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Since the outbreak of coronavirus disease 2019 (COVID-19), there has been a debate whether pregnant women are at a specific risk for COVID-19 and whether it might be vertically transmittable through the placenta. We present a series of five placentas of SARS coronavirus 2 (SARS-CoV-2)-positive women who had been diagnosed with mild symptoms of COVID-19 or had been asymptomatic before birth. We provide a detailed histopathologic description of morphological changes accompanied by an analysis of presence of SARS-CoV-2 in the placental tissue. All placentas were term deliveries (40th and 41st gestational weeks). One SARS-CoV-2-positive patient presented with cough and dyspnoea. This placenta showed prominent lymphohistiocytic villitis and intervillositis and signs of maternal and foetal malperfusion. Viral RNA was present in both placenta tissue and the umbilical cord and could be visualized by in situ hybridization in the decidua. SARS-CoV-2 tests were negative at the time of delivery of 3/5 women, and their placentas did not show increased inflammatory infiltrates. Signs of maternal and/or foetal malperfusion were present in 100% and 40% of cases, respectively. There was no transplacental transmission to the infants. In our cohort, we can document different time points regarding SARS-CoV-2 infection. In acute COVID-19, prominent lymphohistiocytic villitis may occur and might potentially be attributable to SARS-CoV-2 infection of the placenta. Furthermore, there are histopathological signs of maternal and foetal malperfusion, which might have a relationship to an altered coagulative or microangiopathic state induced by SARS-CoV-2, yet this cannot be proven considering a plethora of confounding factors.

To assess the prognostic value of early echocardiographic indices of right ventricular function and vasoactive peptides for prediction of bronchopulmonary dysplasia (BPD) or death in very preterm infants. RIMP was significantly increased (median [IQR] 0.3 [0.23-0.38] vs 0.22 [0.15-0.29]), TAPSE decreased (median [IQR] 5.0 [5.0-6.0] vs 6.0 [5.4-7.0] mm), MR-proANP increased (median [IQR] 784 [540-936] vs 353 [247-625] pmol/L), and CT-proET1 increased (median [IQR] 249 [190-345] vs 199 [158-284] pmol/L) in infants who developed BPD or died, as compared to controls. All variables showed significant but weak correlations with each other (r.sub.S -0.182 to 0.359) and predicted BPD/death with similar accuracy (areas under receiver operator characteristic curves 0.62 to 0.77). Multiple regression revealed only RIMP and birth weight as independent predictors of BPD or death. Vasoactive peptide concentrations and echocardiographic assessment employing standardized measures, notably RIMP, on day 7 of life are useful to identify preterm infants at increased risk for BPD or death.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication after preterm birth. Early preventive measures are important to reduce further damage on lung tissue. Thus, early discrimination between infants with and without BPD is of high importance. A low sample entropy (SampEn) of time series of the oxyhemoglobin saturation (SpO 2 -SampEn for short) is associated with an increased risk of hypoxemic events in neonates. We hypothesized that preterm infants have a lower SpO 2 -SampEn compared to term infants. Moreover, that infants with BPD have a lower SpO 2 -SampEn compared to those without BPD. Preterm infants < 32 w gestation and healthy term infants were eligible for study. We recorded SpO 2 over 90 min through the clinical monitoring system with a sampling frequency of 0.98 Hz and calculated the SpO 2 -SampEn at 32 w postmenstrual age (PMA), 36 w PMA, and at discharge. We included 95 term and 180 preterm infants, of whom 44 (24.4%) developed BPD. SpO 2 -SampEn was lower in preterm infants compared to term infants. SpO 2 -SampEn was lower in infants with BPD compared to infants without BPD at 32 w PMA. However, gestational age was the only predictor of SampEn at 32 w PMA. This difference between infants with and without BPD was no longer present at 36 w PMA and discharge. SpO 2 -SampEn can be utilized to discriminate between preterm and term infants and between preterm infants with and without BPD. However, confounding factors such as caffeine therapy, gestational age and the natural boundary of 100% of SpO 2 values have to be considered.

