Birth Defects Research. Part A, Clinical And Molecular Teratology[JOURNAL]
Sun
200 papers
Novel COL4A1 mutation in an infant with severe dysmorphic syndrome with schizencephaly, periventricular calcifications, and cataract resembling congenital infection.
Smigiel R, Cabala M, Jakubiak A … +5 more , Kodera H, Sasiadek MJ, Matsumoto N, Sasiadek MM, Saitsu H
Birth Defects Res A Clin Mol Teratol · 2016 Apr · PMID 26879631 · Publisher ↗
BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, an...
BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. METHODS: TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. RESULTS: Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV α1α1α2 heterotrimers. The mutation was predicted to be damaging. CONCLUSION: We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors.
Interaction between MTHFR 677C>T and periconceptional folic acid supplementation in the risk of Hypospadias.
Dokter EM, van Rooij IA, Wijers CH … +5 more , Groothuismink JM, van der Biezen JJ, Feitz WF, Roeleveld N, van der Zanden LF
Birth Defects Res A Clin Mol Teratol · 2016 Apr · PMID 26879531 · Publisher ↗
BACKGROUND: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the develop...
BACKGROUND: Hypospadias is a congenital malformation with both environmental factors and genetic predisposition involved in the pathogenesis. The role of maternal periconceptional folic acid supplement use in the development of hypospadias is unclear. As folate levels may also be influenced by the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, we hypothesize that a gene-environment interaction between this polymorphism and folic acid use is involved in the etiology of hypospadias. METHODS: We conducted a case-control study among 855 hypospadias cases and 713 population-based controls from the AGORA data- and biobank. Folic acid supplement use was derived from maternal questionnaires and infant and maternal DNA was used to determine the MTHFR C677T polymorphism using Taqman assays. We performed separate analyses for different hypospadias phenotypes (anterior/middle/posterior). RESULTS: Hypospadias was neither associated with folic acid use or the MTHFR C677T polymorphism, nor with their interaction. However, we did find an association with middle hypospadias when no supplements were used (odds ratio = 1.6; 95% confidence interval, 1.1-2.4), especially in infants carrying the CT/TT genotype (odds ratio = 2.5; 95% confidence interval, 1.4-4.7). In addition, more infants with these genotypes seemed to have posterior hypospadias, regardless of folic acid use. CONCLUSION: Our study does not suggest a major role for folic acid supplements or the MTHFR C677T polymorphism in the etiology of hypospadias in general, but not using folic acid and/or carrying the MTHFR C677T polymorphism may be associated with middle and posterior hypospadias. Therefore, we stress the importance of studying gene-environment interactions preferably in stratified analyses for different hypospadias phenotypes.
Prevalence and trend of neural tube defects in five counties in Shanxi province of Northern China, 2000 to 2014.
Liu J, Zhang L, Li Z … +5 more , Jin L, Zhang Y, Ye R, Liu J, Ren A
Birth Defects Res A Clin Mol Teratol · 2016 Apr · PMID 26879384 · Publisher ↗
BACKGROUND: The prevalence of neural tube defects (NTDs) in northern China is among the highest in the world. A massive folic acid supplementation program as a specific countermeasure was introduced in 2009. Examining tr...
BACKGROUND: The prevalence of neural tube defects (NTDs) in northern China is among the highest in the world. A massive folic acid supplementation program as a specific countermeasure was introduced in 2009. Examining trends in NTD prevalence may provide evidence for future intervention. METHODS: Data for 2000 to 2014 in five counties in northern China were obtained through a population-based birth defects surveillance system. All live births, stillbirths of over 20 gestational weeks, and pregnancy terminations because of NTDs at any gestational age were recorded. The prevalence of NTDs by gestational weeks (< 28 vs. ≥ 28), by calendar year, and by subtype was presented. RESULTS: From 2000 to 2014, a total of 234,225 births and 2027 cases of NTDs were recorded. The prevalence of total NTDs was extremely high during 2000 to 2004, but it began to decrease continuously thereafter, from a peak of 120.0/10,000 in 2004 to a low of 31.5/10,000 in 2014. A significant decrease (60%) was observed from 78.8/10,000 in 2009 to 31.5/10,000 in 2014, 5 years after the folic acid supplementation program was introduced. All three major subtypes, namely anencephaly, spina bifida, and encephalocele, showed a decline over this period. Although the perinatal (≥ 28 gestational weeks) prevalence of NTDs decreased progressively, the pre-perinatal (< 28 gestational weeks) prevalence of NTDs remained high until 2011 and then decreased. CONCLUSION: The prevalence of NTDs remains high despite a substantial and continuous decrease over the past 15 years. To further reduce NTD risk in the population, fortification staples with folic acid should be considered.
