Risk of postpartum readmission after hypertensive disorder of pregnancy and variation by discharge antihypertensive medication prescription.

BACKGROUND: Patients with hypertensive disorders of pregnancy have a high rate of postpartum readmission. OBJECTIVE: This study aimed to evaluate whether the type of antihypertensive medication prescribed at discharge was associated with postpartum readmission after a hypertensive disorder of pregnancy. STUDY DESIGN: This was a retrospective cohort study of 57,254 pregnancies complicated by hypertensive disorders of pregnancy between 2012 and 2018 in the electronic obstetrical database of Kaiser Permanente Northern California. Postpartum readmissions occurred within 6 weeks after discharge from delivery hospitalization. Cox regression models were used to evaluate the association between the type of antihypertensive medication prescription at discharge (none, labetalol only, nifedipine only, or 2 or more antihypertensive medications) and postpartum readmission, adjusted for type of hypertensive disorder of pregnancy, final inpatient systolic and diastolic blood pressures, age, body mass index, mode of delivery, insurance status, race and ethnicity, delivery facility, comorbidity score, smoking, preterm delivery, parity, and Neighborhood Deprivation Index. RESULTS: Among eligible patients with a hypertensive disorder of pregnancy, 1696 (3.0%) were readmitted within 6 weeks. Approximately 86% of patients were discharged without a prescription for antihypertensive medication; among those discharged with a prescription for antihypertensive medication, most were prescribed either labetalol only (54%) or nifedipine only (30%). The unadjusted readmission risk was the highest for patients discharged with a prescription for labetalol only (7.6%), lower for those discharged with a prescription for nifedipine only (3.6%) or 2 or more antihypertensive medications (3.2%), and the lowest for those discharged without a prescription for antihypertensive medication (2.5%). In the adjusted models, compared with discharge without a prescription for antihypertensive medication, discharge with a prescription for labetalol only was associated with a 63% (hazard ratio, 1.63; 95% confidence interval, 1.41-1.88) greater incidence of postpartum readmission, and discharge with a prescription for nifedipine only and discharge with a prescription for 2 or more antihypertensive medications were associated with 26% (hazard ratio, 0.74; 95% confidence interval, 0.59-0.93) and 47% (hazard ratio, 0.53; 95% confidence interval, 0.38-0.74) lower incidence of postpartum readmission, respectively. There was no strong evidence to suggest that the effect of the type of antihypertensive medication at discharge on the incidence of readmission varied by race and ethnicity (interaction P=.88). The results indicating an elevated risk associated with labetalol use were consistent in models that excluded patients with prepregnancy hypertension. CONCLUSION: Discharge with a prescription for nifedipine alone or multiple antihypertensive medications (vs no medication) was associated with a lower incidence of readmission, whereas discharge with a prescription for labetalol alone was associated with an elevated readmission incidence. A large-scale, prospective research to compare the effectiveness of commonly prescribed hypertension medications at discharge is warranted.

Adverse short- and long-term outcomes among infants with mild neonatal encephalopathy.

BACKGROUND: Studies in newborns with mild neonatal encephalopathy (mNE) demonstrated normal outcomes, but recent literature suggests otherwise. METHODS: This retrospective cohort study examined inborn infants between 2014 and 2017. Biochemical and clinical characteristics determined the presence of NE and an encephalopathy score categorized infants as Definite or Possible mNE. An Unexposed control group consisted of newborns not meeting the inclusion criteria. Long-term outcomes assessed included cerebral palsy, seizures, developmental disorder, and motor and speech delay. The association of mNE with seizure disorder by 3 years of age was assessed with logistic regression and developmental disorders with Cox proportional hazards models. RESULTS: Of the 156,501 births, we identified 130 with Definite mNE and 445 with Possible mNE (0.8 and 2.8 per 1000 births, respectively). Both groups had significantly higher rates of any developmental disorder and motor and speech delay when compared to the Unexposed (p < 0.05, except for p = 0.07 for motor delay in the Possible NE group). The Definite mNE group had higher rates of developmental disorder and motor and speech delay when compared to the Unexposed with hazard ratios (95% CI) 2.0 (1.2-3.2), 3.7 (1.5-8.8), and 2.1 (1.3-3.5), respectively. CONCLUSIONS: An estimate of short- and long-term consequences of mNE suggests that there may be a higher risk of adverse outcome. IMPACT: Infants with mild NE are at significant risk for adverse short- and long-term outcomes. The risk of having an abnormal long-term outcome at 3 years of age were doubled in the mild NE group compared to the Unexposed group. Randomized clinical trials are needed as neuroprotective strategies may mitigate these.

