Changes in In-Hospital Survival and Long-Term Neurodevelopmental Outcomes of Extremely Preterm Infants: A Retrospective Study of a Japanese Tertiary Center.

OBJECTIVES: The objective of this study was to elucidate whether the survival and long-term neurodevelopmental outcomes of extremely preterm infants have improved in a Japanese tertiary center with an active treatment policy for infants born at 22-23 weeks of gestation. STUDY DESIGN: This single-centered retrospective cohort study enrolled extremely preterm infants treated at Saitama Medical Center, Saitama Medical University, from 2003 to 2014. Patients with major congenital abnormalities were excluded. Primary outcomes were in-hospital survival and severe neurodevelopmental impairment (NDI) at 6 years of age, which was defined as having severe cerebral palsy, severe cognitive impairment, severe visual impairment, or deafness. We assessed the changes in primary outcomes between the first (period 1; 2003-2008) and the second half (period 2; 2009-2014) of the study period and evaluated the association between birth-year and primary outcomes using multivariate logistic regression models. RESULTS: Of the 403 eligible patients, 340 (84%) survived to discharge. Among 248 patients available at 6 years of age, 43 (14%) were classified as having severe NDI. Between the 2 periods, in-hospital survival improved from 155 of 198 (78%) to 185 of 205 (90%), but severe NDI increased from 11 of 108 (10%) to 32 of 140 (23%). In multivariate logistic regression models adjusted for gestational age, birthweight, sex, singleton birth, and antenatal corticosteroids, the aOR (95% CI) of birth-year for in-hospital survival and severe NDI was 1.2 (1.1-1.3) and 1.1 (1.0-1.3), respectively. CONCLUSION: Mortality among extremely preterm infants has improved over the past 12 years; nevertheless, no significant improvement was observed in the long-term neurodevelopmental outcomes.

Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: To determine the trends in inhaled nitric oxide (iNO) utilization in the late phase of hospitalization in a large Japanese cohort of extremely preterm infants and evaluate its benefit on long-term outcomes. STUDY DESIGN: This was a retrospective multicenter cohort study of 15 977 extremely preterm infants born at <28 weeks of gestational age between 2003 and 2016, in the Neonatal Research Network, Japan. Demographic characteristics, morbidity, and mortality were compared between extremely preterm infants with and without post-acute iNO therapy. Multivariable logistic analysis was performed to determine factors associated with post-acute iNO and its impact on neurodevelopmental outcomes at 3 years of age. RESULTS: Post-acute iNO utilization rates increased from 0.3% in 2009 to 1.9% in 2016, even under strict insurance coverage rules starting in 2009. Gestational age (1-week increment; aOR 0.82, 95% CI 0.76-0.88), small for gestational age (1.47, 1.08-1.99), histologic chorioamnionitis (1.50, 1.21-1.86), 5-minute Apgar score <4 (1.51, 1.10-2.07), air leak (1.92, 1.30-2.83), and bubbly/cystic appearance on chest X-Ray (1.68, 1.37-2.06) were associated with post-acute iNO. Post-acute iNO was not associated with neurodevelopmental outcomes at 3 years of age. CONCLUSIONS: The increasing post-acute iNO utilization rate among extremely preterm infants has been concurrent with improved survival rates of extremely preterm infants in Japan. Infants treated with post-acute iNO had more severe disease and complications than the comparison group, but there were no differences in neurodevelopmental outcome at 3 years. This suggests post-acute iNO may benefit extremely preterm infants.

In-Hospital Outcomes in Large for Gestational Age Infants at 22-29 Weeks of Gestation.

OBJECTIVE: To estimate the risks of mortality and morbidities in large for gestational age (LGA) infants relative to appropriate for gestational age infants born at 22-29 weeks of gestation. STUDY DESIGN: Data on 156 587 infants were collected between 2006 and 2014 in 852 US centers participating in the Vermont Oxford Network. We defined LGA as sex-specific birth weight above the 90th centile for gestational age measured in days. Generalized additive models with smoothing splines on gestational age by LGA status were fitted on mortality and morbidity outcomes to estimate adjusted relative risks and their 95% CIs. RESULTS: Compared with appropriate for gestational age infants, being born LGA was associated with decreased risks of mortality, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, late-onset sepsis, severe retinopathy of prematurity, and chronic lung disease. Early onset sepsis and severe intraventricular hemorrhage were increased among LGA infants, but these risks were not homogeneous across the gestational age range. CONCLUSIONS: Being born LGA was associated with lower risks for all the examined outcomes except for early onset sepsis and severe intraventricular hemorrhage.

The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm.

