Drugs use in pregnancy in the Valencia Region and the risk of congenital anomalies

Background Despite the potential risks of drug use during pregnancy, consumption has increased in recent decades. Objective To identify the risk of congenital anomalies (CA) associated with the use of drugs in primary care in pregnant women resident in the Valencia Region. Methods A case-control study, considering a case as a less than one year old live birth in 2009–2010, diagnosed with a CA and resident in the Valencia Region, obtained from the CA population-based registry. Controls were selected from the Metabolic Disease Registry, and the drugs prescribed and dispensed from the Integral Management of Pharmaceutical Services. Crude odds ratio (OR) was calculated with its 95% confidence intervals and adjusted OR was calculated using logistic regression. Results A total of 1.913 cases and 3.826 controls were identified. The most frequently used drug groups were those acting on the musculoskeletal, nervous and respiratory systems, on the blood and blood forming organs, and anti-infection drugs. The most common drugs used were ibuprofen, dexketoprofen, paracetamol, amoxicillin, ferrous sulphate, and a combination of folic acid. A significantly increased risk of CA was identified for drugs acting on the musculoskeletal system (adjusted OR 1.14 [95% confidence interval 1.02–1.28]). A significantly decreased risk was observed for drugs acting on the blood and blood forming organs (adjusted OR 0.87 [95% confidence interval 0.78–0.98]). Conclusions Associations between drugs and CA in pregnant women resident in the Valencia Region have been identified for drugs that act as risk factors of CA, and for drugs that act as protective factors of CA. Antecedentes El consumo de medicamentos durante el embarazo se ha incrementado en las últimas décadas. Objetivo Identificar el riesgo de anomalías congénitas (AC) asociado a la utilización de medicamentos en atención ambulatoria en embarazadas residentes en la Comunitat Valenciana. Métodos Estudio de casos-controles, considerando caso a menores de un año nacidos vivos en 2009-2010 diagnosticados de AC y residentes en la Comunitat Valenciana, obtenidos del registro poblacional de AC. Los controles se seleccionaron del Registro de Metabolopatías y la medicación prescrita y dispensada se obtuvo del módulo Gestión Integral de Prestación Farmacéutica. Se calcularon las odds ratio (OR) y los intervalos de confianza al 95% y las OR ajustadas mediante regresión logística. Resultados Se identificaron 1.913 casos y 3.826 controles. Los grupos de medicamentos más frecuentemente prescritos y dispensados fueron: los que actúan sobre los sistemas musculoesquelético, nervioso, respiratorio, sobre la sangre y órganos hematopoyéticos, y antiinfecciosos. Los medicamentos más habituales fueron: ibuprofeno, dexketoprofeno, paracetamol, amoxicilina, sulfato de hierro y una combinación de ácido fólico. Se identificó un aumento del riesgo de anomalías congénitas significativo para los fármacos de acción sobre el sistema musculoesquelético (OR ajustada de 1,14 [intervalo de confianza al 95% 1,02-1,28]). Se observó una disminución del riesgo significativa en el grupo que actúa sobre la sangre y los órganos hematopoyéticos (OR ajustada de 0,87 [intervalo de confianza al 95% 0,78-0,98]). Conclusiones Se han identificado asociaciones de medicamentos con AC en mujeres embarazadas residentes en la Comunitat Valenciana, tanto para fármacos que actúan como factores de riesgo de AC como para fármacos que actúan como factores protectores de AC

La validez del Conjunto Mínimo Básico de Datos como fuente de identificación de las anomalías congénitas en la Comunitat Valenciana

