Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

OBJECTIVE: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1). STUDY DESIGN: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 220-286 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days. Time of last ANS dose prior to delivery was analyzed as a continuous variable (using 169 hours for durations >168 hours or no steroid exposure). Associations between ANS, Indo-D1, and SIP were obtained from a multilevel hierarchical generalized linear mixed model after covariate adjustment. This yielded aOR and 95% CI. RESULTS: Of 6851 infants, 243 had SIP (3.5%). ANS exposure occurred in 6393 infants (93.3%) and IndoD1 was given to 1863 infants (27.2%). The time (median, IQR) from last dose of ANS to delivery was 32.5 hours (6-81) vs 37.1 hours (7-110) for infants with or without SIP, respectively (P = .10). Indo-D1 was given to 51.9 vs 26.3% of infants with SIP vs no SIP, respectively (P < .0001). Adjusted analysis indicated no interaction between time of last ANS dose and Indo-D1 for SIP (P = .7). Indo-D1 but not ANS was associated with increased odds of SIP (aOR: 1.73, 1.21-2.48, P = .003). CONCLUSION: The odds of SIP were increased after receipt of Indo-D1. Exposure to ANS prior to Indo-D1 was not associated with an increase in SIP.

Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities.

Importance: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials. Objective: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids. Design, Setting, and Participants: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded. Exposure: Infants were classified as having no, partial, or complete exposure to antenatal steroids. Main Outcomes and Measures: The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center. Results: A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]). Conclusions and Relevance: In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.

Birth length is the strongest predictor of linear growth status and stunting in the first 2 years of life after a preconception maternal nutrition intervention: the children of the Women First trial.

BACKGROUND: The multicountry Women First trial demonstrated that nutritional supplementation initiated prior to conception (arm 1) or early pregnancy (arm 2) and continued until delivery resulted in significantly greater length at birth and 6 mo compared with infants in the control arm (arm 3). OBJECTIVES: We evaluated intervention effects on infants' longitudinal growth trajectory from birth through 24 mo and identified predictors of length status and stunting at 24 mo. METHODS: Infants' anthropometry was obtained at 6, 12, 18, and 24 mo after the Women First trial (registered at clinicaltrials.gov as NCT01883193), which was conducted in low-resource settings: Democratic Republic of Congo, Guatemala, India, and Pakistan. Longitudinal models evaluated intervention effects on infants' growth trajectory from birth to 24 mo, with additional modeling used to identify adjusted predictors for growth trajectories and outcomes at 24 mo. RESULTS: Data for 2337 (95% of original live births) infants were evaluated. At 24 mo, stunting rates were 62.8%, 64.8%, and 66.3% for arms 1, 2, and 3, respectively (NS). For the length-for-age z-score (LAZ) trajectory, treatment arm was a significant predictor, with adjusted mean differences of 0.19 SD (95% CI: 0.08, 0.30; P < 0.001) and 0.17 SD (95% CI: 0.07, 0.27; P < 0.001) for arms 1 and 2, respectively. The strongest predictors of LAZ at 24 mo were birth LAZ <-2 and <-1 to ≥-2, with adjusted mean differences of -0.76 SD (95% CI: -0.93, -0.58; P < 0.001) and -0.47 SD (95% CI: -0.56, -0.38; P < 0.001), respectively. For infants with ultrasound-determined gestational age (n = 1329), the strongest predictors of stunting were birth LAZ <-2 and <-1 to ≥- 2: adjusted relative risk of 1.62 (95% CI: 1.39, 1.88; P < 0.001) and 1.46 (95% CI: 1.31, 1.62; P < 0.001), respectively. CONCLUSIONS: Substantial improvements in postnatal growth are likely to depend on improved intrauterine growth, especially during early pregnancy.

Model for severe intracranial hemorrhage and role of early indomethacin in extreme preterm infants.

