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.

Perinatal aspects of sars-cov-2 infection during pregnancy: A potential cause for concern

Ever since the beginning of COVID-19 pandemic, uncertainty regarding clinical presentation and differences among various subpopulations exist. With more than 209,870,000 confirmed cases and more than 4,400,000 deaths worldwide, we are facing the new era of health crisis which will undoubtedly impair global health, economic and social circumstances. In the past year, numerous genetic mutations which code SARS-CoV-2 proteins led to the occurrence of new viral strains, with higher transmission rates. Apart from the implementation of vaccination, the effect of SARS-CoV-2 on pregnancy outcome and maternal fetal transmission remains an important concern. Although neonates diagnosed with COVID-19 were mostly asymptomatic or presented with mild disease, the effect on early pregnancy is yet to be evident. While positive finding of SARS-CoV-2 RNA in some samples such as amniotic fluid, placental tissue, cord blood and breast milk exists, additional research should confirm its association with transplacental transmission.Copyright © 2022, Dr. Mladen Stojanovic University Hospital. All rights reserved.

COVID-19 in Early Pregnancy. Clinical Implications and Methodological Considerations

There is limited information on the effects of COVID-19 early in pregnancy on the risk of major congenital malformations (MCMs). Initial research has been limited by small samples, lack of attention to the timing of infection during pregnancy, lack of an appropriate control group, and biased selection of participants. The International Registry of Coronavirus Exposure in Pregnancy (IRCEP) was designed to estimate the relative risk of adverse perinatal outcomes among women with COVID-19 at specific times during gestation. Adult women were eligible to enroll if they had a SARS-CoV-2 test, regardless of the results, or clinically confirmed COVID-19 during pregnancy. Self-administered questionnaires collected data on the infection, pregnancy outcomes, and potential confounders. The analysis of MCMs included women with either a positive SARS-CoV-2 PCR test or a clinical diagnosis of COVID-19 during the first trimester (exposed group) or a negative SARS-CoV-2 test (reference) that enrolled while pregnant. Of 17,163 participants enrolled between June 2020 and July 2021, 1,727 had a SARS-CoV-2 infection during the first trimester and 10,235 had a negative test during pregnancy. Restriction to participants with complete follow-up reduced the sample size to 92 exposed and 292 unexposed reference pregnancies. MCMs were reported in three (3.3%) exposed and eight (2.7%) unexposed (RR 1.2;95% CI 0.32-4.2) newborns. No specific pattern of malformations was observed. The accumulated evidence is most compatible with no major teratogenic effects associated with maternal SARS-CoV-2 infection. Multiple biases need to be considered and addressed when estimating and interpreting the effects of COVID-19 early in pregnancy. The biggest methodological challenges for IRCEP were retention of participants enrolled in early pregnancy, and the potential bias introduced when participants enroll after pregnancy outcomes are known. Studies that allow enrollment after the outcome is known may select pregnancies with the outcome;those that exclude them would select survivors.

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.

Fetal impact of cystic fibrosis transmembrane conductance regulator modulator use during assisted and natural reproduction and partner pregnancy in men with cystic fibrosis

Background: Increasing availability of highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapy (HEMT) has improved the quality of life and long-term prognosis for many people with CF. Thus, more people with CF are considering parenthood. Almost all menwith CF (MwCF) are infertile because of congenital bilateral absence of the vas deferens (CBAVD). Based on CF animal models, CBAVD occurs early in gestation and is unlikely to be reversible using HEMT, but assisted reproductive techniques (ARTs) can enable MwCF to father children using the sperm in their testes. Animal reproductive models suggest no HEMT teratogenicity, and the amount of exposure of the fetus to HEMT via absorption of seminal fluid through the vaginal wall is predicted to be negligible, although to ensure no sperm exposure to HEMT, the life span of sperm would require MwCF to discontinue CFTR modulators for approximately 3 months before ART. Because abrupt discontinuation of CFTR modulators may result in health decline, MwCF and their providers must consider all potential risks. There are no published data in MwCF regarding use of HEMT during conception and partner pregnancy. Method(s): Beginning in August 2021, CF center staff in the United States, United Kingdom, and Australia completed a two-page anonymous questionnaire regarding MwCF who used CFTR modulators during ART (sperm retrieval and in vitro fertilization) or natural conception with subsequent partner pregnancy. Result(s): Providers have submitted 34 surveys for MwCF on CFTR modulators whose partner became pregnant after use of ART (n = 32) or natural conception (n = 2). The median age of the samplewas 32 (range 24- 43). Fifteen were homozygous for F508del, median percentage predicted forced expiratory volume in 1 second was 76% (range (22-111%), and median body mass index was 24 kg/m2 (range 18.5-32.1). Twenty-three were taking elexacaftor/tezacaftor/ivacaftor. The median time that MwCF were taking CFTR modulators before partner conception was 18 months (range 0-82). One newly diagnosed man initiated HEMT after sperm retrieval. Four MwCF stopped CFTR modulators before sperm retrieval, one of whom experienced pulmonary decline. None of the 19 MwCF whose condom use during pregnancy was known used condoms. Fetal complications in partners of MwCF included three first-trimester miscarriages, two* COVID, two breech presentation, two* vaginal bleeding, and one vasa previa. None of the complications were deemed definitively related to use of CFTR modulators. One MwCF experienced testicular infection after sperm retrieval#. Postpartum complications included three# infants with hypoxemia requiring neonatal intensive care unit stay, three maternal blood loss, one forceps delivery, and one caesarean section. No congenital anomalies were reported for any infant. (*/# overlap). Conclusion(s): Use of CFTR modulator therapy during partner conception and pregnancy in 34 MwCF has not resulted in higher-than-expected miscarriage rates or congenital anomalies. Providers should consider the risk to the health of MwCF combined with the lack of teratogenicity in animal reproductive models and limited safety data in the human fetus before discontinuing CFTR modulators before ART or natural partner conception. Survey collection is ongoing;results will be updated for presentationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved

A novel cystic fibrosis-pregnancy service: Two-year review after introduction of elexacaftor/tezacaftor/ivacaftor

Background: As a quality service improvement response since elexacaftor/ tezacaftor/ivacaftor (ELX/TEZ/IVA) became available and the yearly average number of cystic fibrosis (CF) pregnancies (n = 7 pre-2020, n = 33 in 2021) increased significantly at an adult CF center (~600 people with CF), a monthly multidisciplinary CF-maternal health virtual clinic was established with antenatal virtual CF exercise classes dedicated to providing adaptive, specialist support to this cohort, aswell as outreach guidance and education to local obstetric teams. Method(s): This was a single-center retrospective reviewof Royal Brompton Hospital CF-Maternal Health multidisciplinary team clinic records and a patient survey from March 2020 to March 2022. Result(s): Of 47 pregnancies in 41 women (median age 30;) eligible for ELX/ TEZ/IVA at start of pregnancy, 40% (n = 19) were unplanned, and 19% (n = 9) used assisted conception. Three women with a history of infertility conceived naturally, having required assisted conception for previous pregnancies, and five women had multiple pregnancies during the study period. ELX/TEZ/IVA was continued in 60% (n = 28), delayed in 28% (n = 13), and stopped in 13% (n = 6) of pregnancies through maternal choice and careful clinical counselling. Pre-pregnancy pulmonary status was poorer in women who continued than in those who delayed or stopped (Table 1). Of those who stopped, 85% (n = 5) restarted because of pulmonary deterioration by the third trimester. Prenatal CF complications included at least one episode of minor hemoptysis in 21% (n = 9/41) of women, at least one infective exacerbation in 55% of pregnancies (n = 26/47), and noninvasive ventilation in one woman. Other pregnancy-associated complications included one case of ovarian hyperstimulation syndrome, one case of sub-segmental pulmonary embolism, and two cases of pregnancy-induced hypertension. Excluding 10 first trimester terminations, 10 current pregnancies, and one patient relocation, obstetric outcomes available for 26 pregnancies confirmed a live birth rate of 85% (n = 22/26) and a 15% first-trimester miscarriage rate (n = 4). Obstetric complications included preterm delivery rate of 23% (n = 6/26), including two cases of COVID infection resulting in two neonatal intensive care unit admissions, one case of endometritis after cesarean section, and a fourthdegree perineal tear. There were no ectopic pregnancies, maternal or neonatal deaths, or reports of infant cataracts or congenital malformations. Median gestational age was 37/40 weeks (range 29-40). Mode of delivery was via cesarean section in 45% (n = 10/22, of which twowere emergency) and vaginal in 55% (n = 12/22), of which 83% (n = 10/12) were via induction of labor for diabetes (CF or gestational) indication. Deliveries were supported and occurred equally at local obstetric units and in tertiarycare obstetric hospital settings (50%, n = 11/22). Patient-experience survey responses cited high levels of confidence in health optimization and prioritization during pregnancy and praised excellent inter-health care provider communication and peer-to-peer emotional support provided among expectant mothers in the virtual prenatal exercise groups. Table 1. Baseline demographic and clinical characteristics of elexacaftor/tezacaftor/ivacaftoreligible expectant mothers according to therapeutic decision (Table Presented) Conclusion(s): In the absence of clinical trial safety data, the novel approach of a dedicated CF-maternal health multidisciplinary team clinic with local obstetric outreach support has ensured regular specialist clinical and emotional peer-to-peer support for this cohort of women eligible for ELX/ TEZ/IVA to ensure optimal outcomes and experiences of their pregnancies, where appropriate, close to home.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

The current state of knowledge about COVID-19 vaccines during pregnancy

More than a year since the start of the COVID-19 pandemic, the global administration of the COVID-19 vaccines hopes to confer sustained protection against SARS-CoV-2 and stop this difficult to predict situation. They are highly effective, especially at preventing the severe form of disease and reducing the death rate from COVID-19. Pregnant women represent a high-risk category of population for infectious diseases, including COVID-19, and need to be considered for vaccination. Because the results of clinical trials of COVID-19 vaccines in pregnant women are not yet published, many questions remain to be answered. There are now available data and information in real-life data, including healthcare pregnant women or in women who did not know they were pregnant at the time of vaccination. This work aims to present the current state of knowledge about COVID-19 vaccines during pregnancy based on reported cases from medical literature. These cases of COVID-19 vaccination will be more and more, and in the future, we will be supplementarily adding data about the benefits and effects of vaccination on pregnancy, fetal and infant development, and their immunity. Today we affirm: anti-COVID-19 vaccines during pregnancy are reported to be as safe and effective as in the general population. Because a higher rate of miscarriage in early pregnancy has been observed to be associated with COVID-19, it may seem sagacious to recommend vaccination before planning a pregnancy to gain immunity at the time of conception.Copyright © 2021.

IUGR And Preterm Labor Occurrence In Pregnant Women With Early Pregnancy Vaginal Bleeding And History Of COVID-19 Infection

Background Vaginal bleeding is a common complication that may occur at any time during pregnancy. Up to 22% of women asked at delivery reported that vaginal bleeding occurred at some time during pregnancy. Preterm delivery is the delivery before 37 weeks of gestation, which involves approximately 12% of all pregnancies. If vaginal bleeding happens during pregnancy, some adverse outcomes including mortality before and after birth, low birth weight and preterm delivery will be increased. Vaginal bleeding is associated with two-fold increased risk of preterm delivery. Methods This prospective cohort study included 60 cases of pregnant female with first or second trimester vaginal bleeding at Obstetrics& Gynecology Department, Faculty of Medicine, of Damanhur Medical National Institute. The duration of the study was from April 2021 to April 2022. In the study 4 cases refused to complete the study and other 56 completed. Results There was significant decrease in birth weight and Apgar score with increase severity of vaginal bleeding. There was significant increase in neonatal intensive care unit (NICU) admission, intrauterine growth restriction (IUGR) occurrence and preterm labor with increase severity of vaginal bleeding. There was significant positive correlation between vaginal bleeding and IUGR and NICU admission. There was significant negative correlation between vaginal bleeding and Birth weight and APGAR score. Conclusion It seems that previous COVID-19 infection does not affect greatly pregnancy outcomes associated with vaginal bleeding. Vaginal bleeding was the main parameter affecting pregnancy outcomes.Copyright © 2022 Authors. All rights reserved.

