Patterns of peripartum depression and anxiety during the pre-vaccine COVID-19 pandemic.

BACKGROUND: Pregnant people are vulnerable to new or worsening mental health conditions. This study aims to describe prevalence and course of depression and anxiety symptoms in pregnancy during the pre-vaccine COVID-19 pandemic. METHODS: This is a prospective cohort study of pregnant individuals with known or suspected COVID-19. Participants completed Edinburgh Postnatal Depression Scale (EPDS) and Generalized-Anxiety Disorder-7 (GAD-7) questionnaires, screening tools for depression and anxiety, at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum. Prevalence of elevated depressive and anxiety symptoms at each visit was described. Univariable logistic regression analysis was used to determine the association between demographic and clinical factors and those with elevated depression or anxiety symptoms. RESULTS: 317 participants were included. The prevalence of elevated antepartum depression symptoms was 14.6%, 10.3%, and 20.6% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. The rate of elevated anxiety symptoms was 15.1%, 10.0%, and 17.3% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. A prior history of depression and/or anxiety (p's < 0.03), as well as higher EPDS and GAD-7 scores at enrollment (p's < 0.04) associated with elevated depression and anxiety symptoms throughout pregnancy and the postpartum period. Quarantining during pregnancy was associated with elevated anxiety symptoms at 34weeks gestational age in univariate (P = 0.027) analyses. COVID-19 diagnosis and hospitalization were not associated with elevated depression or anxiety symptoms. CONCLUSIONS: Elevated depression and anxiety symptoms were prevalent throughout pregnancy and the postpartum period, particularly in those with prior depression and/or anxiety and who quarantined. Strategies that target social isolation may mitigate potential adverse consequences for pregnant people, and continued vigilance in recognition of depression and anxiety in pregnancy should be considered.

Physician personal breastfeeding experience and clinical care of the breastfeeding dyad.

BACKGROUND: Prior research suggests that physicians' personal experience with breastfeeding may influence their attitudes toward breastfeeding. This phenomenon has not been explored in well-newborn care physician leaders, whose administrative responsibilities often include drafting and approval of hospital breastfeeding and formula supplementation policies. METHODS: We conducted a mixed-methods study, surveying physicians in the Better Outcomes through Research for Newborns (BORN) network. We examined physician attitudes toward recommending breastfeeding and their breastfeeding experience. Qualitative analysis was conducted on responses to the question: "How do you think your breastfeeding experience influences your clinical practice?" RESULTS: Of 71 participants, most (92%) had a very positive attitude toward breastfeeding with 75% of respondents reporting personal experience with breastfeeding. Of these, 68% had a very positive experience, 25% had a somewhat positive experience, and 6% had a neutral experience. Four themes emerged with respect to the effect of breastfeeding experience on practice: (1) empathy with breastfeeding struggles, (2) increased knowledge and skills, (3) passion for breastfeeding benefits, and (4) application of personal experience in lieu of evidence-based medicine, particularly among those who struggled with breastfeeding. CONCLUSIONS: Well-newborn care physician leaders reported positive attitudes about breastfeeding, increased support toward breastfeeding persons, and a perception of improved clinical lactation skills. Those who struggled with breastfeeding reported increased comfort with recommending formula supplementation to their own patients. Medical education about evidence-based breastfeeding support practices and provision of lactation support to physicians has the potential to affect public health through improved care for the patients they serve.

Newborn weight change and predictors of underweight in the neonatal period in Guinea-Bissau, Nepal, Pakistan and Uganda.

