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The effect of supplementation with the omega 3 polyunsaturated fatty acid (n3 PUFA) docosahexaenoic acid (DHA) on membrane composition and amyloid-β₁₋₄₂ (Aβ₄₂) secretion was studied in human amyloid-β protein precursor-transfected Chinese Hamster Ovary (CHO) cells. Twenty-four hour incubation with a range of DHA concentrations resulted in a dose-dependent increase in membrane DHA and eicosapentaenoic acid content and a decrease in arachidonic acid content. In addition, DHA supplementation caused a dose-dependent reduction in the secreted Aβ₄₂ levels and resulted in a 4-8 fold decrease in extracellular prostaglandin E₂ (PGE₂) levels. Tocopherol, which was added to DHA to prevent oxidation, may have contributed to the effect of DHA, since it slightly decreased extracellular Aβ₄₂ and PGE₂ levels when given alone. The addition of selective COX2 inhibitors Celebrex and curcumin to the culture medium resulted in a significant and comparable inhibition of PGE₂ release, but did not inhibit Aβ₄₂ secretion, and even significantly increased Aβ₄₂ production in this cell system. Together, the present data show that, whereas both DHA and COX2 inhibitors may reduce PGE₂ production, only DHA in the presence of tocopherol significantly reduced Aβ₄₂ production and concurrently changed membrane lipid composition in CHO cells. It is concluded that in this in vitro setting DHA reduced Aβ₄₂ secretion through membrane-related, but not PGE₂-related mechanisms. [ABSTRACT FROM AUTHOR]

Brain health is a pressing global concern. Poor diet quality is a recognized major environmental risk factor for brain disorders and one of the few that is modifiable. There is substantial evidence that nutrition impacts brain development and brain health across the life course. So why then is the full potential of nutrition not utilized to improve brain function? This commentary, which is based on discussions of the European Brain Research Area BRAINFOOD cluster, aims to highlight the most urgent research priorities concerning the evidence base in the area of nutrition and brain health and identifies 3 major issues that need to be addressed: (1) increase causal and mechanistic evidence on the link between nutrition and brain health, (2) produce effective messages/education concerning the role of food for brain health, and (3) provide funding to support collaborative working across diverse stakeholders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Extracellular vesicles (EVs) play a crucial role in mediating communication between cells across species and kingdoms. The intercellular communication facilitated by EVs through autocrine and paracrine signalling mechanisms is essential for cell survival, maintaining normal metabolic functions and ensuring overall bodily homeostasis and health. Extracellular vesicles are present in various bodily fluids, such as pleural effusions, plasma, breast milk, amniotic fluid, semen and saliva. Additionally, the generation and release of EVs contribute to the removal of cellular waste. Patients with obesity exhibit a higher release and amount of circulating EVs than individuals with normal weight. This increased EV release in obesity might contribute to the inflammatory state characteristic of this metabolic condition, because higher levels of pro-inflammatory molecules are found within their cargo. However, interpreting results related to EV abundance, cargo and biological actions can be complicated by several factors; these include variations in cell sources, a wide age range (from children to the elderly), a mix of females and males, medication use and health status, a range of body weights (from normal weight to morbid obesity) and differences between in vitro assays using cell lines versus primary cultures. This article addresses the shortcomings, limitations and gaps in knowledge, providing a framework for enhancing our understanding of the physiological effects of EVs on obesity., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Gestational diabetes mellitus (GDM) is associated with increased postpartum risk for metabolic dysfunction-associated steatotic liver disease (MASLD). GDM-related MASLD predisposes to advanced liver disease, necessitating a better understanding of its development in GDM. This preclinical study evaluated the MASLD development in a lean GDM mouse model with impaired insulin secretion capacity. Lean GDM was induced by short-term 60% high-fat diet and low-dose streptozotocin injections (60 mg/kg for 3 days) before mating in C57BL/6N mice. The control dams received only high-fat diet or low-fat diet. Glucose homeostasis was assessed during pregnancy and postpartum, whereas MASLD was assessed on postpartum day 30 (PP30). GDM dams exhibited a transient hyperglycemic phenotype during pregnancy, with hyperglycaemia reappearing after lactation. Lower insulin levels and impaired glucose-induced insulin response were observed in GDM mice during pregnancy and postpartum. At PP30, GDM dams displayed higher hepatic triglyceride content compared controls, along with increased MAS (MASLD) activity scores, indicating lipid accumulation, inflammation, and cell turnover indices. Additionally, at PP30, GDM dams showed elevated plasma liver injury markers. Given the absence of obesity in this double-hit GDM model, the results clearly indicate that impaired insulin secretion driven pregnancy hyperglycaemia has a distinct contribution to the development of postpartum MASLD., (© 2024. The Author(s).)

Oligosaccharides and sialic acids (Sia) are bioactive components in milk that contribute to newborn development and health. Hyperglycemia in pregnancy (HIP) can have adverse effects on both mother and infant. HIP is associated with low-grade systemic inflammation. Inflammation influenced glycan composition, particularly of Sia-containing structures. We hypothesize that HIP and high-fat diet influence milk oligosaccharide composition, particularly sialylated oligosaccharides. Furthermore, we propose that milk Sia content influences pup brain Sia content. To test these hypotheses we (i) characterize mouse milk oligosaccharides and Sia concentrations in mouse milk of a GDM mouse model with dietary fat intake intervention; and (ii) determine Sia levels in offspring brains. The concentrations of oligosaccharides and Sia in mouse milk and offspring's brains were quantified using UPLC-FLD analysis. Analyses were performed on surplus samples from a previous study, where HIP was induced by combining high-fat diet (HF) feeding and low-dose streptozotocin injections in C57Bl/6NTac female mice. The previous study described the metabolic effects of HIP on dams and offspring. We detected 21 mouse milk oligosaccharides, including 9 neutral and 12 acidic structures using UPLC-MS. A total of 8 structures could be quantified using UPLC-FLD. Maternal HIP and HF diet during lactation influenced sialylated oligosaccharide concentrations in mouse milk and total and free sialic acid concentrations. Sia content in offspring brain was associated with total and free Neu5Gc in mouse milk of dams, but no correlations with HIP or maternal diet were observed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fan Liu reports financial support was provided by China Scholarship Council., (© 2024 The Authors.)

