Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO
            <sub>2</sub>
            targets: the PHELBI follow-up study

Thomé, Ulrich; Genzel‐Boroviczény, Orsolya; Bohnhorst, Bettina; Schmid, Manuel; Fuchs, Hans; Rohde, Oliver; Avenarius, Stefan; Topf, Hans-Georg; Zimmermann, Andrea; Faas, Dirk; Timme, Katharina; Kleinlein, Barbara; Buxmann, Horst; Schenk, Wilfried; Segerer, Hugo; Teig, Norbert; Bläser, A.; Hentschel, Roland; Heckmann, Matthias; Schlößer, Rolf; Peters, Jochen; Rossi, Rainer; Rascher, Wolfgang; Böttger, Ralf; Seidenberg, J.; Hansen, Gesine; Zernickel, Maria; Bode, Harald; Dreyhaupt, Jens; Muche, Rainer; Hummler, Helmut

doi:10.1136/archdischild-2016-311581

Cited by 30 publications

(35 citation statements)

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“…Capnography during PSG is challenging, 16 particularly in neonates. Although existing literature suggests no effect of permissive hypercapnia, during the first few days of life, on neurodevelopmental outcome, 17,18 there are no published data on the effect of sustained hypercapnia during sleep on neurocognitive outcomes in preterm infants.…”

Section: Introductionmentioning

confidence: 92%

“…36 Existing literature suggests no effect of permissive hypercapnia on neurodevelopmental outcome. 17,18 Additionally, the Childhood Adenotonsillectomy, or CHAT, trial did not report any correlation of percentage of total sleep time (TST) with ETCO 2 > 50 mm Hg with changes on the cognitive and behavioral assessment at median age of 7.1 years. The median ETCO 2 , while asleep, of that study sample was 45 mm Hg, 34 which is a little lower than in our study.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, we have utilized a separate measure (mean ETCO 2 ) for correlation. The second point of interest is that in the study on infants with permissive hypercapnia, 18 neurocognitive outcomes were correlated to arterial CO 2 levels only within the first 14 days of life. However, in our study, ETCO 2 was estimated at a median chronological age of 4 months.…”

Section: Discussionmentioning

confidence: 99%

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Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Bandyopadhyay

Harmon

Slaven

et al. 2017

Journal of Clinical Sleep Medicine

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Study Objectives: Neurocognitive deficits have been shown in school-aged children with sleep apnea. The effect of obstructive sleep apnea (OSA) on the neurodevelopmental outcome of preterm infants is unknown. Methods: A retrospective chart review was performed for all preterm infants (< 37 weeks) who had neonatal polysomnography (PSG) and completed neurodevelopmental assessment with the Bayley Scales of Infant and Toddler Development, 3rd Edition, between 2006 to 2015 at Riley Hospital. Exclusion criteria included grade IV intraventricular hemorrhage, tracheostomy, cyanotic heart disease, severe retinopathy of prematurity, craniofacial anomalies, or central and mixed apnea on PSG. Sleep apnea was defined as an apnea-hypopnea index (AHI) > 1 event/h. Regression analyses were performed to find a relationship between PSG parameters and cognitive, language, and motor scores. Results: Fifteen patients (males: n = 10) were eligible for the study. Median postmenstrual age at the time of the PSG was 41 weeks (37-46). Median AHI for the cohort was 17.4 events/h (2.2-41.3). Median cognitive, language, and motor scores were 90 (65-125), 89 (65-121), and 91 (61-112), respectively. Mean end-tidal CO2 (median 47 mm Hg ) negatively correlated with cognitive scores (P = .01) but did not significantly correlate with language or motor scores. AHI was not associated with cognitive, language, or motor scores. Conclusions: The median score for cognitive, language, and motor scores for preterm infants with neonatal OSA were within one standard deviation of the published norm. Mean end-tidal CO2, independent of AHI, may serve as a biomarker for predicting poor cognitive outcome in preterm infants with neonatal OSA. Commentary: A commentary on this article appears in this issue on page 1233. Keywords: obstructive sleep apnea, polysomnography, infant, newborn Citation: Bandyopadhyay A, Harmon H, Slaven JE, Daftary AS. Neurodevelopmental outcomes at two years of age for premature infants diagnosed with neonatal obstructive sleep apnea.

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Section: Introductionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Bandyopadhyay

Harmon

Slaven

et al. 2017

Journal of Clinical Sleep Medicine

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“…This resulted in a considerable overlap in actual PCO 2 values between the study groups. Although the randomized assignment to a target group did not significantly influence important clinical outcomes, there were trends suggesting that the higher target range could be associated with an increased risk of bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) [15], but does not affect neurodevelopment [16]. Effects such as these may be more evident in analyses based on actual PCO 2 values rather than on the prescribed target ranges.…”

Section: Introductionmentioning

confidence: 99%

Influence of PCO<sub>2</sub> Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants

Thomé¹,

Dreyhaupt

Genzel‐Boroviczény

et al. 2018

Neonatology

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Background: Levels or fluctuations in the partial pressure of CO₂ (PCO₂) may affect outcomes for extremely low birth weight infants. Objectives: In an exploratory analysis of a randomized trial, we hypothesized that the PCO₂ values achieved could be related to significant outcomes. Methods: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO₂. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ² test, and the Fisher exact test as well as by multiple logistic regression. Results: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO₂. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO₂). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO₂ (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). Conclusions: Birth weight and respiratory morbidity, as measured by MAP × FiO₂, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO₂. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.

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“…The PHELBI study (a large prospective randomized multicenter study examining the adverse effects of permissive hypercapnia done for 2 weeks following very premature births) found permissive hypercapnia did not further compromise neurodevelopmental outcomes at age 2 years. 10 In this study, hypercapnia was identified on overnight PSG performed a mean of 4 months following birth.…”

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confidence: 99%

Infants Sleep for Brain

Grigg-Damberger

Wolfe

2017

Journal of Clinical Sleep Medicine

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Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO ₂ targets: the PHELBI follow-up study

Abstract: Background

Cited by 30 publications

References 30 publications

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Influence of PCO<sub>2</sub> Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants

Infants Sleep for Brain

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Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO 2 targets: the PHELBI follow-up study

Abstract: Background

Cited by 30 publications

References 30 publications

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

Influence of PCO<sub>2</sub> Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants

Infants Sleep for Brain

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Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO ₂ targets: the PHELBI follow-up study