Infants Born at Late Preterm Gestation: Management during the Birth Hospitalization.

OBJECTIVE: To examine the admission practices, frequency of common clinical morbidities, and rates of medical intervention in infants born at 34-36 weeks gestational age (GA, late preterm). STUDY DESIGN: This retrospective, single institution, cohort study analyzed electronic health records of infants born late preterm from 2019 through 2021. Infants with known congenital anomalies necessitating neonatal intensive care unit admission were excluded. Analysis included descriptive and inferential statistics. RESULTS: The study included 1022 infants: 209 (21%) 34 weeks GA, 263 (26%) 35 weeks GA, and 550 (54%) 36 weeks GA. Sixty-three percent of infants at 35 weeks GA and 78% of infants of 36 weeks GA remained in well newborn care throughout the birth hospitalization; infants born at 34 weeks GA were ineligible for well newborn care. The need for respiratory support was 32%, 18%, and 11% in infants of 34, 35, and 36 weeks GA, respectively. Supplemental tube feeds were administered in 55%, 24%, and 8% of infants of 34, 35, and 36 weeks GA, respectively. Most infants born at 34 weeks GA (91%) were placed in an incubator; this was less frequent in infants at 35 (37%) and 36 weeks (16%). Tachypnea, hypoglycemia, and hypothermia were noted in 40%, 61%, and 57% of infants, respectively. A subset of these infants (30% with tachypnea, 23% with hypoglycemia, and 46% with hypothermia) required medical intervention for these abnormalities. CONCLUSIONS: This single-center study provides an outlook on the care of infants born late preterm. Multicenter studies can contextualize these findings in order to develop clinical benchmarks and quality markers for this large population of infants.

Characterizing Long COVID in Children and Adolescents.

Importance: Most research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment. Objective: To identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC. Design, Setting, and Participants: Multicenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 89 prolonged symptoms across 9 symptom domains. Results: A total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents. Conclusions and Relevance: This study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

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.

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.

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) 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.

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.

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.

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.

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.

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 symptomatic depression and anxiety 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 at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum. Prevalence of symptomatic depression and anxiety at each visit was described. Univariable logistic regression analysis was used to determine the association between demographic and clinical factors and symptomatic depression or anxiety. Results: 317 participantswere included. The prevalence of antepartum depression was 14.6%, 10.3%, and 20.6% at 34weeks gestational age, 6-8weeks postpartum, and 6months postpartum, respectively. The rate of anxiety 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 depression and anxiety throughout pregnancy and the postpartum period. Quarantining during pregnancy was associated with symptomatic anxiety at 34weeks gestational age in univariate (P=0.027) analyses. COVID-19 diagnosis and hospitalization were not associated with depression or anxiety. Conclusions: Depression and anxiety 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.

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

Anti-SARS-CoV-2 antibodies have been found in human-milk after COVID-19 infection and vaccination. However, little is known about their persistence in milk after booster vaccination and breakthrough infection. In this study, human-milk, saliva and blood samples were collected from 33 lactating individuals before and after mRNA-based vaccination and COVID-19 breakthrough infections. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires. Evaluation of maternal and infant symptomatology revealed that infected mothers reported more symptoms than vaccinated mothers. We found that after vaccination, human-milk anti-SARS-CoV-2 antibodies persisted for up to 8 months. In addition, distinct patterns of human milk IgA and IgG production we observed after breakthrough infection compared to 3-dose vaccination series alone, indicating a differential central and mucosal immune profiles in hybrid compared with vaccine-induced immunity. To investigate passively-derived milk antibody protection in infants, we examined the persistence of these antibodies in infant saliva after breastfeeding. We found that IgA was more abundant in infant saliva compared to IgG and persist in infant saliva longer after feeding. Our results delineate the differences in milk antibody response to vaccination as compared to breakthrough infection and emphasize the importance of improving the secretion of IgA antibodies to human milk after vaccination to improve the protection of breastfeeding infants.

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.

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.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

Clinical Decision Support for Newborn Weight Loss: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The Newborn Weight Tool (NEWT) can inform newborn feeding decisions and might reduce health care utilization by preventing excess weight loss. Clinical decision support (CDS) displaying NEWT might facilitate its use. Our study's objective is to determine the effect of CDS displaying NEWT on feeding and health care utilization. METHODS: At an hospital involved in NEWT development, we randomly assigned 2682 healthy infants born ≥36 weeks gestation in 2018-2019 either to CDS displaying NEWT with an electronic flag if most recent weight was ≥75th weight loss centile or to a control of usual care with NEWT accessed at clinician discretion. Our primary outcome was feeding type concordant with weight loss, defined as exclusive breastfeeding for those not flagged, exclusive breastfeeding or supplementation for those flagged once, and supplementation for those flagged more than once. Secondary outcomes included inpatient and outpatient utilization in the first 30 days. We used χ2 and Student's t tests to compare intervention infants with control and to compare trial infants with those born in 2017. RESULTS: Feeding was concordant with for 1854 (74.5%) trial infants and did not differ between randomized groups (P = .65); concordant feeding was higher for all trial infants than for infants born in 2017 (64.4%; P < .0005). Readmission occurred for 51 (3.8%) CDS infants and 45 (3.4%) control infants (P = .56). Among the 60% of trial infants with outpatient records available, there were 3.5 ± 1.7 visits with no differences between randomized groups (P = .10). CONCLUSIONS: At an hospital involved in NEWT development, CDS displaying NEWT did not alter either feeding or health care utilization compared with discretionary NEWT access.

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals. Thirty women vaccinated with mRNA vaccines (from December 2020 through August 2021) were matched with 30 naturally infected women (from March 2020 through January 2021) by gestational age of exposure. Neutralization activity against the 5 SARS-CoV-2 spike sequences was measured by a SARS-CoV-2-pseudotyped spike virion assay. Effective nAbs against SARS-CoV-2 were present in maternal and cord plasma after both infection and vaccination. Compared with WT spike protein, these nAbs were less effective against the Delta and Mu spike variants. Vaccination during the third trimester induced higher cord-nAb levels at delivery than did infection during the third trimester. In contrast, vaccine-induced nAb levels were lower at the time of delivery compared with infection during the first trimester. The transfer ratio (cord nAb level divided by maternal nAb level) was greatest in mothers vaccinated in the second trimester. SARS-CoV-2 vaccination or infection in pregnancy elicits effective nAbs with differing neutralization kinetics that are influenced by gestational time of exposure.