RF18 Contribution of severe neonatal morbidity to neurodevelopment at 2 years of age among very preterm infants: a mediation analysis

ObjectiveTo characterise the excess risk for death, grade 3–4 intraventricular haemorrhage (IVH), bronchopulmonary dysplasia (BPD) and stage 3–5 retinopathy of prematurity independently associated with birth small for gestational age (SGA) among very preterm infants, stratified by completed weeks of gestation.MethodsRetrospective cohort study using the Optum Neonatal Database. Study infants were born <32 weeks gestation without severe congenital anomalies. SGA was defined as a birth weight <10th percentile. The excess outcome risk independently associated with SGA birth among SGA babies was assessed using adjusted risk differences (aRDs).ResultsOf 6708 infants sampled from 717 US hospitals, 743 (11.1%) were SGA. SGA compared with non-SGA infants experienced higher unadjusted rates of each study outcome except grade 3–4 IVH among survivors. The excess risk independently associated with SGA birth varied by outcome and gestational age. The highest aRD for death (0.27; 95% CI 0.13 to 0.40) occurred among infants born at 24 weeks gestation and declined as gestational age increased. In contrast, the peak aRDs for BPD among survivors (0.32; 95% CI 0.20 to 0.44) and the composites of death or BPD (0.35; 95% CI 0.24 to 0.46) and death or major morbidity (0.35; 95% CI 0.24 to 0.45) occurred at 27 weeks gestation. The risk-adjusted probability of dying or developing one or more of the evaluated morbidities among SGA infants was similar to that of non-SGA infants born approximately 2–3 weeks less mature.ConclusionThe excess risk for neonatal morbidity and mortality associated with being born SGA varies by adverse outcome and gestational age.

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Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants

Clinical Epigenetics ◽

10.1186/s13148-020-00942-1 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Todd M. Everson ◽

T. Michael O’Shea ◽

Amber Burt ◽

Karen Hermetz ◽

Brian S. Carter ◽

...

Keyword(s):

Dna Methylation ◽

Preterm Infants ◽

Risk Score ◽

Neonatal Morbidity ◽

Differential Methylation ◽

Neonatal Health ◽

Very Preterm Infants ◽

Very Preterm ◽

Bonferroni Adjustment ◽

Morbidity Risk

Abstract Background Infants born very preterm are more likely to experience neonatal morbidities compared to their term peers. Variations in DNA methylation (DNAm) associated with these morbidities may yield novel information about the processes impacted by these morbidities. Methods This study included 532 infants born < 30 weeks gestation, participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants study. We used a neonatal morbidity risk score, which was an additive index of the number of morbidities experienced during the NICU stay, including bronchopulmonary dysplasia (BPD), severe brain injury, serious neonatal infections, and severe retinopathy of prematurity. DNA was collected from buccal cells at discharge from the NICU, and DNAm was measured using the Illumina MethylationEPIC. We tested for differential methylation in association with the neonatal morbidity risk score then tested for differentially methylated regions (DMRs) and overrepresentation of biological pathways. Results We identified ten differentially methylated CpGs (α Bonferroni-adjusted for 706,278 tests) that were associated with increasing neonatal morbidity risk scores at three intergenic regions and at HPS4, SRRD, FGFR1OP, TNS3, TMEM266, LRRC3B, ZNF780A, and TENM2. These mostly followed dose–response patterns, for 8 CpGs increasing DNAm associated with increased numbers of morbidities, while for 2 CpGs the risk score was associated with decreasing DNAm. BPD was the most substantial contributor to differential methylation. We also identified seven potential DMRs and over-representation of genes involved in Wnt signaling; however, these results were not significant after Bonferroni adjustment for multiple testing. Conclusions Neonatal DNAm, within genes involved in fibroblast growth factor activities, cellular invasion and migration, and neuronal signaling and development, are sensitive to the neonatal health complications of prematurity. We hypothesize that these epigenetic features may be representative of an integrated marker of neonatal health and development and are promising candidates to integrate with clinical information for studying developmental impairments in childhood.

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Trends in survival, neonatal morbidity and neurodevelopmental outcome of very preterm infants in Tainan, Southern Taiwan, 1995–2016

Journal of the Formosan Medical Association ◽

10.1016/j.jfma.2020.12.025 ◽

2021 ◽

Author(s):

Lan-Wan Wang ◽

Yung-Chieh Lin ◽

Shan-Tair Wang ◽

Chao-Ching Huang ◽

Kuo-Inn Tsou ◽

...

Keyword(s):

Preterm Infants ◽

Neurodevelopmental Outcome ◽

Neonatal Morbidity ◽

Very Preterm Infants ◽

Very Preterm ◽

Southern Taiwan

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Introduction of a Quality Improvement Bundle Is Associated with Reduced Exposure to Mechanical Ventilation in Very Preterm Infants

Neonatology ◽

10.1159/000518392 ◽

2021 ◽

pp. 1-8

Author(s):

Stacey Chi-Yan Lo ◽

Risha Bhatia ◽

Calum T. Roberts

Keyword(s):

Mechanical Ventilation ◽

Quality Improvement ◽

Preterm Infants ◽

Demographic Data ◽

Neonatal Morbidity ◽

Very Preterm Infants ◽

Very Preterm ◽

Antenatal Steroids ◽

Cord Clamping ◽

The Impact

Introduction: Exposure to mechanical ventilation (MV) is a risk factor for bronchopulmonary dysplasia (BPD) in very preterm infants (VPTIs). We assessed the impact of a quality improvement (QI) bundle in VPTIs (<32 week gestation) on exposure to MV. Methods: We introduced a QI bundle consisting of deferred cord clamping (DCC), nasal bubble continuous positive airway pressure (bCPAP) in the delivery room (DR), and minimally invasive surfactant therapy (MIST). We compared respiratory outcomes and neonatal morbidity in historical pre-QI (July–December 2017) and prospective post-QI (February–July 2019) cohorts (QICs) of VPTIs. We pre-specified an adjusted analysis to account for the effects of gestational age, sex, antenatal steroids, and any demographic data that significantly differed between cohorts. Results: The pre-QI and post-QICs included 87 and 98 VPTIs, respectively. The post-QIC had decreased rates of MV in the DR (adjusted odds ratio [aOR] 0.26, 95% confidence interval [CI] 0.09–0.71), in the first 72 h of life (aOR 0.27, 95% CI 0.11–0.62) and during admission (aOR 0.28, 95% CI 0.12–0.66). Rates of BPD, combined BPD/death, and BPD severity were similar. The post-QIC was less likely to be discharged with home oxygen (aOR 0.27, 95% CI 0.08–0.91). Necrotising enterocolitis grade ≥2 increased (aOR 19.01, 95% CI 1.93–188.6) in the post-QIC. Conclusion: In this rapid-cycle QI study, implementation of a QI bundle consisting of DCC, early nasal bCPAP, and MIST in VPTIs was associated with reduced rates of MV in the DR, in the first 72 h of life and during admission, and reduced need for home oxygen.

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Association between development of early cortical activity on amplitude-integrated EEG and 5-years neurodevelopmental outcome in the preterm infant

10.1101/562488 ◽

2019 ◽

Author(s):

Maria Feldmann ◽

Valentin Rousson ◽

Thi Dao Nguyen ◽

Vera Bernet ◽

Cornelia Hagmann ◽

...

Keyword(s):

Preterm Infants ◽

Neurodevelopmental Outcome ◽

Neonatal Morbidity ◽

Population Group ◽

Cognitive Outcome ◽

List Type ◽

Very Preterm Infants ◽

Very Preterm ◽

Preterm Born

AbstractAimTo analyse the association between early aEEG and cognitive outcome at early school-age in very preterm infants.MethodsProspective cohort study including infants with gestational age (GA) <32.0 weeks, undergoing continuous aEEG recording during first 4 days of life. Semiquantitative and quantitative (maximum/minimum amplitude) measures were averaged over the recording period. Cognitive outcome was assessed with the Kaufman-Assessment Battery for Children at 5 years of age. Uni- and multivariate logistic regressions were calculated between aEEG parameters and normal cognitive outcome (IQ≥85).ResultsAmong 118 monitored preterm children, 89 were assessed at median(IQR) corrected age of 68.6 months (65.5-71.2) [48% female, median(IQR) GA 29.9(28.2,30.9) weeks, mean(SD) birth weight 1235(363) grams]. Mean(SD) IQ was 97.8(12.7). IQ<85 occurred in 21.3 %, cerebral palsy was found in 3.4%. Despite univariate associations of total maturity scores, cycling subscores, background pattern and minimum aEEG amplitude with normal cognitive outcome none of the associations remained significant after adjustment for confounders. Socioeconomic status was identified as independent predictor of neurodevelopmental outcome.ConclusionIn this cohort of very preterm infants, early short-term aEEG was not predictive of later cognitive outcome. Further research is needed to explore how aEEG could help to inform long-term prognosis in this population group.Key notesPreterm born infants are at high risk for neurodevelopmental impairment.Early amplitude integrated electroencephalography characteristics are univariately associated with cognitive outcome at 5 years of age in preterm born children.However, socioeconomic factors and neonatal morbidity were stronger predictors of long-term neurodevelopmental outcome than early aEEG measures.

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