Birth Defects Research. Part A, Clinical And Molecular Teratology[JOURNAL]
Sun
200 papers
Application of data screening to drug exposure in large risk factor studies of birth defects.
Louik C, Werler M, Anderka M … +1 more , Mitchell AA
Birth Defects Res A Clin Mol Teratol · 2015 Aug · PMID 26259777 · Full text
BACKGROUND: Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying...
BACKGROUND: Birth defects are the leading cause of infant death. While causes of most are unknown, those that might be due to medication use are among the most preventable. This study describes an approach to identifying those medications that most warrant attention by using a "screen" program that calculates odds ratios for pairs of exposures and specific birth defects. METHODS: We discuss the development of this tool and illustrate its application to two large risk factor studies, the Slone Epidemiology Center's Birth Defects Study and the Centers for Disease Control and Prevention's National Birth Defects Prevention Study, ideal settings for the systematic study of risks and relative safety of drugs in relation to birth defects while recognizing the inherent limitations of such an approach. RESULTS: Suggestions for establishing criteria for exposures and outcomes that balance the need for specific details with the practical considerations of sample size and volume of output are presented. Selection of appropriate exposure reference categories and control groups is also discussed, as well as the need to address potential confounding. An example that motivated a detailed investigation of possible associations between a medication (butalbital) and selected specific birth defects is provided. CONCLUSION: While screening programs such as the one described can be a valuable tool for exploring potential associations in large data bases, they must be applied with caution. The issue of multiple testing and chance findings is a major concern. While statistics are a necessary component, human judgment must be an integral part of the process.
Issues involved in the phenotypic classification of orofacial clefts ascertained through a state birth defects registry for the North Carolina Cleft Outcomes Study.
Aylsworth AS, Allori AC, Pimenta LA … +6 more , Marcus JR, Harmsen KG, Watkins SE, Ramsey BL, Strauss RP, Meyer RE
Birth Defects Res A Clin Mol Teratol · 2015 Nov · PMID 26251069 · Publisher ↗
BACKGROUND: Epidemiologic studies involving birth defects are extremely sensitive to phenotype accuracy and precision. We devised a case review and classification protocol for a project to study school achievement in chi...
BACKGROUND: Epidemiologic studies involving birth defects are extremely sensitive to phenotype accuracy and precision. We devised a case review and classification protocol for a project to study school achievement in children with idiopathic, nonsyndromic orofacial clefts to improve the reliability of phenotypic classification from the statewide birth defects registry. METHODS: Surveillance-program abstraction data and medical records at the birth or treating hospitals were used when available. Exclusion criteria included: median cleft lip; Tessier cleft; premaxillary agenesis; presence of a recognizable syndrome, phenotype, association, or sequence (other than Robin sequence); clefts with other malformations not considered to be normal or common variants in the newborn; and cases with documented or suspected genetic or teratogenic causes. RESULTS: Of 712 children identified with orofacial clefts, 153 were excluded, leaving 559 nonsyndromic orofacial cleft cases of unknown cause in the final study. These cases were grouped into the following clinically meaningful types: cleft lip with or without cleft alveolus; cleft lip and cleft palate; and cleft palate only. This review and classification process resulted in the elimination of 21.5% of the original cohort of identified cases, with most exclusions being due to suspected syndromic associations. CONCLUSION: Verbatim descriptions of the clinical findings are critical for accurate classification of diagnoses. This review process improved the precision of orofacial cleft phenotype classification for our study. Precision would have been further improved if all of the cases had verbatim descriptions of diagnoses and all medical records could have been reviewed by the classification team.
Polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele.
Mazumdar M, Valeri L, Rodrigues EG … +9 more , Ibne Hasan MO, Hamid R, Paul L, Selhub J, Silva F, Mostofa MG, Quamruzzaman Q, Rahman M, Christiani DC
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26250961 · Full text
BACKGROUND: Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced n...
BACKGROUND: Arsenic induces neural tube defects in many animal models. Additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. We sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. METHODS: Fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural Bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. We assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. Inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. Candidate single-nucleotide polymorphisms were identified through review of the literature. RESULTS: Drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the AA/AG genotype of rs2236225 (MTHFD1), the GG genotype of rs1051266 (SLC19A1), the TT genotype of rs7560488 (DNMT3A), and the GG genotype of rs3740393 (AS3MT) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively. CONCLUSION: Our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways.
Descriptive epidemiology of birth defects thought to arise by new mutation.
Langlois PH, Scheuerle AE
Birth Defects Res A Clin Mol Teratol · 2015 Nov · PMID 26228797 · Publisher ↗
BACKGROUND: The current study is the first to examine the association of a broad range of sociodemographic factors with conditions thought to arise most of the time by de novo mutation. METHODS: Data were taken from 1999...
BACKGROUND: The current study is the first to examine the association of a broad range of sociodemographic factors with conditions thought to arise most of the time by de novo mutation. METHODS: Data were taken from 1999 to 2009 from the Texas Birth Defects Registry (TBDR), a statewide active surveillance program. We used Poisson regression to generate crude and adjusted measures of association; the latter included models with all variables and with a parsimonious subset of variables. RESULTS: There were 1694 cases with any of the phenotypes in the panel, 1100 cases in a subpanel with ≥90% of cases thought to arise de novo, 523 with chromosomal deletion disorders, and 243 with imprinting disorders. In the most parsimonious models, there was an increasing time trend in all groups except imprinting (p ≤ 0.01). Plurality (twins, triplets, etc.) was associated with greater risk of all groups except chromosomal deletions (p ≤ 0.01). Parental age showed strong trends with all groups; paternal age was most important for the total and imprinting groups (p ≤ 0.0001), and maternal age for the others (p ≤ 0.04). De novo mutation phenotypes were more prevalent among offspring of fathers who are non-Hispanic White compared with some other race/ethnic groups. CONCLUSION: This study suggests that birth defects arising by new mutation may be more prevalent among offspring of older parents and in plural births. The increasing time pattern and race/ethnic pattern may be related to greater use of or access to genetic tests. This approach to mutation epidemiology seems feasible for birth defects registries to consider.
Assessing congenital malformation risk from medications used in pregnancy: The contribution of NBDPS in pregnancy labeling of prescription drug products.
Tassinari MS, Sahin L, Yao LP
Birth Defects Res A Clin Mol Teratol · 2015 Aug · PMID 26223007 · Publisher ↗
BACKGROUND: Obtaining human pregnancy data to inform product labeling is important for drug and biological products. METHODS: Collection and analyses of safety data on their use during pregnancy is usually performed afte...
BACKGROUND: Obtaining human pregnancy data to inform product labeling is important for drug and biological products. METHODS: Collection and analyses of safety data on their use during pregnancy is usually performed after approval. RESULTS: The Centers for Disease Control National Birth Defects Prevention Study has provided important data on the relationship between drug use in pregnancy and birth defects. CONCLUSION: The Pregnancy and Lactation Labeling Rule will set new and improved standards for the inclusion of information about the use of prescription drugs and biological products during pregnancy; the National Birth Defects Prevention Study, along with other data sources, will be critical for providing safety data to inform product labeling.
Evaluating cost and resource use associated with pulse oximetry screening for critical congenital heart disease: Empiric estimates and sources of variation.
Reeder MR, Kim J, Nance A … +4 more , Krikov S, Feldkamp ML, Randall H, Botto LD
Birth Defects Res A Clin Mol Teratol · 2015 Nov · PMID 26215888 · Publisher ↗
BACKGROUND: Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital...