OBJECTIVE: To assess the association between maternal prepregnancy body mass index and adequacy of pregnancy weight gain in relation to neurocognitive function in school-aged children born extremely preterm. STUDY DESIGN: Study participants were 535 ten-year-old children enrolled previously in the prospective multicenter Extremely Low Gestational Age Newborns cohort study who were products of singleton pregnancies. Soon after delivery, mothers provided information about prepregnancy weight. Prepregnancy body mass index and adequacy of weight gain were characterized based on this information. Children underwent a neurocognitive evaluation at 10 years of age. RESULTS: Maternal prepregnancy obesity was associated with increased odds of a lower score for Differential Ability Scales-II Verbal IQ, for Developmental Neuropsychological Assessment-II measures of processing speed and visual fine motor control, and for Wechsler Individual Achievement Test-III Spelling. Children born to mothers who gained an excessive amount of weight were at increased odds of a low score on the Oral and Written Language Scales Oral Expression assessment. Conversely, children whose mother did not gain an adequate amount of weight were at increased odds of a lower score on the Oral and Written Language Scales Oral Expression and Wechsler Individual Achievement Test-III Word Reading assessments. CONCLUSION: In this cohort of infants born extremely preterm, maternal obesity was associated with poorer performance on some assessments of neurocognitive function. Our findings are consistent with the observational and experimental literature and suggest that opportunities may exist to mitigate risk through education and behavioral intervention before pregnancy.

Latent class analysis shows that paediatricians' opinions about the advanced resuscitation of extremely preterm infants were diverse and influenced by personal beliefs.

AIM: The aim of this study was to survey paediatricians, who taught neonatal resuscitation in Brazil, about when they would apply advanced resuscitation in the delivery room for newborn infants born at 23-26 weeks of gestational age. METHODS: This cross-sectional study focused on an electronic questionnaire that was sent to paediatricians who acted as instructors for the Brazilian Neonatal Resuscitation Program from December 2011 to September 2013. The primary outcome was the gestational age at which the respondent would apply advanced resuscitation in the delivery room. Latent class analysis identified the profiles of the instructors, and logistic regression identified the variables associated with belonging to one of the derived classes. RESULTS: The 560 (82%) instructors who agreed to participate fell into three latent classes: pro-resuscitation, intermediate and pro-limitation, with high, intermediate and low probabilities of performing advanced resuscitation in neonates born at 23-26 weeks. In the multivariate model, group membership was associated with the paediatrician's age, years of practice and personal importance of religion and the patient's birthweight, future quality of life and probability of death. CONCLUSION: The opinions of paediatricians performing advanced resuscitation on extremely preterm infants in the delivery room were diverse and influenced by personal beliefs.

Circulating Inflammatory-Associated Proteins in the First Month of Life and Cognitive Impairment at Age 10 Years in Children Born Extremely Preterm.

OBJECTIVES: To evaluate whether in children born extremely preterm, indicators of sustained systemic inflammation in the first month of life are associated with cognitive impairment at school age. STUDY DESIGN: A total of 873 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborn Study from 2002 to 2004 were evaluated at age 10 years. We analyzed the relationship between elevated blood concentrations of inflammation-associated proteins in the first 2 weeks ("early elevations"; n = 812) and the third and fourth week ("late elevations"; n = 532) of life with neurocognition. RESULTS: Early elevations of C-reactive protein, tumor necrosis factor-α, interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and erythropoietin were associated with IQ values >2 SD below the expected mean (ORs: 2.0-2.3) and with moderate to severe cognitive impairment on a composite measure of IQ and executive function (ORs: 2.1-3.6). Additionally, severe cognitive impairment was associated with late protein elevations of C-reactive protein (OR: 4.0; 95% CI 1.5, 10), IL-8 (OR: 5.0; 1.9, 13), ICAM-1 (OR: 6.5; 2.6, 16), vascular endothelial growth factor-receptor 2 (OR: 3.2; 1.2, 8.3), and thyroid-stimulating hormone (OR: 3.1; 1.3, 7.3). Moderate cognitive impairment was most strongly associated with elevations of IL-8, ICAM-1, and vascular endothelial growth factor-receptor 2. When 4 or more inflammatory proteins were elevated early, the risk of having an IQ <70 and having overall impaired cognitive ability was more than doubled (ORs: 2.1-2.4); the presence of 4 or more inflammatory protein elevated late was strongly linked to adverse cognitive outcomes (ORs: 2.9-4.8). CONCLUSIONS: Extremely preterm children who had sustained elevations of inflammation-related proteins in the first postnatal month are more likely than extremely preterm peers without such elevations to have cognitive impairment at 10 years.

Effects of Targeting Higher or Lower Oxygen Saturations in Centers with More Versus Less Separation between Median Saturations.

Subgroup analysis of the Canadian Oxygen Trial to compare outcomes of extremely preterm infants in centers with more versus less separation between median arterial oxygen saturations in the two target ranges. Centers with more separation observed lower rates of death or disability in the 85%-89% range than in the 91%-95% target range.

Duration of breastfeeding in preterm infants followed at a secondary referral service / Duração do aleitamento materno em prematuros acompanhados em serviço de referência secundário

Objective: Identify and analyze variables associated with shorter duration of breastfeeding in preterm infants. Methods: Retrospective cohort of premature infants followed up at secondary referral service in the period of 2010-2015. Inclusion: first appointment in the first month of corrected age and have undergone three or more consultations. Exclusion: diseases that impaired oral feeding. Outcome: duration of breastfeeding. A total of 103 preterm infants were evaluated, accounting for 28.8% of the preterm infants born in the municipality in that period, with a power of study of 80%. Descriptive analysis, t-test, chi-square test, Kaplan-Meier curves and Cox regression were used. p-values <0.05 were considered significant. Results: The median duration of breastfeeding among preterm infants was 5.0 months. The risk of breastfeeding discontinuation among preterm infants with gestational age <32 weeks was 2.6-fold higher than for those born at 32 weeks or more and the risk of breastfeeding interruption in preterm infants who were receiving breastfeeding supplementation in the first outpatient visit was 3-fold higher when compared to those who were exclusively breastfed in the first consultation. Conclusions: The median duration of breastfeeding in preterm infants was below the recommended one and discontinuation was associated with gestational <32 weeks and the fact that the infant was no longer receiving exclusive breastfeeding in the first outpatient visit. When these two variables were associated, their negative effect on the median duration of breastfeeding was potentiated.

Objetivo: Identificar e analisar as variáveis associadas à menor duração do aleitamento materno em prematuros. Métodos: Coorte retrospectiva de prematuros acompanhados em centro de referência secundária, de 2010 a 2015. Inclusão: primeira consulta no primeiro mês de idade corrigida para prematuridade e ter feito três ou mais consultas. Exclusão: doenças que impossibilitassem a alimentação via oral. Desfecho: duração do aleitamento materno. Avaliaram-se 103 prematuros, 28,8% dos prematuros do município no período, com poder do estudo de 80%. Usaram-se análise descritiva, teste t, qui quadrado de Pearson, curvas de Kaplan-Meier e regressão de Cox. Considerou-se significativo o p-valor<0,05. Resultados: A duração mediana do aleitamento materno entre os prematuros foi de cinco meses. O risco de interrupção do aleitamento materno entre prematuros de idade gestacional inferior a 32 semanas foi 2,6 vezes maior em relação aos que nasceram com 32 semanas ou mais e o risco de interrupção do aleitamento materno em prematuros que estavam em aleitamento materno complementado na primeira consulta ambulatorial foi três vezes maior em relação aos que estavam em aleitamento materno exclusivo na primeira consulta. Conclusões: A duração mediana do aleitamento materno em prematuros encontrou-se aquém do preconizado e sua interrupção se associou à idade gestacional inferior a 32 semanas e ao fato de não estar mais em aleitamento materno exclusivo na primeira consulta ambulatorial. Quando essas duas variáveis se associaram, potencializou-se sua interferência negativa na duração mediana do aleitamento materno.

[Duration of breastfeeding in preterm infants followed at a secondary referral service]. / Duração do aleitamento materno em prematuros acompanhados em serviço de referência secundário.

OBJECTIVE: Identify and analyze variables associated with shorter duration of breastfeeding in preterm infants. METHODS: Retrospective cohort of premature infants followed up at secondary referral service in the period of 2010-2015. INCLUSION: first appointment in the first month of corrected age and have undergone three or more consultations. Exclusion: diseases that impaired oral feeding. OUTCOME: duration of breastfeeding. A total of 103 preterm infants were evaluated, accounting for 28.8% of the preterm infants born in the municipality in that period, with a power of study of 80%. Descriptive analysis, t-test, chi-square test, Kaplan-Meier curves and Cox regression were used. p-values<0.05 were considered significant. RESULTS: The median duration of breastfeeding among preterm infants was 5.0 months. The risk of breastfeeding discontinuation among preterm infants with gestational age <32 weeks was 2.6-fold higher than for those born at 32 weeks or more and the risk of breastfeeding interruption in preterm infants who were receiving breastfeeding supplementation in the first outpatient visit was 3-fold higher when compared to those who were exclusively breastfed in the first consultation. CONCLUSIONS: The median duration of breastfeeding in preterm infants was below the recommended one and discontinuation was associated with gestational <32 weeks and the fact that the infant was no longer receiving exclusive breastfeeding in the first outpatient visit. When these two variables were associated, their negative effect on the median duration of breastfeeding was potentiated.