Volume 49, Issue 6 - Special Section: Coronavirus Disease 2019 (COVID-19) in Obstetrics

After more than 1 year of the SARS-CoV-2 pandemic, a great deal of knowledge on how this virus affects pregnant women, the fetus and the newborn has accumulated. The gap between different guidelines how to handle newborn infants during this pandemic has been minimized, and the American Academy of Pediatrics (AAP)’s recommendations are now more in accordance with those of the World Health Organization (WHO). In this article we summarize present knowledge regarding transmission from mother to the fetus/newborn. Although both vertical and horizontal transmission are rare, SARS-CoV-2 positivity is associated with an increased risk of premature delivery and higher neonatal mortality and morbidity. Mode of delivery and cord clamping routines should not be affected by the mother’s SARS-CoV-2 status. Skin to skin contact, rooming in and breastfeeding are recommended with necessary hygiene precautions. Antibodies of infected or vaccinated women seem to cross both the placenta and into breast milk and likely provide protection for the newborn.

Despite the overwhelming number of coronavirus disease 2019 (COVID-19) cases worldwide, data regarding the optimal clinical guidance in pregnant patients is not uniform or well established. As a result, clinical decisions to optimize maternal and fetal benefit, particularly in patients with critical COVID-19 in the early preterm period, continue to be a challenge for obstetricians. There is often uncertainty in clinical judgment about fetal monitoring, timing of delivery, and mode of delivery because of the challenge in balancing maternal and fetal interests in reducing morbidity and mortality. The obstetrician and critical care team should empower pregnant patients or their surrogate decision maker to make informed decisions in response to the team’s clinical evaluation. A clinically grounded ethical framework, based on the concepts of the moral management of medical uncertainty, beneficence-based obligations, and preventive ethics, should guide the decision-making process.

Objectives The impact of the COVID-19 pandemic and the public health measures introduced to control it, on mental health, is largely unknown. Research conducted during past epidemics found that pregnant women are more vulnerable psychologically. The aim of this study was to investigate antenatal depressive and anxiety symptoms during this pandemic in Greece. Methods All women receiving routine antenatal care, during a three-month period, starting one week after the total lockdown in Greece, in a University department, were asked to fill in two questionnaires, the Edinburg Postnatal Depression Scale (EPDS) and the State-Trait Anxiety Inventory (STAI). Results Overall, 505 women (93.3% of the eligible population) agreed to participate. The prevalence of antenatal depression (EPDS score≥13) in the population of the study was 13.5%. Unplanned pregnancy (OR: 2.447; 95% CI: 1.235–4.846), smoking (OR: 2.268; 95% CI: 1.166–4.411) and antenatal anxiety (OR: 5.074; 95% CI: 2.898–8.883) increased the risk of antenatal depression during the COVID-19 pandemic. State (current)-anxiety affected 34.1% of the participants, whereas Trait (lifetime)-anxiety affected 15.8%. The State-anxiety score (median) was significantly higher than the Trait-anxiety (median) (41 vs. 36; p<0.001), revealing an increase in the levels of anxiety in the pandemic, while there was also a positive linear correlation between the two scales (rho=0.592; p<0.001). Conclusions The unprecedented situation of the COVID-19 pandemic has increased anxiety, but not depression levels of pregnant women in Greece. Population level interventions to address adverse effects on anxiety status in the initial phases of similar situations may be helpful in the future.

Objectives The outbreak of COVID-19 affects both physical and mental health of pregnant women. This study focuses on their psychological status, and analyzes the main factors affecting their emotions of pregnant women so as to provide guidance for psychological counseling and social intervention during epidemics. Methods Multiple researchers distributed a questionnaire online via the Internet. Pregnant women volunteered, and the questionnaire was automatically collected in the background. Results The 298 valid questionnaires recovered showed that 82 cases of pregnant women were in states of anxiety, accounting for 27.51%, of which 78.05% were mild (82 cases), 19.51% were moderate (16 cases), and 2.44% were severe (2 cases). Moreover, 31.21% of pregnant women were in states of depression (93 cases), of which 52.69% were mild (49 cases), 40.86% were moderate (38 cases), and 6.45% were severe (6 cases). The risk factors for states of anxiety or depression were fear of fetal malformation or genetic disease, history of adverse pregnancy, can’t do routine prenatal examination, and insufficient support and care from husbands and families. Besides, 16 cases had sought psychological help during the epidemic, among whom 62.50% (10 cases) experienced anxiety, 68.75% (11 cases) had depression. Conclusions During the outbreak of COVID-19, obstetricians may take use of the Internet, based on the advantages in epidemic prevention, controlling health education, and popularizing science. In addition, husbands and family members should provide greater care for pregnant women, to protect their mental health during public health incidents.

Objectives This study aimed to evaluate anxiety and depression in pregnant women during this global disease. Methods This was a cross-sectional study recruiting 120 pregnant women. The study was conducted at the outpatient clinic of a tertiary hospital. We recruited women attending for antenatal care. Anxiety was evaluated using an Arabic validated Kuwait University Anxiety Scale (KUAS). Depression was evaluated using a validated Arabic form of the Edinburgh Postnatal Depression Scale (EPDS). Results The study included 48 (40%) nulliparous and 72 (60%) multiparous women. The mean KUAS scores for nulliparous and multiparous women were 45.27±10.78 and 47.28±10.62. Both nulliparous and multiparous women had a fairly high possibility of depression . Fifty-three (44.2%) of them reported scores ≥ of 14. Ninety-three (77.5%) women thought that COVID-19 pandemic would affect their pregnancies. There was a significant association between the number of women reporting fear related to the COVID-19 pandemic and their KUAS and EPDS scores (p-value <0.001 each). Conclusions COVID-19 affected the mental health of pregnant women to a great extent. Care should be directed to measures that would decrease the impact of this pandemic on vulnerable populations.

Objectives To explore attitudes to COVID-19 vaccination among perinatal women. Methods A nationwide online, cross-sectional survey was conducted in Qatar from 15th October 2020 to 15th November 2020 with voluntary participation open to all adult residents. Of the respondents, the population group for this study comprised the 341 pregnant and breastfeeding participants. The survey utilized a composite questionnaire incorporating a validated instrument to measure vaccine attitudes. The responses were recorded and analysed with statistical analysis being performed with SPSS software. Outcome measures included intentions towards vaccination and potential factors influencing vaccine hesitancy (contextual factors, vaccine specific concerns and group/individual influences). Results Perinatal women exhibited a vaccine hesitancy rate of 25% towards COVID-19 immunisation. The main concerns of the group were of infection risks and main factor determining vaccine hesitancy was of vaccine specific safety concerns. Previous vaccine “acceptors” showed vaccine hesitancy to COVID-19 immunisation. A third of the group cited non availability of the vaccine as a concern. Conclusions COVID-19 vaccine trials amongst pregnant and lactating women have lagged behind those for general populations and this has compounded concerns around safety in this special group. Perinatal women constitute a vulnerable group and play an important role in vaccination of wider family members. This study highlights the need for trials and data for COVID-19 vaccine in this group to be able to achieve appreciable numbers needed for herd immunity and ultimately control of the pandemic.

Objectives The aim of our study is to present the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy and evaluate its impact on maternal and neonatal outcomes. Methods We retrospectively reviewed the medical records of all COVID-19 positive pregnant women who were admitted to “Alexandra” maternity hospital from March to December 2020 (n=40). The infection status was determined via real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swab specimen. We documented the demographic features, clinical status, pregnancy characteristics and maternal and fetal outcomes. Results Forty COVID-19 positive pregnant women were admitted to our clinic during the study period. Mean maternal age was 27.6 years. Gestational age (GA) ranged from 10–42 weeks of pregnancy with mean GA calculated at 38 +3  weeks. Associated comorbidities included hypertension, hypothyroidism, epilepsy, hepatitis B and asthma. Thirty-five out of 40 women delivered within the study period. Cesarean section was performed in 57.1% of the cases. Most of the cases (87.5%) were asymptomatic while ventilation was required for only one patient. All neonates tested negative for SARS-CoV-2. Neither maternal nor neonatal deaths occurred. Conclusions In alignment to other studies, our data show that the course of coronavirus disease 2019 (COVID-19) during pregnancy in the majority of cases is mild and neonatal outcomes also appear favorable.

Objectives To compare clinical characteristics and outcomes of infants born to COVID-19 to non COVID-19 mothers at delivery in a community hospital in Queens, New York. Methods Case-control study conducted March 15 to June 15, 2020. Cases were infants born to mothers with laboratory-confirmed COVID-19 infection at delivery. The infant of non COVID-19 mother born before and after each case were selected as controls. Results Of 695 deliveries, 62 (8.9%) infants were born to COVID-19 mothers; 124 controls were selected. Among cases, 18.3% were preterm compared to 8.1% in controls (p=0.04). In preterm cases, birth weight was not significantly different between groups. However, there was a significantly higher proportion of neonatal intensive care unit (NICU) admissions, need for respiratory support, suspected sepsis, hyperbilirubinemia, feeding intolerance and longer length of stay (LOS) in preterm cases. Among term cases, birth weight and adverse outcomes were not significantly different between cases and controls except for more feeding intolerance in cases. All infants born to COVID-19 mothers were COVID-19 negative at 24 and 48 h of life. No infants expired during birth hospitalization. Conclusions Significantly, more infants of COVID-19 mothers were premature compared to controls. Preterm cases were more likely to have adverse outcomes despite having similar birth weight and gestational age. These differences were not seen among full term infants. Health care providers should anticipate the need for NICU care when a COVID-19 mother presents in labor.

Objectives To investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on fetal Doppler parameters. Methods This was a prospective case-control study conducted in Ankara City Hospital with confirmed SARS-CoV-2 infected pregnants between August 1, 2020 and October 1, 2020. There were 54 COVID-19 confirmed pregnant women and 97 age-matched pregnant women as a control group between 28 and 39 weeks. Infection was confirmed based on positive real-time polymerase-chain reaction results. Demographic features, uterine artery (right, left), umblical artery, middle cerebral artery, ductus venosus, cerebro-placental ratio, and cerebral-placental-uterine ratio Doppler parameters were investigated in both groups. Results Two groups were similar in terms of demographic features and no difference was found for fetal Doppler parameters. Conclusions COVID-19 seems to have no adverse effect on fetoplacental circulation in mild and moderate patients during the acute phase of the infection.

Objectives In the current Severe Acute Respiratory Distress Coronavirus 2 (SARS-CoV-2) pandemic there is still great uncertainty about the effects of an infection in pregnancy especially regarding a possible fetal transmission of antibodies to SARS-CoV-2 and the longevity of this immunity. Methods Sixteen women who were infected with SARS-CoV-2 during pregnancy and their offspring were included. The antibody response to SARS-CoV-2 was measured in mother and umbilical cord blood peripartum and in a follow-up examination 6–11 weeks after birth. Medical history, symptoms regarding SARS-CoV-2, obstetric and neonatal information were queried following recommendations by the WHO. Results A total of 73% of the women and one third of the infants developed antibodies to SARS-CoV-2 spike (S) protein receptor binding domain (RBD), with a long interval between infection and birth proving favorable for a transplacentar transfer of antibodies to the neonates. All infants showed declining or vanishing antibody-titers in the follow-up examination, while the titers of their mothers were stable or even increased. Conclusions Our results demonstrate that transplacental transfer of SARS-CoV-2-specific antibodies is possible, but also indicate that the immunity that may be gained as a result might decrease in newborns postpartum. This provides important evidence that could be useful for further studies covering vaccination during pregnancy.

Objectives The Severe Acute Respiratory Distress Corona Virus 2 (SARS-CoV-2) pandemic poses special challenges for the society and especially the medical staff. Even if a rather mild course is assumed among pregnant women the measures to prevent transmission of the infection are of outstanding importance. Methods To screen asymptomatic pregnant women during admission to our university maternal hospital we focused on anti-SARS-CoV-2-specific IgG and IgA antibody responses. Hundred and fifty one women admitted to the hospital for childbirth or caesarean delivery were included. In case of suspicious anti-SARS-CoV-2-antibody levels an RT-PCR was performed to confirm an ongoing infection with SARS-CoV-2. Results A total of 89% showed negative results for anti-SARS-CoV-2-IgA antibodies, whereas 3% were borderline and 7% positive (both labeled as suspicious). In only one patient with suspicious serology we detected SARS-CoV-2-RNA in the following RT-PCR. 2% presented anti-SARS-CoV-2-IgG antibodies, all being positive for anti-SARS-CoV-2-IgA. The observed positive rate of our study collective of 10.6% seemed much higher than the expected one (1.3%) based on the reports of the Robert Koch Institute and the specifications given by the test’s manufacturer. The expected positive predictive value (PPV) was 4.3–6.7 times higher than the observed one. Conclusions To our knowledge this is the first report of anti-SARS-CoV-2-antibody levels in the peripartum period of asymptomatic women. As the positive anti-SARS-CoV-2 serology poorly correlated with the confirmatory RT-PCR and the fact that mainly the detection of the virus by PCR correlates with the patient’s infectiousness we suggest to rather perform a SARS-CoV-2-PCR-based admission screening in perinatal centers to prevent the spread of the disease.

Objectives This study aims to detect the SARS-CoV-2 infection prevalence in asymptomatic pregnant women. Methods A group of 195 asymptomatic pregnant women who attended the prenatal care outclinic and to the obstetric emergency department was tested concomitantly for SARS-CoV-2 by RT-PCR and serological tests. Results The virus was detected by RT-PCR in two (1.02%) cases and 17 (8.71%) patients had antibodies detected by immunochromatographic tests. Conclusions Due to the high risk of this emerging infection in the health of pregnant women, fetuses and newborns, we suggest the universal screening of all pregnant women admitted to hospital through the combined method RT-PCR and serological.

Objectives For women with Swyer Syndrome, a 46,XY gonadal dysgenesis, full term pregnancies are possible after oocyte donation. According to literature, mode of delivery is almost always by Caesarean section for various reasons. Medical indications are multiple pregnancies and related complications, preeclampsia, an androgynous shaped pelvis and failed induction of labor. Elective Caesarean sections were performed based on maternal request and medical recommendation. Methods Following careful examination and shared decision making, we planned a spontaneous delivery with a patient with Swyer syndrome and tested the different hypotheses regarding anatomical and functional features according to literature. In addition, deliveries of women with Swyer Syndrome were analyzed in a German multicenter case series. Results A total of seven women with Swyer syndrome with a total of 10 pregnancies were identified, who later gave birth to twelve live-born children. Seven out of 10 births were performed by elective and non-elective Caesarean section, three births took place vaginally. Conclusions In summary, the risk of Caesarean section delivery has increased, but spontaneous delivery can be attempted in the event of inconspicuous findings.

Objectives To present the consequences of and risk factors for abnormal bleeding after ECV (external cephalic version). Methods We conducted a retrospective chart review at a single center in Japan. Abnormal bleeding was defined as vaginal bleeding and/or intrauterine hemorrhage. We descriptively assessed birth outcomes among women with abnormal bleeding, and investigated the risk factors using a logistic regression analysis. Results Of 477 women who received ECV, 39 (8.2%) showed abnormal bleeding, including 16 (3.4%) with intrauterine hemorrhage. Of the 16 women with intrauterine hemorrhage, 14 required emergency cesarean section; none experienced placental abruption, a low Apgar score at 5 min (<7), or low umbilical cord artery pH (<7.1). Among 23 women who had vaginal bleeding without intrauterine hemorrhage, four cases underwent emergency cesarean section and one case of vaginal delivery involved placental abruption. The risk of abnormal bleeding was higher in women with a maximum vertical pocket (MVP) of <40 mm in comparison to those with an MVP of >50 mm (adjusted odds ratio [OR]: 3.48, 95% confidence interval [CI]: 1.23–9.90), as was higher in women with unsuccessful ECV than in those with successful ECV (aOR: 4.54, 95% CI: 1.95–10.6). Conclusions A certain number of women who underwent ECV had abnormal bleeding, including vaginal bleeding and/or intrauterine hemorrhage, many of them resulted in emergency cesarean section. Although all of cases with abnormal bleeding had good birth outcomes, one case of vaginal bleeding was accompanied by placental abruption. Small amniotic fluid volume and unsuccessful ECV are risk factors for abnormal bleeding.

Objectives To determine the causes of fetal death among the stillbirths using two classification systems from 22 weeks of gestation in a period of three years in high-risk pregnancies. This is a retrospective observational study. Methods The National Institute of Perinatal Health in Mexico City is a Level 3 care referral center attending high-risk pregnancies from throughout the country. The population consisted of patients with fetal death during a three-year period. Between January 2016 and December 2018, all stillbirths were examined in the Pathology Department by a pathologist and a medical geneticist. Stillbirth was defined as a fetal death occurring after 22 weeks of gestation. Results Main outcome measures: Causal analysis of fetal death using the International Statistical Classification of Disease and Related Health Problems-Perinatal Mortality (ICD-PM) and initial causes of fetal death (INCODE) classification systems. A total of 297 stillborn neonates were studied. The distribution of gestational age in antepartum stillbirths (55.2%) showed a bimodal curve, 36% occurred between 24 and 27 weeks and 32% between 32 and 36 weeks. In comparison, the majority (86%) of intrapartum deaths (44.8%) were less than 28 weeks of gestation. Of the 273 women enrolled, 93 (34%) consented to a complete fetal autopsy. The INCODE system showed a present cause in 42%, a possible cause in 54% and a probable cause in 93% of patients. Conclusions The principal causes of antepartum death were fetal abnormalities and pathologic placental conditions and the principal causes of intrapartum death were complications of pregnancy which caused a premature labor and infections.

Objectives Neonates who develop moderate to severe encephalopathy following perinatal asphyxia will benefit from therapeutic hypothermia. Current National Institute of Child Health and Human Development (NICHD) criteria for identifying encephalopathic neonates needing therapeutic hypothermia has high specificity. This results in correctly identifying neonates who have already developed moderate to severe encephalopathy but miss out many potential beneficiaries who progress to develop moderate to severe encephalopathy later. The need is therefore not just to diagnose encephalopathy, but to predict development of encephalopathy and extend the therapeutic benefit for all eligible neonates. The primary objective of the study was to develop and validate the statistical model for prediction of moderate to severe encephalopathy following perinatal asphyxia and compare with current NICHD criteria. Methods The study was designed as prospective observational study. It was carried out in a single center Level 3 perinatal unit in India. Neonates>35 weeks of gestation and requiring resuscitation at birth were included. Levels of resuscitation and blood gas lactate were used to determine the pre-test probability, Thompson score between 3 and 5 h of life was used to determine post-test probability of developing encephalopathy. Primary outcome measure: Validation of Prediction of Encephalopathy in Perinatal Asphyxia (PEPA) score by Holdout method. Results A total of 55 babies were included in the study. The PEPA score was validated by Holdout method where the fitted receiver-operating characteristic (ROC) area for the training and test sample were comparable (p=0.758). The sensitivity and specificity of various PEPA scores for prediction of encephalopathy ranged between 74 and 100% in contrast to NICHD criteria which was 42%. PEPA score of 30 had a best combination of sensitivity and specificity of 95 and 89% respectively. Conclusions PEPA score has a higher sensitivity than NICHD criteria for prediction of Encephalopathy in asphyxiated neonates.

Objectives It is not clear, which factors affect extracellular DNA (ecDNA) concentrations in healthy women with singleton uncomplicated pregnancies, although deoxyribonucleases (DNases) are hypothesized to be responsible for the cleavage of plasma ecDNA. The aim of this study was to analyze potential determinants of total ecDNA including plasma DNase activity. Methods Plasma samples were collected from 48 healthy women with singleton uncomplicated pregnancies in the third trimester (gestation week 37). DNA was isolated and quantified using fluorometry and real time PCR. DNase activity was assessed using the single radial enzyme-diffusion method. Results Neither ecDNA, nor DNase activity were affected by maternal age or BMI. DNase activity negatively correlated with total plasma ecDNA (r=−0.40, p=0.007). Similar associations were found for ecDNA of nuclear and mitochondrial origin, but not with fetal DNA quantified using Y-targeted PCR in male fetus-bearing pregnancies. Conclusions The role of plasma ecDNA of fetal and maternal origin is studied in the pathogenesis of pregnancy-complications. The results indicate that plasma DNase activity could negatively regulate ecDNA concentrations and should, thus, be analyzed in preeclampsia, preterm birth and other ecDNA-related pregnancy complications.

SPEAKERS ABSTRACTS The application of super slow review of ultrasound clips to a diagnosis of fetal tachyarrhythmia Name and surname: Jun Yoshimatsu Institution: National Cerebral and Cardiovascular Center Email: yoshimatsu.jun.hp@ncvc.go.jp Objective Fetal arrhythmias occur in 1–2% of all pregnant cases. Premature atrial contraction (PAC), premature ventricular contraction (PVC) which are clinically benign are relatively common and do not require therapy. In contrast supraventricular tachycardias (SVTs), atrial flutter (AFL), ventricular tachycardia which are life-threatening are relatively rare but require treatment. These tachyarrhythmias easily complicate fetal congestive heart failure which can be followed by a fetal death. Thus, prenatal treatment for SVT and AFL is warranted to convert to sinus rhythm. Recently our group demonstrated that protocol-defined transplacental treatment for fetal SVT and AFL was effective and tolerable in 90% of cases. In order to choose the appropriate medication for fetal tachyarrhythmia the accurate diagnosis is important. Because fetal electrocardiography is still not available fetal echocardiography is commonly used for the diagnosis of fetal arrhythmia. The M-mode and Doppler echocardiography may achieve prenatal identification of arrhythmic types. The easier method helps more accurate and precise diagnosis of it. Recent advances of ultrasound examination technology allows a high spatial resolution and high temporal resolution at the same time. The image editing of video clips of four chamber view, which is the most easier image plane, is applicable for the diagnosis of fetal arrhythmias. We conducted the research to innovate the useful video clip editing method including a super slow motion for the precise diagnosis of fetal arrhythmias. Method From our fetal echocardiography database, 55 fetal echocardiography video clips (35 AFL, 20 SVT) were reviewed. Four chamber view clips of each case were selected. Every clips were edited into 10% speed. One examiner inserted the clip maker at the timing of atrial contraction and ventricular contraction. The intervals between ventricular contraction and atrial contraction were measured. Also the number of times of contraction of atrium and ventricle and their relations were recorded. Results Every contractions of each portion (atrium and ventricle) could be detected easily with edited video clips. The differentiation between AFL and SVT could be done completely by counting the number of contractions of atrium and ventricle. Also the V-A intervals and the A-V intervals could be measured in one hundredth seconds. In all cases, the diagnosis is compatible with that had made postnatally. Conclusion The first step of this study was depended on the examiner’s naked eyes helped by editing application. The accuracy of each steps of this study were satisfactory. This is the preliminary step to conduct the deep learning of Artificial Intelligence (AI). The most important point of using AI is setting up what to teach and how to teach. Our study showed the possibility of the application of AI to make a diagnosis of fetal tachyarrhythmia.