Biomarker-based text messages to promote lactation success in mothers of critically Ill infants: a randomized controlled pilot study.

OBJECTIVE: Infrequent breast pumping limits mother's own milk production in mothers of infants admitted to the neonatal intensive care unit. We aimed to determine the feasibility and benefit of biomarker-based personalized text messages on pumping frequency and milk sodium levels. A secondary aim examined lactation outcomes. STUDY DESIGN: In this randomized controlled pilot study, 51 mothers were randomized to receive personalized text messages regarding pumping frequency or standard care. RESULTS: There were no differences in pumped milk volume or sodium level, however, there was a trend towards the intervention group pumping more frequently, which was significant on day 5 (p = 0.035), and they lactated nearly 9 days longer. Post-hoc analysis found the intervention group tended to be more likely to pump ≥ 500 mL by day14 (p = 0.08), a marker of long-term lactation success. CONCLUSION: Personalized biomarker-based text messages are feasible and may support lactation in mothers of critically ill infants.

COVID-19 booster enhances IgG mediated viral neutralization by human milk in vitro.

Background: Facilitated by the inability to vaccinate, and an immature immune system, COVID-19 remains a leading cause of death among children. Vaccinated lactating mothers produce specific SARS-CoV-2 antibodies in their milk, capable of neutralizing the virus in vitro. Our objective for this study is to assess the effect of COVID-19 booster dose on SARS-CoV-2 antibody concentration and viral neutralization in milk, plasma, and infant stool. Methods: Thirty-nine mothers and 25 infants were enrolled from December 2020 to May 2022. Milk, maternal plasma, and infants' stool were collected at various time-points up to 12 months following mRNA COVID-19 vaccination. A subgroup of 14 mothers received a booster dose. SARS-CoV-2 antibody levels and their neutralization capacities were assessed. Results: Booster vaccination led to significantly higher IgG levels within human milk and breastfed infants' stool. In vitro neutralization of VSV-gfp-SARS-CoV-2-S-gp, a laboratory safe SARS-CoV-2 like pseudovirus, improved following the booster, with a 90% increase in plasma neutralization and a 60% increase in milk neutralization. We found that post-booster neutralization by human milk was highly correlated to SARS-CoV-2 IgG level. In support of our correlation result, Protein G column depletion of IgG in milk yielded a significant reduction in viral neutralization (p = 0.04). Discussion: The substantial increase in neutralizing IgG levels in milk and breastfed infants' stool post-booster, coupled with the decrease in milk neutralization capabilities upon IgG depletion, underscores the efficacy of booster doses in augmenting the immune response against SARS-CoV-2 in human milk.

A systematic review of contaminants in donor human milk.

Donor human milk (DHM) from a milk bank is the recommended feeding method for preterm infants when the mother's own milk (MOM) is not available. Despite this recommendation, information on the possible contamination of donor human milk and its impact on infant health outcomes is poorly characterised. The aim of this systematic review is to assess contaminants present in DHM samples that preterm and critically ill infants consume. The data sources used include PubMed, EMBASE, CINAHL and Web of Science. A search of the data sources targeting DHM and its potential contaminants yielded 426 publications. Two reviewers (S. T. and D. L.) conducted title/abstract screening through Covidence software, and predetermined inclusion/exclusion criteria yielded 26 manuscripts. Contaminant types (bacterial, chemical, fungal, viral) and study details (e.g., type of bacteria identified, study setting) were extracted from each included study during full-text review. Primary contaminants in donor human milk included bacterial species and environmental pollutants. We found that bacterial contaminants were identified in 100% of the papers in which bacterial contamination was sought (16 papers) and 61.5% of the full data set (26 papers), with the most frequently identified genera being Staphylococcus (e.g., Staphylococcus aureus and coagulase-negative Staphylococcus) and Bacillus (e.g., Bacillus cereus). Chemical pollutants were discovered in 100% of the papers in which chemical contamination was sought (eight papers) and 30.8% of the full data set (26 papers). The most frequently identified chemical pollutants included perfluoroalkyl substances (six papers), toxic metal (one paper) and caffeine (one paper). Viral and fungal contamination were identified in one paper each. Our results highlight the importance of establishing standardisation in assessing DHM contamination and future studies are needed to clarify the impact of DHM contaminants on health outcomes.

