Publications by authors named "Alexander Makatsariya"

38 Publications

Hydroxychloroquine in obstetric antiphospholipid syndrome: rationale and results of an observational study of refractory cases.

J Matern Fetal Neonatal Med 2021 May 27:1-8. Epub 2021 May 27.

The First I.M. Sechenov Moscow State Medical University (Sechenov University), Moscow, Russia.

Background: The current recommended therapy of obstetric antiphospholipid syndrome (APS) is a long-term anticoagulant therapy that affects the final event, namely, when the thrombosis has already occurred. Unfortunately, this schedule is not always effective and fails despite the correct risk stratification and an adequate adjusted dose.

Materials And Methods: From 2013 to 2020 we observed 217 women with antiphospholipid antibodies and obstetric morbidities who were treated with conventional treatment protocol (aspirin low doses ± LMWH). Among them 150 (69.1%) successfully completed pregnancy with delivery and live birth on the background of LMWH and aspirin therapy and in 67 (30.9%) women despite a traditional therapy regimen, obstetric complications were noted. Later, 56 of these 67 women became pregnant again and were offered traditional therapy plus hydroxychloroquine. Fifteen women refused HCQ treatment due to possible potential side effects. The final cohort consisted of 41 women with positive antiphospholipid antibodies and obstetric and thrombotic complications who received LMWH, aspirin low doses and HCQ at a dose of 200-400mg per day from the beginning of pregnancy.

Results: Forty-one aPL women treated with HCQ after failed previous anticoagulant therapy had live births in 32 cases (78%). Adding of HCQ to the combination of LMWH and LDA showed good overall obstetric results and increased the number of live births in another 32 women. So, a total of 182 (83.8%) of initial 217 aPL-women ended their pregnancies with live birth after adding the HCQ to the traditional therapy with LMWH and low doses of aspirin.

Conclusion: In 20-30% of cases the live birth despite anticoagulation cannot be achieved. Perhaps APS is not just anticoagulation. The study of pathophysiological mechanisms suggests that some patients will benefit from other therapy (in addition to anticoagulant). Therapy that affects the early effects of aPL on target cells (monocytes, endothelial cells, etc.) or before binding to receptors-this therapy will be preferable and potentially less harmful than the officially accepted one to date. From this point of view, HCQ looks promising and can be used as an alternative candidate for women with refractory obstetric antiphospholipid syndrome. Adding HCQ should be considered in some selected patients with failed pregnancy after treatment with anticoagulants.
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http://dx.doi.org/10.1080/14767058.2021.1908992DOI Listing
May 2021

Early ADAMTS13 testing associates with pre-eclampsia occurrence in antiphospholipid syndrome.

Thromb Res 2021 Apr 27;203:101-109. Epub 2021 Apr 27.

Department of Gynaecology and Obstetrics, First Moscow State Medical University (Sechenov University), Russian Federation; Department of Haematology, CHU Nîmes, Univ Montpellier, Nîmes, France; Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France; UA 011 INSERM- Université de Montpellier, Institut Desbrest d'Epidémiologie et de Santé Publique, Montpellier, France. Electronic address:

Introduction: Women with obstetric antiphospholipid syndrome (oAPS) still develop placental diseases, mainly pre-eclampsia (PEcl), which diagnosis is associated with reduced ADAMTS13 levels. Testing ADAMTS13 in newly pregnant oAPS may provide evidence for risk stratification.

Materials And Methods: We retrospectively investigated the prognostic value of ADAMTS13 activity, antigen and antibodies on stored plasma samples obtained prior to beginning low-molecular weight heparin-low dose aspirin treatment in 513 oAPS women.

Results: Some women had evidences of early positive ADAMTS13 antibodies and low ADAMTS13 activity:antigen ratio, suggestive of ADAMTS13 dysfunction. Women with a subsequent PEcl had higher ADAMTS13 antibodies (p < 0.0001), and lower ADAMTS13 activity and activity:antigen ratios (p < 0.0001). In multivariate analysis, these markers were significant risk factors for PEcl and for the most devastating PEcl subgroups (early-onset PEcl, severe PEcl, PEcl with no living child after 28 days). ADAMTS13-related markers showed acceptable discrimination power to predict clinical events, particularly for ADAMTS13 activity:antigen ratio in predicting PEcl cases with no living child after 28 days (AUC: 0.844 (0.712-0.974), p < 0.0001), with excellent negative predictive value (0.990).

Conclusions: The characterization of ADAMTS13 in newly pregnant women with oAPS depicts the risk of PEcl occurrence. ADAMTS13 might help identify pregnant women with oAPS not requiring escalating treatment strategies to prevent PEcl.
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http://dx.doi.org/10.1016/j.thromres.2021.04.021DOI Listing
April 2021

The Influence of Treatment of Inflammatory Arthritis During Pregnancy on the Long-Term Children's Outcome.

Front Pharmacol 2021 18;12:626258. Epub 2021 Mar 18.

Rheumatology and Clinical Immunology Unit, ASST Spedali Civili and University of Brescia, Brescia, Italy.

The management of reproductive issues in women with inflammatory arthritis has greatly changed over decades. In the 1980-1990s, women with refractory forms of arthritis were either not able to get pregnant or did choose not to get pregnant because of their disabling disease. Hence, the traditional belief that pregnancy can induce a remission of arthritis. The availability of biologic agents has allowed a good control of aggressive forms of arthritis. The main topic of discussion during preconception counselling is the use of drugs during pregnancy and breastfeeding. Physicians are now supported by international recommendations released by the European League Against Rheumatism and the American College of Rheumatology, but still they must face with cultural reluctance in accepting that a pregnant woman can take medications. Patient-physician communication should be centered on the message that active maternal disease during pregnancy is detrimental to fetal health. Keeping maternal disease under control with drugs which are not harmful to the fetus is the best way to ensure the best possible outcome for both the mother and the baby. However, there might be concerns about the influence of the exposure to medications on the newborn's health conditions. Particularly, studies suggesting an increased risk of autism-spectrum-disorders in children born to women with rheumatoid arthritis has raised questions about neuropsychological impairment in the offspring of women with chronic arthritis. As a multidisciplinary group of rheumatologists and child neuropsychiatrists, we conducted a study on 16 women with chronic forms of arthritis whose diagnosis was determined before pregnancy and their 18 school-age children. The children underwent a complete neurological examination and validated tests/questionnaires. Behavioral aspects of somatization and anxiety/depression (internalizing problem) or an "adult profile" were found in nearly one third of children. Children at a high risk of neurodevelopmental problems were born to mothers with a longer history of arthritis and were breastfeed for less than 6 months of age or were not breastfeed at all. No association was found with other maternal characteristics such as autoantibody existence and disease activity during and after the pregnancy.
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http://dx.doi.org/10.3389/fphar.2021.626258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013697PMC
March 2021

Challenging anticoagulation cases: Cancer-associated venous thromboembolism and chemotherapy-induced thrombocytopenia - A case-based review of clinical management.

