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.

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.

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.

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.

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.

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.

Psychological aspects of infertility due to various causes--prospective study.

SUBJECTS AND METHODS: One hundred and twenty infertile couples (30 each among unexplained infertility, anovulation, tubal factor, and male factor groups) and 30 fertile couples as controls were evaluated for psychological assessment by different psychological test instruments. Initial evaluation was done at recruitment, followed by reassessment at 3, 6, 9 and 12 months during the infertility work-up, and at the end when the specific diagnosis and the management and prognosis were disclosed. RESULTS: Psychological components were found to play a significant role in infertility of unknown etiology, especially in the male partner. They affected the personality and social behavior of the male partner and caused anxiety, but led to depression in the female partner. In cases of organically caused infertility, partners were worried about the other's reaction. Anxiety was significantly greater in the partner with the fertility problem than in the other partner. Life events were significant in the partner in whom the fertility problem was detected. Periodic psychological assessment was not affected by infertility work-up on the male partner in any of the groups, whereas anovulation and tubal factor infertility showed a significant psychological effect on the female partner at the end of work-up. Depression and anxiety in the female partner were evident soon after the investigation started.

The need for clinical evaluation and semen analysis of infertile men.

OBJECTIVE: Although many men in Third World countries are reluctant to participate in an infertility work-up, we collected data from a group of husbands of females attending our infertility clinic. We intend to present these results as motivation for other men to realize the importance of an evaluation when they are involved in a barren marriage. STUDY METHODS: A detailed history was taken, and physical and urogenital examination was carried out on 400 male partners of women attending the infertility clinic of PGIMER Chandigarh. Semen analysis was interpreted as normal or abnormal according to the WHO manual. RESULTS: Age of the male partners of 400 infertile couples and their duration of infertility correlated with the pregnancy rate. Fifty percent of the men with a past history of infection, medical or surgical problems had abnormal semen analysis. The presence of urogenital abnormalities had a significant correlation with low sperm count and low motility. Social problems related to alcohol and smoking produced low pregnancy rates. CONCLUSION: A detailed history, examination and work-up of male partners of infertility couples is as important as in the female partner. Counseling and treatment may improve pregnancy rates.

Serial plasma fibronectin levels in pre-eclamptic and normotensive women.

OBJECTIVE: Endothelial cell damage has been put forward as an underlying factor for development of pre-eclampsia. This study was carried out to see if fibronectin, which is a marker of endothelial damage, could be used as a marker of pre-eclampsia. METHODS: A longitudinal study was conducted on 100 normotensive primigravidae registered before 20 weeks of gestation. These subjects were followed until delivery and three blood samples were collected, first at registration, i.e. before 20 weeks, second around 28 weeks and third at 36 weeks or later till delivery. Fibronectin levels were assayed by ELISA and women observed for any signs of pre-eclampsia. RESULTS: Fourteen subjects developed pre-eclampsia. Fibronectin levels were observed to rise as pregnancy advanced but the rise was significantly higher in subjects who developed pre-eclampsia. The fibronectin levels were also significantly higher in these 14 subjects even in the first sample, i.e. before 20 weeks of gestation when compared with normotensive subjects (P < 0.01). CONCLUSIONS: Fibronectin levels could be used as an early valuable biomarker for the development of pre-eclampsia.

Is hysterosalpingography an important tool in modern gynecological practice?

OBJECTIVE: To assess the value of hysterosalpingography (HSG) in diagnosing tubal patency and peritubal adhesions. PATIENTS AND METHODS: HSG was followed whenever possible by diagnostic laparoscopy with chromopertubation to give the final prognosis in cases of infertility. RESULTS: Normal HSG findings were obtained in 669 women, and abnormal ones in 306. No significant correlation was found between age of patient, duration, type of infertility, and HSG findings. Tubal blockage was seen in 89.2% and uterine factor in 9.4% of cases. Peritubal adhesions were suggestive in 12.75% of cases. On laparoscopy, done in about half of these women, findings were in agreement with HSG in 59.87% of cases. Follow-up was carried out whether the woman conceived, had a laparotomy, or required further investigations. CONCLUSION: Although somewhat insensitive, the high specificity of hysterosalpingography makes it very helpful for ruling out tubal disease, even where endoscopic evaluation is available.

Comparison of ondansetron with ondansetron and dexamethasone in prevention of PONV in diagnostic laparoscopy.

PURPOSE: To compare the efficacy of ondansetron-dexamethasone combination with ondansetron alone for prevention of postoperative nausea and vomiting (PONV). METHODS: This double blind, randomized study was carried out in 51 female patients, aged 20-40 yr, ASA-1 physical status undergoing gynecological diagnostic laparoscopy. Group 1 (n = 26) received 4 mg ondansetron i.v. and group 2 (n = 25) received a combination of 4 mg ondansetron and 8 mg dexamethasone i.v. soon after induction of anesthesia. Postoperatively patients were assessed hourly for four hours and then at 24 hr for nausea, vomiting, pain and post anesthetic discharge score. Vomiting occurring up to two hours was considered early vomiting and from 2-24 hr as delayed vomiting. RESULTS: The postoperative nausea score was lower in patients receiving a combination of ondansetron and dexamethasone (3.76) than ondansetron alone (4.38) at 0 hr (P < 0.01), 2 hr (P < 0.05) and 24 hr (P < 0.01). In group 1, 38.5% of patients had a nausea score of > or = 5 (major nausea) compared with only 12% of patients in group 2 (P < 0.025). The overall incidence of vomiting was greater in group 1 (35%) than in group 2 (8%) (P < 0.05). The combination group showed better control of delayed vomiting compared with the ondansetron group (4% vs 35%) (P < 0.01). CONCLUSION: The combination of ondansetron and dexamethasone provides adequate control of PONV, with delayed PONV being better controlled than early PONV.