Diagnosis of Neonatal Late-Onset Infection in Very Preterm Infant: Inter-Observer Agreement and International Classifications.

BACKGROUND: The definition of late-onset bacterial sepsis (LOS) in very preterm infants is not unified. The objective was to assess the concordance of LOS diagnosis between experts in neonatal infection and international classifications and to evaluate the potential impact on heart rate variability and rate of "bronchopulmonary dysplasia or death". METHODS: A retrospective (2017-2020) multicenter study including hospitalized infants born before 31 weeks of gestation with intention to treat at least 5-days with antibiotics was performed. LOS was classified as "certain or probable" or "doubtful" independently by five experts and according to four international classifications with concordance assessed by Fleiss's kappa test. RESULTS: LOS was suspected at seven days (IQR: 5-11) of life in 48 infants. Following expert classification, 36 of them (75%) were considered as "certain or probable" (kappa = 0.41). Following international classification, this number varied from 13 to 46 (kappa = -0.08). Using the expert classification, "bronchopulmonary dysplasia or death" occurred less frequently in the doubtful group (25% vs. 78%, p < 0.001). Differences existed in HRV changes between the two groups. CONCLUSION: The definition of LOS is not consensual with a low international and moderate inter-observer agreement. This affects the evaluation of associated organ dysfunction and prognosis.

Quiet Sleep Organization of Very Preterm Infants Is Correlated With Postnatal Maturation.

Background: Sleep is an important determinant of brain development in preterm infants. Its temporal organization varies with gestational age (GA) and post-menstrual age (PMA) but little is known about how sleep develops in very preterm infants. The objective was to study the correlation between the temporal organization of quiet sleep (QS) and maturation in premature infants without severe complications during their neonatal hospitalization. Methods: Percentage of time spent in QS and average duration of time intervals (ADI) spent in QS were analyzed from a cohort of newborns with no severe complications included in the Digi-NewB prospective, multicentric, observational study in 2017-19. Three groups were analyzed according to GA: Group 1 (27-30 weeks), Group 2 (33-37 weeks), Group 3 (>39 weeks). Two 8-h video recordings were acquired in groups 1 and 2: after birth (T1) and before discharge from hospital (T2). The annotation of the QS phases was performed by analyzing video recordings together with heart rate and respiratory traces thanks to a dedicated software tool of visualization and annotation of multimodal long-time recordings, with a double expert reading. Results are expressed as median (interquartile range, IQR). Correlations were analyzed using a linear mixed model. Results: Five newborns were studied in each group (160 h of recording). Median time spent in QS increased from 13.0% [IQR: 13-20] to 28.8% [IQR: 27-30] and from 17.0% [IQR: 15-21] to 29.6% [IQR: 29.5-31.5] in Group 1 and 2, respectively. Median ADI increased from 54 [IQR: 53-54] to 288 s [IQR: 279-428] and from 90 [IQR: 84-96] to 258 s [IQR: 168-312] in Group 1 and 2. Both groups reach values similar to that of group 3, respectively 28.2% [IQR: 24.5-31.3] and 270 s [IQR: 210-402]. The correlation between PMA and time spent in QS or ADI were, respectively 0.73 (p < 10-4) and 0.46 (p = 0.06). Multilinear analysis using temporal organization of QS gave an accurate estimate of PMA (r 2 = 0.87, p < 0.001). Conclusion: The temporal organization of QS is correlated with PMA in newborns without severe complication. An automated standardized continuous behavioral quantification of QS could be interesting to monitor during the hospitalization stay in neonatal units.