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1.  Role of infant sex in the association between air pollution and preterm birth 
Annals of epidemiology  2015;25(11):874-876.
doi:10.1016/j.annepidem.2015.08.005
PMCID: PMC4671488  PMID: 26475983
Preterm birth; Air pollution; Sex differences
2.  Prepregnancy Obesity and Risks of Stillbirth 
PLoS ONE  2015;10(10):e0138549.
Background
We examined the association of maternal obesity with risk of stillbirth, focusing on whether the pattern of results varied by gestational age or maternal race-ethnicity or parity.
Methods
Analyses included 4,012 stillbirths and 1,121,234 liveborn infants delivered in California from 2007–2010. We excluded stillbirths due to congenital anomalies, women with hypertensive disorders or diabetes, and plural births, to focus on fetuses and women without these known contributing conditions. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI). Separate models were run for stillbirths delivered at 20–23, 24–27, 28–31, 32–36, 37–41 weeks, relative to liveborn deliveries at 37–41 weeks.
Results
For stillbirth at 20–23 weeks, RRs were elevated for all race-ethnicity and parity groups. The RR for a 20-unit change in BMI (which reflects the approximate BMI difference between a normal weight and an Obese III woman) was 3.5 (95% CI 2.2, 5.6) for nulliparous white women and ranged from 1.8 to 5.0 for other sub-groups. At 24–27 weeks, the association was significant (p<0.05) only for multiparous non-Hispanic whites; at 28–31 weeks, for multiparous whites and nulliparous whites and blacks; at 32–36 weeks, for multiparous whites and nulliparous blacks; and at 37–41 weeks, for all groups except nulliparous blacks. The pattern of results was similar when restricted to stillbirths due to unknown causes and somewhat stronger when restricted to stillbirths attributable to obstetric causes.
Conclusion
Increased risks were observed across all gestational ages, and some evidence of heterogeneity of the associations was observed by race-ethnicity and parity.
doi:10.1371/journal.pone.0138549
PMCID: PMC4605840  PMID: 26466315
3.  Exposure to Leadership WalkRounds in neonatal intensive care units is associated with a better patient safety culture and less caregiver burnout 
BMJ quality & safety  2014;23(10):814-822.
Background
Leadership WalkRounds (WR) are widely used in healthcare organisations to improve patient safety. The relationship between WR and caregiver assessments of patient safety culture, and healthcare worker burnout is unknown.
Methods
This cross-sectional survey study evaluated the association between receiving feedback about actions taken as a result of WR and healthcare worker assessments of patient safety culture and burnout across 44 neonatal intensive care units (NICUs) actively participating in a structured delivery room management quality improvement initiative.
Results
Of 3294 administered surveys, 2073 were returned for an overall response rate of 62.9%. More WR feedback was associated with better safety culture results and lower burnout rates in the NICUs. Participation in WR and receiving feedback about WR were less common in NICUs than in a benchmarking comparison of adult clinical areas.
Conclusions
WR are linked to patient safety and burnout. In NICUs, where they occurred more often, the workplace appears to be a better place to deliver and to receive care.
doi:10.1136/bmjqs-2013-002042
PMCID: PMC4167964  PMID: 24825895
4.  Copy Number Variation in Bronchopulmonary Dysplasia 
doi:10.1002/ajmg.a.36659
PMCID: PMC4167221  PMID: 24975634
copy number variation; genome-wide association study (GWAS); chronic lung disease of infancy; bronchopulmonary dysplasia; genetic predisposition to disease; premature; very low birth weight infant
5.  Elevated tumor necrosis factor-alpha (TNF-α) and hyperlipidemia in pregnancies resulting in early preterm birth 
Objective
To determine whether pregnancies resulting in early preterm birth (< 30 weeks) were more likely than term pregnancies to have elevated mid-trimester tumor necrosis factor alpha (TNF-α) levels co-occurring with lipid patterns suggestive of hyperlipidemia.
Study Design
Patterns were examined using stored non-fasted serum samples from 108 California and 734 Iowa singleton pregnancies collected as part of statewide prenatal screening. The frequency of elevated mid-pregnancy serum TNF-α levels and lipid patterns suggestive of hyperlipidemia (e.g. elevated total cholesterol (TC), low-density-lipoproteins (LDLs), or triglycerides (TGs), decreased high-density lipoproteins (HDLs)) (considered independently and by co-occurrence) were compared in pregnancies resulting in early preterm birth to those resulting in term birth using logistic regression models.
