Supplementation with antioxidant micronutrients in pregnant women with obesity: a randomized controlled trial.

BACKGROUND/OBJECTIVE: Obesity increases maternal morbidity and adversely affects child health. Maternal inflammation may play a role in adverse outcomes. The objective of this study was to determine whether providing a higher dose of antioxidant micronutrients to pregnant women with obesity would raise concentrations of key antioxidant vitamins and impact inflammation and oxidative stress during pregnancy. SUBJECTS/METHODS: This was a double-blind, randomized controlled trial. We recruited pregnant women with a body mass index (BMI) ≥ 30 kg/m2 at their initial prenatal visit ( < 13 weeks gestation) and collected blood and urine samples at baseline, 24-28 weeks, and 32-36 weeks to measure micronutrient concentrations (vitamin C, E, B6 and folate), markers of inflammation (C-reactive protein, interleukin-6, 8, and 1ß) and oxidative stress (8-epi-PGF2α and malondialdehyde). We collected maternal and infant health data from enrollment to delivery as secondary outcomes. We enrolled 128 participants (64 in each arm), and 98 (49 in each arm) completed follow-up through delivery. INTERVENTION: Both groups received a standard prenatal vitamin containing the recommended daily allowance of micronutrients in pregnancy. In addition, the intervention group received a supplement with 90 mg vitamin C, 30 αTU vitamin E, 18 mg vitamin B6, and 800 µg folic acid, and the control group received a placebo. RESULTS: The intervention group had higher vit B6 (log transformed (ln), ß 24-28 weeks: 0.76 nmol/L (95% CI: 0.40, 1.12); ß 32-36 weeks: 0.52 nmol/L (95% CI: 0.17, 0.88)) than the control group. Vitamins C, E, erythrocyte RBC folate concentrations did not differ by randomization group. The intervention did not impact biomarkers of inflammation or oxidative stress. There were no differences in maternal or neonatal clinical outcomes by randomization group. CONCLUSIONS: Higher concentrations of antioxidant vitamins during pregnancy increased specific micronutrients and did not impact maternal inflammation and oxidative stress, which may be related to dosing or type of supplementation provided. CLINICAL TRIAL REGISTRATION: Clinical Trial Identification Number: NCT02802566; URL of the Registration Site: www. CLINICALTRIALS: gov .

Clinical Characteristics and Breastfeeding Outcomes in Term Dyads Following In-Hospital Supplementation with Pasteurized Donor Human Milk or Formula.

Background: Pasteurized donor human milk (PDHM) supplementation for healthy infants is an emerging practice. Little is known about demographics or breastfeeding outcomes for dyads whose mothers choose PDHM versus formula. Research Aims: To identify relationships between in-hospital supplementation choice and (1) dyad characteristics and breastfeeding intent, and (2) breastfeeding outcomes at 1 month. Materials and Methods: This exploratory prospective cohort study surveyed healthy dyads requiring medically indicated supplementation. Participants completed questionnaires including demographics, breastfeeding intent, and self-efficacy during hospitalization, and self-efficacy and lactation outcomes at 1 month. Results: Of 39 participants, 24 (62%) supplemented with formula and 15 (38%) with PDHM. Formula dyads were more likely than PDHM dyads to have a delivery body mass index (BMI) ≥30 kg/m2 (58% versus 20%, p = 0.02), and less likely to have attained greater than a college degree (33% versus 7%, p = 0.02); formula dyads also reported lower breastfeeding intent scores (12.0 versus 15.5, p = 0.002). Breastfeeding self-efficacy scores were similar but decreased for both groups over 1 month. At 1 month, mothers who chose formula were more likely to continue to provide breast milk to their infants (84% versus 72%). Direct breastfeeding rates were similar (72% versus 68%); of participants directly breastfeeding at 1 month, PDHM dyads were 1.5 times more likely to provide maternal expressed milk. Conclusions: Differences in maternal education, BMI, and breastfeeding intent were found between feeding groups. Results suggest an association between PDHM choice and initial breastfeeding intent and breastfeeding self-efficacy and provision of maternal expressed milk at 1 month.

Human Milk Hormone Intake in the First Month of Life and Physical Growth Outcomes in Preterm Infants.

CONTEXT: Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood. OBJECTIVE: To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants. DESIGN/METHODS: In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations. MAIN OUTCOME MEASURES: Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks' postmenstrual age (PMA). RESULTS: Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks' PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (-0.36 [-0.64, -0.07]). Insulin was not associated with growth outcomes. CONCLUSIONS: Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.

A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR.

Animal studies have demonstrated the therapeutic potential of polyphenol-rich pomegranate juice. We recently reported altered white matter microstructure and functional connectivity in the infant brain following in utero pomegranate juice exposure in pregnancies with intrauterine growth restriction (IUGR). This double-blind exploratory randomized controlled trial further investigates the impact of maternal pomegranate juice intake on brain structure and injury in a second cohort of IUGR pregnancies diagnosed at 24-34 weeks' gestation. Ninety-nine mothers and their eligible fetuses (n = 103) were recruited from Brigham and Women's Hospital and randomly assigned to 8 oz pomegranate (n = 56) or placebo (n = 47) juice to be consumed daily from enrollment to delivery. A subset of participants underwent fetal echocardiogram after 2 weeks on juice with no evidence of ductal constriction. 57 infants (n = 26 pomegranate, n = 31 placebo) underwent term-equivalent MRI for assessment of brain injury, volumes and white matter diffusion. No significant group differences were found in brain volumes or white matter microstructure; however, infants whose mothers consumed pomegranate juice demonstrated lower risk for brain injury, including any white or cortical grey matter injury compared to placebo. These preliminary findings suggest pomegranate juice may be a safe in utero neuroprotectant in pregnancies with known IUGR warranting continued investigation.Clinical trial registration: NCT04394910, https://clinicaltrials.gov/ct2/show/NCT04394910 , Registered May 20, 2020, initial participant enrollment January 16, 2016.

Macronutrient Intake from Human Milk, Infant Growth, and Body Composition at Term Equivalent Age: A Longitudinal Study of Hospitalized Very Preterm Infants.

The variable macronutrient content of human milk may contribute to growth deficits among preterm infants in the neonatal intensive care unit (NICU). In a longitudinal study of 37 infants < 32 weeks gestation, we aimed to (1) determine the between-infant variation in macronutrient intake from human milk and (2) examine associations of macronutrient intake with growth outcomes. We analyzed 1626 human milk samples (median, 43 samples/infant) with mid infrared spectroscopy. Outcomes at term equivalent age were weight, length, head circumference, fat mass, and fat-free mass. Median (range) intakes from human milk were: protein 1.37 (0.88, 2.43) g/kg/day; fat 4.20 (3.19, 5.82) g/kg/day; carbohydrate 8.94 (7.72, 9.85) g/kg/day; and energy 82.5 (68.7, 99.3) kcal/kg/day. In median regression models adjusted for birth size and gestational age, and other covariates, greater intakes of fat and energy were associated with higher weight (0.61 z-scores per g/kg/day fat, 95% CI 0.21, 1.01; 0.69 z-scores per 10 kcal/kg/day, 95% CI 0.28, 1.10), whereas greater protein intake was associated with greater body length (0.84 z-scores per g/kg/day protein, 95% CI 0.09, 1.58). Higher fat intake was also associated with higher fat mass and fat-free mass. Macronutrient intakes from human milk were highly variable and associated with growth outcomes despite routine fortification.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.