Altered cord serum 25‐hydroxyvitamin D signaling and placental inflammation is associated with pre‐term birth

Budhwar, Snehil; Verma, Priyanka; Verma, Rachna; Gupta, Shantanu; Rai, S.B.; Rajender, Singh; Singh, Kiran

doi:10.1111/aji.13201

Cited by 13 publications

(11 citation statements)

References 45 publications

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“…In contrast, a cohort of pregnant women from the US reported maternal vitamin D was associated with higher newborn weight and head circumference but not with placental weight 58 . However, an Indian study showed that insufficient cord serum 25(OH)D enhanced placental inflammation in neonates born preterm 59 . Authors suggested that the decreased expression of vitamin D receptor and cathelicidin anti-microbial peptide in placentae from preterm birth neonates in their study may have contributed to placental inflammation 59 .…”

Section: Discussionmentioning

confidence: 99%

“…However, an Indian study showed that insufficient cord serum 25(OH)D enhanced placental inflammation in neonates born preterm 59 . Authors suggested that the decreased expression of vitamin D receptor and cathelicidin anti-microbial peptide in placentae from preterm birth neonates in their study may have contributed to placental inflammation 59 .…”

Section: Discussionmentioning

confidence: 99%

“…En contraste, una cohorte de embarazadas en los Estados Unidos reportó que la vitamina D materna se asoció con mayor peso y circunferencia cefálica del recién nacido, pero no con peso placentario 58 . Sin embargo, un estudio hindú mostró que una 25(OH)D en sangre de cordón insuficiente aumentó la inflamación placentaria en recién nacidos pretérmino 59 . Los autores sugirieron que en su estudio, una disminución de la expresión del receptor de vitamina D y del péptido antimicrobiano catelicidina en las placentas de recién nacidos pretérmino, pudieron haber contribuido a la inflamación placentaria 59 .…”

Section: Discussionunclassified

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Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort

Gonzalez‐Fernandez¹,

An²,

Plourde³

et al. 2021

Colomb Med

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Background: Multiple infections, nutrient deficiencies and inflammation (MINDI) occur in indigenous communities, but their associations with perinatal outcomes have not been described. Objective: To assess maternal and cord blood micronutrient and inflammation status in peripartum mothers from the Ngäbe-Buglé comarca in Panama, and their associations with placental and infant outcomes. Methods: In 34 mother-newborn dyads, placental weight and diameter were measured, and maternal and cord blood were processed for complete cell counts, serum C-reactive protein, ferritin, serum transferrin receptor (sTfR), vitamins A and D. Blood volumes were calculated using Nadler’s formula. Results: Mothers had low plasma volume (<2.8 L, 96%), vitamin A (52.9%), vitamin D (29.4%), iron (58.8%) and hemoglobin (23.5%), but high hematocrit (>40%, 17.6%) and inflammation (C-reactive protein >8.1 mg/L, 85.3%). Birthweights were normal, but the low placental weight (35.3%), low head circumference Z-scores (17.6%), and low cord hemoglobin (5.9%), iron (79.4%), vitamin A (14.7%) and vitamin D (82.3%) were identified. Maternal and cord vitamin D were highly correlated. Higher maternal plasma volume was associated with heavier placentae (β= 0.57), and higher cord D (β= 0.43) and eosinophils (β= 0.43) with larger placentae. Hemoconcentration (higher cord hematocrit) was associated with lower newborn weight (β= -0.48) and head circumference (β= -0.56). Inflammation [higher maternal neutrophils (β= -0.50), and cord platelets (β= -0.32)] was associated with the lower newborn length and head circumference. Conclusion: Maternal-newborn hemoconcentration, subclinical inflammation and multiple nutrient deficiencies, particularly neonatal vitamin D deficiency, were identified as potential targets for interventions to improve pregnancy outcomes in vulnerable communities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionunclassified

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Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort

Gonzalez‐Fernandez¹,

An²,

Plourde³

et al. 2021

Colomb Med

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“…Budhwar et al reported that VD deficiency disturbed homeostasis of the inflammatory response in the placenta, activating the cytokine network and followed by spontaneous premature preterm delivery [57]. At the same time, Dutra et al observed a correlation between maternal VD levels and VDR gene polymorphisms, as well as the risk of premature birth [58].…”

