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Objective: To determine whether training traditional birth attendants to manage several common perinatal conditions could reduce neonatal mortality in the setting of a resource poor country with limited access to healthcare. Design: Prospective, cluster randomised and controlled effectiveness study. Setting: Lufwanyama, an agrarian, poorly developed district located in the Copperbelt province, Zambia. All births carried out by study birth attendants occurred at mothers’ homes, in rural village settings. Participants: 127 traditional birth attendants and mothers and their newborns (3559 infants delivered regardless of vital status) from Lufwanyama district. Interventions: Using an unblinded design, birth attendants were cluster randomised to intervention or control groups. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. Control birth attendants continued their existing standard of care (basic obstetric skills and use of clean delivery kits). Main outcome measures: The primary outcome was the proportion of liveborn infants who died by day 28 after birth, with rate ratios statistically adjusted for clustering. Secondary outcomes were mortality at different time points; and comparison of causes of death based on verbal autopsy data. Results: Among 3497 deliveries with reliable information, mortality at day 28 after birth was 45% lower among liveborn infants delivered by intervention birth attendants than control birth attendants (rate ratio 0.55, 95% confidence interval 0.33 to 0.90). The greatest reductions in mortality were in the first 24 hours after birth: 7.8 deaths per 1000 live births for infants delivered by intervention birth attendants compared with 19.9 per 1000 for infants delivered by control birth attendants (0.40, 0.19 to 0.83). Deaths due to birth asphyxia were reduced by 63% among infants delivered by intervention birth attendants (0.37, 0.17 to 0.81) and by 81% within the first two days after birth (0.19, 0.07 to 0.52). Stillbirths and deaths from serious infection occurred at similar rates in both groups. Conclusions: Training traditional birth attendants to manage common perinatal conditions significantly reduced neonatal mortality in a rural African setting. This approach has high potential to be applied to similar settings with dispersed rural populations. Trial registration: Clinicaltrials.gov NCT00518856.
Lufwanyama is a vast, sparsely populated and under-developed rural district located in Zambia’s Copperbelt province (estimated population 63 185, size 3803 square miles (9849 km2), density about 6.4 people/km2).13 During the study, Lufwanyama had 12 government supported rural health centres staffed by nurse midwives or clinical officers; the district had no resident doctors and no hospital. We used an unblinded, cluster randomised and controlled study in which traditional birth attendants were randomly allocated to receive training and equipment to render them proficient in a set of skills targeting common causes of neonatal mortality (intervention group), or to continue with their existing standard of care (control group). Each cluster was defined as all of the births delivered by a given birth attendant. Because the interventions were applied at district level, we used an effectiveness study building on an existing infrastructure for healthcare delivery. Beyond provision of training and essential equipment and creating a system by which to document the outcomes of deliveries by the birth attendants, the study minimised oversight and contact with the birth attendants so as not to interfere with their routine delivery of obstetric care. Before the study, traditional birth attendants had been trained in basic obstetric and newborn care (including mouth to mouth assisted breathing) and clean delivery techniques, and used clean delivery kits for every delivery. They were required to refer all high risk pregnancies to be delivered at a health centre. The birth attendants maintained a link to the formal health sector through the Lufwanyama rural health centre and were supported by the Lufwanyama District Health Management Team. Although the study was carried out with the approval of the Lufwanyama District Health Management Team, no formal link existed between the study and the healthcare sector. After enrolling in the study, the birth attendants received additional training on basic record keeping, the reporting aspects of the trial, and the importance of maintaining regular contact with the mother and infant pair, even after the delivery. Subsequently the birth attendants were randomly allocated (1:1) to intervention or control groups. Randomisation was done by generating 120 allocation slips (60 intervention and 60 control), which were placed in an opaque container. During a public ceremony, witnessed by all the birth attendants and study staff, the participants individually took a slip from the box and the group allocation was announced to the whole group. Using a public ceremony to carry out randomisation was consistent with local customs. After randomisation, the control birth attendants returned to their villages and continued their existing standard of care; the intervention birth attendants remained to receive further training. Intervention birth attendants each took part in two, one week training workshops, carried out in June and August 2006. The trainers, members of the study team, used a variety of techniques, including interactive lectures, demonstrations, small group sessions, and skills practice using infant manikins. To be judged competent, each birth attendant had to satisfactorily complete a one on one skills assessment with one of the trainers. After the initial training, both intervention and control birth attendants took part in refresher workshops every three or four months throughout the study, again with one to one skills assessments for each intervention birth attendant. During the baseline and subsequent refresher training, the birth attendants were