The expression and biological function of chemokine CXCL12 and receptor CXCR4/CXCR7 in placenta accreta spectrum disorders.

OBJECTIVES: Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment. MATERIALS AND METHODS: Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion. RESULTS: Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta. CONCLUSIONS: Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.

Intraplacental Villous Artery Doppler as an Independent Predictor for Placenta-Mediated Disease and Its Comparison with Uterine Artery Doppler and/or Placental Biochemical Markers in Predictive Models: A Prospective Cohort Study.

OBJECTIVES: To validate intraplacental villous artery (IPVA) Doppler as a predictor for placenta-mediated diseases (PMDs), to compare its predictive value with uterine artery (UtA) Doppler and placental biochemical markers, and to assess its value in predictive PMD models. METHODS: IPVA and UtA indices (pulsatility index [PI] and resistance index [RI]) were recorded at 18-24 weeks of gestation in a cohort of 117 women. The predictive values of IPVA, UtA, and placental biochemical markers were analyzed and compared between the PMD group (the women who developed preeclampsia or intrauterine growth restriction) and the non-PMD group (the women who remained healthy throughout pregnancy and 3 months postpartum) using the receiver-operating characteristic curves. Logistic regression was used to compare predictive models for PMDs based on IPVA, UtA, and/or biochemical markers. RESULTS: 31 (26.5%) women developed PMD (17 preeclampsia and 14 intrauterine growth restriction). IPVA PI was significantly higher in the PMD group than in the non-PMD group (p = 0.001). UtA PI and RI values remained nonsignificant between both groups (p = 0.066 and 0.104, respectively). IPVA PI from the 3 main branches of the placenta, and specifically the central main stem villi, showed a strong association with PMDs in comparison to UtA (p = 0.03 and 0.001 vs. 0.29). Model prediction including IPVA and UtA PI with or without placental biomarkers did not add any further significance to IPVA PI alone (p = 0.03, 0.41, and 0.36). CONCLUSIONS: IPVA PI appears superior to UtA PI or RI and placental biomarkers in PMD prediction. Model prediction for PMDs including IPVA, UtA Doppler, and biochemical markers did not enhance prediction values compared to IPVA Doppler alone.

Small RNA (sRNA) expression in the chorioallantois, endometrium and serum of mares following experimental induction of placentitis.

Intrauterine infection and inflammation remain a major cause of preterm labour in women and mares, with little known about small RNA (sRNA) expression in tissue or circulation. To better characterise placental inflammation (placentitis), we examined sRNA expression in the endometrium, chorioallantois and serum of mares with and without placentitis. Disease was induced in 10 mares via intracervical inoculation of Streptococcus equi ssp. zooepidemicus, either with moderate or high levels of inoculum; three uninoculated gestationally matched mares were used as controls. Matched chorioallantois and endometrium were sampled in two locations: Region 1, gross inflammation near cervical star with placental separation and Region 2, gross inflammation without placental separation. In Region 1, 26 sRNAs were altered in chorioallantois, while 20 were altered in endometrium. Within Region 2, changes were more subdued in both chorioallantois (10 sRNAs) and endometrium (two sRNAs). Within serum, we identified nine significantly altered sRNAs. In summary, we have characterised the expression of sRNA in the chorioallantois, the endometrium and the serum of mares with experimentally induced placentitis using next-generation sequencing, identifying significant changes within each tissue examined. These data should provide valuable information about the physiology of placental inflammation to clinicians and researchers alike.

Early-Pregnancy Circulating Antioxidant Capacity and Hemodynamic Adaptation in Recurrent Placental Syndrome: An Exploratory Study.

