Band 14, Heft 1

Objectives Midline defects in the brain may be related to genetic syndromes. Association with facial anomalies and skeletal deformities has been described. Case presentation In the present case, a routine second trimester scan revealed cerebral abnormalities (corpus callosum agenesis, cerebellar cleft due to vermian hypoplasia, ventriculomegaly), suspected cortical developmental disorder, hypertelorism, a hypoplastic nasal bone, a small median cleft lip and palate, abnormal facial profile, as well as syndactyly of the left hand involving the fourth and fifth finger. Genetic testing revealed a normal karyotype. Subsequent trio exome sequencing did not identify any pathogenic variants or variants of unknown significance. The vaginal delivery at term and postnatal adaptation were uneventful. Postnatal neurosonographic imaging and clinical evaluation confirmed the prenatal findings. Both mother and child were discharged in healthy condition with scheduled follow-ups. Differential diagnoses of the present anomalies include Hartsfield-Bixler-Demyer Syndrome, Oro-Facial-Digital-Syndromes, Ectrodactyly Ectodermal Dysplasia Cleft Lip/Palate Syndrome and Acrocallosal Syndrome. Conclusions Invasive diagnostic and genetic testing are recommended when multiple fetal anomalies suggest a potential genetic syndrome. While not all cases reveal an underlying genetic cause, prenatal findings can provide valuable information to help parents and healthcare providers make informed decisions about the continuation of the pregnancy.

Objectives Choriocarcinoma, an aggressive form of gestational trophoblastic neoplasia, can be divided into gestational and non-gestational types, each with distinct biological activity and prognosis. We report a case of gestational choriocarcinoma. Case presentation A 38-year-old woman (2 Gravida, 2 Para) presented at our clinic four weeks after her second cesarean section with persistent vaginal bleeding and decreasing hemoglobin to 6.8 mg/L. In the ultrasound examination, retained placental tissue was suspected. Since conservative management with misoprostol was not effective, a curettage was performed. The histopathological result revealed a gestational choriocarcinoma invading the myometrium (CK18 positive, HPL positive, beta-hCG positive, p63 negative, PLAP positive, Ki67 (MIB-1)>80 %). Beta-hCG was 50,607 IU/L at the time of diagnosis. The computed tomography (CT) scan revealed bilateral pulmonary metastases. There were no metastases to the liver, lymph nodes, skeleton or brain. In accordance with FIGO recommendations [stage III, Score 8 (high risk) choriocarcinoma] a multi-drug chemotherapy after EMACO-regimen was started 9.5 weeks postpartum during 14 days for seven cycles. The patient has been in tumor remission since then. Conclusions Choriocarcinoma is a differential diagnosis of vaginal peripartum bleeding and might likely be underdiagnosed. Risk factors like a prior hydatidiform mole or abortion, Asian, Indian American, African American or Hispanic ethnicity, advanced maternal age (>40 years), blood group A, or high/increasing beta-hCG postpartum should be taken into consideration.

Objectives To highlight the importance of serial echocardiography in preterm infants with bronchopulmonary dysplasia (BPD) to diagnose recurrent pulmonary vein stenosis (PVS) and understand its contribution to respiratory deteriorations. Case presentation A preterm female infant born at 23+5 weeks gestation had numerous complications related to extreme prematurity, including BPD. She was diagnosed with PVS on echocardiogram after experiencing recurrent respiratory deteriorations and pulmonary hypertensive crises. Initial management involved transcutaneous balloon dilatation. A serial echocardiographic programme was implemented, with weekly monitoring of PVS. She suffered multiple respiratory deteriorations secondary to recurrence of PVS, necessitating repeat cardiac catheterisations and transcatheter stenting. Systemic macrolide therapy with sirolimus was used as adjunctive therapy. Conclusions Extremely prematurely born infants who develop BPD are at higher risk of recurrent PVS. We demonstrate that serial echocardiographic monitoring facilitates early diagnosis and prompt intervention of PVS. Any respiratory deterioration in such infants should be assessed by an echocardiogram.

Objectives This report describes the case of an infant with congenital thrombotic thrombocytopenic purpura. Case presentation An infant who presented after birth with severe neonatal indirect hyperbilirubinemia, thrombocytopenia and hemolytic anemia. His initial neonatal course was complicated with hypoxemic respiratory failure due to persistent pulmonary hypertension of the newborn, acute kidney injury and disseminated intravascular coagulopathy. After surviving the acute neonatal presentation, he presented with stress-induced recurrent hemolytic anemia and thrombocytopenia. The diagnosis of congenital TTP was suspected and confirmed by low ADAMTS13 activity, the absence of ADAMTS13 inhibitors, and the identification of a homozygous variant in the ADAMTS13  gene. Conclusions Although rare, congenital TTP needs to be considered by neonatologists when dealing with a neonate with hemolytic jaundice, anemia, and thrombocytopenia. PPHN can complicate the initial presentation of congenital TTP.

Objectives To describe the clinical presentation and response to medication in two cases of self-limiting KCNQ2 -related epilepsy. Case presentation Both infants were born at term and had tonic seizures during the first two weeks after birth. The first infant had frequent seizures at presentation requiring two weeks of hospital stay. The second infant was born three months later and was only briefly admitted to hospital. The first infant was conceived by sperm for in vitro fertilization donated by the second case’s father. Trio genome sequencing in case one successfully identified a pathogenic KCNQ2 variant in the proband, which was also confirmed in the proband for case 2 by targeted Sanger sequencing. The second case’s father was an asymptomatic carrier of the pathogenic variant. Both infants responded to Carbamazepine. At more than six months of age, they are currently seizure free and developmentally normal. Conclusions Self-limited epilepsies with onset in neonates (SeLNE) are usually autosomal dominant disorders characterized by the neonatal onset of focal motor seizures and the absence of neurodevelopmental complications. KCNQ2 , encoding a voltage-gated potassium channel subunit, K V 7.2, is the most common gene associated with SeLNE. Careful history taking and a genetic diagnosis can help to make the correct therapeutic choices.

Objectives Partial trisomy of chromosome 1 has been reported following unbalanced translocations with partial monosomies of other chromosomes and rarely as a pure partial duplication. We aim to discuss partial trisomy 1q with cytogenetics and describe our findings of this uncommon chromosomal aneuploidy. Case presentation A male term neonate presented with antenatal ventriculomegaly and early fetal growth restriction. He was dysmorphic at birth and his postnatal course was complicated by transient myeloproliferative disorder, neonatal seizures, skin rash, conjugated hyperbilirubinemia, and milk protein allergy. Etiological work-ups including congenital infections, immunological disorders, and inborn error of metabolisms were negative. The findings of transient myeloproliferative disorder in association with partial 1q trisomy which have not been previously described in the literature, raise the possibility of abnormal vasculature of generalized nature, resulting in cutis marmorata, signs of intestinal inflammation, and abnormal cerebral vascular supply. Conclusions This case study highlights the importance of pooling cases with similar locations of duplication, segment size, and related chromosomal deficiency together to understand distinct clinical phenotypes.

Objectives Intra-amniotic colonisation or infection caused by Candida albicans is rare. Given the shortage of reported cases, evidence on antifungal strategies and the choice of type and timing of delivery is limited. Case presentation We report a case of intra-amniotic colonisation by C. albicans in a pregnant woman with a previous history of cervical cerclage and candidal vaginosis at 25 weeks of gestational age (GA). The diagnosis was made following preterm premature rupture of membranes at GA 28 weeks and 6 days. Treatment was started with amphotericin B and was replaced by fluconazole due to an anaphylactic reaction. The persistence of C. albicans in the amniotic fluid after 24 days of treatment prompted the decision to plan an elective caesarean delivery at 32 weeks’ GA. The infant showed no signs of fungaemia and had an uneventful clinical course after 14 days of treatment with fluconazole. Conclusions Conservative management with intravenous fluconazole in pregnant women with intra-amniotic colonisation by C. albicans at early GA, can contribute to the prolongation of pregnancy while protecting the foetus from fungal disease.

Objectives To compare clinical presentation and diagnostic evaluation to identify differences in treatment between pregnant and nonpregnant patients with appendicitis. Methods Retrospective case-control study comparing 12 pregnant and 60 nonpregnant, age-matched patients who had an appendectomy for acute appendicitis (pathology confirmed) between January 1, 2011 and June 30, 2019. We compared maternal characteristics, laboratory test results, physical examination findings, diagnostic work-up, surgical modality, and surgical outcomes. Results There was no difference in symptom profile and pain intensity at presentation between groups. More pregnant patients had right upper quadrant tenderness (83.3% vs. 31 %, p=0.03) and were more likely to have more than one imaging diagnostic modality (75% vs. 15 %, p<0.01). In nonpregnant patients, computed tomography was the main diagnostic modality (90 %) whereas there was more variation in imaging for pregnant patients. For pregnant patients, time from presentation to surgery (20.0 ± 11.8 h vs. 9.9 ± 4.9 h; p=0.01) and time from presentation to receipt of antibiotics (14.5 ± 12.0 h vs. 5.9 ± 3.2 h, p<0.01) were twice that of nonpregnant patients. Surgery duration was similar between groups (pregnant: 54.8 ± 31.3 min vs. nonpregnant: 45.6 ± 19.5 min, p=0.34). All nonpregnant patients underwent laparoscopic appendectomy. Seven pregnant patients underwent laparoscopy, three had laparotomy, and two began with laparoscopy that was converted to laparotomy. More pregnant patients perforated (25 % vs. 3.3 %, p=0.03). Conclusions Despite having similar presentations, it took twice as long to treat pregnant patients with antibiotics and perform an appendectomy. More perforations occurred in pregnant patients compared to nonpregnant patients.

Objectives Intravenous immunoglobulin (IVIG) in pregnancy has been used to treat hematologic conditions, but there is limited literature on its use in acute Parvovirus B19 infection. The purpose of this report is to highlight IVIG treatment recommendations based on low reticulocyte counts and high middle cerebral artery peak systolic velocity (MCA-PSV) values to prevent fetal hydrops, as well as identify which patients would benefit from high-dose IVIG administration in the setting of acute Parvovirus B19 infection in the second trimester. Case presentation We present the treatment of acute Parvovirus B19 infection with IVIG in two affected pregnancies, as an alternative to percutaneous umbilical blood sampling (PUBS) and intrauterine transfusion (IUT). Conclusions IVIG may be useful for Parvovirus B19 treatment in patients with erythropoietic suppression, in patients who decline PUBS/IUT with elevated MCA-PSV, and in patients who have difficult access to the placental cord insertion site, unsuccessful attempt at PUBS, or relative contraindications (i.e. significant abdominal surgery, high BMI).

Objectives With the advancement of next-generation sequencing (NGS), whole-exome sequencing (WES) has proven useful in diagnosing various diseases, particularly neurodevelopmental disorders, during both the prenatal and postnatal periods. In this study, we examined the correlation between the results of chromosomal microarray analysis (CMA) and WES in pregnant women, as compared to conventional karyotype analysis and ultrasound (US) findings. Methods Fetal US were performed on pregnant females referred to our clinic with suspected fetal anomalies, as well as those who had anomalies detected by targeted US. Comprehensive counseling was provided to all parents. Karyotyping, CMA, and WES were offered for all fetuses through amniocentesis, CVS, and cordocentesis. We compared the demographic data and ultrasound findings of pregnant females with normal and abnormal WES results. Results WES results indicated a normal karyotype in 14 pregnant females and an abnormal karyotype in 12 pregnant females. CMA showed an abnormal karyotype in three of the pregnant females, whose WES results were normal. US findings were more frequently observed in pregnant females with abnormal WES results. Conclusions Among the organ systems, the cardiac system is at the highest risk for anomalies. The risk further increases when multiple system anomalies are present. Incorporating WES alongside CMA may enhance diagnostic accuracy and be beneficial for subsequent pregnancies. Our US results do not align with the existing literature, and further evaluations with larger patient populations are needed to reconcile these findings with current research.

Objectives Haemolytic disease of the fetus and newborn (HDFN) occurs due to maternal IgG alloantibodies that actively cross the placenta and bind to paternally derived fetal antigens on the erythrocytes. The aims of this study were to describe the Slovenian cohort of patients with severe HDFN, who required fetal treatment, to review the fetal treatment strategies, and to describe pregnancy and neurodevelopmental outcomes. Case series presentation Data on patients who developed severe HDFN between 2006 and 2021 and were treated at our institution were collected retrospectively. Primary care pediatricians were contacted regarding neurodevelopmental outcomes of surviving infants. There were 19 pregnancies affected with severe HDFN. The most commonly implicated antigen was RhD. Seventeen children were liveborn. Sixteen fetuses were treated with intrauterine transfusion (IUT). Two children had developmental delay at the corrected age of 2 years. Conclusions In this study, the Slovenian national cohort of severe cases of HDFN is described for the first time. Prevalence of RhD alloimmunization was higher in comparison to the literature. A combined treatment with therapeutic plasmapheresis, immunoglobulins and IUT was successful. Three quarters of newborns were born in the late preterm period. Overall survival rate and long-term neonatal adverse outcomes in our cohort were in line with the literature.