Thromb Res 2021 03 4;199:38-42. Epub 2021 Jan 4.

Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria; I. M. Sechenov First Moscow State Medical University, Moscow, Russia. Electronic address:

Patients with cancer undergoing chemotherapy are at risk of thrombocytopenia. The co-incidence of cancer-associated venous thromboembolism (VTE) and thrombocytopenia is a frequent complication in patients with cancer. Especially in certain tumour entities at high VTE risk, chemotherapeutic agents with myelosuppressive effects are part of the standard of care. The management of cancer-associated VTE in the setting of chemotherapy-induced thrombocytopenia is challenging, in the absence of evidence from high-quality studies. Thrombocytopenia is associated with both increased risk of recurrent VTE and risk of bleeding during anticoagulation. In this case-based concise review, we aimed at summarizing available literature and expert consensus guidance on the treatment of cancer-associated VTE in patients with chemotherapy-induced thrombocytopenia.
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http://dx.doi.org/10.1016/j.thromres.2020.12.016DOI Listing
March 2021

Prediction of delivery after 40 weeks by antepartum ultrasound in singleton nulliparous women: a prospective cohort study.

Am J Obstet Gynecol MFM 2020 11 17;2(4):100193. Epub 2020 Aug 17.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Background: Induction of labor at 39 weeks of gestation is associated with better maternal and perinatal outcomes than expectant management. However, a policy of induction of labor implies the identification of women who will deliver after 40 weeks, who are at higher risk of adverse outcome.

Objective: This study primarily aimed to elucidate the role of antepartum ultrasound in predicting the onset of spontaneous labor in a cohort of low-risk singleton pregnancies, and secondarily to compare its diagnostic performance with that of other ultrasonographic and clinical parameters.

Study Design: This was a prospective study including singleton nulliparous women undergoing a dedicated ultrasound assessment at 36 to 38 weeks of gestation. The primary outcome was delivery ≥40 weeks of gestation. The ultrasound parameters explored were cervical length, posterior cervical angle, angle of progression, and head-perineum distance. Multivariate logistic regression, Kaplan-Meier, and area under the curve analyses were used to test the strength of association and diagnostic performance of variables considered in predicting delivery ≥40 weeks.

Results: A total of 457 women were included, and 49.2% delivered ≥40 weeks. Cervical length was longer (30 vs 19 mm; P≤.0001) and posterior cervical angle wider (105° vs 98°, P≤.0001) in women delivering ≥40 weeks than those delivering <40 weeks. Similarly, head-perineum distance was longer (48 vs 40 mm; P=.001) and angle of progression narrower (93° vs 95°; P=.04) in pregnancies delivering after 40 weeks. Conversely, there was no difference in the modified Bishop score between the 2 study groups (P=.689). In multivariable logistic regression analysis, cervical length (adjusted odds ratio, 1.307) and head-perineum distance (adjusted odds ratio, 1.227) were independently associated with delivery ≥40 weeks. Cervical length showed an area under the curve of 0.896 in predicting a delivery after 40 weeks. Integration of head-perineum distance in the diagnostic algorithm did not increase the performance of the model. A cervical length of 24 mm at 36 to 37 weeks of gestation showed the best combination of sensitivity and specificity in predicting delivery ≥40 weeks, with a shorter latency between ultrasound assessment and birth.

Conclusion: Antepartum ultrasound can reliably identify a subset of nulliparous women at higher risk of delivering beyond 40 weeks. A cervical length >24 mm at 36 to 37 weeks of gestation shows the optimal combination of sensitivity and specificity in predicting delivery ≥40 weeks. The findings from this study can help in identifying those women for whom elective induction of labor at 39 weeks of gestation would be beneficial in reducing the risk of adverse pregnancy outcome.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100193DOI Listing
November 2020

Role of ante-partum ultrasound in predicting vaginal birth after cesarean section: A prospective cohort study.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 21;256:385-390. Epub 2020 Nov 21.

Department of Obstetric-Section and Gynecology, University of Chieti, Chieti, Italy.

Introduction: Vaginal birth after caesarean delivery is associated with better outcomes compared to repeat caesarean section. Accurate antenatal risk stratification of women undergoing a trial of labor after caesarean section is crucial in order to maximize perinatal and maternal outcomes. The primary aim of this study was to explore the role of antepartum ultrasound in predicting the probability of vaginal birth in women attempting trial of labor; the secondary aim was to build a multiparametric prediction model including pregnancy and ultrasound characteristics able to predict vaginal birth and compare its diagnostic performance with previously developed models based exclusively upon clinical and pregnancy characteristics.

Methods: Prospective study of consecutive singleton pregnancies scheduled for trial of labor undergoing a dedicated antepartum ultrasound assessment at 36-38 weeks of gestation. Head circumference, estimated fetal weight cervical length, sub-pubic angle were recorded before the onset of labour. The obstetricians and midwives attending the delivery suite were blinded to the ultrasound findings. Multivariate logistic regression and area under the curve analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting vaginal birth. Comparison with previously reported clinical models developed by the Maternal-Fetal Medicine Unit Network (Grobman's models) was performed using De Long analysis.

Results: A total of 161women who underwent trial of labor were included in the study. Among them 114 (70.8 %) women had successful vaginal birth. At multivariable logistic regression analysis maternal height (adjusted odds ratio (aOR):1.24;9 5% Confidence Interval (CI)1.17-1.33), previous C-section for arrest labor (aOR:0.77; 95 %CI0.66-0.93), cervical dilation at admission (aOR:1.35 ; 95 %CI1.12-1.74), fetal head circumference (aOR:0.77 ; 5%CI0.43-0.89), subpubic angle (aOR:1.39 95 %CI1.11-1.99) and cervical length (aOR:0.82 95 % CI0.54-0.98) were independently associated with VBAC. A model integrating these variables had an area under curve of 0.839(95 % CI 0.710-0.727) for the prediction of vaginal birth, significantly higher than those achieved with intake (0.694; 95 %CI0.549-0.815; p = 0.01) and admission (0.732: 95 % CI 0.590-0.84; p = 0.04) models reported by Grobman.

Conclusion: Antepartum prediction of vaginal birth after a caesarean section is feasible. Fetal head circumference, subpubic angle and cervical length are independently associated and predictive of vaginal birth. Adding these variables to a multiparametric model including maternal parameters improves the diagnostic accuracy of vaginal birth compared to those based only on maternal characteristic.
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http://dx.doi.org/10.1016/j.ejogrb.2020.11.056DOI Listing
January 2021

Venous thrombosis risk factors in pregnant women.

J Perinat Med 2020 Oct 26. Epub 2020 Oct 26.

Department of Obstetrics and Gynecology, Russian Academy of Sciences, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Objectives: Assess all risk factors of venous thromboembolism (VTE) in pregnancy and puerperium.

Methods: Different guidelines for VTE prevention have been analyzed.

Results: Various recommendations have appeared for practitioners during the last 10-15 years on the basis of the risk factors analysis in order to prevent VTE in pregnant women more effectively. Nevertheless, none of these recommendations can yet take into account all risk factors, although convenient scoring systems have emerged for risk assessment and clear recommendations on anti-thrombotic prophylaxis regimens in risk groups in recent years.

Conclusions: VTE is the third most common cause of death on Earth after myocardial infarctions and strokes, according to the World Health Organization. Pregnancy is a unique condition of woman, when enormous changes occur in functioning of the most important systems of homeostasis in a relatively short time. These are physiological hypercoagulation, slowing of blood flow, increase in circulating blood volume, etc. However, while being physiological, these changes increase the risks of venous thromboembolism by almost six times. In some cases, there appears an imbalance or dissociation between the functioning of natural antithrombotic systems and the activation of coagulation as a consequence of genetically or acquired determined causes (genetic thrombophilia, antiphospholipid syndrome, comorbidities, obstetric complications and other exogenous and endogenous factors). Accordingly, identification of risk factors, their systematization, and determination of VTE risks in pregnancy and puerperium is one of the most important tasks of clinical medicine. This article will review historical understanding of thrombosis in pregnant women, progress in understanding VTE risk factors in pregnant women, and available reserves in identifying new risk factors during pregnancy and puerperium in order to stratify risks more efficiently.
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http://dx.doi.org/10.1515/jpm-2020-0011DOI Listing
October 2020

The pathogenic role of circulating Hashimoto's Thyroiditis-derived TPO-positive IgG on fetal loss in naïve mice.

Am J Reprod Immunol 2021 01 20;85(1):e13331. Epub 2020 Sep 20.

Laboratory of the Mosaic of Autoimmunity, Saint Petersburg State University, Saint Petersburg, Russia.

Problem: Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies.

Aim: We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model.

Method Of Study: Naïve ICR female mice, infused intravenously with 100 μg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P < .001) in comparison with mice passively transferred with commercial IgG or PBS. Moreover, we observed embryos small for date in the mice passively transferred with anti-TPO-positive IgG, exemplified by reduced weight of embryos and placentae (P = .001). Histopathological examination revealed delay in fetal development in 50% cases of anti-TPO-positive IgG-treated mice. Importantly, pathological changes in the transition zone, state of glycogen cells, and significant structural changes in the labyrinth part of placenta were observed in all anti-TPO-positive IgG samples.

Conclusion: The current study shows in the first time, a direct proof of concept, on the association of human TPO-positive IgG from Hashimoto's thyroiditis patients on fetal loss induction in murine model.
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http://dx.doi.org/10.1111/aji.13331DOI Listing
January 2021

Sonoelastographic Assessment of the Uterine Cervix in the Prediction of Imminent Delivery in Singleton Nulliparous Women Near Term: A Prospective Cohort Study.

J Ultrasound Med 2021 Mar 25;40(3):559-568. Epub 2020 Aug 25.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Objectives: To explore the role of newly developed software to assess cervical sonoelastography in predicting the onset of spontaneous delivery in singleton pregnancies at term and to compare its diagnostic performance with that provided by the cervical length (CL) and posterior cervical angle (PCA).

Methods: This work was a prospective study including nulliparous singleton pregnancies at gestational ages of 37 weeks to 38 weeks 6 days. The CL, PCA, hardness ratio (HR), and mean strain from the internal os and external os were obtained by a transvaginal ultrasound approach using semiautomatic software (E-Cervix; Samsung Medison Co, Ltd, Seoul, Korea). Multivariate logistic regression and area under the curve analyses were used to test the strength of the association and the diagnostic performance of the variables considered in predicting delivery within 7 days.

Results: A total of 398 women were included, and 24.6% delivered within 7 days. The CL was shorter (19.5 versus 2 7 mm; P = .0001), PCA narrower (99° versus 102°; P = .02) HR lower (35.3 versus 40.7; P = .0001), mean strain from the external os higher (0.41 versus 0.35; P = .0001), and mean strain from the internal os higher (0.38 versus 0.33; P = .0001) higher in women who delivered within 7 days from the assessment. At the multivariable logistic regression analysis, the CL (adjusted odds ratio, 1.307) and HR (adjusted odds ratio, 1.227) were the only variables independently associated with delivery within 1 week. A model combining the CL and HR showed an area under the curve of 0.873 in predicting delivery within 7 days, higher than that obtained by using the CL and HR singularly (P ≤ .0001).

Conclusions: The HR assessed by sonoelastography improves the efficacy of the CL in predicting imminent delivery in nulliparous women close to term.
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http://dx.doi.org/10.1002/jum.15434DOI Listing
March 2021

Correlation between estimated fetal weight and weight at birth in infants with gastroschisis and omphalocele.

J Matern Fetal Neonatal Med 2020 Aug 19:1-6. Epub 2020 Aug 19.

Department of Obstetrics, Federal University of São Paulo, Sao Paulo, Brazil.

Background: An accurate estimated fetal weight (EFW) calculated with traditional formulae in cases of abdominal wall defects (AWDs) can be challenging. As a result of reduced abdominal circumference, fetal weight may be underestimated, which could affect prenatal management. Siemer et al. proposed a formula without the use of abdominal circumference, but it is not used in our protocols yet.

Objectives: Our aim was to evaluate the correlation of EFW and birth weight in fetuses with AWD by using Hadlock 1, Hadlock 2, and Siemer et al.'s formulae. Our secondary goal was to evaluate how often fetuses classified as small for gestational age (SGA) were in fact SGA at birth.

Study Design: This was a retrospective cohort study of gestations complicated by gastroschisis and omphalocele at two tertiary-care centers in Brazil and Italy during an 8-year period. Of a total of 114 cases, 85 (44 cases of gastroschisis and 41 cases of omphalocele) met our criteria.

Results: The last prenatal scan was performed 5.2 (±4.1) days before birth. The mean gestational age at birth was 37.2 (±1.8) weeks. Correlation of EFW with birth weight was calculated with the three formulae with and without adjustment for weight gain between scan and birth, with the use of the Spearman coefficient. The correlation between EFW and weight at birth was positive according to all three formulae for the infants with gastroschisis. This finding was not confirmed in the infants with omphalocele. All formulae overestimated the number of SGA cases: although only 17.6% of fetuses were actually SGA at birth, the Hadlock formulae had classified nearly 35% of them as SGA, and Siemer et al.'s formula, 15.3%.

Conclusion: All three formulae yielded a good correlation between EFW in the last scan and birth weight in the infants with gastroschisis but not for those with omphalocele. Cases of SGA were overestimated.
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http://dx.doi.org/10.1080/14767058.2020.1808615DOI Listing
August 2020

"APS pregnancy - The offspring".

