Impact of COVID-19 and vaccination on first and second trimester screening results.

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (ßHCG) between infected women and controls. Moreover, these levels were not different between "Infected + vaccinated" and "Only vaccinated" groups. However, median values of PAPP-A and ßHCG were higher in "Infected + vaccinated" and "Only vaccinated" groups compared with "Infected" and "Control" groups (P < 0.001). Median values of unconjugated Estriol (uE3) and ßHCG markers were not different between "Only vaccinated" and "Control" groups, yet both markers were elevated in "Infected" and "Infected + vaccinated" groups compared with other groups. AFP values were higher in "Infected" group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in "Infected" and "Vaccinated" groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS.

Laparoscopic management of second trimester ruptured cornual heterotopic pregnancy with subsequent live birth delivery: A case report and literature review.

OBJECTIVE: Heterotopic pregnancy (HP) is the coexistence of extra- and intrauterine gestation implantation sites. A rare case of a second-trimester ruptured cornual HP (CHP) treated with laparoscopic cornual resection with the primary repair is presented. Risk factors, clinical presentations, treatments, and outcomes of CHPs are also reviewed. CASE REPORT: A 35-year-old pregnant woman with CHP presented with lower abdominal pain with hemoperitoneum and her hemoglobin level dropped. Laparoscopic management of a ruptured HP was performed, leaving the surplus intrauterine fetus intact. She delivered a 2360 g male infant via cesarean section at 34 weeks' gestation due to preterm premature rupture of membranes. We found a well-healed wound over the left uterine cornua during the cesarean section. CONCLUSION: Ruptured CHP is a rare but life-threatening complication of an obstetric emergency. Although the pregnant uterus becomes congested and fragile, using reliable laparoscopic energy devices and barbed sutures, successful treatment is feasible.

Vaccination from the early second trimester onwards gives a robust SARS-CoV-2 antibody response throughout pregnancy and provides antibodies for the neonate.

OBJECTIVES: Preventive measures against COVID-19 are essential for pregnant women. Pregnant women are particularly vulnerable to emerging infectious pathogens due to alterations in their physiology. We aimed to determine the optimum timing of vaccination to protect pregnant women and their neonates from COVID-19. METHODS: A prospective observational longitudinal cohort study in pregnant women who received COVID-19 vaccination. We collected blood samples to evaluate levels of antispike, receptor binding domain and nucleocapsid antibodies against SARS-CoV-2 before vaccination and 15 days after the first and second vaccination. We determined the neutralizing antibodies from mother-infant dyads in maternal and umbilical cord blood at birth. If available, immunoglobulin A was measured in human milk. RESULTS: We included 178 pregnant women. Median antispike immunoglobulin G levels increased significantly from 1.8 to 5431 binding antibody units/ml and receptor binding domain from 6 to 4466 binding antibody units/ml. Virus neutralization showed similar results between different weeks of gestation at vaccination (P >0.3). CONCLUSION: We advise vaccination in the early second trimester of pregnancy for the optimum balance between the maternal antibody response and placental antibody transfer to the neonate.

Effectiveness of electroconvulsive therapy in acute management of delirious mania in COVID-19 positive woman in second trimester pregnancy.

Delirious mania has been described as a state of acute excitement, fluctuating sensorium, affective and catatonic symptoms. Electroconvulsive therapy (ECT) despite being an effective treatment modality in such cases, has been under-utilised during pregnancy, mainly due to safety concerns. Here, we report the effectiveness of ECT in acute management of delirious mania in a 24 weeks pregnant woman who also tested COVID-19 positive during hospitalisation. Patient presented with three weeks history of acute manic excitement with period of altered sensorium and catatonic symptoms with no response to trials of two antipsychotic agents. After organic causes ruled out, patient was planned for ECT while ongoing antipsychotic was continued. After the first ECT session, patient tested positive for COVID-19, though asymptomatic and had to be shifted to COVID-19 isolation facility. Complete resolution of psychiatric symptoms occurred after fifth ECT. All five ECT sessions, including those in COVID-19 isolation facility were carried out under supervision of a multidisciplinary team. None of the ECT sessions had any major adverse event. Symptom remission sustained even following ECT discontinuation. No neonatal or maternal adverse effects observed after an uneventful delivery at 35 weeks. Both mother and child continued to maintain well in follow-up period of one year on oral olanzapine. In this unusual concurrent presentation of mania, delirium and catatonic symptoms during second trimester pregnancy, we highlighted the effectiveness and safety of ECT as a viable treatment modality. Additionally, management challenges posed by patient testing COVID-19 positive and then, administering ECT in COVID-19 isolation facility using personal protective equipment by multidisciplinary team has been highlighted.

Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunoglobulin G Levels After the Pfizer-BioNTech Booster Dose for Coronavirus Disease 2019 (COVID-19) Vaccination During the Second Trimester of Pregnancy.

OBJECTIVE: To evaluate maternal and neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody levels at birth after a third (booster) dose of the Pfizer-BioNTech messenger RNA (Pfizer) coronavirus disease 2019 (COVID-19) vaccine during the second trimester of pregnancy, and compare them with those in women who received two vaccine doses during the second trimester. METHODS: We conducted a prospective cohort study of women admitted to the delivery ward at a single center who received the third Pfizer COVID-19 vaccine dose (booster group) at 17-30 weeks of pregnancy and who did not have previous SARS-CoV-2 infection. Maternal and neonatal antibody levels were measured on admission for delivery and in the umbilical cord blood after birth. Antibody levels for the booster group were compared with those in a historical control group of pregnant women who received their second vaccine dose (two-dose group) within the same gestational age window. RESULTS: Between October 2021 and February 2022, antibody levels were measured in 121 women and 109 neonates at a mean±SD of 15.3±3.9 weeks after booster vaccination. Neonatal titers measured two times higher than maternal titers, with inverse correlation between maternal and neonatal titers at birth and time interval from third vaccination. The two-dose group included 121 women and 107 neonates, with antibody levels measured at a mean±SD of 14.6±2.6 weeks after the second dose. Median [interquartile range] maternal antibody titers were higher in the booster group (4,485 [2,569-9,702] AU/mL) compared with the two-dose group (1,122 [735-1,872] AU/mL) (P<.001). Furthermore, neonatal antibody titers were higher in the booster group (8,773 [5,143-18,830] AU/mL) compared with the two-dose group (3,280 [2,087-5,754] AU/mL) (P<.001). CONCLUSION: Maternal and neonatal SARS-CoV-2 IgG antibody titers after second-trimester maternal Pfizer COVID-19 vaccination were significantly higher after the booster dose compared with the two-dose vaccination series. Although there is uncertainty as to whether antibody levels correlate with protection, these data support the importance of booster vaccination during pregnancy to restore maternal and neonatal protection against COVID-19.

Placental pathology in a pregnant woman with severe COVID-19 and successful ECMO treatment: a case report.

BACKGROUND: Infection with SARS-CoV-2 during pregnancy can lead to a severe condition in the patient, which is challenging for obstetricians and anaesthesiologists. Upon severe COVID-19 and a lack of improvement after multidrug therapy and mechanical ventilation, extracorporeal membrane oxygenation (ECMO) is introduced as the last option. Such treatment is critical in women with very preterm pregnancy when each additional day of the intrauterine stay is vital for the survival of the newborn. CASE PRESENTATION: We report a case of a 38-year-old woman at 27 weeks of gestation treated with multidrug therapy and ECMO. The woman was admitted to the intensive care unit (ICU) with increasing fever, cough and dyspnoea. The course of the pregnancy was uncomplicated. She was otherwise healthy. At admission, she presented with severe dyspnoea, with oxygen saturation (SpO2) of 95% on passive oxygenation, heart rate of 145/min, and blood pressure of 145/90. After confirmation of SARS-CoV-2 infection, she received steroids, remdesivir and convalescent plasma therapy. The foetus was in good condition. No signs of an intrauterine infection were visible. Due to tachypnea of 40/min and SpO2 of 90%, the woman was intubated and mechanically ventilated. Due to circulatory failure, the prothrombotic activity of the coagulation system, further saturation worsening, and poor control of sedation, she was qualified for veno-venous ECMO. An elective caesarean section was performed at 29 weeks on ECMO treatment in the ICU. A preterm female newborn was delivered with an Apgar score of 7 and a birth weight of 1440 g. The newborn had no laboratory or clinical evidence of COVID-19. The placenta showed the following pathological changes: large subchorionic haematoma, maternal vascular malperfusion, marginal cord insertion, and chorangioma. CONCLUSIONS: This case presents the successful use of ECMO in a pregnant woman with acute respiratory distress syndrome in the course of severe COVID-19. Further research is required to explain the aetiology of placental disorders (e.g., maternal vascular malperfusion lesions or thrombotic influence of COVID-19). ECMO treatment in pregnant women remains challenging; thus, it should be used with caution. Long-term assessment may help to evaluate the safety of the ECMO procedure in pregnant women.

