Metabolic alterations unravel the maternofetal immune responses with disease severity in pregnant women infected with SARS-CoV-2.

Pregnancy being an immune compromised state, coronavirus disease of 2019 (COVID-19) disease poses high risk of premature delivery and threat to fetus. Plasma metabolome regulates immune cellular responses, therefore we aimed to analyze the change in plasma secretome, metabolome, and immune cells with disease severity in COVID-19 positive pregnant females and their cord blood. COVID-19 reverse transcriptase-polymerase chain reaction positive pregnant females (n = 112) with asymptomatic (Asy) (n = 82), mild (n = 21), or moderate (n = 9) disease, healthy pregnant (n = 18), COVID-19 positive nonpregnant females (n = 7) were included. Eighty-two cord blood from COVID-19 positive and seven healthy cord blood were also analyzed. Mother's peripheral blood and cord blood were analyzed for untargeted metabolome profiling and cytokines by using high-resolution mass spectrometry and cytokine bead array. Immune scan was performed only in mothers' blood by flow cytometry. In Asy severe acute respiratory syndrome coronavirus 2 infection, the amino acid metabolic pathways such as glycine, serine, l-lactate, and threonine metabolism were upregulated with downregulation of riboflavin and tyrosine metabolism. However, with mild-to-moderate disease, the pyruvate and nicotinamide adenine dinucleotide (NAD+ ) metabolism were mostly altered. Cord blood mimicked the mother's metabolomic profiles by showing altered valine, leucine, isoleucine, glycine, serine, threonine in Asy and NAD+ , riboflavin metabolism in mild and moderate. Additionally, with disease severity tumor necrosis factor-α, interferon (IFN)-α, IFN-γ, interleukin (IL)-6 cytokine storm, IL-9 was raised in both mothers and neonates. Pyruvate, NAD metabolism and increase in IL-9 and IFN-γ had an impact on nonclassical monocytes, exhausted T and B cells. Our results demonstrated that immune-metabolic interplay in mother and fetus is influenced with increase in IL-9 and IFN-γ regulated pyruvate, lactate tricarboxylic acid, and riboflavin metabolism with context to disease severity.

SCOPE: Surveillance of COVID-19 in pregnancy- results of a multicentric ambispective case-control study on clinical presentation and maternal outcomes in India between April to November 2020.

OBJECTIVE: To determine the clinical manifestations, risk factors, treatment modalities and maternal outcomes in pregnant women with lab-confirmed COVID-19 and compare it with COVID-19 negative pregnant women in same age group. DESIGN: Multicentric case-control study. DATA SOURCES: Ambispective primary data collection through paper-based forms from 20 tertiary care centres across India between April and November 2020. STUDY POPULATION: All pregnant women reporting to the centres with a lab-confirmed COVID-19 positive result matched with controls. DATA QUALITY: Dedicated research officers extracted hospital records, using modified WHO Case Record Forms (CRF) and verified for completeness and accuracy. STATISTICAL ANALYSIS: Data converted to excel files and statistical analyses done using STATA 16 (StataCorp, TX, USA). Odds ratios (ORs) with 95% confidence intervals (CI) estimated using unconditional logistic regression. RESULTS: A total of 76,264 women delivered across 20 centres during the study period. Data of 3723 COVID positive pregnant women and 3744 age-matched controls was analyzed. Of the positive cases 56·9% were asymptomatic. Antenatal complications like preeclampsia and abruptio placentae were seen more among the cases. Induction and caesarean delivery rates were also higher among Covid positive women. Pre-existing maternal co-morbidities increased need for supportive care. There were 34 maternal deaths out of the 3723(0.9%) positive mothers, while covid negative deaths reported from all the centres were 449 of 72,541 (0·6%). CONCLUSION: Covid-19 infection predisposed to adverse maternal outcomes in a large cohort of Covid positive pregnant women as compared to the negative controls.

Categorisation of peritoneal serous effusions using the International System for Reporting Serous Fluid Cytopathology-A study on gynaecological samples.

BACKGROUND: Cytology of serous effusions is an indispensable diagnostic tool for the diagnosis of non-neoplastic as well as neoplastic effusions, aiding in the categorisation, staging, and prognostication of the patient. This study focuses on reclassifying cases of peritoneal fluid cytology following the International System for Reporting Serous Fluid Cytopathology (TIS), highlighting various challenges encountered and adding to the body of data regarding the risk of malignancy (ROM), focussing on peritoneal effusions due to gynaecological causes. METHODS: Peritoneal effusion samples were retrieved from our department's archives and reclassified according to the TIS. The ROM for each category was calculated based on available surgical follow-up. RESULTS: A total of 818 peritoneal effusions were studied. Following the definitions and guidelines of the TIS, the cases were reclassified with 125 (15.2%) in the category of non-diagnostic (ND), 595 (72.7%) as negative for malignancy (NFM), 26 (3.2%) as atypia of undetermined significance (AUS), 12 (1.5%) as suspicious for malignancy (SFM), and 60 (7.3%) as malignant (MAL). The respective ROM values for each category were 16.9%, 12.1%, 50%, 80%, and 100%, respectively. By considering the MAL and SFM groups as positive, and the ND, NFM, and AUS groups as negative, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were determined as 85.2%, 36.7%, 99.1%, 91.7%, and 84.5%, respectively. CONCLUSIONS: Peritoneal cytology categorisation following the proposed TIS offered a practical approach for categorisation of the fluids received. The ROMs reported in our study were mostly concordant with those published according to the TIS.

Breastfeeding and Contraceptive Methods in Women With Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-COV-2) Infection in Peripartum Period.

Objective: This study aimed to assess the exclusive breastfeeding and contraceptive methods among women delivering within 1-week of a positive test for severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) infection. Materials and methods: In this study, 106 women with SARS-CoV-2 infection who were either asymptomatic or had mild disease were included. They were admitted for maternity care at a tertiary center between May to September 2020. The data was collected during their hospital stay and subsequently by telephonic or in-person interviews at 4-6 weeks and 8-10 weeks postpartum for contraceptive use, breastfeeding and use of facemask and hand-hygiene. Results: Sixty-three (59.4%) women had vaginal delivery and 43 (40.6%) required cesarean-section. Only one of the 98 newborns who were tested for SARS-CoV-2 turned out positive. Initiation of breastfeeding was delayed by an average of three days due to preparing the Reverse transcription polymerase chain reaction (RT-PCR) report. Exclusive breastfeeding was practiced by 69% and mixed feeding by 26%.Pre breastfeeding hand hygiene and facemask use declined after discharge (100% to 53.75% at 8-10 weeks postpartum). Out of 106, 86 (81%) women used no contraception at 8-10 weeks postpartum, continued with post-placental-IUD in 8/106 (7.5%) and tubal-sterilization during cesarean in 8/106 (7.5%) cases. Only 4/106 (4%) adopted alternative methods like barrier contraception. Conclusion: The practice of exclusive breastfeeding remains unchanged among women who suffered from SARS-CoV-2 infection in the peripartum period while uptake of postpartum contraception was minimal except for the women who opted for long term contraceptive methods in the immediate postpartum period.

Executive Summary of Evidence and Consensus-Based Clinical Practice Guidelines for Management of Obesity and Overweight in Midlife Women: An AIIMS-DST Initiative.

Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. The key clinical questions specific to weight management in midlife women were finalized with the help of a multidisciplinary team of experts in the guideline development group. Phase I including a systematic and/or narrative review, grading of evidence, and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method, and GRADE approach. The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the health-care provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviors. Before initiating the management, a comprehensive assessment of clinical and lifestyle-related parameters should be completed. A personalized behavioral lifestyle modification program addressing the midlife-specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife-specific barriers for sustenance of healthy weight. These recommendations will be useful in opportunistic screening and management of obesity in midlife women across health-care settings.

Executive summary of evidence and consensus-based clinical practice guideline for management of obesity and overweight in postpartum women: An AIIMS-DST initiative.

INTRODUCTION: Postpartum obesity is a public health concern. There is a need to counsel women about their postpartum weight management, accounting for various barriers they face. Limited literature in the Indian context underscored the need to develop the clinical practice guideline to be used by healthcare providers in Indian healthcare settings. METHODS: The guideline was formulated by following the standardised methodology proposed by the National Health and Medical Research Council. Various steps such as identification of the patient population, assembly of the guideline development groups, identification of the key clinical questions, guideline development methods, grading the quality of evidence and recommendations and guideline translation were carried out to develop and validate the clinical practice recommendations. RESULTS: The evidence and consensus-based clinical practice guideline has been developed, providing recommendations for key topics of interest for first-line treatment of obesity (lifestyle-related management). Recommendations focus on screening and initiating discussion with overweight and obese postpartum women as well as those who had normal pre-pregnancy body mass index but have retained excessive weight in the postpartum period. Recommendations highlight the evaluation and management of dietary, physical activity and breastfeeding behaviour. Recommendations also account for behavioural modification techniques to improve adherence to the prescribed weight management advice. Duration and frequency of follow-ups as well as the advice to be disseminated have also been discussed in the recommendations. CONCLUSION: The guideline provides clinical practice points that can be used by healthcare providers, postpartum women and policymakers for opportunistic screening and management of postpartum obesity.

