Exome sequencing in every pregnancy? Results of trio exome sequencing in structurally normal fetuses.

OBJECTIVE: This study aimed to assess the detection rate of clinically significant results of prenatal exome sequencing (pES) in low-risk pregnancies and apparently normal fetuses in non-consanguineous couples. METHODS: A retrospective analysis of pES conducted at a single center from January 2020 to September 2023 was performed. Genetic counseling was provided, and detailed medical histories were obtained. High-risk pregnancies were excluded due to major ultrasound anomalies, sonographic soft markers, abnormal maternal biochemical screening, or family history suggestive of monogenic diseases as well as cases with pathogenic and likely pathogenic (P/LP) chromosomal microarray results. Exome analysis focused on ∼2100 genes associated with Mendelian genetic disorders. Variant analysis and classification followed the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: Among 1825 pES conducted, 1020 low-risk cases revealed 28 fetuses (2.7%) with potentially clinically significant variants indicating known monogenic diseases, primarily de novo dominant variants (64%). Among these 28 cases, 9 fetuses (0.9%) had the potential for severe phenotypes, including shortened lifespan and intellectual disability, and another 12 had the potential for milder phenotypes. Seven cases were reported with variants of uncertain significance (VUS) that, according to the ACMG criteria, leaned toward LP, constituting 0.7% of the entire cohort. Termination of pregnancy was elected in 13 out of 1020 cases (1.2%) in the cohort, including 7/9 in the severe phenotypes group, 2/12 in the milder phenotype group, and 4/7 in the VUS group. CONCLUSION: The 2.7% detection rate highlights the significant contribution of pES in low-risk pregnancies. However, it necessitates rigorous analysis, and comprehensive genetic counseling before and after testing.

Intrauterine Blood Transfusion for Parvo B19-Induced Fetal Anemia: Neuroimaging Findings and Long-Term Neurological Outcomes.

INTRODUCTION: We aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization. METHODS: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group - fetuses affected by congenital parvo B19 infection; and a control group - fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly. RESULTS: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p < 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly. CONCLUSION: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation.

Fetal and neonatal brain injury in twins complicated by twin anemia polycythemia sequence.

OBJECTIVES: To determine the rate of fetal and neonatal brain lesions and define risk factors for such lesions in pregnancies complicated by Twin Anemia Polycythemia Sequence (TAPS). METHODS: A retrospective cohort study of monochorionic twin pregnancies which were diagnosed with TAPS in a single tertiary medical center between 2013 and 2021. Pregnancies were followed with fetal brain neurosonogram every 2 weeks and fetal brain MRI (magnetic resonance imaging) was performed when indicated at 28-32 weeks of gestation; post-natal brain imaging included neonatal brain ultrasound. Pregnancies with pre- and post-natal brain lesions were compared to those without such findings. RESULTS: Overall, 23 monochorionic diamniotic pregnancies were diagnosed with TAPS over the study period resulting in perinatal survival of 91.3% (42/46). In 6/23 (26%) pregnancies and 7/46 (15.2%) fetuses pre- or post-natal brain lesions were detected, of whom five were the polycythemic twins and two were the anemic twins. Brain findings included intra-cerebral hemorrhage and ischemic lesions and were diagnosed prenatally in 6/7 (85.7%) cases. No risk factors for severe brain lesions were identified. CONCLUSIONS: TAPS may place the fetuses and neonates at increased risk for cerebral injuries. Incorporation of fetal brain imaging protocols may enhance precise prenatal diagnosis and allow for accurate parental counseling and post-natal care.

High rate of abnormal findings in Prenatal Exome Trio in low risk pregnancies and apparently normal fetuses.

