Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes

Yefet, Enav; Kuzmin, Olga; Schwartz, Naama; Basson, Flora; Nachum, Zohar

doi:10.1159/000458409

Cited by 26 publications

(25 citation statements)

References 15 publications

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“…Among them, the overall incidence rate of APO was 33.80% (vs 6.04% in women with normal MS‐AFP). In other studies, the proportion of women with elevated MS‐AFP and the incidence rate of APO among them were even higher . However, although clearly knowing the high risks of APO for them, we do not have any intervention.…”

Section: Discussionmentioning

confidence: 77%

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A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

Zhang

Chan

et al. 2019

J of Obstet and Gynaecol

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Aim It has been reported in numerous studies that elevated maternal serum alpha‐fetoprotein (MS‐AFP) is associated with adverse pregnancy outcomes (APO), such as pre‐eclampsia, stillbirth, preterm birth and fetal growth restriction. However, the mechanism linking elevated MS‐AFP and APO is obscure. In this study, we tried to explore the mechanism by using pregnant rats. Methods Lipopolysaccharide (LPS) was used to induce placental inflammation in pregnant rats. Maternal serum and placental inflammatory cytokines and placental morphology were used to assess the level of placental inflammation. The incidences of APO and the levels of MS‐AFP were evaluated. The expressions of alpha‐fetoprotein (AFP) in the related organs and fetal serum AFP levels were detected. Results Compared to saline‐treated pregnant rats, LPS led to elevated maternal serum and placental inflammatory cytokines and a higher rate of placental inflammation. Lipopolysaccharide resulted in the features of APO and at the same time elevated MS‐AFP. Maternal serum alpha‐fetoprotein levels were significantly correlated to the evaluation parameters of APO. Lipopolysaccharide did not increase the expressions of AFP in fetal liver, maternal liver and placenta, but reduced the fetal serum AFP levels. Conclusion The phenomenon that elevated MS‐AFP is associated with APO, which has been reported in human pregnancies, is observed in our rat model. Placental inflammation can be the potential cause linking the two manifestations together. Although the source of elevated MS‐AFP is not identified, fetal blood circulation is suspected. Our study may provide an animal model for the future studies on this subject.

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Section: Discussionmentioning

confidence: 77%

“…In other studies, the proportion of women with elevated MS-AFP and the incidence rate of APO among them were even higher. 33,34 However, although clearly knowing the high risks of APO for them, we do not have any intervention. Intensifying routine antenatal care does not improve their pregnancy outcomes.…”

Section: Discussionmentioning

confidence: 99%

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

Zhang

Chan

et al. 2019

J of Obstet and Gynaecol

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“…pregnancy. However, these hormones have not been useful in the development of molecular 48 metrics to estimate GA or to phenotype complicated pregnancies prior to overt clinical 49 manifestations of specific pathologic states like preeclampsia (PE) [3,4], a pregnancy-related 50 vascular disorder affecting 5-8% of all pregnancies [5,6]. 51 PE is thought to be a multisystem disorder of pregnancy driven by alterations in placental 52 function and resolved by the delivery of the placenta and fetus [7].…”

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confidence: 99%

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Hao

You

Chen

et al. 2018

Preprint

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1Background: Placental protein expression plays a crucial biological role during normal and 2 complicated pregnancies. We hypothesized that: (1) circulating pregnancy-associated, placenta-3 related protein levels throughout gestation reflect the uncomplicated, full-term temporal 4 progression of human gestation, and effectively estimates gestational ages (GAs); (2) 5 pregnancies with underlying placental pathology, such as preeclampsia (PE), are associated with 6 disruptions in this GA estimation in early gestation; (3) malfunctions of this GA estimation can 7 be employed to identify impending PE. In addition, to explore the underlying biology and PE 8 etiology, we set to compare protein gestational patterns of human and mouse, using pregnant 9 heme oxygenase-1 (HO-1) heterozygote (Het) mice, a mouse model reflecting PE-like 10 symptoms. 11Methods: Serum levels of circulating placenta-related proteins -leptin (LEP), chorionic 12 somatomammotropin hormone like 1 (CSHL1), elabela (ELA), activin A, soluble fms-like 13 tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF)-were quantified by ELISA in 14 blood serially collected throughout human pregnancies (20 normal subjects with 66 samples, and 15 20 PE subjects with 61 samples). Linear multivariate analysis of the targeted serological protein 16 levels was performed to estimate the normal GA. Logarithmic transformed mean-squared errors 17 of GA estimations were used to identify impending PE. Then the human gestational protein 18 patterns were compared to those in the pregnant HO-1 mice. 19Results: An elastic net (EN)-based gestational dating model was developed (R 2 = 0.76) and 20 validated (R 2 = 0.61) using the serum levels of the 6 proteins at various GAs from women with 21 normal uncomplicated pregnancies (n = 10 for training and n = 6 for validation). In pregnancies 22 complicated by PE (n = 14), the EN model was not (R 2 = -0.17) associated with GA at sampling 23 3 3 in PE. Statistically significant deviations from the normal GA EN model estimations were 24 observed in PE-associated pregnancies between GAs of 16-30 weeks (P = 0.01). The EN model 25 developed with 5 proteins (ELA excluded due to the lack of robustness of the mouse ELA essay) 26 performed similarly on normal human (R 2 = 0.68) and WT mouse (R 2 = 0.85) pregnancies. 27 Disruptions of this model were observed in both human PE-associated (human: R 2 = 0.27) and 28 mouse HO-1 Het (mouse: R 2 = 0.30) pregnancies. LEP out performed sFlt-1 and PlGF in 29 differentiating impending PE at early human and late mouse gestations. 30 Conclusions: As revealed in both human and mouse GA EN analyses, temporal serological 31 placenta-related protein patterns are tightly regulated throughout normal human pregnancies and 32 can be significantly disrupted in pathologic PE states. LEP changes earlier during gestation than 33 the well-established late GA PE biomarkers (sFlt-1 and PlGF). Our HO-1 Het mouse analysis 34 provides direct evidence of the causative action of HO-1 deficiency in LEP upregulation in a...

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“…The lack of clinical acceptance of amniocentesis has been an incentive to explore IAI and the intra-amniotic environment through alternative and noninvasive techniques, for instance by sampling cervical mucus, vaginal fluid, or maternal blood. We, as physicians, already have experience in noninvasive techniques to predict other outcomes [10][11][12]. We wondered whether noninvasive sampling of the intrauterine environment might be an alternative strategy to amniocentesis (Fig.…”

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confidence: 99%

Noninvasive Sampling of the Intrauterine Environment in Women with Preterm Labor and Intact Membranes

2017

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Spontaneous preterm birth has enormous consequences for newborns, children, and families. Intra-amniotic inflammation (IAI) is the leading cause of spontaneous preterm delivery, mainly at earlier gestational ages. Amniocentesis is the only method used to identify IAI in clinical practice. Although it is an invasive procedure with a very low risk of complications, many women and physicians are hesitant about amniocentesis on this indication. This has been an incentive to explore IAI and the intra-amniotic environment through noninvasive techniques, such as sampling cervical mucus, vaginal fluid, or maternal blood. With this overview, we aim to provide a concise update on the state of the art of the noninvasive sampling of the intrauterine environment in women with preterm labor and intact membranes. So far, it is unknown whether this screening helps improve our knowledge about the impact of IAI on the neonatal and long-term outcome, but we believe it merits this review.

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Predictive Value of Second-Trimester Biomarkers and Maternal Features for Adverse Pregnancy Outcomes

Cited by 26 publications

References 15 publications

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

A rat model of placental inflammation explains the unexplained elevated maternal serum alpha‐fetoprotein associated with adverse pregnancy outcomes

Changes in pregnancy-related serum biomarkers early in gestation are associated with later development of preeclampsia

Noninvasive Sampling of the Intrauterine Environment in Women with Preterm Labor and Intact Membranes

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