Do trials reduce uncertainty? Assessing impact through cumulative meta-analysis of neonatal RCTs.

OBJECTIVE: To assess the impact of the latest randomized controlled trial (RCT) to each systematic review (SR) in Cochrane Neonatal Reviews. STUDY DESIGN: We selected meta-analyses reporting the typical point estimate of the risk ratio for the primary outcome of the latest study (n=130), mortality (n=128) and the mean difference for the primary outcome (n=44). We employed cumulative meta-analysis to determine the typical estimate after each trial was added, and then performed multivariable logistic regression to determine factors predictive of study impact. RESULTS: For the stated primary outcome, 18% of latest RCTs failed to narrow the confidence interval (CI), and 55% failed to decrease the CI by ⩾20%. Only 8% changed the typical estimate directionality, and 11% caused a change to or from significance. Latest RCTs did not change the typical estimate in 18% of cases, and only 41% changed the typical estimate by at least 10%. The ability to narrow the CI by >20% was negatively associated with the number of previously published RCTs (odds ratio 0.707). Similar results were found in analysis of typical estimates for the outcomes of mortality and mean difference. CONCLUSION: Across a broad range of clinical questions, the latest RCT failed to substantially narrow the CI of the typical estimate, to move the effect estimate or to change its statistical significance in a majority of cases. Investigators and grant peer review committees should consider prioritizing less-studied topics or requiring formal consideration of optimal information size based on extant evidence in power calculations.

Network analysis: a novel method for mapping neonatal acute transport patterns in California.

OBJECTIVE: The objectives of this study are to use network analysis to describe the pattern of neonatal transfers in California, to compare empirical sub-networks with established referral regions and to determine factors associated with transport outside the originating sub-network. STUDY DESIGN: This cross-sectional database study included 6546 infants <28 days old transported within California in 2012. After generating a graph representing acute transfers between hospitals (n=6696), we used community detection techniques to identify more tightly connected sub-networks. These empirically derived sub-networks were compared with state-defined regional referral networks. Reasons for transfer between empirical sub-networks were assessed using logistic regression. RESULTS: Empirical sub-networks showed significant overlap with regulatory regions (P<0.001). Transfer outside the empirical sub-network was associated with major congenital anomalies (P<0.001), need for surgery (P=0.01) and insurance as the reason for transfer (P<0.001). CONCLUSION: Network analysis accurately reflected empirical neonatal transfer patterns, potentially facilitating quantitative, rather than qualitative, analysis of regionalized health care delivery systems.

Prospective economic evaluation alongside the non-invasive ventilation trial.

OBJECTIVE: To determine the cost-effectiveness of nasal continuous positive pressure (nCPAP) compared with nasal intermittent positive pressure ventilation (NIPPV) in the context of the reported randomized clinical trial. STUDY DESIGN: Using patient-level data from the clinical trial, we undertook a prospectively planned economic evaluation. We measured costs, from a third-party payer perspective in all patients, and from a societal perspective in a subgroup with a time horizon through the earlier of discharge, death or 44 weeks post-menstrual age. RESULTS: From the third-party payer perspective, the mean cost of hospitalization per infant was statistically similar, $143 745 in the NIPPV group compared to $140 403 in the nCPAP group. Cost-effectiveness evaluation revealed a 61% probability that NIPPV is more expensive and less effective than nCPAP. Similar results were found in subgroup analysis from a societal perspective. CONCLUSION: In addition to being clinically equivalent, economic evaluation confirms that NIPPV, as employed in this trial, is also not economically favorable.

The impact of maternal characteristics on the moderately premature infant: an antenatal maternal transport clinical prediction rule.

OBJECTIVE: Moderately premature infants, defined here as those born between 30°/7 and 346/7 weeks gestation, comprise 3.9% of all births in the United States and 32% of all preterm births. Although long-term outcomes for these infants are better than for less mature infants, morbidity and mortality are still substantially increased in comparison with infants born at term. There is an added survival benefit resulting from birth at a tertiary neonatal care center, and although many of these infants require tertiary level care, delivery at lower level hospitals and subsequent neonatal transfer are still common. Our primary aim was to determine the impact of maternal characteristics and antenatal medical management on the early neonatal course of the moderately premature infant. The secondary aim was to create a clinical prediction rule to determine which infants require intubation and mechanical ventilation in the first 24 h of life. Such a prediction rule could inform the decision to transfer maternal-fetal patients before delivery to a facility with a Level III neonatal intensive care unit (NICU), where optimal care could be provided without the requirement for a neonatal transfer. STUDY DESIGN: Data for this analysis came from the cohort of infants in the Moderately Premature Infant Project (MPIP) database, a multicenter cohort study of 850 infants born at gestational age 30°/7 and 346/7 weeks, with birth weight between 591 to 3540 g. [corrected], who were discharged to home alive. We built a logistic regression model to identify maternal characteristics associated with need for tertiary care, as measured by administration of surfactant. Using statistically significant covariates from this model, we then created a numerical decision rule to predict need for tertiary care. RESULT: In multivariate modeling, four factors were associated with reduction in the need for tertiary care, including non-White race (odds ratio (OR)=0.5, (0.3, 0.7)), older gestational age, female gender (OR=0.6 (0.4, 0.8)) and use of antenatal corticosteroids (OR=0.5, (0.3, 0.8)). The clinical prediction rule to discriminate between infants who received surfactant, versus those who did not, had an area under the curve of 0.77 (0.73, 0.8). CONCLUSION: Four antenatal risk factors are associated with a requirement for Level III NICU care as defined by the need for surfactant administration. Future analyses will examine a broader spectrum of antenatal characteristics and revalidate the prediction rule in an independent cohort.

