Effects of the WHO Labour Care Guide on cesarean section in India: a pragmatic, stepped-wedge, cluster-randomized pilot trial.

Cesarean section rates worldwide are rising, driven by medically unnecessary cesarean use. The new World Health Organization Labour Care Guide (LCG) aims to improve the quality of care for women during labor and childbirth. Using the LCG might reduce overuse of cesarean; however, its effects have not been evaluated in randomized trials. We conducted a stepped-wedge, cluster-randomized pilot trial in four hospitals in India to evaluate the implementation of an LCG strategy intervention, compared with routine care. We performed this trial to pilot the intervention and obtain preliminary effectiveness data, informing future research. Eligible clusters were four hospitals with >4,000 births annually and cesarean rates ≥30%. Eligible women were those giving birth at ≥20 weeks' gestation. One hospital transitioned to intervention every 2 months, according to a random sequence. The primary outcome was the cesarean rate among women in Robson Group 1 (that is, those who were nulliparous and gave birth to a singleton, term pregnancy in cephalic presentation and in spontaneous labor). A total of 26,331 participants gave birth. A 5.5% crude absolute reduction in the primary outcome was observed (45.2% versus 39.7%; relative risk 0.85, 95% confidence interval 0.54-1.33). Maternal process-of-care outcomes were not significantly different, though labor augmentation with oxytocin was 18.0% lower with the LCG strategy. No differences were observed for other health outcomes or women's birth experiences. These findings can guide future definitive effectiveness trials, particularly in settings where urgent reversal of rising cesarean section rates is needed. Clinical Trials Registry India number: CTRI/2021/01/030695 .

Development and Utility of Tools to Identify Preventable Perinatal Deaths: Results from a Community-based Interventional Study in Two Districts of Karnataka State, India.

BACKGROUND: The presently used perinatal death certificate devised by the World Health Organization is incomplete and does not help in identifying "preventability." OBJECTIVE: To develop tools that can help identify (1) preventable perinatal death and (2) preventable and/or avoidable cause for perinatal deaths. MATERIALS AND METHODS: As a prerequisite for conduct of a community-based interventional study in two different districts of Karnataka state, two information tools, Perinatal death reporting form (PeNDReF) and perinatal death audit report (PeNDAR), were designed. The process involved series of preparatory and review meetings, before and after the field work to list facilities available, categorize facilities, identify causality, assess risk factors, and assert preventability of a perinatal death. The process was repeated over a period of 6 months and the information tools, PeNDReF and PeNDAR, were finalized. Doctors and paramedical personnel of both the districts were trained to fill the tools, which were analyzed to ascertain contributing risk factors and identify preventable perinatal death. RESULTS: The use of PeNDAR led to identification of 5.7% of perinatal deaths as "preventable" and 19% as "possibly preventable." The use of PeNDReF helped in the identification of risk factors (maternal anemia 49.6%, age of marriage <20 years 18.7%, and maternal weight <50 kg 9.1%), avoidable/preventable factors related to quality of care, transport, and referral. CONCLUSIONS: These tools are useful for identifying "preventable" perinatal deaths and avoidable/preventable factors.

Documentation and Reporting of Perinatal Deaths in Two Districts of Karnataka, India: A Situational Analysis.

OBJECTIVE: In Karnataka state, perinatal mortality rate is almost equal to infant mortality rate. This preliminary study was conducted in two districts of Karnataka to study potential problems to start of perinatal death audit. METHODS: Hospitals providing maternal and child health care services, which met study inclusion criteria, in Dakshina Kannada and Koppal Districts were included. Following variables were studied: (i) Documentation and reporting systems in these hospitals; (ii) Role of health care personnel in documentation and reporting (iii) Existing system of audit, if any. RESULTS: Totally 94 hospitals met our criteria with Dakshina Kannda District having 63 (67.02%) and the rest in Koppal District. Documentation and reporting was poor in Koppal District and inadequate in Dakshina Kannada district. Health care personnel were apprehensive about perinatal death audit. CONCLUSION: Problems identified need to be addressed before starting perinatal death audit.