Executive summary of evidence and consensus-based Clinical Practice Guidelines for management of obesity and overweight in midlife women: An AIIMS-DST initiative.

BACKGROUND AND AIMS: Weight gain is an independent risk factor for decline in cardiometabolic and overall health-related quality of life in midlife women. The AIIMS-DST initiative aims to develop and validate stepwise recommendations specific for weight management in midlife women. METHODS: The key clinical questions specific to weight management in midlife women were finalised with the help of a multidisciplinary team of experts in the guideline development group (GDG). Phase I included a systematic and/or narrative review to gather evidence, grading of evidence and expert opinion was sought to develop clinical practice recommendations for each clinical question. Phase II focused on validation of clinical practice recommendations using the peer-review, Delphi method and GRADE approach. RESULTS: -The guidelines provide clinical practice points to address challenges encountered by midlife women in their attempts to manage obesity via lifestyle modification techniques. The initiation of discussion would help the healthcare provider to identify the weight management needs of the women, educate women on different modalities of weight management, and empower them to incorporate corrective lifestyle behaviours. Before initiating the management, a comprehensive assessment of clinical and lifestylerelated parameters should be completed. A personalised behavioural lifestyle modification program addressing the midlife specific barriers for optimal metabolic, musculoskeletal, and mental health should be planned. A consistent follow-up is required for maintenance of corrective eating and activity habits by addressing midlife specific barriers for sustenance of healthy weight. CONCLUSION: These recommendations will be useful in opportunistic screening and management of obesity in midlife women across healthcare settings.

Spontaneous vaginoperitoneal fistula as a rare complication of carcinoma ovary: a case report.

BACKGROUND: Spontaneous vaginoperitoneal fistula formation in a case of carcinoma ovary is a very rare occurrence and has never been reported. CASE PRESENTATION: A 55-year-old postmenopausal lady presented with complaints of abdominal distention and mass coming out of the vagina for the last 10 days. On examination, she had tense ascites, uterovaginal prolapse and hard, fixed mass felt anteriorly on per-rectal examination. Biochemical investigations and radiological imaging suggested advanced stage ovarian neoplasm. She was planned for neoadjuvant chemotherapy. During the second cycle of chemotherapy, she developed spontaneous vaginoperitoneal fistula which was confirmed on exploratory laparotomy where interval debulking surgery was performed in collaboration with gastro-surgeons on a semi-emergency basis. The postoperative course was uneventful. CONCLUSION: Spontaneous vaginoperitoneal fistula is a rare complication and should be kept in mind while managing advanced ovarian neoplasm.

Androgen insensitivity syndrome: Can cytology help?

Androgen insensitivity syndrome (AIS) is described as a patient's clinical (phenotypical) presentation as a female with male karyotyping. Classically, patients are normal looking females with complaints of primary amenorrhea. The gonads may be found as extra-genital swellings; rarely, the testes may undergo malignant transformation. Thus, gonadectomy is indicated in these patients on attaining puberty. A rare and interesting case of clinically unsuspected AIS in a young female who presented with primary amenorrhea and inguinal swelling is reported. The initial diagnosis was suggested on fine needle aspiration cytology (FNAC) from the inguinal swelling that showed the presence of Sertoli cells. Further family history revealed two similar siblings; karyotyping and histopathology confirmed the diagnosis of AIS in the patient. This case highlights the importance of FNAC in early diagnosis and a multidisciplinary approach to confirm the diagnosis and help in appropriate management.

Obstetric outcomes in pregnant women with seizure disorder: A hospital-based, longitudinal study.

OBJECTIVE: To study the association of seizure disorder with adverse obstetric outcome in terms of maternal and perinatal complications. MATERIALS AND METHODS: This longitudinal study was conducted at Maulana Azad Medical College, New Delhi over 15 months among women attending the antenatal clinic (ANC) outpatient department. Fifty pregnant women with seizure disorder with their first ANC visit before 28 weeks were recruited as the case group, excluding patients with eclampsia. The control group included 120 matched healthy pregnant women. After obtaining informed consent, subjects were recruited and followed till one week postpartum and obstetric outcomes were analyzed. RESULTS: Women with seizure disorder had significantly increased incidence of severe preeclampsia (cases =8%, controls =0%, p<0.001), antepartum hemorrhage (cases =4%, controls =0%, p<0.001), babies with early neonatal complications such as asphyxia (cases =4.1%, controls =0.5%, p=0.04), respiratory distress (cases =14.5%, controls =5.1%, p=0.02), necrotizing enterocolitis (cases =2.0%, controls =0%, p=0.04), early neonatal death (cases =2.0%, controls =0%, p=0.04) and Neonatal Intensive Care Unit admission (cases =20.8%, controls =8.6%, p<0.001) when compared with women without seizure disorder. No significant difference was observed in rates of induction of labor, cesarean section, abortion, congenital anomalies in babies, still births. Conclusion: Women with seizure disorder are at higher risk of hypertensive disorders, antepartum hemorrhage, and early neonatal complications. CONCLUSION: Women with seizure disorder are at higher risk of hypertensive disorders, antepartum hemorrhage, and early neonatal complications. Appropriate obstetric, pediatric and neurology care is required during preconception, pregnancy, labor, delivery, and postpartum.

A validation study of early warning system in high-risk pregnant women.

High-risk obstetric patients have chances of deterioration which can be detected by any early warning score. This study was aimed to assess the suitability of the Obstetrics National Early Warning System (ONEWS) for the pregnant women. This prospective study was conducted on 500 high-risk pregnant women attending a tertiary care teaching hospital. The ONEWS charts were plotted for each of them. The primary outcome measure was composite adverse maternal outcome (CAMO) in the form of one or more among mortality, severe maternal morbidity and intensive care unit admissions. Of the 500 women who participated, 200 (40%) had a score ≥3 (triggered an intervention). The CAMO among the triggered group [59.5% (n=119)] was significantly higher compared to that in the non-triggered group [13.3% (n=40) (P=0.001)]. The area under the receiver operating characteristic curve was 0.800 (95% confidence interval 0.752-0.847). The sensitivity of the ONEWS in predicting CAMO was 74.8 per cent, specificity 76.2 per cent, positive predictive value 59.5 per cent and negative predictive value 86.7 per cent at a cut-off score of 3. ONEWS appears to be a useful tool for predicting adverse maternal outcomes in high-risk pregnant women.

Clinical Validation of Mobile Cardiotocograph Device for Intrapartum and Antepartum Monitoring Compared to Standard Cardiotocograph: An Inter-Rater Agreement Study.

Objective: Electronic fetal monitoring (EFM) using cardiotocograph (CTG) is commonly used both to assess fetal wellbeing in late antepartum and for intervention during intrapartum period. We validated the performance of indigenously developed mobile cardiotocograph (CTG) device with wireless probes compared to standard CTG device. Materials and methods: We sequentially used mobile and standard CTG devices in 495 pregnant women in labour and 359 pregnant women with gestation > 32 weeks. The CTG interpreted by two independent obstetricians in a blinded manner were compared to estimate the agreement by kappa (k) statistic. Results: High level of agreements between mobile and standard CTG devices for both intrapartum (87.9%; kappa 0.61) and antepartum monitoring (91.2%; kappa 0.60) were observed. Most of the pregnant women (80% in intrapartum and 70% in antepartum groups) and all nurses and obstetricians preferred the mobile CTG device over standard CTG device. Conclusion: The mobile CTG device can reliably be used for both intrapartum and antepartum monitoring instead of the standard CTG devices. The smaller size, portability and ability to transmit the recordings for second opinion make it suitable for use by midwives for appropriate triaging and referral. Wider availability of CTG and interpretation support at the peripheral facilities would assist identifying at-risk pregnancies and foetuses for timely referral and appropriate action to reduce perinatal deaths, stillbirths and birth asphyxi.

Role of intravenous iron sucrose in correction of anemia in antenatal women with advanced pregnancy.