Results
While no differences between preterm and term pregnancies were evident when TNF-α or target lipid abnormalities occurred in isolation, early preterm pregnancies were two to four times more likely than term pregnancies to have elevated TNF-α levels co-occurring with indicators of hyperlipidemia (37.5% versus 13.9% in the California sample (adjusted OR 4.0, 95% CI 1.1 – 16.3) and 26.3% versus 14.9% in the Iowa sample (adjusted OR 2.7, 95% CI 1.1 – 6.3)). Observed differences were not explicable to any maternal or infant characteristics.
Conclusion
Pregnancies resulting in early preterm birth were more likely than term pregnancies to have elevated mid-pregnancy TNF-α levels co-occurring with lipid patterns suggestive of hyperlipidemia. Patterns offer clues for further study of the signaling of early parturition in preterm birth.
doi:10.1016/j.ajog.2014.02.019
PMCID: PMC4117727  PMID: 24831886
6.  Baby-MONITOR: A Composite Indicator of NICU Quality 
Pediatrics  2014;134(1):74-82.
BACKGROUND AND OBJECTIVES:
NICUs vary in the quality of care delivered to very low birth weight (VLBW) infants. NICU performance on 1 measure of quality only modestly predicts performance on others. Composite measurement of quality of care delivery may provide a more comprehensive assessment of quality. The objective of our study was to develop a robust composite indicator of quality of NICU care provided to VLBW infants that accurately discriminates performance among NICUs.
METHODS:
We developed a composite indicator, Baby-MONITOR, based on 9 measures of quality chosen by a panel of experts. Measures were standardized, equally weighted, and averaged. We used the California Perinatal Quality Care Collaborative database to perform across-sectional analysis of care given to VLBW infants between 2004 and 2010. Performance on the Baby-MONITOR is not an absolute marker of quality but indicates overall performance relative to that of the other NICUs. We used sensitivity analyses to assess the robustness of the composite indicator, by varying assumptions and methods.
RESULTS:
Our sample included 9023 VLBW infants in 22 California regional NICUs. We found significant variations within and between NICUs on measured components of the Baby-MONITOR. Risk-adjusted composite scores discriminated performance among this sample of NICUs. Sensitivity analysis that included different approaches to normalization, weighting, and aggregation of individual measures showed the Baby-MONITOR to be robust (r = 0.89–0.99).
CONCLUSIONS:
The Baby-MONITOR may be a useful tool to comprehensively assess the quality of care delivered by NICUs.
doi:10.1542/peds.2013-3552
PMCID: PMC4067636  PMID: 24918221
infant; newborn; quality of care; performance measurement
7.  Nosocomial Infection Reduction in VLBW Infants With a Statewide Quality-Improvement Model 
Pediatrics  2011;127(3):419-426.
OBJECTIVE:
To evaluate the effectiveness of the California Perinatal Quality Care Collaborative quality-improvement model using a toolkit supplemented by workshops and Web casts in decreasing nosocomial infections in very low birth weight infants.
DESIGN:
This was a retrospective cohort study of continuous California Perinatal Quality Care Collaborative members' data during the years 2002–2006. The primary dependent variable was nosocomial infection, defined as a late bacterial or coagulase-negative staphylococcal infection diagnosed after the age of 3 days by positive blood/cerebro-spinal fluid culture(s) and clinical criteria. The primary independent variable of interest was voluntary attendance at the toolkit's introductory event, a direct indicator that at least 1 member of an NICU team had been personally exposed to the toolkit's features rather than being only notified of its availability. The intervention's effects were assessed using a multivariable logistic regression model that risk adjusted for selected demographic and clinical factors.
RESULTS:
During the study period, 7733 eligible very low birth weight infants were born in 27 quality-improvement participant hospitals and 4512 very low birth weight infants were born in 27 non–quality-improvement participant hospitals. For the entire cohort, the rate of nosocomial infection decreased from 16.9% in 2002 to 14.5% in 2006. For infants admitted to NICUs participating in at least 1 quality-improvement event, there was an associated decreased risk of nosocomial infection (odds ratio: 0.81 [95% confidence interval: 0.68–0.96]) compared with those admitted to nonparticipating hospitals.
