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Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.

ABSTRACT: IMPORTANCE:Chorioamnionitis is strongly linked to preterm birth and neonatal infection. The association between histological and clinical chorioamnionitis and cognitive, behavioral, and neurodevelopmental outcomes among extremely preterm neonates is less clear. We evaluated the impact of chorioamnionitis on 18- to 22-month neurodevelopmental outcomes in a contemporary cohort of extremely preterm neonates. OBJECTIVE:To compare the neonatal and neurodevelopmental outcomes of 3 groups of extremely low-gestational-age infants with increasing exposure to perinatal inflammation: no chorioamnionitis, histological chorioamnionitis alone, or histological plus clinical chorioamnionitis. DESIGN, SETTING, AND PARTICIPANTS:Longitudinal observational study at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Two thousand three hundred ninety extremely preterm infants born at less than 27 weeks' gestational age (GA) between January 1, 2006, and December 31, 2008, with placental histopathology and 18 to 22 months' corrected age follow-up data were eligible. MAIN EXPOSURE:Chorioamnionitis. MAIN OUTCOMES AND MEASURES:Outcomes included cerebral palsy, gross motor functional limitation, behavioral scores (according to the Brief Infant-Toddler Social and Emotional Assessment), cognitive and language scores (according to the Bayley Scales of Infant and Toddler Development, Third Edition), and composite measures of death/neurodevelopmental impairment. Multivariable logistic and linear regression models were developed to assess the association between chorioamnionitis and outcomes while controlling for important variables known at birth. RESULTS:Neonates exposed to chorioamnionitis had a lower GA and higher rates of early-onset sepsis and severe periventricular-intraventricular hemorrhage as compared with unexposed neonates. In multivariable models evaluating death and neurodevelopmental outcomes, inclusion of GA in the model diminished the association between chorioamnionitis and adverse outcomes. Still, histological plus clinical chorioamnionitis was associated with increased risk of cognitive impairment as compared with no chorioamnionitis (adjusted odds ratio [OR], 2.38 [95% CI, 1.32 to 4.28] without GA; adjusted OR, 2.00 [95% CI, 1.10 to 3.64] with GA as a covariate). Histological chorioamnionitis alone was associated with lower odds of death/neurodevelopmental impairment as compared with histological plus clinical chorioamnionitis (adjusted OR, 0.68 [95% CI, 0.52 to 0.89] without GA; adjusted OR, 0.66 [95% CI, 0.49 to 0.89] with GA as a covariate). Risk of behavioral problems did not differ statistically between groups. CONCLUSIONS AND RELEVANCE:Antenatal exposure to chorioamnionitis is associated with altered odds of cognitive impairment and death/neurodevelopmental impairment in extremely preterm infants.

SUBMITTER: Pappas A

PROVIDER: S-EPMC4219500 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.

Pappas Athina A Kendrick Douglas E DE Shankaran Seetha S Stoll Barbara J BJ Bell Edward F EF Laptook Abbott R AR Walsh Michele C MC Das Abhik A Hale Ellen C EC Newman Nancy S NS Higgins Rosemary D RD

JAMA pediatrics 20140201 2

<h4>Importance</h4>Chorioamnionitis is strongly linked to preterm birth and neonatal infection. The association between histological and clinical chorioamnionitis and cognitive, behavioral, and neurodevelopmental outcomes among extremely preterm neonates is less clear. We evaluated the impact of chorioamnionitis on 18- to 22-month neurodevelopmental outcomes in a contemporary cohort of extremely preterm neonates.<h4>Objective</h4>To compare the neonatal and neurodevelopmental outcomes of 3 group ...[more]

PMID: 24378638

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Project description:IMPORTANCE:Low-grade periventricular-intraventricular hemorrhage is a common neurologic morbidity among extremely low-gestational-age neonates, yet the outcomes associated with this morbidity are not fully understood. In a contemporary multicenter cohort, we evaluated the impact of such hemorrhages on early (18-22 month) neurodevelopmental outcomes of extremely premature infants. OBJECTIVE:To compare neurodevelopmental outcomes at 18 to 22 months' corrected age for extremely low-gestational-age infants with low-grade (grade 1 or 2) periventricular-intraventricular hemorrhage with those of infants with either no hemorrhage or severe (grade 3 or 4) hemorrhage demonstrated on cranial ultrasonography. DESIGN:Longitudinal observational study. SETTING:Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. PARTICIPANTS:A total of 1472 infants born at less than 27 weeks' gestational age between January 1, 2006, and December 31, 2008, with ultrasonography results within the first 28 days of life and surviving to 18 to 22 months with complete follow-up assessments were eligible. MAIN EXPOSURE:Low-grade periventricular-intraventricular hemorrhage. MAIN OUTCOME MEASURES:Outcomes included cerebral palsy; gross motor functional limitation; cognitive and language scores according to the Bayley Scales of Infant Development, 3rd Edition; and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences. RESULTS:Low-grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared with infants without hemorrhage. Compared with low-grade hemorrhage, severe hemorrhage was associated with decreased adjusted continuous cognitive (?, -3.91 [95% CI, -6.41 to -1.42]) and language (?, -3.19 [-6.19 to -0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (odds ratio [OR], 1.46 [0.74 to 2.88]) and mild language impairment (OR, 1.35 [0.88 to 2.06]). CONCLUSIONS AND RELEVANCE:At 18 to 22 months, the neurodevelopmental outcomes of extremely low-gestational-age infants with low-grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. Additional study at school age and beyond would be informative.

Project description:RationaleThe relationship between respiratory function at hospital discharge and the severity of later respiratory disease in extremely low gestational age neonates is not well defined.ObjectivesTo test the hypothesis that tidal breathing measurements near the time of hospital discharge differ between extremely premature infants with bronchopulmonary dysplasia (BPD) or respiratory disease in the first year of life and those without these conditions.MethodsStudy subjects were part of the PROP (Prematurity and Respiratory Outcomes Program) study, a longitudinal cohort study of infants born at less than 29 gestational weeks followed from birth to 1 year of age. Respiratory inductance plethysmography was used for tidal breathing measurements before and after inhaled albuterol 1 week before anticipated hospital discharge. Infants were breathing spontaneously and were receiving less than or equal to 1 L/min nasal cannula flow at 21% to 100% fraction of inspired oxygen. A survey of respiratory morbidity was administered to caregivers at 3, 6, 9, and 12 months corrected age to assess for respiratory disease. We compared tidal breathing measurements in infants with and without BPD (oxygen requirement at 36 wk) and with and without respiratory disease in the first year of life. Measurements were also performed in a comparison cohort of term infants.ResultsA total of 765 infants survived to 36 weeks postmenstrual age, with research-quality tidal breathing data in 452 out of 564 tested (80.1%). Among these 452 infants, the rate of postdischarge respiratory disease was 65.7%. Compared with a group of 18 term infants, PROP infants had abnormal tidal breathing patterns. However, there were no clinically significant differences in tidal breathing measurements in PROP infants who had BPD or who had respiratory disease in the first year of life compared with those without these diagnoses. Bronchodilator response was not significantly associated with respiratory disease in the first year of life.ConclusionsExtremely premature infants receiving less than 1 L/min nasal cannula support at 21% to 100% fraction of inspired oxygen have tidal breathing measurements that differ from term infants, but these measurements do not differentiate those preterm infants who have BPD or will have respiratory disease in the first year of life from those who do not. Clinical trial registered with www.clinicaltrials.gov (NCT01435187).

Project description:Background and objectivesAKI is associated with poor short- and long-term outcomes. Questions remain about the frequency and timing of AKI, and whether AKI is a cause of death in extremely low gestational age neonates.Design, setting, participants, & measurementsThe Recombinant Erythropoietin for Protection of Infant Kidney Disease Study examines the kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo Neuroprotection study, a randomized, placebo-controlled trial of recombinant human erythropoietin. We included 900 of 941 patients enrolled in Preterm Epo Neuroprotection. Baseline characteristics were compared by primary exposure (severe AKI versus none/stage 1 AKI) using unadjusted logistic regression models. Cox regression models estimated the relationship between severe AKI and death after adjustment for potential confounders. Time-dependent AKI was modeled as a binary outcome and a categorical variable by stage of AKI. We fit Cox models using time-dependent AKI status lagged by <7 days before death. Landmark analyses examined the relationship of death with development of severe AKI.ResultsSevere AKI occurred in 168 of 900 (19%, 95% confidence interval, 17% to 20%) neonates, and stage 3 AKI occurred in 60 (7%, 95% confidence interval, 5% to 8%). Stage 3 AKI occurring 7 days before death (hazard ratio, 3.88; 95% confidence interval, 1.26 to 11.96), intraventricular hemorrhage (hazard ratio, 2.01; 95% confidence interval, 1.01 to 3.99) and sepsis (hazard ratio, 2.85; 95% confidence interval, 1.12 to 7.22) were all independently associated with death. Severe AKI occurring 7 days before death (hazard ratio, 2.21; 95% confidence interval, 0.92 to 5.26) was associated with death but not statistically significant. In a landmark analysis, after adjusting for potential confounders, late (after day 14 and before day 28) severe AKI was strongly associated with higher hazard of death (hazard ratio, 4.57; 95% confidence interval, 1.82 to 11.5).ConclusionsSevere AKI occurs frequently in extremely low gestational age neonates. Stage 3 AKI is associated with mortality, and this association is present 7 days before death.

Project description:Importance:Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm. Objective:To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood. Design, Setting, and Participants:Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks' gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months' corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors. Main Outcomes and Measures:Punctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months' CA. Results:Of 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, -2.2; 95% CI, -5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, -3.0; 95% CI, -6.4 to 0.4). Conclusions and Relevance:Histologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months' CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.

Project description:Importance:Deferred cord clamping (DCC) is recommended for term and preterm neonates to reduce neonatal complications. Information on the association of DCC with outcomes for extremely low-gestational-age neonates is limited. Objective:To compare neonatal outcomes after DCC and immediate cord clamping (ICC) in extremely low-gestational-age neonates. Design, Setting, and Participants:In this retrospective cohort study, eligible neonates born between January 1, 2011, and December 31, 2015, were divided into 2 groups: DCC and ICC. Neonates were recruited from tertiary neonatal intensive care units participating in the Canadian Neonatal Network, and analysis began in January 2018. Neonates were eligible if they were born at 22 to 28 weeks' gestational age and admitted to a participating Canadian Neonatal Network neonatal intensive care unit during the study period. Neonates who were born outside a tertiary-level neonatal intensive care unit, were moribund at birth, needed palliative care before delivery, had major congenital anomalies, or lacked cord clamping information were excluded. Main Outcomes and Measures:Composite of severe neurological injury (intraventricular hemorrhage grade ≥3 with or without persistent periventricular echogenicity) or mortality before discharge. Results:Of 8221 admitted neonates, 4680 were included in the study, of whom 1852 (39.6%) received DCC and 2828 (60.4%) received ICC. There were 974 (52.7%) male neonates in the DCC group and 1540 (54.5%) male neonates in the ICC group. Median (interquartile range) gestational age was 27 (25-28) weeks for the DCC group and 26 (25-27) weeks for the ICC group. Median (interquartile range) birth weight was 930 (760-1120) g and 870 (700-1060) g for DCC and ICC groups, respectively. Neonates who received DCC had significantly reduced odds of the composite outcome of severe neurological injury or mortality (adjusted odds ratio [AOR], 0.80; 95% CI, 0.67-0.96), mortality (AOR, 0.74; 95% CI, 0.59-0.93), and severe neurological injury (AOR, 0.80; 95% CI, 0.64-0.99). The odds of bronchopulmonary dysplasia (AOR, 1.00; 95% CI, 0.84-1.19), retinopathy of prematurity stage 3 or higher (AOR, 0.94; 95% CI, 0.71-1.25), necrotizing enterocolitis stage 2 or higher (AOR, 0.86; 95% CI, 0.66-1.12), late-onset sepsis (AOR, 1.02; 95% CI, 0.85-1.22), and receipt of 2 or more blood transfusions (AOR, 0.93; 95% CI, 0.79-1.10) did not differ between the groups. Propensity score-matched analyses revealed lower odds of mortality (AOR, 0.79; 95% CI, 0.65-0.95), late-onset sepsis (AOR, 0.81; 95% CI, 0.69-0.95), and treatment for hypotension (AOR, 0.75; 95% CI, 0.60-0.95) in the DCC group. Conclusions and Relevance:In this study of extremely low-gestational-age neonates who received DCC or ICC, DCC was associated with reduced risk for the composite outcome of severe neurological injury or mortality.

Dataset Information

Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.

Publications

Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.

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