The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk ...of gastroschisis in offspring.
PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk RR and the 95% confidence interval CI. I
statistic for heterogeneity and publication bias was calculated.
Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I
= 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I
= 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I
= 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I
= 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I
= 39.4%).
These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
Surveillance of congenital anomalies is important to identify potential teratogens.
This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 ...population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models.
Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing.
The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung 6.5% (3.5% to 9.4%) and decreased prevalence of limb reduction defects -2.8% (-4.2% to -1.5%) are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.
ObjectivesTo 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.SettingFifteen 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.ParticipantsLive 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.Results18 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 conclusionsPrenatal 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.
Rare diseases (RDs) encompass a heterogeneous group of life-threatening or chronically debilitating conditions that individually affect a small number of subjects but overall represent a major public ...health issue globally. There are still limited data on RD burden due to the paucity of large population-based epidemiological studies. The aim of this research was to provide survival estimates of patients with a RD residing in Tuscany, Italy. Cases collected in the Rare Diseases Registry of Tuscany with diagnosis between 1st January 2000 and 31th December 2018 were linked to the regional health databases in order to retrieve information on mortality of all subjects. Survival at 1, 5 and 10 years from diagnosis with 95% confidence intervals (CI) was estimated by sex, age class, nosological group and subgroup using the Kaplan-Meier method. The effect of sex, age and period of diagnosis (years 2000-2009 or 2010-2018) on survival was estimated using Cox proportional hazards regression. Survival at 1, 5 and 10 years from diagnosis was 97.3%, 88.8% and 80.8%, respectively. Respiratory diseases and peripheral and central nervous system disorders were characterized by the lowest survival at 5 and 10 years. Despite a modest higher prevalence of RDs among females (54.0% of the total), male cases had a significant increased risk of death (hazard ratio, HR 1.48, 95% CI 1.38-1.58). Cases diagnosed during 2010-2018 period had a risk of death significantly lower than those diagnosed during 2000-2009 (HR 0.81, 95% CI 0.82-0.96), especially for immune system disorders (HR 0.48, 95% CI 0.26-0.87), circulatory system diseases (HR 0.61, 95% CI 0.45-0.84) and diseases of the musculoskeletal system and connective tissue (HR 0.64, 95% CI 0.49-0.84). An earlier diagnosis as well as the improvement in the efficacy of treatment resulted in a decreased risk of death over the years for specific RDs. The linkage between a population-based registry and other regional databases exploited in this study provides a large and accurate mass of data capable of estimating patients' life-expectancy and increasing knowledge on the collective burden of RDs.
Background/Objectives: Orofacial clefts (OFCs) are some of the most common congenital anomalies worldwide. The aim of this case–control study was to evaluate the association of OFCs with selected ...maternal characteristics. Methods: Data on isolated non-syndromic cases of OFCs were extracted from the population-based registry of congenital anomalies of Tuscany. A sample of live-born infants without any congenital anomaly was used as the control group. We investigated the association with sex and some maternal characteristics: age, body mass index, smoking, and education. Adjusted odds ratios (OR) were calculated using a logistic regression model. Analyses were performed for the total OFCs and separately for cleft lip (CL) and cleft palate (CP). Results: Data on 219 cases and 37,988 controls were analyzed. A higher proportion of males (57.9%) was observed, particularly for CL. A decreasing trend among the maternal age classes was observed (OR:0.81 (95%CI 0.70–0.94)). Underweight mothers had a higher prevalence of OFCs, in particular for CL (OR:1.88 (95%CI 1.08–3.26)). Conclusions: We found an association of OFCs with lower maternal age. The association with maternal age remains controversial and further epidemiological evidence is needed through multicenter studies. We observed that CL was more common in underweight mothers, suggesting actions of primary prevention.
Objectives To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in ...prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies).Design Questionnaire and population based observational study.Setting 24 EUROCAT registries covering 570 000 births annually in 15 countries.Participants Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy for fetal anomaly at any gestation.Main outcome measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries.Results 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ2=338, df=23, I2=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01).Conclusions EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.
