Trimester-Specific Reference Ranges for Saturated, Monounsaturated and Polyunsaturated Fatty Acids in Serum of Pregnant Women: A Cohort Study from the ECLIPSES Group.

In the course of pregnancy, increasing importance is being placed on maintaining optimal fatty acid (FA) levels and particularly n-3 PUFAs to ensure correct fetal development. However, reference ranges for FA have been reported in only a few studies. Our objective is to provide quantitative reference intervals for SFAs, MUFAs, and PUFAs (n-6 and n-3) in a large population of healthy pregnant women from a developed country. A prospective study of pregnant women (n = 479) was conducted from the first trimester (T1) to the third trimester (T3). A total of 11 fatty acids were analyzed in serum by gas chromatography mass spectrometry and were expressed as absolute (µmol/L) and relative (percentage of total FA) concentration units. Serum concentrations of SFAs, MUFAs, n-6 PUFAs, n-3 PUFAs, various FA ratios, and the EFA index were determined. The reference intervals (2.5/97.5 percentiles) in absolute values from T1 ranged from 1884.32 to 8802.81 µmol/L for SFAs, from 959.91 to 2979.46 µmol/L for MUFAs, from 2325.77 to 7735.74 µmol/L for n-6 PUFAs, and from 129.01 to 495.58 µmol/L for n-3 PUFAs. These intervals mainly include the values of other studies from European populations. However, reference ranges vary according to some maternal factors. The FA levels proposed, obtained from a large sample of pregnant women, will be a useful tool for assessing the degree of adequacy of FAs in pregnant women and will help to carry out dietary interventions based on certain maternal factors.

Systematic review and meta-analysis of vitamin D deficiency in different pregnancy on preterm birth: Deficiency in middle pregnancy might be at risk.

BACKGROUND: Current studies suggest that vitamin D deficiency during pregnancy can produce a certain effect for preterm birth (PTB), but there is no research showing whether vitamin D deficiency has a consistent effect in different pregnancies; thus, we conducted a systematic review and meta-analysis of 24 observational studies, grouping them according to the gestational age at the time of serum sampling, to investigate whether vitamin D deficiency in different periods of gestation has different effects on PTB and to provide an evidence-based basis for pregnant women to measure and supplement vitamin D. METHODS: The databases PubMed-Medline, EMBASE, the Cochrane Library, Web of Science, EBSCO, CBM, and CNKI were searched until February 2020. Two researchers independently assessed the eligibility and quality of studies, and STATA 12.0 software was used for meta-analysis. RESULT: Seven cohort studies, 13 case-control studies, and 4 cross-sectional studies were included from 2500 articles by inclusion and exclusion criteria. After adjusting for age, race, and other confounding factors, meta-analysis results showed that vitamin D deficiency in the first trimester, the second trimester, and the third trimester did not increase the risk of PTB (odds ratio (OR) = 1.01, 95% confidence interval (CI) (0.88, 1.16), P = .867; OR = 1.12, 95%CI (0.92, 1.37), P = .249; OR = 1.05, 95%CI (0.87, 1.27), P = .602). However, there was moderate heterogeneity in the study of vitamin D deficiency in the second trimester, and subgroup analysis suggested that vitamin D deficiency in the second trimester may increase the risk of PTB (OR = 1.33, 95%CI (1.15, 1.54), P = .000). A sensitivity analysis of the second trimester showed that excluding any 1 study did not significantly change the results. CONCLUSIONS: Vitamin D deficiency in early and late pregnancy may not be associated with PTB, while vitamin D deficiency in middle pregnancy is likely to have an important effect on PTB. Vitamin D levels should be measured in the second trimester of pregnancy, and vitamin D supplements should be provided if necessary.

Maternal selenium status plays a crucial role on clinical outcomes of pregnant women with COVID-19 infection.

Adequate maternal selenium level is essential for immune response and healthy pregnancy. This study aimed to shed light on the selenium status of pregnant women with COVID-19 and the effects of potential deficiency in serum selenium levels. Totally 141 pregnant women, 71 of them were COVID-19 patients, in different trimesters were included in the study. Maternal serum selenium levels, demographic and clinical parameters were determined. Serum selenium levels of pregnant women in the second (p: .0003) and third (p: .001) trimesters with COVID-19 were significantly lower than in the healthy group. Maternal selenium level was found to be negatively correlated with gestational week (p < .0001, r: -.541), D-dimer (p: .0002, r: -.363) and interleukin-6 (IL-6) level (p: .02, r: -.243). In the second trimester, serum selenium level positively correlated with white blood cell (p: .002, r: .424), neutrophil (p: .006, r: .39), lymphocyte (p: .004, r: .410) count and hemoglobin (p: .02, r: .323), hematocrit (p: .008, r: .38) status. In the third trimester, it was found that maternal selenium level positively correlated with monocyte (p: .04, r: .353) and negatively correlated with C-reactive protein level (p: .03, r: -.384). Serum selenium level was gradually decreased during the pregnancy period, however, this natural decrease was enhanced together with COVID-19 infection. The reason might be increased selenium needs depended on the immune response against infection. The decrease in maternal selenium level was found to be related to IL-6 and D-dimer levels, which indicate selenium's role in disease progression.

Complex patterns of circulating fatty acid levels in gestational diabetes mellitus subclasses across pregnancy.

BACKGROUND & AIMS: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. METHODS: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). CONCLUSIONS: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

Long-Chain Polyunsaturated Fatty Acid Concentrations and Association with Weight Gain in Pregnancy.

Lower concentrations of omega-3 (ω-3) and higher concentrations of omega-6 (ω-6) have been associated with excess weight in adults; however, the information on this relationship in pregnancy remains in its infancy. This study aimed to investigate the association between plasma levels of ω-3 and ω-6 long-chain polyunsaturated fatty acids (PUFAs) and weight gain during the gestational period. This is a prospective cohort study involving 185 pregnant women registered with the prenatal services of a municipality in the northeast of Brazil. The dosage of the serum concentration of fatty acids and the anthropometric measurements were carried out at the baseline, and the women's weight information in the first, second, and third trimesters was collected from their pregnancy cards. Serum fatty acids were determined with the help of gas chromatography. The response variable of this study is the latent variable weight gain in pregnancy, derived from three variables: gestational weight in the first, second, and third trimesters. The main exposure was the plasma concentrations of PUFAs. Structural equation modeling was used for the data analysis. The mean age of the pregnant women was 26.74 years old (SD: 5.96 years). Most of the women had not completed high school (84%) and had a low income (70.86%). It was observed that the ω-3 PUFAs, represented by ALA plasm (alpha-linolenic acid), DHA (docosahexaenoic acid), and the EPA/ALA ratio (eicosapentaenoic acid to alpha-linolenic acid ratio), were negatively associated with the weight gain during pregnancy construct (-0.20, -0.12, and -0.14, respectively). Meanwhile, the PUFAs represented by the ratio between the ω-6 category acids ARA and LA (arachidonic acid and linoleic acid) had a direct and positive association (0.22) with that construct. Excess maternal weight gain was associated with ω-3 and ω-6 plasma levels. The women with the greatest gestational weight gain were the ones that presented the highest ARA/LA ratio (ω-6) and the lowest plasma concentrations of ALA, DHA, and EPA/ALA ratio (ω-3).

Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy.

BACKGROUND: For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations. METHODS: Pregnant women enrolled at 10-14 weeks gestation were randomized to 400 or 4400 IU vitamin D3/day. Data on health, safety, circulating 25(OH)D, and 9 immune-mediators were collected at each trimester. Associations between immune-mediators and 25(OH)D at baseline and at second and third trimesters were examined. RESULTS: Baseline TGF-ß and second and third trimesters IFN-γ and IL-2 were associated with baseline 25(OH)D. Baseline immune-mediators were associated with immune-mediators at second and third trimesters for all immune-mediators except IL-5 and IL-10. Race was associated with baseline TGF-ß, VEGF and IL-10 and with IL-10 at second and third trimesters. CONCLUSIONS: Both treatment groups had increased 25(OH)D at second and third trimesters, greatest in the 4400 IU group. Though associations between baseline 25(OH)D and baseline TGF-ß and second and third trimester IFN-γ and IL-2 were noted, vitamin D supplementation throughout pregnancy did not impact immune-mediators at later trimesters. Supplementing with vitamin D before conception conceivably influences immune-mediator responses during pregnancy. IMPACT: In this vitamin D supplementation clinical trial, baseline (first trimester) but not increasing plasma 25(OH)D concentration impacted select plasma immune-mediator profiles in pregnant women. Baseline 25(OH)D was associated with baseline TGF-ß and with IFN-γ and IL-2 at second and third trimesters. Baseline IFN-γ, CRP, TGF-ß, TNF-α, VEGF, IL-2, and IL-4 were associated with concentrations at second and third trimesters for respective immune-mediators; however, 25(OH)D concentration at second and third trimesters were not. Some racial differences existed in immune-mediator concentrations at baseline and at second and third trimesters. This study assesses the impact of vitamin D supplementation on multiple immune-mediators in pregnant women of different racial/ethnic groups using longitudinal data from a relatively large randomized controlled trial. This study found that race was associated with baseline TGF-ß, VEGF, and IL-10 and with IL-10 at second and third trimesters, a novel finding that sheds light where relationships were less well defined. The results of this study suggest that vitamin D supplementation before conception or early in pregnancy, rather than during pregnancy, may be necessary to significantly impact immune-mediator response. This study sets premise for future clinical trials to evaluate the effect of vitamin D supplementation before conception or prior to pregnancy.

Effects of iodine supplementation during pregnancy on pregnant women and their offspring: a systematic review and meta-analysis of trials over the past 3 decades.

OBJECTIVE: The current systematic review aimed to provide comprehensive data on the effects of iodine supplementation in pregnancy and investigate its potential benefits on infant growth parameters and neurocognitive development using meta-analysis. METHODS: A systematic review was conducted on trials published from January 1989 to December 2019 by searching MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar. For most maternal and neonatal outcomes, a narrative synthesis of the data was performed. For birth anthropometric measurements and infant neurocognitive outcomes, the pooled standardized mean differences (SMDs) with 95% CIs were estimated using fixed/random effect models. RESULTS: Fourteen trials were eligible for inclusion in the systematic review, of which five trials were included in the meta-analysis. Although the findings of different thyroid parameters are inconclusive, more consistent evidence showed that iodine supplementation could prevent the increase in thyroglobulin concentration during pregnancy. In the meta-analysis, no differences were found in weight (-0.11 (95% CI: -0.23 to 0.01)), length (-0.06 (95% CI: -0.21 to 0.09)), and head circumference (0.26 (95% CI: -0.35 to 0.88)) at birth, or in cognitive (0.07 (95% CI: -0.07 to 0.20)), language (0.06 (95% CI: -0.22 to 0.35)), and motor (0.07 (95% CI: -0.06 to 0.21)) development during the first 2 years of life in infants between the iodine-supplemented and control groups. CONCLUSION: Iodine supplementation during pregnancy can improve the iodine status in pregnant women and their offspring; however, according to our meta-analysis, there was no evidence of improved growth or neurodevelopmental outcomes in infants of iodine-supplemented mothers.

Early-Life Effects of Vitamin D: A Focus on Pregnancy and Lactation.

Vitamin D is an endocrine regulator of calcium and bone metabolism. Yet, its effects include other systems, such as innate and adaptive immunity. Unique to pregnancy, circulating 1,25-dihydroxyvitamin D (1,25[OH]2D) increases early on to concentrations that are 2-3 times prepregnant values. At no other time during the lifecycle is the conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D directly related and optimized at ≥100 nmol/L. Vitamin D deficiency appears to affect pregnancy outcomes, yet randomized controlled trials of vitamin D supplementation achieve mixed results depending on when supplementation is initiated during pregnancy, the dose and dosing interval, and the degree of deficiency at the onset of pregnancy. Analysis of trials on an intention-to-treat basis as opposed to the use of 25(OH)D as the intermediary biomarker of vitamin D metabolism yields differing results, with treatment effects often noted only in the most deficient women. Immediately after delivery, maternal circulating 1,25(OH)2D concentrations return to prepregnancy baseline, at a time when a breastfeeding woman has increased demands of calcium, beyond what was needed during the last trimester of pregnancy, making one question why 1,25(OH)2D increases so significantly during pregnancy. Is it to serve as an immune modulator? The vitamin D content of mother's milk is directly related to maternal vitamin D status, and if a woman was deficient during pregnancy, her milk will be deficient unless she is taking higher doses of vitamin D. Because of this relative "deficiency," there is a recommendation that all breastfed infants receive 400 IU vitamin D3/day starting a few days after birth. The alternative - maternal supplementation with 6,400 IU vitamin D3/day, effective in safely raising maternal circulating vitamin D, that of her breast milk, and effective in achieving sufficiency in her recipient breastfeeding infant - remains a viable option. Additional research is needed to understand vitamin D's influence on pregnancy health and the effect of maternal supplementation on breast milk's immune signaling.

Multiple Micronutrients and Docosahexaenoic Acid Supplementation during Pregnancy: A Randomized Controlled Study.

Maternal dietary intake during pregnancy needs to meet increased nutritional demands to maintain metabolism and to support fetal development. Docosahexaenoic acid (DHA) is essential for fetal neuro-/visual development and in immunomodulation, accumulating rapidly within the developing brain and central nervous system. Levels available to the fetus are governed by the maternal diet. In this multicenter, parallel, randomized controlled trial, we evaluated once-daily supplementation with multiple micronutrients and DHA (i.e., multiple micronutrient supplementation, MMS) on maternal biomarkers and infant anthropometric parameters during the second and third trimesters of pregnancy compared with no supplementation. Primary efficacy endpoint: change in maternal red blood cell (RBC) DHA (wt% total fatty acids) during the study. Secondary variables: other biomarkers of fatty acid and oxidative status, vitamin D, and infant anthropometric parameters at delivery. Supplementation significantly increased RBC DHA levels, the omega-3 index, and vitamin D levels. Subscapular skinfold thickness was significantly greater with MMS in infants. Safety outcomes were comparable between groups. This first randomized controlled trial of supplementation with multiple micronutrients and DHA in pregnant women indicated that MMS significantly improved maternal DHA and vitamin D status in an industrialized setting-an important finding considering the essential roles of DHA and vitamin D.

Association of gestational weight gain rate with infant anaemia in China: a birth cohort study.

Excessive gestational weight gain (GWG) increases the risk of maternal anaemia during pregnancy, but whether it is associated with offspring anaemia has not been investigated. We aimed to prospectively investigate the association of GWG rate in the second/third trimester with infant Hb concentration and anaemia risk. The present study comprised 13 765 infants born during 2006-2009 to mothers who participated in a trial on prenatal micronutrient supplementation. The GWG was calculated by subtracting the maternal weight at enrolment from that at end-pregnancy. The GWG rate was calculated as dividing the GWG by number of weeks between the two measurements and classified into quintiles within each category of maternal BMI. Infant Hb concentrations were measured at 6 and 12 months of age, and anaemia was defined as an Hb concentration <110 g/l. Of the 13 765 infants, 949 (6·9 %) were anaemic at 6 months and 728 (5·3 %) at 12 months. The GWG rate was inversely and linearly associated with the infant Hb concentrations at both 6 and 12 months (P < 0·001 for linearity). Compared with the middle quintile of GWG rate, the highest quintile was associated with an increased risk of anaemia at 6 months (adjusted OR 1·30, 95 % CI 1·07, 1·59) and 12 months (adjusted OR 1·74, 95 % CI 1·40, 2·17). The associations were consistently mediated by maternal anaemia during pregnancy (P < 0·001). In conclusion, excessive GWG rate appears to be associated with an increased risk of infant anaemia, partly independent of maternal anaemia during pregnancy that mediates the association.

Maternal Dietary Intakes, Red Blood Cell Indices and Risk for Anemia in the First, Second and Third Trimesters of Pregnancy and at Predelivery.

As anemia remains a major public health problem in Ghana, we examined the effect of dietary intakes, and antenatal care (ANC) practices on red cell indices and anemia prevalence during the pregnancy continuum for 415 women. Dietary history was taken using the Food and Agriculture Organization minimum dietary diversity indicator for women (MDD-W). Intake of ≥5 food groups was a proxy for micronutrient adequacy. Odds for anemia and meeting the MDD-W were estimated using ordinal and binary logistic regressions respectively. Intakes of 41.4% were micronutrient inadequate. At any time point in pregnancy, 54.4% were anemic (mild = 31.1%; moderate = 23.1%; severe = 0.2%) with 10%-point variation across the first (57.3%), second (56.4%) and third (53.3%) trimesters and pre-delivery (47.7%); 27.8% were anemic throughout pregnancy while 17.1% were never anemic. Morphologically, microcytic (79.4%) and hypochromic (29.3%) anemia were most prevalent, indicating nutritional deficiencies. Planning the pregnancy was a significant determinant for meeting the MDD-W. Overall, adolescence, poor diet, suboptimum ANC and underweight were associated with moderate and severe anemia. In specific time-points, dietary counselling, malaria, iron-folic acid supplementation, sickle cell disease and preeclampsia were observed. Decline of anemia during pregnancy suggests the positive impact of ANC services and supports strengthening education on dietary diversification during ANC.

Diagnosis, treatment, and management of gestational hypothyroidism. The TIROGEST study.

INTRODUCTION: There is no agreement on the procedures to be used for diagnosis and treatment of gestational thyroid dysfunction. Controversy still exists on the normal range of thyroid-stimulating hormone (TSH) levels and use of gestational hypothyroidism (GH) screening. The aim of this study was to assess diagnosis and treatment of thyroid dysfunction during pregnancy in a group of Spanish hospitals. STUDY DESIGN: This was a retrospective, multicenter study in pregnant females with GH attending Spanish healthcare centers from March 2013 to July 2014. Variables analyzed included diagnosis criteria for GH (availability of universal screening for gestational thyroid disorders and TSH reference values (RVs) by trimester of pregnancy): risk factors for GH, iodine intake from food or supplementation, gestational age (at diagnosis/treatment) and l-thyroxine treatment. RESULTS: Fourteen centers participated in the study. Universal screening was performed in only half of the centers, and only 14% had their own TSH RVs. Overall, 257 pregnant women were enrolled, 53.7% with hypothyroidism (HT) diagnosed before pregnancy (pre-GH) and 46.3% with HT diagnosed during pregnancy (intra-GH). A comparison of intra-GH and pre-GH women showed that intra-GH women made their first visit later (59.7% vs. 75.4% respectively before week 12, p=0.007) and had more frequently high TSH levels (>2.5µIU/ml) during the first trimester (94.4% vs. 67.0% respectively, p<0.001). CONCLUSIONS: Our results suggest that GH may be underdiagnosed or inadequately diagnosed in most healthcare centers. These findings suggest the need of improving the current practice in Spain.

Food-basket intervention to reduce micronutrient deficiencies among Maasai-pregnant women in Tanzania: a quasi-experimental study.

BACKGROUND: Micronutrients comprised of vitamin and mineral nutrients that are needed during pregnancy for foetal growth, development and maturation, as well as for reducing/preventing maternal complications. However, micronutrient-rich foods (vegetables and fruits) are lacking in the Ngorongoro Conservation Area as a result of restrictions on cultivation in conservation areas and the unavailability of vegetables and fruits in local markets. The present study introduced a food basket intervention and assessed the effectiveness of the food baskets with respect to addressing anaemia, vitamin A and iron deficiencies among pregnant Maasai women within the Ngorongoro Conservation Area. METHODS: The quasi-experimental study included Misigiyo ward as a control group (provided education only) and Olbalbal ward as an intervention group (provided food baskets and education). The study assessed haemoglobin, serum ferritin and retinol at baseline and during follow-up. Haemoglobin, serum ferritin and retinol were quantitatively (duplicate) measured with HemoCue™ (HemoCue AB, Ängelholm, Sweden), Maglumi 800 (Snibe Diagnostic, Shenzhen, China) and vitamin A enzyme-linked immunosorbent assay, respectively. Dependent and independent t-tests were used to compare the micronutrient blood levels between and within the groups. RESULTS: The present study found a statistically significant increase in serum retinol (P < 0.001) in the intervention group compared to the control group; moreover, baseline serum retinol was positively associated with the follow-up serum retinol, whereas baseline haemoglobin and serum ferritin were negatively associated. CONCLUSIONS: The food basket intervention holds promise with repect to reducing micronutrient deficiency, especially in communities where micronutrient-rich foods are scarce.

[Effects of vitamin D supplementation in early pregnancy on high-risk groups of gestational diabetes mellitus].

OBJECTIVE: To investigate the effect of vitamin D supplementation(VD) in early pregnancy on the serum 25-hydroxyvitamin D(25-OH-D) level and the risk of gestational diabetes mellitus(GDM). METHODS: From October to December 2017, a total of 101 pregnant women with high risk factors for GDM were enrolled in the first pregnancy consultation at the nutrition clinic of Haidian Maternal and Child Health Hospital, and were randomly divided into intervention group and control group. The intervention group was supplemented with 700 U VD and 100 mg of calcium at the beginning of pregnancy, and the control group was supplemented with 100 U VD and 100 mg of calcium at the same time, and the intervention time was until delivery. RESULTS: After intervention, the mean serum 25-OH-D level in the intervention group was(92. 08±29. 69) nmol/L, and that in the control group was(69. 99±25. 10) nmol/L. The serum levels of 25-OH-D in the pregnant women, gestational age and cord blood were higher than those in the control group(P<0. 05). The incidence of GDM in the intervention group was 18. 37%, and the incidence rate in the control group was 28. 85%(P>0. 05). Compared with the control group, the OR value of the risk of GDM in the intervention group was 0. 56(95% CI 0. 22-1. 42)( P<0. 05). CONCLUSION: The supplementation of VD in early pregnancy can significantly improve the VD nutrition level of pregnant women, but does not significantly reduce the incidence of GDM.

Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian women.

BACKGROUND: In winter in Mongolia, 80% of adults have 25-hydroxyvitamin D (25(OH)D) concentrations <25 nmol/l (<10 ng/ml) and 99% have <50 nmol/l (<20 ng/ml). The vitamin D dose to avert deficiency during pregnancy in this population is unknown. METHODS: We conducted a randomized, controlled, double-blind trial of daily 600, 2000, or 4000 IU vitamin D3 for pregnant women in Mongolia (Clinicaltrials.gov #NCT02395081). We examined 25(OH)D concentrations at baseline (12-16 weeks' gestation), 36-40 weeks' gestation and in umbilical cord blood, using enzyme linked fluorescent assay. Sample size was determined to detect 0.4 standard deviation differences in 25(OH)D concentrations with 80% power. FINDINGS: 119 pregnant women were assigned 600 IU, 121 assigned 2000 IU and 120 assigned 4000 IU from February 2015 through December 2016. Eighty-eight percent of participants took ≥80% of assigned supplements. At baseline, 25(OH)D concentrations were similar across arms; overall mean ±â€¯standard deviation concentration was 19 ±â€¯22 nmol/l; 91% were < 50 nmol/l. At 36-40 weeks, 25(OH)D concentrations increased to 46 ±â€¯21, 70 ±â€¯23, and 81 ±â€¯29 nmol/l for women assigned 600, 2000, and 4000 IU, respectively (p < 0.0001 across arms; p = 0.002 for 2000 vs. 4000 IU). Mean umbilical cord 25(OH)D concentrations differed by study arm (p < 0.0001 across arms; p < 0.0001 for 2000 vs. 4000 IU) and were proportional to maternal concentrations. There were no adverse events, including hypercalcemia, attributable to vitamin D supplementation. INTERPRETATION: Daily supplementation of 4000 IU during pregnancy is safe and achieved higher maternal and neonatal 25(OH)D concentrations than 2000 IU. Daily 600 IU supplements are insufficient to prevent vitamin D deficiency in Mongolia. FUND: Anonymous foundation and Brigham and Women's Hospital.

Vitamin D and gestational diabetes mellitus: a systematic review based on data free of Hawthorne effect.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasingly prevalent disorder, associated with low blood vitamin D level. OBJECTIVES: To evaluate the relationship between vitamin D and GDM. SEARCH STRATEGY: EMBASE, MEDLINE, Cochrane Library and China Biology Medicine disc were searched up to May 2017. The references of previous studies were screened. SELECTION CRITERIA: Observational studies on the relationship between vitamin D and GDM free from Hawthorne effect and randomised controlled trials of vitamin D supplementation during pregnancy for preventing or treating GDM were included. DATA COLLECTION AND ANALYSIS: Data and information of included articles were extracted by duplicate using piloted tables. Newcastle-Ottawa Scale and Cochrane Handbook were used for quality assessment. Random-effects models were used for meta-analyses. Heterogeneity tests, sensitivity analysis and analysis of publication bias were conducted. MAIN RESULTS: Eighty-seven observational studies and 25 randomised controlled trials involving 55 859 and 2445 women, respectively, were included. Low blood vitamin D level during pregnancy was associated with a higher risk of GDM (OR 1.850, 95% CI 1.471-2.328). Blood vitamin D level for women with GDM were lower than in the control women. Blood vitamin D level was associated with fasting plasma glucose (FPG) and homeostasis model of assessment for insulin resistance index (HOMA-IR) (r = -0.100 and r = -0.351), whereas the correlation between blood vitamin D level and fasting insulin (FINS) might be concealed by publication bias. Vitamin D intervention during pregnancy could change the blood levels of vitamin D, FINS, FPG, HOMA-IR, glutathione, C-reactive protein and lipid. CONCLUSIONS: Low blood vitamin D level could increase the risk of GDM, and vitamin D supplementation during pregnancy could ameliorate the condition of GDM. TWEETABLE ABSTRACT: Low blood vitamin D increases gestational diabetes mellitus (GDM) risk. Vitamin D supplementation ameliorates GDM condition.

Maternal serum vitamin D and parathormone concentrations during gestation and in umbilical cord blood - pilot study.

OBJECTIVE: We wanted to define levels of vitamin D (25(OH)D), parathormone (PTH), calcium (Ca), phosphorus (P) and the correlations between them during gestation as well as in umbilical cord blood. METHODS: The study included 37 healthy singleton pregnant women in the course of gestation with no medical history concerning systemic diseases, nor with negative obstetrics and gynecological history. Biochemical parameters were determined using commercially available kits. RESULTS: In the studied group, there were no significant differences in serum vitamin D, PTH, Ca and P concentrations in each trimester and during delivery. The negative significant association between serum 25(OH)D and PTH level was observed (r=-0.25; p< 0.05). Vitamin D levels during the summer season were significantly higher than observed in winter time in I (p< 0.01) and II trimester (p< 0.05), but not in III trimester. There was positive correlation between maternal serum and cord blood 25(OH)D (r= 0.74; p < 0.01). It was noted that 38-48% mothers had severe deficiency of vitamin D. CONCLUSION: The study showed that regardless of the supplementation only 11-21% of studied pregnant women had optimal levels of vitamin D. The association between maternal and cord blood 25(OH)D suggested that inadequate vitamin D stores- during pregnancy may lead to a deficiency of this vitamin in newborns.

Severe selenium deficits in pregnant women irrespective of autoimmune thyroid disease in an area with marginal selenium intake.

OBJECTIVES: Selenium (Se) deficiency is related to an increased risk of preterm labor, miscarriage, preeclampsia, gestational diabetes, and other obstetric complications. As the Se status declines during pregnancy, we hypothesized that the decline may be exacerbated in women with autoimmune thyroid disease (AITD). MATERIAL AND METHODS: Pregnant women (n=74; 30 [23-38] years) were consecutively recruited from the district of Warsaw, Poland, and divided into healthy subjects (HS, n=45), and women with a diagnosis of AITD (AITD, n=29). Thyroglobulin antibodies (TG-aAb), thyroid peroxidase antibodies (TPO-aAb), TSH, free T3, free T4, total T3, and total T4, as well as urine iodine excretion were determined. Se status was assessed by serum Se and selenoprotein P (SELENOP) concentrations. Thyroid volume was evaluated by ultrasonography. RESULTS: Serum Se and SELENOP concentrations were relatively low in both control and AITD women. A Se deficit according to WHO definition (<45µg/l) was observed in 0%, 3.4%, 28.6% and 4.5%, 18.2%, 35.5% of women in the AITD and HS group, respectively, during the 1st, 2nd, and 3rd trimester. From first to third trimester, TPO-aAb and TG-aAb declined in AITD by 71% and 60%, respectively. The decline in TPO- and TG-aAb was unrelated to the Se status. CONCLUSIONS: In this area of habitual low Se intake, a high proportion of women developed a severe Se deficit during pregnancy, irrespective of AITD status. This decline must be considered as a preventable risk factor for pregnancy complications of relevance to both the unborn child and the pregnant mother.

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

BACKGROUND: Exposures during the prenatal period may have lasting effects on maternal and child health outcomes. To better understand the effects of the in utero environment on children's short- and long-term health, large representative pregnancy cohorts with comprehensive information on a broad range of environmental influences (including biological and behavioral) and the ability to link to prenatal, child and maternal health outcomes are needed. The Research Program on Genes, Environment and Health (RPGEH) pregnancy cohort at Kaiser Permanente Northern California (KPNC) was established to create a resource for conducting research to better understand factors influencing women's and children's health. Recruitment is integrated into routine clinical prenatal care at KPNC, an integrated health care delivery system. We detail the study design, data collection, and methodologies for establishing this cohort. We also describe the baseline characteristics and the cohort's representativeness of the underlying pregnant population in KPNC. METHODS: While recruitment is ongoing, as of October 2014, the RPGEH pregnancy cohort included 16,977 pregnancies (53 % from racial and ethnic minorities). RPGEH pregnancy cohort participants consented to have blood samples obtained in the first trimester (mean gestational age 9.1 weeks ± 4.2 SD) and second trimester (mean gestational age 18.1 weeks ± 5.5 SD) to be stored for future use. Women were invited to complete a questionnaire on health history and lifestyle. Information on women's clinical and health assessments before, during and after pregnancy and women and children's health outcomes are available in the health system's electronic health records, which also allows long-term follow-up. DISCUSSION: This large, racially- and ethnically-diverse cohort of pregnancies with prenatal biospecimens and clinical data is a valuable resource for future studies on in utero environmental exposures and maternal and child perinatal and long term health outcomes. The baseline characteristics of RPGEH Pregnancy Cohort demonstrate that it is highly representative of the underlying population living in the broader community in Northern California.

A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women.

This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4-40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 µg/L (interquartile range, IQR 0.29-0.53), copper: 165.0 µg/dL (IQR 144.0-187.0), zinc: 57.0 µg/dL (IQR 50.0-64.0), and selenium: 94.0 µg/L (IQR 87.0-101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower (p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters (p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper (p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia.