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No 8 (2017)

Articles

Proinflammatory factors of mitochondrial origin in the pathogenesis of recurrent miscarriages and early preterm births

Bulatova Y.S., Tetruashvili N.K., Vysokikh M.Y.

Abstract

Objective. To carry out a systematic analysis of the data available in the current literature on the influence of proinflammatory factors of mitochondrial origin (mtDAMPs) in the early stages of gestation. Material and methods. The paper analyzes the literature data in the past 10years, by using the search database PubMed. Results. The review outlines the presented results of studies, which suggest that there are variants of interaction of proinflammatory factors of mitochondrial origin (mtDAMPs) in the pathogenesis of recurrent miscarriage and early preterm labor. It provides evidence for an excessive inflammatory response that prevents normal trophoblast invasion and pregnancy complications Conclusion. There is a need for further investigations to set up a system for assessing the individual risk of pregnancy losses and for evaluating the effectiveness of treatment, by selecting the most informative inflammatory markers of mitochondrial origin.
Obstetrics and Gynecology. 2017;(8):5-9
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Vitamins and trace elements in the prevention of minor malformations

Gromova O.A., Torshin I.Y., Tetruashvili N.K.

Abstract

Objective. To analyze the relationship between the provision of vitamins and trace elements during pregnancy and the so-called minor malformations Material and methods. The review presents the results of a systematic analysis of foreign and Russian studies of the associations between trace element deficiencies and the pathogenesis, incidence, and severity of fetal congenital malformations (CMFs). Results. Trace element deficiencies during pregnancy are associated with obvious CMFs (syndactyly and other limb defects, impaired dentition, hernias, etc.) and CMF that manifested itself in early childhood (congenital heart defects, defects of the ureter, gallbladder, etc.). An analysis has shown that folates fall far short of being not the only trace element that is needed to prevent malformations, including the so-called minor ones (defects of the limbs, teeth, etc.). For example, zinc that regulates the activity of more than 1200 zinc-dependent proteins, as well as vitamin A and vitamin PP have no less an important role to play in the prevention of defects of dentition, fingers, auricles, lungs, diaphragm, and gallbladder. Deficiencies of zinc, vitamins A, E, D, and C and any of the B vitamins (including folates, pyridoxine and cyanocobalamin) stimulate the development of both minor and major malformations. Conclusion. The data from basic researches and evidence-based medicine indicate that it is necessary to mandatorily use vitamin-mineral complexes, including all the above trace elements, for the effective primary prevention of any fetal malformations.
Obstetrics and Gynecology. 2017;(8):10-20
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Assisted reproductive technologies in married couples at high risk for genetic disorders. Preimplantation genetic screening

Kulakova E.V., Kalinina E.A., Trofimov D.Y., Makarova N.P., Khechumyan L.R., Dudarova A.K.

Abstract

Objective. To carry out a systematic analysis of the data available in the current literature on the role of preimplantation genetic screening (PGS) in the effectiveness of assisted reproductive technology (ART) programs. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The paper describes current methods for GS, indications for the latter, as well as the clinical effectiveness of IVF programs with PGS. Conclusion. The data on the effectiveness of PGS are presently controversial. According to the Cochrane systematic review, there is no strong evidence that PGS is effective in increasing live birth rates. The data on PGS use in men with impaired spermatogenesis are also uncertain. However, PGS is increasingly being used in IVF clinics, by leaning on the opposite points of view that whatever PGS procedure is performed, its application increases embryo implantation rates and reduces the risk of spontaneous abortions, thereby enhancing the effectiveness of ART programs and increasing the chance of having a healthy baby.
Obstetrics and Gynecology. 2017;(8):21-27
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Hemostatic system dysfunctions and carcinogenesis: State-of-the-art

Vorobyev A.V., Makatsaria A.D., Bitsadze V.O., Brenner B.

