Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.

Listeriosis in pregnancy: under-diagnosis despite over-treatment.

OBJECTIVE: To compare the symptomatology of pregnant women with suspected listeriosis to culture confirmed listeriosis. STUDY DESIGN: All cases of suspected and culture confirmed pregnancy-associated listeriosis from a single center were retrospectively reviewed assessing demographics, clinical, laboratory and pathological findings, and maternal, fetal and neonatal outcomes. RESULTS: Listeriosis was identified in seven patients, none of whom belonged to the 117 women with suspected listeriosis. Women with confirmed infection were more likely to exhibit fever (P=0.01), flu-like symptoms (P=0.006), threatened preterm labor (P=0.05) and inflammatory markers (P=0.02), but less likely to exhibit gastrointestinal complaints (P=0.004) in comparison with suspected non-confirmed cases. Confirmed cases resulted in preterm delivery (n=5) and stillbirth (n=2). Neonatal complications included meningitis, respiratory disease and sepsis. Maternal outcomes were favorable. CONCLUSION: Although 'febrile gastroenteritis' is a poor predictor of listeriosis in pregnancy, fever, premature contractions and inflammatory markers are important risk indices prompting workup and adequate empiric treatment.

Cardiac hemodynamics before, during and after elective cesarean section under spinal anesthesia in low-risk women.

OBJECTIVE: The aim of this study was to describe maternal central hemodynamic parameters before and during delivery as well at the early puerperium in healthy women undergoing elective cesarean section (CS) at term. STUDY DESIGN: The noninvasive Cardiac System (NICaS, NI Medical, Petah-Tikva, Israel) is a regional impedance device that measures cardiac output (CO) and its derivatives with a good correlation with the gold standard Swan-Ganz catheter. We performed a prospective longitudinal study of healthy women with a singleton pregnancy at term. Maternal hemodynamic parameters were assessed by the NICaS at six time points: a few minutes before undergoing an elective CS, immediately after receiving spinal anesthesia, immediately after delivery of the fetus and placenta, after abdominal fascia closure, and within 24 to 36 and 48 to 72 h postpartum. RESULT: Sixty-one consenting women were recruited during the study period (January 2015 to June 2015). Baseline (pre-CS) mean arterial pressure (MAP) was 87.7±7.9 mm Hg, baseline CO was 7.5±1.7 l per min and baseline total peripheral resistance (TPR) was 994±301 dyne × s per cm5. After spinal anesthesia CO significantly increased by 13%, no significant changes were observed in MAP or TPR. Immediately after delivery, a nadir for all parameters was reached: MAP and TPR were significantly reduced by 8% and 26%, respectively (comparing to pre-CS), and CO further increased by 9% (24% comparing to pre-CS). After fascia closure, partial recoveries of all parameters were observed. Twenty-four to thirty-six hours postpartum MAP returned to pre-CS values, while CO and TPR reached -9% and +11% comparing to baseline, respectively. None of the parameters differed significantly between 24 to 36 and 48 to 72 h postpartum. CONCLUSION: Significant hemodynamic changes (reduction of TPR and increase of CO) take place at the time of delivery of fetus and placenta. Knowledge of normal hemodynamic values using a reliable noninvasive technique during various stages of pregnancy and the postpartum period is feasible, and might assist clinicians in assessing the level of patient deviation from expected cardiac performance, especially in high-risk women.

The effect of glucose administration on perceived fetal movements in women with decreased fetal movement, a double-blinded placebo-controlled trial.

OBJECTIVE: To assess the effect of maternal glucose administration on perceived fetal movements. STUDY DESIGN: This was a randomized, double-blinded placebo-controlled trial. Patients 28-41 weeks singleton gestation complaining of decreased fetal movements (DFM) were assigned to receive either 500 cc dextrose 5% (group A) or 500 cc normal saline (group B) intravenously. Primary outcome was number of fetal movements recorded during the following 30 min. Secondary outcomes included need for admission or induction of labor owing to persistent DFM. Maternal glucose levels were taken before and after intervention. A sample size of 50 patients was planned in order to detect a 30% increase in fetal movements in group A. RESULTS: Between February 2011 and April 2013, 50 patients were recruited. Demographic characteristics were similar among groups. There was no difference in the number of fetal movements recorded (7±6 vs 8.8±6 movements/30 min, group A and B, respectively, P=0.39). Similar number of patients had persistent DFM that required admission (8 vs 10 patients, P=0.77, OR 1.4, confidence interval (CI) 0.38-5.3); of those admitted, similar number of patients had induction of labor (3 vs 6 patients, P=0.64, OR 0.4, CI 0.03-3.8). Maternal glucose levels were similar at recruitment (88±19 vs 83±15 mg dl(-1) P=0.36) but were significantly higher in group A (161±37 vs 75±15 mg dl(-1) P<0.0001) after intervention. CONCLUSION: In women with DFM, maternal glucose administration has no effect on perceived fetal movement and its clinical use is questionable.

Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria.

OBJECTIVE: To examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia. STUDY DESIGN: Retrospective cohort study. Data from all hospitalized pregnant women between 2009 and 2014 with new onset isolated proteinuria of over 300 mg/24 h at admission were obtained. Follow-up was performed from the time of admission to the hospital to the time of discharge postpartum. Obstetrical, maternal and neonatal outcomes were obtained. RESULT: Ninety-five pregnant women diagnosed with new onset isolated proteinuria were followed to term. Thirteen women developed pre-eclampsia during pregnancy and eight developed pre-eclampsia postpartum. Maternal characteristics for progression to pre-eclampsia were greater maximal values of proteinuria. Earlier pre-eclampsia onset was associated with early-onset proteinuria and multiple gestation. Although greater values of proteinuria were associated with increased risk for intrauterine growth restriction and lower Apgar scores, maternal outcome was favorable, regardless of pre-eclampsia progression. Isolated proteinuria progressing to pre-eclampsia was associated with late pre-eclampsia onset and favorable maternal and neonatal outcomes. CONCLUSION: A significant proportion of women with new onset isolated proteinuria will develop pre-eclampsia. In these women, close follow-up is recommended until after delivery.

Conservative management of preterm premature rupture of membranes beyond 32 weeks' gestation: is it worthwhile?

We aimed to investigate whether conservative management of preterm premature rupture of membranes (PPROM) at 32-34 weeks' gestation improves outcome. In this retrospective analysis of singleton pregnancies, the study group included patients with PPROM at 28-34 weeks' gestation and the control group included patients presented with spontaneous preterm delivery at 28-34 weeks' gestation. Both groups were subdivided according to gestational age - early (28-31 weeks' gestation) versus late (32-34 weeks' gestation). Adverse neonatal outcome included neonatal death, intraventricular haemorrhage grade 3/4, respiratory distress syndrome, periventricular leucomalacia and neonatal sepsis. The study and control groups included 94 and 86 women, respectively. The study group had a lower incidence of adverse neonatal outcome at the earlier weeks (28-31), compared with the control group at the same gestational age. In contrast, at 32-34 weeks' gestation no difference in the risk for adverse neonatal outcome was noticed. Additionally, within the study group, chorioamnionitis rate was significantly higher among those who delivered at 32-34 weeks' gestation (p < 0.01). No advantage for conservative management of PPROM was demonstrated beyond 31 weeks' gestation. Moreover, conservative management of PPROM at 32-34 weeks' gestation may expose both mother and neonate to infectious morbidity.

Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells.

Estrogen receptors (ERα and ERß), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERß expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERß, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival.

Considerable evidence has been published demonstrating the importance of lipoxygenase enzymes for vascular smooth muscle cell (VSMC) growth. The current study sets out to determine whether or not 12-lipoxygenase (12LO) is also important for human placental VSMC survival. Both a pharmacological and two 12LO antisense knockdown approaches were applied. The 12LO inhibitor baicalien induced a 2-2.5-fold increase in cell death, which appeared to result from apoptosis, as indicated by DNA fragmentation, activation of procaspase 3 to caspase 3 and cytochrome C release from the mitochondria to the cytosol. This apoptosis could be prevented by treatment with the 12LO product, 12 hydroxyeicosatetraenoic acid (12HETE). Human platelet-type 12LO-antisense knockdown, by either plasmid transfection or adeno-associated virus (AAV) infection also induced substantial VSMC death over controls, which could also be prevented by treatment with 12HETE, but not 5HETE. Hence, biochemical 12LO inhibition or 12LO-antisense knockdown in VSMC can induce programmed cell death. These observations suggest a previously unrecognized association between human VSMC survivability and 12LO.

Outcome of twin pregnancy in women ≥45 years old: a retrospective cohort study.

OBJECTIVE: To investigate prematurity rate in women aged ≥45 carrying a twin pregnancy. Other maternal and neonatal outcomes are also described. DESIGN: Retrospective cohort study. SETTING: Women delivering a twin pregnancy at a single tertiary medical center. POPULATION: The study included all women aged 45 years and over carrying a twin pregnancy who delivered at 20 weeks gestation or beyond over a 9-year period from May 2000 to May 2009. METHODS: Women aged 45 years and over were identified, all conceived by in vitro fertilization with ovum donation. The study group was compared to a control group of women <40 years with twin pregnancies conceived by IVF who delivered during the same time period. MAIN OUTCOME MEASURE(S): Maternal complications during pregnancy and neonatal outcome. RESULTS: During the study period 32 women ≥45 years delivered twins. The control group included 109 women. The rate of delivery before 37 weeks as well as before 32 weeks were very high in our study group (65% versus 40%, p = 0.01 and 15% versus 5.0%, p = 0.05, respectively). The rate of maternal life-threatening complications including blood product transfusion and maternal admission to the intensive care unit were also significantly higher in our study group compared to the control group (18% versus 2%, p = 0.018 and 6.3% versus none, p = 0.05). CONCLUSIONS: Women ≥45 years old with twin pregnancy carry a higher risk of maternal and perinatal complications.

The neurocognitive outcome of IUGR children born to mothers with and without preeclampsia.

OBJECTIVE: To examine long-term behavioral and neurodevelopmental outcome of children born growth restricted and exposed to hypertension in utero at 9 years of age. METHODS: Somatic growth and neurocognitive outcomes were evaluated at age 9-10 years of age in 42 children born with intra uterine growth restriction (IUGR) after pregnancies complicated by hypertensive disorder (17 with maternal preeclampsia and 25 after gestational hypertension). This study group was compared to a control group of 78 IUGR children born after normotensive pregnancy. RESULTS: Only weight was found to be significantly lower in the hypertensive-IUGR group, versus the normotensive IUGR children. No significant differences were found in any of the neurocognitive parameters including IQ, school achievements, and neurodevelopmental score at age 9-10 years. CONCLUSION: IUGR is a well known risk factor for later cognitive difficulties but maternal hypertensive disorder does not seem to add significantly to this risk.

Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome.

Antiphospholipid antibody syndrome (APS) is associated with adverse pregnancy outcomes and maternal complications including thrombotic events and early pre-eclampsia. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents a unique form in the spectrum of pre-eclampsia. This report describes four patients with pregnancy-associated hepatic infarctions. All four had APS and HELLP syndrome, which was complete in one patient and incomplete in three patients, with elevated liver enzymes in all, and either thrombocytopenia or hemolysis in two. In the literature, we found descriptions of an additional 24 patients who had 26 pregnancies with concomitant hepatic infarction. Of the total 28 patients, anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC) were assessed in 16 patients, out of whom 15 were found to be positive. Hepatic infartction during pregnancy was associated almost always with APS, with HELLP (2/3 complete, 1/3 incomplete), and only in one-third of the pregnancies with pre-eclampsia (PE).

Placental apoptosis in discordant twins.

OBJECTIVE: To investigate placental apoptosis in discordant dichorial twins. METHODS: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome. RESULTS: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the latter (P< 0.02 Wilcoxon rank test). CONCLUSIONS: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted.

Effect of fetal gender on first trimester markers and on Down syndrome screening.

OBJECTIVES: The purpose of the present study was to evaluate whether a gender-related difference exists in first trimester markers used for Down syndrome screening, namely nuchal translucency (NT), maternal serum pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (beta-hCG), and whether this has an influence on screening performance. METHODS: A total of 1325 patients with a singleton pregnancy underwent combined first trimester screening at 10-13 weeks' gestation. Maternal serum PAPP-A and free beta-hCG were analyzed by fluoroimmunoassay, nuchal translucency (NT) was measured by transvaginal sonography. Only patients with normal outcomes and known fetal gender were included in the study. Data were categorized by gestational age and by fetal gender. RESULTS: There were no significant gender-related differences in NT and PAPP-A levels. However, free beta-hCG was significantly higher (p=0.00004) in the presence of a female fetus than in the presence of a male fetus. Women with female fetuses had a higher median calculated Down syndrome risk (1:5490) compared to those having males (1:6451). This difference was not, however, statistically significant. CONCLUSION: First trimester free beta-hCG is significantly higher in pregnancies with a female fetus.

Anti-insulin antibodies and the natural autoimmune response in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by the finding of ample serum autoantibodies. The role and the origin of many of these antibodies are still obscure. The aim of this work was to study the occurrence of anti-insulin antibodies (AIA) in SLE, and to postulate, based on AIA determination, on the mechanisms involved in the production of some autoantibodies in SLE. IgG and lgM AIA, anti-DNA antibodies (ADA) and anti-tetanus toxoid antibodies (ATA) were determined using ELISA in sera and B-lymphocytes culture media of 24 SLE patients, 10 healthy controls and 19 insulin-dependent diabetes mellitus (IDDM) patients. B- and T-lymphocytes were isolated using Ficoll gradient, depleted of T-cells using cyclosporin A, EBV infected and grown in medium. The frequencies of IgM-AIA and IgG-ADA were higher in SLE patients than in healthy controls (P < 0.02 and P < 0.05, respectively). The rate of IgM-AIA in SLE and IDDM was comparable, while IgG-AIA was significantly less common in SLE than in IDDM (P < 0.05). The prevalence of ATA in SLE patients and healthy controls was similar. These findings increase the spectrum of the humoral autoimmune response in SLE and suggest that part of it (natural autoantibodies) is independent of antigen driven response.

Low molecular weight heparin and warfarin in the treatment of patients with antiphospholipid syndrome during pregnancy.

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia.

OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.

Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias.

OBJECTIVE: To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications. METHODS: The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy. RESULTS: Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 +/- 5.0 weeks and 1175 +/- 590 g, respectively, compared to 37.6 +/- 2.3 weeks and 2719 +/- 526 g, respectively, in the treated pregnancies (p < 0.001). CONCLUSIONS: This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.