analysis.

PURPOSE: The significance of niacin in embryonic development has clinical implications in the counseling of pregnant women and may be used to inform nutrition recommendations. This study, therefore, aims to review the associations between maternal periconceptional niacin intake and congenital anomalies. METHODS: A systematic search of Ovid MEDLINE, ClinicalTrials.gov, AMED, CENTRAL, Emcare, EMBASE, Maternity & Infant Care and Google Scholar was conducted between inception and 30 September 2020. Medical subject heading terms included "nicotinic acids" and related metabolites, "congenital anomalies" and specific types of congenital anomalies. Included studies reported the association between maternal niacin intake and congenital anomalies in their offspring and reported the measure of association. Studies involved solely the women with co-morbidities, animal, in vitro and qualitative studies were excluded. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale (NOS). A random effects-restricted maximum likelihood model was used to obtain summary estimates, and multivariable meta-regression model was used to adjust study-level covariates. RESULTS: Of 21,908 retrieved citations, 14 case-control studies including 35,743 women met the inclusion criteria. Ten studies were conducted in the U.S, three in Netherlands and one in South Africa. The meta-analysis showed that expectant mothers with an insufficient niacin intake were significantly more likely to have babies with congenital abnormalities (odds ratio 1.13, 95% confidence interval 1.02-1.24) compared to mothers with adequate niacin intake. A similar association between niacin deficiency and congenital anomalies was observed (OR 1.15, 95% CI 1.03-1.26) when sensitivity analysis was conducted by quality of the included studies. Meta-regression showed neither statistically significant impact of study size (p = 0.859) nor time of niacin assessment (p = 0.127). The overall quality of evidence used is high-thirteen studies achieved a rating of six or seven stars out of a possible nine based on the NOS. CONCLUSION: Inadequate maternal niacin intake is associated with an increased risk of congenital anomalies in the offspring. These findings may have implications in dietary counseling and use of niacin supplementation during pregnancy.

Maternal periconceptional folic acid supplements use and fetus risk for limb defects.

BACKGROUND: Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. OBJECTIVE: To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. METHODS: Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. RESULTS: A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. CONCLUSIONS: Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

Gene Environment Interactions in the Etiology of Neural Tube Defects.

Human structural congenital malformations are the leading cause of infant mortality in the United States. Estimates from the United States Center for Disease Control and Prevention (CDC) determine that close to 3% of all United States newborns present with birth defects; the worldwide estimate approaches 6% of infants presenting with congenital anomalies. The scientific community has recognized for decades that the majority of birth defects have undetermined etiologies, although we propose that environmental agents interacting with inherited susceptibility genes are the major contributing factors. Neural tube defects (NTDs) are among the most prevalent human birth defects and as such, these malformations will be the primary focus of this review. NTDs result from failures in embryonic central nervous system development and are classified by their anatomical locations. Defects in the posterior portion of the neural tube are referred to as meningomyeloceles (spina bifida), while the more anterior defects are differentiated as anencephaly, encephalocele, or iniencephaly. Craniorachischisis involves a failure of the neural folds to elevate and thus disrupt the entire length of the neural tube. Worldwide NTDs have a prevalence of approximately 18.6 per 10,000 live births. It is widely believed that genetic factors are responsible for some 70% of NTDs, while the intrauterine environment tips the balance toward neurulation failure in at risk individuals. Despite aggressive educational campaigns to inform the public about folic acid supplementation and the benefits of providing mandatory folic acid food fortification in the United States, NTDs still affect up to 2,300 United States births annually and some 166,000 spina bifida patients currently live in the United States, more than half of whom are now adults. Within the context of this review, we will consider the role of maternal nutritional status (deficiency states involving B vitamins and one carbon analytes) and the potential modifiers of NTD risk beyond folic acid. There are several well-established human teratogens that contribute to the population burden of NTDs, including: industrial waste and pollutants [e.g., arsenic, pesticides, and polycyclic aromatic hydrocarbons (PAHs)], pharmaceuticals (e.g., anti-epileptic medications), and maternal hyperthermia during the first trimester. Animal models for these teratogens are described with attention focused on valproic acid (VPA; Depakote). Genetic interrogation of model systems involving VPA will be used as a model approach to discerning susceptibility factors that define the gene-environment interactions contributing to the etiology of NTDs.

First data from the new, unified database of the Hungarian case-control surveillance of congenital abnormalities.

