Cohort selection and the estimation of racial disparity in mortality of extremely preterm neonates.

BACKGROUND: Racial disparities in preterm neonatal mortality are long-standing. We aimed to assess how cohort selection influences mortality rates and racial disparity estimates. METHODS: With 2014-2018 California data, we compared neonatal mortality rates among Black and non-Hispanic White very low birth weight (VLBW, <1500 g) or very preterm infants (22-29 weeks gestational age). Relative risks were estimated by different cohort selection criteria. Blinder-Oaxaca decomposition quantified factors contributing to mortality differential. RESULTS: Depending upon standard selection criteria, mortality ranged from 6.2% (VLBW infants excluding first 12-h deaths) to 16.0% (22-29 weeks' gestation including all deaths). Black observed neonatal mortality was higher than White infants only for delivery room deaths in VLBW infants (5.6 vs 4.2%). With risk adjustment accounting for higher rate of low gestational age, low Apgar score and other factors, White infant mortality increased from 15.9 to 16.6%, while Black infant mortality decreased from 16.7 to 13.7% in the 22-29 weeks cohort. Across varying cohort selection, risk adjusted survival advantage among Black infants ranged from 0.70 (CL 0.61-0.80) to 0.84 (CL 0.76-0.93). CONCLUSIONS: Standard cohort selection can give markedly different mortality estimates. It is necessary to reduce prematurity rates and perinatal morbidity to improve outcomes for Black infants. IMPACT: In this population-based observational cohort study that encompassed very low birth weight infant hospitalizations in California, varying standard methods of cohort selection resulted in neonatal mortality ranges from 6.2 to 16.0%. Across all cohorts, the only significant observed Black-White disparity was for delivery room deaths in Very Low Birth Weight births (5.6 vs 4.2%). Across all cohorts, we found a 16-30% survival advantage for Black infants. Cohort selection can result in an almost three-fold difference in estimated mortality but did not have a meaningful impact on observed or adjusted differences in neonatal mortality outcomes by race and ethnicity.

Validation of ICD-10-CM Diagnosis Codes for Gestational Age at Birth.

BACKGROUND: The International Classification of Diseases , 10th Revision, Clinical Modification (ICD-10-CM) introduced diagnosis codes for week of gestation. Our objective was to assess the validity of these codes among live births, which could have major utility in perinatal research and quality improvement. METHODS: We used linked birth certificate and patient discharge data from births in California during 2016-2019 (N = 1,843,992). We identified gestational age using Z3A.xx ICD-10-CM diagnosis codes in birthing patient discharge data and compared it with the gold standard of obstetric estimate, as recorded on the birth certificate. We further assessed sensitivity and specificity of gestational age categories (≥37 weeks, <37 weeks, <32 weeks, <28 weeks), given these categories are frequently of interest, and evaluated differences in validity of preterm birth (<37 weeks' gestation) by patient characteristics. RESULTS: One-million seven-hundred seventy-thousand one-hundred three patients had a gestational age recorded in patient discharge and birth certificate data. When comparing gestational age in patient discharge data with birth certificate data, the concordance correlation coefficient was 0.96 (95% confidence interval [CI] = 0.96, 0.96) and the mean difference between the two measurements was 0.047 weeks (95% CI = 0.046, 0.047 weeks). Ninety-five percent of the differences between the two measurements were between -1.00 week and +1.09 weeks. Sensitivity and specificity were 0.94 to 1.00 for all gestational age categories and were 0.94 to 1.00 for preterm birth across sociodemographic groups. CONCLUSIONS: We found week-specific gestational age at delivery ICD-10-CM diagnosis codes in patient discharge data to have high validity when compared with the best obstetric estimate on the birth certificate.

Measuring Variation in Interpregnancy Interval: Identifying Hotspots for Improvement Initiatives.

