Publications by authors named "Rosemary D Higgins"

214 Publications

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

J Pediatr 2021 Jun 19. Epub 2021 Jun 19.

National Institute of Child Health and Human Development, Bethesda, MD; Department of Global and Community Health, George Mason University, Fairfax, VA.

Objective: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants.

Study Design: EPT infants (24-27 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed.

Results: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22 months corrected age (P = .002).

Conclusions: EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2021.06.026DOI Listing
June 2021

Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy.

Pediatrics 2021 Jun 13;147(6). Epub 2021 May 13.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background And Objectives: Early determination of prognosis is important in neonates with hypoxic-ischemic encephalopathy (HIE). Our objective was to test scoring systems developed earlier (original scoring system) and develop new prognostic models.

Methods: Secondary analysis of data from the multicenter randomized controlled trial of longer, deeper, or usual care cooling in neonatal HIE (NCT01192776) that enrolled 364 neonates diagnosed with moderate or severe HIE. The primary outcome was death or moderate or severe disability at 18 to 22 months, and secondary outcome was death during initial hospitalization. Testing of early neurologic clinical examination (<6 hours of age) and the original scoring system for prognostic ability was done, followed by development of new scoring systems and classification and regression tree (CART) models by using early clinical variables (<6 hours of age).

Results: For death or disability, the original scoring system correctly classified 75% (95% confidence interval: 69%-81%), whereas the new scoring system correctly classified 78% (73%-82%), and the CART model correctly classified 76% (72%-81%). Early neurologic clinical examination also had a correct classification rate of 76% (71%-80%). Depth and duration of cooling did not affect prediction. Only a few components of the early neurologic examination were associated with poor outcome. For death, the original scoring system correctly classified 72% (66%-77%), the new scoring system 68% (63%-72%), the new CART model 87% (83%-90%), and early neurologic evaluation 81% (77%-85%).

Conclusions: The 3 models (scoring system, CART, and early neurologic evaluation) were comparable in predicting death or disability. For in-hospital death, CART models were superior to scoring systems and early neurologic examination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-048678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168606PMC
June 2021

COVID-19 Vaccine Considerations during Pregnancy and Lactation.

Am J Perinatol 2021 05 1;38(6):523-528. Epub 2021 May 1.

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0041-1726390DOI Listing
May 2021

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.

Objective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial.

Study Design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed.

Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40).

Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41372-021-01018-5DOI Listing
March 2021

Phenobarbital and Clonidine as Secondary Medications for Neonatal Opioid Withdrawal Syndrome.

Pediatrics 2021 03;147(3)

Environmental Influences on Child Health Outcomes Program, Office of the Director, National Institutes of Health, Rockville, Maryland.

Background And Objectives: Despite the neonatal opioid withdrawal syndrome (NOWS) epidemic in the United States, evidence is limited for pharmacologic management when first-line opioid medications fail to control symptoms. The objective with this study was to evaluate outcomes of infants receiving secondary therapy with phenobarbital compared with clonidine, in combination with morphine, for the treatment of NOWS.

Methods: We performed a retrospective cohort study of infants with NOWS from 30 hospitals. The primary outcome measures were the length of hospital stay, duration of opioid treatment, and peak morphine dose. Outcomes were compared by group by using analysis of variance and multivariable linear regression controlling for relevant confounders.

Results: Of 563 infants with NOWS treated with morphine, 32% ( = 180) also received a secondary medication. Seventy-two received phenobarbital and 108 received clonidine. After adjustment for covariates, length of hospital stay was 10 days shorter, and, in some models, duration of morphine treatment was 7.5 days shorter in infants receiving phenobarbital compared with those receiving clonidine, with no difference in peak morphine dose. Infants were more likely to be discharged from the hospital on phenobarbital than clonidine (78% vs 29%, < .0001).

Conclusions: Among infants with NOWS receiving morphine and secondary therapy, those treated with phenobarbital had shorter length of hospital stay and shorter morphine treatment duration than clonidine-treated infants but were discharged from the hospital more often on secondary medication. Further investigation is warranted to determine if the benefits of shorter hospital stay and shorter duration of morphine therapy justify the possible neurodevelopmental consequences of phenobarbital use in infants with NOWS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-017830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919109PMC
March 2021

Site-Level Variation in the Characteristics and Care of Infants With Neonatal Opioid Withdrawal.

Pediatrics 2021 01 21;147(1). Epub 2020 Dec 21.

Department of Pediatrics, School of Medicine, University of Louisville, Louisville, Kentucky.

Background And Objectives: Variation in pediatric medical care is common and contributes to differences in patient outcomes. Site-to-site variation in the characteristics and care of infants with neonatal opioid withdrawal syndrome (NOWS) has yet to be quantified. Our objective was to describe site-to-site variation in maternal-infant characteristics, infant management, and outcomes for infants with NOWS.

Methods: Cross-sectional study of 1377 infants born between July 1, 2016, and June 30, 2017, who were ≥36 weeks' gestation, with NOWS (evidence of opioid exposure and NOWS scoring within the first 120 hours of life) born at or transferred to 1 of 30 participating hospitals nationwide. Site-to-site variation for each parameter within the 3 domains was measured as the range of individual site-level means, medians, or proportions.

Results: Sites varied widely in the proportion of infants whose mothers received adequate prenatal care (31.3%-100%), medication-assisted treatment (5.9%-100%), and prenatal counseling (1.9%-75.5%). Sites varied in the proportion of infants with toxicology screening (50%-100%) and proportion of infants receiving pharmacologic therapy (6.7%-100%), secondary medications (1.1%-69.2%), and nonpharmacologic interventions including fortified feeds (2.9%-90%) and maternal breast milk (22.2%-83.3%). The mean length of stay varied across sites (2-28.8 days), as did the proportion of infants discharged with their parents (33.3%-91.1%).

Conclusions: Considerable site-to-site variation exists in all 3 domains. The magnitude of the observed variation makes it unlikely that all infants are receiving efficient and effective care for NOWS. This variation should be considered in future clinical trial development, practice implementation, and policy development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2020-008839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780957PMC
January 2021

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

N Engl J Med 2020 12;383(27):2639-2651

From the Department of Pediatrics, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia (H.K., B.S., A.S.C.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B., K.J.J., J.A.W.); the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto (S.R.H., V.Y.C.), and the Department of Pediatrics, University of California, Los Angeles, Los Angeles (U.D.) - both in California; the Biostatistics and Epidemiology Division, RTI International, Research Triangle Park (S.T., M.M.C.), and the Department of Pediatrics, Duke University School of Medicine, Durham (C.M.C.) - both in North Carolina; the Biostatistics and Epidemiology Division, RTI International, Rockville (J.E.N., A.D.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland; the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (B.R.V., A.R.L.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (W.A.C.); the University of Rochester School of Medicine and Dentistry, Rochester, NY (C.T.D., M.F.C.); the Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston (K.A.K.), and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas (M.H.W.); the University of New Mexico Health Sciences Center, Albuquerque (R.K.O.); the Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City (R.K.O., B.A.Y.); the Department of Pediatrics, Indiana University School of Medicine, Indianapolis (B.B.P., G.M.S.); Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati (B.B.P., K.S.), the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W.), and Nationwide Children's Hospital and the Department of Pediatrics, Ohio State University College of Medicine, Columbus (R.S.); the Department of Pediatrics, Dalhousie University, Halifax, NS, Canada (R.K.W.); the Department of Neonatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston (J.A.F.Z.); the Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO (W.E.T.); Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta (R.M.P.); the Department of Pediatrics, Wayne State University, Detroit (S.C.); and the College of Health and Human Services, George Mason University, Fairfax, VA (R.D.H.).

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.

Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.

Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.

Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2020248DOI Listing
December 2020

Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial.

J Pediatr 2021 03 13;230:106-111.e6. Epub 2020 Nov 13.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Pregnancy and Perinatology Branch, Bethesda, MD; George Mason University, Fairfax, VA.

Objective: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours.

Study Design: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age.

Results: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively.

Conclusions: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia.

Trial Registration: Clinicaltrials.gov: NCT00614744.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914162PMC
March 2021

Blood Biomarkers and 6- to 7-Year Childhood Outcomes Following Neonatal Encephalopathy.

Am J Perinatol 2020 Oct 10. Epub 2020 Oct 10.

Department of Global and Community Health, George Mason University, Fairfax, Virginia.

Objective:  This study aimed to profile the cytokine/chemokine response from day 0 to 7 in infants (≥36 weeks of gestational age) with neonatal encephalopathy (NE) and to explore the association with long-term outcomes.

Study Design:  This was a secondary study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network randomized controlled trial of whole body hypothermia for NE. Eligible infants with moderate-severe NE were randomized to cooling or normothermia. Blood spots were collected on days 0 to 1, 2 to 4, and 6 to 7. Twenty-four cytokines/chemokines were measured using a multiplex platform. Surviving infants underwent neurodevelopmental assessment at 6 to 7 years. Primary outcome was death or moderate-severe impairment defined by any of the following: intelligence quotient <70, moderate-severe cerebral palsy (CP), blindness, hearing impairment, or epilepsy.

Results:  Cytokine blood spots were collected from 109 participants. In total 99 of 109 (91%) were assessed at 6 to 7 years; 54 of 99 (55%) developed death/impairment. Neonates who died or were impaired had lower early regulated upon activation normal T cell expressed and secreted (RANTES) and higher day 7 monocyte chemotactic protein (MCP)-1 levels than neonates who survived without impairment. Though TNF-α levels had no association with death/impairment, higher day 0 to 1 levels were observed among neonates who died/developed CP. On multiple regression analysis adjusted for center, treatment group, sex, race, and level of hypoxic ischemic encephalopathy, higher RANTES was inversely associated with death/impairment (odds ratio (OR): 0.31, 95% confidence interval [CI]: 0.13-0.74), while day seven MCP-1 level was directly associated with death/impairment (OR: 3.70, 95% CI: 1.42-9.61). Targeted cytokine/chemokine levels demonstrated little variation with hypothermia treatment.

Conclusion:  RANTES and MCP-1 levels in the first week of life may provide potential targets for future therapies among neonates with encephalopathy.

Key Points: · Elevation of specific cytokines and chemokines in neonates with encephalopathy has been noted along with increased risk of neurodevelopmental impairment in infancy.. · Cytokine/chemokines at <7 days were assessed among neonates in a trial of hypothermia for HIE.. · Neonates who died or were impaired at 6 to 7 years following hypoxic-ischemic encephalopathy had lower RANTES and higher MCP-1 levels than those who survived without impairment..
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1717072DOI Listing
October 2020

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

Pediatrics 2020 10 17;146(4). Epub 2020 Sep 17.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland; and.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2019-3318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546092PMC
October 2020

Blood myo-inositol concentrations in preterm and term infants.

J Perinatol 2021 Feb 15;41(2):247-254. Epub 2020 Sep 15.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age.

Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values.

Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants).

Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41372-020-00799-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889639PMC
February 2021

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

J Pediatr 2020 Jul 30. Epub 2020 Jul 30.

College of Health and Human Services, George Mason University, Fairfax, VA.

Objective: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation.

Study Design: Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score <70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage.

Results: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week.

Conclusions: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2020.07.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855243PMC
July 2020

Perinatal COVID-19 Infection Prevention: Infographics for Patients and Providers.

Am J Perinatol 2020 10 19;37(12):1185-1188. Epub 2020 Jul 19.

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1714387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645813PMC
October 2020

Racial/Ethnic Disparities Among Extremely Preterm Infants in the United States From 2002 to 2016.

JAMA Netw Open 2020 06 1;3(6):e206757. Epub 2020 Jun 1.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Importance: Racial/ethnic disparities in quality of care among extremely preterm infants are associated with adverse outcomes.

Objective: To assess whether racial/ethnic disparities in major outcomes and key care practices were changing over time among extremely preterm infants.

Design, Setting, And Participants: This observational cohort study used prospectively collected data from 25 US academic medical centers. Participants included 20 092 infants of 22 to 27 weeks' gestation with a birth weight of 401 to 1500 g born at centers participating in the National Institute of Child Health and Human Development Neonatal Research Network from 2002 to 2016. Of these infants, 9316 born from 2006 to 2014 were eligible for follow-up at 18 to 26 months' postmenstrual age (excluding 5871 infants born before 2006, 2594 infants born after 2014, and 2311 ineligible infants including 64 with birth weight >1000 g and 2247 infants with gestational age >26 6/7 weeks), of whom 745 (8.0%) did not have known follow-up outcomes at 18 to 26 months.

Main Outcomes And Measures: Rates of mortality, major morbidities, and care practice use over time were evaluated using models adjusted for baseline characteristics, center, and birth year. Data analyses were conducted from 2018 to 2019.

Results: In total, 20 092 infants with a mean (SD) gestational age of 25.1 (1.5) weeks met the inclusion criteria and were available for the primary outcome: 8331 (41.5%) black infants, 3701 (18.4%) Hispanic infants, and 8060 (40.1%) white infants. Hospital mortality decreased over time in all groups. The rate of improvement in hospital mortality over time did not differ among black and Hispanic infants compared with white infants (black infants went from 35% to 24%, Hispanic infants went from 32% to 27%, and white infants went from 30% to 22%; P = .59 for race × year interaction). The rates of late-onset sepsis among black infants (went from 37% to 24%) and Hispanic infants (went from 45% to 23%) were initially higher than for white infants (went from 36% to 25%) but decreased more rapidly and converged during the most recent years (P = .02 for race × year interaction). Changes in rates of other major morbidities did not differ by race/ethnicity. Death before follow-up decreased over time (from 2006 to 2014: black infants, 14%; Hispanic infants, 39%, white infants, 15%), but moderate-severe neurodevelopmental impairment increased over time in all racial/ethnic groups (increase from 2006 to 2014: black infants, 70%; Hispanic infants, 123%; white infants, 130%). Rates of antenatal corticosteroid exposure (black infants went from 72% to 90%, Hispanic infants went from 73% to 83%, and white infants went from 86% to 90%; P = .01 for race × year interaction) and of cesarean delivery (black infants went from 45% to 59%, Hispanic infants went from 49% to 59%, and white infants went from 62% to 63%; P = .03 for race × year interaction) were initially lower among black and Hispanic infants compared with white infants, but these differences decreased over time.

Conclusions And Relevance: Among extremely preterm infants, improvements in adjusted rates of mortality and most major morbidities did not differ by race/ethnicity, but rates of neurodevelopmental impairment increased in all groups. There were narrowing racial/ethnic disparities in important care practices, including the use of antenatal corticosteroids and cesarean delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2020.6757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287569PMC
June 2020

Early working memory is a significant predictor of verbal and processing skills at 6-7 years in children born extremely preterm.

Early Hum Dev 2020 08 23;147:105083. Epub 2020 May 23.

University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Objective: The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18-22 months corrected age, was associated with executive function at 6-7 years in a cohort of children born extremely preterm.

Study Design: Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive function.

Results: Children who had achieved object permanence mastery at a corrected age of 18-22 months had higher mean scores on the WISC-IV tests of verbal comprehension and processing speed at age 6-7 years. Regression models indicated that object permanence scores were significant predictors of both verbal comprehension and processing speeds scores, after controlling for other factors. When analyzed by subgroup for sex, these results were significant for girls but not for boys.

Conclusions: This study found that an early mastery of object permanence was associated with higher scores in areas of verbal comprehension and processing speed in girls. These results have implications for potentially identifying young children born preterm that are at greater risk for difficulties with cognitive and working memory skills at school age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2020.105083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384388PMC
August 2020

Association of Antenatal Corticosteroids and Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm Children.

Obstet Gynecol 2020 06;135(6):1377-1386

Department of Pediatrics, the University of Alabama at Birmingham, Birmingham, Alabama; Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina; the Department of Pediatrics, Children's Hospital of Michigan and Hutzel Women's Hospital, Wayne State University, Detroit, Michigan; the Department of Pediatrics, University of Iowa, Iowa City, Iowa; the Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California; the Department of Pediatrics, UT Southwestern, Dallas, Texas; the Department of Obstetrics and Gynecology and Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama; the Department of Global and Community Health, George Mason University, Fairfax, Virginia; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Maryland.

Objective: To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone.

Methods: This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics.

Results: Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups.

Conclusion: In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone.

Clinical Trial Registration: ClinicalTrials.gov, NCT00063063.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/AOG.0000000000003882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278037PMC
June 2020

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies.

JAMA Pediatr 2020 07 6;174(7):e200593. Epub 2020 Jul 6.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland.

Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies.

Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants.

Design, Setting, And Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020.

Main Outcomes And Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death.

Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008).

Conclusions And Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2020.0593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199167PMC
July 2020

Assessment of an Updated Neonatal Research Network Extremely Preterm Birth Outcome Model in the Vermont Oxford Network.

JAMA Pediatr 2020 05 4;174(5):e196294. Epub 2020 May 4.

Office of Research, George Mason University College of Health and Human Services, Fairfax, Virginia.

Importance: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals.

Objective: To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States.

Design, Setting, And Participants: This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks' 0 days' to 25 weeks' 6 days' gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019.

Exposures: Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids.

Main Outcomes And Measures: The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months' corrected age and measures of hospital resource use (days of hospitalization and ventilator use).

Results: Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age-only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%).

Conclusions And Relevance: An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2019.6294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052789PMC
May 2020

Neonatal oxygen saturations and blood pressure at school-age in children born extremely preterm: a cohort study.

J Perinatol 2020 06 28;40(6):902-908. Epub 2020 Feb 28.

Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA.

Objective: To explore the relationship between neonatal oxygen saturation and BP at age 6-7 years in a cohort of infants born extremely preterm.

Study Design: Infants <28 weeks gestation were assigned to a higher or lower oxygen saturation target. Oximeter data were monitored throughout the neonatal period. A subset of survivors was seen at age 6. BP was measured and compared by group assignment, achieved saturations, and time spent in hypoxemia (saturations <80%).

Results: There was no difference in systolic or diastolic BP between assigned groups. Median achieved weekly oxygen saturation was not associated with BP. Longer duration of hypoxemia during the first week of age was associated with higher systolic BP.

Conclusions: Neither target nor actual median oxygen saturations in this study was associated with BP at school age. Increased duration of hypoxemia in the first postnatal week was associated with higher systolic BP at 6-7 years of age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41372-020-0619-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260090PMC
June 2020

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

J Pediatr 2019 12 6;215:41-49.e4. Epub 2019 Sep 6.

Division of Neonatal Medicine, Department of Pediatrics, Brown University, Providence, RI.

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 (β = -4.76; 95% CI, -7.47 to -2.05; P < .001) and language scores were 5 points lower (β = -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2019.07.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988387PMC
December 2019

Oxygen Saturation and Retinopathy of Prematurity.

Clin Perinatol 2019 09 12;46(3):593-599. Epub 2019 Jun 12.

College of Health and Human Services, George Mason University, 4400 University Drive, 2G7, Peterson Family Health Science Hall, Room 5415, Fairfax, VA 22030, USA. Electronic address:

Retinopathy of prematurity (ROP) is a serious disease affecting premature infants. Rates of ROP increase with decreasing gestational age. Duration of oxygen exposure is correlated with ROP. Many studies evaluating oxygen have been performed to assess impact on ROP. This article describes recent findings for oxygen saturation target studies and suggests area of future study for ROP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clp.2019.05.008DOI Listing
September 2019

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.

Pediatrics 2019 08 23;144(2). Epub 2019 Jul 23.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Objective: Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood.

Methods: This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment).

Results: The cohort ( = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; = .04) were significantly higher with bevacizumab therapy.

Conclusions: In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/peds.2018-3537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855825PMC
August 2019

The ACT NOW Clinical Practice Survey: Gaps in the Care of Infants With Neonatal Opioid Withdrawal Syndrome.

Hosp Pediatr 2019 08 19;9(8):585-592. Epub 2019 Jul 19.

Children's Hospital at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Objectives: The incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold over the last 10 years. Standardized NOWS care protocols have revealed many improved patient outcomes. Our objective for this study is to describe results of a clinical practice survey of NOWS management practices designed to inform future clinical studies in the diagnosis and management of NOWS.

Methods: A cross-sectional survey was administered to medical unit directors at 32 Institutional Development Award States Pediatric Clinical Trial Network and 22 Neonatal Research Network sites in the fall of 2017. Results are presented as both the number and percentage of positive responses. Ninety-five percent Wilson confidence intervals (CIs) were generated around estimates, and χ and Fisher's exact tests were used to compare the association between unit type and reporting of each protocol.

Results: Sixty-two responses representing 54 medical centers were received. Most participating NICU and non-ICU sites reported protocols for NOWS management, including NOWS scoring (98% NICU; 86% non-ICU), pharmacologic treatment (92% NICU; 64% non-ICU), and nonpharmacologic care (79% NICU; 79% non-ICU). Standardized protocols for pharmacologic care and weaning were reported more frequently in the NICU (92% [95% CI: 80%-97%] and 94% [95% CI: 83%-98%], respectively) compared with non-ICU settings (64% [95% CI: 39%-84%] for both) ( < .05 for both comparisons). Most medical centers reported morphine as first-line therapy (82%; 95% CI: 69%-90%) and level 3 and level 4 NICUs as the location of pharmacologic treatment (83%; 95% CI: 71%-91%).

Conclusions: Observed variations in care between NICUs and non-ICUs revealed opportunities for targeted interventions in training and standardized care plans in non-ICU sites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1542/hpeds.2019-0089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663517PMC
August 2019

Achieved oxygen saturations and retinopathy of prematurity in extreme preterms.

Arch Dis Child Fetal Neonatal Ed 2020 Mar 22;105(2):138-144. Epub 2019 Jun 22.

College of Health and Human Services, George Mason University, Fairfax, Virginia, USA.

Objective: To identify achieved oxygen saturations (SpO) associated with increased risk of severe retinopathy of prematurity (ROP).

Design: This is a secondary analysis of the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT)randomised controlled trial. SpO was recorded up to 36 weeks' postmenstrual age. Saturations through 9 postnatal weeks were explored graphically, and logistic regression models were created to predict severe ROP.

Setting: 20 centres of the National Institute of Child Health and Human Development Neonatal Research Network.

Patients: 984 surviving infants of 24-27 weeks' gestational age born in 2005-2009.

Interventions: SUPPORT targeted SpO to a lower (85%-89%) or higher (91%-95%) range through 36 weeks' postmenstrual age or off respiratory support.

Main Outcome Measures: Severe ROP defined as threshold ROP, ophthalmological surgery or bevacizumab treatment.

Results: There were statistically significant interactions between duration of oxygen supplementation and percentage of time in certain achieved saturation ranges. Specifically, for infants who spent at least 2 weeks on oxygen in postnatal weeks 1-5, a higher percentage of time at 91%-96% SpO was associated with increased odds of severe ROP. For infants who spent at least 3 weeks on oxygen in postnatal weeks 6-9, a higher percentage of time at 97%-100% SpO was associated with increased odds of severe ROP. Other significant risk factors were lower gestational age and birth weight, non-Hispanic white versus black race, prospectively defined severe illness, late-onset sepsis or meningitis, and clinical centre.

Conclusions: Among extremely preterm survivors to discharge, the association between SpO and severe ROP depended on the timing and duration of oxygen supplementation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2018-316464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925651PMC
March 2020

Outcomes of Extremely Preterm Infants With Birth Weight Less Than 400 g.

JAMA Pediatr 2019 05;173(5):434-445

National Institute of Child Health and Human Development, Bethesda, Maryland.

Importance: Birth weight (BW) is an important predictor of mortality and morbidity. At extremely early gestational ages (GAs), BW may influence decisions regarding initiation of resuscitation.

Objective: To characterize outcomes of liveborn infants with a BW less than 400 g.

Design, Setting, And Participants: This retrospective multicenter cohort study analyzed extremely preterm infants born between January 2008 and December 2016 within the National Institute of Child Health and Human Development Neonatal Research Network. Infants with a BW less than 400 g and a GA of 22 to 26 weeks were included. Active treatment was defined as the provision of any potentially lifesaving intervention after birth. Survival was analyzed for the entire cohort; neurodevelopmental impairment (NDI) was examined for those born between January 2008 and December 2015 (birth years with outcomes available for analysis). Neurodevelopmental impairment at 18 to 26 months' corrected age (CA) was defined as a Bayley Scales of Infant and Toddler Development, Third Edition, cognitive composite score less than 85, a motor composite score less than 85, moderate or severe cerebral palsy, gross motor function classification system score of 2 or greater, bilateral blindness, and/or hearing impairment. Data were analyzed from September 2017 to October 2018.

Exposures: Birth weight less than 400 g.

Main Outcomes And Measures: The primary outcome was survival to discharge among infants who received active treatment. Analysis of follow-up data was limited to infants born from 2008 to 2015 to ensure children had reached assessment age. Within this cohort, neurodevelopmental outcomes were assessed for infants who survived to 18 to 26 months' CA and returned for a comprehensive visit.

Results: Of the 205 included infants, 121 (59.0%) were female, 133 (64.9%) were singletons, and 178 (86.8%) were small for gestational age. Almost half (101 of 205 [49.3%]) received active treatment at birth. A total of 26 of 205 infants (12.7%; 95% CI, 8.5-18.9) overall survived to discharge, and 26 of 101 actively treated infants (25.7%; 95% CI, 17.6-35.4) survived to discharge. Within the subset of infants with a BW less than 400 g and a GA of 22 to 23 weeks, 6 of 36 actively treated infants (17%; 95% CI, 6-33) survived to discharge. Among infants born between 2008 and 2015, 23 of 90 actively treated infants (26%; 95% CI, 17-36) survived to discharge. Two infants died after discharge, and 2 were lost to follow-up. Thus, 19 of 90 actively treated infants (21%; 95% CI, 13-31) were evaluated at 18 to 26 months' CA. Moderate or severe NDI occurred in 14 of 19 infants (74%).

Conclusions And Relevance: Infants born with a BW less than 400 g are at high risk of mortality and significant morbidity. Although 21% of infants survived to 18 to 26 months' CA with active treatment, NDI was common among survivors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2019.0180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503635PMC
May 2019

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

J Pediatr 2019 05 6;208:156-162.e5. Epub 2019 Feb 6.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Objective: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment.

Study Design: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation.

Results: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids.

Conclusions: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment.

Trial Registration: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.12.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486854PMC
May 2019

Prolonged duration of early antibiotic therapy in extremely premature infants.

Pediatr Res 2019 06 22;85(7):994-1000. Epub 2019 Jan 22.

Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-019-0300-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531328PMC
June 2019

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm.

Pediatr Res 2019 09 12;86(3):339-347. Epub 2018 Dec 12.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children.

Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30' later, evening).

Results: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p < 0.01; girls p = 0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p = 0.04), subscapular, and abdominal skinfold thicknesses (both p < 0.01).

Conclusion: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-018-0243-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561840PMC
September 2019

Reply.

J Pediatr 2019 04 24;207:264. Epub 2018 Dec 24.

Cincinnati Children's Hospital Medical Center Cincinnati, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.11.056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636836PMC
April 2019

Behavioral problems are associated with cognitive and language scores in toddlers born extremely preterm.

Early Hum Dev 2019 01 4;128:48-54. Epub 2018 Dec 4.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Objective: To evaluate the relationship of parent-reported child behaviors on the Child Behavior Checklist (CBCL) to cognition, language, and motor skills on the Bayley Scales of Infant and Toddler Development - III (Bayley-III) in toddlers born extremely preterm.

Study Design: Toddlers born extremely preterm (gestational ages 22 0/7 to 26 6/7 weeks) were tested at 22-26 months corrected age with Bayley-III while parents completed the CBCL. Socio-demographic variables and medical history were recorded. Linear regression models were used to assess the relationship of Bayley-III cognitive, motor, and language scores with CBCL scores, adjusting for medical and socio-demographic factors.

Results: Internalizing, affective, and pervasive development problem behavior scores on the CBCL correlated significantly with lower Bayley-III cognitive, language, and motor scores on unadjusted and adjusted analyses. Although externalizing and anxiety problems were significantly associated with cognitive and language scores on unadjusted analysis, the relationships were not significant after adjusting for socio-economic factors. CBCL scores were similar for boys and girls, with the exception of the pervasive developmental problem scale; boys had significantly more problems than girls (p = 0.02).

Conclusions: This study showed that parent reported behavior problems were related to lower cognitive, language, and motor development in toddlers born extremely preterm. Early findings of behavioral problems in toddlers born extremely premature may help identify children at greater risk for later learning difficulties. Adding a measure of behavior to the evaluation of these children may help better understand factors that can contribute to delays, especially in cognition and language.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2018.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425758PMC
January 2019
-->