Placental Histopathologic Findings of a Large Cohort of Patients With SARS-CoV-2 Infection During Pregnancy.

Pregnant individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at a higher risk for adverse pregnancy outcomes. Previous small cohort studies have shown increased frequency of placental lesions associated with maternal vascular malperfusion, fetal vascular malperfusion, and inflammation among patients with SARS-CoV-2, without controlling for cardiometabolic risk factors among many such patients. We aimed to evaluate whether SARS-CoV-2 infection during pregnancy is independently associated with placental abnormalities when controlling for risk factors that could affect placental histopathology. Retrospective cohort study of placentas from singleton pregnancies in Kaiser Permanente Northern California from March to December 2020. Pathologic findings were compared among those with confirmed cases of SARS-CoV-2 during pregnancy and those without. We examined the association between SARS-CoV-2 infection and categorical placental pathologies, controlling for maternal age, gestational age, prepregnancy body mass index, gestational hypertension, preeclampsia/eclampsia, preexisting diabetes, history of thrombosis, and stillbirth. A total of 2,989 singleton gestation placentas were analyzed, 416 (13%) from pregnancies with SARS-CoV-2 infection and 2,573 (86%) from those without infection. Among placentas from pregnancies with SARS-CoV-2, 54.8% had evidence of inflammation, 27.1% maternal malperfusion abnormality, 20.7% massive perivillous fibrin or chronic villitis, 17.3% villous capillary abnormality, and 15.1% fetal malperfusion. After controlling for risks factors and stratifying interval time between SARS-CoV-2 infection and delivery, no association was found between placental abnormalities and SARS-CoV-2 infection during pregnancy. SARS-CoV-2 infection was not associated with an increased risk of placentally mediated adverse outcomes during pregnancy, compared with placentas sent for other indications, in this large diverse cohort.

The effect of hospital phototherapy on early breastmilk feeding.

BACKGROUND: The effect of phototherapy on breastmilk feeding is unclear. OBJECTIVE: To estimate the effect of inpatient phototherapy on breastmilk feeding at 2-month well-child visits. METHODS: We performed a retrospective cohort study using electronic health record data. From births at 16 Kaiser Permanente Northern California hospitals (2013-2017), we identified a cohort of infants ≥ 35 weeks' gestation with total serum bilirubin levels close to the American Academy of Pediatrics 2004 phototherapy threshold during their birth hospitalisation. We compared self-reported breastmilk feeding at 2-month well-child visits among those who had and had not received birth hospitalisation phototherapy, adjusting for bilirubin levels and other confounding variables. We used multiple imputation (K = 200) to address missing data. RESULTS: Approximately a quarter of infants in the cohort (24.5%) received phototherapy during their birth hospitalisation. At the 2-month visit, exclusive breastmilk feeding was less common (RR 0.91, 95% interval [CI] 0.88, 0.95) among those who received phototherapy (41.3%) than those who did not (45.2%). However, no association remained after adjusting for potential confounders (RR 0.99, 95% CI 0.95, 1.04; average treatment effect on the treated [ATET] -0.2%, 95% CI -2.0%, 1.5%). In contrast, any breastmilk feeding was similar between infants who did (76.8%) and did not get phototherapy (77.9%). After adjusting for confounders, phototherapy had a slightly positive association with any breastmilk feeding at 2 months (RR 1.02, 95% CI 1.00, 1.04). Among infants who received phototherapy, the proportion being fed any breastmilk at the 2-month visit was an estimated 1.6 percentage points higher than it would have been if they had not received phototherapy (ATET 1.6%, 95% CI 0.1%, 3.1%). Multiple imputation results were similar. CONCLUSIONS: Birth hospitalisation phototherapy can be delivered in a way that does not adversely affect breastmilk feeding at 2 months.

Trends and racial and ethnic disparities in the prevalence of pregestational type 1 and type 2 diabetes in Northern California: 1996-2014.

