Alka Kriplani

Cardiac disease in pregnancy

Objectives: To evaluate the maternal and fetal outcome of pregnancies complicated by cardiac disease in a developing country. Methods: A retrospective analysis was carried out of 207 pregnancies in women with cardiac disease who delivered at ≥28 weeks of gestation from June 1994 through December 2000 at a tertiary care center. Results: Rheumatic heart disease (n=183, 88%) with isolated mitral stenosis (n=71) was the predominant cardiac problem. Septal defects were the most common form of congenital heart disease (n=24). In 28 (13.52%) women, the diagnosis of cardiac disease was made during pregnancy. Cardiac complications were noted in 62 (29.95%) and fetal complications in 42 (20.28%) pregnancies. Patients in NYHA class I/II (n=175, 84.54%) had fewer maternal complications and their babies had a higher birth weight than those in NYHA class III/IV (n=32, 15.45%). Cardiac intervention was performed prior to pregnancy in 111 (60.65%) patients with rheumatic heart disease: PTMC/CMV in 73 and valve replacement (VR) in 38. Maternal and fetal outcome was better in patients with prosthetic valves (n=38) and the majority (97.4%) of them remained in NYHA class I/II. Cardiac intervention was safely carried out during pregnancy in 10 women (PTMC in 7, CMV in l, and VR in 2). One of them developed congestive cardiac failure during labor. None of the newborns of the 41women who had received anticoagulants had any congenital malformation. Conclusions: Rheumatic heart disease was the predominant type. Patients in NYHA class I/II had a better maternal and fetal outcome than those in NYHA class III/IV. Surgical correction of the cardiac lesion prior to pregnancy was associated with better pregnancy outcome. Pregnant women with prosthetic valves tolerated pregnancy well.

Maternal and perinatal outcome in thyrotoxicosis complicating pregnancy

In this report we describe 32 pregnancies complicated by hyperthyroidism cared for over a 7-year period at AIIMS, New Delhi. In 6 cases hyperthyroidism was diagnosed during pregnancy; others were diagnosed before conception and were on antithyroid therapy during pregnancy. For control of thyrotoxicosis thiourea derivatives, carbimazole (CMZ) and propylthiouracil (PTU), were both used. The dosage of antithyroid drugs could be decreased or stopped in the third trimester in only 28% cases, while 50% cases did not require any change in the dosage during gestation and 21% required an increase in dosage with advancing gestation to control thyrotoxicosis. Maternal and fetal complications included preterm labour (25%), PIH (22%), thyroid crisis (9%) and intrauterine growth retardation (13%). Thyroid status of neonates was found abnormal in 9% cases, including 1 case (3%) of neonatal thyrotoxicosis with goitre and 2 (6%) cases of neonatal hypothyroidism. One maternal death occurred due to thyroid storm. No case of stillbirth or perinatal death occurred in the present study. In our experience of 32 cases maternal and fetal complications are reported with increased frequency, requiring close surveillance of thyroid status to maintain euthyroidism and intensive fetal monitoring during pregnancy to achieve good maternal and perinatal outcome.

Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study

Summary Background An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study. Methods Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10–18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Findings Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02–1·23] and for HPV 18 1·04 [0·92–1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29–0·38] for HPV 16 and 0·51 [0·43–0·59] for HPV 18) and one-dose default (0·09 [0·08–0·11] for HPV 16 and 0·12 [0·10–0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2–5·1). Interpretation Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment. Funding Bill & Melinda Gates Foundation.

Management and outcome of pregnancies complicated with adnexal masses

Abstract Our purpose was to evaluate the pathologic features and outcome of pregnancies that were complicated with adnexal masses and were managed surgically. A review of patients who had persistent adnexal masses during pregnancy and needed surgical removal of tumours was performed from January 1998 to April 2001. There were 14 cases of persistent adnexal masses identified among 2000 deliveries. There were 13 patients who had surgical interventions: nine (69.2%) had surgery during ongoing pregnancy (at mean gestational age 17±3.7 weeks), two (15.3%) with caesarean section, one (7.6%) after evacuation of missed abortion and one (7.5%) after delivery. Out of 13, ten (76.9%) were benign [mature cystic teratoma, six (46.9%); serous cyst adenoma, two (15.3%); mucinous cyst adenoma, one (7.6%); paratubal cyst, one (7.6%)] and three (23%) were malignant (one immature teratoma, one papillary cyst adenocarcinoma and one krukenberg tumour]. Both patients operated on after 24 weeks had preterm delivery. The worst outcome in the form of PPROM and preterm delivery at 28 weeks occurred in a patient who underwent emergency surgery. The incidence of malignancy was four- to fivefold greater in our series than reported in the literature. Ultrasound was unable to distinguish malignant cases. Pregnancy outcome was poorer if surgical intervention was done after >24 weeks and that, too, was done as emergency surgery.

