Background: Apnea and bradycardia of prematurity (ABP) are possible risks towards damage of the developing brain. Objectives: To characterize the influence of neonatal factors on ABP and to determine the relationship of ABP to neurodevelopmental outcome. Methods: ABP was described in very low birth weight infants (n = 83) using the frequency and severity of ABP episodes with a clinical score considering heart rate, oxygenation, duration and interventions performed during each episode. Neonatal factors were analyzed for their relationship to ABP using regression analysis. Neurodevelopment was investigated using the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II at a corrected age of 13 months. Power of ABP parameters to predict outcome was assessed by logistic regression analysis. Results: ABP typically started within the first week after birth. Spontaneous resolution occurred at a postmenstrual age (PMA) of 36.0 ± 2.2 (31.1–44.1) weeks. A delayed resolution (>36 weeks PMA) and a higher average daily ABP score during a defined developmental period (31–37 weeks PMA) were associated with a higher incidence of unfavorable outcome (MDI or PDI <69 or death). Conclusion: ABP is an age-specific phenomenon. However, more severe courses than expected for PMA or the resolution at a later PMA indicated an increased risk of neurodevelopmental disturbances at a corrected age of 13 months.

IMPORTANCE Rates of survival for infants born at the border of viability are still low and vary considerably among neonatal intensive care units. OBJECTIVE To determine whether higher survival rates and better short-term outcomes for infants born at 22 or 23 weeks' gestation may be achieved by active prenatal and postnatal care. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of 106 infants born at 22 or 23 weeks of gestation at a level III neonatal intensive care unit at EXPOSURES Active prenatal and postnatal care.MAIN OUTCOMES AND MEASURES Survival until hospital discharge and survival without neonatal or short-term severe complications (defined as high-grade intraventricular hemorrhage, surgery for abdominal complications, bronchopulmonary dysplasia, or retinopathy of prematurity). RESULTSOf 106 liveborn infants (45 born at 22 weeks and 61 born at 23 weeks and 6 days), 20 (19%) received palliative care (17 born at 22 weeks and 3 born at 23 weeks), and 86 (81%) received active care (28 born at 22 weeks and 58 born at 23 weeks). Of the 86 infants who received active care (mean [SD] maternal age, 32 [6] years), 58 (67%) survived until hospital discharge (17 born at 22 weeks and 41 born at 23 weeks). Eighty-five infants survived without severe complications, with 1 infant born at 22 weeks excluded because of missing data (6 of 27 [22%] born at 22 weeks, and 16 of 58 [28%] born at 23 weeks). Survival was predicted by the Apgar score after 5 minutes (odds ratio, 0.62 [95% CI, 0.46-0.84]) and birth weight (odds ratio, 0.001 [95% CI, 0.00-0.40]). CONCLUSIONS AND RELEVANCE One in 4 infants born at the border of viability and offered active care survived without severe complications. This finding should be considered for individualized parental approaches and decision making. Active follow-up information is required to determine childhood outcomes.

Background: Human breast milk could be an important stem cell source for the development of newborn and preterm infants, but quantitative data on the stem cell content in breast milk at various gestational stages are needed to determine the clinical value of breast milk as a source of stem cells. Breast milk also contains milk fat globules, lipid droplets of different sizes, debris and dead cells and these components hamper flow cytometry analysis of human breast milk samples.Methods: Here, we originally used standard protocols for flow cytometry to characterize cell populations in human breast milk but failed to discriminate between cells and noncellular components. We then applied a centrifugation protocol to separate cream and skim milk from the cell-containing pellet and used a novel staining protocol with DRAQ5™ and SYTOX ® blue dye as well as antibodies to characterize cells within the pellet fraction.Results: Flow cytometry analysis identified viable DRAQ5™ + /SYTOX ® Blue − cells and determined the content of CD11b + monocytes and TRA-1-81 + putative stem cells in human breast milk samples.Conclusions: Hence, we developed a novel and reliable flow cytometry based-approach to quantify subpopulation of cells in human breast milk with a high content of milk fat globules, lipid droplets, and particles. This approach will improve the identification and quantification of breast milk cells and allow standardizing the flow cytometry-based evaluation of the stem cell content.

Over one third of pregnancies with ROH were terminated and the parental decision was based on risk factors associated with adverse outcome. Neonatal death was rare in the actively treated infants and the overall outcome promising. Our study illustrates that only careful analysis of the whole process, from prenatal diagnosis via parental decision-making to postnatal outcome, allows sensible interpretation of outcome data.

