Stillbirths in India: Current Status, Challenges, and the Way Forward.

Stillbirth is a major public health challenge and a multifaceted issue that leads to significant financial, physical, mental, financial, and psychosocial implications. India has made substantial progress in stillbirth reduction. Yet, many challenges continue and the absolute number of stillbirths remain high. This paper presents the national and state level burden of stillbirths and discusses about the magnitude, risk factors, causes and inequities in stillbirths. A few additional approaches for reduction of preventable stillbirths have been suggested. The authors argue that the institutional mechanisms need to be developed to ensure all stillbirths are registered in a timely manner. There is a need for standard definition for classification of stillbirths and document the cause, to roll-out suitable interventions. There is a need for state specific interventions to address different causes, as Indian states have variable stillbirth rates. The stillbirth audits should be institutionalised as a continuous quality improvement exercise to bring local accountability and reduce stillbirth rate. The healthcare system and providers must be trained to offer bereavement support to the affected mothers and families. These approaches should be implemented through primary healthcare system as well.

Agromet wheat app for estimation of phenology and yield of wheat under Punjab conditions.

The field experiments were conducted at the Research Farm, Punjab Agricultural University, Ludhiana, during rabi seasons of 2017-18 and 2018-19. The wheat varieties, viz. PBW-725, PBW-677, and HD-3086, were sown on 25th October, 15th November, and 5th December during both the crop seasons. Regression equations between grain yield, dry matter, and growing degree days were developed, and their performance efficiency was evaluated using mean square error (MSE), root mean square error (RMSE), mean absolute percentage error (MAPE), Akaike information criteria (AIC), and Schwarz-Bayesian information criteria (SBC), and the lowest values of AIC and SBC were used for wheat yield prediction. Based on historical data, agroclimatic index-based regression models were also developed for grain yield prediction at vegetative and reproductive stages under different dates of sowing. At the reproductive stage, the accumulated growing degree day (AGDD)-based model for 25th October sowing that gave 16 percent error, followed by 15th November sowing with 5.7 percent error, is the best model for yield prediction having minimum error. "Agromet wheat app," which is a mobile-based android app, was developed. This app is simple and has easy user interface which gives information about wheat management practices, weather, and insect-disease warnings and calculation of growing degree days at different phenophases of wheat in English and regional language Punjabi for three agroclimatic zones, viz., submountain undulating zone (Gurdaspur), central plain zone (Ludhiana), and western zone (Bathinda).

Factors affecting seasonal changes in blood pressure in North India: A population based four-seasons study.

OBJECTIVE: There are no community based, longitudinal, intra individual epidemiological studies on effect of weather and season on blood pressure (BP). We evaluated the effect of season and temperature on prevalence and epidemiology of BP in tropical climate. METHODS AND RESULTS: It was a longitudinal cross sectional survey of rural and urban subjects in their native surroundings. BP was measured in four different seasons in same subjects. A total of 978 subjects (452 rural and 521 urban) were included in the current analysis. Demographic characteristics such as age, gender, education, occupational based physical activity and body mass index (BMI) were recorded. Mean BP, both systolic and diastolic were significantly higher in winter season as compared to summer season. Mean difference between winter and summer was 9.01 (95% CI: 7.74-10.28, p<0.001) in systolic BP and 5.61 (95% CI: 4.75-6.47, p<0.001) in diastolic BP. This increase in BP was more marked in rural areas and elderly subjects. Prevalence of hypertension was significantly higher during winter (23.72%) than in summer (10.12%). CONCLUSION: BP increases significantly during winter season as compared to summer season. Increase is more marked in rural areas and elderly subjects. Seasonal variation in BP should be taken into account while looking at prevalence of hypertension in epidemiological studies.

Impact of SurePath® liquid-based preparation in cytological analysis of peritoneal washing in practice of gynecologic oncology.

