Association of Sickle Cell Disease With Racial Disparities and Severe Maternal Morbidities in Black Individuals.

2023

808-817

08/2023

2168-6211

IMPORTANCE: Little is known about the association between sickle cell disease (SCD) and severe maternal morbidity (SMM).

OBJECTIVE: To examine the association of SCD with racial disparities in SMM and with SMM among Black individuals.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a retrospective population-based investigation of individuals with and without SCD in 5 states (California [2008-2018], Michigan [2008-2020], Missouri [2008-2014], Pennsylvania [2008-2014], and South Carolina [2008-2020]) delivering a fetal death or live birth. Data were analyzed between July and December 2022.

EXPOSURE: Sickle cell disease identified during the delivery admission by using International Classification of Diseases, Ninth Revision and Tenth Revision codes.

MAIN OUTCOMES AND MEASURES: The primary outcomes were SMM including and excluding blood transfusions during the delivery hospitalization. Modified Poisson regression was used to estimate risk ratios (RRs) adjusted for birth year, state, insurance type, education, maternal age, Adequacy of Prenatal Care Utilization Index, and obstetric comorbidity index.

RESULTS: From a sample of 8 693 616 patients (mean [SD] age, 28.5 [6.1] years), 956 951 were Black individuals (11.0%), of whom 3586 (0.37%) had SCD. Black individuals with SCD vs Black individuals without SCD were more likely to have Medicaid insurance (70.2% vs 64.6%), to have a cesarean delivery (44.6% vs 34.0%), and to reside in South Carolina (25.2% vs 21.5%). Sickle cell disease accounted for 8.9% and for 14.3% of the Black-White disparity in SMM and nontransfusion SMM, respectively. Among Black individuals, SCD complicated 0.37% of the pregnancies but contributed to 4.3% of the SMM cases and to 6.9% of the nontransfusion SMM cases. Among Black individuals with SCD compared with those without, the crude RRs of SMM and nontransfusion SMM during the delivery hospitalization were 11.9 (95% CI, 11.3-12.5) and 19.8 (95% CI, 18.5-21.2), respectively, while the adjusted RRs were 3.8 (95% CI, 3.3-4.5) and 6.5 (95% CI, 5.3-8.0), respectively. The SMM indicators that incurred the highest adjusted RRs included air and thrombotic embolism (4.8; 95% CI, 2.9-7.8), puerperal cerebrovascular disorders (4.7; 95% CI, 3.0-7.4), and blood transfusion (3.7; 95% CI, 3.2-4.3).

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, SCD was found to be an important contributor to racial disparities in SMM and was associated with an elevated risk of SMM among Black individuals. Efforts from the research community, policy makers, and funding agencies are needed to advance care among individuals with SCD.

10.1001/jamapediatrics.2023.1580

JAMA Pediatr

37273202

Racial and Ethnic Disparities in Sudden Unexpected Infant Death Among US Infants Born Preterm.

2023

113498

05/2023

1097-6833

OBJECTIVE: To investigate among US infants born at <37 weeks gestation (a) racial and ethnic disparities in sudden unexpected infant death (SUID) and (b) state variation in SUID rates and non-Hispanic Black (NHB)-non-Hispanic White (NHW) SUID disparity ratio.

METHODS: In this retrospective cohort analysis of linked birth and death certificates from 50 states from 2005 to 2014, SUID was defined by the following International Classification of Diseases, 9th or 10th edition, codes listed on death certificates: (7980, R95 or Recode 135; ASSB: E913, W75 or Recode 146; Unknown: 7999 R99 or Recode 134). Multivariable models were used to assess the independent association between maternal race and ethnicity and SUID, adjusting for several maternal and infant characteristics. The NHB-NHW SUID disparity ratios were calculated for each state.

RESULTS: Among 4 086 504 preterm infants born during the study period, 8096 infants (0.2% or 2.0 per 1000 live births) experienced SUID. State variation in SUID ranged from the lowest rate of 0.82 per 1000 live births in Vermont to the highest rate of 3.87 per 1000 live births in Mississippi. Unadjusted SUID rates across racial and ethnic groups varied from 0.69 (Asian/Pacific Islander) to 3.51 (NHB) per 1000 live births. In the adjusted analysis, compared with NHW infants, NHB and Alaska Native/American Indian preterm infants had greater odds of SUID (aOR, 1.5;[95% CI, 1.42-1.59] and aOR, 1.44 [95% CI, 1.21-1.72]) with varying magnitude of SUID rates and NHB-NHW disparities across states.

CONCLUSIONS: Significant racial and ethnic disparities in SUID among preterm infants exist with variation across US states. Additional research to identify the drivers of these disparities within and across states is needed.

10.1016/j.jpeds.2023.113498

J Pediatr

37211205

Correction To: Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2023

05/2023

1530-0447

10.1038/s41390-023-02662-7

Pediatr Res

37225780

County-Level Maternal Vulnerability and Preterm Birth in the US.

2023

e2315306

05/2023

2574-3805

IMPORTANCE: Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed.

OBJECTIVE: To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023.

EXPOSURE: The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence.

MAIN OUTCOMES AND MEASURES: The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category.

RESULTS: Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.

10.1001/jamanetworkopen.2023.15306

JAMA Netw Open

37227724

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

2023

e2312277

05/2023

2574-3805

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

10.1001/jamanetworkopen.2023.12277

JAMA Netw Open

37155165

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2023

1772-1779

05/2023

1530-0447

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.

METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.

RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.

CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.

IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

10.1038/s41390-022-02279-2

Pediatr Res

36042329

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants.

2023

e2312277

05/2023

2574-3805

IMPORTANCE: Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended.

OBJECTIVE: To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022.

EXPOSURE: Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth.

MAIN OUTCOMES AND MEASURES: The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age.

RESULTS: A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%).

CONCLUSIONS AND RELEVANCE: Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

10.1001/jamanetworkopen.2023.12277

JAMA Netw Open

37155165

Trends in Resources for Neonatal Intensive Care at Delivery Hospitals for Infants Born Younger Than 30 Weeks' Gestation, 2009-2020.

2023

e2312107

05/2023

2574-3805

IMPORTANCE: In an ideal regionalized system, all infants born very preterm would be delivered at a large tertiary hospital capable of providing all necessary care.

OBJECTIVE: To examine whether the distribution of extremely preterm births changed between 2009 and 2020 based on neonatal intensive care resources at the delivery hospital.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 822 Vermont Oxford Network (VON) centers in the US between 2009 and 2020. Participants included infants born at 22 to 29 weeks' gestation, delivered at or transferred to centers participating in the VON. Data were analyzed from February to December 2022.

EXPOSURES: Hospital of birth at 22 to 29 weeks' gestation.

MAIN OUTCOMES AND MEASURES: Birthplace neonatal intensive care unit (NICU) level was classified as A, restriction on assisted ventilation or no surgery; B, major surgery; or C, cardiac surgery requiring bypass. Level B centers were further divided into low-volume (<50 inborn infants at 22 to 29 weeks' gestation per year) and high-volume (≥50 inborn infants at 22 to 29 weeks' gestation per year) centers. High-volume level B and level C centers were combined, resulting in 3 distinct NICU categories: level A, low-volume B, and high-volume B and C NICUs. The main outcome was the change in the percentage of births at hospitals with level A, low-volume B, and high-volume B or C NICUs overall and by US Census region.

RESULTS: A total of 357 181 infants (mean [SD] gestational age, 26.4 [2.1] weeks; 188 761 [52.9%] male) were included in the analysis. Across regions, the Pacific (20 239 births [38.3%]) had the lowest while the South Atlantic (48 348 births [62.7%]) had the highest percentage of births at a hospital with a high-volume B- or C-level NICU. Births at hospitals with A-level NICUs increased by 5.6% (95% CI, 4.3% to 7.0%), and births at low-volume B-level NICUs increased by 3.6% (95% CI, 2.1% to 5.0%), while births at hospitals with high-volume B- or C-level NICUs decreased by 9.2% (95% CI, -10.3% to -8.1%). By 2020, less than half of the births for infants at 22 to 29 weeks' gestation occurred at hospitals with high-volume B- or C-level NICUs. Most US Census regions followed the nationwide trends; for example, births at hospitals with high-volume B- or C-level NICUs decreased by 10.9% [95% CI, -14.0% to -7.8%) in the East North Central region and by 21.1% (95% CI, -24.0% to -18.2%) in the West South Central region.

CONCLUSIONS AND RELEVANCE: This retrospective cohort study identified concerning deregionalization trends in birthplace hospital level of care for infants born at 22 to 29 weeks' gestation. These findings should serve to encourage policy makers to identify and enforce strategies to ensure that infants at the highest risk of adverse outcomes are born at the hospitals where they have the best chances to attain optimal outcomes.

10.1001/jamanetworkopen.2023.12107

JAMA Netw Open

37145593

Healthcare Costs of Major Morbidities Associated with Prematurity in US Children's Hospitals.

2023

53-62.e4

05/2023

1097-6833

OBJECTIVE: To evaluate the healthcare costs attributed to major morbidities associated with prematurity, namely, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and nosocomial infections.

STUDY DESIGN: This was a retrospective analysis of infants born at 24-30 weeks of gestation, admitted to children's hospitals in the Pediatric Health Information System between 2009 and 2018. Charges were adjusted by geographical price index, converted to costs using cost-to-charge ratios, inflated to 2018 US$, and total costs were accumulated for the initial hospitalization. Quantile regressions, which are less prone to bias from extreme outliers, were used to examine the incremental costs attributed to each morbidity across the entire cost distribution, including the median.

RESULTS: There were 19 232 patients from 30 children's hospitals who were eligible. Higher costs were seen in lower gestational age, more severe morbidity, and those with higher number of comorbidities. Patients with surgical NEC, severe ROP, and severe BPD were the costliest with median total costs of $430 860, $413 825, and $399 495, respectively. Quantile regressions showed surgical NEC had the highest adjusted median incremental total cost ($48 621; 95% CI, $39 617-$57 626) followed by severe BPD ($35 773; 95% CI, $32 018-$39 528) and severe ROP ($22 561; 95% CI, $16 699-$28 423). Quantile regressions also revealed that surgical NEC, severe BPD, and severe ROP had increasing incremental costs at higher total cost percentiles, indicating these morbidities have a greater cost impact on the costliest patients.

CONCLUSIONS: Severe BPD, surgical NEC, and severe ROP are the costliest morbidities and contribute the most incremental costs especially for the higher costs patients.

10.1016/j.jpeds.2022.11.038

J Pediatr

36509157

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

2023

1772-1779

05/2023

1530-0447

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood.

METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period.

RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment.

CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development.

IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

10.1038/s41390-022-02279-2

Pediatr Res

36042329