Early Cerebrovascular Autoregulation in Neonates with Congenital Heart Disease.

Neonates with congenital heart disease (CHD) display delayed brain development, predisposing them to impaired cerebrovascular autoregulation (CAR) and ischemic brain injury. For this paper, we analyzed the percentage of time with impaired CAR (%time impaired CAR) during the first 72 h after birth, the relation with clinical factors, and survival in 57 neonates with CHD. The primary outcome was a correlation coefficient of cerebral oxygenation (rcSO2) and mean arterial blood pressure (MABP, mmHg) for two hours on a daily basis. The %time impaired CAR ranged from 9.3% of the studied time on day one to 4.6% on day three. Variables associated with more %time impaired CAR were the use of inotropes (day 1, B = 19.5, 95%CI = 10.6-28.3; day 3, B = 11.5, 95%CI = 7.1-16), lower MABP (day 1, B = -0.6, 95%CI = -1.2-0.0), and dextro-transposition of the great arteries (dTGA) (16.2%) compared with other CHD types (2.0-5.0%; day 1, p = 0.022). Survival was not an associated variable. To summarize, impaired CAR was found in CHD neonates in up to 9.3% of the studied time. More evidence is necessary to evaluate an association with inotropes, dTGA, %time impaired CAR, and long-term outcome, further in larger cohorts.

Neonatal Hemoglobin Levels in Preterm Infants Are Associated with Early Neurological Functioning.

BACKGROUND: Neonatal anemia may compromise oxygen transport to the brain. The effects of anemia and cerebral oxygenation on neurological functioning in the early neonatal period are largely unknown. OBJECTIVE: This study aimed to determine the association between initial hemoglobin levels (Hb) and early neurological functioning in preterm infants by assessing their general movements (GMs). METHODS: A retrospective analysis of prospectively collected data on preterm infants born before 32 weeks of gestation was conducted. We excluded infants with intraventricular hemorrhage > grade II. On day 8, we assessed infants' GMs, both generally as normal/abnormal and in detail using the general movement optimality score (GMOS). We measured cerebral tissue oxygen saturation (rcSO2) on day 1 using near-infrared spectroscopy. RESULTS: We included 65 infants (median gestational age 29.9 weeks [IQR 28.2-31.0]; median birth weight 1,180 g [IQR 930-1,400]). Median Hb on day 1 was 10.3 mmol/L (range 4.2-13.7). Lower Hb on day 1 was associated with a higher risk of abnormal GMs (OR = 2.3, 95% CI: 1.3-4.1) and poorer GMOSs (B = 0.9, 95% CI: 0.2-1.7). Hemoglobin strongly correlated with rcSO2 (rho = 0.62, p < 0.01). Infants with lower rcSO2 values tended to have a higher risk of abnormal GMs (p = 0.06). After adjusting for confounders, Hb on day 1 explained 44% of the variance of normal/abnormal GMs and rcSO2 explained 17%. Regarding the explained variance of the GMOS, this was 25% and 16%, respectively. CONCLUSIONS: In preterm infants, low Hb on day 1 is associated with impaired neurological functioning on day 8, which is partly explained by low cerebral oxygenation.

A comparison of the early motor repertoire of very preterm infants and term infants.

OBJECTIVE: To obtain reference data on the early motor repertoire of very preterm infants compared with healthy term infants at three months' post-term age. STUDY DESIGN: In this observational study, using Prechtl's method on the assessment of the early motor repertoire, we compared the quality of fidgety movements and the concurrent motor optimality score - revised of infants with a gestational age <30 weeks and/or a birth weight <1000 g with healthy infants with a gestational age of 37-42 weeks. RESULTS: One hundred eighty very preterm and 180 healthy term infants participated. The median motor optimality scores - revised of very preterm infants were significantly lower in comparison to those of term infants, with scores of 24 (25th-75th percentiles: 23-26) and 26 (25th-75th percentiles: 26-28), respectively. Fidgety movements were aberrant (abnormal or absent) more often in very preterm infants than in term infants. The odds ratio was 4.59 (95% CI, 1.51-13.92). Compared with term infants, very preterm infants had poorer scores on the subscales age-adequate movement repertoire, observed postural patterns, and movement character with odds ratios ≥2.97. We found no differences regarding observed movement patterns. CONCLUSION: This study provides reference data on the early motor repertoire of very preterm and healthy term infants. It demonstrates that the early motor repertoire of very preterm infants is poorer than that of term infants, a finding consistent with existing knowledge that prematurity increases the risk of poor neurodevelopment.

