Pulmonary hypertension (PH) is a complication of bronchopulmonary dysplasia (BPD) but the true impact of PH in patients with BPD remains unclear. We sought to systematically review and meta-analyze ...incidence of PH in BPD and compare clinical outcomes of BPD patients with PH to those without PH in preterm infants.
Medline, Embase, PsychINFO and CINAHL were searched from January 2000 through December 2015. Cohort, case-control and randomized studies were included. Case-reports, case-series and letters to editors and studies with high risk of bias were excluded. Study design, inclusion/exclusion criteria, diagnostic criteria for BPD and PH and outcomes were extracted independently by two co-authors.
The pooled incidence of PH in patients with BPD (any severity) was 17% (95% confidence interval (CI) 12 to 21; 7 studies) and 24% (95% CI 17 to 30; 9 studies) in moderate-severe BPD. Patients with BPD have higher unadjusted odds of developing PH compared to those without BPD (odds ratio (OR) 3.00; 95% CI 1.18 to 7.66; 4 studies). Patients with BPD and PH were at higher odds of mortality (OR 5.29; 95% CI 2.07 to 13.56; 3 studies) compared with BPD without PH, but there was no significant difference in duration of initial hospitalization, duration of supplemental oxygen requirement or need for home oxygen. No studies included in this review reported on long-term pulmonary or neurodevelopmental outcomes.
PH occurs in one out of 4 to 5 preterm neonates with BPD. Patients with BPD and PH may have higher odds of mortality; however, there is urgent need for high quality studies that control for confounders and provide data on long-term outcomes.
Summary
In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid‐net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The ...registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.
Purpose
Remote ischemic conditioning (RIC) is a maneuver involving brief cycles of ischemia reperfusion in an individual’s limb. In the early stage of experimental NEC, RIC decreased intestinal ...injury and prolonged survival by counteracting the derangements in intestinal microcirculation. A single-center phase I study demonstrated that the performance of RIC was safe in neonates with NEC. The aim of this phase II RCT was to evaluate the safety and feasibility of RIC, to identify challenges in recruitment, retainment, and to inform a phase III RCT to evaluate efficacy.
Methods
RIC will be performed by trained research personnel and will consist of four cycles of limb ischemia (4-min via cuff inflation) followed by reperfusion (4-min via cuff deflation), repeated on two consecutive days post randomization. The primary endpoint of this RCT is feasibility and acceptability of recruiting and randomizing neonates within 24 h from NEC diagnosis as well as masking and completing the RIC intervention.
Results
We created a novel international consortium for this trial and created a consensus on the diagnostic criteria for NEC and protocol for the trial. The phase II multicenter-masked feasibility RCT will be conducted at 12 centers in Canada, USA, Sweden, The Netherlands, UK, and Spain. The inclusion criteria are: gestational age < 33 weeks, weight ≥ 750 g, NEC receiving medical treatment, and diagnosis established within previous 24 h. Neonates will be randomized to RIC (intervention) or no-RIC (control) and will continue to receive standard management of NEC. We expect to recruit and randomize 40% of eligible patients in the collaborating centers (78 patients; 39/arm) in 30 months. Bayesian methods will be used to combine uninformative prior distributions with the corresponding observed proportions from this trial to determine posterior distributions for parameters of feasibility.
Conclusions
The newly established NEC consortium has generated novel data on NEC diagnosis and defined the feasibility parameters for the introduction of a novel treatment in NEC. This phase II RCT will inform a future phase III RCT to evaluate the efficacy and safety of RIC in early-stage NEC.
Antibiotic exposure at the beginning of life can lead to increased antimicrobial resistance and perturbations of the developing microbiome. Early-life microbiome disruption increases the risks of ...developing chronic diseases later in life. Fear of missing evolving neonatal sepsis is the key driver for antibiotic overtreatment early in life. Bias (a systemic deviation towards overtreatment) and noise (a random scatter) affect the decision-making process. In this perspective, we advocate for a factual approach quantifying the burden of treatment in relation to the burden of disease balancing antimicrobial stewardship and effective sepsis management.
Up to 7% of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis. The prevalence of culture-proven ...early-onset sepsis is 0·1% or less in high-income countries, suggesting substantial overtreatment. We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of antibiotic treatment.
We did this randomised controlled intervention trial in Dutch (n=11), Swiss (n=4), Canadian (n=2), and Czech (n=1) hospitals. Neonates of gestational age 34 weeks or older, with suspected early-onset sepsis requiring antibiotic treatment were stratified into four risk categories by their treating physicians and randomly assigned 1:1 using a computer-generated list stratified per centre to procalcitonin-guided decision making or standard care-based antibiotic treatment. Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded. Only principal investigators were masked for group assignment. Co-primary outcomes were non-inferiority for re-infection or death in the first month of life (margin 2·0%) and superiority for duration of antibiotic therapy. Intention-to-treat and per-protocol analyses were done. This trial was registered with ClinicalTrials.gov, number NCT00854932.
