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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

Time to positivity of blood cultures in neonatal late-onset bacteraemia.

OBJECTIVE: To determine the time to positivity (TTP) of blood cultures among infants with late-onset bacteraemia and predictors of TTP >36 hours. DESIGN: Retrospective cohort study. SETTING: 16 birth centres in two healthcare systems. PATIENTS: Infants with positive blood cultures obtained >72 hours after birth. OUTCOME: The main outcome was TTP, defined as the time interval from specimen collection to when a neonatal provider was notified of culture growth. TTP analysis was restricted to the first positive culture per infant. Patient-specific and infection-specific factors were analysed for association with TTP >36 hours. RESULTS: Of 10 235 blood cultures obtained from 3808 infants, 1082 (10.6%) were positive. Restricting to bacterial pathogens and the first positive culture, the median TTP (25th-75th percentile) for 428 cultures was 23.5 hours (18.4-29.9); 364 (85.0%) resulted in 36 hours. Excluding coagulase-negative staphylococci (CoNS), 275 of 294 (93.5%) cultures were flagged positive by 36 hours. In a multivariable model, CoNS isolation and antibiotic pretreatment were significantly associated with increased odds of TTP >36 hours. Projecting a 36-hour empiric duration at one site and assuming that all negative evaluations were associated with an empiric course of antibiotics, we estimated that 1164 doses of antibiotics would be avoided in 629 infants over 10 years, while delaying a subsequent antibiotic dose in 13 infants with bacteraemia. CONCLUSIONS: Empiric antibiotic administration in late-onset infection evaluations (not targeting CoNS) can be stopped at 36 hours. Longer durations (48 hours) should be considered when there is pretreatment or antibiotic therapy is directed at CoNS.

Perinatal Complications in Individuals in California With or Without SARS-CoV-2 Infection During Pregnancy.

Importance: Additional research from population-based studies is needed to inform the treatment of SARS-CoV-2 infection during pregnancy and to provide health risk information to pregnant individuals. Objective: To assess the risk of perinatal complications associated with SARS-CoV-2 infection and to describe factors associated with hospitalizations. Design, Setting, and Participants: This population-based cohort study included 43 886 pregnant individuals with longitudinal electronic health record data from preconception to delivery who delivered at Kaiser Permanente Northern California between March 1, 2020, and March 16, 2021. Individuals with diagnostic codes for COVID-19 that did not have a confirmatory polymerase chain reaction test for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 infection detected by polymerase chain reaction test (from 30 days before conception to 7 days after delivery) as a time varying exposure. Main Outcomes and Measures: Severe maternal morbidity including 21 conditions (eg, acute myocardial infarction, acute renal failure, acute respiratory distress syndrome, and sepsis) that occurred at any time during pregnancy or delivery; preterm birth; pregnancy hypertensive disorders; gestational diabetes; venous thromboembolism (VTE); stillbirth; cesarean delivery; and newborn birth weight and respiratory conditions. Standardized mean differences between individuals with and without SARS-CoV-2 were calculated. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for the association between SARS-CoV-2 infection and perinatal complications and hospitalization and to consider the timing of SARS-CoV-2 infection relative to outcomes. Results: In this study of 43 886 pregnant individuals (mean [SD] age, 30.7 [5.2] years), individuals with a SARS-CoV-2 infection (1332 [3.0%]) were more likely to be younger, Hispanic, multiparous individuals with a higher neighborhood deprivation index and obesity or chronic hypertension. After adjusting for demographic characteristics, comorbidities, and smoking status, individuals with SARS-CoV-2 infection had higher risk for severe maternal morbidity (HR, 2.45; 95% CI, 1.91-3.13), preterm birth (<37 weeks; HR, 2.08; 95% CI, 1.75-2.47), and VTE (HR, 3.08; 95% CI, 1.09-8.74) than individuals without SARS-CoV-2. SARS-CoV-2 infection was also associated with increased risk of medically indicated preterm birth (HR, 2.56; 95% CI, 2.06-3.19); spontaneous preterm birth (HR, 1.61; 95% CI, 1.22-2.13); and early (HR, 2.52; 95% CI, 1.49-4.24), moderate (HR, 2.18; 95% CI, 1.25-3.80), and late (HR, 1.95; 95% CI, 1.61-2.37) preterm birth. Among individuals with SARS-CoV-2 infection, 76 (5.7%) had a hospitalization; pregestational diabetes (HR, 7.03; 95% CI, 2.22-22.2) and Asian or Pacific Islander (HR, 2.33; 95% CI, 1.06-5.11) and Black (HR, 3.14; 95% CI, 1.24-7.93) race and ethnicity were associated with an increased risk of hospitalization. Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with increased risk of severe maternal morbidity, preterm birth, and VTE. The study findings inform clinicians and patients about the risk of perinatal complications associated with SARS-CoV-2 infection in pregnancy and support vaccination of pregnant individuals and those planning conception.

Update on Phototherapy and Childhood Cancer in a Northern California Cohort.

OBJECTIVES: We aimed to reassess the relationship between phototherapy and cancer in an extended version of a previous cohort and to replicate a report from Quebec of increased cancer risk after phototherapy beginning at age 4 years. METHODS: This cohort study included 139 100 children born at ≥35 weeks' gestation from 1995 to 2017, followed through March 16, 2019, in Kaiser Permanente Northern California hospitals who had a qualifying bilirubin level from -3 mg/dL to +4.9 mg/dL from the American Academy of Pediatrics phototherapy threshold; an additional 40 780 children and 5 years of follow-up from our previous report. The exposure was inpatient phototherapy (yes or no), and the outcomes were various types of childhood cancer. We used Cox proportional hazard models, controlling for propensity-score quintiles, and allowed for time-dependent exposure effects to assess for the risk of cancer after a latent period. RESULTS: Over a mean (SD) follow-up of 8.2 (5.7) years, the crude incidence of cancer per 100 000 person-years was 25.1 among those exposed to phototherapy and 19.2 among those not exposed (233 cases of cancer). After propensity adjustment, phototherapy was not associated with any cancer (hazard ratio [HR]: 1.13, 95% confidence interval [CI]: 0.83-1.54), hematopoietic cancer (HR: 1.17, 95% CI: 0.74-1.83), or solid tumors (HR: 1.01, 95% CI: 0.65-1.58). We also found no association with cancer diagnoses at age ≥4 years. CONCLUSIONS: We did not confirm previous, concerning associations between phototherapy and adjusted risk of any cancer, nonlymphocytic leukemia, or brain and/or central nervous systems tumors in later childhood.

COVID-19 prevalence, symptoms, and sociodemographic disparities in infection among insured pregnant women in Northern California.

BACKGROUND: Research on COVID-19 during pregnancy has mainly focused on women hospitalized for COVID-19 or other reasons during their pregnancy. Little is known about COVID-19 in the general population of pregnant women. OBJECTIVE: To describe the prevalence of COVID-19, symptoms, consequent healthcare use, and possible sources of COVID-19 exposure among a population-based sample of pregnant women residing in Northern California. METHODS: We analyzed data from 19,458 members of Kaiser Permanente Northern California who were pregnant between January 2020 and April 2021 and responded to an online survey about COVID-19 testing, diagnosis, symptoms, and their experiences during the COVID-19 pandemic. Medical diagnosis of COVID-19 during pregnancy was defined separately by self-report and by documentation in electronic health records (EHR). We examined relationships of COVID-19 with sociodemographic factors, underlying comorbidities, and survey measures of COVID-19-like symptoms, consequent healthcare utilization, and possible COVID-19 exposures. RESULTS: Among 19,458 respondents, the crude prevalence of COVID-19 was 2.5% (n = 494) according to self-report and 1.4% (n = 276) according to EHR. After adjustment, the prevalence of self-reported COVID-19 was higher among women aged <25 years compared with women aged ≥35 years (prevalence ratio [PR], 1.75, 95% CI: 1.23, 2.49) and among Hispanic women compared with White women (PR, 1.91, 95% CI: 1.53, 2.37). Prevalence of self-reported COVID-19 was higher among women affected by personal or partner job loss during the pandemic (PR, 1.23, 95% CI: 1.02, 1.47) and among women living in areas of high vs. low neighborhood deprivation (PR, 1.74, 95% CI: 1.33, 2.27). We did not observe differences in self-reported COVID-19 between women with and without underlying comorbidities. Results were similar for EHR-documented COVID-19. Loss of smell or taste was a unique and common symptom reported among women with COVID-19 (42.3% in self-reported; 54.0% in EHR-documented). Among women with symptomatic COVID-19, approximately 2% were hospitalized, 71% had a telehealth visit, and 75% quarantined at home. Over a third of women with COVID-19 reported no known exposure to someone with COVID-19. CONCLUSIONS: Observed COVID-19 prevalence differences by sociodemographic and socioeconomic factors underscore social and health inequities among reproductive-aged women. Women with COVID-19 reported unique symptoms and low frequency of hospitalization. Many were not aware of an exposure to someone with COVID-19.