Hypoxic/ischemic hits predispose to necrotizing enterocolitis in (near) term infants with congenital heart disease: a case control study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating disease that is relatively frequently diagnosed in term infants with congenital heart disease (CHD), compared with term infants without CHD, in whom NEC is rare. The exact pathogenesis of NEC in term infants with CHD is unknown, but it is hypothesized that ischemia of the intestines plays a pivotal role. We aimed to explore whether (near) term CHD infants, who develop NEC, exhibit more clinical signs of hypoxia/ischemia and low body perfusion directly after birth and during the first 48 hours after admission to the neonatal intensive care unit, when compared with (near) term CHD infants who did not develop NEC. METHODS: 956 infants with CHD born after ≥ 35 weeks of gestational age were retrospectively reviewed for this case-control study between January 1999 and February 2020. We included infants with radiographically confirmed pneumatosis intestinalis and controls matched by type of CHD. Seven infants were diagnosed with transposition of the great arteries, six with left and four with right ventricular outflow tract obstruction. Several parameters suggestive of (relative) hypoxia/ischemia were used for analyses. RESULTS: We included sixteen CHD infants with NEC and selected sixteen controls. There were no significant demographic differences between both groups. Apgar score at one and five minutes (median [IQR]) were lower in infants who developed NEC compared with control infants (8 [7-8]) vs. (9 [8-9], P = .011) and (8 [8-9]) vs. (9 [9-10], P = .009). A higher proportion of infants with NEC required respiratory support in the delivery room (11(69) vs. 2(13), P = .001). The (median [IQR]) diastolic blood pressure on the second day after admission (39 mmHg [34-42], vs. 43 mmHg [37-51], P = .112) and lowest (median [IQR]) pH in the 48 hours after admission (7.24 [7.17-7.35] vs. 7.38 ([7.27-7.43], P = .157) were not significantly lower in NEC infants but both demonstrated a similar direction towards (relative) hypoxia/ischemia in NEC infants. CONCLUSIONS: Our clinical results support a hypoxic/ischemic pathophysiology of NEC in (near) term CHD infants, with lower Apgar scores, more respiratory support in the delivery room and a tendency towards a lower diastolic blood pressure and pH in CHD infants who develop NEC.

Onset of brain injury in infants with prenatally diagnosed congenital heart disease.

BACKGROUND: The exact onset of brain injury in infants with congenital heart disease (CHD) is unknown. Our aim was, therefore, to assess the association between prenatal Doppler flow patterns, postnatal cerebral oxygenation and short-term neurological outcome. METHODS: Prenatally, we measured pulsatility indices of the middle cerebral (MCA-PI) and umbilical artery (UA-PI) and calculated cerebroplacental ratio (CPR). After birth, cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) were assessed during the first 3 days after birth, and during and for 24 hours after every surgical procedure within the first 3 months after birth. Neurological outcome was determined preoperatively and at 3 months of age by assessing general movements and calculating the Motor Optimality Score (MOS). RESULTS: Thirty-six infants were included. MOS at 3 months was associated with MCA-PI (rho 0.41, P = 0.04), UA-PI (rho -0.39, P = 0.047, and CPR (rho 0.50, P = 0.01). Infants with abnormal MOS had lower MCA-PI (P = 0.02) and CPR (P = 0.01) and higher UA-PI at the last measurement (P = 0.03) before birth. In infants with abnormal MOS, rcSO2 tended to be lower during the first 3 days after birth, and FTOE was significantly higher on the second day after birth (P = 0.04). Intraoperative and postoperative rcSO2 and FTOE were not associated with short-term neurological outcome. CONCLUSION: In infants with prenatally diagnosed CHD, the prenatal period may play an important role in developmental outcome. Additional research is needed to clarify the relationship between preoperative, intra-operative and postoperative cerebral oxygenation and developmental outcome in infants with prenatally diagnosed CHD.

Predicting intestinal recovery after necrotizing enterocolitis in preterm infants.

BACKGROUND: Intestinal recovery after NEC is difficult to predict in individuals. We evaluated whether several biomarkers predict intestinal recovery after NEC in preterm infants. METHODS: We measured intestinal tissue oxygen saturation (rintSO2) and collected urinary intestinal-fatty acid binding protein (I-FABPu) levels 0-24 h and 24-48 h after NEC onset, and before and after the first re-feed. We assessed intestinal recovery in two ways: time to full enteral feeding (FEFt; below or equal/above group's median) and development of post-NEC complications (recurrent NEC/post-NEC stricture). We determined whether the rintSO2, its range, and I-FABPu differed between groups. RESULTS: We included 27 preterm infants who survived NEC (Bell's stage ≥ 2). Median FEFt was 14 [IQR: 12-23] days. Biomarkers only predicted intestinal recovery after the first re-feed. Mean rintSO2 ≥ 53% combined with mean rintSO2range ≥ 50% predicted FEFt < 14 days with OR 16.7 (CI: 2.3-122.2). The rintSO2range was smaller (33% vs. 51%, p < 0.01) and I-FABPu was higher (92.4 vs. 25.5 ng/mL, p = 0.03) in case of post-NEC stricture, but not different in case of recurrent NEC, compared with infants without complications. CONCLUSION: The rintSO2, its range, and I-FABPu after the first re-feed after NEC predicted intestinal recovery. These biomarkers have potential value in individualizing feeding regimens after NEC.

