Clinical course of novel COVID-19 infection in pregnant women.

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.

Epitope-Specific Response of Human Milk Immunoglobulins in COVID-19 Recovered Women.

The breastfeeding of infants by mothers who are infected with SARS-CoV-2 has become a dramatic healthcare problem. The WHO recommends that infected women should not abandon breastfeeding; however, there is still the risk of contact transmission. Convalescent donor milk may provide a defense against the aforementioned issue and can eliminate the consequences of artificial feeding. Therefore, it is vital to characterize the epitope-specific immunological landscape of human milk from women who recovered from COVID-19. We carried out a comprehensive ELISA-based analysis of blood serum and human milk from maternity patients who had recovered from COVID-19 at different trimesters of pregnancy. It was found that patients predominantly contained SARS-CoV-2 N-protein-specific immunoglobulins and had manifested the antibodies for all the antigens tested in a protein-specific and time-dependent manner. Women who recovered from COVID-19 at trimester I-II showed a noticeable decrease in the number of milk samples with sIgA specific to the N-protein, linear NTD, and RBD-SD1 epitopes, and showed an increase in samples with RBD conformation-dependent sIgA. S-antigens were found to solely induce a sIgA1 response, whereas N-protein sIgA1 and sIgA2 subclasses were involved in 100% and 33% of cases. Overall, the antibody immunological landscape of convalescent donor milk suggests that it may be a potential defense agent against COVID-19 for infants, conferring them with a passive immunity.

Vertical Transmission of SARS-CoV-2 in Second Trimester Associated with Severe Neonatal Pathology.

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.

Maternal and neonatal outcomes in 80 patients diagnosed with non-Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy.

This cohort study of the International Network on Cancer, Infertility and Pregnancy (INCIP) reports the maternal and neonatal outcomes of 80 pregnant patients diagnosed with non-Hodgkin lymphoma (NHL) between 1986 and 2019, focussing on 57 (71%) patients with diffuse large B-cell lymphoma (DLBCL). Of all 80 patients, 54 (68%) pregnant patients received chemotherapy; mostly (89%) CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens. Four early pregnancies were terminated. Among 76 ongoing pregnancies, there was one stillbirth (1·3%). Overall, there was a high incidence of small for gestational age neonates (39%), preterm delivery (52%), obstetric (41%) and neonatal complications (12·5%), and this could not exclusively be explained by the receipt of antenatal chemotherapy. Half of preterm deliveries (46%) were planned in order to tailor oncological treatment. The 3-year progression-free and overall survival for patients with DLBCL treated with rituximab-CHOP was 83·4% and 95·7% for limited stage (n = 29) and 60·6% and 73·3% for advanced stage (n = 15). Of 36 pregnant patients who received rituximab, five (13%) cases with neonatal complications and three (8%) with maternal infections were reported. In conclusion, standard treatment for DLBCL can be offered to pregnant patients in obstetric centres that cater for high-risk patients.

Obstetric and maternal outcomes in patients diagnosed with Hodgkin lymphoma during pregnancy: a multicentre, retrospective, cohort study.

BACKGROUND: Outcomes for mother and child following a diagnosis of Hodgkin lymphoma during pregnancy are underinvestigated, and antenatal management of the disease has not been reported on widely. The aim of this study was to assess obstetric outcomes, antenatal management, and maternal survival in patients with Hodgkin lymphoma diagnosed during pregnancy who were registered in the International Network on Cancer, Infertility and Pregnancy (INCIP) database. METHODS: We did a multicentre, retrospective cohort study including oncological and obstetric data from 134 pregnant patients diagnosed with Hodgkin lymphoma between Jan 1, 1969, and Aug 1, 2018. Data collected from the INCIP database were obtained from 17 academic centres in Belgium, Czech Republic, Denmark, Greece, Israel, Italy, Mexico, the Netherlands, Russia, the UK, and the USA. We analysed patients' management over three epochs (before 1995, 1995-2004, and 2005-18). Obstetric outcomes (birthweight, obstetric or neonatal complications, and admission to a neonatal intensive care unit [NICU]) of patients who received antenatal chemotherapy were compared to those of patients who did not receive antenatal treatment. Maternal progression-free and overall survival was assessed by disease stage at diagnosis in pregnant patients and compared with outcomes of non-pregnant patients with Hodgkin lymphoma selected from databases of three tertiary centres, matched for stage and prognostic score. All patients included in survival analyses received standard doxorubicin, bleomycin, vinblastine and dacarbazone (ABVD) therapy since Jan 1, 1997. FINDINGS: Of the 134 pregnant patients diagnosed with Hodgkin lymphoma during pregnancy. 72 (54%) patients initiated antenatal chemotherapy, 56 (42%) did not receive treatment during pregnancy, and 6 (4%) received only radiotherapy. Over the years, chemotherapy was increasingly commenced during pregnancy. The incidence of neonates who were small for gestational age did not differ between chemotherapy-exposed neonates (15 [22%] of 69) and non-exposed neonates (six [16%] of 42; p=0·455). Admission to NICU also did not differ between groups (19 [29%] exposed to antenatal chemotherapy vs 12 [35%] unexposed to antenatal chemotherapy). Birthweight percentiles were lower in neonates prenatally exposed to chemotherapy compared with non-exposed neonates (p=0·035). Patients receiving antenatal therapy had more obstetric complications than those without antenatal therapy (p=0·005), the most common complications being preterm contractions (nine [12%] vs three [7%]) and preterm rupture of membranes (four [5%] vs 0). For the maternal survival analyses, we compared 77 pregnant patients and 211 non-pregnant, matched controls. 5-year progression-free survival for patients with early-stage Hodgkin lymphoma was 82·6% (95% CI 67·4-91·1) for 62 pregnant patients and 88·3% (81·6-92·7) for 142 controls (hazard ratio [HR] 1·80, 95% CI 0·84-3·87; p=0·130; 5-year overall survival was 97·3% (82·3-99·6) and 98·4% (93·6-99·6; HR 1·63, 0·35-7·65; p=0·534). In patients with advanced-stage disease (15 pregnant patients and 69 non-pregnant controls), 5-year progression-free survival was 90·9% (95% CI 50·8-98·7) versus 74·0% (60·9-83·3); HR 0·36, 95% CI 0·04-2·90; p=0·334. 5-year overall survival was 100% (no events occurred) and 96·2% (95% CI 85·5-99·1; HR cannot be estimated; p=0·146). INTERPRETATION: Occurrence of preterm contractions or preterm rupture of membranes was higher in patients with Hodgkin lymphoma receiving antenatal treatment compared with those who did not initiate treatment during pregnancy. Maternal survival did not differ between pregnant and non-pregnant patients with Hodgkin lymphoma, suggesting that antenatal chemotherapy or deferral of treatment until postpartum in selected patients can be considered, with regular obstetric follow-up to safeguard foetal growth. FUNDING: European Research Council, Research foundation Flanders, and Charles University Ministry of Health of the Czech Republic.

Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients.

BACKGROUND: Awareness is growing that cancer can be treated during pregnancy, but the effect of this change on maternal and neonatal outcomes is unknown. The International Network on Cancer, Infertility and Pregnancy (INCIP) registers the incidence and maternal, obstetric, oncological, and neonatal outcomes of cancer occurring during pregnancy. We aimed to describe the oncological management and obstetric and neonatal outcomes of patients registered in INCIP and treated in the past 20 years, and assess associations between cancer type or treatment modality and obstetric and neonatal outcomes. METHODS: This descriptive cohort study included pregnant patients with cancer registered from all 37 centres (from 16 countries) participating in the INCIP registry. Oncological, obstetric, and neonatal outcome data of consecutive patients diagnosed with primary invasive cancer during pregnancy between Jan 1, 1996, and Nov 1, 2016, were retrospectively and prospectively collected. We analysed changes over time in categorical patient characteristics, outcomes, and treatment methods with log-binomial regression. We used multiple logistic regression to analyse preterm, prelabour rupture of membranes (PPROM) or preterm contractions, small for gestational age, and admission to the neonatal intensive care unit (NICU). The INCIP registry study is registered with ClinicalTrials.gov, number NCT00330447, and is ongoing. FINDINGS: 1170 patients were included in the analysis and 779 (67%) received treatment during pregnancy. Breast cancer was the most common malignant disease (462 [39%]). Every 5 years, the likelihood of receiving treatment during pregnancy increased (relative risk [RR] 1·10, 95% CI 1·05-1·15), mainly related to an increase of chemotherapeutic treatment (1·31, 1·20-1·43). Overall, 955 (88%) of 1089 singleton pregnancies ended in a livebirth, of which 430 (48%) of 887 pregnancies ended preterm. Each 5 years, we observed more livebirths (RR 1·04, 95% CI 1·01-1·06) and fewer iatrogenic preterm deliveries (0·91, 0·84-0·98). Our data suggest a relationship between platinum-based chemotherapy and small for gestational age (odds ratio [OR] 3·12, 95% CI 1·45-6·70), and between taxane chemotherapy and NICU admission (OR 2·37, 95% CI 1·31-4·28). NICU admission seemed to depend on cancer type, with gastrointestinal cancers having highest risk (OR 7·13, 95% CI 2·86-17·7) and thyroid cancers having lowest risk (0·14, 0·02-0·90) when compared with breast cancer. Unexpectedly, the data suggested that abdominal or cervical surgery was associated with a reduced likelihood of NICU admission (OR 0·30, 95% CI 0·17-0·55). Other associations between treatment or cancer type and outcomes were less clear. INTERPRETATION: Over the years, the proportion of patients with cancer during pregnancy who received antenatal treatment increased, especially treatment with chemotherapy. Our data indicate that babies exposed to antenatal chemotherapy might be more likely to develop complications, specifically small for gestational age and NICU admission, than babies not exposed. We therefore recommend involving hospitals with obstetric high-care units in the management of these patients. FUNDING: Research Foundation-Flanders, European Research Council, Charles University, Ministry of Health of the Czech Republic.