Outcomes and care practices for preterm infants born at less than 33 weeks’ gestation: A quality-improvement study

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality in children younger than 5 years. We report the changes in neonatal outcomes and care practices among very preterm infants in Canada over 14 years within a national, collaborative, continuous quality-improvement program. METHODS: We retrospectively studied infants born at 23–32 weeks’ gestation who were admitted to tertiary neonatal intensive care units that participated in the Evidence-based Practice for Improving Quality program in the Canadian Neonatal Network from 2004 to 2017. The primary outcome was survival without major morbidity during the initial hospital admission. We quantified changes using process-control charts in 6-month intervals to identify special-cause variations, adjusted regression models for yearly changes, and interrupted time series analyses. RESULTS: The final study population included 50 831 infants. As a result of practice changes, survival without major morbidity increased significantly (56.6% [669/1183] to 70.9% [1424/2009]; adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06–1.10, per year) across all gestational ages. Survival of infants born at 23–25 weeks’ gestation increased (70.8% [97/137] to 74.5% [219/294]; adjusted OR 1.03, 95% CI 1.02–1.05, per year). Changes in care practices included increased use of antenatal steroids (83.6% [904/1081] to 88.1% [1747/1983]), increased rates of normothermia at admission (44.8% [520/1160] to 67.5% [1316/1951]) and reduced use of pulmonary surfactant (52.8% [625/1183] to 42.7% [857/2009]). INTERPRETATION: Network-wide quality-improvement activities that include better implementation of optimal care practices can yield sustained improvement in survival without morbidity in very preterm infants

Outcomes and resource usage of infants born at ≤ 25 weeks gestation in Canada

Objectives: To determine the outcomes and resource usage of infants born at ≤ 25 weeks gestational age (GA). Methods: Retrospective study of infants born between April 2009 and September 2011 at ≤ 25 weeks\u27 GA in all neonatal intensive care units in Canada with follow-up in the neonatal follow-up clinics. Short-term morbidities, neurodevelopmental impairment, significant neurodevelopmental impairment, and resource utilization of infants born at ≤ 24 weeks were compared with neonates born at 25 weeks. Results: Of 803 neonates discharged alive, 636 (80.4%) infants born at ≤ 25 weeks\u27 GA were assessed at 18 to 24 months. Caesarean delivery, lower birth weight, and less antenatal steroid exposure were more common in infants born ≤ 24 weeks as compared with 25 weeks. They had significantly higher incidences of ductus arteriosus ligation, severe intracranial hemorrhage, retinopathy of prematurity as well as longer length of stay, central line days, days on respiratory support, days on total parenteral nutrition, days on antibiotics, and need for postnatal steroids. Neurodevelopmental impairment rates were 68.9, 64.5, and 55.6% (P=0.01) and significant neurodevelopmental impairment rates were 39.3, 29.6, and 20.9% (P\u3c0.01) for infants ≤ 23, 24, and 25 weeks GA, respectively. Postdischarge service referrals were higher for those ≤ 23 weeks. Nonsurviving infants born at 25 weeks GA had higher resource utilization during admission than infants born less than 25 weeks. Conclusions: Adverse outcomes and resource usage were significantly higher among infants born ≤ 24 weeks GA as compared with 25 weeks GA

Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33weeks\u27 gestation

Importance: Neonatal hypothermia has been associated with higher mortality and morbidity; therefore, thermal control following delivery is an essential part of neonatal care. Identifying the ideal body temperature in preterm neonates in the first few hours of lifemay be helpful to reduce the risk for adverse outcomes. Objectives: To examine the association between admission temperature and neonatal outcomes and estimate the admission temperature associated with lowest rates of adverse outcomes in preterm infants born at fewer than 33 weeks\u27 gestation.. Design, Setting, And Participants: Retrospective observational study at 29 neonatal intensive care units in the Canadian Neonatal Network. Participants included 9833 inborn infants born at fewer than 33 weeks\u27 gestation who were admitted between January 1, 2010, and December 31, 2012.. Exposure: Axillary or rectal body temperature recorded at admission.. Main Outcomes And Measures: The primary outcomewas a composite adverse outcome defined as mortality or any of the following: severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infection. The relationships between admission temperature and the composite outcome as well as between admission temperature and the components of the composite outcome were evaluated using multivariable analyses.. Results: Admission temperatures of the 9833 neonates were distributed as follows: lower than 34.5°C (1%); 34.5°C to 34.9°C (1%); 35.0°C to 35.4°C (3%); 35.5°C to 35.9°C (7%); 36.0°C to 36.4°C (24%); 36.5°C to 36.9°C (38%); 37.0°C to 37.4°C (19%); 37.5°C to 37.9°C (5%); and 38.0°C or higher (2%). After adjustment for maternal and infant characteristics, the rates of the composite outcome, severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, and nosocomial infection had a U-shaped relationship with admission temperature (a \u3e 0 [P \u3c .05]). The admission temperature at which the rate of the composite outcome was lowest was 36.8°C (95%CI, 36.7°C-37.0°C). Rates of severe neurological injury, severe retinopathy of prematurity, necrotizing enterocolitis (95%CI, 36.3°C-36.7°C), bronchopulmonary dysplasia, and nosocomial infection (95%CI, 36.9°C-37.3°C) were lowest at admission temperatures ranging from 36.5°C to 37.2°C.. Conclusions And Relevance: The relationship between admission temperature and adverse neonatal outcomes was U-shaped. The lowest rates of adverse outcomes were associated with admission temperatures between 36.5°C and 37.2°C.

