To estimate the risk of major congenital anomalies after exposure to selective serotonin reuptake inhibitors during pregnancy.
A retrospective cohort study based on national population-based ...registers (years 1996-2006) of births, congenital anomalies, and terminations of pregnancy because of severe fetal anomalies (maintained by National Institute for Health and Welfare, source offspring population n=635,583) and drug reimbursements (Social Insurance Institution) linked by a personal identification number. Offspring exposed to selective serotonin reuptake inhibitors during the first trimester (n=6,976) were compared with unexposed referent offspring.
Overall major congenital anomalies were not more common in selective serotonin reuptake inhibitor-exposed offspring compared with unexposed referent offspring (adjusted odds ratio OR 1.08, 95% confidence interval CI 0.96-1.22). Fluoxetine was associated with an increased risk of isolated ventricular septal defects (adjusted OR 2.03, 95% CI 1.28-3.21) and paroxetine was associated with an increased risk of right ventricular outflow tract defects (adjusted OR 4.68, 95% CI 1.48-14.74). Citalopram use was associated with neural tube defects (adjusted OR 2.46, 95% CI 1.20-5.07). Fetal alcohol spectrum disorders were 10-times more common in the selective serotonin reuptake inhibitor-exposed offspring than in unexposed referent offspring.
Fluoxetine use is associated with an increased risk of isolated ventricular septal defects and paroxetine is associated with right ventricular outflow tract defects. The absolute risk for these specific cardiac anomalies is small but should guide clinicians not to consider fluoxetine or paroxetine the first option when prescribing selective serotonin reuptake inhibitors to women planning pregnancy. Special attention should be given to alcohol use in pregnant women using selective serotonin reuptake inhibitors.
Study question What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in ...Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist?Methods This was a population based, observational study using data on 11 353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends.Summary answer and limitations Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10 000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD.What this study adds In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification.Funding, competing interests, data sharing The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.
Offspring of cancer survivors (CS) may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. Our population‐based cohort study aimed to investigate the risk ...for congenital anomalies in offspring of CS compared to offspring of their siblings. Using the Finnish Cancer Registry, Central Population Register, and Hospital Discharge Register, we identified hospital contacts due to congenital anomalies in 6,862 offspring of CS (early‐onset cancer between 1953 and 2004) and 35,690 offspring of siblings. Associations between congenital anomalies and cancer were evaluated using generalized linear regression modelling. The ratio of congenital anomalies in offspring of CS (3.2%) was slightly, but non‐significantly, elevated compared to that in offspring of siblings (2.7%) prevalence ratio (PR) 1.07, 95% confidence interval (CI) 0.91–1.25. When offspring of childhood and adolescent survivors (0–19 years at cancer diagnosis) were compared to siblings' offspring, the risk for congenital anomalies was non‐significantly increased (PR 1.17, 95% CI 0.92–1.49). No such increase existed for offspring of young adult survivors (20–34 years at cancer diagnosis) (PR 1.01, 95% CI 0.83–1.23). The risks for congenital anomalies were elevated among offspring of CS diagnosed with cancer in the earlier decades (1955–1964: PR 2.77, 95% C I 1.26–6.11; and 1965–1974: PR 1.55, 95% C I 0.94–2.56). In our study, we did not detect an overall elevated risk for congenital anomalies in offspring of survivors diagnosed in young adulthood. An association between cancer exposure of the parent and congenital anomalies in the offspring appeared only for those CS who were diagnosed in the earlier decades.
What's new?
Offspring of cancer survivors may be at risk for congenital anomalies due to the mutagenic therapies received by their parents. This largest population‐based study on female and male early‐onset cancer survivors to date investigated the risk for congenital anomalies in offspring of cancer survivors compared to offspring of their siblings. While an overall elevated risk in offspring of survivors diagnosed in young adulthood was not detected, there was an association between parent cancer and congenital anomalies for survivors diagnosed in the earlier decades. Though the results are reassuring, possible effects of emerging therapies on offspring should continue to be monitored.
Abstract
Background and aims.
Effects of caseload and organization of care on outcomes of biliary atresia (BA) remain unclear. We compared outcomes before and after national centralization of BA ...treatment in Finland with a population of 5.4 million people and 60,000 live births/year.
Methods.
All children born in Finland from 1987 to 2010 with BA were included. Complete patient identification was ascertained from the national Register of Congenital Malformations. Hospital records were reviewed for confirmation of the diagnosis, treatment, and follow-up data. Clearance of jaundice (serum bilirubin ≤20 μmol/l) and survival modalities were compared before and after centralization from five centers to Helsinki.
Results.
