Two prophylactic pain management regimens for medical abortion ≤63 days' gestation with mifepristone and misoprostol: A multicenter, randomized, placebo-controlled trial.

OBJECTIVE: To determine if either prophylactic tramadol 50 mg or ibuprofen 400 mg/metoclopramide 10 mg result in lower maximal pain compared to placebo in women ≤63 days' gestation having a mifepristone-misoprostol medical abortion. STUDY DESIGN: We conducted a randomized, placebo-controlled trial in Nepal, South Africa, and Vietnam. Participants seeking medical abortion received active treatment or placebo, taken at time of misoprostol and repeated 4 hours later. All had access to additional analgesia. The primary outcome was mean maximum pain score within 8 hours. Participants self-assessed maximum pain using an 11-point numeric rating scale recorded in paper diaries; we analyzed these data using intention-to-treat analysis. Secondary outcomes included use of additional analgesia, side effects, and satisfaction. RESULTS: We enrolled 563 patients between June 2016 and October 2017; 5 participants failed to follow up. Mean adjusted maximum pain scores within 8 hours in both active arms were lower than placebo (tramadol: n = 188, 6.78 (95% confidence interval [CI] 6.46, 7.11); ibuprofen/metoclopramide: n = 187, 6.43 (95% CI 6.10, 6.75); placebo: n = 188, 7.42 (95% CI 7.10, 7.74); p = 0.0001). Additional analgesia was used by 97 (52.2%) participants in the tramadol group, 80 (43.0%) in the ibuprofen/metoclopramide group, and 103 (55.7%) in the placebo group, p = 0.04. More dizziness (p = 0.004), headache (p = 0.03), and vomiting (p < 0.001) occurred in the tramadol group. More participants reported experienced pain was the same or less than expected in the ibuprofen/metoclopramide group (p = 0.05); overall abortion satisfaction did not differ by group (p = 0.44). CONCLUSIONS: Compared with placebo, tramadol or ibuprofen/metoclopramide co-administered with misoprostol and repeated 4 h later resulted in lower mean maximum pain scores that failed to achieve clinical significance. Women who received ibuprofen/metoclopramide were least likely to use additional analgesia and reported fewer side effects. IMPLICATIONS: Given that tramadol, ibuprofen, and metoclopramide are inexpensive, globally available; and, ibuprofen and metoclopramide are included on the World Health Organization Essential Medicines List, these medicines could be considered for prophylactic pain management during medical abortion.

Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial.

INTRODUCTION: Vitamin B12 deficiency is widely prevalent across many low- and middle-income countries, especially where the diet is low in animal sources. While many observational studies show associations between B12 deficiency in pregnancy and infant cognitive function (including memory, language and motor skills), evidence from clinical trials is sparse and inconclusive. METHODS AND ANALYSIS: This double-blind, multicentre, randomised controlled trial will enrol 720 vegetarian pregnant women in their first trimester from antenatal clinics at two hospitals (one in India and one in Nepal). Eligible mothers who give written consent will be randomised to receive either 250 mcg methylcobalamin or 50 mcg (quasi control), from enrolment to 6 months post-partum, given as an oral daily capsule. All mothers and their infants will continue to receive standard clinical care. The primary trial outcome is the offspring's neurodevelopment status at 9 months of age, assessed using the Development Assessment Scale of Indian Infants. Secondary outcomes include the infant's biochemical B12 status at age 9 months and maternal biochemical B12 status in the first and third trimesters. Maternal biochemical B12 status will also be assessed in the first trimester. Modification of association by a priori identified factors will also be explored. ETHICAL CONSIDERATIONS AND DISSEMINATION: The study protocol has been approved by ethical committees at each study site (India and Nepal) and at University College London, UK. The study results will be disseminated to healthcare professionals and academics globally via conferences, presentations and publications. Researchers at each study site will share results with participants during their follow-up visits.Trial registration numberCTRI/2018/07/015048 (Clinical Trial Registry of India); NCT04083560 (ClinicalTrials.gov).

Severity of Hyperemesis Gravidarum and Associated Maternal factors.

BACKGROUND: Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy. It is one of the most common cause of early pregnancy admissions and associated with various maternal risk factors . Very few studies have been conducted among Nepalese women with hyperemesis gravidarum. This study aims to identify various maternal risk factors among Nepalese women and its severity using pregnancy unique quantification of emesis scoring. METHODS: This is a cross sectional observational study conducted at Paropakar Maternity and Women's Hospital. Total duration of the study period was for one year from February 2018 to Janurary 2019. A total of 144 patients meeting the inclusion criteria were included in the study.The severity of the hyperemesis gravidarum was assessed and classified using pregnancy unique quantification of emesis scoring. Various maternal demographic, obstetric and personal factors were studied in relation to the incidence and severity of hyperemesis gravidarum. RESULTS: Moderate (49.30%) to severe(50.69%) hyperemesis gravidarum were admitted in the hospital. Most women were nulliparous from 20-24 years age group. Among all categories of BMI, underweight had more severe hyperemesis gravidarum (63.63%) and overweight patient had increased incidence of moderate hyperemesis gravidarum (66.66%). Women with previous dysmenorrhea had severe hyperemesis gravidarum (54.05%) and non-smoker had severe hyperemesis gravidarum (52.03%) while smoker had moderate hyperemesis gravidarum (57.14%). CONCLUSIONS: Pregnant women of age group of 20-24 years, nulliparity and underweight were associated with severe hyperemesis gravidarum.

