How the placenta-brain lipid axis impacts the nutritional origin of child neurodevelopmental disorders: Focus on attention deficit hyperactivity disorder and autism spectrum disorder.

Dietary fish is a rich source of omega-3 (n-3) fatty acids, and as such, is believed to have played an important role in the evolution of the human brain and its advanced cognitive function. The long chain polyunsaturated fatty acids, particularly the n-3 docosahexanoic acid (DHA), are critical for proper neurological development and function. Both low plasma DHA and obesity in pregnancy are associated with neurodevelopmental disorders such as attention deficit and hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in childhood, and n-3 supplementation has been shown to improve symptoms, as reviewed herein. The mechanisms underlying the connection between maternal obesity, n-3 fatty acid levels and offspring's neurological outcomes are poorly understood, but we review the evidence for a mediating role of the placenta in this relationship. Despite promising data that n-3 fatty acid supplementation mitigates the effect of maternal obesity on placental lipid metabolism, few clinical trials or animal studies have considered the neurological outcomes of offspring of mothers with obesity supplemented with n-3 FA in pregnancy.

Consumption of a Low Carbohydrate Diet in Overweight or Obese Pregnant Women Is Associated with Longer Gestation of Pregnancy.

Studies of obstetric outcomes in women consuming low-carbohydrate diets have reported conflicting results. Most studies have defined low-carbohydrate diets by the percentage that carbohydrates contribute to overall energy intake, rather than by an absolute amount in grams per day (g/d). We hypothesised that a low absolute carbohydrate diet affects obstetric outcomes differently than a low percentage carbohydrate diet. Dietary data were collected from overweight or obese women in the Study of Probiotic IN Gestational diabetes at 16- and 28-weeks' gestation. Obstetric outcomes were compared between women whose carbohydrate intake was in the lowest quintile vs quintiles 2-5. Mean gestation was increased in women whose absolute carbohydrate intake was in the lowest quintile at 16 and at both 16- and 28-weeks' gestation compared with all other women (16: 39.7 vs. 39.1 weeks, p = 0.008; 16 and 28: 39.8 vs. 39.1, p = 0.005). In linear regression analysis, a low absolute carbohydrate intake at 16 and at 28 weeks' gestation was associated with increased gestation at delivery (16: p = 0.04, adjusted R2 = 0.15, 28: p = 0.04, adjusted R2 = 0.17). The coefficient of beta at 16 weeks' gestation was 0.50 (95% CI 0.03-0.98) and at 28 weeks' gestation was 0.51 (95%CI 0.03-0.99) meaning that consumption of a low absolute carbohydrate diet accounted for an extra 3.5 days in gestational age. This finding was not seen in women whose percentage carbohydrate intake was in the lowest quintile. Low-carbohydrate consumption in pregnancy is associated with increased gestational age at delivery.

Dietary Blueberry and Soluble Fiber Supplementation Reduces Risk of Gestational Diabetes in Women with Obesity in a Randomized Controlled Trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM. OBJECTIVES: We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM. METHODS: Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (<20 weeks of gestation) and randomly assigned to 1 of the following 2 groups for 18 wk: intervention (280 g whole blueberries and 12 g soluble fiber per day) and standard prenatal care (control). Both groups received nutrition education and maintained 24-h food recalls throughout the study. Data on anthropometrics, blood pressure, and blood samples for biochemical analyses were collected at baseline (<20 weeks), midpoint (24-28 weeks), and end (32-36 weeks) of gestation. Diagnosis of GDM was based on a 2-step glucose challenge test (GCT). Data were analyzed using a mixed-model ANOVA. RESULTS: Maternal weight gain was significantly lower in the dietary intervention than in the control group at the end of the trial (mean ± SD: 6.8 ± 3.2 kg compared with 12.0 ± 4.1 kg, P = 0.001). C-reactive protein was also lower in the intervention than in the control group (baseline: 6.1 ± 4.0 compared with 6.8 ± 7.2 mg/L; midpoint: 6.1 ± 3.7 compared with 7.5 ± 7.3 mg/L; end: 5.5 ± 2.2 compared with 9.5 ± 6.6 mg/L, respectively, P = 0.002). Blood glucose based on GCT was lower in the intervention than in the control (100 ± 33 mg/dL compared with 131 ± 40 mg/dL, P < 0.05). Conventional lipids (total, LDL, and HDL cholesterol and triglycerides) did not differ between groups over time. No differences were noted in infant birth weight. CONCLUSIONS: Whole blueberry and soluble fiber supplementation may prevent excess gestational weight gain and improve glycemic control and inflammation in women with obesity.This trial was registered at clinicaltrials.gov as NCT03467503.