BACKGROUND: Despite concern for adverse perinatal outcomes in women with diabetes mellitus before pregnancy, recent data on the prevalence of pregestational type 1 and type 2 diabetes mellitus in the United States are lacking. OBJECTIVE: The purpose of this study was to estimate changes in the prevalence of overall pregestational diabetes mellitus (all types) and pregestational type 1 and type 2 diabetes mellitus and to estimate whether changes varied by race-ethnicity from 1996-2014. STUDY DESIGN: We conducted a cohort study among 655,428 pregnancies at a Northern California integrated health delivery system from 1996-2014. Logistic regression analyses provided estimates of prevalence and trends. RESULTS: The age-adjusted prevalence (per 100 deliveries) of overall pregestational diabetes mellitus increased from 1996-1999 to 2012-2014 (from 0.58 [95% confidence interval, 0.54-0.63] to 1.06 [95% confidence interval, 1.00-1.12]; Ptrend <.0001). Significant increases occurred in all racial-ethnic groups; the largest relative increase was among Hispanic women (121.8% [95% confidence interval, 84.4-166.7]); the smallest relative increase was among non-Hispanic white women (49.6% [95% confidence interval, 27.5-75.4]). The age-adjusted prevalence of pregestational type 1 and type 2 diabetes mellitus increased from 0.14 (95% confidence interval, 0.12-0.16) to 0.23 (95% confidence interval, 0.21-0.27; Ptrend <.0001) and from 0.42 (95% confidence interval, 0.38-0.46) to 0.78 (95% confidence interval, 0.73-0.83; Ptrend <.0001), respectively. The greatest relative increase in the prevalence of type 1 diabetes mellitus was in non-Hispanic white women (118.4% [95% confidence interval, 70.0-180.5]), who had the lowest increases in the prevalence of type 2 diabetes mellitus (13.6% [95% confidence interval, -8.0 to 40.1]). The greatest relative increase in the prevalence of type 2 diabetes mellitus was in Hispanic women (125.2% [95% confidence interval, 84.8-174.4]), followed by African American women (102.0% [95% confidence interval, 38.3-194.3]) and Asian women (93.3% [95% confidence interval, 48.9-150.9]). CONCLUSIONS: The prevalence of overall pregestational diabetes mellitus and pregestational type 1 and type 2 diabetes mellitus increased from 1996-1999 to 2012-2014 and racial-ethnic disparities were observed, possibly because of differing prevalence of maternal obesity. Targeted prevention efforts, preconception care, and disease management strategies are needed to reduce the burden of diabetes mellitus and its sequelae.

Prevalence and neonatal factors associated with autism spectrum disorders in preterm infants.

OBJECTIVES: To determine the prevalence of autism spectrum disorders (ASD) across gestational age, examine the risk of ASD by gestational age controlling for other risk factors, and identify potential risk factors in the neonatal intensive care unit. STUDY DESIGN: A retrospective cohort of infants born at ≥ 24 weeks between January 1, 2000, and December 31, 2007 at 11 Kaiser Permanente Northern California hospitals (n = 195,021). ASD cases were defined by a diagnosis made at a Kaiser Permanente ASD evaluation center, by a clinical specialist, or by a pediatrician. Cox proportional hazards regression models were used to evaluate the association between gestational age and ASD as well as potential risk factors in the neonatal intensive care unit and ASD. RESULTS: The prevalence of ASD in infants <37 weeks was 1.78% compared with 1.22% in infants born ≥ 37 weeks (P < .001). Compared with term infants, infants born at 24-26 weeks had an adjusted hazard ratio (HR) for a diagnosis of ASD of 2.7 (95% CI 1.5-5.0). Infants born at 27-33 weeks (adjusted HR 1.4, 95% CI 1.1-1.8) and 34-36 weeks (adjusted HR 1.3, 95% CI 1.1-1.4) were also at increased risk. High frequency ventilation and intracranial hemorrhage were associated with ASD in infants < 34 weeks. CONCLUSIONS: ASD was ~ 3 times more prevalent in infants <27 weeks compared with term infants. Each week of shorter gestation was associated with an increased risk of ASD. High frequency ventilation and intracranial hemorrhage were associated with ASD among infants <34 weeks.

Maternal treatment with selective serotonin reuptake inhibitors during pregnancy and delayed neonatal adaptation: a population-based cohort study.

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) use is common in pregnancy. It is associated with delayed neonatal adaptation. Most previous studies have not adjusted for the severity of maternal mental health disorders or examined the impact of SSRI type and dosage. We examined whether treatment with SSRIs in late pregnancy (after 20 weeks) is associated with delayed neonatal adaptation independent of maternal depression and anxiety. DESIGN, SETTING AND PATIENTS: Retrospective population-based birth cohort of 280 090 term infants born at 15 Kaiser Permanente Northern California hospitals, 2011-2019. Individual-level pharmacy, maternal, pregnancy and neonatal data were obtained from electronic medical records. EXPOSURE: Dispensed maternal SSRI prescription after 20 weeks of pregnancy. MAIN OUTCOME MEASURES: Delayed neonatal adaptation defined as a 5 min Apgar score ≤5, resuscitation at birth or admission to a neonatal intensive care unit for respiratory support. Secondary outcomes included each individual component of the primary outcome and more severe neonatal outcomes (pulmonary hypertension, hypoxic-ischaemic encephalopathy and seizures). RESULTS: 7573 (2.7%) infants were exposed to SSRIs in late pregnancy. Delayed neonatal adaptation occurred in 11.2% of exposed vs 4.4% of unexposed infants (relative risk 2.52 (95% CI 2.36 to 2.70)). After multivariable adjustment, there was an association between SSRI exposure and delayed neonatal adaptation (adjusted OR 2.14 (95% CI 1.96 to 2.32)). This association was dose dependent. Escitalopram and fluoxetine were associated with the highest risk of delayed neonatal adaptation. CONCLUSIONS: Infants exposed to SSRIs have increased risks of delayed adaptation in a type and dose-dependent relationship, pointing toward a causal relationship.

Construction of a comprehensive fetal monitoring database for the study of perinatal hypoxic ischemic encephalopathy.

This article describes the methods used to build a large-scale database of more than 250,000 electronic fetal monitoring (EFM) records linked to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome. The database can be used to investigate how birth outcome is related to clinical and EFM features. The main steps involved in building the database were: (1) Acquiring the raw EFM recording and clinical records for each birth. (2) Assigning each birth to an objectively defined outcome class that included normal, acidosis, and hypoxic-ischemic encephalopathy. (3) Removing all personal health information from the EFM recordings and clinical records. (4) Preprocessing the deidentified EFM records to eliminate duplicates, reformat the signals, combine signals from different sensors, and bridge gaps to generate signals in a format that can be readily analyzed. (5) Post-processing the repaired EFM recordings to extract key features of the fetal heart rate, uterine activity, and their relations. (6) Populating a database that links the clinical information, EFM records, and EFM features to support easy querying and retrieval. •A multi-step process is required to build a comprehensive database linking electronic temporal fetal monitoring signals to a comprehensive set of clinical information about the infant, the mother, the pregnancy, labor, and outcome.•The current database documents more than 250,000 births including almost 4,000 acidosis and 400 HIE cases. This represents more than 80% of the births that occurred in 15 Northern California Kaiser Permanente Hospitals between 2011-2019. This is a valuable resource for studying the factors predictive of outcome.•The signal processing code and schemas for the database are freely available. The database will not be permitted to leave Kaiser firewalls, but a process is in place to allow interested investigators to access it.

Invited commentary: does neonatal hyperbilirubinemia cause asthma?

In an analysis of data from the US Collaborative Perinatal Project, Huang et al. (Am J Epidemiol. 2013;178(12):1691-1697) report an association between neonatal total serum bilirubin levels and childhood asthma. To consider the implications of this finding, we need to evaluate whether the association is causal. The results do not appear to be due to chance or any obvious biases. It is likely that the observed association is the result of a common cause of both hyperbilirubinemia and asthma (confounding). Polymorphisms in the glutathione S-transferase gene are a potential genetic confounder. The glutathione S-transferase M1-null phenotype has been linked to both neonatal hyperbilirubinemia and asthma in several studies. Before making any changes in practice aimed at lowering peak bilirubin levels to reduce asthma risk, it is vital to determine not only whether the association between higher bilirubin levels and asthma risk is causal, but also whether interventions to reduce peak bilirubin levels (or their duration) are associated with decreased risk of asthma (without evidence of other adverse effects). The study by Huang et al. should encourage further investigation of these questions.

Black race is not protective against hazardous bilirubin levels.

Although black race is considered protective against hyperbilirubinemia, black infants appear at increased risk of kernicterus. We found that although black infants have a lower risk of developing total serum bilirubin levels ≥ 20 mg/dL than white infants, they appear at greater risk of developing levels ≥ 30 mg/dL.

Prenatal Opioid Exposure and Neurodevelopmental Outcomes.

The opioid epidemic in the United States has resulted in a significant increase in opioid use disorder among pregnant women and a concomitant increase in the incidence of neonatal opioid withdrawal syndrome. The long-term consequences of prenatal opioid exposure on neurodevelopmental outcomes are not fully understood. Animal studies indicate increased neuronal apoptosis and decreased neuronal proliferation and myelination with opioid exposure in-utero. Meta-analyses of human studies suggest decreased cognition and psychomotor performance in infancy and deficits in cognition and language in preschool. However, current studies have primarily focused on heroin or methadone exposure and have been limited by small sample size, inadequate comparison groups, and the inability to account for additional risk factors and exposures such as polysubstance abuse, poor prenatal care, neonatal withdrawal and treatment with opioids, and unsupportive home environment. Future studies should aim to better understand the potential impact of these confounding factors on the neurodevelopmental trajectory of exposed infants. This review discusses the up-to-date literature, current gaps in knowledge, and considerations for future studies in the arena of prenatal opioid exposure and neurodevelopmental outcomes.

NICU Versus Mother/Baby Unit Admission for Low-Acuity Infants Born at 35 Weeks' Gestation.

OBJECTIVES: To estimate the effect of NICU admission of low-acuity infants born at 35 weeks' gestation versus care in a mother/baby unit, on inpatient and outpatient medical outcomes. METHODS: This retrospective cohort study included 5929 low-acuity infants born at 350/7 to 356/7 weeks' gestation at 13 Kaiser Permanente Northern California hospitals with level II or level III NICUs between January 1, 2011, and December 31, 2021. Exclusion criteria included congenital anomalies and early respiratory support or antibiotics. We used multivariable regression and regression discontinuity analyses to control for confounding variables. RESULTS: Infants admitted to the NICU within 2 hours of birth (n = 862, 14.5%) had a 58 hour adjusted (98-hour unadjusted) longer length of stay. NICU admission was associated with an increased probability of a length of stay ≥96 hours (67% vs 21%; adjusted odds ratio [aOR], 4.94; 95% confidence interval [CI], 3.96-6.16). Regression discontinuity results suggested a similar (57 hour) increase in length of stay. Readmission risk, primarily for jaundice, was lower for those admitted to the NICU (3% vs 6%; aOR, 0.43; 95% CI, 0.27-0.69). Infants admitted to the NICU were slightly less likely to be receiving exclusive breast milk at 6-month follow-up (15% vs 25%; aOR, 0.73; 95% CI, 0.55-0.97; adjusted marginal risk difference -5%). CONCLUSIONS: Admitting low-acuity infants born at 35 weeks' gestation to the NICU was associated with decreased readmission, but with longer length of stay and decreased exclusive breast milk feeding at 6 months. Routine NICU admission may be unnecessary for low-acuity infants born at 35 weeks' gestation.

Independent Impact of Eat, Sleep, Console Assessment on Neonatal Opioid Withdrawal Syndrome.

Compared with the Finnegan Neonatal Abstinence Scoring System (FNASS), the Eat, Sleep, Console (ESC) approach reduces pharmacotherapy and length of stay (LOS) for neonatal opioid withdrawal syndrome (NOWS) infants. The independent outcome contribution of ESC is unknown as the approach combines ESC assessment with additional management changes. Our objective was to evaluate ESC assessment's independent impact on outcomes compared with FNASS. We conducted a retrospective cohort study of in utero opioid-exposed infants ≥35 weeks gestation managed with FNASS versus ESC. Outcomes included pharmacotherapy initiation, LOS, length of pharmacotherapy, and emergency department visit/readmissions. Among 151 FNASS and 100 ESC managed infants, pharmacotherapy initiation (P = .47), LOS for all infants (P = .49), and LOS for pharmacologically treated infants (P = .68) were similar. Length of pharmacotherapy did not differ (P = .84). Emergency department evaluation/NOWS readmission was equally rare (P = .65). Using equivalent models of care, comparison of ESC and FNASS assessment tools showed no difference in NOWS outcomes.

Accuracy of diagnostic codes for prenatal opioid exposure and neonatal opioid withdrawal syndrome.

OBJECTIVE: Determine the accuracy of diagnostic codes in identifying Prenatal Opioid Exposure (POE) and Neonatal Opioid Withdrawal Syndrome (NOWS). STUDY DESIGN: A cross-sectional study of 374,222 mother-infant dyads with delivery from 01/01/2010 to 12/31/2019. We ascertained maternal diagnostic codes for opioid use during pregnancy and infant diagnostic codes for drug exposure and withdrawal. We assessed sensitivity and positive predictive value (PPV) for POE and NOWS, defined using laboratory, pharmacy, and clinical data. RESULTS: Maternal codes had low sensitivity (36.4%) and PPV (34.7%) for POE. Infant codes for drug exposure were neither sensitive for POE (14%) nor NOWS (31.6%) and had low PPV. Codes for newborn withdrawal had low sensitivity (31.6%) for detecting NOWS, but high PPV (85%). Sensitivity improved (95.1%) for NOWS requiring pharmacologic treatment. CONCLUSIONS: Diagnostic codes identify POE and NOWS poorly. Improved case identification would include pharmacy and laboratory results, and clearly defined criteria for evidence of withdrawal.

Total serum bilirubin exceeding exchange transfusion thresholds in the setting of universal screening.

OBJECTIVE: To describe the incidence and predictors of total serum bilirubin (TSB) levels that meet or exceed American Academy of Pediatrics (AAP) exchange transfusion (ET) thresholds in the setting of universal screening. STUDY DESIGN: We conducted a retrospective cohort analysis of electronic data on 18 089 newborns ≥35 weeks gestation born at Northern California Kaiser Permanente Medical Care Program hospitals implementing universal TSB screening in 2005 to 2007, with chart review for subjects with TSB levels reaching the AAP threshold for ET. RESULTS: The outcome developed in 22 infants (0.12%); 14 (63.6%) were <38 weeks gestation. Only one infant received an ET; none of the infants had documented sequelae. The first TSB was at least high-intermediate risk on the AAP risk-nomogram for all 22 infants and high-risk for those ≥38 weeks, but was less than the phototherapy level in 15 infants (68%). Of these 15 infants, 2 failed phototherapy and 13 did not have a TSB repeated in <24 hours. However, re-testing all infants at high-intermediate risk or greater would have required 2166 additional bilirubin tests. CONCLUSION: Screening was sensitive but not specific for predicting exchange threshold.

The Effect of Readmission for Phototherapy on Early Breast Milk Feeding.

OBJECTIVES: To estimate the effect of readmission for inpatient phototherapy on parent-reported exclusive and any breast milk feeding at 2-month well-child visits. METHODS: We performed a retrospective cohort study using electronic health record data. From births at 16 Kaiser Permanente Northern California hospitals (2013-2017), we identified a cohort of infants ≥35 weeks' gestation with outpatient total serum bilirubin levels ranging from 1 mg/dL below to 2.9 mg/dL above the American Academy of Pediatrics phototherapy threshold at <15 days of age. We compared breast milk feeding at 2-month well-child visits among those readmitted and not readmitted to the hospital for phototherapy, adjusting for bilirubin and other confounding variables. RESULTS: Approximately one-quarter (26.5%) of the cohort (n = 7729) were readmitted for phototherapy. Almost half (48.5%) of the infants who were not readmitted for phototherapy received exclusively breast milk at the 2-month visit compared with slightly fewer infants who were readmitted (42.9%). In both groups of infants, most (82.2% not readmitted and 81.2% readmitted) received any breast milk. Readmission for phototherapy was associated with a lower adjusted risk of exclusive breast milk feeding (adjusted risk ratio 0.90; 95% confidence interval [CI], 0.84 to 0.96), corresponding to a marginal absolute reduction in exclusive breast milk feeding of 5.0% (95% CI, -7.9% to -2.1%). It was not associated with a reduction in any breast milk feeding (adjusted risk ratio, 1.00; 95% CI, 0.97 to 1.02). CONCLUSIONS: Infants readmitted for phototherapy were more likely to receive any formula, but no less likely to receive any breast milk at 2-month well-child visits.

The clinical burden of extremely preterm birth in a large medical records database in the United States: Mortality and survival associated with selected complications.

BACKGROUND: Preterm birth is a leading cause of infant mortality, particularly for those born extremely prematurely (EP; <28 weeks' gestational age [GA]). Survivors are predisposed to complications such as bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). AIMS: To examine the epidemiology, complications, and mortality/survival among EP infants. STUDY DESIGN: Retrospective analysis of electronic medical records from the Kaiser Permanente Northern California database. SUBJECTS: EP infants live-born between 22 and <28 weeks' GA from 1997 to 2016. OUTCOME MEASURES: Cumulative all-cause mortality/survival were analyzed and stratified by GA (22 to <24, 24 to <26, 26 to <28 weeks), complications (BPD/CLD, IVH, ROP), and birth period (1997 to 2003, 2004 to 2009, 2010 to 2016). Cox proportional hazard models were constructed to assess the mortality risk associated with BPD/CLD or IVH. RESULTS: 2154 EP infants were identified; of these, 916 deaths were recorded. Mortality was highest during the first 3 months (41.7 % cumulative mortality), and few were reported after 2 years (42.5 % cumulative mortality). Mortality decreased with higher GA and over more recent birth periods. BPD/CLD and IVH grade 3/4 were associated with increased mortality risk versus no complications (adjusted hazard ratios 1.41 and 1.78, respectively). CONCLUSIONS: The risk of mortality is high during the first few months of life for EP infants, and is even higher for those with BPD and IVH. Despite an overall trend toward increased survival for EP infants, strategies targeting survival of EP infants with these complications are needed.

The clinical burden of extremely preterm birth in a large medical records database in the United States: complications, medication use, and healthcare resource utilization.

INTRODUCTION: Approximately 5% of global preterm births are extremely premature (EP), defined as occurring at less than 28 weeks gestational age. Advances in care have led to an increase in the survival of EP infants during the neonatal period. However, EP infants have a higher risk of developing complications such as bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). BPD and other respiratory morbidities are particularly prevalent among this population. To understand the healthcare resource utilization (HRU) of EP infants in the United States, the clinical and economic burden of extreme prematurity was examined in this retrospective study of data extracted from electronic medical records in the Kaiser Permanente Northern California (KPNC) health system. METHODS: The analysis included data from EP infants live-born between January 1997 and December 2016, and focused on complications and HRU up to 3 years corrected age (CA), covering the period up to December 2018. Stillbirths, infants born at <22 weeks gestational age, and infants with major congenital malformations were excluded. Complications of interest (BPD, IVH, and ROP) and medication use were compared by age group (≤1 year, >1 year and ≤2 years, and >2 years and ≤3 years CA). Analysis of HRU included hospital readmissions, ambulatory visits, and emergency room (ER) visits. RESULTS: A total of 2154 EP births (0.32% of total live births and 4.0% of preterm births that met the inclusion/exclusion criteria) were analyzed. The prevalence of EP birth showed a declining trend over time. ROP was the most commonly recorded complication during the birth hospitalization (37.1% any stage; 2.9% Stages 3 and 4). BPD was recorded in 34.3% of EP infants. IVH (any grade) was recorded in 22.7% of EP infants (6.4% Grades III and IV). A majority (78.7%) of EP infants were diagnosed with at least one respiratory condition during the first year CA, the most common being pneumonia (68.9%); the prevalence of respiratory conditions decreased over the second and third years CA. During the first 3 years CA, the most common medications prescribed to children born EP were inhaled bronchodilators (approximately 30% of children); at least 15% of children received systemic corticosteroids and inhaled steroids during this period. During the first 3 years CA, at least one hospital readmission was recorded for 16.4% of children born EP; 57.1% of these readmissions were related to respiratory conditions. At least one ER visit was recorded for 33.8% of children born EP, for which 53.1% were due to a respiratory condition. Ambulatory visits were recorded for 54.2% of EP children, for which 82.9% were due to a respiratory condition. CONCLUSIONS: The short- and long-term clinical burden of EP birth was high. The onset of BPD, IVH, and ROP was common during the birth hospitalization for EP infants. Medication use, hospital readmission, and clinic visits (ER and ambulatory) occurred frequently in these children during the first 3 years CA, and were commonly due to respiratory conditions. Strategies prioritizing the reduction of risk and severity of respiratory conditions may alleviate the clinical burden of EP birth over the long term.