Objetivo Evaluar la validez del Conjunto Mínimo Básico de Datos (CMBD) para identificar anomalías congénitas mayores en la Comunitat Valenciana. Métodos Se realizó un estudio epidemiológico retrospectivo. Del CMBD se seleccionaron las altas en menores de un año nacidos en 2007, residentes en la Comunitat Valenciana con código de anomalía congénita (740-759 CIE9-MC) y una muestra aleatoria de menores de un año sin altas con estos códigos. Tras revisar la documentación clínica, se clasificaron como verdaderos positivos y negativos y falsos positivos y negativos. Se calcularon el valor predictivo positivo y negativo y la sensibilidad. Se analizaron la concordancia de los diagnósticos entre el CMBD y la documentación clínica utilizando la prueba kappa. Resultados Se identificaron 2305 altas de 1651 pacientes. En los 544 pacientes de la muestra, 4 tenían alguna anomalía congénita mayor. El valor predictivo positivo fue del 56,4% (intervalo de confianza del 95% [IC95%]: 53,9-58,8) y el negativo fue del 99,3% (IC95%: 98,6-100,0). La sensibilidad del CMBD fue del 68,6% (IC95%: 66,1-71,1). Los códigos más frecuentes en los verdaderos positivos fueron: 745.5 (Comunicación interauricular), 745.4 (Comunicación interventricular) y 747.0 (Ductus arterioso persistente), y en los falsos positivos: 747.0, 745.5 y 752.51 (Criptorquidia). El 25,5% de los diagnósticos con anomalía congénita del CMBD no estaban en la historia clínica. Considerando todos los diagnósticos codificados en el CMBD, la concordancia fue de 0,70 (IC95%: 0,68-0,72). Conclusiones El CMBD es la principal fuente de información para la identificación de casos para el Registro Poblacional de Anomalías Congénitas de la Comunitat Valenciana, pero su principal limitación es el elevado número de casos falsos positivos que detecta. Objective To assess the validity of the Spanish Minimum Basic Data Set (MBDS) for identifying major congenital anomalies in the Valencian Community. Methods A retrospective epidemiological study was carried out. Children under the age of one year, born in 2007 and residing in the Valencian Community with congenital anomalies code 740-759 CIE9-MC, were selected from the MBDS, in addition to a random sample of children under the age of 1 year without these discharge codes. Having reviewed the clinical documentation, the cases were classified as true positives and negatives and false positives and negatives. Positive and negative predictive value and sensitivity were calculated. The kappa test was applied to analyse diagnostic consistency between the MBDS and the clinical documentation. Results A total of 2305 discharges of 1651 patients were identified. 4 out of the 5434 patients sampled had a major congenital abnormality. The positive predictive value was 56.4% (95% confidence interval [95%CI]: 53.9-58.8) and the negative predictive value was 99.3% (95%CI: 98.6-100.0). MBDS sensitivity was 68.6% (95%CI: 66.1-71.1). The most common codes in the true positives were: 745.5 (atrial septal defect), 745.4 (ventricular septal defect) and 747.0 (patent ductus arteriosus) and in the false positives: 747.0, 745.5 and 752.51 (cryptorchidism). 25.5% of diagnoses with congenital anomaly from the MBDS were not in the clinical documentation. Considering all diagnoses coded in the MBDS, the correlation was 0.70 (95%CI: 0.68-0.72) Conclusions The MBDS is the main source of information to detect cases in the registry of congenital anomalies of the Valencian Community. Its main limitation is the high number of false positive cases detected

Exploring Research Priorities of Parents Who Have Children With Down Syndrome, Cleft Lip With or Without Cleft Palate, Congenital Heart Defects, and Spina Bifida Using ConnectEpeople:A Social Media Coproduction Research Study

Background: Using social media for research purposes is novel and challenging in terms of recruitment, participant knowledge about the research process, and ethical issues. This paper provides insight into the recruitment of European parents of children with specific congenital anomalies to engage in coproduction research by using social media. Secret Facebook groups, providing optimal security, were set up for newly recruited research-aware parents (RAPs) to communicate privately and confidentially with each other and for the research team to generate questions and to interpret findings. Objective: This study aimed to use social media for the recruitment and engagement of parents in research and to determine the research priorities of parents who have children with Down syndrome, cleft lip with or without cleft palate, congenital heart defects, and spina bifida. Methods: The design was exploratory and descriptive with 3 phases. Phase 1 included the recruitment of RAPs and generation of research questions important to them; phase 2 was a Web-based survey, designed using Qualtrics software, and phase 3 included analysis and ranking of the top 10 research questions using an adapted James Lind Alliance approach. Simple descriptive statistics were used for analysis, and ethical approval was obtained from the Ethics Filter Committee of the Institute of Nursing and Health Research, Ulster University. Results: The recruitment of 32 RAPs was a sensitive process, varying in the time taken to consent (mean 51 days). However, parents valued the screening approach using the State-Trait Anxiety Inventory as a measure to ensure their well-being (mean 32.5). In phase 1, RAPs generated 98 research questions. In phase 2, 251 respondents accessed the Web-based survey, 248 consented, and 80 completed the survey, giving a completeness rate of 32.3% (80/248). Most parents used social media (74/80, 92%). Social media, online forums, and meeting in person were ranked the most preferable methods for communication with support groups networks and charities. Most respondents stated that they had a good understanding of research reports (71/80, 89%) and statistics (68/80, 85%) and could differentiate among the different types of research methodologies (62/80, 78%). Phase 3 demonstrated consensus among RAPs and survey respondents, with a need to know the facts about their child's condition, future health, and psychosocial and educational outcomes for children with similar issues. Conclusions: Social media is a valuable facilitator in the coproduction of research between parents and researchers. From a theoretical perspective, ocularcentrism can be an applicable frame of reference for understanding how people favor visual contact.This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 733001.info:eu-repo/semantics/publishedVersio

Beta-Blocker Use in Pregnancy and Risk of Specific Congenital Anomalies: A European Case-Malformed Control Study.

