Prenatal detection of congenital heart defects has been known to decrease mortality and morbidity in children born with such defects. This thesis describes the increase of prenatal detection of two... Show morePrenatal detection of congenital heart defects has been known to decrease mortality and morbidity in children born with such defects. This thesis describes the increase of prenatal detection of two outflow-tract anomalies, by adding an additional mandatory plane to the national screening program. The second part of this thesis, studies the development of the fetal brain in children affected by congenital heart defects. These children are known to have worse neurodevelopmental outcome than their healthy counterparts. There is some evidence describing a prenatal origin of the delay in neurodevelopment. In the studies that were described in part two of this thesis, we have used a deep-learning algorithm that can assess the maturation (or development) of the fetal brain. We have found small delays in brain maturation as compared to healthy control fetuses. The clinical significance of these outcomes however, remains unclear. A multifactorial cause of brain damage in children with CHD is much more likely. Whatever the exact cause of the long-term neurodevelopmental delay in children with congenital heart defects is, the correlation is undeniable. And thus, expecting parents must be informed of this matter. Show less
Objectives Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze... Show moreObjectives Presumably, changes in fetal circulation contribute to the delay in maturation of the cortex in fetuses with congenital heart defect (CHD). The aim of the current study is to analyze fetal brain development based on hemodynamic differences, using novel brain-age prediction software. Methods We have performed detailed neurosonography, including acquiring 3D volumes, prospectively in cases with isolated CHD from 20 weeks onwards. An algorithm that assesses the degree of fetal brain-age automatically was used to compare CHD cases to controls. We stratified CHD cases according to flow and oxygenation profiles by lesion physiology and performed subgroup analyses. Results A total of 616 ultrasound volumes of 162 CHD cases and 75 controls were analyzed. Significant differences in maturation of the cortex were observed in cases with normal blood flow toward the brain (-3.8 days, 95%CI [-5.5; -2.0],P = <.001) and low (-4.0 days, 95% CI [-6.7; -1.2]P = <.05; hypoplastic left heart syndrome[HLHS]) and mixed (-4.4 days, 95%CI [-6.4; -2.5]p = <.001) oxygen saturation in the ascending aorta (TGA) and in cardiac mixing (eg, Fallot) cases. Conclusion The current study shows significant delay in brain-age in TGA and Fallot cases as compared to control cases. However, the small differences found in this study questions the clinical relevance. Show less
Introduction: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and... Show moreIntroduction: Congenital heart defects are associated with neurodevelopmental delay. It is hypothesized that fetuses affected by congenital heart defect have altered cerebral oxygen perfusion and are therefore prone to delay in cortical maturation. The aim of this study was to determine the difference in fetal brain age between consecutive congenital heart defect cases and controls in the second and third trimester using ultrasound.Material and methods: Since 2014, we have included 90 isolated severe congenital heart defect cases in the Heart And Neurodevelopment (HAND)-study. Every 4 weeks, detailed neurosonography was performed in these fetuses, including the recording of a 3D volume of the fetal brain, from 20 weeks onwards. In all, 75 healthy fetuses underwent the same protocol to serve as a control group. The volumes were analyzed by automated age prediction software which determines gestational age by the assessment of cortical maturation.Results: In total, 477 volumes were analyzed using the age prediction software (199 volumes of 90 congenital heart defect cases; 278 volumes of 75 controls). Of these, 16 (3.2%) volume recordings were excluded because of imaging quality. The age distribution was 19-33 weeks. Mixed model analysis showed that the age predicted by brain maturation was 3 days delayed compared with the control group (P = .002).Conclusions: This study shows that fetuses with isolated cases of congenital heart defects show some delay in cortical maturation as compared with healthy control cases. The clinical relevance of this small difference is debatable. This finding was consistent throughout pregnancy and did not progress during the third trimester.Keywords: congenital heart defects; fetus; malformations of cortical development; neurodevelopmental outcome; ultrasonography. Show less
ObjectivesThe aim of this study was to analyze the annual detection rate (DR) of transposition of the great arteries (TGA) and tetrology of Fallot (ToF), after the introduction of the three‐vessel... Show moreObjectivesThe aim of this study was to analyze the annual detection rate (DR) of transposition of the great arteries (TGA) and tetrology of Fallot (ToF), after the introduction of the three‐vessel view as a mandatory plane in 2012.MethodsAll registered TGA and ToF cases were retrospectively extracted from our registry between 2007 and 2016. We compared the DR in a 10‐year period, before 2011, with the DR of TGA and ToF after 2012.ResultsIn the period before 2012, 23 of the 52 TGA cases were prenatally detected (44.2%), compared with 42 of the 51 cases (82.4%) after 2012. For ToF, the DRs increased from 28 of 64 cases (43.8%) to 42 of 62 cases (67.7%) in the aforementioned periods. The increase in DRs for both defects was statistically significant (P ≤ 0.001 and P ≤ 0.05).ConclusionsIn this nationally organized prenatal screening program with a quality monitoring system and a uniform protocol, DRs of 82.4% for TGA and 67.7% for ToF were reached after the introduction of the three‐vessel view as a mandatory item. The three‐vessel view significantly contributes to the detection of these conotruncal anomalies. Show less
Recently, Desai et al. described six subjects with deletions in the ATAD3 gene cluster (Desai et al. 2017). Most of these patients died within their first week of life and one died after 7 months,... Show moreRecently, Desai et al. described six subjects with deletions in the ATAD3 gene cluster (Desai et al. 2017). Most of these patients died within their first week of life and one died after 7 months, but one was still alive at 30 years of age. Harel et al. (2016) described three patients with biallellic variations in ATAD3A, one of whom died in the second week of life but the other two were alive at 24 and 26 years, respectively. For pre- and postnatal management it is important to understand why some patients die very early, whereas others seem to have a much milder clinical affect. Show less
Mheen, L. van de; Everwijn, S.M.P.; Haak, M.C.; Manten, G.T.R.; Zondervan, H.A.; Knapen, M.F.C.M.; ... ; Pajkrt, E. 2016
Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical... Show moreCongenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990-2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI -6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of -0.51 (95%CI -0.84; -0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score -0.70 95%CI -0.99; -0.41) in left-sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. Show less
Congenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical... Show moreCongenital heart defects (CHDs) are associated with neurodevelopmental (ND) delay. This study aims to assess evidence for impaired prenatal brain development, in fetuses with CHD. A systematical search was performed, and 34 studies evaluating the fetal brain [magnetic resonance imaging (MRI) or ultrasound] in isolated CHD were included (1990-2015). Data regarding cerebral abnormalities, head circumference growth and middle cerebral artery flow were extracted. Prenatal MRI was studied in ten articles (445 fetuses), resulting in a pooled prevalence of 18% (95%CI -6%; 42%) for combined structural and acquired cerebral abnormalities. Prenatal head circumference was studied in 13 articles (753 fetuses), resulting in a pooled z-score of -0.51 (95%CI -0.84; -0.18). Doppler was studied in 21 articles (1412 fetuses), resulting in a lower middle cerebral artery pulsatility index (z-score -0.70 95%CI -0.99; -0.41) in left-sided CHD only. We conclude that prenatal MRI and ultrasound demonstrate brain abnormalities, delay in head growth and brainsparing in subgroups of CHD. However, large MRI studies are scarce, and ultrasound data are biased towards severe and left-sided CHD. Long-term follow-up studies correlating prenatal findings with postnatal ND outcome are limited, and data are lacking to support counseling families regarding ND outcome based on prenatal findings suggestive of altered brain development. Show less
Mheen, L. van de; Everwijn, S.M.P.; Knapen, M.F.C.M.; Haak, M.C.; Engels, M.A.J.; Manten, G.T.R.; ... ; Pajkrt, E. 2015
