Prediction of fetal blood group antigens from maternal plasma using Ion AmpliSeq HD technology.

BACKGROUND: Fetal blood group (BG) and platelet (HPA) antigens may trigger maternal immunization, causing a fetal disease. Noninvasive prenatal diagnostics (NIPT) predicts fetal genotype, identifying pregnancies with no risk. All current techniques detect fetal antigen alleles with unspecific background and without estimation of fetal fraction, thus new protocols for detection of fetal BG/HPA alleles with ultrahigh sensitivity still need to be tested to improve NIPT. AIM: To design NIPT of clinically important antigens using Ion AmpliSeq HD technology. METHODS: Plasma DNA from 36 pregnant women (9-33 week of gestation, 24 immunized with anti-HPA-1a,-3b,-15a, -K, or -D+C+S), with known BG/HPA genotypes of their neonates/partners, was tested on Ion S5 System using the Ion AmpliSeq HD designer custom gene panel. NGS contained 25 rs-targets encoding relevant BG/HPA antigens and 10 markers. RESULTS: Using the NGS protocol, 76 out of 85 differences in fetal/maternal BG/HPA genotypes were determined in concentration above 2% fetal paternally inherited allele chimerism. The level of unspecific reads for BG/HPA alleles was below 0.87%. In 24 immunized women NGS revealed feto-maternal incompatibility in 11 cases (from 2.44% to 7.41%) and excluded in 10 (<0.05%), three cases had inconclusive results (1.79%, 0.19%, 0.11%). The presence of fetal DNA was confirmed in each case by detecting markers with at least 2% chimerism. CONCLUSION: The use of Ion AmpliSeq HD technology improves the prediction of feto-maternal incompatibility, increasing the sensitivity of BG/HPA NIPT and serving confirmation of the fetal DNA at the same workflow.

Clinical management of coronavirus disease 2019 (COVID-19) in pregnancy: recommendations of WAPM-World Association of Perinatal Medicine.

These guidelines follow the mission of the World Association of Perinatal Medicine, which brings together groups and individuals throughout the world with the goal of improving outcomes of maternal, fetal and neonatal (perinatal) patients. Guidelines for auditing, evaluation, and clinical care in perinatal medicine enable physicians diagnose, treat and follow-up of COVID-19-exposed pregnant women. These guidelines are based on quality evidence in the peer review literature as well as the experience of perinatal expert throughout the world. Physicians are advised to apply these guidelines to the local realities which they face. We plan to update these guidelines as new evidence become available.

Prediction of fetal blood group and platelet antigens from maternal plasma using next-generation sequencing.

BACKGROUND: Fetuses whose mothers have produced antibodies to red blood cell (RBC) or platelet antigens are at risk of being affected by hemolytic disease or alloimmune thrombocytopenia, respectively, only if they inherit the incompatible antigen. Noninvasive diagnosis of the fetal antigen is employed for management of immunized pregnancies, but the specific detection of SNPs, encoding the majority of antigens, in maternal plasma is still a challenge. We applied targeted next-generation sequencing (NGS) to predict the fetal antigen based on the detection of fetomaternal chimerism. METHODS AND MATERIALS: The DNA of 13 pregnant women (with anti-K [3] anti-k [1], anti-Fya [1], anti-D + C + Jka [1], anti-D + E + K [1], anti-HPA-1a [1], anti-HPA-3b [1], anti-HPA-5b [1], and nonimmunized [3]) was sequenced using primers for regions encoding RhD, RhC, Rhc, RhE/e, K/k, Fya/b, Jka/b, MN, Ss, and HPA-1, 2, 3, 5, 15, 4 X-polymorphisms on the Ion Torrent Personal Genome Machine (PGM) System (Thermo Fisher Scientific, Inc., Waltham, MA, USA). RESULTS: NGS results were in agreement with the phenotype/genotype of women and their neonates (except for the unsuccessful detection of MN and RhC). NGS determined fetal allele chimerism for K, k, Fya, Fyb, Jka, Jkb, S, RhE (from 0.42% to 6.08%); RhD, Rhc (100%); HPA-1a, -2b, -3a, 3b, -5b, -15a, 15b (from 0.23% to 4.11%). NGS revealed fetal chimerism for incompatible antigens (from 0.7% to 4.8%) in 7 immunized cases, excluded in 3 (with anti-K, anti-Fya , anti-HPA-3b). CONCLUSION: The designed NGS predicts the fetal RBC and platelet antigen status universally in cases with various clinically significant antibodies as well as providing confirmation of the presence of fetal DNA. However, some improvement of the unsuccessful primers is required.

