Daniel C. Vijlbrief

B-type natriuretic peptide and rebound during treatment for persistent pulmonary hypertension.

OBJECTIVEnTo investigate whether serum B-type natriuretic peptide (BNP) is a useful biomarker in evaluating the course of persistent pulmonary hypertension of the newborn (PPHN) and the effectiveness of treatment.nnnSTUDY DESIGNnProspective follow-up study of infants with clinical and echocardiographic signs of PPHN, who were treated with inhaled nitric oxide (iNO). Of 24 patients with PPHN who were treated, serum BNP levels were determined longitudinally in 21. BNP levels were compared between infants with (n = 6) and without rebound PPHN (n = 15).nnnRESULTSnBNP levels in all infants with PPHN were not significantly different at the initial start of iNO. BNP levels decreased in both groups during iNO treatment. In the infants in whom rebound PPHN developed after weaning from iNO, a significantly higher increase was found in BNP (283 pmol/L to 1232 pmol/L) compared with that in infants without rebound (98 pmol/L to 159 pmol/L). This occurred before the onset of clinical deterioration. BNP again decreased significantly after iNO treatment was restarted.nnnCONCLUSIONSnBNP, a biomarker of cardiac ventricular strain, proved to be useful in evaluating the efficacy of PPHN treatment, and moreover, BNP helps to predict a rebound of PPHN.

Cerebral oxygenation and echocardiographic parameters in preterm neonates with a patent ductus arteriosus: an observational study

Background A haemodynamically significant patent ductus arteriosus (hsPDA) is clinically suspected and confirmed by echocardiographic examination. A hsPDA decreases cerebral blood flow and oxygen saturation by the ductal steal phenomenon. Aim To determine the relationship between echocardiographic parameters, cerebral oxygenation and a hsPDA in preterm infants. Methods 380 preterm infants (<32u2005weeks gestational age) born between 2008 and 2010 were included. Blinded echocardiographic examination was performed on the second, fourth and sixth day after birth. Examinations were deblinded when hsPDA was clinically suspected. Regional cerebral oxygen saturation (rScO2) was continuously monitored by near-infrared spectroscopy during 72u2005h after birth, and afterwards for at least 1u2005h before echocardiography. Echocardiographic parameters included ductal diameter, end-diastolic flow in the left pulmonary artery, left atrium/aorta ratio and ductal flow pattern. Results rScO2 was significantly related only to ductal diameter over time. Mixed modelling analysed the course of rScO2 over time, where infants were divided into four groups: a closed duct, an open haemodynamically insignificant duct (non-sPDA), a hsPDA, which was successfully closed during study period (SC hsPDA) or a hsPDA, which was unsuccessfully closed during study period (UC hsPDA). SC hsPDA infants showed the highest rScO2 on day 6, while UC hsPDA infants had the lowest rScO2 values. Conclusions Ductal diameter is the only echocardiographic parameter significantly related to cerebral oxygenation over time. Cerebral oxygenation takes a different course over time depending on the status of the duct. Low cerebral oxygenation may be suggestive of a hsPDA.

Cardiac Biomarkers as Indicators of Hemodynamic Adaptation during Postasphyxial Hypothermia Treatment

Background: Little is known about the effects of hypothermia on the cardiovascular system in term newborns with neonatal encephalopathy. Objectives: To evaluate whether mild hypothermia for neonatal encephalopathy is cardioprotective as indicated by the cardiac biomarkers cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP). Methods: This was an observational cohort study of infants treated for perinatal asphyxia. In infants, mild total body hypothermia treatment of 33.5°C during 72 h was initiated (n = 20). Samples of cTnI and BNP were collected before the start of hypothermia, at 24 and 48 h after birth, and after rewarming (84 h). BNP and cTnI values were then compared with BNP and cTnI values of asphyxiated infants not treated with hypothermia (n = 28). Results: No differences were found between the groups in clinical patient characteristics or inotropic support. The hypothermia-treated patients seemed to be clinically more affected (5-min Apgar score, p < 0.05; umbilical artery pH, p = 0.08), but showed similar encephalopathy scores. Significantly lower values for BNP were found in hypothermia- compared to nonhypothermia-treated infants at 48 h and at normothermia after rewarming [144 pmol/l (95–286) vs. 75 pmol/l (45–143), 182 pmol/l (73–341) vs. 43 pmol/l (24–163)]. No differences were found for cTnI concentrations between both groups. Conclusions: The raised, but similar, cTnI values between hypothermia- and nonhypothermia-treated infants indicate similar myocardial damage in both groups. The lower BNP levels during hypothermia treatment suggest that hypothermia after perinatal asphyxia exerts a beneficial effect on cardiac function.

Late-onset Sepsis in Preterm Infants Can Be Detected Preclinically by Fecal Volatile Organic Compound Analysis: A Prospective, Multicenter Cohort Study

BackgroundnThe intestinal microbiota has increasingly been considered to play a role in the etiology of late-onset sepsis (LOS). We hypothesize that early alterations in fecal volatile organic compounds (VOCs), reflecting intestinal microbiota composition and function, allow for discrimination between infants developing LOS and controls in a preclinical stage.nnnMethodsnIn 9 neonatal intensive care units in the Netherlands and Belgium, fecal samples of preterm infants born at a gestational age ≤30 weeks were collected daily, up to the postnatal age of 28 days. Fecal VOC were measured by high-field asymmetric waveform ion mobility spectrometry (FAIMS). VOC profiles of LOS infants, up to 3 days prior to clinical LOS onset, were compared with profiles from matched controls.nnnResultsnIn total, 843 preterm born infants (gestational age ≤30 weeks) were included. From 127 LOS cases and 127 matched controls, fecal samples were analyzed by means of FAIMS. Fecal VOCs allowed for preclinical discrimination between LOS and control infants. Focusing on individual pathogens, fecal VOCs differed significantly between LOS cases and controls at all predefined time points. Highest accuracy rates were obtained for sepsis caused by Escherichia coli, followed by sepsis caused by Staphylococcus aureus and Staphylococcus epidermidis.nnnConclusionsnFecal VOC analysis allowed for preclinical discrimination between infants developing LOS and matched controls. Early detection of LOS may provide clinicians a window of opportunity for timely initiation of individualized therapeutic strategies aimed at prevention of sepsis, possibly improving LOS-related morbidity and mortality.

Elevated renal tissue oxygenation in premature fetal growth restricted neonates: An observational study

Background Fetal growth restriction (FGR) is associated with an increased risk for kidney disease in later life. Studies reporting on early signs of renal disturbances in FGR are sparse and mostly include invasive measurements, which limit the possibility for early identification and prevention. We aim to investigate whether renal tissue oxygen saturation (rSO2) measured with near-infrared spectroscopy (NIRS) and the derived value fractional tissue oxygen extraction (FTOE) differ between premature FGR and control neonates in the first three days after birth. Methods Nine FGR and seven control neonates born <32 weeks of gestation were included. FGR was defined as biometry <p10 combined with prenatal signs of placental insufficiency. Renal rSO2 was measured continuously with NIRS for 72 hours. FTOE was calculated as: (arterial saturation-rSO2)/arterial saturation. Renal artery blood flow (pulsatility and resistance index) was measured within 24 hours after birth. A linear mixed model approach was used (intercept ± slope = r) to analyze the NIRS parameters. Results Renal rSO2 was higher in FGR neonates compared to controls (94% vs. 83%; pgroup = 0.002). During the first three days after birth, renal rSO2 decreased in FGR neonates and increased in controls (r = -0.25 vs. r = 0.03; pinteraction = 0.001). Renal FTOE was lower in FGR neonates (0.02 vs. 0.14; pgroup = 0.01) and increased slightly during three days after birth, while it remained stable in controls (r = 0.003 vs. r = -0.0001; pinteraction = 0.001). Renal artery blood flow was similar between groups. Conclusions FGR neonate kidneys showed higher rSO2 as measured with NIRS and lower derived values of FTOE in the first three days after birth. We speculate that this was caused by either a reduced oxygen consumption due to impaired renal maturation or increased renal oxygen supply. How these observations correlate with short- and long-term renal function needs further investigation before renal NIRS can be implemented in screening and prevention in clinical practice.

Primary coronary stent implantation is a feasible bridging therapy to surgery in very low birth weight infants with critical aortic coarctation

BACKGROUNDnSurgical treatment of critical aortic coarctation (CoA) is difficult in very low birth weight (VLBW) infants ≤1500u202fg and preferably postponed until 3u202fkg with prostaglandins (PGE).nnnOBJECTIVESnTo investigate the procedure and outcome of primary coronary stent implantation as bridging therapy to surgery in VLBW infants with CoA.nnnMETHODSnRetrospective evaluation of primary CoA stenting in VLBW infants from 2010 to 2015.nnnRESULTSnFive VLBW infants with a median gestational age of 29u202fweeks (27-32) underwent primary CoA stenting. Indication was cardiac failure in 4 and severe hypertension in 1 patient. Age and weight at intervention were 14u202fdays (range 12-16) and 1200u202fg (680-1380), respectively. Stent diameter ranged 3-5u202fmm. The femoral artery used for intervention was occluded in all infants without clinical compromise. Severe restenosis and aneurysm occurred in 1 VLBW infant and was successfully treated with covered coronary stents. Median age at surgical correction was 200u202fdays (111-804) and weight 5500u202fg (4500-11,400). No reinterventions were required during a median postoperative follow-up of 2.8u202fyears (0.1-5.0). Neurodevelopmental outcomes were normal and comparable between patients and siblings (4/5 gemelli).nnnCONCLUSIONSnPrimary coronary stent implantation in VLBW infants with critical CoA is a feasible bridging therapy to surgery.

788 Fetal Hypoxia-Ischemia is Related to Circulatory Compromise in Preterm Infants

Background and Aims Impairment of gas exchange and blood flow through the placenta leads to hypoxia and hypercapnia. This causes increased systemic vascular resistance and tachycardia, thus compromising the cardiovascular system of the foetus. The biomarker B-type natriuretic peptide (BNP) can be used to identify significant cardiovascular compromise in infants. The aim of the present study was to investigate whether BNP can be used to identify those preterm infants with significant cardiovascular compromise during peripartum period. Methods In this retrospective cohort study all infants born after a gestational age of less than 32 weeks were evaluated. Maternal, fetal and infant factors associated with prenatal and perinatal hypoxia-ischemia were related to BNP levels after birth. Pathologic examination of the placenta was routinely performed. Results In total 164 infants were evaluated. Infants with increased placental ischemia and a higher placental maturation score had elevated levels of BNP at birth (r² 0.12; p<0.001). Furthermore BNP was found to be associated with (chronic) prenatal hypoxia-ischemia (nucleated red blood cells (r² 0.22; p<0.001); intrauterine growth retardation (r² 0.18; p<0.01); postnatal thrombocytopenia), and acute perinatal hypoxia (umbilical artery pH (r² 0.14; p<0.001); serum lactate (r² 0.11; p<0.001). Conclusion Elevated BNP levels after birth are found in those preterm infants with significant perinatal hypoxia-ischemia and are possibly related to placental dysfunction. If BNP levels are related to prenatal signs of circulatory compromise needs further investigation.

618 Benefit of Prenatal Diagnosis of Complex Congenital Heart Defects on Neonatal Morbidity

Background and Aims As survival rates in neonatal cardiac surgery improve over time, morbidity becomes more important in complex congenital heart disease (cCHD). We investigated whether prenatal diagnosis of cCHD affects preoperative and early postoperative morbidity in neonates. Methods Retrospective observational study, performed between July 1st 2004 and July 1st 2011, including 247 infants with cCHD requiring surgery within the neonatal period. 113/247 patients were diagnosed with cCHD by prenatal screening (PreDx). Morbidity was based on preoperative use of high dose prostaglandin E and pre- and postoperative cardiac function, ventilation time, length of admission (LOF), inotropic support requirement and presence of severe complications (resuscitation, acute kidney and liver injury, and neurological events). Results Complexity of cCHD was higher in children diagnosed PreDx. After correction of complexity, median pre-operative ventilation time (3 vs 0 days), LOF (7 vs 9 days) and preoperative cardiac function were significantly better in PreDx neonates; and correction of acidosis, preoperative inotropic support and high dose prostaglandin E was significantly less common. Severe complications occurred significantly less when PreDx. There were no significant differences in postoperative morbidity and overall mortality. Conclusions Prenatal diagnosis of cCHD improves pre-operative morbidity significantly. The patient condition is better compared to postDx and the need for preoperative intensive care treatment is less. Seemingly, intensive care treatment can achieve a good pre-operative condition, even in neonates deteriorated due to an at birth unknown cCHD. This could explain why post-operative morbidity was equal in both groups.

Placental Pathology is Related to Postnatal Circulatory Compromise in Preterm Infants

Background: Impairment of gas exchange and blood flow through the placenta leads to hypoxia and hypercapnia, causing increased systemic vascular resistance and tachycardia, influencing the cardiovascular system of the fetus. The biomarker B-type natriuretic peptide (BNP) can be used to identify significant cardiovascular disease in infants.Objective: To investigate whether placental pathology was associated with significant cardiovascular compromise in the premature infant as diagnosed by elevated BNP-levels after birth.Methods: From October 2009 until October 2010 134 infants born with GA< 32 weeks were evaluated. Placenta pathology was performed and related to BNP levels at admission, within 6 hours after birth.Results: Chorioamnionitis was present in 32%, signs of pathologic increased maturation in 55,2%. Increased placental maturation showed strong correlation with clinical diagnosis of pre-eclampsia (PE) (r=0.59,p< 0.001). BNP-levels were elevated in pregnancies complicated by clinical or pathological signs of PE (median 56 p/mol/l vs. 106 p/mol/L;p< 0.05). The highest BNP-levels were found in those infants where PE was complicated by fetal distress (91pmol/L vs. 390pmol/L;p< 0.01). The presence of chorioamnionitis was associated with lower BNP-levels, although this was not statistically significant (55 pmol/L vs. 94 pmol/L;p= 0.12) and possibly related to PE in the other group.Conclusion: This study shows that those infants, where maternal, pathological or clinical, PE was complicated by signs of fetal distress, are the most likely to have cardiovascular compromise at birth. Whether this is directly related to fetal cardiovascular adaptation to placental vascular pathology needs further investigation.

142 B-Type Natriuretic Peptide as Early Biomarker for Evaluation of Persistent Pulmonary Hypertension Treatment in Neonates

142 B-Type Natriuretic Peptide as Early Biomarker for Evaluation of Persistent Pulmonary Hypertension Treatment in Neonates