Neonatal anthropometric indicators of infant growth and mortality in Burkina Faso.

OBJECTIVE: Most evidence supporting screening for undernutrition is for children aged 6-59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birthweight, weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso. DESIGN: Data arose from a randomized controlled trial evaluating neonatal azithromycin administration for prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < -2), stunting (LAZ < -2), and underweight (WAZ < -2) at 6 months of age was estimated using logistic regression models adjusted for the child's age and sex. SETTING: Five regions of Burkina Faso. PARTICIPANTS: Infants aged 8 to 27 days followed until 6 months of age. RESULTS: Of 21,832 infants enrolled in the trial, 7.9% were low birthweight (<2500 g), 13.3% were wasted, 7.7% were stunted, and 7.4% were underweight at enrollment. All anthropometric deficits were associated with mortality by 6 months of age, with WAZ the strongest predictor (WAZ < -2 to ≥ -3 at enrollment versus WAZ ≥ -2: adjusted odds ratio, aOR, 3.91, 95% confidence interval, CI, 2.21 to 6.56). Low WAZ was also associated with wasting, stunting, and underweight at 6 months. CONCLUSIONS: Interventions for identifying infants at highest risk of mortality and growth failure should consider WAZ as part of their screening protocol.

Associations between Antenatal Care Visit Attendance and Infant Mortality and Growth.

This study examines the association between antenatal care (ANC) attendance and infant mortality and growth outcomes. The study used data from the Nouveux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) trial conducted in Burkina Faso. This analysis included 21,795 neonates aged 8 to 27 days who were enrolled in the trial and had ANC data available. Infants were followed until 6 months of age. The analysis adjusted for potential confounders including infant's sex, maternal age, education, urbanicity, geographic region, season (dry versus rainy), pregnancy type (singleton versus multiple), number of previous pregnancies, if the infant was breastfed, and if the facility had an onsite physician to account for level of care. We used logistic and linear regression models to evaluate the association between ANC visits and all-cause infant mortality and infant growth measurements at 6 months. There was no significant association between ANC visits and 6-month mortality. Higher ANC attendance was associated with improved growth outcomes in infants at 6 months of age. After adjusting for potential confounders, each additional ANC visit was associated with a 0.03 kg increase in mean weight, 0.07 cm increase in mean length, 0.04 SD increase in mean mid-upper-arm circumference, 0.04 SD increase in mean height-for-age, 0.04 SD mean weight-for-age, and 0.02 SD mean weight-for-length Z-scores. These mean differences were statistically significant (except for weight-for-length Z-scores) but may not be clinically meaningful. Further research is warranted to explore the relationship between ANC attendance and longer-term health outcomes among infants.

Mass Azithromycin Distribution to Prevent Child Mortality in Burkina Faso: The CHAT Randomized Clinical Trial.

Importance: Repeated mass distribution of azithromycin has been shown to reduce childhood mortality by 14% in sub-Saharan Africa. However, the estimated effect varied by location, suggesting that the intervention may not be effective in different geographical areas, time periods, or conditions. Objective: To evaluate the efficacy of twice-yearly azithromycin to reduce mortality in children in the presence of seasonal malaria chemoprevention. Design, Setting, and Participants: This cluster randomized placebo-controlled trial evaluating the efficacy of single-dose azithromycin for prevention of all-cause childhood mortality included 341 communities in the Nouna district in rural northwestern Burkina Faso. Participants were children aged 1 to 59 months living in the study communities. Interventions: Communities were randomized in a 1:1 ratio to receive oral azithromycin or placebo distribution. Children aged 1 to 59 months were offered single-dose treatment twice yearly for 3 years (6 distributions) from August 2019 to February 2023. Main Outcomes and Measures: The primary outcome was all-cause childhood mortality, measured during a twice-yearly enumerative census. Results: A total of 34 399 children (mean [SD] age, 25.2 [18] months) in the azithromycin group and 33 847 children (mean [SD] age, 25.6 [18] months) in the placebo group were included. A mean (SD) of 90.1% (16.0%) of the censused children received the scheduled study drug in the azithromycin group and 89.8% (17.1%) received the scheduled study drug in the placebo group. In the azithromycin group, 498 deaths were recorded over 60 592 person-years (8.2 deaths/1000 person-years). In the placebo group, 588 deaths were recorded over 58 547 person-years (10.0 deaths/1000 person-years). The incidence rate ratio for mortality was 0.82 (95% CI, 0.67-1.02; P = .07) in the azithromycin group compared with the placebo group. The incidence rate ratio was 0.99 (95% CI, 0.72-1.36) in those aged 1 to 11 months, 0.92 (95% CI, 0.67-1.27) in those aged 12 to 23 months, and 0.73 (95% CI, 0.57-0.94) in those aged 24 to 59 months. Conclusions and Relevance: Mortality in children (aged 1-59 months) was lower with biannual mass azithromycin distribution in a setting in which seasonal malaria chemoprevention was also being distributed, but the difference was not statistically significant. The study may have been underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03676764.