Gastroschisis in a fetus with a congenital neuroblastoma: Association or coincidence?
Rosa RF, Michelon L, Masiero Á … +7 more , Faria AE, De Souza VF, Dietrich C, Targa LV, Provenzi VO, Pires SR, Zen PR
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26875914 · Publisher ↗
BACKGROUND: Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common m...
BACKGROUND: Gastroschisis is the most common abdominal wall defect. It is characterized by herniation of the intestine and other abdominal organs through a defect in the abdominal wall. Neuroblastoma is the most common malignant tumor observed during the neonatal period. It is a neuroendocrine tumor derived from neural crest cells that develops into the adrenal gland. CASE: We report on the undescribed association between gastrochisis and congenital neuroblastoma, diagnosised during the prenatal period. The mother was a 20-year-old healthy pregnant woman in her second pregnancy. Obstetric ultrasound examination showed a fetus presenting an abdominal wall defect on the right side of the umbilical cord, compatible with gastroschisis, and a hyperechogenic and spherical solid lesion on the left adrenal gland. Fetal magnetic resonance imaging disclosed similar features associated to a heterogeneous aspect of the liver. The diagnosis of metastatic neuroblastoma was confirmed after birth through liver biopsy. At 2 days of life, the prothrombrin time was abnormal, and the patient needed vitamin K. CONCLUSION: We cannot rule out the possibility that a clotting defect, commonly observed in disseminated malignancies such as a metastatic neuroblastoma may be associated with the etiology of the gastroschisis, as this defect may result from a thrombosis occurring around 3 to 4 weeks of gestation, a period when neuroblasts development occurs into the adrenal medulla. However, we cannot exclude the possibility that both events may have occurred simultaneously by chance.
Elevated congenital anomaly rates and incorporated cesium-137 in the Polissia region of Ukraine.
Wertelecki W, Koerblein A, Ievtushok B … +5 more , Zymak-Zakutnia N, Komov O, Kuznietsov I, Lapchenko S, Sosyniuk Z
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26871487 · Publisher ↗
BACKGROUND: Investigations soon after the 1986 Chornobyl (Chernobyl in Russian) accident of exposed populations residing elsewhere in Europe led government and international agencies to conclude that exposures to cesium-...
BACKGROUND: Investigations soon after the 1986 Chornobyl (Chernobyl in Russian) accident of exposed populations residing elsewhere in Europe led government and international agencies to conclude that exposures to cesium-137 (Cs-137) were not teratogenic. Our observations of elevated population rates of neural tube defects (NTDs) and microcephaly and microphthalmia (M/M) in the Rivne Province in Ukraine, which were among the highest in Europe, prompted this follow-up investigation inclusive of whole-body counts (WBCs) of Cs-137 among ambulatory patients and pregnant women residing in Polissia, the most polluted region in Rivne. METHODS: Yearly (2000-2012) population rates of NTDs and M/M and WBC patterns of ambulatory patients (2001-2010) and pregnant women (2011-2013) in Polissia and non-Polissia regions of Rivne were analyzed. RESULTS: The NTD and M/M population rates in Rivne remain elevated and are statistically significantly higher in Polissia than in non-Polissia. The WBCs among residents in Polissia are statistically significantly higher than among those from non-Polissia. CONCLUSION: NTD and M/M rates are highest in the Polissia region of Rivne and are among the highest in Europe. In Polissia, the WBCs of Cs-137 are above officially set permissible upper limits. The results are based on aggregate data of NTDs and M/Ms and average WBC values. Further investigations of causality of the high rates of NTDs and M/Ms are needed and urgent strengthening policies and implementations to reduce exposures to teratogens, in particular radioactive nuclides and alcohol, and consumption of folic acid supplements are indicated.
Congenital anomalies of the kidney and the urinary tract: A murmansk county birth registry study.
Postoev VA, Grjibovski AM, Kovalenko AA … +3 more , Anda EE, Nieboer E, Odland JØ
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26833755 · Publisher ↗
BACKGROUND: Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects. The combined prevalence in Europe was 3.3 per 1000 in 2012. The risk factors for these anomalies are not...
