Prevention Of Defects Research Articles

Experimental study and numerical modeling of heat and mass transfer in rubberwood during kiln drying

Rubberwood (Hevea brasiliensis) is a major raw material used in furniture factories in southern Thailand. Proper kiln drying of the lumber plays a significant role on the efficient utilization of the final product. Overall quality-reducing defects in such a materials are inevitable, unless a correct and proper drying process is used. Therefore, the objective of the present study was to develop a three-dimensional numerical model of heat and moisture transfer during the drying process and to conduct physical experiments in order to compare the results between the two approaches. For this purpose, an innovative kiln dryer was designed in the laboratory which will also contribute to the prevention of defects in the wood. The results show that the samples dried at a temperature of 120 °C experienced faster decreases in their moisture content compared to those dried at temperatures of 100 °C and 80 °C. The drying temperature and moisture content of the samples were successfully predicted by the simulation model created in this investigation and the two approaches demonstrated good agreement for temperature and moisture with root mean square errors of 0.50 and 0.19, standard errors of 0.38 and 0.16, and mean absolute errors of 0.94 and 2.18, respectively. These results will help rubberwood drying facilities prevent wood deformation while reducing the drying time required.

Medical expert assessment of defects in the provision of medical care for emergency surgical abdominal pathology

The article presents a literature review on the assessment of defects and medical care, as well as the prevention of defects and conflict situations that arise during the treatment of patients with emergency surgical abdominal pathology. Unfortunately, mortality among urgent surgical patients and diseases of the abdominal organs is in the leading positions among all causes of death, despite the improvement of diagnostic methods, the emergence of new medical equipment and drugs, as well as the developed standards of approaches to the treatment of this category of patients. The paper presents statistics on the incidence of abdominal pathology and the mortality rate among the population of our country. We have studied clinical guidelines and standards for the provision of medical care to patients with acute abdominal pathology and analyzed the work on the assessment of medical care, medical errors, conflicts between the patient and the surgeon, as well as the works describing the individual characteristics of various diseases over the past decades. The article discusses in detail the causes of professional errors and defects in medical care, which include: information and deontological defects, defects in the organization of the treatment process, defects in diagnosis and defects in the treatment itself. Studied in detail the stages of the examination to assess the medical care provided. Examples of the course of the main surgical diseases of the abdominal organs in various groups of patients are described. The possible measures to prevent professional errors in doctors and patients have been studied in detail.

Sliver defect formation in single crystal Ni-based superalloy castings

Sliver is a typical grain defect in single crystal Ni-based superalloy castings produced by Bridgman directional solidification. However, its formation mechanism has yet to be fully understood. In this study, the formation of sliver defects was investigated with respect to the defect morphological features, the microstructure of defect initiation points, and the solidification conditions. Experiment results showed that sliver defects were originated from fragmentation of dendrite trunks and could developed to various morphologies. The misorientation range of sliver grains was between 3.2° to 12°. Microstructural analysis results indicated that the dendrites fragmented abruptly without significant plastic deformation. And the dendrite fragmentation could be facilitated by oxide inclusions and solidification pores. It was also found that the sliver defects were prone to occur at the interface where primary dendrite converge to the mold inner wall. Based on the low misorientation level of sliver grains in the experimental observation, the critical solid volume fraction range for fragmentation was suggested to be 0.6–0.8. The dendrite fragmentation was attributed to the non-uniform stress distribution in dendrite during solidification. In addition, the effect of airfoil geometry of a typical blade casting and defect prevention methodology were discussed.

Prevalence of birth defects among infants with neonatal abstinence syndrome in Illinois, 2015-2016.

Opioid use has reached historically high levels across the United States and infants exposed during pregnancy are at risk of developing a drug withdrawal syndrome called neonatal abstinence syndrome (NAS). The prevalence of birth defects among Illinois infants exhibiting NAS has not been estimated. We linked birth certificate data for Illinois-resident infants born in Illinois in 2015 or 2016 to previously collected NAS and Adverse Pregnancy Outcome Reporting System birth defect data. We examined the prevalence of selected specific birth defects and of newborn infants with one or more of the National Birth Defects Prevention Network's (NBDPN) birth defects, comparing infants with and without NAS. We used logistic regression to estimate the odds ratio for having one or more NBDPN birth defects in infants with and without NAS, after adjusting for other risk factors. Of 302,043 Illinois-resident births, 899 (3.0/1,000 live births) had NAS, and 4,250 (140.7/10,000 live births) had one or more NBDPN birth defect. Infants with an NBDPN birth defect were 1.9 (95% CI [1.3, 2.9]) times more likely to have developed NAS at delivery, and specifically, there was a higher prevalence of ventricular septal defect, club foot, and oral cleft, among infants with NAS when compared to those born without. Elevated prevalence rates and odds ratios add to the growing evidence of an association between NAS and birth defects. Other studies have found similar associations between opioid exposure and the birth defects identified in this analysis.

