Caitlin Shannon

First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review.

BACKGROUNDnThe dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure.nnnSTUDY DESIGNnTo identify eligible reports, we searched Medline, reviewed reference lists of published reports, and contacted experts to identify all prospective trials of any design of medical abortion using 200 mg mifepristone followed by misoprostol in women with viable pregnancies up to 63 days gestation. Two authors independently extracted data from each study. We used logistic regression models to explore associations between 15 characteristics of the trial groups and, separately, the rates of medical abortion failure and of ongoing pregnancy.nnnRESULTSnWe identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age >8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions.nnnCONCLUSIONSnEarly medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe.

Timing of initiation patterns of breastfeeding and infant survival: prospective analysis of pooled data from three randomised trials.

BACKGROUNDnAlthough the benefits of exclusive breastfeeding for child health and survival, particularly in the post-neonatal period, are established, the independent beneficial effect of early breastfeeding initiation remains unclear. We studied the association between timing of breastfeeding initiation and post-enrolment neonatal and post-neonatal mortality up to 6 months of age, as well as the associations between breastfeeding pattern and mortality.nnnMETHODSnWe examined associations between timing of breastfeeding initiation, post-enrolment neonatal mortality (enrolment 28 days), and post-neonatal mortality up to 6 months of age (29-180 days) in a large cohort from three neonatal vitamin A trials in Ghana, India, and Tanzania. Newborn babies were eligible for these trials if their mother reported that they were likely to stay in the study area for the next 6 months, they could feed orally, were aged less than 3 days, and the primary caregiver gave informed consent. We excluded infants who initiated breastfeeding after 96 h, did not initiate, or had missing initiation status. We pooled the data from both randomised groups of the three trials and then categorised time of breastfeeding initiation as: at ≤1 h, 2-23 h, and 24-96 h. We defined breastfeeding patterns as exclusive, predominant, or partial breastfeeding at 4 days, 1 month, and 3 months of age. We estimated relative risks using log binomial regression and Poisson regression with robust variances. Multivariate models controlled for site and potential confounders.nnnFINDINGSnOf 99u2008938 enrolled infants, 99u2008632 babies initiated breastfeeding by 96 h of age and were included in our prospective cohort. 56u2008981 (57·2%) initiated breastfeeding at ≤1 h, 38u2008043 (38·2%) at 2-23 h, and 4608 (4·6%) at 24-96 h. Compared with infants initiating breastfeeding within the first hour of life, neonatal mortality between enrolment and 28 days was higher in infants initiating at 2-23 h (adjusted relative risk 1·41 [95% CI 1·24-1·62], p<0·0001), and in those initiating at 24-96 h (1·79 [1·39-2·30], p<0·0001). These associations were similar when deaths in the first 4 days of life were excluded (1·32 [1·10-1·58], p=0·003, for breastfeeding initiation at 2-23 h, and 1·90 [1·38-2·62], p=0·0001, for initiation at 24-96 h). When data were stratified by exclusive breastfeeding status at 4 days of age (p value for interaction=0·690), these associations were also similar in magnitude but with wider confidence intervals for initiation at 2-23 h (1·41 [1·12-1·77], p=0·003) and for initiation at 24-96 h (1·51 [0·63-3·65], p=0·357). Exclusive breastfeeding was also associated with the lower mortality during the first 6 months of life (1-3 months mortality: exclusive vs partial breastfeeding at 1 month 1·83 [1·45-2·32], p<0·0001, and exclusive breastfeeding vs no breastfeeding at 1 month 10·88 [8·27-14·31], p<0·0001).nnnINTERPRETATIONnOur findings suggest that early initiation of breastfeeding reduces neonatal and early infant mortality both through increasing rates of exclusive breastfeeding and by additional mechanisms. Both practices should be promoted by public health programmes and should be used in models to estimate lives saved.nnnFUNDINGnBill & Melinda Gates Foundation through a grant to the WHO.

Effect of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial

BACKGROUNDnResults of randomised controlled trials of newborn (age 1-3 days) vitamin A supplementation have been inconclusive. The WHO is coordinating three large randomised trials in Ghana, India, and Tanzania (Neovita trials). We present the findings of the Neovita trial in Ghana.nnnMETHODSnThis study was a population-based, individually randomised, double-blind, placebo-controlled trial in the Brong Ahafo region of Ghana. The trial participants were infants aged at least 2 h, identified at home or facilities on the day of birth or in the next 2 days, able to feed orally, and likely to stay in the study area for at least 6 months. They were randomly assigned (ratio 1:1) to receive either one oral dose of vitamin A (50,000 IU) or placebo immediately after recruitment. The research team and parents of the infants were masked to treatment assignment. Follow-up home visits were undertaken every 4 weeks, when data were recorded for deaths, facility use, and care seeking. The primary outcome was post-supplementation mortality to 6 months of age. Analysis was by intention to treat. Potential adverse events were recorded at 1 and 3 days after supplementation. This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR)CTRN12610000582055.nnnFINDINGSnWe assessed 26,414 livebirths for eligibility between Aug 16, 2010, and Nov 7, 2011. We recruited 22,955 newborn infants, with 11,474 randomly assigned to receive vitamin A and 11,481 to receive placebo. Loss to follow-up was low with vital status at 6 months of age reported for 22,698 (98·9%) infants. We recorded 278 post-supplementation deaths to 6 months of age in the vitamin A group (mortality risk 24·5 in 1000 supplemented infants) and 248 deaths in the placebo group (mortality risk 21·8 per 1000 supplemented infants), relative risk (RR) 1·12 (95% CI 0·95-1·33; p=0·183) and risk difference (RD) 2·66 (95% CI -1·25 to 6·57; p=0·18). Adverse events within 3 days of supplementation did not differ by trial group. 122 infants died in the first 3 days after supplementation; 70 (0·6%) in the vitamin A and 52 (0·5%) in the placebo group (risk ratio [RR] 1·35, 95% CI 0·94-1·93, p=0·102). 53 infants were reported to have a bulging fontanelle; 32 (0·3%) in the vitamin A group and 21 (0·2%) in the placebo group (RR 1·53, 0·88-2·62, p=0·130).nnnINTERPRETATIONnThe results of this trial do not support inclusion of newborn vitamin A supplementation as a child survival strategy in Ghana.nnnFUNDINGnBill & Melinda Gates Foundation grant to the WHO.

Efficacy of Early Neonatal Vitamin A Supplementation in Reducing Mortality During Infancy in Ghana, India and Tanzania: Study Protocol for a Randomized Controlled Trial

BackgroundVitamin A supplementation of 6-59 month old children is currently recommended by the World Health Organization based on evidence that it reduces mortality. There has been considerable interest in determining the benefits of neonatal vitamin A supplementation, but the results of existing trials are conflicting. A technical consultation convened by WHO pointed to the need for larger scale studies in Asia and Africa to inform global policy on the use of neonatal vitamin A supplementation. Three trials were therefore initiated in Ghana, India and Tanzania to determine if vitamin A supplementation (50,000 IU) given to neonates once orally on the day of birth or within the next two days will reduce mortality in the period from supplementation to 6 months of age compared to placebo.Methods/DesignThe trials are individually randomized, double masked, and placebo controlled. The required sample size is 40,200 in India and 32,000 each in Ghana and Tanzania. The study participants are neonates who fulfil age eligibility, whose families are likely to stay in the study area for the next 6 months, who are able to feed orally, and whose parent(s) provide informed written consent to participate in the study. Neonates randomized to the intervention group receive 50,000 IU vitamin A and the ones randomized to the control group receive placebo at the time of enrolment. Mortality and morbidity information are collected through periodic home visits by a study worker during infancy. The primary outcome of the study is mortality from supplementation to 6 months of age. The secondary outcome of the study is mortality from supplementation to 12 months of age. The three studies will be analysed independent of each other. Subgroup analysis will be carried out to determine the effect by birth weight, sex, and timing of DTP vaccine, socioeconomic groups and maternal large-dose vitamin A supplementation.DiscussionThe three ongoing studies are the largest studies evaluating the efficacy of vitamin A supplementation to neonates. Policy formulation will be based on the results of efficacy of the intervention from the ongoing randomized controlled trials combined with results of previous studies.Trial RegistrationGhana: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000582055; India: CLINICALTRIALS.GOV - NCT01138449; Tanzania: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055.

Vaccination timing of low-birth-weight infants in rural Ghana: a population-based prospective cohort study.

Abstract Objective To investigate delays in first and third dose diphtheria–tetanus–pertussis (DTP1 and DTP3) vaccination in low-birth-weight infants in Ghana, and the associated determinants. Methods We used data from a large, population-based vitamin A trial in 2010–2013, with 22u2009955 enrolled infants. We measured vaccination rate and maternal and infant characteristics and compared three categories of low-birth-weight infants (2.0–2.4 kg; 1.5–1.9 kg; and <u20091.5 kg) with infants weighing ≥u20092.5 kg. Poisson regression was used to calculate vaccination rate ratios for DTP1 at 10, 14 and 18 weeks after birth, and for DTP3 at 18, 22 and 24 weeks (equivalent to 1, 2 and 3 months after the respective vaccination due dates of 6 and 14 weeks). Findings Compared with non-low-birth-weight infants (nu2009=u200918u2009979), those with low birth weight (nu2009=u20093382) had an almost 40% lower DTP1 vaccination rate at age 10 weeks (adjusted rate ratio, aRR: 0.58; 95% confidence interval, CI: 0.43–0.77) and at age 18 weeks (aRR: 0.63; 95% CI: 0.50–0.80). Infants weighing 1.5–1.9 kg (nu2009=u2009386) had vaccination rates approximately 25% lower than infants weighing ≥u20092.5 kg at these time points. Similar results were observed for DTP3. Lower maternal age, educational attainment and longer distance to the nearest health facility were associated with lower DTP1 and DTP3 vaccination rates. Conclusion Low-birth-weight infants are a high-risk group for delayed vaccination in Ghana. Efforts to improve the vaccination of these infants are warranted, alongside further research to understand the reasons for the delays.

Determinants of morbidity associated with infant male circumcision: community-level population-based study in rural Ghana.

Male circumcision services have expanded throughout Africa as part of a long‐term HIV prevention strategy. We assessed the effect of type of service provider (formal and informal) and hygiene practices on circumcision‐related morbidities in rural Ghana.

Neonatal vaccination of low birthweight infants in Ghana

Objectives Global vaccination policy advocates for identifying and targeting groups who are underserved by vaccination to increase equity and uptake. We investigated whether birth weight and other factors are determinants of neonatal BCG vaccination in order to identify infants underserved by vaccination. Methods We used logistic regression to calculate adjusted ORs (AORs) for the association between birth weight (categorised as non-low birth weight (NLBW) (≥2.50u2005kg) and low birth weight (LBW) (2–2.49u2005kg, 1.50–1.99u2005kg and <1.50u2005kg)) and non-vaccination with BCG at the end of the neonatal period (0–27u2005days). We assessed whether this association varied by place of delivery and infant illness. We calculated how BCG timing and uptake would improve by ensuring the vaccination of all facility-born infants prior to discharge. Results There was a strong dose–response relationship between LBW and not receiving BCG in the neonatal period (p-trend<0.0001). Infants weighing 1.50–1.99u2005kg had odds of non-vaccination 1.6 times (AOR 1.64; 95% CI 1.30 to 2.08), and those weighing <1.50u2005kg 2.4 times (AOR 2.42; 95% CI 1.50 to 3.88) those of NLBW infants. Other determinants included place of delivery, distance to the health facility and socioeconomic status. Neither place of delivery nor infant illness modified the association between birth weight and vaccination (p-interaction all >0.19). Facility-born infants were vaccinated at a mean of 6u2005days, suggesting that they were not vaccinated in the facility at birth but were referred for vaccination. Conclusions LBW is a risk factor for neonatal under-vaccination, even for facility-born infants. Ensuring vaccination at facility births would substantively improve timing and equitable BCG vaccination.

Population-based rates, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa: a multi-country prospective cohort study

Summary Background Modelled mortality estimates have been useful for health programmes in low-income and middle-income countries. However, these estimates are often based on sparse and low-quality data. We aimed to generate high quality data about the burden, timing, and causes of maternal deaths, stillbirths, and neonatal deaths in south Asia and sub-Saharan Africa. Methods In this prospective cohort study done in 11 community-based research sites in south Asia and sub-Saharan Africa, between July, 2012, and February, 2016, we conducted population-based surveillance of women of reproductive age (15–49 years) to identify pregnancies, which were followed up to birth and 42 days post partum. We used standard operating procedures, data collection instruments, training, and standardisation to harmonise study implementation across sites. Verbal autopsies were done for deaths of all women of reproductive age, neonatal deaths, and stillbirths. Physicians used standardised methods for cause of death assignment. Site-specific rates and proportions were pooled at the regional level using a meta-analysis approach. Findings We identified 278u2008186 pregnancies and 263u2008563 births across the study sites, with outcomes ascertained for 269u2008630 (96·9%) pregnancies, including 8761 (3·2%) that ended in miscarriage or abortion. Maternal mortality ratios in sub-Saharan Africa (351 per 100u2008000 livebirths, 95% CI 168–732) were similar to those in south Asia (336 per 100u2008000 livebirths, 247–458), with far greater variability within sites in sub-Saharan Africa. Stillbirth and neonatal mortality rates were approximately two times higher in sites in south Asia than in sub-Saharan Africa (stillbirths: 35·1 per 1000 births, 95% CI 28·5–43·1 vs 17·1 per 1000 births, 12·5–25·8; neonatal mortality: 43·0 per 1000 livebirths, 39·0–47·3 vs 20·1 per 1000 livebirths, 14·6–27·6). 40–45% of pregnancy-related deaths, stillbirths, and neonatal deaths occurred during labour, delivery, and the 24 h postpartum period in both regions. Obstetric haemorrhage, non-obstetric complications, hypertensive disorders of pregnancy, and pregnancy-related infections accounted for more than three-quarters of maternal deaths and stillbirths. The most common causes of neonatal deaths were perinatal asphyxia (40%, 95% CI 39–42, in south Asia; 34%, 32–36, in sub-Saharan Africa) and severe neonatal infections (35%, 34–36, in south Asia; 37%, 34–39 in sub-Saharan Africa), followed by complications of preterm birth (19%, 18–20, in south Asia; 24%, 22–26 in sub-Saharan Africa). Interpretation These results will contribute to improved global estimates of rates, timing, and causes of maternal and newborn deaths and stillbirths. Our findings imply that programmes in sub-Saharan Africa and south Asia need to further intensify their efforts to reduce mortality rates, which continue to be high. The focus on improving the quality of maternal intrapartum care and immediate newborn care must be further enhanced. Efforts to address perinatal asphyxia and newborn infections, as well as preterm birth, are critical to achieving survival goals in the Sustainable Development Goals era. Funding Bill & Melinda Gates Foundation.

