Novel corona virus disease (COVID-19) in pregnancy: What clinical recommendations to follow?

Pregnancy is a state of partial immune suppression which makes pregnant women more vulnerable to viral infections, and the morbidity is higher even with seasonal influenza. Therefore, the COVID‐19 epidemic may have serious consequences for pregnant women. Although the vast majority of cases of COVID‐19 are currently in China, the risk of outward transmission appears to be significantly raising global concern. Human to human transmission of the virus is proven to occur,1, 2 perhaps even from asymptomatic patients,3, 4 and the mortality is substantial, especially among frail, elderly patients with comorbidities.5 Although there have been some criticisms surrounding suppression of early warnings, and slow initial response followed by heavy‐handed quarantine measures, as well as concerns expressed about the capacity to cope with the large number of patients, and shortage of protective equipment and in‐hospital infections leading to deaths among a substantial number of healthcare professionals,6, 7 China's effort to contain the disease and slow down its spread in China and world‐wide has been commendable. A large number of cases requiring hospitalization and intensive care is a serious burden even for affluent countries with well‐developed healthcare systems. However, the Chinese government, its health professionals, and the public, have set a new standard for handling the epidemic, and they have certainly contributed to reducing the potential risk of outbreak in neighboring countries with weaker healthcare systems. Furthermore, Chinese researchers and health professionals have generously shared their data, knowledge, experience and expertise that has helped to develop diagnostic tools, clinical management algorithms, set up clinical trials, and accelerate vaccine development. Clinical course and outcome of a substantial number of COVID‐19 patients have been reported, and recommendations regarding the care of such patients have been issued by several national health authorities across the world. However, the practices seem to vary considerably

Fetal heart rate variability with hypoxemia in an instrumented sheep model

Abstract Objective We examined the effect of hypoxemia on fetal heart rate variability using the instrumented fetal sheep model. Methods In this prospective study, 19 pregnant sheep were instrumented under general anesthesia at a mean gestational age of 127 days. After a 5-day recovery, hypoxaemia was induced by attaching the mother to a re-breathing circuit. Hypoxemia was further extended till 120 minutes, following which it was reversed till matenal and fetal pO2 returned back to baseline. The heart rate recordings at baseline, hypoxemia of 30 and 120 minutes, and recovery were analysed to calculate short term variation (STV) in 16 epochs of 3.75sec each, every minute. Phase rectified signal averaging (window length L= 10, time T= 2 and Scale S=T) was used to calculate acceleration capacity (AC) and deceleration capacity (DC). Results At baseline, mean (SD) fetal pO2 was 2.90±0.38 kPa. Acute hypoxaemia was associated with a significant reduction in mean pO2 at 30 (1.60±0.37 kPa) and 120 (1.50±0.16 kPa) minutes. Mean (SD) fetal pO2 at recovery was 2.80±0.32 kPa. The median STV, AC and DC were 1.307 msec (IQR: 0.515 to 2.508), 1.295 (IQR: 0.990 to 2.685) BPM and 1.197 (IQR: 0.850 to 1.836) BPM respectively, at baseline. With 30-minute hypoxaemia, the values were 1.323 (IQR 0.753 to 2.744) msecs, 1.696 (IQR: 1.310 to 3.013) BPM & 1.584 (IQR 1.217 to 4.132) BPM. With 120-minute hypoxaemia, the values were 1.760 (IQR: 0.928 ? 4.656) msecs, 3.098 (IQR: 1.530 ? 5.163) BPM & 3.054 (IQR: 1.508 ? 4.522) BPM. At recovery they changed to 0.962 (IQR: 0.703 ? 1.154) msecs, 1.228 (IQR: 1.071 ? 2.234) BPM & 1.086 (IQR: 0.873 ? 1.568) BPM respectively. Hypoxemia for 30 and 120 minutes were associated with a significant increase in the DC compared to baseline (p = 0.014 & 0.017 respectively). The changes in STV and AC were not significant. Conclusion Acute hypoxaemia is associated with a significant increase in the deceleration capacity of the fetal heart rate. This article is protected by copyright. All rights reserved.Peer reviewe

Static and functional hemodynamic profiles of women with abnormal uterine artery doppler at 22-24 weeks of gestation

Published version. Source at http://doi.org/10.1371/journal.pone.0157916. License CC BY 4.0.Objective To compare cardiac function, systemic hemodynamics and preload reserve of women with increased (cases) and normal (controls) uterine artery (UtA) pulsatility index (PI) at 22–24 weeks of gestation. Materials and Methods A prospective cross-sectional study of 620 pregnant women. UtA blood flow velocities were measured using Doppler ultrasonography, and PI was calculated. Mean UtA PI ≥ 1.16 (90th percentile) was considered abnormal. Maternal hemodynamics was investigated at baseline and during passive leg raising (PLR) using impedance cardiography (ICG). Preload reserve was defined as percent increase in stroke volume (SV) 90 seconds after passive leg raising compared to baseline. Results Mean UtA PI was 1.49 among cases (n = 63) and 0.76 among controls (n = 557) (p < 0.0001). Eighteen (28.6%) cases and 53 (9.5%) controls developed pregnancy complications (p <0.0001). The mean arterial pressure and systemic vascular resistance were 83 mmHg and 1098.89±293.87 dyne s/cm5 among cases and 79 mmHg and 1023.95±213.83 dyne s/cm5 among controls (p = 0.007 and p = 0.012, respectively). Heart rate, SV and cardiac output were not different between the groups. Both cases and controls responded with a small (4–5%) increase in SV in response to PLR, but the cardiac output remained unchanged. The preload reserve was not significantly different between two groups. Conclusion Pregnant women with abnormal UtA PI had higher blood pressure and systemic vascular resistance, but similar functional hemodynamic profile at 22–24 weeks compared to controls. Further studies are needed to clarify whether functional hemodynamic assessment using ICG can be useful in predicting pregnancy complications

Utjecaj brzine doze pulsnoga zračenja na nastanak mikronukleusa u limfocitima periferne ljudske krvi

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7±0.2) Gy at different rates and cytogenetic damage was quantifi ed using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.Mikronukleus-test pokazao se osjetljivim pokazateljem oštećenja u limfocitima periferne ljudske krvi te se primjenjuje kao biološki dozimetar posumnja li se na prekomjerno izlaganje ionizirajućem zračenju. Mikronukleusi kao mjera oštećenja kromosoma često se rabe za procjenu učinaka zračenja u biološkim sustavima. Ovdje je istraženo djelovanje pulsnoga elektronskoga snopa od 8 MeV, dobivenog s pomoću elektronskoga akceleratora marke Microtron, na nastanak mikronukleusa u rasponu brzina doza od 35 Gy min-1 do 352.5 Gy min-1. Brzine doza mijenjale su se mijenjajući brzinu ponavljanja pulsa (tzv. pulse repetition rate, krat. PRR). Za mjerenje apsorbirane doze pri različitim PRR-ovima rabio se Frickeov dozimetar. Dozimetrijska su mjerenja također poslužila za ujednačavanje doze elektronskoga snopa. Za istraživanje utjecaja brzine doze, uzorci krvi ozračeni tako da apsorbiraju dozu od (4.7±0.2) Gy pri različitim brzinama doze, a zatim se s pomoću mikronukleus-testa utvrdilo citogenetsko oštećenje. Pokus s pulsnim snopovima energije 8 MeV upućuje na neovisnost broja mikronukleusa o brzinama doze u rasponu ispitanome u ovom istraživanju. Naše ranije istraživanje utjecaja doze pulsnoga elektronskoga zračenja energije 8 MeV upozorilo je na linearni do kvadratni odgovor izmjerenih parametara. Stoga se akcidentalna doza može procijeniti s pomoću linearnih do kvadratnih parametara odgovora na dozu, bez potrebe za korekcijom s pomoću brzine doze

Knowledge about preventive dentistry versus self-reported competence in providing preventive oral healthcare – a study among Nepalese dentists