Abstract

Objective. To carry out a systematic analysis of the data available in the current literature on the pathogenetic interaction of malignant neoplasms as a risk factor for thrombotic events and on the impact of hemostatic system activation on the potentiation of tumor growth and metastasis. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in e-Library and PubMed, and Cochrane Library on this topic. Results. Current views are given on the pathogenetic features of functioning of the hemostatic system during tumor growth. The first category of such factors is represented by specific tumor-dependent one; the second category includes general pathological risk factors; the third does therapy-dependent risk factors. Conclusion. Malignant neoplasms are a risk factor for thrombotic events while hemostatic system activation promotes tumor growth and metastasis.
Obstetrics and Gynecology. 2017;(8):28-33
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The diagnostic role of microRNAs as biological markers of external (retrocervical) endometriosis

Almova I.K., Bobrov M.Y., Chuprynin V.D., Khilkevich E.G., Chursin V.V., Melnikov M.V., Buralkina N.A., Veredchenko A.V.

Abstract

Objective. To analyze the data available in the current literature on the role of microRNAs as biological markers of external genital endometriosis. Material and methods. The review includes the data of foreign and Russian authors, which have been found in PubMed, by using the key words: biomarkers of endometriosis; microRNAs and endometriosis; and biomarkers of external genital endometriosis. The search depth was 5 years. Results. The differential expression of microRNAs in the eutopic and ectopic endometrium may suggest that microRNAs can play an important role in the development of endometrioid lesions. It is proven that miRNAs are active regulators of gene expression in endometriosis and associated reproductive dysfunctions. Detection of circulating miRNAs in plasma and other biological fluids in terms of their relative stability increases the likelihood that they may be investigated and proposed as non-invasive biomarkers for the diagnosis of endometriosis. Development of new exposure methods that can block the expression or mimic the function of miRNAs can represent new facets of treatment and prevention of a disease recurrence. Conclusion. The investigations confirm the prospects and relevance of studying the role of microRNAs as diagnostic markers of external genital endometriosis. The development of non-invasive biomarkers will be able to substantially reduce the time of diagnosis of external genital endometriosis, followed by timely treatment.
Obstetrics and Gynecology. 2017;(8):34-40
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The reproductive system of patients who have undergone reconstructive plastic surgery of the uterus

Dobrokhotova Y.E., Mikhaleva L.M., Nasyrova N.I., Aponovich I.A., Zalesskaya S.A.

Abstract

Objective. To consider the issues of fertility restoration in patients who have undergone reconstructive plastic surgery of the uterus. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in PubMed on this topic. Results. Based on numerous publications, the authors analyzed the anatomical and functional state of the endometrium and myometrium (including scar tissue), as well as the functional activity of the ovaries in patients who had undergone reconstructive plastic surgery of the uterus for obstetric and gynecological indications. Conclusion. In modern obstetrics, the concept of uterine preservation in placenta increta and subsequent metroplasty has been actively realized in recent years. In gynecology, the organ-sparing approach in patients with uterine myoma allows myomectomy to be actively used; and this trend is now becoming traditional and sustainable.
Obstetrics and Gynecology. 2017;(8):42-48
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Cerebrovascular diseases and pregnancy

Krasnopolsky V.I., Logutova L.S., Akhvlediani K.N., Travkina A.A., Petrukhin V.A., Lubnin A.Y., Kheireddin A.S., Budykina T.S., Aksenov A.N., Golovin A.A., Melnikov A.P.

Abstract

Objective. To study the course of pregnancy and to optimize delivery in women with cerebrovascular diseases. Subjects and methods. A total of 102 pregnant women aged 17 to 42 years with cerebrovascular diseases (CVD) (strokes) were followed up. In 25 of them, stroke occurred during this pregnancy. All the women underwent general clinical examination, hemostatic study, ultrasound and instrumental techniques, and consultations by a neurologist, a neurosurgeon, and an anesthesiologist. Results. After the examination, a delivery plan was consultatively elaborated: 47 (46.1%) pregnant women delivered a baby via cesarean delivery, 55 (53.9%) had vaginal deliveries, including obstetrical forceps and fetal vacuum extraction ones in 3 (2.9%) in 16 (15.7%) cases, respectively. 104 babies (two twins) were born; 97 (93.3%) infants were satisfactorily discharged home together with their mothers; 7 (6.7%), including four of the twins and other three babies after a premature birth, were transferred to the second nursing step. There were no maternal and perinatal deaths. Conclusion. Successful treatment and adequate management of pregnancy in this group of patients depends on the clear interaction of obstetricians/gynecologists, neurologists, neurosurgeons, anesthesiologists, and neonatologists. To optimize the management of pregnant women with CVD with the participation of a group of specialists makes it possible to safely increase the frequency of vaginal delivery in these patients.
Obstetrics and Gynecology. 2017;(8):50-58
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Specific features of redox reactions in the blood of women with physiological or complicated pregnancy

Skripnichenko Y.P., Pyataeva S.V., Volodina M.A., Tsvirkun D.V., Baranov I.I., Vysokikh M.Y., Kuzmich I.N.

Abstract

Much attention is now paid to investigations of of the processes of oxidative stress in pregnant women. An imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the function of the antioxidant system can lead to cell and tissue structural damage, by inducing various pathologic processes. During pregnancy, in both its normal and abnormal course, the total level of oxidative stress increases. In abnormal pregnancy, the formed ROS and RNS, which trigger a cascade of free radical reactions leading to the formation of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and nitrosyl derivatives (NDs), which serve as objective indicators of oxidative damage to proteins. Objective. To determine the level of the products of ROS, RNS, and antioxidant enzymes in the peripheral blood of pregnant women in different trimesters in the presence of preterm labor (PL), preeclampsia (PE), fetal growth restriction (FGR), and physiological pregnancy (PP). Subjects and methods. The course of pregnancy and the outcomes of labor were analyzed in 131 women from 4 groups. The level of oxidative stress was estimated from the blood concentrations of lipid peroxidation products, such as MDA and 4-HNE, protein peroxidation products, such as NDs, the content of the antioxidant enzymes glutathione peroxidase and superoxide dismutase, and the activity of catalase. Results. In physiological pregnancy, the levels of MDA and peroxynitrite adducts significantly increased. The PL group showed no significant differences in MDA levels between the trimesters. In this group, the level of NDs increased during the second trimester. The PE group displayed increased oxidative stress with pregnancy progression. In this group, the level of NDs rose in the second trimester. In the FGR group, the level of MDA increased with pregnancy progression in the presence of lower concentrations of NDs in the second trimester and their elevation in the third trimester. Comparison of the PL and PE groups with the PP group revealed significant increases in NDs and 4-HNE and decreases in glutathione peroxidase in the PL group and catalase activity in the PE activity. On the contrary, the catalase activity was higher in the FGR group than that in the PP group. Conclusion. The investigations confirmed increased oxidative stress levels during physiological pregnancy. The women with PE and those with PR were observed to have elevated blood levels of oxidative stress products in the presence of attenuation of the antioxidant systems. On the contrary, the women with FGR had enhanced activity of the antioxidant enzyme catalase, with a decline in NDs in the second trimester and its dramatic rise in the third trimester. The findings suggest that it is necessary to continue investigations of oxidative stress and activity of the antioxidant enzymes in both women with physiological pregnancy and those with abnormal pregnancy to create a shared understanding of normal and abnormal reactions.
Obstetrics and Gynecology. 2017;(8):60-66
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The course and outcomes of pregnancy in women with idiopathic recurrent miscarriage during immunocytic therapy

Saribegova V.A., Tetruashvili N.K., Krechetova L.V., Agadzhanova A.A., Vtorushina V.V.

Abstract

Pregravid preparation that can be done by different methods occupies a special place in the treatment of idiopathic recurrent miscarriage (RM). Objective. To assess the course and outcomes of pregnancies in women with idiopathic RM, whose pregravid preparation included immunocytic therapy (ICT). Subjects and methods. The investigation enrolled 127 women with RM. The pregravid preparation encompassed ICT as monotherapy (Group 1, n = 45) and that in combination with dydrogesterone (Group 2; n = 39). Group 3 (n = 23) consisted of women who received no pregravid preparation. Results. The investigation showed that the course of pregnancy was characterized by significantly fewer complications in women undergoing pregravid preparation. Preterm labor was more common in Group 3. The course and outcome of pregnancy did not differ in the groups of women receiving different types of pregravid preparation. Conclusion. The findings make it possible to recommend that ICT should be included in a pregravid preparation program for married couples with idiopathic RM.
Obstetrics and Gynecology. 2017;(8):68-73
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First-trimester prediction of preeclampsia: Validation of screening algorithms in a Russian population

Kholin A.M., Muminova K.T., Balashov I.S., Khodzhaeva Z.S., Borovikov P.I., Ivanets T.Y., Gus A.I.

Abstract

Objective. To make an external evaluation of the effectiveness of three published algorithms in the first-trimester prediction of preeclampsia (PE) in a prospective cohort study of a Russian population. Material and methods. Clinical and anamnestic factors, echographicparameters (uterine artery pulsatility index), and biochemical markers (PAPP-A, PlGF, and sFlt-1) during singleton pregnancies were prospectively analyzed during combined screening at 11-13 weeks’ gestation. After receiving information on pregnancy outcomes, the risks for early-onset (<34 weeks) or late-onset (≥34 weeks) PE were calculated using the algorithms proposed by Poon (2009), Parra-Cordero (2013), and Crovetto (2015). The effectiveness of predictive algorithms was compared with that presented in the original publications and evaluated for factors explaining the prediction differences. Results. Three algorithms for the prediction of both early- and late-onset PE were examined in 4000pregnant women. Labor was induced in 29 (0.7%) women before 34 weeks’ pregnancy due to early-onset PE and in 73 (1.8%) women after 34 weeks’ gestation due to late-onset PE. Gestational hypertension was diagnosed in 119 (2.9%) cases. The area under the ROC curve for early-onset PE tests was 0.79 (0.76-0.81), 0.69 (0.66-0.72), and 0.75 (0.72-0.78) and that for late-onset PE tests was 0.74 (0.71-0.77), 0.65 (0.62-0.68), and 0.66 (0.630.69). The sensitivity of tests for early-onset PE ranged from 31.6% to 57.8%; that of tests for late-onset PE was 25.5 to 37.2% with an overall false-positive rate of 10%. Conclusion. External validation of algorithms in the first-trimester prediction of PE in a Russian population has demonstrated the high negative predictive value of the sensitivity that is lower than stated in the original studies and, in general, the moderate effectiveness in the prediction of early-onset PE. There is a need for further investigations to determine the most optimal algorithms for predicting PE.
Obstetrics and Gynecology. 2017;(8):74-84
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Analysis of proand antioxidant activity in the blood of women with different phenotypes of polycystic ovary syndrome and infertility

Darenskaya M.A., Kolesnikov S.I., Grebenkina L.A., Danusevich I.N., Lazareva L.M., Nadelyaeva Y.G., Darzhaev Z.Y., Nikitina O.A., Bazarova T.A., Kolesnikova L.I.

Abstract

Objective. To reveal the specific features of the process of lipid peroxidation in reproductive-aged women with different phenotypes of polycystic ovary syndrome (PCOS). Subjects and methods. Forty-eight reproductive-aged women with PCOS and infertility were examined and divided into 2 subgroups according to the availability of criteria: 1) classical phenotypes; 2) non-classical phenotypes. Infertile women without PCOS (n = 31) and healthy women (n = 28) were used as comparison groups. Results. There were statistically significant differences in the examined parameters between the patients with different phenotypes of PCOS. At the same time, in the phenotype subgroups versus the controls and the infertile women without PCOS, the changes were mainly compensatory: slightly decreased superoxide dismutase activity and α-tocopherol concentrations and elevated retinol levels in the classical phenotype group and reduced levels of end thiobarbituric acid-reacting products of lipid peroxidation, increased a-tocopherol concentrations, and lower glutathione levels in the non-classical phenotype subgroup. Conclusion. In general, in PCOS, and in its classic hyperandrogenic phenotypes in particular, the changes in the lipid peroxidation processes are adaptive in nature, which allows one to recommend a personalized approach to combination treatment of this category of patients.
Obstetrics and Gynecology. 2017;(8):86-91
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Study of gene expressions in the eutopic endometrium of women with endometrioid ovarian cysts

Kuznetsova M.V., Pshenichnyuk E.Y., Burmenskaya O.V., Asaturova A.V., Trofimov D.Y., Adamyan L.V.

