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 .

Maternal Predictors of Breast Milk Plasmalogens and Associations with Infant Body Composition and Neurodevelopment.

PURPOSE: Ethanolamine-containing plasmalogens (pPEs) are a unique class of breastmilk (BM) glycerophospholipids containing a vinyl-ether at the sn-1 and a polyunsaturated fatty acid (PUFA) at the sn-2 position of the glycerol moiety. pPEs are present in the milk fat globule membrane, accumulate in the infant brain, and have been implicated in infant development. The study objectives were to: (1) describe the composition of BM pPEs and the variation in monomers at both the sn-1 and sn-2 positions; and (2) quantify the associations between BM pPEs and maternal predictors (body mass index, race, dietary fatty acid intake, gestational age at birth, and days' postpartum). Secondary objectives were to explore the relationship between BM pPEs and infant anthropometrics and neurodevelopment. METHODS: This was a secondary analysis of 39 mother-infant dyads in the control group of a randomized controlled trial of vitamin D supplementation during lactation. BM samples and data regarding maternal diet, infant anthropometrics (weight, fat mass index, and fat-free mass index by dual-energy X-ray absorptiometry), and infant development were collected at 1 month (visit 1 [V1], n = 37) and 4 months' (visit 4 [V4], n = 39) postpartum. BM pPEs were extracted and quantified by using ultra-HPLC/high-resolution MS/MS at V1 and V4 and expressed as percent mass of total phospholipids. Associations of pPEs with infant development and anthropometrics were modeled using linear regression. FINDINGS: C(18:0) vinyl ethers and C(18:2) polyunsaturated fatty acid-enriched pPEs predominate in BM. Specific pPEs, as a proportion of total phospholipids, decreased between V1 and V4. Higher maternal body mass index was associated with lower BM pPEs in unadjusted models, but this association was attenuated after adjustment for race, diet, and days' postpartum. Maternal fatty acid intake, gestational age, and days' postpartum were not associated with BM pPEs. Total pPEs at V1 were negatively associated with infant fat mass index and positively associated with fat-free mass index at V1 and V4. BM pPE concentrations were not correlated with neurodevelopmental outcomes. IMPLICATIONS: BM pPEs decrease over lactation and are associated with lower infant adiposity and higher lean mass. CLINICALTRIALS: gov identifier: NCT00412074.

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.

Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Newborn Body Composition, Growth and Length of Gestation: A Randomized Controlled Pilot Study.

Maternal obesity, a state of chronic low-grade metabolic inflammation, is a growing health burden associated with offspring adiposity, abnormal fetal growth and prematurity, which are all linked to adverse offspring cardiometabolic health. Higher intake of anti-inflammatory omega-3 (n-3) polyunsaturated fatty acids (PUFA) in pregnancy has been associated with lower adiposity, higher birthweight and longer gestation. However, the effects of n-3 supplementation specifically in pregnant women with overweight and obesity (OWOB) have not been explored. We conducted a pilot double-blind randomized controlled trial of 72 pregnant women with first trimester body mass index (BMI) ≥ 25 kg/m2 to explore preliminary efficacy of n-3 supplementation. Participants were randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. Neonatal body composition, fetal growth and length of gestation were assessed. For the 48 dyads with outcome data, median (IQR) maternal BMI was 30.2 (28.2, 35.4) kg/m2. In sex-adjusted analyses, n-3 supplementation was associated with higher neonatal fat-free mass (ß: 218 g; 95% CI 49, 387) but not with % body fat or fat mass. Birthweight for gestational age z-score (-0.17 ± 0.67 vs. -0.61 ± 0.61 SD unit, p = 0.02) was higher, and gestation longer (40 (38.5, 40.1) vs. 39 (38, 39.4) weeks, p = 0.02), in the treatment vs. placebo group. Supplementation with n-3 PUFA in women with OWOB led to higher lean mass accrual at birth as well as improved fetal growth and longer gestation. Larger well-powered trials of n-3 PUFA supplementation specifically in pregnant women with OWOB should be conducted to confirm these findings and explore the long-term impact on offspring obesity and cardiometabolic health.

Maternal obesity, fish intake, and recurrent spontaneous preterm birth.

OBJECTIVE: Moderate fish intake in early pregnancy is associated with decreased risk of preterm birth (PTB). Obesity during pregnancy is characterized by inflammation and insufficiency of essential fatty acids. The objective of this study was to measure the association between fish intake during pregnancy and risk of recurrent spontaneous (s) PTB among lean, overweight, and obese women. DESIGN: This is secondary analysis of a randomized controlled trial of omega-3 fatty acid supplementation for recurrent PTB prevention, 2005-2006. The primary exposure was fish intake at time of enrollment (16-22.9-week gestation). The primary outcomes were sPTB <37 weeks and sPTB <35 weeks. Maternal prepregnancy body mass index was treated as an effect modifier. SUBJECTS: Eight hundred and fifty-two women were included, 47% were lean, 25% overweight, and 28% obese. RESULTS: In this cohort, among lean, but not overweight or obese women, ≥1 serving of fish per week was associated with decreased frequency of sPTB <37 weeks compared with <1 serving of fish per week (45.1% versus 27.5%, p = .001) and spontaneous PTB <35 (21.4% versus 11.6%, p = .01). In adjusted models, as fish intake increased, the predicted probability of sPTB decreased in lean women but increased in overweight and obese women (p for interaction < .10). CONCLUSION: Fish intake was associated with lower probability of sPTB in lean women and higher probability in obese women. These findings warrant further investigation to understand the dietary or metabolic factors associated with obesity that may modulate benefit of fish intake during pregnancy.

Maternal Pre-Pregnancy Obesity Attenuates Response to Omega-3 Fatty Acids Supplementation During Pregnancy.

Maternal obesity is associated with adverse offspring outcomes. Inflammation and deficiency of anti-inflammatory nutrients like omega(n)-3 polyunsaturated fatty acids (PUFA) may contribute to these associations. Fetal supply of n-3 PUFA is dependent on maternal levels and studies have suggested that improved offspring outcomes are associated with higher maternal intake. However, little is known about how maternal obesity affects the response to n-3 supplementation during pregnancy. We sought to determine (1) the associations of obesity with PUFA concentrations and (2) if the systemic response to n-3 supplementation differs by body mass index (BMI). This was a secondary analysis of 556 participants (46% lean, 28% obese) in the Maternal-Fetal Medicine Units Network trial of n-3 (Docosahexaenoic acid (DHA) + Eicosapentaenoic acid (EPA)) supplementation, in which participants had 2g/day of n-3 (n = 278) or placebo (n = 278) from 19 to 22 weeks until delivery. At baseline, obese women had higher plasma n-6 arachidonic acid concentrations (ß: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (ß: 0.26 unit; 95% CI: 0.05, 0.48) compared to lean women. In the adjusted analysis, women in all BMI groups had higher n-3 concentrations following supplementation, although obese women had attenuated changes (ß = -2.04%, CI: -3.19, -0.90, interaction p = 0.000) compared to lean women, resulting in a 50% difference in the effect size. Similarly, obese women also had an attenuated reduction (ß = 0.94 units, CI: 0.40, 1.47, interaction p = 0.046) in the n-6/n-3 ratio (marker of inflammatory status), which was 65% lower compared to lean women. Obesity is associated with higher inflammation and with an attenuated response to n-3 supplementation in pregnancy.

Maternal BMI, Mid-pregnancy Fatty Acid Concentrations,and Perinatal Outcomes.

PURPOSE: Maternal body mass index (BMI) and systemic fatty acid (FA) concentrations affect inflammatory balance in pregnancy and play a key role in fetal growth and well-being. Little is known about how maternal BMI may affect the association between key FA concentrations and neonatal outcomes. The objective of this study was to examine the associations between the maternal omega (n)6:n3 FA ratio and neonatal outcomes according to maternal pre-pregnancy BMI category. METHODS: This study is a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of omega-3 FA supplementation to prevent recurrent preterm birth. At consent (16-22 weeks of pregnancy), women were randomized to either the intervention arm (2g of n3 FAs) or the control arm (placebo). For the present analysis, the primary exposure was the ratio of proinflammatory to anti-inflammatory (n6:n3) FAs at 25 to 28 weeks of pregnancy. The primary outcome was fetal growth as measured by using birth-weight-for-gestational-age z score, birth-length-for-gestational-age z score, and head-circumference-for-gestational-age z score. BMI categories were defined as lean (18.5-24.9 kg/m²) and overweight/obese (OWOB) (≥25.0 kg/m²). Final analysis was stratified according to BMI and adjusted for education, race, parity, smoking status, total fish intake at the time of the blood draw, and number of days in the study at the time of delivery. FINDINGS: A total of 440 participants were included in this analysis; 49% were lean, and 51% were OWOB. After adjustment for covariates, a higher maternal n6:n3 FA ratio was associated with impaired fetal growth (birth-weight-for-gestational-age z score, ß = -0.04 per unit increase in n6:n3; 95% CI, -0.07 to -0.01), 1day shorter length of gestation (ß = -0.14 week; 95% CI, -0.27 to -0.01), higher incidence of neonatal respiratory distress syndrome (odds ratio, 1.37; 95% CI, 1.04 to 1.80), and increased length of neonatal hospital stay (ß = 0.29 day; 95% CI, 0.003 to 0.58) in OWOB, but not lean, participants. IMPLICATIONS: Higher maternal inflammation during pregnancy, as measured by using the n6:n3 FA ratio, may be a marker of adverse perinatal and neonatal outcomes, particularly among OWOB women.

Maternal Obesity, 25-Hydroxy Vitamin D Concentration, and Bone Density in Breastfeeding Dyads.

OBJECTIVE: To examine the association between maternal body mass index (BMI) and serum 25-hydroxy vitamin D [25(OH)D] concentration and bone density in mother-infant pairs. STUDY DESIGN: The study was a secondary analysis of 234 exclusively breastfeeding dyads who were recruited in the first postpartum month for a randomized controlled trial of maternal vs infant vitamin D supplementation. Mean 25(OH)D concentrations and bone mineral density (BMD) were compared by BMI group. The adjusted association between maternal BMI and 25(OH)D and bone density was examined at 1, 4, and 7 months postpartum. RESULTS: Obese breastfeeding women had lower 25(OH)D concentrations and higher BMD than lean women at all 3 time points (P < .01). Higher maternal BMI was associated with lower maternal serum levels of 25(OH)D at 1, 4, and 7 months postpartum (adjusted ß = -0.45 ng/ml per kg/m2, 95% CI -.076, -0.14, at 1 month) and higher BMD at the same time points (ß = 0.006 BMD z score; 95% CI 0.003, 0.01 at 1 month). Seventy-six percent of infants were vitamin D deficient at 1 month of age. Infants born to overweight and obese mothers had lower 25(OH)D concentrations than infants of lean mothers (P < .01). For infants in the maternal supplementation group, higher maternal BMI was associated with lower 25(OH)D concentrations at 4 months (ß = -0.68; 95% CI -1.17, -0.20) and lower bone density at 7 months (ß = -0.001; 95% CI -0.002, -0.0001). CONCLUSIONS: In exclusively breastfeeding dyads, maternal obesity is associated with lower maternal and infant serum 25(OH)D concentrations, which may impact infant bone density. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00412074.

Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats.

OBJECTIVE: Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring. RESEARCH DESIGN AND METHODS: Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet. RESULTS: Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.