Perinatal Health Outcomes Across Rural and Nonrural Counties Within a Single Health System Catchment.

Background: Perinatal health outcomes are influenced by a variety of socioeconomic, behavioral, and economic factors that reduce access to health services. Despite these observations, rural communities continue to face barriers, including a lack of resources and the fragmentation of health services. Objective: To evaluate patterns in health outcomes, health behaviors, socioeconomic vulnerability, and sociodemographic characteristics across rural and nonrural counties within a single health system catchment area. Methods: Socioeconomic vulnerability metrics, health care access as determined by licensed provider metrics, and behavioral data were obtained from FlHealthCHARTS.gov and the County Health Rankings. County-level birth and health data were obtained from the Florida Department of Health. The University of Florida Health Perinatal Catchment Area (UFHPCA) was defined as all Florida counties where ≥5% of all infants were delivered at Shands Hospital between June 2011 and April 2017. Results: The UFHPCA included 3 nonrural and 10 rural counties that represented more than 64,000 deliveries. Nearly 1 in 3 infants resided in a rural county, and 7 out of 13 counties did not have a licensed obstetrician gynecologist. Maternal smoking rates (range 6.8%-24.8%) were above the statewide rate (6.2%). Except for Alachua County, breastfeeding initiation rates (range 54.9%-81.4%) and access to household computing devices (range 72.8%-86.4%) were below the statewide rate (82.9% and 87.9%, respectively). Finally, we found that childhood poverty rates (range 16.3%-36.9%) were above the statewide rate (18.5%). Furthermore, risk ratios suggested negative health outcomes for residents of counties within the UFHPCA for each measure, except for infant mortality and maternal deaths, which lacked sample sizes to adequately test. Conclusions: The health burden of the UFHPCA is characterized by rural counties with increased maternal death, neonatal death, and preterm birth, as well as adverse health behaviors that included increased smoking during pregnancy and lower levels of breastfeeding relative to nonrural counties. Understanding perinatal health outcomes across a single health system has potential to not only estimate community needs but also facilitate planning of health care initiatives and interventions in rural and low-resource communities.

Does Preterm Status Hinder the Timely Diagnosis of Intestinal Atresia?

Intestinal atresia is one of the most common causes of bowel obstruction in newborns. Unfortunately, this diagnosis is often missed or delayed in extremely preterm infants because of complications of prematurity including feeding intolerance and necrotizing enterocolitis. Here we report 2 cases of jejunoileal atresia in extremely preterm infants who were diagnosed beyond 30 days of age. Case 1 had jejunoileal atresia type IIIa, whereas case 2 had type IV jejunoileal atresia complicated by short bowel syndrome. Ideally, intestinal atresia should be diagnosed as early as possible in a patient's hospital course to attain full enteral feedings earlier and avoid prolonged hospitalization. Planned surgical intervention prior to the development of sepsis or bowel perforation is associated with better outcomes. Ultimately, this report serves as a reminder to physicians that intestinal atresia remains an important differential for infants, including preterm infants, with feeding intolerance in the first days to weeks of age.

Leveraging mHealth and a milk expression frequency biomarker during postpartum to prolong lactation among parents of critically ill infants: a pilot study.

OBJECTIVE: To assess the feasibility and potential benefits of personalized biomarker-based text messages in prolonging lactation among parents of critically ill infants. STUDY DESIGN: Thirty-six participants were randomized to receive either daily texts with Mother's Own Milk (MOM) sodium levels or standard care. Surveys at months 1 and 3 assessed whether infants were receiving exclusive MOM feeding, any MOM feeding, and whether the parent was still lactating. Kaplan-Meier and log-rank tests were used for time-to-event analysis within and between intervention and control groups. RESULTS: Participants were predominantly on Medicaid (72%), delivered infants <1500 g, and by c-section (56%). Kaplan-Meier probabilities at month 3 suggest prolonged MOM feeding (63% [0.95CI, 0.43-0.91] vs. 41% [0.95CI, 0.21-0.67]) and lactation (63% [0.95CI, 0.42-0.95] vs. 37% [0.95CI, 0.18-0.76]) in the enhanced group compared to the control group. CONCLUSION: Personalized biomarker-based text messages are feasible and may prolong lactation and MOM feeding among parents of critically ill infants.

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

OBJECTIVE: Assess presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stool, mother's plasma and milk following maternal vaccination. DESIGN: Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. All mothers were vaccinated during lactation except three, which were vaccinated during pregnancy. Milk, maternal plasma, and infants' stool was collected pre-vaccination and at periods up to 6 months following COVID-19 vaccine series initiation/completion. SARS-CoV-2 antibody levels and their neutralization capacities were assessed. RESULTS: SARS-CoV-2-specific IgA and IgG levels were higher in infant stool post-maternal vaccination amongst milk-fed compared to controls. Maternal SARS-CoV-2-specific IgA and IgG concentrations decreased over 6 months post-vaccination but remained higher than pre-vaccination levels. We observed improved neutralization capacity in milk and plasma after COVID-19 vaccination. CONCLUSIONS: The presence of SARS-CoV-2-specific antibodies in infant stool following maternal vaccination offers further evidence of the lasting transfer of these antibodies through breastfeeding.

A Randomized Trial of an Exclusive Human Milk Diet in Neonates with Single Ventricle Physiology.

OBJECTIVE: To determine whether weight gain velocity (g/kg/day) 30 days after the initiation of feeds after cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet. STUDY DESIGN: In this multicenter, randomized, single blinded, controlled trial, term neonates 7 days of age or younger with single ventricle physiology and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed. RESULTS: We enrolled 107 neonates (exclusive human milk = 55, control = 52). Baseline demographics and characteristics were similar between the groups. The median weight gain velocity at study completion was higher in exclusive human milk vs control group (12 g/day [IQR, 5-18 g/day] vs 8 g/day [IQR, 0.4-14 g/day], respectively; P = .03). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively; P = .04). The incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between the groups. CONCLUSIONS: Neonates with single ventricle physiology have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet after stage 1 surgical palliation. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov (www. CLINICALTRIALS: gov, Trial ID: NCT02860702).

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

Objective Assess the presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stools, mother's plasma, and human milk following maternal vaccination. Design Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. Human milk, maternal plasma, and infants' stools were collected pre-vaccination and at periods up to 6 months following COVID-19 vaccine series initiation/completion. SARS-CoV-2 antibody levels and their neutralization capacities were assessed in collected samples. Results SARS-CoV-2-specific IgA and IgG levels were higher in infant stool post-maternal vaccination amongst milk-fed compared to pre-COVID controls. Human milk and plasma SARS-CoV-2-specific IgA and IgG concentrations decreased over 6 months post-vaccination but remained higher than pre-vaccination levels. We observed improved neutralization capacity in milk antibodies over time. Conclusions The presence of neutralizing SARS-CoV-2-specific antibodies in infant stool following maternal vaccination offers further evidence of the lasting transfer of these antibodies through breastfeeding and their protective effect.

Antepartum Breast Pump Education for Mothers and Their Support Person: Effect on Time to First Expression and Lactation Outcomes-A Randomized Controlled Pilot Study.

Objective: To determine the effect of providing antenatal education regarding milk expression to the support person (SP) of mothers of preterm infants on time to initial milk expression following delivery and daily volume of expressed mother's own milk. Methods: Sixty-one mothers delivering infants <35 weeks gestation and their SP were randomized to receive antenatal education regarding milk expression or to receive standard care. Time to initiation of milk expression was determined through self-report and verified through the electronic medical records. Expressed milk volume was measured on days 1-7 and weekly for 3 weeks. Results: No difference in time to first expression or expressed milk volume was found between groups. Posthoc analysis suggests those in the antenatal education group were more likely to express without nursing assistance and expressed more frequently during days 1-5. Conclusions: SP antenatal education may be an important step in supporting lactation in mothers of critically ill infants. Further research is needed to determine whether SP education during both the antenatal and early postpartum periods could improve lactation success. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04006509.

Lung Ultrasound in the Neonatal Intensive Care Unit: Does It Impact Clinical Care?

A neonatal point-of-care ultrasound has multiple applications, but its use has been limited in neonatal intensive care units in the Unites States. An increasing body of evidence suggests that lung ultrasound performed by the neonatologist, at the bedside, is reliable and accurate in differentiating neonatal respiratory conditions, predicting morbidity, and guiding invasive interventions. Recent research has shown that a lung ultrasound can assist the clinician in accurately identifying and managing conditions such as respiratory distress syndrome, transient tachypnea of the newborn, and bronchopulmonary dysplasia. In this review, we discuss basic lung ultrasound terminology, evidence for applications of neonatal lung ultrasound, and its use as a diagnostic and predictive tool for common neonatal respiratory pathologies.

Detection of SARS-CoV-2-Specific IgA in the Human Milk of COVID-19 Vaccinated Lactating Health Care Workers.

Background: In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), emerged. In December 2020, two mRNA-based COVID-19 vaccines were approved for use in the United States, which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants' immunity. Certain vaccines given to pregnant and lactating mothers provide immunity to infants through transmission across the placenta, umbilical cord (IgG), and human milk (IgA). Human milk produced by mothers with a history of COVID-19 infection contains SARS-CoV-2 IgA and IgG. The purpose of this study is to determine whether SARS-CoV-2-specific immunoglobulins are found in human milk after the COVID-19 vaccination, and to characterize the types of immunoglobulins present. Methods: This is a prospective observational study conducted at Shands Hospital, University of Florida, from December 2020 to March 2021. Twenty-two lactating health care workers who received the SARS-CoV-2 mRNA vaccine (Pfizer/BioNTech or Moderna) made up the sample group. Plasma and human milk were collected at three time points (prevaccination, post-first vaccine dose, and post-second vaccine dose). SARS-CoV-2-specific IgA and IgG in human milk and in plasma were measured by enzyme-linked immunosorbent assay (ELISA). Maternal demographics were compiled. Results: We found significant secretion of SARS-CoV-2-specific IgA and IgG in human milk and plasma after SARS-CoV-2 vaccination. Conclusions: Our results show that the mRNA-based COVID-19 vaccines induce SARS-CoV-2-specific IgA and IgG secretion in human milk. Further studies are needed to determine the duration of this immune response, its capacity to neutralize the COVID-19 virus, the transfer of passive immunity to breastfeeding infants, and the potential therapeutic use of human milk IgA to combat SARS-CoV-2 infections and COVID-19.

Effect of Postpartum Depo Medroxyprogesterone Acetate on Lactation in Mothers of Very Low-Birth-Weight Infants.

Objective: This study examined the effect of postpartum administration of depo medroxyprogesterone acetate (DMPA) on milk production, time to onset of secretory activation, lactation duration, and infant consumption of mother's own milk (MOM) in mothers of preterm very low-birth-weight (VLBW) infants. Materials and Methods: We conducted a secondary analysis of data from mothers who delivered infants weighing ≤1,500 g and at ≤32 weeks' gestation. The volume of milk produced was measured on days 1-7, 14, and 21 by weighing all expressed milk on an electronic scale. Time to secretory activation was determined through self-report of a feeling of breast fullness. Information on lactation duration and the percent of feeds consisting of MOM consumed by infants was obtained from the medical records. Results: Mothers who received postpartum DMPA were more likely to be African American (72.4% versus 31.4%; p = 0.0006), unemployed (65.5% versus 44.5%; p = 0.027), and Medicaid eligible (89.7% versus 67.2%; p = 0.019). There were no differences in daily milk production between mothers who received DMPA before hospital discharge (n = 29) compared with those who did not (n = 141). When mothers who reached secretory activation before receiving DMPA were removed from analysis, receiving DMPA was associated with a later onset of secretory activation (103.7 versus 88.6 hours; p = 0.028). There were no statistically significant differences between the study groups in lactation duration or infant MOM consumption. Conclusions: DMPA, when administered postpartum to mothers of preterm VLBW infants, delayed secretory activation, but had no detrimental effect on milk production or lactation duration. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01892085.

Measures of Lactation Outcomes in Women Delivering Preterm Infants.

BACKGROUND: Mother's own milk (MOM) is well known to decrease prematurity-related morbidities, yet mothers delivering preterm infants often produce insufficient quantities of milk to provide these benefits. Although a critical need exists for research to support lactation success in this vulnerable population, development and investigation of interventions to increase available MOM for infant consumption requires consistent, valid, and reliable measures of lactation outcomes. OBJECTIVES: The aim of this study was to compare and contrast methods of measuring lactation outcomes in mothers of preterm infants and evaluate their advantages and disadvantages. METHODS: Measures of lactation outcomes were reviewed and synthesized. Insights on best practices and future research directions are provided. RESULTS: Volume of MOM produced, lactation duration, and time to onset of secretory activation are important measures of lactation success. The most valid and reliable measure of milk production is likely weighing each vial of expressed milk combined with test weighing when infants breastfeed. Measures of lactation duration should include actual days mothers lactated rather than limiting to infant consumption of MOM as a proxy for duration and include not only whether mothers are lactating at infant discharge but whether they are also lactating at other health-relevant time points during hospitalization. Although time to onset of secretory activation is an important lactation outcome, information regarding valid and reliable indicators of onset in women delivering preterm infants is limited, and investigation of such indicators is a research priority. Variables that may affect lactation outcomes, including time to initiation of expression following delivery, duration of expression sessions, expression method, time spent in skin-to-skin care, maternal demographics and comorbidities, as well as maternal intent to lactate, must be considered when researchers investigate lactation outcomes in mothers of very low birth weight infants. DISCUSSION: Consistent and valid measures of lactation outcomes are required to produce reliable results from which evidence-based practice recommendations can be developed in order to improve lactation success in this vulnerable population.

Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants.

BACKGROUND: Inconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants. RESEARCH AIMS: To compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production. METHODS: Indicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1-7 and then weekly for 6 weeks. RESULTS: In 69 mothers of infants born ≤ 32 weeks' gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1-7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 (p = .028 and .011), those with only normal lactose levels produced more on Day 42 (p = .026) and those with only normal sodium levels on Day 28 (p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2-5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2-5 (all p < .020). CONCLUSION: Mothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.

BACKGROUND: Delivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants. OBJECTIVE: The aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years. METHODS: Pediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37-42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures. RESULTS: The mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0-1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1-3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34). CONCLUSION: Our results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.

Consumption of Mother's Own Milk by Infants Born Extremely Preterm Following Implementation of a Donor Human Milk Program: A Retrospective Cohort Study.

OBJECTIVE: To compare mothers' own milk (MOM) consumption by infants born extremely preterm before and after implementation of a donor human milk (DHM) program and determine healthcare provider's knowledge and practices regarding DHM. STUDY DESIGN: One hundred fifty-seven infants born at <30 weeks of gestation were enrolled during 3 time-periods. Group 1: before DHM program implementation, Group 2: the year following implementation, and Group 3: the second year after implementation. The proportion of feeds consisting of MOM for 6 weeks following birth was analyzed using a generalized linear mixed model. The study's second phase surveyed healthcare providers regarding knowledge and practices concerning DHM. RESULTS: Group 1 consumed feeds with a greater proportion of MOM than Group 3 during weeks 1 (P < .001) and 3 (P = .007) and more than both Group 2 (P = .033) and 3 (P = .021) in week 4. During the first 14 days, Group 1 consumed feeds with 23.6% more MOM than Group 3 (P = .002) and had a greater odds of consuming feeds with > 90% MOM (P < .001) than Group 3. During days 1-28, Group 1 consumed feeds with 22% more MOM than Group 3 (P = .003) and had greater odds of consuming feeds with >90% MOM than Group 2 (P = .020) and 3 (P = .004). Knowledge regarding DHM was inconsistent among providers and they were unlikely to communicate potential risks and benefits of DHM to mothers. CONCLUSIONS: Following implementation of a DHM program, MOM consumption decreased over 2 years. Strategies focused on lactation success are necessary to increase MOM consumption.