Population Improvement Bias Observed in Estimates of the Impact of Antenatal Steroids to Outcomes in Preterm Birth.

OBJECTIVE: To examine the hypothesis that increasing rates and differential uptake of antenatal steroids would bias estimation of impact of antenatal steroids on neonatal death and severe (grade III-IV) intraventricular hemorrhage (IVH). STUDY DESIGN: The study population included infants born between 24 and 28 weeks of gestational age in the California Perinatal Quality Care Collaborative. Outcomes were in-hospital mortality and severe IVH. Mixed multivariable logistic regression models estimated the effect of antenatal steroid exposure, one model accounting for individual risk factors as fixed effects, and a second model incorporating a predicted probability factor estimating overall risk status for each time period. RESULTS: The study cohort included 28 252 infants. Antenatal steroid exposure increased from 80.1% in 2005 to 90.3% in 2016, severe IVH decreased from 14.5% to 9.0%, and mortality decreased from 12.8% to 9.1%. When stratified by group, 3-year observed outcomes improved significantly in infants exposed to antenatal steroids (12.5%-8.6% for IVH, 11.5%-8.8% for death) but not in those not exposed (20.7%-19.1% and 16.6%-15.5%, respectively). Women not receiving antenatal steroids had greater risk profile (such as no prenatal care) and greater predicted probability for severe IVH and mortality. Both outcomes exhibited little change (P > .05) over time for the group without antenatal steroids. In contrast, in women receiving antenatal steroids, observed and adjusted rates for both outcomes decreased (P < .0001). CONCLUSIONS: As the population's proportion of antenatal steroid use increased, the observed positive effect of antenatal steroids also increased. This apparent increase may be designated as the "population improvement bias."

Factors Associated with Successful First High-Risk Infant Clinic Visit for Very Low Birth Weight Infants in California.

OBJECTIVES: To determine rates of at least 1 high-risk infant follow-up (HRIF) visit by 12 months corrected age, and factors associated with successful first visit among very low birth weight (VLBW) infants in a statewide population-based setting. STUDY DESIGN: We used the linked California Perinatal Quality of Care Collaborative and California Perinatal Quality of Care Collaborative-California Children's Services HRIF databases. Multivariable logistic regression examined independent associations of maternal, sociodemographic, neonatal clinical, and HRIF program factors with a successful first HRIF visit among VLBW infants born in 2010-2011. RESULTS: Among 6512 VLBW children referred to HRIF, 4938 (76%) attended a first visit. Higher odds for first HRIF visit attendance was associated with older maternal age (OR, 1.48; 95% CI, 1.27-1.72; 30-39 vs 20-29 years), lower birth weight (OR, 2.11; 95% CI, 1.69-2.65; ≤750 g vs 1251-1499 g), private insurance (OR, 1.65; 95% CI, 1.19-2.31), a history of severe intracranial hemorrhage (OR, 1.61; 95% CI, 1.12-2.30), 2 parents as primary caregivers (OR, 1.18, 95% CI 1.03-1.36), and higher HRIF program volume (OR, 2.62; 95% CI, 1.88-3.66; second vs lowest quartile); and lower odds with maternal race African American or black (OR, 0.65; 95% CI, 0.54-0.78), and greater distance to HRIF program (OR, 0.69; 95% CI, 0.57-0.83). Rates varied substantially across HRIF programs, which remained after risk adjustment. CONCLUSIONS: In a population-based California VLBW cohort, maternal, sociodemographic, and home- and program-level disparities were associated with HRIF non-attendance. These findings underscore the need to identify challenges in access and resource risk factors during hospitalization in the neonatal intensive care unit, provide enhanced education about the benefits of HRIF, and create comprehensive neonatal intensive care unit-to-home transition approaches.

Birth Hospitalization Costs and Days of Care for Mothers and Neonates in California, 2009-2011.