The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight.

Background Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. Methods and Findings We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown–rump length measured at 8–13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25–31), median height was 162 cm (IQR 157–168), median weight was 61 kg (IQR 55–68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487–2,222). The median pregnancy duration was 39 wk (IQR 38–40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8–16). The median birthweight was 3,300 g (IQR 2,980–3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. Conclusions This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.

Effect of oral contraceptive containing ethinyl estradiol combined with drospirenone vs. desogestrel on clinical and biochemical parameters in patients with polycystic ovary syndrome.

BACKGROUND A prospective randomized trial was conducted to compare efficacy of a drospirenone-containing combined oral contraceptives (COC) with desogestrel-containing COC in women with polycystic ovary-syndrome (PCOS) not desirous of child-bearing. STUDY DESIGN Sixty women were randomized into study group [ethinylestradiol (EE) 30 mcg+drospirenone 3 mg] and control group (EE 30 mcg+desogestrel 150 mcg), treated for 6 months and followed up at 1 month, 3 months, 6 months, during treatment and 3 and 6 months post-treatment. Acne and hirsutism scoring, bodyweight, body mass index (BMI), blood pressure (BP), ultrasound parameters, lipid profile, glycemic profile and hormonal profile were compared. RESULTS Cycles were regular in both groups during treatment. Effect of regular cycles persisted in 44.83% (13/30) vs. 17.24% (5/30) in study vs. control group at 6 months post-treatment with 33.3% decreased hirsutism score in the study group (versus no change in control group) even at 6 months after stopping treatment. With treatment, BMI fell by 0.52 kg/m(2) in the study group; systolic and diastolic BP fell in the study group while it rose in the control group. Low-density lipoprotein significantly decreased and high-density lipoprotein was elevated in the study group (p<.05). The study group showed a significant fall in fasting/postprandial blood sugar and insulin and total testosterone against a rise in the control group. CONCLUSION In women with PCOS, a drospirenone containing COC has better outcome in terms of persistent regular cycles, antiandrogenic effect, fall in BMI and BP, better lipid profile, favorable glycemic and hormonal profile than desogestrel-containing COC.

Differential Gene Expression in Granulosa Cells from Polycystic Ovary Syndrome Patients with and without Insulin Resistance: Identification of Susceptibility Gene Sets through Network Analysis

CONTEXT Polycystic ovary syndrome (PCOS) is a heterogeneous, genetically complex, endocrine disorder of uncertain etiology in women. OBJECTIVE Our aim was to compare the gene expression profiles in stimulated granulosa cells of PCOS women with and without insulin resistance vs. matched controls. RESEARCH DESIGN AND METHODS This study included 12 normal ovulatory women (controls), 12 women with PCOS without evidence for insulin resistance (PCOS non-IR), and 16 women with insulin resistance (PCOS-IR) undergoing in vitro fertilization. Granulosa cell gene expression profiling was accomplished using Affymetrix Human Genome-U133 arrays. Differentially expressed genes were classified according to gene ontology using ingenuity pathway analysis tools. Microarray results for selected genes were confirmed by real-time quantitative PCR. RESULTS A total of 211 genes were differentially expressed in PCOS non-IR and PCOS-IR granulosa cells (fold change≥1.5; P≤0.001) vs. matched controls. Diabetes mellitus and inflammation genes were significantly increased in PCOS-IR patients. Real-time quantitative PCR confirmed higher expression of NCF2 (2.13-fold), TCF7L2 (1.92-fold), and SERPINA1 (5.35-fold). Increased expression of inflammation genes ITGAX (3.68-fold) and TAB2 (1.86-fold) was confirmed in PCOS non-IR. Different cardiometabolic disease genes were differentially expressed in the two groups. Decreased expression of CAV1 (-3.58-fold) in PCOS non-IR and SPARC (-1.88-fold) in PCOS-IR was confirmed. Differential expression of genes involved in TGF-β signaling (IGF2R, increased; and HAS2, decreased), and oxidative stress (TXNIP, increased) was confirmed in both groups. CONCLUSIONS Microarray analysis demonstrated differential expression of genes linked to diabetes mellitus, inflammation, cardiovascular diseases, and infertility in the granulosa cells of PCOS women with and without insulin resistance. Because these dysregulated genes are also involved in oxidative stress, lipid metabolism, and insulin signaling, we hypothesize that these genes may be involved in follicular growth arrest and metabolic disorders associated with the different phenotypes of PCOS.