Noninvasive prenatal HPA-1 typing in HPA-1a negative pregnancies selected in the Polish PREVFNAIT screening program.

BACKGROUND: Anti-HPA-1a alloantibodies in HPA-1a negative mothers can lead to fetal/neonatal alloimmune thrombocytopenia (FNAIT). Noninvasive prenatal testing (NIPT) of HPA-1a determines fetuses at risk and the course of maternal antenatal treatment. STUDY DESIGN AND METHODS: The aim was to develop and validate HPA-1a NIPT by real-time polymerase chain reaction (PCR) or next-generation sequencing (NGS) for a high-throughput screening setting. DNA from 328 plasma samples of 299 HPA-1a negative pregnant women was examined for HPA-1a by real-time PCR and in two cases also by NGS (Ion Torrent). The results were compared with neonatal HPA-1a genotyping in 281 cases. RESULTS: HPA-1a NIPT was negative in 44 of 51 HPA-1a negative fetuses, inconclusive in five, and false positive in two. In 228 of 229 HPA-1a positive fetuses, the NIPT results were positive (mean threshold cycle 36.0 ± 1.7) and inconclusive in one. In 22 cases with HPA-1a positive fetuses analyzed twice, the sensitivity of HPA-1a detection was significantly higher at 28 weeks compared with 16 to 20 weeks. NGS efficiently detected the ITGB3 coding HPA-1a/b (1% and 5% fetal HPA-1a reads). CONCLUSION: Real-time PCR is reliable to predict the fetal HPA-1a positive genotype in a screening study, but false-positive results are reported in 4%, with unnecessary prenatal treatment if anti-HPA-1a is detected.

Ultrasound guided balloon catheterisation: a new method of fetal lower urinary tract obstruction management.

OBJECTIVES: Fetal lower urinary tract obstruction (LUTO), most often associated with presence of posterior urethral valves, poses high risk of perinatal mortality or postnatal renal failure. Looking for a method of causative treatment we have devel-oped a technique of fetal urethroplasty with a coronary angioplasty balloon catheter inserted under an ultrasonographic guidance via an 18-gauge needle introduced transabdominally to fetal bladder. MATERIAL AND METHODS: We have used this procedure in three women with singleton pregnancies (two primiparas and one multipara, 32-35 years of age), diagnosed with fetal megacystis at 12-16 weeks of gestation. Urethral catheterization was carried out at 16-18 weeks and an unobstructed urine flow was achieved in all three cases immediately after the procedure, followed by a resolution of megacystis and normalization of amniotic fluid volume. RESULTS: In all three cases, the post-procedure period was uneventful. In the first two fetuses, amniotic fluid volume re-mained normal until 30 weeks of gestation when a gradual development of oligohydramnios and some signs of renal cystic dysplasia were observed. Nevertheless, both pregnancies were continued till term (37 and 39 weeks, respectively) and two boys without signs of pulmonary hypoplasia were delivered. The third patient is currently 25 weeks pregnant; volume of amniotic fluid in her fetus is normal and no signs of urinary flow obstruction or renal dysplasia have been recorded thus far. CONCLUSIONS: Although some technical aspects of the procedure still need to be established, it seems worth consideration as a form of potentially least traumatic intrauterine intervention in fetuses with lower urinary tract obstruction.

Early vesico-amniotic shunting - does it change the prognosis in fetal lower urinary tract obstruction diagnosed in the first trimester?

OBJECTIVES: The aim of the study was to assess the outcome of vesico-amniotic shunting performed before 16 weeks of pregnancy in fetuses with severe megacystis diagnosed in the first trimester of pregnancy. MATERIAL AND METHODS: Between January 2008 and October 2012 severe megacystis with the bladder length > 15 mm was diagnosed in 17 fetuses. The procedure of early vesico-amniotic shunting (VAS) was offered to 8 patients with presumably isolated LUTO. The procedure of VAS was performed in 6 fetuses. Before the intervention one or two procedures of vesicocentesis and urine analysis were performed. RESULTS: In all treated cases shunts provided urinary tract decompression. All babies were born prematurely, 2 of them died due to premaurity, 3 of them survived and have normal renal function at the age of 5-6 years. In 4/5 children accompanying malformations were later diagnosed, in 1 born prematurely neonate necropsy was not performed. CONCLUSIONS: Our results suggest that early vesico-amniotic shunting in fetal LUTO is feasible and may potentially prevent not only pulmonary hypoplasia but also renal insufficiency. However, the rationale of the procedure needs further investigation due to a high risk of long-term morbidity and co-existing malformations in children Before offering the therapy detailed counseling of the parents about the possible pros and cons of the therapy is necessary.

14 Years of Polish Experience in Non-Invasive Prenatal Blood Group Diagnosis.

BACKGROUND: Blood cell antigens may cause maternal alloimmunization leading to fetal/newborn disorders. Non-invasive prenatal diagnostics (NIPD) of the blood group permits the determination of feto-maternal incompatibility. AIM: To evaluate 14 years of blood group NIPD at the Institute of Hematology and Transfusion Medicine (IHTM) in Warsaw. METHODS: Plasma DNA from 536 RhD-negative, 24 Rhc-negative, 26 RhE-negative, 43 K-negative, and 42 HPA-1a-negative pregnant women was examined by real-time PCR to detect RHD, RHCE*c, RHCE*E, RHCE*C, KEL*01 and HPA*1A, respectively. We tested for CCR5, SRY or bi-allelic polymorphisms and quantified the total or fetal DNA. RESULTS: The results of fetal antigen status prediction by NIPD in all but one case (false-positive result of KEL*01) were correct taking neonate serology as a reference. It was confirmed that all negative results of NIPD contained fetal DNA except for four cases where there was no difference between the parents' polymorphisms. CONCLUSIONS: A fetal genotype compatible with the mother was determined in 25% of all pregnancies tested at the IHTM for the fetal blood group. These cases were not at risk of disease, so it was possible to avoid invasive procedures.

[Fetal cardiac interventions - are we ready for them?]. / Interwencyjne zabiegi kardiologiczne u plodów - czy jestesmy do nich przygotowani?

OBJECTIVE: The aim of the study was to analyze types and methods of intrauterine fetal cardiac interventions performed between June 2011 and December 2013, and to assess the perinatal management of the neonates. METHODS: The program was developed after analysis of the available literature, practical individual training in Linz, Austria, and simulation of the procedure in a dissecting-room. The rules for anesthesia in pregnant women and their fetuses were developed. The interventions were performed in fetuses with critical cardiac defects, in the operating room, under ultrasonographic control. The protocol was approved by the Local Bioethics Committee at the Centre of Postgraduate Medical Education. MATERIAL: We included fetuses with critical aortic stenosis (n=29), critical pulmonary stenosis (n=2), and closed or extremely restricted foramen ovale (n=7). Between June 2011 and December 2013, the team comprised of JD, MD and AK conducted 42 interventions in 35 fetuses, including 32 balloon aortic valvuloplasties (in 29 fetuses), 2 pulmonary valvuloplasties, 4 balloon atrial septostomies and 4 atrial septal stent placement. Three fetuses required both, aortic valvuloplasty and fenestration of the atrial septum. RESULTS: Out of the 42 procedures, 41 (97%) were technically successful. We recorded 3 cases of fetal demise associated with the intervention. We modulated the protocol of anesthesia given to pregnant women, switching from general to local anesthesia with intravenous sedation. We always provided additional fetal anesthesia with fentanyl and atracurium via the umbilical vein. CONCLUSIONS: Based on our 2.5-year experience, it seems safe to conclude that all types of fetal cardiac interventions may be successfully conducted at Polish centers. The procedures are safe for the pregnant women and improve fetal status. Most of the neonates treated prenatally were referred in good general condition to a tertiary pediatric cardiology and cardiac surgery center

[PREVFNAIT prevention of foetal/neonatal alloimmune thrombocytopenia (FNAIT) in Polish foetuses and newborns--the PREVFNAIT program]. / Zapobieganie alloimmunologicznej maloplytkowosci plodów i noworodków (AIMPN) w Polsce--program PREVFNAIT.

The scientific goals related to the grant include 1) estimation of FNAIT prevalence in Poland and 2) search for biomarkers to predict the risk of the antibody production and severity of fetal thrombocytopenia. Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT) is caused by destruction of fetal blood platelets due to maternal antibodies. This condition, which most commonly results from incompatibility between the mother and the fetus for the Human Platelet Antigen-1a (HPA-1a), may lead to intracranial hemorrhage, damage of the central nervous system (CNS) and even death of the fetus or the newborn. It can be the cause of strokes in term newborns. FNAIT is usually attributed to the presence of anti-HPA-1a antibodies. Its incidence rate is estimated at approximately 1/1000-2000 live births. In the absence of a screening program, it is usually diagnosed after birth of a child with symptoms of thrombocytopenia or CNS hemorrhage. Monitoring of antibody production and thrombocytopenia treatment to effectively minimize the risk of stroke are therefore launched only at the next pregnancy. Testing indications are broader to include fetal ultrasound for symptoms of stroke to the CNS, ventricular enlargement or hydrocephalus, and obstetric failure. Diagnostic process is also recommended prior to the planned cordocentesis, in vitro fertilization and in sisters of mothers with children with FNAIT history. HPA-1a testing remains the best method for diagnosing pregnancies at risk. The detection frequency for FNAIT in Poland remains low. Therefore, the Institute of Hematology and Transfusion Medicine (IHTM) will have performed such HPA-1a antigen testing in 30 000 Polish women within the framework of the PREVFNAIT program by March 2016. HPA-1a negative women (2% of the population) are a risk group for production of anti- HPA-1a antibodies responsible for FNAIT therefore all of them will be monitored for the presence and activity of anti-HPA-1a antibodies. Such testing will be performed free of charge for the women.

[Standardization of the quantitative flow cytometric test with anti-D antibodies for fetomaternal hemorrhage in RhD negative women]. / Standaryzacja metody ilosciowej oceny przecieku plodowo-matczynego u kobiet RhD ujemnych przy pomocy cytometrii przeplywowej z uzyciem przeciwcial anty-D.

BACKGROUND: In order to determine the appropriate dose of anti-D immunoglobulin to be administered as a preventive measure against hemolytic disease of the fetus/newborn in the subsequent pregnancy it is necessary to assess the number of fetal red blood cells that infiltrate/penetrate into the maternal circulation as a result of fetomaternal hemorrhage (FMH). One of the quantitative methods of FMH analysis is based on flow cytometry (FACS) which makes use of monoclonal antibodies to RhD antigen (anti-D test). The aim of the study was to further develop the method, evaluate its sensitivity and reproducibility and to compare it with the test based on the detection of fetal hemoglobin (HbF). MATERIAL AND METHODS: The FACS study involved 20 RhD negative pregnant women and 80 RhD negative women after delivery. The following monoclonal antibodies were used: BRAD 3 FITC (anti-RhD antigen), CD45 PerCP (anti leukocyte antigen CD45), and anti-HbF PE. RESULTS: The fluorescence intensity of cells incubated with BRAD 3 FITC was demonstrated to depend on the RhD antigen expression, though the anti-D test also detects the weak D variant. The CD45 PerCP antibodies increased the sensitivity of anti-D test since they eliminated the leukocytes which non-specifically bind anti-D from the analysis. The presence of anti-D antibodies in maternal plasma does not affect the quantitative assessment of the fetal RhD positive fetal cells with BRAD 3 FITC. In case of FMH, the results of the anti-D test were similar to those with anti-HbF antibodies. CONCLUSIONS: The flow cytometric test with anti-D and anti-CD45 is useful in the assessment of the fetomaternal hemorrhage in RhD negative women. The sensitivity of the test is estimated at 0.05%.

Feto-maternal haemorrhage assessment in a woman with a large population of red blood cells containing fetal haemoglobin.

BACKGROUND: FMH quantification is necessary to calculate an individual dose of prophylactic anti-RhD immunoglobulin and to diagnose fetal anaemia causes. We encountered a healthy woman with a numerous RBCs containing fetal haemoglobin (HbF). AIMS: To investigate the cause of this sign and the correct evaluation of fetal RBCs in maternal circulation. MATERIALS AND METHODS: Patients samples and artificial mixtures were tested by microscopic Kleihaur-Betke (KB) and flow cytometric (FC) tests with anti-HbF + anti-CA (carbonic anhydrase), and with anti-D. The patient's blood count with reticulocyte parameters, and concentration of bilirubin, haptoglobin, iron, transferrin, ferritin, hepcidin, sTR, HbF, HbA2 were measured. Genes coding the beta- and gamma-globin were sequenced. RESULTS: It was impossible to distinguish the population of fetal and maternal HbF positive cells using KBT and FC with anti-HbF. Application of anti-CA and anti-D allowed to separate them. Maternal blood haematological and biochemical parameters were normal but HbF was 3.3% of total Hb concentration (normal < 1%). There were no mutations in the beta- and gamma-globin genes, but Xmn I polymorphism at -158 position in gamma-globin gene was detected in the homozygous state. CONCLUSION: A very large population of HbF positive cells sometimes can be detect in a healthy woman. Implementation of the various procedures for FMH assessment is necessary in the such case, otherwise, the detection of fetal erythrocytes may not be possible or can give false results.

What's with the boys? Lower birth weight in boys from HPA-1a alloimmunized pregnancies - New insights from a large prospective screening study in Poland.

Fetomaternal incompatibility in human platelet antigens (HPAs) can cause maternal alloimmunization, which in turn may lead to thrombocytopenia with or without intracranial hemorrhage (ICH) in the fetus or newborn. Retrospective studies suggest that boys from alloimmunized mothers may have higher risk of ICH and lower birth weight than girls. The objective of this study was to assess how maternal HPA-1a alloimmunization, sex of the neonate and birth weight relates in a large prospective cohort. Through a national screening study in Poland (PREVFNAIT) involving HPA-1 typing of 24,259 pregnant women during 2013-2017, 606 HPA-1a negative pregnant women and their offspring were identified and included. Various multivariate models were used to assess if and how maternal HPA-1a alloimmunization status was associated with birth weight and risk of having a small for gestational age (SGA) neonate, and if and how sex of the neonate mattered. Most immunized pregnancies had male fetuses (69 %). Women carrying a male fetus had increased likelihood of having an SGA newborn if they were HPA-1a alloimmunized compared to non-immunized mothers. Increasing maternal anti-HPA-1a antibody levels were significantly associated with reduced birth weight and SGA risk among male-fetus pregnancies, but not if the fetus was female. In conclusion, anti-HPA-1a antibodies in a male fetus pregnancy is associated with increased risk of SGA and lower birth weight, especially if the antibody level is high. Sex of the fetus may therefore be considered as a new clinical predictor of more severe FNAIT neonatal outcome.

Management Options for Fetal Bronchopulmonary Sequestration.

To evaluate the prenatal course and perinatal outcome of fetuses with bronchopulmonary sequestration (BPS) managed expectantly or using minimally invasive methods. This was a retrospective study of 29 fetuses with suspected BPS managed between 2010 and 2021 in three fetal medicine centers in Poland. Medline was searched to identify cases of BPS managed expectantly or through minimally-invasive methods. In 16 fetuses with BPS, there was no evidence of cardiac compromise. These fetuses were managed expectantly. Thirteen hydropic fetuses with BPS qualified for intrauterine intervention: a thoraco-amniotic shunt (TAS) was inserted in five fetuses, laser coagulation of the feeding vessel was performed in seven cases, and one fetus had combined treatment. In the combined data from the previous and the current study of various percutaneous interventions for BPS associated with hydrops, the survival rate was 91.2% (31/34) for TAS, 98.1% (53/54) for laser coagulation, and 75% (3/4) for intratumor injection of sclerosant. After taking into account cases with available data, the rate of preterm birth before 37 weeks in the group treated with laser coagulation was 14.3% (7/49) compared to 84.6% (22/26) in the group treated with TAS. The need for postnatal sequestrectomy was lower in the group of fetuses treated with laser coagulation 23.5% (12/51) in comparison to fetuses treated with TAS 84% (21/26). In fetuses with BPS without hydrops, progression of the lesion's volume, leading to cardiac compromise, is unlikely. In hydropic fetuses with BPS, intrauterine therapy using minimally invasive methods prevents fetal demise. Both, the rate of preterm birth and the need for postnatal surgery is significantly lower in the group treated with laser coagulation compared to the group treated with TAS.

Comparative Genomic Hybridization to Microarrays in Fetuses with High-Risk Prenatal Indications: Polish Experience with 7400 Pregnancies.