In low- and middle-income countries (LMIC), growth impairment is common; however, the trajectory of growth over the course of the first month has not been well characterised. To describe newborn growth trajectory and predictors of growth impairment, we assessed growth frequently over the first 30 days among infants born ≥2000 g in Guinea-Bissau, Nepal, Pakistan and Uganda. In this cohort of 741 infants, the mean birth weight was 3036 ± 424 g. For 721 (98%) infants, weight loss occurred for a median of 2 days (interquartile range, 1-4) following birth until weight nadir was reached 5.9 ± 4.3% below birth weight. At 30 days of age, the mean weight was 3934 ± 592 g. The prevalence of being underweight at 30 days ranged from 5% in Uganda to 31% in Pakistan. Of those underweight at 30 days of age, 56 (59%) had not been low birth weight (LBW), and 48 (50%) had reached weight nadir subsequent to 4 days of age. Male sex (relative risk [RR] 2.73 [1.58, 3.57]), LBW (RR 6.41 [4.67, 8.81]), maternal primiparity (1.74 [1.20, 2.51]) and reaching weight nadir subsequent to 4 days of age (RR 5.03 [3.46, 7.31]) were highly predictive of being underweight at 30 days of age. In this LMIC cohort, country of birth, male sex, LBW and maternal primiparity increased the risk of impaired growth, as did the modifiable factor of delayed initiation of growth. Interventions tailored to infants with modifiable risk factors could reduce the burden of growth impairment in LMIC.

Infant Outcomes Following Maternal Infection With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): First Report From the Pregnancy Coronavirus Outcomes Registry (PRIORITY) Study.

Infant outcomes after maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not well described. In a prospective US registry of 263 infants, maternal SARS-CoV-2 status was not associated with birth weight, difficulty breathing, apnea, or upper or lower respiratory infection through 8 weeks of age.

Management and Early Outcomes of Neonates Born to Women with SARS-CoV-2 in 16 U.S. Hospitals.

OBJECTIVE: There is a paucity of evidence to guide the clinical care of late preterm and term neonates born to women with perinatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The objective of this case series is to describe early neonatal outcomes and inpatient management in U.S. hospitals. STUDY DESIGN: We solicited cases of mother-infant dyads affected by novel coronavirus disease 2019 (COVID-19) from the Better Outcomes through Research for Newborns (BORN) Network members. Using a structured case template, participating sites contributed deidentified, retrospective birth hospitalization data for neonates ≥35 weeks of gestation at birth with mothers who tested positive for SARS-CoV-2 before delivery. We describe demographic and clinical characteristics, clinical management, and neonatal outcomes. RESULTS: Sixteen U.S. hospitals contributed 70 cases. Birth hospitalizations were uncomplicated for 66 (94%) neonates in which 4 (6%) required admission to a neonatal intensive care unit. None required evaluation or treatment for infection, and all who were tested for SARS-CoV-2 were negative (n = 57). Half of the dyads were colocated (n = 34) and 40% directly breastfed (n = 28). Outpatient follow-up data were available for 13 neonates, all of whom remained asymptomatic. CONCLUSION: In this multisite case series of 70 neonates born to women with SARS-CoV-2 infection, clinical outcomes were overall good, and there were no documented neonatal SARS-CoV-2 infections. Clinical management was largely inconsistent with contemporaneous U.S. COVID-19 guidelines for nursery care, suggesting concerns about the acceptability and feasibility of those recommendations. Longitudinal studies are urgently needed to assess the benefits and harms of current practices to inform evidence-based clinical care and aid shared decision-making. KEY POINTS: · Birth hospitalizations were uncomplicated for late preterm and term infants with maternal COVID-19.. · Nursery management of dyads affected by COVID-19 varied between hospitals.. · Adherence to contemporaneous U.S. clinical guidelines for nursery care was low.. · Breastfeeding rates were lower for dyads roomed separately than those who were colocated..

The Effect of Early Limited Formula on Breastfeeding, Readmission, and Intestinal Microbiota: A Randomized Clinical Trial.