Between May 21, 2009, and Feb 14, 2015, we screened 2440 neonates with suspected early-onset sepsis. 622 infants were excluded due to lack of parental consent, 93 were ineligible for reasons unknown (68), congenital malformation (22), or surgery in the first week of life (3). 14 neonates were excluded as 100% data monitoring or retrieval was not feasible, and one neonate was excluded because their procalcitonin measurements could not be taken. 1710 neonates were enrolled and randomly assigned to either procalcitonin-guided therapy (n=866) or standard therapy (n=844). 1408 neonates underwent per-protocol analysis (745 in the procalcitonin group and 663 standard group). For the procalcitonin group, the duration of antibiotic therapy was reduced (intention to treat: 55·1 vs 65·0 h, p<0·0001; per protocol: 51·8 vs 64·0 h; p<0·0001). No sepsis-related deaths occurred, and 9 (<1%) of 1710 neonates had possible re-infection. The risk difference for non-inferiority was 0·1% (95% CI −4·6 to 4·8) in the intention-to-treat analysis (5 0·6% of 866 neonates in the procalcitonin group vs 4 0·5% of 844 neonates in the standard group) and 0·1% (−5·2 to 5·3) in the per-protocol analysis (5 0·7% of 745 neonates in the procalcitonin group vs 4 0·6% of 663 neonates in the standard group).
Procalcitonin-guided decision making was superior to standard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis. Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study-related death.
The Thrasher Foundation, the NutsOhra Foundation, the Sophia Foundation for Scientific research.
Human milk analyzers are increasingly used to rapidly measure the macronutrient content in breast milk for individual target fortification, to reduce the risk of postnatal growth restriction. ...However, many milk analyzers are used without calibration, validation or quality assurance.
To investigate measurement quality between different human milk analyzers, to test whether accuracy and precision of devices can be improved by establishing individual calibration curves, and to assess long-term stability of measurements, following good clinical laboratory practice (GCLP).
Sets of identical breast milk samples were sent to 13 participating centres in North America and Europe, for a total of 15 devices. The study included 3 sets of samples: A) initial assessment of the device's performance consisting of 10 calibration samples with random replicates; B) long term stability and quality control consisting of 2 batches of samples to be measured every time before the device is used, over 6 months; C) ring trial consisting of 2 samples to be measured monthly. The devices tested were Unity SpectraStar (n = 5) and MIRIS Human Milk Analyzer (n = 10).
There are significant variations in accuracy and precision between different milk analyzers' fat, protein and lactose measurements. However, the accuracy of measurements can be improved by establishing individual correction algorithms. Repeated measurements are more robust when coming from a larger batch volume. Long term stability also varies between devices.
The variations in measurements between devices are clinically significant and would impact both daily dietary prescriptions, and the outcomes of clinical studies assessing the effect of targeted adjustment of nutrient intake in preterm babies. This study shows that it is crucial to follow GCLP when using milk analyzers to ensure proper measurement of macronutrients, similar to what is required of other medical devices.
Appropriate use of antibiotics is life-saving in neonatal early-onset sepsis (EOS), but overuse of antibiotics is associated with antimicrobial resistance and long-term adverse outcomes. Large ...international studies quantifying early-life antibiotic exposure along with EOS incidence are needed to provide a basis for future interventions aimed at safely reducing neonatal antibiotic exposure.
To compare early postnatal exposure to antibiotics, incidence of EOS, and mortality among different networks in high-income countries.
This is a retrospective, cross-sectional study of late-preterm and full-term neonates born between January 1, 2014, and December 31, 2018, in 13 hospital-based or population-based networks from 11 countries in Europe and North America and Australia. The study included all infants born alive at a gestational age greater than or equal to 34 weeks in the participating networks. Data were analyzed from October 2021 to March 2022.
Exposure to antibiotics started in the first postnatal week.
The main outcomes were the proportion of late-preterm and full-term neonates receiving intravenous antibiotics, the duration of antibiotic treatment, the incidence of culture-proven EOS, and all-cause and EOS-associated mortality.