OBJECTIVE: The study aimed to determine if single year birth certificate data can be used to identify regional and hospital variation in rates of short interpregnancy interval (IPI < 6 months). STUDY DESIGN: IPI was estimated for multiparous women ages 15 to 44 years with singleton live births between 2015 and 2016. Perinatal outcomes, place of birth, maternal race, and data for IPI calculations were obtained by using birth certificates. IPI frequencies are presented as observed rates. RESULTS: The cohort included 562,039 multiparous women. Short IPI rates were similar to those obtained with analyses by using linked longitudinal data and confirmed the association with preterm birth. Short IPI rates varied by race and Hispanic nativity. There was substantial hospital (0.8-9%) and regional (2.9-6.2%) variation in short IPI rates. CONCLUSION: IPI rates can be reliably obtained from current year birth certificate data. This can be a useful tool for quality improvement projects targeting interventions and rapidly assessing their progress to promote optimal birth spacing. KEY POINTS: · Near-real time regional and hospital IPI rates can be reliably obtained from current year birth certificate data.. · Substantial variations in rates of short IPI exist between hospital and perinatal regions.. · IPI rates from individual birth certificates can be a tool to target and assess interventions..

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."

Reduction in racial disparities in severe maternal morbidity from hemorrhage in a large-scale quality improvement collaborative.

BACKGROUND: Eliminating persistent racial/ethnic disparities in maternal mortality and morbidity is a public health priority. National strategies to improve maternal outcomes are increasingly focused on quality improvement collaboratives. However, the effectiveness of quality collaboratives for reducing racial disparities in maternity care is understudied. OBJECTIVE: To evaluate the impact of a hemorrhage quality-improvement collaborative on racial disparities in severe maternal morbidity from hemorrhage. STUDY DESIGN: We conducted a cross-sectional study from 2011 to 2016 among 99 hospitals that participated in a hemorrhage quality improvement collaborative in California. The focus of the quality collaborative was to implement the national maternal hemorrhage safety bundle consisting of 17 evidence-based recommendations for practice and care processes known to improve outcomes. This analysis included 54,311 women from the baseline period (January 2011 through December 2014) and 19,165 women from the postintervention period (October 2015 through December 2016) with a diagnosis of obstetric hemorrhage during delivery hospitalization. We examined whether racial/ethnic-specific severe maternal morbidity rates in these women with obstetric hemorrhage were reduced from the baseline to the postintervention period. In addition, we conducted Poisson Generalized Estimating Equation models to estimate relative risks and 95% confidence intervals for severe maternal morbidity comparing each racial/ethnic group with white. RESULTS: During the baseline period, the rate of severe maternal morbidity among women with hemorrhage was 22.1% (12,002/54,311) with the greatest rate observed among black women (28.6%, 973/3404), and the lowest among white women (19.8%, 3124/15,775). The overall rate fell to 18.5% (3553/19,165) in the postintervention period. Both black and white mothers benefited from the intervention, but the benefit among black women exceeded that of white women (9.0% vs 2.1% absolute rate reduction). The baseline risk of severe maternal morbidity was 1.34 times greater among black mothers compared with white mothers (relative risk, 1.34; 95% confidence interval, 1.27-1.42), and it was reduced to 1.22 (1.05-1.40) in the postintervention period. Sociodemographic and clinical factors explained a part of the black-white differences. After controlling for these factors, the black-white relative risk was 1.22 (95% confidence interval, 1.15-1.30) at baseline and narrowed to 1.07 (1.92-1.24) in the postintervention period. Results were similar when excluding severe maternal morbidity cases with transfusion alone. After accounting for maternal risk factors, the black-white relative risk for severe maternal morbidity excluding transfusion alone was reduced from a baseline of 1.33 (95% confidence interval, 1.16-1.52) to 0.99 (0.76-1.29) in the postintervention period. The most important clinical risk factor for disparate black rates for both severe maternal morbidity and severe maternal morbidity excluding transfusion alone was cesarean delivery, potentially providing another opportunity for quality improvement. CONCLUSION: A large-scale quality improvement collaborative reduced rates of severe maternal morbidity due to hemorrhage in all races and reduced the performance gap between black and white women. Improving access to highly effective treatments has the potential to decrease disparities for care-sensitive acute hospital-focused morbidities.

Composite neonatal morbidity indicators using hospital discharge data: A systematic review.

