Diabetes insipidus (DI) is a disorder of the hypothalamic-pituitary axis resulting in abnormal sodium (Na) balance, dilute urine, and hypertonic dehydration. DI may impact lactation by impacting hormones necessary for lactation maintenance or through DI-related alterations in pituitary function and Na metabolism. Two lactating mothers with DI presented to a breastfeeding and lactation medicine (BFLM) clinic with a concern of poor infant growth. Breast milk electrolytes and macronutrient concentrations were normal. Both mothers had normal electrolyte values but lacked the normal doubling in serum prolactin levels after pumping. Both experienced an increase in milk production after the use of dopamine blocker metoclopramide. Infant growth improved after frenotomy and supplementation. After intervention, one of the two mothers achieved her goal of fully breastfeeding. Further research should investigate the role of the Na-potassium pump in the production of breast milk and the secretion of prolactin and oxytocin in lactating mothers with DI.

Objective:The objective was to explore variation of macronutrient and bioactive content between levels of human milk-derived human milk fortifier (HM-HMF), and between donor human milk (DHM) from commercial vs non-profit banks. Study Design:We analyzed the concentration of macronutrients, Immunoglobulin A (IgA), and cortisol in multiple lots of each HM-HMF product (20, 24, 26, 28, and 30 kcal/oz) using multiple methods. Result:At each level of caloric density (p<0.0001), protein, carbohydrate, and caloric concentration in HM-HMF increased with minor exceptions while fat and cortisol concentrations did not differ. Total IgA concentrations differed by product type (p <0.0001). Protein concentration did not differ between commercial and non-profit donor milk banks while carbohydrates, fat, calories, and cortisol were higher, and IgA was lower. Lot-to-lot variability of all DHM components was lower in commercial DHM. Conclusion:This study expands data on the variability in the composition of DHM originating from various sources.

BACKGROUND:Breastfeeding and Lactation Medicine (BFLM) programs at academic medical centers have the potential to transform the care of lactating people. Our hospital system initiated a BFLM program in 2016, culminating in a division in 2022. OBJECTIVES:To describe the impacts of a multidisciplinary academic BFLM program in its first 8 years. METHODS:We created an outpatient BFLM clinic and support group, increased BFLM and lactation consultant (LC) coverage, dedicated a medical director and nurse manager for lactation, and expanded University-wide education. In 2017, our neonatal intensive care unit (NICU) instituted a donor milk program. We started an in-person fellowship in 2017 and a virtual fellowship program in 2022. In 2019, we founded a lactation research consortium. These services coalesced to form the first Division of Breastfeeding and Lactation Medicine in 2022. We tracked our impact using process outcomes (numbers of providers, visits, grants) and patient outcomes (breastfeeding rates). Simple frequencies and p-control charts were used to track access to care and breastfeeding outcomes. RESULTS:From 2016 to 2024, we increased inpatient and outpatient care by BFLM providers and LCs. Breastfeeding rates on the postpartum floors increased by 7% between 2016 and 2024 (p < 0.01). In the NICU, there was a trend toward increased patients receiving any breastmilk and discharged receiving any maternal milk. Challenges included staff training, reimbursement, medical record infrastructure, and creating/accessing accurate data reports. CONCLUSION:A multidisciplinary BFLM program at a large academic medical center showed promise for improving patient access to care and breastfeeding outcomes.

Background: Breastfeeding and Lactation Medicine (BFLM) programs at academic medical centers are uncommon but expanding. Our academic medical center, with a long legacy of leadership in BFLM, established a BFLM program in 2016 and launched a dedicated division in 2022. Objectives: To describe the strategy, services, measures, and challenges facing our multidisciplinary academic BFLM program in its first 8 years. Methods: To support the development of the Division, we proved clinical need, built capacity, and determined key outcomes. We organized partnerships across clinical and research programs and developed leadership and reporting structures. These services and programs coalesced to form the first Division of Breastfeeding and Lactation Medicine in 2022, including multiple specialties (pediatrics, obstetrics, family medicine, nutrition research, toxicology, public health, dentistry) and provider types (nursing, lactation consultants, physicians, midwife, nurse practitioner, PhD, dentist). Challenges included variable buy-in, staff training, reimbursement, medical record infrastructure, and data reports. Challenges to research included funding and clinical integration. Conclusion: A multidisciplinary BFLM Division at a large academic medical center was formed, spanning our clinical, research, and educational missions. Integration into traditional academic structures brings essential resources, enables participation in medical center leadership, and promotes the sustainability of divisional activities.