CONCLUSIONS:
The structured intervention approach to quality improvement in the NICU setting, using a toolkit along with attendance at a workshop and/or Web cast, is an effective means by which to improve care outcomes.
doi:10.1542/peds.2010-1449
PMCID: PMC3387911  PMID: 21339273
central-line–associated bloodstream infection; nosocomial infection; quality improvement; quality-improvement toolkits; quality-improvement evaluation
8.  A Genome-Wide Association Study (GWAS) for Bronchopulmonary Dysplasia 
Pediatrics  2013;132(2):290-297.
OBJECTIVE:
Twin studies suggest that heritability of moderate-severe bronchopulmonary dysplasia (BPD) is 53% to 79%, we conducted a genome-wide association study (GWAS) to identify genetic variants associated with the risk for BPD.
METHODS:
The discovery GWAS was completed on 1726 very low birth weight infants (gestational age = 250–296/7 weeks) who had a minimum of 3 days of intermittent positive pressure ventilation and were in the hospital at 36 weeks’ postmenstrual age. At 36 weeks’ postmenstrual age, moderate-severe BPD cases (n = 899) were defined as requiring continuous supplemental oxygen, whereas controls (n = 827) inhaled room air. An additional 795 comparable infants (371 cases, 424 controls) were a replication population. Genomic DNA from case and control newborn screening bloodspots was used for the GWAS. The replication study interrogated single-nucleotide polymorphisms (SNPs) identified in the discovery GWAS and those within the HumanExome beadchip.
RESULTS:
Genotyping using genomic DNA was successful. We did not identify SNPs associated with BPD at the genome-wide significance level (5 × 10−8) and no SNP identified in previous studies reached statistical significance (Bonferroni-corrected P value threshold .0018). Pathway analyses were not informative.
CONCLUSIONS:
We did not identify genomic loci or pathways that account for the previously described heritability for BPD. Potential explanations include causal mutations that are genetic variants and were not assayed or are mapped to many distributed loci, inadequate sample size, race ethnicity of our study population, or case-control differences investigated are not attributable to underlying common genetic variation.
doi:10.1542/peds.2013-0533
PMCID: PMC3727675  PMID: 23897914
genome-wide association study (GWAS); chronic lung disease; genetic predisposition to disease; premature; very low birth weight infant
9.  The Impact of Statistical Choices on Neonatal Intensive Care Unit Quality Ratings Based on Nosocomial Infection Rates 
Objective
To examine the extent to which performance assessment methodologies affect the percent of neonatal intensive care units (NICUs) and very low birth weight (VLBW) infants included in performance assessments, distribution of NICU performance ratings, and level of agreement in those ratings.
Design
Cross-sectional study based on risk-adjusted nosocomial infection rates.
Setting
NICUs belonging to the California Perinatal Quality Care Collaborative 2007–2008.
Participants
126 California NICUs and 10,487 VLBW infants.
Main Exposure
Three performance assessment choices: 1. Excluding “low-volume” NICUs (those caring for < 30 VLBW infants in a year) vs. a criterion based on confidence intervals, 2. Using Bayesian vs. frequentist hierarchical models, and 3. Pooling data across one vs. two years.
Main Outcome Measures
Proportion of NICUs and patients included in quality assessment, distribution of ratings for NICUs, and agreement between methods using the kappa statistic.
Results
Depending on the methods applied, between 51% and 85% of NICUs were included in performance assessment, the percent of VLBW infants included in performance assessment ranged from 72% to 96%, between 76–87% NICUs were considered “average,” and the level of agreement between NICU ratings ranged from 0.26 to 0.89.
Conclusions
The percent of NICUs included in performance assessment and their ratings can shift dramatically depending on performance measurement methodology. Physicians, payers, and policymakers should continue to closely examine which existing performance assessment methodologies are most appropriate for evaluating pediatric care quality.
doi:10.1001/archpediatrics.2011.41
PMCID: PMC4104272  PMID: 21536958
Quality; quality improvement; performance incentives; pay-for-performance; public reporting; neonatal intensive care units; Very Low Birth Weight infants; Nosocomial infections
10.  Association of Early Preterm Birth with Abnormal Levels of Routinely Collected First and Second Trimester Biomarkers 
American journal of obstetrics and gynecology  2013;208(6):492.e1-492.e11.