OBJECTIVE: To provide population-based estimates of the hospital-related costs of maternal and newborn care, and how these vary by gestational age and birth weight. STUDY DESIGN: We conducted a retrospective analysis of 2009-2011 California in-hospital deliveries at nonfederal hospitals with the infant and maternal discharge data successfully (96%) linked to birth certificates. Cost-to-charge ratios were used to estimate costs from charges. Physician hospital payments were estimated by mean diagnosis related group-specific reimbursement and costs were adjusted for inflation to December 2017 values. After exclusions for incomplete or missing data, the final sample was 1 265 212. RESULTS: The mean maternal costs for all in-hospital deliveries was $8204, increasing to $13 154 for late preterm (32-36 weeks) and $22 702 for very preterm (<32 weeks) mothers. The mean cost for all newborns was $6389: $2433 for term infants, $22 102 for late preterm, $223 931 for very preterm infants, and $317 982 for extremely preterm infants (<28 weeks). Preterm infants were 8.1% of cases but incurred 60.9% of costs; for very preterm and extremely preterm infants, these shares were 1.0% and 36.5%, and 0.4% and 20.0%, respectively. Overall, mothers incurred 56% of the total costs during the delivery hospitalization. CONCLUSIONS: Both maternal and neonatal costs are skewed, with this being much more pronounced for infants. Preterm birth is much more expensive than term delivery, with the additional costs predominately incurred by the infants. The small share of infants who require extensive stays in neonatal intensive care incur a large share of neonatal costs and these costs have increased over time.

The Relationship of Nosocomial Infection Reduction to Changes in Neonatal Intensive Care Unit Rates of Bronchopulmonary Dysplasia.

OBJECTIVE: To examine whether recent reductions in rates of nosocomial infection have contributed to changes in rates of bronchopulmonary dysplasia (BPD) in a population-based cohort. STUDY DESIGN: This was a retrospective, population-based cohort study that used the California Perinatal Quality Care Collaborative database from 2006 to 2013. Eligible infants included those less than 30 weeks' gestational age and less than 1500 g who survived to 3 days of life. Primary variables of interest were rates of nosocomial infections and BPD. Adjusted rates of nosocomial infections and BPD from a baseline period (2006-2010) were compared with a later period (2011-2013). The correlation of changes in rates across periods for both variables was assessed by hospital of care. RESULTS: A total of 22 967 infants from 129 hospitals were included in the study. From the first to second time period, the incidence of nosocomial infections declined from 24.7% to 15% and BPD declined from 35% to 30%. Adjusted hospital rates of BPD and nosocomial infections were correlated positively with a calculated 8% reduction of BPD rates attributable to reductions in nosocomial infections. CONCLUSIONS: Successful interventions to reduce rates of nosocomial infections may have a positive impact on other comorbidities such as BPD. The prevention of nosocomial infections should be viewed as a significant component in avoiding long-term neonatal morbidities.

Maternal Asthma, Preterm Birth, and Risk of Bronchopulmonary Dysplasia.

OBJECTIVE: To study the relationship between maternal asthma and the development of bronchopulmonary dysplasia (BPD). STUDY DESIGN: Using a large population-based California cohort, we investigated associations between maternal asthma and preterm birth subtype, as well as maternal asthma and BPD. We used data from 2007-2010 maternal delivery discharge records of 2 009 511 pregnancies and International Classification of Diseases, Ninth Revision codes. Preterm birth was defined as <37 weeks gestational age (GA), with subgroups of <28 weeks, 28-32 weeks, and 33-37 weeks GA, as well as preterm subtype, defined as spontaneous, medically indicated, or unknown. Linkage between the 2 California-wide datasets yielded 21 944 singleton preterm infants linked to their mother's records, allowing estimation of the risk of BPD in mothers with asthma and those without asthma. RESULTS: Maternal asthma was associated with increased odds (OR, 1.42; 95% CI, 1.38-1.46) of preterm birth at <37 weeks GA, with the greatest risk for 28-32 GA (aOR, 1.60; 95% CI, 1.47-1.74). Among 21 944 preterm infants, we did not observe an elevated risk for BPD in infants born to mothers with asthma (aOR, 1.03; 95% CI, 0.9-1.2). Stratification by maternal treatment with antenatal steroids revealed increased odds of BPD in infants whose mothers had asthma but did not receive antenatal steroids (aOR, 1.54; 95% CI, 1.15-2.06), but not in infants whose mothers had asthma and were treated with antenatal steroids (aOR, 0.85; 95% CI, 0.67-1.07). CONCLUSION: Asthma in mothers who did not receive antenatal steroid treatment is associated with an increased risk of BPD in their preterm infants.

Referral of very low birth weight infants to high-risk follow-up at neonatal intensive care unit discharge varies widely across California.

OBJECTIVES: To determine rates and factors associated with referral to the California Children's Services high-risk infant follow-up (HRIF) program among very low birth weight (BW) infants in the California Perinatal Quality of Care Collaborative. STUDY DESIGN: Using multivariable logistic regression, we examined independent associations of demographic and clinical variables, neonatal intensive care unit (NICU) volume and level, and California region with HRIF referral. RESULTS: In 2010-2011, 8071 very low BW infants were discharged home; 6424 (80%) were referred to HRIF. Higher odds for HRIF referral were associated with lower BW (OR 1.9, 95% CI 1.5-2.4; ≤ 750 g vs 1251-1499 g), higher NICU volume (OR 1.6, 1.2-2.1; highest vs lowest quartile), and California Children's Services Regional level (OR 3.1, 2.3-4.3, vs intermediate); and lower odds with small for gestational age (OR 0.79, 0.68-0.92), and maternal race African American (OR 0.58, 0.47-0.71) and Hispanic (OR 0.65, 0.55-0.76) vs white. There was wide variability in referral among regions (8%-98%) and NICUs (<5%-100%), which remained after risk adjustment. CONCLUSIONS: There are considerable disparities in HRIF referral, some of which may indicate regional and individual NICU resource challenges and barriers. Understanding demographic and clinical factors associated with failure to refer present opportunities for targeted quality improvement initiatives.

Variations in definitions of mortality have little influence on neonatal intensive care unit performance ratings.

OBJECTIVE: To measure the influence of varying mortality time frames on performance rankings among regional neonatal intensive care units (NICUs) in a large state. STUDY DESIGN: We performed a cross-sectional data analysis of very low birth weight infants receiving care at 24 level 3 NICUs. We tested the effect of 4 definitions of mortality: (1) death between admission and end of birth hospitalization or up to 366 days; (2) death between 12 hours of age and the end of birth hospitalization or up to 366 days; (3) death between admission and 28 days; and (4) death between 12 hours of age and 28 days. NICUs were ranked by quantifying their deviation from risk-adjusted expected mortality and dividing them into 3 tiers: top 6, bottom 6, and in between. RESULTS: There was wide interinstitutional variation in risk-adjusted mortality for each definition (observed minus expected z-score range, -6.08 to 3.75). However, mortality-based NICU rankings and classification into performance tiers were very similar for all institutions in each of our time frames. Among all 4 definitions, NICU rank correlations were high (>0.91). Few NICUs changed relative to a neighboring tier with changes in definitions, and none changed by more than one tier. CONCLUSION: The time frame used to ascertain mortality had little effect on comparative NICU performance.

Factors associated with failure to screen newborns for retinopathy of prematurity.

OBJECTIVES: To evaluate ROP screening rates in a population-based cohort; and to identify characteristics of patients that were missed. STUDY DESIGN: We used the California Perinatal Quality Care Collaborative data from 2005-2007 for a cross-sectional study. Using eligibility criteria, screening rates were calculated for each hospital. Multivariable regression was used to assess associations between patient clinical and sociodemographic factors and the odds of missing screening. RESULTS: Overall rates of missed ROP screening decreased from 18.6% in 2005 to 12.8% in 2007. Higher gestational age (OR = 1.25 for increase of 1 week, 95% CI, 1.21-1.29), higher birth weight (OR = 1.13; 95% CI, 1.10-1.15), and singleton birth (OR = 1.2; 95% CI, 1.07-1.34) were associated with higher probability of missing screening. Level II neonatal intensive care units and neonatal intensive care units with lower volume were more likely to miss screenings. CONCLUSION: Although ROP screening rates improved over time, larger and older infants are at risk for not receiving screening. Furthermore, large variations in screening rates exist among hospitals in California. Identification of gaps in quality of care creates an opportunity to improve ROP screening rates and prevent impaired vision in this vulnerable population.

Factors influencing breast milk versus formula feeding at discharge for very low birth weight infants in California.