BACKGROUND:Infant sleep is critical for cognitive, emotional, and long-term health outcomes. Although diet-sleep relationships are established, limited research has explored how polyunsaturated fatty acids (PUFAs) in human milk (HM) relate to infant sleep. OBJECTIVES:This study aims to examine associations between PUFAs in HM and sleep patterns in 2-mo-old infants exclusively fed with HM. METHODS:This cross-sectional secondary analysis used data from a lactation cookie trial involving 131 parents of healthy, term infants. Participants provided a fasting HM sample and completed sociodemographic and Brief Infant Sleep Questionnaire surveys. Multivariate linear models were adjusted for infant sex assigned at birth, weight-for-length z-scores, maternal prepregnancy body mass index, and daily feedings. RESULTS:Participants self-identified as 81.7% White, 13.3% Hispanic, with 25.9% reporting an annual income <US$45,000. Infants slept a mean of 14.67 h [standard deviation (SD) = 2.65]. PUFAs constituted 20.91% (SD = 4.47) of total milk fatty acids, with omega-3 and omega-6 comprising 1.75% (SD = 0.53) and 19.16% (SD = 4.09), respectively. Significant positive associations were observed between total sleep and omega-3 [B = 1.06, standard error (SE) = 0.47, P = 0.026], omega-6 (B = 0.14, SE = 0.06, P = 0.022), alpha-linolenic acid (ALA) (B = 1.10, SE = 0.53, P = 0.040), and linoleic acid (LA) (B = 0.15, SE = 0.06, P = 0.016). When sleep was partitioned into diurnal or nocturnal, greater omega-3 and omega-6, particularly ALA and LA, were significantly associated with increased diurnal sleep duration: (ALA, B = 1.11, SE = 0.39, P = 0.005; LA, B = 0.12, SE = 0.05, P = 0.009). No significant associations were observed with nocturnal sleep. CONCLUSIONS:Higher HM proportions of omega-3 and omega-6, particularly ALA and LA, were associated with greater diurnal sleep in exclusively HM-fed 2 month olds. Further research is needed to explore underlying mechanisms and long-term developmental impacts. This trial was registered at clinicaltrials.gov as NCT04805008.

Nipple pain is a common reason for premature breastfeeding cessation. There exists anecdotal evidence that one cause of lactational nipple pain is a ductal obstruction, but there is no published literature describing this phenomenon. Herein we present two case reports for two patients who experienced breast and nipple pain concurrent with milk flow reduction. Both patients removed a small stone-like obstructing object from their nipple; this action was painful for one of the patients, resulting in immediate release of milk and relief from breast pain. Both patients experienced recurrence of stone formation in their nipple ducts. We analyzed the mineral composition of the obstructing objects and breast milk using inductively coupled mass spectroscopy. We use literature on teat obstructions in dairy cows and dacryolith and sialolith formation to propose hypotheses as to how the formation of obstructing objects in milk ducts might occur. Future research directions for determining the pathophysiology, clinical presentation, and management of human nipple duct obstructions are discussed.

BackgroundMaternal stress is pervasive in the neonatal intensive care unit (NICU). Maternal stress is associated with changes in human milk (HM) immunomodulatory agents, which may impact neonatal health. We sought to determine the association between maternal stress, HM immunoglobulin A (IgA) and cortisol, and to assess how these milk components correlate with infant immune and neurodevelopmental outcomes. We then compared how these associations persist over time.MethodsThe study design involved a cohort study of exclusively breastfeeding mothers and their singleton moderately preterm (28–34 weeks) infants admitted to the NICU. We collected maternal serum, maternal saliva, and first-morning whole milk samples, and administered maternal stress questionnaires at 1 and 5 weeks postpartum. We analyzed the samples for HM IgA (using a customized immunoassay in skim milk) and for HM and salivary cortisol (using a chemiluminescent immunoassay). Infant illness was assessed using the Score for Neonatal Acute Physiology II (SNAP II) and SNAP II with Perinatal Extension (SNAPPE II), and infant neurodevelopment were assessed using the Test of Infant Motor Performance. We analyzed changes in HM IgA and cortisol over time using paired t-tests. Furthermore, we performed correlation and regression analyses after adjusting for gestational age (GA), corrected GA, and infant days of life.ResultsIn our study, we enrolled 26 dyads, with a mean maternal age of 28.1 years, consisting of 69% white, 19% Black, and 8% Hispanic. Cortisol: Salivary and HM cortisol were closely associated in week 1 but not in week 5. Though mean salivary cortisol remained stable over time [2.41 ng/mL (SD 2.43) to 2.32 (SD 1.77), p = 0.17], mean HM cortisol increased [1.96 ng/mL (SD 1.93) to 5.93 ng/mL (SD 3.83), p < 0.001]. Stress measures were inversely associated with HM cortisol at week 1 but not at week 5. IgA: HM IgA decreased over time (mean = −0.14 mg/mL, SD 0.53, p < 0.0001). High maternal stress, as measured by the Parental Stressor Scale: neonatal intensive care unit (PSS:NICU), was positively associated with HM IgA at week 5 (r = 0.79, P ≤ 0.001). Higher IgA was associated with a lower (better) SNAP II score at week 1 (r = −0.74, p = 0.05). No associations were found between maternal stress, salivary cortisol, HM cortisol, or HM IgA and neurodevelopment at discharge (as assessed using the TIMP score). Furthermore, these relationships did not differ by infant sex.ConclusionMaternal stress showed associations with HM cortisol and HM IgA. In turn, HM IgA was associated with lower measures of infant illness.

OBJECTIVE:In 2017, our Level IV NICU switched from providing bovine-derived (BOV-fort) to human milk-derived fortifiers (HM-fort) and donor human milk (DHM) to premature infants born ≤ 30 weeks or ≤1250 g. Following this change, providers anecdotally observed increased hypoglycemia, hypercalcemia, and hyperphosphatemia. This study investigated potential laboratory differences between infants fed Bovine vs. Human milk derived fortifier. METHODS:Lab measurements from 402 infants (232 BOV-fort, 170 HM-fort) born between 2015 and 2019 were compared between groups. RESULTS:The proportion of infants ever having a blood glucose ≤ 45 mg/dL (p < 0.0001) was higher in the HM-fort group. The proportion of infants ever experiencing a phosphorus > 8.0 mg/dL were higher in the HM-fort group (p < 0.0001). The proportion of infants ever experiencing calcium > 11.4 mg/dL was higher in the HM-Fort group (p = 0.019). CONCLUSIONS:Provision of HM-Fort and DHM to extremely premature infants is associated with metabolic derangements.

The objective of this study is to develop and evaluate natural language processing (NLP) and machine learning models to predict infant feeding status from clinical notes in the Epic electronic health records system. The primary outcome was the classification of infant feeding status from clinical notes using Medical Subject Headings (MeSH) terms. Annotation of notes was completed using TeamTat to uniquely classify clinical notes according to infant feeding status. We trained 6 machine learning models to classify infant feeding status: logistic regression, random forest, XGBoost gradient descent, k-nearest neighbors, and support-vector classifier. Model comparison was evaluated based on overall accuracy, precision, recall, and F1 score. Our modeling corpus included an even number of clinical notes that was a balanced sample across each class. We manually reviewed 999 notes that represented 746 mother-infant dyads with a mean gestational age of 38.9 weeks and a mean maternal age of 26.6 years. The most frequent feeding status classification present for this study was exclusive breastfeeding [n = 183 (18.3%)], followed by exclusive formula bottle feeding [n = 146 (14.6%)], and exclusive feeding of expressed mother’s milk [n = 102 (10.2%)], with mixed feeding being the least frequent [n = 23 (2.3%)]. Our final analysis evaluated the classification of clinical notes as breast, formula/bottle, and missing. The machine learning models were trained on these three classes after performing balancing and down sampling. The XGBoost model outperformed all others by achieving an accuracy of 90.1%, a macro-averaged precision of 90.3%, a macro-averaged recall of 90.1%, and a macro-averaged F1 score of 90.1%. Our results demonstrate that natural language processing can be applied to clinical notes stored in the electronic health records to classify infant feeding status. Early identification of breastfeeding status using NLP on unstructured electronic health records data can be used to inform precision public health interventions focused on improving lactation support for postpartum patients.

