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
Objectives: To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left sided congenital heart defects (CHDs), and analyze genetic content. Methods: Between 2003 and... Show moreObjectives: To demonstrate the spectrum of copy number variants (CNVs) in fetuses with isolated left sided congenital heart defects (CHDs), and analyze genetic content. Methods: Between 2003 and 2012, 200 fetuses were identified with left sided CHD. Exclusion criteria were chromosomal rearrangements, 22q11.2 microdeletion and/or extra-cardiac malformations (n=64). We included cases with additional minor anomalies (n=39), such as single umbilical artery. In 54 of 136 eligible cases, stored material was available for array analysis. CNVs were categorized as either (likely) benign, (likely) pathogenic or of unknown significance. Results: In 18 of the 54 isolated left sided CHDs we found 28 rare CNVs (prevalence 33%, average 1.6 CNV per person size 10.6kb – 2.2Mb). Our interpretation yielded clinically significant CNVs in 2 of 54 cases (4%) and variants of unknown significance in 3 other cases (6%). Conclusions: In left sided CHDs that appear isolated, with normal chromosome analysis and 22q11.2 FISH analysis, array analysis detects clinically significant CNVs. When counselling parents of a fetus with a left sided CHD it must be taken into consideration that aside from the cardiac characteristics, the presence of extra-cardiac malformations and chromosomal abnormalities influence the treatment plan and prognosis. 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
A primigravid woman with polyhydramnios and preterm contractions presented at 25 weeks pregnancy. Fetal ultrasound revealed periventricular cysts and cerebral hypoplasia. The neonate was born in a... Show moreA primigravid woman with polyhydramnios and preterm contractions presented at 25 weeks pregnancy. Fetal ultrasound revealed periventricular cysts and cerebral hypoplasia. The neonate was born in a poor condition, with increased serum lactate and pyruvate levels. Whole exome sequencing detected FBXL4 gene mutations causing recessive mitochondrial myopathy. 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