BACKGROUND: Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry is being implemented in the United States and internationally; however, few data are available on the associated in-hospital costs and use of resources. METHODS: Time and motion study in well-baby nurseries at two large urban hospitals in Utah using different approaches to pulse oximetry screening. Two observers recorded the time for each screening step together with provider and equipment characteristics. Structured questionnaire provided additional information on labor and equipment costs. RESULTS: Fifty-three CCHD screens were observed. At site A (n = 22), screening was mostly done by medical assistants (95%) using disposable probes (100%); at site B (n = 31), screening was mostly performed by certified nursing assistants (90%) using reusable probes (90%). Considering only first screens (n = 53), the median screen time was 8.6 min (range: 3.2-23.2), with no significant difference between sites. The overall cost ($ in 2014) of screening per baby was $24.52 at site A and $2.60 at site B. Nearly all the variation in cost (90%) was due to the cost of disposable probes; labor costs were similar between sites. CONCLUSION: CCHD screening by means of pulse oximetry is reasonably fast for most babies, leading to relative small labor costs with little variation by provider type. The main driver of costs is equipment: in a high throughput setting, reusable probes are currently associated with considerable cost saving compared with disposable probes. As programs expand to universal screening, improved and cheaper technologies could lead to considerable economies of scale.
Erratum to 'Maternal prepregnancy body mass index and risk of neural tube defects: A population-based case-control study in Shanxi Province, China'.
Li Z, Liu J, Ye R … +4 more , Zhang L, Pei L, Zheng X, Ren A
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26192717 · Publisher ↗
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Poor sleep during the periconceptional period increases risk for neural tube defects in offspring.
Li Z, Zhang L, Jin L … +3 more , Ye R, Raynes-Greenow C, Ren A
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26184080 · Publisher ↗
BACKGROUND: Poor sleep has been studied in relation to various diseases. Few studies have investigated the effect of poor sleep on birth defects. METHODS: We examined the association of maternal poor sleep during pericon...
BACKGROUND: Poor sleep has been studied in relation to various diseases. Few studies have investigated the effect of poor sleep on birth defects. METHODS: We examined the association of maternal poor sleep during periconceptional period and the risk of neural tube defects (NTDs) in offspring based on a large case-control study in northern China. The subjects included 629 NTD cases and 858 normal controls investigated between 2002 and 2007. Maternal sleep status was collected by health workers within first week after delivery. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of NTDs in association with poor sleep. RESULTS: The proportion of mothers with frequent poor sleep (≥4 days/week on average) was markedly higher in NTDs group (5.9%) than in control group (1.2%). In the multivariate analysis, frequent poor sleep was significantly associated with an increased risk of total NTDs (adjusted OR, 4.1; 95% CI, 1.9-8.8) and spina bifida subtype (adjusted OR, 6.4; 95% CI, 2.8-14.5). Frequent poor sleep showed a significant interaction with body mass index (BMI). Relative to women who reported poor sleep <4 days/week and with BMI < 24, frequent poor sleep showed a markedly higher increased risk of NTDs among overweight or obese women (adjusted OR, 11.8; 95% CI, 1.4-97.6) than women with BMI < 24 (adjusted OR, 2.5; 95% CI,1.1-5.9). CONCLUSION: Maternal frequent poor sleep during the periconceptional period may increase the risk for all NTDs and spina bifida. The association appears to be independent of some lifestyle factors that are closely associated with sleep quality.
Preventable spina bifida and anencephaly in Europe.
Obeid R, Pietrzik K, Oakley GP … +3 more , Kancherla V, Holzgreve W, Wieser S
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26178749 · Publisher ↗
BACKGROUND: Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. METHODS: Using surveillance data from...