Abstract

Objective. To identify the genes, the expression of which in the eutopic proliferative endometrium differs in patients with endometrioid ovarian cysts (EOC) compared to that in the eutopic proliferative endometrium of women without endometriosis. Subjects and methods. Two patient groups (10 women with EOC (a study group) and 10 women without endometriosis (a control group)) were examined. All the patients underwent a full clinical-anamnestic examination: history data collection, general physical and gynecological examinations, pelvic ultrasonography, clinical and laboratory examination. Eutopic endometrial tissue pipelle biopsy specimens were obtained directly intraoperatively before hysteroscopy, with subsequent endometrectomy and histological examination. Total RNA was isolated from the specimens; an expression prof ile was subsequently obtained by microarray hybridization using the GeneChip Human Exon 1.0 ST Arrays (Affymetrix, USA) according to the manufacturer’s protocol. Results. The eutopic proliferative endometrium of the women with EOC (a study group) showed increased expression of 27 genes and decreased expression of 17 genes (the microarray measures the expression level of a total of 14318 transcripts) as compared with that from the women without endometriosis (a control group). All these genes are encountered in the works on eutopic endometrial expression; thus, our results are largely consistent with the published data, which makes these genes promising biomarkers for endometriosis. Conclusion. The obtained data on the increased expression of the FOS, EGR-1, FOSB, DUSP1, ZFP36, JUNB, and JUN genes in the eutopic proliferative endometrium of women with EOC agree with the results of previously published works, which makes these genes promising biomarkers to create real-time PCR-based diagnostic systems for the determination of mRNA levels in endometrial tissues.
Obstetrics and Gynecology. 2017;(8):93-102
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Results of preimplatation genetic screening of embryos in married couples with sperm DNA fragmentation

Kiseleva Y.Y., Azova M.M., Kodyleva T.A., Ushakova I.V., Kirillova A.O., Ekimov A.N., Rakitko A.S., Volodyaeva T.O., Mishieva N.G., Abubakirov A.N.

Abstract

Objective. To determine the frequency of aneuploidies (monosomies, trisomies, disomies, nullisomies) from all chromosomes, as well as DNA deletions and amplifications in the embryos from couples with higher and normal sperm nuclear DNA fragmentation levels. Subjects and methods. An array-based preimplatation genetic screening program was applied to 170 couples; each couple underwent estimation of sperm concentration, motility and morphology according to the 2010 WHO standards, as well as sperm nuclear DNA fragmentation levels by the TUNEL method. Results. A relationship was found between the level of paternal sperm DNA fragmentation and the frequency of obtaining embryos with a normal karyotype. With the increased level of DNA fragmentation, this figure is 47.96% vs 66.17% with its normal level (p < 0.02). There was also a substantially increased frequency of embryo DNA deletions and amplifications with a higher level of paternal sperm DNA fragmentation (35.89% vs 5.39% with its normal level; p < 0.001). Fragmentation does not have a statistically significant impact on abnormal chromosome number. Conclusion. This study has demonstrated a correlation between the level of paternal sperm DNA fragmentation and the frequency of structural karyotype abnormalities in embryos.
Obstetrics and Gynecology. 2017;(8):104-108
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Progesterone and reproductive losses

Radzinsky V.E., Ordiyants I.M., Pobedinskaya O.S., Zykov E.V.

Abstract

Objective. To evaluate the efficiency of incorporating the micronized progesterone pragisan into a package of measures to prevent and treat miscarriage during early pregnancy. Subjects and methods. The investigation enrolled 30 women who had received first trimester threatened miscarriage treatment and 32 patients with clinical signs of threatened miscarriage who had refused treatment for various reasons. Threatened miscarriage was diagnosed based on complaints and ultrasound diagnosis (shortening of the cervix and dilation of the internal os). Results. The incorporation of the micronized progesterone pragisan into a package of measures aimed at preserving and prolonging pregnancy showed its high efficacy in patients with threatened miscarriage. Pregnancy could be preserved and prolonged to full term by 29 out of the 30 women with threatened miscarriage in the pragisan group and by only 19 (59.4%) in the group of those who had refused treatment. The timely restoration of vaginal biocenosis was also shown to contribute to the normalization of the course of pregnancy. Conclusion. The pronounced clinical efficacy, convenient dosing, and no adverse reactions of pragisan suggest that the drug may be incotporated into a package of measures to treat threatened miscarriage.
Obstetrics and Gynecology. 2017;(8):109-114
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Role of hypothalamic (trigger) neuropeptides in the genesis of hot flushes. Prospects for new therapeutic approaches to treating vasomotor menopausal symptoms

Yureneva S.V., Ebzieva Z.K.

Abstract

Objective. To carry out a systematic analysis of the data available in the current literature on the impact of the neuropeptide regulation of the hypothalamic-pituitary-ovarian axis, which in conjunction with estrogen deficiency underlie the development of vasomotor menopausal manifestations. To determine a vector of new pharmacological approaches in the therapy of menopausal disorders, by taking into account the findings of these studies. Material and methods. The review includes the data of Russian and foreign articles published in the past 10 years and found in Medscape and Pubmed on this topic. Results. The paper describes the possible mechanisms for the involvement of hypothalamic neuronal triggers in the pathogenesis of hot flushes, as well as the varying effect of pharmacological agents in reducing the severity of vasomotor symptoms. It presents new pathogenetically sound approaches to therapy for vasomotor symptoms in the treatment of menopausal syndrome. Conclusion. There is a need for further investigations of the effect of novel medications on neuronal vasomotor triggers in the optimal therapy regimens for menopausal disorders.
Obstetrics and Gynecology. 2017;(8):115-120
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Surgical treatment for primary hyperparathyroidism in pregnancy: A clinical case

Ilyicheva E.A., Sinitsyn V.A., Chonskaya M.A., Rozhanskaya E.V.

Abstract

Background. Primary hyperparathyroidism is very rarely detected during pregnancy because of the paucity of clinical symptoms and the lack of its history. Medical management of hyperparathyroidism during pregnancy can lead to severe disorders in both the mother and the fetus. A case report. The paper gives the results of examination and treatment in a 31-year-old pregnant woman with a complicated obstetric history. Severe hypercalcemia (more than 3.5 mmol/l) resistant to medical therapy, a high parathyroid hormone level, and a tumor of the left parathyroid gland threw no doubt about the diagnosis. The patient underwent parathyroid adenomectomy with intraoperative monitoring of the time course of changes in intact parathyroid hormone, resulting in the recovery of the patient, carrying of a pregnancy, and birth of a healthy baby. Conclusion. The timely diagnosis and surgical correction of primary hyperparathyroidism in pregnancy is accompanied by elimination of the negative implications of the disease on the course of pregnancy and childbirth.
Obstetrics and Gynecology. 2017;(8):121-124
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The health status of a baby born to a heart transplant woman: A dinical case

Shatalova E.A., Zubkov V.V., Kravchenko N.F., Vanko L.V., Ionov O.V., Ryumina I.I., Degtyareva A.V.

Abstract

Background. The number of pregnancies following solid organ transplantation is increasing all over the world. There are now few articles in the literature on the health status of babies born to mothers with transplanted organs. A case report. The paper presents a clinical observation of the health status of an infant born to a heart transplant patient at his birth and at the age of 5 years, whose prenatal development proceeded during maternal use of azathioprine and tacrolimus. Complex clinical and laboratory examination did not reveal gross malformations in the baby. His severe status at birth and during neonatal period is due to prematurity, congenital pneumonia, and birth asphyxia. Conclusion. The pregnancy outcomes may be favorable in women after heart transplantation. The given clinical case shows the absence of gross malformation in the child and the correspondence of his psycho-motor and physical development with age. However, there is a need for investigations using a larger sample of infants born to mothers with transplanted organs in order to elaborate tactics of their management in the neonatal period and at an older age.
Obstetrics and Gynecology. 2017;(8):126-131
pages 126-131 views

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