Infant mortality and growth failure after oral azithromycin among low birthweight and underweight neonates: A subgroup analysis of a randomized controlled trial.

BACKGROUND: Low birthweight (birthweight <2500 grams, g) and underweight (weight-for-age Z-score, WAZ, < -2) infants have higher risk of poor outcomes compared to their well-nourished peers. We evaluated the role of azithromycin for reducing mortality and improving growth outcomes in low birthweight and/or underweight infants. METHODS: Infants aged 8-27 days of age weighing ≥2500 g at enrollment in Burkina Faso were randomized 1:1 to a single, oral dose of azithromycin (20 mg/kg) or matching placebo. We evaluated mortality and anthropometric outcomes in four subgroups: 1) both low birthweight and underweight at enrollment; 2) low birthweight-only; 3) underweight-only; 4) neither low birthweight nor underweight. FINDINGS: Of 21,832 enrolled infants, 21,320 (98%) had birthweight measurements and included in this analysis. Of these, 747 (3%) were both low birthweight and underweight, 972 (5%) were low birthweight-only, 825 (4%) were underweight-only, and 18,776 (88%) were neither low birthweight nor underweight. Infants who were both low birthweight and underweight receiving azithromycin had lower odds of underweight at 6 months compared to placebo (OR 0.65, 95% CI 0.44 to 0.95), but the treatment group by subgroup interaction was not statistically significant (P = 0.06). We did not find evidence of a difference between groups for other outcomes in any subgroup. INTERPRETATION: Azithromycin may have some growth-promoting benefits for the highest risk infants, but we were unable to demonstrate a difference in most outcomes in low birthweight and underweight infants. As a secondary analysis of a trial, this study was underpowered for rare outcomes such as mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03682653.

Neonatal Azithromycin Administration and Growth during Infancy: A Randomized Controlled Trial.

Observational studies have linked early-life antibiotic exposure to increased risk of obesity in children in high income settings. We evaluated whether neonatal antibiotic exposure led to changes in infant growth at 6 months of age in Burkina Faso. Neonates aged 8 to 27 days of age who weighed at least 2,500 g at the time of enrollment were randomized in a 1:1 fashion to a single oral 20-mg/kg dose of azithromycin or equivalent volume of placebo from April 2019 through December 2020. Weight, length, and mid-upper-arm circumference (MUAC) were measured at baseline and 6 months of age. Growth outcomes, including weight gain in grams per day, length change in millimeters per day, and changes in weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and MUAC were compared among neonates randomized to azithromycin compared with placebo. Among 21,832 neonates enrolled in the trial, median age at enrollment was 11 days, and 50% were female. We found no evidence of a difference in weight gain (mean difference -0.009 g/day, 95% confidence interval [CI]: -0.16 to 0.14, P = 0.90), length change (mean difference 0.003 mm/day, 95% CI: -0.002 to 0.007, P = 0.23), or WAZ (mean difference -0.005 SD, 95% CI: -0.03 to 0.02, P = 0.72), WLZ (mean difference -0.01 SD, 95% CI: -0.05 to 0.02, P = 0.39), LAZ (mean difference 0.01, 95% CI: -0.02 to 0.04, P = 0.47), or MUAC (mean difference 0.01 cm, 95% CI: -0.02 to 0.04, P = 0.49). These results do not suggest that azithromycin has growth-promoting properties in infants when administered during the neonatal period. Trial registration: ClinicalTrials.gov NCT03682653.