Objective
To examine the relationship between typically measured prenatal screening biomarkers and early preterm birth in euploid pregnancies.
Study Design
Included were 345 early preterm cases (< 30 weeks) and 1,725 controls drawn from a population-based sample of California pregnancies that all had both first and second trimester screening results. Logistic regression analyses were used to compare patterns of biomarkers in cases and controls and to develop predictive models. Replicability of the biomarker-early preterm relationships revealed by the models was evaluated by examining the frequency and associated adjusted relative risks (RRsadj) for early preterm birth and for preterm birth in general (< 37 weeks) in pregnancies with identified abnormal markers compared to those without these markers in a subsequent independent California cohort of screened pregnancies (n = 76,588).
Results
The final model for early preterm birth included first trimester pregnancy-associated plasma protein A (PAPP-A) ≤ the 5th percentile, second trimester alpha-fetoprotein (AFP) ≥ the 95th percentile, and second trimester inhibin (INH) ≥ the 95th percentile (odds ratios 2.3 to 3.6). In general, pregnancies in the subsequent cohort with a biomarker pattern found to be associated with early preterm delivery in the first sample were at an increased risk for early preterm birth and preterm birth in general (< 37 weeks) (RRsadj 1.6 to 27.4). Pregnancies with two or more biomarker abnormalities were at particularly increased risk (RRsadj 3.6 to 27.4).
Conclusion
When considered across cohorts and in combination, abnormalities in routinely collected biomarkers reveal predictable risks for early preterm birth.
doi:10.1016/j.ajog.2013.02.012
PMCID: PMC3672244  PMID: 23395922
Preterm Birth; Prenatal Screening; Biomarkers
11.  Accounting for variation in length of NICU stay for extremely low birth weight infants 
Objective
To develop a length of stay (LOS) model for extremely low birth weight (ELBW) infants.
Study Design
We included infants from the California Perinatal Quality Care Collaborative with birth weight 401–1,000 grams who were discharged to home. Exclusion criteria were congenital anomalies, surgery, and death. LOS was defined as days from admission to discharge. As patients who died or were transferred to lower level of care were excluded, we assessed correlation of hospital mortality rates and transfers torisk adjusted LOS.
Results
There were 2,012 infants with median LOS 79 days (range 23–219). Lower birth weight, lack of antenatal steroids, and lower Apgar score were associated with longer LOS. There was negligiblecorrelation between risk-adjusted LOS and hospital mortality rates (r = 0.0207) and transfer-out rates (r = 0.121).
Conclusion
Particularly because ELBW infants have extended hospital stays, identification of unbiased and informative risk-adjusted LOS for these infants is an important step in benchmarking best practice and improving efficiency in care.
doi:10.1038/jp.2013.92
PMCID: PMC3815522  PMID: 23949836
Length of stay; Extremely low birth weight
12.  Population-Level Correlates of Preterm Delivery among Black and White Women in the U.S 
PLoS ONE  2014;9(4):e94153.
Objective
This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery.
Methods
We examined county-level prevalence of preterm delivery (20–31 or 32–36 weeks gestation) among singletons born 1998–2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group.
Results
The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20–31 weeks and 55% for delivery at 32–36 weeks (based on R-squared values). Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall.
Conclusions
Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites.
doi:10.1371/journal.pone.0094153
PMCID: PMC3989227  PMID: 24740117
13.  Do Practicing Clinicians Agree with Expert Ratings of Neonatal Intensive Care Unit Quality Measures? 
Objective
To assess the level of agreement when selecting quality measures for inclusion in a composite index of neonatal intensive care quality (Baby-MONITOR) between two panels: one comprised of academic researchers (Delphi) and another comprised of academic and clinical neonatologists (Clinician).
Design/Methods
In a modified Delphi process, a panel rated twenty eight quality measures. We assessed clinician agreement with the Delphi panel by surveying a sample of forty eight neonatal intensive care practitioners. We asked the clinician group to indicate their level of agreement with the Delphi panel for each measure using a five- point scale (much too high, slightly too high, reasonable, slightly too low, and much too low). In addition, we asked clinicians to select measures for inclusion in the Baby-MONITOR based on a yes or no vote and a pre-specified two-thirds majority for inclusion.
Results
Twenty three (47.9%) of the clinicians responded to the survey. We found high levels of agreement between the Delphi and clinician panels, particularly across measures selected for the Baby-MONITOR. Clinicians selected the same nine measures for inclusion in the composite as the Delphi panel. For these nine measures, 74% of clinicians indicated that the Delphi panel rating was ‘reasonable’.
Conclusions
Practicing clinicians agree with an expert panel on the measures that should be included in the Baby-MONITOR, enhancing face validity.
doi:10.1038/jp.2011.199
PMCID: PMC3963391  PMID: 22241483
infant; newborn; quality of health care; measurement; composite indicator
14.  Hospital-wide breastfeeding rates vs. breastmilk provision for very low birth weight infants 
Aim
To investigate the relationship between breastmilk feeding in very low birth weight infants in the neonatal intensive care unit and breastmilk feeding rates for all newborns by hospital.
Methods
This was a cross-sectional study of 111 California hospitals in 2007 and 2008. Correlation coefficients were calculated between overall hospital breastfeeding rates and very low birth weight infant breastmilk feeding rates. Hospitals were categorized in quartiles by crude and adjusted very low birth weight infant rates to compare rankings between measures.
Results
Correlation between very low birth weight infants and overall breastfeeding rates varied by neonatal intensive care unit level of care, from 0.13 for intermediate hospitals to 0.48 for regional hospitals. For hospitals categorized in the top quartile according to overall breastfeeding rate, only (46%) were in the top quartile for both crude and adjusted very low birth weight infant rates. On the other hand, when considering the lowest quartile for overall breastfeeding hospitals, 3 of 27 (11%) actually were performing in the top quartile of performance for very low birth weight infant rates.
Conclusions
Reporting hospital overall breastfeeding rates and neonatal intensive care unit breastmilk provision rates separately may give an incomplete picture of quality of care.
doi:10.1111/apa.12096
PMCID: PMC3566354  PMID: 23174012
Preterm infants; Neonatal intensive care; Breastmilk; Breastfeeding; Quality improvement
15.  Variations in Definitions of Mortality Have Little Influence on NICU Performance Ratings 
The Journal of pediatrics  2012;162(1):50-5.e2.
Objective
To measure the influence of varying mortality time frames on performance rankings among regional NICUs in a large state.
Study design
We carried out cross-sectional data analysis of VLBW infants cared for at 24 level 3 NICUs. We tested the effect of four definitions of mortality: (1) deaths between admission and end of birth hospitalization or up to 366 days; (2) deaths between 12 hours of age and end of birth hospitalization or up to 366 days; (3) deaths between admission and 28 days; and (4) deaths between 12 hours of age and 28 days. NICUs were ranked by quantifying their deviation from risk-adjusted expected mortality and splitting them into three tiers: top six, bottom six, and in-between.
Results
There was wide inter-institutional variation in risk-adjusted mortality for each definition (observed minus expected Z-score range, -6.08 to 3.75). However, mortality-rate-based NICU rankings, and their classification into performance tiers, were very similar for all institutions for each of our time frames. Among all four 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.
doi:10.1016/j.jpeds.2012.06.002
PMCID: PMC3782108  PMID: 22854328
Infant; newborn; quality of care; performance measurement; mortality
16.  Maternal Morbidity during Childbirth Hospitalization in California 
Objective
To determine the incidence and risk factors for maternal morbidity during childbirth hospitalization.
Methods
Maternal morbidities were determined using ICD9-CM and vital records codes from linked hospital discharge and vital records data for 1,572,909 singleton births in California, 2005-2007. Sociodemographic, obstetric, and hospital volume risk factors were estimated using mixed effects logistic regression models.
Results
The maternal morbidity rate was 241/1000 births. The most common morbidities were episiotomy, pelvic trauma, maternal infection, postpartum hemorrhage, and severe laceration. Preeclampsia (Adjusted Odds Ratio [AOR] 2.96; 95% CI 2.8,3.13), maternal age over 35 years, (AOR 1.92; 1.79,2.06), vaginal birth after cesarean, (AOR 1.81; 1.47,2.23), and repeat cesarean birth (AOR 1.99; 1.87,2.12) conferred the highest odds of severe morbidity. Non-white women were more likely to suffer morbidity.
