Intestinal dysbiosis is believed to be a contributing factor in the development of Necrotizing Enterocolitis (NEC), a severe gastrointestinal disease that disproportionally affects preterm infants. Routine probiotic administration of bacterial strains.

Vitamin A is an essential micronutrient that supports optimal maternal and fetal health during pregnancy. It is important for vision, immune function, cellular growth and development, and formation of fetal organs. While vitamin A deficiency remains a public health concern in low-and middle-resource countries, emerging evidence suggests marginal to deficient vitamin A status during pregnancy exists in developed countries. Marginal vitamin A status is associated with low birth weight and preterm birth in some, but not all, studies. Other studies link maternal vitamin A status with cord blood antioxidant activity and reduced risk of preeclampsia. This review summarizes current evidence on vitamin A status in pregnant women and association with birth outcomes such as low birth weight, preterm birth, neonatal intensive care unit (NICU) admission, and preeclampsia.

Infants born large-for-gestational-age (LGA) are increasingly common because of the rising rates of maternal obesity and diabetes. Some infants born LGA require hospitalization and nutrition support, yet no specific growth standards exist to guide nutrition management. Feeding practices based on weight-based guidelines for infants born at appropriate weight for gestational age may unintentionally promote overfeeding and increase long-term obesity risk. This Clinical Dilemma explores the challenges of feeding hospitalized infants born LGA and highlights the urgent need for research to develop evidence-based growth standards for this at-risk population.

Preterm birth (PTB, <37 weeks gestation) is the leading cause of infant mortality and significant health and socioeconomic burdens that affects millions of newborns and families. While docosahexaenoic acid (DHA) supplementation has shown promise in reducing PTB risk, its effectiveness at reducing the most consequential early PTB (ePTB, <34 weeks gestation) depends on baseline DHA levels, with lower DHA levels and intake linked to a higher risk of PTB and ePTB that can be reduced by high-dose DHA supplementation. Given the higher costs of high-dose DHA, personalized treatment strategies based on baseline DHA levels are needed. We proposed a novel Bayesian personalized change-point model to optimize DHA supplementation strategies based on individual baseline DHA intake. By incorporating Bayesian change-point, dynamic linear, and normal mixture models, our approach estimates optimal DHA baseline thresholds and distribution. We applied this model to real-world data and simulated trials to demonstrate its ability to improve secondary analysis and trial design by adjusting for baseline DHA heterogeneity. This personalized approach can help clinicians identify optimal DHA supplementation doses for individual patients, and it can be applied to other trial studies where the heterogenous characteristics of patients can be quantified.

Background/Objectives: Parents achieving recommended eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intake can improve the health of parents and their children. Evidence links higher DHA intake to lower preterm birth (PTB) risk. With parental intake poorly defined, the objective is to characterize EPA and DHA intake by parents with children in households in a diverse, urban city. Methods: Parents with ≥1 child in the household completed a validated seven-question food frequency questionnaire to assess consumption of foods contributing most to EPA and DHA intake in American diets during the cross-sectional Voices of Child Health in Chicago Panel Survey (May–July 2022). Female respondents reported prior PTB. Home/residence information was linked to the Childhood Opportunity Index (COI). Multivariable linear regression and survey-weighted models evaluated parental characteristics associated with EPA+DHA intake. Pairwise comparisons estimated intake differences (mean (SE)) among groups. Results: Chicago parents (n = 1057) reported lower-than-recommended EPA+DHA intake and mothers consumed less compared to fathers (difference: 27.1 (11.4) mg/d; p = 0.02). Prior PTB was associated with lower EPA+DHA intake, yet DHA-containing supplement use, which occurred in ~25% of parents, was associated with higher intake (p < 0.05). Lower household income and a lower COI were associated with lower intake while parental race and ethnicity categories were also associated with intake (all p < 0.05); intake differed for mothers and fathers based on Black race and Hispanic ethnicity categories. Conclusions: The findings suggest that efforts aimed at improving parental EPA+DHA intake to improve the health of families should account for multidimensional influences on household food choices.

