Levels of serum‐circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre‐eclampsia, gestational hypertension, and/or fetal growth restriction

Nanjo, Sakiko; Minami, Sawako; Mizoguchi, Masahiro; Yamamoto, Masayuki; Yahata, Tetsutaro; Toujima, Saori; Shiro, Michihisa; Kobayashi, Aya; Muragaki, Yasuteru; Ino, Kazuhiko

doi:10.1111/jog.13452

Cited by 17 publications

(12 citation statements)

References 32 publications

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“…Our findings are consistent with the results published by Nanjo et al [23] who demonstrated that prior to delivery, women with GH presented with significantly higher sFlt-1 levels than those without. Moreover, they found a significant correlation between the levels of circulating angiogenic factors shortly before delivery and the severity of hypertensive disorders in pregnancy [23]. Also, in our study, sFlt-1 concentrations increased with maternal blood pressure and were the highest in patients with arterial pressure exceeding 180/110 mmHg.…”

Section: Discussionsupporting

confidence: 93%

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

et al. 2019

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Background. Placental soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor, is considered an etiological factor of endothelial damage in pregnancy pathologies. An increase in the sFlt-1 level is associated with alterations of endothelial integrity. In contrast, vitamin D exerts a protective effect and low concentrations of 25(OH)D may have an adverse effect on common complications of pregnancy, such as gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM). The aim of this study was to analyze the levels of sFlt-1 in Polish women with physiological pregnancies and pregnancies complicated by GH, PE, and GDM. Moreover, we analyzed relationships between the maternal serum sFlt-1 level and the sFlt-1 to 25(OH)D ratio and the risk of GH and PE. Material and Methods. The study included 171 women with complicated pregnancies; among them are 45 with GH, 23 with PE, and 103 with GDM. The control group was comprised of 36 women with physiological pregnancies. Concentrations of sFl-1 and 25(OH)D were measured before delivery, with commercially available immunoassays. Results. Women with GH differed significantly from the controls in terms of their serum sFlt-1 levels (5797 pg/ml vs. 3531 pg/ml, p=0.0014). Moreover, a significant difference in sFlt-1 concentrations was found between women with PE and those with physiological pregnancies (6074 pg/ml vs. 3531 pg/ml, p<0.0001). GDM did not exert a statistically significant effect on serum sFlt-1 levels. Both logistic regression and ROC analysis demonstrated that elevated concentration of sFlt-1 was associated with greater risk of GH (AUC=0.70, p=0.0001) and PE (AUC=0.82, p<0.0001). Also, the sFlt-1 to 25(OH)D ratio, with the cutoff values of 652 (AUC=0.74, p<0.0001) and 653 (AUC=0.88, p<0.0001), respectively, was identified as a significant predictor of GH and PE. Conclusions. Determination of the sFlt-1/25(OH)D ratio might provide additional important information and, thus, be helpful in the identification of patients with PE and GH, facilitating their qualification for intensive treatment and improving the neonatal outcomes.

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Section: Discussionsupporting

confidence: 93%

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

et al. 2019

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“…As mentioned above, the placenta plays a key role in sFlt1 and PlGF production and a defective placentation, typical of PE, significantly contributes to increased circulating antiangiogenic sFlt1 levels 40 . sFlt1 increase lead to decreased maternal PlGF concentration 30,35,41,42 and sFlt1 levels were directly correlated to PE severity 18,[43][44][45] . In the present study, the reduced PE severity in GDM patients was confirmed by the reduced percentage of pathological uterine/umbilical Doppler and the increased weights of fetal-placental unit that we reported in GDM-PE relative to PE pregnancies.…”

Section: Discussionmentioning

confidence: 93%

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Nuzzo

Giuffrida

Moretti

et al. 2021

Sci Rep

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Gestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.

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“…Indeed, most studies about angiogenic and anti-angiogenic factors found similar profiles between SGA and AGA infants [ 34 , 35 ]. Only one study, to our knowledge, found discordant angiogenic profiles between preeclampsia alone and preeclampsia with SGA [ 36 ]. But these three studies focussed on less premature infants than our study.…”

Section: Discussionmentioning

confidence: 99%

Bronchopulmonary dysplasia in neonates born to mothers with preeclampsia: Impact of small for gestational age

et al. 2018

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Background and objectivesSmall for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population.MethodsRetrospective single-center cohort study including 141 neonates born between 24 and 30 weeks’ gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks’ postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2–15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9–11.3]).ConclusionsSmall for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia.Registration numberCNIL no. 1747084.

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Levels of serum‐circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre‐eclampsia, gestational hypertension, and/or fetal growth restriction

Cited by 17 publications

References 32 publications

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM)

Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Bronchopulmonary dysplasia in neonates born to mothers with preeclampsia: Impact of small for gestational age

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