Correlation between placental histopathology and perinatal outcome in COVID-19.

Objectives: An alarming rate of adverse perinatal outcomes as well as maternal deaths has been reported worldwide during this pandemic. It would be prudent to start thinking on the lines of acute or chronic intrauterine fetal hypoxia due to placental microvascular pathology or villitis caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. Autopsy studies of deceased patients with severe COVID-19 have revealed the presence of diffuse pulmonary alveolar damage, thrombosis, and microvascular injuries. It is expected that similar pathological features such as microvascular injuries could be found in the placenta of infected pregnant women. Materials and Methods: Placentas of singleton pregnancies from 42 SARS-CoV-2 positive mothers delivered at term were submitted for histopathological examination. Those with multifetal gestation, hypertensive disorder, fetal growth restriction, structural or chromosomal anomalies in the fetus, thrombophilia, prolonged prelabor rupture of membranes, and placenta accreta spectrum were excluded from the study. Histopathological examination was done by two pathologists independently and only those results concurred by both were reported. Histopathological features and corresponding neonatal outcome were analyzed. Results: Reports of 42 placentas from patients with SARS-CoV-2, delivered at term (37-40 weeks) were analyzed in our study. Features of maternal vascular malperfusions (MVM) were present in 45% (n = 19) cases. Features of fetal vascular malperfusions (FVM) were present in 23.8% (n = 10) cases. There were 47.6% (n = 20) cases showing at least one feature of acute inflammatory pathology (AIP) and 42.8% (n = 18) showing features of chronic inflammatory pathology (CIP). Neonatal respiratory distress syndrome was found in 19% (n = 8) of the neonates. Correspondingly, nearly all placentas (n = 7) of these neonates showed features of MVM, FVM, AIP and CIP. There was no maternal or neonatal mortality in our study group. Conclusion: The main findings of our study include maternal as well as fetal vascular malperfusions and placental inflammatory pathology. These findings provide an outline for better understanding of etiological factors and pathogenesis of adverse perinatal outcomes in SARS-CoV-2 infection.

Metaproteomic data of maize rhizosphere for deciphering functional diversity.

Metaproteomics is a powerful tool for obtaining data on all proteins recovered directly from environmental samples at a given time. It provides a direct evidence of functional diversity and structure among microbiota present in niches and significant insights into microbial activity together with metabolomics, which is the study of the intermediate and end-products of cellular processes. Metaproteomics is a comparatively new approach which is facing a number of empirical, technical, computational and experimental design challenges that needs to be addressed. Presently only little efforts have been made to have information on microbial proteins in rhizospheric soil of maize through metagemonics approach but there is no direct evidence on functions of microbial community in this very important niche. Since rhizosphere microbiome plays important role in plant growth and development the present study is conducted to optimize the metaproteomic extraction protocol from maize rhizosphere and analyse functionality of microbial communities. We present metaproteome data from maize rhizospheric soil. Isolation of metaproteome from maize rhizosphere collected from ICAR-IISS, Mau experimental Farm was done with the standardized protocol at our laboratory and metaproteome analysis was done with the standardized pipeline. In total 696 proteins with different functions representing 244 genus and 393 species were identified. The proteome data provides direct evidence on the biological processes in soil ecosystem and is the first reported reference data from maize rhizosphere. The LC MS/MS proteomic data are available via ProteomeXchange with identifier PXD014519.

Bone densitometry status and its associated factors in peri and post menopausal females: A cross sectional study from a tertiary care centre in India.

OBJECTIVE: Osteoporosis is a skeletal disorder characterized by diminished bone strength that increases the risk of fracture at instances of trivial trauma. Asians have a lower bone mass than the west. The present study was designed to add data from India on women above the age of 40 years with respect to low bone mineral density (BMD) and its associated high risk factors. MATERIALS AND METHODS: After a written informed consent, a detailed history was taken. Basal metabolic index was recorded, and biochemical and endocrine tests were done, followed by dual X ray absorptiometry scan. RESULTS: Average age of the study population was 46.54 years and BMI 26.58. The prevalence of osteopenia in the study was 36%, and that of osteoporosis, 4%; the overall prevalence of low BMD being 40%. Proportion of women with low BMD increased with advancing age and menopausal status. On endocrine evaluation, 53.44% cases with insufficient vitamin D, 62.5% with hyperparathyroidism, 100% with hypothyroidism, 75% with hyperthyroidism suffered from low BMD. Among chronic diseases, 75% women with diabetes, 33.3% with hypertension, 25% with deranged liver function and 50% with rheumatoid arthritis were found to have low BMD. 46.75% women with sun exposure less than one hour daily had poor bone mineralization. The proportion of women with normal BMD decreased from 84.09% to 43.33% with decrease in daily physical work. On logistic regression analysis, insufficient serum vitamin D concentrations, less physical work and inadequate sun exposure were found to be significantly associated with low BMD. CONCLUSION: Low BMD is not a disorder confined to postmenopausal women alone. It is widely prevalent in women above 40 years of age. Screening women above 40 in the absence of any high risk factors has the potential of nipping this silent killer in the bud.

Pubic Symphysis Diastasis: A Case Series and Literature Review.

Separation of pubic symphysis during delivery is a rare complication resulting in considerable and prolonged morbidity for parturient women. The usual presentation is that of something giving way in the region of the symphysis pubis sometimes with an audible crack at the time of delivery. Unbearable pain on moving from side-to-side and on performing any weight-bearing activity (such as walking or climbing stairs) precludes ambulation in the immediate postpartum period. This could be accompanied by disruption of the sacroiliac joint, hemorrhage, or urine incontinence in severe cases. Radiography, ultrasound, and magnetic resonance imaging are the diagnostic modalities that aid confirmation of diagnosis. The magnitude of separation does not correlate well with the severity of symptoms. Treatment modalities range from conservative management (including analgesics, pelvic binders, transcutaneous nerve stimulation) and chiropractic management to orthopedic interventions such as external fixation or open reduction and internal fixation. Since postpartum pain is frequently dismissed as attributable to labor and childbirth, the diagnosis of pubic symphysis diastasis is often delayed and sometimes missed altogether. Since there is no consensus in the scientific literature on the definition, etiopathogenesis, and management of this rare complication, we attempted to review the literature on the subject and present a series of two cases.

Pre-eclampsia: Molecular events to biomarkers.

Pre-eclampsia is a hypertensive disorder in pregnancy, which accounts for 10-15% of the maternal and perinatal mortality worldwide. Abnormal placental development and tissue hypoxia are its main etiologic factors. The present diagnostic methods of blood pressure monitoring and renal function evaluation are insufficient in the early detection of pre-eclampsia. Since molecular events portent well ahead of the disease onset, biomarker research for the early diagnosis of pre-eclampsia has recently generated ambitious clinical targets. However, no clinically validated biomarker has so far been reported for the prediction of pre-eclampsia. Therefore, this review takes stock of the current understanding of pre-eclampsia from a molecular biology perspective and critically evaluates the following diagnostic potentials claimed for the biomarkers: placental proteins, angiogenic markers, and cell-free fetal DNA (cffDNA) in maternal circulation. Though the emerging evidences in favor of the fetal-specific epigenetic marker, hypermethylated RASSF1A of cffDNA, are highlighted, it pitches for a broader strategy of 'combination biomarker approach' for the reliable forecasting and triaging of pre-eclampsia.

Fetal-specific hypermethylated RASSF1A quantification in pregnancy.

OBJECTIVE: To quantify cell free fetal DNA (cffDNA) with fetal specific epigenetic marker, hypermethylated RASSF1A, in maternal plasma of normal pregnant women from 20 weeks of gestation and to assess its relationship with maternal age, height, pre-pregnancy weight and body mass index (BMI). METHODS: Hundred normal pregnant women within the gestational age of 21-40 weeks were randomly selected and grouped into five (n = 20). Group 1: 21-24, Group 2: 25-28, Group 3: 29-32, Group 4: 33-36 and Group 5: 37-40 weeks. Maternal plasma DNA was extracted, digested with methylation-sensitive restriction enzyme, BstUI and the fetal specific DNA (cffDNA) was quantified by Real-time polymerase chain reaction (qRT-PCR). RESULTS: The mean hypermethylated RASSF1A concentrations in different gestational groups were Group 1: 30.1 ± 14.9, Group 2: 52.6 ± 22.18, Group 3: 93.2 ± 19.08, Group 4: 172.8 ± 26.81 and Group 5: 337.8 ± 52.9 copies/ml. Pearson's correlation analysis showed highly significant positive correlation between cffDNA and gestational age (r = 0.899, p < 0.001). BMI was also found to be positively related to cffDNA (r = 0.217, p < 0.05). However, it did not show any correlation with maternal age, height and pre-pregnancy weight. CONCLUSIONS: The gestational age-dependent increase of hypermethylated RASSF1A; the fetal specific epigenetic marker in maternal plasma was demonstrated, in an Indian study group of normal pregnant women. Findings would form the basis of future studies involving pregnancy complications that would aid in the early diagnosis of placental pathologies with hypermethylated RASSF1A.

Evaluation of fetal hypermethylated RASSF1A in pre-eclampsia and its relationship with placental protein-13, pregnancy associated plasma protein-A and urine protein.

OBJECTIVES: Cell free fetal DNA (cffDNA) and its hypermethylated RASSF1A gene signify a recent advancement in non-invasive prenatal diagnosis of feto-placental anomalies like pre-eclampsia. The study uses hypermethylated RASSF1A gene to quantify cffDNA and to assess its relationship with placental and urine proteins in pre-eclampsia cases. DESIGN AND METHODS: DNA was isolated from plasma samples of clinically diagnosed cases of pre-eclampsia (n=103) and normal pregnancy (n=616) from 21weeks of gestation. Through methylation sensitive enzyme (BstUI) digestion; followed by real time-polymerase chain reaction (RT-PCR), quantification of hypermethylated RASSF1A was done. Immunoassays determined: placental protein-13 (pp-13) and pregnancy associated plasma protein A (PAPP-A) and pyrogallol red molybdate assay for 24h urine protein. RESULTS: Highly significant differences between control and pre-eclampsia cases for hypermethylated RASSF1A concentrations were found; Group I: 33±7.35 vs 74.46±16.71, Group II: 53.75±16.65 vs 244.22±35.68, Group III: 93.25±19.08 vs 412.31±80.18, Group IV: 144.30±18.13 vs 1056.89±153.78, Group V: 307.55±40.76 vs 2763.76±259.76copies/ml. Multivariate Pearson's correlation analysis of hypermethylated RASSF1A with pp-13, PAPP-A and urine proteins showed positive and very highly significant (P<0.001) associations. CONCLUSIONS: Diagnostic potential of fetal specific, hypermethylated RASSF1A was evaluated. Its positive relationship with placental and urine proteins submit the case for considering it as a reliable marker for pre-eclampsia.

Efficacy of single dose Nevirapine in reducing viral load in HIV positive mother in labour and transmission of HIV infection to new born babies as part of prevention of parent to child transmission.

BACKGROUND: Prevention of parent to child transmission (PPTCT) program was initiated in Armed Forces to reduce the vertical transmission of HIV by instituting single dose Nevirapine (sdNVP) in untreated HIV positive mothers in labour. The aim of this study was to evaluate the role of sdNVP to decrease viral load of HIV infected mother during labour and its efficacy in prevention of mother to child transmission of HIV. METHODS: Thirty antenatal women tested positive for HIV at our PPTCT centre and delivered between Jan 2006 and May 2008 were evaluated. During labour these women were given sdNVP. Newborns were given syrup Nevirapine. The babies were tested for HIV infection at 48 h and six weeks after delivery. RESULTS: Thirty HIV positive women delivered at our centre and four newborns were found positive for HIV infection at 48 h. After six weeks interval three neonates were detected for HIV infection as one infant at six weeks was found to be negative for HIV infection. CONCLUSION: The protection rate of Nevirapine in untreated HIV positive women is not ideal. It is recommended that all HIV positive women should be offered Highly Active Antiretroviral therapy as primary mode for PPTCT.

Serum Cholesterol and Ceruloplasmin Levels in Second Trimester can Predict Development of Pre-eclampsia.

BACKGROUND: Pre-eclampsia is one of the leading causes of high rates of maternal and perinatal mortality and morbidity. Pathophysiology of pre-eclampsia is still obscure. Currently, there are no screening tests for pre-eclampsia that are reliable, valid, and economical. Parameters of oxidative stress could be early markers of endothelial dysfunction that predates clinical pre-eclampsia. AIM: This study was to study ceruloplasmin in nulliparous women as marker of oxidative stress and lipid profile to evaluate their value in prediction of pre-eclampsia. MATERIALS AND METHODS: Prospective observational study. 306 nulliparous women had their serum lipid profile and ceruloplasmin levels measured at 14-16 weeks period of gestation as sample 1 and at 18-20 weeks as sample 2. All cases were followed up till the end of pregnancy for development of pre-eclampsia. RESULTS: There was no statistically significant difference between the normals and pre-eclampsia cases at 14-16 week for all the oxidative stress parameters (P > 0.05), but at 18-20 week, there was statistically significant difference between the normals and pre-eclampsia cases in cholesterol and ceruloplasmin parameters (P < 0.05). CONCLUSION: Cholesterol and ceruloplasmin levels in second trimester (18-20 weeks) can predict the development of pre-eclampsia.

A comparative study of the different diagnostic criteria of gestational diabetes mellitus and its incidence.

BACKGROUND: High prevalence of diabetes and genetic predisposition to metabolic syndrome among Indians places Indian women at risk to develop gestational diabetes mellitus (GDM) and its complications. Literature defines multiple criteria for GDM. This prospective study compares available diagnostic criteria for GDM in Indian women and their correlation with perinatal morbidity. METHOD: Nine hundred and forty-eight consecutive voluntary nondiabetic pregnant women were recruited for the study. Seven hundred and twenty-three of these (mean age 23.45 years; 75.7% < 25 years) who reported for the follow-up were screened for GDM at 24-28 weeks gestation by American College of Obstetrics and Gynaecology (ACOG) guidelines and World Health Organization (WHO) criteria. Glycated haemoglobin (HbA1c) and fasting and two-hours postglucose plasma insulin levels were also analysed. Pregnancy outcome was known for 291 of these. Concordance of risk factors and perinatal complications was analysed with respect to GDM. RESULTS: Prevalence of GDM at 24-28 weeks gestation was found to be 4.8% by WHO criteria, 6.36% by Carpenter and Coustan's criteria, and 3.5% by O'Sullivan's criteria. Prevalence was marginally higher in women of higher age, having past history of abortion or family history of diabetes mellitus (DM) (P > 0.05). None of these women had HbA1c > 6%. Relative risk of abnormal delivery (pregnancy outcome) was 1.93, 1.39, and 1.17 in women with GDM by O'Sullivan's, WHO, and Carpenter's criteria, respectively (P > 0.05). Abnormal deliveries were marginally higher in women with high postglucose load insulin levels. Mean weight of the newborns was essentially the same in GDM and nonGDM women by any of the criteria. One-hour and two-hours postglucose values were more sensitive in diagnosing GDM by O'Sullivan's criteria while fasting plasma glucose value had the poorest specificity with 2.5% of nonGDM women having values above the cut-off. Modifications of these criteria did not im-prove their predictive value for abnormal delivery over that of O'Sullivan's criteria. CONCLUSION: Prevalence of GDM and abnormal delivery in women < 35 years of age is low. Therefore, global screening for GDM may not be very useful in women < 25 years of age unless family history of DM or past history of abortion is present. Existing evidence is inadequate to justify the switchover from O'Sullivan's criteria for diagnosis of GDM.

Acute Abdomen in Gynaecological Practice.

Acute abdomen in pregnancy is due to consequence of pregnancy itself or is totally unrelated to pregnancy. During pregnancy, a woman is at an increased risk of acute abdomen due to various physiological changes. The article discusses the various conditions which can present as acute abdomen in women during pregnancy and in non-pregnant state. The clinician often has a difficult task in diagnosing and managing acute abdomen in pregnancy. Clinical evaluation is further confounded by various anatomical and physiological changes occurring in pregnancy. The growing gravid uterus too causes difficulty in detailed examination. The general reluctance to use conventional X-rays because of pregnancy should be set aside when faced with a seriously ill mother. A reluctance to operate during pregnancy adds unnecessary delay, which increases morbidity for both the mother and the fetus. Adnexal accidents should always be kept in mind in a woman with acute abdomen even if she is not pregnant. Such mistakes should be avoided as prompt diagnosis and appropriate therapy are crucial. A general approach to acute abdominal conditions in pregnancy is to manage these problems considering the risk to mother regardless of the pregnancy.