Early cerebral and intestinal oxygenation in the risk assessment of necrotizing enterocolitis in preterm infants.

BACKGROUND AND AIM: Predicting necrotizing enterocolitis (NEC) might help in preventing its devastating consequences. We aimed to investigate whether early cerebral and intestinal tissue oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) predict the onset of NEC. STUDY DESIGN: Prospective observational case-control study. SUBJECTS: Infants with gestational age (GA) <32 weeks were included. For every NEC case we matched two controls based on GA, birth weight (BW), and a patent ductus arteriosus. OUTCOME MEASURES: Cerebral oxygenation and intestinal oxygenation were prospectively monitored two-hours daily during the first five days after birth and once a week thereafter until five weeks after birth or until NEC developed. We used Kaplan-Meier analyses to determine the ability of near-infrared spectroscopy (NIRS) measurements, including their variability, to predict the development of NEC. RESULTS: We included ten infants (median (range) GA 27.1 (24.6-29.4) weeks, BW 903 (560-1630) grams) who developed NEC at median postnatal day 13 (range: 4-43 days), and 20 matched controls. Infants with cerebral rSO2 <70% within the first 48 h after birth developed NEC significantly more often than infants with cerebral rSO2 ≥70% (odds ratio 9.00 (95% CI 1.33-61.14). Intestinal FTOE was higher in infants who developed NEC compared to controls during the last NIRS measurement at median 2 days (range: 1-7) before NEC onset (median 0.65 vs. 0.44). CONCLUSIONS: Cerebral oxygenation monitoring early after birth might be valuable in the risk assessment of NEC development. Additionally, our results suggest that intestinal oxygenation is impaired before the onset of clinical NEC.

Amplitude-integrated electroencephalography during the first 72 h after birth in neonates diagnosed prenatally with congenital heart disease.

BackgroundLittle is known on amplitude-integrated electroencephalography (aEEG) during the first few days after birth in neonates with congenital heart disease (CHD). Our aim was, therefore, to assess electrocortical activity using aEEG within the first 72 h after birth in neonates diagnosed prenatally with CHD, and to define independent prenatal and postnatal predictors for abnormal aEEG.MethodsNeonates with CHD who were admitted to the neonatal intensive care unit between 2010 and 2017 were retrospectively included. We assessed aEEG background patterns, sleep-wake cycling, and epileptic activity during the first 72 h after birth and defined prenatal and postnatal clinical parameters associated with aEEG patterns.ResultsSeventy-two neonates were included. Twenty-six (36%) had mildly abnormal and six (8%) had severely abnormal aEEG background patterns at some point during the study period. Sleep-wake cycling was present in 97% of the neonates. Subclinical seizures were common (15%), whereas none of the neonates had clinical seizures. Only treatment with sedatives was a significant predictor for abnormal aEEG background patterns, explaining 56% of the variance.ConclusionAbnormal aEEG background patterns are common and are strongly associated with treatment with sedatives in neonates with prenatally diagnosed CHD. Future studies should assess the association between early postnatal aEEG abnormalities and neurodevelopmental outcome.

Cerebral and Renal Oxygen Saturation Are Not Compromised in the Presence of Retrograde Blood Flow in either the Ascending or Descending Aorta in Term or Near-Term Infants with Left-Sided Obstructive Lesions.

BACKGROUND: In infants with left-sided obstructive lesions (LSOL), the presence of retrograde blood flow in either the ascending or descending aorta may lead to diminished cerebral and renal blood flow, respectively. OBJECTIVES: Our aim was to compare cerebral and renal tissue oxygen saturation (rSO2) between infants with LSOL with antegrade and retrograde blood flow in the ascending aorta and with and without diastolic backflow in the descending aorta. METHODS: Based on 2 echocardiograms, the study group was categorized according to the direction of blood flow in the ascending and descending aorta. We measured cerebral and renal rSO2 using near-infrared spectroscopy and calculated fractional tissue oxygen extraction (FTOE). RESULTS: Nineteen infants with LSOL, admitted to the NICU between 0 and 28 days after birth, were included. Infants with antegrade blood flow (n = 12) and infants with retrograde blood flow in the ascending aorta (n = 7) had similar cerebral rSO2 and FTOE during both echocardiograms. Only during the first echocardiogram, infants with retrograde blood flow in the ascending aorta had lower renal FTOE (0.14 vs. 0.32, p = 0.04) and tended to have higher renal rSO2 (80 vs. 65%, p = 0.09). The presence of diastolic backflow in the descending aorta was not associated with cerebral or renal rSO2 and FTOE during the first (n = 8) as well as the second echocardiogram (n = 10). CONCLUSIONS: Retrograde blood flow in the ascending aorta was not associated with cerebral oxygenation, while diastolic backflow in the descending aorta was not associated with renal oxygenation in infants with LSOL.

Brain Injury and Neurodevelopmental Outcome in Congenital Heart Disease: A Systematic Review.

CONTEXT: Brain injury during prenatal and preoperative postnatal life might play a major role in neurodevelopmental impairment in infants with congenital heart disease (CHD) who require corrective or palliative surgery during infancy. A systematic review of cerebral findings during this period in relation to neurodevelopmental outcome (NDO), however, is lacking. OBJECTIVE: To assess the association between prenatal and postnatal preoperative cerebral findings and NDO in infants with CHD who require corrective or palliative surgery during infancy. DATA SOURCES: PubMed, Embase, reference lists. STUDY SELECTION: We conducted 3 different searches for English literature between 2000 and 2016; 1 for prenatal cerebral findings, 1 for postnatal preoperative cerebral findings, and 1 for the association between brain injury and NDO. DATA EXTRACTION: Two reviewers independently screened sources and extracted data on cerebral findings and neurodevelopmental outcome. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Abnormal cerebral findings are common during the prenatal and postnatal preoperative periods. Prenatally, a delay of cerebral development was most common; postnatally, white matter injury, periventricular leukomalacia, and stroke were frequently observed. Abnormal Doppler measurements, brain immaturity, cerebral oxygenation, and abnormal EEG or amplitude-integrated EEG were all associated with NDO. LIMITATIONS: Observational studies, different types of CHD with different pathophysiological effects, and different reference values. CONCLUSIONS: Prenatal and postnatal preoperative abnormal cerebral findings might play an important role in neurodevelopmental impairment in infants with CHD. Increased awareness of the vulnerability of the young developing brain of an infant with CHD among caregivers is essential.

Near-infrared spectroscopy as a predictor of clinical deterioration: a case report of two infants with duct-dependent congenital heart disease.

BACKGROUND: Some infants with congenital heart disease are at risk of in-hospital cardiac arrest. To better foresee cardiac arrest in infants with congenital heart disease, it might be useful to continuously assess end-organ perfusion. Near-infrared spectroscopy is a non-invasive method to continuously assess multisite regional tissue oxygen saturation. CASE PRESENTATION: We report on two infants with duct-dependent congenital heart disease who demonstrated a gradual change in cerebral and/or renal tissue oxygen saturation before cardiopulmonary resuscitation was required. In both cases, other clinical parameters such as heart rate, arterial oxygen saturation and blood pressure did not indicate that deterioration was imminent. CONCLUSIONS: These two cases demonstrate that near-infrared spectroscopy might contribute to detecting a deteriorating clinical condition and might therefore be helpful in averting cardiopulmonary collapse and need for resuscitation in infants with congenital heart disease.

Cerebral oxygen saturation during the first 72h after birth in infants diagnosed prenatally with congenital heart disease.

BACKGROUND: Evidence suggests that hypoxic-ischemic brain injury in infants with congenital heart disease already occurs during early life. The aim of our study was, therefore, to assess the course of regional cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) during the first 72h after birth in infants with prenatally diagnosed duct-dependent congenital heart disease. In addition, we identified clinical parameters that were associated with rcSO2. MATERIALS AND METHODS: We included 56 infants with duct-dependent congenital heart disease. We measured arterial oxygen saturation (SpO2) and rcSO2 during the first 72h after birth. Simultaneously, we calculated FTOE. RESULTS: We observed median rcSO2 values of approximately 60%, a decreasing FTOE from 0.34 on day 1 to 0.28 on day 3 and stable preductal SpO2 values around 90%. Several clinical variables were associated with rcSO2. In a multiple linear regression model only type of CHD and preductal SpO2 were significant predictors of rcSO2 during the first three days after birth. Infants with a duct-dependent pulmonary circulation had up to 12% lower rcSO2 values than infants with a duct-dependent systemic circulation. CONCLUSION: We demonstrated that, during the first three days after birth, cerebral oxygen saturation is low in infants with duct-dependent congenital heart disease. Furthermore, this study provides preoperative reference values of rcSO2 and FTOE in infants with duct-dependent CHD.