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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., Competing Interests: Data sharingFor data access, please see Carlson et al.5,15,16 Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 STATEMENT: Low choline status in preterm infants who are managed by conventional nutrition is plausibly linked to the risk of developing necrotizing enterocolitis., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Early preterm birth (ePTB) - born before 34 weeks of gestation - poses a significant public health challenge. Two randomized trials indicated an ePTB reduction among pregnant women receiving high-dose docosahexaenoic acid (DHA) supplementation. One of them is Assessment of DHA on Reducing Early Preterm Birth (ADORE). A survey employed in its secondary analysis identified women with low DHA levels, revealing that they derived greater benefits from high-dose DHA supplementation. This survey's inclusion in future trials can provide critical insights for informing clinical practices., Objective: To optimize a Phase III trial design, ADORE Precision, aiming at assessing DHA supplement (200 vs. 1000 mg/day) on reducing ePTB among pregnant women with a low baseline DHA., Methods: We propose a Bayesian Hybrid Response Adaptive Randomization (RAR) Design utilizing a finite mixture model to characterize gestational age at birth. Subsequently, a dichotomized ePTB outcome is used to inform trial design using RAR. Simulation studies were conducted to compare a Fixed Design, an Adaptive Design with early stopping, an ADORE-like Adaptive RAR Design, and two new Hybrid Designs with different hyperpriors., Discussion: Simulation reveals several advantages of the RAR designs, such as higher allocation to the more promising dose and a trial duration reduction. The proposed Hybrid RAR Designs addresses the statistical power drop observed in Adaptive RAR. The new design model shows robustness to hyperprior choices. We recommend Hybrid RAR Design 1 for ADORE Precision, anticipating that it will yield precise determinations, which is crucial for advancing our understanding in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Background: Maternal intake of eggs and nutrients contained within eggs during pregnancy have the potential to impact fetal neurodevelopment; however, this area is understudied. The purpose of this study was to determine whether maternal egg and choline intake and nutrient interactions between choline, lutein and zeaxanthin (L/Z), and DHA predict fetal neurodevelopment in a large cohort of pregnant women ( n  = 202). NCT02709239., Methods: Food frequency questionnaires were used to assess egg and nutrient intake during pregnancy. Fetal neurodevelopment was measured using fetal biomagnetometry at 32 and 36wks gestation, and fetal autonomic indices (SDNN, RMSSD) and brain maturation indices (fABAS) were calculated. Generalized linear models tested the relationships between choline intake, egg intake, and nutrient interactions with fetal neurodevelopment., Results: Maternal egg intake predicted RMSSD at 32wks and fABAS at 36wks. The interaction between choline and L/Z intake predicted fABAS at 32wks and 36wks and the interaction between choline intake, L/Z intake, and DHA predicted fABAS at 36wks. At 36wks, SDNN was predicted by L/Z intake and interactions between choline and L/Z, L/Z and DHA, and choline, L/Z, and DHA., Conclusion: Eggs and the nutrients contained within eggs showed synergistic associations with fetal neurodevelopment, and consumption should be encouraged among pregnant women.

Background: Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired., Objective: To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation., Study Design: This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose., Results: Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97)., Conclusion: The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice., Competing Interests: Declaration of competing interest SEC has received honorariums for presentations about DHA in infancy and pregnancy. KMG was the PI of R01HD086001. SEC, BJG and CJV were PIs of R01HD083292, CJV was an employee of RB Nutrition, which produces infant formulas and supplements with DHA at the time the study was conducted, however, RB was not involved in the study execution or analysis. She conducted this study through her role as an Adjunct Professor at The University of Cincinnati. The other authors have no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: DHA is an essential omega-3 (ω-3; n-3) fatty acid that has well-established benefits for the fetus. DHA also has the potential to influence the health of the mother, but this area is understudied., Objectives: The objective of this secondary analysis was to determine if DHA was related to maternal heart rate (HR) and heart rate variability (HRV) metrics in a large cohort of pregnant women., Methods: In the parent trial (1R01HD086001) eligible participants (≥18 y old, English speaking, carrying a singleton pregnancy, 12-20 wk of gestation) were randomly assigned to consume 200 mg/d or 800 mg/d DHA for the duration of their pregnancy (n = 300). Weight, blood pressure, and magnetocardiograms (MCGs) were collected at 32 wk and 36 wk of gestation (n = 221). Measures of HR and HRV in time-, frequency-, and nonlinear-domains were determined from the isolated maternal MCG. Treatment group and timepoint were examined as predictors in association with HR and HRV metrics using random-intercept mixed-effects ANOVA unadjusted and adjusted models accounting for weight and dietary DHA intake., Results: Women receiving the higher dose of DHA (800 mg/d) during pregnancy had lower HR, lower sympathetic index, higher vagally mediated HRV indices, and greater HRV complexity when compared with the women who received the lower dose (200 mg/d; all P < 0.05). All the dose relations remained significant even after controlling for the effect of time, maternal weight, and dietary DHA intake., Conclusions: DHA supplementation increases vagal tone in pregnant women. Longitudinal studies examining the potential link between DHA, enhanced vagal tone, and reported reduction in early preterm birth are warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Achieving maternal docosahexaenoic acid (DHA) status equal to or greater than the infant's DHA status at delivery is known as maternal-newborn DHA equilibrium (EQ) and is thought to be important for optimizing newborn DHA status throughout infancy. The objective of this study was to determine the daily DHA intake during pregnancy most likely to result in EQ. The participants ( n = 1145) were from two randomized control trials of DHA supplementation in pregnancy. DHA intake was estimated using an abbreviated food frequency questionnaire. Total DHA exposure during pregnancy was calculated as a weighted average of the estimated DHA intake throughout pregnancy and the randomized DHA dose (200, 800, 1000 mg). Red blood cell DHA was measured from maternal and cord blood plasma at delivery and EQ status was calculated. The DHA intake required to achieve EQ was estimated by regression. In terms of DHA exposure, the point estimate and 95% confidence interval to achieve EQ was 643 (583, 735) mg of DHA/day. The results of our trial suggest an intake of 650 mg of DHA/day is necessary to increase the potential for EQ at delivery. The clinical benefits of achieving EQ deserves continued study.

