Multi-criteria decision making to validate performance of RBC-based formulae to screen [Formula: see text]-thalassemia trait in heterogeneous haemoglobinopathies.

BACKGROUND: India has the most significant number of children with thalassemia major worldwide, and about 10,000-15,000 children with the disease are born yearly. Scaling up e-health initiatives in rural areas using a cost-effective digital tool to provide healthcare access for all sections of people remains a challenge for government or semi-governmental institutions and agencies. METHODS: We compared the performance of a recently developed formula SCS[Formula: see text] and its web application SUSOKA with 42 discrimination formulae presently available in the literature. 6,388 samples were collected from the Postgraduate Institute of Medical Education and Research, Chandigarh, in North-Western India. Performances of the formulae were evaluated by eight different measures: sensitivity, specificity, Youden's Index, AUC-ROC, accuracy, positive predictive value, negative predictive value, and false omission rate. Three multi-criteria decision-making (MCDM) methods, TOPSIS, COPRAS, and SECA, were implemented to rank formulae by ensuring a trade-off among the eight measures. RESULTS: MCDM methods revealed that the Shine & Lal and SCS[Formula: see text] were the best-performing formulae. Further, a modification of the SCS[Formula: see text] formula was proposed, and validation was conducted with a data set containing 939 samples collected from Nil Ratan Sircar (NRS) Medical College and Hospital, Kolkata, in Eastern India. Our two-step approach emphasized the necessity of a molecular diagnosis for a lower number of the population. SCS[Formula: see text] along with the condition MCV[Formula: see text] 80 fl was recommended for a higher heterogeneous population set. It was found that SCS[Formula: see text] can classify all BTT samples with 100% sensitivity when MCV[Formula: see text] 80 fl. CONCLUSIONS: We addressed the issue of how to integrate the higher-ranked formulae in mass screening to ensure higher performance through the MCDM approach. In real-life practice, it is sufficient for a screening algorithm to flag a particular sample as requiring or not requiring further specific confirmatory testing. Implementing discriminate functions in routine screening programs allows early identification; consequently, the cost will decrease, and the turnaround time in everyday workflows will also increase. Our proposed two-step procedure expedites such a process. It is concluded that for mass screening of BTT in a heterogeneous set of data, SCS[Formula: see text] and its web application SUSOKA can provide 100% sensitivity when MCV[Formula: see text] 80 fl.

Iron Overload and Anemia in Rhesus Hemolytic Disease of Newborn: A Prospective Observational Study.

This study assessed the prevalence of iron overload in infants born to Rh isoimmunized mothers. Infants born to Rh isoimmunized mothers with Indirect Coomb's Test (ICT) titers ≥1:16 were prospectively enrolled and followed until 3 mo. Hemoglobin and serum ferritin were estimated at birth and 3 mo of age. The outcomes were the incidence of iron overload (at birth and 3 mo), anemia, and the need for transfusions in the first 3 mo. Seventy-four infants were enrolled, nearly half receiving intrauterine transfusion (IUT). Sixty (82.2%) had hyperferritinemia at birth. The median (1st, 3rd quartile) ferritin levels were 456 (321, 631) µg/L. Infants who received IUTs had significantly higher serum ferritin levels at birth. Fifty-one (76.1%) infants had hyperferritinemia at 3 mo. Over three months of follow-up, 53 (71.6%) infants had anemia, of which 33 (48.5%) required packed red blood cells (PRBC) transfusion. These findings suggest that iron overload is common in these infants in the first 3 mo.

Association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women in India.

BACKGROUND: Human leukocyte antigen (HLA) restriction plays an important role in the susceptibility to alloimmunization against red blood cell (RBC) antigens. The prevalence of anti-D alloimmunization in RhD negative pregnancy is still quite high in our population. Thus, we planned this study to determine the association of HLA-DRB1 alleles with anti-D alloimmunization in RhD negative pregnant women. MATERIAL AND METHODS: RBC antibody screen (ABS) was performed for RhD negative pregnant women attending the antenatal clinic our institute. Those with a negative result were included in the 'non-alloimmunized' (NAL) group ('Control' group), while those with anti-D alloantibody on performing antibody identification were included in the alloimmunized (AL) group of the study (n = 50 each). ABS and identification were done using column agglutination technique. The HLA-DRB1 typing was done by Luminex based reverse sequence specific oligonucleotide probing (SSOP) using commercial kits. The HLA-DRB1 allele frequency was compared in both the groups. RESULTS: There was a significant difference between the two groups in terms of gravida (p < 0.001) and history of anti-D immunoprophylaxis (p < 0.001). The frequency of HLA-DRB1*03 and HLA-DRB1*04 alleles was significantly higher in the AL group than the NAL group: 40 % versus 18 % [Odds Ratio (OR): 3.04, 95 % CI: 1.21-7.6; p = 0.015] for HLA-DRB1*03 alleles and 18 % versus 4 % (OR: 5.27, 95 % CI: 1.08-25.78, p = 0.025) for HLA-DRB1*04 alleles. CONCLUSION: The frequency of HLADRB1*03 and HLADRB1*04 alleles was significantly higher in RhD negative pregnant women alloimmunized with anti-D alloantibody.

