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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bronchopulmonary 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.
This 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.
Two 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.
MR-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.
Plasma 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.
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.
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.
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.
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.
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.
To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life.
A 3-step simulation approach ...was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens.
A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L.
To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment.
Background
Retinopathy of prematurity (ROP) is a vision‐threatening disease of preterm neonates. The use of beta‐adrenergic blocking agents (beta‐blockers), which modulate the vasoproliferative ...retinal process, may reduce the progression of ROP or even reverse established ROP.
Objectives
To determine the effect of beta‐blockers on short‐term structural outcomes, long‐term functional outcomes, and the need for additional treatment, when used either as prophylaxis in preterm infants without ROP, stage 1 ROP (zone I), or stage 2 ROP (zone II) without plus disease or as treatment in preterm infants with at least prethreshold ROP.
Search methods
We searched the Cochrane Neonatal Review Group Specialized Register; CENTRAL (in the Cochrane Library Issue 7, 2017); Embase (January 1974 to 7 August 2017); PubMed (January 1966 to 7 August 2017); and CINAHL (January 1982 to 7 August 2017). We checked references and cross‐references and handsearched s from the proceedings of the Pediatric Academic Societies Meetings.
Selection criteria
We considered for inclusion randomised or quasi‐randomised clinical trials that used beta‐blockers for prevention or treatment of ROP in preterm neonates of less than 37 weeks' gestational age.
Data collection and analysis
We used the standard methods of Cochrane and the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence.
Main results
We included three randomised trials (N = 366) in this review. Two of these studies were at high risk of bias. All studies reported on prevention of ROP and compared oral propranolol with placebo or no treatment. We found no trials assessing beta‐blockers in infants with established stage 2 or higher ROP with plus disease.
In one trial, study medication was started after one week of life, i.e. prior to the first ROP screening. The other two trials included preterm infants if they had stage 2 or lower ROP without plus disease. Based on the GRADE assessment, we considered evidence to be of low quality for the following outcomes: rescue treatment with anti‐VEGF or laser therapy; and arterial hypotension or bradycardia requiring inotropic support. Evidence was of moderate quality for the following outcomes: progression to stage 2 with plus disease; progression to stage 3 ROP; and progression to stage 4 or 5 ROP.
Meta‐analysis of three trials (N = 366) suggested beneficial effects of oral beta‐blockers on the risk of requiring anti‐VEGF agents (typical risk ratio (RR) 0.32, 95% confidence interval (CI) 0.12 to 0.86; I² = 0%; typical risk difference (RD) −0.06, 95% CI −0.10 to −0.01; I² = 75%; number needed to treat for an additional beneficial outcome (NNTB) 18, 95% CI 14 to 84) and laser therapy (typical RR 0.54, 95% CI 0.32 to 0.89; typical RD −0.09, 95% CI −0.16 to −0.02; I² = 31%; NNTB 12, 95% CI 8 to 47). Meta‐analysis of two trials (N = 161) demonstrated a beneficial effect of oral beta‐blockers on progression to stage 3 ROP (typical RR 0.60, 95% CI 0.37 to 0.96; I² = 0%; typical RD −0.15, 95% CI −0.28 to −0.02; I² = 73%; NNTB 7, 95% CI 5 to 67). There was no significant effect of oral beta‐blockers on progression to stage 2 ROP with plus disease or to stage 4 or 5 ROP. Although meta‐analysis did not indicate a significant effect of beta‐blockers on arterial hypotension or bradycardia, propranolol dosage in one study was reduced by 50% in infants of less than 26 weeks' gestational age due to severe hypotension, bradycardia, and apnoea in several participants. Analyses did not indicate significant effects of beta‐blockers on complications of prematurity or mortality. None of the trials reported on long‐term visual impairment.
Authors' conclusions
Limited evidence of low‐to‐moderate quality suggests that prophylactic administration of oral beta‐blockers might reduce progression towards stage 3 ROP and decrease the need for anti‐VEGF agents or laser therapy. The clinical relevance of those findings is unclear as no data on long‐term visual impairment were reported. Adverse events attributed to oral propranolol at a dose of 2 mg/kg/d raise concerns regarding systemic administration of this drug for prevention of ROP at the given dose. There is insufficient evidence to determine the efficacy and safety of beta‐blockers for prevention of ROP due to high risk of bias in two included trials and the lack of long‐term functional outcomes. We would encourage researchers to conduct large, well‐designed trials to confirm or refute the role of beta‐blockers for prevention and treatment of ROP in preterm infants. Trials should report on long‐term visual impairment. Researchers should consider dose‐finding studies of systemic beta‐blockers and topical administration of beta‐blockers, in order to optimise drug delivery and minimise adverse events.
To assess the feasibility of volumetric capnography in spontaneously breathing very preterm infants at 36 weeks postmenstrual age (PMA) and its association with clinical markers of lung disease ...including the duration of respiratory support and bronchopulmonary dysplasia (BPD).
We obtained mainstream volumetric capnography measurements in 143 very preterm infants at 36 weeks PMA. BPD was categorized into no, mild, moderate, and severe according to the 2001 National Heart, Lung and Blood Institute workshop report. Normalized capnographic slopes of phase II (SnII) and phase III (SnIII) were calculated. We assessed the effect of BPD, duration of respiratory support, and duration of supplemental oxygen on capnographic slopes.
SnIII was steeper in infants with moderate to severe BPD (76 ± 25/L) compared with mild (31 ± 20/L) or no BPD (26 ± 18/L) (P < .001). The association of SnIII with moderate to severe BPD persisted after adjusting for birth weight z-score, respiratory rate, and airway dead space to tidal volume ratio. The diagnostic usefulness of SnIII to discriminate between infants with and without moderate to severe BPD was high (area under the curve, 0.94; 95% CI, 0.89-0.99).
Volumetric capnography is feasible in spontaneously breathing preterm infants at 36 weeks PMA and reflects the degree of lung disease. This promising bedside lung function technique may offer an objective, continuous physiological outcome measure for assessment of BPD severity.
ClinicalTrials.gov: NCT02083562.
Extremely preterm infants commonly suffer from respiratory distress syndrome. Ventilatory management of these infants starts from birth and includes decisions such as timing of respiratory support in ...relation to umbilical cord management, oxygenation targets, and options of positive pressure support. The approach of early intubation and surfactant administration through an endotracheal tube has been challenged in recent years by primary noninvasive respiratory support and newer methods of surfactant administration via thin catheters. Available data comparing the thin catheter method to endotracheal tube and delayed extubation in extremely preterm infants born before 28 weeks of gestation did not show differences in survival free of bronchopulmonary dysplasia. Data from numerous randomized trials comparing conventional ventilation with high‐frequency oscillatory ventilation did not show differences in meaningful outcomes. Among conventional modes of ventilation, there is good evidence to favor volume‐targeted ventilation over pressure‐limited ventilation. The former reduces the combined risk of bronchopulmonary dysplasia or death and several important secondary outcomes without an increase in adverse events. There are no evidence‐based guidelines to set positive end‐expiratory pressure in ventilated preterm infants. Recent research suggests that the forced oscillation technique may help to find the lowest positive end‐expiratory pressure at which lung recruitment is optimal. Benefits and risks of the various modes of noninvasive ventilation depend on the clinical setting, degree of prematurity, severity of lung disease, and competency of staff in treating associated complications. Respiratory care after discharge includes home oxygen therapy, lung function monitoring, weaning from medication started in the neonatal unit, and treatment of asthma‐like symptoms.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective This multicenter, international, retrospective study aims to investigate whether respiratory system reactance (Xrs) assessed by respiratory oscillometry on the 7th day of life is associated ...with respiratory outcomes in preterm infants below 32 weeks’ gestation. Methods Sinusoidal pressure oscillations (2–5 cmH 2 O peak-to-peak, 10 Hz) were superimposed on the positive end-expiratory pressure (PEEP). We assessed the association of Xrs z-score with the duration of respiratory support using linear regression and with bronchopulmonary dysplasia (BPD, according to Jensen et al . 2019) using logistic regression. We used the likelihood ratio test to evaluate whether Xrs z-score adds significantly to clinical predictors, including gestational age (GA), birth weight (BW) and the National Institute of Child Health and Human Development (NICHD) BPD prediction model. Results One hundred and thirty-seven infants (median (Q1, Q3) GA=28.43 (26.11, 30.29) weeks) were included; 44 (32%) developed BPD. Xrs z-score was significantly associated with the duration of respiratory support (R 2 =0.35). Xrs z-score was significantly higher in infants who developed BPD (p<0.001); the optimal cut-off value was 2.6, associated with 77% sensitivity and 80% specificity. In univariable analysis, per z-score increase in Xrs, the OR for BPD increased by 60% and the respiratory support by eight days. In multivariable analysis, Xrs z-score added significantly to the NICHD model and to GA and BW z-score to predict respiratory support duration (p=0.016 and p=0.014, respectively) and BPD development (p=0.003 and p<0.001, respectively). Conclusion Xrs z-score on the 7th day after birth improves the prediction of respiratory outcome in preterm infants.
PDF