Lupus 2020 Oct 4;29(11):1336-1345. Epub 2020 Aug 4.

Department of Obstetrics and Gynecology, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Background: Antiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates.

Methods: A keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS).

Results: Offspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported.

Conclusions: The limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.
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http://dx.doi.org/10.1177/0961203320947154DOI Listing
October 2020

COVID-19, neutrophil extracellular traps and vascular complications in obstetric practice.

J Perinat Med 2020 Nov;48(9):985-994

Department of Obstetrics and Gynecology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

An issue of the novel coronavirus infection spreading is currently in the first place among others in the list of the international medical community. Due to lack of information, conflicting research findings, multicomponent effect of the virus on the body host, as well as various consequences that the virus triggers in the body, now every medical specialty does study the viral attack pathogenesis. Recent months showed that vascular complications are the most severe in the Coronavirus Disease 2019 (COVID-19) and are the main cause of death in the patients. The mechanisms of vascular complications are complex and affect both the hemostatic system and immune responses, "inflammatory storm", disorders of the renin-angiotensin-aldosterone system, endotheliopathy, etc. Due to the leading role of vascular complications in the viral infection pathogenesis, several groups of patients are at extra risk, including pregnant women, patients with a burdened obstetric history, with hereditary thrombophilia and antiphospholipid syndrome, and patients after in vitro fertilization (IVF). In this category of pregnant women, use of low-molecular-weight heparins (LMWH) is particularly important for both prevention of vascular and obstetric complications, and for pathogenetic therapy of COVID-19.
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http://dx.doi.org/10.1515/jpm-2020-0280DOI Listing
November 2020

Administration of antenatal corticosteroid is associated with reduced fetal growth velocity: a longitudinal study.

J Matern Fetal Neonatal Med 2020 Jul 29:1-6. Epub 2020 Jul 29.

Department of Obstetrics and Gynecology Foggia, Università di Chieti, Chieti, Italy.

Objective: To elucidate whether antenatal administration of corticosteroids in pregnancies with threatened preterm labor affects growth velocity.

Methods: A cohort of 262 pregnancies exposed to antenatal corticosteroids longitudinally studied and delivered from 36 weeks (cases) were compared to an unexposed group of 270 women (controls).

Methods: Fetal growth was assessed analyzing the growth velocity of head circumference (HC), abdominal circumference (AC), femur length (FL) and estimated fetal weight (EFW). Growth velocity (GV) was calculated as the difference in the Z-score between the biometric measurements recorded at the time of steroids administration and at 36 week of gestation, divided by the time interval (expressed in days) between the two scans and multiplied by 100. Similarly, changes in the Pulsatility Index (PI) of uterine, umbilical (UA), middle cerebral (MCA) arteries and cerebroplacental ratio (CPR) during the same time interval were also computed.

Results: Median gestational age at steroid administration (30.2 weeks vs 30.4) and follow-up ultrasound (36.4 weeks vs 36.4) were similar between cases and controls. In pregnancies exposed to antenatal corticosteroids, growth velocity in the HC (-0.61 vs. 0.12;  ≤ 0.001), AC (-0.55 vs. -0.04;  ≤ 0.001) and EFW (-0.89 vs. 0.06;  ≤ 0.001) were lower when compared to pregnancies not exposed to steroid therapy, while there was no difference in the growth velocity of FL (-0.05 vs 0.19;  = .06) or in any of the Doppler parameters explored.

Conclusion: In pregnancies exposed to antenatal steroid therapy, there is a significant reduction in fetal growth velocity not otherwise associated with changes in cerebroplacental Dopplers.
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http://dx.doi.org/10.1080/14767058.2020.1800634DOI Listing
July 2020

Fetal Cardiac Remodeling Is Affected by the Type of Embryo Transfer in Pregnancies Conceived by in vitro Fertilization: A Prospective Cohort Study.

Fetal Diagn Ther 2020 Jul 13:1-7. Epub 2020 Jul 13.

Department of Obstetrics and Gynecology, University Hospital of Chieti, Chieti, Italy.

Objective: Pregnancies conceived via intracytoplasmic sperm injection (ICSI) are associated with a higher risk of fetal cardiac remodeling. The aim of this study was to evaluate whether the type of embryo transfer may affect the magnitude of fetal cardiac remodeling in pregnancies conceived via ICSI.

Methods: Prospective cross-sectional study including 212 pregnancies conceived by ICSI (111 with frozen and 101 with fresh embryos) and 120 spontaneously conceived gestations. All women underwent ultrasound biometric evaluation, Doppler, and echocardiographic assessment, including evaluation of left and right atrial areas and sphericity index (SI), at 20-24 weeks of gestation. The χ2 and Kruskal-Wallis H tests were used to analyze the data.

Results: There was no difference in maternal characteristics, gestational age at ultrasound, Doppler, and fetal weight among the study groups. In pregnancies conceived by ICSI, left and right atrial areas were higher (p < 0.0001) and SI was lower (p < 0.0001) compared to spontaneously conceived pregnancies. Left (p = 0.004) and right (p = 0.023) atrial areas and left (p = 0.036) and right (p = 0.002) SIs were more affected in ICSI pregnancies conceived by fresh embryos.

Conclusion: The risk of fetal cardiac remodeling is higher in pregnancies conceived by ICSI and independent from fetal size and Doppler. The magnitude of these changes is affected by the type of ICSI technique and is higher in pregnancies conceived by fresh embryos.
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http://dx.doi.org/10.1159/000508987DOI Listing
July 2020

In utero exposure to Azathioprine in autoimmune disease. Where do we stand?

Autoimmun Rev 2020 Sep 30;19(9):102525. Epub 2020 Mar 30.

Synapse Research Institute, Maastricht, the Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands.

Azathioprine (AZA), an oral immunosuppressant, is safe during pregnancy. Some reports suggested different impairments in the offspring of mothers with autoimmune diseases (AI) exposed in utero to AZA. These observations are available from retrospective studies or case reports. However, data with respect to the long-term safety in the antenatally exposed child are still lacking. The aim of this study is to summarize the current knowledge in this field and to focus on the need for a prospective study on this population. We performed a PubMed search using several search terms. The actual data show that although the risk of congenital anomalies in offspring, as well as the infertility risk, are similar to those found in general population, there is a higher incidence of prematurity, of lower weight at birth and an intra-uterine delay of development. There is also an increased risk of materno- fetal infections, especially cytomegalovirus infection. Some authors raise the interrogations about neurocognitive impairment. Even though the adverse outcomes might well be a consequence of maternal illness and disease activity, interest has been raised about a contribution of this drug. However, the interferences between the external agent (in utero exposure to AZA), with the host (child genetic susceptibility, immune system anomalies, emotional status), environment (public health, social context, availability of health care), economic, social, and behavioral conditions, cultural patterns, are complex and represent confounding factors. In conclusion, it is necessary to perform studies on the medium and long-term outcome of children born by mothers with autoimmune diseases, treated with AZA, in order to show the safety of AZA exposure. Only large-scale population studies with long-term follow-up will allow to formally conclude in this field. TAKE HOME MESSAGES.
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http://dx.doi.org/10.1016/j.autrev.2020.102525DOI Listing
September 2020

Neonatal thrombosis.