Section: Vdr Protein Level In Placentasmentioning

confidence: 99%

Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

et al. 2021

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(1) Background: Considerable evidence indicates that the occurrence of preeclampsia (PE) is associated with a reduced vitamin D (VD) level. Several studies have found that VD deficiency is correlated with disturbed trophoblast invasion, reduced angiogenesis and increased vasoconstriction. Because the vitamin D receptor (VDR) and CYP27B1 and CYP2R1 hydrolases are strongly involved in VD metabolism, the goal of the present study was to evaluate their genes and proteins expression in the placentas from preeclamptic women. (2) Methods: Samples and clinical data were obtained from 100 Polish women (41 women with preeclampsia and 59 healthy pregnant controls). The whole PE group was divided into subgroups according to gestation week of pregnancy ending before and after 34 gestational weeks (early/late-onset preeclampsia (EOPE/LOPE)). However, finally, to reduce confounding by differences in gestational age, the EOPE group was excluded from the analysis of mRNA and protein placental expression, and we focus on the comparison between LOPE and control groups. The placental VDR, CYP27B1 and CYP2R1 mRNA expression was analyzed using RT-PCR, and placental protein levels were determined by ELISA assay. (3) Results. (3.1) Placental gene expression: Expression levels of both genes, CYP27B1 (1.17 vs. 1.05 in controls, p = 0.006) and CYP2R1 (2.01 vs. 1.89 in controls, p = 0.039), were significantly higher in preeclamptic placentas than in the control group. Interestingly, VDR expression was significantly lower in placentas from the PE group (1.15 vs. 1.20 in controls, p = 0.030). After dividing all preeclamptic women into subgroups only for the CYP27B1 gene, a significantly higher placental expression in the LOPE subgroup than the healthy controls was observed (padj = 0.038). (3.2) Placental protein expression: The results revealed that protein expression levels of CYP27B1 in the preeclamptic group were similar (5.32 vs. 5.23 in controls, p = 0.530). There was a significant difference in median VDR and CYP2R1 protein levels between studied groups (VDR: 2.56 vs. 3.32 in controls, p < 0.001; CYP2R1: 1.32 vs. 1.43 in controls, p = 0.019). After stratification of preeclamptic women into subgroups, a significant difference was observed only in the VDR protein level. The medians in the LOPE subgroups were significantly lower compared to the healthy control group. In the whole study group, the placental VDR protein level was inversely correlated with systolic and diastolic blood pressure (all p < 0.001), and positively correlated with gestational age (p < 0.001) and infant birth weight (p = 0.014). (4) Conclusions: Lower mRNA and protein expression of VDR in preeclamptic placentas, and also VDR protein expression, could play a pivotal role in preeclampsia development. Additionally, the higher mRNA expression of both CYP27B1 and CYP2R1 hydrolase genes in placentas from preeclamptic women could indicate the compensatory role of these enzymes in preeclampsia etiology. Our results also indicate that placental VDR protein level could be one of the factors modulating blood pressure in pregnant women, as well as influencing gestational age and infant birth weight. Considering the importance of these findings, future studies are warranted.

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“…Thus, HMGB1 may play a role in cervical ripening as increased gene expression of HMGB1 has been detected in cervix from preterm mothers 80 . PTB may also occur due to decreased levels of the anti‐inflammatory molecule vitamin D within cord serum, which may trigger inflammation by increasing proinflammatory molecules such as HMGB1 in the placenta 81 . In addition, patients who suffer from intra‐amniotic inflammation deliver early when subjected to high concentrations of HMGB1 and IL‐6 within the amniotic fluid 82 .…”

Section: The Role Of Hmgb1 Throughout Gestationmentioning

confidence: 99%

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

Saito-Reis

Padron

Ing

et al. 2020

American J Rep Immunol

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A proinflammatory response driven by high‐mobility group box 1 (HMGB1) is important for the success of both the early stages of pregnancy and parturition initiation. However, the tight regulation of HMGB1 within these two stages is critical, as increased HMGB1 can manifest into pregnancy‐related pathologies. Although during the early stages of pregnancy HMGB1 is critical for the development and implantation of the embryo, and uterine decidualization, high levels within the uterine cavity have been linked to pregnancy failure. In addition, chronic inflammation, resultant from increased HMGB1 within the maternal circulation and gestational tissues, also increases the risk for preterm labor, preterm birth, or infant mortality. Due to the link between HMGB1 and several pregnancy pathologies, the possibility of leveraging HMGB1 as a biomarker has been assessed. However, data are limited that demonstrate how known HMGB1 inhibitors could reduce inflammation within pregnancy. Thus, further research is warranted to improve our understanding of the potential of HMGB1 as a therapeutic target to reduce inflammation within pregnancy. This review aims to describe what is understood about the role of HMGB1 that drives inflammation throughout pregnancy and highlight its potential as a biomarker and therapeutic target within this context.

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Altered cord serum 25‐hydroxyvitamin D signaling and placental inflammation is associated with pre‐term birth

Cited by 13 publications

References 45 publications

Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort

Maternal and cord blood parameters are associated with placental and newborn outcomes in indigenous mothers: A case study in the MINDI cohort

Placental mRNA and Protein Expression of VDR, CYP27B1 and CYP2R1 Genes Related to Vitamin D Metabolism in Preeclamptic Women

High‐mobility group box 1 is a driver of inflammation throughout pregnancy

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