Evaluating the Use of a Decision Aid for Parents Facing Extremely Premature Delivery: A Randomized Trial.

OBJECTIVE: To assess decisional conflict and knowledge about prematurity among mothers facing extreme premature delivery when the counseling clinicians were randomized to counsel using a validated decision aid compared with usual counseling. STUDY DESIGN: In this randomized trial, clinicians at 5 level III neonatal intensive care units in the US were randomized to supplement counseling using the decision aid or to counsel mothers in their usual manner. We enrolled mothers with threatened premature delivery at 220/7 to 256/7 weeks of gestation within 7 days of their counseling. The primary outcome was the Decisional Conflict Scale (DCS) score. One hundred mothers per group were enrolled to detect a clinically relevant effect size of 0.4 in the Decisional Conflict Scale. Secondary outcomes included knowledge about prematurity; scores on the Preparedness for Decision Making scale; and acceptability. RESULTS: Ninety-two clinicians were randomized and 316 mothers were counseled. Of these, 201 (64%) mothers were enrolled. The median gestational age was 24.1 weeks (IQR 23.7-24.9). In both groups, DCS scores were low (16.3 ± 18.2 vs 16.8 ± 17, P = .97) and Preparedness for Decision Making scores were high (73.4 ± 28.3 vs 70.5 ± 31.1, P = .33). There was a significantly greater knowledge score in the decision aid group (66.2 ± 18.5 vs 57.2 ± 18.8, P = .005). Most clinicians and parents found the decision aid useful. CONCLUSIONS: For parents facing extremely premature delivery, use of a decision aid did not impact maternal decisional conflict, but it significantly improved knowledge of complex information. A structured decision aid may improve comprehension of complex information. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01713894.

Reliability of a Noninvasive Measure of V./Q. Mismatch for Bronchopulmonary Dysplasia.

RATIONALE: Currently used definitions of bronchopulmonary dysplasia (BPD) lack a continuous measure of disease severity. OBJECTIVES: To determine if an indirect measure of V./Q. mismatch is reliable when simplified to facilitate more widespread use for grading disease severity in BPD at 36 weeks postmenstrual age. METHODS: We used prospectively collected data from 32 preterm infants undergoing an oxygen reduction test at 36 weeks postmenstrual age to perform a simplified indirect assessment of V./Q. mismatch for each infant. Independent raters applied the model, and interrater reliability for a quantitative measure of mismatch was measured by intraclass correlation coefficient. A receiver operating characteristic curve evaluated the impact of increasing degrees of V./Q. mismatch on diagnosing BPD as defined by oxygen reduction test failure. MEASUREMENTS AND MAIN RESULTS: Concordance for the quantitative measure of V./Q. mismatch between independent raters improved from 0.72 (confidence interval [CI], 0.48-0.86) to 0.93 (CI, 0.87-0.96) after refinement of instructions for applying the simplified model. Higher degrees of mismatch were increasingly predictive of oxygen reduction test failure, with a receiver operating characteristic curve analysis area under the curve of 0.83 (CI, 0.68-0.99; P = 0.03). CONCLUSIONS: A simplified indirect measure of V./Q. mismatch for diagnosing and grading disease severity in BPD has high reliability and can be performed with data obtained during a standard oxygen reduction test. This should facilitate more widespread investigation of this model as a technique for characterizing BPD severity.

Effects of placental transfusion in extremely low birthweight infants: meta-analysis of long- and short-term outcomes.