BACKGROUND: Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects. The combined prevalence in Europe was 3.3 per 1000 in 2012. The risk factors for these anomalies are not clearly identified. The aims of our study were to calculate the birth prevalences of urinary malformations in Murmansk County during 2006 to 2011 and to investigate related prenatal risk factors. METHODS: The Murmansk County Birth Registry was the primary source of information and our study included 50,936 singletons in the examination of structure, prevalence and proportional distribution of CAKUTs. The multivariate analyses of risk factors involved 39,322 newborns. RESULTS: The prevalence of CAKUTs was 4.0 per 1000 newborns (95% confidence interval [CI], 3.4-4.5) and did not change during the study period. The most prevalent malformation was congenital hydronephrosis (14.2% of all cases). Diabetes mellitus or gestational diabetes (odds ratio [OR] = 4.77; 95% CI, 1.16-19.65), acute infections while pregnant (OR = 1.83; 95% CI, 1.14-2.94), the use of medication during pregnancy (OR = 2.03; 95% CI, 1.44-2.82), and conception during the summer (OR = 1.75; 95% CI 1.15-2.66) were significantly associated with higher risk of CAKUTs. CONCLUSION: The overall fourfold enhancement of the occurrence of urinary malformations in Murmansk County for the 2006 to 2011 period showed little annual dependence. During pregnancy, use of medications, infections, pre-existing diabetes mellitus, or gestational diabetes were associated with increased risk of these anomalies, as was conception during summer. Our findings have direct applications in improving prenatal care in Murmansk County and establishing targets for prenatal screening and women's consultations.
Association between maternal aluminum exposure and the risk of congenital heart defects in offspring.
Liu Z, Lin Y, Tian X … +9 more , Li J, Chen X, Yang J, Li X, Deng Y, Li N, Liang J, Li S, Zhu J
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26707789 · Publisher ↗
BACKGROUND: Aluminum (Al) is the third most common element in the earth' s crust and has been reported to be teratogenic. However, there is lack of understanding about the association between maternal aluminum exposure a...
BACKGROUND: Aluminum (Al) is the third most common element in the earth' s crust and has been reported to be teratogenic. However, there is lack of understanding about the association between maternal aluminum exposure and the risks of birth defects such as congenital heart defects (CHDs). METHODS: A multi-center, hospital-based case-control study was performed at four maternal and child tertiary hospitals in China. A total of 223 cases with CHDs and 223 controls without any abnormalities were recruited according to the inclusion and matching criteria. Hair samples were prepared and measured by inductively coupled plasma mass spectrometry (ICP-MS). The correlation between CHDs and maternal aluminum concentrations was estimated by a 1:1 conditional logistic regression. RESULTS: The geometric mean and median of hair aluminum levels in isolated or multiple CHD cases was significantly higher than in controls (p < 0.05). A significant association was found between increased hair aluminum concentrations and the risk of total CHDs in offspring (adjusted odds ration [aOR], 2.32; 95% confidence interval [CI], 1.72-3.13), especially in some subtypes of CHDs, such as septal defects (aOR, 2.17; 95% CI, 1.15-4.10), conotruncal defects (aOR, 5.42; 95%CI, 2.43-12.10), and right ventricular outflow track obstruction (aOR, 2.43; 95% CI, 1.08-5.44). However, there was no statistically significant association with left ventricular outflow track obstruction (aOR, 1.66; 95% CI, 0.95-2.88). CONCLUSION: A high maternal aluminum concentration may significantly increase the risk of delivering a child with a CHD, such as a septal defect, conotruncal heart defect and right-side obstruction.
Acardiac twinning: High resolution three-dimensional reconstruction of a low resistance case.
van Lier MG, Lopriore E, Vandenbussche FP … +6 more , Streekstra GJ, Siebes M, Nikkels PG, Oepkes D, van Gemert MJ, van den Wijngaard JP
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26691208 · Publisher ↗
BACKGROUND: Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin. Although four acardiac mor...
BACKGROUND: Acardiac twinning is a rare anomaly of monochorionic twin pregnancies. Acardiac fetuses lack a functional heart but are passively perfused by arterial blood from their pump co-twin. Although four acardiac morphological types have been classified, the various paths of anatomical and circulatory acardiac twin development, and the potential influence of acardiac size and perfusion flow as possible predictors of pump twin morbidity and mortality are poorly understood. This report presents the first high resolution three-dimensional reconstruction of the vasculature of an acardiac twin by cryomicrotome imaging. CASE: A small, approximately 7.5-cm-diameter ball-shaped acardius amorphous of 30 5/7 weeks had caused pump twin cardiac decompensation that necessitated an emergency cesarian section. The pump twin survived well. The acardiac body had a partially intact vascular system with large diameter arteries and veins and multiple zones that appeared devoid of perfusion. The three-dimensional reconstruction showed neither recognizable organ structures nor identifiable blood vessels except for the umbilical artery and vein. CONCLUSION: Our case showed a small acardiac mass with large diameter vessels and consequential low outflow resistance that caused pump twin complications. This indicates that the development of a method that allows pump twin prognosis is likely more successful if based on the use of acardiac versus pump twin perfusion flows than on body volume ratios.
Impact of prenatal diagnosis on the outcome of patients with a transposition of great arteries: A 24-year population-based study.
Debost-Legrand A, Ouchchane L, Francannet C … +7 more , Goumy C, Perthus I, Beaufrère AM, Gallot D, Lemery D, Lusson JR, Laurichesse-Delmas H
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26690971 · Publisher ↗
BACKGROUND: Transposition of great arteries (TGA) defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections is one of the most common congenital heart defects. Prenatal diag...
BACKGROUND: Transposition of great arteries (TGA) defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections is one of the most common congenital heart defects. Prenatal diagnosis of TGA remains difficult. To determine the impact of antenatal diagnosis we evaluated the sensitivity of antenatal detection and the neonatal mortality of TGA considering two study periods and two major types of TGA. METHODS: A cross-sectional study was performed. Data were collected from a French population-based birth defect registry. From 1988 to 2012, 94 fetuses with TGA were registered. The study period was subdivided into the 1988 to 1999 period and the 2000 to 2012 period. Two types of TGA were considered: isolated TGA (n = 66) and associated TGA (n = 28). A stratified analysis was performed considering the study periods and the types of TGA. RESULTS: Considering the study periods, the sensitivity of prenatal detection of TGA increased significantly (9.8% vs. 51.5%, p = 0.0001). The same trend was found for associated TGA (4.8% vs. 33.3%, p = 0.002) and isolated TGA (21.1% vs. 100%, p < 0.001). A late diagnosis of TGA (7 days after birth) was observed in 13.2% of cases. Neonatal mortality decreased significantly over time for isolated TGA (25.0% vs. 0 p = 0.01). Prenatal diagnosis of both types of TGA did not improve survival. CONCLUSION: We demonstrated that prenatal diagnosis and neonatal mortality of TGA varied greatly according to the malformation type and the study period. This could be explained by an improvement in terms of medical management.
Hospitalization charges for children with birth defects in Texas, 2001 to 2010.
Moffitt KB, Case AP, Farag NH … +1 more , Canfield MA
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26690723 · Publisher ↗
BACKGROUND: State-specific information about hospitalizations of children with birth defects can improve understanding of changes in occurrence, treatment practices, and health care financing policies. This study analyze...
BACKGROUND: State-specific information about hospitalizations of children with birth defects can improve understanding of changes in occurrence, treatment practices, and health care financing policies. This study analyzed aggregated data on hospital charges and length of stay for a large, diverse population. METHODS: We extracted hospitalization data for children diagnosed with birth defects from the Texas Hospital Inpatient Discharge Public Use Data File (2001-2010). Analyses compared total charges and length of stay for children with and without a diagnosis code of any birth defect among 45 standard categories. We also examined trends for total charges by expected payer type. RESULTS: In Texas, 431,296 hospital stays were reported for children with birth defects, with total charges of $24.8 billion. Mean hospital stay for children with birth defects was more than twice that of those without, whereas mean of hospital total charges was approximately six times greater. Pyloric stenosis accounted for the largest number of hospitalizations, followed by certain cardiac defects. Pediatric hospitalizations for birth defects increased 273.7%, compared with a 214.7% increase overall. The percentage of charges with Medicaid as expected payer (2004-2010) ranged from 56.5 to 62.0%. CONCLUSION: Charges associated with these conditions are far greater than those associated with pediatric hospitalizations for other causes, whether in the newborn period or beyond. However, these charges vary depending on specific diagnoses, expected payer source, and year of treatment.
Parental risk factors of anorectal malformations: Analysis with a regional population-based control group.
Zwink N, Rissmann A, Pötzsch S … +3 more , Reutter H, Jenetzky E, CURE-Net Consortium
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26690556 · Publisher ↗
BACKGROUND: Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational di...
BACKGROUND: Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational diabetes, chronic cardiovascular and respiratory diseases, periconceptional folic acid and multivitamin intake. METHODS: Data from the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared with data from the Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg, Germany. Controls were matched to cases by gender and birth year of the child. Crude and adjusted odds ratios (95% confidence intervals) were calculated for potential risk factors using multivariable logistic regression. RESULTS: In total, 158 ARM patients and 474 healthy infants born between 1993 and 2008 in Germany were included. Maternal age at birth of ARM cases and birth plurality were significantly higher and gestational age and weight significantly lower compared with controls (p < 0.0001). We observed significantly increased risks for ARMs associated with maternal smoking before conception and the first trimester of pregnancy (odds ratio = 2.23, 95% confidence interval 1.04-4.79, p = 0.039) and maternal chronic respiratory diseases (odds ratio = 29.25, 95% confidence interval 8.22-104.14, p < 0.0001). No statistically significant increased risk or protective effect was found for the other investigated factors. CONCLUSION: This study suggests an association between the occurrence of ARMs in the offspring and periconceptional maternal smoking as well as maternal chronic respiratory diseases. In addition, there might be a sign of an association for maternal diabetes, although not statistically significant. It can be assumed that the power is far too low to provide reliable estimates.