CONTEXT: Peritoneal washing is performed for staging of gynecologic tumors to detect subclinical intraperitoneal metastases. AIM: The aim of the present study was to assess the impact of SurePath™ liquid-based cytology (LBC) in peritoneal washing in various gynecological malignancies. SETTINGS AND DESIGN: An audit of peritoneal-fluid/washing (January 2012 to July 2013) was performed with corresponding gynecologic specimens. All peritoneal washings were processed using both conventional and LBC technique. Suspicious cases on cytology were reported along with gynecologic specimens. RESULTS: There were a total of 393 peritoneal fluids. Eighty-three (21.1%) were positive for malignancy, and the corresponding histology was available in 352 (89.6%) cases. Sixty-nine positive samples had ovarian malignancies and 5 had uterine causes. There were 9 cases of peritoneal washings in which no histopathology was available. The most common cause of positive peritoneal cytology was ovarian serous carcinoma in 55/84 (65.5%) cases. Other causes included mucinous cystadenocarcinoma, dysgerminoma, squamous cell carcinoma in teratoma, yolk sac tumor, and granulosa cell tumor. Uterine causes included 2/45 (4.4%) cases of endometrioid adenocarcinoma, » (25%) cases of clear cell carcinoma, ½ (50%) cases of carcinosarcoma, and » (25%) cervix carcinoma. On review of positive cases (n = 83), 10 cases were identified, which had nil (n = 4) to low cellularity (<3 tumor clusters/smear; n = 6) on conventional smears, and were confirmed malignant on LBC. CONCLUSIONS: The most common ovarian malignancy causing positive peritoneal cytology is papillary serous carcinoma. Endometrioid adenocarcinoma rarely leads to positive peritoneal cytology. LBC technique leads to concentration of tumor cells causing reduction in false negative cases, especially in hemorrhagic and low-cellular cases.

Loop-mediated isothermal amplification assay for detection of Mycobacterium tuberculosis complex in infertile women.

BACKGROUND: Female genital tuberculosis (FGTB) has a profound impact on the reproductive health of patients including infertility. Conventional diagnostic techniques have low sensitivity and specificity as well as long turnaround time. There is a need of developing newer, rapid and practically adaptable technique, especially in low-income countries. OBJECTIVE: To standardize and evaluate loop-mediated isothermal amplification (LAMP) technique for diagnosis of FGTB. METHODS: A total of 300 endometrial biopsy samples from infertile females were subjected to Ziehl-Neelsen (ZN) staining, Lowenstein-Jensen culture, automated culture (BACTEC mycobacterial growth indicator tube), histopathological examination (HPE), nucleic acid amplification by polymerase chain reaction (PCR) and LAMP technique. Composite gold standard (either smear/culture/HPE/PCR positive) was considered for calculation of outcome parameters. RESULTS: The observed sensitivities of ZN smear, culture, HPE, PCR and LAMP were 2.94%, 10.29%, 8.82%, 95.59% and 66.18%, respectively. Overall concordance between PCR and LAMP was 63%, which shows a good agreement. CONCLUSION: This study is the first to evaluate LAMP in the diagnosis of FGTB and found it to be a rapid and convenient technique, especially in low resource endemic settings.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

AIMS: Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. MATERIALS AND METHODS: In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. RESULTS: The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. CONCLUSION: Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy.

Comparison of haematological and biochemical changes between non-anaemic and anaemic primigravid women in a north Indian population to establish normative values.

Pregnancy is accompanied by several haemodynamic, biochemical and haematological changes, which may lead to severe problems, if they are not suitably addressed. The current study highlights the haematological and biochemical differences observed in anaemic (AP) and non-anaemic primigravida (NAP), in the 2nd trimester, in a north Indian population. There were significant differences (p < 0.05) in the body weight and body temperature of NAP compared with AP. A significant decrease (p < 0.001) in haematological parameters including haemoglobin, haematocrit, erythrocyte count, MCH and MCHC, was observed in AP; however, MCV was found to be significantly higher (p = 0.038). Many biochemical parameters viz. potassium, albumin, total protein and calcium levels were significantly reduced (p < 0.01) in AP, except alkaline phosphatase whose level was found significantly increased (p < 0.01). The findings of the study suggest that haematological and biochemical changes take place in anaemia during pregnancy. Further, the results obtained should be used for establishing normative values for similar populations.

Fine needle aspiration cytology in ovarian lesions: an institutional experience of 584 cases.

OBJECTIVE: To assess the diagnostic value of fine needle aspiration cytology (FNAC) in ovarian lesions. METHODS: This was a retrospective study of ultrasound-guided (US) FNAC of 584 ovarian lesions from January 1998 to July 2010. The lesions were categorized into non-neoplastic lesions, neoplastic lesions and inadequate aspirates. The results were compared with the corresponding histopathology whenever available. RESULTS: Of the 584 lesions, 180 (30.8%) were reported as non-neoplastic (48 non-specific inflammation, 11 tuberculosis, 63 functional cysts and 58 endometriotic cysts), 249 (42.6%) as neoplastic (81 benign lesions/tumours and 168 malignant) and 155 (26.5%) as inadequate. Based on the subsequent histopathology, which was available in 121 (20.7%), the cases were divided into those that were concordant and discordant. Concordant cases comprised 92/121 (76%), including 28 non-neoplastic lesions (seven non-specific inflammation, nine functional cysts and 12 endometriotic cysts), 42 surface epithelial tumours (13 benign and 29 malignant), 10 germ cell tumours (five mature cystic teratomas and five mixed germ cell tumours), seven sex-cord stromal tumours (three granulosa cell tumours, one sclerosing stromal tumour, one strümal leutoma, one Sertoli Leydig cell tumour and one malignant Sertoli cell tumour) and five miscellaneous lesions (one plasma cell tumour, two leiomyosarcomas and two cases of necrosis). Discordant cases comprised 29/121 (24%) (21were inconclusive or inadequate on cytology), including four endometriotic cysts, 14 surface epithelial tumours (one cystadenofibroma, one borderline mucinous tumour and 12 carcinomas), five germ cell tumours (two immature teratomas and three mature cystic teratomas), two thecomas, one fibroma, one sclerosing stromal tumour, one fibrosarcoma and one myxoma. FNAC sensitivity for a diagnosis of malignancy was 85.7%, specificity 98.0%, positive predictive value 97.7%, negative predictive value 87.7% and accuracy 92.0%, if 21 inconclusive/inadequate FNACs were excluded; with the latter taken as false negatives, sensitivity was 73.7% and accuracy 76.0%. CONCLUSION: FNAC has a high specificity for diagnosis of ovarian/adnexal lesions but greater experience is required for the accurate subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate results.

OS001. Pregnancy outcome in subsequent pregnancies after eclampsia.

INTRODUCTION: Eclampsia in the previous pregnancy may have impact on future reproductive performance of the women. Few studies have been conducted in recent years to review the subsequent pregnancy outcome. In this study women with previous eclampsia were followed up in subsequent pregnancy and outcome was compared with normotensive control group. OBJECTIVES: To study the risk of recurrence of hypertension and associated complications in subsequent pregnancies following eclampsia. METHODS: Fifty-three pregnant women with previous history of eclampsia were supervised and delivered in PGIMER, Chandigarh, India (2001 April-2011 March) were studied prospectively. The pregnancy outcome was compared with 106 age and gravida matched controls who had remained normotensive in previous pregnancies. The data analysis was done by Chi-square test and Student 't' test. RESULTS: Amongst women with previous eclampsia eight women (15%) were found to have underlying chronic hypertension. The incidence of gestational hypertension and pre-eclampsia was 37.7% amongst these women, compared to 7.5% in control group (p=0.0001). Preterm deliveries mainly due to preterm inductions were higher (32%) amongst women with previous eclampsia compared to 12% amongst controls (p=0.0004). Incidence of intra uterine growth restriction was significantly higher amongst cases (15% vs 1.5%, p=0.0003). CONCLUSION: Women with previous eclampsia have higher incidence of chronic hypertension. These women are at significant risk to develop hypertensive disorders of pregnancy and its related complications. The recurrence of eclampsia is low with aggressive and vigilant antenatal care.

Temporal trends of malondialdehyde in stored human plasma.

Malondialdehyde (MDA) is widely used as oxidative stress biomarker in biomedical research. Plasma is stored in deep freezers generally till analysis. Effect of such storage on MDA values, which may be variable and prolong, was incidentally observed in the ongoing study which is to estimate oxidative stress with oral iron. Plasma from blood samples of pregnant women (20-30 years age) in third trimester of singleton pregnancy (n = 139), consuming oral iron tablets was stored at -20 °C with intention of MDA estimation, as soon as possible. However logistic problems led this storage for prolonged and variable period (1-708 days). When values of MDA estimated using "Ohkawa" 79 method and readings were plotted against time to check the temporal effect, it showed a hyperbolic curve. Standard deviation (SD) was lowest when samples were tested within 3 weeks time. The samples analyzed within 3 weeks had mean ± SD value of 31.59 ± 26.11 µmol/L, while 123.7 ± 93.97 and 366.5 ± 189.8 µmol/L for samples stored for 1-3 and 4 months to 1 year respectively. Mean ± SD were 539.9 ± 196.8 in the samples store for more than a year. Rate of change in values was also lowest (0.0433 µmol/L/day) in the samples tested within first 3 weeks, which rose to 1.2 µmol/L/day during 3 month's storage. This rate peaked at storage of 120 days (1.87 µmol/L/day) and fell to 0.502 µmol/L/day in the second year of storage. It is concluded that at -20 °C, only 3 weeks of storage time should be considered valid for fairly acceptable stability in MDA values.

Atypical squamous cells and low-grade squamous intraepithelial lesion in cervical cytology: cytohistological correlation and implication for management in a low-resource setting.

OBJECTIVES: To perform an audit of all cervical smears reported as atypical squamous cells (ASC) and low-grade squamous intraepithelial lesion (LSIL) as in the Bethesda system (TBS) 2001, and determine their histological follow-up and outcome when available, in order to define the threshold for colposcopic referral. MATERIAL AND METHODS: A total of 25,203 cervical smears were screened over a period of 3 years (January 2006 - December 2008) and all ASC and LSIL smears were reviewed with the corresponding histological follow-up. All cervical intraepithelial neoplasia (CIN) grade 2 lesions and above (CIN2+) were considered as clinically significant lesions for analysis. RESULTS: Out of 25,203 cervical smears, 424 (1.7%) were reported as ASC and 113 (0.4%) as LSIL. Additionally, three were reported as atypical cells, not otherwise specified. The ASC : SIL ratio was 2.18 : 1. Follow-up histology was available in 153 (36.8%) of the ASC cases and revealed CIN2+ lesions in 22 (14.4%). Follow-up histology was available in 50 (44.2%) of LSIL cases and revealed clinically significant abnormalities in five (10%), all of which were CIN2. CIN3 and invasive squamous carcinomas were seen in 5.9% and 1.4%, respectively, of cases of ASC, and not seen in LSIL. Reclassification of ASC smears into ASC-US (ASC-undetermined significance) and ASC-H (ASC- high grade SIL not excluded) revealed ASC-H in 2.6% of all ASC smears, with a clinically significant outcome in 45.4%. CONCLUSION: In a low-resource setting where human papillomavirus testing is unaffordable, the threshold for colposcopic referral and follow-up histology should be ASC rather than SIL.

Severe anaemia in pregnancy: a tertiary hospital experience from northern India.

Anaemia is a major health problem among woman of reproductive age group, particularly in developing countries. We undertook this study to determine the maternal and perinatal outcome in patients with severe anaemia in pregnancy, with a haemoglobin concentration of < 7 g/dl. The in-hospital data were analysed for 12 months between January 2007 and December 2007 and 2.15% (n = 96) of women were found to have severe anaemia. Out of these, 18.75% had pre-term premature rupture of membranes and 5.12% of all deliveries were pre-term. Hypertensive diseases of pregnancy were seen in 17.7%; abruption in 3.12% and 9.37% had congestive cardiac failure. Postpartum haemorrhage was seen in 25.5% of the patients and 8.33% had puerperal pyrexia. Fetal distress was seen in 26% of and 33.33% had small for gestational age neonates; there were 16.66% stillbirths and 4.16% neonatal deaths. Of the 96 severely anaemic women, six died after admission. Our study shows that efforts must be taken towards safe motherhood and spreading awareness about the various consequences of anaemia, which is usually preventable with early correction.

Advanced germ cell malignancies of the ovary: should neo-adjuvant chemotherapy be the first line of treatment?

Malignant germ cell tumours of the ovary, though classically known for 'young age' and 'early stage' at presentation, are not uncommonly identified at advanced stages. Little is available in literature on the role of neo-adjuvant chemotherapy (NACT) in this group of tumours. Two patients with advanced stage ovarian germ cell tumours, including one with 45XO/46XY chromosomal mosaicism, were treated at our Institute with neo-adjuvant chemotherapy with Bleomycin, Etoposide and Cisplatin followed by surgery. Besides marked clinical improvement, intraoperatively both the patients presented no difficulty otherwise expected with widespread tumours, and histopathology report revealed no evidence of viable tumour. The article discusses the experience and suggested course of management of these tumours with NACT, which could be offered to patients with advanced malignancy in whom high surgical morbidity is anticipated or in whom only an operative biopsy was performed at laparatomy. Behaviour and management guidelines of dysgenetic gonads with XY mosaicism have also been discussed.

Steroid responsive prolonged thrombocytopenia in dengue.

Prolonged thrombocytopenia in a usual case of dengue virus infection is uncommon. Dengue-related thrombocytopenia is self-limiting and responds within 3-5 days. An underlying immunological disorder may be responsible for delayed return of platelet count to a normal level. We present a case of prolonged thrombocytopenia in a case of dengue hemorrhagic fever. The response to steroids suggests a possible immunological dysfunction.

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting.

OBJECTIVES: To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001. METHODS: A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out. RESULTS: AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old (P = 0.010). CONCLUSION: The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.

Correlation of 2-hour and 4-hour urinary proteins with 24-hours proteinuria in hospitalized patients with preeclampsia.

OBJECTIVE: To determine whether 2-hour and 4-hour urinary proteins correlate with 24-hour proteinuria in patients with preeclampsia. STUDY DESIGN: Protein estimation was done from 2-hour, 4-hour, and 24-hour urine samples in 50 women with preeclampsia and the results were compared. RESULTS: Statistical analysis demonstrated no significant difference in the mean protein excretion when comparing the 2-hour values with the 24-hour and further comparing 4-hour values with the 24-hour value. The values of 2-hour and 4-hour urine proteins in total volume (TV) correlated well with 24-hour value for mild & severe disease (p<0.001). Amount of the protein excretion in 2-hour and 4-hour samples predicted mild preeclampsia with positive predictive value of 100% and negative predictive value (NPV) of 80%. NPV of both the samples for severe preeclampsia was 100%. CONCLUSION: 2-hour and 4-hour proteinuria can be used for initial assessment of preeclampsia thereby avoiding the inconvenience and delay in treatment.

First and second trimester induced abortions in women with cardiac disorders: a 12-year analysis from a developing country.

This was a retrospective analysis of induced abortions (1st and 2nd trimester) in women with cardiac disease over a 12-year period (September 1994-December 2006). Of the 3,096 women who underwent an induced abortion during this period, 65 (2.1%) had an associated cardiac disease (NYHA class I or II = 58, class III or IV = 7). Their mean age was 29.6 years and 48/65 (73.9%) had opted for concurrent sterilisation. Nearly all 1st trimester abortions (52/53) were performed by suction evacuation. Among the 12 women undergoing 2nd trimester abortions, seven received vaginal misoprostol with or without oral mifepristone, four received varying combinations of intracervical dinoprostone, extra-amniotic saline (EAS) and oxytocin and elective hysterotomy was performed in one. Complications observed among the 1st trimester terminations were incomplete abortion in 1/53 (1.8%) and prolonged bleeding in 3/53 (5.6%). Method failure was the only complication seen in 2/12 (16.6%) 2nd trimester abortions. There was no major morbidity or mortality. Mifepristone and misoprostol used for 2nd trimester induced abortions were found to be safe in the few women so treated.

Pregnancy complicated by severe chronic hypertension: a 10-year analysis from a developing country.

OBJECTIVE: To assess pregnancy outcome in patients with severe chronic hypertension. METHODS: A retrospective analysis of a 10-year period (1995-2004) in a referral hospital in northern India. The outcome was compared with those women with mild chronic hypertension who registered in the hypertensive disorders with pregnancy clinic immediately before and after each woman with severe chronic hypertension. RESULTS: Hospital data identified 25 such women. Superimposed preeclampsia (36.4% versus 8%), preterm delivery (86.4% versus 42%), and perinatal mortality (27.2% versus none) were increased in patients with severe chronic hypertension as compared to those with mild hypertension. CONCLUSIONS: The small number of cases reflects the lack of antenatal supervision in developing countries. A much larger number of women are referred in the third trimester with eclampsia or severe preeclampsia, at which time it is not possible to identify whether or not they had underlying hypertension. Adverse events were found to occur more often in patients with severe chronic hypertension compared with those with mild hypertension.