Background: Human milk comprises large fat globules enveloped by a native phospholipid membrane, whereas infant formulas contain small, protein-coated lipid droplets. Previous experimental studies indicated that mimicking the architecture of human milk lipid droplets in infant milk formula (IMF) alters lipid metabolism with lasting beneficial impact on later metabolic health., Objectives: To evaluate in a follow-up (FU) study of a randomized, controlled trial whether a Concept IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids beneficially impacts long-term body mass index (BMI in kg/m 2 ) trajectories and blood pressure at school age., Methods: Fully formula-fed infants were randomly assigned to Concept IMF (n = 115) or Control IMF with conventional, small lipid droplets containing vegetable oils (n = 108) for the first 4 mo of age. A group of 88 breastfed infants served as a reference. During FU, anthropometrics were collected at 1, 3, 4, and 5 y of age, and blood pressure only at the last visit., Results: Compared to Control, Concept group children had consistently lower mean BMI values during FU, with the most marked difference at 1 y of age (difference in means -0.71 kg/m 2 , 95% confidence interval (CI): -1.13, -0.29; P = 0.001); mean values were close to the breastfed group (P > 0.05). Contrary, the mean BMI values of the Control group were higher compared with the breastfed group during FU from 1 to 5 y of age (differences in means from 0.59 to 0.96 kg/m 2 , respectively; P < 0.02). At 5 y of age, the Concept group had a lower mean diastolic and arterial blood pressure compared with the Control group; -4.3mm Hg (95% CI: -7.3, -1.3; P = 0.005) and -3.7 mm Hg (95% CI: -6.5, -0.9; P = 0.01), respectively., Conclusions: Early life feeding of an innovative IMF with large, milk phospholipid-coated lipid droplets enriched with dairy lipids results in a BMI trajectory closer to breastfed infants and a lower blood pressure at school age. This trial was registered at the Dutch Trial Register as NTR3683 and NTR5538., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In low-income countries, where socioeconomic adversities and perinatal distress are common, adverse birth outcomes are significant public health problems. In these settings, perinatal distress, i.e., high symptoms of anxiety, depression, and/or stress during pregnancy, may be linked with adverse birth outcomes. However, few prospective studies have investigated the impact of perinatal distress on adverse birth outcomes such as preterm birth (gestational age <37 weeks), low birth weight (<2.5 kg), and small for gestational age birth (birth weight below the 10th percentile for gestational age and sex)., Objectives: Our main objective was to assess the influence of perinatal distress on adverse birth outcomes. Secondly, to investigate if perinatal distress is an independent risk factor or a mediator in the pathway between socioeconomic adversity and adverse birth outcomes., Methods: In a prospective cohort study following 991 women from before 20 weeks of gestation until delivery in northern Ethiopia, we collected self-reported data on distress at a mean of 14.8 (standard deviation [SD] = 1.9) and 33.9 (SD = 1.1) weeks of gestation. Distress was measured using the Edinburgh Postnatal Depression Scale, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Perceived Stress Scale. To determine birth outcomes, gestational age was estimated from the last menstrual period, fundal palpation, and/or ultrasound, while birth weight was obtained from delivery records and measured within three days after birth for those delivered at home. Logistic regression and mediation analysis were employed to evaluate the impact of perinatal distress on adverse birth outcomes., Results: Perinatal anxiety (OR [95% CI] 1.08 [1.02, 1.13]), depression (1.07 [1.03, 1.11]), stress (1.14 [1.07, 1.22]), and total distress (1.15 [1.07, 1.23]) were all associated with low birth weight, and small for gestational age birth but none did with preterm birth. Mediation analysis demonstrated that perinatal distress was a mediator in the pathway between socioeconomic adversity and adverse birth outcomes., Conclusion: Our study revealed that perinatal distress was linked with adverse birth outcomes and acted as a mediator between socioeconomic adversity and these outcomes. Our findings highlight the importance of screening women for distress and providing appropriate interventions, focusing on women experiencing socioeconomic adversity. Integrating mental health services into primary maternal care in low-income countries could be an effective approach to achieve this., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Misgina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Hyperglycaemia in pregnancy (HIP) is a pregnancy complication characterized by mild to moderate hyperglycaemia that negatively impacts short- and long-term health of mother and child. However, relationships between severity and timing of pregnancy hyperglycaemia and postpartum outcomes have not been systemically investigated. We investigated the impact of hyperglycaemia developing during pregnancy (gestational diabetes mellitus, GDM) or already present pre-mating (pre-gestational diabetes mellitus, PDM) on maternal health and pregnancy outcomes. GDM and PDM were induced in C57BL/6NTac mice by combined 60% high fat diet (HF) and low dose streptozotocin (STZ). Animals were screened for PDM prior to mating, and all underwent an oral glucose tolerance test on gestational day (GD)15. Tissues were collected at GD18 or at postnatal day (PN)15. Among HFSTZ-treated dams, 34% developed PDM and 66% developed GDM, characterized by impaired glucose-induced insulin release and inadequate suppression of endogenous glucose production. No increased adiposity or overt insulin resistance was observed. Furthermore, markers of non-alcoholic fatty liver disease (NAFLD) were significantly increased in PDM at GD18 and were positively correlated with basal glucose levels at GD18 in GDM dams. By PN15, NAFLD markers were also increased in GDM dams. Only PDM affected pregnancy outcomes such as litter size. Our findings indicate that GDM and PDM, resulting in disturbances of maternal glucose homeostasis, increase the risk of postpartum NAFLD development, related to the onset and severity of pregnancy hyperglycaemia. These findings signal a need for earlier monitoring of maternal glycaemia and more rigorous follow-up of maternal health after GDM and PDM pregnancy in humans. KEY POINTS: We studied the impact of high-fat diet/streptozotocin induced hyperglycaemia in pregnancy in mice and found that this impaired glucose tolerance and insulin release. Litter size and embryo survival were compromised by pre-gestational, but not by gestational, diabetes. Despite postpartum recovery from hyperglycaemia in a majority of dams, liver disease markers were further elevated by postnatal day 15. Maternal liver disease markers were associated with the severity of hyperglycaemia at gestational day 18. The association between hyperglycaemic exposure and non-alcoholic fatty liver disease signals a need for more rigorous monitoring and follow-up of maternal glycaemia and health in diabetic pregnancy in humans., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The prevalence of gestational diabetes mellitus (GDM) has increased in recent years, along with the higher prevalence of obesity in women of reproductive age. GDM is a pathology associated with vascular dysfunction in the fetoplacental unit. GDM-associated endothelial dysfunction alters the transfer of nutrients to the foetus affecting newborns and pregnant women. Various mechanisms for this vascular dysfunction have been proposed, of which the most studied are metabolic alterations of the vascular endothelium. However, different cell types are involved in GDM-associated endothelial dysfunction, including platelets. Platelets are small, enucleated cell fragments that actively take part in blood haemostasis and thrombus formation. Thus, they play crucial roles in pathologies coursing with endothelial dysfunction, such as atherosclerosis, cardiovascular diseases, and diabetes mellitus. Nevertheless, platelet function in GDM is understudied. Several reports show a potential relationship between platelet volume and mass with GDM; however, platelet roles and signaling mechanisms in GDM-associated endothelial dysfunction are unclear. This review summarizes the reported findings and proposes a link among altered amount, volume, mass, reactivity, and function of platelets and placenta development, resulting in fetoplacental vascular dysfunction in GDM., (© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

This study aimed to determine the association between hemoglobin (Hb) concentration and Hb change, during early to mid-pregnancy with the risk of gestational diabetes mellitus (GDM). This was a clinic-based retrospective cohort study of 1951 healthy pregnant women (18-45 years old) with a singleton gestation attending antenatal care at government health clinics. Hb concentration at first prenatal visit and each trimester was extracted from the antenatal cards. Hb changes from first prenatal visit to first and second trimester as well as from second to third trimester were calculated. Multivariate logistic regression was used with adjustment for covariates. Women with GDM had significantly higher Hb concentrations (Hb 1) at first prenatal visit (< 12 weeks) compared with non-GDM women (11·91 g/dl v .11·74 g/dl). Hb 1 and Hb changes (Hb change 2) from first prenatal visit to the second trimester (23-27th weeks) were significantly associated with GDM risk, with an adjusted OR of 1·14 (95 % CI 1·01, 1·29) and 1·25 (95 % CI 1·05, 1·49), respectively. The significant associations between Hb 1 and Hb change 2 with the risk of GDM were found among non-Malays, overweight/obese and women aged 35 years and above. Women with higher Hb concentrations in early pregnancy were at higher risk of GDM, and such association was significant among women aged 35 years and above, non-Malays and overweight/obese. This raises a potential concern for elevated Fe status in early pregnancy as a risk factor of GDM among Fe-replete women.

The intestinal microbiota plays a major role in infant health and development. However, the role of the breastmilk microbiota in infant gut colonisation remains unclear. A systematic review was performed to evaluate the composition of the breastmilk microbiota and evidence for transfer to/colonisation of the infant gut. Searches were performed using PUBMED, OVID, LILACS and PROQUEST from inception until 18th March 2020 with a PUBMED update to December 2021. 88 full texts were evaluated before final critique based on study power, sample contamination avoidance, storage, purification process, DNA extraction/analysis, and consideration of maternal health and other potential confounders. Risk of skin contamination was reduced mainly by breast cleaning and rejecting the first milk drops. Sample storage, DNA extraction and bioinformatics varied. Several studies stored samples under conditions that may selectively impact bacterial DNA preservation, others used preculture reducing reliability. Only 15 studies, with acceptable sample size, handling, extraction, and bacterial analysis, considered transfer of bacteria to the infant. Three reported bacterial transfer from infant to breastmilk. Despite consistent evidence for the breastmilk microbiota, and recent studies using improved methods to investigate factors affecting its composition, few studies adequately considered transfer to the infant gut providing very little evidence for effective impact on gut colonisation.

A balanced communication between the mother, placenta and foetus is crucial to reach a successful pregnancy. Several windows of exposure to environmental toxins are present during pregnancy. When the women metabolic status is affected by a disease or environmental toxin, the foetus is impacted and may result in altered development and growth. Gestational diabetes mellitus (GDM) is a disease of pregnancy characterised by abnormal glucose metabolism affecting the mother and foetus. This disease of pregnancy associates with postnatal consequences for the child and the mother. The whole endogenous and exogenous environmental factors is defined as the exposome. Endogenous insults conform to the endo-exposome, and disruptors contained in the immediate environment are the ecto-exposome. Some components of the endo-exposome, such as Selenium, vitamins D and B 12 , adenosine, and a high-fat diet, and ecto-exposome, such as the heavy metals Arsenic, Mercury, Lead and Copper, and per- and polyfluoroakyl substances, result in adverse pregnancies, including an elevated risk of GDM or gestational diabesity. The impact of the exposome on the human placenta's vascular physiology and function in GDM and gestational diabesity is reviewed., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pregnancy complications including fetal growth restriction, preeclampsia, and preterm birth, as well as gestational diabetes, affect one in every four to five pregnancies. Accumulating evidence indicates that increased production of reactive oxygen species accompanies these complications. Given that reactive oxygen species are cell stress-inducing agents, they may have a causal role in disease pathophysiology, although the exact mechanisms by which they contribute to pregnancy complications are not completely understood. Since many environmental and lifestyle factors and exposures are known to modulate reactive oxygen species production, the exposome of pregnant women could contribute to increased generation of reactive oxygen species. The objective of this review is to provide a comprehensive overview of the endogenous and exogenous exposome factors that regulate reactive species in healthy and complicated pregnancies. We also provide a description of dietary interventions aimed at the reduction of reactive species in order to attenuate adverse pregnancy outcome. Dietary interventions in general hold minimal risk in pregnancy and could therefore be considered a promising therapeutic approach., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study examined the association between height and the risk of Gestational Diabetes Mellitus (GDM), and whether this association was mediated or moderated by early pregnancy body mass index (BMI) and gestational weight gain (GWG) that are known independent risk factors for GDM. Data of a retrospective cohort of pregnant women (N = 1,945) were extracted from antenatal clinic cards. The cut-off values of height in relation to risk of GDM were identified using receiver operating characteristic analysis and four categories of height were derived: < 150 cm, 150-155 cm, 156-160 cm, and > 160cm. Mediation analysis was performed using the Preacher and Hayes bootstrapping method while the moderation effect was tested with multiple regression analysis with interaction terms. Although there was no mediation effect of BMI and GWG on the association between height and risk of GDM, both factors moderated this association with a significant association between shorter height and risk of GDM was observed in overweight / obese women (height < 150 cm: AOR = 1.41, 95% CI = 1.03-2.44; height 156-160 cm: AOR = 1.48, 95% CI = 1.03-2.14). Overweight / obese women with height < 150 cm and excessive GWG at the end of the second trimester (AOR = 2.25, 95% CI = 1.45-4.17) had significantly higher risk of GDM than those without these factors. Short stature (< 150 cm) was significantly associated with GDM risk among OW/OB women with excessive gestational weight gain at the end of second trimester. This finding underscores the importance of maintaining a healthy BMI during reproductive age and gaining weight in recommended range during pregnancy., Competing Interests: Jacques Bindels and Yvonne Yee Siang are employees of Nutricia Research Foundation (Netherlands) and of Danone Specialized Nutrition (Malaysia), respectively. Eline van der Beek was employed by Danone Nutricia Research at the time of the study was conducted (former employee). The authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Pregnant women may develop gestational diabetes mellitus (GDM), a disease of pregnancy characterised by maternal and fetal hyperglycaemia with hazardous consequences to the mother, the fetus, and the newborn. Maternal hyperglycaemia in GDM results in fetoplacental endothelial dysfunction. GDM-harmful effects result from chronic and short periods of hyperglycaemia. Thus, it is determinant to keep glycaemia within physiological ranges avoiding short but repetitive periods of hyper or hypoglycaemia. The variation of glycaemia over time is defined as 'glycaemia dynamics'. The latter concept regards with a variety of mechanisms and environmental conditions leading to blood glucose handling. In this review we summarized the different metrics for glycaemia dynamics derived from quantitative, plane distribution, amplitude, score values, variability estimation, and time series analysis. The potential application of the derived metrics from self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) in the potential alterations of pregnancy outcome in GDM are discussed., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Under- and overnutrition are co-existing health issues in several countries across Asia. Poor complementary feeding (CF) is a significant determinant of malnutrition in children and a major cause of morbidity and mortality. The purpose of this narrative review is to summarize the most recent evidence regarding the CF practices in 3 countries with a high prevalence of stunting and overweight, and currently undergoing rapid economic and nutritional transition: China, India, and Indonesia. We focused particularly on the adequacy of CF, based on the WHO feeding indicators (2021) regarding timing, frequency, diversity, as well as the consumption of specific food groups. According to the findings, the majority of infants in the 3 countries are introduced to CF at an inappropriate time: either too early (particularly in urban/rural areas of China and Indonesia) or too late (India) compared with the WHO recommendation. Furthermore, in all countries, diets are characterized by a low variety and frequency of CF and consist mainly of staple foods with poor nutritional quality, such as rice, cereals, or noodles. Nutrient-dense and protein-rich foods, such as foods of animal origin, are either inadequately consumed (rural areas of China and India) or introduced too late (urban areas of China and Indonesia) in the diets of children. In all countries, the consumption of fruit and vegetables, especially during the early CF period, is poor. In contrast, a significant proportion of both urban and rural children, particularly in Indonesia and India, are consuming energy-dense/nutrient-poor snacks and sugary drinks during the CF period. The described practices may pose a significant risk for the development of energy and/or nutrient gaps, magnifying the double and triple burden of malnutrition present in these countries. Further research is warranted to understand the significance of the observed practices for stunting and/or overweight/obesity risk., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Early-life diets may have a long-lasting impact on metabolic health. This study tested the hypothesis that an early-life diet with large, phospholipid-coated lipid droplets (Concept) induces sustained improvements of hepatic mitochondrial function and metabolism. Young C57BL/6j mice were fed Concept or control (CTRL) diet from postnatal day 15 (PN15) to PN42, followed by western style (WSD) or standard rodent diet (AIN) until PN98. Measurements comprised body composition, insulin resistance (HOMA-IR), tricarboxylic acid (TCA) cycle- and β-oxidation-related hepatic oxidative capacity using high-resolution respirometry, mitochondrial dynamics, mediators of insulin resistance (diacylglycerols, DAG) or ceramides) in subcellular compartments as well as systemic oxidative stress. Concept feeding increased TCA cycle-related respiration by 33% and mitochondrial fusion protein-1 by 65% at PN42 (both p 0.05). At PN98, CTRL, but not Concept, mice developed hyperinsulinemia (CTRL/AIN 0.22 ± 0.44 vs. CTRL/WSD 1.49 ± 0.53 nmol/l, p 0.05 and Concept/AIN 0.20 ± 0.38 vs. Concept/WSD 1.00 ± 0.29 nmol/l, n.s.) and insulin resistance after WSD (CTRL/AIN 107 ± 23 vs. CTRL/WSD 738 ± 284, p 0.05 and Concept/AIN 109 ± 24 vs. Concept/WSD 524 ± 157, n.s.). WSD-induced liver weight was 18% lower in adult Concept-fed mice and β-oxidation-related respiration was 69% higher (p 0.05; Concept/WSD vs. Concept/AIN) along with lower plasma lipid peroxides (CTRL/AIN 4.85 ± 0.28 vs. CTRL/WSD 5.73 ± 0.47 µmol/l, p 0.05 and Concept/AIN 4.49 ± 0.31 vs. Concept/WSD 4.42 ± 0.33 µmol/l, n.s.) and were in part protected from WSD-induced increase in hepatic cytosolic DAG C16:0/C18:1. Early-life feeding of Concept partly protected from WSD-induced insulin resistance and systemic oxidative stress, potentially via changes in specific DAG and mitochondrial function, highlighting the role of early life diets on metabolic health later in life., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breastfeeding (duration) can be positively associated with infant growth outcomes as well as improved cognitive functions during childhood and later life stages. (Prolonged) exposure to optimal lipid quantity and quality, i.e., the supramolecular structure of lipids, in mammalian milk, may contribute to these beneficial effects through nutritional early-life programming. In this pre-clinical study, we exposed male C57BL/6J mice from post-natal Days 16 to 42 (i.e., directly following normal lactation), to a diet with large lipid droplets coated with bovine milk fat globule membrane-derived phospholipids, which mimic more closely the supramolecular structure of lipid droplets in mammalian milk. We investigated whether exposure to this diet could affect growth and brain development-related parameters. As these outcomes are also known to be affected by the post-weaning social environment in mice, we included both individually housed and pair-wise housed animals and studied whether effects of diet were modulated by the social environment. After Day 42, all the animals were fed standard semi-synthetic rodent diet. Growth and body composition were assessed, and the mice were subjected to various behavioral tests. Individual housing attenuated adolescent growth, reduced femur length, and increased body fat mass. Adult social interest was increased due to individual housing, while cognitive and behavioral alterations as a result of different housing conditions were modest. The diet increased adolescent growth and femur length, increased lean body mass, reduced adolescent anxiety, and improved adult cognitive performance. These effects of diet exposure were comparable between individually and socially housed mice. Hence, early life exposure to a diet with lipid droplets that mimic the supramolecular structure of those in mammalian milk may improve adolescent growth and alters brain function in both socially and individually housed mice. These findings suggest that lipid structure in infant milk formula may be a relevant target for nutritional solutions, targeting both healthy infants and infants facing growth challenges., Competing Interests: This study was funded by Danone Nutricia Research (DNR). LS and EB were employed by DNR at the time that this study was conducted. The remaining authors declare that the research was conducted in the absence of any other commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Heijningen, Karapetsas, van der Beek, van Dijk and Schipper.)

Background/objectives: Low early pregnancy serum 25-hydroxy vitamin D (25[OH]D) levels can increase gestational diabetes mellitus (GDM) risk, although inconsistent findings related to that association have been reported. This study examined the association of serum vitamin D with GDM and the possible influencers on this association., Subjects/methods: This study included 259 pregnant women within the Seremban Cohort Study (SECOST). Blood samples at < 14 weeks of gestation were drawn to determine serum 25(OH)D levels. GDM diagnosis was made at 24 to 32 weeks of gestation using a standard procedure. Association between serum vitamin D and GDM was tested using binary logistic regression., Results: Nearly all women (90%) had mild (68.3%) or severe (32.2%) vitamin D deficiency (VDD). Non-GDM women with mild VDD had a significantly higher mean vitamin D intake than GDM women with mild VDD (t = 2.04, p < 0.05). Women with higher early pregnancy serum vitamin D levels had a greater risk of GDM. However, this significant association was only identified among those with a family history of type 2 diabetes mellitus (T2DM) and in women with a body mass index indicating overweight or obese status., Conclusions: The high prevalence of VDD in this sample of pregnant women underscores the need for effective preventive public health strategies. Further investigation of this unexpected association between serum vitamin D level and GDM risk in predominantly VDD pregnant women and the potential effects of adiposity and family history of T2DM on that association is warranted., Competing Interests: Conflict of Interest: Yvonne Yee Siang Tee and Jacques Bindels are employees of Danone Specialized Nutrition (Malaysia) and of Nutricia Research Foundation (Netherlands), respectively. Eline van der Beek was employed by Danone Nutricia Research at the time of the study was conducted (former employee). None of the authors had any personal or financial conflict of interest., (©2022 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Lipids are essential for healthy infant growth and development. The structural complexity of lipids in human milk is not present in infant milk formula (IF). A concept IF was developed mimicking more closely the structure and composition of human milk fat globules. The current study evaluates whether a concept IF with large, milk phospholipid-coated lipid droplets (mode diameter 3 to 5 μm) is equivalent to standard IF with regard to growth adequacy and safety in healthy, term Asian infants. In this randomized, double-blind, controlled trial, infants were randomized after parents decided to introduce formula. Infants received a standard IF with (Control) or without the specific prebiotic mixture scGOS/lcFOS (9:1 ratio; Control w/o prebiotics), or a Concept IF with large, milk phospholipid-coated lipid droplets and the prebiotic mixture. A group of 67 breastfed infants served as a reference. As a priori defined, only those infants who were fully intervention formula-fed ≤28 days of age were included in the equivalence analysis (Control n = 29; Control w/o prebiotics n = 28; Concept n = 35, per-protocol population). Primary outcome was daily weight gain during the first four months of life, with the difference between the Concept and Control as the key comparison of interest. Additionally, adverse events, growth and tolerance parameters were evaluated. Equivalence of daily weight gain was demonstrated between the Concept and Control group after additional correction for ethnicity and birthweight (difference in estimated means of 0.1 g/d, 90%CI [-2.30, 2.47]; equivalence margin +/- 3 g/d). No clinically relevant group differences were observed in secondary growth outcomes, tolerance outcomes or number, severity or relatedness of adverse events. This study corroborates that an infant formula with large, milk phospholipid-coated lipid droplets supports adequate growth and is well tolerated and safe for use in healthy infants.

(1) Background: Postpartum weight may increase compared to pre-pregnancy due to weight retention or decrease due to weight loss. Both changes could pose deleterious effects on maternal health and subsequent pregnancy outcomes. Therefore, this study aimed to assess postpartum weight change and its associated factors. (2) Methods: A total of 585 women from the KI lte-Awlaelo T igray E thiopia (KITE) cohort were included in the analysis. (3) Results: The mean pre-pregnancy body mass index and weight gain during pregnancy were 19.7 kg/m 2 and 10.8 kg, respectively. At 18 to 24 months postpartum, the weight change ranged from -3.2 to 5.5 kg (mean = 0.42 kg [SD = 1.5]). In addition, 17.8% of women shifted to normal weight and 5.1% to underweight compared to the pre-pregnancy period. A unit increase in weight during pregnancy was associated with higher weight change (β = 0.56 kg, 95% CI [0.52, 0.60]) and increased probability to achieve normal weight (AOR = 1.65, 95% CI [1.37, 2.00]). Food insecurity (AOR = 5.26, 95% CI [1.68, 16.50]), however, was associated with a shift to underweight postpartum. Interestingly, high symptoms of distress (AOR = 0.13, 95% CI [0.03, 0.48]) also negatively impacted a change in weight category. (4) Conclusions: In low-income settings such as northern Ethiopia, higher weight gain and better mental health during pregnancy may help women achieve a better nutritional status after pregnancy and before a possible subsequent pregnancy.

Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Being born small-for-gestational-age, especially with subsequent catch-up growth, is associated with impaired metabolic health in later-life. We previously showed that a postnatal diet with an adapted lipid droplet structure can ameliorate some of the adverse metabolic consequences in intrauterine growth-restricted (IUGR) rats. The aim of the present work was to explore possible underlying mechanism(s) and potential biomarkers. To this end, serum metabolomics was performed in postnatal day (PN) 42 and PN96 samples of the above-mentioned rat offspring, born after uterine vasculature ligation. Blood samples were collected at PN42, directly after a postnatal dietary intervention with either complex lipid matrix (CLM) or control (CTRL) diet, and at PN96 after a subsequent western-style diet (WSD). Offspring of Non-operated (NOP) dams fed CTRL in early life were included as control group. In the PN42 metabolomics data, 11 co-abundance modules of metabolites were identified, of which four were significantly correlated to adult blood glucose levels at PN96. Further analyses showed that Lysophosphatidylcholine(18:2) (LysoPC(18:2)) levels were reduced by ligation (p < 0.01) and restored in CLM fed animals (p < 0.05). LysoPC(18:2) levels at PN42 correlated inversely with adult blood glucose levels. These data indicate that early-life LysoPC(18:2) blood levels may predict adult blood glucose levels and are affected by a postnatal diet with an adapted lipid droplet structure in IUGR offspring., (© 2021. The Author(s).)

Background and Aims: This study aimed to examine the associations between the total protein intake as well as types and sources of proteins with the gestational diabetes mellitus (GDM) risk. Method and Results: This was a prospective cohort study of the pregnant women in Malaysia. In this study, the total, animal, and plant protein intakes were assessed using a semi-quantitative food frequency questionnaire. Of the 452 women, 48 (10.62%) were diagnosed with GDM. From pre-pregnancy to second trimester, most of the women had 10-20% of energy intake from protein (88.9-90.3%) and ≥75% of recommended protein intake (74.6-86.5%). The women in the highest tertile (T3) of total animal protein intake [adjusted odds ratio (AOR) = 2.76, 95% CI = 1.27-6.04] and red meat protein (AOR = 2.69, 95% CI = 1.27-5.70), specifically in the second trimester, had significantly higher GDM risk compared with the women in the middle tertile of intake (T2). Interestingly, the women in the T3 of egg protein in the second trimester were significantly at lower GDM risk (AOR = 0.43, 95% CI = 0.18-0.91) compared with those in T2. Conclusion: The highest tertile of animal protein (≥42.15 g/day) intake, particularly red meat protein in the second trimester was positively associated with the GDM risk, whereas the highest tertile of egg protein was inversely associated with the GDM risk. Protein intake before or during early pregnancy was not associated with the GDM risk. These findings underscore the importance of sources and types of protein intake, particularly after the first trimester of pregnancy, in relation to GDM risk., Competing Interests: The authors declare that this study received funding from Danone Dumex (Malaysia). The funder had the following involvement in the study: methodology, interpretation of data and review of manuscript., (Copyright © 2021 Yong, Mohd Shariff, Mohd Yusof, Rejali, Tee, Bindels and van der Beek.)

Background: In low-income countries, the high prevalence of pre-pregnancy undernutrition remains a challenge for the future health of women and their offspring. On top of good nutrition, adequate gestational weight gain has been recognized as an essential prerequisite for optimal maternal and child health outcomes. However, good-quality data on factors influencing gestational weight gain is lacking. Therefore, this study was aimed to prospectively identify pre-conception and prenatal factors influencing gestational weight gain in Ethiopia., Methods: A population based prospective study was undertaken between February 2018 and January 2019 in the Tigray region, northern Ethiopia. Firstly, the weight of non-pregnant women of reproductive age living in the study area was measured between August and October 2017. Subsequently, eligible pregnant women identified during the study period were included consecutively and followed until birth. Data were collected through an interviewer-administered questionnaire and anthropometric measurements complemented with secondary data. Gestational weight gain, i.e., the difference between 32 to 36 weeks of gestation and pre-pregnancy weights, was classified as per the Institute of Medicine (IOM) guideline. Linear, spline, and logistic regression models were used to estimate the influence of pre-conception and prenatal factors on gestational weight gain., Results: The mean gestational weight gain (standard deviation[SD]) was 10.6 (2.3) kg. Overall, 64.0% (95% CI 60.9, 67.1) of the women did not achieve adequate weight gain. Factors associated with higher gestational weight gain were higher women empowerment (B 0.60, 95% CI 0.06, 1.14), dietary diversity (B 0.39, 95% CI 0.03, 0.76), pre-pregnancy body mass index (B 0.13, 95% CI 0.05, 0.22), and haemoglobin (B 0.54, 95% CI 0.45, 0.64). Additionally, adequate prenatal care (B 0.58, 95% CI 0.28, 0.88) was associated with higher gestational weight gain., Conclusions: Adequate gestational weight gain was not achieved by most women in the study area, primarily not by those who were underweight before pregnancy. Interventions that advance women's empowerment, dietary quality, pre-pregnancy nutritional status, and prenatal care utilization may improve gestational weight gain and contribute to optimizing maternal and child health outcomes., (© 2021. The Author(s).)

A concept infant formula (IF) was developed with physical properties of lipid droplets mimicking more closely those in human milk. This paper describes the unique design of a randomised controlled trial evaluating the impact of the concept IF on infant growth and body composition development whilst applying a cohort-like recruitment approach that fully supports breastfeeding practices of the study population. Subjects entered the study between birth and 1 months of age, and whenever parents decided to introduce formula were randomised to one of three study formulas; the concept IF comprising large lipid droplets coated by milk phospholipids and containing a specific mixture of prebiotics, a standard IF with the specific prebiotic mixture or a standard IF without the prebiotic mixture. The primary objective was to evaluate the impact of the concept IF on growth and body composition outcomes during the first year of life with a follow-up at 2, 3, 4 and 5 years of age. In addition, stool, saliva and buccal smear samples and parameters assessing safety, gastrointestinal tolerance and cognitive outcomes were collected. The applied cohort-like enrolment approach is distinctly different from standard clinical safety or efficacy studies and may provide valuable insights on trial design for the evaluation of IF while carefully considering breastfeeding practices.

Objective: To assess a broad range of factors associated with pre-pregnancy nutritional status, a key step towards improving maternal and child health outcomes, in Ethiopia., Design: A baseline data analysis of a population-based prospective study., Setting: Kilite-Awlaelo Health and Demographic Surveillance Site, eastern zone of Tigray regional state, northern Ethiopia., Participants: We used weight measurements of all 17 500 women of reproductive age living in the surveillance site between August 2017 and October 2017 as a baseline. Subsequently, 991 women who became pregnant were included consecutively at an average of 14.8 weeks (SD: 1.9 weeks) of gestation between February 2018 and September 2018. Eligible women were married, aged 18 years or older, with a pre-pregnancy weight measurement performed, and a gestational age ≤20 weeks at inclusion., Outcome Measures: The outcome measure was pre-pregnancy nutritional status assessed by body mass index (BMI) and mid-upper arm circumference (MUAC). Undernutrition was defined as BMI of <18.5 kg/m 2 and/or MUAC of <21.0 cm. BMI was calculated using weight measured before pregnancy, and MUAC was measured at inclusion. Linear and spline regressions were used to identify factors associated with pre-pregnancy nutritional status as a continuous and Poisson regression with pre-pregnancy undernutrition as a dichotomous variable., Results: The mean pre-pregnancy BMI and MUAC were 19.7 kg/m 2 (SD: 2.0 kg/m 2 ) and 22.6 cm (SD: 1.9 cm), respectively. Overall, the prevalence of pre-pregnancy undernutrition was 36.2% based on BMI and/or MUAC. Lower age, not being from a model household, lower values of women empowerment score, food insecurity, lower dietary diversity, regular fasting and low agrobiodiversity showed significant associations with lower BMI and/or MUAC., Conclusion: The prevalence of pre-pregnancy undernutrition in our study population was very high. The pre-pregnancy nutritional status could be improved by advancing community awareness on dietary practice and gender equality, empowering females, raising agricultural productivity and strengthening health extension. Such changes require the coordinated efforts of concerned governmental bodies and religious leaders in the Ethiopian setting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The contribution and impact of beverage intake to total nutrient and energy intake may be substantial. Given the link between lifestyle, diet, and the risk of pregnancy complications, this study investigated the association between the quantity and types of beverages with gestational diabetes mellitus (GDM) risk. The study included 452 women from the Seremban Cohort Study (SECOST). The mean energy by beverage intake was 273 ± 23.83 kcal/day (pre-pregnancy), 349 ± 69.46 kcal/day (first trimester) and 361 ± 64.24 kcal/day (second trimester). Women significantly increased intake of maternal milks and malted drinks, but significantly reduced the intake of carbonated drinks and other drinks from before until the second trimester of pregnancy. For chocolate drinks, carbonated drinks, and soy milk, women increased intake from pre-conception to the first trimester, but reduced their intake from the first to the second trimester. While higher intake of cultured-milk drinks was associated with an increased risk of GDM, higher fruit juice intake was associated with a lower risk of GDM. However, these associations were only observed for intake prior to pregnancy and during the first trimester. Further research is needed to corroborate these findings and investigate the contributions of different beverages to overall diet quality as well as adverse health outcomes during pregnancy.

Background & Aim: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula., Methods: Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis., Results: At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups., Conclusions: In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further reductions in protein content., Clinical Trial Registry: This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677., Competing Interests: Conflict of interest The study was funded by Danone Nutricia Research. Marieke Abrahamse-Berkeveld and Bert J.M. van de Heijning are employees of Nutricia Research. Eline M. van der Beek was an employee of Nutricia Research when the study was conducted. They had no role in the execution of the study or in the statistical analyses of the results., (Copyright © 2021. Published by Elsevier Ltd.)

Macrosomia, usually defined as infant birth weight of ≥4000 g, does not consider gestational age, sex, or country/region-specific differences in mean birth weight and maternal body weight. This issue is particularly relevant for Asia, where 60% of the world's population lives, due to variations in maternal size and birth weights across populations. Large for gestational age (LGA), defined as birth weight > 90th centile, is a more sensitive measure as it considers gestational age and sex, though it is dependent on the choice of growth charts. We aimed to review reporting of macrosomia and LGA in Asia. We reviewed the literature on prevalence and risk of macrosomia and LGA in Asia over the last 29 years. Prevalence of macrosomia ranged from 0.5% (India) to 13.9% (China) while prevalence of LGA ranged from 4.3% (Korea) to 22.1% (China), indicating substantial variation in prevalence within and between Asian countries. High pre-pregnancy body mass index, excessive gestational weight gain, and impaired glucose tolerance conferred risk of macrosomia/LGA. Incidence of macrosomia and LGA varies substantially within and between Asian countries, as do the growth charts and definitions. The latter makes it impossible to make comparisons but suggests differences in intrauterine growth between populations. Reporting LGA, using standardized country/regional growth charts, would better capture the incidence of high birth weight and allow for comparison and identification of contributing factors. Better understanding of local drivers of excessive intrauterine growth could enable development of improved strategies for prevention and management of LGA., (© 2021 Japan Society of Obstetrics and Gynecology.)

Feeding mice in early life a diet containing an experimental infant milk formula (Nuturis®; eIMF), with a lipid structure similar to human milk, transiently lowered body weight (BW) and fat mass gain upon Western-style diet later in life, when compared with mice fed diets based on control IMF (cIMF). We tested the hypothesis that early-life eIMF feeding alters the absorption or the postabsorptive trafficking of dietary lipids in later life. Male C57BL/6JOlaHsd mice were fed eIMF/cIMF from postnatal day 16-42, followed by low- (LFD, American Institute of Nutrition (AIN)-93 G, 7 wt% fat) or high-fat diet (HFD, D12451, 24 wt% fat) until day 63-70. Lipid absorption rate and tissue concentrations were determined after intragastric administration of stable isotope (2H or 13C) labelled lipids in separate groups. Lipid enrichments in plasma and tissues were analysed using GC-MS. The rate of triolein absorption was similar between eIMF and cIMF fed LFD: 3·2 (sd 1·8) and 3·9 (sd 2·1) and HFD: 2·6 (sd 1·7) and 3·8 (sd 3·0) % dose/ml per h. Postabsorptive lipid trafficking, that is, concentrations of absorbed lipids in tissues, was similar in the eIMF and cIMF groups after LFD. Tissue levels of absorbed TAG after HFD feeding were lower in heart (-42 %) and liver (-46 %), and higher in muscle (+81 %, all P < 0·05) in eIMF-fed mice. In conclusion, early-life IMF diet affected postabsorptive trafficking of absorbed lipids after HFD, but not LFD. Changes in postabsorptive lipid trafficking could underlie the observed lower BW and body fat accumulation in later life upon a persistent long-term obesogenic challenge.

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses., Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years., Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis., Results: No significant differences were observed in any of the blood parameters between the formula groups ( n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group ( n = 36) ( p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group ( p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group ( p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group ( p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1., Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.

Food insecurity may exacerbate adverse maternal health outcomes during pregnancy, however, this association has not been well established, particularly in the context of developing countries. This study aimed to identify the associations between household food insecurity and gestational diabetes mellitus (GDM) risk among urban pregnant women. Household food insecurity was assessed using the translated 10-item Radimer/Cornell hunger scale. Logistic regression models were used to estimate the associations between food insecurity status and GDM risk. About 35.6% of women experienced food insecurity, with 25.2% reported household food insecurity, 8.0% individual food insecurity, and 2.4% child hunger. Food insecure women were at significantly higher risk of developing GDM compared to food secure women (AOR = 16.65, 95% CI = 6.17-24.98). The significant association between food insecurity and GDM risk was influenced by pre-pregnancy BMI, parity and rate of GWG at second trimester. Food insecure women with parity ≥ 2 (AOR = 4.21, 95% CI = 1.98-8.92), overweight/obese BMI prior to pregnancy (AOR = 12.11, 95% CI = 6.09-24.10) and excessive rate of GWG in the second trimester (AOR = 9.66, 95% CI = 4.27-21.83) were significantly more likely to develop GDM compared to food secure women. Food insecurity showed strong association with GDM risk in that the association was influenced by maternal biological and physical characteristics. Multipronged interventions may be necessary for food insecure pregnant women who are not only at risk of overweight/obesity prior to pregnancy but also may have excessive gestational weight gain, in order to effectively reduce GDM risk.

The worldwide prevalence of overweight and obesity in women of reproductive age is rapidly increasing and a risk factor for the development of gestational diabetes (GDM). Excess adipose tissue reduces insulin sensitivity and may underlie adverse outcomes in both mother and child. The present paper describes the rationale and design of the PRegnancy Outcomes and Maternal Insulin Sensitivity (PROMIS) study, an exploratory cohort study to obtain detailed insights in insulin sensitivity and glucose metabolism during pregnancy and its relation to pregnancy outcomes including early infancy growth. We aim to recruit healthy pregnant women with a body mass index (BMI) ≥ 25 kg/m 2 before 12 weeks of gestation in Northern Netherlands. A total of 130 woman will be checked on fasted (≤7.0 mmol/L) or random (≤11.0 mmol/L) blood glucose to exclude pregestational diabetes at inclusion. Subjects will be followed up to six months after giving birth, with a total of nine contact moments for data collection. Maternal data include postprandial measures following an oral meal tolerance test (MTT), conducted before 16 weeks and repeated around 24 weeks of gestation, followed by a standard oral glucose tolerance test before 28 weeks of gestation. The MTT is again performed around three months postpartum. Blood analysis is done for baseline and postprandial glucose and insulin, baseline lipid profile and several biomarkers of placental function. In addition, specific body circumferences, skinfold measures, and questionnaires about food intake, eating behavior, physical activity, meal test preference, mental health, and pregnancy complications will be obtained. Fetal data include assessment of growth, examined by sonography at week 28 and 32 of gestation. Neonatal and infant data consist of specific body circumferences, skinfolds, and body composition measurements, as well as questionnaires about eating behavior and complications up to 6 months after birth. The design of the PROMIS study will allow for detailed insights in the metabolic changes in the mother and their possible association with fetal and postnatal infant growth and body composition. We anticipate that the data from this cohort women with an elevated risk for the development of GDM may provide new insights to detect metabolic deviations already in early pregnancy. These data could inspire the development of new interventions that may improve the management of maternal, as well as offsrping complications from already early on in pregnancy with the aim to prevent adverse outcomes for mother and child.

Early-life stress (ES) exposure increases the risk of developing obesity. Breastfeeding can markedly decrease this risk, and it is thought that the physical properties of the lipid droplets in human milk contribute to this benefit. A concept infant milk formula (IMF) has been developed that mimics these physical properties of human milk (Nuturis ® , N-IMF). Previously, we have shown that N-IMF reduces, while ES increases, western-style diet (WSD)-induced fat accumulation in mice. Peripheral and central inflammation are considered to be important for obesity development. We therefore set out to test the effects of ES, Nuturis ® and WSD on adipose tissue inflammatory gene expression and microglia in the arcuate nucleus of the hypothalamus. ES was induced in mice by limiting the nesting and bedding material from postnatal day (P) 2 to P9. Mice were fed a standard IMF (S-IMF) or N-IMF from P16 to P42, followed by a standard diet (STD) or WSD until P230. ES modulated adipose tissue inflammatory gene expression early in life, while N-IMF had lasting effects into adulthood. Centrally, ES led to a higher microglia density and more amoeboid microglia at P9. In adulthood, WSD increased the number of amoeboid microglia, and while ES exposure increased microglia coverage, Nuturis ® reduced the numbers of amoeboid microglia upon the WSD challenge. These results highlight the impact of the early environment on central and peripheral inflammatory profiles, which may be key in the vulnerability to develop metabolic derangements later in life.

Introduction: Maternal nutrition during pregnancy is linked with birth outcomes including fetal growth, birth weight, congenital anomalies and long-term health through intra-uterine programming. However, a woman's nutritional status before pregnancy is a strong determinant in early embryo-placental development, and subsequently outcomes for both mother and child. Therefore, the aim of this study was to investigate the association between dietary macronutrient intake in the preconception period with birth weight., Methods: We studied a group of 1698 women from the Dutch Perined-Lifelines linked birth cohort with reliable detailed information on preconception dietary macronutrient intake (using a semi quantitative food frequency questionnaire) and data available on birth weight of the offspring. Birth weight was converted into gestational age adjusted z-scores, and macronutrient intake was adjusted for total energy intake using the nutrient residual method. Preconception BMI was converted into cohort-based quintiles. Multivariable linear regression was performed, adjusted for other macronutrients and covariates., Results: Mean maternal age was 29.5 years (SD 3.9), preconception BMI: 24.7 kg/m2 (SD 4.2) and median daily energy intake was 1812 kcal (IQR 1544-2140). Mean birth weight was 3578 grams (SD 472). When adjusted for covariates, a significant association (adjusted z score [95% CI], P) between polysaccharides and birth weight was shown (0.08 [0.01-0.15], 0.03). When linear regression analyses were performed within cohort-based quintiles of maternal BMI, positive significant associations between total protein, animal protein, fat, total carbohydrates, mono-disaccharides and polysaccharides with birth weight were shown in the lowest quintile of BMI independent of energy intake, intake of other macronutrients and covariates., Conclusion: Out of all macronutrients studied, polysaccharides showed the strongest association with birth weight, independent of energy intake and other covariates. Our study might suggest that specifically in women with low preconception BMI a larger amount of macronutrient intake was associated with increased birth weight. We recommend that any dietary assessment and advise during preconception should be customized to preconception weight status of the women., Competing Interests: Authors EB and FL are (part-time) employees of Danone Nutricia Research, Utrecht, The Netherlands. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To examine the gestational weight gain (GWG) trajectory and its possible association with pregnancy outcomes., Design: GWG trajectories were identified using the latent class growth model. Binary logistic regression was performed to examine the associations between adverse pregnancy outcomes and these trajectories., Setting: Negeri Sembilan, Malaysia., Participants: Two thousand one hundred ninety-three pregnant women., Results: Three GWG trajectories were identified: 'Group 1 - slow initial GWG but followed by drastic GWG', 'Group 2 - maintaining rate of GWG at 0·58 kg/week' and 'Group 3 - maintaining rate of GWG at 0·38 kg/week'. Group 1 had higher risk of postpartum weight retention (PWR) (adjusted OR (AOR) 1·02, 95 % CI 1·01, 1·04), caesarean delivery (AOR 1·03, 95 % CI 1·01, 1·04) and having low birth weight (AOR 1·04, 95 % CI 1·02, 1·05) compared with group 3. Group 2 was at higher risk of PWR (AOR 1·18, 95 % CI 1·16, 1·21), preterm delivery (AOR 1·03, 95 % CI 1·01, 1·05) and caesarean delivery (AOR 1·02, 95 % CI 1·01, 1·03), but at lower risk of having small-for-gestational-age infants (AOR 0·97, 95 % CI 0·96, 0·99) compared with group 3. The significant associations between group 1 and PWR were observed among non-overweight/obese women; between group 1 and caesarean delivery among overweight/obese women; group 2 with preterm delivery and caesarean delivery were only found among overweight/obese women., Conclusions: Higher GWG as well as increasing GWG trajectories was associated with higher risk of adverse pregnancy outcomes. Promoting GWG within the recommended range should be emphasised in antenatal care to prevent the risk of adverse pregnancy outcomes.

Background: Although physical activity (PA) in pregnancy benefits most women, not much is known about pregnancy-related changes in PA and its association with gestational diabetes mellitus (GDM) risk. The aim of this study was to identify the trajectory of PA during pregnancy and possible associations with the risk of GDM., Methods: This was a prospective cohort study of 452 pregnant women recruited from 3 health clinics in a southern state of Peninsular Malaysia. PA levels at the first, second, and third trimester were assessed using the Pregnancy Physical Activity Questionnaire. GDM was diagnosed at 24-28 weeks of gestation following the Ministry of Health Malaysia criteria. Group-based trajectory modeling was used to identify PA trajectories. Three multivariate logistic models were used to estimate the odds of trajectory group membership and GDM., Results: Two distinct PA trajectories were identified: low PA levels in all intensity of PA and sedentary behavior (Group 1: 61.1%, n = 276) and high PA levels in all intensity of PA as well as sedentary behavior (Group 2: 38.9%, n = 176). Moderate and high intensity PA decreased over the course of pregnancy in both groups. Women in group 2 had significantly higher risk of GDM in two of the estimated logistic models. In all models, significant associations between PA trajectories and GDM were only observed among women with excessive gestational weight gain in the second trimester., Conclusions: Women with high sedentary behavior were significantly at higher risk of GDM despite high PA levels by intensity and this association was significant only among women with excessive GWG in the second trimester. Participation in high sedentary behavior may outweigh the benefit of engaging in high PA to mitigate the risk of GDM.

We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). To understand the underlying mechanisms, we now explored parameters possibly involved in this long-term effect. Male C57BL/6JOlaHsd mice, fed rodent diets containing eIMF or cIMF from postnatal (PN) day 16-42, were sacrificed at PN42. Hepatic proteins were measured using targeted proteomics. Lipids were assessed by LC-MS/MS (acylcarnitines) and GC-FID (fatty-acyl chain profiles). Early life growth and body composition, cytokines, and parameters of bile acid metabolism were similar between the groups. Hepatic concentrations of multiple proteins involved in β-oxidation (+ 17%) the TCA cycle (+ 15%) and mitochondrial antioxidative proteins (+ 28%) were significantly higher in eIMF versus cIMF-fed mice (p < 0.05). Hepatic L-carnitine levels, required for fatty acid uptake into the mitochondria, were higher (+ 33%, p < 0.01) in eIMF-fed mice. The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. We speculate that eIMF feeding programs the metabolic handling of dietary lipids.

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (-66%, p<0.001) and upon correction for liver weight (-44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype., Competing Interests: The authors have read the journal’s policy and have the following competing interests: OR received salary and bench fee support via a grant awarded by Danone Nutricia Research. BvdH and EMvdB are employees of Danone Nutricia Research. HJV was a consultant for Danone Nutricia Research outside the submitted work, for which his institution was financially compensated. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.