BACKGROUND: Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. METHODS: Using surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT), we estimated the total prevalence of spina bifida and anencephaly per 10,000 births between 2000 and 2010. We also estimated additional lifetime direct medical costs among individuals with spina bifida, compared with those without, in Germany for the year 2009. RESULTS: During the study period, there were 7478 documented cases of spina bifida and anencephaly among the 9,161,189 births, with an estimated average combined prevalence of 8.16 per 10,000 births (95% confidence interval, 7.98 - 8.35). For the 241 spina bifida-affected live births in 2009 in Germany, the estimated additional lifetime direct medical costs compared with non-spina bifida affected births were €65.5 million. Assuming a 50% reduction in the prevalence if folic acid has been provided to all women before pregnancy, 293 spina bifida cases could have been prevented in Germany in 2009. The estimated lifetime direct medical cost saving for the live births in 2009 was €32.9 million assuming a 50% reduction, or €26.1 million assuming a 40% risk reduction. CONCLUSION: Europe has an epidemic of spina bifida and anencephaly compared with countries with mandatory folic acid fortification policy. Primary prevention through mandatory folic acid fortification would considerably reduce the number of affected pregnancies, and associated additional costs.
CMV-induced embryonic mouse organ of corti dysplasia: Network architecture of dysfunctional lateral inhibition.
Melnick M, Jaskoll T
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26178632 · Full text
BACKGROUND: Congenital cytomegalovirus infection is the major nongenetic cause of sensorineural hearing loss at birth and beyond. Among other pathologies, there is a striking dysplasia/hyperplasia of organ of Corti hair...
BACKGROUND: Congenital cytomegalovirus infection is the major nongenetic cause of sensorineural hearing loss at birth and beyond. Among other pathologies, there is a striking dysplasia/hyperplasia of organ of Corti hair and supporting cells. METHODS: Using an in vitro embryonic mouse model of cytomegalovirus-induced cochlear teratogenesis that mimics the known human pathology, and functional signaling network modeling, we tested the hypothesis that cytomegalovirus disrupts the highly ordered organ of Corti hair and supporting cells pattern by dysregulating Notch and Fgfr3, their cognate ligands and downstream effectors. RESULTS: Several novel emergent properties of the critical lateral inhibition subnetwork became apparent. The subnetwork has classic small-world properties such as short paths between most gene pairs, few long-distance links, and considerable clustering. Concomitantly, the calculated probability that our specific gene expression dataset is from dysplastic organs of Corti is highly significant (p < 1 × 10(-12) ). Furthermore, we determined that the subnetwork has a highly heterogeneous scale-free topology in which the highly linked genes (hubs), Notch and Fgfr3, play a central role in mediating interactions among the less linked genes. CONCLUSION: This phenomenon has important biologic and therapeutic implications.
Register based study of anorectal anomalies over 26 years: Associated anomalies, prevalence, and trends.
Godse AS, Best KE, Lawson A … +2 more , Rosby L, Rankin J
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26173562 · Publisher ↗
BACKGROUND: Anorectal anomalies are atresias or stenoses of the anal canal and rectum with or without fistulous connections with the bladder, urethra, perineum, or vestibule. The aim of this study was to describe the epi...
BACKGROUND: Anorectal anomalies are atresias or stenoses of the anal canal and rectum with or without fistulous connections with the bladder, urethra, perineum, or vestibule. The aim of this study was to describe the epidemiology of anorectal anomalies, including associated anomalies, prevalence, and temporal trends. METHODS: Anorectal anomalies occurring in late miscarriages (>20 gestation weeks), terminations of pregnancy for fetal anomaly (any gestation), stillbirths (≥24 gestation weeks) and live births, delivered from 1985 to 2010, notified to the Northern Congenital Abnormality Survey (NorCAS) were included in this population-based case series. RESULTS: There were 278 cases among 892,194 live births. Twenty (7.2%) cases occurred in twin pregnancies and 24 (8.7%) with chromosomal anomalies/genetic syndromes were excluded. There were 234 cases (total prevalence = 2.7, 95% confidence interval [CI]: 2.4, 3.1 per 10,000 live and stillbirths). There was no evidence of a trend in prevalence over time (Chi(2) test for trend: p = 0.789). There was a male predominance (70.9%). Of the 234 cases, 167 (71.4%) were live born, two (0.9%) were late miscarriages, seven (3.0%) were stillbirths, and 58 (24.8%) were terminations of pregnancy for fetal anomaly. There was no significant association with maternal age at delivery (p = 0.095). 7.2% of isolated cases (cases with no other congenital anomalies) were diagnosed prenatally. CONCLUSION: The prevalence of anorectal anomalies in this study is comparable to other case series. There was no evidence of a temporal increase in prevalence. We confirmed a male predominance of anorectal anomalies and no significant association with maternal age. Birth Defects Research (Part A) 103:597-602, 2015. © 2015 Wiley Periodicals, Inc.
Heme oxygenase-1 promoter polymorphisms and risk of spina bifida.
Fujioka K, Yang W, Wallenstein MB … +4 more , Zhao H, Wong RJ, Stevenson DK, Shaw GM
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26173399 · Full text
BACKGROUND: Spina bifida is the most common form of neural tube defects (NTDs). Etiologies of NTDs are multifactorial, and oxidative stress is believed to play a key role in NTD development. Heme oxygenase (HO), the rate...
BACKGROUND: Spina bifida is the most common form of neural tube defects (NTDs). Etiologies of NTDs are multifactorial, and oxidative stress is believed to play a key role in NTD development. Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, has multiple protective properties including mediating antioxidant processes, making it an ideal candidate for study. The inducible HO isoform (HO-1) has two functional genetic polymorphisms: (GT)n dinucleotide repeats and A(-413)T SNP (rs2071746), both of which can affect its promoter activity. However, no study has investigated a possible association between HO-1 genetic polymorphisms and risk of NTDs. METHODS: This case-control study included 152 spina bifida cases (all myelomeningoceles) and 148 non-malformed controls obtained from the California Birth Defects Monitoring Program reflecting births during 1990 to 1999. Genetic polymorphisms were determined by polymerase chain reaction and amplified fragment length polymorphisms/restriction fragment length polymorphisms using genomic DNA extracted from archived newborn blood spots. Genotype and haplotype frequencies of two HO-1 promoter polymorphisms between cases and controls were compared. RESULTS: For (GT)n dinucleotide repeat lengths and the A(-413)T SNP, no significant differences in allele frequencies or genotypes were found. Linkage disequilibrium was observed between the HO-1 polymorphisms (D': 0.833); however, haplotype analyses did not show increased risk of spina bifida overall or by race/ethnicity. CONCLUSION: Although, an association was not found between HO-1 polymorphisms and risk of spina bifida, we speculate that the combined effect of low HO-1 expression and exposures to known environmental oxidative stressors (low folate status or diabetes), may overwhelm antioxidant defenses and increase risk of NTDs and warrants further study.
What we don't know can hurt us: Nonresponse bias assessment in birth defects research.
Strassle PD, Cassell CH, Shapira SK … +3 more , Tinker SC, Meyer RE, Grosse SD
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26173046 · Full text
BACKGROUND: Nonresponse bias assessment is an important and underutilized tool in survey research to assess potential bias due to incomplete participation. This study illustrates a nonresponse bias sensitivity assessment...
BACKGROUND: Nonresponse bias assessment is an important and underutilized tool in survey research to assess potential bias due to incomplete participation. This study illustrates a nonresponse bias sensitivity assessment using a survey on perceived barriers to care for children with orofacial clefts in North Carolina. METHODS: Children born in North Carolina between 2001 and 2004 with an orofacial cleft were eligible for inclusion. Vital statistics data, including maternal and child characteristics, were available on all eligible subjects. Missing 'responses' from nonparticipants were imputed using assumptions based on the distribution of responses, survey method (mail or phone), and participant maternal demographics. RESULTS: Overall, 245 of 475 subjects (51.6%) responded to either a mail or phone survey. Cost as a barrier to care was reported by 25.0% of participants. When stratified by survey type, 28.3% of mail respondents and 17.2% of phone respondents reported cost as a barrier. Under various assumptions, the bias-adjusted estimated prevalence of cost as barrier to care ranged from 16.1% to 30.0%. Maternal age, education, race, and marital status at time of birth were not associated with subjects reporting cost as a barrier. CONCLUSION: As survey response rates continue to decline, the importance of assessing the potential impact of nonresponse bias has become more critical. Birth defects research is particularly conducive to nonresponse bias analysis, especially when birth defect registries and birth certificate records are used. Future birth defect studies which use population-based surveillance data and have incomplete participation could benefit from this type of nonresponse bias assessment. Birth Defects Research (Part A) 103:603-609, 2015. © 2015 Wiley Periodicals, Inc.
