Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Differential Iron Status and Trafficking in Blood and Placenta of Anemic and Non-anemic Primigravida Supplemented with Daily and Weekly Iron Folic Acid Tablets.

ABSTRACT: The molecular mechanism of iron transfer across placenta in response to maternal anemic status/ iron supplementation is not clear. We hypothesized that maternal iron/ anemia status during early trimesters can be utilized as a biomarker tool to get estimates of placental iron status. Early interventions can be envisaged to maintain optimum placental/ foetal iron levels for healthy pregnancy outcomes. One hundred twenty primigravida were recruited and divided into non-anemic and anemic group on the basis of hemoglobin levels. The groups were randomly allocated to receive daily and weekly iron folic acid (IFA) tablets till six weeks postpartum. Hematological and iron status markers in blood and placenta were studied along with the delivery notes. Weekly IFA supplementation in anemic primigravidas resulted in significantly reduced levels of hematological markers (p < 0.01); whereas non-anemic primigravidas showed lower ferritin and iron levels, and higher soluble transferrin receptor levels (p < 0.05). At baseline, C-reactive protein and cortisol hormone levels were also significantly lower in non-anemic primigravidas (p < 0.05). A significantly decreased placental ferritin expression (p < 0.05); and an increased placental transferrin expression was seen in anemic primigravidas supplemented with weekly IFA tablets. A significant positive correlation was observed between serum and placental ferritin expression in anemic pregnant women (r = 0.80; p < 0.007). Infant weight, gestational length and placental weight were comparable in both the supplementation groups. To conclude, mother's serum iron / anemia status switches the modulation in placental iron transporter expression for delivering the optimum iron to the foetus for healthy pregnancy outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India: CTRI/2014/10/005135.

Association of dietary intake below recommendations and micronutrient deficiencies during pregnancy and low birthweight.

Background Pregnancy is associated with biochemical changes leading to increased nutritional demands for the developing fetus that result in altered micronutrient status. The Indian dietary pattern is highly diversified and the data about dietary intake patterns, blood micronutrient profiles and their relation to low birthweight (LBW) is scarce. Methods Healthy pregnant women (HPW) were enrolled and followed-up to their assess dietary intake of nutrients, micronutrient profiles and birthweight using a dietary recall method, serum analysis and infant weight measurements, respectively. Results At enrolment, more than 90% of HPW had a dietary intake below the recommended dietary allowance (RDA). A significant change in the dietary intake pattern of energy, protein, fat, vitamin A and vitamin C (P < 0.001) was seen except for iron (Fe) [chi-squared (χ2) = 3.16, P = 0.177]. Zinc (Zn) deficiency, magnesium deficiency (MgDef) and anemia ranged between 54-67%, 18-43% and 33-93% which was aggravated at each follow-up visit (P ≤ 0.05). MgDef was significantly associated with LBW [odds ratio (OR): 4.21; P = 0.01] and the risk exacerbate with the persistence of deficiency along with gestation (OR: 7.34; P = 0.04). Pre-delivery (OR: 0.57; P = 0.04) and postpartum (OR: 0.37; P = 0.05) anemia, and a vitamin A-deficient diet (OR: 3.78; P = 0.04) were significantly associated with LBW. LBW risk was much higher in women consuming a vitamin A-deficient diet throughout gestation compared to vitamin A-sufficient dietary intake (OR: 10.00; P = 0.05). Conclusion The studied population had a dietary intake well below the RDA. MgDef, anemia and a vitamin A-deficient diet were found to be associated with an increased likelihood of LBW. Nutrient enrichment strategies should be used to combat prevalent micronutrient deficiencies and LBW.

Management of pregnancy at and beyond 41 completed weeks of gestation in low-risk women: a secondary analysis of two WHO multi-country surveys on maternal and newborn health.

BACKGROUND: The World Health Organization (WHO) recommends induction of labour (IOL) for women who have reached 41 completed weeks of pregnancy without spontaneous onset of labour. Many women with prolonged pregnancy and/or their clinicians elect not to induce, and chose either elective caesarean section (ECS) or expectant management (EM). This study intended to assess pregnancy outcomes of IOL, ECS and EM at and beyond 41 completed weeks. METHODS: This study is a secondary analysis of the WHO Global Survey (WHOGS) and the WHO Multi-country Survey (WHOMCS) conducted in Africa, Asia, Latin America and the Middle East. There were 33,003 women with low risk singleton pregnancies at ≥41 completed weeks from 292 facilities in 21 countries. Multilevel logistic regression model was used to assess associations of different management groups with each pregnancy outcome accounted for hierarchical survey design. The results were presented by adjusted odds ratios (aORs) with 95% confidence intervals (CIs) after adjusting for age, education, marital status, parity, previous caesarean section (CS), birth weight, and facility capacity index score. RESULTS: The prevalence of prolonged pregnancy at facility setting in WHOGS, WHOMCS and combined databases were 7.9%, 7.5% and 7.7% respectively. Regarding to maternal adverse outcomes, EM was significantly associated with decreased risk of CS rate consistently in both databases i.e. (aOR0.76; 95% CI: 0.66-0.87) in WHOGS, (aOR0.67; 95% CI: 0.59-0.76) in WHOMCS and (aOR0.70; 95% CI: 0.64-0.77) in combined database, compared to IOL. Regarding the adverse perinatal outcomes, ECS was significantly associated with increased risks of neonatal intensive care unit admission (aOR1.76; 95% CI: 1.28-2.42) in WHOMCS and (aOR1.51; 95% CI: 1.19-1.92) in combined database compared to IOL but not significant in WHOGS database. CONCLUSIONS: Compared to IOL, ECS significantly increased risk of NICU admission while EM was significantly associated with decreased risk of CS. ECS should not be recommended for women at 41 completed weeks of pregnancy. However, the choice between IOL and EM should be cautiously considered since the available evidences are still quite limited.

Evaluation of the Role of Umbilical Cord Serum and Autologous Serum Therapy in Reepithelialization After Keratoplasty: A Randomized Controlled Clinical Trial.

PURPOSE: To evaluate the role of umbilical cord serum (UCS) and autologous serum (AS) therapy in reepithelialization of corneal graft after keratoplasty in a randomized controlled trial. METHODS: A total of 105 eyes with epithelial defect (ED) after keratoplasty (penetrating keratoplasty-67 and anterior lamellar keratoplasty-38) on the first postoperative day were included in the study. The eyes were randomized into three groups: UCS (n=35), AS (n=35), and artificial tears (AT) (n=35). All patients received standard postoperative medical therapy. The primary outcome measure was time to epithelialization, and secondary outcome measures were best-corrected visual acuity and graft clarity. RESULTS: The ED healed completely in 103 eyes. The mean time for complete reepithelialization was 2.5±2.1, 3.1±2.2, and 4.5±1.4 days in UCS, AS, and AT groups, respectively. The mean percentage decrease in the size of the ED was significantly better in the UCS and AS groups as compared with the AT group (P=0.001). The rate of reepithelialization was comparable between the AS and UCS groups (P=0.3). On bivariate analysis, significant correlation was found between the mean size of postoperative ED, grade of the donor cornea (P=0.001), and the presence of preoperative ED (P=0.001). No complications were associated with the use of serum therapy. CONCLUSION: Most of the cases of postkeratoplasty corneal ED can be managed with AT only. The serum therapy (AS/UCS) helps in the faster reepithelialization of postkeratoplasty ED as compared with AT and may be considered as a treatment option for early epithelial healing.

Micronutrients Drift During Daily and Weekly Iron Supplementation in Non-anaemic and Anaemic Pregnancy.

