Prevention Of Defects Research Articles

Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.

Effect of osseodensification on the increase in ridge thickness and the prevention of buccal peri-implant defects: an in vitro randomized split mouth pilot study

BackgroundImplant installation with conventional drilling can create buccal bone defects in areas of limited ridge thickness. Implant installation with osseodensification may aid in preventing buccal bone defects in these situations. This in vitro pilot study evaluated the impact of osseodensification on the increase in alveolar ridge thickness and the prevention of buccal peri-implant defects.MethodsTen fresh pig mandibles with limited bone thickness were selected for use in an experimental randomized split mouth pilot study. Two site-preparation protocols were used: conventional drilling with cutting burs (CTL, n = 10) and osseodensification with Densah® burs (OD, n = 10). After implant bed preparation, 20 implants (4.5 × 10 mm) were placed in the prepared sites and the insertion torque was recorded. Clinical and photographic analysis evaluated ridge thickness and the extent (height, width, and area) of bone defects in the buccal and lingual bone walls following implant placement. Three-dimensional measurements were performed using STL files to analyze the increase in buccal ridge thickness following site preparation and implant placement. The height of the buccal bone defect was considered as the primary outcome of this study. Defect width, area, implant insertion torque, and linear buccal ridge increase after implant site preparation and installation were also assessed. Non-parametric evaluations were carried out with the Mann–Whitney test to verify intergroup differences.ResultsThere was no statistically significant difference between groups in the baseline ridge thickness. OD presented a significantly higher insertion torque, associated with reduced buccal and lingual bone defect width, in comparison to CTL.ConclusionsThe increase in buccal ridge thickness after site preparation and implant placement was significantly higher in OD compared to CTL. Osseodensification increased the ridge thickness through expansion and reduced buccal bone defects after implant installation.

Risk of birth defects by pregestational type 1 or type 2 diabetes: National Birth Defects Prevention Study, 1997-2011.

Previous studies found consistent associations between pregestational diabetes and birth defects. Given the different biological mechanisms for type 1 (PGD1) and type 2 (PGD2) diabetes, we used National Birth Defects Prevention Study (NBDPS) data to estimate associations by diabetes type. The NBDPS was a study of major birth defects that included pregnancies with estimated delivery dates from October 1997 to December 2011. We compared self-reported PGD1 and PGD2 for 29,024 birth defect cases and 10,898 live-born controls. For case groups with ≥5 exposed cases, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the association between specific defects and each diabetes type. We calculated crude ORs (cORs) and 95% CIs with Firth's penalized likelihood for case groups with 3-4 exposed cases. Overall, 252 (0.9%) cases and 24 (0.2%) control mothers reported PGD1, and 357 (1.2%) cases and 34 (0.3%) control mothers reported PGD2. PGD1 was associated with 22/26 defects examined and PGD2 was associated with 29/39 defects examined. Adjusted ORs ranged from 1.6 to 70.4 for PGD1 and from 1.6 to 59.9 for PGD2. We observed the strongest aORs for sacral agenesis (PGD1: 70.4, 32.3-147; PGD2: 59.9, 25.4-135). For both PGD1 and PGD2, we observed elevated aORs in every body system we evaluated, including central nervous system, orofacial, eye, genitourinary, gastrointestinal, musculoskeletal, and cardiac defects. We observed positive associations between both PGD1 and PGD2 and birth defects across multiple body systems. Future studies should focus on the role of glycemic control in birth defect risk to inform prevention efforts.

Pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects.

To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects. This is a population-based, case-control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile. US National Birth Defects Prevention Study, 1997-2011. Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect. Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2-1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse. This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.

In-process quality improvement: Concepts, methodologies, and applications

This article presents the concepts, methodologies, and applications of In-Process Quality Improvement (IPQI) in complex manufacturing systems. As opposed to traditional quality control concepts that emphasize process change detection, acceptance sampling, and offline designed experiments, IPQI focuses on integrating data science and system theory, taking full advantage of in-process sensing data to achieve process monitoring, diagnosis, and control. The implementation of IPQI leads to root cause diagnosis (in addition to change detection), automatic compensation (in addition to off-line adjustment), and defect prevention (in addition to defect inspection). The methodologies of IPQI have been developed and implemented in various manufacturing processes. This paper provides a brief historical review of the IPQI, summarizes the developments and applications of IPQI methodologies, and discusses some challenges and opportunities in the current data-rich manufacturing systems. Future research directions are discussed at the end of the article with a special focus on leveraging emerging machine learning tools to address quality improvements in data-rich advanced manufacturing systems.

