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Perinatal Regionalization for Very Low-Birth-Weight and Very Preterm Infants: A Meta-analysis

Sarah Marie Lasswell, MPH; Wanda Denise Barfield, MD, MPH; Roger William Rochat, MD; Lillian Blackmon, MD
JAMA. 2010;304(9):992-1000. doi:10.1001/jama.2010.1226.
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Context For more than 30 years, guidelines for perinatal regionalization have recommended that very low-birth-weight (VLBW) infants be born at highly specialized hospitals, most commonly designated as level III hospitals. Despite these recommendations, some regions continue to have large percentages of VLBW infants born in lower-level hospitals.

Objective To evaluate published data on associations between hospital level at birth and neonatal or predischarge mortality for VLBW and very preterm (VPT) infants.

Data Sources Systematic search of published literature (1976–May 2010) in MEDLINE, CINAHL, EMBASE, and PubMed databases and manual searches of reference lists.

Study Selection and Data Extraction Forty-one publications met a priori inclusion criteria (randomized controlled trial, cohort, and case-control studies measuring neonatal or predischarge mortality among live-born infants ≤1500 g or ≤32 weeks' gestation delivered at a level III vs lower-level facility). Paired reviewers independently assessed publications for inclusion and extracted data using standardized forms. Discrepancies were decided by a third reviewer. Publications were reviewed for quality by 3 authors based on 2 content areas: adjustment for confounding and description of hospital levels. We calculated weighted, combined odds ratios (ORs) using a random-effects model and comparative unadjusted pooled mortality rates.

Data Synthesis We observed increased odds of death for VLBW infants (38% vs 23%; adjusted OR, 1.62; 95% confidence interval [CI], 1.44-1.83) and VPT infants (15% vs 17%; adjusted OR, 1.55; 95% CI, 1.21-1.98) born outside of level III hospitals. Consistent results were obtained when restricted to higher-quality evidence (mortality in VLBW infants, 36% vs 21%; adjusted OR, 1.60; 95% CI, 1.33-1.92 and in VPT infants, 7% vs 12%; adjusted OR, 1.42; 95% CI, 1.06-1.88) and infants weighing less than 1000 g (59% vs 32%; adjusted OR, 1.80; 95% CI, 1.31-2.46). No significant differences were found through subgroup analysis of study characteristics. Meta-regression by year of publication did not reveal a change over time (slope, 0.00; P = .87).

Conclusion For VLBW and VPT infants, birth outside of a level III hospital is significantly associated with increased likelihood of neonatal or predischarge death.

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Figure 1. Selection of Publications
Graphic Jump Location

aBecause of the broad search strategy, many records on neonatal care and general hospital organization were returned but were unrelated to this review.
bFor example, data graphed but point estimates not given, rates given without group N.
cThere were 3 sets of studies (7 studies total1824) that based data on the same or partially overlapping infant populations. One study was included from each set (3 studies18,22,24), leaving 4 excluded.19,2123

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Figure 2. Meta-regression of Association Between Hospital Level of Birth and Neonatal/Predischarge Mortality by Year of Publication
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Each circle in the plot represents a study, and the circumference of each circle is proportional to study population size. These data represent change in published evidence over time, not actual outcome measures at a given time. Because each study includes its own unique range of birth dates (eTable), calculation of change by infant birth date was not possible.

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Figure 3. Meta-analysis Results of Adequate- and High-Quality Publications on Very Low-Birth-Weight (VLBW) Infants, Stratified by Level of Adjustment for Confounding
Graphic Jump Location

Case mix indicates adjustment for demographic and/or socioeconomic status variables; extensive indicates adjustment for case mix plus maternal/perinatal risk factors and infant illness severity. CI indicates confidence interval. Size of data markers indicates size of study population.
aIncluded data are for urban populations and combine reported black/white race strata and birth weight strata (750-1000 g and 1001-1500 g).
bIncluded data combine reported birth date interval strata (1980-1984, 1985-1989, and 1990-1994) and birth weight strata (500-1000 g and 1001-1500 g).
cRaw death counts are not reported in Cifuentes et al13 and Kamath et al16 and are not stratified by hospital level in Howell et al.15 These studies are not included in combined death/birth counts.

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Figure 4. Meta-analysis Results of Adequate- and High-Quality Publications on Extremely Low-Birth-Weight Infants
Graphic Jump Location

CI indicates confidence interval. Size of data markers indicates size of study population.
aIncluded data are for urban populations and combine reported black/white race strata.
bIncluded data combine reported birth weight strata (500-749 g and 750-1000 g).
cIncluded data combine reported birth date interval strata (1980-1984, 1985-1989, and 1990-1994).
dThe study by Kamath et al16 does not report raw death count data and is not included in combined death/birth counts.

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Figure 5. Meta-analysis Results of Adequate- and High-Quality Publications on Very Preterm Infants
Graphic Jump Location

CI indicates confidence interval. Size of data markers indicates size of study population. Inborn infants are those born in a level III hospital; outborn infants are those born in a lower-level hospital then transferred to a level III hospital.
aIncluded data combine reported gestational age strata (<26 weeks, 27-29 weeks, and 30-31 weeks).

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