Assessment of risk factors for cystic periventricular leukomalacia.

AIM: Periventricular leukomalacia (PVL) is an important cause of cerebral palsy in premature infants, and cystic PVL is the most serious form of the disease. The risk factors for cystic PVL in singleton fetuses at a gestational age of <35 weeks are unclear. METHODS: This study included 2013 singleton birth infants delivered at a gestational age of <35 weeks in Kagoshima City Hospital between 2006 and 2017. The findings for 30 infants with cystic PVL were compared with those for 63 matched control infants by gestational age and birth weight. RESULTS: The cystic PVL was associated with increased incidence of recurrent late deceleration (L/D) (43.4% vs. 15.9%, P = 0.004) and loss of variability (LOV) (10.0% vs. 0.0%, P = 0.03) in fetal heart rate monitoring and late-onset circulatory dysfunction (LCD) (33.3% vs. 11.1%, P = 0.02). Logistic regression analysis revealed that recurrent L/D (odds ratio [OR] = 3.57, 95% confidence interval [CI]: 1.29-10.15, P = 0.01) and LCD (OR = 3.41, 95% CI: 1.09-11.04, P = 0.03) were risk factors associated with cystic PVL. LOV was not included in the multivariate analysis as there were too few cases in both the cystic PVL and control groups. CONCLUSION: Recurrent L/D, LOV and LCD are strongly associated with cystic PVL. In cases of fetal acidosis related to recurrent L/D or loss of variability, cystic PVL may occur.

Extracorporeal membrane oxygenation in 61 neonates: Single-center experience.

BACKGROUND: There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants. METHODS: A review was carried out of 61 neonates with ECMO between January 1995 and December 2015 at a single center. ECMO was used in neonates with oxygenation index >20 after conventional treatment. Background factors, such as etiology, vascular access mode (veno-venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO (within 24 h after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD). RESULTS: Survival to hospital discharge was achieved in 35 infants (57%), while the remaining 26 died during hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared with those with adverse outcome (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was significantly higher for those with VV than VA vascular access mode (78%, 18/23 vs 45%, 17/38, respectively; P = 0.016), and for those with than without early ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (86%, 12/14), persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47-37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5). CONCLUSIONS: Neonates with early ECMO and those with ECMO duration <8 days may benefit from ECMO with respect to SHD.

Polymyxin B-immobilized fiber column direct hemoperfusion and continuous hemodiafiltration in premature neonates with systemic inflammatory response syndrome.

BACKGROUND: There have been no previous studies regarding whether combined use of Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) and continuous hemodiafiltration (CHDF) is helpful in the treatment of preterm infants with systemic inflammatory response syndrome (SIRS) and hypercytokinemia. METHODS: A retrospective review was carried out of 18 SIRS infants born at gestational week 24-28. Eight with blood interleukin (IL)-6 ≥ 1000 pg/mL were treated actively with 2 h PMX-DHP followed by 2 h PMX-DHP and CHDF. Ten with IL-6 < 500 pg/mL were treated conventionally (with neither PMX-DHP nor CHDF) and served as controls. RESULTS: Demographic characteristics were similar except for IL-6, arterial-to-alveolar oxygen tension ratio (a/APO2 ), and number of immature neutrophils between the two groups. Baseline a/APO2 was significantly lower in infants with than without active treatment (0.44 vs 0.67, respectively, P = 0.002). After 4 h treatment, the IL-6 decreased to < 500 pg/mL in all eight infants, and a/APO2 improved significantly to 0.62 (P = 0.006). Bronchopulmonary dysplasia occurred in a similar proportion (63%, 5/8 vs 80%, 8/10, respectively), but the number of days on inhaled oxygen (30 vs 47 days, respectively, P = 0.033) and tracheal intubation (36 vs 51 days, respectively, P = 0.040) was significantly lower in infants with than without active treatment. Prevalence of adverse events was similar (13%, 1/8 vs 50%, 5/10 for active vs conventional treatment, respectively). CONCLUSION: Active treatment with PMX-DHP and CHDF was helpful in the reduction of days on inhaled oxygen and tracheal intubation in preterm SIRS infants with hypercytokinemia. Further prospective randomized studies are warranted.

Effects of infant flow Bi-NCPAP on apnea of prematurity.

BACKGROUND: Infant flow biphasic nasal continuous positive airway pressure (Bi-NCPAP) and regular NCPAP (Re-NCPAP) are equally useful with respect to the rate of successful weaning from mechanical ventilation. It remains unclear, however, whether Bi-NCPAP or Re-NCPAP is more effective for reducing apnea of prematurity (AOP). METHODS: A multicenter randomized controlled study was conducted of 66 infants assigned to receive Bi-NCPAP and 66 assigned to receive Re-NCPAP for respiratory support after extubation. Primary outcome was the number of AOP events during the 48 h observation period after successful extubation, defined as no reintubation and no adverse events associated with the use of NCPAP during the observation period. The secondary outcome was successful extubation. Reintubation was at the discretion of the attending physician. RESULTS: Baseline characteristics were similar between the two groups. The number of AOP events during the 48 h observation period was significantly lower in infants with Bi-NCPAP than in those with Re-NCPAP (5.2 ± 6.5 vs 10.3 ± 10.9 per infant, respectively; P = 0.002). The rate of successful extubation tended to be greater in those with Bi-NCPAP than in those with Re-NCPAP (92.4%, 61/66 vs 80.3%, 53/66, respectively; P = 0.074). Adverse events occurred in only one of 132 infants: erosive dermatitis developed on the nose after application of Re-NCPAP. The risk of reintubation did not differ significantly between the two groups (7.6%, 5/66 for Bi-NCPAP vs 18.2%, 12/66 for Re-NCPAP; P = 0.117). CONCLUSIONS: Bi-NCPAP was superior to Re-NCPAP for reduction of AOP following extubation.

Calcium concentration in hypoxic-ischemic encephalopathy during hypothermia.

BACKGROUND: The aim of this study was to investigate the relationship between prognosis and the changes in serum-ionized calcium concentration in neonates with hypoxic-ischemic encephalopathy (HIE) before and during brain hypothermia (BHT). METHODS: Serum samples were obtained from 16 HIE neonates who underwent BHT. All patients underwent developmental testing at 18 months of age. RESULTS: Mean serum-ionized calcium concentration in the poor outcome group (developmental quotient [DQ], <80; nine infants) was significantly lower than in the good outcome group (DQ >80; seven infants), both immediately before and after 6 h of BHT. Mean serum-ionized calcium concentration significantly decreased in both groups for 6 h, and the lowest adjusted serum-ionized calcium during 6 h of BHT was <1.05 mmol/L, known as the cut-off value for poor outcome, in 57.1% of the good outcome group. CONCLUSION: The influx of calcium into cells continues regardless of neurological prognosis during the early phase of BHT, but BHT might protect some high-risk patients against neurological damage at low adjusted serum-ionized calcium concentration.

Outcome of infants with hypoxic ischemic encephalopathy treated with brain hypothermia.

AIM: The aim of this study was to determine perinatal factors associated with cerebral palsy (CP) in infants treated with brain hypothermia (BHT). MATERIAL AND METHODS: We carried out a retrospective review of 23 infants with hypoxic ischemic encephalopathy in whom BHT was applied within 6 h after birth. Outcome regarding the presence or absence of CP was assessed at the age of 18 months. Oxygen extraction fraction (OEF) was measured before, during and after BHT at the jugular sinus. RESULTS: Three infants died and 12 developed CP (poor outcome group). The remaining eight infants did not have CP at 18 months old (favorable outcome group). There were no differences in gestational age, birthweight, pH, base deficit, or lactate level between infants with favorable and poor outcomes. Infants with flat trace on electroencephalography on admission were less likely to have favorable outcome (0.0% [0/8] vs 53% [8/15], respectively, P = 0.02), while those with Apgar score at 10 min ≥5 (57% [8/14] vs 0.0% [0/9], P = 0.007) or ≥6 (70% [7/10] vs 7.7% [1/13], P = 0.002), OEF ≥ 13.3% during BHT (64% [7/11] vs 8.3% [1/12], P = 0.009), and OEF ≥ 18.5% after BHT (73% [8/11] vs 0.0% [0/12], P = 0.002) were more likely to have favorable outcome compared with those with counterpart characteristics. CONCLUSION: Infants with an Apgar score at 10 min ≥5, activity on electroencephalography on admission, and higher OEF during and after BHT were likely to have a favorable outcome.

Predicting onset of chronic lung disease using cord blood cytokines.

BACKGROUND: Applicability of cord blood interleukin-6 (IL-6) and interleukin-8 (IL-8) as markers for early prediction of the onset of chronic lung disease (CLD) due to intrauterine infection was investigated in the present study. METHODS: Eighty very low-birthweight infants with chorioamnionitis were divided into two groups: the CLD group (42 patients) and the non-CLD group (38 patients), according to the presence or absence of CLD, and the clinical background and cord blood IL-6 and IL-8 levels in each group were compared and investigated. RESULTS: The CLD group had significantly longer duration of mechanical ventilation and hospitalization (P < 0.05) and significantly higher IL-6 and IL-8 (P < 0.01) than the non-CLD group. Using the receiver operating characteristic curves of CLD onset for both IL-6 and IL-8, the cut-off value of IL-6 for predicting onset of CLD was 48.0 pg/mL, and its sensitivity and specificity were 76% and 96%, respectively. The cut-off value for IL-8 was 66.0 pg/mL, and its sensitivity and specificity were 71% and 82%, respectively. CONCLUSION: The cord blood levels of both IL-6 and IL-8 were significantly higher in the CLD group, indicating that both IL-6 and IL-8 are useful predictors of onset of CLD.

Septic neonate rescued by polymyxin B hemoperfusion.

Sepsis caused by group B streptococcus has been well controlled with aminobenzylpenicillin, but the incidence of Escherichia coli sepsis has increased in proportion. E. coli is a Gram-negative bacillus associated with poor prognosis due to the release of endotoxins. Conventional treatment with antibiotics alone may not be sufficient because the inflammatory response exacerbates the unstable hemodynamic status. Polymyxin B hemoperfusion has been established as a treatment option for septic shock in adults. Polymyxin B hemoperfusion adsorbs endotoxins and cannabinoids such as anandamide and 2-arachidonoylglycerol. Reported herein is a case of severe septic shock induced by E. coli. The concomitant use of polymyxin B hemoperfusion rapidly reduced the requirement for catecholamines and the patient was discharged without short-term neurological or respiratory sequelae. It is suggested that polymyxin B hemoperfusion might be an innovative therapy for severe sepsis, and could improve outcome.

Micafungin versus fluconazole for prophylaxis against fungal infections in premature infants.

BACKGROUND: We conducted a comparative clinical study to evaluate the prophylactic effects of micafungin (MCFG) and fluconazole (FLCZ) on the incidence of fungal infections in extremely low-birthweight infants who were born at a gestational age of less than 26 weeks and weighed less than 1000 g. METHODS: With a combination of enteral administration of miconazole (6 mg/kg/day), FLCZ and MCFG were administered intravenously at a dose of 5 mg/kg/day and 3 mg/kg/day, respectively. The prophylaxis was classified as a failure when fungal infections were identified within the first 21 days after birth. RESULTS: The prophylaxis was successful in seven of 18 cases (39%) in the FLCZ group and 15 of 21 cases (71%) in the MCFG group, indicating that the success rate was significantly higher in the latter group. CONCLUSION: MCFG was superior to FLCZ as prophylaxis against fungal infections in extremely low-birthweight infants.

Risk Factors for Mortality and Neurodevelopmental Impairment among Neonates Born at 22-23 Weeks' Gestation.

INTRODUCTION: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22-23 weeks' gestational age, which currently remain unclear. METHODS: This retrospective case-control study included 104 infants delivered at 22-23 weeks' gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors' follow-up (61/65) was achieved in this study. RESULTS: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks' gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (<5th percentile) was higher (14.7 vs. 1.5%, p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. CONCLUSIONS: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22-23 weeks' gestation. NDI at 36-42 months' chronological age was associated with PVHI.