BACKGROUND: Risks and benefits of increasing placental transfusion in extremely preterm infants (extremely low birthweight [ELBW], <1000 g) are ill defined. We performed a meta-analysis to compare long- and short-term outcomes of ELBW infants in trials of enhanced placental transfusion regimens. STUDY DESIGN AND METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) of delayed umbilical cord clamping or umbilical cord milking in compliance with PRISMA and Cochrane Collaborative guidelines for systematic reviews. We searched multiple databases for medical literature up to December 2012. Inclusion criteria were preterm infants less than 30 weeks and less than 1000 g birthweight, randomly assigned to enhanced placental transfusion (either delayed cord clamping or cord milking) versus immediate cord clamping. The primary outcome was standardized neurodevelopmental outcome at 18 to 24 months corrected age using a standardized scale. Several short-term outcomes were also evaluated as secondary variables. RESULTS: We found 19 studies of which 10 studies could be included (n = 199). Three reported neurodevelopmental outcomes, none of which showed significant rates of disability. Two reported these at 18 to 24 months (n = 42) but used different scales preventing pooling. Short-term benefits of enhanced placental strategies included better blood pressure and hemoglobin on admission, along with reduced blood transfusions, a trend to reduced intraventricular hemorrhage, and episodes of late-onset sepsis. CONCLUSIONS: Strategies to enhance placental transfusion may improve short-term outcomes of ELBW infants. However, paucity of data on neurodevelopmental outcomes and safety concerns tempers enthusiasm for these interventions. Appropriately designed RCTs to assess short-term and longterm outcomes are needed in ELBW infants.

Cloning of partial cDNAs for the chicken glucocorticoid and mineralocorticoid receptors and characterization of mRNA levels in the anterior pituitary gland during chick embryonic development.

Virtually nothing is known about glucocorticoid receptor (GR) or mineralocorticoid receptor (MR) gene expression in any avian species. Here we report the cloning of partial cDNAs for chicken GR and MR. These partial cDNAs were used as probes to characterize expression of GR and MR mRNA and to identify the full-length transcripts within the chicken genome. Chicken GR and MR sequences predicted from the genome sequence were compared with those of representatives of other vertebrate classes. GR and MR genes are located on chicken chromosomes 13 and 4, respectively. Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR) results indicate that GR and MR are widely expressed in many tissues. Characterization of mRNA levels in the anterior pituitary gland during chick embryonic development by quantitative real time RT-PCR demonstrates decreased MR and increased GR gene expression between embryonic days 12 and 17. Plasma levels of corticosteroids increased during this same period. This is the first study of GR and MR gene expression in any avian species and the first analysis of changes in pituitary MR gene expression during embryonic development of any species.

ATP accelerates respiration of mitochondria from rat lung and suppresses their release of hydrogen peroxide.

Lung mitochondria were isolated by differential centrifugation from pentobarbital-anesthetized male rats. One to three millimolar Mg2+-ATP increased the consumption of oxygen of lung mitochondria oxidizing 10 mM succinate > fourfold (P < 0.01) whereas ATP increased the respiration of liver mitochondria by < 35%. ATP also hyperpolarized partially uncoupled lung mitochondria in the presence of the mitochondria-specific antagonist, oligomycin. However, only 20% of the ATPase activity in the lung mitochondria was blocked by oligomycin compared to a blockade of 91% for liver mitochondria. We investigated the effect of reducing the non-mitochondrial ATPase activity in the lung preparation. A purer suspension of lung mitochondria from a Percoll gradient was inhibited 95% by oligomycin. The volume fraction identified as mitochondria by electron microscopy in this suspension (73.6+/- 3.5%) did not differ from that for liver mitochondria (69.1+/- 4.9%). ATP reduced the mean area of the mitochondrial profiles in this Percoll fraction by 15% (P <0.01) and increased its state 3 respiration with succinate as substrate by 1.5-fold (P < 0.01) with no change in the state 4 respiration measured after carboxyatractyloside. Hence, ATP increased the respiratory control ratio (state 3/state 4, P <0.01). In contrast, state 3 respiration with the complex 1-selective substrates, glutamate and malate, did not change with addition of ATP. The acceleration of respiration by ATP was accompanied by decreased production of H2O2. Thus ATP-dependent processes that increase respiration appear to improve lung mitochondrial function while minimizing the release of reactive oxygen species.