OBJECTIVE: Data on the value of exome sequencing in fetuses with no structural anomalies are limited, especially in the early stages of pregnancy and in low risk pregnancies. We investigated the yield of targeted clinical prenatal trio exome sequencing (pES) in pregnancies with and without fetal structural anomalies. METHODS: We performed pES in 353 pregnancies: Group 1 included 143 pregnancies with high clinical suspicion for a genetic disease: pregnancies with increased nuchal translucency, ultrasound structural defects, intrauterine growth restriction, polyhydramnios, or effusion/nuchal edema. Group 2 included 210 pregnancies with no notable abnormal fetal ultrasound findings. 2a. Low risk pregnancies with minor ultrasound findings, referred to the geneticist due to mildly increased risk for genetic disease (50); and 2b. Normal pregnancy surveillance (160). RESULTS: Overall, 26 (7.36%) fetal analyses had pathogenic (P)/likely pathogenic (LP) variants. In group 1, 20/143 (13.99%) cases had P/LP variants. In group 2, 6/210 (2.86%) cases were found to have P/LP variants [5/50 in (2a) and 1/160 in (2b)]. CONCLUSION: These results show a high rate of abnormal findings on pES even in apparently normal pregnancies.

"One-stop shop" for the evaluation of the infertile patient: hystero-salpingo foam sonography combined with two and three dimensional ultrasound and sonohysterography.

Hysterosalpingo-foam sonography (HyFoSy) is considered an acceptable alternative for hysterosalpingography (HSG). By combining HyFoSy with two and three-dimensional (2D and 3D) ultrasound and hysterosonography, a complete fertility work-up can be done. We aimed to evaluate the value of a combined ultrasound examination for fertility work-up. During the study period 113 women were examined. Five of 113 (4.4%) examinations were abandoned due to intra-uterine adhesions that were detected by hysterosonography, and five (4.4%) were abandoned due to technical difficulties. Of 103 women who had completed the examination, 2D ultrasound revealed six patients with hydrosalpinx (5.8%) and sonographic signs of adenomyosis in 13 (12.6%) patients. By combining 2D ultrasound with hysterosonography, two (1.9%) fibroids that were penetrating the uterine cavity and seven (6.8%) endometrial polyps were detected. HyFoSy showed bilateral patent tubes in 58 patients (56.3%), unilateral tubal occlusion in 29 (28.1%) and bilateral tubal occlusion in 16 (15.5%). This study shows that the 'one-stop shop' examination is feasible. The combined examination had detected 16 pathological findings that would have not been detected by HyFoSy alone. Hence, it should be offered to couples undergoing routine infertility work-up.IMPACT STATEMENTWhat is already known on this subject? The accuracy of the HyFoSy alone has been evaluated in different studies, but this presented ultrasound scan is integrating 4 different modalities in one exam (2D scanning of the pelvis, 3D scanning of the uterus, hysterosonography and HyFoSy) and we were able to evaluate the female pelvic organs, including the uterine cavity, the tubes and the ovaries, in order to expand the range of diagnosed pathologies.What do the results of this study add? The concept of 'one-stop shop' for the evaluation of female pelvis in couples suffering from infertility is feasible, has comparable accuracy as HSG for tubal occlusion, and higher detection rate for uterine malformations.What are the implications of these findings for clinical practice and/or further research? We suggest to incorporate this examination in routine fertility work-up.

Fetal and neonatal brain lesions following laser ablation for twin-to-twin-transfusion-syndrome as detected by pre- and post-natal brain imaging.

OBJECTIVE: To determine the rate of and risk factors for fetal and neonatal brain lesions following laser ablation for twin-to-twin transfusion syndrome (TTTS). METHODS: A retrospective cohort study of 83 women with monochorionic twin pregnancies who underwent ablation for TTTS at a single tertiary hospital. Post-laser survivors were followed-up with fetal neurosonogram every 2 weeks and fetal brain MRI at 28-32 weeks of gestation; post-natal brain imaging included neurosonogram. Cases with pre- and post-natal brain lesions were compared to those without. RESULTS: 153 fetuses survived the immediate post-laser period and underwent brain imaging. Of these, 17 (11.11%) exhibited brain lesions on prenatal imaging studies, and 36 (32.4%) on post-natal ultrasound. Later gestational age (GA) at the time of ablation (23.0 vs. 21.4 weeks, p = 0.0244), post-laser twin-anemia-polycythemia-sequence (TAPS) (29.41% vs. 9.56%, p = 0.035) and birthweight discordancy (30% vs. 9%, p = 0.0025) were associated with prenatal brain lesions. Earlier GA at delivery (31.0 weeks vs. 32.2, p = 0.0002) and post-laser TAPS (25% vs. 9.33%, p = 0.038) were associated with post-natal brain lesions. CONCLUSIONS: Survivors of ablation for TTTS are at risk for brain lesions, which can be detected prenatally. Incorporation of neurosonogram and fetal brain MRI into the routine surveillance of such pregnancies should be considered.

Do Serial Sonographic Assessments of Fetuses with Isolated Congenital Diaphragmatic Hernia Help Us Predict Survival?

OBJECTIVE: The aim of this study was to assess the ability of serial prenatal sonographic measurements, and specifically changes in the observed-to-expected lung-to-head ratio (O/E LHR) throughout gestation and to predict survival in congenital diaphragmatic hernia (CDH). METHODS: Retrospective study of CDH fetuses evaluated prenatally and treated postnatally in a single tertiary center, 2008-2020. Sonographic evaluations included side of herniation, liver involvement, and O/E LHR. All data were calculated to assess ability to predict survival. RESULTS: Overall, 94 fetuses were evaluated prenatally and delivered in our medical center. Among them, 75 had isolated CDH and 19 nonisolated. CDH was categorized as left (n = 76; 80.8%), right (n = 16; 17.0%), or bilateral (n = 2; 2.2%). Overall perinatal survival rate was 57% for all live-born infants, 68% in isolated CDH, and 40% in nonisolated (excluding 2 cases that underwent fetoscopic endoluminal tracheal occlusion and did not survive). The O/E LHR was lower in cases with perinatal death compared to survivors. In cases with multiple evaluations, the minimal O/E LHR was the most accurate predictor of survival and need for perinatal extracorporeal membrane oxygenation (ECMO) support. This remained significant when excluding twin pregnancies or when evaluating only isolated left CDH. In addition to disease severity, the side of herniation and liver position was associated with preoperative mortality. CONCLUSION: O/E LHR is associated with perinatal survival. In cases with multiple evaluations, the minimal O/E LHR is the most accurate and significant predictor of perinatal mortality and need for ECMO support.

Pregnancy outcome after multifetal pregnancy reduction of triplets to twins versus reduction to singletons.

RESEARCH QUESTION: Does fetal reduction of triplet pregnancies to singleton result in superior obstetric and neonatal outcomes compared with triplets reduced to twins? DESIGN: A historical cohort study including 285 trichorionic and dichorionic triplet pregnancies that underwent abdominal fetal reduction at 11-14 weeks in a single tertiary referral centre. The study population comprised two groups: reduction to twins (n = 223) and singletons (n = 62). Main outcome measures were rates of pregnancy complications, preterm delivery and neonatal outcomes. Non-parametric statistical methods were employed. RESULTS: Triplet pregnancies reduced to twins delivered earlier (36 versus 39 weeks, P < 0.001) with higher prevalence of Caesarean section (71.1% versus 32.2%, P < 0.001) compared with triplets reduced to singletons. Preterm delivery rates were significantly higher in twins compared with singletons prior to 37 weeks (56.9% versus 13.6%, P < 0.001), 34 weeks (20.2% versus 3.4%, P = 0.002) and 32 weeks (9.6% versus 0%, P = 0.01). No significant difference was found in the rate of pregnancy loss before 24 weeks (1.3% in twins versus 4.8% in singletons, P = 0.12) or in the rate of intrauterine fetal death after 24 weeks (0.4% versus 0%, P = 1.0). Both groups had comparable obstetrical complications and neonatal outcomes, except for higher rates of neonatal intensive care unit admission in twins (31.9% versus 6.8%, P < 0.001). CONCLUSIONS: Reduction of triplets to singletons rather than twins resulted in superior obstetric outcomes without increasing the procedure-related complications. However, because the rate of extreme prematurity in pregnancies reduced to twins was low, the overall outcome of those pregnancies was favourable. Therefore, the option of reduction to singletons should be considered in cases where the risk of prematurity seems exceptionally high.

