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.

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.

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.

Randomized controlled trial of early, small-volume formula supplementation among newborns: A study protocol.

Childhood undernutrition is a major health burden worldwide that increases childhood morbidity and mortality and causes impairment in infant growth and developmental delays that can persist into adulthood. The first weeks and months after birth are critical to the establishment of healthy growth and development during childhood. The World Health Organization recommends immediate and exclusive breastfeeding (EBF). In infants for whom EBF may not meet nutritional and caloric demands, early, daily, small-volume formula supplementation along with breastfeeding may more effectively avoid underweight wasting and stunting in early infancy than breastfeeding alone. The primary objective of this randomized controlled trial is to evaluate the efficacy of formula for 30 days among low birth weight (LBW) infants <6 hours of age and those not LBW with weights <2600 grams at 4 days of age. We will compare breastfeeding and formula (up to 59 milliliters administered daily) through 30 days of infant age vs recommendations for frequent EBF without supplementation, and test the hypothesis that formula increases weight-for-age z-score at 30 days of infant age. The trial will enroll and randomize 324 mother-infant pairs in Guinea-Bissau and Uganda, and follow them for 6 months for outcomes including growth, intestinal microbiota, breastfeeding duration, infant dietary intake, and adverse events. Conservatively estimating 20% loss to follow up, this sample size provides ≥80% power per weight stratum for intervention group comparison to detect a difference of 0.20 with respect to the outcome of WAZ at day 30. This trial was approved by the University of California, San Francisco Institutional Review Board (19-29405); the Guinea-Bissau National Committee on Ethics in Health (Comite Nacional de Etica na Saude, 075/CNES/INASA/2020); the Higher Degrees, Research and Ethics Committee of Makerere University (871); and the Uganda National Council of Science and Technology (HS1226ES). We plan to disseminate study results in peer-reviewed journals and international conferences. Trial registration number: NCT04704076.

Transient Effect of Infant Formula Supplementation on the Intestinal Microbiota.

Breastfeeding is the gold standard for feeding infants because of its long-term benefits to health and development, but most infants in the United States are not exclusively breastfed in the first six months. We enrolled 24 infants who were either exclusively breastfed or supplemented with formula by the age of one month. We collected diet information, stool samples for evaluation of microbiotas by 16S rRNA sequencing, and blood samples for assessment of immune development by flow cytometry from birth to 6 months of age. We further typed the Bifidobacterium strains in stool samples whose 16S rRNA sequencing showed the presence of Bifidobacteriaceae. Supplementation with formula during breastfeeding transiently changed the composition of the gut microbiome, but the impact dissipated by six months of age. For example, Bifidobacterium longum, a bacterial species highly correlated with human milk consumption, was found to be significantly different only at 1 month of age but not at later time points. No immunologic differences were found to be associated with supplementation, including the development of T-cell subsets, B cells, or monocytes. These data suggest that early formula supplementation, given in addition to breast milk, has minimal lasting impact on the gut microbiome or immunity.

Supplementation Practices and Donor Milk Use in US Well-Newborn Nurseries.

BACKGROUND AND OBJECTIVES: Guidelines encourage exclusive breastfeeding for healthy newborns but lack specificity regarding criteria for medically indicated supplementation, including type, timing, and best practices. We set out to describe practice patterns and provider perspectives regarding medically indicated supplementation of breastfeeding newborns across the United States. METHODS: From 2017 to 2018, we surveyed the Better Outcomes through Research for Newborns representative from each Better Outcomes through Research for Newborns hospital regarding practices related to medically indicated supplementation. We used descriptive statistics to compare practices between subgroups defined by breastfeeding prevalence and used qualitative methods and an inductive approach to describe provider opinions. RESULTS: Of 96 providers representing discrete hospitals eligible for the study, 71 participated (74% response rate). Practices related to criteria for supplementation and pumping and to type and caloric density of supplements varied widely between hospitals, especially for late preterm infants, whereas practices related to lactation consultant availability and hand expression education were more consistent. The most commonly reported criterion for initiating supplementation was weight loss of ≥10% from birth weight, and bottle-feeding was the most commonly reported method; however, practices varied widely. Donor milk use was reported at 20 (44%) hospitals with ≥81% breastfeeding initiation and 1 (4%) hospital with <80% breastfeeding initiation (P = .001). CONCLUSIONS: Strategies related to supplementation vary among US hospitals. Donor milk availability is concentrated in hospitals with the highest prevalence of breastfeeding. Implementation of evidence-based management of supplementation among US hospitals has the potential to improve the care of term and late preterm newborns.

Pilot Analysis of Early Lactobacillus rhamnosus GG for Infant Colic Prevention.

We conducted a secondary analysis of data from a trial of Lactobacillus rhamnosus GG (LGG) supplementation as a pilot study to assess whether LGG prevents infant colic. For the first 6 months of life, infants received a daily dose of 10 billion colony-forming units of LGG or a control (n = 184). We compared the likelihood of a diagnosis of colic before 4 months of age, based on parent-reported symptoms or a physician diagnosis of colic. Out of the 184 infants, 18 (9.8%) had colic. There were no differences between the 2 groups in the percentage of infants with colic based on symptoms (control 5.4% vs LGG 9.8%; P = 0.19); physician diagnosis (control 3.2% vs LGG 7.6%; P = 0.26); or either symptoms or diagnosis combined (control 6.5% vs LGG 13.0%; P = 0.13). In this pilot study, early infant LGG supplementation does not appear to prevent the later development of colic.

Utility of Decision Rules for Transcutaneous Bilirubin Measurements.

BACKGROUND: Transcutaneous bilirubin (TcB) meters are widely used for screening newborns for jaundice, with a total serum bilirubin (TSB) measurement indicated when the TcB value is classified as "positive" by using a decision rule. The goal of our study was to assess the clinical utility of 3 recommended TcB screening decision rules. METHODS: Paired TcB/TSB measurements were collected at 34 newborn nursery sites. At 27 sites (sample 1), newborns were routinely screened with a TcB measurement. For sample 2, sites that typically screen with TSB levels also obtained a TcB measurement for the study. Three decision rules to define a positive TcB measurement were evaluated: ≥75th percentile on the Bhutani nomogram, 70% of the phototherapy level, and within 3 mg/dL of the phototherapy threshold. The primary outcome was a TSB level at/above the phototherapy threshold. The rate of false-negative TcB screens and percentage of blood draws avoided were calculated for each decision rule. RESULTS: For sample 1, data were analyzed on 911 paired TcB-TSB measurements from a total of 8316 TcB measurements. False-negative rates were <10% with all decision rules; none identified all 31 newborns with a TSB level at/above the phototherapy threshold. The percentage of blood draws avoided ranged from 79.4% to 90.7%. In sample 2, each rule correctly identified all 8 newborns with TSB levels at/above the phototherapy threshold. CONCLUSIONS: Although all of the decision rules can be used effectively to screen newborns for jaundice, each will "miss" some infants with a TSB level at/above the phototherapy threshold.

Donor milk in the newborn nursery at the University of Iowa Children's Hospital.

There is a paucity of literature on the topic of banked donor breastmilk use for healthy newborns. Herein, we describe two cases demonstrating the day-to-day medically indicated use of pasteurized, banked donor breastmilk in the University of Iowa Children's Hospital newborn nursery. These cases may inform scientific opinion about the role of banked donor milk for healthy newborns and may also facilitate research on the use of banked donor milk for this population.

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.

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.

Respiratory syncytial virus testing during bronchiolitis episodes of care in an integrated health care delivery system: a retrospective cohort study.

BACKGROUND: Bronchiolitis has the highest incidence rate of any lower respiratory infection among infants and children <2 years of age. Respiratory syncytial virus (RSV) is the most common etiology of bronchiolitis. The American Academy of Pediatrics does not recommend routine RSV testing for infants and children with bronchiolitis. The clinical predictors of RSV testing are unknown. OBJECTIVES: The aims of this study were to identify the rates and predictors of RSV testing during bronchiolitis and to explore the relationship between RSV test results and antibiotic treatment among infants and children aged <2 years. METHODS: A retrospective study was conducted of 123,264 infants ≥32 weeks' gestational age (GA) who were born at 1 of 6 Northern California Kaiser Permanente Medical Center Program hospitals between 1996 and 2004. A bronchiolitis episode of care (EOC) was defined as ≥1 medical encounters with a bronchiolitis diagnosis code followed by 14 clear days without a bronchiolitis-related medical encounter. Descriptive statistics were used to report the frequency of tests, and logistic regression was used to assess the effect of hospitalization, chronologic age, gestational age, and season on the frequency of testing for RSV. Rapid direct fluorescent antibody testing was performed during the study. RESULTS: The birth cohort was 51.2% male and 42.7% white, 20.8% Hispanic, 20.3% Asian, 8.4% African American, and 7.9% other. Of 23,748 bronchiolitis EOCs, 4969 (20.9%) had ≥1 test for RSV. Overall, 44.2% of all tests were positive for RSV. Physicians ordered RSV tests in 30.4% and 26.7% of bronchiolitis EOCs for infants born at 32 to 33 and 34 to 36 weeks' GA, respectively, compared with 17.9% of bronchiolitis EOCs for infants born at ≥41 weeks' GA. Bronchiolitis hospitalization, younger chronologic age, prematurity, and RSV season were associated with RSV testing in a multivariate model controlling for other variables, with an adjusted odds ratio (AOR) of 28.55 (95% CI, 24.99-36.62) for hospitalization status; AOR of 6.89 (95% CI, 5.19-9.15) for chronologic age <1 month; AOR of 0.85 (95% CI, 0.76-0.95) for GA >41 weeks; and AOR of 2.48 (95% CI, 2.24-2.74) for RSV season (December-March). Among hospitalized infants who were tested and had a diagnostic code suggesting treatment with antibiotics, use of antibiotics was significantly lower among those with a positive RSV test (63.4%) than those with a negative RSV test (75.5%) (χ(2) test; P < 0.001). CONCLUSIONS: Approximately 20% of these children with bronchiolitis EOCs were tested for RSV; of those tested, about half were positive. In this integrated health care system, hospitalization with bronchiolitis, chronologic age, gestational age <37 weeks, neonatal oxygen exposure, and bronchiolitis EOC during the RSV season were the factors associated with testing for RSV.