Antenatal screening of depressive and manic symptoms in south Brazilian childbearing women: A transversal study in advance of the pandemic scenario.

BACKGROUND: The diagnosis of mood disorders (MD) during pregnancy is challenging and may bring negative consequences to the maternal-fetal binomial. The long waitlist for specialized psychiatric evaluation in Brazil contributes to the treatment omission. Almost 20.0% of women treated with antidepressants have a positive screening for bipolar disorder. Therefore, it has been recommended the investigation of depressive and bipolar disorder during prenatal care. Unfortunately, the screening for mood disorders is not a reality in Brazil and many childbearing women remain undiagnosed. The objective of this study is to observe the frequency of MD and the effectiveness of screening scales for routine use by health professionals during prenatal care in high-risk pregnancies. METHODOLOGY/PRINCIPAL FINDINGS: This cross-sectional study included 61 childbearing women in their second trimester who were interviewed using the Edinburgh Postnatal Depression Scale (EPDS) and the Mood Disorder Questionnaire (MDQ). The cut-off point was EPDS ≥ 13 and MDQ ≥ 7 and the SCID-5 was the gold standard diagnosis. MD were diagnosed in 24.6% of the high-risk pregnancies. EDPS was positive in 19.7% and the frequency of major depression was 8.2%. 16.4% of the childbearing women were diagnosed with bipolar disorder, while MDQ was positive in 36.1%. 11.5% of the women had EPDS and MDQ positive. EPDS sensitivity was 80.0% and specificity 92.1%, whereas MDQ presented a sensitivity of 70.0% and specificity of 70.6%. CONCLUSION/SIGNIFICANCE: There is a high prevalence of MD in high-risk pregnancies. The routine use of EPDS simultaneously to MDQ during antenatal care is effective and plays an important role in early diagnosis, counselling, and promotion of perinatal mental health.

Bizarre Chorionic-type Trophoblast in Second-trimester and Third-trimester Placentas: Clinicopathologic Characterization of a Placental Pseudoneoplastic Lesion.

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.

Evidence of vertical transmission of SARS-CoV-2 and interstitial pneumonia in second-trimester twin stillbirth in asymptomatic woman. Case report and review of the literature.

Data on the vertical transmission rate of COVID-19 in pregnancy are limited, although data reporting mother-fetal transmission in the second trimester of pregnancy are controversial. We described a case of second-trimester twin stillbirth in a woman with SARS-CoV-2 infection in which placental and fetal markers of infection were detected, despite the absence of respiratory syndrome. The patient developed clinical chorioamnionitis and spontaneously delivered 2 stillborn infants. Placental histology and immunohistochemistry demonstrated SARS-CoV-2 infection mostly within the syncytiotrophoblast, and fetal autopsy showed the development of interstitial pneumonia. Our findings demonstrated that in utero vertical transmission is possible in asymptomatic pregnant women with SARS-CoV-2 infection and that infection can lead to severe morbidity in the second trimester of pregnancy.

Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy.