BACKGROUND: To develop a model for prediction of severe intracranial hemorrhage (ICH) or death based on variables from the first 12 h of age and to compare mortality and morbidities with and without exposure to early indomethacin. METHODS: This retrospective cohort study included extreme preterm (220/7-266/7 weeks) infants born at National Institute of Child Health and Human Development Neonatal Research Network sites. Primary outcome was a composite of severe ICH and/or death. RESULTS: Of 4624 infants, 1827 received early indomethacin. Lower gestation, lack of antenatal steroids exposure, lower 1-min Apgar, male sex, and receipt of epinephrine were associated with severe ICH or death. Early indomethacin was associated with a lower risk of patent ductus arteriosus, bronchopulmonary dysplasia, and higher risk of spontaneous intestinal perforation. CONCLUSIONS: A model for early prediction of severe ICH/death was developed and validated. Early indomethacin was associated with a lower risk of patent ductus arteriosus and bronchopulmonary dysplasia and a higher risk of spontaneous intestinal perforation. CLINICAL TRIAL REGISTRATION: Not applicable. IMPACT: Modern data on severe ICH and neonatal morbidities in relation to prophylactic indomethacin are scarce in the published literature. Prophylactic indomethacin was associated with a lower risk of patent ductus arteriosus and bronchopulmonary dysplasia and a higher risk of intestinal perforation. A risk estimator for severe intracranial hemorrhage/death was developed in a large cohort of extremely preterm infants. The risk estimator developed based on a large cohort of patients provides an estimate of severe intracranial bleeding for an individual infant.

Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies.

OBJECTIVE: To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia. METHODS: We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT. RESULTS: Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively. CONCLUSIONS: PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial.

OBJECTIVE: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age. STUDY DESIGN: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. RESULTS: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively. CONCLUSIONS: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01883193.

HIV incidence in South African blood donors from 2012 to 2016: a comparison of estimation methods.

BACKGROUND: Measuring incidence is important for monitoring and maintaining the safety of the blood supply. Blood collected from repeat-donors has provided the opportunity to follow blood donors over time and has been used to estimate the incidence of viral infections. These incidence estimates have been extrapolated to first-time donors using the ratio of NAT yield cases in first-time versus repeat-donors. We describe a model to estimate incidence in first-time donors using the limiting antigen (LAg) avidity assay and compare its results with those from established models. METHODS: HIV-positive first-time donations were tested for recency using the LAg assay. Three models were compared; incidence estimated for (1) first-time donors using LAg avidity, (2) first-time and repeat-donors separately using the NAT yield window period (WP) model and (3) repeat-donors using the incidence/WP model. RESULTS: HIV incidence in first-time donors was estimated at 3·32 (CI 3·11, 3·55) and 3·81 (CI 3·07, 4·73) per 1000 PY using the LAg assay and NAT yield WP models, respectively. Incidence in repeat-donors was between 2·0- and 2·5-fold lower than in first-time donors estimated at 1·56 (CI 1·37, 1·77) and 1·94 (CI 1·86-2·01) per 1000 PY using the NAT yield/WP and incidence/WP models, respectively. CONCLUSION: Testing HIV-positive donations using the LAg assay provides a reliable method to estimate incidence in first-time donors for countries that collect the majority of blood from first-time donors and do not screen with NAT.

Early Hypoxic Respiratory Failure in Extreme Prematurity: Mortality and Neurodevelopmental Outcomes.

OBJECTIVES: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO). METHODS: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race. RESULTS: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6). CONCLUSIONS: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants.

NT-proBNP levels in the identification and classification of pulmonary transfusion reactions.

BACKGROUND: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions. STUDY DESIGN AND METHODS: We performed a secondary analysis of a case-control study of pulmonary transfusion reactions at four academic hospitals. We evaluated clinical data and measured NT-proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank-Sum tests to compare NT-proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls. RESULTS: Pre-transfusion NT-proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre-transfusion NT-proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT-proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80). CONCLUSIONS: NT-proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre-transfusion NT-proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.

Are census data accurate for estimating coverage of a lymphatic filariasis MDA campaign? Results of a survey in Sierra Leone.