The prevalence of chronic hypertension is increasing in pregnant women. Beta-blockers are among the most prevalent anti-hypertensive agents used in early pregnancy. The objective of this study was to investigate whether first-trimester use of beta-blockers increases the risk of specific congenital anomalies in offspring. A population-based case-malformed control study was conducted in 117,122 registrations of congenital anomalies from 17 European Concerted Action on Congenital Anomalies and Twins (EUROCAT) registries participating in EUROmediCAT with data for all or part of the period between 1995 and 2013. Associations previously reported in the literature (signals) were tested and an exploratory analysis was performed to identify new signals. Odds ratios of exposure to any beta-blocker or to a beta-blocker subgroup were calculated for each signal anomaly compared with two control groups (non-chromosomal, non-signal anomalies and chromosomal anomalies). The exploratory analyses were performed for each non-signal anomaly compared with all the other non-signal anomalies. The signals from the literature (congenital heart defects, oral clefts, neural tube defects and hypospadias) were not confirmed. Our exploratory analysis revealed that multi-cystic renal dysplasia had significantly increased odds of occurring after maternal exposure to combined alpha- and beta-blockers (adjusted odds ratio 3.8; 95% confidence interval 1.3-11.0). Beta-blocker use in the first trimester of pregnancy was not found to be associated with a higher risk of specific congenital anomalies in the offspring, but a new signal between alpha- and beta-blockers and multi-cystic renal dysplasia was found. Future large epidemiological studies are needed to confirm or refute our findings

Children with Hirschsprung's disease have high morbidity in the first 5 years of life

Background Hirschsprung's disease is a rare congenital anomaly of the colon with absence of the ganglionic nerve cells. The treatment of the anomaly is surgical. Methods This population-based data-linkage cohort study was part of the EUROlinkCAT project and investigated mortality and morbidity for the first 5 years of life for European children diagnosed with Hirschsprung's disease. Nine population-based registries in five countries from the European surveillance of congenital anomalies network (EUROCAT) participated. Data on children born 1995–2014 and diagnosed with Hirschsprung's disease were linked to hospital databases. All analyses were adjusted for region and length of follow-up, which differed by registry. Results The study included 680 children with Hirschsprung's disease. One-year survival was 97.7% (95% CI: 96.4–98.7). Overall, 85% (82–87) had a code for a specified intestinal surgery within the first year increasing to 92% (90–94) before age 5 years. The median age at the first intestinal surgery up to 5 years was 28 days (11–46) and the median number of intestinal surgical procedures was 3.5 (3.1–3.9). Thirty days mortality after neonatal surgery (within 28 days after birth) was 0.9% (0.2–2.5) for children with a code for intestinal surgery within the first 28 days after birth and there were no deaths for children with a code for stoma surgery in the neonatal period. Conclusion Children with Hirschsprung's disease have a high morbidity in the first 5 years of life requiring more surgical procedures in addition to the initial surgery. Mortality after neonatal surgery is low

Surveillance of multiple congenital anomalies; searching for new associations

\ua9 2023, The Author(s).Many human teratogens are associated with a spectrum of congenital anomalies rather than a single defect, and therefore the identification of congenital anomalies occurring together more frequently than expected may improve the detection of teratogens. Thirty-two EUROCAT congenital anomaly registries covering 6,599,765 births provided 123,566 cases with one or more major congenital anomalies (excluding chromosomal and genetic syndromes) for the birth years 2008–2016. The EUROCAT multiple congenital anomaly algorithm identified 8804 cases with two or more major congenital anomalies in different organ systems, that were not recognized as part of a syndrome or sequence. For each pair of anomalies, the odds of a case having both anomalies relative to having only one anomaly was calculated and the p value was estimated using a two-sided Fisher’s exact test. The Benjamini–Hochberg procedure adjusted p values to control the false discovery rate and pairs of anomalies with adjusted p values < 0.05 were identified. A total of 1386 combinations of two anomalies were analyzed. Out of the 31 statistically significant positive associations identified, 20 were found to be known associations or sequences already described in the literature and 11 were considered “potential new associations” by the EUROCAT Coding and Classification Committee. After a review of the literature and a detailed examination of the individual cases with the anomaly pairs, six pairs remained classified as new associations. In summary, systematically searching for congenital anomalies occurring together more frequently than expected using the EUROCAT database is worthwhile and has identified six new associations that merit further investigation

The burden of disease for children born alive with Turner syndrome—A European cohort study

