Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.

Background The purpose of this study was to investigate obstetric and maternal outcome of pregnant patients with Hodgkin lymphoma (HL). Methods Clinical data of pregnant patients diagnosed with HL were registered by the International Network on Cancer, Infertility and Pregnancy (INCIP). For survival analysis of patients that received ABVD-based treatment between 1997 and 2018, matched non-pregnant controls were selected based on stage and prognostic score at diagnosis. Findings The majority of the 134 included patients were diagnosed with early stage HL (75%) and nodular sclerosis subtype (81%). The median gestational age at diagnosis was 20 weeks (range 3-37). 58% of patients initiated with antenatal treatment and over the years chemotherapy was increasingly prescribed during pregnancy. 90% of pregnancies ended in a live birth. 19% of neonates were small for gestational age and, customised birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared to non-exposed neonates (p=0.035) Progression-free survival (PFS) and overall survival (OS) of pregnant patients was not significantly different from non-pregnant controls. Five-year PFS and OS for early stage HL was 82.5% and 97.3% for 62 pregnant patients and 88.2% and 98.4% for 142 non-pregnant patients, respectively. Subgroup analysis of patients that initiated chemotherapy during pregnancy or had a pregnancy-related delay to initiate treatment was reassuring. For advanced stage HL 5-year PFS and OS survival was 90•9% and 100% for 15 pregnant patients and 74.0% and 96.2% for 69 corresponding controls, respectively. Low numbers did not allow solid conclusions. Interpretation The increasing trend to treat HL during pregnancy might impact foetal growth, whereas the maternal overall survival remains intact. Our reassuring results can only be consolidated if management during pregnancy adheres as much as possible to standard protocols.

The effects of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in women on the gestation course and the health of the fetus, particularly in the first and second trimesters, remain very poorly explored. This report describes a case in which the normal development of pregnancy was complicated immediately after the patient had experienced Coronavirus disease 2019 (COVID-19) at the 21st week of gestation. Specific conditions included critical blood flow in the fetal umbilical artery, fetal growth restriction (1st percentile), right ventricular hypertrophy, hydropericardium, echo-characteristics of hypoxic-ischemic brain injury (leukomalacia in periventricular area) and intraventricular hemorrhage at the 25th week of gestation. Premature male neonate delivered at the 26th week of gestation died after 1 day 18 h due to asystole. The results of independent polymerase chain reaction (PCR), mass spectrometry and immunohistochemistry analyses of placenta tissue, umbilical cord blood and child blood jointly indicated vertical transmission of SARS–CoV-2 from mother to the fetus, which we conclude to be the major cause for the development of maternal vascular malperfusion in the studied case.

Objectives: Evaluation of clinical course of COVID-19 during pregnancy and maternal and perinatal outcomes of this pregnancy. Methods: 66 women with polymerase chain reaction (PCR)confirmed SARS-CoV-2 and their 42 neonates were included in the prospective observational study. Demographic, epidemiological, clinical, laboratory and instrumental data of pregnancy, delivery, postpartum period, including pharmacotherapy and neonatal outcomes were analyzed. Results: 15 (22.7%) women were asymptomatic, 25 (38%) had mild disease, while moderate and severe forms were detected in 20 (30.2%) and 6 (9.1%) cases, respectively. Additional oxygenation was required in 6 (9%) cases: 4 (6%) received CPAP therapy and 2 (3%)mechanical ventilation. Main clinical symptoms were cough (51.5%), anosmia (34.9%), and hyperthermia (33.3%). Laboratory changes included increased levels of lactate dehydrogenase (LDH), creatinine, D-dimer, and C-reactive protein (CRP), anemia, and leukopenia. All pregnant women received low molecular weight heparin and interferon alfa-2b according to the National clinical recommendations. Antimicrobial drugs included Amoxicillin/Clavulanic acid (46%) and macrolides (28%) or carbapenems in severe cases of disease. Spontaneous abortion was reported in 6.1% of cases. Eight preterm (19%) and 34 term deliveries (81%) occurred. The mean weight of neonates was (3283 ± 477) g, 1-and 5-min Apgar score was (7.8 ± 0.6) and (8.7 ± 0.5), respectively. No cases of neonatal COVID-19 infection were reported. Conclusions: Mostly, the manifestations of COVID-19 were mild. However, 9% of cases were severe, and could contribute to preterm delivery or maternal morbidity. Main predictors of severe COVID-19 course in pregnant women were a decrease in the levels of erythrocytes and lymphocytes and increase in the levels of alanine aminotransferase and CRP. Elimination of the virus in pregnant women required more time due to altered immunity. No evidence of vertical transmission during pregnancy and delivery was found. However, the possibility of this cannot be excluded.

Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs. The fetal/maternal concentration ratio ranged from 0.5 to 0.58 for nilotinib and from 0.05 to 0.22 for imatinib. The placental/maternal ratio was higher for imatinib than for nilotinib. Theoretical pharmacokinetic modeling of passive placental crossing was insufficient to predict the in vivo data because the calculated fetal/maternal ratio was close to 1 for both drugs. We propose that active placental transport contributes to fetal protection against TKI exposure during pregnancy.