'The obesity paradox': a reconsideration of obesity and the risk of preterm birth.

OBJECTIVE: The association between obesity and spontaneous preterm births (sPTBs) has been shown to be influenced by obesity-attendant comorbidities. Our objective was to better understand the complex relationship of obesity and its attendant comorbidities with sPTBs. STUDY DESIGN: A retrospective analysis utilizing maternally linked hospital and birth certificate records of 2 049 196 singleton California deliveries from 2007 to 2011. Adjusted relative risks (aRRs) for sPTBs were estimated using multivariate Poisson regression modeling. RESULTS: Obese women had higher aRRs for sPTBs than their normal body mass index (BMI) controls. aRRs (95% confidence interval) increased with increasing BMI category: Obese I=1.10 (1.08 to 1.12); Obese II=1.15 (1.12 to 1.18); and Obese III=1.26 (1.22 to 1.30). When comparing only obese women without comorbidities to their normal BMI controls, aRRs reversed, that is, obese women had lower aRRs of sPTBs: Obese I=0.96 (0.94 to 0.98), Obese II=0.95 (0.91 to 0.98); and Obese III=0.98 (0.94 to 1.03). This same reversal of aRR direction was also observed among women with comorbidities: 0.92 (0.89 to 0.96); 0.89 (0.85 to 0.93); and 0.89 (0.85 to 0.93), respectively. Increasing BMI increased the aRRs for sPTBs among patients with gestational diabetes (P<0.05), while decreasing the risk among patients with chronic hypertension and pregnancy-related hypertensive disease (P<0.05). CONCLUSIONS: The obesity and preterm birth paradox is an example of what has been described as 'Simpson's Paradox'. Unmeasured confounding factors mediated by comorbidities may explain the observed protective effect of obesity upon conditioning on the presence or absence of comorbidities and thus resolve the paradox.

Variation in quality report viewing by providers and correlation with NICU quality metrics.

BACKGROUND: To examine variation in quality report viewing and assess correlation between provider report viewing and neonatal intensive care unit (NICU) quality. METHODS: Variation in report viewing sessions for 129 California Perinatal Quality Care Collaborative NICUs was examined. NICUs were stratified into tertiles based on their antenatal steroid (ANS) use and hospital-acquired infection (HAI) rates to compare report viewing session counts. RESULTS: The number of report viewing sessions initiated by providers varied widely over a 2-year period (median=11; mean=25.5; s.d.=45.19 sessions). Report viewing was not associated with differences in ANS use. Facilities with low HAI rates had less frequent report viewing. Facilities with high report views had significant improvements in HAI rates over time. CONCLUSIONS: Available audit and feedback reports are utilized inconsistently across California NICUs despite evidence that report viewing is associated with improvements in quality of care delivery. Further studies are needed for reports to reach their theoretical potential.

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

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

Effects of delivery room quality improvement on premature infant outcomes.

OBJECTIVE: Delivery room management interventions have been successfully implemented via collaborative quality improvement (QI) projects. However, it is unknown whether these successes translate to reductions in neonatal morbidity and mortality. STUDY DESIGN: This was a prospective pre-post intervention study of three nonrandomized hospital groups within the California Perinatal Quality Care Collaborative. A collaborative QI model (Collaborative QI) was compared with a single-site QI model (NICU QI) and a non-participant population when implementing evidence-based delivery room practices. The intervention period was between June 2011 and May 2012. Infants born with gestational age between 22 weeks 0 days and 29 weeks 6 days and birth weight ⩽1500 g were included. Outcomes were mortality and select morbidities (bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP) and necrotizing enterocolitis (NEC)). Outcomes were compared between the baseline (January 2010 to May 2011) and post-intervention period (June 2012 to May 2013) within each comparison group. RESULTS: Ninety-five hospitals were included with 4222 infants in the baseline period and 4186 infants in the post-intervention period. The Collaborative QI group had significantly reduced odds of developing BPD post-intervention (odds ratio (OR) 0.8, 95% confidence interval (CI) 0.65 to 0.99) or composite BPD-death (OR 0.83, 95% CI 0.69 to 1.00). In both the Collaborative QI and non-participants there were also reductions in IVH, severe IVH, composite severe IVH-death, severe ROP and composite severe ROP-death. CONCLUSION: Hospitals dedicated to improving delivery room practices can impact neonatal outcomes.

Opportunities for maternal transport for delivery of very low birth weight infants.

OBJECTIVE: To assess frequency of very low birth weight (VLBW) births at non-level III hospitals. STUDY DESIGN: Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500 g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models. RESULTS: Of the 1 508 143 births, 13 919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24 h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively. CONCLUSION: Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.

Characteristics of neonatal transports in California.

OBJECTIVE: To describe the current scope of neonatal inter-facility transports. STUDY DESIGN: California databases were used to characterize infants transported in the first week after birth from 2009 to 2012. RESULTS: Transport of the 22 550 neonates was classified as emergent 9383 (41.6%), urgent 8844 (39.2%), scheduled 2082 (9.2%) and other 85 (0.4%). In addition, 2152 (9.5%) were initiated for delivery attendance. Most transports originated from hospitals without a neonatal intensive care unit (68%), with the majority transferred to regional centers (66%). Compared with those born and cared for at the birth hospital, the odds of being transported were higher if the patient's mother was Hispanic, <20 years old, or had a previous C-section. An Apgar score <3 at 10 min of age, cardiac compressions in the delivery room, or major birth defect were also risk factors for neonatal transport. CONCLUSION: As many neonates receive transport within the first week after birth, there may be opportunities for quality improvement activities in this area.

Extreme hyperbilirubinemia and rescue exchange transfusion in California from 2007 to 2012.

OBJECTIVE: To evaluate the impact of statewide learning collaboratives that used national guidelines to manage jaundice on the serial prevalence of extreme hyperbilirubinemia (EHB, total bilirubin ⩾25 mg dl(-1)) and exchange transfusions introduced in California Perinatal Quality Care Collaborative (CPQCC) hospitals in 2007. STUDY DESIGN: Adverse outcomes were retrieved from statewide databases on re-admissions for live births ⩾35 weeks' gestation (2007 to 2012) in diverse CPQCC hospitals. Individual and cumulative select perinatal risk factors and frequencies were the outcomes measures. RESULTS: For 3 172 762 babies (2007 to 2012), 92.5% were ⩾35 weeks' gestation. Statewide EHB and exchange rates decreased from 28.2 to 15.3 and 3.6 to 1.9 per 100 000 live births, respectively. From 2007 to 2012, the trends for TB>25 mg dl(-1) rates were -0.92 per 100 000 live births per year (95% CI: -3.71 to 1.87, P=0.41 and R(2)=0.17). CONCLUSION: National guidelines complemented by statewide learning collaboratives can decrease or modify outcomes among all birth facilities and impact clinical practice behavior.

Women's prepregnancy underweight as a risk factor for preterm birth: a retrospective study.

OBJECTIVE: To investigate the distribution of known factors for preterm birth (PTB) by severity of maternal underweight; to investigate the risk-adjusted relation between severity of underweight and PTB, and to assess whether the relation differed by gestational age. DESIGN: Retrospective cohort study. SETTING: State of California, USA. METHODS: Maternally linked hospital and birth certificate records of 950 356 California deliveries in 2007-2010 were analysed. Singleton live births of women whose prepregnancy body mass index (BMI) was underweight (<18.5 kg/m2 ) or normal (18.50-24.99 kg/m2 ) were analysed. Underweight BMI was further categorised as: severe (<16.00), moderate (16.00-16.99) or mild (17.00-18.49). PTB was grouped as 22-27, 28-31, 32-36 or <37 weeks (compared with 37-41 weeks). Adjusted multivariable Poisson regression modeling was used to estimate relative risk for PTB. MAIN OUTCOME MEASURES: Risk of PTB. RESULTS: About 72 686 (7.6%) women were underweight. Increasing severity of underweight was associated with increasing percent PTB: 7.8% (n = 4421) in mild, 9.0% (n = 1001) in moderate and 10.2% (475) in severe underweight. The adjusted relative risk of PTB also significantly increased: adjusted relative risk (aRR) = 1.22 (95% CI 1.19-1.26) in mild, aRR = 1.41 (95% CI 1.32-1.50) in moderate and aRR = 1.61 (95% CI 1.47-1.76) in severe underweight. These findings were similar in spontaneous PTB, medically indicated PTB, and the gestational age groupings. CONCLUSION: Increasing severity of maternal prepregnancy underweight BMI was associated with increasing risk-adjusted PTB at <37 weeks. This increasing risk was of similar magnitude in spontaneous and medically indicated births and in preterm delivery at 28-31 and at 32-36 weeks of gestation. TWEETABLE ABSTRACT: Increasing severity of maternal underweight BMI was associated with increasing risk of preterm birth.

Inhaled nitric oxide use in preterm infants in California neonatal intensive care units.

OBJECTIVE: To describe inhaled nitric oxide (iNO) exposure in preterm infants and variation in neonatal intensive care unit (NICU) use. STUDY DESIGN: This was a retrospective cohort study of infants, 22 to 33+6/7 weeks of gestational age (GA), during 2005 to 2013. Analyses were stratified by GA and included population characteristics, iNO use over time and hospital variation. RESULTS: Of the 65 824 infants, 1718 (2.61%) received iNO. Infants, 22 to 24+6/7 weeks of GA, had the highest incidence of iNO exposure (6.54%). Community NICUs (n=77, median hospital use rate 0.7%) used less iNO than regional NICUs (n=23, median hospital use rate 5.8%). In 22 to 24+6/7 weeks of GA infants, the median rate in regional centers was 10.6% (hospital interquartile range 3.8% to 22.6%). CONCLUSION: iNO exposure varied with GA and hospital level, with the most use in extremely premature infants and regional centers. Variation reflects a lack of consensus regarding the appropriate use of iNO for preterm infants.

Body Mass Index Change between Pregnancies and Risk of Spontaneous Preterm Birth.

Objective Studies have reported an increased risk of spontaneous preterm birth associated with elevated prepregnancy body mass index (BMI) among nulliparous but not multiparous women. We examined whether changes in BMI and weight between pregnancies contributed to risk of preterm birth among obese (BMI > 29 kg/m(2)) women. Study Design This study utilized maternally linked California birth records of sequential singleton births between 2007 and 2010. Preterm birth was defined as 20 to 31 or 32 to 36 weeks of gestation. BMI was examined as category change and by tertile of weight change. Primary analyses included women without diabetes or hypertensive disorders; these women were compared with those without prior preterm birth, women with preterm deliveries preceded by spontaneous preterm labor, and women without any exclusions (i.e., diabetes or hypertensive disorders). Results Analyses showed that obesity was not associated with increased risk of spontaneous preterm birth among multiparous women. Women whose BMI increased had a decreased risk of spontaneous preterm birth at 32 to 36 weeks. Change in BMI or weight between pregnancies did not substantively alter results. Conclusion Among multiparous women, obesity was associated with reduced risk of spontaneous preterm delivery. This observed association is complex and may be influenced by maternal age, gestational age, placental insufficiency, and altered immune response.

Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth weight infants.

OBJECTIVE: To determine the association between antenatal steroids administration and intraventricular hemorrhage rates. METHODS: We used cross-sectional data from the California Perinatal Quality Care Collaborative during 2007 to 2013 for infants ⩽32 weeks gestational age. Using multivariable logistic regression, we evaluated the effect of antenatal steroids on intraventricular hemorrhage, stratified by gestational age. RESULTS: In 25 979 very-low-birth weight infants, antenatal steroid use was associated with a reduction in incidence of any grade of intraventricular hemorrhage (odds ratio=0.68, 95% confidence interval: 0.62, 0.75) and a reduction in incidence of severe intraventricular hemorrhage (odds ratio=0.51, 95% confidence interval: 0.45, 0.58). This association was seen across gestational ages ranging from 22 to 29 weeks. CONCLUSIONS: Although current guidelines recommend coverage for preterm birth at 24 to 34 weeks gestation, our results suggest that treatment with antenatal steroids may be beneficial even before 24 weeks of gestational age.

Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth.

OBJECTIVE: To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes. DESIGN: Population-based cohort. SETTING: California, United States of America. POPULATION: From a total population of 1 004 039 live singleton births in 2009 and 2010, 841 665 pregnancies with linked birth certificate and hospital discharge records were included. METHODS: Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125 202 pregnancies with available first-trimester and second-trimester serum biomarker results. MAIN OUTCOME MEASURE: PTB by subtype. RESULTS: In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ≥ 60 months, low first-trimester pregnancy-associated plasma protein A, high second-trimester α-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32 weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2). CONCLUSIONS: Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies. TWEETABLE ABSTRACT: Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

Estimating the quality of neonatal transport in California.

OBJECTIVE: To develop a strategy to assess the quality of neonatal transport based on change in neonatal condition during transport. STUDY DESIGN: The Canadian Transport Risk Index of Physiologic Stability (TRIPS) score was optimized for a California (Ca) population using data collected on 21 279 acute neonatal transports, 2007 to 2009, using models predicting (2/3) and validating (1/3) mortality within 7 days of transport. Quality Change Point 10th percentile (QCP10), a benchmark of the greatest deterioration seen in 10% of the transports by top-performing teams, was established. RESULT: Compared with perinatal variables (0.79), the Ca-TRIPS had a validation receiver operator characteristic area for prediction of death of 0.88 in all infants and 0.86 in infants transported after day 7. The risk of death increased 2.4-fold in infants whose deterioration exceeded the QCP10. CONCLUSION: We present a practical, benchmarked, risk-adjusted, estimate of the quality of neonatal transport.

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 to 1000 g 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 to risk-adjusted LOS. RESULTS: There were 2012 infants with median LOS 79 days (range 23 to 219). Lower birth weight, lack of antenatal steroids and lower Apgar score were associated with longer LOS. There was negligible correlation 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.

Therapeutic hypothermia during neonatal transport: data from the California Perinatal Quality Care Collaborative (CPQCC) and California Perinatal Transport System (CPeTS) for 2010.

OBJECTIVE: To evaluate cooling practices and neonatal outcomes in the state of California during 2010 using the California Perinatal Quality Care Collaborative and California Perinatal Transport System databases. STUDY DESIGN: Database analysis to determine the perinatal and neonatal demographics and outcomes of neonates cooled in transport or after admission to a cooling center. RESULT: Of the 223 infants receiving therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) in California during 2010, 69% were cooled during transport. Despite the frequent use of cooling in transport, cooling center admission temperature was in the target range (33-34 °C) in only 62 (44%). Among cooled infants, gestational age was <35 weeks in 10 (4.5%). For outborn and transported infants, chronologic age at the time of cooling initiation was >6 h in 20 (11%). When initiated at the birth hospital, cooling was initiated at <6 h of age in 131 (92.9%). CONCLUSION: More than half of the infants cooled in transport do not achieve target temperature by the time of arrival at the cooling center. The use of cooling devices may improve temperature regulation on transport.

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). STUDY DESIGN: In a modified Delphi process, a panel rated 28 quality measures. We assessed clinician agreement with the Delphi panel by surveying a sample of 48 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. RESULT: In all, 23 (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'. CONCLUSION: Practicing clinicians agree with an expert panel on the measures that should be included in the Baby-MONITOR, enhancing face validity.

Hypothermia in very low birth weight infants: distribution, risk factors and outcomes.

OBJECTIVE: The objective of this study was to study the epidemiology of neonatal hypothermia in preterm infants using World Health Organization (WHO) temperature criteria. STUDY DESIGN: A population-based cohort of 8782 very low birth weight (VLBW) infants born in California neonatal intensive care units in 2006 and 2007. Associations between admission hypothermia and maternal and neonatal characteristics and outcomes were determined using logistic regression. RESULT: In all, 56.2% of infants were hypothermic. Low birth weight, cesarean delivery and a low Apgar score were associated with hypothermia. Spontaneous labor, prolonged rupture of membranes and antenatal steroid administration were associated with decreased risk of hypothermia. Moderate hypothermia was associated with higher risk of intraventricular hemorrhage (IVH). Moderate and severe hypothermic conditions were associated with risk of death. CONCLUSION: Hypothermia by WHO criteria is prevalent in VLBW infants and is associated with IVH and mortality. Use of WHO criteria could guide the need for quality improvement projects targeted toward the most vulnerable infants.

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

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

Neonatal mortality among low birth weight infants during the initial months of the academic year.

OBJECTIVE: Proper management of very low weight (<1500 g) infants requires specific expertise. During July and August, pediatric interns start new rotations and advance in responsibilities by postgraduate level. We test the hypothesis that low weight births in teaching hospitals exhibit increased neonatal mortality during the initial training months. STUDY DESIGN: Population-based cohort of 5184 very low weight and 15 232 moderately low weight infants in California from 19 regional teaching hospitals with medical training programs. Logistic regression methods controlled for both individual covariates and temporal patterns in neonatal mortality. RESULT: We found no difference in neonatal mortality between very low weight infants born in teaching hospitals during July and August and those born in other months (adjusted odds ratio (AOR): 0.98, 95% confidence interval (CI), 0.78 to 1.23). Investigation of moderately low birth weight infants also indicated no increased neonatal mortality. CONCLUSION: Infants most likely to die in the neonatal period do not appear to be at elevated risk of neonatal mortality during July and August.