Towards a Common Etiopathogenesis: Periodontal Disease and Endometriosis.

CONTEXT: Periodontal disease and endometriosis are seen to share a common pathogenesis. There is only one report suggesting the possible association between the two conditions. AIMS: To study the association between endometriosis and periodontal disease. SETTINGS AND DESIGN: This was a case-control study. SUBJECTS AND METHODS: Periodontal screening was carried out in 25 women with endometriosis and 25 women without endometriosis. Severity of periodontal disease was classified based on the extent of loss of attachment. STATISTICAL ANALYSIS USED: Student's t-test, Mann-Whitney U test, and Karl Pearson correlation coefficient tests were used for statistical analysis. Results: The proportion of women with severe periodontitis was seen to be higher among women with endometriosis (70%). CONCLUSIONS: The results of the present study indicate the existence of a relationship between endometriosis and periodontal disease. However, further studies among larger cohorts of endometriosis may provide evidence about the association.

Correction to: Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy.

The original version of this article unfortunately contained a mistake. Ambika Devi K was not listed among the authors. The corrected authorship is given below.

Aberrant gene-specific DNA methylation signature analysis in cervical cancer.

Multicomponent molecular modifications such as DNA methylation may offer sensitive and specific cervical intraepithelial neoplasia and cervical cancer biomarkers. In this study, we tested cervical tissues at various stages of tumor progression for 5-methylcytosine and 5-hydroxymethylcytosine levels and also DNA promoter methylation profile of a panel of genes for its diagnostic potential. In total, 5-methylcytosine, 5-hydroxymethylcytosine, and promoter methylation of 33 genes were evaluated by reversed-phase high-performance liquid chromatography, enzyme-linked immunosorbent assay based technique, and bisulfate-based next generation sequencing. The 5-methylcytosine and 5-hydroxymethylcytosine contents were significantly reduced in squamous cell carcinoma and receiver operating characteristic curve analysis showed a significant difference in (1) 5-methylcytosine between normal and squamous cell carcinoma tissues (area under the curve = 0.946) and (2) 5-hydroxymethylcytosine levels among normal, squamous intraepithelial lesions and squamous cell carcinoma. Analyses of our next generation sequencing results and data from five independent published studies consisting of 191 normal, 10 low-grade squamous intraepithelial lesions, 21 high-grade squamous intraepithelial lesions, and 335 malignant tissues identified a panel of nine genes ( ARHGAP6, DAPK1, HAND2, NKX2-2, NNAT, PCDH10, PROX1, PITX2, and RAB6C) which could effectively discriminate among the various groups with sensitivity and specificity of 80%-100% (p < 0.05). Furthermore, 12 gene promoters (ARHGAP6, HAND2, LHX9, HEY2, NKX2-2, PCDH10, PITX2, PROX1, TBX3, IKBKG, RAB6C, and DAPK1) were also methylated in one or more of the cervical cancer cell lines tested. The global and gene-specific methylation of the panel of genes identified in our study may serve as useful biomarkers for the early detection and clinical management of cervical cancer.

Arterial Resistance in Late First Trimester as a Predictor of Subsequent Pregnancy-Related Hypertension.

OBJECTIVES: This study aimed to examine the association between indicators of arterial resistance occurring late in the first trimester and the subsequent development of pregnancy-related hypertension. METHODS: This study took place between May 2014 and August 2015 and included 329 consecutive women with singleton pregnancies attending the antenatal clinics of a medical college in Karnataka, India, during this period. Pulse pressure (PP) and uterine artery Doppler parameters were recorded between 11-14 gestational weeks. Consequently, women were followed-up until after delivery for subsequent hypertension. RESULTS: Hypertension occurred more frequently if PP was high (17.6% versus 14.4% of pregnancies without high PP; P = 0.713), if a diastolic notch (DN) was present (15.1% versus 12.8% of pregnancies with an absent DN; P = 0.612) and if the resistive index (RI) was raised (22.2% versus 14.3% of pregnancies without raised RI; P = 0.366). A raised pulsatility index (PI) was significantly associated with hypertension (P = 0.013). The risk of hypertension was approximately seven-fold higher if two or more arterial resistance indicators were used, except with a present DN plus a raised RI or a present DN plus high PP. All arterial resistance indicators showed negative predictability (>85.6%) and good specificity (≥95.0%), except for the presence of a DN. A population-specific cut-off PI value of 1.72 had high negative predictability (92.8%) and good sensitivity (70.8%) and specificity (65.1%). CONCLUSION: Raised PI in the late first trimester was a significant predictor of hypertension later in pregnancy. A combination of arterial resistance indicators may enhance prediction of subsequent hypertension.

Prevalence of human papillomavirus types and phylogenetic analysis of HPV-16 L1 variants from Southern India.

BACKGROUND: The human papillomavirus (HPV) and its variants show wide geographical distribution and have been reported to cause cervical lesions. With cervical neoplasia as the leading cancer in Indian women, the aim of the present study was to evaluate the multiple infection HPV type distribution and variant genotypes in cervical samples from the coastal Karnataka region, India. MATERIALS AND METHODS: A total of 212 samples were screened by nested polymerase chain reaction using PGMY9/11 and GP5+/6+ primers. HPV positive samples were sequenced to identify the types and a phylogenetic tree was constructed using the neighbor-joining method. RESULTS: Sequence analysis identified a total of 14 HPV types distributed in 20%, 73.3% and 82.5% of non-malignant, pre-malignant [low grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL)] and cervical cancer samples. The distribution of high risk HPV in cancer samples was HPV 16, 76.4%, HPV18, 11.7%, HPV81, 2.9%, HPV31, 1.4%, HPV35, 1.4% and HPV 45, 1.4%. Multiple infections were observed in 11.8% of tumor samples with HPV 16 contributing to 62.5% of cases. In non-malignant samples, 20% of HPV positive samples were detected with HPV16, 82.3%, HPV33, 5.8% and HPV58, 5.8% and very low incidence of multiple infections. Comparative phylogenetic analysis of HPV variants identified 9 HPV sequences as new papillomavirus species, predominantly classified as European lineage type. CONCLUSIONS: The findings for HPV infections associated with progression of cervical cancer in coastal Karnataka region and HPV variant analysis provide baseline data for prevention and HPV vaccination programs.

Variables influencing the integrity of lower uterine segment in post-cesarean pregnancy.

BACKGROUND: There is significant increase in proportion of cases with previous cesarean delivery requiring obstetric care. The available literature fails to provide uniform opinion on each woman's characteristics to identify risk of uterine rupture while planning trial of labor after cesarean. OBJECTIVE: To study the association of abnormal lower uterine segment with some of the present and previous obstetric variables including patient characteristics and surgical techniques at previous cesarean operation. MATERIALS AND METHODS: Consenting consecutive 96 post-cesarean singleton pregnancies admitting after 36 weeks gestation at the same facility from July 2011 to December 2012 for repeat cesarean, were studied. Only the cases with cephalic presentation and vertex as presenting part, having no placenta previa, polyhydramnios, uterine anomaly or fibroid and those who had previous one lower segment cesarean were recruited. Based on the intra-operative finding the lower uterine segment (LUS) was categorized into those having a normal and abnormal (grades 2-4) LUS. Sonographic assessment of LUS thickness and any abnormalities if any were noted. The findings of abnormal LUS (direct observation at surgery and sonographic impression within a week before surgery) were looked for association with some of the present and previous obstetric variables including patient characteristics and surgical techniques at previous cesarean operation using Student t, Chi square or Fisher's exact test for analysis as appropriate. Receiver operating curve analysis was used to determine the optimal cut off value for prediction of LUS integrity by ultrasound. RESULTS: Of the women recruited for the study, 36 were admitted in early labor and ultrasound evaluation of LUS was performed in 48 of the remaining 60 women admitted antenatal for elective cesarean delivery. There were 38 abnormal LUS (39.6%) with 22 of them (57.9%) graded as 'thinned out LUS'. The incidence of scar dehiscence (grade 3, cases 5) was 5.2% of 96 cases and there were no cases of scar rupture. Proportion of cases with abnormal LUS was significantly high when primary cesarean was done in preterm (p = 0.02); it was a single layer uterine closure (p = 0.02), and inter-cesarean interval was 54 months (p = 0.01). Abnormal LUS was also seen to be associated with maternal age beyond 35 years (p = 0.2), when cesarean was performed in labor (p = 0.5), following 18 h of rupture of membranes (p = 0.75), for a baby weight more than 3 kg (p = 0.4), and different suture materials (polyglactin 910 and chromic catgut) were used to close uterus at primary cesarean delivery (p = 0.1), and also if they had post-partum fever (p = 0.3). Ultrasound measurement of LUS by abdominal scan correlated with the intra-operative LUS grading and a thickness of more than 3.2 mm within a week before delivery and was seen to be the safe cut off above which most of the women had a normal LUS (sensitivity 92.3%, specificity 81.1%). CONCLUSION: Factors at primary cesarean operation significantly influence the state of LUS at term in subsequent pregnancy .

DNA promoter methylation-dependent transcription of the double C2-like domain ß (DOC2B) gene regulates tumor growth in human cervical cancer.

Double C2-like domain ß (DOC2B) gene encodes for a calcium-binding protein, which is involved in neurotransmitter release, sorting, and exocytosis. We have identified the promoter region of the DOC2B gene as hypermethylated in pre-malignant, malignant cervical tissues, and cervical cancer cell lines by methylation-sensitive dimethyl sulfoxide-polymerase chain reaction and bisulfite genome sequencing; whereas, it was unmethylated in normal cervical tissues (p < 0.05). The promoter hypermethylation was inversely associated with mRNA expression in SiHa, CaSki, and HeLa cells and treatment with demethylating agent 5-aza-2-deoxycytidine restored DOC2B expression. The region -630 to +25 bp of the DOC2B gene showed robust promoter activity by a luciferase reporter assay and was inhibited by in vitro artificial methylation with Sss1 methylase prior to transient transfections. Overexpression of the DOC2B gene in SiHa cells when compared with controls showed significantly reduced colony formation, cell proliferation, induced cell cycle arrest, and repressed cell migration and invasion (p < 0.05). Ectopic expression of DOC2B resulted in anoikis-mediated cell death and repressed tumor growth in a nude mice xenograft model (p < 0.05). DOC2B expressing cells showed a significant increase in intracellular calcium level (p < 0.05), impaired AKT1 and ERK1/2 signaling, and induced actin cytoskeleton remodeling. Our results show that promoter hypermethylation and silencing of the DOC2B gene is an early and frequent event during cervical carcinogenesis and whose reduced expression due to DNA promoter methylation may lead to selective cervical tumor growth.

Mitochondrial DNA variation analysis in cervical cancer.

This study was undertaken to investigate the mitochondrial DNA (mtDNA) variation in non-malignant and malignant cervical tissue samples. We have identified 229 and 739 variations non-malignant and malignant tissues respectively distributed over 321 locations in the D-loop (50 in non-malignant and 166 in malignant; 216 variations), coding region (139 in non-malignant and 455 in malignant; 594 variations) tRNA and rRNA genes (39 in non-malignant and 119 in malignant; 158 variations). Besides, 77 novel and 34 various other disease associated variations were identified in non-malignant and malignant samples. A total of 236 tumor specific variations in 201 locations representing 30.1% in D-loop, 59.3% in coding regions and 10.6% in RNA genes were also identified. Our study shows that D loop (in 67 locations) is highly altered followed by ND5 (35 locations) region. Moreover, mtDNA alterations were significantly higher in malignant samples by two tailed Fisher's exact test (P≤0.05) with decreased mtDNA copy numbers. Bioinformatic analysis of 59 non-synonymous changes predicted several variations as damaging leading to decreased stability of the proteins. Taken together, mtDNA is highly altered in cervical cancer and functional studies are needed to be investigated to understand the consequence of these variations in cervical carcinogenesis and their potential application as biomarkers.

Plastic spatula with narrow long tip provides higher satisfactory smears for Pap test.

BACKGROUND: Ayre spatula for cervical smear collection is being used despite the suggestion that different modified spatulas provide more satisfactory sampling. AIMS: To see whether the cytological pickup improves with the use of long tipped spatula. SETTING AND DESIGN: Rurally based University Hospital; crossover study. MATERIALS AND METHODS: Pap smear using Ayre spatula in 500 and with plastic narrow long tip (Szalay) spatula in 500 clinic attending women was taken and analyzed. Crossover smears were taken with modified spatula in 163 and using Ayre spatula in 187 women after 2 weeks of initial smears. The same pathologist made cytological reporting for all smears and was unaware of the type of spatula used. RESULTS: Smears from Ayre spatula had significantly higher reports of inadequate smears (94 of 500 vs. 68 of 500 for Ayre and Szalay, respectively; P = 0.032) and it remained so even after crossover (94 of 187 vs. 70 of 163 for Ayre and Szalay, respectively; P = 0.2). Cellular quality appeared better with smears taken using Szalay spatula, but the overall abnormal smear detection rate remained similar with either collection tool (χ(2) = 1.5; P = 0.2). CONCLUSIONS: Proportion of satisfactory smears is higher when long tip plastic spatula is used for collection of sample.

Periodontal disease and pregnancy hypertension: a clinical correlation.

BACKGROUND: Periodontal disease is thought to be associated with increased risk of systemic diseases and adverse pregnancy outcomes, including pregnancy hypertension (PH). The aim of the present study is to find the prevalence of periodontal disease in females with PH in a rural-based medical institute. METHODS: The present case control study was performed with 200 females, 100 with PH and 100 without PH. Antenatal periodontal screening was performed within 72 hours of their hospital admission for delivery. The periodontal parameters assessed were oral hygiene index-simplified, gingival index, mean probing depth, and loss of attachment. RESULTS: Prevalence of periodontal disease was 65.5% and was significantly higher (P <0.0001) in females with hypertension (relative risk = 1.5; 95% confidence interval [CI] = 1.3 to 1.9). Socioeconomic status, education, occupation, and body mass index did not appear to influence the relationship between periodontal disease and PH on bivariate multiple logistic regression analysis. Nulliparous females were at higher odds to develop periodontal disease and PH (odds ratio = 1.7; 95% CI = 0.5 to 6.1). As the severity of periodontal disease increased from moderate to severe, the severity of hypertension also increased (r(2) = 0.8 and 0.5 for moderate and severe periodontal disease, respectively). CONCLUSION: Periodontal disease is more prevalent in females with PH.

Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy.

BACKGROUND: There are many studies documenting increased prevalence of periodontal infection in women with preeclampsia. But, very few studies have attempted to establish causal relationship between the two. OBJECTIVE: To find out causal circumstantial evidence by isolating specific periodontal pathogens in oral and placental samples. MATERIALS AND METHODS: Antenatal periodontal screening and subgingival plaque collection was carried out in ten women with hypertension in pregnancy and ten normotensive controls on their hospital admission at term for cesarean delivery. Placental biopsy was obtained after aseptic placental collection at the time of elective cesarean delivery. Subgingival plaque and placental biopsy were studied for Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola, Prevotella intermedia and Aggregatibacter actinomycetemcomitans using quantitative polymerase chain reaction technique. Periodontist and laboratory personnel were unaware of case or control status. Periodontal status was not informed to the obstetrician recruiting the cases and laboratory. Microbiology report was not revealed till end of the study. RESULTS: Periodontal pathogens were found to be high in the group with hypertension than the controls. P gingivalis was found in all the samples from subgingival plaque and placenta, irrespective of the periodontal disease status. CONCLUSION: In cases with hypertension, periodontal pathogens are present in higher proportion in subgingival plaque and placenta.

A thought for tramadol hydrochloride as labor analgesic.

AIMS: To evaluate and compare the analgesic efficacy and adverse effects of tramadol and meperidine in labor. SUBJECTS AND METHODS: One hundred sixty-three of the 213 parturients at term in active labor were randomly assigned to one of three groups to receive intramuscularly either tramadol 50 mg (N = 54), tramadol 100 mg (N = 55) or meperidine 75 mg (N = 54). Single person who was not aware of the given drug (NS) assessed analgesic effect using visual analogue scale (VAS). Maternal side effects, effect on labor, and perinatal outcome were also studied. STATISTICAL ANALYSIS: Effect of the drugs used on maternal and fetal wellbeing was compared within study groups in reference to the control group. The quantitative analysis was done using unpaired t-test and for qualitative analysis chi-square test was applied. RESULTS: Proportion of cases with satisfactory to good pain relief (VAS difference >5) after 2 h of administration was 35.2 (19 of 54), 61.8 (34 of 55) and 70.3% (38 of 54) in tramadol 50 mg, tramadol 100 mg and meperidine 75 mg groups, respectively. Nausea and/or vomiting (11% vs. 7%), drowsiness (20.4% vs. 5.5%) and fatigue (16.7% vs. 6%) were significantly high in meperidine than in tramadol groups (P<0.05). Proportion of cases with nonreassuring fetal heart rate and neonates with <7 Apgar were high in the meperidine group. Meconium stained liquor was seen equally in tramadol 100 mg and meperidine groups, and was lower in tramadol 50 mg group. All the intervention groups had relatively shorter observed active phase of labor than controls. CONCLUSIONS: Tramadol 100 mg is an equally effective labor analgesic as meperidine with less maternal and perinatal side effects.

Sonographic assessment of lower uterine segment at term in women with previous cesarean delivery.

OBJECTIVE: To correlate lower uterine segment (LUS) thickness measured by abdominal sonography at term pregnancy with that measured manually using caliper at cesarean delivery and to find out minimum LUS thickness indicative of its integrity in women with previous cesarean. METHODS: In 106 women with previous cesarean delivery and 68 with unscarred uterus, abdominal sonographic assessment of LUS was carried out within a week of delivery. Sonographic measurements were correlated with manual measurement of lower flap of LUS using Vernier calipers in 96 of these women (64 with previous cesarean and 32 of unscarred uterus) who had elective cesarean delivery. RESULTS: Sonographically determined LUS was thinner among women with previous cesarean delivery than in those without (4.58 SD 1.05 vs. 4.8 SD 0.8; t = 1.986; p = 0.04). Women with vaginal birth after cesarean had thicker LUS than women with repeat cesarean delivery (4.4 SD 0.97 vs. 4.48 SD 1.0). The findings were not influenced by engaged fetal head status or amount of bladder fullness. Directly measured LUS thickness using Vernier calipers before delivery of the baby confirmed ultrasound measurements, but showed smaller differences between them. There were eight cases with defective uterine scar at cesarean. LUS thickness at term of 3 mm provided 87.5% sensitivity and specificity, and was found to have negative predictive value of 98%. But in two of seven cases the actual LUS was not measurable despite sonographic measurement of 3 mm, and there were two records of scar dehiscence in those with 3 and 4 mm of LUS thickness. CONCLUSION: LUS thickness of 3 mm measured by abdominal ultrasonography prior to delivery at term in women with previous cesarean is suggestive of stronger LUS but is not a reliable safeguard for trial of labor.

Effectiveness of subcutaneous injection of sterile water to the lower back for pain relief in labor.

The analgesic efficacy of subcutaneous injection of sterile water compared to isotonic saline was investigated in a randomized, controlled study on a total of 100 women in the active phase of labor and who complained of low back pain. Pain perception was rated on a numerical rating scale before and at 10 and 45 minutes after the injection. The initial pain score was the same in both groups and pain relief was expressed by both groups irrespective of the solution injected, but the sterile water group had significantly higher relief scores compared to those receiving saline. This was not influenced by maternal age, parity, education, body mass index, cervical dilatation at intervention or fetal size, suggesting that subcutaneous injection of sterile water to the lower back provides relief from back pain during labor.