BackgroundBronchopulmonary dysplasia (BPD) is a major complication in preterm infants <32 weeks. We aimed to assess whether plasma levels of mid-regional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET-1) predict respiratory morbidity.MethodsThis was a prospective, two-center, observational cohort study. MR-proANP and CT-proET-1 were measured at day 7 (±2) of life. Associations with duration of supplemental oxygen and the composite outcome of moderate or severe BPD or death (BPD/death) were investigated.ResultsTwo hundred and twenty-nine infants <32 weeks were included (median gestational age [GA] 29.6 weeks [interquartile range 29.0–30.7], median birth weight 1150 g [IQR 840–1410]). MR-proANP and CT-proET-1 were associated with the duration of supplemental oxygen in univariable analysis (both p < 0.001) but not after adjusting for co-factors. Infants with BPD/death showed higher plasma levels of MR-proANP (623.50 pmol/L [IQR 458.50–881.38] vs. 308.35 pmol/L [IQR 216.72–538.10]; p < 0.001) and CT-proET-1 (255.40 pmol/L [IQR 202.60–311.15] vs. 198.30 pmol/L [IQR 154.70–297.95]; p = 0.015) compared to infants without BPD/death. Levels of both biomarkers were significantly associated with BPD/death in univariable models but not after adjusting for co-factors.ConclusionsMR-proANP and CT-proET-1 are associated with the duration of supplemental oxygen and the composite outcome BPD/death, but their prognostic value does not complement that of clinical risk factors.ImpactPlasma levels of MR-proANP and CT-proET-1, measured on day 7 of life (±2 days) are associated in univariable analyses with duration of supplemental oxygen and the combined outcome of BPD or death in VLGA infants.Associations between both biomarkers and respiratory morbidity do not persist in multivariable models, in particular when gestational age is included.MR-proANP and CT-proET-1 have limited additional value to predict respiratory morbidity in VLGA infants compared to clinical parameters.

Background Retinopathy of prematurity (ROP) is a major complication in preterm infants. We assessed if plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP) and C-terminal pro-endothelin-1 (CT-proET1) serve as early markers for subsequent ROP development in preterm infants <32 weeks gestation. Methods Prospective, two-centre, observational cohort study. MR-proANP and CT-proET1 were measured on day seven of life. Associations with ROP ≥ stage II were investigated by univariable and multivariable logistic regression models. Results We included 224 infants born at median (IQR) 29.6 (27.1–30.8) weeks gestation and birth weight of 1160 (860–1435) g. Nineteen patients developed ROP ≥ stage II. MR-proANP and CT-proET1 levels were higher in these infants (median (IQR) 864 (659–1564) pmol/L and 348 (300–382) pmol/L, respectively) compared to infants without ROP (median (IQR) 299 (210–502) pmol/L and 196 (156–268) pmol/L, respectively; both P  < 0.001). MR-proANP and CT-proET1 levels were significantly associated with ROP ≥ stage II in univariable logistic regression models and after adjusting for co-factors, including gestational age and birth weight z-score. Conclusions MR-proANP and CT-proET1 measured on day seven of life are strongly associated with ROP ≥ stage II in very preterm infants and might improve early prediction of ROP in the future. Impact Plasma levels of midregional pro-atrial natriuretic peptide and C-terminal pro-endothelin-1 measured on day seven of life in very preterm infants show a strong association with development of retinopathy of prematurity ≥ stage II. Both biomarkers have the potential to improve early prediction of retinopathy of prematurity. Vasoactive peptides might allow to reduce the proportion of screened infants substantially.

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF. Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping. Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not LCI or M(1)/M(0). There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes. These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.

Background K. oxytoca generally has a benign susceptibility profile and low virulence but can cause invasive infections in vulnerable populations, like preterm infants. We aim to describe how whole-genome sequencing (WGS) was used to inform management of a prolonged K. oxytoca outbreak on a neonatal intensive care unit (NICU) and implications for outbreak response involving similar organisms. Methods We retrospectively reviewed outbreak-associated clinical and environmental isolates from a Swiss NICU. WGS was used to track evolution of resistance and highlighted multiple concurrent outbreaks. WGS was performed using a MiSeq or NextSeq 500 Illumina sequencer. The resulting genome sequences were analysed using Ridom SeqSphere. The current report conforms to ORION reporting guidelines. Results Of 152 Klebsiella spp. patient-derived isolates, 83 were genotyped using WGS, along with six environmental isolates. This confirmed two outbreak waves (November 2021-February 2022, ST18 wildtype; July 2022-June 2023, main cluster ST18 KI β-lactamase hyperproducer), with multiple genotypically connected clusters during the second wave. Confirmed sepsis ( K. oxytoca ST18 wildtype) occurred in four preterm or low birthweight infants. Twins presented a genotypically identical ST with a different susceptibility phenotype (ST18 wildtype vs. K1 OXY-hyperproducer). WGS combined with epidemiological investigation and environmental sampling identified an environmental source. There was a second outbreak wave after source removal, presumably due to the prolonged presence of colonised infants with typically long NICU stays and insufficient standard infection prevention and control measures to prevent transmission. Conclusion WGS use in NICU outbreaks involving low-virulence bacteria can support identification and removal of potentiating environmental sources. These measures, however, will often be insufficient to contain the outbreak, and ongoing WGS surveillance of ubiquitous species may uncover multiple concurrent outbreaks, presumably driven by continuing transfer-transmission between different sources and infants in the NICU. Maximising standard infection prevention and control (IPC) measures is appropriate in this context.

Poor control of body temperature is associated with mortality and major morbidity in preterm infants. We aimed to quantify its dynamics and complexity to evaluate whether indices from fluctuation analyses of temperature time series obtained within the first five days of life are associated with gestational age (GA) and body size at birth, and presence and severity of typical comorbidities of preterm birth. We recorded 3h-time series of body temperature using a skin electrode in incubator-nursed preterm infants. We calculated mean and coefficient of variation of body temperature, scaling exponent alpha (Talpha) derived from detrended fluctuation analysis, and sample entropy (TSampEn) of temperature fluctuations. Data were analysed by multilevel multivariable linear regression. Data of satisfactory technical quality were obtained from 285/357 measurements (80%) in 73/90 infants (81%) with a mean (range) GA of 30.1 (24.0-34.0) weeks. We found a positive association of Talpha with increasing levels of respiratory support after adjusting for GA and birth weight z-score (p<0.001; R2 = 0.38). Dynamics and complexity of body temperature in incubator-nursed preterm infants show considerable associations with GA and respiratory morbidity. Talpha may be a useful marker of autonomic maturity and severity of disease in preterm infants.

BackgroundWe aimed at investigating whether early lung mechanics in non-intubated infants below 32 weeks of gestational age (GA) are associated with respiratory outcome.MethodsLung mechanics were assessed by the forced oscillation technique using a mechanical ventilator (Fabian HFOi, ACUTRONIC Medical Systems AG, Hirzel, Switzerland) that superimposed small-amplitude oscillations (10 Hz) on a continuous positive airway pressure. Measurements were performed during regular tidal breathing using a face mask on days 2, 4, and 7 of life. Respiratory system resistance (Rrs) and reactance (Xrs) were computed from flow and pressure.ResultsOne hundred and seventy-seven measurements were successfully performed in 68 infants. Infants had a mean (range) GA of 29.3 (24.1–31.7) weeks and a birth weight of 1257 (670–2350)g. Xrs was associated with the duration of respiratory support (R2 = 0.39, p < 0.001). A multilevel regression model, including Xrs and GA, explained the duration of respiratory support better than GA alone (R2 = 0.51 vs. 0.45, p = 0.005, likelihood ratio test).ConclusionAssessment of Xrs in the first week of life is feasible and improves prognostication of respiratory outcome in very preterm infants on noninvasive respiratory support.

BackgroundCardiorespiratory stability of preterm infants is a prerequisite for discharge from the neonatal intensive care unit (NICU) but very difficult to predict. We aimed to assess whether characterizing heart rate fluctuation (HRF) within the first days of life has prognostic utility.MethodsWe conducted a prospective cohort study in 90 preterm infants using a previously validated surface diaphragmatic electromyography (sEMG) method to derive interbeat intervals. We characterized HRF by time series parameters including sample entropy (SampEn) and scaling exponent alpha (ScalExp) obtained from daily 3-h measurements. Data were analyzed by multivariable, multilevel linear regression.ResultsWe obtained acceptable raw data from 309/330 sEMG measurements in 76/90 infants born at a mean (range) of 30.2 (24.7–34.0) weeks gestation. We found a significant negative association of SampEn with duration of respiratory support (R2 = 0.53, p < 0.001) and corrected age at discontinuation of caffeine therapy (R2 = 0.35, p < 0.001) after adjusting for sex, gestational age, birth weight z-score, and sepsis.ConclusionsBaseline SampEn calculated over the first 5 days of life carries prognostic utility for an estimation of subsequent respiratory support and pre-discharge cardiorespiratory stability in preterm infants, both important for planning of treatment and utilization of health care resources.