BACKGROUND/AIMS: Placental syndromes (PS) refer to pregnancy complications that include gestational hypertension, (pre)eclampsia, HELLP syndrome, and/or placental insufficiency-induced fetal growth restriction. These disorders are characterized by increased oxidative stress. This study aims to test the hypothesis that the abnormal hemodynamic adaptation to pregnancy, typical for early PS pregnancy, is accompanied by abnormal maternal levels of antioxidants relative to those in normal pregnancy. METHODS: Before, and at 12, 16, and 20 weeks pregnancy, we measured trolox equivalent antioxidant capacity (TEAC), uric acid (UA), and TEACC (TEAC corrected for UA) in maternal serum of former PS patients, who either developed recurrent PS (rPS; n = 16) or had a normal next pregnancy (non-rPS; n = 23). Concomitantly, we also measured various hemodynamic variables. RESULTS: rPS differed from non-rPS by higher TEACC levels before pregnancy (178 vs. 152 µM; p = 0.02) and at 20 weeks pregnancy (180 vs. 160 µM; p = 0.04). Only non-rPS responded to pregnancy by significant rises in hemodynamic measures. CONCLUSION: These data indicate that rPS pregnancies are preceded by an increase in antioxidant capacity, presumably induced by subclinical vascular injury and low-grade chronic inflammation.

A placenta clinic approach to the diagnosis and management of fetal growth restriction.

Effective detection and management of fetal growth restriction is relevant to all obstetric care providers. Models of best practice to care for these patients and their families continue to evolve. Since much of the disease burden in fetal growth restriction originates in the placenta, the concept of a multidisciplinary placenta clinic program, managed primarily within a maternal-fetal medicine division, has gained popularity. In this context, fetal growth restriction is merely one of many placenta-related disorders that can benefit from an interdisciplinary approach, incorporating expertise from specialist perinatal ultrasound and magnetic resonance imaging, reproductive genetics, neonatal pediatrics, internal medicine subspecialties, perinatal pathology, and nursing. The accurate diagnosis and prognosis for women with fetal growth restriction is established by comprehensive clinical review and detailed sonographic evaluation of the fetus, combined with uterine artery Doppler and morphologic assessment of the placenta. Diagnostic accuracy for placenta-mediated fetal growth restriction may be enhanced by quantification of maternal serum biomarkers including placenta growth factor alone or combined with soluble fms-like tyrosine kinase-1. Uterine artery Doppler is typically abnormal in most instances of early-onset fetal growth restriction and is associated with coexistent preeclampsia and underlying maternal vascular malperfusion pathology of the placenta. By contrast, rare but potentially more serious underlying placental diagnoses, such as massive perivillous fibrinoid deposition, chronic histiocytic intervillositis, or fetal thrombotic vasculopathy, may be associated with normal uterine artery Doppler waveforms. Despite minor variations in placental size, shape, and cord insertion, placental function remains, largely normal in the general population. Consequently, morphologic assessment of the placenta is not currently incorporated into current screening programs for placental complications. However, placental ultrasound can be diagnostic in the context of fetal growth restriction, for example in Breus' mole and triploidy, which in turn may enhance diagnosis and management. Several examples are illustrated in our figures and supplementary videos. Recent advances in the ability of multiparameter screening and intervention programs to reduce the risk of severe preeclampsia will likely increase efforts to deliver similar improvements for women at risk of fetal growth restriction. Placental pathology is important because the underlying pathologies associated with fetal growth restriction have a wide range of recurrence risks. Rare conditions such as massive perivillous fibrinoid deposition or chronic histolytic intervillositis may recur in >50% of subsequent pregnancies. Postpartum care in a placenta-focused program can provide effective counseling for modifiable maternal risk factors, and can assist in planning future pregnancy care based on the pathologic basis of fetal growth restriction.

Circulating endothelial progenitor cells in pregnant women with premature rupture of membranes: potential association with placental disorders.

The frequency of preterm labour has risen over the last few years. Plasma oestrogen concentrations differ between patients who deliver before term and those who deliver at term. Oestrogen can influence the kinetics of circulating endothelial progenitor cells (cEPCs). Here, we attempted to identify the potential association of cEPCs with the incidence of complications typical of prematurity. The study groups consisted of 60 pregnant women with premature rupture of membranes (PROM; less than 37 weeks) and 50 term pregnant women (more than 38 weeks). cEPCs were isolated from term pregnant women and pregnant women with PROM and then migratory, proliferative, tubulogenic and functional properties of these cells along with serum secretion of important EPC chemotactic cytokines were analysed. In addition, the effect of 17ß-oestradiol on biological features of cEPCs harvested from pregnant women was investigated. Our results showed that an increased concentration of oestrogen in women with PROM was associated with increased numbers of cEPCs, with these cells having increased oestrogen receptor α expression together with augmented proliferative, migratory and colony-formation properties. 17ß-oestradiol induced proliferation, migration and angiogenic secretory activity of cEPCs from pregnant women. Overall, circulation mobilisation of EPCs in pregnant women may be associated with placental disorders.