Influence of maternal age on birth and infant outcomes at 6 months: a cohort study with quantitative bias analysis.

BACKGROUND: Maternal age is increasingly recognized as a predictor of birth outcomes. Given the importance of birth and growth outcomes for children's development, wellbeing and survival, this study examined the effect of maternal age on infant birth and growth outcomes at 6 months and mortality. Additionally, we conducted quantitative bias analysis (QBA) to estimate the role of selection bias and unmeasured confounding on the effect of maternal age on infant mortality. METHODS: We used data from randomized-controlled trials (RCTs) of 21 555 neonates in Burkina Faso conducted in 2019-2020. Newborns of mothers aged 13-19 years (adolescents) and 20-40 years (adults) were enrolled in the study 8-27 days after birth and followed for 6 months. Measurements of child's anthropometric measures were collected at baseline and 6 months. We used multivariable linear regression to compare child anthropometric measures at birth and 6 months, and logistic regression models to obtain the odds ratio (OR) of all-cause mortality. Using multidimensional deterministic analysis, we assessed scenarios in which the difference in selection probability of adolescent and adult mothers with infant mortality at 6 months increased from 0% to 5%, 10%, 15% and 20% if babies born to adolescent mothers more often died during the first week or were of lower weight and hence were not eligible to be included in the original RCT. Using probabilistic bias analysis, we assessed the role of unmeasured confounding by socio-economic status (SES). RESULTS: Babies born to adolescent mothers on average had lower weight at birth, lower anthropometric measures at baseline, similar growth outcomes from enrolment to 6 months and higher odds of all-cause mortality by 6 months (adjusted OR = 2.17, 95% CI 1.35 to 3.47) compared with those born to adult mothers. In QBA, we found that differential selection of adolescent and adult mothers could bias the observed effect (OR = 2.24, 95% CI 1.41 to 3.57) towards the null [bias-corrected OR range: 2.37 (95% CI 1.49 to 3.77) to 2.84 (95% CI 1.79 to 4.52)], whereas unmeasured confounding by SES could bias the observed effect away from the null (bias-corrected OR: 2.06, 95% CI 1.31 to 2.64). CONCLUSIONS: Our findings suggest that delaying the first birth from adolescence to adulthood may improve birth outcomes and reduce mortality of neonates. Babies born to younger mothers, who are smaller at birth, may experience catch-up growth, reducing some of the anthropometric disparities by 6 months of age.

Effect of Neonatal Azithromycin on All-Cause and Cause-Specific Infant Mortality: A Randomized Controlled Trial.

Mass azithromycin distribution reduces all-cause childhood mortality in some high-mortality settings in sub-Saharan Africa. Although the greatest benefits have been shown in children 1 to 5 months old living in areas with high mortality rates, no evidence of a benefit was found of neonatal azithromycin in a low-mortality setting on mortality at 6 months. We conducted a 1:1 randomized, placebo-controlled trial evaluating the effect of a single oral 20-mg/kg dose of azithromycin or matching placebo administered during the neonatal period on all-cause and cause-specific infant mortality at 12 months of age in five regions of Burkina Faso. Neonates were eligible if they were between the ages of 8 and 27 days and weighed at least 2,500 g at enrollment. Cause of death was determined via the WHO 2016 verbal autopsy tool. We compared all-cause and cause-specific mortality using binomial regression. Of 21,832 infants enrolled in the study, 116 died by 12 months of age. There was no significant difference in all-cause mortality between the azithromycin and placebo groups (azithromycin: 52 deaths, 0.5%; placebo, 64 deaths, 0.7%; hazard ratio, 0.81; 95% CI, 0.56-1.17; P = 0.30). There was no evidence of a difference in the distribution of causes of death (P = 0.40) and no significant difference in any specific cause of death between groups. Mortality rates were low at 12 months of age, and there was no evidence of an effect of neonatal azithromycin on all-cause or cause-specific mortality.