The aim of this study was to determine the suitability of the comparative genomic hybridization to microarray (aCGH) technique for prenatal diagnosis, but also to assess the frequency of chromosomal aberrations that may lead to fetal malformations but are not included in the diagnostic report. We present the results of the aCGH in a cohort of 7400 prenatal cases, indicated for invasive testing due to ultrasound abnormalities, high-risk for serum screening, thickened nuchal translucency, family history of genetic abnormalities or congenital abnormalities, and advanced maternal age (AMA). The overall chromosomal aberration detection rate was 27.2% (2010/7400), including 71.2% (1431/2010) of numerical aberrations and 28.8% (579/2010) of structural aberrations. Additionally, the detection rate of clinically significant copy number variants (CNVs) was 6.8% (505/7400) and 0.7% (57/7400) for variants of unknown clinical significance. The detection rate of clinically significant submicroscopic CNVs was 7.9% (334/4204) for fetuses with structural anomalies, 5.4% (18/336) in AMA, 3.1% (22/713) in the group of abnormal serum screening and 6.1% (131/2147) in other indications. Using the aCGH method, it was possible to assess the frequency of pathogenic chromosomal aberrations, of likely pathogenic and of uncertain clinical significance, in the groups of cases with different indications for an invasive test.

[The first successful fetal aortic balloon valvuloplasty in Poland]. / Pierwsza w Polsce skuteczna przezskórna plastyka balonowa zastawki aortalnej u plodu.

Prenatal aortic valvuloplasty is performed only in few perinatal centers in the world. Critical aortic stenosis which can lead to hypoplastic left heart syndrome or severe fetal heart failure with nonimmune hydrops is an indication for this procedure. Prenatal intervention can change the natural course of the disease. Authors present the first successful fetal balloon aortic valvuloplasty in Poland. It was performed in a 29-week fetus with critical aortic stenosis, severe impairment of left ventricular function, heart failure and fetal hydrops. After successful intervention, without any complications, left ventricular function and fetal condition improved gradually Effective fetal intervention was possible after few months of preparation and building a team of specialists. This is the first successful fetal cardiac intervention in Poland, which opens the way to the new era of fetal cardiology and hopefully will lead to improve results in children with this critical heart defect.

[Calculation of feto-maternal haemorrhage volume using various morphological parameters and various formulas]. / Obliczanie objetosci krwawienia plodowo-matczynego z zastosowaniem róznych parametrów morfologicznych i róznych wzorów.

UNLABELLED: Quantification of FMH is essential for determination of an accurate dose of anti-RhD Ig in antepartum and postpartum immunoprophylaxis of HDFN. Doses of anti-RhD are established with reference to the volume of RhD positive foetal red blood cells in the circulation of RhD negative voluntaries. Results obtained from flow cytometry, microscopic Kleihauer-Betke test or serological test indicate percentage of these cells. THE AIM OF THE STUDY: To compare results of FMH volume calculation using various formulas. MATERIAL AND METHODS: EDTA blood samples from 51 mothers and 51 cord blood samples from their newborns were analyzed. Five formulas were based on following parameters: percentage of foetal red blood cells in the blood sample from mother, mother's body weight and Hct, maternal and foetal MCV. RESULTS: The range of maternal Hct was 25.7-46.2% (mean 34.3%), ratio of foetal MCV to maternal MCV was 1.09-1.41 (mean 1.19), body weight of mothers 56-99 kg (mean 73.5 kg) and calculated volume of their blood 3600-7425 mi (mean 5100 ml). For 0.4% FMH we predicted 2, 3 or 4 doses of anti-RhD Ig 500 IU (100 microg) and 1, 2 or 3 doses of anti-RhD Ig 750 IU (150 microg) depending on the woman. CONCLUSIONS: The formula with individual maternal and foetal morphological parameters is much more accurate for calculation of the volume of FMH and doses of anti-RhD Ig than often used formula with average values of the parameters.

Fetal Cardiac Interventions-Are They Safe for the Mothers?

The aim of fetal cardiac interventions (FCI), as other prenatal therapeutic procedures, is to bring benefit to the fetus. However, the safety of the mother is of utmost importance. The objective of our study was to evaluate the impact of FCI on maternal condition, course of pregnancy, and delivery. 113 mothers underwent intrauterine treatment of their fetuses with critical heart defects. 128 percutaneous ultrasound-guided FCI were performed and analyzed. The patients were divided into four groups according to the type of FCI: balloon aortic valvuloplasty (fBAV), balloon pulmonary valvuloplasty (fBPV), interatrial stent placement (IAS), and balloon atrioseptoplasty (BAS). Various factors: maternal parameters, perioperative data, and pregnancy complications, were analyzed. There was only one major complication-procedure-related placental abruption (without need for blood products transfusion). There were no cases of: procedure-related preterm prelabor rupture of membranes (pPROM), chorioamnionitis, wound infection, and anesthesia associated complications. Tocolysis was only necessary only in two cases, and it was effective in both. None of the patients required intensive care unit admission. The procedure was effective in treating polyhydramnios associated with fetal heart failure in six out of nine cases. Deliveries occurred at term in 89%, 54% were vaginal. The results showed that FCI had a negligible impact on a further course of pregnancy and delivery.