Formal selection of measures for a composite index of NICU quality of care: Baby-MONITOR.

OBJECTIVE: To systematically rate measures of care quality for very low birth weight infants for inclusion into Baby-MONITOR, a composite indicator of quality. STUDY DESIGN: Modified Delphi expert panelist process including electronic surveys and telephone conferences. Panelists considered 28 standard neonatal intensive care unit (NICU) quality measures and rated each on a 9-point scale taking into account pre-defined measure characteristics. In addition, panelists grouped measures into six domains of quality. We selected measures by testing for rater agreement using an accepted method. RESULT: Of 28 measures considered, 13 had median ratings in the high range (7 to 9). Of these, 9 met the criteria for inclusion in the composite: antenatal steroids (median (interquartile range)) 9(0), timely retinopathy of prematurity exam 9(0), late onset sepsis 9(1), hypothermia on admission 8(1), pneumothorax 8(2), growth velocity 8(2), oxygen at 36 weeks postmenstrual age 7(2), any human milk feeding at discharge 7(2) and in-hospital mortality 7(2). Among the measures selected for the composite, the domains of quality most frequently represented included effectiveness (40%) and safety (30%). CONCLUSION: A panel of experts selected 9 of 28 routinely reported quality measures for inclusion in a composite indicator. Panelists also set an agenda for future research to close knowledge gaps for quality measures not selected for the Baby-MONITOR.

Are families prepared for discharge from the NICU?

OBJECTIVE: (1) Quantify and compare the family's and the nurse's perception regarding the family's discharge preparedness. (2) Determine which elements contribute to a family's discharge preparedness. STUDY DESIGN: We studied the families of all the infants discharged from a neonatal intensive care unit after a minimum of a 2-week admission. The families rated their overall discharge preparedness with a 9-point Likert scale on the day of discharge. Independently, the discharging nurse evaluated the family's discharge preparedness. Families were considered discharge 'prepared' if they rated themselves and the nurse rated their technical and emotional preparedness as >or=7 on the Likert scale. RESULT: We had 867 (58%) family-nurse pairs who completed the survey. Most families (87%) were prepared for discharge as assessed by the concordant questionnaire (Likert scores of >or=7 by the parent and the nurse). In multivariate analysis, confidence in their child's health and maturity (odds ratios, OR=2.5 95% confidence interval, CI (1.2, 5.3)), their readiness for their infants to come home (OR=2.9 95% CI (1.0, 8.3)), and selecting a pediatrician (OR=4.2 95% CI (1.6, 11.0)) were statistically significant. CONCLUSION: Assistance with pediatrician selection and home preparation may improve the percentage of families prepared for discharge.

Economic evaluation of recombinant human copper zinc superoxide dismutase administered at birth to premature infants.

OBJECTIVE: To determine the cost-effectiveness of recombinant human superoxide dismutase (rhSOD) in the prevention of chronic respiratory morbidity, defined as use of respiratory medications, in preterm infants. STUDY DESIGN: This retrospective economic evaluation was undertaken using data from a previously published randomized controlled trial of the use of rhSOD in neonates of birthweight 600 to 1200 g. This ancillary study measured all relevant direct medical costs from birth to 1 year corrected age using resource data collected for infants from the clinical trial. Unit costs were derived from secondary datasets in similar populations, stratified by level of care or diagnosis. All costs were expressed in 2003 US dollars. RESULT: rhSOD was associated with a highly favorable incremental cost of only $378 per chronic respiratory morbidity averted at 1 year corrected age. There was a 95% probability that the therapy would be considered cost-effective if a decision maker was willing to pay $7000 to avert one infant with long-term significant respiratory illness, and a 52% probability that it would actually reduce costs while improving outcomes. These results were more pronounced among infants <27 weeks gestational age at birth. CONCLUSION: Based on resource data from a single randomized trial, this retrospective analysis supports the potential economic desirability of rhSOD treatment in this population.