compensated for their travel costs and provided with food and lodging while attending the workshops. None of the participants received salary support or other incentives for their participation in the study. The intervention had two components: training in a modified version of the neonatal resuscitation protocol, and single dose amoxicillin coupled with facilitated referral of infants to a health centre. The neonatal resuscitation protocol, a modification of that endorsed by the American Academy of Pediatrics and American Heart Association,5 aimed to reduce mortality from neonatal hypothermia and birth asphyxia. The resuscitation protocol consists of a series of standardised procedures, some of which are to be carried out at every delivery and some of which are done only as needed. The resuscitation protocol is not synonymous with positive pressure ventilation but rather is a continuum of interventions that may culminate in ventilation. In fact, if the early steps of the protocol are used effectively, positive pressure ventilation should only be required in a few deliveries. In our adaptation of the resuscitation protocol, the birth attendants were trained to rapidly dry and warm the newborn, clear airways, and evaluate respiratory effort, colour, and tone. The use of supplemental oxygen, adrenaline (epinephrine), or other drugs, and training in chest compressions, endotracheal intubation, and other advanced steps were beyond the resource potential for the rural community studied, so were not used. The sequence of steps in the resuscitation protocol as adapted for Lufwanyama traditional birth attendants included immediately drying the infant and swaddling in a second dry blanket to avoid hypothermia, suctioning the infant’s mouth and nose with a soft rubber suction bulb, and optimally positioning the infant’s airway, followed by an assessment of the infant’s breathing. Intervention birth attendants were also trained to stimulate the infants, when indicated, by gently rubbing their back or feet5 and to provide positive pressure ventilation for infants with inadequate or absent respiratory effort by using a reusable, resuscitator mask (Laerdal, Pediatric Pocket Resuscitator; Laerdal, Wappingers Falls, New York; see web extra on bmj.com). Stimulation was continued briefly when infants were not vigorous, but if there was absent or poor respiratory effort the birth attendants were trained to immediately begin positive pressure ventilation. Although the birth attendants were expected to maintain regular contact with the mother and infant pair during the first week after birth and to refer neonates for care if they appeared unwell, intervention birth attendants were also trained to recognise cardinal symptoms and signs of possible sepsis (see web extra on bmj.com).14 15 On identifying a neonate with any of these findings, intervention birth attendants administered a single dose of oral amoxicillin (powder from two 250 mg amoxicillin capsules mixed with 8 mL chlorinated water) and then referred the mother and infant pair to the nearest health facility, ideally accompanying them. Amoxicillin was selected because of its known safety record and high therapeutic index, its anticipated activity against common pathogens causing neonatal sepsis, and because it can be stored without refrigeration. We chose the 500 mg dose to maximise therapeutic levels of drug in instances where sepsis might have reduced enteric absorption. Both intervention and control birth attendants were issued with one clean delivery kit per birth. Each kit contained a plastic delivery sheet, a cord cutter, cotton cord ties, one pair of latex gloves, soap, and a candle with matches (for deliveries at night). In addition, each intervention birth attendant received a resuscitator mask and polypropylene bottle with chlorinated water, plus, for each delivery, two absorbent flannel blankets (one for drying the infant, the other for swaddling), a soft rubber bulb syringe, two 250 mg amoxicillin capsules, a 2 ounce (59 ml) mixing cup and spoon, and a 3 ml oral syringe. Intervention birth attendants received laminated reference cards summarising the neonatal resuscitation protocol and the trigger conditions for antibiotics with facilitated referral (see web extra). A team of 16 data collectors was responsible for ascertaining the final vital status of the infants. The data collectors were recruited from, and in all but one case resided within, the Lufwanyama community. Each data collector was assigned to cover a specific geographical zone in Lufwanyama and was responsible for following the activities of all of the birth attendants who resided in that zone. To accomplish this, each data collector received a mountain bicycle and was required to maintain weekly face to face contact with their assigned birth attendants, to keep an up to date record of the pregnant women each birth attendant was following and their estimated delivery dates, and to determine whether any of these mothers had delivered. To ensure that all births were reported, the data collectors queried the birth attendants if expected delivery dates passed without the birth being reported. The birth attendants completed a standardised birth record for every delivery, capturing basic information about the mother’s antenatal status, interventions provided during delivery, and the infant’s vital status on the day of delivery. The birth attendants were instructed to inform their assigned data collector within 48 hours of a delivery. The data collector then retrieved the delivery report from the birth attendant, reviewed and verified the contents of the report with the birth attendant, and carried out up to two follow-up visits (at one and four weeks) with the mother and infant pair. At the first visit, the birth attendant guided the data collector to the mother’s home and made introductions. Baseline data collected included maternal household demographic and economic data, data regarding payments made to the birth attendant by the mother, and maternal reproductive history. Additionally, the visits at one and four weeks assessed the vital status of the infant. Data collectors submitted case report forms to the field manager each month, which were entered into the database (CSPro; US Census Bureau, Washington, DC) at the LUNESP offices, using dual data entry. The study was closely monitored by the research team throughout the period of data collection, and the computerised data were cross checked with the paper records at the end of the trial to ensure accuracy. If a neonate died at any time during the first month after birth (including stillbirths), the data collectors were trained to interview the mother or guardian of the infant, using the World Health Organization’s verbal autopsy algorithm16 to help define the most likely cause of death. A panel of three Boston based neonatologists, who had no contact with the birth attendants or data collectors and were blinded to group allocation, independently reviewed the delivery reports and verbal autopsy findings to ascribe a presumptive cause of death for each case, selecting from among serious infection, birth asphyxia, prematurity, tetanus, congenital malformation, diarrhoea, stillbirth, other, or unknown; concordance of two reviewers was required. The study was powered to detect a 35% difference between the two birth cohorts in the proportion of liveborn neonates delivered by the birth attendants surviving to day 28 after birth.17 18 19 Since the study only assessed outcomes among deliveries carried out by the traditional birth attendants, we did not assess referrals who delivered at health facilities. We calculated the sample size using the formula for proportions in unmatched studies assuming 80% power, a two sided α of 0.05, and a coefficient of variation of 0.25. According to official mortality statistics, the neonatal mortality rate in Zambia is about 30-40 per 1000 live births.20 21 Assuming 60 clusters per arm with an estimated 28 births per birth attendant, 1680 participants per study arm would provide sufficient power, for a total of 3360 neonates—that is, a decline from 40 per 1000 live births to 26 per 1000 live births, rate ratio 0.35. Given the rural and isolated nature of Lufwanyama and based on discussions with the Lufwanyama District Health Management Team, we made the assumption that the neonatal mortality rate in the district might be lower than reported. Therefore, given potential year to year fluctuations in infant mortality, uncertainties about the baseline neonatal mortality estimates in Lufwanyama, and the magnitude of potential loss to follow-up, we presumptively increased the target sample size to 4000. For the purposes of sample size estimation, it was assumed that the study groups would be of equal sizes. In practice, we recognised that some imbalance could occur. This was because the randomisation only controlled the distribution of intervention skills among the birth attendants. For evident practical and ethical reasons, randomisation could not influence the number of deliveries each birth attendant would actually carry out over the ensuing years, nor control the process by which Lufwanyama mothers selected birth attendants for their deliveries. The primary end point was the proportion of liveborn infants who died by day 28 after birth. Additional mortality outcomes included comparisons of proportions of stillbirths, and mortality rates at different time points during the 28 days. To estimate the possible effect of misclassification of failed resuscitations as stillbirths, we compared stillbirth rates between the two groups and calculated overall mortality rates including and excluding stillbirths (defined as babies born after six months of gestation without any movement, spontaneous breathing, or heartbeat during or after the delivery). Each cluster was defined as all babies delivered by a given birth attendant during the study, and roughly corresponded to the catchment area in which each birth attendant operated, although adjacent catchment areas often overlapped. The need to adjust for clustering rested on the assumption of a “by traditional birth attendant” effect associated with outcomes, such that individual outcomes could not be combined as if they were independent events. For the mortality end points, we carried out a modified intention to treat analysis, where participants who were lost during follow-up were treated as missing rather than as deaths. We also carried out a sensitivity analysis for our primary end point in which participants who were lost to follow-up were analysed under the assumption that they represented unrecorded deaths. The Wilcoxon rank sum test was used to contrast the mean number of babies delivered by intervention or control birth attendants. We calculated cluster adjusted rate ratios and 95% confidence intervals using binomial regression in a generalised estimating equation to regress the risk of death as a function of assigned treatment group. We adjusted for clustering of babies within a birth attendant by specifying an exchangeable correlation matrix.22 Models presented labelled as cluster adjusted did not adjust for other covariates. We adjusted models labelled as cluster adjusted and covariate adjusted for both clustering at birth attendant level and for imbalances in baseline covariates, including years of education, birth attendants’ marital status, and whether the birth attendant reported that being a birth attendant was her primary job. These covariates were selected for inclusion in the model after the baseline characteristics of the birth attendants had been inspected for imbalances. The birth attendants and mothers provided written informed consent, using forms in English and the local languages Bemba and Lamba. A data safety monitoring board provided a single mid-point evaluation; the nominal significance value to adjust for the mid-point analysis, based on the O’Brien-Fleming stopping rules, was 0.0489 (nominal z score 1.97) (EAST software; Cytel, Cambridge, MA).
