Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

A multi-program analysis of cleft lip with cleft palate prevalence and mortality using data from 22 International Clearinghouse for Birth Defects Surveillance and Research programs, 1974-2014.

BACKGROUND: Cleft lip with cleft palate (CLP) is a congenital condition that affects both the oral cavity and the lips. This study estimated the prevalence and mortality of CLP using surveillance data collected from birth defect registries around the world. METHODS: Data from 22 population- and hospital-based surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) in 18 countries on live births (LB), stillbirths (SB), and elective terminations of pregnancy for fetal anomaly (ETOPFA) for CLP from 1974 to 2014 were analyzed. Prevalence and survival (survival for LB only) estimates were calculated for total and subclassifications of CLP and by pregnancy outcome. RESULTS: The pooled prevalence of total CLP cases was 6.4 CLP per 10,000 births. The prevalence of CLP and all of the pregnancy outcomes varied across programs. Higher ETOPFA rates were recorded in most European programs compared to programs in other continents. In programs reporting low ETOPFA rates or where there was no ascertainment of ETOPFA, the rate of CLP among LB and SB was higher compared to those where ETOPFA rates were ascertained. Overall survival for total CLP was 91%. For isolated CLP, the survival was 97.7%. CLP associated with multiple congenital anomalies had an overall survival of 77.1%, and for CLP associated with genetic/chromosomal syndromes, overall survival was 40.9%. CONCLUSIONS: Total CLP prevalence reported in this study is lower than estimates from prior studies, with variation by pregnancy outcomes between programs. Survival was lower when CLP was associated with other congenital anomalies or syndromes compared to isolated CLP.

Prevalence and mortality among children with anorectal malformation: A multi-country analysis.

PURPOSE: We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.

A Multicountry Analysis of Prevalence and Mortality among Neonates and Children with Bladder Exstrophy.

OBJECTIVE: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. STUDY DESIGN: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. RESULTS: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. CONCLUSIONS: Prevalence of BE varied by program and showed a decreasing trend from 2000 to -2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. KEY POINTS: · Total prevalence of BE was 2.58 per 100,000 births.. · Prevalence decreased from 2000 to 2014.. · The first-week mortality was 9.3%..

Analysis of early neonatal case fatality rate among newborns with congenital hydrocephalus, a 2000-2014 multi-country registry-based study.

BACKGROUND: Congenital hydrocephalus (CH) comprises a heterogeneous group of birth anomalies with a wide-ranging prevalence across geographic regions and registry type. The aim of the present study was to analyze the early neonatal case fatality rate (CFR) and total birth prevalence of newborns diagnosed with CH. METHODS: Data were provided by 25 registries from four continents participating in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) on births ascertained between 2000 and 2014. Two CH rates were calculated using a Poisson distribution: early neonatal CFR (death within 7 days) per 100 liveborn CH cases (CFR) and total birth prevalence rate (BPR) per 10,000 births (including live births and stillbirths) (BPR). Heterogeneity between registries was calculated using a meta-analysis approach with random effects. Temporal trends in CFR and BPR within registries were evaluated through Poisson regression modeling. RESULTS: A total of 13,112 CH cases among 19,293,280 total births were analyzed. The early neonatal CFR was 5.9 per 100 liveborn cases, 95% confidence interval (CI): 5.4-6.8. The CFR among syndromic cases was 2.7 times (95% CI: 2.2-3.3) higher than among non-syndromic cases (10.4% [95% CI: 9.3-11.7] and 4.4% [95% CI: 3.7-5.2], respectively). The total BPR was 6.8 per 10,000 births (95% CI: 6.7-6.9). Stratified by elective termination of pregnancy for fetal anomalies (ETOPFA), region and system, higher CFR were observed alongside higher BPR rates. The early neonatal CFR and total BPR did not show temporal variation, with the exception of a CFR decrease in one registry. CONCLUSIONS: Findings of early neonatal CFR and total BPR were highly heterogeneous among registries participating in ICBDSR. Most registries with higher CFR also had higher BPR. Differences were attributable to type of registry (hospital-based vs. population-based), ETOPFA (allowed yes or no) and geographical regions. These findings contribute to the understanding of regional differences of CH occurrence and early neonatal deaths.

Survival of infants born with esophageal atresia among 24 international birth defects surveillance programs.

