Anjoo Agarwal

Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant

Hypovitaminosis D is common in India. In the present prospective partially randomised study of vitamin D (D₃) supplementation during pregnancy, subjects were randomised in the second trimester to receive either one oral dose of 1500 μg vitamin D₃ (group 1, n 48) or two doses of 3000 μg vitamin D₃ each in the second and third trimesters (group 2, n 49). Maternal 25-hydroxyvitamin D (25(OH)D) at term, cord blood (CB) alkaline phosphatase (ALP), neonatal serum Ca and anthropometry were measured in these subjects and in forty-three non-supplemented mother-infant pairs (usual care). Median maternal 25(OH)D at term was higher in group 2 (58·7, interquartile range (IQR) 38·4-89·4 nmol/l) v. group 1 (26·2, IQR 17·7-57·7 nmol/l) and usual-care group (39·2, IQR 21·2-73·4 nmol/l) (P = 0·000). CB ALP was increased (>8.02 μkat/l or >480 IU/l) in 66·7 % of the usual-care group v. 41·9 % of group 1 and 38·9 % of group 2 (P = 0·03). Neonatal Ca and CB 25(OH)D did not differ significantly in the three groups. Birth weight, length and head circumference were greater and the anterior fontanelle was smaller in groups 1 and 2 (3·08 and 3·03 kg, 50·3 and 50·1 cm, 34·5 and 34·4 cm, 2·6 and 2·5 cm, respectively) v. usual care (2·77 kg, 49·4, 33·6, 3·3 cm; P = 0·000 for length, head circumference and fontanelle and P = 0·003 for weight). These differences were still evident at 9 months. We conclude that both 1500 μg and two doses of 3000 μg vitamin D₃ had a beneficial effect on infant anthropometry, the larger dose also improving CB ALP and maternal 25(OH)D.

Impact of maternal body mass index on obstetric outcome

Aim:  The purpose of the present study was to correlate effect of maternal body mass index (BMI) on obstetric outcome. The studies conducted so far are from Western developed countries and there is a paucity of data from developing countries.

Evaluation of mifepristone as a once a month contraceptive pill.

OBJECTIVE The purpose of this study was to assess the efficacy and safety of mifepristone as a contraceptive pill. STUDY DESIGN A prospective case-control study was conducted in a tertiary care center of North India. The study group (n = 86) was given 200-mg mifepristone tablets on the 16th day of the menstrual cycle. The control group (n = 92) received combined oral contraceptive (COC) as per protocol. Subjects were followed for drug compliance, satisfaction, side effects, and failure. RESULTS Acceptability of mifepristone was significantly higher in educated population (P < .001), with fewer side effects (P = .001), good satisfaction (P < .001), and higher compliance rate (P = .05). The oral contraceptive pill group had higher adverse biochemical parameters. CONCLUSION Mifepristone can be used as a monthly contraceptive pill effectively.

Alteration in Endometrial Proteins during Early- and Mid-Secretory Phases of the Cycle in Women with Unexplained Infertility

Background Compromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility. Methods 2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women. Results Nine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women. Conclusions De-regulation of the expression of Sorcin, Cofilin-1, Apo-A1 and Ran, during early- to mid-secretory phase may have physiological significance and it may be one of the causes for altered differentiation and/or maturation of endometrium, in women with unexplained infertility.

Impact of grandmultiparity on obstetric outcome in low resource setting

Aim:  This study was undertaken to evaluate the impact of grandmultiparity on obstetric outcome in a low resource setting.

Consequences of delay in obstetric care for maternal and perinatal outcomes.

This article discusses a study conducted in a tertiary hospital in Lucknow India with pregnant women presenting at the hospital with hemodynamic instability or loss of consciousness as eligible for inclusion in the study. The study highlights that the cost of travel and health services coupled with the difficulty in arranging motorized transport and poor road infrastructure were the mains reasons for delay in reaching health facilities and consequently the increased maternal mortality rate. Copyright

Evaluation of pregnant women with scarred uterus in a low resource setting

Aim:  Management of post cesarean pregnancy continues to be a dilemma. The present study was undertaken to evaluate the outcome of such pregnancies in a resource constrained setting so that an appropriate management protocol can be decided.

PI3K/Akt/mTOR signaling & its regulator tumour suppressor genes PTEN & LKB1 in human uterine leiomyomas.

Background & objectives: Despite their high occurrence and associated significant level of morbidity manifesting as spectrum of clinical symptoms, the pathogenesis of uterine leiomyomas (ULs) remains unclear. We investigated expression profile of tumour suppressor genes PTEN (phosphatase and tensin homolog deleted on chromosome ten) and LKB1 (liver kinase B1), and key signaling components of P13K (phosphatidylinositol 3-kinase)/Akt (protein kinase B)/mTOR (mammalian target of rapamycin) pathway in leiomyomas and adjacent normal myometrium in women of reproductive age, to explore the possibility of targeting this pathway for future therapeutic implications. Methods: Real time PCR (qPCR) was used to quantify relative gene expression levels of PTEN, Akt1, Akt2, mTOR, LKB1 and VEGFA (vascular endothelial growth factor A) in leiomyoma as compared to adjacent normal myometrium. Immunohistochemistry was subsequently performed to analyze expression of PTEN, phospho-Akt, phospho-mTOR, phospho-S6, LKB1 and VEGFA in leiomyoma and adjacent normal myometrium. Results: Significant upregulation of PTEN (2.52 fold; P=0.03) and LKB1 (3.93 fold; P=0.01), and downregulation of VEGFA (2.95 fold; P=0.01) genes were observed in leiomyoma as compared to normal myometrium. Transcript levels of Akt1, Akt2 and mTOR did not vary significantly between leiomyoma and myometrium. An increased immunoexpression of PTEN (P=0.015) and LKB1 (P<0.001) and decreased expression of VEGFA (P=0.01) was observed in leiomyoma as compared to myometrium. Immunostaining for activated (phosphorylated) Akt, mTOR and S6 was absent or low in majority of leiomyoma and myometrium. Interpretation & conclusions: Upregulation of PTEN and LKB1 in concert with negative or low levels of activated Akt, mTOR and S6 indicates that PI3K/Akt/mTOR pathway may not play a significant role in pathogenesis of leiomyoma.

Aberrant Akt Activation During Implantation Window in Infertile Women With Intramural Uterine Fibroids

The objective of the study was to examine the expression and cellular distribution of key signaling components of the phosphatidylinositol-3-kinase (PI3K)/Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Protein Kinase B (PKB/Akt) pathway during the window of implantation in infertile women with noncavity-distorting intramural uterine fibroids (n = 21) as compared to fertile controls (n = 15). Relative gene expression analysis of PIK3CA, PTEN, Akt1, and Akt2 genes in midluteal endometrial biopsies was performed by real-time polymerase chain reaction. Immunohistochemistry was used to evaluate the expression of PIK3CA, PTEN, phospho-PTEN, Akt1, Akt2, phospho-Akt1 (serine 473), phospho-Akt1 (threonine 308), and Ki67 proteins. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay was performed for apoptosis detection. In comparison to fertile controls, significant upregulation of Akt1 messenger RNA levels (2.16-fold; P < .05); cell-specific upregulation of the proteins phospho-PTEN (P < .05), Akt1 (P < .05), Akt2 (P < .05), and p-Akt (S473; P < .001); and downregulation of PTEN (P < .01) were observed in endometrium of infertile women with intramural fibroids. The ratio of p-PTEN/PTEN and p-Akt1 (S473)/Akt1 was also significantly higher in infertile women. Increased Ki67 labeling index in the glandular epithelium and significantly lower apoptotic index in glandular epithelium and stroma were seen in infertile women during the window of implantation. Aberrant Akt activation and the associated imbalance in endometrial proliferation and apoptosis observed in infertile women with intramural fibroids during the midsecretory phase might contribute to impaired endometrial receptivity leading to infertility in these patients.

Fetomaternal outcomes in pregnant women with hepatitis E infection; still an important fetomaternal killer with an unresolved mystery of increased virulence in pregnancy

Objective: Hepatitis is a prevalent infection in developing countries. While hepatitis B and C are deepening their roots in the developed world, hepatitis A and E are common in the developing world. The uniqueness of hepatitis is in its transformation from a relatively self-limiting disease in the non-pregnant state, to a highly virulent disease during pregnancy. Materials and Methods: This retrospective observational study was conducted in the Department of Obstetrics and Gynecology, King George’s Medical University, Lucknow, for a period of six months from June 2016 to November 2016 [probably during an endemic peak of hepatitis E virus (HEV)] to observe the clinical outcomes in HEV-infected pregnant women. Results: A total of 32 anti-HEV immunoglobulin M-positive pregnant women were included, and fetomaternal outcomes were analyzed. Hepatitis E positivity was significantly associated with maternal mortality, intrauterine demise with prematurity, and premature rupture of membranes was the most common fetal complication noted. Conclusion: The difference in extent of virulence of infection and variations in maternal morbidity, mortality, and rates of intrauterine demise, signify the presence of some factors that play a role and need to be further studied and evaluated.