Development and validation of a simplified algorithm for neonatal gestational age assessment – protocol for the Alliance for Maternal Newborn Health Improvement (AMANHI) prospective cohort study

Objective The objective of the Alliance for Maternal and Newborn Health Improvement (AMANHI) gestational age study is to develop and validate a programmatically feasible and simple approach to accurately assess gestational age of babies after they are born. The study will provide accurate, population–based rates of preterm birth in different settings and quantify the risks of neonatal mortality and morbidity by gestational age and birth weight in five South Asian and sub–Saharan African sites. Methods This study used on–going population–based cohort studies to recruit pregnant women early in pregnancy (<20 weeks) for a dating ultrasound scan. Implementation is harmonised across sites in Ghana, Tanzania, Zambia, Bangladesh and Pakistan with uniform protocols and standard operating procedures. Women whose pregnancies are confirmed to be between 8 to 19 completed weeks of gestation are enrolled into the study. These women are followed up to collect socio–demographic and morbidity data during the pregnancy. When they deliver, trained research assistants visit women within 72 hours to assess the baby for gestational maturity. They assess for neuromuscular and physical characteristics selected from the Ballard and Dubowitz maturation assessment scales. They also measure newborn anthropometry and assess feeding maturity of the babies. Computer machine learning techniques will be used to identify the most parsimonious group of signs that correctly predict gestational age compared to the early ultrasound date (the gold standard). This gestational age will be used to categorize babies into term, late preterm and early preterm groups. Further, the ultrasound–based gestational age will be used to calculate population–based rates of preterm birth. Importance of the study The AMANHI gestational age study will make substantial contribution to improve identification of preterm babies by frontline health workers in low– and middle– income countries using simple evaluations. The study will provide accurate preterm birth estimates. This new information will be crucial to planning and delivery of interventions for improving preterm birth outcomes, particularly in South Asia and sub–Saharan Africa.

Safety of tubal ligation by minilaparotomy provided by clinical officers versus assistant medical officers: study protocol for a noninferiority randomized controlled trial in Tanzanian women

BackgroundFemale sterilization by tubal ligation is a safe, extremely effective, and permanent way to limit childbearing. It is the most popular modern contraceptive method worldwide. The simplest way to provide tubal ligation is by a procedure called minilaparotomy, generally performed with the clientxa0under local anesthesia with systemic sedation and analgesia. In Tanzania, unmet need for family planning is high and has declined little in the past decade. Access to tubal ligation is limited throughout the country, in large part because of a lack of trained providers. Clinical officers (COs) are midlevel health workers who provide diagnosis, treatment, and minor surgeries. They are more prevalent than physicians in poorer and rural communities. Task shifting—the delegation of some tasks to less-specialized health workers, including task shifting of surgical procedures to midlevel cadres—has improved access to lifesaving interventions in resource-limited settings. It is a cost-effective way to address shortages of physicians, increasing access to services. The primary objective of this trial is to establish whether the safety of tubal ligation by minilaparotomy provided by COs is noninferior to the safety of tubal ligation by minilaparotomy provided by physicians (assistant medical officers [AMOs]), as measured by rates of major adverse events (AEs) during the procedure and through 42xa0days of follow-up.Methods/designIn this facility-based, multicenter, noninferiority randomized controlled trial, we are comparing the safety of tubal ligation by minilaparotomy performed by trained COs versus by trained AMOs. The primary outcome is safety, defined by the overall rate of major AEs occurring during the minilaparotomy procedure and through 42xa0days of follow-up. The trial will be conducted among 1970 women 18xa0years of age or older presenting for tubal ligation at 7 study sites in northern Tanzania.DiscussionIf no major safety issues are identified, the data from this trial may facilitate changes in the Tanzanian government’s regulations, allowing appropriately trained COs to provide tubal ligation by minilaparotomy. Positive findings may have broader implications. Task shifting to provide long-acting contraceptives, if proven safe, may be an effective approach to increasing contraceptive access in low- and middle-income countries.Trial registrationClinicalTrials.gov, NCT02944149. Registered on 14 October 2016.