Efficacy, acceptability and side effects of the levonorgestrel intrauterine system for menorrhagia.

Objective: To evaluate the efficacy, acceptability, and possible side effects of a levonorgestrel‐releasing intrauterine system for menorrhagia. Methods: Sixty‐three women with menorrhagia but without uterine enlargement, endometrial hyperplasia with atypia, or endometrial carcinoma were enrolled in this prospective, open, nonrandomized clinical trial. An intrauterine system releasing 20 μg/day of levonorgestrel (LNG‐IUS; Mirena, Shering, Finland) was inserted in the postmenstrual phase. Menstrual pattern, number of bleeding days, and subjective and objective estimation of menstrual blood loss using a pictorial blood loss assessment chart (PBAC) were recorded before insertion and at specific intervals for 4 years. Hemoglobin levels and endometrial thickness were evaluated at baseline and at 12 months. Treatment continuation and hysterectomy rates were noted as well as side effects. Results: The device was expelled spontaneously in 6 patients (9.52%) and removed prematurely in 9 patients (14.3%); 3 patients (4.8%) were lost to follow‐up; and 45 patients (71.4%) continued with the LNG‐IUS. Menorrhagia was cured in 35 (77.7%) of these 45 patients at 3 months and in all patients at 36 months. There was a significant decrease in the mean number of bleeding days (P = 0.01) and PBAC score (P = 0.00) at 1 month, and the decrease continued with treatment duration. The subjective blood loss reduction was considerable as well, and at 12 months the mean ± SD rise in hemoglobin concentration was 1.06 ± 1.7 g/dL (P = 0.000). Endometrial thickness was decreased by 3.4 ± 3.53 mm (P = 0.0001) at 12 months. The most common side effect was intermenstrual spotting during the first 6 months, and 18 patients (28.57%) developed amenorrhea. Conclusion: Using the LNG‐IUS is an effective and well‐accepted option overall for the medical management of menorrhagia.

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

BACKGROUND To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. METHODS This was a cross-sectional study of 546 sexually active women aged > or =30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (kappa) and Chi-square test. RESULTS Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (kappa=76.31%, 95% confidence interval [CI]: 64.97-82.29%, p=0.04)-complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (kappa=63.7%, 95% CI: 55.2-72.2%) and 95.3% for physician-collected samples (kappa=80.4%, 95% CI: 71.8-89.0%). CONCLUSIONS Self-HPV sampling compares favourably with physician-sampling and cytology. A rapid, affordable, HPV self-test kit can be used as the primary method of cervical cancer screening in low-resource situations.

Role of tranexamic acid in management of dysfunctional uterine bleeding in comparison with medroxyprogesterone acetate.

Summary Currently, tranexamic acid (TXA) is used as 4 g/day in menorrhagia This prospective randomised study included 100 cases to assess efficacy and safety of 2 g/day TXA in dysfunctional uterine bleeding (DUB) vs cyclical 10 mg twice-daily medroxyprogesterone acetate (MPA) for 3 cycles. Follow-ups were made monthly for 3 months during therapy, then 3 months after. Mean pictorial blood loss assessment chart (PBAC) score decreased from 356.9 to 141.6 in the TXA group and from the pre-treatment 370.9 to 156.6 with MPA and mean reduction of blood loss was 60.3% with TXA and 57.7% with MPA after 3 months (p < 0.005 in both groups). Lack of response during treatment was seen in three patients (6.1%) TXA and in 13 patients (28.9%) with MPA (p = 0.003). In patients who reported 3 months after stopping the treatment, 66.7% in TXA group and 50% in MPA had recurrence of menorrhagia, (p = 0.155). During the 6 months study period more hysterectomies were performed in the MPA than in the TXA group (17.8% vs 4%; p = 0.002). We conclude that TXA in 2 g/day dosage is an effective and safe option in DUB.