J Matern Fetal Neonatal Med 2020 Mar 23:1-9. Epub 2020 Mar 23.

Department of Obstetrics and Gynecology, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Neonatal thromboembolism in pediatric patients is a rare but life-threatening condition mainly caused by combinations of at least 2 prothrombotic triggering risk factors such as the central venous lines, septic condition, and prematurity. Other risk factors include asphyxia, dehydration, liver dysfunction, inflammation, and maternal condition. Neonatal hemostatic system is different from one of the older children and adults. Coagulation proteins do not cross the placenta but are synthesized in the fetus from an early stage. In the term neonate, concentrations of several procoagulant proteins, particularly the vitamin K dependent and contact factors are reduced when compared with adults. Conversely, levels of antithrombin, heparin cofactor II and protein C and S are low at birth and fibrinolysis system is characterized by the decreased level of plasminogen and alpha-1-antiplasmin, increased tissue plasminogen activator. These features all tend to be gestational dependent and are more present in the preterm infant. Primarily in this context neonates appear to be at a higher risk of thrombosis than older children. Thrombotic complications reach their peak in the group of children born at 22-27 weeks. The role of inherited thrombophilic risk factors in neonatal VTE development is poorly defined. The presence of inherited and acquired thrombophilia in mother and newborn is also responsible for the development of thrombosis in neonates and should be considered. Thrombophilia in the mother can lead to increased coagulation potential and prethrombotic conditions during pregnancy, causing thrombotic vasculopathy at the placental level. The benefit of identifying thrombophilia in the sick preterm newborns who are in the group of risk for development of thrombotic complications may facilitate the thromboprophylaxis. Further research regarding assessment of risk factors, diagnostics and treatment strategy is required.
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http://dx.doi.org/10.1080/14767058.2020.1743668DOI Listing
March 2020

Identification of large-for-gestational age fetuses using antenatal customized fetal growth charts: Can we improve the prediction of abnormal labor course?

Eur J Obstet Gynecol Reprod Biol 2020 May 10;248:81-88. Epub 2020 Mar 10.

Department of Medicine and Surgery, Obstetrics and Gynaecology Unit, University of Parma, Parma, Italy. Electronic address:

Introduction: Fetal overgrowth is an acknowledged risk factor for abnormal labor course and maternal and perinatal complications. The objective of this study was to evaluate whether the use of antenatal ultrasound-based customized fetal growth charts in fetuses at risk for large-for-gestational age (LGA) allows a better identification of cases undergoing caesarean section due to intrapartum dystocia.

Material And Methods: An observational study involving four Italian tertiary centers was carried out. Women referred to a dedicated antenatal clinic between 35 and 38 weeks due to an increased risk of having an LGA fetus at birth were prospectively selected for the study purpose. The fetal measurements obtained and used for the estimation of the fetal size were biparietal diameter, head circumference, abdominal circumference and femur length, were prospectively collected. LGA fetuses were defined by estimated fetal weight (EFW) >95th centile either using the standard charts implemented by the World Health Organization (WHO) or the customized fetal growth charts previously published by our group. Patients scheduled for elective caesarean section (CS) or for elective induction for suspected fetal macrosomia or submitted to CS or vacuum extraction (VE) purely due to suspected intrapartum distress were excluded. The incidence of CS due to labor dystocia was compared between fetuses with EFW >95th centile according WHO or customized antenatal growth charts.

Results: Overall, 814 women were eligible, however 562 were considered for the data analysis following the evaluation of the exclusion criteria. Vaginal delivery occurred in 466 (82.9 %) women (435 (77.4 %) spontaneous vaginal delivery and 31 (5.5 %) VE) while 96 had CS. The EFW was >95th centile in 194 (34.5 %) fetuses according to WHO growth charts and in 190 (33.8 %) by customized growth charts, respectively. CS due to dystocia occurred in 43 (22.2 %) women with LGA fetuses defined by WHO curves and in 39 (20.5 %) women with LGA defined by customized growth charts (p 0.70). WHO curves showed 57 % sensitivity, 72 % specificity, 24 % PPV and 91 % NPV, while customized curves showed 52 % sensitivity, 73 % specificity, 23 % PPV and 91 % NPV for CS due to labor dystocia.

Conclusions: The use of antenatal ultrasound-based customized growth charts does not allow a better identification of fetuses at risk of CS due to intrapartum dystocia.
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http://dx.doi.org/10.1016/j.ejogrb.2020.03.024DOI Listing
May 2020

Prenatal risk factors for urgent atrial septostomy at birth in fetuses with transposition of the great arteries: a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2020 Feb 10:1-9. Epub 2020 Feb 10.

Department of Obstetrics and Gynaecology, Ospedali Riuniti, University of Foggia, Foggia, Italy.

To explore the role of fetal echocardiography in predicting the risk of urgent balloon atrial septostomy (BAS) at birth in fetuses diagnosed with transposition of the great arteries (TGA). Medline, Embase, and Cochrane databases were searched. The primary aim was to explore the differences in prenatal echocardiographic parameters among fetuses diagnosed with TGA that required urgent BAS within 24 h of birth due to life-threatening cyanosis compared to those who did not require such procedure. Random-effect meta-analyses were used to compute the data. Six studies (292 fetuses) were included. Restrictive appearance of the FO was present in 64.5% (95% CI = 39.8-85.7) of fetuses with TGA requiring BAS at birth compared to 7.9% (95% CI = 2.1-16.8) not requiring such procedure (OR = 71.1; 95% CI = 8.3-608.5,  < .0001). Hypermobile appearance of the atrial septum was present in 39.1% (95% CI = 26.4-56.5) of fetuses requiring BAS at birth compared to 9.8% (95% CI = 1.4-24.3) of those which did (OR 3.6; 95% CI = 1.4-9.0,  = .05). There was no difference in the prevalence of redundant ( = .374) or fixed ( = .051) atrial septum, bidirectional flow in the DA ( = .26) or an abnormal size of the DA ( = .06) in fetuses requiring urgent BAS at birth compared to those which did not. Mean (±SD) size of the right atrium was smaller in the fetuses with TGA undergoing urgent BAS at birth (23.4 ± 6.7) compared to those which did not (29.2 ± 6.2,  = .01). The mean (±SD) ratio between the FO and the aortic valve diameters (1.01 ± 0.41 versus 1.41 ± 0.43,  = .009) and the mean (±SD) ratio between the FO diameter and the septal length (0.36 ± 0.13 versus 0.51 ± 0.14,  = .001) were significantly smaller in fetuses requiring compared to those not undergoing urgent BAS at birth. The diagnostic accuracy of each independent ultrasound marker of the need for urgent BAS showed an overall good specificity but a low sensitivity. Fetal echocardiography prior to birth can stratify the risk of BAS in fetuses with TGA. Further studies are needed to validate these findings and build individualized multiparametric predictive models in order to more accurately identify those fetuses with TGA at a higher risk of urgent BAS after birth.
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http://dx.doi.org/10.1080/14767058.2020.1725883DOI Listing
February 2020

Outcome of fetal echogenic bowel: A systematic review and meta-analysis.

Prenat Diagn 2021 Mar 21;41(4):391-399. Epub 2021 Feb 21.

Department of Obstetrics and Gynecology, University of Foggia, Foggia, Italy.

The main aim of this systematic review was to explore the outcome of fetuses with isolated echogenic bowel (EB) on antenatal ultrasound. Inclusion criteria were singleton pregnancies with isolated EB no associated major structural anomalies at the time of diagnosis. The outcomes observed were: chromosomal anomalies, cystic fibrosis (CF), associated structural anomalies detected only at follow-up scans and at birth, regression during pregnancy, congenital infections, intra-uterine (IUD), neonatal (NND) and perinatal (PND) death. Twenty-five studies (12 971 fetuses) were included. Chromosomal anomalies occurred in 3.3% of the fetuses, mainly Trisomy 21 and aneuploidies involving the sex chromosomes. Cystic fibrosis occurred in 2.2%. Congenital infections affected 2.2%, mainly congenital Cytomegalovirus (CMV) infection. The majority of fetuses with EB experienced regression or disappearance of the EB at follow-up scans. Associated anomalies were detected at a follow-up scan in 1.8%. Associated anomalies were detected at birth and missed at ultrasound in 2.1% of cases. IUD occurred in 3.2% of cases while the corresponding figures for NND and PND were 0.4% and 3.1%. Fetuses with EB are at increased risk of adverse perinatal outcome, highlighting the need for a thorough antenatal management and postnatal follow-up. Assessment during pregnancy and after birth should be performed in order to look for signs of fetal aneuploidy, congenital infections and associated structural anomalies.
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http://dx.doi.org/10.1002/pd.5638DOI Listing
March 2021

Infertility in women with systemic autoimmune diseases.

Best Pract Res Clin Endocrinol Metab 2019 12 2;33(6):101369. Epub 2019 Dec 2.

Department of Obstetrics and Gynecology of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Infertility consists by definition in" failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse" while the term subfertility means a delay to achieve pregnancy. Several factors can contribute to infertility or subfertility in patients with systemic autoimmune diseases. The association of systemic autoimmune conditions with endometriosis, celiac disease and thyroid autoimmunity that are well known causes of infertility and/or subfertility need to be taken in consideration when difficulties in the onset of pregnancy is reported. The majority of the used antirheumatic drugs do not interfere with fertility. However, the use of cyclophosphamide, limited to severe disease, can provoke premature ovarian failure; to preserve fertility a preventive treatment is available. Nonsteroidal anti-inflammatory drugs can cause temporary infertility and corticosteroids are associated to a prolonged time to pregnancy in some rheumatic diseases. Data on the association of antiphospholipid antibodies (aPL) with infertility are still debated but in general an increased rate of aPL is described patients undergoing medically assisted reproductive techniques. In systemic lupus erythematosus aPL and other autoantibodies (i.e. anti-oocytes) can contribute to the infertility of some patients. Subfertility, rather than infertility, is observed in patients with rheumatoid arthritis; the particular physical conditions of these women can also account for this. Physicians should not forget the patients' age, that is mandatory in order to preserve their chance to have children.
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http://dx.doi.org/10.1016/j.beem.2019.101369DOI Listing
December 2019

Prenatal imaging features and postnatal outcomes of isolated fetal duplex renal collecting system: A systematic review and meta-analysis.

Prenat Diagn 2020 03 28;40(4):424-431. Epub 2020 Jan 28.

Department of Medical and Surgical Sciences, Institute of Obstetrics and Gynecology, University of Foggia, Foggia, Italy.

Objectives: To perform a systematic review of studies reporting the outcome of fetuses with a prenatal diagnosis of isolated duplex collecting system (DCS).

Methods: Inclusion criteria were studies reporting the outcome of fetuses with a prenatal diagnosis of isolated DCS, defined as DCS not associated with other major structural anomalies at the time of diagnosis. The outcomes observed were: imaging features of DCS on prenatal ultrasound, associated anomalies detected exclusively at prenatal follow-up ultrasound and at birth, abnormal karyotype, symptoms at birth (including vesicoureteral reflux [VUR] and urinary tract infections [UTI]), need for and type of surgical approach, complications after surgery, and accuracy of prenatal ultrasound in correctly identifying this anomaly.

Results: Eleven studies (284 fetuses with a prenatal diagnosis of DCS) were included. On ultrasound, DCS was associated with ureterocele in 70.7% and with megaureter in 36.6% of cases. Worsening of pelvic/ureteric dilatation was reported to occur in 41.3% of fetuses. At birth, 4.3% of fetuses affected by DCS showed associated renal anomalies. After birth, VUR and UTI presented in 51.3% and 21.7% of children respectively, while 33.6% required surgery. Prenatal diagnosis of DCS was confirmed in 90.9% of included cases.

Conclusion: DCS diagnosed prenatally is associated with a generally good outcome. Prenatal ultrasound has a good diagnostic accuracy, while detailed postnatal assessment is required in order to identify associated renal anomalies.
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http://dx.doi.org/10.1002/pd.5622DOI Listing
March 2020

Antepartum ultrasound prediction of failed vacuum-assisted operative delivery: a prospective cohort study.

J Matern Fetal Neonatal Med 2019 Nov 12:1-7. Epub 2019 Nov 12.

Foggia University Hospital, Foggia, Italy.

Failed vacuum-assisted delivery (VD) is associated with increased risk of maternal perineal trauma and neonatal morbidity. Knowledge of the risk factors related to failed VD is essential in the clinical decision-making. To elucidate the strength of association and the predictive accuracy of different ante-partum ultrasound parameters in predicting the risk of failed VD prior to the onset of Labor and to test the diagnostic performance of a multiparametric model including pregnancy and Labor characteristics, ante and intra-partum ultrasound in anticipating failed VD. Prospective study of consecutive singleton pregnancies complicated by VD undergoing a dedicated ultrasound assessment at 36-38 weeks of gestation. Head circumference (HC), estimated fetal weight (EFW) and subpubic angle and (SPA) were recorded before the onset of Labor. At the time of the VD, occiput position, head perineum distance (HPD) and angle of progression (AOP) were also recorded. Multivariate logistic regression and area under the curve (AUC) analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal, Labor and ultrasound characteristics in predicting g failed VD. Four hundred eight pregnancies with successful and 26 with failed VD were included in the analysis. Fetuses experiencing failed VD had a larger HC (1.21 versus 1.07 MoM;  = .0001), a higher EFW -value (0.56 versus 0.33 values;  = .002) and a narrower SPA (114 versus 122  = .0001) compared to those having a successful VD. At multivariable logistic regression analysis, maternal height (aOR 0.89 95% CI 0.76-0.98), nulliparity (aOR: 1.14 95% CI 1.06-1.36), HC MoM (aOR: 1.24 95% CI 1.13-1.55) and SPA angle (aOR: 0.82 95% CI 0.67-0.95), but not EFW ( = .08) were independently associated with failed VD. When intrapartum ultrasound variables were added to the multivariate model, fetal occipital position (aOR: 1.45 95th CI 1.11-1.99) and HPD (aOR: 0.77 95th CI 0.44-0.96) were independently associated with failed VD. A multiparametric model integrating pregnancy and Labor characteristics and ante-partum ultrasound variables had an AUC of 0.837 (95% CI 0.797-0.876) for the prediction of failed VE. The addition of intra-partum ultrasound variables to the prediction model, improved the accuracy for failed VD provided by maternal and antepartum ultrasound characteristics with an AUC of 0.913 (0.888-0.937). Antepartum prediction of failed VD is feasible. HC, SPA but not EFW are independently associated and predictive of failed VD. Adding these variables to a multiparametric model including maternal and intrapartum ultrasound parameters improves the diagnostic accuracy for failed VD.
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http://dx.doi.org/10.1080/14767058.2019.1683540DOI Listing
November 2019

Autoimmune diseases and pregnancy.

Best Pract Res Clin Endocrinol Metab 2019 12 11;33(6):101322. Epub 2019 Sep 11.

Department of Obstetrics and Gynecology of I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.

Pregnancy in autoimmune diseases remains an argument of debate. In last years great improvements were done and with the correct medical support women with disease such as Systemic Lupus Erythematosus or Antiphospholipid Syndrome can afford a pregnancy and have healthy babies. The starting point is a good counselling. Women should be informed about risks that can occur taking some medications while pregnant and, on the other hand, that there are medications that can be safety assumed during pregnancy. Furthermore, there are known maternal risks factor such as the presence of antiphospholipid antibodies or anti-Ro/SSA antibodies that must be carefully manage by both rheumatologists and obstetrics. In addition, also disease activity during pregnancy can represent an issue. For all these reason, a multidisciplinary approach is mandatory in order to give our patients an optimal medical support, before, during and after pregnancy.
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http://dx.doi.org/10.1016/j.beem.2019.101322DOI Listing
December 2019

Diagnostic accuracy of Doppler ultrasound in predicting perinatal outcome in pregnancies at term: A prospective longitudinal study.

Acta Obstet Gynecol Scand 2020 01 9;99(1):42-47. Epub 2019 Oct 9.

Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Introduction: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term.

Material And Methods: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36 and 37  weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data.

Results: In all, 600 consecutive singleton pregnancies from 36 weeks of gestation were included in the study. Mean MCA PI (1.1 ± 0.2 vs 1.5 ± 0.4, P < 0.001) and cerebroplacental ratio (1.4 ± 0.4 vs 1.9 ± 0.6, P < 0.001) were lower, whereas uterine arteries PI (0.8 ±0.2 vs 0.7 ±0.3, P = 0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P = 0.399) or estimated fetal weight centile (P = 0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P = 0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P = 0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P = 0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P = 0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P = 0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor.

Conclusions: MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.
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http://dx.doi.org/10.1111/aogs.13705DOI Listing
January 2020

Post-partum pelvic floor dysfunction assessed on 3D rotational ultrasound: a prospective study on women with first- and second-degree perineal tears and episiotomy.

J Matern Fetal Neonatal Med 2021 Feb 10;34(3):445-455. Epub 2019 Jul 10.

Women´s Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Sciences, Women'S Health and Perinatology Research Group, UiT - The Arctic University of Norway, Tromsø, Norway.

To evaluate the morphology and biometry of pelvic floor structures 3 months after birth in women experiencing first- or second-degree perineal tears or undergoing episiotomy during labor. Prospective observational study including nulliparous women delivering at term with a clinical diagnosis of first- or second-degree perineal tears after birth or undergoing episiotomy. The role of Kristeller maneuver during labor in affecting pelvic structure and function is also explored. All women underwent 2D trans-perineal and 3D endovaginal or endoanal ultrasound 3 months after birth. 115 women assessed 3 months after delivery were enrolled in the study. Compared with controls, women who experienced first-degree perineal tears had higher bladder neck-symphysis (versus 20.9 ± 4.9 versus 16.1 ± 4.9 mm,  = .017), bladder wall-pubic symphysis (22.4 ± 7.4 versus 14.2 ± 9.5 mm,  = .02) and anorectal angle-symphysis distance (12.5 ± 4.7 versus 9.3 ± 4.3 mm,  = .018). Furthermore, they have thicker internal and external anal sphincter. The incidence of partial right and left pubo-rectalis muscle avulsion was higher in women experiencing first-degree vaginal tear during labor (16.2 versus 0%,  = .004 for both). In women affected by second-degree tears, the occurrence of partial avulsion of the right and left pubo-rectalis muscle was 16.2%, while Oasis was detected in 10.8% of the cases. Women receiving Kristeller maneuver during labor had a higher incidence of either right or left puborectalis muscle avulsion. Women who had either first- and second-degree perineal tears or episiotomy show signs of abnormal pelvic morphometry on 3D rotational ultrasound 3 months after birth.
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http://dx.doi.org/10.1080/14767058.2019.1609932DOI Listing
February 2021

Unusual thrombosis or pregnancy complications associated to ovarian cancers: two clinical cases.

J Matern Fetal Neonatal Med 2021 May 21;34(9):1430-1434. Epub 2019 Jul 21.

Department of Obstetrics and Gynecology, First I.M. Sechenov Moscow State Medical University, Moscow, Russia.

Aim: Using illustrative cases of two patients with ovarian cancer who developed unusual thrombosis in pregnancy, to describe the difficulties in diagnosing and managing such patients.

Methods: We present the analysis of two cases of thrombosis of unusual localization (central artery of the retina and transverse and sigmoid sinus thrombosis) during pregnancy in women with hidden ovarian cancer.

Results: In both cases, the symptomatic of unususal thrombosis was interpreted as a manifestation of eclampsia, leading to a choice of non-optimal obstetric tactics on a background of hidden ovarian cancer, which in both cases were diagnosed only postpartum.

Conclusions: Pregnancy itself is a risk factor for thrombotic complications and in case malignancy develops in parallel with pregnancy, this risk is multiplied. In patients with ovarian cancer, difficulties arise both in detecting the tumor itself due to the enlarged uterus and in interpreting some of the symptoms, which can be regarded as a manifestation of pregnancy complications.
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http://dx.doi.org/10.1080/14767058.2019.1638359DOI Listing
May 2021

Recurrent thrombocytopenia in pregnancy: is it always an obstetric complication?

Intern Emerg Med 2020 10 25;15(7):1271-1274. Epub 2019 Jun 25.

UOSD and Research Unit of Thrombosis and Haemostasis, Fondazione IRCCS "Casa Sollievo Della Sofferenza", San Giovanni Rotondo, Foggia, Italy.

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http://dx.doi.org/10.1007/s11739-019-02136-xDOI Listing
October 2020

Ultrasound assessment of the cervix in predicting successful membrane sweeping: a prospective observational study.

J Matern Fetal Neonatal Med 2021 Mar 27;34(6):852-858. Epub 2019 May 27.

Department of Obstetrics and Gynecology, University Hospital of Northern Norway, Tromso, Norway.

Objective: Membrane sweeping has been shown to potentially reduce the need for formal induction of labor. The primary aim of this study was to elucidate the role of ultrasound assessment of the cervix in predicting successful membrane sweeping in singleton pregnancies at term; the secondary aim was to build a multiparametric prediction model integrating, maternal, pregnancy and ultrasound characteristics, able to anticipate spontaneous delivery at term.

Methods: Prospective observational study including singleton pregnancies at term undergoing membrane sweeping. Cervical length (CL) and posterior cervical angle (PCA) were assessed on ultrasound immediately before the procedure. Primary outcome was successful membrane sweeping, defined as spontaneous vaginal birth without formal induction within the 24hours. A subgroup analysis was computed considering women experiencing spontaneous vaginal birth within 48 hours from the procedure. The secondary outcome was to explore the diagnostic performance of a multiparametric model including maternal, pregnancy, and ultrasound assessment of the cervix in predicting spontaneous vaginal birth following membrane sweeping. Multivariate logistic regression and area under the curve (ROC) analyses were used to compute the data.

Results: One hundred fifty-nine singleton pregnancies undergoing membrane sweeping were included in the analysis. Successful membrane sweeping within 24 hours occurred in 68/159 women (36.5%). Parity (aOR = 1.87, 95% confidence interval [CI] 1.2-2.44), gestational age (aOR = 1.32, 95% CI 1.14-1.76), CL (aOR = 0.47, 95%CI 0.31-0.69) and PCA (aOR = 1.22, 95%CI 1.07-1.41) were independently associated with spontaneous vaginal birth within 24 hours from sweeping. The AUC of the constructed model was 0.796 (95% CI 0.727-0.865). Likewise, CL (aOR = 0.80, 95%CI 0.72-0.89), PCA (aOR = 1.19, 95%CI 1.10-1.28) and gestational age at the procedure (aOR = 1.65, 95%CI 1.09-1.86;  = .04) were independently associated with delivery within 48 hours with an AUC of 0.737 (95%CI 0.659-0.815).

Conclusions: Cervical ultrasound assessment of the cervix prior to membrane sweeping is associated with spontaneous vaginal birth within 24 and 48 hours from the procedure. The combination of cervical ultrasonographic parameters with parity and gestational age can predict the chances of delivery within 24 or 48 hours from membrane sweeping. The findings from this study support the use of ultrasound assessment of the cervix prior to membrane sweeping in order to more accurately predict the likelihood of spontaneous vaginal delivery.
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http://dx.doi.org/10.1080/14767058.2019.1619689DOI Listing
March 2021

Outcome of isolated fetal talipes: A systematic review and meta-analysis.

Acta Obstet Gynecol Scand 2019 11 6;98(11):1367-1377. Epub 2019 Jun 6.

Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.

Introduction: The aim of this systematic review was to explore the outcome of fetuses with a prenatal diagnosis of isolated talipes.

Material And Methods: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched. The outcomes explored were: associated anomalies detected at follow-up ultrasound examination; fetal magnetic resonance imaging (MRI) and birth; chromosomal abnormalities detected with standard and chromosomal microarray analysis, intrauterine, neonatal, and perinatal death, and termination of pregnancy; rate of surgical and nonsurgical treatment; neurodevelopmental outcome; and false-positive rate of prenatal diagnosis. Meta-analyses of proportions were used to combine data.

Results: Twenty-five studies (1567 fetuses) were included. Associated anomalies were detected in 7.8% (95% CI 0.1%-29.3%) of cases at follow-up ultrasound, and in 4.0% (95% CI 0.1%-13.2%) of cases, fetal MRI identified anomalies not detected at ultrasound assessment. Similarly, 7.0% (95% CI 3.4%-11.7%) of cases labeled as isolated talipes on prenatal imaging were found to have associated anomalies at birth. Abnormal karyotype was present in 3.6% (95% CI 1.7%-6.2%) of fetuses, whereas no anomaly was found at chromosomal microarray analysis, although this outcome was reported by only 1 study. Intrauterine death occurred in 0.99% (95% CI 0.4%-1.9%) of fetuses, whereas the corresponding figures for neonatal death and termination of pregnancy were 1.5% (95% CI 0.6%-2.6%) and 2.2% (95% CI 1.2%-3.4%), respectively. Surgical management of anomalies after birth was found in 41.7% (95% CI 27.0%-57.2%) of fetuses with isolated talipes, and 54.8% (95% CI 31.5%-77.0%) had nonsurgical management of the anomalies after birth. Abnormal neurodevelopmental outcome was reported in 7.6% (95% CI 1.0%-19.4%) of children, although this analysis was affected by the small number of included cases and short time of follow up.

Conclusions: Isolated talipes detected on prenatal ultrasound carries a generally good prognosis. The incidence of additional abnormalities detected on fetal MRI, aneuploidy, or neurodevelopmental disability is relatively low. However, longitudinal ultrasound assessment during pregnancy and a thorough postnatal evaluation are recommended to rule out associated anomalies that may significantly impact short- and long-term prognosis.
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http://dx.doi.org/10.1111/aogs.13637DOI Listing
November 2019

Skin pathologies in pregnancy.

J Perinat Med 2019 May;47(4):371-380

Faculty of Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

Progesterone is a hormone responsible for pregnancy maintenance and the amount of progesterone increases in a woman's body during pregnancy, as well as the level of female sex hormones, estrogens are also upregulated. Due to these changes the cutaneous sensitivity to external stimuli (meteorological factors, bacteria, etc.) increases. In general, all skin changes during pregnancy can be divided into three groups: physiological changes (hormone-associated), nonspecific or dermatoses that existed before pregnancy or were triggered by it, and specific pregnancy-related dermatoses, which appear during pregnancy and resolve in the postpartum period. In this brief  review, we describe the dermatoses commonly seen in pregnancy and present our own clinical examples. We hope the review will be of some practical help for dermatologists and obstetricians.
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http://dx.doi.org/10.1515/jpm-2018-0338DOI Listing
May 2019