Repeat Doses of Sotrovimab for Recurrence of COVID-19 in a High-Risk Pregnancy

Background: Myasthenia gravis (MG) is an autoimmune disorder leading to variable degrees of skeletal muscle weakness. During pregnancy, infections can trigger exacerbations and should be treated promptly and aggressively.(1) Sotrovimab is a monoclonal antibody used as monotherapy in high-risk, symptomatic non-hospitalized patients at risk of developing COVID-19 disease. (2) It is thought to have retained activity against SARS-CoV-2 omicron variant. (3) Limited data are available on its use in pregnancy. Case: A 39-year-old woman with severe generalized MG, was referred to our joint neuro-obstetric multidisciplinary service. Her two previous pregnancies were complicated by severe exacerbations of MG necessitating intensive care admissions, and preterm labour. Her long-term therapy included high dose steroids, intravenous immune globulin (IVIG) and plasma exchanges. In this pregnancy, she additionally received rituximab in the first-trimester, allowing her prednisolone to be weaned to 20 mg daily, with ongoing 3-weekly IVIG. She received 3 doses of the Pfizer COVID-19 vaccine. At 19 weeks she developed mild coryzal symptoms, sore throat and myalgia. Lateral flow and polymerase chain reaction tests in the community confirmed infection with SARS-CoV-2. She was treated with sotrovimab with uneventful recovery at home. At 31 weeks, she again tested positive for SARS-CoV-2, after reporting mild COVID-19 symptoms. She received a second dose of sotrovimab and had a quick recovery. Subsequent SARS-CoV-2 genotyping indicated she had contracted the Omicron-BA.2 variant. Fetal surveillance for growth (SARS-CoV-2) and arthrogryposis (MG) did not raise concerns. At 35+3 weeks, she went into spontaneous labour and was delivered by caesarean section for evolving chorioamnionitis, with uneventful recovery for mother and baby. Discussion(s): We report a case of repeated treatment with sotrovimab (in second and third trimesters) of a high-risk, non-hospitalized pregnant woman, who was re-infected with SARS-CoV-2. We identified no immediate maternal, fetal or neonatal complications following two doses of sotrovimab for mild COVID-19.

Aplasia cutis congenita in dizygotic twin infants

Aplasia cutis congenita (ACC) is often sporadic, but familial cases have been reported. We report a case of a dichorionic diamniotic twin pregnancy in which both the male and female twins had matching areas of aplasia cutis on their scalps. An Irish couple sought fertility treatment using a donor egg and paternal sperm. Successful in vitro fertilization (IVF) and the transfer of two embryos resulted in a diamniotic dichorionic twin pregnancy. Two fetal poles were noted at the 12-week ultrasound (US) scans. The mother suffered from a minor urinary tract infection during the first trimester but had no other history of infection, including herpes simplex virus or COVID- 19. She was known to be varicella immune prior to pregnancy. The twins were born by elective caesarean section owing to breech presentation. Twin one was female and twin two was male. Both infants were born with scarring on the crown of their head, which was consistent with ACC. Cranial US showed no underlying bony abnormality. The rest of the cutaneous examination was normal and there were no other congenital anomalies. ACC is a rare, heterogeneous group of disorders characterized by the congenital absence of skin, which can be focal or widespread. It is thought to affect 1-3 per 10 000 live births. The exact cause of ACC is unclear. Various hypotheses have been suggested, including defective closure of the neural tube or embryonic fusion lines, intrauterine trauma, placental insufficiency, fetus papyraceus, amniotic membrane adhesions, intrauterine infections, teratogens and genetic mutations. The classification of ACC is based on the area affected, type of skin irregularity, associated congenital defects and mode of inheritance. Scalp ACC without multiple anomalies (category 1) is generally associated with an autosomal dominant or sporadic pattern of inheritance. These twins may have an autosomal dominant mutation that led to this phenotype. ACC can also be associated with fetus papyraceus or placental infarct. This is less likely in this case as only two embryos were transferred, and the pregnancy was dichorionic. Most cases of ACC associated with fetus papyraceus occur in monozygotic pregnancies. ACC lesions often heal spontaneously by re-epithelialization resulting in a hairless superficial scar. Twin one had a slightly smaller area affected by ACC and overlying eschar resolved several weeks after birth. Twin two has had no hair growth in the area. This case highlights the difficulties in ascertaining the aetiology of this rare condition in twin pregnancies.