High doses of alcohol during pregnancy cause DNA damages in osteoblasts of newborns rats.
Carvalho IC, Dutra TP, Andrade DP … +3 more , Balducci I, Pacheco-Soares C, Rocha RF
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26690304 · Publisher ↗
BACKGROUND: Alcohol exerts teratogenic effects and its consumption during pregnancy can cause deficit of bone development. The aim of the current study was to evaluate the genotoxic effects of prenatal exposure to ethano...
BACKGROUND: Alcohol exerts teratogenic effects and its consumption during pregnancy can cause deficit of bone development. The aim of the current study was to evaluate the genotoxic effects of prenatal exposure to ethanol on newborn rat osteoblasts. METHODS: Wistar rats were initially divided into two groups: Ethanol group which received Ethanol 20% V/V in liquid diet and solid diet ad libitum, and Control group, which received solid diet and water ad libitum. Each group received a specific diet for 8 weeks before breeding and throughout three weeks of gestation and the treatment was finished on the day the pups were killed. On the fifth day of life, the pups from each group were killed for removal of the calvaria and isolation of osteogenic cells by sequential enzymatic digestion. The cells were cultured for a maximum period of 14 days. The detection of genotoxic effects of alcohol was investigated by the comet and the micronucleus assay. RESULTS: Micronucleus and comet assay showed significant increases in DNA damage at 7 days in Ethanol group (p = 0.0302, p = 0.0446, respectively). However, at 14 days both assay showed no significant difference between the groups (p = 0.6194, p = 0.8326, respectively). CONCLUSION: Our results showed that prenatal exposure to ethanol induced DNA damage in osteoblasts, as shown by micronucleus formation and higher percentage of DNA in the comet tail. It can be concluded that prenatal exposure to ethanol damages osteoblast DNA in newborns exposed to high doses of ethanol during pregnancy, suggesting that prenatal ethanol consumption has a direct effect on fetal osteoblasts.
Hypothesis acardiac twin pregnancies: Pathophysiology-based hypotheses suggest risk prediction by pump/acardiac umbilical venous diameter ratios.
van Gemert MJ, Pistorius LR, Benirschke K … +5 more , Bonsel GJ, Vandenbussche FP, Paarlberg KM, van den Wijngaard JP, Nikkels PG
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26689996 · Publisher ↗
BACKGROUND: A total of 75% of monozygotic twins share 1 monochorionic placenta where placental anastomoses cause several serious complications, for example, acardiac twinning. Acardiac twins lack cardiac function but gro...
BACKGROUND: A total of 75% of monozygotic twins share 1 monochorionic placenta where placental anastomoses cause several serious complications, for example, acardiac twinning. Acardiac twins lack cardiac function but grow by perfusion of arterial blood from the pump twin. This rare pregnancy has 50% natural pump twin mortality but accurate risk prediction is currently impossible. Recent guidelines suggest prophylactic surgery before 18 weeks, suggesting 50% unnecessary interventions. We hypothesize that (1) adverse pump twin outcome relates to easy-to-measure pump/acardiac umbilical venous diameter (UVD) ratios, representing acardiac perfusion by the pump's excess cardiac output. This hypothesis suggests that (2) UVD-ratios are large, mildly varying in cases without complications but small and decreasing when complications develop, thus predicting that (3) UVD-ratios may allow risk prediction of pump twins. In this exploratory clinical pilot, we tested whether UVD-ratio measurements support these predictions. METHODS: We included 7 uncomplicated (expectant management), 3 elective surgical, and 17 complicated cases (pump decompensation, emergency intervention/delivery or demise). Nine UVD-ratios were measured sonographycally and 18 by pathology. RESULTS: Uncomplicated cases have larger, two serial measurements showing mildly varying UVD-ratios; elective surgical cases show larger UVD-ratios; complicated cases have smaller, two serial measurements showing decreasing UVD-ratios. There were no false-positives, no false-negatives and noncrossing linear trendlines of uncomplicated and complicated cohorts. CONCLUSION: Our data provide first evidence that UVD-ratios allow risk prediction of pump twins. More early uncomplicated and late complicated cases are needed, for example, in a prospective trial, before the separation between uncomplicated and complicated cohorts is accurate enough to support a well-founded decision on (early) intervention.
Residential agricultural pesticide exposures and risks of selected birth defects among offspring in the San Joaquin Valley of California.
Carmichael SL, Yang W, Roberts E … +5 more , Kegley SE, Brown TJ, English PB, Lammer EJ, Shaw GM
Birth Defects Res A Clin Mol Teratol · 2016 Jan · PMID 26689858 · Publisher ↗
BACKGROUND: We examined associations of birth defects with residential proximity to commercial agricultural pesticide applications in California. Subjects included 367 cases representing five types of birth defects and 7...
BACKGROUND: We examined associations of birth defects with residential proximity to commercial agricultural pesticide applications in California. Subjects included 367 cases representing five types of birth defects and 785 nonmalformed controls born 1997 to 2006. METHODS: Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for covariates. Overall, 46% of cases and 38% of controls were classified as exposed to pesticides within a 500 m radius of mother's address during a 3-month periconceptional window. RESULTS: We estimated odds ratios (ORs) for 85 groups and 95 chemicals with five or more exposed cases and control mothers. Ninety-five percent confidence intervals (CI) excluded 1.0 for 11 ORs for groups and 22 ORs for chemicals, ranging from 1.9 to 3.1 for groups and 1.8 to 4.9 for chemicals except for two that were <1 (noted below). CONCLUSION: For groups, these ORs were for anotia/microtia (n = 95 cases) and dichlorophenoxy acids/esters and neonicotinoids; anorectal atresia/stenosis (n = 77) and alcohol/ethers and organophosphates (these ORs were < 1.0); transverse limb deficiencies (n = 59) and dichlorophenoxy acids/esters, petroleum derivatives, and triazines; and craniosynostosis (n = 79) and alcohol/ethers, avermectins, neonicotinoids, and organophosphates. For chemicals, ORs were: anotia/microtia and five pesticides from the groups dichlorophenoxy acids/esters, copper-containing compounds, neonicotinoids, organophosphates, and triazines; transverse limb deficiency and six pesticides - oxyfluorfen and pesticides from the groups copper-containing compounds, 2,6-dinitroanilines, neonicotinoids, petroleum derivatives and polyalkyloxy compounds; craniosynostosis and 10 pesticides - oxyfluorfen and pesticides from the groups alcohol/ethers, avermectins, n-methyl-carbamates, neonicotinoids, ogranophosphates (two chemicals), polyalkyloxy compounds (two chemicals), and pyrethroids; and congenital diaphragmatic hernia (n = 62) and a copper-containing compound.
Epidemiologic characteristics and time trend in the prevalence of anotia and microtia in China.
Deng K, Dai L, Yi L … +3 more , Deng C, Li X, Zhu J
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26681129 · Publisher ↗
BACKGROUND: Previous studies have shown an inconsistent time trend on the prevalence of anotia and microtia. Little has been reported on the epidemiologic characteristics of anotia and microtia in the Chinese population....
BACKGROUND: Previous studies have shown an inconsistent time trend on the prevalence of anotia and microtia. Little has been reported on the epidemiologic characteristics of anotia and microtia in the Chinese population. METHODS: Data from 1996-2007 were obtained from the Chinese Birth Defects Monitoring Network in China. Birth prevalence of anotia and microtia were assessed according to demographic characteristics and annual time trend. Poisson regression was used to calculate crude and adjusted prevalence ratios (APRs) and 95% confidence intervals (CIs) for selected demographic characteristics and subgroups of anotia and microtia. RESULTS: A total of 1933 cases with anotia/microtia were identified among 6,308,594 live births, stillbirths, and terminations of pregnancy, yielding a rate of 3.06 per 10,000 births. Isolated anotia/microtia had a prevalence of 2.25 per 10,000 births, whereas among nonisolated cases, the prevalence was 0.81 per 10,000 births. The prevalence rates of anotia/microtia increased significantly during 1996-2007 (p < 0.05). Birth prevalence of isolated anotia/microtia was significantly higher among western births (APR, 1.24; 95% CI, 1.10-1.40), mothers residing in urban areas (APR, 1.29; 95% CI, 1.15-1.46), mothers more than 35 years of age (APR, 1.26; 95% CI, 1.01-1.57), and males (APR, 1.38; 95% CI, 1.24-1.53). No significant associations were observed between nonisolated anotia/microtia and geographic areas, maternal residence, and infant sex (except for maternal age). CONCLUSION: An increasing trend of the birth prevalence of anotia and microtia is observed in China. Higher prevalence risk of isolated anotia and microtia is found among western births, mothers residing in urban areas, older mothers, and males.
Array-based molecular karyotyping in fetal brain malformations: Identification of novel candidate genes and chromosomal regions.
Krutzke SK, Engels H, Hofmann A … +8 more , Schumann MM, Cremer K, Zink AM, Hilger A, Ludwig M, Gembruch U, Reutter H, Merz WM
Birth Defects Res A Clin Mol Teratol · 2016 Jan · PMID 26680650 · Publisher ↗
BACKGROUND: For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS: Here, we used array-base...