BACKGROUND: Neonatal morbidity is associated with lifelong impairments, but the absence of a consensual definition and the need for large data sets limit research. OBJECTIVES: To inform initiatives to define standard outcomes for research, we reviewed composite neonatal morbidity indicators derived from routine hospital discharge data. DATA SOURCES: PubMed (updated on October 12, 2018). The search algorithm was based on three components: "morbidity," "neonatal," and "hospital discharge data." STUDY SELECTION AND DATA EXTRACTION: Studies investigating neonatal morbidity using a composite indicator based on hospital discharge data were included. Indicators defined for specific conditions (eg congenital anomalies, maternal addictions) were excluded. The target population, objectives, component morbidities, diagnosis and procedure codes, validation methods, and prevalence of morbidity were extracted. SYNTHESIS: For each study, we assessed construct validity by describing the methods used to select the indicator components and evaluated whether the authors assessed internal and external validity. We also calculated confidence intervals for the prevalence of the morbidity composite. RESULTS: Seventeen studies fulfilled inclusion criteria. Indicators targeted all (n = 4), low-/moderate-risk (n = 9), and very preterm (VPT, n = 4) infants. Components were similar for VPT infants, but domains and diagnosis codes within domains varied widely for all and low-/moderate-risk infants. Component selection was described for 8/17 indicators and some form of validation reported for 12/17. Neonatal morbidity prevalence ranged from 4.6% to 9.0% of all infants, 0.4% to 8.0% of low-/moderate-risk infants, and 17.8% to 61.0% of VPT infants. CONCLUSIONS: Multiple neonatal morbidity indicators based on hospital discharge data have been used for research, but their heterogeneity limits comparisons between studies. Standard neonatal outcome measures are needed for benchmarking and synthesis of research results.

Cytomegalovirus Infection among Infants in Neonatal Intensive Care Units, California, 2005 to 2016.

AIM: The main purpose of this article is to assess trends in cytomegalovirus (CMV) infection reported among infants in California neonatal intensive care units (NICUs) during 2005 to 2016. STUDY DESIGN: The California Perinatal Quality Care Collaborative collects data on all very low birth weight (VLBW, birth weight ≤ 1,500 g) and acutely ill infants > 1,500 g, representing 92% of NICUs in California. We compared clinical characteristics and length of hospital stay among infants with and without reported CMV infection (CMV-positive viral culture or polymerase chain reaction). RESULTS: During 2005 to 2016, CMV infection was reported in 174 VLBW infants and 145 infants > 1,500 g, or 2.7 (range: 1.5-4.7) and 1.2 (range: 0.8-1.7) per 1,000 infants, respectively (no significant annual trend). Among infants > 1,500 g, 12 (8%) versus 4,928 (4%) of those reported with versus without CMV infection died (p < 0.05). The median hospital stay was significantly longer among infants reported with versus without CMV infection for both VLBW infants (98 vs. 46 days) and infants > 1,500 g (61 vs. 14 days) (p < 0.001). CONCLUSION: Reports of CMV infection remained stable over a 12-year period. Although we were not able to assess whether infection was congenital or postnatal, CMV infection among infants > 1,500 g was associated with increased mortality.

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.

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.

Improving Maternal Safety at Scale with the Mentor Model of Collaborative Improvement.

BACKGROUND: Obstetric safety bundles, consisting of action steps shown to improve outcomes, have been developed to address the most common and preventable causes of maternal morbidity and mortality. Implementing these best practices across all birthing facilities remains an important and challenging clinical and public health priority. METHODS: The California Maternal Quality Care Collaborative (CMQCC) developed an innovative external mentor model for large-scale collaborative improvement in which participating organizations were subdivided into small teams of six to eight hospitals, led by a paired dyad of physician and nurse leaders. The mentor model preserves the active sharing that enhances improvement across a large group of facilities working on the same project while enabling individualized attention to teams. The mentor model was tested by implementing the obstetric hemorrhage safety bundle (which consists of 17 key practices in four domains) in multiple California hospitals. RESULTS: A total of 126 hospitals were engaged to simultaneously implement the safety bundle. The adoption rates for the recommended practices in the four action domains were (1) Readiness, 78.9%; (2) Recognition and Prevention, 76.5%; (3) Response, 63.1%; and (4) Reporting and Systems Learning, 58.7%. Mentors (31/40) and participating teams (48 responses from 39/126 hospitals) provided feedback in an exit survey. Among the respondents, 64.5% of mentors and 72.9% of participants agreed that compared to a traditional collaborative structure, the mentor model was better suited for quality improvement at scale. CONCLUSION: The mentor model was successful in providing individualized support to teams and enabled implementation of the hemorrhage safety bundle across a diverse group of 126 hospitals.

