Plasma proteomics reveals gestational age-specific responses to mechanical ventilation and identifies the mechanistic pathways that initiate preterm lung injury

Respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. To assess the effects on fetal and neonatal morbidity and mortality, on maternal mortality and morbidity, and on the child in later life of administering corticosteroids to the mother before anticipated preterm birth. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 October 2005). Randomised controlled comparisons of antenatal corticosteroid administration (betamethasone, dexamethasone, or hydrocortisone) with placebo or with no treatment given to women with a singleton or multiple pregnancy, expected to deliver preterm as a result of either spontaneous preterm labour, preterm prelabour rupture of the membranes or elective preterm delivery. Two review authors assessed trial quality and extracted data independently. Twenty-one studies (3885 women and 4269 infants) are included. Treatment with antenatal corticosteroids does not increase risk to the mother of death, chorioamnionitis or puerperal sepsis. Treatment with antenatal corticosteroids is associated with an overall reduction in neonatal death (relative risk (RR) 0.69, 95% confidence interval (CI) 0.58 to 0.81, 18 studies, 3956 infants), RDS (RR 0.66, 95% CI 0.59 to 0.73, 21 studies, 4038 infants), cerebroventricular haemorrhage (RR 0.54, 95% CI 0.43 to 0.69, 13 studies, 2872 infants), necrotising enterocolitis (RR 0.46, 95% CI 0.29 to 0.74, eight studies, 1675 infants), respiratory support, intensive care admissions (RR 0.80, 95% CI 0.65 to 0.99, two studies, 277 infants) and systemic infections in the first 48 hours of life (RR 0.56, 95% CI 0.38 to 0.85, five studies, 1319 infants). Antenatal corticosteroid use is effective in women with premature rupture of membranes and pregnancy related hypertension syndromes. The evidence from this new review supports the continued use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk of preterm birth. A single course of antenatal corticosteroids should be considered routine for preterm delivery with few exceptions. Further information is required concerning optimal dose to delivery interval, optimal corticosteroid to use, effects in multiple pregnancies, and to confirm the long-term effects into adulthood.

Mass spectrometry is the method of choice for deep and reliable exploration of the (human) proteome. Targeted mass spectrometry reliably detects and quantifies pre-determined sets of proteins in a complex biological matrix and is used in studies that rely on the quantitatively accurate and reproducible measurement of proteins across multiple samples. It requires the one-time, a priori generation of a specific measurement assay for each targeted protein. SWATH-MS is a mass spectrometric method that combines data-independent acquisition (DIA) and targeted data analysis and vastly extends the throughput of proteins that can be targeted in a sample compared to selected reaction monitoring (SRM). Here we present a compendium of highly specific assays covering more than 10,000 human proteins and enabling their targeted analysis in SWATH-MS datasets acquired from research or clinical specimens. This resource supports the confident detection and quantification of 50.9% of all human proteins annotated by UniProtKB/Swiss-Prot and is therefore expected to find wide application in basic and clinical research. Data are available via ProteomeXchange (PXD000953-954) and SWATHAtlas (SAL00016-35).

The reason why some infants with respiratory distress syndrome fail to respond to surfactant, or respond only transiently, is incompletely understood. We hypothesized that resuscitation with large breaths at birth might damage the lungs and blunt the effect of surfactant. Five pairs of lamb siblings were delivered by cesarean section at 127-128 d of gestation. One lamb in each pair was randomly selected to receive six manual inflations of 35-40 mL/kg ("bagging") before the start of mechanical ventilation, a volume roughly corresponding to the inspiratory capacity of lamb lungs after prophylactic surfactant supplementation. Both siblings were given rescue porcine surfactant, 200 mg/kg, at 30 min of age. Blood gases and deflation pressure-volume (P-V) curves of the respiratory system were recorded until the lambs were killed at 4 h. The P-V curves became steeper after surfactant in the control group, but no such effect was seen in those subjected to bagging. At 4 h, inspiratory capacity and maximal deflation compliance were almost three times higher (p < 0.01) in the controls than in the bagged lambs. The latter were also more difficult to ventilate and tended to have less well expanded alveoli and more widespread lung injury in histologic sections. We conclude that a few inflations with volumes that are probably harmless in other circumstances might, when forced into the surfactant-deficient lung immediately at birth, compromise the effect of subsequent surfactant rescue treatment. Our findings challenge current neonatal resuscitation practice of rapidly establishing a normal lung volume by vigorous manual ventilation.