OBJECTIVE: To investigate incidence and factors influencing breast milk feeding at discharge for very low birth weight infants (VLBW) in a population-based cohort. STUDY DESIGN: We used data from the California Perinatal Quality Care Collaborative to calculate incidence of breast milk feeding at hospital discharge for 6790 VLBW infants born in 2005-2006. Multivariable logistic regression was used to examine which sociodemographic and medical factors were associated with breast milk feeding. The impact of removing risk adjustment for race was examined. RESULTS: At initial hospital discharge, 61.1% of VLBW infants were fed breast milk or breast milk supplemented with formula. Breast milk feeding was more common with higher birth weight and gestational age. After risk adjustment, multiple birth was associated with higher breast milk feeding. Factors associated with exclusive formula feeding were Hispanic ethnicity, African American race, and no prenatal care. Hospital risk-adjusted rates of breast milk feeding varied widely (range 19.7% to 100%) and differed when race was removed from adjustment. CONCLUSIONS: A substantial number of VLBW infants were not fed breast milk at discharge. Specific groups may benefit from targeted interventions to promote breast milk feeding. There may be benefit to reporting risk-adjusted rates both including and excluding race in adjustment when considering quality improvement initiatives.

From paradox to disparity: trends in neonatal death in very low birth weight non-Hispanic black and white infants, 1989-2004.

OBJECTIVES: To examine temporal trends in race-specific neonatal death in California to determine whether the overall decline in mortality attenuated the paradoxical survival advantage of very low birth weight (VLBW; birth weight < 1500 g) non-Hispanic black infants relative to VLBW non-Hispanic white infants. STUDY DESIGN: The data set comprised the California birth cohort file on non-Hispanic black and non-Hispanic white VLBW neonatal mortality for 1989-2004. Logistic regression methods were used to control for potentially confounding maternal characteristics. RESULTS: In 1989 and 1990, non-Hispanic black VLBW infants demonstrated a paradox of lower neonatal mortality (adjusted odds ratio [aOR] = 0.84; 95% confidence interval [CI] = 0.75-0.94). This survival advantage disappeared after 1991, however. In 2003 and 2004, the incidence of neonatal mortality increased in non-Hispanic black VLBW infants but decreased in non-Hispanic white VLBW infants, resulting in a racial disparity (aOR = 1.34; 95% CI = 1.14-1.56). CONCLUSIONS: An initial survival paradox transformed into a disparity. The magnitude of this non-Hispanic black/non-Hispanic white VLBW disparity rose to its highest levels in the last 2 years of the study period. Moreover, the steady mortality increase in VLBW non-Hispanic black VLBW infants since 2001 reversed the secular decline in neonatal mortality in this population. Our findings underscore the need to augment strategies to improve the health trajectory of gestation in non-Hispanic black women.

School outcomes of late preterm infants: special needs and challenges for infants born at 32 to 36 weeks gestation.

OBJECTIVE: Because limited long-term outcome data exist for infants born at 32 to 36 weeks gestation, we compared school outcomes between 32- to 33-week moderate preterm (MP), 34-36 week late preterm (LP) and full-term (FT) infants. STUDY DESIGN: A total of 970 preterm infants and 13 671 FT control subjects were identified from the Early Childhood Longitudinal Study-Kindergarten Cohort. Test scores, teacher evaluations, and special education enrollment from kindergarten (K) to grade 5 were compared. RESULTS: LP infants had lower reading scores than FT infants in K to first grade (P < .05). Adjusted risk for poor reading and math scores remained elevated in first grade (P < .05). Teacher evaluations of math skills from K to first grade and reading skills from K to fifth grade were worse for LP infants (P < .05). Adjusted odds for below average skills remained higher for math in K and for reading at all grades (P < .05). Special education participation was higher for LP infants at early grades (odds ratio, 1.4-2.1). MP infants had lower test and teacher evaluation scores than FT infants and twice the risk for special education at all grade levels. CONCLUSIONS: Persistent teacher concerns through grade 5 and greater special education needs among MP and LP infants suggest a need to start follow-up, anticipatory guidance, and interventions for infants born at 32 to 36 weeks gestation.

Promoting antenatal steroid use for fetal maturation: results from the California Perinatal Quality Care Collaborative.

OBJECTIVE: The California Perinatal Quality Care Collaborative (CPQCC) was formed to seek perinatal care improvements by creating a confidential multi-institutional database to identify topics for quality improvement (QI). We aimed to evaluate this approach by assessing antenatal steroid administration before preterm (24 to 33 weeks of gestation) delivery. We hypothesized that mean performance would improve and the number of centers performing below the lowest quartile of the baseline year would decrease. STUDY DESIGN: In 1998, a statewide QI cycle targeting antenatal steroid use was announced, calling for the evaluation of the 1998 baseline data, dissemination of recommended interventions using member-developed educational materials, and presentations to California neonatologists in 1999-2000. Postintervention data were assessed for the year 2001 and publicly released in 2003. A total of 25 centers voluntarily participated in the intervention. RESULTS: Antenatal steroid administration rate increased from 76% of 1524 infants in 1998 to 86% of 1475 infants in 2001 (P < .001). In 2001, 23 of 25 hospitals exceeded the 1998 lower-quartile cutoff point of 69.3%. CONCLUSIONS: Regional collaborations represent an effective strategy for improving the quality of perinatal care.