Neonatal azithromycin administration for prevention of infant mortality.

Background: Biannual mass azithromycin administration reduces all-cause childhood mortality in some sub-Saharan African settings, with the largest effects in children aged 1-5 months. Azithromycin has not been distributed to children <1 month due to risk of infantile hypertrophic pyloric stenosis (IHPS). Methods: This 1:1 placebo-controlled trial, randomized neonates aged 8-27 days to a single oral dose of azithromycin (20 mg/kg) or equivalent volume of placebo in 5 regions of Burkina Faso during 2019 and 2020. The primary outcome was all-cause mortality at 6 months of age. Infants were evaluated at 21 days after treatment and at 3 and 6 months of age for vital status; family and provider surveillance for IHPS continued throughout. Results: Of 21,832 enrolled neonates, 10,898 were allocated to azithromycin and 10,934 to placebo. At 6 months of age, 92 infants had died, 42 (0.44%) in the azithromycin group and 50 (0.52%) in the placebo group (hazard ratio 0.85, 95% confidence interval 0.56 to 1.28, P=0.46). A single IHPS case was detected, which was in the azithromycin arm. Serious adverse events, including death and hospitalization within 28 days of treatment, occurred in 0.27% of infants in the azithromycin group and 0.14% in the placebo group, for an absolute risk difference 0.14 percentage points, 95% confidence interval 0.01 to 0.26. Conclusions: Overall mortality was lower than anticipated when the trial was designed, thus limiting its power. The available data do not support the routine use of azithromycin for prevention of mortality in neonates in sub-Saharan African settings similar to the one in which this trial was conducted. Trial registration: ClinicalTrials.gov NCT03682653.

Antenatal care attendance and risk of low birthweight in Burkina Faso: a cross-sectional study.

BACKGROUND: Low birthweight is a major contributor to infant mortality. We evaluated the association between antenatal care (ANC) attendance and low birthweight among newborns in 5 regions of Burkina Faso. METHODS: We utilized data from the baseline assessment of a randomized controlled trial evaluating azithromycin distribution during the neonatal period for prevention of infant mortality. Neonates were eligible for the trial if the weighed at least 2500 g at enrollment and were 8-27 days of age. Data on ANC attendance and birthweight was extracted from each child's carnet de santé, a government-issued health card on which pregnancy and birth-related data are recorded. We used linear and logistic regression models adjusting for potentially confounding variables to evaluate the relationship between ANC attendance (as total number of visits and ≥ 4 antenatal care visits) and birthweight (continuously and categorized into < 2500 g versus ≥2500 g). RESULTS: Data from 21,223 births were included in the analysis. The median number of ANC visits was 4 (interquartile range 3 to 5) and 69% of mothers attended at least 4 visits. Mean birthweight was 2998 g (standard deviation 423) and 8.1% of infants were low birthweight (< 2500 g). Birthweight was 63 g (95% CI 46 to 81 g, P < 0.001) higher in newborns born to mothers who had attended ≥4 ANC visits versus < 4 visits. The odds of low birthweight among infants born to mothers with ≥4 ANC visits was 0.71 (95% CI 0.63 to 0.79, P < 0.001) times the odds of low birthweight among infants born to mothers who attended < 4 ANC visits. CONCLUSIONS: We observed a statistically significant association between ANC attendance and birthweight, although absolute differences were small. Improving access to ANC for all women may help improve birth outcomes. TRIAL REGISTRATION: The parent trial is registered at clinicaltrials.gov: NCT03682653 ; first registered 24 September 2018.

Access to Improved Sanitation and Nutritional Status among Preschool Children in Nouna District, Burkina Faso.