IMPORTANCE: BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in the third trimester was found to be associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn. OBJECTIVE: To evaluate maternal and neonatal SARS-CoV-2 immunoglobulin G (IgG) antibody levels at birth after mRNA COVID-19 vaccination during the second trimester of pregnancy. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted at a single medical center in Haifa, Israel, from May to July 2021, included women with a singleton pregnancy over 24 weeks of gestation at least 7 days after receipt of their second COVID-19 vaccine dose who were not known to be previously infected with COVID-19. EXPOSURES: BNT162b2 (Pfizer/BioNTech) vaccination. MAIN OUTCOMES AND MEASURES: The primary outcomes were SARS-CoV-2 IgG antibody titers measured in the parturient at admission and in the umbilical cord blood within 30 minutes after delivery. Secondary outcomes were the correlation between antibody titers, feto-maternal characteristics, maternal adverse effects after vaccination, and time interval from vaccination to delivery. RESULTS: Antibody levels were measured for 129 women (mean [SD] age, 31.9 [4.9] years) and 114 neonates, with 100% of the tests having positive results. The mean (SD) gestational age at administration of the second vaccine dose was 24.9 (3.3) weeks. Neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1-17 643.5] AU/mL vs 1185.2 [146.6-32 415.1] AU/mL). A positive correlation was demonstrated between maternal and neonatal antibodies (r = 0.92; 95% CI, 0.89-0.94). Multivariable analysis revealed that for each week that passed since receipt of the second vaccine dose, maternal and neonatal antibody levels changed by -10.9% (95% CI, -17.2% to -4.2%; P = .002) and -11.7% (95% CI, -19.0 to -3.8%; P = .005), respectively. For each 1-year increase in the mother's age, maternal and neonatal antibody levels changed by -3.1% (95% CI, -5.3% to -0.9%; P = .007) and -2.7% (95% CI, -5.2% to -0.1%; P = .04), respectively. CONCLUSIONS AND RELEVANCE: In this cohort study, receipt of the BNT162b2 mRNA COVID-19 vaccine during the second trimester of pregnancy was associated with maternal and neonatal humoral responses, as reflected in maternal and neonatal SARS-CoV-2 IgG antibody levels measured after delivery. These findings support COVID-19 vaccination of pregnant individuals during the second trimester to achieve maternal protection and newborn safety during the pandemic.

Disruptions to Abortion Care in Louisiana During Early Months of the COVID-19 Pandemic.

Objectives. To examine changes in abortions in Louisiana before and after the COVID-19 pandemic onset and assess whether variations in abortion service availability during this time might explain observed changes. Methods. We collected monthly service data from abortion clinics in Louisiana and neighboring states among Louisiana residents (January 2018‒May 2020) and assessed changes in abortions following pandemic onset. We conducted mystery client calls to 30 abortion clinics in Louisiana and neighboring states (April‒July 2020) and examined the percentage of open and scheduling clinics and median waits. Results. The number of abortions per month among Louisiana residents in Louisiana clinics decreased 31% (incidence rate ratio = 0.69; 95% confidence interval [CI] = 0.59, 0.79) from before to after pandemic onset, while the odds of having a second-trimester abortion increased (adjusted odds ratio [AOR] = 1.91; 95% CI = 1.10, 3.33). The decrease was not offset by an increase in out-of-state abortions. In Louisiana, only 1 or 2 (of 3) clinics were open (with a median wait > 2 weeks) through early May. Conclusions. The COVID-19 pandemic onset was associated with a significant decrease in the number of abortions and increase in the proportion of abortions provided in the second trimester among Louisiana residents. These changes followed service disruptions.

Mifepristone prior to osmotic dilators for dilation and evacuation cervical preparation: A randomized, double-blind, placebo-controlled pilot study.

OBJECTIVES: To evaluate mifepristone impact on osmotic dilator placement and procedural outcomes when given 18 to 24 hours before dilator placement for dilation and evacuation (D&E) at 18 weeks 0 days to 23 weeks 6 days gestation. STUDY DESIGN: We performed a randomized, double-blind, placebo-controlled trial from April 2019 through February 2021, enrolling participants undergoing osmotic dilator (Dilapan) placement for a planned, next-day D&E. Participants took mifepristone 200 mg or placebo orally 18 to 24 hours before dilator placement. We used a gestational age-based protocol for minimum number of dilators. Our primary outcome was the proportion of participants for whom 2 or more additional dilators could be placed compared to the minimum gestational age-based standard. We secondarily evaluated cervical dilation after dilator removal in the operating room, subjective procedure ease, and complication rates (cervical laceration, uterine perforation, blood transfusion, infection, hospitalization, or extramural delivery). RESULTS: Of the planned 66 participants, we enrolled 44 (stopped due to coronavirus disease 2019-related obstacles), and 41 (19 mifepristone; 22 placebo) completed the study. We placed 2 or more additional dilators compared to standard in 7 (36.8%) and 3 (13.6%) participants after mifepristone and placebo, respectively (p = 0.14). We measured greater median initial cervical dilation in the mifepristone (3.2 cm[2.6-3.6]) compared to placebo (2.6 cm[2.2-3.0]) group, p = 0.03. Surgeon's perception of procedure being "easy" (8/19[42.1] vs 9/22[40.9], respectively, p = 1.00) and complication rate (3/19[15.8%] vs 3/22[13.6], respectively, p = 1.00) did not differ. CONCLUSION: Our underpowered study did not demonstrate a difference in cervical dilator placement, but mifepristone 18 to 24 hours prior to dilators increases cervical dilation without increasing complications. IMPLICATIONS: Mifepristone 18 to 24 hours prior to cervical dilator placement may be a useful adjunct to cervical dilators based on increased cervical dilation at time of procedure; however, logistical barriers, such as an additional visit, may preclude routine adoption without definite clinical benefit.

Current Data on COVID-19 mRNA-Vaccine Safety during Pregnancy Might Be Subject to Selection Bias. Reply to Stroobandt, S.; Stroobandt, R. Data of the COVID-19 mRNA-Vaccine V-Safe Surveillance System and Pregnancy Registry Reveals Poor Embryonic and Second Trimester Fetal Survival Rate. Comment on "Stuckelberger et al. SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland. Viruses 2021, 13, 1199".

We would like to thank Stroobandt, S. and Stroobandt, R. for showing interest in our paper [...].

Data of the COVID-19 mRNA-Vaccine V-Safe Surveillance System and Pregnancy Registry Reveals Poor Embryonic and Second Trimester Fetal Survival Rate. Comment on Stuckelberger et al. SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland. Viruses 2021, 13, 1199.

Dr. Sarah Stuckelberger and her colleagues should be commended for their cross-sectional study assessing the willingness of Swiss pregnant and breastfeeding women to be vaccinated against SARS-CoV-2 [...].

The Potential Role of Chemerin, Lipocalin 2, and Apelin in the Diagnosis and Pathophysiology of Gestational Diabetes Mellitus.

The exact role of adipokines in the pathogenesis of gestational diabetes mellitus (GDM) still remains not fully clear, and multiple studies have analyzed their potential contribution to the pathophysiology of this pregnancy complication. This study is aimed at evaluating serum chemerin, lipocalin 2, and apelin concentrations in GDM and healthy pregnant patients, assessing the correlation between these adipokines, and suggesting the potential role of these cytokines in the diagnosis and pathophysiology of GDM. The study comprised 237 pregnant women: 153 with GDM and 84 with physiological pregnancy. Serum concentrations of chemerin, lipocalin 2, and apelin were obtained at 24-29 weeks of gestation. The mean concentrations of chemerin and lipocalin 2 were significantly higher in the GDM group. The concentration of apelin was slightly higher in the GDM group, but not statistically significant. The strong positive correlation between chemerin and lipocalin 2 concentrations was noticed in both groups. Our data suggest that maternal chemerin and lipocalin 2 may play a significant role in the pathophysiology of GDM. We imply that these adipokines could potentially be established as novel biomarkers for the early identification of GDM. However, more studies are needed to analyze the effect of these adipokines on glucose metabolism during early pregnancy.