IntroductionCongenital anomalies (CAs) are a major cause of infant mortality, childhood morbidity and long-term disability. Over 130 000 children born in Europe every year will have a CA. This paper ...describes the EUROlinkCAT study, which is investigating the health and educational outcomes of children with CAs for the first 10 years of their lives.Methods and analysisEUROCAT is a European network of population-based registries for the epidemiological surveillance of CAs. EUROlinkCAT is using the EUROCAT infrastructure to support 22 EUROCAT registries in 14 countries to link their data on births with CAs to mortality, hospital discharge, prescription and educational databases. Once linked, each registry transforms their case data into a common data model (CDM) format and they are then supplied with common STATA syntax scripts to analyse their data. The resulting aggregate tables and analysis results are submitted to a central results repository (CRR) and meta-analyses are performed to summarise the results across all registries. The CRR currently contains data on 155 594 children with a CA followed up to age 10 from a population of 6 million births from 1995 to 2014.EthicsThe CA registries have the required ethics permissions for routine surveillance and transmission of anonymised data to the EUROCAT central database. Each registry is responsible for applying for and obtaining additional ethics and other permissions required for their participation in EUROlinkCAT.DisseminationThe CDM and associated documentation, including linkage and standardisation procedures, will be available post-EUROlinkCAT thus facilitating future local, national and European-level analyses to improve healthcare. Recommendations to improve the accuracy of routinely collected data will be made.Findings will provide evidence to inform parents, health professionals, public health authorities and national treatment guidelines to optimise diagnosis, prevention and treatment for these children with a view to reducing health inequalities in Europe.
Objective
To investigate the relationship between prepregnancy maternal body mass index (BMI) and congenital anomalies (CAs).
Design
Case‐control study on data collected by the registry of CAs of ...Tuscany (Italy) and birth certificates from 2005 to 2017.
Main exposure
Maternal prepregnancy BMI.
Main outcome measures
Any major CAs and groups of organ‐specific anomalies. Odds ratios (ORs) were estimated using logistic regression models adjusted for maternal factors.
Results
Maternal BMI ≥25 was significantly associated with all nervous system anomalies (OR = 1.61, 95% confidence interval 95% CI 1.13–2.29) and with neural tube defects (OR = 2.03, 95% CI 1.00–4.12); maternal underweight was significantly associated with orofacial clefts (OR = 1.67, 95% CI 1.12–2.48). After stratification by education, in the low education group, mothers with BMI ≥25 had an increased risk of nervous system anomalies (OR = 2.19, 95% CI 1.01–4.76), whereas underweight mothers had an increased risk of nervous system anomalies (OR = 3.89, 95% CI 1.44–10.53), orofacial clefts (OR = 2.59, 95% CI 1.24–5.42), and urinary anomalies (OR = 1.74, 95% CI 1.07–2.82). In the medium/high education group, the only significantly increased risk was found in mothers with BMI ≥25 for nervous system anomalies (OR = 1.50, 95% CI 1.00–2.25).
Conclusion
Main results have shown a positive association of maternal BMI ≥25 with nervous system anomalies and maternal underweight with orofacial clefts. The study has also evidenced the impact of social status and provided clues to the role of maternal ethnic background.
This population-based study aimed to assess the prevalence of congenital hypothyroidism (CH) and overt hypothyroidism (OH) and their association with congenital heart defects (CHDs) in patients with ...Down syndrome (DS). The population included all live births residing in Tuscany (Italy) diagnosed with DS recorded in the Registry of Congenital Defects and in the Registry of Rare Diseases of Tuscany in the years 2003-2017. The prevalence of CH and OH in DS patients was calculated by sex and by period. The association of CH and OH with CHDs in DS patients was assessed using multivariate logistic regression. The cohort included 228 subjects. The prevalence of CH and OH was 11.4% (95%CI: 7.4-16.7%) and 12.7% (95%CI: 8.5-12.3%), respectively, with no significant difference by sex. A significant increase in the prevalence of CH (
< 0.0001) was found in the years 2010-2017 compared to the previous period, and among preterm infants (
= 0.009). The presence of CH was associated with a higher prevalence of CHDs (adjusted OR = 2.24,
= 0.082). A significant association between ventricular septal defects (VSDs) and the occurrence of OH (adjusted OR = 3.07,
= 0.025) was also observed. This study confirmed the higher prevalence of both CH and OH in DS compared to the general population. Furthermore, the risk of association between DS and CHDs was higher in the presence of CH, while VSDs are associated with OH, providing relevant insights into the epidemiology of hypothyroidism in DS and associated anomalies.
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