Immunohistochemical Interferon Gamma Expression in Chronic Intervillositis of Unknown Etiology

Background. Chronic intervillositis of unknown etiology (CIUE) is a rare cause of recurrent early pregnancy loss. Upregulated interferon gamma (IFNg) expression in syncytiotrophoblast has been shown in a small cohort of high grade CIUE cases suggesting this may play a role in pathogenesis;however, the extent of IFNg expression in this disease remains unclear. This study compares IFNg expression in CIUE to placenta from non-CIUE spontaneous early pregnancy losses and normal early gestations by immunohistochemistry. Method(s): Ethics approval is obtained for a tissue-based study comparing late first to mid second trimester archival placental tissue from high grade CIUE (CHG;18 cases), low grade CIUE (CLG, 12 cases), elective termination (NP, 13 cases), euploid spontaneous pregnancy losses (ESPL, 18 cases), and aneuploid spontaneous pregnancy losses (ASPL, 17 cases). 2 cases of third trimester pregnancy loss associated with placental COVID19 infection are included as examples of chronic histiocytic intervillositis of a known etiology. Atypical mycobacterial granuloma is employed as a positive control. IFNg expression is assessed on whole tissue sections by automated immunostaining and graded semiquantitatively by multiplying staining intensity (3+ same as control staining;2+ between 3+ and 1+;1+ just visible at 200x;0+ no staining visible at 200x) by distribution (1 <5%;2 5-50%;3 >50%) for a score from 0-9. Data are compared by 2-tailed independent t-test. Result(s): Focal positive syncytiotrophoblast IFNg staining is seen in 35% of CHG, 42% of LGH, and 4% of non-CIUE cases (0% NP, 0% ESPL, 12% ASPL). IFNg expression in CIUE placenta is characterized by luminal orientation in syncytiotrophoblast while the ASPL cases show non-luminally oriented cytoplasmic staining. IFNg is not expressed in other placental cell types. The average IFNg grade is 1.3 (range 1-9) for CHG, 0.7 (range 1-2) for CLG, 0 for NP and ESPL, and 12% (range 1-2) for ASPL. There is a statistically significant difference between CIUE and non-CIUE placenta (p = .0015) but not between CHG and CLG (overall p = .42;positive cases only p = .17). Occasional lymphocytes in the maternal intervillus space strongly express IFNg and these appear more abundant in areas with more prominent histiocytic inflammation. COVID19 placental tissue does not express IFNg but IFNgpositive lymphocytes are present in the intervillus space. Conclusion(s): A subset of high grade and low grade CIUE express IFNg suggesting this represents a distinct subgroup of CIUE. IFNg expression appears to correlate with grade implying IFNg expression is related to inflammation intensity although the difference is not statistically significant. Future studies of CIUE, particularly those assessing therapies, may benefit from separate assessment of IFNg positive cases.

Placenta Proteins of Women Infected SARS-COV-2 in the First Trimester of Pregnancy Remains Unchanged

Objectives: To compare the biochemical and biophysical parameters of non-invasive prenatal screening of women infected with SARSCOV-2 in the first trimester of pregnancy with those of healthy pregnant women.. Method(s): The study was conducted on a case-control model with 547 women who underwent a double test between May 21 and November 29, 2021. 136 of these 547 women were involved in the case group, which was exposed with SARS-COV-2 viral infection, and 411 were women recruited in the control group, concept form was obtained from all subjects who underwent the study. Subjects' SARSCOV-2 infection was confirmed by RT-PCR, and double tests were conducted on the recovered women. Result(s): The mean age of the SARS-COV-2 infected group was 30.9 years, and the mean age of the healthy group was 30.8 years (p > 0.05). 1. The mean (SD) of PAPP-A in the infected group was 1.94 (+/-2.66) MOM, in the non-infected group was 1.97 (+/-2.00) MOM. The mean (SD) of beta-hCG in the infected group was 1.67 (+/-3.33) MOM and in the non-infected group was 6.28 (+/-8.66) MOM. With a significance level of 0.05, there were no significant differences in the mean (p = 0.120) of serum proteins between the SARS-COV-2 group and the non-SARS group. 2. During the ultrasound examination of both groups, the mean (SD) of the infected group NT 1.60 (+/-0.56) MOM and the non-infected group NT 1.63 (+/-0.78) MOM, the infected group DV 1.04 (+/-0.19) MOM and the non-infected group DV 1.34 (+/-5.85) MOM, the infected group HR 166.27 (+/-47.85) MOM and the non-infected group HR 161.67 (+/-0.19) MOM. Nuchal translucency (NT) p = 0.620, venous flow (DV) p = 0.54, and fetal heart rate (HR) p = 0.076. There were no significant differences. Conclusion(s): There were no significant differences between serum PAPP-A, free beta-hCG protein, and fetal ultrasound in women with SARS-COV-2 during the first trimester of pregnancy.

