The significance of rare chromosomal abnormalities and fetoplacental mosaicism in prenatal diagnosis in the non-invasive prenatal testing era / A ritka kromoszóma-rendellenességek és a fetoplacentaris mozaikosság jelentosége a praenatalis diagnosztikában a nem invazív szurovizsgálatok tükrében.

Összefoglaló. Bevezetés és célkituzés: A gyakori autoszomális trisomiák és a nemi kromoszómaeltérések a mikroszkóppal észlelheto kromoszóma-rendellenességek kb. 80-85%-át képviselik. A ritka kromoszóma-rendellenességek klinikai következménye jelentos, kimutatásukat a jelenlegi szurovizsgálatok ugyan nem célozzák, de a teljes kromoszómaszerelvényt vizsgáló, nem invazív praenatalis tesztelés új lehetoséget nyitott a korai felismerésükre. Módszer: Retrospektív analízis (2014-2019) a mikroszkóppal kimutatható kromoszóma-rendellenességek eloszlására, a fetoplacentaris mozaikosság elofordulására, klinikai összefüggéseire a praenatalis vizsgálatok tükrében egy hazai tercier centrumban. Eredmények: 2504 invazív beavatkozást végeztünk és 200 kromoszómaeltérést mutattunk ki (8%), melyek közül újonnan kialakult, ritka rendellenesség 27 volt (13,5%). Ritka autoszomális trisomia 14, poliploidia 6, de novo szerkezeti kromoszómaeltérés 5, marker kromoszóma 2 esetben igazolódott. A fetoplacentaris mozaikosság aránya a gyakori/ritka kromoszómaeltérésekben 12,4%/77,8% volt (p = 0,001), 17/40 esetben lepényre korlátozódott. A gyakori trisomiákkal kóros tarkóredo-vastagság 58%-ban, major ultrahangeltérés 35%-ban társult, melyek jelentosen különböztek a ritka kromoszómaeltérésekben (11%, p = 0,006; 67%, p = 0,047). A ritka kromoszómaeltérések jellemzo praenatalis major ultrahangeltérése a facialis dysmorphismus volt. A teljes kromoszómaszerelvényt vizsgáló praenatalis tesztelés a ritka kromoszómaeltérések 12 lepényi mozaikos esetében (44%) feltételezhetoen álpozitív, 1 esetben (3,7%) álnegatív eredményt generált volna, miközben a ritka autoszomális trisomiák 2 esetében ultrahangeltérés nélkül is korán detektálta volna a ritka magzati kromoszómaeltérést (7,4%). Következtetés: A normális tarkóredo-vastagság esetén észlelt major ultrahangeltérések felhívhatják a figyelmet a döntoen mozaikos ritka kromoszóma-rendellenességekre. A teljes kromoszómaszerelvényt vizsgáló, nem invazív szuroteszt a korai diagnosztika alternatívája lehet, a mozaikosságból adódó álpozitív eredményekre azonban számítani kell. A fetoplacentaris mozaikosság ismerete fontos klinikai információt biztosít, mely befolyásolhatja a terhesség kimenetelét, a terhesség követésének módját. A pontos citogenetikai karakterizálás elengedhetetlen. Orv Hetil. 2021; 162(29): 1156-1165. INTRODUCTION AND OBJECTIVE: To determine the prevalence of microscopically visible de novo atypical chromosomal aberrations and fetoplacental mosaicism in a prenatal tertial referral center, and to investigate the maternal and fetal characteristics in connection with genomewide non-invasive prenatal screening. METHOD: Retrospective cohort study from 2014 to 2019 of pregnancies with invasive genetic analysis. RESULTS: In the cohort of 2504 cases, the proportion of CVS was 53.3%. We diagnosed 200 chromosomal aberrations (8%), including 13.5% of de novo rare chromosomal aberrations (14 rare autosomal trisomies, 6 polyploidies, 5 structural aberrations and 2 small supernumerary marker chromosomes). The rate of fetoplacental mosaicism was 12.4%/77.8% in common/atypical chromosomal aberrations (p = 0.001) and confined to placenta in 17/40 cases. Associated ultrasound abnormalities were abnormal nuchal translucency and major malformations in 58% and 35% with common trisomies and 11% (p = 0.006) and 67% (p = 0.047) with true mosaic cases of rare abnormalities, respectively. Major ultrasound malformation was facial dysmorphism with rare aberrations. Potential application of genomewide non-invasive prenatal test in atypical chromosomal aberrations presumably would have been false-positive in 12 cases (44%), false-negative in 1 case (3.7%), and would have early detected 2 cases of rare autosomal trisomies (7.4%) without ultrasound anomalies. CONCLUSION: Structural ultrasound malformations with normal nuchal translucency thickness may be indicative of rare chromosomal aberrations. Application of genomewide non-invasive prenatal test is an alternative of early diagnostic methods with a potential of discordant results due to mosaicism. Knowledge about the presence of fetoplacental mosaicism influences risk estimation and genetic counseling, detailed cytogenetic characterization is of utmost importance. Orv Hetil. 2021; 162(29): 1156-1165.

[The relationship between inflammatory and immunological processes during pregnancy. Practical aspects]. / A gyulladásos és immunológiai folyamatok kapcsolata a várandósság alatt. Gyakorlati vonatkozások.

The aim of this review is to explore, in addition to revealing the biological background, new conceptual and therapeutic approaches for reproductive clinicians to provide better and more effective care for sterile and infertile couples. In humans, 75% of unsuccessful pregnancies are the result of failures of implantation, and implantation failure is the limiting factor for in vitro fertilization treatment. A modified "good" inflammation is necessary for implantation and parturition, but for most of pregnancy, inflammation threatens the continuation of pregnancy. During this period, maintaining the non-inflammatory condition is extremely important, enabling the maternal epigenetic effects to occur in the fetus, making it possible for the offspring to adapt as much as possible to the extrauterine life. In the maintenance of the non-inflammatory condition of pregnancy, a large amount of progesterone hormone produced by the placenta (after the luteo-placental shift) plays a crucial role. It has been reported that the role of inflammation during implantation is an ancestral response to the embryo as a foreign body. During normal pregnancy, this inflammation is initiated by the trophoblast and involves the suppression of neutrophil infiltration, the recruitment of natural killer cells to the site of implantation as well as the production of a range of proinflammatory cytokines. During the "implantation window", the uterus is primed to produce several inflammatory signals such as prostaglandin E2 and a range of proinflammatory cytokines, including TNF, IL6 and IFNγ. The feto-placental unit is a semi-foreign graft called a "semi allograft", and the recognition of pregnancy by the mother (host) and the resulting maternal immune tolerance is an essential part of successful pregnancy and the birth of a healthy fetus. Because of the functional or absolute reduction of circulating progesterone (due to the decreasing hormone production of the physiologically "aging" placenta after around the 36th week of pregnancy) progesterone effects become insufficient. Therefore it is unable to suppress the production of IL8 and other inflammatory cytokines and the term inflammation, leading to cervical ripening, uterus contractions and parturition ("good" inflammation). Orv Hetil. 2019; 160(32): 1247-1259.

Ultrasonography of sciatic nerve endometriosis.

INTRODUCTION: We describe the ultrasonographic findings of sciatic nerve endometriosis. METHODS: Two premenopausal women with catamenial sciatica symptoms were examined, the first without a history of endometriosis, the second with previously confirmed endometriosis of the ovary. Ultrasonography, extending from the sciatic notch to the level of the ischial tuberosity showed that the sciatic nerve was "engulfed" in a large, perineural, hypoechogenic, inhomogeneous lesion with an irregular contour corresponding to an endometrioma. The nerve was enlarged, but it was discernible within the lesion, except at its most cranial part. MRI of the pelvis showed intrapelvic extension in both patients. RESULTS: The first patient was treated with a gonadotropin-releasing hormone agonist, leading to complete morphological regression and normalization of nerve structure, parallel with symptomatic resolution. CONCLUSIONS: These cases illustrate that ultrasound is a feasible imaging modality for sciatic nerve endometriosis that may even be used to monitor morphological regression of endometrial tissue during treatment. Muscle Nerve 54: 500-505, 2016.

Maternal factors in the origin of isolated anorectal malformations - a population-based case-control study.

OBJECTIVE: In most patients affected by isolated anorectal malformation (IARM), the etiology is unknown. Thus, the aim of this study was to analyze the possible role of maternal risk factors in the origin of IARM. METHODS: The study samples included 231 cases with IARM, 361 matched and 38 151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Cases with IARM were evaluated in the function of maternal diseases and related drug use. RESULTS: The findings of this case-control study suggested that cases with IARM have an obvious male excess. The mothers of cases with IARM had a lower incidence of severe nausea and vomiting in pregnancy and a higher incidence of acute infectious diseases in the urinary tract. CONCLUSIONS: Lack of nausea and vomiting in pregnancy and the higher incidence of urinary tract infections may have a role in the development of IARM.

Maternal factors in the origin of infantile hypertrophic pyloric stenosis: A population-based case-control study.

In most patients affected by isolated infantile hypertrophic pyloric stenosis (IHPS) the etiology is largely unknown. Thus, the aim of this study was to estimate possible maternal risk factors in the origin of IHPS. The study samples included 241 cases with IHPS, 357 matched controls and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Exposures that had been medically recorded in prenatal maternity logbooks during the critical period of IHPS were evaluated separately. The findings of this case-control study suggested that--beyond the well-known robust male excess (85.5%)--maternal hyperthyroidism (OR with 95% CI: 4.17, 1.53-11.38) and oral nalidixic acid treatment (OR with 95% CI: 6.53, 3.03-14.06) associated with a higher risk for IHPS in their children. In conclusion, our findings suggest that cases with IHPS had mothers with a higher proportion of hyperthyroidism and nalidixic acid treatment during pregnancy.

Birth outcomes of patients with isolated anorectal malformations: A population-based case-control study.

In most patients affected by isolated anorectal malformation (IARM) the etiology is largely unknown. Thus, the aim of our project was to analyze possible risk factors for IARM. In the first step, birth outcomes of cases with IARM were analyzed on the basis of maternal socio-demographic variables, and these data are presented in this paper. Gestational age at delivery, birthweight, preterm birth, low birthweight and small for gestational age of cases with IARM were evaluated in the function of maternal age, birth/pregnancy order, marital and employment status of mothers in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. The study samples included 231 live-born cases with IARM, 361 matched and 38 151 population controls without any defect. IARMs are more frequent in males, twins and newborn infants with low birthweight and small-for-gestational-age, the latter being the consequence of intrauterine growth restriction. In addition, mothers of cases were younger but with higher birth order, and had lower socio-economic status. These maternal variables are characteristic for the gypsy population in Hungary. The higher proportion of gypsy women among the mothers of cases with IARM was confirmed during the home visits of the study. Male sex and intrauterine growth restriction of cases, in addition to low socioeconomic status and gypsy origin of mothers may have a role in the risk of IARMs.

Birth outcomes of male and female patients with infantile hypertrophic pyloric stenosis--a population-based case-control study.

OBJECTIVE: Most of the patients are affected by isolated infantile hypertrophic pyloric stenosis (IHPS) beyond the polygenic predisposition, the other factors in the multifactorial etiology are largely unknown. The main characteristic of IHPS is the robust male predominance, thus the aim of this study was to analyze birth outcomes in males and females whether they are different or not. METHODS: The study samples included 241 cases with IHPS, 357 matched, and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. RESULTS: The findings of this case-control study confirmed the well-known strong male excess (85.5%). The mean gestational age was somewhat longer and it is associated with a lower rate of preterm births. Mean birth weight did not show significant differences among the study groups, but the rate of low birthweight was higher in cases with IHPS. However, these differences were found only in males. Thus, intrauterine fetal growth restriction is characteristic only for male cases with IHPS. CONCLUSIONS: Our study confirmed the well-known obvious male excess of cases with IHPS, but our findings suggest some differences in birth outcomes of male and female cases. Male cases with IHPS had intrauterine fetal growth restriction while females did not. These data may indicate some differences in the pathogenesis of IHPS in males and females.

Maternal factors in the origin of isolated oesophageal atresia: A population-based case-control study.

BACKGROUND: In most patients affected by isolated oesophageal atresia (IOA) the etiology is largely unknown. Thus, the aim of this study was to analyze potential risk factors in mothers. METHODS: The study samples included 221 cases with IOA, 356 matched and 38,151 population controls without any defect in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996. Only those exposures were evaluated that were medically recorded in prenatal maternity logbooks during the critical period of IOA. RESULTS: The findings of this case-control study suggested that the mothers of cases with IOA had a higher proportion of first delivery and lower socioeconomic status. Acute respiratory diseases (odds ratio [OR] 95% confidence interval [CI], 3.8, 1.8-8.1) and essential hypertension treated with nifedipine (OR 95% CI, 3.8, 1.7-8.7) in the mothers of cases associated with a higher risk for IOA in their children. CONCLUSION: First delivery, lower socioeconomic status, acute respiratory diseases and essential hypertension treated with nifedipine in the mothers may associate with a higher risk for IOA in their children.

The effects of remifemin on subjective symptoms of menopause.

The authors studied the changes in subjective symptoms of menopause in 2016 Hungarian women who had been treated with an isopropanol extract of Cimicifuga racemosa (black cohosh). The inclusion criteria were age (40-65 y). Kupperman index (20), and refusal or contraindication for estrogen therapy. The severity of the symptoms was evaluated at the start of the study and at the end of 4, 8, and 12 weeks of treatment. The average decrease in Kupperman index after 12 weeks of therapy was 17.64 points (P<.001). Based on the weighted symptom scores, the most favorable changes were found in hot flashes (-6.31 points), sweating (-2.86 points), insomnia (-2.27 points), and anxiety (-2.00 points) (P<.001 in each case). The isopropanol extract of C racemosa was found to be effective in the alleviation of menopausal symptoms.

Simultaneous bilateral occurrence of a mixed mesodermal tumor and cystadenocarcinoma in the ovary.

The mixed mesodermal tumor is a very uncommon malignancy. The aggressiveness of this lesion is illustrated by extremely poor prospects for afflicted patients: postoperative survival is usually shorter than 24 months. According to the literature, malignant mixed tumor of the ovary is rather rare and its occurrence with other malignancy is exceptional. We report here a case of a 62-years old woman with serous cystadenocarcinoma in the right ovary and a heterologous malignant mixed mesodermal tumor in the left one. Both tumors expressed cytokeratins, while only the mesodermal tumor expressed S-100 and focal NSE.