Circulating Anti-PLAC1 Antibodies during Pregnancy and in Women with Reproductive Failure: A Preliminary Analysis

The aims of this study were to determine the prevalence of anti-PLAC1 antibodies in normal pregnant women and in women with infertility or recurrent pregnancy loss (RPL). Secondary outcomes were the development of complications associated with anti-PLAC1 seropositivity and the rate of seroconversion during pregnancy. Sera from 103 healthy pregnant women and 45 women with unexplained infertility or RPL were analyzed by ELISA. The prevalence of anti-PLAC1 antibodies was 2% in healthy pregnant women and 4.5% in women with unexplained infertility or RPL (P=0.355). There was no detectable association of seropositivity with increased risk of pregnancy complications. Finally, 2% of women seroconverted during pregnancy. The prevalence of anti-PLAC1 antibodies in women with unexplained infertility or RPL is not significantly higher than the prevalence in normal pregnant women. However, the sample size in this study was too small. The exposure to the PLAC1 antigen during pregnancy can lead to the spontaneous development of antibodies.

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Systematic review and meta-analysis of female lifestyle factors and risk of recurrent pregnancy loss

Scientific Reports ◽

10.1038/s41598-021-86445-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ka Ying Bonnie Ng ◽

George Cherian ◽

Alexandra J. Kermack ◽

Sarah Bailey ◽

Nick Macklon ◽

...

Keyword(s):

Systematic Review ◽

General Population ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Meta Analysis ◽

Lifestyle Factors ◽

Caffeine Intake ◽

Increased Risk ◽

Secondary Outcomes

AbstractIt is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12–1.28 and OR 1.21, 95% CI 1.06–1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25–2.50 and OR 1.35, 95% CI 1.07–1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.

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Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm10020179 ◽

2021 ◽

Vol 10 (2) ◽

pp. 179

Author(s):

Emma Rasmark Roepke ◽

Ole Bjarne Christiansen ◽

Karin Källén ◽

Stefan R. Hansson

Keyword(s):

Cohort Study ◽

Preterm Birth ◽

Pregnancy Complications ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Placental Abruption ◽

Late Pregnancy ◽

High Risk Population ◽

Risk Population ◽

Increased Risk

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.

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Pregnancy-Related Complications in Women with Recurrent Pregnancy Loss: A Prospective Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm9092833 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2833 ◽

Cited By ~ 1

Author(s):

Carlo Ticconi ◽

Adalgisa Pietropolli ◽

Monia Specchia ◽

Elena Nicastri ◽

Carlo Chiaramonte ◽

...

Keyword(s):

Cohort Study ◽

Prospective Cohort Study ◽

Pregnancy Complications ◽

Prospective Cohort ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Placenta Previa ◽

Intrauterine Fetal Death ◽

Healthy Women ◽

Increased Risk

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353–5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10–6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112–2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.

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Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss

Thrombosis and Haemostasis ◽

10.1160/th12-03-0177 ◽

2012 ◽

Vol 108 (10) ◽

pp. 693-700 ◽

Cited By ~ 5

Author(s):

Juliano Bertinato ◽

Carolina Bueno ◽

Kelma da Silva ◽

Mário de Carvalho ◽

Rossana Francisco ◽

...

Keyword(s):

