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  • 1
    Online Resource
    Online Resource
    Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial : A Secondary Analysis of a Randomized Clinical Trial
    American Medical Association (AMA) ; 2023
    In:  JAMA Network Open Vol. 6, No. 5 ( 2023-05-31), p. e2315315-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 5 ( 2023-05-31), p. e2315315-
    Abstract: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. Objective To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. Design, Setting, and Participants This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. Intervention Infants were randomized to 10 days of hydrocortisone or placebo treatment. Main Outcomes and Measures Infants’ baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. Results Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. Trial Registration ClinicalTrials.gov Identifier: NCT01353313
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2023.15315
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 12 ( 2022-12-08), p. e2245826-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 12 ( 2022-12-08), p. e2245826-
    Abstract: Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age. Design, Setting, and Participants This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures Culture-confirmed LOM. Main Outcomes and Measures Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 ( P   & amp;lt; .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 ( P   & amp;lt; .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P  = .008). LP performance varied by center among all LOS evaluations (10%-59%, P   & amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, P   & amp;lt; .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus , 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.45826
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 3
    Online Resource
    Online Resource
    Early-Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm
    Elsevier BV ; 2023
    In:  The Journal of Pediatrics Vol. 259 ( 2023-08), p. 113443-
    Details
    In: The Journal of Pediatrics, Elsevier BV, Vol. 259 ( 2023-08), p. 113443-
    Type of Medium: Online Resource
    ISSN: 0022-3476
    URL: Article
    DOI: 10.1016/j.jpeds.2023.113443
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2005245-5
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  • 4
    Online Resource
    Online Resource
    Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm
    American Medical Association (AMA) ; 2024
    In:  JAMA Pediatrics
    Details
    In: JAMA Pediatrics, American Medical Association (AMA)
    Abstract: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. Objective To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. Design, Setting, and Participants This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). Main Outcomes and Measures The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age. Results Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%] ; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%] ; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. Conclusions and Relevance For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.
    Type of Medium: Online Resource
    ISSN: 2168-6203
    URL: Article
    DOI: 10.1001/jamapediatrics.2024.0125
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2024
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  • 5
    Online Resource
    Online Resource
    Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants
    American Medical Association (AMA) ; 2023
    In:  JAMA Network Open Vol. 6, No. 5 ( 2023-05-08), p. e2312277-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 5 ( 2023-05-08), p. e2312277-
    Abstract: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. Objective To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks’ postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years’ corrected age in extremely preterm infants. Design, Setting, and Participants This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks’ gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Exposure Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. Main Outcomes and Measures The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years’ corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years’ corrected age. Results A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%] ) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Conclusions and Relevance Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2023.12277
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 6
    Online Resource
    Online Resource
    Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities
    American Medical Association (AMA) ; 2022
    In:  JAMA Network Open Vol. 5, No. 9 ( 2022-09-26), p. e2233331-
    Details
    In: JAMA Network Open, American Medical Association (AMA), Vol. 5, No. 9 ( 2022-09-26), p. e2233331-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    URL: Article
    DOI: 10.1001/jamanetworkopen.2022.33331
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 7
    Online Resource
    Online Resource
    Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia
    Elsevier BV ; 2020
    In:  The Journal of Pediatrics Vol. 219 ( 2020-04), p. 152-159.e5
    Details
    In: The Journal of Pediatrics, Elsevier BV, Vol. 219 ( 2020-04), p. 152-159.e5
    Type of Medium: Online Resource
    ISSN: 0022-3476
    URL: Article
    DOI: 10.1016/j.jpeds.2019.12.028
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2005245-5
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  • 8
    Online Resource
    Online Resource
    Association of Accelerometry‐Measured Physical Activity and Cardiovascular Events in Mobility‐Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Journal of the American Heart Association Vol. 6, No. 12 ( 2017-12-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 12 ( 2017-12-02)
    Abstract: Data are sparse regarding the value of physical activity ( PA ) surveillance among older adults—particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Methods and Results Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home‐based activity data were collected by hip‐worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [ SD ] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84–0.96; P =0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65–0.89 [ P =0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow‐up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85–0.96 [ P =0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63–0.90 [ P =0.002]) were significantly associated with lower cardiovascular event rates. Conclusions Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score 〉 10 on the Short Physical Performance Battery) both using baseline and longitudinal data. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01072500.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.117.007215
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 9
    Online Resource
    Online Resource
    The LatMix Summer Campaign: Submesoscale Stirring in the Upper Ocean
    American Meteorological Society ; 2015
    In:  Bulletin of the American Meteorological Society Vol. 96, No. 8 ( 2015-08-01), p. 1257-1279
    Details
    In: Bulletin of the American Meteorological Society, American Meteorological Society, Vol. 96, No. 8 ( 2015-08-01), p. 1257-1279
    Abstract: Lateral stirring is a basic oceanographic phenomenon affecting the distribution of physical, chemical, and biological fields. Eddy stirring at scales on the order of 100 km (the mesoscale) is fairly well understood and explicitly represented in modern eddy-resolving numerical models of global ocean circulation. The same cannot be said for smaller-scale stirring processes. Here, the authors describe a major oceanographic field experiment aimed at observing and understanding the processes responsible for stirring at scales of 0.1–10 km. Stirring processes of varying intensity were studied in the Sargasso Sea eddy field approximately 250 km southeast of Cape Hatteras. Lateral variability of water-mass properties, the distribution of microscale turbulence, and the evolution of several patches of inert dye were studied with an array of shipboard, autonomous, and airborne instruments. Observations were made at two sites, characterized by weak and moderate background mesoscale straining, to contrast different regimes of lateral stirring. Analyses to date suggest that, in both cases, the lateral dispersion of natural and deliberately released tracers was O(1) m2 s–1 as found elsewhere, which is faster than might be expected from traditional shear dispersion by persistent mesoscale flow and linear internal waves. These findings point to the possible importance of kilometer-scale stirring by submesoscale eddies and nonlinear internal-wave processes or the need to modify the traditional shear-dispersion paradigm to include higher-order effects. A unique aspect of the Scalable Lateral Mixing and Coherent Turbulence (LatMix) field experiment is the combination of direct measurements of dye dispersion with the concurrent multiscale hydrographic and turbulence observations, enabling evaluation of the underlying mechanisms responsible for the observed dispersion at a new level.
    Type of Medium: Online Resource
    ISSN: 0003-0007 , 1520-0477
    URL: Article
    URL: Article
    DOI: 10.1175/BAMS-D-14-00015.1
    DOI: 10.1175/BAMS-D-14-00015.3
    Language: English
    Publisher: American Meteorological Society
    Publication Date: 2015
    detail.hit.zdb_id: 2029396-3
    detail.hit.zdb_id: 419957-1
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  • 10
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    Online Resource
    Dispersion in the Open Ocean Seasonal Pycnocline at Scales of 1–10 km and 1–6 days
    American Meteorological Society ; 2020
    In:  Journal of Physical Oceanography Vol. 50, No. 2 ( 2020-02), p. 415-437
    Details
    In: Journal of Physical Oceanography, American Meteorological Society, Vol. 50, No. 2 ( 2020-02), p. 415-437
    Abstract: Results are presented from two dye release experiments conducted in the seasonal thermocline of the Sargasso Sea, one in a region of low horizontal strain rate (~10 −6 s −1 ), the second in a region of intermediate horizontal strain rate (~10 −5 s −1 ). Both experiments lasted ~6 days, covering spatial scales of 1–10 and 1–50 km for the low and intermediate strain rate regimes, respectively. Diapycnal diffusivities estimated from the two experiments were κ z = (2–5) × 10 −6 m 2 s −1 , while isopycnal diffusivities were κ H = (0.2–3) m 2 s −1 , with the range in κ H being less a reflection of site-to-site variability, and more due to uncertainties in the background strain rate acting on the patch combined with uncertain time dependence. The Site I (low strain) experiment exhibited minimal stretching, elongating to approximately 10 km over 6 days while maintaining a width of ~5 km, and with a notable vertical tilt in the meridional direction. By contrast, the Site II (intermediate strain) experiment exhibited significant stretching, elongating to more than 50 km in length and advecting more than 150 km while still maintaining a width of order 3–5 km. Early surveys from both experiments showed patchy distributions indicative of small-scale stirring at scales of order a few hundred meters. Later surveys show relatively smooth, coherent distributions with only occasional patchiness, suggestive of a diffusive rather than stirring process at the scales of the now larger patches. Together the two experiments provide important clues as to the rates and underlying processes driving diapycnal and isopycnal mixing at these scales.
    Type of Medium: Online Resource
    ISSN: 0022-3670 , 1520-0485
    URL: Article
    DOI: 10.1175/JPO-D-19-0019.1
    Language: Unknown
    Publisher: American Meteorological Society
    Publication Date: 2020
    detail.hit.zdb_id: 2042184-9
    detail.hit.zdb_id: 184162-2
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