Streptococcus mutans in the oral cavity as a risk factor for threatened miscarriage.

OBJECTIVES: The aim of this study was to investigate the bacterial colonization of the oral and vaginal ecosystem in pregnant women during the first trimester of pregnancy. MATERIAL AND METHODS: We analyzed 162 pregnant women, (99 women with threatened abortion and 63 women with healthy pregnancies). We collected oral and vaginal swabs, using PCR analysis to assess the presence of various bacteria (S. mutans, E. faecalis, E. coli, Lactobacillus acidophilus, Prevotella intermedia, Gardnerella vaginalis, S. agalactiae). RESULTS: Results showed that the presence of Streptococcus mutans in the oral cavity was significantly more common in women with threatened abortion compared to those with healthy pregnancies (p = 0.046). The presence of Lactobacillus acidophilus in the vagina was significantly more common in women with healthy pregnancies (p = 0.041). CONCLUSIONS: Our study suggests that the presence of Streptococcus mutans in the oral cavity may be a risk factor for threatened abortion.

Perinatal palliative care for family with prenatal diagnosis of Matthew-Wood syndrome.

Matthew-Wood syndrome (MWS) is a rare autosomal recessive disorder caused by pathogenic variants of the STRA6 gene. Several studies in the available literature comprise patients with pathogenic variants of gene STRA6 with various phenotypic expressions: from lethal forms of MWS to non-lethal anophthalmia. These reports mainly describe new pathogenic variants and phenotypic expression but do not describe medical or paramedical care for the affected families. In our case report, we describe the second case of MWS in the same family and the benefits of including the patient's family in the perinatal palliative care program. The first pregnancy was terminated with a cesarean section; the boy was intubated in the delivery room and died soon after. The mother was not allowed to say farewell or keep any remembrances of her child. In the second pregnancy, the family was involved in the perinatal palliative care program, and all paramedical aspects, crucial from the parent's perspective, were planned and implemented. Palliative perinatal care enables complex care for the pregnant woman and her family. The possibility of palliative perinatal care is significant in decision-making in families with a high risk of lethal disease in subsequent pregnancies.

The impact of the COVID-19 pandemic on the course of miscarriages.

OBJECTIVES: Miscarriage is the most common complication of pregnancy. Infections are well-known causes of pregnancy loss. It has been suggested that infection with SARS-CoV-2 virus may also have an adverse effect on the course of early pregnancy, causing miscarriage. AIM: To assess the impact of the COVID-19 pandemic on pregnancy loss during the first half of pregnancy. MATERIAL AND METHODS: The clinical records of patients hospitalized at the Department of Fetal Medicine and Gynecology; Medical University of Lodz were retrospectively reviewed. The study was done during the pandemic (March 2020 to the end of March 2022) and the previous 2 years due to missed abortion, indicated by no fetal heartbeat and spontaneous (complete or incomplete) abortion with vaginal bleeding. RESULTS: While 682 women were hospitalized due to miscarriage in the first half of pregnancy in the period 2018-2020, there were 516 hospitalized during the pandemic. No differences in the proportion of missed and spontaneous abortions with bleeding were found between the group of patients before and during the epidemic SARS CoV-2. COVID-19 exposure appears to have an impact on earlier pregnancy loss. CONCLUSIONS: There is no evidence that the COVID-19 pandemic predisposes to the abnormal course of pregnancy in its first half. OBJECTIVES: Miscarriage is the most common complication of pregnancy. Infections are well-known causes of pregnancy loss. It has been suggested that infection with SARS-CoV-2 virus may also have an adverse effect on the course of early pregnancy, causing miscarriage. AIM: To assess the impact of the COVID-19 pandemic on pregnancy loss during the first half of pregnancy. MATERIAL AND METHODS: The clinical records of patients hospitalized at the Department of Fetal Medicine and Gynecology; Medical University of Lodz were retrospectively reviewed. The study was done during the pandemic (March 2020 to the end of March 2022) and the previous 2 years due to missed abortion, indicated by no fetal heartbeat and spontaneous (complete or incomplete) abortion with vaginal bleeding. RESULTS: While 682 women were hospitalized due to miscarriage in the first half of pregnancy in the period 2018-2020, there were 516 hospitalized during the pandemic. No differences in the proportion of missed and spontaneous abortions with bleeding were found between the group of patients before and during the epidemic SARS CoV-2. COVID-19 exposure appears to have an impact on earlier pregnancy loss. CONCLUSIONS: There is no evidence that the COVID-19 pandemic predisposes to the abnormal course of pregnancy in its first half.

Prenatal karyotype results from 2169 invasive tests.

OBJECTIVES: Foetal karyotyping is a basic tool used to diagnose the most common genetic syndromes. Although new molecular methods such as FISH, MLPA or QF-PCR allow rapid prenatal testing, they are of limited value when diagnosing less frequent chromosomal abnormalities. Chromosomal microarray analysis offers higher test resolution than traditional karyotyping and has been recommended as first-line genetic testing in prenatal diagnosis. The aim of the study was to confirm whether foetal karyotyping remains a valid approach to prenatal diagnosis by analysing its performance in a large population of pregnant women with a high risk of chromosomal aberration. MATERIAL AND METHODS: An analysis was performed of 2169 foetal karyotypes from two referral university centres for prenatal diagnostics in Lodz, Poland. RESULTS: Amniocentesis and foetal karyotyping were performed when screening methods had indicated a high risk of chromosomal aberration, or when prenatal ultrasound had proved foetal abnormality. The study group included 205 (9.4%) abnormal foetal karyotypes. Rare aberrations were observed in 34 cases (e.g., translocations, inversions, deletions and duplication). A marker chromosome was present in five cases. CONCLUSIONS: One third of the chromosomal abnormalities observed in the prenatal tests were rarer aberrations (i.e., not trisomy 21, 18 or 13). As many of these could not be detected by the new molecular methods, foetal karyotyping remains an important component of prenatal diagnosis.

Cases of tetrasomy 9p and trisomy 9p in prenatal diagnosis-Analysis of noninvasive and invasive test results.

Objective: Tetrasomy 9p and trisomy 9p are rare chromosomal aberrations. The phenotypes of tetrasomy 9p and trisomy 9p are variable. Most cases are diagnosed in the postnatal period. The study aims to analyze the prenatal phenotype of tetrasomy 9p and trisomy 9p in terms of ultrasound and screening tests. Methods: A set of 1573 prenatal tests performed from 2016 to 2021 was reviewed to identify all cases with trisomy 9p and tetrasomy 9p. In four cases with 9p gain, non-invasive and invasive test results were analyzed. Results: Four cases with the 9p gain were diagnosed in the prenatal period: two cases with tetrasomy 9p and two cases with trisomy 9p. Nasal bone hypoplasia and ventriculomegaly are common features of 9p gain. In two out of four cases with the 9p gain, an increased risk of trisomy 21 was found in the combined first-trimester screening test. Conclusion: Trisomy 9p and tetrasomy 9p are characterized by a variable phenotype in the prenatal period, manifesting in genetically abnormal fetuses. The tetrasomy 9p and trisomy 9p may suggest trisomy 21 in the first trimester.

Prenatal Sonographic Features of Rare Chromosome 13 Aberrations.

Objective: Trisomy 13 is one of the most common chromosome aberrations diagnosed in the prenatal period, and is associated with some specific dysmorphic features. Rare chromosome 13 aberrations other than trisomy 13 may cause other fetal abnormalities. The aim of the study was to analyze cases with those rare chromosome 13 aberrations. Methods: We analyzed all prenatal tests performed in the Department of Clinical Genetics of the Medical University of Lodz from 2016 to 2021 to find all chromosome 13 aberrations. Results: The most common aberration of chromosome 13 was a simple trisomy 13 (n = 16). We found five rare chromosome 13 aberrations other than simple chromosome 13 trisomy: mosaic trisomy 13 mos 47,XX,+13[11]/46,XX[10], mosaic monosomy 13 mos 46,XY,-13,+mar[9]/46,XY[31], duplication 13q21.1-q31, deletion 13q34 and deletion 13q31.1-q34. The deletion 13q31.1-q34 occurred in monochorionic diamniotic twin pregnancy. Conclusion: Rare aberrations accounted for 24% of all chromosome 13 aberrations. Cases with mosaic monosomy of chromosome 13 and microdeletion 13q had similar abnormalities of the external genitalia and facial dysmorphia. The case with duplication 13q was very similar to the clinical features of chromosome 13 trisomy. Mosaic trisomy 13 can occur without any accompanying anatomical defects.

Fetal Nasal Bone Hypoplasia in the Second Trimester as a Marker of Multiple Genetic Syndromes.

Nasal bone hypoplasia is associated with a trisomy of chromosome 21, 18 or 13. Nasal bone hypoplasia can also be seen in other, rarer genetic syndromes. The aim of the study was to evaluate the potential of nasal bone hypoplasia, in the second trimester of pregnancy, as a marker of fetal facial dysmorphism, associated with pathogenic copy number variation (CNV). This retrospective analysis of the invasive tests results in fetuses with nasal bone hypoplasia, after excluding those with trisomy 21, 18 and 13. In total, 60 cases with nasal bone hypoplasia were analyzed. Chromosomal aberrations were found in 7.1% of cases of isolated nasal bone hypoplasia, and in 57% of cases of nasal bone hypoplasia with additional malformations. Additionally, in four of nine cases with non-isolated nasal bone hypoplasia but normal CMA results, a monogenic disease was diagnosed. Non-isolated hypoplastic nasal bone appears to be an effective objective marker of fetal facial dysmorphism, associated with pathogenic CNVs or monogenic diseases. In isolated cases, chromosomal microarray testing can be of additional value if invasive testing is performed, e.g., for aneuploidy testing after appropriate counseling.

Occurrence of c.976 G>T (p.Val326Leu) and c.452 G>A (p.Trp151Ter) variants in DHCR7 gene in population of polish women with recurrent miscarriage.

INTRODUCTION: Recurrent miscarriage is a serious clinical problem that affects 1-5 % of all couples trying to conceive. Although the incidence of Smith-Lemli-Opitz Syndrome (SLOS, OMIM #270400), an autosomal recessive condition caused by variants in the DHCR7 gene, is very low, (1:83 000), the observed carrier frequency of DHCR7 gene variants in the Polish population is high, ranging from 1:24 to 1:31. It is possible that this carriage may be responsible for early pregnancy loss. OBJECTIVES: The aim of the study is to determine the carrier frequency of the p c.976 G>T (p.Val326Leu) and c.452 G>A (p.Trp151Ter) variants in the DHCR7 gene in patients experiencing recurrent miscarriage. METHODS: The study group included 480 patients: a study group of 380 with at least 2 miscarriages before the 20th week of pregnancy, and a control group of 100 who had not experienced miscarriage. The variants were identified by genotyping: c.976 G>T (p.Val326Leu) by the TaqMan® SNP Genotyping Assay system, and c.452 G>A (p.Trp151Ter) using the BfaI restriction enzyme. Statistical analysis was performed using R software. RESULTS: No examples of c.976 G>T (p.Val326Leu) were found in either group. c.452 G>A (p.Trp151Ter) was found in 22 participants from the study group and 4 from the control group; however, this difference was not significant (Chi2 test p = 0.61). CONCLUSIONS: Being a carrier of the c.976 G>T (p.Val326Leu) and c.452 G>A (p.Trp151Ter) variants in theDHCR7 gene is not a risk factor for recurrent miscarriage in the Polish population.

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study.

INTRODUCTION: Multifactorial pathogenesis of diabetic kidney disease (DKD) consists of a combination of metabolic, environmental, and genetic factors. A genome-wide association study has shown that ELMO1 is a candidate gene for DKD occurrence and progression. The aim of this study was to assess the association of a single nucleotide polymorphism (rs741301) of the ELMO1 gene with DKD in Polish patients with type 2 diabetes (T2DM). MATERIAL AND METHODS: This was a case/control study of 272 T2DM patients with or without DKD. Patients were divided into groups depending on DKD definition according to the American Diabetes Association (ADA) and the National Kidney Foundation (NKF). The association of the rs741301 polymorphism with DKD was assessed in the whole study group as well as in the subgroups stratified according to the presence of DKD. RESULTS: There was no association between rs741301 polymorphisms and the presence of DKD in relation to the ADA definition (p = 0.6) or the NKF definition (p = 0.5) of DKD and with estimated glomelural filtration rate (eGFR) value reflecting the stage of the chronic kidney disease (p = 0.8). CONCLUSIONS: Even though the results of this study are negative, there is still a great need for larger studies assessing the genetic susceptibility to DKD to identify patients who are particularly prone to this complication.

Conservative treatment of abnormally located intrauterine pregnancies (cervical and cesarean scar pregnancies): a multicenter analysis (Polish series).

Objectives: To analyze the effectiveness and outcome of conservative treatment in cases of abnormally located intrauterine pregnancies (cervical and cesarean scar).Study design: A retrospective analysis was performed of 30 pregnant women hospitalized due to abnormally located intrauterine pregnancies. The analyzed group comprised 24 pregnant women with abnormally located pregnancies. The patients were divided into two groups: the first group consisted of patients treated systemically with methotrexate, while the second of those treated locally by administration of methotrexate (MTX) and/or potassium chloride (KCl) by gestational sac puncture.Results: The analyzed group comprised 24 pregnant women with abnormally located pregnancies. Eight patients were diagnosed with cervical pregnancy (CP) and 16 patients were diagnosed with cesarean scar pregnancy (CSP). Six patients were excluded from the study: two with spontaneous abortions, two heterotopic pregnancies, and two cornual pregnancies. Twelve analyzed patients underwent MTX systemic administration (five patients with CP, seven with CSP). In five patients, systemic treatment was ineffective; they were qualified for additional local therapy with gestational sac (GS) puncture and MTX or KCl administration to the sac and additional administration of MTX to the trophoblast area. In second group of 12 patients (three CP, nine CSP), local treatment (GS puncture with MTX or MTX + KCl) was used as the first line treatment. One patient underwent combined treatment (local + systemic).Conclusions: Conservative treatment should be the gold standard procedure in abnormally located intrauterine pregnancies. It is noticeable that MTX / KCl is more effective in a direct administration to the GS. In four cases, systemic MTX did not produce the desired effects. In these cases, the treatment was assisted by local administration of MTX or KCl, resulting in the termination of an abnormally located pregnancy.

The absence of fetal nasal bones in ultrasound examination between 11 + 0 and 13 + 6 weeks of gestation versus the occurrence of trisomies 21, 18, and 13.

OBJECTIVES: One part of the ultrasound examination of fetuses in the first trimester of gestation is visualization of the nasal bones. Numerous studies have demonstrated a correlation between the absence of nasal bones and abnormal fetal karyotype. AIM: To assess the utility of ultrasound visualization of nasal bones during the first trimester of pregnancy as a marker of the most common chromosomal trisomies. MATERIAL AND METHODS: Ultrasound visualization of nasal bones was carried out in 941 fetuses from a high-risk group between 11 + 0 and 13 + 6 weeks of gestation. Amniocentesis was performed to determine karyotype in all 941 cases. RESULTS: Normal fetal karyotype was observed in 847 cases, trisomy 21 in 45 cases, trisomy 18 in 16 cases and trisomy 13 in 10 cases. Other abnormal karyotypes were detected in the remaining 23 cases. The absence of nasal bones demonstrated 27% sensitivity, 97% specificity and a positive predictive value of 35% as an indicator of trisomy 21 in the study group, and 12% sensitivity, 97% specificity and 12% positive predictive value for trisomies 18 and 13. CONCLUSIONS: The absence of nasal bones in ultrasound examination in the first trimester of pregnancy is characterized by low sensitivity and high specificity as a marker of the most common trisomies. Visualization of fetal nasal bone is a poor marker of aneuploidy and should not be taken into account in risk calculation algorithms.

Influence of human Papilloma Virus (hPV) infection on early pregnancy.

OBJECTIVES: HPV infection in early pregnancy may be a cause of miscarriage. Pregnancy significantly increases the risk of HPV infection. While ascending intrauterine infection with colonization of the trophoblast is commonly observed, descend- ing hematogenous infection should also be considered. The aim of the study is to assess the prevalence of HPV infection and its influence on pregnancy. MATERIAL AND METHODS: The study was conducted in the years 2010-2015 on a group of 143 pregnant women. The study group consisted of 84 women with abnormal course of the first trimester of pregnancy. The control group consisted of 59 women with normal pregnancy who delivered healthy neonates. Samples of cervix tissue along with samples of tropho- blast or placenta were taken for the study. The presence and genotype of the HPV virus were detected using a BIOTOOL B&M Labs set. Statistical analysis was conducted using R software. RESULTS: The rate of HPV infection in the entire studied population was 13% (19/143): the virus was confirmed in 18% (15/84) of patients in the study group and in 7% (4/59) of the control group. HR HPV was detected in 13 patients in the study group and three patients in the control group. HR HPV infection was more frequent in patients with an abnormal course of the first trimester of pregnancy (p = 0.03). HR HPV trophoblast infection was found only in patients in the study group (p = 0.02). In two members of the study group, the HPV virus was found in the trophoblast only. CONCLUSIONS: The obtained results may confirm the presence of adverse effects of HPV infection on early pregnancy. HR HPV trophoblast infection was observed only in women with 1st trimester complications. The presence of HPV only in trophoblast samples in some patients may suggest a descending - hematogenous route of primary infection.

Cell-free fetal DNA testing in prenatal diagnosis: Recommendations of the Polish Gynecological Society and the Polish Human Genetics Society.

This paper contains a joint position of the Polish Gynecological Society and Polish Human Genetics Society on the cell-free fetal DNA testing in prenatal diagnosis. We present situations where the cell-free fetal DNA testing should be applied and cases in which performing of the test is not useful. We indicate what diagnostic steps should be performed before the test and how the test results should be interpreted and followed.

Genetic causes of recurrent miscarriages.

Recurrent miscarriage is an important problem in reproductive health, which affects 1-5% of couples. The aim of this article is to summarize current knowledge on the genetic causes of recurrent miscarriage. It presents the most common parental genetic disorders (karyotype abnormalities, recessive diseases carrier status, dominant diseases and thrombophilia) connected with recurrent pregnancy loss, as well as research into other possible genetic causes. This review also sets out to demonstrate changes in the embryonic/fetal genome that may lead to abortions, and discusses the methods used to assess miscarried material, together with their advantages and disadvantages. Knowledge of the genetic background of miscarriages is important for prognosis, as well as the potential planning of prenatal diagnostics in subsequent pregnancies.

A novel mutation (c.T3816 > C) in the androgen receptor gene in a 46,XY female patient with androgen insensitivity syndrome.

INTRODUCTION: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD), and are associated with a variety of phenotypes ranging from phenotypic women (Complete Androgen Insensitivity Syndrome or CAIS) to milder degrees of undervirilisation (Partial Androgen Insensitivity Syndrome or PAIS) or men with infertility only (Mild Androgen Insensitivity Syndrome or MAIS). In this paper, we present the results of clinical, endocrine and molecular trials in a patient hospitalised because of primary amenorrhoea with typical phenotype of CAIS. MATERIAL AND METHODS: The main objective of this study was to determine the molecular cause of androgen insensitivity syndrome in a 46,XY female patient. Molecular analysis of the AR gene was conducted using MSSCP (Multitemperature Single Strand Conformation Polymorphism) and sequencing methods. RESULTS: MSSCP analysis showed changes in electrophoretic mobility in exon 8 of the AR gene. Sequencing analysis revealed a missense mutation which has not been previously described. This is a c.T3816 > C transition mutation which causes a S901P substitution in the amino acid chain (based on the latest NCBI reference sequence NM 000044.2). CONCLUSIONS: The identified c.T3816 > C mutation in AR gene provides further evidence for the correlation between specific AR mutations and phenotype corresponding to androgen insensitivity.

Ultrasound and echocardiographic findings obtained in the second and third trimesters of gestation in fetuses with normal karyotype and increased nuchal translucency.

INTRODUCTION: Numerous papers have proven that an increased nuchal translucency is connected with a raised risk of chromosomal aberrations, but few analyses are related to the further state of fetuses with a normal karyotype. THE AIM OF THE STUDY: The aim of the study was to estimate the risk of cardiac defects and other developmental disorders in fetuses with increased nuchal translucency and normal findings of a standard cytogenetic examination. METHODS: The authors carried out a retrospective analysis of 5183 examinations of 3376 patients who reported to the Department of Diagnosis and Prophylaxis of Congenital Malformations in the Polish Mother's Memorial Hospital in Lódz in the period from January 2008 to March 2011 for prenatal ultrasound and echocardiographic examinations. The authors analyzed the results of the examinations performed in the second and third trimesters of gestation in fetuses with an increased nuchal translucency of ≥3 mm in the first trimester and with a normal karyotype. RESULTS: Fifty-seven patients (1.7% of the examined group) fulfilled the criteria necessary to be included in the study. In 31 pregnant women (54%) structural defects or anomalies of the fetus were found. Cardiac anomalies were detected in 17 fetuses (29.8%). The authors detected various types of cardiac defects such as tetralogy of Fallot, ventricular septal defect, atrioventricular septal defect, transposition of the great arteries and hypoplastic left heart syndrome. CONCLUSIONS: In more than half of the fetuses with an increased nuchal translucency (NT ≥ 3 mm) and a normal karyotype, developmental defects of various organs appeared in the further course of pregnancy: mainly heart defects that were either isolated, or accompanied other anomalies.