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics. DESIGN: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test. RESULTS: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions. CONCLUSIONS: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.

A low intensity dietary intervention for reducing excessive gestational weight gain in an overweight and obese pregnant cohort.

PURPOSE: Excessive gestational weight gain is associated with detrimental outcomes to both the mother and baby. Currently, the best approach to prevent excessive gestational weight gain in overweight and obese women is undetermined. The present study aimed to evaluate the effectiveness of a group-based outpatient dietary intervention in pregnancy to reduce excessive gestational weight gain. METHODS: In this retrospective study, overweight and obese pregnant women who attended a single 90-min group education session were compared to women who received standard care alone. Total gestational weight gain, maternal and neonatal outcomes were compared between the intervention and control groups. Data were analysed using Student t, Mann-Whitney and Chi-squared tests as appropriate. A 24-h dietary recall was analysed and compared to the Australian National Nutrition Survey. RESULTS: A significant reduction in gestational weight gain was observed with this intervention (P = 0.010), as well as in the rate of small for gestational age births (P = 0.043). Those who attended the intervention had saturated fat and sodium intake levels that exceeded recommendations. Intake of pregnancy-specific micronutrients including folate, calcium and iron were poor from diet alone. CONCLUSIONS: A low-intensity antenatal dietary intervention may be effective in reducing excessive gestational weight gain, although multi-disciplinary interventions yield the best success. Further research is required to identify the optimal modality and frequency to limit excessive gestational weight gain. Dietary interventions tailored to ethnicity should also be explored. LEVEL OF EVIDENCE: Level II, controlled trial without randomization.

Factors Associated with the Need for Insulin as a Complementary Treatment to Metformin in Gestational Diabetes Mellitus.

OBJECTIVE: To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). METHODS: A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. RESULTS: A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG) < 90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p = 0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p = 0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p = 0,032). CONCLUSION: Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG < 90 mg/dL and primiparity were protective factors.

OBJETIVO: Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). MéTODOS: Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 com gestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas com metformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. RESULTADOS: Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ) < 90 mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,235­0,815]; p = 0,009), bem como a primiparidade (RP: 0,280 [0,111­0,704]; p = 0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.063­4.039]; p = 0,032). CONCLUSãO: A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ < 90 mg/dL e a primiparidade foram fatores de proteção.

Factors associated with the need for insulin as a complementary treatment to metformin in gestational diabetes mellitus / Fatores associados à necessidade de insulina como tratamento complementar à metformina na diabetes mellitus gestacional

Abstract Objective To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). Methods A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. Results A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG)<90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p=0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p=0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p=0,032). Conclusion Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG<90 mg/dL and primiparity were protective factors.