BACKGROUND: Esophageal atresia (EA) affects around 2.3-2.6 per 10,000 births world-wide. Infants born with this condition require surgical correction soon after birth. Most survival studies of infants with EA are locally or regionally based. We aimed to describe survival across multiple world regions. METHODS: We included infants diagnosed with EA between 1980 and 2015 from 24 birth defects surveillance programs that are members of the International Clearinghouse for Birth Defects Surveillance and Research. We calculated survival as the proportion of liveborn infants alive at 1 month, 1- and 5-years, among all infants with EA, those with isolated EA, those with EA and additional anomalies or EA and a chromosomal anomaly or genetic syndrome. We also investigated trends in survival over the decades, 1980s-2010s. RESULTS: We included 6,466 liveborn infants with EA. Survival was 89.4% (95% CI 88.1-90.5) at 1-month, 84.5% (95% CI 83.0-85.9) at 1-year and 82.7% (95% CI 81.2-84.2) at 5-years. One-month survival for infants with isolated EA (97.1%) was higher than for infants with additional anomalies (89.7%) or infants with chromosomal or genetic syndrome diagnoses (57.3%) with little change at 1- and 5-years. Survival at 1 month improved from the 1980s to the 2010s, by 6.5% for infants with isolated EA and by 21.5% for infants with EA and additional anomalies. CONCLUSIONS: Almost all infants with isolated EA survived to 5 years. Mortality was higher for infants with EA and an additional anomaly, including chromosomal or genetic syndromes. Survival improved from the 1980s, particularly for those with additional anomalies.

Prevalence and mortality in children with congenital diaphragmatic hernia: a multicountry study.

PURPOSE: This study determined the prevalence, mortality, and time trends of children with congenital diaphragmatic hernia (CDH). METHODS: Twenty-five hospital- and population-based surveillance programs in 19 International Clearinghouse for Birth Defects Surveillance and Research member countries provided birth defects mortality data between 1974 and 2015. CDH cases included live births, stillbirths, or elective termination of pregnancy for fetal anomalies. Prevalence, cumulative mortality rates, and 95% confidence intervals (CIs) were calculated using Poisson regression and a Kaplan-Meier product-limit method. Joinpoint regression analyses were conducted to assess time trends. RESULTS: The prevalence of CDH was 2.6 per 10,000 total births (95% CI: 2.5-2.7), slightly increasing between 2001 and 2012 (average annual percent change = 0.5%; 95% CI:-0.6 to 1.6). The total percent mortality of CDH was 37.7%, with hospital-based registries having more deaths among live births than population-based registries (45.1% vs. 33.8%). Mortality rates decreased over time (average annual percent change = -2.4%; 95% CI: -3.8 to 1.1). Most deaths due to CDH occurred among 2- to 6-day-old infants for both registry types (36.3%, hospital-based; 12.1%, population-based). CONCLUSIONS: The mortality of CDH has decreased over time. Mortality remains high during the first week and varied by registry type.

A multi-country study of prevalence and early childhood mortality among children with omphalocele.

BACKGROUND: Omphalocele is the second most common abdominal birth defect and often occurs with other structural and genetic defects. The objective of this study was to determine omphalocele prevalence, time trends, and mortality during early childhood, by geographical region, and the presence of associated anomalies. METHODS: We conducted a retrospective study with 23 birth defect surveillance systems in 18 countries who are members of the International Clearinghouse for Birth Defects Surveillance and Research that submitted data on cases ascertained from 2000 through 2012, approximately 16 million pregnancies were surveyed that resulted in live births, stillbirths, or elective terminations of pregnancy for fetal anomalies (ETOPFA) and cases with omphalocele were included. Overall prevalence and mortality rates for specific ages were calculated (day of birth, neonatal, infant, and early childhood). We used Kaplan-Meier estimates with 95% confidence intervals (CI) to calculate cumulative mortality and joinpoint regression for time trend analyses. RESULTS: The prevalence of omphalocele was 2.6 per 10,000 births (95% CI: 2.5, 2.7) and showed no temporal change from 2000-2012 (average annual percent change = -0.19%, p = .52). The overall mortality rate was 32.1% (95% CI: 30.2, 34.0). Most deaths occurred during the neonatal period and among children with multiple anomalies or syndromic omphalocele. Prevalence and mortality varied by registry type (e.g., hospital- vs. population-based) and inclusion or exclusion of ETOPFA. CONCLUSIONS: The prevalence of omphalocele showed no temporal change from 2000-2012. Approximately one-third of children with omphalocele did not survive early childhood with most deaths occurring in the neonatal period.

Correction to: Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

In the original publication, the starting point in time for the three feeding trials.

Trisomy 13 and 18-Prevalence and mortality-A multi-registry population based analysis.