Sociocultural factors that affect pregnancy outcomes in two dissimilar immigrant groups in the United States.

OBJECTIVE: To compare perinatal risks and outcomes in foreign- and U.S.-born Asian-Indian and Mexican women. STUDY DESIGN: We evaluated 6.4 million U.S. vital records for births during 1995-2000 to white, foreign- and U.S.-born Asian-Indian and Mexican women. Risks and outcomes were compared by use of chi2 and logistic regression. RESULTS: With the exception of increased teen pregnancy and tobacco use, the favorable sociodemographic profile and increased rate of adverse outcomes seen in foreign-born Asian Indians persisted in their U.S.-born counterparts. In contrast, foreign-born Mexicans had an adverse sociodemographic profile but a low incidence of low birth weight (LBW), whereas U.S.-born Mexicans had an improved sociodemographic profile and increased LBW, prematurity and neonatal death. CONCLUSIONS: Perinatal outcomes deteriorate in U.S.-born Mexican women. In contrast, the paradoxically increased incidence of LBW persists in U.S.-born Asian-Indian women. Further research is needed to identify the social and biologic determinants of perinatal outcome.

Perinatal outcomes in two dissimilar immigrant populations in the United States: a dual epidemiologic paradox.

OBJECTIVE: Previous studies have addressed perinatal outcomes in Hispanic, black, and white non-Hispanic women and demonstrated that although foreign-born Mexican American women have many demographic and socioeconomic risk factors, their rates of low birth weight (LBW) infants and infant mortality are similar to those of white women. This phenomenon has been termed an epidemiologic paradox. There have been no population-based studies on women of Asian Indian origin, a relatively new, highly educated, and affluent immigrant group that has been reported to have a high rate of LBW infants. The objective of this study was to define the sociodemographic risk profile and perinatal outcomes in women of Asian Indian birth and to compare these outcomes to foreign-born Mexican American and US-born black and white women. METHODS: The vital records for self-reported foreign-born Asian Indian (0.8%) and Mexican women (26.7%) and US-born black (31.2%) and white women (31.2%) were extracted from California's 1 622 324 births, 1995-1997. Sociodemographic risk profiles; the percentage of LBW, very low birth weight (VLBW), prematurity, and intrauterine growth retardation (less than third percentile); and percentage of fetal, neonatal, and postneonatal death rates were compared. Logistic models were used to estimate the importance of selected sociodemographic and medical factors to the prediction of LBW infants in each racial/ethnic group. RESULTS: When compared with whites, US-born blacks and foreign-born Mexican mothers were at increased risk for adverse perinatal outcomes on the basis of higher levels of inadequate prenatal care, teen births, Medi-Cal paid delivery, and lower levels of maternal and paternal education. Foreign-born Asian Indian mothers had good prenatal care, were rarely teenagers, had dramatically higher levels of both maternal and paternal education, and had the lowest percentage of deliveries paid for by Medi-Cal. Black infants had the highest rates of prematurity; intrauterine growth retardation; LBW; and fetal, neonatal, and postneonatal mortality. Paradoxically, despite their high-risk profile, Mexicans did not have elevated levels of LBW or neonatal mortality. Conversely, Asian Indian infants, although seemingly of low sociodemographic risk, had high levels of LBW, growth retardation, and fetal mortality. Logistic regression analysis of independent risk factors for giving birth to an LBW infant showed higher maternal education, early access to prenatal care, and having private insurance to be protective in white non-Hispanic and black but not in Asian Indian and Mexican-born women. CONCLUSIONS: Despite their high socioeconomic status and early entry into care, foreign-born Asian Indian women have a paradoxically higher incidence of LBW infants and fetal deaths when compared with US-born whites. Factors that protect from giving birth to an LBW infant in white women were not protective among Asian Indian women. Current knowledge regarding factors that confer a perinatal advantage or disadvantage is unable to explain this new epidemiologic paradox. These findings highlight the need for additional research into both epidemiologic and biological risk factors that determine perinatal outcomes.