Maternal and perinatal outcomes of SARS-CoV-2 infection in unvaccinated pregnancies during Delta and Omicron waves.

OBJECTIVE: There is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves. METHODS: This was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection. RESULTS: During the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001). CONCLUSIONS: Among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effects of erythropoietin on spontaneous and oxytocin induced myometrial contractions in the nonpregnant rat.

OBJECTIVE: Erythropoietin (EPO) is a glycoprotein hormone that regulates erythropoiesis. EPO activity has also been detected in a variety of tissue including the nervous system, and female and male reproductive organs. It has been shown that EPO causes relaxation in vascular smooth muscle. In the present study, we have investigated effects of EPO on spontaneous and oxytocin-induced contractions of non-pregnant rat myometrium. MATERIALS AND METHODS: Myometrial stripes were obtained from adult Wistar rats at the oestrous stage. The samples were placed in an isolated organ chamber under physiological conditions and 1 g passive tension. Epoetin beta (rEPO) was added cumulatively at 0.1, 1 and 10 IU/ml concentrations to the myometrial samples showing regular spontaneous contractions for periods of 30 min. Frequency and amplitude of contractions were electrophysiologically recorded and analyzed by using a BIOPAC data acquisition system. RESULTS: rEPO inhibited both area under curve and frequency of spontaneous contractions (ANOVA, n1, 2 = 9, f1 = 20.938, f2 = 20.492, p1,2 = 0.000). The inhibitory effect was insignificant at 0.1 mIU/ml rEPO level (Tukey HSD, p1 = 0.051, p2 = 0.581). In the oxytocin treated myometrial samples, a single dose of 1 IU/ml rEPO was studied. The area under curve and frequency values of these samples were inhibited by rEPO (Student's t-test, n = 9, t1 = 4.776, p1 = 0.000; t2 = 2.835, p2 = 0.012, respectively). CONCLUSIONS: rEPO inhibited spontaneous and oxytocin-induced rat myometrial contractions at 1 and 10 IU/ml concentrations. It appeared that the effect was dose-dependent.

Discrepancy of pre- and postoperative grades of patients with endometrial carcinoma.

PURPOSE: To investigate the diagnostic accuracy of endometrial curettage in patients with endometrial carcinoma. In this retrospective study, pre- and postoperative histopathologic findings of patients with endometrial cancer were investigated. METHODS: 168 patients with the final diagnosis of endometrial cancer were enrolled in the study. Pre- and postoperative histopathologic diagnoses and grades (according to the 1988 FIGO classification) of the patients were compared retrospectively. RESULTS: 22 patients were diagnosed as having endometrial hyperplasia and the remaining 136 patients had endometrial carcinoma preoperatively. Overall discrepancy rate of grades was 39% (31% upgrade, 8% downgrade; p < 0.05). There was also 9% discrepancy between the pre- and postoperative histopathological types. CONCLUSION: It has been suggested that since endometrial cancer patients with low grades according to the preoperative pathologic diagnosis have a potential to upgrade, the management of these patients if myometrial invasion is less than one-half thickness, simply by hysterectomy plus bilateral salpingo-oophorectomy (without lymph node sampling), might actually miss some patients who actually deserve surgical staging. Further studies are needed to draw a sufficient conclusion.

Effects of raloxifene and estradiol on bone turnover parameters in intact and ovariectomized rats.

This study was designed to investigate effects of raloxifene (RLX) and estradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. RLX (2 mg/kg) and estradiol (30 microg/kg) were injected to two groups of animals for a period of 6 weeks at two daily intervals. In the second model, rats (n = 24) were ovx and allowed to recover for a period of at least 3 weeks. Control group received vehicle alone. Remaining rats were divided into two groups and injected with RLX (2 mg/kg) and estradiol (30 microg/kg) for 6 weeks. Urine samples were collected from all animals 24 h after the last drug administration. Urinary deoxypyridinoline (DPD) was measured by ELISA. Serum parathyroid hormone (PTH), calcitonin, and osteocalcin levels were measured by immunoradiometric method. Serum concentrations of alkaline phosphatase (ALP), Ca, and inorganic phosphate were determined by enzymatic-colorimetric method. Lumbar vertebrae (L2) of all animals were dissected out and processed for histopathological evaluation. Removal of ovaries significantly elevated urinary DPD levels (p < 0.01) compared with intact controls. Treatment of both intact and ovx rats with estradiol resulted in significant decreases (p < 0.01) in DPD values. RLX administration had no significant effect in the intact rats, but it remarkably reduced bone turnover in the ovx animals (p < 0.001). Both estradiol and RLX produced conflicting effects on serum ALP, osteocalcin, and PTH levels in both animal models. These findings suggest that RLX exerts its protective effects by reducing bone resorption, similar to that of estradiol, in ovx rats.

Hyperhomocysteinemia may be a resistance factor in tocolytic treatment with beta mimetics.

Homocysteine is an intermediate amino acid in the methionine metabolism which does not take place in the structure of proteins. Plasma homocysteine levels can be elevated by a variety of genetic and nutritional factors. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases and common obstetric problems. Mildly elevated levels of homocysteine have been implicated in a number of disease processes such as atherosclerotic vascular disease and adverse obstetrical outcome. It was shown that the presence of high homocysteine concentrations in the in vitro system had an activating role in myometrial contractions. It is hypothesized that hyperhomocysteinemia in pregnancy is associated with preterm labor in consequence of myometrial contractions. Hyperhomocysteinemia, therefore, could be a treatable cause of this important public health and obstetric concern.