OBJECTIVE: To determine whether using 10 mL formula after each breastfeeding before copious maternal milk production affects breastfeeding duration, readmission, and intestinal microbiota through 1 month of age. STUDY DESIGN: In this randomized controlled trial, we enrolled 164 exclusively breastfeeding newborns, 24-72 hours old, whose weight loss was ≥75th percentile for age, and whose mothers had not yet begun mature milk production. Enrolled newborns were assigned randomly to either supplement breastfeeding with early limited formula (ELF), 10 mL of formula after each breastfeeding stopped at the onset of copious maternal milk production (intervention), or to continue exclusive breastfeeding (control). Outcomes assessed through 1 month included breastfeeding duration, readmission, and intestinal microbiota. RESULTS: At 1 week of age, 95.8% of infants receiving ELF and 93.5% of control infants were still breastfeeding (P > .5); readmission occurred for 4 (4.8%) control infants and none of the infants receiving ELF (P = .06). At 1 month of age, 86.5% of infants receiving ELF and 89.7% of control infants were still breastfeeding (P > .5); 54.6% of infants receiving ELF and 65.8% of controls were breastfeeding without formula (P = .18). ELF did not lead to decreased abundance of Lactobacillus or Bifidobacterium and was not associated with expansion of Clostridium. CONCLUSION: In this population of healthy newborns with weight loss ≥75th percentile, ELF did not interfere with breastfeeding at 1 month, breastfeeding without formula at 1 month, or intestinal microbiota. ELF may be an important therapeutic option for newborns with the potential to reduce readmission rates. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02313181.

Barriers to exclusive breast-feeding in Indonesian hospitals: a qualitative study of early infant feeding practices.

OBJECTIVE: Although initiating breast-feeding is common in Indonesia, rates of exclusive breast-feeding are low. Our objective was to identify early barriers to exclusive breast-feeding in Indonesian hospitals. DESIGN: Qualitative. Semi-structured interviews were conducted in April-June 2015. The data were analysed using thematic analysis. SETTING: Indonesian provinces of Jakarta, Banten and West Java. SUBJECTS: Fifty-four participants including public health officials, hospital administrators, health-care professionals and parents. RESULTS: Five themes were identified as contributing to low rates of early exclusive breast-feeding in Indonesian hospitals: (i) quality and quantity of breast-feeding education; (ii) marketing and influence of infant formula manufacturers; (iii) hospital infrastructure; (iv) policy, legislation and protocols; and (v) perceived need for infant formula supplementation. Participants noted that providers and mothers receive inadequate or incorrect education regarding breast-feeding; manufacturers promote infant formula use both inside and outside hospitals; constraints in physical space and hospital design interfere with early breast-feeding; legislation and protocols designed to promote breast-feeding are inconsistently enforced and implemented; and providers and mothers often believe infant formula is necessary to promote infant health. All participants identified numerous barriers to early exclusive breast-feeding that related to more than one identified theme. CONCLUSIONS: Our study identified important barriers to early exclusive breast-feeding in Indonesian hospitals, finding that participants consistently reported multifaceted barriers to early exclusive breast-feeding. Future research should examine whether system-level interventions such the Baby-Friendly Hospital Initiative might improve rates of exclusive breast-feeding by improving breast-feeding education, reducing manufacturer influence, modifying existing infrastructure and providing tools needed for protocols and counselling.

Relationship of newborn weight loss to milk supply concern and anxiety: the impact on breastfeeding duration.