Twin reversed arterial perfusion sequence is more common than generally accepted.
van Gemert MJ, van den Wijngaard JP, Vandenbussche FP
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26172962 · Publisher ↗
BACKGROUND: Approximately 75% of monozygotic twin pregnancies share one monochorionic placenta where placental anastomoses are virtually always present to connect the two fetoplacental circulations. These anastomoses cau...
BACKGROUND: Approximately 75% of monozygotic twin pregnancies share one monochorionic placenta where placental anastomoses are virtually always present to connect the two fetoplacental circulations. These anastomoses cause several serious complications such as acardiac twinning. Acardiac twins lack a functional heart but nevertheless show fetal growth because the normal pump twin perfuses the acardiac body through arterioarterial (AA) and venovenous (VV) anastomoses. The widely accepted 1% monochorionic acardiac incidence dates back to 1944 and the associated 1:35,000 pregnancies to 1953. Our aim was to update this analysis. METHODS: We accepted the 1% (actually 1.1%) monochorionic acardiac incidence due to lack of more precise data, included the recently observed 58% early cessation of acardiac development as well as consequences of assisted reproductive technology, and assessed the incidence of acardiac twinning under conditions of AA-VV anastomoses. RESULTS: Early acardiac monochorionic twinning increased from 1.1% to 1.1/(1-0.58) = 2.6%, from 1:35,000 to 1:9,500 to 11,000 pregnancies, depending on number and method of assisted reproductive technology, and occurs in approximately 1:8 AA-VV anastomoses-containing monochorionic placentas. CONCLUSION: Early acardiac twinning is not a rare event. The 1944-based 1% acardiac monochorionic incidence has a weak basis and could therefore be (much) larger. Knowing this incidence more precisely may contribute to our knowledge of embryonic splitting in unequal cell masses.
Preventing birth defects: The value of the NBDPS case-control approach.
Dolk H
Birth Defects Res A Clin Mol Teratol · 2015 Aug · PMID 26172859 · Publisher ↗
Birth Defect Registries provide a basis for epidemiological research into risk factors, thus facilitating a growing understanding of what causes congenital anomalies and how one might target preventive public health acti...
Birth Defect Registries provide a basis for epidemiological research into risk factors, thus facilitating a growing understanding of what causes congenital anomalies and how one might target preventive public health actions and reduce inequalities. The National Birth Defects Prevention Study (NBDPS) has used 10 U.S. registries as a basis for a large case-control study. This commentary reviews its methodology and selected areas of output. The strengths of NBDPS lie in the quality of diagnostic coding and classification of birth defects and its size. The sources of bias in NBDPS data relate particularly to retrospective exposure ascertainment entailing a long period of recall, incomplete ascertainment of terminations of pregnancy for fetal anomaly, and unknown bias in case selection. NBDPS results have shown the protective effect of healthy dietary patterns, but have not been as informative as expected in relation to furthering understanding of the protective effect of folic acid. NBDPS medication studies are making important contributions to addressing the gap in existing evidence systematically across a wide range of birth defects, but are challenged by the quality of information on exposure, dose and underlying disease condition, and the interpretation of results of multiple testing. Studies of environmental contaminants in collaboration with experts in exposure assessment have linked addresses to residential exposure measures, using the advantages of information on residential history and confounders, but are challenged by the need to consider exposure mixtures. NBDPS could increase its public health impact by placing more emphasis on socioeconomic inequalities.
Factors associated with inpatient hospitalizations among patients aged 1 to 64 years with congenital heart defects, Arkansas 2006 to 2011.
Simeone RM, Oster ME, Hobbs CA … +3 more , Robbins JM, Thomas Collins R, Honein MA
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26172576 · Full text
BACKGROUND: Individuals with congenital heart defects (CHDs) have high hospital resource use. We sought to identify factors associated with hospital costs and multiple hospitalizations among individuals with CHDs. METHOD...
BACKGROUND: Individuals with congenital heart defects (CHDs) have high hospital resource use. We sought to identify factors associated with hospital costs and multiple hospitalizations among individuals with CHDs. METHODS: Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were linked across encrypted patient identifiers to develop a cohort of Arkansas residents aged 1 to 64 years who were hospitalized at least once with a CHD during this time period. Infants were excluded because patient identifiers were missing for 18 to 52% each year. CHDs were identified using principal and secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes. All hospitalizations of individuals ever admitted with a CHD were included. Mean and median patient-level costs were estimated; the association of hospital costs and patient readmissions were examined with linear and logistic regression. RESULTS: There were 1,185,868 inpatient hospitalizations of Arkansas residents aged 1 to 64 years between 2006 and 2011; these were accrued by 603,925 patients. Of those, 2542 patients (0.42%) had at least one hospitalization with a CHD diagnosis. Total costs for these 2542 patients were $126,999,837 and they accumulated 7898 hospitalizations. Factors associated with increased costs included patient age, CHD type, cardiac procedures, and comorbidities. Factors associated with hospital readmission within 1 year included age, CHD type, expected payer, and comorbidities. CONCLUSION: Individuals with CHDs in Arkansas experience variation in hospital use and costs by patient characteristics. Future research should investigate factors associated with readmissions, cardiac procedures, and comorbidities, as these are strongly associated with hospital costs. Birth Defects Research (Part A) 103:589-596, 2015. © 2015 Wiley Periodicals, Inc.
Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta.
Ma W, Wei X, Gu H … +14 more , Li H, Guan K, Liu D, Chen L, Cao S, An D, Zhang H, Huang T, Miao J, Zhao G, Wu D, Liu B, Wang W, Yuan Z
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26172505 · Publisher ↗
BACKGROUND: In previous studies, we found that the deficiency of sensory and motor neurons was a primary defect associated with the spinal malformation. Upon prenatal treatment of spina bifida through in utero stem cell...
BACKGROUND: In previous studies, we found that the deficiency of sensory and motor neurons was a primary defect associated with the spinal malformation. Upon prenatal treatment of spina bifida through in utero stem cell transplantation in a retinoic acid-induced spina bifida rat model, we found that the mesenchymal stem cell (MSCs) survived, migrated, and differentiated into cells of a neural lineage. In the present study, we investigated whether the transplanted MSCs had the potential to differentiate into sensory neurons or to protect sensory neurons in the defective spinal cord. METHODS: Pregnant rats treated with retinoic acid on embryonic day (E) 10, underwent fetal surgery for MSC transplantation on E16. The fetuses were harvested on E20. Immunofluorescence was used to detect the expression of Brn3a protein in the transplanted MSCs and dorsal root ganglion (DRG) neurons in the defective spinal cords. The expression of the transcription factors Brn3a and Runx1 in spinal cords was analyzed using real-time polymerase chain reaction. RESULTS: Some of the transplanted MSCs expressed sensory neuron cell specific phenotypes. The expression of Brn3a and Runx1 was upregulated in the defective spinal cords when compared to controls. The percentage of Brn3a-positive neurons in DRG was also increased after transplantation. CONCLUSION: Our results indicate that the transplantation of MSCs into the spinal cord could promote the transplanted MSCs and the surrounding cells to differentiate toward a sensory neuron cell fate and to play an important role in protecting sensory neurons in DRG. This approach might be of value in the treatment of sensory neuron deficiency in spina bifida aperta.
In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model.
Suter MA, Abramovici AR, Griffin E … +5 more , Branch DW, Lane RH, Mastrobattista J, Rehan VK, Aagaard K
Birth Defects Res A Clin Mol Teratol · 2015 Jul · PMID 26172404 · Full text
BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure...
BACKGROUND: Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure METHODS: Sprague-Dawley rat dams received either saline or 2 mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were killed on day 1 of life, and brain and lung tissues were harvested (N = 3/ group). RESULTS: We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold; p = 0.03) while acetylation is increased (1.79-fold; p = 0.031). Histone deacetylase activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold; p < 0.001; 0.12-fold; p < 0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold; p = 0.038). CONCLUSION: We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of histone deacetylase activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.
Promise and peril: Dissemination of findings from studies of drugs used in pregnancy and their association with birth defects.
Patrick SW, Cooper WO
Birth Defects Res A Clin Mol Teratol · 2015 Aug · PMID 26153150 · Full text
BACKGROUND: When and how to publish birth defects research can be complex, especially in the context of drugs used in pregnancy. Such research frequently involves multiple stakeholders, including regulatory agencies. Res...
BACKGROUND: When and how to publish birth defects research can be complex, especially in the context of drugs used in pregnancy. Such research frequently involves multiple stakeholders, including regulatory agencies. Researchers must balance the potential peril of an unnecessarily panicked populace versus the benefit of protecting the public's health. METHODS: We use a case presentation and contemporary literature to highlight the potential tradeoffs that researchers must consider. We highlight important considerations including the public health impact, examining the likelihood of causality, understanding common considerations when using large data sources, the role of peer review and working in partnership with regulatory agencies. RESULTS: We suggest that plans for analyses, dissemination and risk communication are done best a priori and not post hoc. CONCLUSION: Rigorous research evaluating the impact of drugs used in pregnancy, coupled with effective dissemination strategies, has the potential improve outcomes for mothers and their infants for generations.
Tea consumption is not associated with reduced plasma folate concentration among Chinese pregnant women.
Liu J, Jin L, Zhang Y … +5 more , Zhang L, Li Z, Wang L, Ye R, Ren A
Birth Defects Res A Clin Mol Teratol · 2015 Sep · PMID 26119069 · Publisher ↗
BACKGROUND: The aim of this study was to evaluate the relationship between tea consumption and plasma folate concentration in populations with high and low prevalence of neural tube defects (NTDs) in China. METHODS: Cros...
BACKGROUND: The aim of this study was to evaluate the relationship between tea consumption and plasma folate concentration in populations with high and low prevalence of neural tube defects (NTDs) in China. METHODS: Cross-sectional survey was conducted in three cities/counties in China, in which 1724 pregnant women during early second trimester were recruited and interviewed about tea consumption and folic acid use in 2011 to 2012. A total of 5-ml nonfasting blood sample was collected and plasma folate concentration was determined by microbiological assay. RESULTS: Approximately 16.2% of the women reported that they had ever drank tea during and before the current pregnancy, women with higher educational level, and those who resided in urban were more likely to drink tea. Most of them prefer green tea (55.2%); 13.6% of women drank tea ">6 times/week," and 29.0% of them drank "less than once a week." The median of plasma folate concentration was 48.7 nmol/L in women who drank tea while it is 45.2 nmol/L in women who did not drink tea, with no statistical difference. The results showed there was no association between tea drinking and plasma folate concentration in Chinese pregnant women stratified by folic acid supplementation and other selected characteristics. CONCLUSION: Low level of tea drinking is not associated with decreased plasma folate concentration in the Chinese populations with high and low prevalence of NTDs.
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