Programmatic and Administrative Barriers to High-Risk Infant Follow-Up Care.

OBJECTIVE: This article characterizes programmatic features of a population-based network of high-risk infant follow-up programs and identifies potential challenges associated with attendance from the providers' perspective. STUDY DESIGN: A web-based survey of high-risk infant follow-up program directors, coordinators, and providers of a statewide high-risk infant follow-up system. Frequencies and percentages were used to describe the survey responses. RESULTS: Of the 68 high-risk infant follow-up programs in California, 56 (82%) responded to the survey. The first visit no-show rate between 10 and 30% was estimated by 44% of programs with higher no-show rates for subsequent visits. Common strategies to remind families of appointments were phone calls and mailings. Most programs (54%) did not have a strategy to help families who lived distant to the high-risk infant follow-up clinic. CONCLUSION: High-risk infant follow-up programs may lack resources and effective strategies to enhance follow-up, particularly for those living at a distance.

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.

Reduction of severe maternal morbidity from hemorrhage using a state perinatal quality collaborative.

BACKGROUND: Obstetric hemorrhage is the leading cause of severe maternal morbidity and of preventable maternal mortality in the United States. The California Maternal Quality Care Collaborative developed a comprehensive quality improvement tool kit for hemorrhage based on the national patient safety bundle for obstetric hemorrhage and noted promising results in pilot implementation projects. OBJECTIVE: We sought to determine whether these safety tools can be scaled up to reduce severe maternal morbidity in women with obstetric hemorrhage using a large maternal quality collaborative. STUDY DESIGN: We report on 99 collaborative hospitals (256,541 annual births) using a before-and-after model with 48 noncollaborative comparison hospitals (81,089 annual births) used to detect any systemic trends. Both groups participated in the California Maternal Data Center providing baseline and rapid-cycle data. Baseline period was the 48 months from January 2011 through December 2014. The collaborative started in January 2015 and the postintervention period was the 6 months from October 2015 through March 2016. We modified the Institute for Healthcare Improvement collaborative model for achieving breakthrough improvement to include the mentor model whereby 20 pairs of nurse and physician mentors experienced in quality improvement gave additional support to small groups of 6-8 hospitals. The national hemorrhage safety bundle served as the template for quality improvement action. The main outcome measurement was the composite Centers for Disease Control and Prevention severe maternal morbidity measure, for both the target population of women with hemorrhage and the overall delivery population. The rate of adoption of bundle elements was used as an indicator of hospital engagement and intensity. RESULTS: Compared to baseline period, women with hemorrhage in collaborative hospitals experienced a 20.8% reduction in severe maternal morbidity while women in comparison hospitals had a 1.2% reduction (P < .0001). Women in hospitals with prior hemorrhage collaborative experience experienced an even larger 28.6% reduction. Fewer mothers with transfusions accounted for two thirds of the reduction in collaborative hospitals and fewer procedures and medical complications, the remainder. The rate of severe maternal morbidity among all women in collaborative hospitals was 11.7% lower and women in hospitals with prior hemorrhage collaborative experience had a 17.5% reduction. Improved outcomes for women were noted in all hospital types (regional, medium, small, health maintenance organization, and nonhealth maintenance organization). Overall, 54% of hospitals completed 14 of 17 bundle elements, 76% reported regular unit-based drills, and 65% reported regular posthemorrhage debriefs. Higher rate of bundle adoption was associated with improvement of maternal morbidity only in hospitals with high initial rates of severe maternal morbidity. CONCLUSION: We used an innovative collaborative quality improvement approach (mentor model) to scale up implementation of the national hemorrhage bundle. Participation in the collaborative was strongly associated with reductions in severe maternal morbidity among hemorrhage patients. Women in hospitals in their second collaborative had an even greater reduction in morbidity than those approaching the bundle for the first time, reinforcing the concept that quality improvement is a long-term and cumulative process.

Maternal prepregnancy body mass index and risk of bronchopulmonary dysplasia.