The aim of the study is to determine the prevalence, outcomes, and survival (among live births [LB]), in pregnancies diagnosed with trisomy 13 (T13) and 18 (T18), by congenital anomaly register and region. Twenty-four population- and hospital-based birth defects surveillance registers from 18 countries, contributed data on T13 and T18 between 1974 and 2014 using a common data-reporting protocol. The mean total birth prevalence (i.e., LB, stillbirths, and elective termination of pregnancy for fetal anomalies [ETOPFA]) in the registers with ETOPFA (n = 15) for T13 was 1.68 (95% CI 1.3-2.06), and for T18 was 4.08 (95% CI 3.01-5.15), per 10,000 births. The prevalence varied among the various registers. The mean prevalence among LB in all registers for T13 was 0.55 (95%CI 0.38-0.72), and for T18 was 1.07 (95% CI 0.77-1.38), per 10,000 births. The median mortality in the first week of life was 48% for T13 and 42% for T18, across all registers, half of which occurred on the first day of life. Across 16 registers with complete 1-year follow-up, mortality in first year of life was 87% for T13 and 88% for T18. This study provides an international perspective on prevalence and mortality of T13 and T18. Overall outcomes and survival among LB were poor with about half of live born infants not surviving first week of life; nevertheless about 10% survived the first year of life. Prevalence and outcomes varied by country and termination policies. The study highlights the variation in screening, data collection, and reporting practices for these conditions.

Analysis of Mortality among Neonates and Children with Spina Bifida: An International Registry-Based Study, 2001-2012.

BACKGROUND: Medical advancements have resulted in better survival and life expectancy among those with spina bifida, but a significantly increased risk of perinatal and postnatal mortality for individuals with spina bifida remains. OBJECTIVES: To examine stillbirth and infant and child mortality among those affected by spina bifida using data from multiple countries. METHODS: We conducted an observational study, using data from 24 population- and hospital-based surveillance registries in 18 countries contributing as members of the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). Cases of spina bifida that resulted in livebirths or stillbirths from 20 weeks' gestation or elective termination of pregnancy for fetal anomaly (ETOPFA) were included. Among liveborn spina bifida cases, we calculated mortality at different ages as number of deaths among liveborn cases divided by total number of liveborn cases with spina bifida. As a secondary outcome measure, we estimated the prevalence of spina bifida per 10 000 total births. The 95% confidence interval for the prevalence estimate was estimated using the Poisson approximation of binomial distribution. RESULTS: Between years 2001 and 2012, the overall first-week mortality proportion was 6.9% (95% CI 6.3, 7.7) and was lower in programmes operating in countries with policies that allowed ETOPFA compared with their counterparts (5.9% vs. 8.4%). The majority of first-week mortality occurred on the first day of life. In programmes where information on long-term mortality was available through linkage to administrative databases, survival at 5 years of age was 90%-96% in Europe, and 86%-96% in North America. CONCLUSIONS: Our multi-country study showed a high proportion of stillbirth and infant and child deaths among those with spina bifida. Effective folic acid interventions could prevent many cases of spina bifida, thereby preventing associated childhood morbidity and mortality.

Hypospadias Prevalence and Trends in International Birth Defect Surveillance Systems, 1980-2010.

BACKGROUND: Hypospadias is a common male birth defect that has shown widespread variation in reported prevalence estimates. Many countries have reported increasing trends over recent decades. OBJECTIVE: To analyze the prevalence and trends of hypospadias for 27 international programs over a 31-yr period. DESIGN, SETTING, AND PARTICIPANTS: The study population included live births, stillbirths, and elective terminations of pregnancy diagnosed with hypospadias during 1980-2010 from 27 surveillance programs around the world. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used joinpoint regression to analyze changes over time in international total prevalence of hypospadias across programs, prevalence for each specific program, and prevalence across different degrees of severity of hypospadias. RESULTS AND LIMITATIONS: The international total prevalence of hypospadias for all years was 20.9 (95% confidence interval: 19.2-22.6) per 10000 births. The prevalence for each program ranged from 2.1 to 39.1 per 10000 births. The international total prevalence increased 1.6 times during the study period, by 0.25 cases per 10000 births per year (p<0.05). When analyzed separately, there were increasing trends for first-, second-, and third-degree hypospadias during the early 1990s to mid-2000s. The majority of programs (61.9%) had a significantly increasing trend during many of the years evaluated. Limitations include known differences in data collection methods across programs. CONCLUSIONS: Although there have been changes in clinical practice and registry ascertainment over time in some countries, the consistency in the observed increasing trends across many programs and by degrees of severity suggests that the total prevalence of hypospadias may be increasing in many countries. This observation is contrary to some previous reports that suggested that the total prevalence of hypospadias was no longer increasing in recent decades. PATIENT SUMMARY: We report on the prevalence and trends of hypospadias among 27 birth defect surveillance systems, which indicate that the prevalence of hypospadias continues to increase internationally.

