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An extra virgin olive oil-enriched diet improves maternal, placental, and cord blood parameters in GDM pregnancies.
Gomez Ribot, D, Diaz, E, Fazio, MV, Gómez, HL, Fornes, D, Macchi, SB, Gresta, CA, Capobianco, E, Jawerbaum, A
Diabetes/metabolism research and reviews. 2020;(8):e3349
Abstract
AIMS: To address the effect of a diet enriched in extra virgin olive oil (EVOO) on maternal metabolic parameters and placental proinflammatory markers in Gestational diabetes mellitus (GDM) patients. METHODS Pregnant women at 24-28 weeks of gestation were enrolled: 33 GDM patients which were randomly assigned or not to the EVOO-enriched group and 17 healthy controls. Metabolic parameters were determined. Peroxisome proliferator activated receptor (PPAR) γ and PPARα protein expression, expression of microRNA (miR)-130a and miR-518d (which respectively target these PPAR isoforms) and levels of proinflammatory markers were evaluated in term placentas. Matrix metalloproteinases (MMPs) activity was evaluated in term placentas and umbilical cord blood. RESULTS GDM patients that received the EVOO-enriched diet showed reduced pregnancy weight gain (GDM-EVOO:10.3 ± 0.9, GDM:14.2 ± 1.4, P = .03) and reduced triglyceridemia (GDM-EVOO:231 ± 14, GDM:292 ± 21, P = .02) compared to the non-EVOO-enriched GDM group. In GDM placentas, the EVOO-enriched diet did not regulate PPARγ protein expression or miR-130a expression, but prevented the reduced PPARα protein expression (P = .02 vs GDM) and the increased miR-518d expression (P = .009 vs GDM). Increased proinflammatory markers (interleukin-1β, tumour necrosis factor-α and nitric oxide overproduction) in GDM placentas were prevented by the EVOO-enriched diet (respectively P = .001, P = .001 and P = .01 vs GDM). MMPs overactivity was prevented in placenta and umbilical cord blood in the EVOO-enriched GDM group (MMP-9: respectively P = .01 and P = .001 vs GDM). CONCLUSIONS A diet enriched in EVOO in GDM patients reduced maternal triglyceridemia and weight gain and has antiinflammatory properties in placenta and umbilical cord blood, possibly mediated by the regulation of PPAR pathways.
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Does Exercise During Pregnancy Affect Placental Weight?: A Randomized Clinical Trial.
Barakat, R, Vargas, M, Brik, M, Fernandez, I, Gil, J, Coteron, J, Santacruz, B
Evaluation & the health professions. 2018;(3):400-414
Abstract
Placental weight (PW) is a measure commonly used to summarize growth and aspects of placental function. In a normal pregnancy, it is reasonable to assume that PW is related to aspects of the functional capacity of the placenta. The placenta, as the site for all maternal-fetal oxygen and nutrient exchange, influences birth weight and is thus central to a successful pregnancy outcome. PW is the most common way to characterize placental growth, which relates to placental function. With physical exercise becoming an integral part of life for many women, the question of whether exercise during pregnancy has an adverse effect on the growing fetus is very important. The aim was to examine the influence of an aerobic exercise program throughout pregnancy on PW among healthy pregnant women. A randomized control trial was used (registration trial number: NCT02420288). Women were randomized into an exercise group (EG; n = 33) or a control group (CG; n = 32) that received standard care. The EG trained 3 days/week (55-60 min/session) from gestational Weeks 9-11 until Weeks 38-39. The 85 training sessions involved aerobic, muscular and pelvic floor strength, and flexibility exercises. PW and other pregnancy outcomes were measured. There was high attendance to the exercise program, and no differences in the PW at delivery were observed between study groups (CG = 493.2 ± 119.6 g vs. EG = 495.4 ± 150 g, p = .95). A regular, supervised exercise program throughout pregnancy does not affect the PW in healthy pregnant women.
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Placental lipid droplet composition: Effect of a lifestyle intervention (UPBEAT) in obese pregnant women.
Gázquez, A, Uhl, O, Ruíz-Palacios, M, Gill, C, Patel, N, Koletzko, B, Poston, L, Larqué, E, ,
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2018;(9):998-1005
Abstract
Maternal obesity is associated with adverse outcomes. Placental lipid droplets (LD) have been implicated in maternal-fetal lipid transfer but it is not known whether placental LD fat composition is modifiable. We evaluated the effects of a diet and physical activity intervention in obese pregnant women compared to routine antenatal care (UPBEAT study) on placental LD composition. LD were isolated by ultracentrifugation. Total FAs and phospholipids (phosphatidylcholines, PCs; sphingomyelins, SMs and lyso-phosphatidylcholines, Lyso-PCs) were analyzed by LC-MS/MS. Placenta MFSD2a expression was assessed by western blot. Placental LDs from obese women were comprised of predominantly saturated and monounsaturated FAs. TG and Chol composition was similar between intervention (n = 20) and control (n = 23) groups. PCs containing dihomo-ɣ-linolenic acid in LD were positively associated with gestational weight gain (P < 0.007), and lowered by the intervention. In the whole sample, PCs carrying DHA and arachidonic acid were inversely associated with placental weight. Placenta MFSD2a expression was associated with DHA cord blood metabolites and relationships were observed between LD lipids, especially DHA carrying species, and cord blood metabolites. We describe placenta LD composition for the first time and demonstrate modest, potentially beneficial effects of a lifestyle intervention on LD FAs in obese pregnant women.
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Maternal vitamin D sufficiency and reduced placental gene expression in angiogenic biomarkers related to comorbidities of pregnancy.
Schulz, EV, Cruze, L, Wei, W, Gehris, J, Wagner, CL
The Journal of steroid biochemistry and molecular biology. 2017;:273-279
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INTRODUCTION Maternal circulating 25-hydroxyvitamin D [25(OH)D] has been shown to optimize production of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy at approximately 100nmoles/L, which has pronounced effects on fetal health outcomes. Additionally, associations are noted between low maternal 25(OH)D concentrations and vascular pregnancy complications, such as preeclampsia. To further elucidate the effects of vitamin D activity in pregnancy, we investigated the role of maternal 25(OH)D, the nutritional indicator of vitamin D status, in relation to placental maintenance and, specifically, expression of placental gene targets related to angiogenesis and vitamin D metabolism. METHODS A focused analysis of placental mRNA expression related to angiogenesis, pregnancy maintenance, and vitamin D metabolism was conducted in placentas from 43 subjects enrolled in a randomized controlled trial supplementing 400IU or 4400IU of vitamin D3 per day during pregnancy. Placental mRNA was isolated from biopsies within one hour of delivery, followed by quantitative PCR. We classified pregnant women with circulating concentrations of <100nmoles/L as deficient and those with ≥100nmoles/L as sufficient. The value of each gene's change in the PCR cycle threshold (ΔCT), which is a relative measure of target concentration, was compared with maternal 25(OH)D concentrations <100nmoles/L and ≥100nmoles/L based on a two-sample Wilcoxon test. RESULTS Soluble FMS-like tyrosine kinase 1 (sFlt-1) and vascular endothelial growth factor (VEGF) gene expression was significantly downregulated in the maternal subgroup with circulating 25(OH)D ≥100ng/mL compared to the subgroup <100ng/mL. DISCUSSION Here, we report a significant association between maternal vitamin D status and the expression of sFlt-1 and VEGF at the mRNA level. Achieving maternal circulating 25(OH)D ≥100nmoles/L suggests the impact of maternal vitamin D3 supplementation on gene transcription in the placenta, thereby potentially decreasing antiangiogenic factors that may contribute to vascular pregnancy complications.
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Placental vitamin D metabolism and its associations with circulating vitamin D metabolites in pregnant women.
Park, H, Wood, MR, Malysheva, OV, Jones, S, Mehta, S, Brannon, PM, Caudill, MA
The American journal of clinical nutrition. 2017;(6):1439-1448
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Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans.Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy.Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes.Results: In placental tissue, 25-hydroxyvitamin D3 [25(OH)D3] was strongly correlated (r = 0.83, P < 0.001) with 24,25-dihydroxyvitamin D3 Moreover, these placental metabolites were strongly correlated (r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations (P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 (LRP2, also known as megalin) with 25(OH)D3 and the C3 epimer of 25(OH)D3 [3-epi-25(OH)D3]; cubilin (CUBN) with 25(OH)D3; 25-hydroxylase (CYP2R1) with 3-epi-25(OH)D3; 24-hydroxylase (CYP24A1) with 25(OH)D3, 3-epi-25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]; and 1α-hydroxylase [(CYP27B1) with 3-epi-25(OH)D3 and 1,25(OH)2D3]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment.Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1-associated increase in 1,25(OH)2D3] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D3, suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.
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Effects of Human Maternal Placentophagy on Maternal Postpartum Iron Status: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.
