Reference Values for Placental Weight and Placental:Fetal Weight Ratio in a Swedish Population.

INTRODUCTION: There is important clinical information from placental weight and its ratio to the fetal weight. The aim with this study was to establish reference values for the placental weight and the placental:fetal weight ratio for gestational weeks 13-43 in a Swedish population. MATERIALS AND METHODS: Cases were retrospectively collected from the database used at the Pathology Department at Karolinska University Hospital and information about the placental weight, fetal weight, and gestational age was retrieved. Conditions, which could affect the placental- or fetal weight were excluded. Thereafter percentile curves were calculated for the placental weight and the placental:fetal weight ratio for gestational weeks. RESULTS: A total of 730 cases were included and percentile curves for the placental weight for gestational week 13-43 and placental:fetal weight ratio for gestational week 18-43 are presented. CONCLUSIONS: Reference values for post fixation placental weight and its ratio to fetal weight for a Swedish population are presented. The reference values are lower than the current reference values used in our institution, and this will be of importance when interpreting findings after placental examination.

Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro.

Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between exposure and disease in humans. To address this gap, we tested the effects of a common phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), on adult human ovaries in vitro using an epidemiologically determined human-relevant concentration range (2.05 nM - 20.51 mM). Histomorphological assessments, steroid and cytokine measurements were performed on human ovarian tissue exposed to MEHP for 7 days in vitro. Cell viability and gene expression profile were investigated following 7 days of MEHP exposure using the human granulosa cancer cell lines KGN, and COV434, the germline tumor cell line PA-1, and human ovarian primary cells. Selected differentially expressed genes (DEGs) were validated by RT-qPCR and immunofluorescence in human ovarian tissue. MEHP exposure reduced follicular growth (20.51 nM) and increased follicular degeneration (20.51 mM) in ovarian tissue, while not affecting steroid and cytokine production. Out of the 691 unique DEGs identified across all the cell types and concentrations, CSRP2 involved in cytoskeleton organization and YWHAE as well as CTNNB1 involved in the Hippo pathway, were chosen for further validation. CSRP2 was upregulated and CTNNB1 downregulated in both ovarian tissue and cells, whereas YWHAE was downregulated in cells only. In summary, one-week MEHP exposure of human ovarian tissue can perturb the development and survival of human follicles through mechanisms likely involving dysregulation of cytoskeleton organization and Hippo pathway.

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.

Placental pathology in a large (Swedish) cohort of SARS-CoV-2 infected mothers.

INTRODUCTION: SARS-CoV-2 placentitis is associated with placental destruction and insufficiency and can affect perinatal outcome. The aim of the current study was to contribute with increased knowledge regarding placental histology in maternal SARS-CoV-2 infection during the pregnancy, as well as the correlation to the severity of maternal SARS-CoV-2 infection. MATERIAL AND METHODS: This retrospective observational study included 116 women who had a verified SARS-CoV-2 infection during pregnancy and gave birth between April 2020 and February 2022 in the Stockholm region, Sweden. Placental tissue was evaluated regarding several histopathological parameters, amongst them detection of the triad of characteristics of placental SARS-CoV-2 infection: chronic histiocytic intervillositis, fibrin deposition and villous trophoblast necrosis, and immunohistochemistry for ORF-3 protein expression was used for confirmation. Medical records were reviewed for maternal characteristics and neonatal outcome. RESULTS: SARS-CoV-2 placentitis was present in one-fifth of the examined placentas admitted to the institute due to maternal SARS-CoV-2 infection, out of which 86,4 % were delivered by acute caesarian section (ACS), all on fetal indication, and one pregnancy ended in stillbirth. Half of the cases without placentitis were delivered by ACS, out of which 50 % were on fetal indication. There was a clear tendency of a shorter time gap between confirmed maternal SARS-CoV-2 infection and delivery in the placentitis group. DISCUSSION: The presence of SARS-CoV-2 placentitis does not seem to correlate with maternal factors or the severity of infection. It does correlate with development of placental dysfunction of acute/subacute onset and is often manifested as reduced fetal movements.

A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.

INTRODUCTION: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1-24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. MATERIAL AND METHODS: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. RESULTS: A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). CONCLUSIONS: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.

Severe COVID-19 during pregnancy in Sweden, Norway, and Denmark.

INTRODUCTION: Pregnancy is a risk factor for severe coronavirus disease 2019 (COVID-19) and adverse pregnancy outcomes. We aimed to explore maternal characteristics, pregnancy outcomes, vaccination status, and virus variants among pregnant women admitted to intensive care units (ICU) with severe COVID-19. MATERIAL AND METHODS: We identified pregnant women admitted to ICU in Sweden (n = 96), Norway (n = 31), and Denmark (n = 16) because of severe COVID-19, from national registers and clinical databases between March 2020 and February 2022 (Denmark), August 2022 (Sweden), or December 2022 (Norway). Their background characteristics, pregnancy outcome, and vaccination status were compared with all birthing women and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test-positive pregnant women during the same time period. We calculated the number admitted to ICU per 10 000 birthing and per 1000 SARS-CoV-2 test-positive women during the Index, Alpha, Delta, and Omicron periods. RESULTS: Women admitted to ICU had a higher mean body mass index, were more often of non-Scandinavian origin, had on average lower education and income levels, had a higher proportion of chronic and pregnancy-related conditions, delivered preterm, had neonates with low Apgar scores, and had more infants admitted to neonatal care, compared with all birthing and test-positive pregnant women. Of those admitted to ICU, only 7% had been vaccinated before admission. Overall, the highest proportion of women admitted to ICU per birthing was during the Delta period (4.1 per 10 000 birthing women). In Norway, the highest proportion admitted to ICU per test-positive pregnant women was during the Delta period (17.8 per 1000 test-positive), whereas the highest proportion of admitted per test-positive in Sweden and Denmark was seen during the Index period (15.4 and 8.9 per 1000 test-positive, respectively). CONCLUSIONS: Admission to ICU because of COVID-19 in pregnancy was a rare event in the Scandinavian countries, but women who were unvaccinated, of non-Scandinavian origin, and with lower socio-economic status were at higher risk of admission to ICU. In addition, women admitted to ICU for COVID-19 had higher risk of adverse pregnancy outcomes.

Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models.

Endocrine disrupting chemicals (EDCs) are raising concerns about adverse effects on fertility in women. However, there is a lack of information regarding mechanisms and effects in humans. Our study aims to identify mechanisms of endocrine disruption using two EDCs, diethylstilbestrol (DES) and ketoconazole (KTZ)1. Human ovarian cortical tissue obtained from Caesarean section patients was exposed to 10-9 M - 10-5 M KTZ and 10-10 M - 10-6 M DES in vitro for 6 days. Follicle survival and growth were studied via histology analysis and liquid-chromatography-mass spectrometry-based steroid quantification. RNA-sequencing was performed on COV434, KGN, and primary ovarian cells that were exposed for 24 h. Significantly lower unilaminar follicle densities were observed in DES 10-10 M group, whereas low KTZ exposure reduced secondary follicle density. KTZ 10-5 M reduced levels of pregnenolone and progesterone. RNA-sequencing revealed that 445 and 233 differentially expressed genes (false discovery rate < 0.1) altogether in DES and KTZ exposed groups. Gene set variation analysis showed that both chemicals modulated pathways that are important for folliculogenesis and steroidogenesis. We selected stearoyl-CoA desaturase (SCD) and 7-dehydrocholesterol reductase (DHCR7) for further validation. Up-regulation of both genes in response to KTZ was confirmed by qPCR and in situ RNA hybridization. Further validation with immunofluorescence focused on the expression of SCD in growing follicles in exposed ovarian tissue. In conclusion, SCD may serve as a potential novel human-relevant biomarker of EDC exposure and effects on ovaries.

Treatment of COVID-19 with monoclonal antibodies casirivimab and imdevimab in pregnancy.

PROPOSE: Pregnancy is a risk factor for severe COVID-19. Treatment with monoclonal antibodies has been shown to decrease the risk of progression to severe COVID-19, but there are few reports on treating pregnant women. Here, we describe the clinical outcome of seven hospitalized pregnant women treated with the casirivimab-imdevimab. METHODS/RESULTS: Seven unvaccinated pregnant patients hospitalized due to COVID-19 met the monoclonal antibodies treatment criteria applied at our center. After consultations with obstetricians, the decisions to administer casirivimab-imdevimab to halt the progression of COVID-19 were made by two senior infectious diseases specialists. No patient experienced an adverse drug reaction, and only one patient progressed to severe disease. Two patients had a cesarian section performed during hospitalization, both with delivery of healthy babies. Three patients gave birth to healthy babies at a later time point, while two pregnancies are ongoing. CONCLUSION: The hospitalized pregnant patients who received monoclonal antibodies due to COVID-19 had favorable outcomes, but further research is recommended to fully assess safety and efficacy of monoclonal antibody treatment in pregnancy.

A Case Report of Severe Coagulopathy in Antenatal COVID-19.

Pregnancy is a naturally occurring hypercoagulable state, and COVID-19 can cause profound changes in the coagulation system associated with thromboinflammation. We report a case of a pregnant woman with moderate symptoms of COVID-19 and a severe coagulopathy with unexpected low levels of fibrinogen and factor VIII as well as atypical thrombelastometry results. She developed a severe placental dysfunction with intrauterine fetal distress and perinatal death. The case did not fulfil the criteria for preeclampsia or sepsis, and the adverse outcome was assessed as a direct effect of the COVID-19 infection with placental insufficiency, despite absence of serious maternal pulmonary symptoms. Atypical persistent coagulopathy may serve as an important marker of a serious obstetrical situation in COVID-19.

Pregnancy, delivery, and neonatal outcomes among women with spinal cord injury in Sweden 1997-2015: A population-based cohort study.

INTRODUCTION: The aim of this study was to describe the rate of pregnancy in spinal cord injured women in Sweden as well as pregnancy, delivery, and neonatal outcomes. MATERIAL AND METHODS: This study was based on data from the Swedish Medical Birth Register and the National Patient Register. The study population included women with spinal cord injury who gave birth in Sweden during the period 1997 to 2015. The general population was used as reference and included all non-spinal cord injured patients who gave birth during the same period of time. RESULTS: In the spinal cord injury group, 109 births were identified. Eighty-nine (82%) of them were among paraplegic women and 20 (18%) were among tetraplegic women. Women with spinal cord injury in our study population had urinary tract infections during pregnancy in five cases (5%) and anemia during pregnancy in nine cases (8%), compared with 0.2% and 4%, respectively, in the general population. Compared with the general population more deliveries were induced in the study population, 18 (17%) in the spinal cord injury group and 12% in the general population. Vaginal delivery was achieved in 52 (48%) of the births with 42 of them (39%) being non-instrumental and 10 (9%) being instrumental vaginal deliveries. Elective cesarean section rate was 34% (n = 37). Sixteen infants (15%) were born preterm (gestational week <37). We found an overall low rate of pregnancy and delivery complications. CONCLUSIONS: Our results show predominantly favorable outcomes of pregnancy and delivery in women with spinal cord injury as well as their infants. These results are in concordance with previous research.

Epidural use among women with spontaneous onset of labour - an observational study using data from a cluster-randomised controlled trial.

OBJECTIVE: To investigate whether the proportion of pregnant women who use epidural analgesia during birth differed between women registered at a maternity clinic randomised to Mindfetalness or to routine care. DESIGN: An observational study including women born in Sweden with singleton pregnancies, with spontaneous onset of labour from 32 weeks' gestation. Data used from a cluster-randomised controlled trial applying the intention-to-treat principle in 67 maternity clinics where women were randomised to Mindfetalness or to routine care. ClinicalTrials.gov (NCT02865759). INTERVENTIONS: Midwives were instructed to distribute a leaflet about Mindfetalness to pregnant women at 25 weeks' gestation. Mindfetalness is a self-assessment method for the woman to use to become familiar with the unborn baby's fetal movement pattern. When practising the method in third trimester, the women are instructed to daily lie down on their side, when the baby is awake, and focus on the movements' intensity, character and frequency (but not to count each movement). FINDINGS: Of the 18 501 women with spontaneous onset of labour, 47 percent used epidural during birth. Epidural was used to a lower extent among women registered at a maternity clinic randomised to Mindfetalness than women in the routine-care group (46.2% versus 47.8%, RR 0.97, CI 0.94-1.00, p= 0.04). Epidural was more common among primiparous women, women younger than 35 years, those with educational levels below university, with BMI ≥25 and with a history of receiving psychiatric care or psychological treatment for mental illness. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Pregnant women who were informed about a self-assessment method, with the aim of becoming familiar with the unborn baby's fetal movement pattern, used epidural to a lower extent than women who were not informed about the method. Future studies are needed to investigate and understand the association between Mindfetalness and the reduced usage of epidural during birth.

Country of birth, educational level and other predictors of seeking care due to decreased fetal movements: an observational study in Sweden using data from a cluster-randomised controlled trial.

OBJECTIVES: To identify predictors of seeking care for decreased fetal movements and assess whether care-seeking behaviour is influenced by Mindfetalness. DESIGN: Observational study with data from a cluster-randomised controlled trial. SETTING: 67 maternity clinics and 6 obstetrical clinics in Sweden. PARTICIPANTS: All pregnant women with a singleton pregnancy who contacted the obstetrical clinic due to decreased fetal movements from 32 weeks' gestation of 39 865 women. METHODS: Data were collected from a cluster-randomised controlled trial where maternity clinics were randomised to Mindfetalness or routine care. Mindfetalness is a self-assessment method for women to use daily to become familiar with the unborn baby's fetal movement pattern. OUTCOME MEASURES: Predictors for contacting healthcare due to decreased fetal movements. RESULTS: Overall, 5.2% (n=2059) of women contacted healthcare due to decreased fetal movements, among which 1287 women (62.5%) were registered at a maternity clinic randomised to Mindfetalness and 772 women (37.5%) were randomised to routine care. Predictors for contacting healthcare due to decreased fetal movements were age, country of birth, educational level, parity, prolonged pregnancy and previous psychiatric care (p<0.001). The main differences were seen among women born in Africa as compared with Swedish-born women (2% vs 6%, relative risk (RR) 0.34, 95% CI 0.25 to 0.44) and among women with low educational level compared with women with university-level education (2% vs 5.4%, RR 0.36, 95% CI 0.19 to 0.62). Introducing Mindfetalness in maternity care increased the number of women seeking care due to decreased fetal movements overall. CONCLUSION: Women with country of birth outside Sweden and low educational level sought care for decreased fetal movements to a lesser extent compared with women born in Sweden and those with university degrees. Future research could explore whether pregnancy outcomes can be improved by motivating women in these groups to contact healthcare if they feel a decreased strength or frequency of fetal movements. TRIAL REGISTRATION NUMBER: NCT02865759.

COVID-19 in pregnancy-characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries.

INTRODUCTION: Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems. MATERIAL AND METHODS: This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS-CoV-2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID-19-related. RESULTS: In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID-19. The risk of admission due to COVID-19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID-19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID-19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported. CONCLUSIONS: The risk of admission due to COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.

A Case Series on Critically Ill Pregnant or Newly Delivered Patients with Covid-19, Treated at Karolinska University Hospital, Stockholm.

In this retrospective report, we present five cases of critically ill pregnant or newly delivered women positive for Covid-19 admitted to our obstetrical departments at Karolinska University Hospital. They compose 6% of eighty-three pregnant women that tested positive for SARS-CoV-2 during the period March 25 to May 4, 2020. Three patients were at the time of admission in gestational week between 21 + 4 and 22 + 5 and treated during their antenatal period; meanwhile, the other two were admitted within 1 week postpartum. All of them were in need of intensive care: one was treated with high flow oxygen therapy, the other four with invasive mechanical ventilation (three with endotracheal intubation and one with extracorporeal membrane oxygenation). Age above thirty, overweight, and gestational diabetes are notable factors in the cases presented. At the time of admission, they all presented with symptoms such as fever, cough, and dyspnea. Chest imaging with computer tomography scan was performed in each case and demonstrated multifocal pneumonic infiltrates in all of them, but no pulmonary embolism was confirmed in any. Neither did the echocardiogram indicate any cardiomyopathy. Four of the patients have been discharged from the hospital, with an average of 20 hospital days. One antenatal pregnant woman needed prolonged ECMO therapy; in gestational week 27 + 3, she went into cardiac arrest, resulting in an urgent C-section on maternal indication. At the time of writing, she is still hospitalized. In coherence with other published reports, our cases indicate that critically ill pregnant women infected by SARS-Cov-2 may develop severe respiratory distress syndrome requiring prolonged intensive care. The material is limited for conclusions to be made; more detailed information on symptoms, treatment, and outcomes for pregnant and postpartum women managed in intensive care is therefore needed.

Contagiousness in treated HIV-1 infection.

BACKGROUND: Effective antiretroviral treatment of HIV-1, defined as continuously undetectable virus in blood, has substantial effects on the infectiousness and spread of HIV. AIM: This paper outlines the assessment of the Swedish Reference Group for Antiviral Therapy (RAV) and Public Health Agency of Sweden regarding contagiousness of HIV-infected persons on antiretroviral therapy (ART). Results and Conclusion: The expert group concludes that there is no risk of transmission of HIV during vaginal or anal intercourse if the HIV-infected person fulfils the criteria for effective ART. Summary: The effective antiretroviral therapy (ART) for HIV-1 infection has dramatically reduced the morbidity and mortality among people who live with HIV. ART also has a noticeable effect on the infectiousness and on the spread of the disease in society. Knowledge about this has grown gradually. For ART to be regarded effective, the level of the HIV RNA in the plasma should be repeatedly and continuously undetectable and the patient should be assessed as continually having high adherence to treatment. Based on available knowledge the Swedish Reference Group for Antiviral Therapy (RAV) and the Public Health Agency of Sweden make the following assessment: There is no risk of HIV transmission during vaginal or anal intercourse if the HIV positive person fulfils the criteria for effective treatment. This includes intercourse where a condom is not used. However, there are a number of other reasons for recommending the use of condoms, primarily to protect against the transmission of other STIs (sexually transmitted infections) and hepatitis, as well as unwanted pregnancy. The occurrence of other STIs does not affect the risk of HIV transmission in persons on effective ART. It is plausible that the risk for transmission of HIV infection between people who inject drugs and share injection equipment is reduced if the individual with HIV is on effective ART, but there are no studies that directly show this. The risk of transmission from mother to child during pregnancy, labour and delivery is very low if the mother's treatment is initiated well before delivery and if the treatment aim of undetectable virus levels is attained. This is dependent on healthcare services being aware of the mother's HIV infection at an early stage. In most contacts with health and medical care, including dental care, the risk of transmission is not significant if the patient is on effective treatment, but the risk may remain, although considerably reduced, in more advanced interventions such as surgery. When an incident with risk of transmission occurs, the patient must always inform those potentially exposed about his or her HIV infection.

Reproductive Outcomes After Breast Cancer in Women With vs Without Fertility Preservation.

IMPORTANCE: The practice of fertility preservation (FP) in women with breast cancer (BC) is spreading, but long-term reproductive outcomes after FP are largely unknown. OBJECTIVE: To investigate the long-term reproductive outcomes in women who did or did not undergo FP at the time of BC diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A Swedish nationwide cohort study was conducted to investigate the long-term reproductive outcomes of women with BC receiving FP at 1 of the regional FP programs from 1994 to 2017 (n = 425). Population comparators with BC but without history of FP (n = 850) were sampled from regional BC registers, matched on age, calendar period of diagnosis, and county. Data on live births, assisted reproductive technology (ART) use, and mortality were retrieved from population-based registers. Data analysis was performed from January to September 2020. EXPOSURES: History of having received FP compared with no history of FP (unexposed). MAIN OUTCOMES AND MEASURES: The primary outcome was hazard ratios (HRs) of live births and ART treatments following BC in women with vs without FP and the cumulative incidence of these events in the presence of the competing risk of death. RESULTS: Women who had undergone FP (n = 425) had lower parity (302 [71.1%] were nulliparous compared with 171 [20.1%] in the unexposed group), were younger (mean [SD] age, 32.1 [4.0] vs 33.3 [3.6] years), more often had estrogen receptor-positive tumors (289 [68.0%] vs 515 [60.6%]), and were more often scheduled for chemotherapy (399 [93.9%] vs 745 [87.7%]). Of 425 women exposed to FP, 97 (22.8%) had at least 1 post-BC live birth (mean follow-up, 4.6 years), compared with 74 of 850 women (8.7%) unexposed to FP (mean follow-up, 4.8 years). Overall, live birth rates after BC were significantly higher among women with FP (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.6-3.3). The 5-year and 10-year cumulative incidence of post-BC live births was 19.4% and 40.7% among FP-exposed women vs 8.6% and 15.8% among comparators, respectively. Rates of ART use were also higher in the FP group (aHR, 4.8; 95% CI, 2.2-10.7). The all-cause mortality rate was lower in women exposed to FP (aHR, 0.4; 95% CI, 0.3-0.7), with 5-year cumulative incidence of death of 5.3% (95% CI, 3.1%-9.0%) vs 11.1% (95% CI, 8.7%-14.1%) for women with vs without FP. CONCLUSIONS AND RELEVANCE: In this cohort study of Swedish women after a BC diagnosis, successful pregnancy after BC was possible both in women with and without FP at the time of diagnosis, but a significantly higher likelihood of post-BC live births and ART treatments was observed in women who underwent FP, without any negative association with all-cause survival. This information is valuable for health care clinicians responsible for oncologic treatment and reproductive counseling of women diagnosed with breast cancer at reproductive age.