Access to improved sanitation and hygiene may improve child nutritional status by reducing exposure to enteric pathogens. We evaluated this relationship as part of the Community Health with Azithromycin Trial, a community-randomized trial of azithromycin versus placebo for the prevention of child mortality in rural Burkina Faso. Before the baseline study visit, a door-to-door household survey was conducted for all households in the study area. During the baseline study census, which occurred approximately 9 months after the household survey, a mid-upper arm circumference (MUAC) measurement was obtained from each child. We evaluated the relationship between household improved latrine use compared with unimproved latrines or open defecation and MUAC in children aged 6-59 months. Among 32,172 children with household survey data and MUAC measurements, 931 (2.9%) had an MUAC less than 12.5 cm and were classified as having moderate acute malnutrition (MAM). The odds of MAM were higher in children living in households with an unimproved latrine than those with an improved latrine (adjusted odds ratio: 1.60; 95% CI: 1.11-2.31). Children in households with unimproved latrines and households that practiced open defection had approximate 0.15 cm reduced MUAC compared with those in households with an improved latrine. There was a small, but statistically significant, association between improved latrine and nutritional status in preschool children as measured by MUAC.

Insecticide-treated bed net access and use among preschool children in Nouna District, Burkina Faso.

BACKGROUND: We evaluated universal insecticide-treated bed net access and use in children <5 y of age in a rural area of Burkina Faso. METHODS: A door-to-door enumerative census was conducted in Nouna District, Burkina Faso in December 2018 through April 2019. The most recent mass bed net distribution campaign occurred in June 2016. Heads of households were interviewed about household bed net ownership and use by children <5 y of age. We evaluated the relationship between demographic and socio-economic factors and household universal bed net access and use by children. RESULTS: In 23 610 households with at least one child <5 y of age, 71 329 bed nets were reported (94.5% insecticide-treated). One-third (35.2%) of households had universal access and two-thirds (67.0%) of children slept under an insecticide-treated net the previous night. Children in households with universal access more often slept under a net the previous night (adjusted odds ratio 4.81 [95% confidence interval 4.39-5.26]). CONCLUSIONS: Bed net coverage was substantially less than the 80% World Health Organization target for universal coverage in Nouna District. Insecticide-treated nets were used preferentially for children, but important gaps remain in consistent bed net use in this population. Structural and behavioural interventions are needed to close these gaps.

No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial.

BACKGROUND: Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality. METHODS: Children were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale. RESULTS: Among 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83-1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55-1.29). CONCLUSIONS: We did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns. Registration: The trial was registered at ClinicalTrials.gov, NCT01644721.

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.

"Quality of prenatal and maternal care: bridging the know-do gap" (QUALMAT study): an electronic clinical decision support system for rural Sub-Saharan Africa.

BACKGROUND: Despite strong efforts to improve maternal care, its quality remains deficient in many countries of Sub-Saharan Africa as persistently high maternal mortality rates testify. The QUALMAT study seeks to improve the performance and motivation of rural health workers and ultimately quality of primary maternal health care services in three African countries Burkina Faso, Ghana, and Tanzania. One major intervention is the introduction of a computerized Clinical Decision Support System (CDSS) for rural primary health care centers to be used by health care workers of different educational levels. METHODS: A stand-alone, java-based software, able to run on any standard hardware, was developed based on assessment of the health care situation in the involved countries. The software scope was defined and the final software was programmed under consideration of test experiences. Knowledge for the decision support derived from the World Health Organization (WHO) guideline "Pregnancy, Childbirth, Postpartum and Newborn Care; A Guide for Essential Practice". RESULTS: The QUALMAT CDSS provides computerized guidance and clinical decision support for antenatal care, and care during delivery and up to 24 hours post delivery. The decision support is based on WHO guidelines and designed using three principles: (1) Guidance through routine actions in maternal and perinatal care, (2) integration of clinical data to detect situations of concern by algorithms, and (3) electronic tracking of peri- and postnatal activities. In addition, the tool facilitates patient management and is a source of training material. The implementation of the software, which is embedded in a set of interventions comprising the QUALMAT study, is subject to various research projects assessing and quantifying the impact of the CDSS on quality of care, the motivation of health care staff (users) and its health economic aspects. The software will also be assessed for its usability and acceptance, as well as for its influence on workflows in the rural setting of primary health care in the three countries involved. CONCLUSION: The development and implementation of a CDSS in rural primary health care centres presents challenges, which may be overcome with careful planning and involvement of future users at an early stage. A tailored software with stable functionality should offer perspectives to improve maternal care in resource-poor settings.