Respiratory morbidity in children with congenital heart disease.

OBJECTIVE: To evaluate the respiratory outcome in children with congenital heart disease (CHD), considering recent management procedures and the CHD pathophysiology. DESIGN AND SETTING: Clinical and functional respiratory outcome were evaluated in 8-year-old children with isolated CHD followed up from birth in the prospective population-based EPICARD cohort. PATIENTS: Children were assigned to two groups, based on the pathophysiology of the CHD: CHDs with left-to-right shunt (n = 212) and CHDs with right outflow tract obstruction (n = 113). RESULTS: Current wheezing episodes were observed in 15% of the children with isolated CHD and left-to-right shunt, and 11% of the children with isolated CHD and right outflow tract obstruction (not significant). Total lung capacity (TLC) was the only respiratory function parameter that significantly differed between the two groups. It was lower in children with left-to-right shunt (88.72 ± 0.65% predicted) than in those with right outflow tract obstruction (91.84 ± 0.96, p = 0.006). In multivariate analysis, CHD with left-to-right shunt (coeff. [95% CI]: -3.17 [-5.45; -0.89]) and surgery before the age of 2 months (-6.52 [-10.90; -2.15]) were identified as independent factors associated with significantly lower TLC values. CONCLUSION: Lower TLC remains a long-term complication in CHD, particularly in cases with left-to-right shunt and in patients requiring early repair. These findings suggest that an increase in pulmonary blood flow may directly impair lung development.

Linking a European cohort of children born with congenital anomalies to vital statistics and mortality records: A EUROlinkCAT study.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Association between advanced paternal age and congenital heart defects: a systematic review and meta-analysis.

STUDY QUESTION: Is there an association between advanced paternal age and congenital heart defects (CHD)? SUMMARY ANSWER: Advanced paternal age is associated with a 16% increase in the overall odds of CHD. WHAT IS KNOWN ALREADY: CHD are the most common congenital malformations. Several risk factors for CHD have been identified in the literature, but the association between advanced paternal age and CHD remains unclear. STUDY DESIGN, SIZE, DURATION: We conducted a systematic literature search on MEDLINE and EMBASE (1960-2019) to identify studies assessing the association between advanced paternal age (≥35 years) and the risk of CHD, unrestrictive of language or sample size. We used a combination of Medical Subject Headings (MeSH) terms and free text words such as 'paternal age', 'paternal factors', 'father's age', 'parental age', 'heart', 'cardiac', 'cardiovascular', 'abnormalities, congenital', 'birth defects', 'congenital malformations' and 'congenital abnormalities'. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational studies aiming at assessing the association between paternal age and CHD. The included population could be live births, fetal deaths and terminations of pregnancy for fetal anomaly. To be included, studies had to provide either odds ratios (OR) with their 95% confidence interval (CI) or sufficient information to recalculate ORs with 95% CIs per paternal age category. We excluded studies if they had no comparative group and if they were reviews or case reports. Two independent reviewers selected the studies, extracted the data and assessed risk of bias using a modified Newcastle-Ottawa Scale. We used random-effects meta-analysis to produce summary estimates of crude OR. Associations were also tested in subgroups. MAIN RESULTS AND THE ROLE OF CHANCE: Of 191 studies identified, we included nine studies in the meta-analysis (9 917 011 participants, including 34 447 CHD), including four population-based studies. Five studies were judged at low risk of bias. Only one population-based study specifically investigated isolated CHD. The risk of CHD was higher with advanced paternal age (summary OR 1.16, 95% CI, 1.07-1.25). Effect sizes were stable in population-based studies and in those with low risk of bias. LIMITATIONS AND REASONS FOR CAUTION: The available evidence did not allow to assess (i) the risk of isolated CHD in population-based studies, (ii) the association between paternal age and the risk for specific CHD and (iii) the association between paternal age and CHD after adjustment for other risk factors, such as maternal age. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that advanced paternal age may be a risk factor for CHD. However, because the association is modest in magnitude, its usefulness as a criterion for targeted screening for CHD seems limited. STUDY FUNDING/COMPETING INTEREST(S): None. PROSPERO REGISTRATION NUMBER: CRD42019135061.

Prenatal natural history of congenital pulmonary malformations: MALFPULM population-based cohort study.

OBJECTIVES: To assess prenatal changes in the volume of congenital pulmonary malformations (CPM) and examine whether these changes differ in lesions that appear cystic on ultrasound compared with hyperechoic lesions, and to study the relationship between CPM volume and risk of fetal compression. METHODS: We conducted a nationally representative, multicenter, prospective cohort study, which included 579 ultrasound examinations in 176 pregnant women with a diagnosis of fetal CPM, between March 2015 and November 2016. Several ultrasound examinations were performed between diagnosis and delivery, including measurement of CPM volume. We modeled changes in CPM volume ratio (CVR) as a function of gestational age, overall and for cystic/mixed vs hyperechoic malformations, and examined the association between CVR and signs of compression during pregnancy. RESULTS: When modeling CVR changes over time, there was a statistically significant decrease in CVR with increasing gestational age (P < 0.001), but the pattern of change differed according to CPM phenotype at first ultrasound examination: cystic/mixed CPM were characterized by a monotonic decrease in CVR with increasing gestational age (P = 0.002), whereas hyperechoic CPM showed an initial increase in CVR up to 27 weeks of gestation, followed by a decrease thereafter (P < 0.001). Peak CVR values were predicted as early as 21-22 weeks for cystic/mixed CPMs compared with 25-26 weeks for hyperechoic malformations. Regardless of CPM phenotype, fetuses that showed no sign of compression at any point had substantially lower CVR at first CVR measurement, and the CVR remained relatively constant thereafter. Among the subpopulation of fetuses with no sign of compression at first CVR measurement, the odds of a subsequent compression was 7-fold higher (adjusted odds ratio, 7.0; 95% CI, 1.6-29.9) if initial CVR was > 0.4 vs CVR ≤ 0.4 cm2 . CONCLUSIONS: Predicted changes in CVR during pregnancy differ between cystic and hyperechoic malformations. This may be the result of different pathophysiological mechanisms or differences in the timing of occurrence of these different types of CPM. CVR measured at the initial diagnostic ultrasound examination was strongly associated with the odds of subsequent compression. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.