Prenatal Diagnosis and Outcome of Tracheal Agenesis as Part of Congenital High Airway Obstruction Syndrome. Case Presentation and Literature Review

Tracheal atresia is an extremely rare condition whereby a partial or total obstruction of the trachea is seen. It is almost always lethal, with just a handful of cases that ended with a good outcome. In this study we report on a 15-week male fetus, diagnosed with hyperechogenic lungs, midline heart position and inverted diaphragm. Sonographic findings suggest congenital High Airway Obstruction Syndrome (CHAOS) An ultrasound scan and fetal MRI were not able to point out the exact obstruction level. In spite of extensive counselling, the parents opted to carry on with the pregnancy. Fetal demise was noted on a scan at 19 weeks gestation. After the elective termination of pregnancy, a post-mortem examination showed partial tracheal atresia with no other anomalies. Despite technological progress in CHAOS syndrome, a precise diagnosis and accurate prognosis remain elusive.

Surveillance Program of Romiplostim Use Connected to Pregnancy

Introduction Immune thrombocytopenia (ITP), defined as an isolated low platelet count (<100 × 10 9/L), occurs in approximately 1 in 1000 to 10,000 pregnancies in the United States and is the most common cause of severe thrombocytopenia (platelet count <50 × 10 9/L) detected in the first and second trimesters. Treatment for ITP during pregnancy is limited by the lack of safety evidence for the fetus/infant. The Pregnancy Surveillance Program (PSP) was conducted to collect safety information on pregnancy and fetal outcomes of women exposed to the thrombopoietin receptor agonist romiplostim before conception, during pregnancy, or immediately postpartum. Here, we report pregnancy and birth outcomes as well as adverse events (AEs) for mother and fetus/infant. Methods Pregnancy outcomes data from women of 25 different countries were collected from August 1, 2017-March 15, 2020. Authorization to obtain pregnancy and infant health information as well as follow up with healthcare professionals was obtained from the mothers. One follow-up attempt was made if the mother was unresponsive, and two follow-up attempts were made 6-8 weeks after the mother's estimated date of delivery. Additional follow-ups were conducted when the infant was 6 and 12 months of age. Romiplostim pregnancy exposure cases reported during the data-collection period were entered into the PSP database and reported to global health authorities per local rules and regulations. Abnormal pregnancies were defined as those with at least one serious AE. Birth outcomes included live birth, premature birth, spontaneous abortion, elective termination, and stillbirth. Results Overall, 200 pregnancies were reported, including 11 pregnancies from clinical study sources, and 189 pregnancies from non-trial sources; 188 women were exposed to romiplostim. Two pregnancies were ongoing at the time of data cutoff (March 15, 2020). The median (Q1, Q3) overall duration of romiplostim exposure was 156 (44, 522) days (data available for 56 women), and 28 (7, 60) days during pregnancy (data available for 53 women). Median (Q1, Q3) age for the pregnant women was 30 (27, 33) years. Concomitant medications for ITP were used by 61 (32%) women and included corticosteroids (n=37), immunoglobulins (n=29), and rituximab (n=8). Overall, 43 (23%) women received treatment with romiplostim in the third trimester with median (Q1, Q3) exposure of 21 (7, 63) days. Of the 86 known pregnancy outcomes by trimester exposure (Figure 1), 40 (46.5%) were normal pregnancies with 15% abnormal birth outcomes, and 46 (53.5%) were abnormal pregnancies with 65.2% abnormal birth outcomes; 26 (56.5%) of the abnormal pregnancies were low platelet counts. Three cases of ectopic pregnancy were reported among women receiving romiplostim for ITP prior to conception. In all three women, romiplostim was continued up to, during, and after the ectopic pregnancy. One molar pregnancy was reported in a woman who received romiplostim for chronic ITP for approximately one year before conception. Of the 96 known birth outcomes, 57.3% were normal term, 11.5% were spontaneous abortion, 9.4% were term with complication (inguinal hernia, congenital cytomegalovirus infection, trisomy 8, and single umbilical artery), 9.4% were elective termination, and 12.4% were other outcomes (including 11 premature births, and one stillbirth). Twelve infants (including one case of twins) had thrombocytopenia at birth, of whom nine received immunoglobulins, and three received platelet transfusions. Out of the 12 infants, eight had resolution of thrombocytopenia within a week, and four (including the twins) had no available information about outcomes. No infant had defective immune system development, neoplasm, or bone marrow reticulin formation. One infant was diagnosed with fetal and neonatal alloimmune thrombocytopenia that resolved two months after birth. Among the 12 thrombocytopenic infants, six had good and six had unknown current/discharge health status. Conclusions The available data from the PSP suggested that the risk of adverse birth outcomes was low regardless of the timing of exposure. Additionally, no substantial safety concerns were identified for the mothers, fetuses, and infants due to romiplostim use during pregnancy. The results are complicated, however, by the abnormal pregnancies in women with severe ITP who comprised the majority of cases where romiplostim was used. Figure 1 Figure 1. Disclosures Bussel: UCB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Dova/Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Other: DSMB; Principia/Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Momenta/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; UptoDate: Honoraria; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; RallyBio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cooper: Principia and Sanofi: Consultancy; Sanofi and Principia: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel, accommodations expenses. Lawrence: Amgen Inc: Current Employment, Current equity holder in publicly-traded company. Michel: Amgen: Consultancy; Rigel: Honoraria; Novartis: Consultancy; Argenx: Honoraria; UCB: Honoraria; Alexion: Honoraria. Wang: Amgen Inc: Current Employment, Current equity holder in publicly-traded company. Saad: Amgen: Current Employment, Current equity holder in publicly-traded company.

Staged embolisation of a giant torcular dural sinus malformation in a neonate

Torcular dural sinus malformations (tDSMs) represent a rare subset of paediatric cerebrovascular malformations and are often diagnosed antenatally via ultrasound. The management of these in utero lesions remains controversial as previous studies suggested elective termination of the pregnancy because of their presumably high mortality and severe long-term morbidity. However, more recent evaluations have suggested that the overall prognosis for infants harbouring these lesions may be much better than previously believed. As such, we present the case of a neonate with a giant tDSM, diagnosed in utero, who was treated postnatally via staged transarterial and transvenous embolisation to alleviate worsening obstructive hydrocephalus and brainstem compression. We provide details regarding the surgical approach and long-term neurological outcomes for this patient. To the best of our knowledge, this is one of the largest reported tDSM presented in the literature.

Improving long-term outcomes in pediatric torcular dural sinus malformations with embolization and anticoagulation: a retrospective review of The Hospital for Sick Children experience

OBJECTIVE Torcular dural sinus malformations (tDSMs) are rare pediatric cerebrovascular malformations characterized by giant venous lakes localized to the midline confluence of sinuses. Historical clinical outcomes of patients with these lesions were poor, though better prognoses have been reported in the more recent literature. Long-term outcomes in children with tDSMs are uncertain and require further characterization. The goal of this study was to review a cohort of tDSM patients with an emphasis on long-term outcomes and to describe the treatment strategy. METHODS This study is a single-center retrospective review of a prospectively maintained data bank including patients referred to and cared for at The Hospital for Sick Children for tDSM from January 1996 to March 2019. Each patient’s clinical, radiological, and demographic information, as well as their mother’s demographic information, was collected for review. RESULTS Ten patients with tDSM, with a mean follow-up of 58 months, were included in the study. Diagnoses were made antenatally in 8 patients, and among those cases, 4 families opted for either elective termination (n = 1) or no further care following delivery (n = 3). Of the 6 patients treated, 5 had a favorable long-term neurological outcome, and follow-up imaging demonstrated a decrease or stability in the size of the tDSM over time. Staged embolization was performed in 3 patients, and anticoagulation was utilized in 5 treated patients. CONCLUSIONS The authors add to a growing body of literature indicating that clinical outcomes in tDSM may not be as poor as initially perceived. Greater awareness of the lesion’s natural history and pathophysiology, advancing endovascular techniques, and individualized anticoagulation regimens may lead to continued improvement in outcomes.

Hispanic Acculturation: Associations with Family Planning Behaviors and Attitudes

INTRODUCTION. The purpose of this study was to investigate the association of Hispanic acculturation in the United States (US) with family planning behaviors and attitudes. METHODS. Surveys of 225 Hispanic women were collected that used acculturation measures of number of years lived in US and the Short Acculturation Scale for Hispanics (SASH) along with questions about family planning behaviors including birth control use, sterilization, and abortion. RESULTS. SASH-Language statistically differed (p=0.03) where those with ‘yes birth control’ had significantly lower English acculturation (M=6.10, SD=1.77) than those with ‘no birth control’ (M=7.00, SD=3.16). Greater US acculturation on SASH-Ethnic Social Relations was positively associated with the attitude that finances are important when considering to have children (r=0.18, p<0.05). Number of years lived in the US was positively associated with the attitude that it is a woman’s personal choice to have an elective termination of pregnancy (r=0.19, p<0.01). CONCLUSIONS. Healthcare providers should consider patient acculturation level when discussing family planning topics. It is possible that a more detailed explanation concerning the reasons for family planning is necessary when discussing family planning topics with Hispanic patients who exhibit higher levels of English language acculturation.

Recurrent fetal triploidy: is there a genetic cause?

Triploidy is currently understood as a sporadic genetic disorder, with no recognisable risk of recurrence nor identifiable risk factors. In cases of triploidy, chances of thriving through the second trimester of fetal development are very slim, with most of these pregnancies ending as early miscarriage. We report a case of repeated triploid pregnancies in the same woman, from different fathers, achieving the second trimester of pregnancy; elective termination was decided in both cases, after an amniocentesis revealing a triploid karyotype. Both triploid pregnancies are described and compared; prenatal laboratorial markers, sonographic features, clinical course and pathological findings are analysed and matched with fetal autopsy and placental pathological study. Reported findings strongly point to recurrent triploidy of maternal origin, and so the possibility of a genetic predisposition should be considered. Investigation is required to assess the presence of an underlying genetic mechanism in this setting, thus enabling a better genetic/obstetric counselling.

Congenital High Airway Obstruction Syndrome (CHAOS): No Intervention, No Survival—A Case Report and Literature Review

Congenital high airway obstruction syndrome (CHAOS) is complete or partial obstruction of the fetal upper airway. CHAOS is a rare and fatal condition if no perinatal intervention is done. Antenatal sonographic imaging has typical findings that can help in an early diagnosis, which is important in deciding elective termination of the pregnancy or successful planning of appropriate perinatal management.