Introduction: Maternal-infant equilibrium occurs when cord blood docosahexaenoic acid (DHA) is less than or equal to maternal DHA at delivery. Equilibrium may be an indicator of sufficient DHA for optimal fetal and infant neurodevelopment. The purpose of this study was to test the effect of maternal DHA supplementation on equilibrium status and fetal neurodevelopment., Methods: Women enrolled between 12 and 20 weeks gestation and were randomized to 200 or 800 mg DHA/day until delivery. Maternal red blood cell (RBC) phospholipids were measured at enrollment, 32 weeks, delivery, and in cord blood at delivery. Fetal neurodevelopment was measured at 32 and 36 weeks gestation. Intent-to-treat analyses were conducted to test differences in equilibrium status by group. Fetal outcomes were assessed by equilibrium status and group., Results: Three hundred women enrolled and 262 maternal-infant dyads provided blood samples at delivery. No maternal-infant dyads with maternal RBC-DHA ≤ 6.96% at delivery achieved equilibrium. The incidence of equilibrium was significantly higher in the 800 mg group. There was no effect of maternal group or equilibrium status on fetal neurodevelopment., Conclusion: The significance of maternal-infant DHA equilibrium remains unknown. Ongoing research will test the effect of treatment group, equilibrium, and nutrient status on infant behavior and brain function., Impact: Pregnant women who received a higher dose of docosahexaenoic acid (DHA) were more likely to achieve maternal-infant DHA equilibrium at delivery. Equilibrium status had no effect on fetal neurodevelopment in this sample. While DHA is crucial for early life neurodevelopment, the significance of achieving maternal-infant equilibrium above the lower threshold is uncertain. There is a lower threshold of maternal DHA status where maternal-infant DHA equilibrium never occurs. The lack of equilibrium associated with low maternal DHA status may indicate insufficient maternal status for optimal placental transfer., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Introduction: Offsprings from a prenatal docosahexaenoic acid (DHA) supplementation trial, in which pregnant women were assigned to placebo or 600mg DHA/day, were followed to determine the effect of prenatal DHA supplementation on the behavior and brain function at 5.5 years (n=81 placebo, n=86 supplemented). Methods: Event-related potentials (ERP) were recorded during a visual task requiring a button press (Go) to frequent target stimuli and response inhibition to the rare stimuli (No-Go). Univariate ANOVAs were used to test differences between group and sex for behavioral measures. ERP differences were tested using a three-way mixed-design multivariate analysis of variance (MANOVA). Results: There was a significant sex × group interaction for hit rate and errors of omission; there was no difference between males and females in the placebo group, but DHA males outperformed DHA females. Males overall and the placebo group made more errors requiring response inhibition; DHA females were significantly better than placebo females and DHA males. ERP P2 amplitude was larger in the DHA group. A significant N2 amplitude condition effect was observed in females and DHA group males, but not in placebo group males. Discussion: Prenatal DHA supplementation improved inhibitory performance overall, especially for females in the DHA group, possibly accounting for their conservative behavior during Go trials. Development of brain regions responsible for visual processing may be sensitive to maternal DHA status, evidenced by greater P2 amplitude. Males may benefit more from maternal DHA supplementation, indicated by the N2 condition effect seen only in males in the DHA group.

Maternal obesity is an established risk factor for poor infant neurodevelopmental outcomes; however, the link between maternal weight and fetal development in utero is unknown. We investigated whether maternal obesity negatively influences fetal autonomic nervous system (ANS) development. Fetal heart rate variability (HRV) is an index of the ANS that is associated with neurodevelopmental outcomes in the infant. Maternal-fetal magnetocardiograms were recorded using a fetal biomagnetometer at 36 weeks (n = 46). Fetal HRV was represented by the standard deviation of sinus beat-to-beat intervals (SDNN). Maternal weight was measured at enrollment (12-20 weeks) and 36 weeks. The relationships between fetal HRV and maternal weight at both time points were modeled using adjusted ordinary least squares regression models. Higher maternal weight at enrollment and 36 weeks were associated with lower fetal HRV, an indicator of poorer ANS development. Further study is needed to better understand how maternal obesity influences fetal autonomic development and long-term neurodevelopmental outcomes.

Objective: Obesity and weight gain after breast cancer treatment are common among survivors, yet the relationship between weight and body image has received little attention. The purpose of the current study was to examine the relationship between current body mass index, weight gain since diagnosis, and largest weight fluctuation in adulthood with six dimensions of body image among overweight/obese breast cancer survivors., Methods: The current study used data obtained from a weight control trial with 210 rural overweight/obese breast cancer survivors. Using data collected at baseline, multiple regression models were constructed to examine the relative association of the three weight variables with breast cancer-specific dimensions of body image while controlling for demographic characteristics and cancer treatment-related variables., Results: Largest weight fluctuation in adulthood significantly predicted overall body image (p = 0.01) and was associated with the three socially oriented dimensions of body image: social activity restriction, embarrassment about appearance, and sexuality (all ps = 0.01). Weight gain since diagnosis approached statistical significance in predicting overall body image (p = 0.05) and was associated with embarrassment about appearance (p = 0.03). Current body mass index was not significantly associated with overall body image when controlling for the other weight variables (p = 0.07) and was negatively associated with social activity restriction (p = 0.01) and sexuality (p = 0.01)., Conclusions: Obese breast cancer survivors with a history of a large weight fluctuation in adulthood may be prone to poorer breast cancer-specific body image several years after treatment. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Purpose: Obesity and diet quality are two distinct lifestyle factors associated with morbidity and mortality among breast cancer survivors. The purposes of this study were to examine diet quality changes during a weight loss intervention among breast cancer survivors and to examine whether diet quality change was an important factor related to weight loss., Methods: Participants were overweight/obese breast cancer survivors (n = 180) participating in a weight loss intervention. Diet quality scores were calculated using the Healthy Eating Index (HEI)-2010. Paired sample t-tests were run to examine change in diet quality, and a latent difference model was constructed to examine whether change in diet quality was associated with weight change., Results: Participants significantly improved diet quality (P = 0.001) and lost 13.2 ± 5.8% (mean ± SD) of their weight (P = 0.001). Six-month HEI score was significantly associated with weight loss, controlling for baseline BMI (P = 0.003). Improvement in diet quality was also significantly associated with weight loss (P = 0.01)., Conclusion: Our findings indicate that a weight loss intervention can result in both clinically significant weight loss and improvement in diet quality, and that improved diet quality is predictive of weight loss. Both weight loss and diet quality are implicated in longevity and quality of life for breast cancer survivors., Competing Interests: The authors declare that they have no conflict of interest.

Objective: The objective of this longitudinal study was to determine what typical vitamin D predictors influence the change in vitamin D status from mid-pregnancy to birth., Methods: Plasma 25-hydroxyvitamin D [25(OH)D] was determined at mid-pregnancy (8-20 weeks gestation) and following birth (n = 193). Usual predictors of vitamin D status [body mass index (BMI), race, season] in addition to prenatal supplemental vitamin D intake and docosahexaenoic acid (DHA) status at delivery were assessed for their interaction on the change on plasma 25(OH)D concentration between the two time points., Results: Forty-nine percent of women had inadequate vitamin D status [categorized as deficient (<30 nmol/L) or insufficient (30-49.9 nmol/L) by IOM guidelines] at mid-pregnancy and 82% were deficient or insufficient at birth. Plasma 25(OH)D concentration dropped 61% from mid-pregnancy to birth. Season of birth (F = 7.86, P = 0.006) and mid-pregnancy plasma 25(OH)D concentration (F = 6.17, P = 0.014) were significant variables in the change of vitamin D status while BMI, race, DHA status, and typical vitamin D intake (334 IU/day) from prenatal supplements did not have an effect. Women who delivered in summer and fall had a 1.5-fold greater plasma 25(OH)D concentration than women who delivered in winter in spring (41.1 ± 23.1 and 40.7 ± 20.5 nmol/L summer and fall, respectively, versus 27.7 ± 17.9 and 29.3 ± 21.4 nmol/L in winter and spring, respectively)., Conclusions: Typical supplemental vitamin D intake during pregnancy did not prevent precipitous drops in maternal plasma 25(OH)D concentration. Clinicians and dietitians should be aware of the risk of inadequate vitamin D status in pregnant women in the United States relative to their initial vitamin D status and the season of birth.