Obesity in children remains a major public health problem, with the current prevalence in youth ages 2–19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29–30, 2021, the National Institutes of Health convened a virtual workshop on “Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children.” The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

The establishment of the gut microbiome in early life is critical for healthy infant development. Although human milk is recommended as the sole source of nutrition for the human infant, little is known about how variation in milk composition, and especially the milk microbiome, shapes the microbial communities in the infant gut. Here, we quantified the similarity between the maternal milk and the infant gut microbiome using 507 metagenomic samples collected from 195 mother-infant pairs at one, three, and six months postpartum. We found that the microbial taxonomic overlap between milk and the infant gut was driven by bifidobacteria, in particular by B. longum . Infant stool samples dominated by B. longum also showed higher temporal stability compared to samples dominated by other species. We identified two instances of strain sharing between maternal milk and the infant gut, one involving a commensal ( B. longum ) and one a pathobiont ( K. pneumoniae ). In addition, strain sharing between unrelated infants was higher among infants born at the same hospital compared to infants born in different hospitals, suggesting a potential role of the hospital environment in shaping the infant gut microbiome composition. The infant gut microbiome at one month compared to six months of age was enriched in metabolic pathways associated with de-novo molecule biosynthesis, suggesting that early colonisers might be more versatile and metabolically independent compared to later colonizers. Lastly, we found a significant overlap in antimicrobial resistance genes carriage between the mother’s milk and their infant’s gut microbiome. Taken together, our results suggest that the human milk microbiome has an important role in the assembly, composition, and stability of the infant gut microbiome. ### Competing Interest Statement The authors have declared no competing interest.

Background: Breastfeeding information stored within electronic health records (EHR) has recently been used for pharmacoepidemiological research, however the data are primarily collected for clinical care. Objectives: To characterise breastfeeding information recorded in structured fields in EHR during infant and postpartum health care visits, and to assess the validity of lactation status based on EHR data versus maternal report at research study visits. Methods: We assessed breastfeeding information recorded in structured fields in EHR from one health system for a subset of 211 patients who were also enrolled in a study on breast milk composition between 2014 and 2017 that required participants to exclusively breastfeed their infants until at least 1 month of age. We assessed the frequency of breastfeeding information in EHR during the first 12 months of age and compared lactation status based on EHR with maternal report at 1 and 6-month study visits (reference standard). Results: The median number of breastfeeding records in the EHR per infant was six (interquartile range 3) with most observations clustering in the first few weeks of life and around well-infant visits. At the 6-month study visit, 93.8% of participants were breastfeeding and 80.1% were exclusively breastfeeding according to maternal report. Sensitivity of EHR data for identifying ever breastfeeding was at or near 100%, and sensitivity for identifying ever exclusive breastfeeding was 98.0% (95% CI: 95.0%, 99.2%). Sensitivities were 97.3% (95% CI: 93.9%, 98.9%) for identifying any breastfeeding and 94.4% (95% CI: 89.7%, 97.0%) for exclusive breastfeeding, and positive predictive values were 99.5% (95% CI: 97.0%, 99.9%) for any breastfeeding and 95.0% (95% CI: 90.4%, 97.4%) for exclusive breastfeeding. Conclusions: Breastfeeding information in structured EHR fields have the potential to accurately classify lactation status. The validity of these data should be assessed in populations with a lower breastfeeding prevalence.

INTRODUCTION: Human milk (HM) is the optimal source of nutrition for infants and has been implicated in multiple aspects of infant health. Although much of the existing literature has focused on the individual components that drive its nutrition content, examining HM as a biological system is needed for meaningful advancement of the field. Investigation of the nonnutritive bioactive components of HM and the maternal, infant, and environmental factors which affect these bioactives is important to better understand the importance of HM provision to infants. This information may inform care of clinical populations or infants who are critically ill, hospitalized, or who have chronic diseases and may benefit most from receiving HM. METHODS: In this narrative review, we reviewed literature examining maternal and infant influences on HM composition with a focus on studies published in the last 10 years that were applicable to clinical populations. RESULTS: We found multiple studies examining HM components implicated in infant immune and gut health and neurodevelopment. Additional work is needed to understand how donor milk and formula may be used in situations of inadequate maternal HM. Furthermore, a better understanding of how maternal factors such as maternal genetics and metabolic health influence milk composition is needed. CONCLUSION: In this review, we affirm the importance of HM for all infants, especially clinical populations. An understanding of how HM composition is modulated by maternal and environmental factors is important to progress the field forward with respect to mechanistic links between HM biology and infant health outcomes.

To examine the racial, ethnic and cultural differences in postpartum participation of women who participated in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) during pregnancy by completing a retrospective analysis of observational data on 35,903 women who enrolled in Minnesota WIC during pregnancy, from April 2018 to March 2020. Descriptive analyses were completed using chi-square tests of association to show differences in postpartum WIC participation by maternal demographics and health risk codes of the WIC participants. Binary logistic regression and multivariate logistic regression were used to obtain odds ratios to compare the likelihood of postpartum WIC participation across different races, ethnicities and cultural groups. Asian/Pacific Islander, East African, Hispanic, Hmong, Multigenerational Black, and Other Black pregnant participants were more likely than White participants to return to WIC postpartum (adjusted odds ratio (AOR) 2.54, 95% confidence interval (CI) 1.87–3.46; AOR 3.35, 95% CI 2.40–4.66; 1.30, 95% CI 1.10–1.54; AOR 6.76, 95% CI 4.39–10.42; AOR 1.40, 95% CI 1.11–1.77, AOR 1.52, 95% CI 1.26–1.83, respectively). American Indian pregnant participants were less likely than White participants to return to WIC postpartum (AOR 0.70, 95% CI 0.54–0.92). These findings can help the Minnesota WIC program, as well as other WIC programs, better understand which cultural groups may need more specific outreach strategies to keep women participating in the program after giving birth. Further research is needed to understand why postpartum women choose to participate, or choose not to participate, in WIC. It is already known that culture, race and ethnicity influence the likelihood of WIC program participation. Research also has shown that WIC participation can have positive impacts on the health of women, infants and children. This research adds depth to previous findings on prenatal WIC participation by describing the differences in postpartum WIC participation by race, ethnicity and cultural group. This research can be used for outreach planning within the WIC program.

<b><i>Objective:</i></b> The objective of this study was to determine the feasibility and safety of enhanced early (PN) (early initiation of intralipids and faster advancement of glucose infusion rate) during the first week of life for very low birth weight (VLBW) preterm infants. <b><i>Methods:</i></b> 90 VLBW preterm infants (&#x3c;32 weeks gestational age at birth) admitted to the University of Minnesota Masonic Children’s Hospital between August 2017 and June 2019 were included. Enrolled infants were stratified by gestational age-groups and randomized to either the enhanced nutrition protocol (intervention group) or the standard PN protocol (standard group). Welch’s two-sample <i>t</i> tests were used to investigate differences in calorie and protein intake, insulin use, days of hyperglycemia, hyperbilirubinemia, and hypertriglyceridemia, and proportion of bronchopulmonary dysplasia, necrotizing enterocolitis, and death between groups. <b><i>Results:</i></b> Intervention and standard groups were similar in baseline characteristics. The intervention group received higher weekly mean caloric intake (102.6 [SD 24.9] kcal/kg/day versus 89.7 [SD 30.2] kcal/kg/day; <i>p</i> = 0.001) and higher mean caloric intake on days of life 2–4 (<i>p</i> &#x3c; 0.05 for all). Both groups received the recommended protein intake (≥4 g/kg/day). There were no significant differences in safety or feasibility outcomes between groups (all <i>p</i> values &#x3e;0.12). <b><i>Conclusion:</i></b> Utilization of an enhanced nutrition protocol during the first week of life resulted in increased caloric intake and was feasible with no evidence of harm. Follow-up of this cohort is needed to determine if enhanced PN will result in improved growth and neurodevelopment.

Background: Our previous studies revealed that human milk oligosaccharides (HMOs) have health benefits for nursing infants and their concentrations change dynamically over 24-months of lactation. Yet, the extent to which HMOs vary over the short-term (days) and in response to acute factors such as maternal diet is unclear. Objectives The purpose of this study is to determine the stability of HMO concentrations over 7-days and in response to a standard meal and sugar-sweetened beverage (SSB) over 6-hours. Methods: In this ancillary study, lactating mothers were enrolled at 6-weeks postpartum. Participants received in-person instructions and materials to complete procedures at home. In the one-week experiment (N = 11), mothers pumped a milk sample at 07:00-hours for 7-consecutive days. In the 6-hour experiment (N = 35), mothers pumped a milk sample after an overnight fast at 06:00-hours and then consumed a standard meal plus SSB provided by the study team. Mothers pumped a milk sample every hour for 6-consecutive hours. Samples were analyzed for the 19 most abundant HMOs. Repeated measures ANOVA was used to test changes in HMO concentrations over time, reported as F(dftime, dferror) = F-value, P-value. Results: Concentrations of all assayed HMOs were stable over 7-consecutive days, including, for example, the most widely studied HMOs in relation to infant health, 2’-fucosyllactose (2’FL) (F(2,17) = 0.39, P = 0.65), disialyl-lacto-N-tetraose (DSLNT) (F(4, 37) = 0.60, P = 0.66), and lacto-N-neotetraose (LNnT) (F(3, 32) = 1.5, P = 0.23). Concentrations of all assayed HMOs were stable in response to a standard meal plus SSB. For example, fasted baseline concentrations of 2’FL, DSLNT, and LNnT were 2310 ± 1620 μg/mL, 560 ± 290 μg/mL, and 630 ± 290 μg/mL, respectively, and there were no changes in 2’FL (F(4, 119) = 1.9, P = 0.13), DSLNT (F(4, 136) = 0.39, P = 0.83), and LNnT (F(4, 120) = 0.64, P = 0.63) over 6-consecutive hours. Conclusions: HMO concentrations are stable over one-week of lactation and are not acutely affected by a standard meal plus SSB in mothers.

Purpose: Human milk (HM) is a unique biological fluid that is enriched with a variety of factors, including microRNAs (miRNAs) that potentially provide both short- and long-term benefits to the infants. miRNAs are packaged within exosomes, making them bioavailable to infants. Gestational diabetes mellitus (GDM) may affect the abundance of exosomal miRNAs in HM, providing a mechanism for growth and adiposity variation in infants of mothers with GDM in early life. Therefore, the purposes of this study were to examine the impact of GDM on select miRNAs (miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d) involved in metabolism and to examine the association of these miRNAs with measures of infant body composition in the first 6 months of life. Methods: Milk samples were collected from a cohort of 94 mothers (62 mothers without GDM and 32 mothers with GDM) matched on body mass index strata at 1 month post partum. miRNA abundance was measured by real-time polymerase chain reaction. Linear regression models were used to examine potential differences in miRNA abundance in women with and without GDM, testing associations between miRNA abundance and infant growth and body composition measures from 1 to 6 months. Findings: The abundances of miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d were reduced in milk from mothers with GDM. Independent of GDM status, higher maternal diet quality was associated with increased abundance of each of the measured miRNAs. miRNA-148a was negatively associated with infant weight, percentage of body fat, and fat mass, whereas miRNA-30b was positively associated with infant weight and fat mass at 1 month of age. There was no association of milk miRNA-148a and miRNA-30b with infant weight at 1 month of age or with body composition measures at 3 months of age; however, miRNA-148a was negatively associated with infant weight at 6 months of age. Implications: If supported by randomized dietary supplementation or other intervention trials, HM miRNAs may be a therapeutic target to mitigate risk of metabolic outcomes in offspring of women with GDM.

