BackgroundHyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.MethodsRetrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.Results66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).ConclusionsMortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.

Introduction: Hemolytic disease of the fetus and newborn (HDFN) occurs when fetal and neonatal erythroid cells are destroyed by maternal erythrocyte alloantibodies, it leads to anemia and hydrops in the fetus, and hyperbilirubinemia and kernicterus in the newborn. Postnatal care consists of intensive phototherapy and exchange transfusions to treat severe hyperbilirubinemia and top-up transfusions to treat early and late anemia. Other postnatal complications have been reported such as thrombocytopenia, iron overload and cholestasis requiring specific management. Areas covered: This review focusses on the current neonatal management and outcome of hemolytic disease and discusses postnatal treatment options as well as literature on long-term neurodevelopmental outcome. Expert commentary: Despite major advances in neonatal management, multiple issues have to be addressed to optimize postnatal management and completely eradicate kernicterus. Except for strict adherence to guidelines, improvement could be achieved by clarifying the epidemiology and pathophysiology of HDFN. Several pharmacotherapeutic agents should be further researched as alternative treatment options in hyperbilirubinemia, including immunoglobulins, albumin, phenobarbital, metalloporphyrins, zinc, clofibrate and prebiotics. Larger trials are warranted to evaluate EPO, folate and vitamin E in neonates. Long-term follow-up studies are needed in HDFN, especially on thrombocytopenia, iron overload and cholestasis.ARTICLE HISTORY

Background: There is no data available whether sedation should be given during minimally invasive surfactant therapy (MIST). Objective: To compare the level of comfort of preterm infants receiving sedation versus no sedation for MIST. Methods: A retrospective study of preterm infants receiving MIST was performed in Leiden University Medical Center in 2014. Sedation (propofol 1 mg/kg) was optional and left to the discretion of the caregiver. Standardized COMFORTneo scores were compared, and COMFORTneo <14 was considered comfortable. Basic characteristics and complications were noted. Results: In 38 infants receiving MIST, 23 received propofol and 15 were not sedated. Mean (SD) gestational age [29 (2) vs. 29 (3) weeks] and birth weight [1,312 (483) vs. 1,469 (588) g] were not different. Median (IQR) COMFORTneo was not different between the groups before [11 (9-15) vs. 10 (8-12)] and after MIST [10 (8-12) vs. 9 (8-10)], but lower in the sedated group during MIST [12 (9-17) vs. 20 (15-23)] with more often COMFORTneo <14 (56 vs. 11%). Duration of MIST [2 (2-4) vs. 3 (2-7) min] and occurrence of bradycardia (13 vs. 33%) and hypotension (21 vs. 18%) were not different. Although not significant, intubation occurred more often in the sedated group (during MIST: 9 vs. 0%, <24 h after MIST: 26 vs. 13%). During MIST, oxygen saturation <80% lasted longer in the sedated group [3 (2-4) vs. 1 (0-2) min], and nasal intermittent positive pressure ventilation was applied more (100 vs. 33%). Conclusions: Preterm infants receiving MIST were more comfortable when sedation was given, but needed ventilation more often. A randomized controlled trial is warranted to test whether the benefit of sedation outweighs the risks of complications.

Incidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome.

Background: Etiology of cholestatic liver disease in neonates with hemolytic disease of the newborn (HDN) has been associated with iron overload due to intrauterine red cell transfusions (IUTs). Data on the incidence and severity of cholestasis in neonates with HDN are scarce, and little is known about pathogenesis, risk factors, neonatal management and outcome. Objective: To evaluate incidence, risk factors, management and outcome of cholestasis in neonates with red cell alloimmune hemolytic disease. Methods: All (near-) term neonates with HDN due to red cell alloimmunization admitted to our center between January 2000 and July 2010 were included in this observational study. Liver function tests (including conjugated bilirubin) were routinely performed in the neonatal period. We recorded the presence of cholestasis, investigated several potential risk factors and evaluated the management and outcome in affected neonates. Results: A total of 313 infants with red cell alloimmune hemolytic disease treated with or without IUTs were included. The incidence of cholestasis was 13% (41/313). Two risk factors were independently associated with cholestasis: treatment with at least one IUT (OR 5.81, 95% CI 1.70–19.80, p = 0.005) and rhesus D type of alloimmunization (OR 4.66, 95% CI 1.05–20.57, p = 0.042). Additional diagnostic tests to investigate possible causes of cholestasis were all negative. In 5 infants (12%), supportive medical and nutritional therapy was started, and one neonate required iron chelation therapy. Conclusion: Cholestasis occurs in 13% of neonates with HDN due to red cell alloimmunization, and it is independently associated with IUT treatment and rhesus D type of alloimmunization.