Source at https://dx.doi.org/10.1186/2Fs12903-017-0366-5 Background: Dentists ’ and dental healthcare providers ’ professional knowledge and attitude towards the prevention of oral diseases may have an impact on the oral health of the general population. The aim of this study was to describe Nepalese dentists ’ competency in giving preventive education and treatment to their patients, and to assess their level of knowledge about preventive dental health. Methods: This was a cross-sectional study of 195 dentists (71 males and 124 females). Knowledge of preventive oral healthcare and self-reported aspects of preventive oral healthcare were assessed using a close-ended multiple- choice questionnaire. Statistical evaluation was done using chi-squared test, independent sample t-test and factor analysis as appropriate. Results: More than 90% of dentists self-reported to be competent in providing preventive treatment and oral hygiene education to their patients. Female dentists reported being more competent in giving oral hygiene education than their male counterparts ( p = 0.045). Dentists scored a mean of 24.06 ± 3.8 [range (15 – 33)] out of 56 on knowledge based on self-reported awareness of seven different aspects of preventive dentistry. More than 70% of the dentists had relatively good knowledge regarding the use of fluoride, whereas the preventive knowledge in other aspects of dental health such as frequency of sugar consumption, xylitol use, dental visits, sealant, gingival health, dental and general health was found to be limited. Conclusions: The majority of participating dentists reported a high level of general competency in providing preventive treatment and oral health education to their patients, whereas their knowledge was found to be limited in some aspects of preventive dentistry

Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: A longitudinal study

This is the peer reviewed version of the following article: Acharya, G., Ebbing, C., Karlsen, H., Kiserud, T. & Rasmussen, S. (2019). Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: A longitudinal study. Ultrasound in Obstetrics and Gynecology, 2019, which has been published in final form at https://doi.org/10.1002/uog.21870. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Objectives - The ratio of middle cerebral artery (MCA) pulsatility index (PI) to umbilical artery (UA) PI, i.e. cerebro‐placental ratio (CPR), has been suggested as a measure of fetal “brain sparing” phenomenon reflecting redistribution of fetal cardiac output as a response to placental insufficiency. Observational studies have shown that low CPR values predict increased risk of adverse perinatal outcomes although evidence from randomized clinical trials is lacking. The inverse ratio, i.e. umbilico‐cerebral ratio (UCR), is preferred by some as it increases with increasing degree of fetal compromise. Monitoring fetal wellbeing requires serial assessment, and for this purpose, appropriate reference values should be based on data from longitudinal studies. However, longitudinal reference ranges for the UCR have not been established. Furthermore, the sex of the fetus influences its growth velocity, cord properties, in utero circadian rhythm, behavioral states and placental function, but whether gestational age‐dependent changes in CPR or UCR differ between male and female fetuses has not been studied. Thus, our objective was to investigate sex‐specific, gestational age‐associated serial changes in CPR and UCR during the second half of pregnancy and establish longitudinal reference ranges. Methods - This was a dual‐center prospective longitudinal study of singleton low risk pregnancies. Doppler blood flow velocity waveforms were obtained serially from the UA and MCA during 19‐41 weeks of gestation, and PIs were determined. CPR and UCR were calculated as the ratios, MCA PI/ UA PI and UA PI/ MCA PI, respectively. The course and outcome of pregnancies was recorded. Sex of the fetus was determined after delivery. Reference intervals were constructed using multilevel modelling and gestational age‐specific Z‐scores of male and female fetuses were compared. Results - Of a total of 299 pregnancies enrolled, 284 women and their fetuses (148 male and 136 female) were included in the final analysis, and 979 paired measurements of UA and MCA PIs were used to construct sex‐specific longitudinal reference intervals. Both CPR and UCR had U‐shaped curves of development during pregnancy, but with opposite directions. There was a small but significant (P=0.007) difference in z‐scores of CPR and UCR between male and female fetuses throughout the second half of pregnancy. Conclusions - We have established longitudinal reference ranges for CPR and UCR suitable for serial monitoring with possibilities to refine the assessment by fetal sex‐specific ranges and the conditioning by a previous measurement. The clinical significance of such refinements needs further evaluation

Fetal Superior Vena Cava Blood Flow and Its Fraction of Cardiac Output: A Longitudinal Ultrasound Study in the Second Half of Pregnancy

Introduction: In the fetus, a large proportion of the superior vena cava blood flow (QSVC) comes from the brain. To provide the possibility of using this blood flow as a representation of fetal brain circulation, we aimed to determine the fetal QSVC and its fraction of cardiac output during the second half of physiological pregnancies. Materials and Methods: This was a prospective longitudinal study specifically designed for studying fetal hemodynamic development. Healthy women with singleton low-risk pregnancies were included. Ultrasonography was performed at 4-weekly intervals from 20+0 gestational weeks to term. Doppler velocity recordings of the superior vena cava (SVC) and cardiac ventricular outflow tracts were used to obtain the time-averaged maximum velocities (TAMxV). Vessel diameters were measured to calculate their cross-sectional areas (CSA): π(diameter/2)2. Blood flow (Q) was computed as: h*TAMxV*CSA, h being the spatial blood velocity profile, to obtain QSVC and cardiac outputs. The sum of left and right ventricular cardiac outputs constituted the combined cardiac output (CCO). Ultrasound biometry based estimated fetal weight and brain weight were used to normalize the flow. QSVC was also expressed as the fraction (%) of CCO. Gestational age specific percentiles were established for each blood flow parameter using multilevel modeling. Results: Totally, 134 of the 142 included women were eligible for the study with 575 sets of observations. The SVC mean diameter (19–52 mm), mean TAMxV (8.83–16.14 cm/s), and QSVC (15.4–192.0 ml/min) increased significantly during the second half of pregnancy (p < 0.001) while the mean QSVC normalized by estimated fetal weight (49 ml/min/kg) and by estimated brain weight (50 ml/min/100 g) were relatively stable. Similarly, the mean CCO increased (156–1,776 ml/min; p < 0.001) while the normalized CCO (509 ± 13 ml/min/kg) and QSVC as a fraction of CCO (10 ± 0.92%) did not change significantly with gestational age. Conclusion: We provide reference values for fetal QSVC which increases significantly with gestation, and constitutes roughly 10% of the fetal CCO at any time during the second half of pregnancy.publishedVersio

Laeverin Protein Expression in Normal and Preeclamptic Placentas using Tissue Microarray Analysis

This is the peer reviewed version of the following article: Nystad, M., Sitras, V.S., Nordbakken, C., Pedersen, M.I. & Acharya, G. (2018). Laeverin Protein Expression in Normal and Preeclamptic Placentas using Tissue Microarray Analysis. Acta Obstetricia et Gynecologica Scandinavica, 97(5), 536-544, which has been published in final form at https://doi.org/10.1111/aogs.13304. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Introduction - Laeverin is a placenta‐specific protein that is normally expressed in the plasma membrane of human trophoblasts. In previous studies, we showed higher expression levels of laeverin gene in preeclamptic compared with normal placentas and found that laeverin protein was ectopically expressed in the cytoplasm of the preeclamptic placentas. Our objective was to investigate laeverin protein expression in normal and preeclamptic placentas combining immunohistochemistry and immunofluorescence. Material and methods - Tissue microarray analysis of 72 placentas, obtained from 33 preeclamptic and 39 uncomplicated pregnancies, was performed. Laeverin was labeled with a specific antibody for immunohistochemistry and immunofluorescence studies. Results - Immunohistochemistry showed that laeverin was expressed in syncytiotrophoblasts, cytotrophoblasts and extravillous trophoblasts in all placentas examined. In preeclamptic placentas (n = 33) compared with normal placentas (n = 39), laeverin was expressed in the cell membrane in 21 (64%) vs. 21 (54%) samples (p = 0.726), in the cytoplasm in 3 (9%) vs. 2 (5%) samples (p = 0.795) and in both the cytoplasm and membrane in 9 (27%) vs. 16 (41%) samples (p = 0.0522). All placental samples that showed cytoplasmic expression of laeverin were obtained from women who delivered before 34 weeks of gestation (early‐onset preeclampsia). Further, immunofluorescence studies showed laeverin expression in the cytoplasm of six preeclamptic (three early‐onset and three late‐onset) and one normal placenta but did not reveal any simultaneous cell membrane and cytoplasmic expression of laeverin. Conclusion - Laeverin is expressed in all trophoblast cell types of normal and preeclamptic placentas. Expression pattern of laeverin in trophoblast cells is heterogeneous and not necessarily membrane‐bound

Reference ranges of fetal superior vena cava blood flow velocities and pulsatility index in the second half of pregnancy: a longitudinal study

Background - Fetal superior vena cava (SVC) is essentially the single vessel returning blood from the upper body to the heart. With approximately 80-85% of SVC blood flow representing cerebral venous return, its interrogation may provide clinically relevant information about fetal brain circulation. However, normal reference values for fetal SVC Doppler velocities and pulsatility index are lacking. Our aim was to establish longitudinal reference intervals for blood flow velocities and pulsatility index of the SVC during the second half of pregnancy. Methods - This was a prospective study of low-risk singleton pregnancies. Serial Doppler examinations were performed approximately every 4 weeks to obtain fetal SVC blood velocity waveforms during 20–41 weeks. Peak systolic (S) velocity, diastolic (D) velocity, time-averaged maximum velocity (TAMxV), time-averaged intensity-weighted mean velocity (TAMeanV), and end-diastolic velocity during atrial contraction (A-velocity) were measured. Pulsatility index for vein (PIV) was calculated. Results - SVC blood flow velocities were successfully recorded in the 134 fetuses yielding 510 sets of observations. The velocities increased significantly with advancing gestation: mean S-velocity increased from 24.0 to 39.8 cm/s, D-velocity from 13.0 to 19.0 cm/s, and A-velocity from 4.8 to 7.1 cm/s. Mean TAMxV increased from 12.7 to 23.1 cm/s, and TAMeanV from 6.9 to 11.2 cm/s. The PIV remained stable at 1.5 throughout the second half of pregnancy. Conclusions - Longitudinal reference intervals of SVC blood flow velocities and PIV were established for the second half of pregnancy. The SVC velocities increased with advancing gestation, while the PIV remained stable from 20 weeks to term

Impact of the COVID-19 pandemic on women's perinatal mental health and its association with personality traits: An observational study

Introduction - The burden of perinatal mental health problems was expected to increase during the COVID-19 pandemic. We prospectively investigated the impact of the COVID-19 pandemic on the mental health of pregnant and postpartum women in Norway and explored associations with their sociodemographic characteristics and personality traits. Material and methods - Sociodemographic information and the self-reported impact of pandemic on wellbeing of pregnant women was collected using an online survey. To assess women's mental health, two validated questionnaires, the Edinburgh Postpartum Depression Scale (EPDS) and the Generalized Anxiety Disorder-7 item Scale (GAD-7), were used prenatally and postnatally. Personality traits were evaluated using HumanGuide, a web-based ipsative psychological evaluation instrument. Results - 772 women were included prenatally, of which 526 also responded to the survey 4–6 weeks postnatally. The median age was 29 years, 53.6% of the women were nulliparous when enrolled, and 35.1% worked in the healthcare sector. The median EPDS (6.0; interquartile range [IQR] 3.0–10.0 vs 6.0; IQR: 3.0–10.0) and the median GAD-7 (5.0; IQR 2.0–9.0 vs 5.0; IQR 2.0–9.0) were similar pre-and postnatally. Prenatally, the proportion of women scoring ≥13 on EPDS and ≥10 on GAD-7 was 14.5% (112/772) and 21.5% (166/772), whereas the postnatal figures were 15.6% (82/526) and 21.5% (113/526), respectively. The differences were not significant (P = 0.59 and P = 0.99). Being Conclusions - During the initial phase of the COVID-19 pandemic, the prevalence of depression (EPDS ≥ 13) and anxiety (GAD-7 ≥ 10) was 14.5% and 21.5%, respectively, among Norwegian pregnant women. Certain sociodemographic characteristics and personality traits were significant predictors of depression and anxiety