Association of Co-Exposure of Antenatal Steroid and Prophylactic Indomethacin with Spontaneous Intestinal Perforation

Objective: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at \u3c26 weeks of gestation or \u3c750 g birth weight. Study design: We conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (\u3e7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. Results: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. Conclusions: In preterm neonates of \u3c26 weeks of gestation or birth weight \u3c750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality

Serial serum brain-type natriuretic peptide (BNP) identifies compromised blood flow in infants with hemodynamically significant patent ductus arteriosus

Background: The physiological correlates of elevated serum brain-type natriuretic peptide (BNP) in hemodynamically significant patent ductus arteriosus (HSPDA) are unclear. Objective: To determine if serial BNP measured at 48-72 hours of age, before and after non-steroidal anti-inflammatory drugs (NSAID) treatment of HSPDA reflect compromised blood flow indices, in infants < 31 weeks of gestational age (GA). Design/methods: In a prospective blinded study, 70 infants < 31 weeks GA, admitted to Winnipeg NICUs from August 2010 to September 2011, had serum BNPs and echocardiograms at 48-72 hours of age, before and after medical treatment of HSPDA. All BNP and logarithm of BNP (logBNP) were correlated by linear regression with contemporaneous blood flow indices for: 1) systemic hemodynamic indices (corrected left and right ventricular outputs [LVO, RVO], RVO/LVO ratio, superior vena cava flow [SVCF], SVCF/LVO); 2) regional blood flow indices (middle cerebral artery flow [MCAF], MCAF/LVO ratio, middle cerebral artery resistive index [MCARI], middle cerebral artery pulsatility index [MCAPI]; celiac artery flow [CAF], CAF/LVO ratio, celiac artery resistive index [CARI], and celiac artery pulsatility index [CAPI]). Results: Twenty-six of 70 infants developed HSPDA at 6 ± 2 days. Both BNP and logBNP had similar correlations with all indices, but logBNP showed better goodness of fit. The best correlation was at 48-72 hours of life. Analyzing systemic hemodynamics, logBNP best correlated with SVCF (β -0.49, R2 0.24, p < 0.0001), SVCF/LVO (β -0.55, R2 0.31, p < 0.0001), RVO/LVO (β -0.59, R2 0.35, p < 0.0001), LVO (β 0.4, R2 0.16, p < 0.0001), and RVO (β -0.35, R2 0.12, p < 0.0001). For regional blood flow, logBNP best correlated with MCARI (β 0.6, R2 0.35, p < 0.0001), MCAPI (β 0.5, R2 0.29, p < 0.001), and MCAF (β -0.34, R2 0.12, p < 0.0001). Conclusions: BNP correlates with blood flow indices in preterm infants with HSPDA mainly at 48-72 hours reflecting the value of pre-symptomatic physiologic prediction by BNP

Pre-symptomatic prediction of morbitidies in preterm infants with patent ductus arteriosus by targeted neonatal echocardiography and brain-type natriuretic peptide

Objectives: Our objective was to compare patent ductus arteriosus (PDA) diameter, PDA score and brain-type natriuretic peptide (BNP) measurements at 48-72 hours of life, for prediction of neonatal morbidities. We hypothesized that use of a PDA score with BNP, may improve pre-symptomatic prediction of PDAs associated with adverse outcomes. Method: Infants < 31 weeks GA were prospectively studied by targeted neonatal echocardiogram (TNE) at 48-72 hours age, composite PDA score and serum BNP assay; the clinical team remained blinded. PDA was independently diagnosed by echocardiography at time of clinical suspicion (6 ± 2 days), and treated at discretion of the clinical team. Primary outcome was survival with one or more of adverse outcomes (intraventricular hemorrhage [IVH], bronchopulmonary dysplasia [BPD], retinopathy of prematurity [ROP], necrotizing enterocolitis [NEC]). Results: A PDA was present in 56 of 70 infants studied at 48-72 hours; 30 were eventually diagnosed with PDA but never required treatment, 19 required medical treatment, 7 surgical ligation. After adjustment for gestation, PDA diameter did not predict any adverse outcome, PDA score was associated with increased risk of any adverse outcome and high BNP was associated with IVH, BPD, or survival with any adverse outcome. Conclusions: Comprehensive PDA evaluation at 48-72 hours of age may predict the subsequent occurrence of adverse outcomes and may be useful to define the PDA treatment threshold

Effects of prophylactic indomethacin in extremely low-birth-weight infants with and without adequate exposure to antenatal corticosteroids

Objective: To examine whether treatment with antenatal corticosteroids modifies the immediate and long-term effects of prophylactic indomethacin sodium trihydrate in extremely low-birth-weight infants