The aim of our study was to observe the temporal distribution of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in premature infants of ≤ 31 weeks of gestational age (GA) during the first weeks of life. NT-proBNP values of 118 preterm infants born ≤ 31 weeks GA were determined during the first week of life, after 4 ± 1 weeks of life, and at a corrected GA of 36 ± 2 weeks. Infants were divided into two groups: those without relevant complications and those with complications related to prematurity. NT-proBNP values of infants without complications define our exploratory reference values. The Median NT-proBNP level of these infants was 1896 ng/l (n = 27, interquartile range (IQR): 1277–5200) during the first week of life, 463 ng/l (n = 26, IQR: 364–704) at 4 ± 1 weeks of life, and 824 ng/l (n = 33, IQR: 714–1233) at a corrected GA of 36 ± 2 weeks. Infants born < 28 + 0 weeks GA had significantly higher NT-proBNP values (n = 9, median: 5200, IQR: 1750–8972) than infants born ≥ 28 + 0–31 weeks GA (n = 18, median: 1528, IQR: 838–3052; p = 0.017). Growth restriction or PDA status could not account for the difference in NT-proBNP values between GA groups. Conclusions: The results of our observational and cross-sectional study describe exploratory reference values for NT-proBNP levels in preterm infants of ≤ 31 weeks GA according to postnatal age. NT-proBNP levels during the first week of life are high and widely distributed in preterm infants and decrease subsequently to reach a distinctly lower and stable plateau at around 1 month of life. Our results suggest an influence of GA on NT-proBNP values in the first week of life. What is Known:• Several complications related to prematurity, e.g., hemodynamically significant PDA, pulmonary hypertension, bronchopulmonary dysplasia, and retinopathy of prematurity, have been associated with a temporary rise in NT-proBNP values in preterm infants during their first weeks of life.What is New:• This observational study provides reference values for NT-proBNP levels of very and extremely preterm infants during their first weeks of life.• In premature infants without complications, NT-proBNP values during their first week of life depend on gestational age at birth.

IMPORTANCEThe inclusion of less invasive surfactant administration (LISA) in the care of preterm infants has been found to be beneficial for respiratory outcomes. Recently, the OPTIMIST trial found higher mortality rates in the subgroup of infants born at 25 to 26 weeks' gestational age (GA) who received surfactant treatment while spontaneously breathing. OBJECTIVETo analyze outcomes among LISA-exposed, highly vulnerable babies born at less than 27 weeks' GA within the large-scale observational cohort of the German Neonatal Network. DESIGN, SETTING, AND PARTICIPANTSIn this cohort study of data from 68 tertiary level neonatal intensive care units in Germany of infants born between 22 weeks 0 days to 26 weeks 6 days of gestation between April 1, 2009, and December 31, 2020, short-term outcomes among infants receiving LISA vs infants not receiving LISA were compared. EXPOSURE Use of LISA within the first 72 hours of life. MAIN OUTCOMES AND MEASURESThe main outcomes were rates of LISA use, use of mechanical ventilation within the first 72 hours (considered failure of LISA), and association of LISA with outcomes, including death from all causes, bronchopulmonary dysplasia (BPD), death and BPD combined, pneumothorax, retinopathy of prematurity, intracerebral hemorrhage, and periventricular leukomalacia. To address potential confounding factors, multivariate logistic regression models were used. RESULTSA total of 6542 infants (3030 [46.3%] female and 3512 [53.7%] male; mean [SD] GA, 25.3(1.1) weeks; mean [SD] birth weight, 715 [180] g) were analyzed; 2534 infants (38.7%) received LISA, which was most frequently given quasi-prophylactically during delivery room management. Among the infants who received LISA, 1357 (53.6%) did not require mechanical ventilation in the first 72 hours compared with 331 infants (8.3%) of 4008 who did not receive LISA. In a multivariate logistic regression model that adjusted for GA, small-for-GA status, sex, multiple birth, inborn status, antenatal steroid use, and maximum fraction of inspired oxygen in the first 12 hours of life, LISA was associated with reduced risks of all-cause death (odds ratio [OR], 0.74; 95% CI, 0.61-0.90; P = .002), BPD (OR, 0.69; 95% CI, 0.62-0.78; P < .001), and BPD or death (OR, 0.64; 95% CI, 0.57-0.72; P < .001) compared with infants without LISA exposure. CONCLUSIONS AND RELEVANCEThe results of this long-term multicenter cohort study suggest that LISA may be associated with reduced risks of adverse outcomes in extremely preterm infants.

The C-terminal pro-fibrillin-1 propeptide asprosin is described as white adipose tissue derived hormone that stimulates rapid hepatic glucose release and activates hunger-promoting hypothalamic neurons. Numerous studies proposed correlations of asprosin levels with clinical parameters. However, the enormous variability of reported serum and plasma asprosin levels illustrates the need for sensitive and reliable detection methods in clinical samples. Here we report on newly developed biochemical methods for asprosin concentration and detection in several body fluids including serum, plasma, saliva, breast milk, and urine. Since we found that glycosylation impacts human asprosin detection we analyzed its glycosylation profile. Employing a new sandwich ELISA revealed that serum and saliva asprosin correlate strongly, depend on biological sex, and feeding status. To investigate the contribution of connective tissue-derived asprosin to serum levels we screened two cohorts with described cartilage turnover. Serum asprosin correlated with COMP, a marker for cartilage degradation upon running exercise and after total hip replacement surgery. This together with our finding that asprosin is produced by primary human chondrocytes and expressed in human cartilage suggests a contribution of cartilage to serum asprosin. Furthermore, we determined asprosin levels in breast milk, and urine, for the first time, and propose saliva asprosin as an accessible clinical marker for future studies.

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