Resumo Objetivo Avaliar os fatores associados à necessidade de insulina como tratamento complementar à metformina em gestantes com diabetes mellitus gestacional (DMG). Métodos Um estudo caso-controle foi realizado de abril de 2011 a fevereiro de 2016 comgestantes portadoras de DMG que necessitaram de tratamentos complementares além de dieta e exercícios físicos. Aquelas tratadas commetformina foram comparadas com aquelas que, além da metformina, também precisaram de combinação com insulina. Foram avaliadas as características maternas e de controle glicêmico. Modelos de regressão logística multinomial foram construídos para avaliar a influência das diferentes terapias nos desfechos neonatais. Resultados Foram avaliadas 475 gestantes que necessitaram de terapia farmacológica. Destas, 366 (77,05%) utilizaram terapia única com metformina, e 109 (22,95%) necessitaram de insulina como tratamento complementar. Na análise da razão de possibilidades (RP), a glicemia de jejum (GJ)<90mg/dL reduziu as chances de necessidade da combinação (RP: 0,438 [0,235-0,815]; p=0,009), bem como a primiparidade (RP: 0,280 [0,111-0,704]; p=0,007). Em gestantes obesas, foi observada uma chance maior de necessidade da combinação (RP: 2.072 [1.063-4.039]; p=0,032). Conclusão A obesidade resultou em um aumento na chance de a mãe precisar de insulina como tratamento complementar à metformina, enquanto a GJ<90 mg/dL e a primiparidade foram fatores de proteção.

Evidence-based recommendations for energy intake in pregnant women with obesity.

BACKGROUND: In women with obesity, excess gestational weight gain (≥270 g/week) occurs in two out of three pregnancies and contributes to metabolic impairments in both mother and baby. To improve obstetrical care, objectively assessed information on energy balance is urgently needed. The objective of this study was to characterize determinants of gestational weight gain in women with obesity. METHODS: This was a prospective, observational study of pregnant women with obesity. The primary outcome was energy intake calculated by the energy intake-balance method. Energy expenditure was measured by doubly-labeled water and whole-room indirect calorimetry and body composition as 3-compartment model by air displacement plethysmography and isotope dilution in early (13-16 weeks) and late pregnancy (35-37 weeks). RESULTS: In pregnant women with obesity (n=54), recommended weight gain (n=8, 15%) during the second and third trimesters was achieved when energy intake was 125±52 kcal/d less than energy expenditure. In contrast, women with excess weight gain (67%) consumed 186±29 kcal/d more than they expended (P<0.001). Energy balance affected maternal adiposity (recommended: -2.5±0.8 kg fat mass, excess: +2.2±0.5, inadequate: -4.5±0.5, P<0.001), but not fetal growth. Weight gain was not related to demographics, activity, metabolic biomarkers, or diet quality. We estimated that energy intake requirements for recommended weight gain during the second and third trimesters were not increased as compared to energy requirements early in pregnancy (34±53 kcal/d, P=0.83). CONCLUSIONS: We here provide the first evidence-based recommendations for energy intake in pregnant women with obesity. Contrary to current recommendations, energy intake should not exceed energy expenditure. FUNDING: This study was funded by the National Institutes of Health (R01DK099175; Redman, U54GM104940 and P30DK072476; Core support). TRIAL REGISTRATION: clinicaltrials.gov: NCT01954342.

Prepregnancy Obesity, Maternal Dietary Intake, and Oxidative Stress Biomarkers in the Fetomaternal Unit.