AIMS: Pregnancy is a phenomenon associated with dynamic changes in physical, mental and biochemical status of body and demands increased nutritional intake for developing foetus. The level of various micronutrients which act as co-factors for antioxidant enzymes or it-self as antioxidants gets altered with the progression of pregnancy. The present longitudinal study summarized the trend of selected micronutrients level in anaemic (AP) and non-anaemic primigravida (NAP) supplemented with daily and weekly oral iron folic acid (IFA) tablet during pregnancy and postpartum. METHODS: A total of 200 primigravida {N = 100; NAP (Hb > 11 g/dl) and N = 100 AP (Hb = 8-11 g/dl) assigned daily (N = 50) and weekly (N = 50) supplementation} were recruited and overnight fasting blood samples were withdrawn at 13-16 weeks, after 3 months and 6 weeks postpartum. The serum iron, copper, zinc, magnesium and manganese were estimated by inductively coupled plasma-atomic emission spectrophotometer. RESULTS: Serum manganese (p < 0.05) at baseline and magnesium (p < 0.01) at postpartum was significantly different between NAP and AP supplemented with daily IFA tablets. The trend of copper found to be increased during pregnancy and later declined at postpartum in both the groups. Daily supplementation resulted in significantly high iron (p < 0.05) in NAP during third trimester. CONCLUSIONS: Hypozincemia and hypomagnesemia was observed in anaemic pregnancy supplemented with weekly and daily IFA respectively. Clear evidence of altered micronutrients levels during healthy and anaemic pregnancy was seen. The reference values may be drawn from this study for the nutritional assessment during pregnancy for healthy pregnancy outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India, http://ctri.nic.in, CTRI/2014/10/005135.

Periodicity of Deliveries - Findings from Six Selected North Indian Hospitals.

We present here a report, based on data obtained from six selected North Indian hospitals, on variations in the number of human deliveries over the period from 1 October 2010 to 30 September 2011. We tried to identify whether there are any cycles exhibited by the data. We discover cyclicity over different months of the year and days of the week whereas cyclicity over different phases of the lunar cycle is not clearly established.

Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study.

BACKGROUND: We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities. METHODS: In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios. RESULTS: From May 1, 2010, to Dec 31, 2011, we included 314,623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23,015 (7.3%) women had potentially life-threatening disorders and 3024 (1.0%) developed an SMO. 808 (26.7%) women with an SMO had post-partum haemorrhage and 784 (25.9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0.826 [95% CI 0.802-0.851]). INTERPRETATION: High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy. FUNDING: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

Emergency contraception - potential for women's health.

Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent.

Prospective analysis of ovarian reserve markers as determinant in response to controlled ovarian stimulation in women undergoing IVF cycles in low resource setting in India.

INTRODUCTION: The objective of this study was to determine whether ovarian reserve markers can predict ovarian response in women undergoing their first cycle of assisted reproduction. MATERIALS AND METHODS: This prospective observational study included 292 infertile patients undergoing their first IVF trial in the Assisted Reproductive Unit in a tertiary care hospital. Day 2 follicle stimulating hormone (FSH), Inhibin B, anti-Mullerian hormone (AMH), antral follicle count (AFC) and ovarian volume was measured before commencement of controlled ovarian hyperstimulation. The main outcome measures were oocytes retrieved and this was correlated with ovarian reserve markers. RESULTS: The mean age was 31.8 (±4.4) years and mean duration of infertility 8.2 (±3.9) years. The correlation between oocytes retrieved and age, day 2 FSH, Inhibin B, AMH, AFC and volume of the ovary was calculated. A negative correlation was found with age (r = -0.22, p < 0.001) and day 2 FSH (r = -0.35, p < 0.001). A positive correlation was seen with AMH (r = 0.15, p = 0.022), AFC (r = 0.48, p < 0.05) and volume (r = 0.17, p = 0.009). In the bivariate analysis, 1 year increase in age was found to decrease the oocytes retrieved count by 0.37 with a significant p value. The independent significant factors found in multiple linear regression analysis were day 2 FSH and AFC. DISCUSSION: The present study concludes that day 2 FSH and AFC are promising biomarkers for ovarian reserve in predicting ovarian response to gonadotropin stimulation in IVF patients.