BACKGROUND:Emerging evidence has suggested negative associations between maternal urinary fluoride adjusted for specific gravity (MUFsg) and offspring intelligence quotient (IQ). Two prior studies report the MUFsg of pregnant women in the US, both in California, and more information is needed on population levels of MUFsg. OBJECTIVES:The primary objective was to measure MUFsg in a large pregnancy cohort of women recruited from health departments and academic hospitals in Ohio and Kansas. A secondary objective was to compare associations between water fluoridation level and estimated fluoride intake from tap water and MUFsg. METHODS:Pregnant women (n=965) from the ADORE (Assessment of DHA on Reducing Early Preterm Birth) cohort provided a urine sample and dietary assessment at enrollment between 14 and 20 wk gestation. MUFsg was measured by fluoride-sensitive electrode and corrected for specific gravity. Water fluoridation levels were obtained for public water systems (PWS), matched to participant residence and multiplied by their tap water intake from dietary assessment. The association between MUFsg and water fluoridation level was estimated using a generalized linear model with gamma distribution and log link. RESULTS:MUFsg (median: 1.0mg/L; Q1, Q3: 0.6, 1.5) was correlated with PWS fluoridation (rs=0.30; p<0.01) and self-reported tap water consumption (rs=0.29; p<0.01). For 87% of the cohort, MUFsg was above the 0.45mg/L safety benchmark for pregnancy proposed in a previous study. Similarly, 76.7% lived in areas with PWS fluoridation ≥0.7mg/L. The median MUFsg (1.0mg/L; Q1, Q3: 0.7, 1.5) of those living in areas with a PWS fluoridation level ≥0.7mg/L was higher than the median MUFsg (0.8mg/L; Q1, Q3: 0.5, 1.2) of women living in areas with PWS fluoridation <0.7mg/L (p<0.01). DISCUSSION:MUFsg in this population of midwestern US women exceeds the safety benchmark for pregnancy. While we cannot account for all sources of fluoride, MUFsg was correlated to PWS fluoridation. Because so many exceeded the safety benchmark for MUFsg, there is a need for MUFsg evaluation in other US regions, especially where the PWS fluoridation exceeds US Department of Health and Human Services recommendations (≥0.7mg/L). https://doi.org/10.1289/EHP14711.

Added sugars (AS) and fructose intake are linked to obesity. Hispanic populations experience high AS intake and obesity rates. It is underexplored if early sugars exposure influences offspring growth, especially across ethnic groups. This secondary analysis examined if AS and fructose intake during pregnancy, infancy, and toddlerhood influenced offspring adiposity at 24 months, and if ethnicity modified outcomes. We hypothesized that higher sugars exposure would predict increased adiposity. Mother-child pairs from a prenatal docosahexaenoic acid supplementation RCT and the offspring follow-up study were included. Dietary intake was assessed at 12 to 20 weeks gestation, and offspring intake at 2 weeks, 6 months, 12 months, and 24 months. Intake was averaged across infancy (Year 1: 2 weeks/6 months) and toddlerhood (Year 2: 12 months/24 months). Anthropometric (n = 130) and dual-energy X-ray absorptiometry (n = 42) data were collected at 24 months. Multiple hierarchical regression examined associations, with interaction terms testing ethnic differences. Higher AS intake in Year 1 predicted higher weight, fat-free mass, and total adiposity. Compared to non-Hispanic offspring, the association of Year 1 fructose intake with weight and Year 2 AS intake with fat-free mass and central fat mass, were weaker in Hispanic offspring. No other significant associations were observed. The relationships between early AS and fructose intake with body composition are dynamic over time and vary by ethnicity. Our findings highlight the potential risks of early sugars exposure on obesity and metabolic health, underscoring the need for further research to inform early-life dietary interventions and public health policies.

Prenatal supplementation with docosahexaenoic acid (DHA) has been reported to improve cognitive outcomes in infancy and early childhood in some studies. Existent studies have examined the effects of some dose of DHA against a true placebo; this report is the first to describe the effects of different doses of prenatal DHA on infant visual attention at 4 and 6 months of age. In a follow-up to a Phase III registered clinical trial (NCT02709239) designed to evaluate the effects of two prenatal doses of DHA supplementation (200 or 800 mg daily) on maternal physiology and fetal neurodevelopment, we assessed 215 infants delivered to these mothers at 4 and 6 months on a visual habituation task augmented with heart rate (HR) to assess visual stimulus processing, and a gap-overlap task to assess engagement and disengagement of attention. Infants of mothers supplemented with 800 mg/day of DHA had shorter look durations (indicative of more rapid visual learning) during habituation at both ages and a somewhat more mature pattern of HR-defined phases of attention. However, DHA dose did not affect infant HR, nor did it affect infant performance in the gap-overlap attention task. Results are consistent with positive effects of prenatal DHA supplementation on later outcomes, with higher benefit seen for a higher dose.

