Participant characteristics in the prevention of gestational diabetes as evidence for precision medicine: a systematic review and meta-analysis.

BACKGROUND: Precision prevention involves using the unique characteristics of a particular group to determine their responses to preventive interventions. This study aimed to systematically evaluate the participant characteristics associated with responses to interventions in gestational diabetes mellitus (GDM) prevention. METHODS: We searched MEDLINE, EMBASE, and Pubmed to identify lifestyle (diet, physical activity, or both), metformin, myoinositol/inositol and probiotics interventions of GDM prevention published up to May 24, 2022. RESULTS: From 10347 studies, 116 studies (n = 40940 women) are included. Physical activity results in greater GDM reduction in participants with a normal body mass index (BMI) at baseline compared to obese BMI (risk ratio, 95% confidence interval: 0.06 [0.03, 0.14] vs 0.68 [0.26, 1.60]). Combined diet and physical activity interventions result in greater GDM reduction in participants without polycystic ovary syndrome (PCOS) than those with PCOS (0.62 [0.47, 0.82] vs 1.12 [0.78-1.61]) and in those without a history of GDM than those with unspecified GDM history (0.62 [0.47, 0.81] vs 0.85 [0.76, 0.95]). Metformin interventions are more effective in participants with PCOS than those with unspecified status (0.38 [0.19, 0.74] vs 0.59 [0.25, 1.43]), or when commenced preconception than during pregnancy (0.21 [0.11, 0.40] vs 1.15 [0.86-1.55]). Parity, history of having a large-for-gestational-age infant or family history of diabetes have no effect on intervention responses. CONCLUSIONS: GDM prevention through metformin or lifestyle differs according to some individual characteristics. Future research should include trials commencing preconception and provide results disaggregated by a priori defined participant characteristics including social and environmental factors, clinical traits, and other novel risk factors to predict GDM prevention through interventions.

An individual's characteristics, such as medical, biochemical, social, and behavioural may affect their response to interventions aimed at preventing gestational diabetes, which occurs during pregnancy. Here, we evaluated the published literature on interventions such as diet, lifestyle, drug treatment and nutritional supplement and looked at which individual participant characteristics were associated with response to these interventions. Certain participant characteristics were associated with greater prevention of gestational diabetes through particular treatments. Some interventions were more effective when started prior to conception. Future studies should consider individual characteristics when assessing the effects of preventative measures.

Iron-Fortified Foods Are Needed To Meet the Estimated Average Requirement for Iron in Australian Infants Aged 6 to 12 Months.

BACKGROUND: Meeting iron intake recommendations is challenging for infants 6-12 mo, especially breastfed infants. Three-quarters of Australian infants 6-12 mo have iron intakes below the estimated average requirement (7 mg), placing them at risk of iron deficiency. After 6 mo, breastmilk is no longer sufficient to meet the increased demand for iron, and iron-rich complementary foods are recommended. Iron-fortified foods may be a means of improving iron intake in infants, particularly those that are breastfed. OBJECTIVES: The aims of the study were as follows: 1) to examine the effect of milk-type and fortified foods on iron intake and the prevalence of inadequacy in infants 6-12 mo; 2) to model the effect of fixed amounts of iron-fortified infant cereal (IFIC) at 6 levels of iron fortification on total iron intake and the prevalence of inadequacy; and 3) to assess the effect IFIC on the intake of other nutrients in the diet. DESIGN: Secondary analysis of cross-sectional dietary intake data of infants 6-12 mo (n = 286) participating in the Australian Feeding Infants and Toddlers Study (OzFITS) 2021. RESULTS: Median (interquartile range) iron intake was 8.9 (7.5, 10.3); 6.3 (4.5, 8.2); and 2.7 (1.5, 4.4) mg/d in formula-fed, combination-fed, and breastfed infants, respectively. The corresponding prevalence of inadequacy was 19%, 67%, and 96%. Infants who consumed fortified foods had higher median iron intakes than those who did not, 6.2 compared with 1.9 mg/d. Dietary modeling showed that consuming 18 g (300 kJ) of IFIC, fortified at 35 mg/100 g dry weight, reduces the prevalence of inadequacy for iron from 75% to 5% for all infants. CONCLUSIONS: Iron intakes are low in Australian infants, especially for breastfed infants in the second half of infancy. Modeling shows that 300 kJ of IFIC, the current manufacturer-recommended serving, fortified at 35 mg/100 g dry weight, added to infant diets would be an effective means to reduce the prevalence of inadequacy for iron.

Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019.

BACKGROUND: Anemia is a common disease which affects around 40% of children and 30% of reproductive age women and can have major health consequences. The present study reports the global, regional and national burden of anemia and its underlying causes between 1990 and 2019, by age, sex and socio-demographic index (SDI). METHODS: Publicly available data on the point prevalence and years lived with disability (YLDs) were retrieved from the global burden of disease (GBD) 2019 study for 204 countries and territories between 1990 and 2019. The point prevalence, YLD counts and rates per 100,000 population were presented, along with their corresponding 95% uncertainty intervals. RESULTS: In 2019, the global age-standardized point prevalence and YLD rates for anemia were 23,176.2 (22,943.5-23,418.6) and 672.4 (447.2-981.5) per 100,000 population, respectively. Moreover, the global age-standardized point prevalence and YLD rate decreased by 13.4% (12.1-14.5%) and 18.8% (16.9-20.8%), respectively, over the period 1990-2019. The highest national point prevalences of anemia were found in Zambia [49327.1 (95% UI: 46,838.5-51,700.1)], Mali [46890.1 (95% UI: 44,301.1-49,389.8)], and Burkina Faso [46117.2 (95% UI: 43,640.7-48,319.2)]. In 2019, the global point prevalence of anemia was highest in the 15-19 and 95+ age groups in females and males, respectively. Also, the burden of anemia was lower in regions with higher socio-economic development. Globally, most of the prevalent cases were attributable to dietary iron deficiency, as well as hemoglobinopathies and hemolytic anemias. CONCLUSIONS: Anemia remains a major health problem, especially among females in less developed countries. The implementation of preventive programs with a focus on improving access to iron supplements, early diagnosis and the treatment of hemoglobinopathies should be taken into consideration.

Do Older Women of Reproductive Age Have Better Diet Quality than Younger Women of Reproductive Age?

There is increasing recognition of the importance of nutrition for reproductive health, but little is known regarding the diet quality of younger vs. older reproductive aged women, and how their intakes relate to dietary recommendations. The purpose of the study was to examine the diets of younger (19-35 years old) compared to older (35-50 years old) reproductive aged women, and how they align with dietary recommendations. Women aged 19-50 years from the 2011-13 Australian National Nutrition and Physical Activity Survey were included (n = 2323). Dietary intakes were assessed by a single 24-h dietary recall and were compared to (i) Australian Dietary Guidelines; (ii) Acceptable Macronutrient Distribution for protein, carbohydrates, and fat; and (iii) Dietary Guideline Index (DGI). Regression analyses comparing younger and older women against recommendations were undertaken, with confounders determined a priori. There was no difference between older and younger women in meeting food group recommendations, with 26% of all women meeting recommendations for fruit, and meat and alternatives, and <20% meeting recommendations for vegetables and alternatives, grains, and dairy. Although there was no difference between older and younger women in total DGI score (mean (SE) 75.6 (1.7) vs. 74.5 (2.5), p > 0.05), older women had higher component scores in limiting saturated fat, consuming low-fat milk, and limiting adding salt during cooking. Continued health promotion for women of reproductive age should be a key priority to improve their own health and that of future generations.

Effect of Selenium and Iodine on Oxidative Stress in the First Trimester Human Placenta Explants.

Imbalanced maternal micronutrient status, poor placentation, and oxidative stress are associated with greater risk of pregnancy complications, which impact mother and offspring health. As selenium, iodine, and copper are essential micronutrients with key roles in antioxidant systems, this study investigated their potential protective effects on placenta against oxidative stress. First trimester human placenta explants were treated with different concentrations of selenium (sodium selenite), iodine (potassium iodide), their combination or copper (copper (II) sulfate). The concentrations represented deficient, physiological, or super physiological levels. Oxidative stress was induced by menadione or antimycin. Placenta explants were collected, fixed, processed, and embedded for laser ablation inductively coupled plasma-mass spectrometry (LA ICP-MS) element imaging or immunohistochemical labelling. LA ICP-MS showed that placenta could uptake selenium and copper from the media. Sodium selenite and potassium iodide reduced DNA damage and apoptosis (p < 0.05). Following oxidative stress induction, a higher concentration of sodium selenite (1.6 µM) was needed to reduce DNA damage and apoptosis while both concentrations of potassium iodide (0.5 and 1 µM) were protective (p < 0.05). A high concentration of copper (40 µM) increased apoptosis and DNA damage but this effect was no longer significant after induction of oxidative stress. Micronutrients supplementation can increase their content within the placenta and an optimal maternal micronutrient level is essential for placenta health.

Maternal folate, one-carbon metabolism and pregnancy outcomes.

Single nucleotide polymorphisms and pre- and peri-conception folic acid (FA) supplementation and dietary data were used to identify one-carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 µg daily FA at 15-week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 µg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L-1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre- and early-pregnancy dietary factors, are independent risk factors for pregnancy complications.

A Review of the Potential Interaction of Selenium and Iodine on Placental and Child Health.

A healthy pregnancy is important for the growth and development of a baby. An adverse pregnancy outcome is associated with increased chronic disease risk for the mother and offspring. An optimal diet both before and during pregnancy is essential to support the health of the mother and offspring. A key mediator of the effect of maternal nutrition factors on pregnancy outcomes is the placenta. Complicated pregnancies are characterized by increased oxidative stress in the placenta. Selenium and iodine are micronutrients that are involved in oxidative stress in placental cells. To date, there has been no comprehensive review investigating the potential synergistic effect of iodine and selenium in the placenta and how maternal deficiencies may be associated with increased oxidative stress and hence adverse pregnancy outcomes. We undertook a hypothesis-generating review on selenium and iodine, to look at how they may relate to pregnancy complications through oxidative stress. We propose how they may work together to impact pregnancy and placental health and explore how deficiencies in these micronutrients during pregnancy may impact the future health of offspring.

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility.

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks' gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99-1.44)) or who had lower selenium concentrations (1.19 (1.01-1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06-2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy.

Association between Maternal Zinc Status, Dietary Zinc Intake and Pregnancy Complications: A Systematic Review.

Adequate zinc stores in the body are extremely important during periods of accelerated growth. However, zinc deficiency is common in developing countries and low maternal circulating zinc concentrations have previously been associated with pregnancy complications. We reviewed current literature assessing circulating zinc and dietary zinc intake during pregnancy and the associations with preeclampsia (PE); spontaneous preterm birth (sPTB); low birthweight (LBW); and gestational diabetes (GDM). Searches of MEDLINE; CINAHL and Scopus databases identified 639 articles and 64 studies were reviewed. In 10 out of 16 studies a difference was reported with respect to circulating zinc between women who gave birth to a LBW infant (≤2500 g) and those who gave birth to an infant of adequate weight (>2500 g), particularly in populations where inadequate zinc intake is prevalent. In 16 of our 33 studies an association was found between hypertensive disorders of pregnancy and circulating zinc; particularly in women with severe PE (blood pressure ≥160/110 mmHg). No association between maternal zinc status and sPTB or GDM was seen; however; direct comparisons between the studies was difficult. Furthermore; only a small number of studies were based on women from populations where there is a high risk of zinc deficiency. Therefore; the link between maternal zinc status and pregnancy success in these populations cannot be established. Future studies should focus on those vulnerable to zinc deficiency and include dietary zinc intake as a measure of zinc status.

In utero Programming of Allergic Susceptibility.

BACKGROUND: Around 30-40% of the world's population will experience allergy, the most common and earliest-onset noncommunicable disease. With a steady rise in the incidence of allergic disease over recent decades, up to 18% of children will suffer a respiratory, food or skin allergy before their 18th birthday. There is compelling evidence that the risk of developing allergy is influenced by early life events and particularly in utero exposures. METHODS: A comprehensive literature review was undertaken which outlines prenatal risk factors and potential mechanisms underlying the development of allergy in childhood. RESULTS: Exposures including maternal cigarette smoking, preterm birth and Caesarean delivery are implicated in predisposing infants to the later development of allergy. In contrast, restricted growth in utero, a healthy maternal diet and a larger family size are protective, but the mechanisms here are unclear and require further investigation. CONCLUSION: To ameliorate the allergy pandemic in young children, we must define prenatal mechanisms that alter the programming of the fetal immune system and also identify specific targets for antenatal interventions.

A review of the impact of dietary intakes in human pregnancy on infant birthweight.

Studies assessing maternal dietary intakes and the relationship with birthweight are inconsistent, thus attempting to draw inferences on the role of maternal nutrition in determining the fetal growth trajectory is difficult. The aim of this review is to provide updated evidence from epidemiological and randomized controlled trials on the impact of dietary and supplemental intakes of omega-3 long-chain polyunsaturated fatty acids, zinc, folate, iron, calcium, and vitamin D, as well as dietary patterns, on infant birthweight. A comprehensive review of the literature was undertaken via the electronic databases Pubmed, Cochrane Library, and Medline. Included articles were those published in English, in scholarly journals, and which provided information about diet and nutrition during pregnancy and infant birthweight. There is insufficient evidence for omega-3 fatty acid supplements' ability to reduce risk of low birthweight (LBW), and more robust evidence from studies supplementing with zinc, calcium, and/or vitamin D needs to be established. Iron supplementation appears to increase birthweight, particularly when there are increases in maternal hemoglobin concentrations in the third trimester. There is limited evidence supporting the use of folic acid supplements to reduce the risk for LBW; however, supplementation may increase birthweight by ~130 g. Consumption of whole foods such as fruit, vegetables, low-fat dairy, and lean meats throughout pregnancy appears beneficial for appropriate birthweight. Intervention studies with an understanding of optimal dietary patterns may provide promising results for both maternal and perinatal health. Outcomes from these studies will help determine what sort of dietary advice could be promoted to women during pregnancy in order to promote the best health for themselves and their baby.

Improving asthma during pregnancy with dietary antioxidants: the current evidence.

The complication of asthma during pregnancy is associated with a number of poor outcomes for the mother and fetus. This may be partially driven by increased oxidative stress induced by the combination of asthma and pregnancy. Asthma is a chronic inflammatory disease of the airways associated with systemic inflammation and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy alone also intensifies oxidative stress through the systemic generation of excess reactive oxidative species (ROS). Antioxidants combat the damaging effects of ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been postulated as potential factors to combat the damaging effects of asthma. In particular, dietary antioxidants may play a role in alleviating the heightened oxidative stress in asthma. Although there are some observational and interventional studies that have shown protective effects of antioxidants in asthma, assessment of antioxidants in pregnancy are limited and there are no antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The aims of this paper are to (i) review the relationships between oxidative stress and dietary antioxidants in adults with asthma and asthma during pregnancy, and (ii) provide the rationale for which dietary management strategies, specifically increased dietary antioxidants, might positively impact maternal asthma outcomes. Improving asthma control through a holistic antioxidant dietary approach might be valuable in reducing asthma exacerbations and improving asthma management during pregnancy, subsequently impacting perinatal health.

Mechanistic examination of walnuts in prevention of breast cancer.

Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and ß-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and ß-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.

Dietary reference intakes for DHA and EPA.

Various organizations worldwide have made dietary recommendations for eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and fish intake that are primarily for coronary disease risk reduction and triglyceride (TG) lowering. Recommendations also have been made for DHA intake for pregnant women, infants, and vegetarians/vegans. A Dietary Reference Intake (DRI), specifically, an Adequate Intake (AI), has been set for alpha-linolenic acid (ALA) by the Institute of Medicine (IOM) of The National Academies. This amount is based on an intake that supports normal growth and neural development and results in no nutrient deficiency. Although there is no DRI for EPA and DHA, the National Academies have recommended that approximately 10% of the Acceptable Macronutrient Distribution Range (AMDR) for ALA can be consumed as EPA and/or DHA. This recommendation represents current mean intake for EPA and DHA in the United States ( approximately 100mg/day), which is much lower than what many groups worldwide are currently recommending. Global recommendations for long-chain omega-3 fatty acids underscore the pressing need to establish DRIs for DHA and EPA because DRIs are recognized as the "official" standard by which federal agencies issue dietary guidance or policy directives for the health and well-being of individuals in the United States and Canada. Because of the many health benefits of DHA and EPA, it is important and timely that the National Academies establish DRIs for the individual long-chain (20 carbons or greater) omega-3 fatty acids.

Use of calcium, folate, and vitamin D3-fortified milk for 6 months improves nutritional status but not bone mass or turnover, in a group of Australian aged care residents.

In residential care, inadequate calcium and folate intakes and low serum vitamin D (25(OH)D) concentrations are common. We assessed whether daily provision of calcium, folate, and vitamin D3-fortified milk for 6 months improved nutritional status (serum micronutrients), bone quality (heel ultrasound), bone turnover markers (parathyroid hormone, C-terminal collagen I telopeptide, terminal propeptide of type I procollagen), and/or muscle strength and mobility in a group of Australian aged care residents. One hundred and seven residents completed the study (mean (SD) age: 79.9 (10.1) years; body weight: 68.4 (15.4) kg). The median (inter-quartile range) volume of fortified milk consumed was 160 (149) ml/day. At the end of the study, the median daily vitamin D intake increased to 10.4 (8.7) µg (P < .001), which is 70% of the adequate intake (15 µg); and calcium density (mg/MJ) was higher over the study period compared with baseline (161 ± 5 mg/MJ vs. 142 ± 4 mg/MJ, P < .001). Serum 25(OH)D concentrations increased by 23 ± 2 nmol/L (83 (107)%, P < .001), yet remained in the insufficient range (mean 45 ± 2 nmol/L). Consumption of greater than the median intake of milk (160 ml/day) (n = 54, 50%) increased serum 25(OH)D levels into the adequate range (53 ± 2 nmol/L) and reduced serum parathyroid hormone by 24% (P = .045). There was no effect on bone quality, bone turnover markers, muscle strength, or mobility. Consumption of fortified milk increased dietary vitamin D intake and raised serum 25(OH)D concentrations, but not to the level thought to reduce fracture risk. If calcium-fortified milk also was used in cooking and milk drinks, this approach could allow residents to achieve a dietary calcium intake close to recommended levels. A vitamin D supplement would be recommended to ensure adequate vitamin D status for all residents.

Flow-mediated dilatation is impaired by a high-saturated fat diet but not by a high-carbohydrate diet.

OBJECTIVE: It is unknown whether a low-fat diet, which may elevate triglycerides and lower high-density lipoprotein (HDL) cholesterol, harms the endothelium. Our aim was to determine whether a low-fat, high-carbohydrate (CARB) diet impaired endothelial vasodilation compared with high saturated fat (SFA), monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) diets. METHODS AND RESULTS: Forty healthy subjects were randomly crossed over to 4, 3-week isocaloric diets high in PUFA, MUFA, or SFA, containing at least 25 g of the relevant fat or a low-fat, CARB, high-glycemic load diet. Flow-mediated dilatation (FMD), fasting blood lipids, high sensitivity C-reactive protein, plasma intercellular, and vascular adhesion molecules plasma E- and P-selectin were measured after each intervention. SFA impaired FMD compared with all other diets (5.41+/-2.45% versus 10.80+/-3.69%; P=0.01). FMD did not change on CARB relative to MUFA or PUFA, despite 23% to 39% rises in triglyceride and 10% to 15% falls in HDL cholesterol. P-selectin was highest after SFA (121+/-52.7 ng/mL) versus MUFA (98+/-44.5 ng/mL; P=0.001) and PUFA (96+/-36.4 ng/mL; P=0.001). CONCLUSIONS: High SFA caused deterioration in FMD compared with high PUFA, MUFA, or CARB diets. Inflammatory responses may also be increased on this diet.