Background: Compared to the exhaustive study of transgenerational programming of obesity and diabetes through exposures in the prenatal period, postnatal programming mechanisms are understudied, including the potential role of breast milk composition linking maternal metabolic status (body mass index and diabetes) and offspring growth, metabolic health and future disease risk. Methods: This narrative review will principally focus on four emergent bioactive compounds [microRNA's (miRNA), lipokines/signalling lipids, small molecules/metabolites and fructose] that, until recently were not known to exist in breast milk. The objective of this narrative review is to integrate evidence across multiple fields of study that demonstrate the importance of these compositional elements of breast milk during lactation and the subsequent effect of breast milk components on the health of the infant. Results: Current knowledge on the presence of miRNA's, lipokines/signalling lipids, small molecules/metabolites and fructose in breast milk and their associations with infant outcomes is compelling, but far from resolved. Two themes emerge: (1) maternal metabolic phenotypes are associated with these bioactives and (2) though existing in milk at low concentrations, they are also associated with offspring growth and body composition. Conclusion: Breast milk research is gaining momentum though we must remain focused on understanding how non-nutritive bioactive components are affected by the maternal phenotype, how they subsequently impact infant outcomes. Though early, there is evidence to suggest fructose is associated with fat mass in the 1st months of life whereas 12,13 diHOME (brown fat activator) and betaine are negatively associated with early adiposity and growth.

It is unclear whether gestational diabetes mellitus (GDM) alters breast milk composition. We prospectively examined associations of GDM status with concentrations of six potentially bioactive elements (glucose, insulin, C‐reactive protein (CRP), interleukin‐6 (IL‐6), leptin, and adiponectin) in human milk. These were measured at both 1 and 3 months postpartum in 189 fully breastfeeding women. Mixed‐effects linear regression assessed GDM status‐related differences in these milk bioactives, adjusting for demographics, maternal factors, and diet. At 1 and 3 months postpartum, milk CRP was higher (1.46 ± 0.31 ng/mL; p < 0.001 and 1.69 ± 0.31 ng/mL; p < 0.001) in women with GDM than in women without GDM, whereas milk glucose (−5.23 ± 2.22 mg/dL; p = 0.02 and −5.70 ± 2.22; p = 0.01) and milk insulin (−0.38 ± 0.17 μIU/mL; p = 0.03 and −0.53 ± 0.17; p = 0.003) were lower in women with GDM. These significant associations remained similar after additional adjustment for maternal weight status and its changes. No difference was found for milk IL‐ 6, leptin, and adiponectin. There was no evidence of association between these milk bioactive compounds and 1 h non‐fasting oral glucose challenge serum glucose in the women without GDM. This prospective study provides evidence that potentially bioactive elements of human milk composition are altered in women with GDM.

Introduction: Maternal and child health (MCH) services are critical for vulnerable populations. Workforce shortages, poor retention, and gaps in necessary trainings impede the capacity of public health systems to address needs. This manuscript characterizes the current MCH workforce, MCH program applicants and graduates, and describe findings within a national context to devise elements of a recruitment and retention strategy. Methods: Data were obtained for public health program applicants, first-destination employment outcomes, and worker perceptions and demographics. Data were stratified according to the MCH and total public health workforce and by local, state, and national totals. Data were characterized by degree type, discipline, demographics, and employment outcomes. Results: MCH staff constitute 11% of the state and local governmental public health workforce. MCH staff are approximately as diverse, have higher educational attainment, and are more likely to hold nursing degrees than the rest of the public health workforce. Yet, just 14% of MCH staff hold any type of public health degree. The MCH pipeline from academia appears modestly sized, with approximately 5% of applicants between 2017 and 2021 applying to a MCH master’s degree. Discussion: The MCH workforce has a lower proportion of formal training or degrees in public health, though trends seem to indicate improvements. However, it is critical that a multi-faceted recruitment and retention strategy be coordinated by a broad range of stakeholders. These efforts will serve to improve the capability and capacity of the public health system to address critical needs of increasingly diverse MCH populations. Significance: In order to modernize and reimagine the academic-public health pipeline, it is critical to better understand how many applicants and graduates exist within Maternal and Child Health programs across the US, and their characteristics. This manuscript connects that information with the most recently available public health workforce information on demographics, workplace perceptions, and intent to leave among staff at state and local health departments. Data presented in this paper allow the most comprehensive characterization of the MCH academia->practice pipeline to-date, identifies a fundamental disconnect in those career pathways, and offers options to repair that break.

High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are significant risk factors for maternal and neonatal health.To assess pre-pregnancy BMI and GWG during pregnan...

Background: A premature infant's discharge from the neonatal intensive care unit (NICU) is dependent on factors such as respiratory stability, adequate growth, and the ability to consume oral feeds. Once infants have achieved respiratory stability, a tool that can better predict age at discharge is desirable. Thus, we conducted a secondary data analysis to assess the association between ultrasound measurements of abdominal muscle thickness and postmenstrual age (PMA) at full oral feedings. Methods: Forty-nine (n = 49) healthy, premature infants (mean gestational age = 32 weeks) were recruited from the NICU. Anthropometric measurements and ultrasound measurements of the rectus abdominis were conducted when infants were medically stable. Fat-free mass (FFM) was obtained using air displacement plethysmography. The relationship between ultrasound measurements of muscle thickness and PMA at full oral feedings was assessed using linear regression analysis. The relationship between FFM z-scores and PMA at full oral feedings was also assessed for comparison. Results: When adjusting for gestational age at birth, PMA at measurement, days of positive pressure respiratory support, weight, and length, ultrasound measurements of abdominal muscle thickness were independently, negatively associated with PMA at full oral feedings (β estimate: −0.71, P =.03). Conclusion: Preliminary results suggest infants with greater abdominal muscle thickness may reach full oral feedings at an earlier PMA (nearly 1 week per millimeter). Thus, ultrasound measurements of abdominal muscle thickness may be helpful in assessing readiness for discharge in healthy preterm infants. Further research is needed for development and validation of a prediction equation.

Background: Body mass index (BMI), a well-known risk factor for poor cardiovascular outcomes, is associated with differential DNA methylation (DNAm). Similarly, metabolic health has also been associated with changes in DNAm. It is unclear how overall metabolic health outside of BMI may modify the relationship between BMI and methylation profiles, and what consequences this may have on downstream cardiovascular disease. The purpose of this study was to identify cytosine-phosphate-guanine (CpG) sites at which the association between BMI and DNAm could be modified by overall metabolic health. Results: The discovery study population was derived from three Women’s Health Initiative (WHI) ancillary studies (n = 3977) and two Atherosclerosis Risk in Communities (ARIC) ancillary studies (n = 3520). Findings were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n = 1200). Generalized linear models regressed methylation β values on the interaction between BMI and metabolic health Z score (BMI × MHZ) adjusted for BMI, MHZ, cell composition, chip number and location, study characteristics, top three ancestry principal components, smoking, age, ethnicity (WHI), and sex (ARIC). Among the 429,566 sites examined, differential associations between BMI × MHZ and DNAm were identified at 22 CpG sites (FDR q < 0.05), with one site replicated in MESA (cg18989722, in the TRAPPC9 gene). Three of the 22 sites were associated with incident coronary heart disease (CHD) in WHI. For each 0.01 unit increase in DNAm β value, the risk of incident CHD increased by 9% in one site and decreased by 6–10% in two sites over 25 years. Conclusions: Differential associations between DNAm and BMI by MHZ were identified at 22 sites, one of which was validated (cg18989722) and three of which were predictive of incident CHD. These sites are located in several genes related to NF-kappa-B signaling, suggesting a potential role for inflammation between DNA methylation and BMI-associated metabolic health.

Objective: We aimed to investigate prospective associations between milk bioactives related to metabolic health (glucose, insulin, leptin, C reactive protein [CRP], and interleukin 6 [IL-6]) and in...

Background: Premature infants are at risk for adverse metabolic and neurodevelopmental outcomes due to growth alterations in early infancy. Monitoring body composition by tracking gains in fat mass (FM) and fat-free mass (FFM) may assist clinicians in preventing obesity and metabolic disease while promoting optimal growth and development. A prospective, observational study was conducted to determine the ability of ultrasound (US) measurements of muscle and adipose tissue thickness to predict whole-body composition (FFM, FM, percent body fat [%BF]). Methods: Sixty-three healthy premature infants were recruited from the University of Minnesota's Neonatal Intensive Care Unit. Anthropometric measurements, air displacement plethysmography, and US measurements of abdomen, biceps, and quadriceps muscle and of adipose tissue thickness were conducted when infants were medically stable. The relationship between US measurements and body composition was assessed using stepwise linear regression analysis. Results: In linear regression analyses, biceps adipose and the sum of adipose thickness measurements were significant predictors of %BF, but prediction models had low R2 (0.17 and 0.16, respectively) and high root-mean-square error. US measurements of muscle thickness were not predictive of whole-body FFM. Conclusion: US measurements of muscle and adipose tissue thickness at the examined sites are not adequate surrogates for whole-body composition in preterm infants. Exploration of alternate measurement sites may improve predictive ability.

CONTEXT: Little is known about the specific breastmilk components responsible for protective effects on infant obesity. Whether 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), an oxidized linoleic acid metabolite and activator of brown fat metabolism, is present in human milk, or linked to infant adiposity, is unknown. OBJECTIVE: To examine associations between concentrations of 12,13-diHOME in human milk and infant adiposity. DESIGN: Prospective cohort study from 2015 to 2019, following participants from birth to 6 months of age. SETTING: Academic medical centers. PARTICIPANTS: Volunteer sample of 58 exclusively breastfeeding mother-infant pairs; exclusion criteria included smoking, gestational diabetes, and health conditions with the potential to influence maternal or infant weight gain. MAIN OUTCOME MEASURES: Infant anthropometric measures including weight, length, body mass index (BMI), and body composition at birth and at 1, 3, and 6 months postpartum. RESULTS: We report for the first time that 12,13-diHOME is present in human milk. Higher milk 12,13-diHOME level was associated with increased weight-for-length Z-score at birth (β = 0.5742, P = 0.0008), lower infant fat mass at 1 month (P = 0.021), and reduced gain in BMI Z-score from 0 to 6 months (β = -0.3997, P = 0.025). We observed similar associations between infant adiposity and milk abundance of related oxidized linoleic acid metabolites 12,13-Epoxy-9(Z)-octadecenoic acid (12,13-epOME) and 9,10-Dihydroxy-12-octadecenoic acid (9,10-diHOME), and metabolites linked to thermogenesis including succinate and lyso-phosphatidylglycerol 18:0. Milk abundance of 12,13-diHOME was not associated with maternal BMI, but was positively associated with maternal height, milk glucose concentration, and was significantly increased after a bout of moderate exercise. CONCLUSIONS: We report novel associations between milk abundance of 12,13-diHOME and adiposity during infancy.

Background: Weight/length (W/L) indices are poor surrogates for adiposity in preterm infants born appropriate for gestational age (AGA) at birth, but whether the association subsequently improves is unknown. Objective: To determine if W/L indices accurately reflect adiposity in premature infants born AGA in later infancy. Methods: Associations between W/L indices and fat mass, fat mass index and percent body fat (%BF) obtained via air displacement plethysmography (ADP) were examined in 260 preterm infants (majority born AGA) at 28 to 63 weeks' postmenstrual age (PMA). Accuracy of W/L indices as indicators of adiposity was assessed by proportion of variance explained (R2) and root mean square error from linear regression of adiposity on W/L indices and proportion of infants misclassified by W/L indices. Accuracy was further compared in term vs preterm infants at term-equivalent age. The impact of early vs late preterm status on associations between W/L indices and %BF was also examined. Results: BMI and W/L were most strongly associated with %BF but yielded poorly fitting models (maximum R2 = 0.35; 53% misclassification). A significant interaction of W/L indices and early vs late preterm status on %BF revealed that estimation of %BF differs by status. Accuracy of W/L indices was worse in preterm infants at term-equivalent age. Conclusions: W/L indices were not good indicators of adiposity in preterm infants from 28 to 63 weeks' PMA (born AGA) with all categories of W/L indices combined. Future research should examine whether results are similar in preterm infants born with disproportionate W/L or who experience disproportionate growth postnatally.