Background:Excessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. Objectives:This study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. Methods:Infants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. Results:For total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. Conclusions:Greater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Docosahexaenoic acid (DHA) supplementation has proven beneficial in reducing preterm births. However, the challenge lies in addressing nonadherence to prescribed supplementation regimens—a hurdle that significantly impacts clinical trial outcomes. Conventional methods of adherence estimation, such as pill counts and questionnaires, usually fall short when estimating adherence within a specific dosage group. Thus, we propose a Bayesian finite mixture model to estimate adherence among women with low baseline red blood cell phospholipid DHA levels (<6%) receiving higher DHA doses. In our model, adherence is defined as the proportion of participants classified into one of the two distinct components in a normal mixture distribution. Subsequently, based on the estimands from the adherence model, we introduce a novel Bayesian adaptive trial design. Unlike conventional adaptive trials that employ regularly spaced interim schedules, the novelty of our proposed trial design lies in its adaptability to adherence percentages across the treatment arm through irregular interims. The irregular interims in the proposed trial are based on the effect size estimation informed by the finite mixture model. In summary, this study presents innovative methods for leveraging the capabilities of Bayesian finite mixture models in adherence analysis and the design of adaptive clinical trials.

OBJECTIVE: There is a signi fi cant racial disparity in preterm birth (PTB), disproportionately affecting pregnancies among Black individuals. Docosahexaenoic acid (DHA) supplementation has been shown to decrease the risk of PTB. 1 It is unknown whether there are differences in DHA ef fi cacy among pregnancies of differing races. This study aimed to investigate the efficacy of prenatal DHA supplementation to prevent PTB ( < 37 weeks of gestation) and early PTB (EPTB; < 34 weeks of gestation) in Black pregnant individuals vs those who were non -Black. STUDY DESIGN: This was a planned secondary analysis from a randomized controlled adaptive design multicenter trial that investigated the ef fi cacy of DHA in reducing EPTB. 2,3 The outcome data were available for 1032 of 1100 pregnant individuals who were randomized to receive a standard prenatal dose of DHA, 200 mg/d (low dose; n=492), or 1000 mg/d (high dose; n=540) from enrollment at < 20 weeks of gestation to delivery. We compared DHA status (maternal red blood cell phospholipid fatty acid DHA [RBC-PL-DHA]) at enrollment and delivery and pregnancy outcomes (PTB at < 37 weeks of gestation and EPTB at < 34 weeks of gestation) by maternal race. Maternal race and ethnicity were selfreported as American Indian or Alaskan Native, Asian, nonHispanic Black or African American, Hispanic, Native Hawaiian or Pacific Islander, White, biracial, and multiracial. For this analysis, maternal race and ethnicity were categorized into 2 groups: Black (participants who categorized themselves as non -Hispanic Black or African American, n=236) and non -Black (participants reporting any other race or ethnicity, n=796). Maternal RBC-PL-DHA as a weight percentage of total fatty acids was measured at enrollment (baseline) and delivery to determine maternal DHA status. A cutoff of 6% RBC-PL-DHA was used to dichotomize high vs low DHA status. 2,4 Bayesian 2 -sample binomial models were used to calculate a posterior probability (PP) that 1000 mg/d was better than 200 mg/d to reduce PTB and EPTB. RESULTS: The baseline DHA level at enrollment was lower among Black study participants than among non -Black study participants (Table). Black participants were more likely to be unmarried, have low income, have obesity, and use tobacco in pregnancy. Risk factors of previous PTB at < 37 weeks of gestation and previous EPTB at < 34 weeks of gestation were 2fold and 4 -fold more common among Black study participants than among non -Black study participants, respectively (Table). Maternal DHA status increased between enrollment and delivery in both race groups, and in both groups, the 1000 -mg dose resulted in a larger increase than the 200 -mg dose (PP=1.00). The absolute increase in maternal RBC-PLDHA from enrollment to delivery was smaller for Black participants than for non -Black (200 -mg dose: 0.33% vs 1.33%, respectively; 1000 -mg dose: 1.50% vs 3.97%, respectively), indicative of lower supplement adherence. 5 All participants in the trial had reductions in PTB at < 37 weeks of gestation with high -dose DHA supplementation; however, only Black participants also had reductions in EPTB with high -dose DHA supplementation (Figure). The rate of PTB was more than 2 -fold higher for Black participants than for non -Black at both DHA doses, whereas the rates of EPTB were 4.5 -fold higher for the 200 -mg dose and 2.9 -fold higher for the 1000 -mg dose. Participants who began the study with high baseline DHA status ( >= 6% RBC-PL-DHA) had a lower rate of EPTB than those who began with low status ( < 6% RBC-PL-DHA) in both race and DHA dose groups. Participants who had high baseline DHA levels at study entry and were assigned to high -dose DHA had the lowest PTB rates, which were similar among race groups, 6.4% PTB in Black participants and 5.8% PTB in non -Black participants (Figure, shown in dark green bars). CONCLUSION: There are racial differences in baseline DHA levels and DHA supplement adherence in pregnancy. High baseline DHA levels and supplementation with high -dose DHA in pregnancy reduce the racial disparity in PTB rates, despite more risk factors for PTB among Black pregnant individuals. Our data demonstrate the importance of optimizing the DHA status of reproductive -aged women and supplementation with higher doses of DHA in pregnancy to mitigate the racial disparity in PTB outcomes.