Perinatal Outcome of Twin Pregnancies Complicated by Rupture of Membranes at 13-20 Weeks: Is Selective Termination an Appropriate Management Option?

OBJECTIVE: To evaluate the outcome of twin pregnancies that were complicated by rupture of membranes at 13-20 weeks of gestation and were managed by expectant management or by selective termination. METHODS: A retrospective cohort study of all bichorionic twin pregnancies that were referred to three fetal medicine units between 2001 and 2016, due to rupture of membranes of one sac at 13-20 weeks of gestation. Women without clinical signs of infection who opted for expectant management or selective termination were included. RESULTS: 20 patients met the inclusion criteria. 7 of them were managed expectantly and 13 underwent selective termination. In the expectant management group there was one case of fetal demise and two cases of neonatal death, resulting in a survival rate of 79 %. The median gestational age at delivery was 30 weeks. 3 neonates suffered from prematurity-related complications and 2 suffered from oligohydramnios-related orthopedic complications. Following selective termination the survival rate was 50 % (all fetuses that were not reduced), the median gestational age at delivery was 39 weeks, and the neonatal outcome was favorable. The maternal outcome was favorable in both groups. CONCLUSION: Selective termination in twin pregnancies complicated by rupture of membranes at 13-20 weeks has a favorable outcome and should be offered.

A false-carrier state for the c.579G>A mutation in the NCF1 gene in Ashkenazi Jews.

BACKGROUND: Mutations in the NCF1 gene that encodes p47phox, a subunit of the NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi CGD patients with this mutation have never been described. METHODS: We used Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis, and measured NADPH oxidase activity and p47phox expression. RESULTS: In an Ashkenazi couple expecting a baby, both parents were found to be heterozygotes for this mutation, as was the fetus. However, segregation analysis in the extended family was consistent with the fetus inheriting both carrier alleles from the parents. MLPA indicated four complete NCF1 genes in the fetus and three in each parent. Gene sequencing confirmed these results. Analysis of fetal leucocytes obtained by cordocentesis revealed substantial oxidase activity with three different assays, which was confirmed after birth. In six additional Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with three complete NCF1 genes of which one was mutated (like the parents), and one individual with in addition a fusion gene of NCF1 with a pseudogene. CONCLUSION: These results point to the existence of a 'false-carrier' state in Ashkenazi Jews and have wide implications regarding pre-pregnancy screening in this and other population groups.

Outcome of early versus late multifetal pregnancy reduction.

Multifetal pregnancy reduction (MPR) is an accepted method of reducing complications of triplet pregnancies and higher-order multifetal pregnancies. Eighty-three pregnancies that underwent early (68 weeks) transvaginal MPR were compared with 125 pregnancies that underwent late (11-14 weeks) transabdominal MPR. Rates of pregnancy loss, preterm delivery, gestational diabetes and hypertensive disorders were similar among both groups. Early MPR was associated with a lower risk for small for gestational age newborns (6.5% versus 19.2%; P = 0.034; OR 0.32; 95% CI 0.11 to 0.92) and a higher risk for single-fetus loss (6% versus 0.8%; P = 0.041; OR 10.58; 95% CI 1.1 to 101.94). Preterm delivery rates seemed to be similar between the two groups. In MPR from triplets, an apparent benefit was observed for early MPR in preterm deliveries before 37 weeks, whereas, in MPR from high-order pregnancies, a benefit was observed for late MPR in deliveries before 32 weeks. Perinatal outcomes of twin pregnancies after early and late MPR seem to be grossly similar. Optimal timing for multifetal reduction depends on other factors, namely, the selectivity of the procedure and patient's preference.

Amniotic fluid discordance in monochorionic diamniotic twin pregnancies is associated with increased risk for twin anemia-polycythemia sequence.

OBJECTIVE: To estimate the risk for twin anemia-polycythemia sequence (TAPS) and adverse perinatal outcome in monochorionic diamniotic (MCDA) twin pregnancies with amniotic fluid discordance (AFD). METHODS: Retrospective cohort study of 34 MCDA pregnancies with AFD (intertwin difference of ≥3 cm in maximal vertical pocket measurement) without meeting the criteria for twin to twin transfusion syndrome or selective intrauterine growth restriction. Perinatal outcome measures and the risk for TAPS were compared with a control group consisted of 101 MCDA twin pregnancies without AFD, twin to twin transfusion syndrome, or selective intrauterine growth restriction. Composite neonatal morbidity was defined as the presence of respiratory distress syndrome, intraventricular hemorrhage grades 3 and 4, necrotizing enterocolitis or sepsis. RESULTS: Overall, in the AFD group, seven twin pairs (20.6%) were complicated by TAPS compared with none in the controls (p < 0.001). In the AFD group, women who developed TAPS had significantly higher AFD compared with women who did not develop TAPS (7.3 cm vs 4.2 cm, p < 0.01). Patients in the AFD group delivered earlier (34.6 vs 35.8 weeks, p < 0.001) and had significantly higher rate of composite neonatal morbidity compared with the control group (13.2 vs 2.5%, p = 0.002). CONCLUSIONS: Despite the overall favorable outcome, MCDA twins with AFD are at increased risk for developing TAPS. © 2016 John Wiley & Sons, Ltd.

Twin Anemia-Polycythemia Sequence: Perinatal Management and Outcome.

OBJECTIVE: To determine the perinatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS). METHODS: All monochorionic twins diagnosed with TAPS between 2011 and 2014 were included. Each twin pair with TAPS (study group) was compared with 2 uncomplicated monochorionic twin pairs who were matched for gestational age at delivery (control group). Neonatal morbidity and mortality were evaluated. RESULTS: During the study period, 179 monochorionic twins were followed at our center, of whom 46 underwent laser ablation due to twin-to-twin transfusion syndrome. TAPS was diagnosed in 10 cases; 8 of them were spontaneous, and 2 occurred following laser surgery. Out of 7 patients diagnosed prenatally with TAPS, 5 cases were managed expectantly, and 2 cases were treated with intrauterine blood transfusion. The rates of severe and mild central nervous system lesions on postnatal ultrasound were similar in the TAPS group and control group (5.0 vs. 2.5%, p = 0.61, and 5.0 vs. 12.5%, p = 0.25, respectively). Additionally, severe neonatal morbidity was comparable between the groups. All neonates were alive at 1 month of age. CONCLUSION: The neonatal outcome of monocohorionic twins affected by TAPS is favorable and comparable to gestational age-matched uncomplicated monochorionic twins.

Circulating angiogenic factors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome and selective intrauterine growth restriction.

OBJECTIVE: To determine maternal plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), placental growth factor (PLGF), and soluble endoglin (sEng) in monochorionic diamniotic (MC/DA) twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) or selective intrauterine growth restriction (sIUGR). STUDY DESIGN: A longitudinal cohort study of pregnant women with MC/DA twins who were classified into 3 groups: (1) uncomplicated MC/DA twins (n = 22), (2) TTTS (n = 23), and (3) sIUGR (n = 15). Maternal plasma samples were obtained between 13-20 and 21-28 weeks of gestation and cord blood samples were collected at delivery. Maternal plasma concentrations of sVEGFR-1, PLGF, and sEng, as well as cord blood levels of sVEGFR-1 were measured by enzyme-linked immunoassay. RESULTS: Maternal plasma levels of sVEGFR-1 and sEng were significantly higher in patients with TTTS at the early and late second trimester compared with normal monochorionic pregnancies (P < .01). In contrast, in the sIUGR group, sVEGFR-1 and sEng levels were significantly higher only at the late second trimester (P < .05). PLGF levels were significantly lower at the early and late second trimester in both TTTS and sIUGR compared with controls (P < .01). Plasma concentrations of sVEGFR-1 were significantly higher among TTTS pregnancies compared with sIUGR at the late second trimester (P = .027). Cord blood levels of sVEGFR-1 were significantly higher in the smaller intrauterine growth restricted twin compared with the normal cotwin. CONCLUSION: Monochorionic pregnancies complicated by TTTS and sIUGR are characterized by decreased angiogenic activity. The disparity in severity of the antiangiogenic state between TTTS and sIUGR suggests that these 2 conditions may represent a continuum.

Regional apparent diffusion coefficient values in 3rd trimester fetal brain.

INTRODUCTION: Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. METHODS: Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. RESULTS: Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. CONCLUSION: ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies.

Compound heterozygosity of HLA-DRB3*01:01 and HLA-DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia.

BACKGROUND: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder in the fetus or neonate caused by maternal alloantibodies directed against fetal platelet (PLT) antigens inherited from the father. The immune-dominant antigen leading to severe FNAIT is the human PLT antigen (HPA)-1, whose polymorphism constitutes an epitope for human leukocyte antigens (HLAs), usually DRB3*0101 leading to an immune response. STUDY DESIGN AND METHODS: In this study our aims were to find whether other allele variants of the ß subunit of the HLA-DR family specifically focused on the HLA residues that bind Position 33 of the HPA-1 integrin contribute to FNAIT development and affect response to treatment and whether coexistence of both anti-HPA-1a and anti-HLA class I specific against the father's antigens leads to a more severe thrombocytopenia in the newborn. We examine the genotype of 23 mothers to newborns with FNAIT compared to a control group. RESULTS: Our results suggested that, when HPA-1 incompatibility with the husband is found, the presence of two HLA alleles (DRB3*01:01 and DRB4*01:01) in the mother increases the risk and severity of FNAIT and reduces the success of a preventive immunoglobulin G treatment. We provide a structural model for the molecular basis of the rational effects of the different HLA alleles. In addition, we found that the presence of both anti-HPA-1 and anti-HLAs did not aggravate FNAIT in comparison to mothers harboring only anti-HPA-1. CONCLUSION: Overall, we suggest that a specific genotyping of the mother in relation to HLA-DRB as well as HPA-1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT.

In-utero treatment of prenatal thoracic abnormalities by thoraco-amniotic shunts, short and long term neuro developmental outcome: A single center experience.

BACKGROUND: Severe primary fetal hydrothorax (PFH) and fetal lung lesions (FLL) such as congenital pulmonary airway malformation (CPAM) and Bronchopulmonary sequestration (BPS) are often treated by thoraco-amniotic shunt (TAS). OBJECTIVES: To compare short and long-term outcome of fetuses treated by TAS due to FLL to those treated due to PFH. METHOD: A retrospective analysis was performed for all fetuses treated by TAS, between the years 2004-2015, evaluating the short and long term neurodevelopmental outcome. Long term neurodevelopment was additionally analyzed prospectively by Vineland adaptive behavioral scale (VABS) standardized questionnaires. RESULTS: 38 fetuses were treated by 52 TAS insertions; of which 13 (35%) due to FLL and 25 due to PFH. Perinatal survival was high (87.9%) with 3 neonatal death and one termination of pregnancy (TOP). High survival rate persisted even in cases requiring recurrent shunt insertion (80% survival). There was no significant difference in short or long term outcome including perinatal survival (84% Vs 90%, P = 0.64) and hydrops resolution (91% Vs 63%, p = 0.19). Long term outcome, including rate of neurodevelopmental abnormalities (23.5% Vs 20%) and VABS score (91.3 ± 13.3 Vs 96.4 ± 14.7), were similar for both groups. CONCLUSION: TAS insertion is effective and resulting in high perinatal survival even in cases when sequential insertion is needed. Short and long- term outcome of neonates with FLL treated by TAS are comparable to neonates treated due to PFH.

Procedure-to-delivery interval after late amniocentesis and the need for routine antenatal corticosteroids.

OBJECTIVES: The aim of this study is to assess the procedure-to-delivery interval (PDI), the obstetric complications, and the early neonatal outcome in patients that did or did not receive glucocorticosteroids (GCSs) before third-trimester amniocentesis (TTA). METHODS: A retrospectively analysis of 445 TTA procedures divided into two groups based on the administration (study group = 220 patients) or not (control group = 225 patients) of GCSs before TTA. The PDI was calculated for all patients. Obstetric and neonatal outcomes were compared between the groups. RESULTS: The rate of procedure-associated complications was similar between the groups. The mean PDI was 47.2 ± 16.8 days. The overall incidence of preterm birth was 11.7%; 9% delivered between 34 and 37 weeks and 2.7% between 28 and 34 weeks. Only nine patients (2%) delivered within seven days following TTA. The incidence of respiratory distress syndrome in the study and control groups was 1.8% and 1.3%, p = .71, respectively. There were no significant differences in other neonatal outcomes in term and preterm deliveries between the study and control groups. CONCLUSIONS: In the present study, the administration of glucocorticoids prior to TTA did not reduce the rates of neonatal complications, which was similar in both groups and not higher than the general population.

Late selective termination and the occurrence of placental-related pregnancy complications: A case control study.

INTRODUCTION: Multiple pregnancies are at increased risk of placental-related complications. The aim of the study was to investigate the prevalence and cumulative incidence of placental-related complications in twin pregnancies undergoing a late selective termination, compared to matched singleton and twin controls. METHODS: A retrospective case-control study of post-selective late termination (≥20 weeks of gestation) singletons performed between 2009 and 2020 at a single tertiary center. Each post-termination pregnancy was matched to 2 singleton and 2 dichorionic twin pregnancies for: mode of conception, maternal age group and parity. The prevalence of composite placental related outcome was determined and compared. Kaplan-Meier curves were constructed, and log rank test was performed to compare the cumulative incidence of placental complications among groups. RESULTS: Included were 90 post-selective termination pregnancies and 360 matched singletons and twins. These were subdivided according to trimester at procedure: 1) late 2nd trimester (N = 43, 20-27.6 weeks); 2) 3rd trimester (N = 47, ≥28 weeks). Placental-related complications presented earlier in the 3rd trimester selective termination group compared to singletons (median 35.5 vs median 37.4 weeks of gestation, P = 0.01). The cumulative incidence of placental-related complications in twins and post-selective termination singletons rose significantly earlier compared to singletons (P < 0.0001). A late 2nd trimester selective termination resulted in a comparable gestational age and cumulative incidence of placental-related complications as singletons. DISCUSSION: Compared to singletons, the cumulative incidence of placental complications rises significantly earlier in post-third trimester selective termination singleton pregnancies. While a late 2nd trimester selective termination results in a cumulative incidence comparable to singletons.

Pregestational, periconceptional, and gestational primary maternal cytomegalovirus infection: prenatal diagnosis in 508 pregnancies.

OBJECTIVE: The objective of the study was to evaluate the vertical transmission rate and fetal risk following primary maternal cytomegalovirus infection before and around conception. STUDY DESIGN: Data of patients referred to fetal medicine clinic in 1 tertiary center in Israel were evaluated. Each included subject had primary maternal cytomegalovirus infection determined by serology, precise gestational dating, and testing of fetal infection. Subjects were assigned to five subgroups: pregestational, periconception, and first, second, or third trimester of pregnancy. RESULTS: Five hundred eight pregnancies were included. None of the 97 pregnancies in the preconception group and 6 of the 130 periconception subjects (4.6%) were congenitally infected. Transmission rates were 34.8%, 42.0%, and 58.6% for the first, second, and third trimesters, respectively (P = .049). Prenatal and postnatal follow-up indicated that third-trimester infection has no clinical effect on the fetus. CONCLUSION: Pre- and periconception maternal infection carries small risk for fetal infection, whereas it is positively correlated to time of maternal infection during pregnancy.