The aim of this study is to observe rise in haematological parameters after treatment with iron sucrose in antenatal patients with moderate anemia with period of gestation 32 to 35 weeks. The study included 45 antenatal patients with period of gestation from 32 to 35 weeks having iron deficiency anemia with haemoglobin levels 7-9 g% and serum ferritin levels less than 12 ng/mL. Intravenous iron sucrose was given in the dose of 200 mg on alternate days, according to the calculated dose. The mean haemoglobin and red blood cell indices were compared on days 7, 14, 21, 28 and at the time of delivery from the baseline value. There was a statistically significant rise in haemoglobin value from baseline on days 14, 21, 28 as well as at the time of delivery (p value <0.0001). The mean rise in haemoglobin values was 0.56 g% on day 14, 1.44 g% on day 21 and 2.0 g% on day 28. At the time of delivery, mean haemoglobin was 11.24 g%. After 28 days of treatment, there was a statistically significant rise in the levels of serum ferritin from 10.33 ± 3.8 ng/mL to 36.89 ± 5.7 ng/mL. Thus, earlier response achieved by iron sucrose can be utilised in the patients presenting at an advanced period of gestation with iron deficiency anemia.

A randomised controlled trial to compare intravenous iron sucrose and oral iron in treatment of iron deficiency anemia in pregnancy.

The aim of this study was to compare the efficacy and safety of intravenous iron sucrose with oral iron therapy in pregnant patients with anemia. The primary outcome of the study was increase in haemoglobin on day 7, 14 & 28 and rise of serum ferritin over 28 days. The study population consisted of 100 patients with singleton pregnancy between 24 and 34 weeks, hemoglobin levels between 7.0-9.0 gm/dL and serum ferritin levels less than 15 ng/mL. The participants in the oral group were given daily 180 mg elemental iron in three divided oral doses for 4 weeks. Total calculated dose of iron sucrose with a target hemoglobin of 11 gm %, was given in 200 mg dose on alternate days. Mean haemoglobin rise was 0.58 gm/dL in the IV group as compared to 0.23 gm/dL in the oral group on day 14 and 1.9 gm/dL in the IV group & 1.3 gm/dL in the oral group on day 28, (p <0.05). In the IV group, 76% of the subjects achieved haemoglobin levels of ≥11 gm% at the time of delivery, as compared to only 54% of the subjects in the oral group who achieved these levels. Serum ferritin value was significantly higher in the IV group, 37.45 ± 5.73 ng/mL as compared to 13.96 ± 1.88 ng/mL in the oral group at 4th week (p <0.001). There was no major side effect in the IV group. 36% subjects in the oral group developed gastrointestinal side effects & 10% of the subjects were non compliant. The rate of hemoglobin rise is faster with intravenous iron sucrose therapy as compared to oral iron therapy which can be beneficial in pregnant women presenting with anemia at a later period of gestation. Intravenous iron sucrose is very well tolerated during pregnancy.

Facility-based review of 296 maternal deaths at a tertiary centre in India: could they be prevented?

AIMS: The aim of this study was to identify causes of maternal mortality at the facility and to assess the standard of care, deficiencies in health services and preventability of these deaths using facility-based maternal death reviews. MATERIAL AND METHODS: This was a prospective study at a tertiary care hospital that included all women who died during pregnancy or within 42 days of being pregnant during 2005-2010. RESULTS: A review of 296 maternal deaths revealed that 59% of these occurred in medical wards. Indirect maternal deaths (54%) outnumbered the direct deaths (46%). Main causes were hepatitis (18%), hemorrhage (10%) and puerperal sepsis (10%). Only 5% of the women had received antenatal care at the facility. One-third (34%) were referred from other centers. The majority (74%) were critically sick at admission. Most of the women (62%) died postpartum. Substandard care and deficient health services were identified in 8% and 20% of the cases, respectively. Sixteen (5%) maternal deaths were deemed preventable and another 36 (12%) possibly preventable. Since most of the preventable deaths (12/16) were due to hemorrhage, measures to control postpartum hemorrhage were promoted at the facility. Findings of the maternal death reviews were regularly conveyed to the State Health Department for prioritization and resource allocation to prevent maternal mortality. CONCLUSION: More maternal deaths occurred in the medical than in the obstetrics wards at the facility. The leading causes were hepatitis, hemorrhage and puerperal sepsis. Most of the deaths were non-preventable as the women were critically sick at admission; however, substandard care and health service deficiency were contributory in some of the cases.

Ascariasis presenting as acute abdomen during pregnancy and puerperium.

Ascariasis can have various clinical presentations. We present three cases of ascariasis in pregnant or postpartum women, presenting with acute abdomen. The diagnosis of ascariasis was made clinically with the passage of ascaris worms in the vomitus or stool and was supported by ultrasonography. All three patients were treated successfully using anthelmintics. One patient underwent exploratory laparotomy.