Placenta histology related to flow and oxygenation in fetal congenital heart disease.

BACKGROUND: Fetuses with congenital heart defects (CHD) show delayed neurodevelopment, fetal growth restriction (FGR) and placenta related complications. The neurodevelopmental delay may be, partly, attributed to placental factors. AIM: As both placental development and fetal aortic flow/oxygenation influence neurodevelopment, placentas were compared within fetal CHD groups based on aortic oxygenation and flow, aiming to unravel the true effects in the developmental processes. STUDY DESIGN: Placental tissues of pregnancies with fetal CHD and healthy controls were selected from biobanks of two Dutch academic hospitals (LUMC, UMCU). Additionally, biometry and Dopplers were assessed. SUBJECTS: CHD cases with reduced oxygenation (RO) towards the fetal brain were compared to cases with reduced flow (RF) in the aortic arch and healthy controls. Genetic abnormalities, termination of pregnancy, fetal demise and/or multiple pregnancies were excluded. OUTCOME MEASURES: Histological outcomes were related to fetal Dopplers and biometry. A placenta severity score was used to assess the severity of placental abnormalities per case. RESULTS: In CHD, significantly more delayed maturation, maternal vascular malperfusion, fetal hypoxia and higher placenta severity scores (median 14 in RO, 14 in RF, 5 in controls, p < 0.001) were observed. Doppler abnormalities (PI UA > p90, PI MCA < p10, CPR < p10) and FGR were more often found in CHD. There were no differences in placental abnormalities, fetal growth and fetal Dopplers between cases with RO and RF. CONCLUSION: Fetal hemodynamics in the ascending aorta could not be related to placenta characteristics. We hypothesize that placental development influences neurodevelopment in excess of hemodynamics in CHD cases.

Factors related to fetal demise in cases with congenital heart defects.

BACKGROUND: Congenital heart defects are the most common congenital anomaly. Despite the increasing survival of these children, there is still an increased incidence of fetal demise, frequently attributed to cardiac failure. Considering that abnormal placental development has been described in congenital heart disease, our hypothesis is that placental insufficiency may contribute to fetal death in congenital heart disease. OBJECTIVE: This study aimed to assess cases with fetal congenital heart disease and intrauterine demise, and analyze factors that are related to the demise. STUDY DESIGN: All congenital heart disease cases diagnosed prenatally during the period January 2002 to January 2021 were selected from the regional prospective congenital heart disease registry, PRECOR. Multiple pregnancies and pregnancies with fetal trisomy 13 or 18, triploidy, and Turner's syndrome were excluded from the analysis, because fetal demise is attributed to the chromosomal abnormality in these cases. Cases were categorized into 4 groups based on the possible cause of fetal death as follows: cardiac failure, additional (genetic) diagnosis, placental insufficiency, and a group in which no cause was found. A separate analysis was performed for isolated congenital heart disease cases. RESULTS: Of the 4806 cases in the PRECOR registry, 112 had fetal demise, of which 43 were excluded from the analysis (13 multiple pregnancies, 30 genetic). Of these, 47.8% were most likely related to cardiac failure, 42.0% to another (genetic) diagnosis, and 10.1% to placental insufficiency. No cases were allocated to the group with an unknown cause. Only 47.8% of the cases had isolated congenital heart disease, and in this group 21.2% was most likely related to placental insufficiency. CONCLUSION: This study shows that in addition to cardiac failure and other (genetic) diagnoses, placental factors play an important role in fetal demise in congenital heart disease, especially in cases of isolated heart defects. Therefore, these findings support the importance of regular ultrasonographic assessment of fetal growth and placental function in fetal congenital heart disease.

Short-term outcome after the prenatal diagnosis of right aortic arch.

OBJECTIVES: To determine the proportion of children that require surgery in the first year of life and thereafter in order to improve the counseling of parents with a fetus with a right aortic arch (RAA). METHODS: Fetuses diagnosed with isolated RAA, defined as the absence of intra- or extracardiac anomalies, between 2007 and 2021 were extracted from the prospective registry PRECOR. RESULTS: In total, 110 fetuses were included, 92 with a prenatal diagnosis of RAA and 18 with double aortic arch (DAA). The prevalence of 22q11 deletion syndrome was 5.5%. Six pregnancies were terminated and five cases were false-positive; therefore, the follow-up consisted of 99 neonates. Surgery was performed in 10 infants (10%) in the first year of life. In total, 25 (25%) children had surgery at a mean age of 17 months. Eight of these 25 (32%) had a DAA. Only one child, with a DAA, required surgery in the first week of life due to obstructive stridor. CONCLUSIONS: Children with a prenatally diagnosed RAA are at a low risk of acute respiratory postnatal problems. Delivery in a hospital with neonatal intensive care and pediatric cardiothoracic facilities seems only indicated in cases with suspected DAA. Expectant parents should be informed that presently 25% of the children need elective surgery and only incidentally due to acute respiratory distress.

Prenatal detection of aortic coarctation in a well-organized screening setting: Are we there yet?

OBJECTIVE: We aimed to assess current prenatal detection rate (DR) of aortic coarctation (CoA) and its impact on neonatal outcome in the Netherlands to evaluate the efficacy of the Dutch screening protocol in which the cardiac four-chamber view, outflow tracts and three-vessel view are compulsory. METHODS: All prenatally and postnatally diagnosed CoA cases between 2012 and 2021 were extracted from our PRECOR-registry. Annual DRs were calculated with a focus on the trend over time and attributing factors for detection. Postnatal outcome was compared between prenatally detected and undetected cases. RESULTS: 49/116 cases (42.2%) were detected prenatally. A higher chance of detection was found for cases with extracardiac malformations (71.4%; p = 0.001) and the more severe cases with an aortic arch hypoplasia and/or ventricular septal defect (63.2%; p = 0.001). Time-trend analysis showed no improvement in DR over time (p = 0.33). Undetected cases presented with acute circulatory shock in 20.9% and were more likely to have severe lactic acidosis (p = 0.02) and impaired cardiac function (p < 0.001) before surgery. CONCLUSION: Even in a well-organized screening program, the DR of CoA still requires improvement, especially in isolated cases. The increased risk of severe lactic acidosis in undetected cases stresses the need for urgent additions to the current screening program, such as implementation of the three-vessel trachea view and measurement of outflow tracts.

Birthweight and isolated congenital heart defects - A systematic review and meta-analysis.

BACKGROUND: Birthweight (BW) is an important prognostic factor in newborns with congenital heart defects (CHD). OBJECTIVES: To give an overview of the literature on BW z-score in children with isolated CHD. SEARCH STRATEGY: A systematic search was performed on isolated CHD and BW in PubMed, Embase, Web of Science, COCHRANE Library and Emcare. SELECTION CRITERIA: Neonates with isolated CHD were included if a BW percentile, BW z-score or % small-or-gestational age (SGA) was reported. DATA COLLECTION AND ANALYSIS: BW z-score and percentage SGA were pooled with random-effect meta-analysis. Quality and risk of bias were assessed using the modified Newcastle Ottawa Scale. MAIN RESULTS: Twenty-three articles (27 893 cases) were included. BW z-scores were retrieved from 11 articles, resulting in a pooled z-score of -0.20 (95% CI -0.50 to 0.11). The overall pooled prevalence of SGA <10th percentile was 16.0% (95% CI 11.4-20.5; 14 studies). Subgroup analysis of major CHD showed similar results (BW z-score -0.23 and percentage SGA 16.2%). CONCLUSIONS: Overall BW in isolated CHD is within range of normality but impaired, with a 1.6-fold higher risk of SGA, irrespective of the type of CHD (major CHD vs all CHD combined). Our findings underline the association between CHD and BW. The use of BW z-scores provides insight into growth of all fetuses with CHD. TWEETABLE ABSTRACT: Infants with a congenital heart defect (CHD) have a lower birthweight z-score and a higher incidence of small-for-gestational age (<10th percentile). This was encountered both in the major CHD-group as well as in all-CHD combined group analysis. Future research on the association between birthweight and CHD should include all types of CHDs (including mild cardiac defects) and placental-related disease, such as pre-eclampsia. We advocate the use of international standardised fetal growth and birthweight charts in CHD research.

Placenta morphology and biomarkers in pregnancies with congenital heart disease - A systematic review.

Impaired placentation is an important contributing factor to intra-uterine growth restriction and pre-eclampsia in fetuses with congenital heart defects (CHD). These pregnancy complications occur more frequently in pregnancies with fetal CHD. One of the most important factors influencing the life of children with CHD is neurodevelopmental delay, which seems to start already in utero. Delayed neurodevelopment in utero may be correlated or even (partly) explained by impaired placentation in CHD cases. This systematic review provides an overview of published literature on placental development in pregnancies with fetal CHD. A systematic search was performed and the Newcastle-Ottawa scale was used to access data quality. Primary outcomes were placenta size and weight, vascular and villous architecture, immunohistochemistry, angiogenic biomarkers and/or placental gene expression. A total of 1161 articles were reviewed and 21 studies were included. Studies including CHD with a genetic disorder or syndrome and/or multiple pregnancies were excluded. Lower placental weight and elevated rates of abnormal umbilical cord insertions were found in CHD. Cases with CHD more frequently showed microscopic placental abnormalities (i.e. abnormal villous maturation and increased maternal vascular malperfusion lesions), reduced levels of angiogenic biomarkers and increased levels of anti-angiogenic biomarkers in maternal serum and umbilical cord blood. Altered gene expression involved in placental development and fetal growth were found in maternal serum and CHD placentas. In conclusion, abnormal placentation is found in CHD. More extensive studies are needed to elucidate the contribution of impaired placentation to delayed neurodevelopment in CHD cases.

Gastro-intestinal function and quality of life are favorable in adolescent and adult gastroschisis patients.

BACKGROUND AND AIMS: Studies on long-term sequelae of gastroschisis are scarce. The limited data suggest increased abdominal complaints in young children. To provide proper counseling for both parents and patients, more information on long-term outcome is needed. This study aims to evaluate long-term outcome regarding GI function, gastroesophageal reflux (GER), health-related quality of life (HRQoL) and cosmetic satisfaction. METHODS: An observational longitudinal cohort study was performed. All patients (N = 43) born between 1982 and 2008 with gastroschisis that were admitted to the University Medical Centre Utrecht, Wilhelmina Children's Hospital were invited to fill in a survey. Data of included patients were compared to validated Dutch reference standards. RESULTS: Fourteen patients responded to the survey. The median follow-up was 18 years. Abdominal pain on weekly basis was present in two patients (14%) and feeding difficulties were present in one patient. Presence of a complication during gastroschisis treatment led to more GI symptoms (80% versus 22%). One patient experienced moderate complaints of regurgitation or dyspepsia. Although the overall HRQoL was lower in teenage gastroschisis patients as compared to healthy controls (73/100 versus 83/100, respectively), we found no relevant difference in overall HRQoL in the other age groups. Seven patients (50%) were satisfied with the cosmetic result of the scar. CONCLUSIONS: GI function and HRQoL in gastroschisis patients seem similar to healthy controls at adolescent and adult age. Complications during gastroschisis treatment led to an increase of abdominal complaints later in life. The surgical technique had no significant effect on the cosmetic results.

Deaths and end-of-life decisions differed between neonatal and paediatric intensive care units at the same children's hospital.

AIM: We compared neonatal deaths and end-of-life decisions in a neonatal intensive care unit (NICU) and paediatric intensive care unit (PICU) in a Dutch tertiary children's hospital. SUBJECTS: All 235 full-term infants who died within 28 days of life between 2003 and 2013 in the NICU (n = 199) and PICU (n = 36) were retrospectively studied. RESULTS: The median length of stay was three days in the NICU and seven days in the PICU (p = 0.003). The main reasons for NICU stays were asphyxia (52.8%) and congenital malformations (42.2%), and in the PICU, they were congenital malformations (97.2%) and primarily cardiac problems (83.3%, p < 0.001). The median age of death was three days in the NICU and eight days in the PICU (p < 0.001), and mortality despite full intensive care treatment was 4.0% and 25.0%, respectively. Intensive treatment was discontinued because of poor survival chances in 25.1% of NICU and 52.8% of PICU cases (p < 0.001), and care was redirected because of expected poor quality of life in 70.9% and 22.2%, respectively. CONCLUSION: Differences between the age at death and end-of-life decisions were found between full-term infants in the NICU and PICU in the same children's hospital. Underlying disorders and doctors' attitudes may have played a role.