BackgroundWe examined the relationship between women's prepregnancy BMI and development of bronchopulmonary dysplasia (BPD) in their preterm offspring, hypothesizing that obesity-associated inflammation may increase risk.MethodsWe studied infants born in California between 2007 and 2011, using linked data from California Perinatal Quality Care Collaborative neonatal intensive care units, hospital discharge, and vital statistics. We included infants with birthweight <1,500 g or gestational age at birth of 22-29 weeks. BPD was defined as continuous supplemental oxygen use at 36 weeks' postmenstrual age.ResultsAmong 12,621 infants, 4,078 (32%) had BPD. After adjustment for maternal race/ethnicity, age, education, payer source, and infant sex, BMI status underweight I (BMI <16.9, odds ratio (OR) 1.7, 95% confidence interval (CI) 1.3-2.1) and obesity III (BMI ⩾40.0, OR 1.3, 95% CI 1.0-1.6) were associated with an increased risk of BPD. When considering maternal BMI as a continuous variable, a nonlinear association with BPD was observed for male infants and infants delivered at 25-29 weeks of gestational age, but not for other subgroups.ConclusionBoth high and low maternal BMI were associated with increased BPD risk. These findings support the notion that BPD is a multi-factorial disease that may sometimes have its origins in utero and be influenced by maternal inflammation.

Labor outcome at extremely advanced maternal age.

BACKGROUND: Women of advanced maternal age (AMA) are at increased risk for cesarean delivery compared to non-AMA women. However, it is unclear whether this association is altered by parity and the presence or absence of a trial of labor. OBJECTIVE: We sought to examine modes of delivery and maternal outcomes among AMA women stratified by parity and the presence or absence of a trial of labor. STUDY DESIGN: This is a retrospective cohort study of all women delivering singletons births at ≥20 weeks' gestation in the state of California from 2007 through 2011. Data were extracted from maternal discharge data linked to infant birth certificate records. We compared non-AMA women (age 20-34 years, reference group) to AMA women who were classified as follows: age 35-39, 40-44, 45-49, and ≥50 years). The primary outcome was route of delivery (cesarean vs vaginal) stratified by parity and whether a trial of labor occurred (prelabor vs intrapartum cesarean delivery). The association between a trial of labor and perinatal morbidity was also studied. RESULTS: There were 1,346,889 women who met inclusion criteria, which included 181 (0.01%) women who were age ≥50 years at the time of delivery. Overall, 34.7% underwent a cesarean delivery and this risk differed significantly by age group (30.5%, 20-34 years; 40.5%, 35-39 years; 47.3%, 40-44 years; 55.6%, 45-49 years; 62.4%, >50 years). Nulliparous women age ≥50 years were significantly less likely to undergo a trial of labor compared to the reference group (relative risk [RR], 0.44; 95% confidence interval [CI], 0.32-0.62). Furthermore, nulliparous women age ≥50 years were significantly more likely to experience an intrapartum cesarean delivery (RR, 2.61; 95% CI, 1.31-5.20), however the majority (74%) who underwent a trial of labor experienced a vaginal delivery. Compared to the reference group, women age ≥50 years were 5 times more likely to experience severe maternal morbidity (1.7% vs 0.3%; RR, 5.08; 95% CI, 1.65-15.61) and their infants 3 times more likely to require neonatal intensive care unit admission (14.9% vs 5.2%; RR, 3.1; 95% CI, 2.2-4.4), however these outcomes were not associated significantly with having undergone a trial of labor, a cesarean delivery following labor, or a prelabor cesarean delivery. Similar trends were observed among multiparous women. CONCLUSION: Compared to non-AMA women, women age ≥50 years with a singleton pregnancy experience significantly higher rates of cesarean delivery. However the majority of those who undergo a trial of labor will have a vaginal delivery. Neither a trial of labor nor a prelabor cesarean delivery is significantly associated with maternal or neonatal morbidity. These data support either approach in women of extremely AMA.

Measuring severe maternal morbidity: validation of potential measures.