Placental but Not Peripheral Plasmodium falciparum Infection During Pregnancy Is Associated With Increased Risk of Malaria in Infancy.

Pregnancy-associated Plasmodium falciparum infection impacts the health of mothers and newborns, but little is known about the effects of these infections on infant susceptibility to malaria. We followed 473 mother-infant pairs during pregnancy and through 2 years of age. We observed that children born to mothers with placental malaria, but not those born to mothers with peripheral infection without evidence of placental sequestration, had increased risk of malaria during the first year of life compared with children born to mothers with no malaria during pregnancy. Malaria infections with placental sequestration have long-lasting impact on infant susceptibility to malaria infection.

Decreased PGF may contribute to trophoblast dysfunction in fetal growth restriction.

Fetal growth restriction (FGR) threatens perinatal health and is correlated with increased incidence of fetal original adult diseases. Most cases of FGR were idiopathic, which were supposed to be associated with placental abnormality. Decreased circulating placental growth factor (PGF) was recognized as an indication of placental deficiency in FGR. In this study, the epigenetic regulation of PGF in FGR placentas and the involvement of PGF in modulation of trophoblast activity were investigated. The expression level of PGF in placental tissues was determined by RT-qPCR, immunohistochemistry and ELISA. DNA methylation profile of PGF gene was analyzed by bisulfite sequencing. Trophoblastic cell lines were treated with ZM-306416, an inhibitor of PGF receptor FLT1, to observe the effect of PGF/FLT1 signaling on cell proliferation and migration. We demonstrated that PGF was downregulated in placentas from FGR pregnancies compared with normal controls. The villous expression of PGF was positively correlated with placental and fetal weight. The CpG island inside PGF promoter was hypomethylated without obvious difference in both normal and FGR placentas. However, the higher DNA methylation at another CpG island downstream exon 7 of PGF was demonstrated in FGR placentas. Additionally, we found FLT1 was expressed in trophoblast cells. Inhibition of PGF/FLT1 signaling by a selective inhibitor impaired trophoblast proliferation and migration. In conclusion, our data suggested that the PGF expression was dysregulated, and disrupted PGF/FLT1 signaling in trophoblast might contribute to placenta dysfunction in FGR. Thus, our results support the significant role of PGF in the pathogenesis of FGR.

Current insights in obstetric antiphospholipid syndrome.

PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is defined as the association of thrombotic events and/or obstetric morbidity in patients persistently positive for antiphospholipid antibodies (aPL). In this review, we will highlight the most important clinical presentations of APS with a focus on the obstetric morbidity, the current management strategies and the outlook for the future. RECENT FINDINGS: The use of aspirin and heparin has improved the pregnancy outcome in obstetric APS and approximately 70% of pregnant women with APS have a successful pregnancy outcome. Unfortunately, the current standard of care does not prevent all pregnancy complications as the current treatment fails in 20-30% of APS pregnancies. This therefore highlights the need for alternative treatments to improve obstetrical outcome. Other treatment options are currently explored and retrospective studies show that pravastatin for example is beneficial in women with aPL-related early preeclampsia. Moreover, the immunmodulator hydroxychloroquine may play a beneficial role in the prevention of aPL-related pregnancy complications. SUMMARY: APS is among the most frequent acquired risk factors for a treatable cause of recurrent pregnancy loss and increases the risk of conditions associated with ischaemic placental dysfunction, such as fetal growth restriction, preeclampsia, premature birth and intrauterine death. Current treatment is mainly based on aspirin and heparin. Studies to inform on alternative treatment options are urgently needed.

Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy.

AIM: Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. METHODS: For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. RESULTS: Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08 IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than 43.50 IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). CONCLUSION: Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation.

Pregnancy and Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is classified as the association of thrombotic events and/or obstetric morbidity in patients persistently positive for antiphospholipid antibodies (aPL). APS is also the most frequently acquired risk factor for a treatable cause of recurrent pregnancy loss and increases the risk of conditions associated with ischemic placental dysfunction, such as stillbirth, intrauterine death, preeclampsia, premature birth, and fetal growth restriction. The use of low-dose aspirin and heparin has improved the pregnancy outcome in obstetric APS and approximately 70% of pregnant women with APS will deliver a viable live infant. However, current management does not prevent all maternal, fetal, and neonatal complications of APS and the current treatment fails in 20 to 30% of APS pregnancies, raising the need to explore other treatments to improve obstetrical outcome. Two clinical studies of retrospective design have suggested that the immunomodulator hydroxychloroquine (HCQ) may play a role in the prevention of pregnancy complications in women with aPL and APS. The randomized controlled multicenter trial of hydroxychloroquine versus placebo during pregnancy in women with antiphospholipid antibodies (HYPATIA) of HCQ versus placebo will provide scientific evidence on the use of HCQ in pregnant women with aPL.

Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability.

AIM: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. METHODS: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the ß-γ system with two monoclonal antibodies against hemoglobin ß-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. RESULTS: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P =  0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P =  1.000). CONCLUSION: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.

A case of placental mesenchymal dysplasia with one year follow-up.

Placental mesenchymal dysplasia (PMD) is a rare placental disease with unknown etiology. Because of the malformation of the placenta, the incidence of the obstetric complications and the poor perinatal outcomes are higher than usual. PMD usually accompanies with Beckwith-Wiedemann syndrome. In this article, the authors report a case of PMD with a live delivery in 35+5 gestational weeks. The phenotype of the neonate was normal. During the one-year follow-up, the development of the child was normal.

[FETAL LOSSES DURING THE MATURATION OF THE PLACENTA AND THE RELATIONSHIP WITH SOME PROCOAGULANT CONDITIONS.]

Among the major causes and risk factors for fetal loss are chromosomal abnormalities, genetic syndromes, placental abnormalities, thrombophilia (FVL, Fil G20210A, C677T MTHFR, PAl-1 4G /-5G), infection and inflammation (IL-3, IL-4, IL-17, IL-10), antiphospholipid syndrome, maternal diseases such as hypertension, diabetes and obesity. Pregnancy is a prothrombotic state as a result of specific physiological changes with multifactorial ethio-pathogenesis, leading to increased procoagulant factors and structural changes turned a sTasis, inflammatory component and contribution of individual genetic and acquired thrombophilic risk factors. Understanding of the molecular mechanisms of control over the process of embryogenesis, placentation and fetal development and impact of the factors of hemodtasis, inflammation and apoptosis, contributes to the application- of appropriate therapy and increase the chance of successful completion of pregnancy.

MicroRNAs in placental health and disease.

MicroRNAs (miRNAs) constitute a large family of small noncoding RNAs that are encoded by the genomes of most organisms. They regulate gene expression through posttranscriptional mechanisms to attenuate protein output in various genetic networks. The discovery of miRNAs has transformed our understanding of gene regulation and sparked intense efforts intended to harness their potential as diagnostic markers and therapeutic tools. Over the last decade, a flurry of studies has shed light on placental miRNAs but has also raised many questions regarding the scope of their biologic action. Moreover, the recognition that miRNAs of placental origin are released continually in the maternal circulation throughout pregnancy suggested that circulating miRNAs might serve as biomarkers for placental function during pregnancy. Although this generated much enthusiasm, recently recognized challenges have delayed the application of miRNA-based biomarkers and therapeutics in clinical practice. In this review, we summarize key findings in the field and discuss current knowledge related to miRNAs in the context of placental biology.

Placental transcriptome in development and pathology: expression, function, and methods of analysis.