Conclusions
Nearly one in four California women experienced complications during childbirth hospitalization. Significant health disparities in maternal childbirth outcomes persist in the United States.
doi:10.3109/14767058.2012.710280
PMCID: PMC3642201  PMID: 22779781
Childbirth hospitalization; maternal morbidity; risk factors
17.  Factors Associated with Failure to Screen Newborns for Retinopathy of Prematurity 
The Journal of pediatrics  2012;161(5):819-823.
Objectives
To evaluate ROP screening rates in a population-based cohort; 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 socio-demographic 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 (odds ratio [OR] 1.25 for increase of one week, 95% confidence interval [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 NICUs and NICUs 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.
doi:10.1016/j.jpeds.2012.04.020
PMCID: PMC3470784  PMID: 22632876
Retinopathy of Prematurity; Premature; Quality of Care; Neonatal
18.  The Continuum of Maternal Sepsis Severity: Incidence and Risk Factors in a Population-Based Cohort Study 
PLoS ONE  2013;8(7):e67175.
Objective
To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.
Methods
This retrospective cohort study used linked hospital discharge and vital statistics records data for 1,622,474 live births in California during 2005–2007. Demographic and clinical factors were adjusted using multivariable logistic regression with robust standard errors.
Results
1598 mothers developed sepsis; incidence of all sepsis was 10 per 10,000 live births (95% CI = 9.4–10.3). Women had significantly increased adjusted odds (aOR) of developing sepsis if they were older (25–34 years: aOR = 1.29; ≥35 years: aOR = 1.41), had ≤high-school education (aOR = 1.63), public/no-insurance (aOR = 1.22) or a cesarean section (primary: aOR = 1.99; repeat: aOR = 1.25). 791 women progressed to severe sepsis; incidence of severe sepsis was 4.9 per 10,000 live births (95% CI = 4.5–5.2). Women had significantly increased adjusted odds of progressing to severe sepsis if they were Black (aOR = 2.09), Asian (aOR = 1.59), Hispanic (aOR = 1.42), had public/no-insurance (aOR = 1.52), delivered in hospitals with <1,000 births/year (aOR = 1.93), were primiparous (aOR = 2.03), had a multiple birth (aOR = 3.5), diabetes (aOR = 1.47), or chronic hypertension (aOR = 8.51). Preeclampsia and postpartum hemorrhage were also significantly associated with progression to severe sepsis (aOR = 3.72; aOR = 4.18). For every cumulative factor, risk of uncomplicated sepsis increased by 25% (95% CI = 17.4–32.3) and risk of progression to severe sepsis/septic shock increased by 57% (95% CI = 40.8–74.4).
Conclusions
The rate of severe sepsis was approximately twice the 1991–2003 national estimate. Risk factors identified are relevant to obstetric practice given their cumulative risk effect and the apparent increase in severe sepsis incidence.
doi:10.1371/journal.pone.0067175
PMCID: PMC3699572  PMID: 23843991
19.  Missed Opportunities in the Referral of High-Risk Infants to Early Intervention 
Pediatrics  2012;129(6):1027-1034.
OBJECTIVE:
Using a statewide population-based data source, we describe current neonatal follow-up referral practices for high-risk infants with developmental delays throughout California.
METHODS:
From a cohort analysis of quality improvement data from 66 neonatal follow-up programs in the California Children’s Services and California Perinatal Quality Care Collaborative High-Risk Infant Follow-Up Quality of Care Initiative, 5129 high-risk infants were evaluated at the first visit between 4 and 8 months of age in neonatal follow-up. A total of 1737 high-risk infants were evaluated at the second visit between 12 and 16 months of age. We calculated referral rates in relation to developmental status (high versus low concern) based on standardized developmental testing or screening.
RESULTS:
Among infants with low concerns (standard score >70 or passed screen) at the first visit, 6% were referred to early intervention; among infants with high concerns, 28% of infants were referred to early intervention. Even after including referrals to other (private) therapies, 34% infants with high concerns did not receive any referrals. These rates were similar for the second visit.
CONCLUSIONS:
In spite of the specialization of neonatal follow-up programs to identify high-risk infants with developmental delays, a large proportion of potentially eligible infants were not referred to early intervention.
doi:10.1542/peds.2011-2720
PMCID: PMC4074653  PMID: 22614772
early intervention; developmental assessment; developmental delay; health service utilization; neonatal follow-up
20.  Risk of Bronchopulmonary Dysplasia by Second Trimester Maternal Serum Levels of Alpha-fetoprotein, Human Chorionic Gonadotrophin, and Unconjugated Estriol 
Pediatric research  2012;71(4 0 1):399-406.
Although maternal serum alpha-fetoprotein (AFP), human chorionic gonandotrophin (hCG), and estriol play important roles in immunomodulation and immunoregulation during pregnancy, their relationship to the development of bronchopulmonary dysplasia (BPD) in young infants is unknown despite BPD being associated with pre- and postnatal inflammatory factors. The objective of this population-based study was to examine whether second trimester levels of AFP, hCG, and unconjugated estriol (uE3) were associated with an increased risk of BPD. We found that these serum biomarkers were associated with an increased risk of BPD. Risks were especially high when AFP and/or hCG levels were above the 95th percentile and/or when uE3 levels were below the 5th percentile (relative risks (RRs) 3.1 to 6.7). Risks increased substantially when two or more biomarker risks were present (RRs 9.9 to 75.9). Data suggested that pregnancies which had a biomarker risk and yielded an offspring with BPD were more likely to have other factors present that suggested early intrauterine fetal adaptation to a stress including maternal hypertension and asymmetric growth restriction.
doi:10.1038/pr.2011.73
PMCID: PMC3616500  PMID: 22391642
21.  Trends in Cesarean Delivery for Twin Births in the United States: 1995 to 2008 
Obstetrics and gynecology  2011;118(5):1095-1101.
Objective
To estimate trends and risk factors for cesarean delivery for twins in the United States.
Methods
This was a cross-sectional study in which we calculated cesarean rates for twins from 1995 to 2008 using National Center for Health Statistics data. We compared cesarean rates by year and for vertex vs. breech presentation. The order of presentation for a given twin pair could not be determined from the available records and therefore analysis was based on individual discrete twin data. Multivariable logistic regression was used to estimate independent risk factors, including year of birth and maternal factors, for cesarean delivery.
Results
Cesarean rates for twin births increased steadily from 53.4% to 75.0% in 2008. Rates rose for the breech twin category (81.5% to 92.1%) and the vertex twin category (45.1% to 68.2%). The relative increase in cesarean rate for preterm and term infants was similar. After risk adjustment, there was an average increase noted in cesarean delivery of 5% each year during the study period (risk ratio 1.05, 95% confidence interval 1.04, 1.05).
Conclusions
Cesarean delivery rates for twin births increased dramatically from 1995 to 2008. This increase is significantly higher than that which could be explained by an increase in cesarean delivery for breech presentation of either the presenting or second twin.
doi:10.1097/AOG.0b013e3182318651
PMCID: PMC3202294  PMID: 22015878
22.  Antenatal Steroid Administration for Premature Infants in California 
Obstetrics and gynecology  2011;117(3):603-609.
Objectives
To estimate risk factors for premature infants not receiving antenatal steroids in a population-based cohort and to determine whether the gains of a quality improvement collaborative project on antenatal steroid administration were sustained long-term.
Methods
Clinical data for premature infants born in 2005-2007 were obtained from the California Perinatal Quality Care Collaborative, which collects data on more than 90% of neonatal admissions in California. Eligible infants had a birth weight of less than 1500 grams or gestational age less than 34 weeks born at a Collaborative hospital. These data were linked to administrative data from California Vital Statistics. Socio-demographic and medical risk factors for not receiving antenatal steroids were determined. We also examined the effect of birth hospital participation in a prior quality improvement collaborative project. A random effects logistic regression model was used to determine independent risk factors.
Results
Of 15,343 eligible infants, 23.1% did not receive antenatal steroids in 2005-2007. Hispanic mothers (25.6%), mothers younger than age 20 (27.6%), and those without prenatal care (52.2%) were less likely to receive antenatal steroids. Mothers giving birth vaginally (26.8%) and mothers with a diagnosis of “fetal distress” (26.5%) were also less likely to receive antenatal steroids. Rupture of membranes prior to delivery, and multiple gestations were associated with higher likelihood of antenatal steroid administration. Hospitals who participated in a quality improvement collaborative in 1999-2000 had higher rates of antenatal steroid administration (85% vs. 69%, p < 0.0001).
Conclusion
A number of eligible mothers do not receive antenatal steroids. Quality improvement initiatives to improve antenatal steroid administration could target specific high-risk groups.