Effect of early versus delayed cord clamping in neonate on heart rate, breathing and oxygen saturation during first 10 minutes of birth - randomized clinical trial.

BACKGROUND: Delayed cord clamping (DCC) after 180 s reduces iron deficiency up to 8 months of infancy compared to babies who received Early Cord Clamping (ECC) at less than 60 s. Experimentally DCC has shown to improve cardio-vascular stability. To evaluate the effect of delayed (≥180 s) group versus early (≤60 s) cord clamping group on peripheral blood oxygenation and heart rate up to 10 min after birth on term and late preterm infants. METHODS: We conducted a single centred randomized clinical trial in a low risk delivery unit in tertiary Hospital, Nepal. One thousand five hundred ten women, low risk vaginal delivery with foetal heart rate (FHR) ≥ 100 ≤ 160 beats per minute (bpm) and gestational age (≥33 weeks) were enrolled in the study. Participants were randomly assigned to cord clamped ≤60 s of birth and ≥ 180 s. The main outcome measures were oxygen saturation, heart rate from birth to 10 min and time of spontaneous breathing. The oxygen saturation and heart rate, the time of first breath and establishment of regular breathing was analysed using Student t-test to compare groups. We analysed the range of heart rate distributed by different centiles from the time of birth at 30 s intervals until 10 min. RESULTS: The oxygen saturation was 18% higher at 1 min, 13% higher at 5 min and 10% higher at 10 min in babies who had cord clamping in delayed group compared to early group (p < 0.001). The heart rate was 9 beats lower at 1 min and3 beats lower at 5 min in delayed group compared to early group (p < 0.001). Time of first breath and regular breathing was established earlier in babies who had cord clamping at 180 s or more. CONCLUSION: Spontaneously breathing babies subjected to DCC have higher oxygen saturation up to 10 min after birth compared to those who have undergone ECC. Spontaneously breathing babies with DCC have lower heart rates compared to ECC until 390 s. Spontaneously breathing babies receiving DCC have early establishment of breathing compared to ECC. TRIAL REGISTRATION: ISRCTN, 5 April 2016.

Incidence of intrapartum stillbirth and associated risk factors in tertiary care setting of Nepal: a case-control study.

BACKGROUND: Each year, 1.2 million intrapartum stillbirths occur globally. In Nepal, about 50 % of the total number of stillbirths occur during the intrapartum period. An understanding of the risk factors associated with intrapartum stillbirth will facilitate the development of preventative strategies to reduce the associated burden of death. This study was conducted in a tertiary-care setting with the aim to identify risk factors associated with intrapartum stillbirth. METHODS: A case-control study was completed from July 2012 to September 2013. All women who had an intrapartum stillbirth during the study period were included as cases, and 20 % of women with live births were randomly selected upon admission to create the referent population. Relevant information was retrieved from clinical records for case and referent women. In addition, interviews were completed with each woman to determine their demographic and obstetric history. RESULTS: During the study period, 4,476 women were enrolled as referents and 136 women had intrapartum stillbirths. The following factors were found to be associated with an increased risk for intrapartum stillbirth: poor familial wealth quintile (Adj OR 1.8, 95 % CI-1.1-3.4); less maternal education (Adj OR, 3.2 95 % CI-1.8-5.5); lack of antenatal care (Adj OR, 4.8 95 % CI 3.2-7.2); antepartum hemorrhage (Adj OR 2.1, 95 % CI 1.1-4.2); multiple births (Adj. OR-3.0, 95 % CI- 1.9-5.4); obstetric complication during labor (Adj. OR 4.5, 95 % CI-2.9-6.9); lack of fetal heart rate monitoring per protocol (Adj. OR-1.9, 95 % CI 1.5-2.4); lack of partogram use (Adj. OR-2.1, 95 % CI 1.1-4.1); small-for-gestational age (Adj. OR-1.8, 95 % CI-1.2-1.7); preterm birth (Adj. OR-5.4, 95 % CI 3.5-8.2); and being born preterm with a small-for-gestational age (Adj. OR-9.0, 95 % CI 7.3-15.5). CONCLUSION: Being born preterm with a small-for-gestational age was associated with the highest risk for intrapartum stillbirth. Inadequate fetal heart rate monitoring and partogram use are preventable risk factors associated with intrapartum stillbirth; by increasing adherence to these interventions the risk of intrapartum stillbirth can be reduced. The association of the lack of appropriate antenatal care with intrapartum stillbirth indicates that quality antenatal care may improve fetal health and outcomes. TRIAL REGISTRATION: ISRCTN97846009.