BACKGROUND: Both maternal mortality rate and severe maternal morbidity rate have risen significantly in the United Sates. Recently, the Centers for Disease Control and Prevention introduced International Classification of Diseases, 9th revision, criteria for defining severe maternal morbidity with the use of administrative data sources; however, those criteria have not been validated with the use of chart reviews. OBJECTIVE: The primary aim of the current study was to validate the Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria for the identification of severe maternal morbidity. This analysis initially required the development of a reproducible set of clinical conditions that were judged to be consistent with severe maternal morbidity to be used as the clinical gold standard for validation. Alternative criteria for severe maternal morbidity were also examined. STUDY DESIGN: The 67,468 deliveries that occurred during a 12-month period from 16 participating California hospitals were screened initially for severe maternal morbidity with the presence of any of 4 criteria: (1) Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, diagnosis and procedure codes; (2) prolonged postpartum length of stay (>3 standard deviations beyond the mean length of stay for the California population); (3) any maternal intensive care unit admissions (with the use of hospital billing sources); and (4) the administration of any blood product (with the use of transfusion service data). Complete medical records for all screen-positive cases were examined to determine whether they satisfied the criteria for the clinical gold standard (determined by 4 rounds of a modified Delphi technique). Descriptive and statistical analyses that included area under the receiver operating characteristic curve and C-statistic were performed. RESULTS: The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria had a reasonably high sensitivity of 0.77 and a positive predictive value of 0.44 with a C-statistic of 0.87. The most important source of false-positive cases were mothers whose only criterion was 1-2 units of blood products. The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria screen rate ranged from 0.51-2.45% among hospitals. True positive severe maternal morbidity ranged from 0.05-1.13%. When hospitals were grouped by their neonatal intensive care unit level of care, severe maternal morbidity rates were statistically lower at facilities with lower level neonatal intensive care units (P < .0001). CONCLUSION: The Centers for Disease Control and Prevention International Classification of Diseases, 9th revision, criteria can serve as a reasonable administrative metric for measuring severe maternal morbidity at population levels. Caution should be used with the use of these criteria for individual hospitals, because case-mix effects appear to be strong.

Exome Sequencing of Neonatal Blood Spots and the Identification of Genes Implicated in Bronchopulmonary Dysplasia.

RATIONALE: Bronchopulmonary dysplasia (BPD), a prevalent severe lung disease of premature infants, has a strong genetic component. Large-scale genome-wide association studies for common variants have not revealed its genetic basis. OBJECTIVES: Given the historical high mortality rate of extremely preterm infants who now survive and develop BPD, we hypothesized that risk loci underlying this disease are under severe purifying selection during evolution; thus, rare variants likely explain greater risk of the disease. METHODS: We performed exome sequencing on 50 BPD-affected and unaffected twin pairs using DNA isolated from neonatal blood spots and identified genes affected by extremely rare nonsynonymous mutations. Functional genomic approaches were then used to systematically compare these affected genes. MEASUREMENTS AND MAIN RESULTS: We identified 258 genes with rare nonsynonymous mutations in patients with BPD. These genes were highly enriched for processes involved in pulmonary structure and function including collagen fibril organization, morphogenesis of embryonic epithelium, and regulation of Wnt signaling pathway; displayed significantly elevated expression in fetal and adult lungs; and were substantially up-regulated in a murine model of BPD. Analyses of mouse mutants revealed their phenotypic enrichment for embryonic development and the cyanosis phenotype, a clinical manifestation of BPD. CONCLUSIONS: Our study supports the role of rare variants in BPD, in contrast with the role of common variants targeted by genome-wide association studies. Overall, our study is the first to sequence BPD exomes from newborn blood spot samples and identify with high confidence genes implicated in BPD, thereby providing important insights into its biology and molecular etiology.

Estimating Length of Stay by Patient Type in the Neonatal Intensive Care Unit.

Objective Develop length of stay prediction models for neonatal intensive care unit patients. Study Design We used data from 2008 to 2010 to construct length of stay models for neonates admitted within 1 day of age to neonatal intensive care units and surviving to discharge home. Results Our sample included 23,551 patients. Median length of stay was 79 days when birth weight was < 1,000 g, 46 days for 1,000 to 1,500 g, 21 days for 1,500 to 2,500 g, and 8 days for ≥2,500 g. Risk factors for longer length of stay varied by weight. Units with shorter length of stay for one weight group had shorter lengths of stay for other groups. Conclusion Risk models for comparative assessments of length of stay need to appropriately account for weight, particularly considering the cutoff of 1,500 g. Refining prediction may benefit counseling of families and health care systems to efficiently allocate resources.