Human milk is universally recognized as the preferred food for infants during the first 6 mo of life because it provides not only essential and conditionally essential nutrients in necessary amounts but also other biologically active components that are instrumental in protecting, communicating important information to support, and promoting optimal development and growth in infants. Despite decades of research, however, the multifaceted impacts of human milk consumption on infant health are far from understood on a biological or physiological basis. Reasons for this lack of comprehensive knowledge of human milk functions are numerous, including the fact that milk components tend to be studied in isolation, although there is reason to believe that they interact. In addition, milk composition can vary greatly within an individual as well as within and among populations. The objective of this working group within the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to provide an overview of human milk composition, factors impacting its variation, and how its components may function to coordinately nourish, protect, and communicate complex information to the recipient infant. Moreover, we discuss the ways whereby milk components might interact such that the benefits of an intact milk matrix are greater than the sum of its parts. We then apply several examples to illustrate how milk is better thought of as a biological system rather than a more simplistic "mixture" of independent components to synergistically support optimal infant health.

BACKGROUND:Evidence regarding the effects of infant feeding type (exclusive breastfeeding compared with exclusive formula feeding) on the gut microbiota and how it impacts infant growth status is limited. OBJECTIVES:The primary objective was to compare gut microbiota by feeding type and characterize the associations between gut microbiota and infant growth status. METHODS:Stool samples from healthy, full-term infants (4-5 mo-old) who were either exclusively breastfed (BF) or exclusively formula-fed (FF) in Denver, CO, United States were collected, and fecal 16S ribosomal ribonucleic acid gene-based profiling was conducted. Length and weight were measured at the time of stool collection. Length-for-age z-score, weight-for-age z-scores (WAZ), and weight-for-length z-scores were calculated based on the World Health Organization standards. Associations between gut microbial taxa and anthropometric z-scores were assessed by Spearman's rank correlation test. RESULTS:A total of 115 infants (BF n = 54; FF n = 61) were included in this study. Feeding type (BF compared with FF) was the most significant tested variable on gut microbiota composition (P < 1 × 10-⁶), followed by mode of delivery and race. Significant differences were observed in α-diversity, β-diversity, and relative abundances of individual taxa between BF and FF. BF infants had lower α-diversity than FF infants. Abundances of Bifidobacterium and Lactobacillus were greater in the breastfeeding group. FF infants had a higher relative abundance of unclassified Ruminococcaceae (P < 0.001), which was associated with a higher WAZ (P < 0.001) and length-for-age z-score (P < 0.01). Lactobacillus was inversely associated with WAZ (P < 0.05). CONCLUSIONS:Feeding type is the main driver of gut microbiota differences in young infants. The gut microbiota differences based on feeding type (exclusive breast- or formula feeding) were associated with observed differences in growth status. This trial was registered at clinicaltrials.gov as NCT02142647, NCT01693406, and NCT04137445.

Background: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown. Objectives: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy.Methods: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking gal-actagogues. The primary outcome was baseline-to-1-mo changes in human milk production rate (HMPR), measured with a validated milk expression protocol. Secondary outcomes included changes in perceived insufficient milk (PIM) and lactation self-efficacy scores.Results: Among 176 randomly assigned participants (age: 31.3 +/- 5.8 y; 71.0% self-identified as White, 15.3% Hispanic/Latin, 6.3% Black, and 4.0% Asian), 90 participants (51.1%) completed endline HMPR measures and 129 (73.3%) completed secondary outcomes. Imputed models showed a mean increase in HMPR of 5.8 +/- 15.7 mL/h in control participants and 5.5 +/- 17.6 mL/h in the LC participants after 1 mo of daily intake of the cookie. No significant differences were observed with adjusted linear mixed models on the multiply imputed data comparing baseline-to-endline changes in HMPR, PIM, or breastfeeding self-efficacy: mean (SE) difference-in-differences for HMPR, -0.33 (4.97), P = 0.948; PIM scores (range: 5-50), -0.52 (1.83), P = 0.775; and self-efficacy scores (range: 14-70), 0.31 (2.23), P = 0.888, respectively.Conclusions: This study found no evidence for the effect of consuming LCs on HMPR, PIM, or breastfeeding self-efficacy in exclusively breastfeeding parents with an overall adequate perceived milk supply. Recommendations to consume LCs for increasing objective or subjective milk supply may deliver false hope and unnecessary financial costs at a vulnerable time.

Abstract Objectives To review available health and nutrition claims for infant formula products in multiple countries and to evaluate the validity of the evidence used for substantiation of claims. Design International cross sectional survey. Setting Public facing and healthcare professional facing company owned or company managed formula industry websites providing information about products marketed for healthy infants delivered at full term in 15 countries: Australia, Canada, Germany, India, Italy, Japan, Nigeria, Norway, Pakistan, Russia, Saudi Arabia, South Africa, Spain, the United Kingdom, and the United States in 2020-22. Main outcome measures Number and type of claims made for each product and ingredient. References cited were reviewed and risk of bias was assessed for registered clinical trials using the Cochrane risk of bias tool, and for systematic reviews using the Risk Of Bias in Systematic reviews tool. Results 757 infant formula products were identified, each with a median of two claims (range from 1 (Australia) to 4 (US)), and 31 types of claims across all products. Of 608 products with ≥1 claims, the most common claim types were “helps/supports development of brain and/or eyes and/or nervous system” (323 (53%) products, 13 ingredients), “strengthens/supports a healthy immune system” (239 (39%) products, 12 ingredients), and “helps/supports growth and development” (224 (37%) products, 20 ingredients). 41 groups of ingredients were associated with ≥1claims, but many claims were made without reference to a specific ingredient (307 (50%) products). The most common groups of ingredients cited in claims were long chain polyunsaturated fatty acids (278 (46%) products, 9 different claims); prebiotics, probiotics, or synbiotics (225 (37%) products, 19 claims); and hydrolysed protein (120 (20%) products, 9 claims). 161/608 (26%) products with ≥1 claims provided a scientific reference to support the claim—266 unique references were cited for 24 different claim types for 161 products. The reference types most frequently cited were clinical trials (50%, 134/266) and reviews (20%, 52/266). 28% (38/134) of referenced clinical trials were registered, 14% (19/134) prospectively. 58 claims referred to 32 registered clinical trials, of which 51 claims (27 trials) related to a randomised comparison. 46 of 51 claims (90%) referenced registered clinical trial outcomes at high risk of bias, and all cited systematic reviews and pooled analyses, carried a high risk of bias. Conclusions Most infant formula products had at least one health and nutrition claim. Multiple ingredients were claimed to achieve similar health or nutrition effects, multiple claims were made for the same ingredient type, most products did not provide scientific references to support claims, and referenced claims were not supported by robust clinical trial evidence.

Objective To investigate differences in hypoglycemia and extended feed prescriptions among premature infants provided bovine-derived human milk fortifiers (Bov-fort) with mother’s milk or formula vs human milk-derived human milk fortifiers (HM-fort) with mother’s milk or donor human milk. Study design This was a retrospective chart review ( n = 98). Infants receiving HM-fort were matched with infants receiving Bov-fort. Blood glucose values and feed orders were retrieved from the electronic medical record. Results Prevalence of ever having blood glucose <60 mg/dL was 39.1% in the HM-fort group vs. 23.9% in the Bov-fort group ( p = 0.09). Blood glucose ≤45 mg/dL occurred in 17.4% of HM-fort vs 4.3% in Bov-fort ( p = 0.07). Feeds were extended for any reason in 55% of HM-fort vs. 20% of Bov-fort ( p < 0.01). Feed extension due to hypoglycemia occurred in 24% of HM-fort vs. 0% of Bov-fort ( p < 0.01). Conclusion Predominately HM-based feeds are associated with feed extension due to hypoglycemia. Prospective research is warranted to elucidate underlying mechanisms.

Requirements for iron and docosahexaenoic acid (DHA) content of infant formula varies by country. Powdered full-term infant formula purchase data from all major physical stores in the US between 2017-2019 were obtained from CIRCANA, Inc. Iron and DHA composition and scoop sizes for each formula were obtained from manufacturers. The equivalent liquid ounces of prepared formula were calculated. Average iron and DHA content were compared between formula types and to both US and European formula composition requirements. These data represent 55.8 billion ounces of formula. The average iron content of all formula purchased was: 1.80 mg/100 kcal. This iron concentration is within the FDA regulations. However, it exceeds the maximum allowable iron concentration of infant formula (Stage 1) set by the European Commission of 1.3 mg/100 kcal. A total of 96% of formula purchased had an iron concentration of >1.3 mg/100 kcal. DHA is not a required ingredient in US formulas. The average DHA content of all formula purchased was: 12.6 mg/100 kcal. This DHA concentration is far below the minimum required DHA concentrations of infant formula (Stage 1) and follow-on formula (Stage 2) set by the European Commission of 20 mg/100 kcal. These are novel insights into the iron and DHA intake of formula-fed infants in the US. As international infant formulas have entered the US market due to the formula shortage, parents and providers need to be aware of regulatory differences in formula nutrient composition.

Epidemiological data demonstrate that bovine whole milk is often substituted for human milk during the first 12 months of life and may be associated with adverse infant outcomes. The objective of this study is to interrogate the human and bovine milk metabolome at 2 weeks of life to identify unique metabolites that may impact infant health outcomes. Human milk (n = 10) was collected at 2 weeks postpartum from normal-weight mothers (pre-pregnant BMI < 25 kg/m2) that vaginally delivered term infants and were exclusively breastfeeding their infant for at least 2 months. Similarly, bovine milk (n = 10) was collected 2 weeks postpartum from normal-weight primiparous Holstein dairy cows. Untargeted data were acquired on all milk samples using high-resolution liquid chromatography–high-resolution tandem mass spectrometry (HR LC-MS/MS). MS data pre-processing from feature calling to metabolite annotation was performed using MS-DIAL and MS-FLO. Our results revealed that more than 80% of the milk metabolome is shared between human and bovine milk samples during early lactation. Unbiased analysis of identified metabolites revealed that nearly 80% of milk metabolites may contribute to microbial metabolism and microbe–host interactions. Collectively, these results highlight untargeted metabolomics as a potential strategy to identify unique and shared metabolites in bovine and human milk that may relate to and impact infant health outcomes.

It is currently unclear if SARS-CoV-2 infection or mRNA vaccination can also induce IgG and IgA against common human coronaviruses (HCoVs) in lactating parents. Here we prospectively analyzed human milk (HM) and blood samples from lactating parents to measure the temporal patterns of anti-SARS-CoV-2 specific and anti-HCoV cross-reactive IgA and IgG responses. Two cohorts were analyzed: a vaccination cohort (n = 30) who received mRNA-based vaccines for COVID-19 (mRNA-1273 or BNT162b2), and an infection cohort (n = 45) with COVID-19 disease. Longitudinal HM and fingerstick blood samples were collected pre- and post-vaccination or, for infected subjects, at 5 time-points 14-28 days after confirmed diagnosis. The anti-spike(S) and anti-nucleocapsid(N) IgA and IgG antibody levels against SARS-CoV-2 and HCoVs were measured by multiplex immunoassay (mPlex-CoV). We found that vaccination significantly increased the anti-S IgA and IgG levels in HM. In contrast, while IgG levels increased after a second vaccine dose, blood and HM IgA started to decrease. Moreover, HM and blood anti-S IgG levels were significantly correlated, but anti-S IgA levels were not. SARS2 acute infection elicited anti-S IgG and IgA that showed much higher correlations between HM and blood compared to vaccination. Vaccination and infection were able to significantly increase the broadly cross-reactive IgG recognizing HCoVs in HM and blood than the IgA antibodies in HM and blood. In addition, the broader cross-reactivity of IgG in HM versus blood indicates that COVID-19 vaccination and infection might provide passive immunity through HM for the breastfed infants not only against SARS-CoV-2 but also against common cold coronaviruses.

The protein and carbohydrate composition of formula fed infants' diets in the United States (US) has not been described. The aims of this study were to characterize these dietary exposures in infant formula purchased in the US and to estimate the proportion of formula purchased which is hypoallergenic or lactose‐reduced formula.

Bridget E. Young, PhD; Antti E. Seppo, PhD; Nichole Diaz, BA; Casey Rosen-Carole, MD; Anna Nowak-Wegrzyn, MD, PhD; Joseline M. Cruz Vasquez, MPH; Rita Ferri-Huerta, MD; Phuong Nguyen-Contant, PhD; Theresa Fitzgerald, BA; Mark Y. Sangster, PhD; David J. Topham, PhD; Kirsi M. Järvinen, MD, PhD

Importance:Long-term effect of parental COVID-19 infection vs vaccination on human milk antibody composition and functional activity remains unclear. Objective:To compare temporal IgA and IgG response in human milk and microneutralization activity against SARS-CoV-2 between lactating parents with infection and vaccinated lactating parents out to 90 days after infection or vaccination. Design, Setting, and Participants:Convenience sampling observational cohort (recruited July to December 2020) of lactating parents with infection with human milk samples collected at days 0 (within 14 days of diagnosis), 3, 7, 10, 28, and 90. The observational cohort included vaccinated lactating parents with human milk collected prevaccination, 18 days after the first dose, and 18 and 90 days after the second dose. Exposures:COVID-19 infection diagnosed by polymerase chain reaction within 14 days of consent or receipt of messenger RNA (mRNA) COVID-19 vaccine (BNT162b2 or mRNA-1273). Main Outcomes and Measures:Human milk anti-SARS-CoV-2 receptor-binding domain IgA and IgG and microneutralization activity against live SARS-CoV-2 virus. Results:Of 77 individuals, 47 (61.0%) were in the infection group (mean [SD] age, 29.9 [4.4] years), and 30 (39.0%) were in the vaccinated group (mean [SD] age, 33.0 [3.4] years; P = .002). The mean (SD) age of infants in the infection and vaccinated group were 3.1 (2.2) months and 7.5 (5.2) months, respectively (P < .001). Infection was associated with a variable human milk IgA and IgG receptor-binding domain-specific antibody response over time that was classified into different temporal patterns: upward trend and level trend (33 of 45 participants [73%]) and low/no response (12 of 45 participants [27%]). Infection was associated with a robust and quick IgA response in human milk that was stable out to 90 days after diagnosis. Vaccination was associated with a more uniform IgG-dominant response with concentrations increasing after each vaccine dose and beginning to decline by 90 days after the second dose. Vaccination was associated with increased human milk IgA after the first dose only (mean [SD] increase, 31.5 [32.6] antibody units). Human milk collected after infection and vaccination exhibited microneutralization activity. Microneutralization activity increased throughout time in the vaccine group only (median [IQR], 2.2 [0] before vaccine vs 10 [4.0] after the first dose; P = .003) but was higher in the infection group (median [IQR], 20 [67] at day 28) vs the vaccination group after the first-dose human milk samples (P = .002). Both IgA and non-IgA (IgG-containing) fractions of human milk from both participants with infection and those who were vaccinated exhibited microneutralization activity against SARS-CoV-2. Conclusions and Relevance:In this cohort study of a convenience sample of lactating parents, the pattern of IgA and IgG antibodies in human milk differed between COVID-19 infection vs mRNA vaccination out to 90 days. While infection was associated with a highly variable IgA-dominant response and vaccination was associated with an IgG-dominant response, both were associated with having human milk that exhibited neutralization activity against live SARS-CoV-2 virus.