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 (β: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (β: 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 (β = −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 (β = 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

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 (β: 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

Breast Milk from Non-ObeseWomen with a High Omega-6 to Omega-3 Fatty Acid Ratio, but Not fromWomen with Obesity, Increases Lipogenic Gene Expression in 3T3-L1 Preadipocytes, Suggesting Adipocyte Dysfunction

Maternal body mass index is associated with breast milk (BM) fatty acid composition. This study investigated the effects of BM omega (n)-6:n-3 polyunsaturated fatty acids (PUFAs) from non-obese women and women with obesity on the process of adipogenesis in 3T3-L1 preadipocytes. BM samples were collected from non-obese women (BMNO) and women with obesity (BMO) at one month postpartum. The fatty acid composition was measured, and BMNO and BMO groups with the lowest (Q1) and highest (Q4) quartiles of n-6:n-3 PUFA ratios were identified. 3T3-L1 preadipocytes were differentiated in the presence or absence of BM. Lipid accumulation and the expression of genes involved in lipogenesis and lipolysis were measured. Treatment with BMNO containing high (vs. low) n-6:n-3 PUFA ratios significantly increased the mRNA expression of lipogenic genes (acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase); however, there was no effect when cells were treated with BMO (with either low or high n-6:n-3 PUFA ratios). Treatment with BMO (high n-6:n-3 PUFA ratio) caused larger lipid droplets. Our findings demonstrated that BMNO with a high n-6:n-3 PUFA ratio was associated with a higher expression of lipogenic genes, while BMO with a high n-6:n-3 PUFA ratio showed larger lipid droplets, suggesting adipocyte dysfunction. These findings may have implications in the BM-mediated programming of childhood obesity

Mediators of the association between maternal body mass index and breastfeeding duration in 3 international cohorts

Background: Maternal obesity has been associated with shorter breastfeeding duration, but little is known about mediating factors explaining this association. It is important to assess these relationships across diverse populations because breastfeeding is culturally patterned. Objectives: We investigated the association of prepregnancy maternal body mass index (BMI) with breastfeeding outcomes and potential mediators of this relationship in 3 culturally diverse international cohorts. Methods: We analyzed 5120 singleton pregnancies from mother–child cohorts in Spain (INfancia y Medio Ambiente), Greece (Rhea), and the United States (Project Viva). Outcome variables were duration of any and exclusive breastfeeding. A priori hypothesized mediators in the association of maternal prepregnancy BMI with breastfeeding were birthweight (BW), maternal prenatal C-reactive protein (CRP), cesarean delivery, maternal dietary inflammatory index (DII) during pregnancy, gestational age at delivery, and gestational diabetes mellitus (GDM). We estimated the association between BMI and breastfeeding duration using linear regression adjusting for confounders. Mediation analysis estimated direct and indirect effects of maternal overweight/obesity on breastfeeding for each mediator. Results:Women with overweight and obesity had shorter duration of any and exclusive breastfeeding compared with normal-weight women (any: overweight β = −0.79 mo, 95% CI: −1.17, −0.40; obese β = −1.75 mo 95% CI: −2.25, −1.25; exclusive: overweight β = −0.30 mo, 95% CI: −0.42, −0.16; obese β = −0.73 mo, 95% CI: −0.90, −0.55). Significant mediators (% change in effect estimate) of this association were higher CRP (exclusive: 5.12%), cesarean delivery (any: 6.54%; exclusive: 7.69%), and higher DII (any: 6.48%; exclusive: 7.69%). GDM, gestational age, and BW did not mediate the association of maternal weight status with breastfeeding. Conclusions: Higher prepregnancy BMI is associated with shorter duration of any and exclusive breastfeeding. Maternal dietary inflammation, systemic inflammation, and mode of delivery may be key modifiable mediators of this association. Identification of mediators provides potential targets for interventions to improve breastfeeding outcomes.</p

Maternal Diet, Infection, and Risk of Cord Blood Inflammation in the Bangladesh Projahnmo Pregnancy Cohort

Inflammation may adversely affect early human brain development. We aimed to assess the role of maternal nutrition and infections on cord blood inflammation. In a pregnancy cohort in Sylhet, Bangladesh, we enrolled 251 consecutive pregnancies resulting in a term livebirth from July 2016–March 2017. Stillbirths, preterm births, and cases of neonatal encephalopathy were excluded. We prospectively collected data on maternal diet (food frequency questionnaire) and morbidity, and analyzed umbilical cord blood for interleukin (IL)-1α, IL-1β, IL-6, IL-8 and C-reactive protein. We determined associations between nutrition and infection exposures and cord cytokine elevation (≥75% vs. 2) at enrollment. Antenatal and intrapartum infections were observed among 4.8% and 15.9% of the sample, respectively. Low pregnancy intakes of B vitamins (B1, B2, B3, B6, B9 (folate)), fat-soluble vitamins (D, E), iron, zinc, and linoleic acid (lowest vs. middle tertile) were associated with higher risk of inflammation, particularly IL-8. There was a non-significant trend of increased risk of IL-8 and IL-6 elevation with history of ante-and intrapartum infections, respectively. In Bangladesh, improving micronutrient intake and preventing pregnancy infections are targets to reduce fetal systemic inflammation and associated adverse neurodevelopmental outcomes

The role of systemic inflammation linking maternal BMI to neurodevelopment in children

Children of obese mothers are at increased risk of developmental adversities. Maternal obesity is linked to an inflammatory in utero environment, which, in turn, is associated with neurodevelopmental impairments in the offspring. This is an integrated mechanism review of animal and human literature related to the hypothesis that maternal obesity causes maternal and fetal inflammation, and that this inflammation adversely affects the neurodevelopment of children. We propose integrative models in which several aspects of inflammation are considered along the causative pathway linking maternal obesity with neurodevelopmental limitations