SARS-CoV-2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series.

INTRODUCTION: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood. MATERIAL AND METHODS: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress. RESULTS: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain. CONCLUSION: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Outcome of subsequent pregnancies in women with complete uterine rupture: A population-based case-control study.

INTRODUCTION: In the attempt of a trial of labor after a cesarean section approximately one in 200 women experience a complete uterine rupture. As a complete uterine rupture is associated with an adverse perinatal outcome, data regarding subsequent pregnancies are needed to provide proper care and guidance to women with a complete uterine rupture when informing them of future possibilities. The objective of this study was to investigate the fetal and maternal outcomes in subsequent pregnancies after a complete uterine rupture. MATERIAL AND METHODS: Retrospective population-based case-control study. Denmark 1997-2017. A total of 175 women with complete uterine rupture during an attempted trial of labor after cesarean (TOLAC) at term (cases) and a corresponding group of 272 women with no uterine rupture during an attempted TOLAC at term (controls) were labeled as index deliveries. Index deliveries were included from January 1, 1997 to December 31, 2008. From the date of the index delivery to December 31, 2017 the information on subsequent pregnancies and deliveries, and on referral to hospital with any obstetric or gynecological diagnosis were retrieved from the Danish Medical Birth Registry and National Patient Registry. Main outcome measures were miscarriage, perinatal death, neonatal morbidity, preterm birth, and recurrence of uterine rupture. Outcome measures were compared between cases and controls. RESULTS: After the index deliveries; there were 109 pregnancies and 70 deliveries after gestational age 22+0  weeks in the population of cases. In the population of controls, there were 183 pregnancies and 126 deliveries after 22+0  weeks. Cases had a significantly higher risk of miscarriage (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.36-13.17). The incidence of uterine rupture was 8.6% among cases and 0.8% among controls (OR 11.7; 95% CI 1.36-543.1). Among cases, 98.6% had live-born infants, and none of these had severe neonatal morbidity. No significant association was found between previous complete uterine rupture and preterm delivery, placenta previa, hysterectomy in relation to subsequent births, diagnosis such as meno/metrorrhagia, dysmenorrhea, or procedures such as hysteroscopy or hysterectomy. CONCLUSIONS: In pregnancies following complete uterine rupture continuing after 22+0  weeks, maternal and fetal outcomes are good when managed promptly with cesarean delivery.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Operative technique at caesarean delivery and risk of complete uterine rupture in a subsequent trial of labour at term. A registry case-control study.

OBJECTIVE: To estimate the relation of single-layer closure at previous caesarean delivery, and other pre-labour and intra-partum risk factors for complete uterine rupture in trial of vaginal birth after a caesarean (TOLAC) at term. STUDY DESIGN: Population-based case-control study. We identified all women (n = 39 742) recorded in the Danish Medical Birth Registry (DMBR) during a 12-year period (1997-2008) with a singleton pregnancy at term and TOLAC. Among these, all women with a complete uterine rupture were identified (cases). Information from the registry was validated against medical records. Controls were selected in the DMBR as the following two births with TOLAC at term and no uterine rupture. Detailed information from cases and controls was collected from manual review of medical records. Main outcome measure was complete uterine rupture during TOLAC at term. RESULTS: Upon validation, 175 cases and 272 controls met the above criteria. After adjustment for possible confounding factors there was no association between single layer closure and uterine rupture (aOR 1.38, CI: 0.88-2.17). Significant risk factors were: Induction with an unfavourable cervix (aOR 2.10 CI: 1.19-3.71), epidural (aOR 2.17 CI 1.31-3.57), augmentation by oxytocin for more than one hour (aOR 2.03 CI: 1.20-3.44), and birth weight ≥ 4000g (aOR 2.65 CI 1.05-6.64). Previous vaginal delivery (aOR 0.41 CI: 0.25-0.68) and inter-delivery interval of more than 24 months (aOR 0.38 CI: 0.18-0.78) reduced the risk of uterine rupture. CONCLUSION: Single-layer uterine closure did not remain significantly associated to uterine rupture during TOLAC at term after adjustment for confounding factors. Induction of labour with an unfavourable cervix, birth weight ≥ 4000g and indicators of prolonged labour were all major risk factors for uterine rupture.

Can Intrapartum Cardiotocography Predict Uterine Rupture among Women with Prior Caesarean Delivery?: A Population Based Case-Control Study.

OBJECTIVE: To compare cardiotocographic abnormalities recorded during labour in women with prior caesarean delivery (CD) and complete uterine rupture with those recorded in controls with prior CD without uterine rupture. STUDY DESIGN: Women with complete uterine rupture during labour between 1997 and 2008 were identified in the Danish Medical Birth Registry (n = 181). Cases were validated by review of medical records and 53 cases with prior CD, trial of labour, available cardiotocogram (CTG) and complete uterine rupture were included and compared with 43 controls with prior CD, trial of labour and available CTG. The CTG tracings were assessed by 19 independent experts divided into groups of three different experts for each tracing. The assessors were blinded to group, outcome and clinical data. They analyzed occurrence of defined abnormalities and classified the traces as normal, suspicious, pathological or pre-terminal according to international guidelines (FIGO). RESULTS: A pathological CTG during the first stage of labour was present in 77% of cases and in 53% of the controls (OR 2.58 [CI: 0.96-6.94] P = 0.066). Fetal tachycardia was more frequent in cases with uterine rupture (OR 2.50 [CI: 1.0-6.26] P = 0.053). Significantly more cases showed more than 10 severe variable decelerations compared with controls (OR 22 [CI: 1.54-314.2] P = 0.022). Uterine tachysystole was not correlated with the presence of uterine rupture. CONCLUSION: A pathological cardiotocogram should lead to particular attention on threatening uterine rupture but cannot be considered a strong predictor as it is common in all women with trial of labour after caesarean delivery.

Uterine rupture without previous caesarean delivery: a population-based cohort study.

OBJECTIVE: To determine incidence and patient characteristics of women with uterine rupture during singleton births at term without a previous caesarean delivery. STUDY DESIGN: Population based cohort study. Women with term singleton birth, no record of previous caesarean delivery and planned vaginal delivery (n=611,803) were identified in the Danish Medical Birth Registry (1997-2008). Medical records from women recorded with uterine rupture during labour were reviewed to ascertain events of complete uterine rupture. Relative Risk (RR) and adjusted Relative Risk Ratio (aRR) of complete uterine rupture with 95% confidence intervals (95% CI) were ascertained according to characteristics of the women and of the delivery. RESULTS: We identified 20 cases with complete uterine rupture. The incidence of complete uterine rupture among women without previous caesarean delivery was about 3.3/100,000 deliveries. Multiparity (RR 8.99 (95% CI 1.86-43.29)), induction of labour (RR 3.26 (95% CI 1.24-8.57)), epidural analgesia (RR 10.78 (95% CI 4.25-27.39)), and augmentation by oxytocin (RR 9.50 (95% CI 3.15-28.63)) were associated with uterine rupture. Induction of labour was not significantly related to uterine rupture when adjusted for parity, epidural analgesia and augmentation by oxytocin. CONCLUSION: Although uterine rupture is rare, its association with epidural analgesia and augmentation of labour with oxytocin in multipara should be considered. Thus, vigilance should be exercised when labour is obstructed and there is need for epidural analgesia and/or augmentation by oxytocin in multiparous women. Due to the rare occurrence of uterine rupture caution should be exerted when interpreting the findings of this study.

Water immersion and changes in the foetoplacental and uteroplacental circulation: an observational study with the case as its own control.

OBJECTIVE: To evaluate the effect of immersion into water on maternal blood pressure, amount of amniotic fluid and on the foetoplacental- and uteroplacental circulation in healthy women with an uncomplicated singleton pregnancy. METHODS: Twenty-five healthy women were included. Recordings of blood pressure, deepest vertical pocket of amniotic fluid and pulsatility index (PI) measured by Doppler in the umbilical and uterine arteries were obtained. The participants were immersed into water and the measurements were repeated after 5 and 25 min in water and again 15 and 30 min post immersion. RESULTS: The amount of amniotic fluid increased significantly (p < 0.001), and the maternal blood pressure decreased significantly during immersion (p < 0.001). There was no significant effect of immersion on either umbilical- or uterine artery PI. All changes returned toward baseline-level within 30 min after immersion. CONCLUSIONS: Immersion into water increases the amount of amniotic fluid and decreases the maternal blood pressure. Immersion into water has no significant effect on either the foetoplacental or uteroplacental circulation. Further studies are needed in order to explore the effect of immersion in pregnancies complicated by a dysfunctional placenta.

Use of ICD-10 codes to monitor uterine rupture: validation of a national birth registry.

OBJECTIVES: Uterine rupture is a rare but severe complication in pregnancies after a previous cesarean section. In Denmark, the monitoring of uterine rupture is based on reporting of relevant diagnostic codes to the Danish Medical Birth Registry (MBR). The aim of our study was to examine the validity of registration of uterine rupture in the MBR within the population of pregnant women with prior cesarean section by conducting a review of the medical records. STUDY DESIGN: We reviewed 1709 medical records within the population of singleton pregnant woman delivering at term between 1997 and 2007. We retrieved the medical records of all women in the MBR with a code for uterine rupture during labor regardless of whether or not a prior cesarean section had been reported to the registry. In addition medical records of all women with a code for previous cesarean section and delivery of a child with adverse perinatal outcome were retrieved. RESULTS: Among women recorded in the MBR with a previous cesarean section and uterine rupture, only 60.4% actually had a uterine rupture (partial or complete). At least 16.2% of complete uterine ruptures were not reported to the registry. Considering only complete uterine ruptures, the sensitivity and specificity of the codes for uterine rupture were 83.8% and 99.1%, respectively. CONCLUSION: During the study period the monitoring of uterine rupture in the MBR was inadequate.

[Conservative management of deformed twin pregnancy]. / Konservativ behandling af et stort misdannet tvillingeanlæg.

A twin reversed arterial perfusion (TRAP) sequence was diagnosed in a monochoriotic, diamniotic twin pregnancy at GA 12 weeks + 2 days. According to the parents' wish the pregnancy was managed conservatively with close monitoring, with ultrasound biometry and Doppler flow measurements in the umbilical artery, middle cerebral artery and ductus venosus. At GA 34 weeks + 0 days the TRAP twin was growing rapidly and the amnion fluid index was increasing rapidly. An uncomplicated elective section was performed. The acardiac/pump twin weight ratio was 134%. The pump twin was without sequelae.