BACKGROUND: Obesity and pregnancy increase levels of maternal oxidative stress (OS). However, little is known about the maternal, placental, and neonatal OS status. OBJECTIVE: To analyze the relation between prepregnancy obesity and the expression of OS markers and antioxidant capacity in the fetomaternal unit and their association with dietary intake. METHODS: This cross-sectional study included 33 women with singleton, noncomplicated pregnancies. Two groups were formed: women with prepregnancy body mass index (pBMI) within normal range (18.5-24.9 kg/m2, n = 18) and women with pBMI ≥ 30 kg/m2, suggestive of obesity (n = 15). Dietary and clinical information was obtained by questionnaire and from clinical records. Total antioxidant capacity (TAC) and malondialdehyde (MDA) concentration were measured on maternal and cord serum by colorimetric techniques, and placental expression of glutathione peroxidase 4 (GPx4) was measured by immunohistochemistry. RESULTS: Placental GPx4 expression was lower in the group with pBMI suggestive of obesity than in the normal weight group (ß = -0.08, p = 0.03, adjusted for gestational age and magnesium intake). Concentrations of TAC and MDA in maternal and cord blood were not statistically different between groups (p>0.05). Cord MDA concentration was related to maternal MDA concentration (ß = 0.40, p < 0.01), vitamin A intake (tertile 2: ß = -0.04, p = 0.40, tertile 3: ß = 0.13, p = 0.03, vs tertile 1), and placental GPx4 expression (ß = -0.09, p = 0.02). CONCLUSION: Prepregnancy obesity is associated with a decrease in GPx4 expression in the placenta, which is related to OS in the newborn. The influence of micronutrient intake on OS biomarkers highlights the importance of nutritional assessment during pregnancy and adequate prenatal care.

Effect of antenatal dietary interventions in maternal obesity on pregnancy weight-gain and birthweight: Healthy Mums and Babies (HUMBA) randomized trial.

BACKGROUND: Pregnancy interventions that improve maternal and infant outcomes are urgently needed in populations with high rates of obesity. We undertook the Healthy Mums and Babies (HUMBA) randomized controlled trial to assess the effect of dietary interventions and or probiotics in a multiethnic population of pregnant women with obesity, living in an area of high deprivation. OBJECTIVES: To determine whether a culturally tailored dietary intervention and or daily probiotic capsules in pregnant women with obesity reduces the co-primary outcomes of (1) excessive gestational weight gain (mean >0.27 kg/week) and (2) birthweight. STUDY DESIGN: We conducted a 2 × 2 factorial, randomized controlled trial in women without diabetes at pregnancy booking, body mass index ≥30 kg/m2, and a singleton pregnancy. At 12+0 to 17+6 weeks' gestation, eligible women were randomized to a dietary intervention (4 tailored educational sessions at ≤28 weeks' gestation by a community health worker trained in key aspects of pregnancy nutrition plus text messaging until birth) or to routine dietary advice; and to daily capsules containing either (Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12, minimum 6.5 × 109 colony forming units), or placebo, until birth. Analysis was by intention to treat with adjustment for maternal baseline body mass index. Infant outcomes were additionally adjusted for ethnicity, sex, and gestational age at birth. RESULTS: In total, 230 women were recruited between April 2015 and June 2017 (dietary intervention N = 116 vs routine dietary advice N = 114; probiotics N = 115 vs placebo N = 115). Baseline characteristics and demographic variables were similar across all groups. There was no significant difference between intervention groups, for the co-primary outcomes of (1) proportion of women with excessive gestational weight gain (dietary intervention vs routine advice: 79/107 [73.8%] vs 90/110 [81.8%], adjusted relative risk [relative risk, 0.92; 95% confidence interval, 0.80-1.05]; probiotics versus placebo: 89/108 [82.4%] and 80/109 [73.4%], relative risk, 1.14, 95% confidence interval, 0.99-1.31) or (2) birthweight (dietary intervention vs routine advice: 3575 vs 3612 g, adjusted mean difference, -24 g, 95% confidence interval, -146 to 97; probiotics vs placebo: 3685 vs 3504 g, adjusted mean difference, 107 g, 95% confidence interval, -14 to 228). Total maternal weight gain, a secondary outcome, was lower with dietary intervention compared with routine dietary advice (9.7 vs 11.4 kg, adjusted mean difference, -1.76, 95% confidence interval, -3.55 to 0.03). There were no significant differences between intervention groups in other secondary maternal or neonatal outcomes. CONCLUSION: Although dietary education and or probiotics did not alter rates of excessive gestational weight gain or birthweight in this multiethnic, high-deprivation population of pregnant women with obesity, dietary education was associated with a modest reduction in total weight gain with potential future benefit for the health of mothers and their offspring if sustained.