Expediting labor induction in severe pre-eclampsia by earlier initiation of oxytocin after cervical ripening: A randomized study from India.

OBJECTIVE: To observe whether induction of labor (IoL) among women with severe pre-eclampsia (PE) can be expedited by initiating oxytocin early (after 6 h) than after 12 h following cervical ripening with a combined method. METHODS: Women with severe PE and Bishop's < 6 (n = 96) were randomized into two groups. All women received cervical ripening with a combined method (intracervical Foley's plus dinoprostone gel 0.5 mg) following which Group 1 women received oxytocin after 6 h (with Foley's in-situ) and Group 2 after 12 h (after removing Foley's) RESULTS: Majority were nulliparous (63% in group 1 and 77% in group 2) and the mean gestation was similar (35.3 ± 2.98 weeks in group 1 and 35.5 ± 3.09 in group 2). Nearly half the women had partial HELLP/ HELLP (47.9% and 54.1%; in groups 1 and 2, respectively). The induction-delivery interval (IDI) was significantly reduced in group 1 (16 h 6 min vs 22 h 6 min in group 2; p = 0.001). The cesarean section (CS) rate was 37.5% in group 1 and 31.3% in group 2 (p = 0.525), but the study was underpowered to assess this outcome. The neonatal outcome was similar, 92/96 neonates were discharged after a hospital stay of 3-52 days. There were 4 neonatal deaths (1 in group 1 and 3 in group 2) of extreme or very preterm neonates (27-30 + 6 wks) with birth weight of 735-965 gm. CONCLUSION: Among women with severe PE undergoing IoL, initiating oxytocin 6 h after cervical ripening with a combined method reduced the IDI significantly as compared to initiating it after 12 h, with a similar CS rate and neonatal outcome.

Reappraisal of evolving methods in non-invasive prenatal screening: Discovery, biology and clinical utility.

Non-invasive prenatal screening (NIPS) offers an opportunity to screen or determine features associated with the fetus. Earlier, prenatal testing was done with cytogenetic procedures like karyotyping or fluorescence in-situ hybridization, which necessitated invasive methods such as fetal blood sampling, chorionic villus sampling or amniocentesis. Over the last two decades, there has been a paradigm shift away from invasive prenatal diagnostic methods to non-invasive ones. NIPS tests heavily rely on cell-free fetal DNA (cffDNA). This DNA is released into the maternal circulation by placenta. Like cffDNA, fetal cells such as nucleated red blood cells, placental trophoblasts, leukocytes, and exosomes or fetal RNA circulating in maternal plasma, have enormous potential in non-invasive prenatal testing, but their use is still limited due to a number of limitations. Non-invasive approaches currently use circulating fetal DNA to assess the fetal genetic milieu. Methods with an acceptable detection rate and specificity such as sequencing, methylation, or PCR, have recently gained popularity in NIPS. Now that NIPS has established clinical significance in prenatal screening and diagnosis, it is critical to gain insights into and comprehend the genesis of NIPS de novo. The current review reappraises the development and emergence of non-invasive prenatal screen/test approaches, as well as their clinical application, with a focus, on the scope, benefits, and limitations.

Promoter methylation status of key genes and its implications in the pathogenesis of endometriosis, endometrioid carcinoma of ovary and endometrioid endometrial cancer.

Background: Epigenetic processes play an important role in various physiological processes as well as in the pathogenesis of many diseases. The role of altered DNA methylation in the pathogenesis of endometriosis and associated ovarian and endometrial cancers has not been explored in detail. Therefore, this study aimed to determine the promoter methylation status of genes involved in key biological processes in the pathogenesis of these three gynecological diseases. Methods: Tissue samples of endometriosis, endometrioid carcinoma of the ovary, endometrioid endometrial cancer, and control endometrium (n = 10 each) were obtained. DNA was extracted and subjected to bisulfite conversion using commercially available kits. The methylation status of COX2, VEGF, HIF1A, TNF, MYC, and TP53 genes was checked by methylation-specific PCR. The mRNA levels of MYC and TP53 were determined using qRT-PCR in all tissue samples. Results: The promoter methylation status of COX2, VEGF, HIF1A, and TNF genes was significantly reduced in all three diseased study subjects (P < 0.05), whereas no significant difference was observed in the promoter methylation frequency of MYC and TP53 genes. Transcriptional expression of the MYC gene was significantly increased in all diseased groups (P < 0.001) whereas, transcriptional expression of the TP53 gene was significantly reduced in endometriosis and endometrioid carcinoma of the ovary and significantly increased in endometrioid endometrial cancer subjects compared to control subjects (P < 0.001). Conclusion: The findings suggest that the promoter regions of pro-inflammatory and pro-angiogenic genes involved in the common molecular pathophysiology of these three disorders were significantly hypomethylated and could be the reason for their over-expression associated with them. This indicates the role of epigenetics in the pathogenesis of these three diseases.

Hypertrophic Cardiomyopathy and Pregnancy: A Retrospective Analysis From a Tertiary Care Hospital.

Pregnancy in women with hypertrophic cardiomyopathy is not well described. In this retrospective study, we analyzed data on pregnant women with hypertrophic cardiomyopathy who were under follow-up care in the cardiology department of a tertiary care hospital. We reviewed data on all women registered in the hypertrophic cardiomyopathy cohort and those who attended the cardio-obstetric clinic and delivered between January 2010 and June 2019. From these 2 groups, we identified 7 pregnant women with hypertrophic cardiomyopathy who delivered during this period. These 7 women (mean [SD] age, 25 [3.3] years) had a total of 15 pregnancies (range per woman,1-4). This was a high-risk cohort, as 7 (46.7%) pregnancies were in the modified World Health Organization class III. The mean (SD) left ventricular wall thickness was 19.71 (2.56) mm in all pregnancies. Two of the 7 women with left ventricular outflow tract obstruction developed severe symptoms in the third trimester; these improved soon after delivery. Eight pregnancies without obstruction were well tolerated. Two pregnancies occurred after successful alcohol septal ablation. Both remained asymptomatic throughout pregnancy. All women tolerated labor well. Adverse maternal outcomes, including death, were not seen in any patient. All women who became symptomatic during pregnancy had relief of symptoms after delivery. Most women remained asymptomatic or had mild symptoms during pregnancy. Of the women with left ventricular outflow tract obstruction, 28.6% had severe symptoms that improved after delivery. Pregnancy was well tolerated after successful alcohol septal ablation.

The spectrum of ABO haemolytic disease of the fetus and newborn in neonates born to group O mothers.

BACKGROUND AND OBJECTIVES: ABO haemolytic disease of the fetus and newborn (HDFN) is a lesser recognized entity; however, the severity may vary in neonates. This prospective observational study was performed to determine the severity and risk of ABO-HDFN in neonates born to O group mothers. MATERIALS AND METHODS: A total of 260 neonates born to non-alloimmunized blood group O mothers were recruited. Blood group O neonates were excluded from the study. Neonatal direct antiglobulin test (DAT) was performed using the column agglutination technique. They were monitored for clinical and laboratory parameters and followed up at 6-8 weeks. The maternal anti-A and anti-B titres (IgM and IgG) were also done. RESULTS: A total of 176 neonates with blood group A (77/260; 29.6%) and B (99/260; 38.1%) were finally included in the study, and 15 (8.5%) of them were DAT positive. Overall, 26.7% (47/176) neonates received phototherapy, 172 (97.7%) survived and none required readmission. The median (inter-quartile range [IQR]) maternal IgG anti-B titre (32 [32-64]) was significantly higher (p < 0.001) than the IgG anti-A titre (16 [8-64]). The maximum total serum bilirubin in neonates had a significant positive association with neonatal birth weight (p = 0.045), positive DAT (p = 0.006) and requirement of phototherapy (p < 0.001). The relative risk (95% CI) of a DAT-positive neonate requiring phototherapy was 4.55 (3.12-6.33). CONCLUSION: The frequency of ABO incompatibility in neonates born to group O mothers was 67.69% (176/260). The maternal IgG titre of ≥64 could be a good predictor for identifying the neonates at risk of developing hyperbilirubinaemia requiring phototherapy.

