Outcomes of symptomatic gallstone disease in pregnant women: A retrospective study

Gallstone disease with advanced symptoms is one of the common abdominal emergencies during pregnancy and it is considered to be one of the most frequently reported non-obstetric surgical conditions in pregnant women. This study aimed to evaluate the outcomes of surgical cholecystectomy in pregnant women with symptoms of advanced gallstones. This is a retrospective analysis of 2814 pregnant women who attended various wards in government and private hospitals in the governorates of Diyala and Kirkuk in Iraq for more than 2 years, between February 2020 and June 2022. The hospital database was used to confirm the diagnosis of advanced gallstone symptoms in these pregnant women. The incidence of symptomatic gallstones in pregnant women, diagnosis and method of therapeutic management, cholecystectomy according to the pregnancy periods, and perinatal complications of patients according to therapeutic methods were determined. The results confirmed that out of 2814 pregnancies, only 126 (4%) had symptoms of gallstones. It was found that the majority of cases 67 (53%) were within the first trimester of pregnancy and the least 29 (23%) was observed in the second trimester. Acute cholecystitis was the generality 84 (67%) diagnosed in pregnant women with symptomatic gallbladder disease and only 9 (7%) of the patients had undergone prenatal cholecystectomy versus 117 (93%) who were managed conservatively. A total of 20 (16%) cases with undesirable complications were recorded, where 12 cases with low birth weight were noted, where 4 of them underwent surgery and 8 were treated conservatively. It was concluded that a large proportion of women suffer from symptoms of gallstones during pregnancy. Most cases can be managed conservatively, and intervention should be performed as often as needed.Copyright © 2023, Codon Publications. All rights reserved.

Detection of SARS-CoV-2 Antibodies in Matched Pregnant Women and Newborn Blood

Objective: The factors affecting the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies from mother to newborn and the duration of seropositivity rates in these infants have not yet been clearly demonstrated. The objectives of this study were (1) to assess the levels of SARS-CoV-2 spike-specific immunoglobulin G (IgG) in women infected in the pregnancy period and newborns born to these women and (2) to search the transplacental transfer ratio of spike-specific IgG. Method(s): Seventy pregnant women with symptomatic SARS-CoV-2 infection and their newborns were prospectively followed. Anti-SARS-CoV-2 immunoassay was used for the detection of the in vitro quantitative determination of total antibodies to the SARS-CoV-2 spike protein. Discussion(s): Spike-specific IgG was demonstrated in 89.1% (44 of 46) of pregnant women infected more than 14 days before delivery and in 92.6% (43 of 44) of their newborns. Median transfer ratio of spike-specific Ig was 0.87 (interquartile range [IQR], 0.34-0.90), 1.0 (IQR, 0.9-0.29), and 0.81 (IQR, 0.02-1.0) in first trimester (n = 4), second trimester (n = 14), and third trimester (n = 28) pregnant women, respectively. Antibody transfer ratio was correlated with time elapsed from infection (p < 0.001). Peak antibody transfer ratio above 1 was observed at a median 60 to 120 days after the infection from delivery. Antibody transfer ratio was high in pregnant women infected more than 60 days before delivery (p < 0.001). Transfer ratio was significantly higher in the severe-critically symptomatic women (n = 15) than the mild-moderately symptomatic women (n = 55) (p = 0.001). At 3 months, 18 of 25 infants (72%) had spike-specific IgG. Conclusion(s): Timing from infection to delivery and severity of maternal infection are critical in assessing the antibody generation and transport. Higher antibody transfer ratio can be detected in neonates when SARS-CoV-2 infection is present for more than 60 days before birth. Maternally derived antibody can persist for 3 months after birth.Copyright © 2023. The Author(s).

Transplacental transfer of SARS-CoV-2 variant antibodies following COVID-19 vaccination during pregnancy

Problem: Despite being over 3 years into the pandemic, infants remain highly undervaccinated and at a high risk for hospitalization due to COVID-19. Further investigation as to how maternal health decisions for immunization can reduce morbidity from infant COVID-19 by providing passive immunity is necessary. The objective of this study was to describe the rates of SARS-CoV-2 variant antibody transfer from mother to infant cord blood by trimester ofmaternal vaccination. Methods of study: This is an observational cohort study including mother-infant dyads receiving primary or subsequent booster COVID- 19 vaccines during pregnancy.Unvaccinated, but SARS-CoV-2 infected dyads with were included as a comparison group. We quantified median titer and interquartile range (IQR) for SARS-CoV-2 receptor binding domain (RBD) IgG in infant cord blood samples at delivery using the mesoscale discovery platform (electrochemiluminescence). Primary outcome was infant cord IgG titer by trimester of vaccination for the WA1/2022 RBD IgG and current circulating, immune evasive XBB RBD IgG. Secondary outcome is the percent detectable IgG for each variant. Sensitivity analysis was performed based on known SARS-CoV-2 infection. Result(s): Eighty-three mother-infant dyads were included in this analysis. Seven were vaccinated in the first trimester, 37 in the second trimester, 33 in the third trimester, and 6 were unvaccinated and infected. Twenty-three (30%) of the vaccinated group had known SARS-CoV-2 infection. Most received monovalent mRNA COVID-19 vaccines during pregnancy, aside from two who received the viralvectored Ad26.COV2.S, and two received the bivalent mRNA vaccine during pregnancy. The median cord blood WA1/2020 RBD IgG titer was 5370 (412-7296) for first, 1225 (589-3289) for second, 2623 (664-5809) for third trimester in individuals who received aCOVID-19 vaccine dose during pregnancy, and 45 (10-187) in those unvaccinated and infected. After excluding thosewith infection, the cord blood IgG was 514 (106-4182), 1070 (518-2317), and 2477 (664-4470) for first, second, and third trimester, respectively. The rate of detectable WA1/2020 RBD IgG was 100% for all three trimesters, even when excluding infected individuals. For theXBBvariant, cord bloodRBDIgG titer was 284 (43-1296) for first, 66 (32-227) for second, 173 (45-389) for third trimester, and 10 (10-11) in the unvaccinated/infected group. Excluding infections, the cord blood XBB RBD IgG was 54 (10-128), 44 (25-181), and 152 (45-360) for first, second, and third trimester vaccination, respectively. The rate of detectable XBB IgG in those who received a vaccine during pregnancy were 83%, 91%, and 90% for first, second, and third trimester respectively, compared to 17% in the unvaccinated/infected group. Excluding infections, the rate of XBB RBD IgG detection was 66%, 89%, and 95% for first, second, and third trimester vaccination, respectively. Conclusion(s): Vaccination during pregnancy leads to high rates of detectable cord blood IgG specific to SARS-CoV-2 WA1/2020 variant and current circulating variants (XBB), regardless of trimester of vaccination. Infection history leads to higher cord blood IgG in vaccinated;however, infection alone without vaccination leads to lower titer and greater rates of undetectable cord IgG at delivery.

Paxlovid Prophylaxis or Treatment in Pregnancy: Data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry

Background: The US Food and Drug Administration under an Emergency Use Authorization approved use of Paxlovid (nirmatrelavir and ritonavir) for the treatment of mild-to-moderate COVID-19 in adults and children with a positive test for SARS-Co-2 and who are at high risk for progression to severe COVID-19. Pregnant women are at increased risk of severe complications resulting from COVID-19 infection;however, minimal data on the safety of Paxlovid in human pregnancy are available. Objective(s): The objectives of this study are to assess risks of major congenital malformations, spontaneous abortion, elective termination, stillbirth, preterm delivery, small for gestational age infants at birth, or infants who were small for age at one year in pregnancies/infants prenatally exposed to Paxlovid in pregnancy compared to individuals who did not receive this treatment. Design(s): This study involves prospective data from the Organization of Teratology Information Specialists (OTIS) Pregnancy Registry which enrolls pregnant women residing in the US or Canada and captures data through maternal interviews and ion of medical records. Result(s): Among pregnant women participating in the OTIS Pregnancy Registry as of February 1, 2023, 59 reported exposure to Paxlovid in pregnancy;25.4% exposed within 30 days prior to the last menstrual period and through the first trimester, 42.4% exposed in second trimester, and 32.2% exposed in the third trimester. As of January 2023, 17 of those enrolled have completed pregnancy outcomes. One was lost to follow-up. Of the remainder, there were no adverse pregnancy outcomes reported. Conclusion(s): Very limited data are available on this potentially beneficial treatment in pregnancy. To date, no serious signals for this exposure have been detected.

Disruptions in Prenatal Care Visits during the Pandemic: A Population-Based Cohort Study in Manitoba, Canada

Background: Limited evidence exists on the pandemic's role in limiting access and use of prenatal care services and the quality of care for pregnant women. We aimed to investigate the impact of the pandemic restrictions on in-person prenatal care visits (PNCV) and the quality of prenatal care. Method(s): Using the mother-infant-linked administrative health databases in Manitoba, Canada, we conducted a province-wide population-based cohort study among independent pregnancies. We examined the quarterly rates of PNCV before (October 2016-March 2020) and during (April 2020-March 2021) the pandemic. Quality of prenatal care was categorized using the Revised Graduated Prenatal Care Utilization Index (R-GINDEX) into inadequate (<50% visits), intermediate (50%-80% visits), adequate (>80% visits), intensive (high-risk), and no care. Interrupted time series analyses were conducted to assess the immediate and lagged changes in PNCV and quality of care after the implementation of pandemic restrictions. Result(s): Amongst 70,931 pregnancies, we observed no significant mean difference in the overall numbers of PNCV during the pandemic compared to prepandemic (8.2 vs. 8.6,p=0.0837). Prenatal care utilization was 3.4% inadequate and 34.7% adequate before the pandemic and 4.8% and 26.6% during the pandemic, respectively. Restrictions were associated with an abrupt decline in adequate and intermediate care during the first trimester by 11.3% (p<0.001) and 11.98%, respectively, followed by non-significant change throughout the pandemic (beta3=-0.25,p=0.694 and beta3=-0.96,p=0.192, respectively). Moreover, restrictions were associated with an increased rate of inadequate care during the first (beta2=1.52,p=0.007) and second trimesters (beta2=0.78,p=0.208), and not among third trimesters (beta2=-0.44,p=0.094). During the pandemic, we found no significant differences in the rates of intensive prenatal care during the first (p=0.478), second (p=0.614), and third (p=0.608) trimesters compared to pre-pandemic. Conclusion(s): Our findings suggest a decline in adequacy levels of prenatal care services after COVID-19 restrictions were enacted, with a higher impact on pregnancies during their first and second trimesters. Although the overall adequacy of care decreased, there were no changes to the rates of intensive visits. This study will further investigate the impact of the pandemic on virtual PNCV and assess the association between the quality of prenatal care and adverse maternal and neonatal outcomes.