Gryder, LK, Young, SM, Zava, D, Norris, W, Cross, CL, Benyshek, DC
Journal of midwifery & women's health. 2017;(1):68-79
Abstract
INTRODUCTION Advocates of human maternal placentophagy report that encapsulated placenta is an excellent source of dietary iron. Our study compared the effect of ingested encapsulated placenta on maternal postpartum iron status versus that of a beef placebo. METHODS A randomized, double-blind, placebo-controlled pilot study (N = 23) was conducted among healthy human research participants experiencing a normal pregnancy. Maternal iron status was measured via hemoglobin, transferrin, and ferritin taken from blood samples drawn in the participants' homes at 4 time points: the 36th week of pregnancy, within 96 hours of parturition, between days 5 and 7 postpartum, and during week 3 postpartum. Iron concentrations in the encapsulated placenta and encapsulated beef placebo were compared using inductively coupled plasma mass spectrometry. RESULTS Seventy-eight percent (18/23) of study participants' hemoglobin concentrations were above the World Health Organization cutoff for gestational iron deficiency (≥ 11.0 g/dL) during the 36th week of pregnancy. Results revealed no statistically significant differences (hemoglobin, P = .603; ferritin, P = .852; transferrin, P = .936) in maternal iron status (including postpartum iron rebound in the first week postpartum) between women in the placenta supplement (n = 10) and placebo (n = 13) groups. Average iron concentrations were considerably higher in encapsulated placenta (0.664 mg/g) compared to the encapsulated beef placebo (0.093 mg/g) but provided only 24% of the recommended daily allowance (RDA) for iron among lactating women based on the study's maximum daily intake. DISCUSSION The current study suggests that encapsulated placenta supplementation neither significantly improves nor impairs postpartum maternal iron status for women consuming the RDA of dietary iron during pregnancy and lactation, compared to a beef placebo. This may be an especially important finding for women who are iron deficient postpartum and whose only source of supplemental dietary iron is encapsulated placenta, as this may provide an inadequate source of supplemental iron in cases of deficiency.
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mRNA Levels of Placental Iron and Zinc Transporter Genes Are Upregulated in Gambian Women with Low Iron and Zinc Status.
Jobarteh, ML, McArdle, HJ, Holtrop, G, Sise, EA, Prentice, AM, Moore, SE
The Journal of nutrition. 2017;(7):1401-1409
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Background: The role of the placenta in regulating micronutrient transport in response to maternal status is poorly understood.Objective: We investigated the effect of prenatal nutritional supplementation on the regulation of placental iron and zinc transport.Methods: In a randomized trial in rural Gambia [ENID (Early Nutrition and Immune Development)], pregnant women were allocated to 1 of 4 nutritional intervention arms: 1) iron and folic acid (FeFol) tablets (FeFol group); 2) multiple micronutrient (MMN) tablets (MMN group); 3) protein energy (PE) as a lipid-based nutrient supplement (LNS; PE group); and 4) PE and MMN (PE+MMN group) as LNS. All arms included iron (60 mg/d) and folic acid (400 μg/d). The MMN and PE+MMN arms included 30 mg supplemental Zn/d. In a subgroup of ∼300 mother-infant pairs, we measured maternal iron status, mRNA levels of genes encoding for placental iron and zinc transport proteins, and cord blood iron levels.Results: Maternal plasma iron concentration in late pregnancy was 45% and 78% lower in the PE and PE+MMN groups compared to the FeFol and MMN groups, respectively (P < 0.001). The mRNA levels of the placental iron uptake protein transferrin receptor 1 were 30-49% higher in the PE and PE+MMN arms than in the FeFol arm (P < 0.031), and also higher in the PE+MMN arm (29%; P = 0.042) than in the MMN arm. Ferritin in infant cord blood was 18-22% lower in the LNS groups (P < 0.024). Zinc supplementation in the MMN arm was associated with higher maternal plasma zinc concentrations (10% increase; P < 0.001) than in other intervention arms. mRNA levels for intracellular zinc-uptake proteins, in this case zrt, irt-like protein (ZIP) 4 and ZIP8, were 96-205% lower in the PE+MMN arm than in the intervention arms without added zinc (P < 0.025). Furthermore, mRNA expression of ZIP1 was 85% lower in the PE+MMN group than in the PE group (P = 0.003).Conclusion: In conditions of low maternal iron and in the absence of supplemental zinc, the placenta upregulates the gene expression of iron and zinc uptake proteins, presumably in order to meet fetal demands in the face of low maternal supply. The ENID trial was registered at www.controlled-trials.com as ISRCTN49285450.
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Role of antioxidants in gestational diabetes mellitus and relation to fetal outcome: a randomized controlled trial.
Maged, AM, Torky, H, Fouad, MA, GadAllah, SH, Waked, NM, Gayed, AS, Salem, AK
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2016;(24):4049-54
Abstract
OBJECTIVE To examine the effect of antioxidant administration on the oxidative parameters in both blood and placental tissue and its relation to fetal outcome in women with GDM. PATIENTS AND METHODS Two-hundred pregnant women with gestational diabetes mellitus (GDM) were randomized into 2 groups, Group1 received 1 gram L-ascorbic acid per day and Group2 received placebo. RESULTS The use of antioxidants significantly lower the needed insulin dose for blood sugar control (25.6 ± 20.3 versus 40.5 ± 23.7, respectively). In placental tissue homogenates, glutathione (GSH) was 49.6 ± 5.9 versus 62.34 ± 4.99, malondialdahyde (MDA) was 165.7 ± 9.2 versus 264.15 ± 12, superoxide dismutase (SOD) was 0.3 ± 0.3 versus 0.054 ± 0.16 while catalase (CAT) was 14.06 ± 2.4 versus 15.52 ± 3.97 and glutathione peroxidase (GPx) was 14 ± 4.1 versus 26.3 ± 4.26 in antioxidant group compared to the control group (p < 0.001). In maternal blood, GSH was 1.5 ± 0.3 versus 0.74 ± 0.088, CAT was 380.7 ± 11 versus 325.44 ± 21.8, GPx was 52.3 ± 8.7 versus 75.82 ± 6.84 and SOD was 188 ± 15.3 versus 98.56 ± 11.05 in antioxidant group compared to control group (p < 0.001). In neonatal blood, the level of MDA and SOD showed a statistically significant difference between antioxidants and control groups (4 ± 0.7 versus 6.6 7 ±0.66 and1 8 8 ± 15.3 versus 98.5 ± 11.05, respectively) (p < 0.001). The neonatal blood sugar after 1 and 2 hours of delivery was more stable in antioxidant group (56.7 ± 10.9 versus 39.7 ± 11.1 and 58.5 ± 10.8 versus 41.7 ± 13.1, respectively) (p <0.05). The neonates NICU admission was lower in antioxidant group (5 versus 11) (p <0.05). CONCLUSION The use of antioxidants markedly reverses the oxidative stresses in women with GDM with marked improvement on neonatal outcome.
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Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection.
Wiest, DB, Chang, E, Fanning, D, Garner, S, Cox, T, Jenkins, DD
The Journal of pediatrics. 2014;(4):672-7.e2
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OBJECTIVE To determine the pharmacokinetics (PK) and placental transfer of intravenous (i.v.) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis (CA) and determine the PK of i.v. NAC in their infants. STUDY DESIGN In this prospective, double-blind study i.v. NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks' gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from i.v. NAC (12.5-25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates. RESULTS Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL) of NAC was faster than in nonpregnant adults, with a terminal elimination half-life of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8, suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter terminal elimination half-life (5.1 vs 7.5 hours, respectively) and greater CL (53.7 vs 45.0 mL/h/kg, respectively). CONCLUSIONS Maternal CL and placental transfer of NAC was rapid, with umbilical cord concentrations frequently exceeding maternal concentrations. The administration of NAC to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.
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Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation.
Johnston, PC, Powell, LA, McCance, DR, Pogue, K, McMaster, C, Gilchrist, S, Holmes, VA, Young, IS, McGinty, A
Journal of diabetes and its complications. 2013;(4):322-7
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AIM: To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α (p38-MAPKα), Extra Cellular-Signal Regulated Kinase (ERK) and c-Jun NH2-Terminal Kinase (JNK) activity, in the pathogenesis of type 1 diabetic pre-eclampsia, and the putative modulation of these indices by maternal vitamin C and E supplementation. METHODS Placental samples were obtained from a sub-cohort of the DAPIT trial: a randomised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy. Placenta from placebo-treated: normotensive (NT) [n=17], gestational hypertension (GH) [n=7] and pre-eclampsia (PE) [n=6] and vitamin-treated: NT (n=20), GH (n=4) and PE (n=3) was analysed. Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue. Catalytic activities of placental p38-MAPKα, ERK and JNK were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS Nitrotyrosine immunostaining was present in placebo-treated NT, GH and PE placentae, with no significant difference observed between the groups. There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae. ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity. CONCLUSION Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy, possibly due to inherent oxidative stress and peroxynitrite production. Our results suggest that p38-MAPKα, ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation.