Necrotizing enterocolitis (NEC) is a severe multifactorial disease in preterm neonates associated with high morbidity and mortality. Better insight into prognostic values of the many reported factors ...associated with NEC is needed to enable identification of neonates at risk for NEC. The aim was to systematically review the literature to identify independent risk factors for NEC from the literature.
Medline, Cochrane, Embase, Pubmed and Google Scholar were searched systematically for cohort studies reporting prognostic factors for NEC in neonates using multivariable analysis. Studies were scored with the Quality In Prognosis Studies tool (QUIPS).
From 5154 initial hits, 14 prognostic studies were included, with various designs. Study quality was rated high in three studies, moderate or low in the 11 others. Significant prognostic factors for NEC reported in at least two studies were: low birth weight, small for gestational age, low gestational age, assisted ventilation, premature rupture of membranes, black ethnicity, sepsis, outborn, hypotension (all increased risk), surfactant therapy (conflicting results) and cesarean section (lower risk). Meta-analysis was considered not feasible.
High quality studies on prognostic factors for NEC are rare. Several prognostic factors, that are not necessarily causal, are associated with NEC. High quality prognostic research is necessary to establish the predictive values of these factors.
Neonatal intensive care units (NICU) around the world increasingly use music interventions. The most recent systematic review of randomized controlled trials (RCT) dates from 2009. Since then, 15 new ...RCTs have been published. We provide an updated systematic review on the possible benefits of music interventions on premature infants' well-being.
We searched 13 electronic databases and 12 journals from their first available date until August 2016. Included were all RCTs published in English with at least 10 participants per group, including infants born prematurely and admitted to the NICU. Interventions were either recorded music interventions or live music therapy interventions. All control conditions were accepted as long as the effects of the music intervention could be analysed separately. A meta-analysis was not possible due to incompleteness and heterogeneity of the data.
After removal of duplicates the searches retrieved 4893 citations, 20 of which fulfilled the inclusion/exclusion criteria. The 20 included studies encompassed 1128 participants receiving recorded or live music interventions in the NICU between 24 and 40 weeks gestational age. Twenty-six different outcomes were reported which we classified into three categories: physiological parameters; growth and feeding; behavioural state, relaxation outcomes and pain. Live music interventions were shown to improve sleep in three out of the four studies and heart rate in two out of the four studies. Recorded music improved heart rate in two out of six studies. Better feeding and sucking outcomes were reported in one study using live music and in two studies using recorded music.
Although music interventions show promising results in some studies, the variation in quality of the studies, age groups, outcome measures and timing of the interventions across the studies makes it difficult to draw strong conclusions on the effects of music in premature infants.
Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly ...reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth.
We used a national quasi-experimental difference-in-regression-discontinuity approach. We used data from the neonatal dried blood spot screening programme (2010–20) cross-validated against national perinatal registry data. Stratified analyses were done according to gestational age subgroups, and sensitivity analyses were done to assess robustness of the findings. We explored potential effect modification by neighbourhood socioeconomic status, sex, and small-for-gestational-age status.
Data on 1 599 547 singleton neonates were available, including 56 720 births that occurred after implementation of COVID-19 mitigation measures on March 9, 2020. Consistent reductions in the incidence of preterm birth were seen across various time windows surrounding March 9 (± 2 months n=531 823 odds ratio OR 0·77, 95% CI 0·66–0·91, p=0·0026; ± 3 months n=796 531 OR 0·85, 0·73–0·98, p=0·028; ± 4 months n=1 066 872 OR 0·84, 0·73–0·97, p=0·023). Decreases in incidence observed following the March 15 measures were of smaller magnitude, but not statistically significant. No changes were observed after March 23. Reductions in the incidence of preterm births after March 9 were consistent across gestational age strata and robust in sensitivity analyses. They appeared confined to neighbourhoods of high socioeconomic status, but effect modification was not statistically significant.
In this national quasi-experimental study, initial implementation of COVID-19 mitigation measures was associated with a substantial reduction in the incidence of preterm births in the following months, in agreement with preliminary observations elsewhere. Integration of comparable data from across the globe is needed to further substantiate these findings and start exploring underlying mechanisms.
None.
ARDS is a severe pulmonary disease characterized by inflammation. However, inflammation-directed therapies have yet failed to improve the outcome in ARDS patients. One of the reasons may be the ...underestimated complexity of inflammation. Here, we summarize recent insights into the complex interrelations between inflammatory circuits.
Gene expression analysis from animal models or from patients with ARDS, sepsis or trauma show an enormous number of differentially expressed genes with highly significant overlaps between the various conditions. These similarities, however, should not obscure the complexity of inflammation. We suggest to consider inflammation in ARDS as a system controlled by scale-free networks of genome-wide molecular interaction with hubs (e.g. NFκB, C/EBPβ, ATF3), exhibiting nonlinear emergence and the ability to adapt, meaning for instance that mild and life-threatening inflammation in ARDS are distinct processes. In order to comprehend this complex system, it seems necessary to combine model-driven simulations, data-driven modelling and hypothesis-driven experimental studies. Recent experimental studies have illustrated how several regulatory circuits interact during pulmonary inflammation, including the resolution of inflammation, the inflammasome, autophagy and apoptosis.
We suggest that therapeutic interventions in ARDS should be based on a systems approach to inflammation.
Sepsis is a major health issue in preterm infants. Biomarkers are used to diagnose and monitor patients with sepsis, but C-reactive protein (CRP) is proven not predictive at onset of late onset ...neonatal sepsis (LONS) diagnosis. The aim of this study was to evaluate the association of interleukin-6(IL-6), procalcitonin (PCT) and CRP with subsequent sepsis severity and mortality in preterm infants suspected of late onset neonatal sepsis.
The study was conducted at the Erasmus University Medical Center-Sophia Children's Hospital Rotterdam. Patient data from January 2018 until October 2019 were reviewed for all preterm neonates born with a gestational age below 32 weeks with signs and symptoms suggestive of systemic infection, in whom blood was taken for blood culture and for inflammatory biomarkers determinations. Plasma IL-6 and PCT were assessed next to CRP at the moment of suspicion. We assessed the association with 7-day mortality and sepsis severity (neonatal sequential organ failure assessment (nSOFA) score, need for inotropic support, invasive ventilation and thrombocytopenia).
A total of 480 suspected late onset neonatal sepsis episodes in 208 preterm neonates (gestational age < 32 weeks) were retrospectively analyzed, of which 143 episodes were classified as sepsis (29.8%), with 56 (11.7%) cases of culture negative, 63 (13.1%) cases of gram-positive and 24(5.0%) cases of gram-negative sepsis. A total of 24 (5.0%) sepsis episodes resulted in death within 7 days after suspicion of LONS. Both IL-6 (adjusted hazard ratio (aHR): 2.28; 95% CI 1.64-3.16; p < 0.001) and PCT (aHR: 2.91; 95% CI 1.70-5.00; p < 0.001) levels were associated with 7-day mortality; however, CRP levels were not significantly correlated with 7-day mortality (aHR: 1.16; 95% CI (0.68-2.00; p = 0.56). Log IL-6, log PCT and log CRP levels were all significantly correlated with the need for inotropic support.
Our findings show that serum IL-6 and PCT levels at moment of suspected late onset neonatal sepsis offer valuable information about sepsis severity and mortality risk in infants born below 32 weeks of gestation. The discriminative value was superior to that of CRP. Determining these biomarkers in suspected sepsis may help identify patients with imminent severe sepsis, who may require more intensive monitoring and therapy.
In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 ...to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.
Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography ...(EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure.
This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBI
), Respiratory Rate (RR
) and Minute Ventilation (MV
) were computed on a breath-by-breath basis from stable tidal breathing periods.
EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO
(p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT.
EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.
In pregnancy, iron deficiency and iron overload increase the risk for adverse pregnancy outcomes, but the effects of maternal iron status on long-term child health are poorly understood. The aim of ...the study was to systematically review and analyze the literature on maternal iron status in pregnancy and long-term outcomes in the offspring after birth. We report a systematic review on maternal iron status during pregnancy in relation to child health outcomes after birth, from database inception until 21 January 2021, with methodological quality rating (Newcastle-Ottawa tool) and random-effect meta-analysis. (PROSPERO, CRD42020162202). The search identified 8139 studies, of which 44 were included, describing 12,7849 mother–child pairs. Heterogeneity amongst the studies was strong. Methodological quality was predominantly moderate to high. Iron status was measured usually late in pregnancy. The majority of studies compared categories based on maternal ferritin, however, definitions of iron deficiency differed across studies. The follow-up period was predominantly limited to infancy. Fifteen studies reported outcomes on child iron status or hemoglobin, 20 on neurodevelopmental outcomes, and the remainder on a variety of other outcomes. In half of the studies, low maternal iron status or iron deficiency was associated with adverse outcomes in children. Meta-analyses showed an association of maternal ferritin with child soluble transferrin receptor concentrations, though child ferritin, transferrin saturation, or hemoglobin values showed no consistent association. Studies on maternal iron status above normal, or iron excess, suggest deleterious effects on infant growth, cognition, and childhood Type 1 diabetes. Maternal iron status in pregnancy was not consistently associated with child iron status after birth. The very heterogeneous set of studies suggests detrimental effects of iron deficiency, and possibly also of overload, on other outcomes including child neurodevelopment. Studies are needed to determine clinically meaningful definitions of iron deficiency and overload in pregnancy.
Doxapram is used for the treatment of apnea of prematurity in dosing regimens only based on bodyweight, as pharmacokinetic data are limited. This study describes the pharmacokinetics of doxapram and ...keto-doxapram in preterm infants.
Data (302 samples) from 75 neonates were included with a median (range) gestational age (GA) 25.9 (23.9-29.4) weeks, bodyweight 0.95 (0.48-1.61) kg, and postnatal age (PNA) 17 (1-52) days at the start of continuous treatment. A population pharmacokinetic model was developed using non-linear mixed-effects modelling (NONMEM®).
A two-compartment model best described the pharmacokinetics of doxapram and keto-doxapram. PNA and GA affected the formation clearance of keto-doxapram (CL
) and clearance of doxapram via other routes (CL
). For a median individual of 0.95 kg, GA 25.6 weeks, and PNA 29 days, CL
was 0.115 L/h (relative standard error (RSE) 12%) and CL
was 0.645 L/h (RSE 9%). Oral bioavailability was estimated at 74% (RSE 10%).
Dosing of doxapram only based on bodyweight results in the highest exposure in preterm infants with the lowest PNA and GA. Therefore, dosing may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. For switching to oral therapy, a 33% dose increase is required to maintain exposure.
Current dosing regimens of doxapram in preterm infants only based on bodyweight result in the highest exposure in infants with the lowest PNA and GA. Dosing of doxapram may need to be adjusted for GA and PNA to minimize the risk of accumulation and adverse events. Describing the pharmacokinetics of doxapram and its active metabolite keto-doxapram following intravenous and gastroenteral administration enables to include drug exposure to the evaluation of treatment of AOP. The oral bioavailability of doxapram in preterm neonates is 74%, requiring a 33% higher dose via oral than intravenous administration to maintain exposure.
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