Background Turner syndrome is a rare congenital anomaly caused by complete or partial X chromosome monosomy that may affect mortality and morbidity in childhood. Methods This population-based data-linkage cohort study, as part of the EUROlinkCAT project, investigated mortality and morbidity for the first 5 years of life for liveborn European children diagnosed with Turner syndrome. Thirteen population-based registries in 10 countries from the European surveillance of congenital anomalies (EUROCAT) network participated. Data on children born 1995–2014 and diagnosed with Turner syndrome were linked to mortality, hospital and prescription records. Children with any congenital anomaly and children without a congenital anomaly were included for comparison on morbidity. Results Out of a population of 5.8 million livebirths 404 were diagnosed with Turner syndrome prenatally or in infancy and 95.5% survived to their fifth birthday. During the first year of life 72.3% (95% CI 59.5;81.6) of children with Turner syndrome were hospitalized, the median length of stay was 5.6 days (95% CI 3.5;7.7) and 18.7% (95% CI 13.9;23.9) underwent surgery. After the first year of life hospitalizations and length of stay decreased but more children underwent surgery (30.8% [95% CI 17.6;44.7]). In the first 5 years the percentage of children with Turner syndrome having a prescription for antibiotics was 12%–20% per year and increased with the age of child. Conclusions In the first year of life, the burden of disease was relatively high for children with Turner syndrome. The outlook is more positive beyond the first year, though overall morbidity still exceeded that of children without congenital anomalies

Antiasthmatic prescriptions in children with and without congenital anomalies: a population-based study.

OBJECTIVES: To explore the risk of being prescribed/dispensed medications for respiratory symptoms and breathing difficulties in children with and without congenital anomalies. DESIGN: A EUROlinkCAT population-based data linkage cohort study. Data on children with and without congenital anomalies were linked to prescription databases to identify children who did/did not receive antiasthmatic prescriptions. Data were analysed by age, European region, class of antiasthmatic, anomaly, sex, gestational age and birth cohort. SETTING: Children born 2000-2014 in six regions within five European countries. PARTICIPANTS: 60 662 children with congenital anomalies and 1 722 912 reference children up to age 10 years. PRIMARY OUTCOME MEASURE: Relative risks (RR) of >1 antiasthmatic prescription in a year, identified using Anatomical Therapeutic Chemical classification codes beginning with R03. RESULTS: There were significant differences in the prescribing of antiasthmatics in the six regions. Children with congenital anomalies had a significantly higher risk of being prescribed antiasthmatics (RR 1.41, 95% CI 1.35 to 1.48) compared with reference children. The increased risk was consistent across all regions and all age groups. Children with congenital anomalies were more likely to be prescribed beta-2 agonists (RR 1.71, 95% CI 1.60 to 1.83) and inhaled corticosteroids (RR 1.74, 95% CI 1.61 to 1.87). Children with oesophageal atresia, genetic syndromes and chromosomal anomalies had over twice the risk of being prescribed antiasthmatics compared with reference children. Children with congenital anomalies born <32 weeks gestational age were over twice as likely to be prescribed antiasthmatics than those born at term (RR 2.20, 95% CI 2.10 to 2.30). CONCLUSION: This study documents the additional burden of respiratory symptoms and breathing difficulties for children with congenital anomalies, particularly those born preterm, compared with children without congenital anomalies in the first 10 years of life. These findings are beneficial to clinicians and healthcare providers as they identify children with greater morbidity associated with respiratory symptoms, as indicated by antiasthmatic prescriptions

Ten-year survival of children with trisomy 13 or trisomy 18: a multi-registry European cohort study

Objective To investigate the survival to 10 years of age of children with trisomy 13 (T13) and children with trisomy 18 (T18), born 1995–2014. Design Population-based cohort study that linked mortality data to data on children born with T13 or T18, including translocations and mosaicisms, from 13 member registries of EUROCAT, a European network for the surveillance of congenital anomalies. Setting 13 regions in nine Western European countries. Patients 252 live births with T13 and 602 with T18. Main outcome measures Survival at 1 week, 4 weeks and 1, 5 and 10 years of age estimated by random-effects meta-analyses of registry-specific Kaplan-Meier survival estimates. Results Survival estimates of children with T13 were 34% (95% CI 26% to 46%), 17% (95% CI 11% to 29%) and 11% (95% CI 6% to 18%) at 4 weeks, 1 and 10 years, respectively. The corresponding survival estimates were 38% (95% CI 31% to 45%), 13% (95% CI 10% to 17%) and 8% (95% CI 5% to 13%) for children with T18. The 10-year survival conditional on surviving to 4 weeks was 32% (95% CI 23% to 41%) and 21% (95% CI 15% to 28%) for children with T13 and T18, respectively. Conclusions This multi-registry European study found that despite extremely high neonatal mortality in children with T13 and T18, 32% and 21%, respectively, of those who survived to 4 weeks were likely to survive to age 10 years. These reliable survival estimates are useful to inform counselling of parents after prenatal diagnosis