Unstudied infants: outcomes of moderately premature infants in the neonatal intensive care unit.

BACKGROUND: Newborns of 30-34 weeks gestation comprise 3.9% of all live births in the United States and 32% of all premature infants. They have been studied much less than very low birthweight infants. OBJECTIVE: To measure in-hospital outcomes and readmission within three months of discharge of moderately premature infants. DESIGN: Prospective cohort study including retrospective chart review and telephone interviews after discharge. SETTING: Ten birth hospitals in California and Massachusetts. PATIENTS: Surviving moderately premature infants born between October 2001 and February 2003. MAIN OUTCOME MEASURES: (a) Occurrence of assisted ventilation during the hospital stay after birth; (b) adverse in-hospital outcomes-for example, necrotising enterocolitis; (c) readmission within three months of discharge. RESULTS: With the use of prospective cluster sampling, 850 eligible infants and their families were identified, randomly selected, and enrolled. A total of 677 families completed a telephone interview three months after hospital discharge. During the birth stay, these babies experienced substantial morbidity: 45.7% experienced assisted ventilation, and 3.2% still required supplemental oxygen at 36 weeks. Readmission within three months occurred in 11.2% of the cohort and was higher among male infants and those with chronic lung disease. CONCLUSIONS: Moderately premature infants experience significant morbidity, as evidenced by high rates of assisted ventilation, use of oxygen at 36 weeks, and readmission. Such morbidity deserves more research.

Moderately premature infants at Kaiser Permanente Medical Care Program in California are discharged home earlier than their peers in Massachusetts and the United Kingdom.

OBJECTIVE: To compare gestational age at discharge between infants born at 30-34(+6) weeks gestational age who were admitted to neonatal intensive care units (NICUs) in California, Massachusetts, and the United Kingdom. DESIGN: Prospective observational cohort study. SETTING: Fifty four United Kingdom, five California, and five Massachusetts NICUs. SUBJECTS: A total of 4359 infants who survived to discharge home after admission to an NICU. MAIN OUTCOME MEASURES: Gestational age at discharge home. RESULTS: The mean (SD) postmenstrual age at discharge of the infants in California, Massachusetts, and the United Kingdom were 35.9 (1.3), 36.3 (1.3), and 36.3 (1.9) weeks respectively (p = 0.001). Compared with the United Kingdom, adjusted discharge of infants occurred 3.9 (95% confidence interval (CI) 1.4 to 6.5) days earlier in California, and 0.9 (95% CI -1.2 to 3.0) days earlier in Massachusetts. CONCLUSIONS: Infants of 30-34(+6) weeks gestation at birth admitted and cared for in hospitals in California have a shorter length of stay than those in the United Kingdom. Certain characteristics of the integrated healthcare approach pursued by the health maintenance organisation of the NICUs in California may foster earlier discharge. The California system may provide opportunities for identifying practices for reducing the length of stay of moderately premature infants.

Characterising doctor-parent communication in counselling for impending preterm delivery.

OBJECTIVE: To examine the counselling of women admitted to hospital in preterm labour. Such women and their partners are often asked to participate in difficult decisions including mode of delivery, fetal monitoring, and resuscitation. STUDY DESIGN: Questionnaire based descriptive study. STUDY SETTING: A tertiary level perinatal referral centre. PATIENTS: Forty-nine women in preterm labour at 22-30 weeks gestation, admitted in two separate periods between March 1997 and May 1999. INTERVENTION AND OUTCOME MEASURE: Within 24 hours of counselling, parents were asked to complete a questionnaire assessing recall of the management plan, desire for involvement in decision making, anxiety, and feelings of control over their health. A parallel questionnaire was completed by the clinicians. RESULTS: Parents and clinicians on recall agreed well about obstetric issues but poorly about neonatal issues. Overall 27% of parents felt: "I would prefer to have the doctors advise me, rather than asking me to decide". In 79% of cases, clinicians believed parents preferred advice rather than to make decisions, but in 45% of these, they misidentified those who wished to make their decisions. Anxiety levels for one third of the mothers were high, and associated with poorer concordance of recall between parents and clinicians. CONCLUSIONS: Serious deficiencies exist in parent-clinician encounters during extremely preterm labour. Concordance between parents and clinicians is poor and anxiety very high. A quarter of parents appear to prefer to relinquish decision making autonomy, but clinicians cannot correctly identify this subgroup. Standardised counselling in the perinatal period, using formal decision aids, should be investigated.