Optimizing perinatal wellbeing in pregnancy with obesity: a clinical trial with a multi-component nutrition intervention for prevention of gestational diabetes and infant growth and neurodevelopment impairment.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Gestational diabetes mellitus and size at birth modify early adiposity accretion. Evidence from the OBESO cohort.

AIM: To evaluate the association between maternal obesity, gestational diabetes (GDM), and birth size with infant fat-mass (FM) accretion from 1 to 6 months (M). METHODS: Healthy pregnant women and their term babies from the OBESO cohort were studied (1 M-3 M, n = 122; 1 M-6 M, n = 90). Registered maternal data was: pregestational body-mass-index (preBMI), GDM (2hOGTT), medications, gestational weight gain. Macrosomia (>4000 g), large/small for gestational age (LGA/SGA)(weight/age > 90° and < 90°, respectively-WHO) were recorded at birth. Infant FM (air-displacement plethysmography) was measured (1 M, 3 M, 6 M) and FM accretion computed (ΔkgFM from 1 M-3 M and 1 M-6 M). Exclusive breastfeeding (EBF) was assessed. Adjusted-multiple linear regression models were performed. RESULTS: PreBMI was 27.4 ± 5.2 kg/m2. GDM was present in9%(n = 11) of women; 12.3%(n = 15) of them received metformin/insulin. One newborn was LGA; 20.7%(n = 25) were SGA. From 1 M-3 M, SGA was a predictor of higher FM accretion (B:0.28, 95%CI:0.14-0.43); GDM was not associated. From 1 M-6 M, higher FM accretion was observed in SGA newborns (B:0.43, 95%CI:0.19-0.67) and GDM infants (B:0.48, 95%CI:0.06-0.89). In all models (R2 ≥ 0.48, p < 0.001), infant weight and being female were positively associated, while maternal obesity, metformin/insulin, and EBF were not. CONCLUSIONS: GDM appears to program early higher adiposity accretion, independently of excessive fetal growth. SGA was associated with higher FM accretion in early infancy.

Development and validation of anthropometric-based fat-mass prediction equations using air displacement plethysmography in Mexican infants.

BACKGROUND/OBJECTIVES: Fat-mass (FM) assessment since birth using valid methodologies is crucial since excessive adiposity represents a risk factor for adverse metabolic outcomes. AIM: To develop infant FM prediction equations using anthropometry and validate them against air-displacement plethysmography (ADP). SUBJECTS/METHODS: Clinical, anthropometric (weight, length, body-mass index -BMI-, circumferences, and skinfolds), and FM (ADP) data were collected from healthy-term infants at 1 (n = 133), 3 (n = 105), and 6 (n = 101) months enrolled in the OBESO perinatal cohort (Mexico City). FM prediction models were developed in 3 steps: 1) Variable Selection (LASSO regression), 2) Model behavior evaluation (12-fold cross-validation, using Theil-Sen regressions), and 3) Final model evaluation (Bland-Altman plots, Deming regression). RESULTS: Relevant variables in the FM prediction models included BMI, circumferences (waist, thigh, and calf), and skinfolds (waist, triceps, subscapular, thigh, and calf). The R2 of each model was 1 M: 0.54, 3 M: 0.69, 6 M: 0.63. Predicted FM showed high correlation values (r ≥ 0.73, p < 0.001) with FM measured with ADP. There were no significant differences between predicted vs measured FM (1 M: 0.62 vs 0.6; 3 M: 1.2 vs 1.35; 6 M: 1.65 vs 1.76 kg; p > 0.05). Bias were: 1 M -0.021 (95%CI: -0.050 to 0.008), 3 M: 0.014 (95%CI: 0.090-0.195), 6 M: 0.108 (95%CI: 0.046-0.169). CONCLUSION: Anthropometry-based prediction equations are inexpensive and represent a more accessible method to estimate body composition. The proposed equations are useful for evaluating FM in Mexican infants.

Ultra-Processed Food Consumption during Pregnancy and Its Association with Maternal Oxidative Stress Markers.