Background Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs’ attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. Methods Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs’ comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs’ comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. Results About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. Conclusions Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.

Beef is an excellent source of nutrients important for maternal health and fetal development. It is also true that the Mediterranean diet is beneficial for the health of both the mother and offspring; however, the relative value of fresh beef intake within Mediterranean diet patterns during pregnancy is unknown. The objective of this project was two-fold: (1) assess the relationship between beef intake and nutrient intake in a pregnant population; (2) assess the relationship between maternal beef consumption among varying degrees of Mediterranean diet adherence with maternal risk of anemia and infant health outcomes. This is a secondary analysis of an existing cohort of pregnant women (n = 1076) who participated in one of two completed clinical trials examining the effect of a docosahexaenoic acid supplementation on birth and offspring outcomes. Women were enrolled between 12 and 20 weeks of gestation and were followed throughout their pregnancies to collect maternal and infant characteristics, food frequency questionnaires [providing beef intake and Mediterranean diet (MedD) adherence], and supplement intake. Women with the highest fresh beef intake had the highest intake of many micronutrients that are commonly deficient among pregnant women. Fresh beef intake alone was not related to any maternal or infant outcomes. There was a reduced risk of anemia among women with medium to high MedD quality and higher fresh beef intake. Women in the medium MedD group had 31% lower odds of anemia, and women in the high MedD group had 38% lower odds of anemia with every one-ounce increase in fresh beef intake, suggesting that diet quality indices may be misrepresenting the role of fresh beef within a healthy diet. These findings show that beef intake increases micronutrient intake and may be protective against maternal anemia when consumed within a healthy Mediterranean diet pattern.

We undertook this review to determine if it is plausible that choline or phosphatidylcholine (PC) deficiency is a factor in necrotizing enterocolitis (NEC) after two clinical trials found a dramatic and unexpected reduction in NEC in an experimental group provided higher PC compared to a control group. Sources and amounts of choline/PC for preterm infants are compared to the choline status of preterm infants at birth and following conventional nutritional management. The roles of choline/PC in intestinal structure, mucus, mesenteric blood flow, and the cholinergic anti-inflammatory system are summarized. Low choline/PC status is linked to prematurity/immaturity, parenteral and enteral feeding, microbial dysbiosis and hypoxia/ischemia, factors long associated with the risk of developing NEC. We conclude that low choline status exists in preterm infants provided conventional parenteral and enteral nutritional management, and that it is plausible low choline/PC status adversely affects intestinal function to set up the vicious cycle of inflammation, loss of intestinal barrier function and worsening tissue hypoxia that occurs with NEC. In conclusion, this review supports the need for randomized clinical trials to test the hypothesis that additional choline or PC provided parenterally or enterally can reduce the incidence of NEC in preterm infants.Impact statementLow choline status in preterm infants who are managed by conventional nutrition is plausibly linked to the risk of developing necrotizing enterocolitis. [GRAPHICS] .