Pregnant Women ◽

Tissue Factor ◽

Pregnancy Loss ◽

Tissue Factor Pathway Inhibitor ◽

Recurrent Pregnancy Loss ◽

Previous History ◽

Nucleotide Polymorphisms ◽

Genotype Frequencies ◽

Increased Risk ◽

Tissue Factor Pathway

SummaryRecurrent pregnancy loss (RPL) is a multifactorial condition. The effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of RPL is thus far unknown. Our objective was to determine the association of SNPs in the above mentioned genes with RPL. We included 117 non-pregnant women with three or more consecutive losses prior to 20 weeks of pregnancy without a previous history of carrying a fetus to viability, and 264 healthy fertile non-pregnant women who had at least two term deliveries and no known pregnancy losses. The PROC (rs1799809 and rs1799808), SERPINC1 (rs2227589), THBD (rs1042579) and TFPI (rs10931292, rs8176592 and rs10153820) SNPs were analysed by Real Time PCR. Genotype frequencies for PROC 2418A>G, PROC 2405C>T, THBD 1418C>T, TFPI (T-33C and TFPI C-399T) SNPs were similar in cases and controls. The carriers of SERPINC1 786A allele (GA + AA genotypes) had an increased risk for RPL (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.05 – 3.00, p= 0.034) while women carrying the TFPI –287C allele (TC + CC genotypes) had a protection effect on having RPL (OR: 0.46, 95% CI: 0.26 – 0.83, p= 0.009). The TCC haplotype for TFPI T-33C/ TFPI T-287C/ TFPI C-399T SNPs was less frequent in cases (5.7%) than in controls (11.6%) (OR: 0.45, 95% CI: 0.23 – 0.90, p= 0.025). In conclusion, our data indicate that SERPINC1 786G>A variant increases the risk for RPL, while TFPI T-287C variant is protective; however, further studies are required to confirm our findings.

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POS0737 LOW PRECONCEPTIONAL COMPLEMENT LEVEL IS RELATED WITH ADVERSE OBSTETRIC OUTCOME IN A MULTICENTRIC COHORT OF PREGNANCY IN PATIENTS WITH APS AND APL POSITIVITY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1824 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 619.2-620

Author(s):

D. Lini ◽

C. Nalli ◽

L. Andreoli ◽

F. Crisafulli ◽

M. Fredi ◽

...

Keyword(s):

Pregnancy Outcome ◽

Complement Activation ◽

Pregnancy Complications ◽

Antiphospholipid Antibodies ◽

Pregnancy Loss ◽

Adverse Pregnancy Outcome ◽

Obstetric Outcome ◽

Complement Level ◽

Increased Risk ◽

Adverse Pregnancy

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

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Association of Tumor Necrosis Factor-α -308G>A, -238G>A and -376G>A polymorphisms with recurrent pregnancy loss risk in the Greek population

Fertility Research and Practice ◽

10.1186/s40738-021-00101-x ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sofoklis Stavros ◽

Despoina Mavrogianni ◽

Myrto Papamentzelopoulou ◽

Evaggelos Basamakis ◽

Hend Khudeir ◽

...

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Pcr Amplification ◽

Greek Population ◽

Control Group ◽

Increased Risk ◽

Tnf Α ◽

Caucasian Women ◽

Factor Α ◽

And Control

Abstract Background Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, −238G > A, −308G > A and − 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women. Methods This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples. Results The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births. Conclusions This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, −238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.

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Association of VEGF and p53 Polymorphisms and Spiral Artery Remodelling in Recurrent Pregnancy Loss: A Systematic Review and Meta-analysis

Thrombosis and Haemostasis ◽

10.1055/a-1518-1756 ◽

2021 ◽

Author(s):

Tamilmani Subi ◽

Vinodhini Krishnakumar ◽

Chandreswara Raju Kataru ◽

Inusha Panigrahi ◽

Meganathan Kannan

Keyword(s):

Risk Factor ◽

Risk Ratio ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Meta Analysis ◽

Mixed Population ◽

Relative Risk Ratio ◽

Spiral Artery ◽

Prevalence Odds Ratio ◽

Increased Risk

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T and p53 Arg72Pro polymorphisms with Recurrent Pregnancy Loss (RPL), but the outcomes are inconsistent. We have used meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodelling as a major risk factor. The studies were identified from three different reputed databases, namely Science direct, PubMed/Medline and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians and mixed population. For the analysis, the overall prevalence, Odds ratio, Risk ratio, Relative risk ratio and P values were calculated. A total of 3241 RPL cases and 3205 healthy controls from 21 different case-control studies were analysed. RPL was highly prevalent in mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04% and 66.46% respectively) and in Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different population with the spiral artery remodelling as a risk factor encloses the importance of the vasculature during the pregnancy.

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Investigating Association of rs5918 Human Platelets Antigen 1 and rs1800790 Fibrinogen β Chain as Critical Players with Recurrent Pregnancy Loss

Medical Sciences ◽

10.3390/medsci6040098 ◽

2018 ◽

Vol 6 (4) ◽

pp. 98 ◽

Cited By ~ 3

Author(s):

Fatemeh Karami ◽

Maliheh Askari ◽

Mohammad Modarressi

Keyword(s):

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Human Platelets ◽

P Value ◽

Increased Risk ◽

History Of ◽

Polymerase Chain ◽

Β Chain ◽

Larger Sample

Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most important variants including rs5918 T > C and rs1800790 G > A were selected to be studied in women affected by RPL. Three milliliters of peripheral blood were drawn from 110 women with history of at least two consecutive spontaneous abortion and 110 healthy women controls. rs5918 T > C and rs1800790 G > A of HPA-1 and FGB genes, respectively, were selected to be analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR_RFLP) following DNA isolation using QIAamp DNA Blood Mini Kit. Heterozygote genotype (TC) of HPA-1 gene rs5918 polymorphism was significantly associated with risk of RPL (p-value = 0.02). Although, rs1800790 G > A of FGB gene was not associated with RPL, its combination with rs5918 polymorphism was associated with increased risk of RPL. Owing to the critical roles of FGB and HPA-1 genes in coagulation, and thrombosis and several confinements on the meaningful association between the combination of those polymorphism with risk of RPL, including them in the thrombophilia panel may increase detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are required to shed light on the exact role of the studied gene polymorphism, especially rs1800790 G > A of FGB gene variant in pathogenesis of RPL.

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The Danish implementation study on response to pregnancy complications, MAMAACT

European Journal of Public Health ◽

10.1093/eurpub/ckaa165.1070 ◽

2020 ◽

Vol 30 (Supplement_5) ◽

Author(s):

S Villadsen ◽

H Johnsen ◽

T D Rasmussen ◽

J Sørensen ◽

U Christensen ◽

...

Keyword(s):

Pregnant Women ◽

Pregnancy Complications ◽

Smart Phone ◽

Target Group ◽

Warning Signs ◽

Perinatal Health ◽

Vulnerable Groups ◽

Contributing Factors ◽

Increased Risk ◽

Ward Level

Abstract Differential incidence and severity of pregnancy complications are likely important contributing factors to the increased risk of poor pregnancy outcomes among ethnic minority women in Europe. To address this issue, the MAMAACT trial has been developed based on a thorough mixed methods needs assessment and co-creation process, feasibility tested, now implemented in a nationwide complex intervention. The overall aim of the Danish MAMAACT trial is to reduce ethnic and social disparity in stillbirth and newborns' health by improved management of pregnancy complications. The overall target group is all pregnant women, and the specific target group is women of non-Western origin. The hypothesis of MAMAACT is that improved communication between pregnant women and midwives regarding body symptoms that need prompt reaction will improve perinatal health among these vulnerable groups. The intervention consists of postgraduate training of midwives in intercultural communication and a smart phone application and a leaflet, both in six different languages. The app and leaflet target the women and explain the most serious warning signs of pregnancy complications and how to respond to them. MAMAACT is implemented and evaluated in a randomized controlled cluster trial and 10 maternity wards consist the intervention groups, while nine maternity wards are the control groups. The evaluation is a mixed method evaluation focusing on understanding the mechanisms of change, how context at both maternity ward level as well as in the everyday life of women affects the implementation, and finally if effects on health literacy of the women and perinatal health of the children can be documented.

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