Milk supply concern is the most common reason for breastfeeding discontinuation and maternal anxiety is also associated with reduced breastfeeding duration. Newborn excess weight loss (EWL) could trigger milk supply concern and anxiety and might be amenable to modification. Our objective was to determine the relationship between EWL and the development of milk supply concern and anxiety and the effect of such development on breastfeeding duration. We conducted a cohort analysis using data previously obtained from a randomised controlled trial comparing two post-hospital discharge follow-up strategies. For 1107 well, singleton infants born at ≥34 weeks, we extracted data on all inpatient infant weights. EWL was defined as the loss of ≥10% of birthweight. We surveyed mothers to obtain data on state anxiety and milk supply concern at birth and at 2 weeks. Our final outcome was breastfeeding at 6 months. Seventy (6.3%) infants developed EWL during the birth hospitalisation. At 2 weeks, milk supply concern and positive anxiety screen were more common (42% and 18%, respectively) among mothers whose infants had had EWL than among mothers whose infants had not had EWL (20% and 6%, respectively) (P < 0.001 for each comparison). Mothers with milk supply concern at 2 weeks were much less likely to be breastfeeding at 6 months, with odds ratio of 0.47 (0.30, 0.74) in multivariate analysis. EWL may increase milk supply concern and anxiety and these may reduce breastfeeding duration. Ameliorating EWL might alleviate milk supply concern and anxiety and improve breastfeeding duration.

Positive and negative experiences of breast pumping during the first 6 months.

For mothers with breastfeeding difficulties, pumping can be recommended to help establish milk production. However, pumping may present some barriers to successful breastfeeding. Mothers with milk supply concern may be at higher risk of barriers to successful breastfeeding. No previous studies have described experiences of pumping among mothers with milk supply concern. We conducted 10 focus groups of 56 mothers who had milk supply concern in the first month after birth. A paid, trained facilitator led groups in a semi-structured approach. Sessions were audiorecorded and transcribed verbatim. The transcripts were coded independently by two investigators and analysed using grounded theory. We identified five themes related to the experience of pumping among mothers with milk supply concern: (1) additional control over breastfeeding from pumping: 'I would feed and then give him … whatever I could manage to pump to him'. (2) Painful experience: 'The first time I pumped my boobs hurt so bad'. (3) Pumped volume affected milk supply concern: 'Pump and there was hardly anything coming out that's when I started to worry'. (4) Pumping interfered with other nurturing activities: 'While you're pumping, you can't touch the baby'. (5) Frustration from inconsistent provider advice: 'They told me to pump … and then said, "That's going to cause your milk to increase too much" '. Mothers had positive and negative experiences with pumping. Clinicians should assess a mother's experience shortly after she initiates pumping, as further management and counselling may be necessary to avoid barriers to successful breastfeeding.

Breastfeeding and Once-Daily Small-Volume Formula Supplementation to Prevent Infant Growth Impairment.

BACKGROUND: Randomized controlled trials in Guinea-Bissau and Uganda have revealed that the intensive promotion of exclusive breastfeeding (EBF) impairs growth in early infancy. When newborn growth is impaired, small amounts of formula may be combined with breastfeeding to promote growth. METHODS: To determine if breastfeeding combined with once-daily formula supplementation improves growth among at-risk newborns, we conducted a pilot randomized controlled trial in Bissau, Guinea-Bissau and Kampala, Uganda. We randomly assigned 324 healthy breastfeeding newborns who weighed 2000 g to 2499 g at birth or <2600 g at 4 days old to once-daily formula feeding through 30 days as a supplement to frequent breastfeeding followed by EBF from 31 days through 6 months, or to EBF through 6 months. The primary outcome was weight-for-age z score (WAZ) at 30 days. Other outcomes included weight-for-length z score (WLZ), length-for-age z score (LAZ), breastfeeding cessation, adverse events, and serious adverse events through 180 days. RESULTS: Daily formula consumption in the intervention group was 31.9 ± 11.8 mL. The random assignment did not impact WAZ, WLZ, LAZ, breastfeeding cessation, adverse events, or serious adverse events through 180 days. In the intervention and control groups, 19 (12%) and 35 (21%) infants, respectively, reported nonformula supplementation in the first 30 days (P = .02). CONCLUSIONS: Once-daily formula supplementation for 30 days was well-tolerated, but the small volume consumed did not alter growth through 180 days of age. Further research would be required to determine if larger formula volumes, longer duration of treatment, or more frequent feeding are effective at increasing growth for this at-risk population.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

IMPORTANCE: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. OBSERVATIONS: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of four cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n = 10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n = 6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n = 6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n = 600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. CONCLUSIONS AND RELEVANCE: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Development of the breast milk expression experience measure.

Exclusive breastfeeding provides optimal nutrition through 6 months. Recent research has shown that milk expression may affect breastfeeding duration. A woman's experience with milk expression might mediate the effect of milk expression on breastfeeding duration. The objective of this study was to develop a measure to evaluate women's experiences of expressing milk. Based on the available literature, we developed a brief measure of the Breast Milk Expression Experience (BMEE) assessing three dimensions: (1) social support for milk expression; (2) ease of learning how to express milk; and (3) personal experiences of milk expression. All items used 1-5 Likert scales, with higher scores indicating better experiences. We administered the items immediately after expression to 68 mothers who expressed milk post-partum. We evaluated this measure for reliability using Cronbach's alpha. Mothers completing the BMEE were 57% primiparous with 75% vaginal births. The BMEE demonstrated appropriate reliability with a Cronbach's alpha of 0.703 for the summary index and 0.719-0.763 for social support, learning experience and personal experience subscales. The BMEE also indicated good predictive validity; of the six mothers who had a mean score <3 on the 11-item scale post-partum, two (33.3%) were expressing breast milk at 1 month, compared with 37 (80.4%) of the 46 mothers who had a mean score ≥3 on the 11-item scale post-partum (P = 0.012). The BMEE is a promising measure of milk expression experience in this population. Use of this measure may allow improved understanding of women's experiences expressing milk.

Admission and Care Practices in United States Well Newborn Nurseries.

OBJECTIVES: Late preterm and term infants comprise 97.3% of annual births in the United States. Admission criteria and the availability of medical interventions in well newborn nurseries are key determinants of these infants remaining within a mother-infant dyad or requiring a NICU admission and resultant separation of the dyad. The objective of this study was to identify national patterns for well newborn nursery care practices. METHODS: We surveyed a physician representative from each nursery in the Better Outcomes through Research for Newborns Network. We described the admission criteria and clinical management of common newborn morbidities and analyzed associations with nursery demographics. RESULTS: Of 96 eligible nursery representatives, 69 (72%) completed surveys. Among respondents, 59 (86%) used a minimal birth weight criterion for admission to their well newborn nursery. The most commonly used criteria were 2000 g (n = 29, 49%) and 1800 g (n = 19, 32%), with a range between 1750 and 2500 g. All nurseries used a minimal gestational age criterion for admission; the most commonly used criterion was 35 weeks (n = 55, 80%). Eleven percent of sites required transfer to the NICU for phototherapy. Common interventions in the mother's room included dextrose gel (n = 56, 81%), intravenous antibiotics (n = 35, 51%), opiates for neonatal abstinence syndrome (n = 15, 22%), and an incubator for thermoregulation (n = 14, 20%). CONCLUSIONS: Wide variation in admission criteria and medical interventions exists in well newborn nurseries. Further studies may help identify evidence-based optimal admission criteria to maximize care within the mother-infant dyad.

Milk antibody response after 3rd COVID-19 vaccine and SARS-CoV-2 infection and implications for infant protection.

Little is known about the persistence of human milk anti-SARS-CoV-2 antibodies after 2nd and 3rd vaccine doses and infection following 3rd dose. In this study, human milk, saliva, and blood samples were collected from 33 lactating individuals before and after vaccination and infection. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires. We found that after vaccination, milk anti-SARS-CoV-2 antibodies persisted for up to 8 months. In addition, distinct patterns of human milk IgA and IgG production and higher milk RBD-blocking activity was observed after infection compared to 3-dose vaccination. Infected mothers reported more symptoms than vaccinated mothers. We examined the persistence of milk antibodies in infant saliva after breastfeeding and found that IgA was more abundant compared to IgG. Our results emphasize the importance of improving the secretion of IgA antibodies to human milk after vaccination to improve the protection of breastfeeding infants.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults. Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's RE searching COV ID to E nhance R ecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) a de novo RECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study ( n =10,000). The de novo cohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science. Conclusions and Relevance: RECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions. Clinical Trialsgov Identifier: Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT05172011.

Researching COVID to enhance recovery (RECOVER) pregnancy study: Rationale, objectives and design.

IMPORTANCE: Pregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER-Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads. METHODS: RECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through the Eunice Kennedy Shriver National Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators. DISCUSSION: RECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero. CLINICAL TRIALS.GOV IDENTIFIER: Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

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.

Frequency, duration and predictors of bronchiolitis episodes of care among infants ≥32 weeks gestation in a large integrated healthcare system: a retrospective cohort study.

BACKGROUND: Bronchiolitis is common in the first two years of life and is the most frequent cause of hospitalization in this age group. No previous studies have used an episode-of-care analysis to describe the frequency, duration, and predictors of bronchiolitis episodes of care during the first two years. METHODS: We conducted a retrospective cohort study of 123,264 infants ≥32 weeks gestation born at 6 Northern California Kaiser Permanente hospitals between 1996 and 2002. We used electronic medical records to concatenate hospital, emergency department and outpatient health care encounters for bronchiolitis into discrete episodes of care. We used descriptive statistics to report frequency and duration of bronchiolitis episodes and used logistic regression to assess the effect of gestational age and other clinical and demographic predictors on the outcome of bronchiolitis episodes. RESULTS: Among all infants, the rate of bronchiolitis episodes was 162 per 1000 children during the first 2 years of life; approximately 40% required >1 day of medical attention with a mean duration of 7.0 ± 5.9 days. Prematurity was associated with increased risk of bronchiolitis episodes and longer duration. Bronchiolitis episodes rates per 1000 infants were 246 for 32-33 weeks gestational age, 204 for 34-36 weeks, and 148-178 for >36 weeks. Male gender, African-American and Hispanic race/ethnicity, and parental history of asthma were associated with an increased risk of having a bronchiolitis episode and/or longer duration. CONCLUSIONS: Bronchiolitis episodes of care are frequent during the first two years of life and the duration ranges from 1 to 27 days. Prematurity was associated with more frequent and longer duration of bronchiolitis episodes of care, which may reflect illness severity and/or perceived vulnerability.

Experiences and attitudes related to newborn feeding in central Uganda: A qualitative study.

OBJECTIVE: Adequate infant nutrition is a critical cornerstone of population health, yet adherence to recommended breastfeeding practices is low in many countries in sub-Saharan Africa, including Uganda. This study aims to describe local attitudes, experiences and beliefs related to nutrition in early infancy in Central Uganda. DESIGN: We conducted 5 focus group discussions and 12 key informant interviews to gather information on local attitudes, experiences and beliefs related to feeding in early infancy. SETTING: Urban areas of Central Uganda. PARTICIPANTS: Parents and healthcare and public health professionals. RESULTS: Participants reported numerous concerns related to infant health including inadequate infant weight, premature birth, diarrhea, fever, gastrointestinal infection and malnutrition. Awareness of the infant health benefits of exclusive breastfeeding was prevalent but experienced as in balance with maternal factors that might lead to supplementation, including employment demands, physical appearance, pain, poverty and maternal health and malnutrition. Breastfeeding was highly valued, but use of unsafe breast milk supplements was common, including cow's milk, black tea, glucose water, fruit juice, millet, maize, rice, potatoes, soy, sorghum, egg yolk, fish and ghee. Expression of breast milk was viewed as not consonant with local culture. CONCLUSIONS: Participants were aware of the benefits of exclusive breastfeeding but described multiple barriers to achieving it. Supplementation with unsafe breastmilk supplements was considered to be more culturally consonant than milk expression and was reported to be the only affordable potential breast milk substitute for many families.