The incidence of BA was 1 in 20,100 live births. A total of 72 BA patients of whom 64 had undergone surgery for BA were identified. After centralization, the median caseload per center increased from 0 (range, 0-3) to 4 (2-5) patients/year (p < 0.001), clearance of jaundice rate increased from 27% to 75% (p = 0.001), 2-year jaundice-free native liver survival from 25% to 75% (p = 0.002), transplant-free survival from 27% to 75% (p = 0.005), and overall survival from 64% to 92% (p = 0.082). Baseline patient characteristics including type of BA and age at portoenterostomy remained unaltered. In a logistic regression analysis including treatment era, operating center, BA splenic malformation syndrome, and age at portoenterostomy as variables, only treatment in Helsinki after centralization predicted clearance of jaundice (odds ratio 4.2; 95% confidence interval 1.05-16.5; p = 0.043).
Conclusions.
In small countries, BA treatment should be centralized to appointed multidisciplinary teams allowing high quality results with a median of four cases/year.
To study the occurrence of major congenital anomalies (CAs) among children born after IVF (IVF, microinjections, and frozen embryo transfers) and after ovulation inductions with or without ...insemination (other assisted reproductive technologies ART).
Register-based study.
Data regarding CAs were obtained from the Register of Congenital Malformations.
Children from IVF (n = 4,559), children from other ART (n = 4,467), and controls (n = 27,078, a random sample of naturally conceived children) from the Medical Birth Register.
In vitro fertilization and other ART treatment in ordinary practice.
Rate of major CAs. Children from IVF and other ART were compared with control children, both overall and by plurality, controlling for confounding factors by logistic regression.
For IVF children, the adjusted odds ratio (OR) was 1.3 (95% confidence interval CI, 1.1-1.6). Stratifying by gender and plurality showed that the risk was only increased for boys, and the risk was decreased for multiple IVF girls (OR = 0.5, 95% CI 0.2-0.9). The crude OR of major CA for other ART children was 1.3 (95% CI 1.1-1.5), but adjusted differences by gender and plurality were statistically insignificant.
In vitro fertilization was associated with an increased risk for major CAs among singleton boys and a decreased risk among multiple girls. The risk after other ART was only slightly increased.
Aim
The birth prevalence of sacrococcygeal teratoma (SCT) has been reported to range from 1:27 000 to 1:40 000. We assessed the population‐based prevalence and clinical presentation of SCT over ...22 years.
Methods
We identified all cases of SCT, including live births, stillbirths and terminations of pregnancy (TOPs), in the Finnish Register of Congenital Malformations, covering 1987–2008. Data on prenatal diagnoses, pregnancy outcomes, infant deaths and associated anomalies were collected.
Results
One hundred and twenty four SCT cases were identified among 1 331 699 pregnancies. There were 89 (72%) live births, 13 (10%) stillbirths and 22 (18%) TOPs. The total prevalence of SCT was 1:10 700. Tumours were detected in utero in 55% of the pregnancies with SCT. The proportion of perinatal deaths among all SCT births was 28%. Thirty percentage of the cases had associated abnormalities (mainly of the urinary tract and various syndromes).
Conclusion
This nationwide, population‐based study on SCT shows that the total and birth prevalence of SCT in Finland is markedly higher than previously reported. This may reflect true differences between populations, but may also be explained by accurate nationwide registration of SCTs. The high perinatal mortality rate has an impact on counselling of families and planning of deliveries.
Abstract Objectives To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births ...monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects from 1988 to 1998 in Norway, Finland, Northern Netherlands, England and Wales, Ireland, France (Paris, Strasbourg, and Central East), Hungary, Italy (Emilia Romagna and Campania), Portugal, and Israel. Cases of neural tube defects were ascertained among liveborn infants, stillbirths, and pregnancy terminations (where legal). Policies and recommendations were ascertained by interview and literature review. Main outcome measures Incidences and trends in rates of neural tube defects before and after 1992 (the year of the first recommendations) and before and after the year of local recommendations (when applicable). Results The issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of neural tube defects. Conclusions Recommendations alone did not seem to influence trends in neural tube defects up to six years after the confirmation of the effectiveness of folic acid in clinical trials. New cases of neural tube defects preventable by folic acid continue to accumulate. A reasonable strategy would be to quickly integrate food fortification with fuller implementation of recommendations on supplements.
Summary Objective To compare the characteristics of microtia in Finland and in other populations. Methods Retrospective case series and patient questionnaire of 190 microtia patients referred for ...reconstruction of the earlobe to the Helsinki University Central Hospital during the years 1980–2005. Results The prevalence in Finland is 4.34/10,000 and varied in other populations from 0.83 to 17.4/10,000. Microtia is seen more in males (58%), as unilateral (88.4%), right-sided (59.5%) and it is almost always associated with aural atresia or stenosis (93%). There is conductive hearing loss in 96% and sensorineural hearing loss in 8% of the affected ears. 11% of the patients had congenital heart defects, and 5% had anomalies of extremities. Conclusions There is variation in the prevalence and characteristics of microtia in different populations.
PDF