Ultra-processed food (UPF) consumption during gestation may lead to increased oxidative stress (OS) and could affect pregnancy outcomes. This study aims to evaluate the association of UPF consumption during pregnancy with circulating levels of OS markers. Diet was assessed (average of three assessments) in 119 pregnant women enrolled in the OBESO perinatal cohort (Mexico), obtaining quantitative data and the percentage of energy that UPFs (NOVA) contributed to the total diet. Sociodemographic, clinical (pregestational body-mass index and gestational weight gain) and lifestyle data were collected. Maternal circulating levels of OS markers (malondialdehyde (MDA), protein carbonylation (PC), and total antioxidant capacity (TAC)) were determined at the third trimester of pregnancy. Adjusted linear regression models were performed to analyze the association between UPFs and OS markers. UPFs represented 27.99% of the total energy intake. Women with a lower UPF consumption (<75 percentile°) presented a higher intake of fiber, ω-3, ω-6, and a lower ω-6/3 ratio. Linear regression models showed that UPFs were inversely associated with TAC and MDA. Fiber intake was associated with PC. UPF intake during pregnancy may result in an increase in oxidative stress. When providing nutrition care, limiting or avoiding UPFs may be an intervention strategy that could promote a better antioxidant capacity in the body.

Vitamin D Deficiency, Excessive Gestational Weight Gain, and Oxidative Stress Predict Small for Gestational Age Newborns Using an Artificial Neural Network Model.

(1) Background: Size at birth is an important early determinant of health later in life. The prevalence of small for gestational age (SGA) newborns is high worldwide and may be associated with maternal nutritional and metabolic factors. Thus, estimation of fetal growth is warranted. (2) Methods: In this work, we developed an artificial neural network (ANN) model based on first-trimester maternal body fat composition, biochemical and oxidative stress biomarkers, and gestational weight gain (GWG) to predict an SGA newborn in pregnancies with or without obesity. A sensibility analysis to classify maternal features was conducted, and a simulator based on the ANN algorithm was constructed to predict the SGA outcome. Several predictions were performed by varying the most critical maternal features attained by the model to obtain different scenarios leading to SGA. (3) Results: The ANN model showed good performance between the actual and simulated data (R2 = 0.938) and an AUROC of 0.8 on an independent dataset. The top-five maternal predictors in the first trimester were protein and lipid oxidation biomarkers (carbonylated proteins and malondialdehyde), GWG, vitamin D, and total antioxidant capacity. Finally, excessive GWG and redox imbalance predicted SGA newborns in the implemented simulator. Significantly, vitamin D deficiency also predicted simulated SGA independently of GWG or redox status. (4) Conclusions: The study provided a computational model for the early prediction of SGA, in addition to a promising simulator that facilitates hypothesis-driven constructions, to be further validated as an application.

Suplementación de micronutrientes durante el embarazo: revisión narrativa de revisiones sistemáticas y metanálisis / Micronutrient supplementation during pregnancy: narrative review of systematic reviews and meta-analyses

Resumen OBJETIVO: Describir los efectos de la suplementación con vitamina B12, vitamina D, calcio, magnesio, zinc y múltiples micronutrientes asociados con complicaciones perinatales. METODOLOGÍA: Estudio retrospectivo, basado en la búsqueda bibliográfica de revisiones sistemáticas y metanálisis en la base de datos de Medline-PubMed, acerca de la suplementación con Vitamina B12, vitamina D, calcio, magnesio y zinc, además de la suplementación con múltiples micronutrientes en mujeres con embarazo único, sanas y con alteraciones metabólicas, de artículos publicados entre 2012 y 2022. RESULTADOS: Se incluyeron 51 revisiones y metanálisis. De acuerdo con los estudios, la suplementación con vitamina D reduce el riesgo de diabetes gestacional y preeclampsia, y posiblemente el riesgo de bajo peso al nacimiento y de pequeño para la edad gestacional. La suplementación con calcio disminuye el riesgo de hipertensión gestacional y preeclampsia en mujeres con alto riesgo y con bajo consumo de calcio. La suplementación con múltiples micronutrientes demostró un efecto en la reducción del bajo peso al nacimiento, pequeño para la edad gestacional, óbito y, posiblemente, parto pretérmino. Pocos estudios reportan que la suplementación con magnesio disminuye la hospitalización materna y mejora el control glucémico en mujeres con diabetes gestacional. Se requieren más estudios de suplementación con vitamina B12, zinc y magnesio. CONCLUSIÓN: No existe un esquema de referencia de suplementación con micronutrientes efectivo para todas las mujeres; el protocolo debe individualizarse en cuanto al tipo de nutrimento, dosis, características específicas, riesgos individuales y contexto de cada mujer, su consumo dietético y deficiencias, entre otros factores. La suplementación debe formar parte de los programas de salud gestacional, para garantizar la seguridad alimentaria y mejorar las condiciones de salud pública.

Abstract OBJECTIVE: To describe the effects of vitamin B12, vitamin D, calcium, magnesium, zinc and multiple micronutrient (MMS) supplementation on perinatal complications. METHODS: We performed a search of systematic reviews/meta-analyses of supplementation in healthy women, and/or with metabolic disorders, with a single pregnancy (Medline/PubMed; 2012-2022). RESULTS: 51 reviews/meta-analyses were included. Vitamin D supplementation appears to reduce the risk of gestational diabetes (GDM) and preeclampsia; and possibly the risk of low birth weight (LBW) and small for gestational age (SGA). Calcium supplementation reduces the risk of gestational hypertension, preeclampsia, in women at high risk and with low calcium intake. MMS showed an effect in reducing LBW, SGA, stillbirth, and possibly preterm birth. Few studies reported that magnesium supplementation could decrease maternal hospitalization and improve glycemic control in women with GDM. More studies on vitamin B12, zinc and magnesium supplementation are required. CONCLUSION: There is no single effective micronutrient supplementation scheme for all women; this must be individualized in terms of the type of nutrient, dose, specific characteristics, individual risks and context of each woman, her dietary intake/micronutrient deficiencies, among others. Supplementation should be part of a policy to improve gestational clinical care, ensure food security and improve public health conditions.

Diet Quality Is Associated with a High Newborn Size and Reduction in the Risk of Low Birth Weight and Small for Gestational Age in a Group of Mexican Pregnant Women: An Observational Study.

A high-quality diet during pregnancy may have positive effects on fetal growth and nutritional status at birth, and it may modify the risk of developing chronic diseases later in life. The aim of this study was to evaluate the association between diet quality and newborn nutritional status in a group of pregnant Mexican women. As part of the ongoing Mexican prospective cohort study, OBESO, we studied 226 healthy pregnant women. We adapted the Alternated Healthy Eating Index-2010 for pregnancy (AHEI-10P). The association between maternal diet and newborn nutritional status was investigated by multiple linear regression and logistic regression models. We applied three 24-h recalls during the second half of gestation. As the AHEI-10P score improved by 5 units, the birth weight and length increased (ß = 74.8 ± 35.0 g and ß = 0.3 ± 0.4 cm, respectively, p < 0.05). Similarly, the risk of low birth weight (LBW) and small for gestational age (SGA) decreased (OR: 0.47, 95%CI: 0.27-0.82 and OR: 0.55, 95%CI: 0.36-0.85, respectively). In women without preeclampsia and/or GDM, the risk of stunting decreased as the diet quality score increased (+5 units) (OR: 0.62, 95%IC: 0.40-0.96). A high-quality diet during pregnancy was associated with a higher newborn size and a reduced risk of LBW and SGA in this group of pregnant Mexican women.

Complementary feeding practices and their association with adiposity indicators at 12 months of age.

Nutrition during the first 1000 days of life represents a window of opportunity to reduce the risk of metabolic dysfunctions later in life. Exclusive breastfeeding (EBF) and adequate introduction of solid foods are essential to promote metabolic and nutritional benefits. We evaluated the association of infant feeding practices from birth to 6 months (M) with adiposity indicators at 12 M. We performed a secondary analysis of 106 healthy term infants born from a cohort of healthy pregnant women. Type of breastfeeding (exclusive or nonexclusive), the start of complementary feeding (CF) (before (<4 M) or after (≥4 M)), and adiposity (body mass index - BMI, body mass index-for-age - BMI/A, waist circumference - WC, and waist circumference-length ratio - WLR) were evaluated at 12 M using descriptive statistics, mean differences, X2, and linear regression models. During the first 6 M, 28.3% (n = 30) of the infants received EBF. Early CF (<4 M) was present in 26.4% (n = 28) of the infants. Children who started CF < 4 M were less breastfed, received added sugars as the most frequently introduced food category, and showed higher BMI, BMI/A, WC, and WLR; those who consumed added sugars early (<4 M) had a higher WC. Starting CF < 4 M was the main factor associated with a higher WC at 12 M. Unhealthy infant feeding practices, such as lack of EBF, early CF, and early introduction of sugars, may be associated with higher adiposity at 12 M.

Importancia de la suplementación en el embarazo: papel de la suplementación con hierro, ácido fólico, calcio, vitamina D y multivitamínicos.

Health promotion and disease prevention are essential components of prenatal care. Maternal nutrient insufficiencies could negatively impact the morbidity and mortality of the mother-fetus pair as well as the health of the next generations. Although a healthy diet is usually sufficient to meet the increased nutrient needs, supplementation is part of routine care to ensure a healthy pregnancy and optimal fetal development. Currently, iron and folic acid supplementation is the only globally accepted recommendation for all pregnant women. However, there are vulnerable groups of women who could benefit from complementary individualized supplementation schemes. Recently, relevant information has been published related to the supplementation of single and multiple micronutrients with significant effects on maternal and fetal health, which could have implications in the clinical practice of health professionals. This review presents scientific evidence and the recommendations of different entities on the supplementation of iron, folic acid, calcium, vitamin D and multiple micronutrient supplementation during pregnancy.

La promoción de la salud y la prevención de enfermedades son componentes esenciales de la atención prenatal. Las insuficiencias de nutrimentos afectan negativamente la morbimortalidad del binomio madre-hijo, así como a la salud de las siguientes generaciones. Aunque una alimentación saludable generalmente es suficiente para cubrir las necesidades aumentadas de micronutrimentos, la suplementación es parte del cuidado habitual para garantizar un embarazo saludable y el desarrollo óptimo del producto. Actualmente la suplementación de hierro y ácido fólico es la única recomendación mundialmente aceptada para todas las mujeres embarazadas. Por otro lado, existen grupos de mujeres vulnerables que podrían beneficiarse de esquemas de suplementación individualizados complementarios. Recientemente se ha publicado información relevante relacionada con la suplementación de distintos micronutrimentos de forma individual y múltiple con efectos importantes en la salud materno-fetal, lo cual podría tener implicaciones en la práctica clínica de los profesionales de la salud. Esta revisión presenta la evidencia científica y las recomendaciones de distintos organismos sobre la suplementación de hierro, ácido fólico, calcio, vitamina D y suplementación múltiple de vitaminas y minerales durante el embarazo.

Importancia de la vitamina B12 y el folato en la salud perinatal.

Fetal development is characterized by great plasticity and the ability to respond to environmental factors, where DNA methylation is essential for proper embryonic development. One-carbon metabolism provides methyl groups for methylation and fetal DNA development and is highly dependent on maternal nutritional status. During pregnancy, the supply of methyl donors is critical and the demand for nutrients that support this process, such as folate and vitamin B12, is increased. Insufficiency or imbalance of these 2 micronutrients can alter epigenetic patterns, DNA synthesis and repair, and affect fetal growth and development, having negative long-term consequences on the offspring's health. Folate and vitamin B12 status have been associated with wide DNA methylation, as well as with specific genes related to neurological functions, embryonic development, energy metabolism, growth, and leptin. Furthermore, inadequate concentrations of both vitamins have been associated with an increased risk of perinatal outcomes such as neural tube defects, prematurity, low birth weight, pre-eclampsia, as well as maternal and infant obesity and insulin resistance, and decreased infant neurocognitive development. Supplementation, combined with a healthy diet, could be an essential strategy to prevent these results and improve maternal and fetal health.

El desarrollo fetal se caracteriza por una gran plasticidad y capacidad para responder a factores ambientales, donde la metilación del ADN es indispensable para el desarrollo embrionario adecuado. El metabolismo de un carbono proporciona grupos metilo para la metilación y el desarrollo del ADN fetal, y depende en gran medida del estado nutricio materno. El embarazo es una etapa donde el suministro de donantes de metilo es crítico y la demanda de nutrimentos que apoyen este proceso, como lo son el folato y la vitamina B12, está aumentada. La insuficiencia o desequilibrio de estos dos micronutrimentos puede alterar los patrones epigenéticos, la síntesis y reparación del ADN, y afectar procesos del crecimiento y desarrollo fetal, teniendo consecuencias negativas en la salud de la descendencia a largo plazo. El estado del folato y la vitamina B12 se han asociado con la metilación global del ADN, así como con genes específicos relacionados con funciones neurológicas, con el desarrollo embrionario, el metabolismo energético, el crecimiento, y con la leptina. Además, estados alterados de ambas vitaminas se han asociado con mayor riesgo de resultados perinatales como defectos del tubo neural, prematurez, bajo peso al nacer, preeclampsia, así como obesidad y resistencia a la insulina materna e infantil, y disminución del desarrollo neurocognitivo infantil. La suplementación, aunada a una dieta adecuada, podría ser una estrategia necesaria para prevenir dichos resultados y mejorar la salud maternofetal.

Nutrients, Mitochondrial Function, and Perinatal Health.

Mitochondria are active independent organelles that not only meet the cellular energy requirement but also regulate central cellular activities. Mitochondria can play a critical role in physiological adaptations during pregnancy. Differences in mitochondrial function have been found between healthy and complicated pregnancies. Pregnancy signifies increased nutritional requirements to support fetal growth and the metabolism of maternal and fetal tissues. Nutrient availability regulates mitochondrial metabolism, where excessive macronutrient supply could lead to oxidative stress and contribute to mitochondrial dysfunction, while micronutrients are essential elements for optimal mitochondrial processes, as cofactors in energy metabolism and/or as antioxidants. Inadequate macronutrient and micronutrient consumption can result in adverse pregnancy outcomes, possibly through mitochondrial dysfunction, by impairing energy supply, one-carbon metabolism, biosynthetic pathways, and the availability of metabolic co-factors which modulate the epigenetic processes capable of establishing significant short- and long-term effects on infant health. Here, we review the importance of macronutrients and micronutrients on mitochondrial function and its influence on maternal and infant health.

Higher fat mass and fat mass accretion during the first six months of life in exclusively breastfed infants.

BACKGROUND: Early nutrition influences infant growth and body composition, which may play a role in the infant's metabolic programming. Breastfed infants appear to have higher fat mass than formula-fed infants, but most comparisons have been cross-sectional, and evidence is scarce. The aim of this study was to describe fat mass and fat mass accretion during the first six months of life and evaluate differences by type of feeding (OMS). METHODS: Prospective cohort of healthy pregnant women and their infants (Mexico City, 2009-2014). At 1 (T1), 3 (T2) and 6 (T3) months of age, fat mass (FM) (PEAPOD) and type of feeding (feeding questionnaire) were evaluated. RESULTS: We included 109 healthy infants (mean ± SD age: 39 ± 1.1 weeks; birthweight: 2959 ± 294 g). Exclusive/predominant breastfed (EBF) infants had higher FM at T2 and T3 compared with non-EBF (%FM T3: 29.7 ± 5.9% vs 24.7 ± 5.6%, respectively) (p < 0.05). All infants increased their FM throughout time (p < 0.001). EBF infants showed a significant higher FM accretion (ß: 3.61; 95% CI: 1.57-5.66, p < 0.01); the difference was maintained after controlling for confounding variables. CONCLUSIONS: Exclusive/predominant breastfeeding promotes higher accretion of FM during the first six months of life which could have an important effect in the programming of health outcomes later in life.

Anthropometric and clinical correlates of fat mass in healthy term infants at 6 months of age.

BACKGROUND: Body composition in infancy plays a central role in the programming of metabolic diseases. Fat mass (FM) is determined by personal and environmental factors. Anthropometric measurements allow for estimations of FM in many age groups; however, correlations of these measurements with FM in early stages of life are scarcely reported. The aim of this study was to evaluate anthropometric and clinical correlates of FM in healthy term infants at 6 months of age. METHODS: Healthy term newborns (n = 102) from a prospective cohort. Weight, length, skinfolds (biceps, triceps, subscapular and the sum -SFS-) and waist circumference (WC) were measured at 6 months. Body mass index (BMI) and WC/length ratio were computed. Type of feeding during the first 6 months of age was recorded. Air displacement plethysmography was used to asses FM (percentage -%-) and FM index (FMI) was calculated. Correlations and general linear models were performed to evaluate associations. RESULTS: Significant correlations were observed between all anthropometric measurements and FM (% and index)(p < 0.001). Exclusive/predominant breastfed infants had higher FM and anthropometric measurements at 6 months. Models that showed the strongest associations with FM (% and index) were SFS + WC + sex + type of feeding. CONCLUSIONS: Anthropometry showed good correlations with FM at 6 months of age. Skinfolds sum and waist circumference were the strongest anthropometric variables associated to FM. Exclusive/predominant breastfeeding was strongly associated with FM.