Prenatal diagnosis and prevalence of critical congenital heart defects: an international retrospective cohort study.

OBJECTIVES: To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality. SETTING: Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia. PARTICIPANTS: Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014. RESULTS: 18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases. DISCUSSION AND CONCLUSIONS: Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future.

Lack of adverse effects in subchronic and chronic toxicity/carcinogenicity studies on the glyphosate-resistant genetically modified maize NK603 in Wistar Han RCC rats.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.

One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.

Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE).

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu ) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event.

Long-term (30 days) toxicity of NiO nanoparticles for adult zebrafish Danio rerio.

Nickel oxide in the form of nanoparticles (NiO NPs) is extensively used in different industrial branches. In a test on adult zebrafish, the acute toxicity of NiO NPs was shown to be low, however longlasting contact with this compound can lead to its accumulation in the tissues and to increased toxicity. In this work we determined the 30-day toxicity of NiO NPs using a static test for zebrafish Danio rerio. We found the 30-day LC50 value to be 45.0 mg/L, LC100 (minimum concentration causing 100% mortality) was 100.0 mg/L, and LC0 (maximum concentration causing no mortality) was 6.25 mg/L for adult individuals of zebrafish. Considering a broad use of Ni in the industry, NiO NPs chronic toxicity may have a negative impact on the population of aquatic organisms and on food web dynamics in aquatic systems.

Acute toxicity of 31 different nanoparticles to zebrafish (Danio rerio) tested in adulthood and in early life stages - comparative study.

At present, nanoparticles are beginning to influence our lives in many ways and understanding the environmental health and safety aspect of nanomaterials has become a crucial issue. The aim of the work was to assess and compare the acute toxicity of 31 different nanomaterials to fish mature individuals Danio rerio with that to fish early life stages on using evaluation of the 48- and 96- hour LC50 values. A further aim was to evaluate teratogenicity of the nanoparticles tested to fish eggs. The nanoparticles tested were: 8 pure metals, 10 metal oxides, 5 other metal compounds and their mixtures, 2 silicon compounds, 3 calcium compounds, and 3 carbon compounds. Using 48-h and 96-h tests of acute toxicity (according to OECD 203), we evaluated mortality data, LC50 values, occurrence of malformations, as well as hatching time. In our study, 6 kinds of nanoparticles - calcium oxide, copper, copper in the form of oxide and CuZnFe4O4, magnesium oxide, and nickel - caused cumulative mortality. Two kinds of nanoparticles - copper and silver - were toxic for fish with LC50 values of approximately 3 mg/L. We did not observe marked differences between the 48-hour and 96-hour acute toxicity LC50 values, yet the possibility to evaluate hatching time in the 96-h acute fish toxicity test seems to be an advantage against that of the 48-hour toxicity.

Prevalence of esophageal atresia among 18 international birth defects surveillance programs.

BACKGROUND: The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS: The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS: Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35-2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS: On average, EA affected 1 in 4099 births (95% CI, 1 in 3954-4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. Birth Defects Research (Part A), 2012.

Cyclopia: an epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research.

Cyclopia is characterized by the presence of a single eye, with varying degrees of doubling of the intrinsic ocular structures, located in the middle of the face. It is the severest facial expression of the holoprosencephaly (HPE) spectrum. This study describes the prevalence, associated malformations, and maternal characteristics among cases with cyclopia. Data originated in 20 Clearinghouse (ICBDSR) affiliated birth defect surveillance systems, reported according to a single pre-established protocol. A total of 257 infants with cyclopia were identified. Overall prevalence was 1 in 100,000 births (95%CI: 0.89-1.14), with only one program being out of range. Across sites, there was no correlation between cyclopia prevalence and number of births (r = 0.08; P = 0.75) or proportion of elective termination of pregnancy (r = -0.01; P = 0.97). The higher prevalence of cyclopia among older mothers (older than 34) was not statistically significant. The majority of cases were liveborn (122/200; 61%) and females predominated (male/total: 42%). A substantial proportion of cyclopias (31%) were caused by chromosomal anomalies, mainly trisomy 13. Another 31% of the cases of cyclopias were associated with defects not typically related to HPE, with more hydrocephalus, heterotaxia defects, neural tube defects, and preaxial reduction defects than the chromosomal group, suggesting the presence of ciliopathies or other unrecognized syndromes. Cyclopia is a very rare defect without much variability in prevalence by geographic location. The heterogeneous etiology with a high prevalence of chromosomal abnormalities, and female predominance in HPE, were confirmed, but no effect of increased maternal age or association with twinning was observed.