Post Caesarean Section Deep Pelvic Abscess: CT Guided Transgluteal Drainage.

Organ space surgical site infection (SSI), in itself, is a problematic condition for the surgeon and also adds pain and misery to the patient. If it happens along with deep pelvic collection, it further increases the risk of sepsis to the patient. Untreated abdominal or pelvic abscesses are associated with high mortality. This outcome is improved due to advances in image-guided percutaneous interventional techniques. The aim is to drain the collection with minimal morbidity to the patient. We report a case of deep surgical site infection following caesarean section in a COVID-19 positive patient managed with minimal intervention.

Comparison of intracervical Foley catheter combined with a single dose of vaginal misoprostol tablet or intracervical dinoprostone gel for cervical ripening: a randomised study.

We compared two combined methods for cervical ripening before induction of labour (IOL) Women (n = 150) were randomised into Foley's-misoprostol (n = 75) and Foley's-dinoprostone (n = 75) groups. A single dose of vaginal misoprostol tablet (25 µg) or intracervical dinoprostone gel (0.5 mg) were used alongwith intracervical Foley's. The primary outcome was induction-delivery interval (IDI) and secondary outcomes were change in Bishop's score, oxytocin requirement, caesarean section (CS) rate, chorioamnionitis and neonatal outcome. The mean parity, gestation and indications for IOL were similar in the two groups. The IDI (19 h 37 min and 19 h 20 min; p = .683), cervical ripening time, oxytocin requirement, CS rate (18.7 and 25.4%, p = .322) and neonatal outcome were similar. Hyperstimulation developed in 2.7% women with Foley's-misoprostol and in 1.3% with Foley's-dinoprostone (p = .55). No woman had chorioamnionitis. Thus, these two combined methods of cervical ripening and IOL were observed to be similarly efficacious. A low incidence of hyperstimulation and no chorioamnionitis may be attributed to using a single dose of prostaglandins. Misoprostol may be substituted for dinoprostone in resource limited countries.Impact statementWhat is already known on this subject? Combined methods for cervical ripening (intracervical Foley's plus prostaglandins) before induction of labour (IOL) may be similarly or more efficacious than individual methods. Most studies comparing various combined methods have used repeated doses of prostaglandins. A combined method using repetitive doses of prostaglandins may increase the risk of hyperstimulation and also of infection consequent to repeated vaginal examination to administer prostaglandins. These two concerns may be offset by combining a single dose of prostaglandin with intracervical Foley's catheter.What do the results of this study add? Two combined methods for cervical ripening using a single dose of vaginal misoprostol (25 µg) or intracervical dinoprostone gel (0.5 mg) co-administered with intracervical Foley's catheter were found to be similarly efficacious. The IDI (19 h 37 min and 19 h 20 min; p = .683), cervical ripening time, oxytocin requirement, CS rate (18.7 and 25.4%, p = .322) and neonatal outcome were similar. The incidence of hyperstimulation was low (2.7 and 1.3% with Foley's-misoprostol and Foley's-dinoprostone, respectively) and no woman had chorioamnionitis.What are the implications of these findings for clinical practice and/or further research? Combined methods for cervical ripening using a single dose of prostaglandins (misoprostol or dinoprostone) were observed to be similarly efficacious. Misoprostol is a cheaper alternative to dinoprostone and may be utilised in resource limited countries. These methods may be compared with each other in more number of women in order to identify which combined method is more efficient and safe. Clinical Trials Registry of India: CTRI/2017/12/010738.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer.

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

Pregnancy Outcome of Rh D Alloimmunized Pregnancies: A Tertiary Care Institute Experience of a Developing Country.

AIM: To determine the socio-demographic characteristics and pregnancy outcome of Rh D alloimmunized women monitored with MCA PSV (middle cerebral artery peak systolic velocity). MATERIALS AND METHODS: In total, 363 Rh D alloimmunized women attended antenatal clinic or obstetric emergency between January 2006 and December 2014. MCA PSV was the screening method for detection of fetal anemia. Intrauterine blood transfusion (IUT) was given when MCA PSV was > 1.5 MOM. Totally, 162 women (164 fetuses) received 492 transfusions. Forty-eight women had fetal hydrops at presentation. Five women (three received IUT) were lost to follow-up. Pregnancy outcome of 358 women and socio-demographic characteristics of 363 women were analyzed. RESULTS: The perinatal mortality was 421, 66 and 87 per 1000 live births in hydrops group, non-hydrops IUT group and non-IUT group, respectively. CONCLUSION: Rh alloimmunization is still a major cause of perinatal morbidity and mortality. The higher gravidity, previous history of pregnancy wastage, still births and hydrops increase the requirement of intrauterine transfusion. MCA PSV is an excellent tool for monitoring of Rh alloimmunized pregnancies to detect fetal anemia. Early detection and monitoring by MCA PSV improve its outcome.

Diagnostic potential of differentially regulated microRNAs among endometriosis, endometrioid ovarian cancer, and endometrial cancer.

BACKGROUND: There is an increased risk of developing endometrioid ovarian and endometrial cancer in patients with endometriosis and there are no definitive diagnostic biomarkers available for these three associated diseases. Therefore, we evaluated the diagnostic potential of differentially expressed microRNAs (miRNAs) from the tissue samples of endometriosis, endometrioid ovarian cancer, and endometrial cancer to establish them as biomarkers for these diseases. MATERIALS AND METHODS: Ten samples of each, i.e., endometriosis, endometrioid ovarian cancer, endometrial cancer and control healthy endometrium were enrolled after obtaining ethical clearance. Differential expression of miR-16, miR-20a, miR-99b, miR-125a, miR-143, and miR-145 and some of their target genes, i.e., vascular endothelial growth factor (VEGF), hypoxia inducible factor 1A (HIF1A), cyclooxygenase 2 (COX2), and tumor necrosis factor (TNF) were quantified using quantitative reverse transcription polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was performed to predict the diagnostic potential. RESULTS: miR-16 and miR-20a were significantly downregulated, whereas miR-99b, miR-125a, and miR-143 were significantly upregulated in all three diseased samples. miR-145 was significantly upregulated in endometriosis and endometrioid ovarian cancer but significantly downregulated in endometrial cancer. mRNA levels of VEGF, HIF1A, COX2, and TNF were significantly increased in all three diseased samples as compared to control samples. ROC curve analysis revealed that for endometriosis, miR-99b, and miR-125a were giving highest area under curve (AUC) (0.950 and 0.733, respectively), for endometrioid carcinoma of ovary miR-143 was giving highest AUC (0.933) and for endometrioid endometrial cancer miR-16 (AUC = 0.815), miR-99b (AUC = 0.920), and miR-145 (AUC = 0.985) were found to be best predictors. CONCLUSION: These findings suggest that these miRNAs can act as good predictors and discriminators of these three diseases and might serve as potential biomarkers for them.

SARS-CoV-2 and the reproductive system: known and the unknown..!!

BACKGROUND: COVID-19 is the most recent zoonotic outbreak of coronaviruses. Mostly, it invades the cells of the respiratory system by binding to the receptor angiotensin-converting enzyme 2 (ACE2) which is also present in other organs like the kidney, testis, ovaries, breast, heart, and intestine, rendering them prone to be infected. The reproductive potential is a must for the sustenance of any species and it is our prime duty to safeguard the reproductive system of the present generation from such a deadly virus. The previously reported coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) had a detrimental impact on reproductive organs. There is a dearth of sufficient research to provide substantial evidence for the harmful effects of this novel virus on the reproductive system. Hence, our review compiles the knowledge available until now to boost research in this regard and to take the necessary steps in time. MAIN BODY OF ABSTRACT: Here we tried to compile all the data available on the effect of SARS-CoV-2 on the reproductive system as well as vertical transmission of the virus. All related articles published from February to August 2020 were reviewed and thoroughly analyzed. SARS-CoV-2 has been found to affect the sperm concentration and motility, thus degrading the fertility of males. In females, it is suspected that this virus affects the oocyte quality and ovarian function, resulting in infertility or miscarriage. Traces of SARS-CoV-2 virus have also been found in the breast milk of the infected mothers and the semen of infected males. Vertical transmission of SARS-CoV-2 has also been reported in some cases. CONCLUSION: Based on the literature review, SARS-CoV-2 seems to have the potential of affecting both male and female reproductive tracts. This review brings together the findings and observations made in the area of reproductive health during the current pandemic. The reproductive system of the young population is preordained for subsequent disorders, infertility, reduced sperm count, and motility. Therefore, the research and medical practices should focus on possible vulnerability being posed by SARS-CoV-2 to the gametes and future generations. We, hereby, recommend close monitoring of young and pregnant COVID-19 patients concerning reproductive health with utmost priority.

Prognostic role of uterine artery Doppler in early- and late-onset preeclampsia with severe features.

OBJECTIVE: To correlate uterine artery Doppler findings with maternal and neonatal outcomes in early- and late-onset preeclampsia with severe features. METHODOLOGY: Doppler scan was done in both uterine arteries. Maternal and neonatal outcomes in women with abnormal and normal Doppler results were compared. RESULTS: Abnormal Doppler results were present in 45 women (75%). Thirty-four (56.7%) women had abnormal RI, 19 (31.6%) had abnormal PI, and 36 (60%) had diastolic notch. Of the women who participated in the study, 21.6% developed maternal complications, and the majority belonged to the early-onset severe preeclampsia group. Diastolic notch was twofold more frequent in the early group. RI was abnormal in 63% of the early-onset and 50% of the late-onset group. CONCLUSION: Pregnancies with early-onset preeclampsia who had abnormal uterine artery Doppler findings were at high risk for both maternal and neonatal complications, whereas those who had late-onset preeclampsia with abnormal Doppler findings only had an increased risk of perinatal complications.

Non-invasive prenatal rhesus D genotyping using cell-free foetal DNA.

Background & objectives: Non-invasive prenatal diagnosis (NIPD) of rhesus D (RHD) genotype using cell-free foetal DNA is extensively used in many developed countries. Studies on NIPD from India are scarce. The aim of the present study was to evaluate the performance of non-invasive foetal RHD genotyping by targeting exon 10 of the RHD gene using cell-free DNA. Methods: DNA was extracted from the maternal plasma of alloimmunized and non-alloimmunized women between 7 and 34 wk of gestation. RHD sequence was determined by quantitative real time polymerase chain reaction (PCR). Results were compared with RhD phenotype obtained from cord blood samples of neonates. Results: A total of 135 samples from RhD-negative pregnant women were collected. The foetal RHD status was conclusive in all 135 (100%) cases. The highest number of cases reported for RHD genotyping were from Punjab (38.5%) followed by Haryana (24.4%), Himachal Pradesh (17.0%) and Chandigarh Union Territory (13.3%). The non-invasive test correctly predicted the foetal RhD phenotype in 133 of 135 cases, making the accuracy of the test as 98.51 per cent [95% confidence interval (CI): 97.90-99.50%]. The overall sensitivity and specificity of the test were 99.18 per cent (95% CI: 95.52-99.98%) and 92.31 per cent (95% CI: 63.97-99.81%), respectively, with negative and positive predictive values of 99.80 per cent (95% CI: 94.85-99.87%) and 96.31 per cent (95% CI: 62.87-98.84%), respectively. Interpretation & conclusions: Non-invasive foetal RHD determination by single-exon quantitative PCR exhibited high accuracy and could be used in routine clinical practice after confirmatory studies are done.

Change in antiepileptic drug prescription patterns for pregnant women with epilepsy over the years: Impact on pregnancy and fetal outcomes.

AIMS AND OBJECTIVES: The objectives of the study were: (1) to determine if there is a change in pattern of antiepileptic drug (AED) prescription during pregnancy in women with epilepsy (WWE) attending a tertiary care institute in North India and (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE. PATIENTS AND METHODS: The current study was a retrospective analysis of records of WWE attending a medical and surgical disorder clinic of obstetrics and gynecology department of a tertiary care teaching hospital in North India. We retrospectively collected data of all the patients during the 5-year period from 2011 to 2015 (Group A) (n = 177) and compared it with our previously published data during the years 1987-1994 (Group B) (n = 219). RESULTS: There was significantly higher use of (i) levetiracetam (LEV) in Group A compared to Group B when women on monotherapy were compared (P<0.0001) and (ii) LEV (P<0.0001), clobazam (P<0.0001) and lamotrigine (P=0.0004) in Group A compared to Group B when women on polytherapy were compared. A significantly higher (P=0.02) number of women were using more than two antiepileptic drugs simultaneously in Group A compared to Group B. There was a significantly higher incidence (P = 0.001) of small for gestational age babies in Group A. CONCLUSION: Although there is an increase in the use of newer AEDs in WWE during pregnancy in North Indian population, it has not resulted in improved maternal and fetal outcomes. (2) to determine if change in AED prescription pattern has resulted in improved fetal and maternal outcomes in WWE.