The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) is one of the largest case-control data sets of CA-surveillance in the world. We unified all data collected in the HCCSCA between 1980 and 2009 into a new, validated single database that is now open for examination. The details of this unified database are given in this paper. The total number of cases and control newborns is 32,345 and 57,231, respectively. The overall prevalence of CAs recorded in the HCCSCA was 10.7/1000 live-births. Data available for each pregnancy are: CA(s), gender, birth year/month/date, birth weight, gestational age, area of mother's living, maternal age, paternal age, birth order, mother's and father's qualification, employment status and type of employment, mother's marital status, outcome of previous pregnancies, maternal diseases during pregnancy (according to pregnancy months), drug intake during pregnancy (according to pregnancy months), folic acid and/or pregnancy vitamin supplement intake (according to pregnancy months), mother's smoking habits and alcohol consumption patterns. The most frequent anomalies detected were ventricular septal defect (2864), atrial septal defect (1895), polydactyly (1499), hypospadias (1083), and unilateral cleft lip ± palate (961). According to ICD-10, 701 diseases have been found to affect case mothers during pregnancy. Eight hundred and sixteen drugs were identified that had been taken by mothers during pregnancy. The authors are absolutely open for any scientific cooperation based on this database.

[Formula: see text] Addressing the neurodevelopmental needs of children and adolescents with congenital heart disease: A review of the existing intervention literature.

Congenital heart disease (CHD) is among the most prevalent birth defects in the United States. Given that children with CHD are at risk for differences with development, learning, and psychosocial functioning, effective intervention becomes a central tenant of recommendations following neuropsychological consultation and evaluation. The primary focus of this review is to summarize available interventions for children and adolescents with CHD. The existing CHD literature has concentrated on early developmental services, psychopharmacological treatment, and need for academic supports. The literature is limited with regard to intervention studies that target cognitive deficits and psychosocial difficulties. To address this discrepancy, efficacious interventions that have been used to mitigate these concerns within other medical groups are also discussed in an effort to provide options for alternative recommendations and services. The current paper is intended to facilitate comprehensive care for cardiac patients by providing clinicians with a review of the available intervention literature, as well as potential interventions that may serve as supplemental strategies in the interim.

The Effects of Folic Acid in Fetuses and Newborns / 中国药学杂志

Folic acid is one of the essential nutrients for human health. Folic acid supplementation during pregnancy is important to prevent fetal neural tube defects. This article briefly reviews its current clinical use from the basic characteristics and mechanism of folic acid, and also reviews the latest literature of fetal, neonatal and children. The terms such as "fetus", "newborn", "folate", "infant, newborn" [Mesh], and "folic acid" [Mesh] are used to search for relevant research from China National Knowledge Infrastructure, Wanfang, PubMed and The Cochrane Library. Summary of domestic and foreign studies: folic acid may be associated with fetal neural tube defects, the relationship between folic acid and fetal birth defects, fetal growth restriction and perinatal mortality remains to be further studied; in addition, folic acid is associated with neonatal asphyxia and brain injury; may be associated with childhood asthma, mental retardation and immunity. It can be seen that although the correlation between folic acid and various diseases still needs more scientific research, it is recommended that periconception and pregnant should reasonably supplement folic acid.

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation.

Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.

Determinants and seasonality of major structural birth defects among newborns delivered at primary and referral hospital of East and West Gojjam zones, Northwest Ethiopia 2017-2018: case-control study.

OBJECTIVE: Although infant mortality because of birth defect has increased in both developed and developing countries, had not got attention like other health issues at national, regional, or local levels. Documenting the risk factors that influence the occurrence of birth defects and its seasonality will help to inform the community and to develop preventive strategies for the country. RESULTS: Factors associated with higher likelihood of a major structural birth defects included maternal age; neonates born from women living in urban; and in Dega; history of fever during pregnancy; intake of herbal medicine; and drinking alcohol. Counselling for pregnancy preparation and folic acid supplementation was found protective for the likelihood of birth defect.

Sociodemographic, health behavioral, and clinical risk factors for anotia/microtia in a population-based case-control study.

OBJECTIVE: Anotia and microtia are congenital malformations of the external ear with few known risk factors. We conducted a comprehensive assessment of a wide range of potential risk factors using data from the National Birth Defects Prevention Study (NBDPS), a population-based case-control study of non-chromosomal structural birth defects in the United States. METHODS: Mothers of 699 infants with anotia or microtia (cases) and 11,797 non-malformed infants (controls) delivered between 1997 and 2011 were interviewed to obtain information about sociodemographic, health behavioral, and clinical characteristics. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated with logistic regression. RESULTS: Infants with anotia/microtia were more likely to be male (aOR, 1.29; 95% CI, 1.10-1.50) and from a multifetal pregnancy (aOR, 1.68; 95% CI, 1.16-2.42). Cases were also more likely to have parents of Hispanic ethnicity (maternal aOR, 3.19; 95% CI, 2.61-3.91; paternal aOR, 2.11; 95% CI, 1.54-2.88), and parents born outside the United States (maternal aOR, 1.29; 95% CI, 1.06-1.57; paternal aOR, 1.92; 95% CI, 1.53-2.41). Maternal health conditions associated with increased odds of anotia/microtia included obesity (aOR, 1.31; 95% CI, 1.06-1.61) and pre-pregnancy diabetes (type I aOR, 9.89; 95% CI, 5.46-17.92; type II aOR, 4.70; 95% CI, 2.56-8.63). Reduced odds were observed for black mothers (aOR, 0.57; 95% CI, 0.38-0.85) and mothers reporting daily intake of folic acid-containing supplements (aOR, 0.59; 95% CI, 0.46-0.76). CONCLUSION: We identified several risk factors for anotia/microtia, some which have been previously reported (e.g., diabetes) and others which we investigate for perhaps the first time (e.g., binge drinking) that warrant further investigation. Our findings point to some potentially modifiable risk factors and provide further leads toward understanding the etiology of anotia/microtia.

Epigenomic profiling of newborns with isolated orofacial clefts reveals widespread DNA methylation changes and implicates metastable epiallele regions in disease risk.

Cleft lip with or without cleft palate (CL/P) is a common human birth defect whose etiologies remain largely unknown. Several studies have demonstrated that periconceptional supplementation of folic acid can reduce risk of CL/P in offspring. In this study, we tested the hypothesis that the preventive effect of folic acid is manifested through epigenetic modifications by determining whether DNA methylation changes are associated with CL/P. To more readily observe the potential effects of maternal folate on the offspring epigenome, we focused on births prior to mandatory dietary folate fortification in the United States (i.e. birth year 1997 or earlier). Genomic DNA methylation levels were assessed from archived newborn bloodspots in a 182-member case-control study using the Illumina® Human Beadchip 450K array. CL/P cases displayed striking epigenome-wide hypomethylation relative to controls: 63% of CpGs interrogated had lower methylation levels in case newborns, a trend which held up in racially stratified sub-groups. 28 CpG sites reached epigenome-wide significance and all were case-hypomethylated. The most significant CL/P-associated differentially methylated region encompassed the VTRNA2-1 gene, which was also hypomethylated in cases (FWER p = 0.014). This region has been previously characterized as a nutritionally-responsive, metastable epiallele and CL/P-associated methylation changes, in general, were greater at or near putative metastable epiallelic regions. Gene Set Enrichment Analysis of CL/P-associated DMRs showed an over-representation of genes involved in palate development such as WNT9B, MIR140 and LHX8. CL/P-associated DNA methylation changes may partly explain the mechanism by which orofacial clefts are responsive to maternal folate levels.

Folic acid and birth defects / 国际儿科学杂志

Folic acid deficiency is associated with birth defects such as fetal spina bifida and congenital heart disease.Folic acid supplementation during pregnancy can prevent various birth defects, but excessive folic acid may increase the risk of certain diseases.This article reviews the causes of folate deficiency, single nucleotide polymorphisms of folate metabolism-related enzyme genes, the mechanism of birth defects caused by folic acid deficiency, and the correct supplementation of folic acid to prevent birth defects.

Folic acid and birth defects / 国际儿科学杂志

Folic acid deficiency is associated with birth defects such as fetal spina bifida and congenital heart disease. Folic acid supplementation during pregnancy can prevent various birth defects, but excessive fo-lic acid may increase the risk of certain diseases. This article reviews the causes of folate deficiency, single nu-cleotide polymorphisms of folate metabolism-related enzyme genes, the mechanism of birth defects caused by folic acid deficiency, and the correct supplementation of folic acid to prevent birth defects.

Could a trace mineral deficiency be associated with congenital chondrodystrophy of unknown origin (CCUO) in beef cattle in Australia?

Congenital chondrodystrophy of unknown origin (CCUO) has been reported in beef cattle worldwide. A trace mineral deficiency in pregnant dams has been suggested as causing the deformities seen in CCUO calves. An extended outbreak of CCUO in Australia between 2002 and 2009 provided an opportunity to examine the pattern of trace mineral status in gestating cows and the effect of parenteral trace mineral supplementation on a herd at risk of CCUO calves. A property with a strong history of CCUO was identified from a previous case-control study. A randomly selected sample of multiparous (8 to 10 years old) Angus and Angus cross cows (n = 20) was assigned to control (no injection) or supplement group given three injections at the recommended dose rate of chelated mineral supplement (Mn, Zn, Cu and Se) at 6-week intervals in mid- to late gestation. Liver biopsies were performed to measure liver Mn, Zn, Cu and Fe at each injection time and 1 month post-calving. Pasture samples were also collected for analysis. Supplemented cows had higher liver Cu levels compared to control cows (p < 0.001), but there was no difference between supplement and control cows for liver Zn, Fe or Mn. Liver Cu (p < 0.001), Fe (p < 0.001) and Zn (p < 0.001) fell during gestation and liver Mn increased after calving (p < 0.001). Three cows from the control group and two from the supplement group had liver zinc levels below the normal values at the end of the trial. Two cows from the control group and one from the treatment group gave birth to cows with signs of CCUO including superior brachygnathia. All cows except one from the control group had rough dry coats with excessive dander. The role of trace mineral status in the birth of CCUO calves, especially the role of zinc deficiency, requires further investigation.

Parental risk factors of anorectal malformations: Analysis with a regional population-based control group.

BACKGROUND: Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational diabetes, chronic cardiovascular and respiratory diseases, periconceptional folic acid and multivitamin intake. METHODS: Data from the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared with data from the Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg, Germany. Controls were matched to cases by gender and birth year of the child. Crude and adjusted odds ratios (95% confidence intervals) were calculated for potential risk factors using multivariable logistic regression. RESULTS: In total, 158 ARM patients and 474 healthy infants born between 1993 and 2008 in Germany were included. Maternal age at birth of ARM cases and birth plurality were significantly higher and gestational age and weight significantly lower compared with controls (p < 0.0001). We observed significantly increased risks for ARMs associated with maternal smoking before conception and the first trimester of pregnancy (odds ratio = 2.23, 95% confidence interval 1.04-4.79, p = 0.039) and maternal chronic respiratory diseases (odds ratio = 29.25, 95% confidence interval 8.22-104.14, p < 0.0001). No statistically significant increased risk or protective effect was found for the other investigated factors. CONCLUSION: This study suggests an association between the occurrence of ARMs in the offspring and periconceptional maternal smoking as well as maternal chronic respiratory diseases. In addition, there might be a sign of an association for maternal diabetes, although not statistically significant. It can be assumed that the power is far too low to provide reliable estimates.

Birth defects in the newborn population: race and ethnicity.

BACKGROUND: Racial variability in certain prenatal risk factors, such as prenatal vitamin supplementation and termination of pregnancy for fetal anomaly, has altered the racial prevalence of birth defects. Analysis of a single large representative population is required to analyze current racial differences in the prevalence of birth defects in the United States. METHODS: This is a population-based cross-sectional study to analyze racial differences in the prevalence of birth defects. We reviewed all live births in the 2008 Nationwide Inpatient Sample (NIS) database and determined birth prevalence of 55 selected birth defects in Caucasians. We then calculated the relative risk of these birth defects in African-Americans, Hispanics, and Asians relative to Caucasians. RESULT: Overall birth defect prevalence was 29.2 per 1000 in a cohort of 1,048,252 live births, of which 51% were Caucasians. Compared with Caucasians, the risk of overall birth defects was lower in African-Americans (relative risk = 0.9, confidence interval 0.8-0.9) and Hispanics (relative risk = 0.9, confidence interval 0.8-0.9). The risk of overall birth defects was similar in Caucasians and Asians. Relative to the Caucasians, African-Americans had a lower risk of cardiac, genitourinary, and craniofacial malformations but a higher risk of musculoskeletal malformations. Hispanics had a lower risk of genitourinary and gastrointestinal malformation. Asians had a higher risk of craniofacial and musculoskeletal malformations. CONCLUSION: This is a comprehensive description of racial differences in the risk of birth defects in the United States. Observed racial differences in the risk of birth defects may be related to genetic susceptibilities, to cultural or social differences that could modify exposures, or to the many potential combinations between susceptibilities and exposures.