Trends in Perinatal Practices and Neonatal Outcomes of Very Low Birth Weight Infants during a 16-year Period at NEOCOSUR Centers.

OBJECTIVE: To describe trends in mortality, major morbidity, and perinatal care practices of very low birth weight infants born at NEOCOSUR Neonatal Network centers from January 1, 2001, through December 31, 2016. STUDY DESIGN: A retrospective analysis of prospectively collected data from all inborn infants with a birthweight of 500-1500 g and 23-35 weeks of gestation. RESULTS: We examined data for 13 987 very low birth weight infants with a mean birth weight of 1081 ± 281 g and a gestational age of 28.8 ± 2.9 weeks. Overall mortality was 26.8% without significant changes throughout the study period. Decreases in early onset sepsis from 6.3% to 2.8% (P <.001), late onset sepsis from 21.1% to 19.5% (P = .002), retinopathy of prematurity from 21.3% to 13.8% (P <.001), and hydrocephalus from 3.8% to 2.4% (P <.001), were observed. The incidence for bronchopulmonary dysplasia decreased from 17.3% to 16% (P = .043), incidence of severe intraventricular hemorrhage was 10.4%, necrotizing enterocolitis 11.1%, and periventricular leukomalacia 3.8%, and did not change over the study period. Administration of antenatal corticosteroids increased from 70.2% to 82.3% and cesarean delivery from 65.9% to 75.4% (P <.001). The use of conventional mechanical ventilation decreased from 67.7% to 63.9% (P <.001) and continuous positive airway pressure use increased from 41.3% to 64.3% (P <.001). Survival without major morbidity increased from 37.4% to 44.5% over the study period (P <.001). CONCLUSIONS: Progress in perinatal and neonatal care at network centers was associated with an improvement in survival without major morbidity of very low birth weight infants during a 16-year period. However, overall mortality remained unchanged.

rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

Educating neonatal nurses in Brazil: a before-and-after study with interrupted time series analysis.

BACKGROUND: Preterm birth contributes significantly to infant mortality and morbidity, including blindness from retinopathy of prematurity (ROP). Access to intensive neonatal care is expanding in many countries, but care is not always optimal, one factor being that nursing is often by inadequately trained nurse assistants. OBJECTIVE: The aim of this study was to evaluate whether an educational package for nurses improves a range of outcomes including survival rates and severe ROP in 5 neonatal units in Rio de Janeiro, Brazil. METHODS: The study design included an uncontrolled before-and-after study in 5 units, with interrupted time series analysis. Participatory approaches were used to develop a self-administered educational package for control of pain, oxygenation, infection, nutrition, and temperature and to improve supportive care ('POINTS of Care'). Educational materials and DVD clips were developed and training skills of nurse tutors were enhanced. There were two 1-year periods of data collection before and after a 3-month period of self-administration of the education package. RESULTS: Overall, 74% of 401 nurses and nurse assistants were trained. A total of 679 and 563 infants were included in the pre- and post-training periods, respectively. Despite improvement in knowledge and nursing practices, such as the delivery and monitoring of oxygen, there was no change in survival (pre-training 80%, post-training 78.2%), severe ROP (1.6 vs. 2.8%), sepsis (11.3 vs. 12.3 cases per 1,000 infant days) or other outcomes. Outcomes worsened over the pre-intervention period but the change to an improvement after the intervention was not statistically significant. During the study period many trained staff left the units, but few were replaced. CONCLUSIONS: Future studies need to focus on barriers to implementation, team building, leadership and governance, as well as the acquisition of knowledge and skills.

Impact of changing oxygenation policies on retinopathy of prematurity in a neonatal unit in Argentina.

AIMS: To assess the impact of different oxygenation policies on the rate and severity of retinopathy of prematurity (ROP). METHODS: Between January 2003 and December 2006, infants of 1500 g birthweight (BW) or less and/or 32 weeks gestational age (GA) or less, and larger, more mature infants with risk factors for ROP were examined through three different time periods: period 1: high target oxygen saturation levels (88-96%) and treatment at threshold ROP; period 2: low target oxygen saturation levels (83-93%) and treatment at threshold ROP; period 3: low target oxygen saturation and treatment at type 1 ROP. RESULTS: Type 1 ROP was detected more frequently in babies of 32 weeks GA or less (50/365, 13.7%) than in more mature babies (15/1167, 1.3%; p<0.001). The rate of type 1 ROP in period 1 was 6.9%; period 2, 3.6% and period 3, 1.8%. Rates of stage 3 ROP declined over time in both BW/GA groups (from 9.0% to 4.1% to 2.0%) as did rates of plus disease (from 7.5% to 3.6% to 1.8%). Mean BW and GA declined from period 1 to period 3, and death rates remained unchanged. 74.4% of babies received all the examinations required; 48.1% of treatments were undertaken after discharge from the neonatal unit. CONCLUSIONS: Lower target oxygen saturation was associated with a lower rate of severe ROP without increasing mortality, and changed the characteristics of affected babies. Screening criteria need to remain wide enough to identify all babies at risk of ROP needing treatment.

Incidence and risk factors for retinopathy of prematurity in very low and in extremely low birth weight infants in a unit-based approach in southern Brazil.

AIMS: To analyse the incidence and risk factors for retinopathy of prematurity (ROP) and survival rates among extremely low birth weight (ELBW) and very low birth weight (VLBW) preterm infants. METHODS: A prospective cohort study of 352 infants admitted at a teaching hospital, Hospital de Clinicas de Porto Alegre, Brazil, between October 2002 and December 2006, was screened for ROP. The ELBW group comprised infants whose birth weight (BW) was < or = 1000 g and the VLBW group comprised those infants whose BW were > 1000 g and < or = 1500 g. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. RESULTS: Of the 352 neonates screened, 88 were ELBW babies. Survival rates among ELBW and VLBW were 47.8 and 88.7%, respectively. ROP affected 48.9% of ELBW infants and 18.2% of VLBW babies. Threshold disease occurred in 21 patients, 15 of whom were born weighing < 1000 g. Only 2.3% of the neonates born with more than 1000 g developed treatable disease. Univariate analysis showed that gestational age (GA), BW, use of indomethacin and erythropoietin, blood transfusions, and intraventricular haemorrhage were associated with ROP. After logistic regression, the most important adjusted risk factors were BW (OR: 1.002;95% CI: 1.001-1.003; P=0.003), GA (OR: 1.254;95% CI: 1.082-1.455; P=0.003), and use of erythropoietin (OR: 2.486;95% CI: 1.182-5.231; P=0.016). CONCLUSION: This study showed reduced survival rates, high incidence of ROP, and a greater need of treatment among ELBW infants as compared to VLBW babies admitted in this institution.

Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study.

OBJECTIVE: We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants. METHODS: The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis. RESULTS: After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66). CONCLUSIONS: SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.

Retinopatía del prematuro. Frecuencia en el Servicio de Neonatología del Instituto Nacional de Pediatría del 1o. de marzo de 1988 al 28 de febrero de 1989 / Retinopathy of the premature: frequence in the Service of Neonatology of Instituto Nacional de Pediatría from march 1st of 1988 to february 28 of 1989

Se examinaron los ojos de 25 niños recién nacidos prematuros que ingresaron al Servicio de Neonatología del Instituto Nacional de Pediatría en el período comprendido entre 1o. de marzo de 1988 al 28 de febrero de 1989. Todos pesaron menos de 2000 g al momento del nacimiento; llegaron al servicio en sus primeras 24 horas de vida; recibieron oxígeno y fueron dados de alta por mejoría. Cinco de estos niños desarrollaron retinopatía del prematuro en su fase aguda. Cuatro de ellos presentaron una retinopatía grado I y uno, retinopatía grado II de acuerdo a la clasificación Internacional de la Retinopatía del Prematuro publicada en 1984. Los niños que desarrollaron retinopatía, fueron pacientes con peso y una edad gestacional menor al nacimiento; fueron trasfundidos un mayor número de veces; recibieron FIO2 entre 80 y 100% por más tiempo, con una duración total de oxigenoterapia mayor que los niños que no la desarrollaron