MEJORA DEL MECANIZADO MEDIANTE EL REGISTRO Y ANÁLISIS DE VARIABLES DE PROCESO EN LA NUBE

Manufacturing sector faces the challenge of harnessing digital industry. Responding to this challenge, the present work shows different machining processes, as turning, grinding and milling, that have been optimized following Industry 4.0 paradigm. In all cases, this optimization objective has been reached using data platforms where process variables coming from numerical control or sensors are stored, and where optimization algorithms are ran. These improvements are diverse and specific for each process: quality control, cutting tool life improvement, or defect prevention.

Periconceptional folic acid intake in Northwest Russia: a birth registry study

Abstract Introduction Periconceptional use of folic acid supplementation is an evidence-based measure of birth defects prevention. The study was aimed to assess effect of periconceptual use of folic acid on birth defect prevalence in Arkhangelsk county and to investigate socio-demographic factors, which are associated with adherence to this preventive measure. Methods A registry-based study was conducted with data from the Arkhangelsk County Birth Registry for 2012-2015. The study population included 57084 pregnancies to calculate the proportion of women taking folic acid and 53340 pregnancy outcomes without missing data to analyze related socio-demographic characteristics. Results The proportion of women followed a folic acid supplementation before pregnancy was 1.3% (95% CI: 1.2-1.4), during pregnancy - 55.8% (95%CI: 54.6-56.4). Such women had less risk to deliver a newborn with any birth defects (OR = 0,84, 95%CI: 0,75 - 0,95). Considering birth defects prevalence of 38,6 per 1000 newborns in Arkhangelsk county, number needed to prevent one case of birth defect was 142,9. Based on multivariate analysis, nulliparous married women with higher education, aged 30 or more, had a higher chance to use folic acid before and during pregnancy. The history of spontaneous abortion in the mother's medical history and the first pregnancy were negatively associated with the probability of folic acid intake both before and during pregnancy. Conclusions The compliance to periconceptional intake of folic acid among women in the region was low. A level of compliance was associated with such socio-demographic factors as age, education, marital status, gravidity and parity. The findings have direct applications in improving prenatal care in Arkhangelsk county and establishing targets for prenatal counseling. Key messages A level of compliance to primary prevention of birth defects is associated with such socio-demographic factors as age, education, marital status, gravidity and parity. Prenatal counseling in terms of birth defects prevention should be based on socio-demographic characteristics of pregnant women.

Periconceptional stressors and social support and risk for adverse birth outcomes

BackgroundThe prevalence of preterm birth and low birth weight has been increasing slightly in recent years. A few studies have suggested that psychosocial stress during pregnancy may increase risk for these adverse birth outcomes. To extend those observations, we analyzed various major life event stressors separately and cumulatively as potential risk factors for preterm birth and low birth weight using granular categories of each outcome in a large, population-based study. Additionally, we assessed if greater social support buffered any effects.MethodsData were from a nested prevalence study of 4395 women in the National Birth Defects Prevention Study who delivered live-born non-malformed infants (controls) between 2006 and 2011. Participants completed a standardized, computer-assisted interview between 6 weeks and 24 months after delivery that included questions on stress and social support from 3 months before pregnancy to the 3rd month of pregnancy. Cumulative stress and support indices were also calculated. Preterm birth was divided into “early preterm” (< 32 weeks), “late preterm” (32–36 weeks) and “term.” Low birthweight was divided into “very low birth weight” (< 1500 g), “low birth weight” (1500–2499 g) and “normal birth weight” (≥2500 g). Relative risks and 95% confidence intervals (95% CI) were calculated using Poisson regression.ResultsFor women reporting relationship difficulties, there was a suggestive risk of early preterm birth (RR: 1.9, 95%CI: 0.9–3.9) and very low birthweight (RR: 2.0, 95%CI: 0.9–4.4). For women reporting that they or someone close to them were victims of abuse, violence, or crime, there was an increased risk of low birthweight (RR: 1.8, 95%CI: 1.1–2.7) and late preterm birth (RR: 1.5, 95%CI: 1.0–2.2). There were no strong associations observed between social support questions and the various outcomes.ConclusionsOur results add some support to prior evidence that certain stressors may be associated with increase selected adverse birth outcomes risk. We did not find strong evidence that social support buffered the observed risks in our study.

Improved Software Defect Prevention using Transfer Learning

Improved Software Defect Prevention using Transfer Learning

Birth Defects Data From Population-Based Birth Defects Surveillance System in a District of Southern Jiangsu, China, 2014-2018.

As a population-based national surveillance region, Tianning District confronts with great challenges in birth defects (BDs) prevention. We aimed to describe the epidemiology of BDs in infants (including dead fetus, stillbirth, or live birth between 28 weeks of gestation and 42 days after birth) in Tianning District from 2014 to 2018. The data was collected from the national birth defect surveillance system. The prevalence rates of BDs were calculated by poisson distribution. Trends of incidence and the associations of regarding perinatal characteristics with BDs were analyzed by poisson regression. During the study period, the prevalence of BD was 155.49 per 10,000 infants. The ten leading BDs were congenital heart defects (CHD), polydactyly, Congenital malformation of kidney (CMK), syndactyly, cleft palate, hypospadias, Congenital hypothyroidism (CH), congenital atresia of rectum and anus, congenital talipes equinovarus (CTE), and microtia. A significant increase in the prevalence of CHD was observed with a prevalence rate ratio (PRR) of 1.191. Gravidity ≥ 3 (PRR = 1.38) and multiple births (PRR = 2.88) were risk factors for BDs. Premature delivery (PRR = 4.29), fetal death or stillbirth (PRR = 24.79), and infant death (PRR = 43.19) were adverse consequences of BDs. Strengthening publicity and education, improving the ability of diagnosis and monitoring, expanding surveillance time quantum of BDs system may be warranted.

Dynamic Imaging of Mouse Embryos and Cardiac Development in Static Culture.

Dynamic imaging is a powerful approach to assess the function of a developing organ system. The heart is a dynamic organ that undergoes quickmorphological and mechanical changes through early embryonic development. Defining the embyonic mouseheart'snormal function is important for our ownunderstanding of human heartdevelopment and will inform us on treatments and prevention of congenital heart defects (CHD). Traditional methods such as ultrasound or fluorescence-based microscopy are suitablefor live dynamic imaging, are excellent to visualize structure and connect gene expression to phenotypes, but can be of low quality in resolving fine features and lack imaging depth and scale to fully appreciate organ morphogenesis. Additionally, previous methods can be limited in accommodating a live imaging apparatus capable of sustaining whole embryo development for extended periods time. Optical coherence tomography (OCT) is unique in this circumstance because acquisition of three-dimensional images without contrast reagents, at single cell resolution make it a suitablemodality to visualize fine structures in the developing embryo. OCT setups are highly customizable for live imaging because of the tethered imaging arm, due to its setup as a fiber-based interferometer. OCT allows for 4D (3D+time) functional imaging of living mouse embryos and can provide functional and mechanical information to ascertain how the heart's pump function changes through development. In this chapter, we will focus on how we use OCT to visualize live heart dynamics at different stages of development and provide mechanical information to reveal functional properties of the developing heart.

Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects

Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks. To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions. The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection. Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants. We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period. This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83). We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.

Congenital diaphragmatic hernia and maternal dietary nutrient pathways and diet quality.

We examined the association of congenital diaphragmatic hernia (CDH) with maternal dietary intake, using semi-Bayes hierarchical models and principal components analysis to consider intake of nutrients that contribute to one-carbon metabolism and oxidative stress pathways, and a diet quality index. We included data on 825 cases and 11,108 nonmalformed controls born from 1997-2011 whose mother participated in the National Birth Defects Prevention Study (NBDPS), a multisite, population-based case-control study. Exposure data were from maternal telephone interviews, which included a food frequency questionnaire. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were generated from logistic regression models that included nutritional factors as continuous variables and were adjusted for maternal energy intake, race-ethnicity, parity, and vitamin supplement intake. In the semi-Bayes hierarchical model that included all nutrients and confounders, riboflavin was the only nutrient for which the 95% CI excluded 1.0; the aOR for a 1 SD increase was 0.83. The aORs were 0.79 (95% CI 0.69-0.91) for the one-carbon metabolism pathway score, 0.90 (95% CI 0.80-1.01) for oxidative stress, and 0.85 (95% CI 0.77-0.93) for diet quality (the aORs correspond to a 1 SD increase). The findings from this study provide some support for the hypothesis that better prepregnancy nutrition is associated with reduced risk for CDH. These results provide etiologic clues but should be interpreted with caution given the novelty of the investigation.

Modeling shows high potential of folic acid-fortified salt to accelerate global prevention of major neural tube defects.

We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) potentially prevented through mandatory double fortification of iodized salt with folic acid. Using United Nations Children's Fund (UNICEF) and Global Fortification Data Exchange (GFDx) data sets, we modeled country-specific number of FAP SBA cases prevented annually using (a) current coverage of the salt in households worldwide and (b) expected daily amount of folic acid intake from folic acid-fortified iodized salt. Our evidence-based modeling strategy assumed mandatory folic acid fortification of salt at 20 ppm, and that at 200 μg/day intake of folic acid through fortified salt, should achieve 100% prevention of all FAP SBA in countries. One hundred countries that have data on percent of households consuming iodized salt globally were examined; 55 of them have ≥80% households consuming iodized salt. Our model estimated approximately 180,000 cases of FAP SBA could be prevented in these 100 countries through folic acid-fortified iodized salt, and 150,000 of them would be in countries where ≥80% households consuming iodized salt that can be potentially fortified with folic acid. Salt fortification with folic acid could contribute to the prevention of about 65% global FAP SBA cases annually. Our evidence-based model shows that there is high potential to prevent FAP SBA using folic acid-fortified iodized salt. Prevention will reach countries where there is a limited reach of centrally processed folic acid-fortified wheat or maize flour. If this intervention is made feasible by the salt industry, it can accelerate the prevention of FAP SBA significantly.

Asthma Medication Use and Risk of Birth Defects: National Birth Defects Prevention Study, 1997-2011

Evidence regarding associations between maternal asthma medication use and birth defects is mixed. Estimate associations between asthma medciation use and 52 birth defects using National Birth Defects Prevention Study data from 1997 to 2011. We compared self-reported maternal asthma medication use for 28,481 birth defect cases and 10,894 nonmalformed controls. We calculated adjusted odds ratios (95% CIs) to estimate the risk of birth defects associated with early pregnancy asthma medication use (the month before through the third month of pregnancy), controlling for maternal age, race/ethnicity, body mass index, smoking, folic acid-containing supplement use, and parity. We calculated risks by medication groupings: bronchodilators, anti-inflammatories, and both. Overall, 1304 (5%) case and 449 (4%) control women reported early pregnancy asthma medication use. We observed an association between asthma medication use and longitudinal limb deficiency (1.81; 95% CI, 1.27-2.58). Early pregnancy bronchodilator-only use was associated with cleft palate (1.50; 95% CI, 1.11-2.02), cleft lip (1.58; 95% CI, 1.12-2.23), longitudinal limb deficiency (2.35; 95% CI, 1.55-3.54), and truncus arteriosus (2.48; 95% CI, 1.13-5.42). Although early pregnancy anti-inflammatory-only use was not associated with the birth defects studied, use of both medications was associated with biliary atresia (3.60; 95% CI, 1.55-8.35) and pulmonary atresia (2.50; 95% CI, 1.09-5.78). Consistent with previous National Birth Defects Prevention Study analyses, asthma medication use was not associated with most birth defects examined, but we observed modest risks for bronchodilator use and several birth defects. Our findings support maintaining adequate asthma treatment during pregnancy, because early pregnancy asthma exacerbations have been associated with adverse birth outcomes, including birth defects.

Maternal Hypertension-Related Genotypes and Congenital Heart Defects.

Maternal hypertension has been associated with congenital heart defect occurrence in several studies. We assessed whether maternal genotypes associated with this condition were also associated with congenital heart defect occurrence. We used data from the National Birth Defects Prevention Study to identify non-Hispanic white (NHW) and Hispanic women with (cases) and without (controls) a pregnancy in which a select simple, isolated heart defect was present between 1999 and 2011. We genotyped 29 hypertension-related single nucleotide polymorphisms (SNPs). We conducted logistic regression analyses separately by race/ethnicity to assess the relationship between the presence of any congenital heart defect and each SNP and an overall blood pressure genetic risk score (GRS). All analyses were then repeated to assess 4 separate congenital heart defect subtypes. Four hypertension-related variants were associated with congenital heart defects among NHW women (N = 1,568 with affected pregnancies). For example, 1 intronic variant in ARHGAP2, rs633185, was associated with conotruncal defects (odds ratio [OR]: 1.3, 95% confidence interval [CI]: 1.1-1.6). Additionally, 2 variants were associated with congenital heart defects among Hispanic women (N = 489 with affected pregnancies). The GRS had a significant association with septal defects (OR: 2.1, 95% CI: 1.2-3.5) among NHW women. We replicated a previously reported association between rs633185 and conotruncal defects. Although additional hypertension-related SNPs were also associated with congenital heart defects, more work is needed to better understand the relationship between genetic risk for maternal hypertension and congenital heart defects occurrence.

Aplicação da ferramenta FMEA para análise de notificações de queixas técnicas de medicamentos sólidos no contexto de Quality by Design

O controle de qualidade em indústrias farmacêuticas tem sido aprimorado de maneira gradual com a implementação de novas estratégias e tecnologias, de modo a possibilitar a obtenção de produtos cada vez mais eficazes e seguros. Com surgimento do conceito de Quality by Design (QbD), a produção de medicamentos passou a ser otimizada por meio da delimitação dos parâmetros de qualidade dos produtos desde os estágios iniciais de desenvolvimento e planejamento da formulação a partir das características do insumo farmacêutico ativo, visando a prevenção de defeitos e melhoria contínua da cadeia produtiva. Sendo assim, o presente estudo constitui uma análise quantitativa de notificações de irregularidades em medicamentos sólidos publicadas no site oficial da Agência Nacional de Vigilância Sanitária (ANVISA) durante o período de 2017 a 2019, a partir do uso da metodologia de Análise de Modos de Falhas e Efeitos (FMEA) no contexto de QbD. Ao todo, foram analisadas 421 notificações de produtos farmacêuticos irregulares, das quais 28,5% correspondiam a queixas técnicas, sendo 60,0% delas referentes a medicamentos sólidos. Após a avaliação dos dados, verificou-se que aproximadamente 80,0% das não-conformidades encontradas estavam relacionadas a aspecto, dissolução, embalagem, doseamento e pureza, sendo o QbD uma estratégia eficiente para o gerenciamento dos riscos relacionados à produção, visando a redução de custos e implementação de estratégias que possibilitem a diminuição gradativa do número de queixas técnicas destes produtos.&#x0D;

Capture rate of congenital heart defects in the Pediatric Health Information System database.

Congenital heart defects (CHD) are common and are a frequent subject of research using large administrative databases such as the Pediatric Health Information System (PHIS) database. The capture rate of CHD within PHIS, however, has not been described. The PHIS database includes inpatient encounters from over 52 tertiary care pediatric hospitals across the United States. We identified all patients less than 1 year of age with a cardiac defect in PHIS from 2010 to 2014 and compared these results with national prevalence estimates based on the National Birth Defects Prevention Network annual report, which served as the gold standard. The capture rate of CHD in PHIS ranged from 30 to 95% depending on the spectrum of severity and heterogeneity of the cardiac defect. The capture rate was higher for critical CHD (CCHD) at 66%, and all lesions with 70% or greater capture rate (interrupted aortic arch, truncus arteriosus, single ventricle, total anomalous pulmonary venous return, double outlet right ventricle, and hypoplastic left heart syndrome) fell within the CCHD category. Just over half of the predicted CHD patients were identified using the PHIS database. Although there is a high capture rate for CHD that require early hospitalization, there is a low capture rate for defects with a wider spectrum of disease presentation. These attributes of the PHIS database should be used to frame previous and future research using PHIS to study CHD.

On interdisciplinary collaboration and mentoring in Birth Defects Research.

There are many research societies in the world but none like the Teratology Society, now known as, the Society of Birth Defects Research and Prevention. Our Society has thrived in the last 60 years because of its inclusiveness in the diversity of disciplines of our membership, the outstanding interprofessional collaboration, and successful mentorship. This brief commentary offers some anecdotes about our diversity, interprofessional research, and mentoring.

Abstract PR03: Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases

Abstract Background: There is a persistent yet unexplained disparity in the sex ratio among childhood cancer cases, whereby males are more likely to develop several cancers. These patterns are also seen for most birth defects, which are strongly associated with the risk of childhood cancer. We conducted a mediation analysis to estimate whether birth defect status mediates the association between sex and childhood cancer risk. Methods: We linked data from birth, birth defects, and cancer registries to obtain a population-based birth cohort including births from 1992-2013 in Arkansas, Michigan, North Carolina, and Texas. We obtained birth defects diagnoses, including chromosomal and nonchromosomal defects, from statewide, population-based birth defects registries. We focused on “major” defects as defined by the National Birth Defects Prevention Network and the National Birth Defects Prevention Study. Cancer diagnoses that occurred prior to age 18 years were obtained from state cancer registries. We obtained data on child’s sex, birth weight, gestational age, maternal race/ethnicity, maternal age, and plurality from birth records. We conducted counterfactual mediation analysis to estimate the direct and indirect effects of sex on risk of childhood cancer, modeling sex as the exposure, birth defect status as the mediator, and cancer type as the outcome. State, maternal race/ethnicity (white, black, other), maternal age (continuous), and plurality (singleton vs. multiple) were considered potential mediator-outcome confounders. Due to lower success rates of linkage to birth records among adolescent cancer cases, we conducted a sensitivity analysis limiting to cancers diagnosed at age &amp;lt; 5 years. Results: Our dataset included 10,181,074 children (5,208,379 males; 4,972,695 females), including 15,110 with cancer diagnoses (8044 males; 7066 females), 539,567 children with birth defects diagnoses (320,666 males; 218,901 females), and 2,124 co-occurring cases (children with both cancer and one or more birth defect diagnosis: 1,186 males; 938 females). We observed mediation of the association between sex and childhood cancer overall by birth defect status (proportion mediated [PM]: 38%). In analyses of specific cancer types, we observed variation of the estimated proportion mediated among several cancers, including hepatoblastoma (PM: 33%), neuroblastoma (PM: 35%), non-Hodgkin lymphoma (PM: 6%), and soft tissue sarcomas (PM: 25%). In analysis of children age &amp;lt; 5 years at cancer diagnosis, we observed similar results. Conclusions: Our results suggest that birth defects mediate a significant proportion of the overall relationship between sex and childhood cancer. While approximately 60% of the male excess in childhood cancer cases remains unexplained, these findings add to our understanding of the causal pathway of male sex as a risk factor for childhood cancer. Additional studies are under way to characterize the biology underlying these observations. This abstract is also being presented as Poster A66. Citation Format: Erin L. Marcotte, Jeremy M. Schraw, Tania A. Desrosiers, Wendy N. Nembhard, Peter H. Langlois, Mark A. Canfield, Robert E. Meyer, Sharon E. Plon, Philip Lupo. Sex ratio disparities and the risk of childhood cancer: Evaluating the mediating effect of birth defects among 15,000 childhood cancer cases [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr PR03.

Use of antihistamine medications during early pregnancy and selected birth defects: The National Birth Defects Prevention Study, 1997-2011.

It is estimated that approximately 10-15% of pregnant women report antihistamine use during pregnancy. Although antihistamines are generally considered safe during pregnancy, results from published studies are inconsistent. Using a case-control study design we analyzed 41,148 pregnancies (30,091 cases and 11,057 controls) from the National Birth Defects Prevention Study (1997-2011). Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for 64 birth defect groupings in relation to early pregnancy exposure to 14 distinct antihistamines. Models were adjusted for maternal age, race, parity, education level, prenatal care, folic acid use, smoking and alcohol use, and study site. Approximately 13% of cases and controls were exposed to an antihistamine during early pregnancy. Analyses were restricted to those defects where more than five cases were exposed to the antihistamine of interest, generating 340 analyses which yielded 20 (5.9%) significant positive associations (adjusted ORs ranging from 1.21 to 4.34). Only a few of our findings were consistent with previous studies. There is a lack of strong evidence to conclude that birth defects are associated with exposure to antihistamines during early pregnancy.