BACKGROUND: Preventive chemotherapy was administered to 3.2 million Sierra Leoneans in 13 health districts for lymphatic filariasis, onchocerciasis, and soil transmitted helminthes from October 2008 to February 2009. This paper aims to report the findings of a coverage survey conducted in 2009, compare the coverage survey findings with two reported rates for lymphatic filariasis coverage obtained using pre-mass drug administration (MDA) registration and national census projections, and use the comparison to understand the best source of population estimates in calculating coverage for NTD programming in Sierra Leone. METHODOLOGY/PRINCIPAL FINDINGS: Community drug distributors (CDDs) conducted a pre- MDA registration of the population. Two coverage rates for MDA for lymphatic filariasis were subsequently calculated using the reported number treated divided by the total population from: 1) the pre-MDA register and 2) national census projections. A survey was conducted to validate reported coverage data. 11,602 persons participated (response rate of 76.8%). Overall, reported coverage data aggregated to the national level were not significantly different from surveyed coverage (z-test >0.05). However, estimates based on pre-MDA registration have higher agreement with surveyed coverage (mean Kendall's W = 0.68) than coverage calculated with census data (mean Kendall's = 0.59), especially in districts with known large-scale migration, except in a highly urban district where it was more challenging to conduct a pre-MDA registration appropriately. There was no significant difference between coverage among males versus females when the analyses were performed excluding those women who were pregnant at the time of MDA. The surveyed coverage estimate was near or below the minimum 65% epidemiological coverage target for lymphatic filariasis MDA in all districts. CONCLUSION/SIGNIFICANCE: These results from Sierra Leone illustrate the importance of choosing the right denominator for calculating treatment coverage for NTD programs. While routinely reported coverage results using national census data are often good enough for programmatic decision making, census projections can quickly become outdated where there is substantial migration, e.g. due to the impact of civil war, with changing economic opportunities, in urban settings, and where there are large migratory populations. In districts where this is known to be the case, well implemented pre-MDA registration can provide better population estimates. Pre-MDA registration should, however, be implemented correctly to reduce the risk of missing pockets of the population, especially in urban settings.

Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision.

OBJECTIVE: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision. STUDY DESIGN: For infants born at <27 weeks of gestation between 2006 and 2013, prospectively collected maternal and neonatal characteristics and 18- to 26-month corrected age follow-up data were analyzed. Bayley-III cognitive and language scores of infants with discharge CPS supervision were compared with infants without CPS supervision using regression analysis while adjusting for potentially confounding variables, including entering CPS after discharge from the hospital. RESULTS: Of the 4517 preterm infants discharged between 2006 and 2013, 255 (5.6%) were discharged with a need for CPS supervision. Mothers of infants with CPS supervision were significantly more likely to be younger, single, and gravida ≥3; to have less than a high school education; and to have a singleton pregnancy and less likely to have received prenatal care or antenatal steroids. Despite similar birth weight and medical morbidities, the CPS group had longer hospital stays compared with the non-CPS group. In adjusted analysis, cognitive scores were points lower (B = -1.94; 95% CI, -3.88 to -0.08; P = .04) in the CPS at discharge group compared with the non-CPS group. In children who entered CPS supervision after hospital discharge (an additional 106 infants), cognitive scores were 4 points lower (ß = -4.76; 95% CI, -7.47 to -2.05; P < .001) and language scores were 5 points lower (ß = -4.93; 95% CI, -8.00 to -1.86; P = .002). CONCLUSION: Extremely preterm infants discharged from the hospital with CPS supervision or entering CPS postdischarge are at increased risk for cognitive delay at 2 years of age. Opportunities exist to intervene and potentially improve outcomes in this vulnerable group of children.

The impact of recipient factors on the lower-than-expected hemoglobin increment in transfused outpatients with hematologic diseases.

BACKGROUND: Patients with cancer or chronic hematologic disorders frequently receive red blood cell (RBC) transfusions. Based on long-standing assumptions, each RBC unit is thought to increase recipient hemoglobin by 1 g/dL, but smaller increments can occur. A better understanding of recipient factors affecting hemoglobin increments could help providers manage these patients. METHODS: Data were collected as a part of the observational Red Cells in Outpatients Transfusion Outcomes (RETRO) study of outpatients with hematologic or cancer-related diagnoses. Hemoglobin was measured before transfusion and 30 minutes after transfusion. A classification and regression tree (CART) analysis was performed to identify statistically significant associations with clinical variables. A corresponding prediction equation was developed and validated using linear regression. RESULTS: A total of 195 participants had both pre- and posttransfusion hemoglobin values for analysis. The median age was 66 years, and patients received one (73%) or two (27%) RBC units during the transfusion episode. The overall median change in hemoglobin was 0.6 g/dL per RBC unit. Both CART analysis and linear regression identified the following significant predictors of hemoglobin increment: number of units received (positive correlation), patient estimated circulating blood volume (negative correlation), pretransfusion hemoglobin (negative correlation), and patient age (negative correlation). CONCLUSION: In this study of outpatients with hematologic disease, most patients had a hemoglobin increment of less than 1 g/dL/unit. Recipient-specific factors influenced the hemoglobin increment at 30 minutes, and providers should consider circulating blood volume, pretransfusion hemoglobin, and recipient age, when developing patient-specific RBC transfusion plans for this unique cohort.

