Swaraj Batra

Maternal and perinatal outcome in varying degrees of anemia

Objectives: To analyze the maternal and perinatal outcome in varying degrees of anemia. Methods: A total of 447 pregnant women were divided into group I (Hb>11 g%, n=123 women), group II (Hb 9–10.9 g%, n=214 women), group III (Hb 7–8.9 g%, n=79 women) group IV (Hb<7 g%, n=31 women). Their maternal and perinatal outcome, mode of delivery, duration of labor and postpartum complications were noted and analyzed using multiple logistic regression to calculate odds ratios (95% CI) for duration of labor, mode of delivery and low birth babies. Chi square or Fishers exact test was employed for difference in proportions and Students t‐test for testing difference between means. Results: Mean age (27±4.25 years) and number of women with parity >3 were highest in group IV. The patients with Hb<8.9 g% had a 4–6‐fold higher risk of prolonged labor compared to Hb>11 g%. The odds ratios for abnormal delivery (cesarean and operative vaginal deliveries) showed a 4.8‐fold higher risk (95% CI 1.82, 12.7) in patients with Hb ≤7.5 g%. The mean birth weight was maximum in the 9.6–10.5 g% category that fell with both increasing and decreasing hemoglobin values, being lowest in Group IV. Women in Group II had lowest number of low birth weight and IUGR babies, no stillbirths and neonatal deaths, lowest induction and operative delivery rates. Conclusions: Mild anemia fared best in maternal and perinatal outcome. Severe anemia was associated with increased low birth weight babies, induction rates, operative deliveries and prolonged labor.

Human papillomavirus type 16 variant analysis of E6, E7, and L1 genes and long control region in biopsy samples from cervical cancer patients in north India.

ABSTRACT High-risk human papillomaviruses (HPVs), particularly HPV types 16 and 18 (HPV-16 and HPV-18, respectively), play a cardinal role in the etiology of cervical cancer. The most prevalent type, HPV-16, shows intratypic sequence variants that are known to differ in oncogenic potential and geographic distribution. This study was designed to analyze sequence variations in E6, E7, and L1 genes and the LCR (for long control region) of HPV-16 in cervical cancer patients to identify the most prevalent and novel HPV-16 variants and to correlate them with the severity of the disease. Cervical biopsies from 60 HPV-16-positive cancer cases were analyzed by PCR and DNA sequencing. The most frequently observed variations were T350G (100%) in E6, T789C (87.5%) in E7, A6695C (54.5%) in L1, and G7521A (91.1%) in the LCR. In addition, only one novel variant (T527A) in E6 and four new variants each in L1 (A6667C, A6691G, C6906T, and A6924C) and in the LCR (C13T, A7636C, C7678T, and G7799A) were identified. While E7 was found to be highly conserved, the variant 350G of E6 was the most prevalent in all of the histopathological grades. The majority of LCR variants were found at the YY1 transcription factor binding sites. Interestingly, a complete absence of the Asian lineage and a high prevalence of European lineages in E6, E7, L1, and the LCR (85, 86.7, 67.7, and 63.3%, respectively) indicate a possible epidemiological linkage between Europe and India with regard to the dissemination of HPV-16 infections in India.

Visual inspection of the cervix with acetic acid for cervical intraepithelial lesions.

Objective: Evaluation of visual inspection of the cervix with acetic acid (VIA) for screening cervical intraepithelial neoplasia. Methods: In this prospective study, 400 women were screened using the Papanicolaou (PAP) smear, VIA and colposcopy. Those who had positive results with any of the screening methods underwent large loop excision of the transformation zone (LLETZ). The sensitivity and specificity of each of the screening methods was analyzed. Results: The sensitivity of VIA (96.7%) was much higher than that of the Pap smear (50%), and almost as high as that of colposcopy (100%). The specificity of VIA (36.4%) was lower than that of the Pap smear (97%) and colposcopy (96.9%), resulting in high false‐positive rates for VIA. Two cases of endocervical lesions were missed with VIA. Conclusion: Visual inspection of the cervix with acetic acid is very sensitive for ectocervical lesions. The advantages of the VIA method are its low cost and ease of use (it can be used by paramedical workers), its high sensitivity and its immediate results (it is possible to “see and treat” at the first visit). Its main limitation is a high rate of false‐positive results, which may lead to overtreatment if a “see and treat” policy is applied.

Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection

BackgroundRecent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer and cancer tissues were analyzed for the HPV positivity and evaluated for STAT3 expression and its phosphorylation by immunoblotting and immunohistochemistry whereas STAT3-specific DNA binding activity was examined by gel-shift assays.ResultsAnalysis of 120 tissues from cervical precancer and cancer lesions or from normal cervix revealed differentially high levels of constitutively active STAT3 in cervical precancer and cancer lesions, whereas it was absent in normal controls. Similarly, a high level of constitutively active STAT3 expression was observed in HPV-positive cervical cancer cell lines when compared to that of HPV-negative cells. Expression and activity of STAT3 were found to change as a function of severity of cervical lesions from precancer to cancer. Expression of active pSTAT3 was specifically high in cervical precancer and cancer lesions found positive for HPV16. Interestingly, site-specific accumulation of STAT3 was observed in basal and suprabasal layers of HPV16-positive early precancer lesions which is indicative of possible involvement of STAT3 in establishment of HPV infection. In HPV16-positive cases, STAT3 expression and activity were distinctively higher in poorly-differentiated lesions with advanced histopathological grades.ConclusionWe demonstrate that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV16-mediated cervical carcinogenesis.

Calcium supplementation for the prevention of pre-eclampsia.

To study the effect of calcium supplementation during pregnancy on blood pressure and maternal and neonatal outcomes.

Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas

Objectives: To observe the effect of the antioxidant lycopene on the occurrence of pre‐eclampsia and intrauterine growth retardation in primigravida women. Methods: A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16–20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed‐up until delivery for development of pre‐eclampsia, mode of delivery and fetal outcome. Results: The two groups were comparable in their maternal characteristics. Pre‐eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi‐square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2±5.98 mmHg vs. 86.7±3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17±315.76 g vs. 2657±444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033). Conclusions: The results of the present study suggest that the antioxidant lycopene reduces the development of pre‐eclampsia and intrauterine growth retardation in primigravida women.

Human papillomavirus (HPV) DNA detection in self-collected urine

Non‐invasive sampling of human genitals to identify high‐risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self‐collected urine can be used as a simple, non‐invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. Method: Self‐collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry ‘paper smear’ method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. Results: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high‐risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry ‘paper smear’ showed perfect matching positivity for HPV between urine and cervical scrape. Conclusions: The use of urine coupled with its dry collection as ‘paper smear’ facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non‐invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.

Latent celiac disease in reproductive performance of women

OBJECTIVE To investigate the prevalence of positive serologic findings for celiac disease in Indian women with poor reproductive performance. DESIGN Cross-sectional except that the women with intrauterine growth restriction were followed prospectively until delivery. SETTING Department of Obstetrics and Gynecology of a tertiary teaching hospital, New Delhi. PATIENT(S) Eight hundred ninety-three women (104 women with idiopathic recurrent abortion, 104 women with unexplained stillbirth, 230 cases of unexplained infertility, 150 pregnant women with idiopathic intrauterine growth restriction, 305 control cases). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The presence of antigliadin IgA and IgG, anti-tissue transglutaminase IgA by ELISA, and IgA antiendomysium antibody by indirect immunofluorescence microscopy. RESULT(S) The seroprevalence of transglutaminase IgA was 6.70% in the group with recurrent abortion, 5.70% in the group with stillbirth, 5.65% in the group with infertility, 9.33% in the group with intrauterine growth restriction, and 1.30% in the control group. Rates of previous preterm births, low-birth-weight infants, and cesarean section were higher in seropositive women compared with seronegative subjects. CONCLUSION(S) Women having poor reproductive performance had subclinical celiac disease. The serology for celiac disease can be considered in idiopathic cases.

Association between human leukocyte antigen class II alleles and human papillomavirus-mediated cervical cancer in Indian women.

We investigated the association of human leukocyte antigen (HLA) II (DRB1 and DQB1) alleles with susceptibility to human papillomavirus (HPV)-associated cervical precancer and cancer cases in a hospital-based case-control study in a northern Indian population. A total of 202 subjects, including 100 patients comprising 31 cervical precancer (cervical intraepithelial neoplasia [CIN] 2/3) and 69 invasive cervical cancer cases, and 102 healthy controls participated in the study. Both patients and controls were screened for HPV infection using a polymerase chain reaction (PCR-based approach. Low-resolution PCR-sequence specific priming (PCR-SSP) was used to genotype HLA II (DRB1 and DQB1). Our results demonstrate that the DRB1*15 allele/DRB1*15-DQB1*06 haplotype may have a predisposition for HPV infection (p(c) < 0.05) or cervical cancer/precancer (p(c) < 0.05) development, whereas the DRB1*04 allele/DRB1*04-DQB1*03 haplotype might exhibit susceptibility to cervical precancerous lesions (p(c) < 0.05). The DRB1*13 allele/DRB1*13-DQB1*06 haplotype was strongly protective against risk to HPV infection (p(c) < 0.002) as well as cervical cancer (p(c) 0.01). Therefore, we have demonstrated that HLA DR-DQ polymorphisms are involved in genetic susceptibility to cervical cancer or HPV infection in a northern Indian population.

Association of MDM2 and p53 Polymorphisms with the Advancement of Cervical Carcinoma.

Cervical cancer is one of the most common gynecological malignancies that causes a serious health problem worldwide. The aim of the present study was to analyze the association of p53 codon72 (arginine/proline) polymorphism (rs1042522) and Murine Double Minute 2 (MDM2) SNP309 T/G (rs2279744) with the advancement of cervical cancer by using polymerase chain reaction-restriction fragment length polymorphism method followed by direct sequencing. The frequencies of GG genotype at 309 position in the second promoter (P2) of MDM2 and Arginine in codon72 of p53 were found to be 3.5 (odds ratio [OR]=3.51; 95% confidence interval [CI]=1.93-6.4; p<0.0001) and 5 (OR=4.978; 95% CI=2.7-9.2; p<0.0001) fold higher, respectively, in cases than in the control. On gene-gene interactions between MDM2 and p53 polymorphisms, the frequency of MDM2 G/G and p53 Arg/Arg together was found to be 6.5-fold higher in cervical cancer patients compared with healthy controls (OR=6.497; 95% CI=2.987-14.13; p<0.0001). We found an association of p53 codon72 arginine and MDM2 SNP309 GG genotype with different clinical and histological grades, human papillomavirus (HPV) infection, and age at the time of diagnosis of cervical cancer. In conclusion, Arginine at codon72 of p53 and GG genotype at 309 in P2 of MDM2 together reveal a direct proportionality with the tumor grade of cervical cancer along with HPV infection in postmenopausal women.