The placenta is the essential organ of mammalian pregnancy and errors in its development and function are associated with a wide range of human pathologies of pregnancy. Genome sequencing has led to methods for investigation of the transcriptome (all expressed RNA species) using microarrays and next-generation sequencing, and implementation of these techniques has identified many novel species of RNA including: micro-RNA, long noncoding RNA, and circular RNA. These species can physically interact with both each other and regulatory proteins to modify gene expression and messenger RNA to protein translation. Transcriptome analysis is actively used to investigate placental development and dysfunction in pathologies ranging from preeclampsia and fetal growth restriction to preterm labor. Genome-wide gene expression analysis is also being applied to identify prognostic and diagnostic biomarkers of these disorders. In this comprehensive review we summarize transcriptome biology, methods of isolation and analysis, application to placental development and pathology, and use in diagnostic analysis in maternal blood. Key information for analysis methods is organized into quick reference tables where current analysis techniques and tools are cited and compared. We have created this review as a practical guide and starting reference for those interested in beginning an investigation into the transcriptome of the placenta.

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

Haemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta-mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.

Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth.

Assisted reproductive technologies (ART) have been associated with several adverse perinatal outcomes involving placentation and fetal growth. It is critical to examine each intervention individually in order to assess its relationship to the described adverse perinatal outcomes. One intervention ubiquitously used in ART is superovulation with gonadotropins. Superovulation results in significant changes in the hormonal milieu, which persist during the peri-implantation and early placentation periods. Epidemiologic evidence suggests that the treatment-induced peri-implantation maternal environment plays a critical role in perinatal outcomes. In this study, using the mouse model, we have isolated the exposure to the peri-implantation period, and we examine the effect of superovulation on placentation and fetal growth. We report that the nonphysiologic peri-implantation maternal hormonal environment resulting from gonadotropin stimulation appears to have a direct effect on fetal growth, trophoblast differentiation, and gene expression. This appears to be mediated, at least in part, through trophoblast expansion and invasion. Although the specific molecular and cellular mechanism(s) leading to these observations remain to be elucidated, identifying this modifiable risk factor will not only allow us to improve perinatal outcomes with ART, but help us understand the pathophysiology contributing to these outcomes.

Reduced prevalence of placental malaria in primiparae with blood group O.

BACKGROUND: Blood group O protects African children against severe malaria and has reached high prevalence in malarious regions. However, its role in malaria in pregnancy is ambiguous. In 839 delivering Ghanaian women, associations of ABO blood groups with Plasmodium falciparum infection were examined. METHODS: Plasmodium falciparum infection was diagnosed in placental blood samples by microscopy and PCR assays. Present or past infection was defined as the detection of parasitaemia or haemozoin by microscopy, or a positive PCR result. Blood groups were inferred from genotyping rs8176719 (indicating the O allele) and rs8176746/rs8176747 (distinguishing the B allele from the A allele). RESULTS: The majority of women had blood group O (55.4%); present or past P. falciparum infection was seen in 62.3% of all women. Among multiparae, the blood groups had no influence on P. falciparum infection. In contrast, primiparae with blood group O had significantly less present or past infection than women with non-O blood groups (61.5 vs 76.2%, P = 0.007). In multivariate analysis, the odds of present or past placental P. falciparum infection were reduced by 45% in blood group O primiparae (aOR, 0.55 [95% CI, 0.33-0.94]). CONCLUSIONS: The present study shows a clear protective effect of blood group O against malaria in primiparae. This accords with findings in severe malaria and in vitro results. The data underline the relevance of host genetic protection among primiparae, i.e. the high-risk group for malaria in pregnancy, and contribute to the understanding of high O allele frequencies in Africa.

Screening for abnormal placentation and adverse pregnancy outcomes with maternal serum biomarkers in the second trimester.

Second trimester biomarkers were initially introduced with the intent of screening for neural tube defects and then subsequently for Down syndrome. It was soon realized that these markers can be indirect evidence of abnormal placentation and, therefore, can be used for screening for adverse pregnancy outcomes. Several new biomarkers have subsequently been described with conflicting findings regarding their efficiency for screening for adverse pregnancy outcomes. Although a biologically feasible mechanism has been proposed for the role of these biomarkers, they still fall short of an ideal screening test to be clinically useful.