SARS-CoV-2 Anti-Spike IgG Antibodies in Neonates After Maternal Vaccination Against COVID-19 During Pregnancy and Outcomes

Background. Worldwide, attempts to understand the neonatal response and the benefits of immunity conferred by the mother to continue preventing COVID-19 infection in vulnerable groups. Therefore, research on the efficacy of vaccination against SARS-CoV-2 in pregnancy remains as an important tool to prevention of complications. Methods. Cross-sectional study in which blood samples from 379 neonates taken from the umbilical cord. The inclusion criteria were: newborns of mothers with a history of vaccination against SARS-CoV-2 during pregnancy. Infants whose mothers had COVID-19 infection at birth, or receiving any immunosuppressive treatment during pregnancy were excluded. Results. 379 neonates were studied for their antispike IgG levels. The majority were full-term female neonates were of adequate weight for their gestational age and without complications during their birth, 28 neonates required NICU care for their. Antispike IgG levels were obtained in 94.9% . Mothers received first dose at first trimester in 28.4%, second trimester in 51.9% and in the third trimester 19.6). A total of 318 mothers (87.8%) completed the two-dose schedule receiving the same vaccine, six (1.6%) received another anti-COVID vaccine, and the remaining 39 (10.7%) received only one dose of vaccine. 64.9% were vaccinated with the BNT162b2 vaccine, were higher leves when received two vaccine doses compared to only one. Vaccines that stimulated highest levels were mRNA-1273 and BNT162b2, lowest levels were found in the CoronaVac and Ad5-nCoV vaccines. Finally, it should be noted that only four neonates presented levels below 0.8 BAU/ mL (non-positive). Conclusion. This study provides evidence on timing of maternal anti-COVID vaccination, antibody production, and transplacentary transfer ensuring maternal and neonatal protection through vaccination is key to encourage women to be vaccinated against COVID-19 during pregnancy. Follow-up studies in infants are needed to understand the persistence of placental-transferred antispike IgG and the role of breast milk antibodies in maximizing the protection of infants at this stage of risk of severe SARS-Cov-2 disease. These findings have implications for determining new public health and vaccination strategies for pregnant women.

Delta variant neutralizing antibody response following maternal COVID19 vaccination

Objective: To evaluate whether COVID19 vaccination during pregnancy confers immunological response to SARS-CoV-2 Delta variant. Study Design: Prospective cohort study of pregnant patients who had received any available COVID19 vaccine. Maternal and umbilical cord serum was collected at delivery. SARS-CoV-2 neutralization was measured with spike-pseudotyped viruses in HEK-293T-ACE2 cells as a function of reduction in Luc reporter activity using an env-deficient lentiviral system to produce viral particles pseudotyped with the B1.617.2 (Delta variant) spike. Neutralization titers represented the serum dilution at which relative luminescence units (RLU) were reduced by either 50%(ID50) or 80%(ID80) compared with virus control wells. RLU threshold for detection was 20. Result(s): Maternal and neonatal umbilical cord samples were collected from 20 individuals who received COVID19 vaccination during pregnancy. Most (n=16, 80%) received Pfizer, 2 Moderna, 2 Johnson&Johnson. One individual (5%) was vaccinated in first trimester, 11(55%) in second trimester, and 8(40%) in third trimester). Most individuals had detectable levels of neutralizing antibodies to SARS-CoV-2 Delta variant in maternal (n=15, 75%) and neonatal (n=17, 85%) serum. (Figure) No significant difference between maternal and neonatal serum titers. Conclusion(s): COVID19 vaccination during pregnancy yields an immunologic response in maternal serum that results in circulating neutralizing antibodies against SARS-CoV-2 Delta variant in maternal and neonatal serum at delivery. Disclosure: No [Formula presented] Copyright © 2022

The Effects of the COVID-19 Pandemic on Mother-Infant Mental Health Relationship

Maternal health cannot be separated from infant, child and adolescent health, which includes mental health as well. Expecting mothers go through a number of changes during their pregnancy. Due to the specific alterations of their physique and immune system, pregnant mothers are more vulnerable to the Covid-19 infection. This highlights the importance of the vaccinations in their cases. During the pandemic, mental health problems such as anxiety, depression and stress aroused in greater numbers. This affected mothers, and younger children as well. Expecting mothers, without pre-existing mental disorder (>50%) reported a weightier level of anxiety in their first trimester. Also, infants can suffer developmental disadvantages, as their infected mothers are separated from them. Even though evidence is not yet clear in this topic, vertical transmission seems to be fairly uncommon. Treatment guidelines, that could help Covid-19 infected mothers to handle their infants, are scarce. Hence the importance of telehealth has started to be outlined. Separation from the children might be necessary, while the mental health of mother and infant is continuously screened, since the long-term consequences of the symptoms are still unknown. Hence, prevention is imperative to avoid any negative effects. Even still, WHO advises mothers to breastfeed safely, with good respiratory hygiene, emphasizing the importance of skin-to-skin contact of newborns and sharing the room with them. On policy level: investment into pre-, peri-, post-natal care, family supporting national programs, inter-sectoral collaborations, monitoring and research are important elements of prevention and treatment efforts during the Epidemic and the post-Covid-19 era.

Cladribine treatment in turkish MS patients

Introduction: As a high-efficacy multiple sclerosis (MS) treatment, cladribine necessitates empirical data from diverse populations. Objective(s): To study the efficacy and safety data of cladribine treatment in a real-world setting. Method(s): Patients from eight MS clinics in Turkey were involved in the study. We retrieved the demographic, clinical, MRI, safety, laboratory, COVID-19, and pregnancy records of patients with at least six months of follow-up on cladribine treatment. Result(s): Our study included 210 MS patients (52 males, 158 females;193 relapsing and 17 relapsing-progressive MS). The mean age at MS disease onset was 27.6 years (+/-8.5). Before cladribine treatment, 56.7% of patients used first-line, and 41.9% used both first and second-line therapies. During a mean follow-up period of 13.0 months (+/-4.7) following cladribine treatment, 5.7% of patients experienced a relapse. The shortest duration of relapse following cladribine administration was one week, and the longest duration was 15.3 months. Interestingly, 50% of the relapses occurred within the first three months. Among relapsing patients, five switched from fingolimod, two from dimethylfumarate, and one from ocrelizumab and interferon-beta. The mean annualized relapse rate was 0.41 (+/-0.41) in the two years preceding cladribine and 0.11 (+/-0.55) one year following treatment. At baseline, the mean EDSS score was 2.47 (+/-1.63), and 51.9% of patients ranked below EDSS 3. EDSS progression was observed in 7.6% of patients following cladribine treatment. On cladribine, eight patients (9.4%) exhibited radiological progression. There was no difference in NEDA status between patients switching from first or second-line therapy (p=0.43). COVID was observed in 73 patients, 54 of them had a mild disease course, six had a moderate disease course, and one had a severe disease course. There have been no COVID-related fatalities. There were five pregnancies documented, three of which are currently ongoing. One of the pregnancies ended with healthy childbirth, while the other was terminated in the first trimester with a miscarriage. Conclusion(s): Despite the relatively short duration of follow-up, our study demonstrates that cladribine is effective in providing NEDA. Moreover, switching from fingolimod to cladribine may increase the likelihood of early relapse.