Using a motivator and deterrent questionnaire to predict actual donation return behavior among first-time African-origin blood donors.

BACKGROUND: In South Africa, success in recruiting first-time African-origin blood donors at low risk for HIV infection has been tempered by lower-than-anticipated return rates. We studied whether self-reported motivators and deterrents could predict actual donor return among first-time donors. METHODS: We administered a questionnaire on blood donation motivators and deterrents within 2 months after donation to a cohort of first-time African-origin blood donors in 2014 and followed their return behavior for 1 year. Survey responses associated with return within 1 year were assessed using separate multivariate logistic regression models for motivators and deterrents. RESULTS: A total of 2902 first-time African origin donors with median age of 23 years and female predominance (59%) were included. Within 1 year 1574 (54% of donors) attempted at least one additional donation. Donors were more likely to return if they strongly agreed with the statement "Blood donation is an easy way to make a difference" (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-2.9) and "I donated in response to advertisements on the radio, TV or newspaper" (OR, 1.6; 95% CI, 1.2-2.1). English language preference and nonstudent employment status were also associated with donor return. Poor customer service (OR, 0.45; 95% CI, 0.28-0.71), geographic region, and nonstudent employment status were associated with donor return in the deterrent model. CONCLUSIONS: Prosocial motivators and marketing communications predicted return, while poor customer experience predicted nonreturn. This novel design allowed us to study the link between donation motivators and deterrents and actual return for donation in the African context.

Therapeutic impact of red blood cell transfusion on anemic outpatients: the RETRO study.

BACKGROUND: Patients with cancer or other diagnoses associated with chronic anemia often receive red blood cell (RBC) transfusion as outpatients, but the effect of transfusion on functional status is not well demonstrated. STUDY DESIGN AND METHODS: To estimate the effect of transfusion on functional status and quality of life, we measured 6-minute walk test distance and fatigue- and dyspnea-related quality-of-life scores before and 1 week after RBC transfusion in 208 outpatients age ≥50 with at least one benign or malignant hematology/oncology diagnosis. To account for potential confounding effects of cancer treatment, patients were classified into two groups based on cancer treatment within 4 weeks of the study transfusion. Minimum clinically important improvements over baseline were 20 meters in walk test distance, 3 points in fatigue score, and 2 points in dyspnea score. RESULTS: The median improvement in unadjusted walk test distance was 20 meters overall and 30 meters in patients not receiving recent cancer treatment. Fatigue scores improved overall by a median of 3 points and by 4 points in patients without cancer treatment. There was no clinically important change in dyspnea scores. In multiple linear regression analysis, patients who maintained hemoglobin (Hb) levels of 8 g/dL or greater at 1 week posttransfusion, who had not received recent cancer treatment, and who did not require hospitalization during the study showed clinically important increases in mean walk test distance. CONCLUSIONS: Red blood cell transfusion is associated with a modest, but clinically important improvement in walk test distance and fatigue score outcomes in adult hematology/oncology outpatients.

Prolonged duration of early antibiotic therapy in extremely premature infants.

BACKGROUND: Prolonged early antibiotics in extremely premature infants may have negative effects. We aimed to assess prevalence and outcomes of provision of prolonged early antibiotics to extremely premature infants in the absence of culture-confirmed infection or NEC. METHODS: Cohort study of infants from 13 centers born without a major birth defect from 2008-2014 who were 401-1000 grams birth weight, 22-28 weeks gestation, and survived ≥5 days without culture-confirmed infection, NEC, or spontaneous intestinal perforation. We determined the proportion of infants who received prolonged early antibiotics, defined as ≥5 days of antibiotic therapy started at ≤72 h of age, by center and over time. Associations between prolonged early antibiotics and adverse outcomes were assessed using multivariable logistic regression. RESULTS: A total of 5730 infants were included. The proportion of infants receiving prolonged early antibiotics varied from 30-69% among centers and declined from 49% in 2008 to 35% in 2014. Prolonged early antibiotics was not significantly associated with death (adjusted odds ratio 1.17 [95% CI: 0.99-1.40], p = 0.07) and was not associated with NEC. CONCLUSIONS: The proportion of extremely premature infants receiving prolonged early antibiotics decreased, but significant center variation persists. Prolonged early antibiotics were not significantly associated with increased odds of death or NEC.

Neonatal Morbidities among Moderately Preterm Infants with and without Exposure to Antenatal Corticosteroids.

OBJECTIVE: We aimed to compare the rates of "surfactant treated respiratory disease" and other neonatal morbidities among moderately preterm (MPT) infants exposed to no, partial, or a complete course of antenatal corticosteroids (ANS). STUDY DESIGN: This observational cohort study evaluated MPT infants (290/7-336/7 weeks' gestational age), born between January 2012 and November 2013 and enrolled in the "MPT Registry" of the National Institute of Child Health and Human Development Neonatal Research Network. RESULTS: Data were available for 5,886 infants, including 676 with no exposure, 1225 with partial, and 3,985 with a complete course of ANS. Among no, partial, and complete ANS groups, respectively, there were significant differences in rates of delivery room resuscitation (4.1, 1.4, and 1.2%), surfactant-treated respiratory disease (26.5, 26.3, and 20%), and severe intracranial hemorrhage (3, 2, and 0.8%). Complete ANS course was associated with lower surfactant-treated respiratory disease, compared with partial ANS (odds ratio [OR] 0.62; 95% confidence interval [CI] 0.52-0.74), and no ANS groups (OR 0.52; 95% CI 0.41-0.66) on adjusted analysis. CONCLUSION: In MPT infants, ANS exposure is associated with lower delivery room resuscitation, surfactant-treated respiratory disease, and severe intracranial hemorrhage; with the lowest frequency of morbidities associated with a complete course.

Contemporary Risk Factors and Outcomes of Transfusion-Associated Circulatory Overload.

OBJECTIVES: Transfusion-associated circulatory overload is characterized by hydrostatic pulmonary edema following blood transfusion. Restrictive transfusion practice may affect the occurrence and severity of transfusion-associated circulatory overload in critically ill patients. We sought to examine contemporary risk factors and outcomes for transfusion-associated circulatory overload. DESIGN: Case-control study. SETTING: Four tertiary care hospitals. PATIENTS: We prospectively enrolled 200 patients with transfusion-associated circulatory overload identified by active surveillance and 405 controls matched by transfusion intensity. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 20,845 transfused patients who received 128,263 blood components from May 2015 until July 2016, transfusion-associated circulatory overload incidence was one case per 100 transfused patients. In addition to cardiovascular comorbidities, multivariable analysis identified the following independent predictors of transfusion-associated circulatory overload: acute kidney injury, emergency surgery, pretransfusion diuretic use, and plasma transfusion-the latter especially in females. Compared with matched controls, transfusion-associated circulatory overload cases were more likely to require mechanical ventilation (71% vs 49%; p < 0.001), experienced longer intensive care and hospital lengths of stay following transfusion, and had higher mortality (21% vs 11%; p = 0.02) even after adjustment for other potentially confounding variables. CONCLUSIONS: Despite restrictive transfusion practice, transfusion-associated circulatory overload remains a frequent complication of transfusion and is an independent risk factor for in-hospital morbidity and mortality. In addition to cardiovascular and renal risk factors, plasma transfusion was associated with transfusion-associated circulatory overload after controlling for other covariates. Additional research is needed to examine the benefit of reduced erythrocyte or plasma exposure in patients at high risk for transfusion-associated circulatory overload.

Milrinone in congenital diaphragmatic hernia - a randomized pilot trial: study protocol, review of literature and survey of current practices.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is commonly associated with pulmonary hypoplasia and pulmonary hypertension (PH). PH associated with CDH (CDH-PH) is frequently resistant to conventional pulmonary vasodilator therapy including inhaled nitric oxide (iNO) possibly due to right and left ventricular dysfunction. Milrinone is an intravenous inotrope and lusitrope with pulmonary vasodilator properties and has been shown anecdotally to improve oxygenation in PH. We developed this pilot study to determine if milrinone infusion would improve oxygenation in neonates ≥36 weeks postmenstrual age (PMA) with CDH. METHODS/DESIGN: Data on pulmonary vasodilator management and outcome of CDH patients was collected from 18 university NICUs affiliated with the Neonatal Research Network (NRN) from 2011 to 2012. The proposed pilot will be a masked, placebo-controlled, multicenter, randomized trial of 66 infants with CDH with an oxygenation index (OI) ≥10 or oxygen saturation index (OSI) ≥5. The primary outcome is the oxygenation response, as determined by change in OI at 24 h after initiation of study drug. As secondary outcomes, we will determine oxygenation at 48 h and 72 h post-infusion, right ventricular pressures on echocardiogram and the incidence of systemic hypotension, arrhythmias, intracranial hemorrhage, survival without extracorporeal membrane oxygenation, and chronic lung disease (oxygen need at 28 days postnatal age). Finally, we will evaluate the pulmonary and nutritional status at 4, 8 and 12 months of age using a phone questionnaire. RESULTS: Three hundred thirty-seven infants with CDH were admitted to NRN NICUs in 2011 and 2012 of which 275 were ≥36 weeks PMA and were exposed to the following pulmonary vasodilators: iNO (39%), sildenafil (17%), milrinone (17%), inhaled epoprostenol (6%), intravenous epoprostenol (3%), and intravenous PGE1 (1%). ECMO was required in 36% of patients. Survival to discharge was 71%. DISCUSSION: CDH is an orphan disease with high mortality with few randomized trials evaluating postnatal management. Intravenous milrinone is a commonly used medication in neonatal/pediatric intensive care units and is currently used in 17% of patients with CDH within the NRN. This pilot study will provide data and enable further studies evaluating pulmonary vasodilator therapy in CDH. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02951130; registered 14 October 2016.

Use of Blood Donor Screening to Monitor Prevalence of HIV and Hepatitis B and C Viruses, South Africa.

Among 397,640 first-time blood donors screened in South Africa during 2012-2015, HIV prevalence was 1.13%, hepatitis B virus prevalence 0.66%, and hepatitis C virus prevalence 0.03%. Findings of note were a high HIV prevalence in Mpumalanga Province and the near absence of hepatitis C virus nationwide.

Incidence of transfusion reactions: a multicenter study utilizing systematic active surveillance and expert adjudication.

BACKGROUND: Prevalence estimates of the serious hazards of transfusion vary widely. We hypothesized that the current reporting infrastructure in the United States fails to capture many transfusion reactions and undertook a multicenter study using active surveillance, data review, and adjudication to test this hypothesis. STUDY DESIGN AND METHODS: A retrospective record review was completed for a random sample of 17% of all inpatient transfusion episodes over 6 months at four academic tertiary care hospitals, with an episode defined as all blood products released to a patient in 6 hours. Data were recorded by trained clinical research nurses, and serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: Of 4857 transfusion episodes investigated, 1.1% were associated with a serious reaction. Transfusion-associated circulatory overload was the most frequent serious reaction noted, being identified in 1% of transfusion episodes. Despite clinical notes describing a potential transfusion association in 59% of these cases, only 5.1% were reported to the transfusion service. Suspected transfusion-related acute lung injury/possible transfusion-related acute lung injury, anaphylactic, and hypotensive reactions were noted in 0.08, 0.02, and 0.02% of transfusion episodes, respectively. Minor reactions, including febrile nonhemolytic and allergic, were noted in 0.62 and 0.29% of transfusion episodes, respectively, with 30 and 50% reported to the transfusion service. CONCLUSION: Underreporting of cardiopulmonary transfusion reactions is striking among academic, tertiary care hospitals. Complete and accurate reporting is essential to identify, define, establish pathogenesis, and mitigate/treat transfusion reactions. A better understanding of the failure to report may improve the accuracy of passive reporting systems.