Presence of SARS-CoV-2 neutralizing and vaccine spike antibodies in amniotic fluid during the second trimester of pregnancy, detected by amniocentesis (Winner of the SIMP Award, in memory of Professor Giorgio Pardi)

Objective. Thanks to the SARS-CoV-2 vaccination, pregnant women are protected from the complications of COVID-19 infection, but the benefits of this vaccination in preventing morbidity and mortality in the fetus are not yet clear: it is not well understood if and how these antibodies cross the placenta. Indeed antibodies made after a pregnant person has received an mRNA COVID-19 vaccine have been found in amniotic fluid and umbilical cord blood at term and represent a safer method of enhancing neonatal antibody levels than administration of immunoglobulin preparation to the infant. The aim of the study is to test the presence of neutralizing SARS-CoV-2 antibodies and spike antibodies in the amniotic fluid in the second trimester of pregnancy, and then to compare the antibodies level in maternal serum and amniotic fluid to evaluate their correlation. Materials and Methods. This cohort study took place at the Department of Obstetrics and Gynecology of Messina at the AOU Policlinico G. Martino from September 2021 to February 2022;the study consisted of 22 pregnant women who had amniocentesis in the gestational period between 15 weeks plus 6 days and 18 weeks: we analyzed serum and amniotic fluid samples of women who contracted the SARS-CoV-2 infection, or who were vaccinated against the same virus, within one year, or never infected by SARS-CoV-2 or vaccinated against it. During the amniocentesis, all patients underwent a single sample of maternal serum and of amniotic fluid to evaluate SARS-CoV-2 neutralizing antibody and S1 receptor binding domain IgG antibody levels. Inclusion criteria were pregnant women with the need to undergo amniocentesis. Results. 22 pregnant women were enrolled in the study:10 of them were vaccinated with a mRNA COVID-19 vaccine;12 women were not vaccinated, 4 of them had developed COVID-19 infection within one year before the collection and 2 of them developed the infection during pregnancy;the other 6 never developed the infection and have not been vaccinated, enrolled as comparators. Mann-Whitney test showed that vaccinated patients had significantly higher S1 receptor binding domain antibody levels both in amniotic fluid (p < 0.006) and maternal blood (p < 0.005) than not vaccinated women;also SARS-CoV-2 neutralizing antibody levels were higher in pregnant women who developed COVID-19 infection both in amniotic fluid (p < 0.007) and maternal blood (p < 0.004) than not vaccinated women. There was a significantly high correlation between the concentrations of spikes antibody levels in vaccinated pregnant women's serum and amniotic fluid (p = 0.000), and of neutralizing antibody levels in serum and amniotic fluid of women who developed COVID-19 infection (p = 0.000). Conclusions. To the best of our knowledge, the analysis of amniotic fluid and serum showed for the first time that all the vaccinated pregnant women samples had SARS-CoV-2 spikes immunoglobulins both in maternal blood and amniotic fluid. There is a very high correlation between maternal blood and amniotic fluid S1 receptor binding domain antibody levels in vaccinated women: this demonstrates that there is an early transplacental antibody transfer. Also neutralizing antibodies were found in the amniotic fluid of infected pregnant women, with high correlation between concentrations.

First Presentation of ANCA Positive Vasculitis in Pregnancy

Background: Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis presenting for the first time in pregnancy is very rare, but awareness is important as it can cause significant maternal and fetal morbidity and is potentially life-threatening if not recognised or under-treated. Method and Results:We describe a 19-year-old woman who developed ANCA-associated vasculitis in the second trimester of her first pregnancy. She initially presented with a petechial rash and cough at 25 weeks' gestation, and then developed breathlessness. Significant pulmonary haemorrhage was shown on Cross Sectional imaging of the chest, with a corresponding reduction in haemoglobin. She rapidly improved with prednisolone, cyclophosphamide and plasma exchange. SARS-CoV-2 infection identified on routine screening further complicated the management. At 34 weeks' gestation she experienced a flare, with the possibility of superimposed pre-eclampsia (increase in liver enzymes, creatinine and sFlt/PlGF ratio). After multidisciplinary team discussion she underwent a caesarean section. Postnatally she continued cyclophosphamide and started azathioprine. Conclusion(s): ANCA-associated vasculitis can result in life-threatening complications. The initial features can be non-specific, so a high index of suspicion is required, particularly in women with multisystem abnormalities. Close monitoring for potential complications is advised as urgent imaging may be needed. Aggressive immunosuppressive treatment is recommended as steroids alone are usually insufficient. Cyclophosphamide can be used in later pregnancy and can result in a dramatic improvement, as was seen here. If delivery needs to be expedited, mode of birth (i.e. caesarean delivery vs vaginal birth) is dictated by the obstetric picture, with caesarean delivery being indicated for the usual obstetric reasons.

Mother's Pregnancy Trimester Does Not Affect the Differences of IgG SARS-COV-2 Antibody Levels in Pregnant Women after mRNA and Inactivated Coronavirus Disease 2019 Vaccination

BACKGROUND: Since pregnancy increases the risk of coronavirus disease 2019 (COVID-19) and its morbidity in pregnant women, it is necessary and recommended to prevent COVID-19 in pregnant women by vaccination such as by messenger RNA (mRNA) and inactivated vaccines. SARS-CoV-2 antibodies produced from vaccination have different results according to the type of vaccine given. The previous studies showed that IgG SARS-CoV-2 antibody levels were influenced by various factors such as gestational weeks at the time when vaccines were given. Moreover, there have been no previous studies on the effect of gestational age on quantitative IgG levels after the second dose of the vaccine especially in Indonesia during this pandemic due to some restrictions on daily activities. AIM: The aim of this study is to see the effect of giving the COVID-19 vaccine based on maternal gestational age (in trimester units) on maternal immunity (IgG SARS-CoV-2) in Dr. Hasan Sadikin General Hospital Bandung, Bandung Kiwari Hospital and Dr. Slamet Hospital, Garut. METHOD(S): This was a retrospective and cohort study by taking secondary data using consecutive sampling from the previous tests on the levels of SARS-CoV-2 IgG antibodies after two doses of inactivated vaccine and mRNA. Healthy pregnant women 14-34 weeks at the Department of Obstetrics and Gynecology, Dr. Hasan Sadikin (RSHS) Bandung, Bandung Kiwari Hospital, and Dr. Slamet Hospital for the period October 2021 to January 2022 were the target population of this study. Based on inclusion and exclusion criteria, 103 samples met the criteria. Examination of Maternal SARS-CoV-2 IgG Antibody Levels procedures was carried out using Chemiluminescent Microparticle Immunoassay. Statistical analysis was done using IBM SPSS 28.00 and p < 0.05 was considered statistically significant. RESULT(S): There was no significant difference (p = 0.236, p > 0.05) between the mean maternal age in the mRNA and inactivated vaccine groups. The mRNA and inactivated vaccine groups also had no significant difference in the gestational age category (0.70). There was a significant difference (p = 0.0001) between the levels of SARS-CoV-2 IgG antibodies after the vaccine in the mRNA and inactivated vaccine groups. There was no significant difference in the levels of SARS-CoV-2 IgG antibodies in the gestational age group after the mRNA vaccine (p = 0.426) and after the inactivated vaccine (p = 0.293). There was a significant difference (p < 0.05) in the subgroup analysis in each gestational age group (second trimester and third trimester) between SARS-CoV-2 IgG antibody levels after the mRNA vaccine compared to inactivated vaccine. DISCUSSIONS: The mRNA vaccine is based on the principle that mRNA is an intermediate messenger to be translated to an antigen after delivery to the host cell via various routes. However, inactivated vaccines contain viruses whose genetic material has been destroyed by heat, chemicals, or radiation, so they cannot infect cells and replicate but can still trigger an immune response. The administration of the vaccine in the second and third trimesters of pregnancy has the same results in increasing levels of SARS-CoV-2 IgG antibodies after mRNA and inactivated vaccination in this study. CONCLUSION(S): mRNA vaccination in pregnant women is better than inactivated vaccines based on the levels of IgG SARS-CoV-2 antibodies after vaccination. The maternal trimester of pregnancy was not a factor influencing the levels of SARS-CoV-2 IgG antibodies after either mRNA or inactivated COVID-19 vaccinations in this study.Copyright © 2023 Anita Deborah Anwar, Putri Nadhira Adinda Adriansyah, Ivan Christian Channel, Annisa Dewi Nugrahani, Febriani Febriani, Asep Surachman, Dhanny Primantara Johari Santoso, Akhmad Yogi Pramatirta, Budi Handono.

Third level care experience during SARS-CoV-2 pandemic

Objective. As the SARS-CoV-2 Pandemic has widely changed pregnancy experience and assessment, the inpatient and outpatient services have had to be re-organized. Since March 2020, Careggi University Hospital (CUH) has provided a dedicated COVID-pathway: spaces for women with unknown swab status and a COVID-19 ward delivery room. The aim of this study is to analyze the inpatient and outpatient COVID-19 related activities in CUH. Materials and Methods. We prospectively collected data from consecutive COVID-19 pregnancies referred from 2020 to 2022, included in the local branch of the ItOSS surveillance. All patients experienced COVID-19 in pregnancy at various stages of severity and gestational ages. Results. From March 2020 to June 2022, 165 COVID-19 deliveries occurred (169 newborns), while 16 pregnant positive women were admitted without delivering. A single emergency C-section (CS) was performed because of Sars-CoV-2 related ARDS, 15 women experienced serious maternal morbidity and 5 needed ECMO. A single maternal death occurred four months after delivery (C-section). Considering ECMO supported cases during pregnancy or postpartum, the first one tested positive for COVID-19 during the second trimester. She developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a CS at term was performed following obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation and experienced a precipitous vaginal delivery at 31 weeks+6 days of gestation while on ECMO. She was discharged 1 month later in good general conditions. The third patient was an obese (BMI 38) 43-year-old woman who had performed an IVF with embryo donation;she tested positive at 38 weeks+2 days of gestation. A CS was performed because of the worsening of her condition. After the delivery she was admitted in ICU and she underwent ECMO. She died 143 days after the CS by sepsis and multiple organ failure (MOF). For all these pregnancies neonatal outcomes were positive. No perinatal death occurred and only one baby tested positive for SARS-CoV-2 infection at nasal swab sampling (case 3). The anesthesiology team performed neuroassial analgesia intrapartum in all the positive women who needed/requested it. Monoclonal Antibodies (mAbs) have been widely used to treat mild to moderate COVID-19 outpatients (NIH and RCOG recommendations) at risk for developing severe disease. Regarding this specifical therapy, an essential role in the management of the pregnant outpatient was played by the Infectious Disease Department. All patients above 28 weeks requiring hospitalization received LMWH prophylaxis, which was administrated under 28 weeks only in presence of additional risk factors (obesity, IVF, etc.). All new mothers received a ten days LMWH prophylaxis. On the outpatient side, we performed 22 teleconsultations, 43 obstetric ultrasounds (including I trimester screening), 90 obstetric checks with clinical evaluation and home therapy management, 32 fetal monitoring and 47 naso-pharingeal swabs. Conclusions. At Careggi Hospital Maternal Department an extensive re-organization of inpatient and outpatient services has been performed in order to guarantee good practice and management of all pregnant women during the SARS-CoV-2 pandemic. This was only possible thanks to a wide multidisciplinary group which enhanced every professional.

COVID-19 in pregnant patients with ankylosing spondylitis

Objective: To describe the course of COVID-19 in women with AS during pregnancy and the effect of COVID-19 on AS activity. Material and Methods: 75 pregnant women with confirmed AS (modified New York criteria, 1984) were included for prospective observation. 26 of them were followed during the Covid-19 pandemic (03.2020 -04.2022). The average age of the patients was 33.0 ± 3.9 years, the duration of the disease was 117.0 ± 72 months. The activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in the 1st, 2nd and 3rd trimesters of pregnancy was 2.0 ± 1.4;2.0 ± 1.4 and 1.9 ± 1.5, respectively. The Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) was 1.5 [1.3;2.1];1.8 [1.3;2.5] and 1.7 [1.1;2.0], respectively. The delivery period was 38.7 ± 1.6 weeks. Results: COVID-19 was transferred to 4 pregnant women, 3 of them -at the end of the 1st -beginning of the 2nd trimester, one -at 38 weeks of pregnancy. No women have been vaccinated against COVID-19. In 3 cases, the activity of AS was low, in one -high due to axial manifestations and arthritis. In 3 women, the course of COVID-19 was mild, in one -moderate (febrile temperature for more than 3 days);only 1 woman had a dry cough. One pregnant woman canceled AS therapy (certolizumab pegol, CZP), against which the back pain of the inflammatory rhythm increased. In other cases, AS therapy was not canceled, there was no effect of COVID-19 on AS activity. (Table Presented) Conclusion: According to preliminary data, COVID-19 in pregnant women with AS can be characterized by a mild and moderate course. There was no increase in AS activity during ongoing AS therapy.

Large Ovarian Dermoid, a Cause for Fetal Growth Restriction and Oligohydramnios: Rare Instance in Literature

Ovarian dermoids mostly remain asymptomatic during pregnancy. Large dermoids may present with torsion, hemorrhage, or rupture. However, a dermoid cyst causing fetal growth restriction (FGR) and oligohydramnios is a very rare entity. The authors report a case of a large ovarian dermoid (15 x 12 cm) hampering intrauterine fetal growth. Due to the coronavirus disease-2019 (COVID-19) lockdown, the patient was unable to get ultrasound examinations in early gestation, and thereby, surgical intervention was not possible during the second trimester. As a result, this growing teratoma finally led to FGR by either exerting a pressure effect upon the uterus or by dwindling its blood supply. Copyright © The Author(s). 2022.

Nine Maternal Mortalities in 2 Weeks of Second COVID-19 Surge in Indonesia: A Case Series from One Large Tertiary Center

BACKGROUND: The fluctuating COVID-19 cases among the pregnant women’s population encountered increased of cases and maternal mortality. AIM: This research aimed to describe the case of maternal deaths caused by COVID-19. CASE REPORT: We present nine serial cases of maternal death caused by COVID-19 who were admitted to Dr. Soetomo General Academic Hospital for 14 days in June. We found 32 positive COVID-19 obstetric cases and reported nine maternal deaths with a fatality rate of up to 28%. Seven of nine patients had reverse transcription-polymerase chain reaction–confirmed SARS-CoV-2 infection, while two had a positive antigen swab. Half of the patients ≥35 years old, and five of nine patients had Class I obesity as preexisting comorbidity. This study reported the death of pregnant woman at their 2nd trimester and 3rd trimester presenting infected by severe COVID-19. The usual symptoms are dyspnea, cough, fever, and decreased consciousness. The result of chest X-ray examination among eight patients showed bilateral pneumonia. Most of cases were referrals from a secondary hospital due to overload hospital capacity. Three patients were directly transferred to the tertiary hospital without receiving initial treatment. Eight of 9 patients (88.9%) were transferred to intensive care unit and intubated due to low oxygen saturation. CONCLUSION: In conclusion, the limited hospital facility and lack of intensive care capacity for obstetric cases during the second wave of the COVID-19 pandemic may enhance the probability of mortality and morbidity in pregnant women infected by COVID-19.

Prenatal COVID-19 Infection Does Not Increase the Risk of Congenital Hearing Loss

Introduction: The global pandemic caused by the novel coronavirus (SARS-CoV-2), commonly known as COVID-19, has had profound effects at every level of society. Other known viral illnesses during pregnancy, such as cytomegalovirus, can affect the developing fetus and cause congenital hearing loss. The long-term effects of COVID-19, including the risk of congenital hearing loss, are not currently established. Method(s): A retrospective cohort study was performed at a quaternary care facility. Sixty-four consecutive patients with a COVID-19 infection during pregnancy were identified. Charts were reviewed for trimester of positive COVID-19 test, maternal and neonatal comorbidities, symptomatology, vaccination status, and results of newborn screening and follow-up hearing testing, if performed. Result(s): Sixty-four women with positive COVID-19 test during pregnancy (6 in second trimester, 59 in third trimester) were identified. Most (n=54, 84.4%) patients were asymptomatic at time of positive test and 29.7% (n=19) had received at least 1 dose of a COVID-19 vaccine. Newborn hearing screening was performed in 58 patients (90.6%). Failed initial screening occurred in 3 (5.2%) right ears and 4 (7.0%) left ears. Two patients passed on repeat screening, and the remaining 1 patient was found to have a mild conductive hearing loss in the right and middle ear dysfunction on the left. Conclusion(s): This study demonstrates no significant increased risk of congenital hearing loss in prenatal COVID-19 infection. Additional investigation into timing of infection and effect of vaccination status will be performed to provide guidance to women navigating pregnancy during the pandemic.

The prevalence of COVID vaccine acceptance among pregnant women: A systematic review and meta-analysis

COVID pandemic has massively hit every nook of the world. Millions of people were infected and lost their lives to the deadly pandemic. This novel virus destroyed the essential healthcare service globally. Mass vaccination is the only option to halt the virus transmission. This study aimed to estimate the acceptance of the COVID vaccine among pregnant women and breastfeeding mothers. Method: We followed Cochrane collaboration guidelines and the PRISMA reporting system. Studies were identified through a systematic search of indexed articles in Medline (PubMed), Clinical key, Google Scholar, Cochrane Library, and CINAHL databases until March 10, 2022, 26,995 articles were identified in the initial search and 24 articles were included in the review. Result: Twenty four studies comprise 22,947 pregnant and 11,022 breastfeeding women. About 54% of pregnant women and 59% of breastfeeding mothers intended to take the COVID vaccination. Among the pregnant mothers, 21% with comorbidities, 14% in the first trimester, 34% in the second trimester, and 51% in the third trimester were willing to take the COVID vaccine. Risks of infections and comorbidities were the reasons for acceptance of the COVID vaccine in pregnant women. Similarly, adverse effects and safety concerns were top indicators for the rejection of the COVID vaccine. Conclusion: The acceptance of COVID vaccination among pregnant women and breastfeeding mothers are not satisfactory. Therefore, timely guidance would help to address the negative perceptions of vaccines among pregnant women.

IMPACT in PRENATAL EVALUATION of PREGNANT WOMEN with RHEUMATIC DISEASES by the SARS-COV2 PANDEMIC

Background: Due to the SARS-CoV-2 pandemic, an increase in stress, anxiety, and depression has been seen, as well as greater use of substances and a decrease in prenatal care in pregnant women. (1) Women of childbearing age with autoimmune rheumatic diseases (ARDs) experience greater psychological stress, which can negatively influence behavior. (2) Objectives: This study aims to compare changes in prenatal laboratory and ultrasound tests by trimester, as well as the detection of anxiety and depression in pregnant women with ARDs due to the SARS CoV-2 pandemic. Methods: This study was carried out on pregnant patients with ARDs from the Pregnancy and Rheumatic Diseases clinic of the rheumatology department of the University Hospital 'Dr. José Eleuterio González' during the period from February 2018 to August 2021. Two standardized evaluations of anxiety and depression were carried out using the Inventory of Trait and State Anxiety (IDARE) and the Edinburgh Postpartum Depression Scale (EPDS) respectively in the third trimester of pregnancy. Maternal report of alcohol consumption during any trimester of pregnancy, as well as adherence to routine laboratory studies such as structural ultrasound and gesta-tional diabetes screening, was addressed. Positive COVID-19 nasopharynx PCR results were evaluated during pregnancy beginning in the pandemic period (March 2020). The pre-pandemic recruited group was compared with the pandemic group. The comparison of the groups was carried out using the Chi-Square and Fisher tests. A significant value of p < 0.05 was considered. Statistical analysis was performed using the IBM SPSS v.25 program. Results: 50 pregnant patients with ARDs were recruited, of which 24 were included in the pre-pandemic group and 26 in the pandemic group. Compared with the pre-pandemic group, pregnant women recruited during the pandemic had a statistically signifcant higher positivity for state anxiety (p=0.023), likewise trait anxiety, depression, and suicidal ideation were detected more frequently, but the difference was not statistically signifcant, a higher rate of adherence to laboratory and cabinet studies was found, being signifcant for laboratories performed in the 1st and 2nd trimesters (0.005 and 0.025 respectively). See Table 1. Conclusion: A higher frequency of positivity for state anxiety was demonstrated in pregnant women with ARDs recruited during the pandemic, as well as higher trait anxiety, depression, and suicidal ideation, although this increase was not statistically signifcant. On the other hand, concern about the pandemic and health status could positively influence better adherence to screening and routine studies during pregnancy.

The fatal fetal sting of Dengue: experience from a tropical country

Objectives: Dengue is a vector borne infectious disease, endemic in the tropical regions, that may be associated with significant maternal and fetal morbidity and mortality. However, literature is sparse on the rate and factors associated with stillbirths in women suffering from dengue. In this study, we aimed to explore the frequency of stillbirths in dengue infection in pregnancy during the COVID pandemic. We also studied the effect of severity of the disease on fetal morbidity and mortality. Design: Retrospective review of registers and case records Method: We reviewed the data of pregnant women admitted for dengue in the Obstetrics & Gynecology department in a tertiary care hospital of Northern India between September and December, 2021. Data collected included the age, parity, gestation at admission, severity of the maternal disease, other comorbities, maternal outcome, obstetrical outcome during the dengue disease and fetal outcome. Results: Twenty three pregnant women were admitted to the department between September and December 2021. The average age of the women was 26+/-5 years. Half of these women were primigravidas (12 out of 25). Most women were in the third trimester, while one woman each presented in second trimester and the postpartum period. Eleven mothers presented with severe dengue, 11 had dengue with warning signs and only one woman had dengue without warning signs. There were 7 maternal deaths. Three mothers died undelivered. There were 10 stillbirths of 20 deliveries and 22 babies. Majority of the woman delivered preterm. There were 2 twin deliveries. Of the babies who delivered at term, most were liveborn(6 of 7). The stillbirth rate was higher in the severe dengue group, dengue with warning signs and dengue without warning signs were 60%, 36% and nil respectively. Conclusions: The stillbirth rate is high in women with dengue in pregnancy, especially in the third trimester. The chances of stillbirth escalate with the severity of dengue. Maternal mortality is high in women admitted with dengue in pregnancy. Public health strategies to prevent dengue should be strengthened to avoid high stillbirth rates and maternal mortality. The data is limited by the retrospective design and skewed as women with only severe form of dengue would have been admitted.

EFFECT OF THE LOW PREVALENCE FIRST YEAR OF COVID-19 ON WEIGHT CHANGES DURING PREGNANCY IN A MULTIETHNIC AUSTRALIAN POPULATION

Background: Obesity and excessive gestational weight gain are associated with adverse pregnancy outcomes. The impact of the COVID-19 pandemic on weight and weight gain during pregnancy are unknown. Methods: Retrospective cohort study of all singleton pregnancies before (January 2018-January 2020) and during the low prevalence first year of COVID-19 (February 2020-January 2021). Demographic data, booking BMI and rate of weight gain were compared between time periods. Results: 14908 patients (9544 before and 5364 during the COVID-19 first year) met the inclusion criteria. There was a trend towards higher booking BMI (25.5 ± 0.1 kg/m2 during vs 25.3 ± 0.1 kg/m2 before COVID-19, p = 0.08) and higher rate of obesity (17.0% vs 16.5%, p = 0.08) during the COVID-19 first year. Rate of weight gain in pregnancy was greater during COVID-19 (0.539 ± 0.006 kg/week vs 0.505 ± 0.004 kg/week, p < 0.001), driven by the greater difference in rate of 2nd trimester weight gain (0.664 ± 0.010 kg/week during vs 0.571 ± 0.007 kg/week before COVID-19, p < 0.001). After adjusting for maternal age, ethnicity, socioeconomic status and booking BMI, the COVID-19 first year was associated with significantly greater rate of weight gain (β = 0.02, p = 0.001). Rate of weight gain recommended for BMI was achieved in fewer pregnancies during COVID-19 (14.4% vs 16.3%, p = 0.007). Conclusions: The first year of COVID-19 was associated with a greater rate of gestational weight gain and a lower proportion of patients achieving recommended weight gain. This likely reflects the impact of COVID-19 restrictions in the community of Western Sydney and may have contributed to adverse pregnancy outcomes during the low prevalence first year of the COVID-19 pandemic.

LONGITUDINAL SARS-CoV-2 ANTIBODY RESPONSE in PREGNANCY and TRANSPLACENTAL TRANSFER

Background: Longitudinal assessment of SARS-CoV-2 antibody (Ab) response during pregnancy after infection and transplacental transfer may inform durability of maternally derived Ab for mothers and infants. Methods: Between October 2020-September 2021, pregnant people testing SARS-CoV-2 IgG positive by Abbott Architect chemiluminescent immunoassay (CMIA) for anti-nucleocapsid (N) antibody (semi-quantitative index ≥1.4 considered IgG+) during pregnancy or delivery in a seroprevalence study, or identified with RT-PCR+ results via medical records, were invited to enroll in a longitudinal evaluation of maternal Ab responses and transplacental transfer. Maternal blood collected at 1, 2, 3, and 6 months after enrollment and maternal and cord blood collected at delivery were tested with the same assay. Results: Among 40 participants testing IgG+ for anti-N, 31 (78%) had a prior RT-PCR+ result. Median age was 32 years (IQR 29-35);27 (68%) enrolled during pregnancy at median 18 weeks gestation (IQR 13-33), while 13 (33%) enrolled at delivery or early postpartum. Median Abbott index was 3.06 (IQR 1.96-5.74) at first IgG+ result obtained at a median of 9 weeks (IQR 4-16) after RT-PCR+ result, for those with a known RT-PCR. Among 23 participants with ≥2 samples, 50% had IgG results below positivity threshold at median 17 weeks (IQR 12-28) after first IgG+ result (Figure). Seventeen mother-infant pairs had delivery samples collected at median 66 days (IQR 60-71 days) from maternal RT-PCR+ result. Six (35%) maternal samples remained IgG+ (median Abbott index 2.97 [IQR 2.35-7.01]) at delivery (gestational age 30-40 weeks) with all 6 paired cord sera testing IgG+ (median Abbott index 4.30 [IQR 2.93-7.22]). Median placental transfer ratio of maternally derived IgG Abs based on a positive Abbott index was 1.13 (95%CI 0.98-1.30) among mothers with samples remaining IgG+ at delivery. Conclusion: Within 4 months after first IgG+ result primarily in second trimester, about half of pregnant persons had SARS-CoV-2 IgG anti-N Ab levels below the Abbott CMIA positive threshold. Among evaluable mother-infant pairs, two-thirds of mothers no longer tested anti-N IgG+ at delivery. Transplacental transfer of maternal antibodies was confirmed in all infants born to mothers with samples remaining IgG+ at delivery. Durability of maternal SARS-CoV-2 Ab response and transplacental transfer following infection has implications for maternal and neonatal susceptibility to SARS-CoV-2 infection.

MATERNAL SARS-COV-2 INFECTION IN THE SECOND TRIMESTER AND VENTRICULOMEGALY AND DEVELOPMENTAL DELAY IN AN INFANT

Case Report History: Mother is a 23 year old gravida 4 para 1021, with a history of type 1 diabetes since 12 years of age. Prenatal sonogram at 20 weeks of gestation showed normal fetal anatomy with an EFW 21st percentile & 2-vessel cord. She was admitted at 23 weeks of gestation for acute hypoxic respiratory failure secondary to SARS-CoV-2 pneumonia, diabetic ketoacidosis & acute kidney failure. She refused intubation in spite of saturations in low 80s & was treated with high flow nasal cannula, non-rebreather mask, & nasal CPAP. She received convalescent plasma, Remdesivir, Tocilizumab, steroids, hydroxychloroquine, ceftriaxone & azithromycin, and was discharged home on oxygen after 29 days. Prenatal sonogram at 29 weeks of gestation demonstrated severe IUGR (abdominal & head circumference, fetal weight and femur length all < 3rd percentile), ventriculomegaly & a 2-vessel cord. Fetal MRI showed severe lateral ventriculomegaly of the brain, diffuse white matter parenchymal edema, bilateral germinal matrix & intraventricular hemorrhage & severe parenchymal volume loss. Mother was lost to follow up until time of delivery. Physical examination An infant female was born at 39 weeks of gestation via repeat cesarean-section. She was admitted to NICU for severe IUGR. The newborn's birth weight was 2126 g, head circumference 30 cm, length 43.5 cm (all <3rd percentile). Baby had mild hypertonia and tremors, rest of the exam was normal. The newborn was treated for TTN with NCPAP, hypoglycemia requiring IVF and hyperbilirubinemia requiring phototherapy and was extremely slow to feed. Diagnostic work-up CBC, BMP, LFT & CSF microscopy were normal, SARS-CoV-2 PCR was negative. SARS-CoV-2 IgM was negative in serum & CSF, but IgG was positive in serum & CSF. Baby's titers were slightly higher than mother's. US & MRI confirmed ventriculomegaly due to volume loss, a component of hydrocephalus was suspected due to presence of intraventricular hemorrhage, however there was no evidence of raised ICP. Retinal exam, hearing and BAER were normal. Chromosome analysis was normal & Zika titers were negative. The newborn was discharged home after 20 days with weighing 2580 g and head circumference of 32 cm. Placental was 222 g with <10% infarction and moderate acute chorioamnionitis. Infant has significant developmental delay at 1 year of age. Discussion There is definitive evidence of adverse neonatal outcomes in third trimester maternal SARS-CoV-2 infection, effects of earlier infections are not well reported. In our case the neurological injury can't be attributed definitively to fetal SARS-CoV-2 infection as IgM was negative, but the interval of 16 weeks between maternal infection and delivery need to be taken into account. Maternal illness likely contributed to severe acute on chronic fetal hypoxia which resulted in IUGR and in utero IVH with resultant CNS tissue loss and ventriculomegaly. (Figure Presented).

Prenatal Stress and the Microbiome in the Time of COVID- A Prospective Cohort Study

Background: Given the emerging importance of the role of the gut microbiota-brain-axis in mediating prenatal stress-induced neurodevelopmental outcomes, a prospective cohort study was conducted. The COVID-19 Pandemic occurred halfway through study recruitment (n=35). The study aims to a) evaluate perceived stress across gestation, b) determine whether maternal microbiome composition changes with stress, and c) discern the influence of the COVID-19 pandemic on maternal stress, psychometric scores, and alterations in the microbiome. Methods: This longitudinal study design includes five time points across pregnancy and the post-partum period, at which biological samples were collected and psychometrics administered. Samples include maternal rectal and vaginal swabs. Psychometrics include measures of perceived stress, anxiety, depression, sleep, diet, and childhood adversity. Study participants identify as 62.9% White and 31.4% Black or African American. Finally, PacBio full-length 16S rRNA sequencing using SMRT Cell technology is used to identify the maternal rectal and vaginal microbial communities. Results: Participants delivering during the pandemic reporting greater perceived stress (p≤0.05). Of note, there were no significant differences in anxiety or depressive symptoms across gestation in the pre-pandemic participants as compared to participants during the pandemic. During the second trimester, increased depression associated with increased rectal alpha diversity, and increased perceived stress was associated with increased levels of Prevotella, Sneathia, and Gardnerella in the rectal samples. In contrast, participants with increased depressive symptoms during the third trimester had reduced vaginal alpha diversity measures at delivery. Conclusions: Findings suggests maternal perceived stress and depressive symptoms are associated with alterations in maternal microbiota Keywords: Gut Microbiome, Prenatal Maternal Stress, Gut-Brain Axis