Comparison of intracervical Foley catheter used alone or combined with a single dose of dinoprostone gel for cervical ripening: a randomised study.

Prostaglandins and intracervical catheters are similarly effective for cervical ripening and for an induction of labour (IOL). Studies comparing the combined use with either method alone have administered repetitive doses of prostaglandins vaginally, which may increase the risk of tachysystole and chorioamnionitis. These disadvantages may be offset by co-administering a single dose of prostaglandin. Women (n = 110) planned for IOL, ≥37 weeks of gestation and with a Bishop Score of ≤6 were randomised into two groups: intracervical Foley catheter alone or combined with dinoprostone gel (0.5 mg) for 12 hours followed by oxytocin. The primary outcome was the IDI and the others were: change in Bishop Score, caesarean section (CS) requirement, any complications and neonatal outcome. The baseline Bishop was ≤4 in all and >80% were nulliparous. The post-ripening Bishop was significantly higher (6.67 vs. 5.98; p = .045) and the IDI was significantly lower in the combined group (16 hours and 16 minutes vs. 20 hours 44 minutes, p = .002). The CS rate was similar (29.1 vs. 25.5%; p = .669). No woman had hyperstimulation or chorioamnionitis and the neonatal outcomes were similar. Thus, co-administering one dose of an intracervical PGE2 gel with Foley was superior to Foley alone for cervical ripening and IOL. Impact statement What is already known on this subject? Prostaglandins and intracervical balloon catheters used individually are similarly effective for ripening an unfavourable cervix prior to the induction of labour (IOL). A few studies which have compared their found it to result in a shorter cervical ripening time and induction delivery interval (IDI) as compared to prostaglandins alone, though chorioamnionitis was a concern. When compared to balloon catheter used alone, combined use was either similarly or more effective. The studies comparing combined use with either method used alone have administered repetitive doses of prostaglandins vaginally, which may increase the risk of tachysystole, and possibly of chorioamnionitis. Co-administering a single dose of prostaglandin with a balloon catheter may offset these disadvantages. What do the results of this study add? A combined method for cervical ripening using a single dose of intracervical dinoprostone gel (PGE2, 0.5 mg) coadministered with an intracervical Foley catheter was superior to Foley catheter alone. The combined method improved the Bishop score after 12 hours and reduced the IDI significantly compared to the Foley catheter alone; while the caesarean rate and neonatal outcomes were similar. No woman had chorioamnionits or hyperstimulation. What are the implications of these findings for clinical practice and/or further research? The combined methods for cervical ripening should be compared to individual methods in more women, and the combinations may explore the use of other single use prostaglandins like the dinoprostone vaginal insert or misoprostol tablets.

Levetiracetam use during pregnancy in women with epilepsy: Preliminary observations from a tertiary care center in Northern India.

INTRODUCTION: Data on efficacy and safety of levetiracetam (LEV) during pregnancy is still limited. We analyzed efficacy and safety of LEV during pregnancy in North Indian women with epilepsy (WWE) which is being presented here. PATIENTS AND METHODS: This retrospective study included 99 WWE (on treatment with a single antiepileptic drug [AED]) who were evaluated in medical-surgical disorder antenatal clinic of the department of obstetrics and gynecology at a tertiary care teaching hospital and referral center in North India. All the obstetric and fetal data as well as data pertaining to epilepsy were noted meticulously. RESULTS: In this study (n = 99), 35 women received carbamazepine, 28 received LEV, 15 received valproate (VPA), 13 received phenytoin (PHT), three each received oxcarbazepine and lamotrigine, respectively, and two received clobazam. Although the use of VPA was associated with significantly better control of seizures compared to LEV, its use was associated with higher risk of major congenital malformations (13.3%). The incidence of gestational hypertension was lower while incidence of fetal distress was significantly higher in WWE receiving PHT during pregnancy. None of the child born to pregnant women receiving LEV had any congenital malformation. CONCLUSION: LEV is a first-line AED during pregnancy. Future prospective studies using therapeutic drug monitoring during pregnancy may further help in establishing its role during pregnancy.