Platelet alloimmunization is associated with low grade chronic histiocytic intervillositis - A new link to a rare placental lesion?

INTRODUCTION: Maternal alloimmunization against human platelet antigen (HPA)-1a has been implied to mediate both reduced birth weight and chronic placental inflammation. Fetal growth restriction is associated with different types of chronic inflammation in the placenta, mainly chronic histiocytic intervillositis and chronic villitis. The aim of this prospective study was to do a systematic examination of placentas from HPA-1a alloimmunized pregnancies, with focus on the histopathological and immunohistochemical diagnosis of variants of chronic inflammation. MATERIAL AND METHODS: In a Polish-Norwegian study, 48 placentas were examined. The histopathology of placentas from 27 HPA-1a immunized women was compared with 21 placentas from non-immunized HPA-1a negative women (controls). In the group of alloimmunized women, ten received antenatal intravenous immunoglobulin G (IVIg). Tissue sections from formalin fixed paraffin embedded placental tissue were stained with hematoxylin and eosin and microscopically examined with focus on various types of chronic placental inflammations. RESULTS: Chronic histiocytic intervillositis was observed in 40.7% of placentas from HPA-1a alloimmunized pregnancies, compared to none in the control group (p = 0.001). Chronic villitis of unknown etiology was more frequently found in the alloimmunized group, however this difference was not statistically significant. Maternal administration of IVIg did not seem to protect against chronic inflammatory lesions. DISCUSSION: Placentas with detectable maternal anti-HPA-1a antibodies are associated with highly increased risk of low-grade chronic histiocytic intervillositis.

Pregnancy-related cardiac non-elective hospitalizations and pregnancy outcomes. A tertiary referral cardiac center experience.

BACKGROUND: Pregnant women with cardiovascular diseases (CVD) and their offspring are at higher risk of morbidity and mortality. AIMS: To provide data on pregnancy outcomes among women with different types of CVD requiring non-elective cardiac hospitalization in a tertiary referral cardiac center. METHODS: We identified all records of non-elective hospitalizations of pregnant women hospitalized between January 2009 through March 2018, at our institution - a tertiary referral cardiac center. The incidence and types of cardiac complications during pregnancy, as well as the pregnancy and offspring outcomes, were determined. RESULTS: One hundred and sixty-one out of 328 pregnancy-related hospitalizations in 140 pregnancies were non-elective. Cardiac complications occurred in 62 (44%) pregnancies, with the most frequent being episodes of arrhythmia (22.1% pregnancies), followed by heart failure exacerbations (6.4% pregnancies). Maternal mortality reached 2.1% and affected only women with primary cardiomyopathies (CMP). Offspring mortality was 2.8%. Newborns of mothers with cardiac complications had significantly lower Apgar scores and gestational age at delivery, compared to mothers without cardiac complications. CONCLUSIONS: In our series mortality and morbidity among pregnant women with CVD hospitalizations were high. An unfavorable maternal outcome mainly affected women with CMP. Offspring of mothers with cardiovascular complications are prone to have a lower gestational age and Apgar score.

Prenatal Diagnosis by Array Comparative Genomic Hybridization in Fetuses with Cardiac Abnormalities.

Congenital heart defects (CHDs) appear in 8-10 out of 1000 live born newborns and are one of the most common causes of deaths. In fetuses, the congenital heart defects are found even 3-5 times more often. Currently, microarray comparative genomic hybridization (array CGH) is recommended by worldwide scientific organizations as a first-line test in the prenatal diagnosis of fetuses with sonographic abnormalities, especially cardiac defects. We present the results of the application of array CGH in 484 cases with prenatally diagnosed congenital heart diseases by fetal ultrasound scanning (256 isolated CHD and 228 CHD coexisting with other malformations). We identified pathogenic aberrations and likely pathogenic genetic loci for CHD in 165 fetuses and 9 copy number variants (CNVs) of unknown clinical significance. Prenatal array-CGH is a useful method allowing the identification of all unbalanced aberrations (number and structure) with a much higher resolution than the currently applied traditional assessment techniques karyotype. Due to this ability, we identified the etiology of heart defects in 37% of cases.