Burden of disease and risk factors among children under 5 years in China from 1990 to 2019: a perspective of international comparison

Based on the Global Burden of Disease study 2019, the standardized mortality rate and disability-adjusted life years (DALYs) rate of children under 5 years old were selected as evaluation indicators to compare and analyze the current situation and differences of disease burden of children under 5 years old between China and other regions from 1990 to 2019. The change trend and difference of disease burden of children under 5 years old in China were analyzed by sexes. From 1990 to 2019, the all-cause standardized mortality rate of children under 5 years old in China decreased from 1 153.81/100 000 to 160.39/100 000, and the all-cause standardized DALY rate decreased from 104 426.40/100 000 to 16 479.01/100 000. In 2019, neonatal preterm birth, congenital heart anomalies and lower respiratory infections ranked the top three disease burden of children under 5 years old in China. Except that the disease burden of neonatal preterm birth was lower than that in North America, they were much higher than that in Western Europe and North America in the same period. The burden of unintentional injury diseases, including pulmonary aspiration and foreign body in airway and drowning, was higher than that in Western Europe and North America. The standardized mortality and DALY rate of the top ten diseases and injuries in boys and girls under 5 years old in China showed a downward trend (P<0.05), and most of them were higher in boys than girls (P<0.05). From 1990 to 2019, the disease burden of children under 5 years old in China decreased significantly. However, compared other regions, it is still necessary to strengthen the prevention and control of neonatal premature birth, birth defects and unintentional injuries, and take different sex-specific interventions to improve the overall health of children.

Micronutrient Balance Related to Neural Tube Defects and Prevention

Neural tube defects (NTDs) are a common congenital disorder resulting from failed neural tube formation, the precursor of the brain and spinal cord. The complex etiology of NTDs involve both genetic and environmental factors, thus investigating gene‐environment interactions is critical to understanding how NTDs occur or how NTDs may be prevented. For example, iron deficiency is among the most prevalent micronutrient deficiencies in pregnancy and there is evidence that iron deficiency can increase the risk of NTDs. Folic acid (FA) fortification in grain was implemented in the US in 1998 and now in many countries for the purpose of prevention of neural tube defects (NTDs). In 2017, the US Preventive Services Task Force further recommended the consumption of FA‐containing multivitamin/minerals (MVM) for women of childbearing age. Despite the great benefit of FA on NTD prevention, NTDs remain a serious risk.Our studies focus on mouse models of NTDs and I will discuss two projects. First, the benefits of MVM supplementation are emphasized, but a comparison between MVM supplementation and FA alone on neural tube closure and organ development has not been evaluated, particularly in the context of genetic mutations that lead to NTDs. Using a set of NTD models we have compared MMV to FA supplementation. MVM supplementation shows better improvement than FA alone in the penetrance of spinal and cranial NTDs. We are also using human iPSCs to generate organoids that assume a shape similar to the human spinal neural tube, and display neural tube characteristics, for example apical constriction and interkinetic nuclear migration. Subjecting the organoids to various molecular perturbations, such as Rho‐kinase inhibitor‐induced defects in apical constriction, we have found that both MVM and FA largely prevents this molecular deficit. The goal is to use the mouse NTD model and organoid system to better understand how FA/MVM act to prevent NTDs.Second, we are striving to move beyond the relatively non‐specific recommendations of FA/MVM supplementation to more personalized therapies that take into account the molecular underpinning of the NTD. For example, Iron homeostasis is not only controlled by the concentration of iron in diet, but by proteins responsible for its cellular uptake and metabolism. Sorting nexin 3 (Snx3) is known to regulate recycling of the transferrin receptor (TFRC), a mechanism necessary for cellular uptake of iron, and when Snx3 is knocked out in mice, embryos develop cranial NTDs. We hypothesize that in Snx3 mutants, mistrafficking of TFRC results in disrupted iron homeostasis which contributes to the failure of NT closure. Our current studies are evaluating whether intracellular iron levels are altered in Snx3 mutants and whether maternal diets supplemented with iron can prevent NTDs in the Snx3 background. The hope is that by taking into account the biological process that is disrupted, more tailored therapies can be envisioned to better prevent NTDs.

Small Brains, Small Skulls: Effect of Cortex Specific Overexpression of BAF170 on the Mouse Cranium

Cephalization is an important evolutionary and developmental process. Integration of the brain and skull throughout development and evolution produces brains that fit tightly within skulls. We sought to explore brain/skull integration using a mouse model that produces a small brain. Mammalian BAF170 is an intrinsic factor controlling cortical size, and cortex specific overexpression of BAF170 (conditional overexpression) which results in a mouse model in which cortical growth is inhibited. We looked at BAF170cOE mice and their unaffected littermates (controls) at various ages during cortical development, including embryonically at E15.5, as well as early post‐natal timepoints (P0, P14) as the cortex grows dramatically, and timepoints approaching complete cortical and skull growth (P28, P42). Using histological sections, we determined that the area of the cortex and number of nuclei within the cortex were reduced in BAF170cOE mice as compared to unaffected littermates, particularly at post‐natal time points. Using Euclidian Distance Matrix Analysis, we found no difference in skull form embryonically. Mediolateral dimensions of skulls of BAF170cOE mice were reduced by 3‐10% at P0 as compared to controls. At the later post‐natal time‐points (P14, P28, P42) there were significant differences in skull form between genotypes. Skulls of BAF170cOE mice were reduced by almost 20% along the anteroposterior and mediolateral axes. Our data show that the BAF170cOE mouse has a cortex that is reduced in size due to fewer nuclei resulting from overexpression of BAF170. The skull is not a direct target of the BAF170 gene, yet it responds to the change in brain size and shape by adjusting its size and contours to match the brain. The mechanisms that enable that coordination, a target for our future investigation, hold the key to understanding the evolution of human skull shape and encephalization. Additionally, these investigations may identify possible targets for treatment or prevention of craniofacial birth defects.

A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (Ndiscovery =3978; Nreplication =2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case-parental trios (Ndiscovery_TDT =440; Nreplication_TDT =275) and case-control analyses separately in infants (Ndiscovery_CCI =1635; Nreplication_CCI =990) and mothers (case status defined by infant; Ndiscovery_CCM =1703; Nreplication_CCM =1078). In the TDT analysis, the SLC44A2 single nucleotide polymorphism (SNP) rs2360743 was significantly associated with OHD (pdiscovery =4.08 × 10-9 ; preplication =2.44 × 10-4 ). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (pdiscovery =1.61 × 10-7 ; preplication =0.0016). Two other SNPs were suggestively associated (p < 1 × 10-6 ) with OHD in only the discovery sample. In the case-control analyses, no SNPs were genome-wide significant, and, even with relaxed thresholds ( × discovery < 1 × 10-5 and preplication < 0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (pdiscovery =1.42 × 10-6 ; preplication =0.04). Additional SNPs with pdiscovery < 1 × 10-5 were in loci supporting previous findings but did not replicate. Overall, there was modest evidence of an association between rs2360743 and rs55877192 and OHD and some evidence validating previously published findings.

Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.

To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

USE OF POLYMER PACKAGING FOR VARIOUS FOOD PRODUCTS WITH LONG-TERM STORAGE

In the food industry, for thermal preservation of food products, various types of consumer polymer packaging can be used: rigid, semi-rigid, soft, and others. In order for plastic (polymer) packaging to be used for heat sterilization and guarantee long shelf life of food products, it must contain the necessary heat-resistant barrier layer, which will ensure the resistance of the container to high temperatures. Each polymeric material has certain indicators of heat resistance. In the work, we used such types of consumer packaging for food packaging, such as a combined metal can with a polymer lid, С-PET containers. The purpose of the study is to develop the conditions for canning, sterilization modes of food products in the range for new types of consumer polymer for specific thermal equipment. When using various types of containers for thermal sterilization and prevention of physical defects of canned food, it is necessary to take into account such technological features as the sealing strength or depressurization pressure, the sealing method, the presence or absence of a stiffness relief on the lid, the product packaging temperature and other factors. The standard membrane-compensation method was used to measure the sealing strength or the pressure of depressurization of the container, which occurs during sterilization due to thermal expansion of the product. The development of sterilization modes for canned food was carried out in accordance with the approved regulations, which includes an analytical calculation of the mode that ensures the production of industrially sterile canned food, laboratory testing of the selected mode and its production verification. The mode calculation method is based on the data on the heat resistance of the microorganism strain of the test culture, which should guarantee the industrial sterility of canned food. In the work, studies were carried out, as a result of which data were obtained on an important technological parameter of the packaging strength of sealing, without the values of which it is impossible to carry out high-quality thermal sterilization of the product. Scientifically based parameters, hightemperature sterilization regimes for meat, fish, and vegetable products in modern polymer types of consumer packaging have also been developed, which will allow enterprises to produce canned high-quality food products that are safe to use, with high nutritional value.

Maternal periconceptional alcohol consumption and gastroschisis in the National Birth Defects Prevention Study, 1997-2011.

Gastroschisis is particularly prevalent among offspring of young women and has increased over recent decades. Although previous studies suggest that maternal alcohol consumption is associated with increased gastroschisis risk, none have explored whether maternal age modifies that association. The objective of the study was to evaluate associations between self-reported maternal periconceptional alcohol consumption (1month prior through the third month after conception) and risk of gastroschisis among offspring, by maternal age. We used data from the National Birth Defects Prevention Study (NBDPS), a multi-site population-based case-control study. The analysis included 1450 gastroschisis cases and 11,829 unaffected liveborn controls delivered during 1997-2011 in ten US states. We estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the individual and joint effects of alcohol consumption and young maternal age at delivery (<25years vs ≥25years) on gastroschisis risk. We estimated the relative excess risk due to interaction (RERI) to quantify additive interaction. Periconceptional alcohol consumption was common regardless of maternal age (women <25years: cases 38.8%, controls 29.3%; women ≥25: cases 43.5%, controls 39.5%). Compared with women ≥25years who did not consume alcohol, we observed increased risk of gastroschisis among women <25years, with higher estimates among those who consumed alcohol (women <25years who did not consume alcohol. aOR 5.90, 95% CI 4.89, 7.11; women <25years who did consume alcohol: aOR 8.21, 95% CI 6.69, 10.07). Alcohol consumption among women ≥25years was not associated with gastroschisis (aOR 1.12, 95% CI 0.88, 1.42). This suggests super-additive interaction between alcohol consumption and maternal age (RERI-2.19, 95% CI 1.02, 3.36). Periconceptional alcohol consumption may disproportionately increase risk of gastroschisis among young mothers. Our findings support public health recommendations to abstain from alcohol consumption during pregnancy.

Health economic evaluation of noninvasive prenatal testing and serum screening for down syndrome.

Down syndrome (DS), also known as trisomy 21 (T21), is the most common genetic disorder associated with intellectual disability. There are two methods commonly used for prenatal testing of DS: serum screening (SS) for biomarkers in maternal serum and noninvasive prenatal testing (NIPT) for aneuploidy by cell-free DNA (cfDNA) in maternal plasma. However, cost-effectiveness analyses of these two methods are mostly based on data derived from simulations with various models, with theoretical values calculated. In this study, we statistically analyzed clinical DS screening data and pregnancy outcomes during the follow-up of pregnant women in Zhuhai City, China. The economics of the two mainstream prenatal DS screening methods was evaluated from a public health perspective. A retrospective analysis was performed on the data of 17,363 pregnant women who received SS and NIPT during gestation in Zhuhai from 2018 to 2019, and a cost-effectiveness analysis was performed with four screening strategies. In strategy I, all pregnant women received SS, and those with T21 risk ≥1/270 had invasive prenatal diagnosis (IPD). In strategy II, all pregnant women received SS, those with T21 risk ≥ 1/270 had IPD, and those with 1/270 > T21 risk ≥ 1/1,000 had NIPT; then, women at high risk based on NIPT also had IPD. In strategy III, all pregnant women received SS, and those with T21 risk ≥1,000 had NIPT; then, women at high risk based on NIPT results had IPD. In strategy IV, all pregnant women received NIPT and those at high risk based on NIPT results had IPD. Finally, to assess the cost and effectiveness of DS screening, the total costs were calculated as the sum of screening and diagnosis as well as the direct and indirect economic burden during the average life cycle of DS patients. A total of 22 of the 17,363 (1/789) pregnant women had DS, of which only one woman was over 35 years of age. SS detected 1,024 cases at high risk of T21 (≥1/270), 8 cases were true positive, with a positive predictive value of 0.78% and a detection rate of 36.4%. NIPT detected 27 cases at high risk of T21 (Z ≥ 3) and 22 cases of DS, with a positive predictive value of 81.5% and a detection rate of 100%. Strategy I had the largest total cost of 65.54 million CNY, strategy II and III had similar total costs of 40 million CNY, and strategy IV had the lowest total cost of 14.91 million CNY. By comparison, the screening strategy with NIPT alone had the highest health economic value for DS. SS was greatly affected by nuchal translucency and the accuracy of gestational age measured by ultrasonography. Unstandardized ultrasonography was an important reason for the low DS detection rate with SS. The influence of interfering factors on NIPT was much lower than in SS. NIPT can be used as an alternative to SS and as a primary screening strategy of prenatal DS screening for secondary prevention and control of birth defects. NIPT greatly decreased the frequency of IPD and the miscarriages associated with IPD, saved the limited medical and health resources, and greatly increased DS detection rate. Therefore, NIPT has great social and economic benefits.

Skeletal class III malocclusion and bilateral sagittal osteotomy: a concise systematic review

Introduction: In the context of skeletal class III malocclusion, orthognathic surgery is a standardized procedure used to improve the patient's facial appearance and to correct maxillary and mandibular deformities resulting from malocclusions, disease, or trauma. Thus, bilateral sagittal osteotomy of the mandibular ramus is a technique widely used in OS for the correction of mandibular deformities. Objective: the present study evaluated, through a concise systematic review, the main considerations of mandibular advancements through mandibular bilateral sagittal osteotomies in patients with skeletal class III malocclusion. Methods: Clinical studies with qualitative and/or quantitative analysis were included, following the rules of the systematic review-PRISMA. Results: A total of 115 articles were found involving “skeletal class III malocclusion". A total of 45 articles were evaluated in full, and 22 were included and discussed in this study. Bilateral sagittal osteotomy (BSO) is the most used technique in mandibular OS, allowing mandibular movements in the sagittal, vertical, and transverse directions. Several studies show good results and few complications. The size of this space is proportional to the mandibular advancement and/or rotation movements required by the patient's maxillomandibular discrepancy. The prevention of inferior mandibular edge defects is an important issue when planning an BSO traditional non-grafted BSO technique produces a large proportion of defects in the lower edge of the mandible. In cases where the advancement is greater than 10 mm and/or the patient is over 30 years old, the risk of the mandibular defect increases significantly. Also, using a bone graft in the intersegmental gap of a sagittal branch osteotomy is considered an effective clinical method to ensure the desirable intersegmental position as it helps to easily maintain the space. Conclusion: The results showed that bilateral sagittal osteotomy is the most used technique in mandibular orthognathic surgery, allowing mandibular movements in the sagittal, vertical, and transverse directions, with good results and few complications. Furthermore, a bone graft can accelerate bone formation in orthognathic surgery.

V-shaped defects—prevention and treatment (a review)

V-shaped defects—prevention and treatment (a review)

Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias.

The original analysis used NBDPS data from women with haloacetic acid exposure information in eight states who delivered an infant with second- or third-degree hypospadias (cases) or a male infant without a birth defect (controls) between 2000 and 2005. In this bias analysis, we used a uniform distribution to randomly select 11%-14% of employed women that were assumed to change municipal water systems between home and work and imputed new contaminant exposures for tap water beverages consumed at work among the selected women using resampled values from the control population. Multivariable logistic regression was used to estimate the association between hypospadias and haloacetic acid ingestion with the same covariates and exposure cut-points as the original study. We repeated this process across 10,000 iterations and then completed a sensitivity analysis of an additional 10,000 iterations where we expanded the uniform distribution (i.e., 0%, 28%). In both simulations, the average results of the 10,000 iterations were nearly identical to those of the initial study. Our results suggest that household estimates may be sufficient proxies for worksite exposures to haloacetic acids in tap water.

Prevention of Fetal Neural Tube Defect with Folic Acid Supplementation

Prevention of Fetal Neural Tube Defect with Folic Acid Supplementation

A multidisciplinary approach in the management of patients with acne

The article summarizes the data of the scientific publications about the management of patients with androgen-dependent dermatopathies, namely acne, taking into account the current view on the pathogenesis, clinical manifestations and results of the examinations of this group of women. Androgen-dependent dermatopathies are not only a medical problem but also a socio-economic one, as they lead to impaired socialization and reduced quality of life. Acne is one of the most common dermatoses. Acne is a chronic multifactorial disease of the pilosebation complex, which is clinically manifested by polymorphic rash in the form of open and closed comedones, papules, pustules, nodules. The pathogenesis of the disease is based on four main links: changes in the quantitative and qualitative composition of sebum due to hypersecretion of androgens and/or increased sensitivity of receptors to their action, impaired follicular keratinization, inflammation and changes in skin microbiome. Besides the main pathogenetic aspects, trigger factors are taken into account, such as nutrition, stress, smoking, mechanical agents. The current treatment of acne according to dermatological protocols is presented in the article, which is based on a combination of topical therapy with local retinoids and antibiotics, benzoyl peroxide, azelaic acid, in case of severe or ineffective local therapy systemic antibiotics and systemic retinoids are used. However, despite the presence of many treatment regimens for dermatosis, it is often not possible to achieve a lasting effect of treatment, and the adherence of patients to follow the doctor’s recommendations decreases. Given that the leading role in the pathogenesis of acne is due to hyperandrogenic effects on the skin, as well as the fact that the disease reduces the quality of life and self-esteem in patients, it is necessary to involve a wider range of specialists, such as dermatologists, gynecologists, endocrinologists and psychotherapists for successful treatment and prevention of persistent aesthetic skin defects.

Association of MTHFR 677C > T gene polymorphism with neonatal defects: a meta-analysis of 81444 subjects

This meta-analysis was performed to clarify controversial associations of the MTHFR 677 C > T gene polymorphism in maternal and foetal tissue with neonatal defects. It was reported the association of MTHFR 677 C > T gene polymorphism with frequencies of neonatal defects including congenital heart disease (CHD), neural tube defects (NTD), non-syndromic cleft lip and palate (NSCL/P), and Down syndrome (DS). Depending on the neonatal defect subtypes, MTHFR 677 C > T gene polymorphism was associated with NTD, CHD (except for codominant mode of inheritance (TC/CC) and dominant mode of inheritance (TT + TC/CC); p = .167 and p = .054, respectively), DS, and NSCL/P (codominant mode of inheritance (TC/CC), p = .032) in the maternal group. However, in the neonatal group, the MTHFR 677 C > T gene polymorphism was only associated with the frequency of NTD and CHD. Maternal and neonatal MTHFR 677 C > T gene polymorphisms appear to be associated with neonatal defects but differ by defect types. IMPACT STATEMENT What is already known on this subject? Neonatal defects are a signifcant problem and are related to genes involved in the metabolism of homocysteine and folate. What do the results of this study add? The MTHFR 677C > T polymorphism in maternal and neonatal subjects was significantly associated with neonatal defects. When the neonatal subjects were stratified based on disease, the maternal MTHFR 677C > T polymorphism was found to be significantly correlated with all four neonatal defects. In contrast, the polymorphism in newborns was significantly associated with neural tube defects. What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the literature because it collectively analysed neural tube defects, congenital heart disease, cleft lip and palate, and Down syndrome in relation to the 677C > T polymorphism of MTHFR. Thus, we anticipate that this study will serve as a valuable resource for future investigations of neonatal defect prevention and maternal inheritance in newborn diseases.

Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights.

About 20%-30% of children with birth defects have multiple major birth defects in more than one organ system, often referred to as multiple congenital anomalies (MCAs). Evaluating the patterns of MCAs can provide clues to the underlying causes, pathogenic mechanisms, and developmental pathways. We sought to explore selected patterns of MCAs within the National Birth Defects Prevention Study (NBDPS), a population-based, case-control study that excluded cases attributed to known chromosomal or single-gene abnormalities. We defined MCAs as having two or more NBDPS-eligible birth defects and calculated the adjusted observed-to-expected ratio for all observed MCA patterns using co-occurring defect analysis. Of the 50,186 case infants eligible for NBDPS, 2,734 (3.7%) had at least two eligible birth defects. We observed 209 distinct 2-way combinations of birth defects, 297 distinct 3-way combinations, 179 distinct 4-way combinations, and 69 distinct 5-way combinations. Sacral agenesis had the largest proportion of cases with MCAs (70%), whereas gastroschisis had the lowest (3%). Among the cases with MCAs, 63% had a heart defect, 23% had an oral cleft, and 21% had anorectal atresia/stenosis. Of the patterns with adjusted observed-to-expected ratios in the top 20%, most were consistent with the known associations or syndromes, including VATER/VACTERL association and CHARGE syndrome. Most but not all patterns that had the highest adjusted observed-to-expected ratios were instances of known syndromes or associations. These findings highlight the importance of considering birth defect combinations that suggest syndromic patterns in the absence of a formal syndromic diagnosis. New approaches for screening for sequences and associations, and VATER/VACTERL in particular, in surveillance systems with limited resources for manual review may be valuable for improving surveillance system quality. The observed MCA patterns within NBDPS may help focus future genetic studies by generating case groups of higher yield.