Can urinary biomarkers predict acute kidney injury in newborns with critical congenital heart disease?

BACKGROUND: Congenital heart disease (CHD) is the most common congenital malformation group and is the leading cause of newborn mortality in developed countries. Most of the infants with CHD develop preoperative or postoperative acute kidney injury (AKI). Acute kidney injury may develop before the serum creatinine rise and oliguria. Urinary biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, and cystatin C may predict AKI in patients with critical CHD (CCHD) before the serum creatinine rise. In this study, we aimed to determine the AKI incidence among newborn patients with CCHD and investigate the predictivity of urinary biomarkers for AKI. METHODS: Newborns with a gestational age >34 weeks and birth weight >1500 g with a diagnosis of CCHD were enrolled in the study. Blood and urine samples were collected at birth, during the first 24-48 h, and in the preoperative and postoperative periods. RESULTS: A total of 53 CCHD patients requiring surgery during the neonatal period were enrolled in the study. The 24-48 h KIM-1 levels of the cases with exitus were higher (P = 0.007). The 24-48 h cystatin C and preoperative NGAL levels were higher in patients with postoperative AKI (P = 0.02). DISCUSSION: In newborns with CCHD, high KIM-1 levels may predict mortality, whereas high cystatin C and preoperative NGAL levels may be indicative of AKI. These biomarkers deserve further investigation in larger study populations.

Perforated appendicitis after intravenous immunoglobulin therapy in a term neonate with haemolytic jaundice.

Neonatal appendicitis is a rare clinical condition that may cause high morbidity and mortality if diagnosis is delayed. There is usually an underlying disease; it can also be a localized form of necrotizing enterocolitis. Here, we present a term neonate who was treated with intravenous immunoglobulin because of severe isoimmune hemolytic jaundice. The patient developed abdominal symptoms within 10 hours of therapy, was diagnosed with acute perforated appendicitis and completely recovered after surgery.

Cord blood and consecutive chitotriosidase activity: Relationship to prematurity and early prognosis.

BACKGROUND: The aim of this study was to investigate the relationship between plasma chitotriosidase activity, an inflammatory protein secreted mainly from macrophages, and neonatal morbidity and mortality in premature infants. METHODS: Cord blood chitotriosidase activity was studied in healthy control infants (53 term, group 1; 26 late preterm [33-37 gestational weeks], group 2) and 35 preterm infants (≤ 32 weeks; group 3). In group 3, consecutive samples at 3 h, 24 h, 72 h, 7 days, 14 days, and 36 weeks after conception were also analyzed. Group 3 was also evaluated for mortality, respiratory treatment and bronchopulmonary dysplasia (BPD), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC). RESULTS: Cord blood chitotriosidase activity was positively correlated with gestational age and birthweight. SNAPPE-II score was correlated with chitotriosidase activity at 24 h. Consecutive chitotriosidase activity for group 3 was non-significantly higher in infants who died in the early neonatal period. Higher chitotriosidase activity was observed in mechanically ventilated infants than infants treated with non-invasive assisted ventilation. BPD, PDA, IVH and ROP, but not NEC, were related to higher chitotriosidase activity, being significant at some of the time points. CONCLUSION: Neonatal stress such as invasive ventilation may create a risk for the development of BPD, PDA, IVH, and ROP by increasing macrophage activation in preterm infants as reflected in the higher chitotriosidase activity. High chitotriosidase activity may also be associated with disease severity and mortality.

The effect of inhaled nitric oxide therapy on thromboelastogram in newborns with persistent pulmonary hypertension.

UNLABELLED: Studies about the effects of inhaled nitric oxide (iNO) on bleeding time and platelet aggregation in newborns are limited in number and have inconclusive results. Thromboelastogram (TEG) shows the combined effects of coagulation factors and platelet functions. In this preliminary study, we aimed to evaluate the effects of iNO on coagulation using TEG in newborns with persistent pulmonary hypertension (PPH). TEG assays were performed in 10 term infants receiving iNO treatment for PPH and 32 healthy term infants. Samples of the iNO group were collected before and during iNO. Clot reaction time (R), clot kinetics (K), maximum amplitude (MA), and alpha angle were obtained from the TEG tracing. TEG-R values were statistically higher during iNO treatment (7.75 ± 3.34) when compared to the values before iNO (4.83 ± 1.38) and the healthy controls (3.75 ± 0.98). The alpha angle was lower in iNO treated infants at both periods (before iNO, 55.33 ± 8.58; during iNO, 42.90 ± 18.34) compared to the control group (64.95 ± 6.88). MA values before iNO treatment were the lowest (44.43 ± 14.09) and improved with the iNO treatment (48.40 ± 9.49) despite still being lower compared to the controls (53.67 ± 5.56). CONCLUSION: Both PPH and iNO may negatively effect in vitro coagulation tests. Therefore, newborns with PPH requiring iNO treatment should be closely monitored for coagulation problems.

Association of vitamin D receptor gene polymorphisms and bronchopulmonary dysplasia.

BACKGROUND: Vitamin D and its receptor (VDR) have important roles in perinatal lung development. The aim of this study was to investigate the relationship between VDR gene polymorphism and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: VDR Fok I, Bsm I, Apa I, and Taq I polymorphisms were genotyped using restriction fragment length polymorphism in 109 preterm infants (47 with BPD, 62 without BPD). RESULTS: In univariate analysis, Ff (odds ratio (OR) = 3.937, P = 0.022, 95% confidence interval (CI) = 1.22-12.69) and ff (OR = 5.23, P = 0.004, 95% CI = 1.69-16.23) genotypes of Fok I were associated with the increased risk of BPD; whereas tt genotype of Taq 1 was associated with a protective effect against BPD (OR = 0.30, P = 0.04, 95% CI = 0.09-0.94). In multivariate logistic regression analysis, variant Fok 1 genotype increased risk of BPD (OR = 4.11, 95% CI = 1.08-15.68, P = 0.038) independent of patent ductus arteriosus, sepsis, mechanical ventilation, and surfactant treatment. Taq 1, Bsm 1, and Apa 1 polymorphisms did not have any effect. CONCLUSION: After adjusting for multiple confounders, VDR Fok 1 polymorphism was associated with the increased frequency of BPD. Further studies are needed to assess the contribution of VDR signaling to the pathogenesis of BPD and to determine if VDR polymorphisms may be suitable for identifying infants at high risk for BPD.

Medical closure of patent ductus arteriosus does not reduce mortality and development of bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Although, patent ductus arteriosus (PDA) is associated with significant morbidity due to hemodynamic instability in preterm infants, the effect of ductus closure on mortality and morbidity is a controversial issue. The aim is to evaluate the efficacy of oral and intravenous (IV) ibuprofen treatment on ductal closure and effects on mortality and bronchoplumonary dysplasia. MATERIALS AND METHODS: The medical records of 292 premature infants treated at Ege University Neonatal Intensive Care Unit were retrospectively evaluated. Patients were classified into 3 groups as; No PDA, hemodynamically insignificant PDA (hiPDA) and hemodynamically significant PDA (hsPDA) according to the presence and hemodynamical significance of PDA by echocardiography. hsPDA group was treated with IV or oral ibuprofen. RESULTS: Patent ductus arteriosus was diagnosed by routine echocardiography in 145 patients, of whom 78 (53.7%) had hsPDA. All 65 infants with hiPDA had spontaneous PDA closure. Echocardiographic measurements were similar to those patients treated with oral or IV ibuprofen, as in the response rate to treatment without serious adverse effects. The presence of respiratory distress syndrome, surfactant therapy, late sepsis, bronchopulmonary dysplasia (BPD) and mortality rates were significantly higher in patients with hsPDA. However, with stepwise logistic regression; 5(th) min Apgar score (odds ratio [OR], 1.321, 95% confidence interval [CI], 1.063-1.641, P = 0.012) and gestational age (OR, 1.422, 95% CI, 1.212-1.662, P < 0.001) were the only significant variables associated with mortality. Gestational age (OR, 0.680, 95% CI, 0.531-0.871, P = 0.002) was the only significant variable associated with BPD shown with logistic regression. CONCLUSION: Ibuprofen treatment is effective for hsPDA closure with minimal side effects. HiPDA can close spontaneously; therefore treatment decision should be individualized. However, medical treatment of PDA does not reduce mortality and BPD.

Cardiovascular consequences of bronchopulmonary dysplasia in prematurely born preschool children.

BACKGROUND: A limited number of studies have reported various short-term cardiovascular changes in bronchopulmonary dysplasia (BPD) patients in the postsurfactant era. Little is known about the course of these changes in children with BPD. OBJECTIVES: It was the aim of this study to investigate cardiovascular consequences of BPD at preschool ages and to find out possible risk factors related to cardiovascular sequelae. METHODS: Prematurely born children with (n = 21) and without BPD (n = 20) were evaluated with conventional and myocardial tissue Doppler echocardiography at the age of 2-4 years. RESULTS: BPD patients had a decreased pulmonary artery acceleration time and higher left and right ventricular myocardial performance indexes, consistent with higher pulmonary pressures and impaired biventricular systolic and diastolic functions at preschool ages. Low birth weight, disease severity and postnatal cumulative steroid dose were related to these changes. CONCLUSION: Negative effects of BPD on global cardiac performances of both ventricles and pulmonary arterial pressure persist up to preschool ages.

Histological chorioamnionitis: effects on premature delivery and neonatal prognosis.

BACKGROUND: Chorioamnionitis is closely related to premature birth and has negative effects on neonatal morbidity and mortality. METHODS: In this prospective study, 43 mothers who delivered earlier than 35 gestational weeks and their 57 infants were evaluated clinically and with laboratory findings. Placentas and umbilical cords were investigated histopathologically for chorioamnionitis and funisitis. RESULTS: The overall frequency of clinical and histological chorioamnionitis (HCA) was 8.3% and 23.2%, respectively. The frequency of HCA was 47.3% and 83.3% in mothers delivered <32 weeks and <30 weeks, respectively. Maternal demographic and clinical findings and also leukocyte and C-reactive protein values were not indicative of HCA. Infants of mothers with HCA had significantly lower Apgar scores together with higher SNAP-PE-II and CRIB scores. These infants had increased mechanical ventilator and surfactant requirements, higher incidences of patent ductus arteriosus, early sepsis, and bronchopulmonary dysplasia, and higher mortality rates. The effect of HCA on neonatal morbidity and mortality was more prominent than the effect of low birthweight and lower gestational age. CONCLUSION: Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

Neonatal status epilepticus controlled with levetiracetam at Sturge Weber syndrome.

Sturge-Weber syndrome is a rare, sporadic, congenital neurocutaneous syndrome characterized by facial cutaneous vascular malformation, leptomeningeal angioma and eye abnormalities. Seizures develop during the first year of life, may become refractory to multiple anticonvulsants and status epilepticus may develop. A rare subtype of Sturge-Weber syndrome with bilateral facial vascular malformation, unilateral cerebral involvement and neonatal status epilepticus is reported here. Neonatal status epilepticus was successfully controlled with intravenous levetiracetam infusion.

Association between bronchopulmonary dysplasia and MBL2 and IL1-RN polymorphisms.

BACKGROUND: The imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the development of bronchopulmonary dysplasia (BPD) in preterm infants. Mannose binding lectin (MBL) codon 54 and interleukin 1 receptor antagonist gene (IL1-RN) polymorphisms cause genetic predisposition to increased risk of infection and inflammation, therefore may increase the risk of BPD. The aim of this study was to investigate the relationship between MBL, IL1-RN gene polymorphisms and BPD development in preterm infants. METHODS: MBL codon 54 and IL1-RN polymorphisms were studied in 71 infants who were born at <32 weeks of gestation, with the diagnosis of BPD (group 1) and in a control group of preterm infants without BPD (group 2). RESULTS: IL1-RN and MBL2 variant genes were closely associated with increased risk of BPD (both P < 0.001) together with significantly lower birthweight (P < 0.001 and P = 0.001, respectively), lower 5 min Apgar scores (P = 0.009 for both genes) and increased neonatal infection rate (P < 0.001 and P < 0.009, respectively). The IL1 RN 1/1 genotype was protective (odds ratio [OR], 0.075; 95% confidence interval [CI]: 0.019-0.76) while the IL1-RN 2/2 genotype increased the risk for BPD (OR, 11.7; 95%CI: 1.3-103.6). The MBL-AA genotype was protective against BPD (OR, 0.066; 95%CI: 0.02-0.2) whereas the MBL-BB genotype increased the susceptibility for the development of BPD (OR, 23.8; 95%CI: 2.8-200.6). CONCLUSION: MBL and IL 1 RN polymorphisms are closely related to low birthweight and increase the risk of neonatal sepsis and BPD development in preterm infants.

Desferrioxamine treatment of iron overload secondary to RH isoimmunization and intrauterine transfusion in a newborn infant.

Intrauterine transfusion is the standard of care in the management of severe Rh isoimmunization. Desferrioxamine has been used for the treatment of iron overload secondary to hemolysis and intrauterine transfusions in Rh isoimmunization cases. Here, we report a preterm infant born at 34 weeks of gestational age who had formerly received intrauterine transfusions for Rhesus hemolytic disease and presented with severe hyperferritinemia and elevated liver enzymes in the first week of life. Desferrioxamine treatment was started due to a ferritin level of 28,800 ng/ml and continued for 13 weeks. Although the treatment was successful, we observed resistant leukopenia which resolved after the cessation of treatment. In conclusion, iron overload secondary to intrauterine transfusions can be treated successfully with desferrioxamine; however, neonatologists must be aware of the possible side effects of this drug which has been used in only a limited number of newborns.

Mannose-binding lectin gene polymorphism and early neonatal outcome in preterm infants.

BACKGROUND: Mannose-binding lectin (MBL) as a component of innate immunity plays an important role in preterm infants in whom adaptive immunity is not sufficiently developed. Polymorphisms in immunoregulatory genes influence the response to infection and subsequent inflammation. Infection and inflammation have been implicated in the mechanisms responsible for many of the diseases in the preterm newborns. OBJECTIVES: The aim of the study was to investigate the relationship between MBL gene polymorphism and early neonatal outcome in preterm infants. METHODS: Codon 54 and 57 polymorphisms in MBL2 gene were genotyped in 99 preterm infants admitted to the Neonatal Intensive Care Unit at Ege University Children's Hospital. RESULTS: Overall frequencies of sepsis and early-onset sepsis were higher in the group of infants with MBL polymorphism when compared to infants with wild-type MBL genotype (p = 0.008, 0.009, respectively). Maximum Tollner sepsis score in the first 3 days of life was higher for the infants with variant MBL genotype (p = 0.0278). More infants in the variant MBL group had significant patent ductus arteriosus when compared to infants with wild-type MBL (27.8 vs. 9.5% respectively, p = 0.037). CONCLUSION: MBL gene polymorphism was associated with increased frequency of clinical sepsis particularly with early neonatal sepsis and also with higher Tollner sepsis scores and increased frequency of patent ductus arteriosus in infants. Overall mortality and incidence of culture proven sepsis, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia and necrotizing enterocolitis were not found to be related to MBL genotype.

Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency.

Betaine therapy was given for 2 years to a 2-year-old boy with 5,10-methylenetetrahydrofolate reductase deficiency. Used as a methyl donor to lower homocysteine levels through methylation of methionine, betaine has been reported to be effective in treating homocystinuria. Satisfactory biochemical and clinical responses were obtained with the following regimen: betaine started in the newborn period at increasing doses to reach 1 g given six times a day. It is suggested that frequent administration of a moderate dose may provide clinical and biochemical benefit.