BACKGROUND: For the majority of congenital brain malformations, the underlying cause remains unknown. Recent studies have implicated rare copy number variations (CNVs) in their etiology. METHODS: Here, we used array-based molecular karyotyping to search for causative CNVs in 33 fetuses of terminated pregnancies with prenatally detected brain malformations and additional extracerebral anomalies. RESULTS: In 11 fetuses, we identified 15 CNVs (0.08 Mb to 29.59 Mb), comprising four duplications and eleven deletions. All larger CNVs (> 5 Mb) had also been detected by prenatal conventional karyotyping. None of these CNVs was present in our 1307 healthy in-house controls (frequency < 0.0008). Among these CNVs, we prioritized six chromosomal regions (1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, 18q21.1) due to their previous association with human brain malformations or owing to the presence of a single gene expressed in human brain. Prioritized genes within these regions were UBTD2, SKA1, SVIP, and, most convincingly, GPR52. However, re-sequencing of GPR52 in 100 samples from fetuses with brain malformations or patients with intellectual disability and brain malformations revealed no disease-causing mutation. CONCLUSION: Our study suggests chromosomal regions 1q25.1, 5q35.1, 6q25.3-qter, 11p14.3, 15q11.2-q13.1, and 18q21.1 to be involved in human brain development. Within three of these regions, we suggest UBTD2, GPR52, and SKA1 as possible candidate genes. Because the overall detection rate of array-based molecular karyotyping was slightly higher (23%) than that of conventional prenatal karyotyping (20%), we suggest it's use for prenatal diagnostic testing in fetuses with nonisolated brain malformations.
Long-term survival for infants born with orofacial clefts in Western Australia.
Bell JC, Nassar N, Bower C … +2 more , Turner RM, Raynes-Greenow C
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26663708 · Publisher ↗
BACKGROUND: Only two population-based studies have reported survival beyond 15 years for individuals with orofacial clefts (OFC), and only for individuals with isolated OFC. Compared with the general population, long-ter...
BACKGROUND: Only two population-based studies have reported survival beyond 15 years for individuals with orofacial clefts (OFC), and only for individuals with isolated OFC. Compared with the general population, long-term survival was similar for individuals with cleft lip only, and lower for individuals with cleft palate only. Results for those born with isolated cleft lip and cleft palate were inconsistent. METHODS: Using linked population-based health data, including a congenital anomaly register with active surveillance and diagnoses up to 6 years, we compared survival at 1, 5, and 20 years for infants born 1980 to 2010 with, and without OFC. RESULTS: Of the 8112 live born infants in the cohort, 186 died before 20 years; most (81%) died during infancy. Compared with infants without OFC, infants born with all types of isolated OFC ± additional minor anomalies had similar infant survival (around 99%), but we found lower survival for infants with all cleft types and an additional major anomaly (66-84%). From 1 to 5 years, only infants with cleft palate only and an additional major anomaly had lower survival (97%) compared with children without OFC (99.9%). From 5 to 20 years, children with all cleft types, with or without additional major anomalies had similar survival to children without OFC (98-100%). CONCLUSION: Parents with a child diagnosed with an OFC ± additional minor anomalies only can be reassured that the OFC does not influence survival rates in infancy, or long-term. Infant survival was lower only for children with OFC and additional major anomalies.
Clinical, genetic and neuropathological findings in a series of 138 fetuses with a corpus callosum malformation.
Alby C, Malan V, Boutaud L … +13 more , Marangoni MA, Bessières B, Bonniere M, Ichkou A, Elkhartoufi N, Bahi-Buisson N, Sonigo P, Millischer AE, Thomas S, Ville Y, Vekemans M, Encha-Razavi F, Attié-Bitach T
Birth Defects Res A Clin Mol Teratol · 2016 Jan · PMID 26663670 · Publisher ↗
BACKGROUND: Corpus callosum malformation (CCM) is the most frequent brain malformation observed at birth. Because CCM is a highly heterogeneous condition, the prognosis of fetuses diagnosed prenatally remains uncertain,...