PMCID: PMC3072287  PMID: 21446208
23.  Low Apgar Score and Mortality in Extremely Preterm Neonates Born in the United States 
Acta paediatrica (Oslo, Norway : 1992)  2010;99(12):1785-1789.
Aim
To investigate the relationship between low Apgar score and neonatal mortality in preterm neonates.
Methods
Infant birth and death certificate data from the U.S. National Center for Health Statistics for 2001-2002 were analyzed. Primary outcome was 28 day mortality for 690,933 neonates at gestational ages 24-36 weeks. Mortality rates were calculated for each combination of gestational age and five-minute Apgar score. Relative risks of mortality, by high vs. low Apgar score, were calculated for each age.
Results
Distribution of Apgar scores depended on gestational age, the youngest gestational ages having higher proportions of low Apgar scores. Median Apgar score ranged from 6 at 24 weeks, to 9 at 30-36 weeks gestation. The relative risk of death was significantly higher at Apgar scores 0-3 vs. 7-10, including at the youngest gestational ages, ranging from 3.1 (95% confidence interval 2.9, 3.4) at 24 weeks to 18.5 (95% confidence interval 15.7, 21.8) at 28 weeks.
Conclusion
Low Apgar score was associated with increased mortality in premature neonates, including those at 24 to 28 weeks gestational age, and may be a useful tool for clinicians in assessing prognosis and for researchers as a risk prediction variable.
doi:10.1111/j.1651-2227.2010.01935.x
PMCID: PMC2970674  PMID: 20626363
Apgar score; Neonatal mortality; Prematurity
24.  Implementing Pay-for-Performance in the Neonatal Intensive Care Unit 
Pediatrics  2007;119(5):975-982.
Pay-for-performance initiatives in medicine are proliferating rapidly. Neonatal intensive care is a likely target for these efforts because of the high cost, available databases, and relative strength of evidence for at least some measures of quality. Pay-for-performance may improve patient care but requires valid measurements of quality to ensure that financial incentives truly support superior performance. Given the existing uncertainty with respect to both the effectiveness of pay-for-performance and the state of quality measurement science, experimentation with pay-for-performance initiatives should proceed with caution and in controlled settings. In this article, we describe approaches to measuring quality and implementing pay-for-performance in the NICU setting.
doi:10.1542/peds.2006-1565
PMCID: PMC3151255  PMID: 17473099
pay-for-performance programs; quality improvement
25.  Impact of Timing of Birth and Resident Duty-Hour Restrictions on Outcome of Small Preterm Infants 
Pediatrics  2010;126(2):222-231.
OBJECTIVE
To examine the impact of birth at night, on the weekend, and during July or August – the first months of the academic year – and the impact of resident duty-hour restrictions on mortality and morbidity of VLBW infants.
METHODS
Outcomes were analyzed for 11,137 infants with birth weight 501–1250 grams enrolled in the NICHD Neonatal Research Network registry 2001–2005. Approximately half were born before the introduction of resident duty-hour restrictions in 2003. Follow-up assessment at 18–22 months was completed for 4,508 infants. Mortality (7-day and 28-day), short-term morbidities, and neurodevelopmental outcome were examined with respect to the timing of birth: night vs day, weekend vs weekday, and July or August vs other months, and after vs before implementation of resident duty-hour restrictions.
RESULTS
There was no effect of hour, day, or month of birth on mortality and no impact on the risks of short-term morbidities except the risk of ROP requiring operative treatment was lower for infants born during the late night hours than during the day. There was no impact of timing of birth on neurodevelopmental outcome except the risk of hearing impairment or death was slightly lower among infants born in July or August compared with other months. The introduction of resident and fellow duty-hour restrictions had no impact on mortality or neurodevelopmental outcome. The only change in short-term morbidity after duty-hour restrictions were introduced was an increase in the risk of ROP (stage 2 or higher).
CONCLUSION
In this network of academic centers, the timing of birth and the introduction of duty-hour restrictions had little effect on the risks of mortality and morbidity of VLBW infants, suggesting that staffing patterns were adequate to provide consistent care.
doi:10.1542/peds.2010-0456
PMCID: PMC2924191  PMID: 20643715
Neonatal; preterm infants; morbidity/mortality; resident education/training; workforce

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