A total of 757 979 late-preterm and full-term neonates were born in the participating networks during the study period; 21 703 neonates (2.86%; 95% CI, 2.83%-2.90%), including 12 886 boys (59.4%) with a median (IQR) gestational age of 39 (36-40) weeks and median (IQR) birth weight of 3250 (2750-3750) g, received intravenous antibiotics during the first postnatal week. The proportion of neonates started on antibiotics ranged from 1.18% to 12.45% among networks. The median (IQR) duration of treatment was 9 (7-14) days for neonates with EOS and 4 (3-6) days for those without EOS. This led to an antibiotic exposure of 135 days per 1000 live births (range across networks, 54-491 days per 1000 live births). The incidence of EOS was 0.49 cases per 1000 live births (range, 0.18-1.45 cases per 1000 live births). EOS-associated mortality was 3.20% (12 of 375 neonates; range, 0.00%-12.00%). For each case of EOS, 58 neonates were started on antibiotics and 273 antibiotic days were administered.
The findings of this study suggest that antibiotic exposure during the first postnatal week is disproportionate compared with the burden of EOS and that there are wide (up to 9-fold) variations internationally. This study defined a set of indicators reporting on both dimensions to facilitate benchmarking and future interventions aimed at safely reducing antibiotic exposure in early life.
Congenital nasal pyriform stenosis can be a life threatening emergency in neonates which must be included in the differential diagnosis of nasal airway obstruction. We describe the case of a male ...child who developed symptoms 36 h after birth. As the conservative therapy was not successful surgery became necessary.
Abstract
BACKGROUND: Pulmonary hypertension (PH) is a known complication of bronchopulmonary dysplasia (BPD). At our centre, all patients with BPD are screened for PH but its exact incidence and ...impact on clinical outcomes remains unclear.
OBJECTIVES: To determine the incidence of and risk factors for PH in preterm infants with moderate-severe BPD and to compare short-term outcomes in BPD patients with PH and without PH.
DESIGN/METHODS: This was a single centre cohort study of preterm infants < 32 weeks GA born between August 2013 and July 2015 with moderate-severe BPD at 36 weeks postmenstrual age. Patients were categorized into BPD+PH (exposure) and BPD alone (control). PH was defined as right ventricular systolic pressure (RVSP) > 40 mmHg or septum flattening in absence of RVSP. Cases of a) RVSP between 30-40 mmHg with normal/unknown septum status and b) RVSP < 40 mmHg with flat septum were defined as “possible PH” (classified as exposure). Predictors of BPD+PH were sought using logistic regression analyses. Outcomes included mortality, growth parameters and NICU resource utilization. Sensitivity analyses were conducted for all outcomes by re-categorizing “possible PH” cases from exposure to control group. A p value of < 0.05 was considered significant.
RESULTS: Among 92 BPD patients in study period, 87 had echocardiograms completed of whom 24 (28%) had PH. Baseline characteristics were similar in the two groups with the exception of GA and number of surfactant doses (Table). On multiple logistic regression, after correcting for GA and sex, lack of receipt of antenatal corticosteroids was identified as a significant risk factor for PH (adjusted OR 5.3, 95% CI 1.1-25.1, p = 0.039). There were no significant differences in any outcomes (Table). Similar results were obtained with sensitivity analyses.
CONCLUSION: Almost 1 in 3 patients with BPD was identified as having (or possibly having) PH at our centre, with lack of antenatal corticosteroid administration identified as a significant risk factor. No significant differences in outcomes were noted. However, larger prospective studies and long term outcome evaluations are required prior to definitive recommendations regarding screening.
Table 1.
Selected baseline characteristics and outcomes in BPD patients with and without PH
Baseline Characteristics
BPD+PH (n=24)
BPD alone (n=63)
P value
GA
24.7 (2.3)
26.4 (3.7)
0.015
BW
785 (458)
840 (268)
0.409
Sex (Female)
37.5
37.1
0.972
Antenatal Steroids
79.2
83.7
0.107*
Chorioamnionitis
34.8
26.3
0.449
Prolonged Rupture of Membranes (> 24 h)
25.0
20.6
0.66
Oligohydramnios
4.2
14.3
0.273*
Snap II Score
14.0 (13.5)
16.0 (17.0)
0.32
Number of Surfactant doses
1.5 (1.0)
1.0 (1.0)
0.015
Outcome variables
BPD+PH (n=24)
BPD alone (n=63)
P value
Survival to discharge
95.8
98.4
0.478
Discharge weight (grams)
3355 (739)
3260 (1146)
0.851
Discharge head-circumference (cm)
35.0 (2.2)
34.3 (3.7)
0.631
Discharged on oxygen
20.8
19.1
1.000
Length of Stay (days)
93.5 (25.5)
93.0 (38.0)
0.566
Duration of invasive ventilation (days)
17.5 (46.0)
13.0 (33.0)
0.905
Duration of non-invasive ventilation (days)
58.0 (22.5)
67.0 (29.0)
0.072
Duration on supplemental oxygen (days)
81.0 (53.0)
66.5 (43.0)
0.435
Note: All categorical variables reported as percentages and all continuous variables as medians (IQR).
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