BACKGROUND: Corpus callosum malformation (CCM) is the most frequent brain malformation observed at birth. Because CCM is a highly heterogeneous condition, the prognosis of fetuses diagnosed prenatally remains uncertain, making prenatal counseling difficult. METHODS AND RESULTS: We evaluated retrospectively a total of 138 fetuses, 117 with CCM observed on prenatal imaging examination, and 21 after postmortem autopsy. On ultrasound and/or magnetic resonance imaging, CCM was either isolated (N = 40) or associated with other neurological (N = 57) or extra cerebral findings (N = 21/20, respectively). RESULTS: Most fetuses (N = 132) remained without a diagnosis at the time of pregnancy termination. This emphasizes the need to establish a neuropathological classification and to perform a genomic screening using comparative genomic hybridization. A neuropathological examination performed on 138 cases revealed a spectrum of CCMs, classified as follows: agenesis of corpus callosum (55), CC hypoplasia (30), CC dysmorphism (24), and CCM associated with a malformation of cortical development (29). Of interest, after fetopathological examination, only 16/40 malformations were classified as isolated, highlighting the importance of the autopsy following termination of pregnancy. Among the 138 cases, the underlying etiology was found in 46 cases: diabetes (one case), cytomegalovirus infection (one case), 23 chromosome abnormalities, and 21 mendelian conditions. CONCLUSION: In our series of 138 cases of CCM, prenatal and postmortem examinations identified a variety of genetic causes. However, no diagnosis could be established in 67% of cases. The classification based on the underlying neurodevelopmental defects paves the way for further genetic studies and genotype-phenotype correlations.
Elevated body mass index and decreased diet quality among women and risk of birth defects in their offspring.
Carmichael SL, Yang W, Gilboa S … +6 more , Ailes E, Correa A, Botto LD, Feldkamp ML, Shaw GM, National Birth Defects Prevention Study
Birth Defects Res A Clin Mol Teratol · 2016 Mar · PMID 26663631 · Full text
BACKGROUND: We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of t...
BACKGROUND: We examined whether risks of 32 birth defects were higher than expected in the presence of overweight or obese body mass index (BMI) and low diet quality, based on estimating individual and joint effects of these factors and calculating relative excess risk due to interaction. METHODS: Analyses included mothers of 20,250 cases with birth defects and 8617 population-based controls without birth defects born from 1997 to 2009 and interviewed for the National Birth Defects Prevention Study. We used logistic regression to generate adjusted odds ratios (AORs) reflecting the combined effects of BMI and diet quality. We focused analyses on 16 birth defects (n = 11,868 cases, 8617 controls) for which initial results suggested an association with BMI or diet quality. RESULTS: Relative to the reference group (normal weight women with not low diet quality, i.e., >lowest quartile), AORs for low diet quality among normal weight women tended to be >1, and AORs for overweight and obese women tended to be stronger among women who had low diet quality than not low diet quality. For 9/16 birth defects, AORs for obese women who had low diet quality-the group we hypothesized to have highest risk-were higher than other stratum-specific AORs. Most relative excess risk due to interactions were positive but small (<0.5), with confidence intervals that included zero. CONCLUSION: These findings provide evidence for the hypothesis of highest birth defect risks among offspring to women who are obese and have low diet quality but insufficient evidence for an interaction of these factors in their contribution to risk.
Cell death and cell proliferation in human spina bifida.
Avagliano L, Doi P, Tosi D … +8 more , Scagliotti V, Gualtieri A, Gaston-Massuet C, Pistocchi A, Gallina A, Marconi AM, Bulfamante G, Massa V
Birth Defects Res A Clin Mol Teratol · 2016 Feb · PMID 26663582 · Publisher ↗
BACKGROUND: Spina bifida is a multifactorial congenital malformation of the central nervous system. The aim of this study was to ascertain the relevance of cell death/proliferation balance in human spina bifida and to as...
BACKGROUND: Spina bifida is a multifactorial congenital malformation of the central nervous system. The aim of this study was to ascertain the relevance of cell death/proliferation balance in human spina bifida and to assess autophagy distribution and levels during embryo-fetal development in neural tissue. METHODS: Five human cases with myelomeningocoele were compared with 10 healthy human controls and LC3 protein expression was also analyzed in mouse embryos. Cell death was evaluated using TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling) assay; cell proliferation was studied by counting Ki67-positive cells, and autophagy was assessed by observing the presence of LC3 punctuate dots. RESULTS: Comparing human cases and controls (13 to 21 weeks of gestation), we observed a significant increase in TUNEL-positive cells in human spina bifida associated with a significantly decreased proliferation rate, indicating an alteration of the physiological cell rate homeostasis. LC3 distribution was found to be spatiotemporally regulated in both human and murine embryo-fetuses: in early pregnancy a diffuse and ubiquitous LC3 signal was detected. After neural tube closure, an intense LC3-positive signal, normally associated to extra energy requirement, was confined to the Lissauer's tract, the dorsolateral spinal zone containing centrally projecting axons from dorsal root ganglia, at any medullar levels. LC3 signal disappeared from 12 weeks of gestation. CONCLUSION: In conclusion, this study confirms the fundamental role of cell death/proliferation balance during central nervous system development and reports the changing expression of LC3 protein in mouse and human neural tube. Birth Defects Research (Part A) 106:104-113, 2016. © 2015 Wiley Periodicals, Inc.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe