Eric S. Shinwell

The Neonatal European Study of Inhaled Steroids (NEUROSIS): An EU-Funded International Randomised Controlled Trial in Preterm Infants

a Department of Neonatology, University Children’s Hospital, Tubingen , Germany; b Royal Maternity Hospital, and Department of Child Health, Queen’s University, Belfast , UK; c General Faculty Hospital in Prague, Prague , Czech Republic; d Department of Pediatrics and Adolescence and Neonatal Research Laboratory, Oulu University Hospital, University of Oulu, Oulu , Finland; e Department of Neonatology, Kaplan Medical Center, Rehovot, and f Hebrew University, Jerusalem , Israel; g Assistance Publique-Hopitaux de Paris, Service de Medecine Neonatale de Port-Royal and Universite Paris Descartes, Paris , France; h Department of Paediatrics, Children’s Hospital, Azienda Ospedaliero-Universitaria, Ancona , Italy; i Children’s National Medical Center, Washington, D.C. , USA; j Department of Paediatrics, Erasmus MC Sophia Children’s Hospital, Rotterdam , The Netherlands; k Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart , and l Department of Clinical Pharmacology, University Hospital Tubingen, Tubingen , Germany

Outcomes of Multiplets

Outcomes, both short and long term, differ between singletons and multiplets. Recently, a number of large, well-designed studies have clarified these differences, particularly in light of major changes in perinatal and neonatal care that have influenced changing outcomes. Accordingly, this article will review risks for singletons, twins and higher-order multiples as whole groups and also after correction for gestational age and other potential confounding variables that differ markedly between the groups. In addition, we will focus on the effects of certain factors such as antenatal steroid therapy and gender. Finally, we will detail the specific long-term risks for multiples in terms of growth and neurodevelopmental disabilities.

Early adequate maternal weight gain is associated with fewer small for gestational age triplets.

Abstract Objective: To examine whether the recommended weight gain during the first 24 weeks reduces the frequency of SGA triplets. Study design: We used data collected by the Womens Health Division of Matria Healthcare, Inc (Marietta, GA). We studied the frequency of SGA triplets (birth weight <10th percentile by triplet standards) by weight gain, parity, and pregravid BMI category. Adequate weight gain was defined as >16.2 kg at 24 weeks and BMI categories were defined as underweight (<19.8), normal (19.8–26), and obese (BMI>26). Results: We studied 2890 triplet sets. Adequate weight gain reduces the frequency of SGA triplets, irrespective of pregravid BMI category and parity, except for obese nulliparous women. However, the reduced frequency of SGA infants was significant only in underweight nulli-paras (OR 0.3, 95% CI 0.1, 0.9). Conclusion: Higher pregravid BMI and parity seem to reduce the occurrence of SGA triplets. However, lean mothers, especially nulliparas, may be the most important target population for nutritional intervention in triplet pregnancies.

Comparison of hematologic indices and markers of infection in umbilical cord and neonatal blood

Abstract Objective: Evaluation of a neonate for suspected early neonatal sepsis routinely includes blood tests such as complete blood count, C-reactive protein (CRP) and culture. In order to obviate the need for venepuncture, we prospectively compared these tests in paired samples from umbilical cord and peripheral venous blood drawn during the first hours after birth in both preterm and term infants. Methods: Paired blood samples were studied from asymptomatic neonates with risk factors for early sepsis. Data were collected on maternal and neonatal factors that may have influenced the correlation between the tests. Results: Three hundred fifty pairs of samples were studied. Significant correlation between umbilical cord and peripheral venous samples was found for white blood cell (WBC; r = 0.683) and platelets (PLT) (r = 0.54). Correlation for hemoglobin was lower (r = 0.36). No cases of early neonatal sepsis were detected. However, contamination rates were 12% in umbilical cord blood and 2.5% in peripheral venous blood cultures. WBC rose after birth and the 90th percentile rose from 22 500 in umbilical cord blood to 29 700 in peripheral blood. Conclusions: Screening for sepsis with umbilical cord CBC may be useful provided normal ranges are adjusted accordingly.

Correlation of transcutaneous bilirubinometry (TcB) and total serum bilirubin (TsB) levels after phototherapy

Abstract Aim: To investigate the correlation between transcutaneous bilirubinometry (TcB) and total serum bilirubin (TsB) in jaundiced infants before and after, but not during phototherapy. Methods: This study prospectively investigated the correlation between TcB and TsB in term and near term infants before and after phototherapy. Results: Overall 673 pairs of measurements (TcB and TsB) were performed on 371 infants of ≥35 weeks gestation and with birth weight above 2000 g. Of these 337 sets were from 200 infants who had not been treated with phototherapy (Group 1) and 336 measurements from 171 infants taken between 1 h and 5 d after phototherapy (Group 2). The correlation coefficient between TcB and TsB in the whole cohort was r = 0.72. The correlation was low during the first 8 h after phototherapy (r = 0.56), but thereafter the correlation returned to the range of 0.65–0.8. Using the Sobel test, no significant difference was found between the correlation coefficients at the different time periods, with the possible exception of the difference between 1 and 8 h and 9 and 16 h which was of borderline significance with a p value of 0.06. Conclusion: This study demonstrates good correlation between TcB and TsB by 8 h after phototherapy. This adds validity to community-based screening programs employing TcB measurements plotted on TsB nomograms. Such programs may contribute to prevention of tragic cases of bilirubin-induced neurologic damage.

Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia

Background The long‐term effects on neurodevelopment of the use of inhaled glucocorticoids in extremely preterm infants for the prevention or treatment of bronchopulmonary dysplasia are uncertain. Methods We randomly assigned 863 infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to receive early (within 24 hours after birth) inhaled budesonide or placebo. The prespecified secondary long‐term outcome was neurodevelopmental disability among survivors, defined as a composite of cerebral palsy, cognitive delay (a Mental Development Index score of <85 [1 SD below the mean of 100] on the Bayley Scales of Infant Development, Second Edition, with higher scores on the scale indicating better performance), deafness, or blindness at a corrected age of 18 to 22 months. Results Adequate data on the prespecified composite long‐term outcome were available for 629 infants. Of these infants, 148 (48.1%) of 308 infants assigned to budesonide had neurodevelopmental disability, as compared with 165 (51.4%) of 321 infants assigned to placebo (relative risk, adjusted for gestational age, 0.93; 95% confidence interval [CI], 0.80 to 1.09; P=0.40). There was no significant difference in any of the individual components of the prespecified outcome. There were more deaths in the budesonide group than in the placebo group (82 [19.9%] of 413 infants vs. 58 [14.5%] of 400 infants for whom vital status was available; relative risk, 1.37; 95% CI, 1.01 to 1.86; P=0.04). Conclusions Among surviving extremely preterm infants, the rate of neurodevelopmental disability at 2 years did not differ significantly between infants who received early inhaled budesonide for the prevention of bronchopulmonary dysplasia and those who received placebo, but the mortality rate was higher among those who received budesonide. (Funded by the European Union and Chiesi Farmaceutici; ClinicalTrials.gov number, NCT01035190.)

Rehospitalization Through Childhood and Adolescence: Association with Neonatal Morbidities in Infants of Very Low Birth Weight

Objective To evaluate the impact of major neonatal morbidities on the risks for rehospitalization in children and adolescents born of very low birth weight. Study design An observational study was performed on data of the Israel Neonatal Network linked together with the Maccabi Healthcare Services medical records. After discharge from the neonatal intensive care unit, 6385 infants of very low birth weight born from 1995 to 2012 were registered with Maccabi Healthcare Services and formed the study cohort. Multivariable negative binomial regression models were calculated to estimate the adjusted relative risk (aRR) and 95% CI for hospitalization. Results Up to 18 years following discharge, 3956 infants were hospitalized at least once. The median age of follow‐up was 10.7 years with total of follow‐up of 67 454 patient years and 10 895 hospitalizations. The risks for rehospitalization were increased significantly for each of the neonatal morbidities: surgical necrotizing enterocolitis (NEC), aRR 2.71 (95% CI 2.08–3.53), intraventricular hemorrhage grades 3–4, 2.13 (1.85–2.46), periventricular leukomalacia (PVL), 1.83 (1.58–2.13), bronchopulmonary dysplasia, 1.94 (1.72–2.17), and retinopathy of prematurity stages 3–4, 1.59 (1.36–1.85). During the first 4 years, children with surgically treated NEC, intraventricular hemorrhage, PVL, or bronchopulmonary dysplasia had 1.5‐ to 2.5‐fold greater risks for hospitalization compared with those without the specific morbidity. In the 11th‐14th and 15th‐18th years, respectively, surgically treated NEC was associated with a 3.05 (1.32–7.04) and 3.26 (0.99–10.7) aRR for hospitalization, and PVL was associated with a 2.67 (1.79–3.97) and 3.47 (2.03–5.92) aRR for hospitalization. Conclusions Specific major neonatal morbidities as well as the number of morbidities were associated with excess risks of rehospitalization through childhood and adolescence.

Ethics of birth at the limits of viability: the risky business of prediction.

Infants born at the limits of viability present neonatologists in particular and society in general with difficult challenges. Ethical and legal considerations establish a framework for action, although this varies between countries, departments and individuals and shows dynamic changes over time. This brief review includes a vignette telling a familiar story. In this case, the parents ask searching questions and the caring, knowledgeable neonatologist uses up-to-date information to offer empathic and thoughtful guidance - a challenge for all.

Early weight gain does not decrease the incidence of low birth weight and small for gestational age triplets in mothers with normal pre-gestational body mass index.

Abstract Objective: To examine if the recommended weight gain of >680 g/week during the first 24 weeks of pregnancy decreases the frequency of adverse birth weight outcomes in triplet mothers with a normal pregravid BMI. Study design: Retrospective observational study of a large sample of triplet mothers with a normal (19.8–26) pregravid BMI. Adequate, average, and inadequate weight gains were defined as >680, 500–680, and <500 g/week. Outcome measures were the incidence of ≥1 SGA infant and total triplet birth weight <4500 g. Results: Of the 1166 triplet mothers, 208 (17.8%) gained >680 g/week during their pregnancy. This presumed adequate weight gain did not reduce the incidence of SGA triplets or that of total birth weight <4500 g, irrespective of parity. These adverse birth weight outcomes were 2 to 3.5 times lower among multiparous compared to nulliparous mothers. Conclusion: Early weight gain of >680 g/week in triplet mothers with a normal pre-pregnancy BMI is not associated with a decrease in the incidence of adverse outcomes. Weight gain recommendations in triplet pregnancies should be realistic and associated with a low risk-benefit ratio.

Early, rapidly progressive enteral nutrition promotes growth of very low birth weight (VLBW) infants

Abstract Aim: This study describes the effects of a quality improvement program to promote improved postnatal nutrition on the growth of very low birth weight (VLBW) infants. Methods: Daily data regarding nutrition and growth were collected from the medical record of VLBW infants born during 1995–2010. The infants were grouped by year of birth in order to compare infants from before, during and after the policy change. Evaluation of growth included age in days at a return to birth weight and the proportion of infants with weight below the 10th percentile at discharge. Results: The caloric and protein intake improved significantly. The age at a return to birth weight fell (p < 0.01) from 14.6 ± 5 d to 11 ± 8 d after the change. The proportion of infants with a discharge weight below the 10th percentile for corrected age fell (p < 0.01) from 72.1% to 42.1%. Data on enteral feeding showed that increased rate of enteral feeds (EF) was associated with better growth (p < 0.001). Conclusion: Increasing awareness led to increase in caloric and protein intake in VLBW infants. Aggressive EF was associated with more rapid weight gain. However, the provision of protein and calories during the first 2 weeks of life still falls short of the latest European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommendations.