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1.
Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women.
Ganz, AB, Park, H, Malysheva, OV, Caudill, MA
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018;(4):2012-2020
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Abstract
Research has identified reduced circulating 25-hydroxyvitamin D [25(OH)D] in individuals with the rs7041 (c.1296T>G) T allele in the vitamin D binding protein gene ( GC); however, the effects of the T allele on vitamin D biomarkers during pregnancy and lactation are unknown. Thus, we examined the metabolic effects of GC rs7041 on vitamin D biomarkers among third-trimester pregnant ( n = 26), lactating ( n = 28), and nonpregnant/nonlactating ( n = 21) women consuming a single amount of vitamin D (511 IU/d) and related nutrients for 10-12 wk. T allele carriers had less circulating 25(OH)D, regardless of reproductive state [thymine-thymine (TT): 80% of guanine-guanine (GG), P = 0.05; guanine-thymine (GT): 85% of GG, P = 0.1]. Among pregnant women, the T allele attenuated the expected increase in vitamin D binding protein (DBP). Specifically, although GG pregnant women exhibited greater DBP (216%, P < 0.0001) than did GG nonpregnant women, that difference was lessened among GT women, and TT pregnant women did not exhibit greater DBP than TT nonpregnant women. Furthermore, TT pregnant women had greater placental 25(OH)D3 to 24,25-dihydroxyvitamin D ratios (251% of GG, P = 0.07) and less osteocalcin, a bone formation marker, in the cord blood of their neonates (24% of GT, P = 0.02). Overall, the GC rs7041 genotype modified the effects of pregnancy on maternal and placental vitamin D metabolism, with possible functional consequences for fetal bone development and infant health.-Ganz, A. B., Park, H., Malysheva, O. V., Caudill, M. A. Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women.
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New perspectives on placental fatty acid transfer.
Lewis, RM, Childs, CE, Calder, PC
Prostaglandins, leukotrienes, and essential fatty acids. 2018;:24-29
Abstract
The human foetus depends on placental transfer for the fatty acids required for its growth and development. Long chain polyunsaturated fatty acids (LC-PUFAs) may specifically influence neurodevelopment. Therefore, it is important to understand the mechanisms of placental transfer of LC-PUFAs. The simple view of placental fatty acid transfer is that it occurs by diffusion down the maternal to foetal gradient, facilitated by membrane transporters. This view has been complicated by studies highlighting the role of placental metabolism in fatty acid transfer. Most fatty acids taken up by the placenta will be esterified and incorporated into lipid rather than diffusing directly across to the foetus. Furthermore, this esterification is likely to mean that placental intracellular "free" fatty acid concentrations are lower than in foetal plasma which would not be conducive to simple diffusion of fatty acids to the foetus. Placental structure poses additional questions, in particular how fatty acids cross the hydrophilic villous stroma separating the trophoblast from the endothelium and how they cross the endothelium itself. The understanding of placental fatty acid transfer needs to evolve to address these questions. The role of the placenta is not simply to mediate solute transfer; it is also a central endocrine organ of pregnancy. Placental-derived lipid mediators, such as prostaglandins, have well-established roles in parturition and, almost certainly, throughout gestation. Metabolic targeting of specific fatty acids to different lipid pools in the placenta may determine their availability as both nutrients and signalling molecules. Placental transfer will determine fatty acid availability within the foetus as well as influencing maternal levels. Fatty acids and their derivatives may also act as signals to the placenta indicating metabolic states in both mother and foetus. Placental uptake and metabolism of LC-PUFAs are important to meet both foetal and placental demands. This paper will review placental fatty acid transfer and metabolism and highlight issues which need to be addressed.
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3.
Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association.
Sharif, K, Sharif, Y, Watad, A, Yavne, Y, Lichtbroun, B, Bragazzi, NL, Amital, H, Shoenfeld, Y
American journal of reproductive immunology (New York, N.Y. : 1989). 2018;(3):e12991
Abstract
Recurrent pregnancy loss (RPL) affects close to 1% of couples; however, the etiology is known in only about 50% of the cases. Recent studies show that autoimmune dysregulation is a probable cause of RPL, which in some cases may be overlooked. In order for a pregnancy to proceed to term, early modulation of immunologic response is required to induce tolerance to the semi-allogenic fetus. Certain subsets of both the innate and adaptive immune responses play a role in the induction of fetomaternal tolerance. A relatively predominant T-cell helper (Th) 2 and T regulatory (Treg) cell population seem to favor a better pregnancy outcome, whereas Th1 and Th17 cell populations appear to have an opposite effect. Lately, the role of vitamin D in the modulation of immune response was established. Vitamin D has been shown to promote a more favorable environment for pregnancy through various mechanisms, such as enhancement of the shift toward Th2 cells and regulation of immune cell differentiation and cytokine secretion. Therefore, it seems that vitamin D deficiency sways the balance toward a worse outcome and may play a part in recurrent pregnancy loss. This review sheds light on the immunologic changes, which occur in early pregnancy and the regulatory role vitamin D has in the maintenance of this delicate balance.
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Glucose responses to acute and chronic exercise during pregnancy: a systematic review and meta-analysis.
Davenport, MH, Sobierajski, F, Mottola, MF, Skow, RJ, Meah, VL, Poitras, VJ, Gray, CE, Jaramillo Garcia, A, Barrowman, N, Riske, L, et al
British journal of sports medicine. 2018;(21):1357-1366
Abstract
OBJECTIVE To perform a systematic review and meta-analysis to explore the relationship between prenatal exercise and glycaemic control. DESIGN Systematic review with random-effects meta-analysis and meta-regression. DATA SOURCES Online databases were searched up to 6 January 2017. STUDY ELIGIBILITY CRITERIA Studies of all designs were included (except case studies and reviews) if they were published in English, Spanish or French, and contained information on the population (pregnant women without contraindication to exercise), intervention (subjective or objective measures of frequency, intensity, duration, volume or type of acute or chronic exercise, alone ('exercise-only') or in combination with other intervention components (eg, dietary; 'exercise+cointervention') at any stage of pregnancy), comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and outcome (glycaemic control). RESULTS A total of 58 studies (n=8699) were included. There was 'very low' quality evidence showing that an acute bout of exercise was associated with a decrease in maternal blood glucose from before to during exercise (6 studies, n=123; mean difference (MD) -0.94 mmol/L, 95% CI -1.18 to -0.70, I2=41%) and following exercise (n=333; MD -0.57 mmol/L, 95% CI -0.72 to -0.41, I2=72%). Subgroup analysis showed that there were larger decreases in blood glucose following acute exercise in women with diabetes (n=26; MD -1.42, 95% CI -1.69 to -1.16, I2=8%) compared with those without diabetes (n=285; MD -0.46, 95% CI -0.60 to -0.32, I2=62%). Finally, chronic exercise-only interventions reduced fasting blood glucose compared with no exercise postintervention in women with diabetes (2 studies, n=70; MD -2.76, 95% CI -3.18 to -2.34, I2=52%; 'low' quality of evidence), but not in those without diabetes (9 studies, n=2174; MD -0.05, 95% CI -0.16 to 0.05, I2=79%). CONCLUSION Acute and chronic prenatal exercise reduced maternal circulating blood glucose concentrations, with a larger effect in women with diabetes.
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The Role of Vitamin D in Fertility and during Pregnancy and Lactation: A Review of Clinical Data.
Pilz, S, Zittermann, A, Obeid, R, Hahn, A, Pludowski, P, Trummer, C, Lerchbaum, E, Pérez-López, FR, Karras, SN, März, W
International journal of environmental research and public health. 2018;(10)
Abstract
Vitamin D deficiency is common and there exists a huge gap between recommended dietary vitamin D intakes and the poor vitamin D supply in the general population. While vitamin D is important for musculoskeletal health, there are accumulating data suggesting that vitamin D may also be important for fertility, pregnancy outcomes and lactation. Significant changes in vitamin D metabolism during pregnancy such as increased production of the "active vitamin D hormone" calcitriol support the important role of vitamin D in this setting. Observational studies show that vitamin D deficiency is a risk marker for reduced fertility and various adverse pregnancy outcomes and is associated with a low vitamin D content of breast milk. Meta-analyses of randomized controlled trials (RCTs) document that physiological vitamin D supplementation during pregnancy is safe and improves vitamin D and calcium status, thereby protecting skeletal health. Although certain RCTs and/or meta-analyses reported some other beneficial effects, it is still not clear whether vitamin D supplementation improves fertility or decreases the risk of adverse pregnancy outcomes such as low birth weight, pre-eclampsia and neonatal mortality, or reduces wheeze/asthma in the infants. Nevertheless, vitamin D supplementation in pregnant women is frequently required to achieve a sufficient vitamin D status as recommended by nutritional vitamin D guidelines. In this review, we provide an overview of systematic reviews, meta-analyses and large trials reporting clinical data on the role of vitamin D for fertility, pregnancy and lactation.
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Alterations in the vitamin D endocrine system during pregnancy: A longitudinal study of 855 healthy Norwegian women.
Gustafsson, MK, Romundstad, PR, Stafne, SN, Helvik, AS, Stunes, AK, Mørkved, S, Salvesen, KÅ, Thorsby, PM, Syversen, U
PloS one. 2018;(4):e0195041
Abstract
To ensure optimal calcium accrual in the fetal skeleton, a substantial rise occurs in 1,25-dihydroxyvitamin D (1,25(OH)2D), but is dependent on sufficient 25-hydroxyvitamin (25(OH)D). Large longitudinal studies addressing free 25(OH)D and 1,25(OH)2D during pregnancy are scarce. We aimed to assess levels of and relationship between 25(OH)D, 1,25(OH)2D, vitamin D-binding protein (DBP), parathyroid hormone (PTH), and free 25(OH)D during pregnancy; determinants of vitamin D status; and association between vitamin D indices or PTH and pregnancy outcomes (gestational diabetes mellitus and birthweight). Altogether 855 pregnant Norwegian Caucasian women from Trondheim and Stavanger (latitude 63°N and 58°N) were recruited; 94 were lost to follow-up. The study was originally a randomized controlled trial (2007-2009) with gestational diabetes as primary outcome. Data were collected in second and third trimester. In third trimester, 246 (34%) had vitamin D insufficiency and 52 (7%) deficiency (25(OH)D <50 and <30nmol/L, respectively). During wintertime in third trimester, 61 (47%) from Trondheim and 23 (51%) from Stavanger exhibited vitamin D insufficiency. PTH was elevated in 27 (3.7%). Estimate of change between trimesters was (95% CI): 25(OH)D -1.8 (-2.8 to -0.7) nmol/L, DBP 0.62 (0.57 to 0.66) μmol/L, calculated free 25(OH)D -1.7 (-2.0 to -1.4) pmol/L, PTH 0.81 (0.72 to 0.90) pmol/L, 1,25(OH)2D (sub-analysis) 31.4 (CI 24.7 to 38.2) pmol/L. A decrease in 1,25(OH)2D occurred in 45% of those with vitamin D deficiency, and they also exhibited lower levels than women with adequate vitamin D status. No association of vitamin D indices and PTH with pregnancy outcomes was observed. Women in Trondheim displayed lower 25(OH)D levels, despite minor latitudinal differences. Less than one-fifth adhered to the authorities' vitamin D recommendations. These findings demonstrate that hypovitaminosis D is prevalent among pregnant women living in northern latitudes, especially during the dark season, and there is an unmet need to ensure adequate vitamin D intake.
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Establishment of trimester-specific reference range for thyroid hormones during pregnancy.
Nazarpour, S, Ramezani Tehrani, F, Simbar, M, Minooee, S, Rahmati, M, Mansournia, MA, Azizi, F
Clinical biochemistry. 2018;:49-54
Abstract
OBJECTIVE Physiological gestational changes are associated with alterations in thyroid function which require different biochemical interpretation from that of non-pregnant women and necessitate established pregnancy-specific reference ranges. We aimed to identify the trimester-specific ranges of thyroid markers in a healthy population of pregnant Iranian women. METHODS In this self-sequential study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4 and FT4I and first trimester reference range for TPOAb were estimated. The normal and modulus exponential-normal models were fitted by maximum likelihood using STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were determined and used as reference intervals. RESULTS Mean±SD age of participants was 26.8±5.2years. Estimated reference intervals for TSH, T4 and FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9μIU/ml; 78.01-215.19, 93.23-243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively. Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of TSH was low in the 1st trimester, and gradually increased until 2nd trimester, followed by a slight decrease onward. A decreasing trend in TSH levels was observed in higher centiles with advancing gestational age. CONCLUSION This study provides trimester-specific reference ranges for some common thyroid markers among healthy Iranian women in an iodine sufficient area, to prevent biochemical misinterpretations during pregnancy.
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Understanding vitamin D metabolism in pregnancy: From physiology to pathophysiology and clinical outcomes.
Karras, SN, Wagner, CL, Castracane, VD
Metabolism: clinical and experimental. 2018;:112-123
Abstract
This critical time frame of intrauterine life development is considered of major importance on the metabolic imprinting of overall health of the offspring, in later life. This requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Dysregulation of these tightly controlled biophenomena at a systemic and placental level, have been considered as a potential mechanism mediating pathogenesis of preeclampsia and spontaneous birth. In this context, vitamin D has been considered as a significant regulator of both innate and adaptive immunity by regulating cell proliferation, differentiation and apoptosis. Vitamin D metabolism during pregnancy manifests striking differences as compared to the non-pregnant state. Calcitriol is increasing >2-3 fold in the first weeks of pregnancy whereas maternal 25-hydroxyvitamin D crosses the placental barrier and represents the main pool of vitamin D in the fetus. Moreover, during pregnancy, vitamin D receptor and regulatory metabolic enzymes are expressed in the placenta and decidua, indicating a potential critical point in the immunomodulation at the maternal-fetal interface. Considering these effects, maternal hypovitaminosis D during pregnancy has been associated with pregnancy related disorders. This review focuses on the mechanistic basis of these adaptive changes, as a background for the development of pregnancy related disorders, with a discourse on the pathophysiology relating hypovitaminosis D and clinical outcomes.
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Impact of maternal nutritional supplementation in conjunction with a breastfeeding support program during the last trimester to 12 weeks postpartum on breastfeeding practices and child development at 30 months old.
Zhang, Z, Tran, NT, Nguyen, TS, Nguyen, LT, Berde, Y, Tey, SL, Low, YL, Huynh, DTT
PloS one. 2018;(7):e0200519
Abstract
BACKGROUND Maternal nutrition during pregnancy and breastfeeding is important for the healthy growth and development of the fetus and infant. PURPOSE This study aimed to evaluate the long-term effects of a maternal milk supplementation (MMS) in conjunction with a breastfeeding support program on breastfeeding practices including duration of any breastfeeding and exclusive breastfeeding and child neurodevelopment outcomes at 30 months old. METHODS We followed up the offspring of 204 Vietnamese women who completed a randomized controlled trial where the intervention group received MMS with a breastfeeding support program from the last trimester to 12 weeks postpartum while the control group received standard care. At 30 months postpartum, information on child feeding practices was collected and child neurodevelopment was assessed by the Bayley Scales of Infant and Toddler Development (Bayley-III). RESULTS There was no significant difference in the duration of any breastfeeding (ABF) from birth between the groups. However, the intervention group had longer exclusive breastfeeding (EBF) duration (p = 0.0172), higher EBF rate at 6 months (p = 0.0093) and lower risk of discontinuing EBF (p = 0.0071) than the control. Children in the intervention group had significantly higher Bayley-III composite scores in the domains of cognitive (p = 0.0498) and motor (p = 0.0422) functions, as well as a tendency toward better social-emotional behavior (p = 0.0513) than children in the control group. The association between maternal intervention and child development was attenuated after further adjustment for birth weight but not EBF duration, suggesting that improvements in child development may be partially attributed to the benefits of prenatal nutrition supplementation on birth outcomes. CONCLUSIONS MMS with breastfeeding support during late pregnancy and early postpartum significantly improved EBF practices. The intervention was also associated with improvements in neurodevelopment in children at 30 months old.
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Iron status in pregnant women and women of reproductive age in Europe.
Milman, N, Taylor, CL, Merkel, J, Brannon, PM
The American journal of clinical nutrition. 2017;(Suppl 6):1655S-1662S
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Abstract
Understanding the iron status in pregnant women in Europe provides a foundation for considering the role of iron screening and supplementation. However, available reports and studies have used different approaches that challenge the devising of overall summaries. Moreover, data on pregnant women are limited, and thus, data on women of reproductive age provide useful background information including baseline iron stores in pregnant women. This review considered data that are available from >15 European countries including national surveys and relevant clinical studies. In European women of reproductive age, median or geometric mean serum ferritin (SF) concentrations were estimated at 26-38 μg/L. Approximately 40-55% of this population had small or depleted iron stores (i.e., SF concentration ≤30 μg/L), and 45-60% of this population had apparently replete iron stores. The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 10-32% and 2-5%, respectively, depending on the cutoffs used. Approximately 20-35% of European women of reproductive age had sufficient iron stores (SF concentration >70 μg/L) to complete a pregnancy without supplementary iron. During pregnancy, European women in controlled supplementation trials who were not receiving iron supplements displayed increasing prevalences of ID and IDA during pregnancy, which peaked in the middle to late third trimester. Available evidence has suggested that, in gestational weeks 32-39, the median or geometric mean SF concentrations were 6-21 μg/L, and prevalences of ID and IDA were 28-85% and 21-35%, respectively. Women who were taking iron supplements had higher iron status and lower prevalences of ID and IDA, which were dependent on the dose of iron and compliance. The data suggest that, in Europe, the iron status of reproductive-aged women varies by region and worsens in pregnancy without iron supplementation.