Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial.

OBJECTIVE: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age. STUDY DESIGN: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates. RESULTS: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively. CONCLUSIONS: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01883193.

Helping Babies Survive Training Programs: Evaluating a Teaching Cascade in Ethiopia.

BACKGROUND: 2.6 million neonates die annually; the vast majority of deaths occur in low- and middle-income countries (LMICs). The Helping Babies Survive (HBS) programs are commonly used in LMICs to reduce neonatal mortality through education. They are typically disseminated using a train-the-trainer cascade. However, there is little published literature on the extent and cost of dissemination. In 2015, the Ethiopian Ministry of Health and partner organizations implemented a countrywide HBS training cascade for midwives in 169 hospitals. METHODS: We quantified the extent of HBS dissemination, and characterized barriers that impeded successful hospital-based training by surveying a representative from each of the 169 participant hospitals. This occurred from September 2017 to April 2018. We also assessed the cost of the training cascade. To assess acquisition of knowledge and skill in the training cascade, multiple-choice question examinations (MCQE) and objective structured clinical evaluations (OSCE) were conducted. RESULTS: Hospital-based training occurred in 132 participant hospitals (78%). 1,146 midwives, 69% of those employed by participant hospitals, received hospital-based training. Barriers included lack of preparation of hospital-based educators and limited logistical support. The cascade cost an average of 2,105 USD per facility or 197 USD per trainee. Knowledge improved and skills were adequate for regional workshop attendees based on MCQE and OSCE performance. CONCLUSION: The train-the-trainer strategy is an effective and affordable strategy for widespread dissemination of the HBS programs in LMICs. Future studies should assess knowledge and skill acquisition following the variety of pragmatic training approaches that may be employed at the facility-level.

A multicountry randomized controlled trial of comprehensive maternal nutrition supplementation initiated before conception: the Women First trial.

Background: Reported benefits of maternal nutrition supplements commenced during pregnancy in low-resource populations have typically been quite limited. Objectives: This study tested the effects on newborn size, especially length, of commencing nutrition supplements for women in low-resource populations ≥3 mo before conception (Arm 1), compared with the same supplement commenced late in the first trimester of pregnancy (Arm 2) or not at all (control Arm 3). Methods: Women First was a 3-arm individualized randomized controlled trial (RCT). The intervention was a lipid-based micronutrient supplement; a protein-energy supplement was also provided if maternal body mass index (kg/m2) was <20 or gestational weight gain was less than recommendations. Study sites were in rural locations of the Democratic Republic of the Congo (DRC), Guatemala, India, and Pakistan. The primary outcome was length-for-age z score (LAZ), with all anthropometry obtained <48 h post delivery. Because gestational ages were unavailable in DRC, outcomes were determined for all 4 sites from WHO newborn standards (non-gestational-age-adjusted, NGAA) as well as INTERGROWTH-21st fetal standards (3 sites, gestational age-adjusted, GAA). Results: A total of 7387 nonpregnant women were randomly assigned, yielding 2451 births with NGAA primary outcomes and 1465 with GAA outcomes. Mean LAZ and other outcomes did not differ between Arm 1 and Arm 2 using either NGAA or GAA. Mean LAZ (NGAA) for Arm 1 was greater than for Arm 3 (effect size: +0.19; 95% CI: 0.08, 0.30, P = 0.0008). For GAA outcomes, rates of stunting and small-for-gestational-age were lower in Arm 1 than in Arm 3 (RR: 0.69; 95% CI: 0.49, 0.98, P = 0.0361 and RR: 0.78; 95% CI: 0.70, 0.88, P < 0.001, respectively). Rates of preterm birth did not differ among arms. Conclusions: In low-resource populations, benefits on fetal growth-related birth outcomes were derived from nutrition supplements commenced before conception or late in the first trimester. This trial was registered at clinicaltrials.gov as NCT01883193.

A cluster-randomized trial determining the efficacy of caterpillar cereal as a locally available and sustainable complementary food to prevent stunting and anaemia.

OBJECTIVE: We conducted a cluster-randomized controlled trial to assess the efficacy of a cereal made from caterpillars, a micronutrient-rich, locally available alternative animal-source food, on reducing stunting and anaemia in infants in the Democratic Republic of Congo. DESIGN: Six-month-old infants were cluster randomized to receive either caterpillar cereal daily until 18 months of age or the usual diet. At 18 months of age, anthropometric measurements and biological samples were collected. SETTING: The rural Equateur Province in the Democratic Republic of Congo. SUBJECTS: One hundred and seventy-five infants followed from 6 to 18 months of age. RESULTS: Stunting was common at 6 months (35%) and the prevalence increased until 18 months (69%). There was no difference in stunting prevalence at 18 months between the intervention and control groups (67% v. 71%, P = 0.69). Infants in the cereal group had higher Hb concentration than infants in the control group (10.7 v. 10.1 g/dl, P = 0.03) and fewer were anaemic (26 v. 50%, P = 0.006), although there was no difference in estimates of body Fe stores (6.7 v. 7.2 mg/kg body weight, P = 0.44). CONCLUSIONS: Supplementation of complementary foods with caterpillar cereal did not reduce the prevalence of stunting at 18 months of age. However, infants who consumed caterpillar cereal had higher Hb concentration and fewer were anaemic, suggesting that caterpillar cereal might have some beneficial effect. The high prevalence of stunting at 6 months and the lack of response to this micronutrient-rich supplement suggest that factors other than dietary deficiencies also contribute to stunting.

Caterpillar cereal as a potential complementary feeding product for infants and young children: nutritional content and acceptability.

Micronutrient deficiency is an important cause of growth stunting. To avoid micronutrient deficiency, the World Health Organization recommends complementary feeding with animal-source foods. However, animal-source foods are not readily available in many parts of the Democratic Republic of Congo (DRC). In such areas, caterpillars are a staple in adult diets and may be suitable for complementary feeding for infants and young children. We developed a cereal made from dried caterpillars and other locally available ingredients (ground corn, palm oil, sugar and salt), measured its macro- and micronutrient contents and evaluated for microbiologic contamination. Maternal and infant acceptability was evaluated among 20 mothers and their 8-10-month-old infants. Mothers were instructed in the preparation of the cereal and asked to evaluate the cereal in five domains using a Likert scale. Mothers fed their infants a 30-g portion daily for 1 week. Infant acceptability was based on cereal consumption and the occurrence of adverse events. The caterpillar cereal contained 132 kcal, 6.9-g protein, 3.8-mg iron and 3.8-mg zinc per 30 g and was free from microbiologic contamination. Mothers' median ratings for cereal characteristics were (5 = like very much): overall impression = 4, taste = 5, smell = 4, texture = 4, colour = 5, and consistency = 4. All infants consumed more than 75% of the daily portions, with five infants consuming 100%. No serious adverse events were reported. We conclude that a cereal made from locally available caterpillars has appropriate macro- and micronutrient contents for complementary feeding, and is acceptable to mothers and infants in the DRC.

First look: a cluster-randomized trial of ultrasound to improve pregnancy outcomes in low income country settings.

BACKGROUND: In high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown. METHODS/DESIGN: This multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women's and Children's Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18-22 and at 32-36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities. DISCUSSION: In summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately. TRIAL REGISTRATION: Clinicaltrials.gov (NCT # 01990625).

Randomized controlled trial of meat compared with multimicronutrient-fortified cereal in infants and toddlers with high stunting rates in diverse settings.

BACKGROUND: Improved complementary feeding is cited as a critical factor for reducing stunting. Consumption of meats has been advocated, but its efficacy in low-resource settings has not been tested. OBJECTIVE: The objective was to test the hypothesis that daily intake of 30 to 45 g meat from 6 to 18 mo of age would result in greater linear growth velocity and improved micronutrient status in comparison with an equicaloric multimicronutrient-fortified cereal. DESIGN: This was a cluster randomized efficacy trial conducted in the Democratic Republic of Congo, Zambia, Guatemala, and Pakistan. Individual daily portions of study foods and education messages to enhance complementary feeding were delivered to participants. Blood tests were obtained at trial completion. RESULTS: A total of 532 (86.1%) and 530 (85.8%) participants from the meat and cereal arms, respectively, completed the study. Linear growth velocity did not differ between treatment groups: 1.00 (95% CI: 0.99, 1.02) and 1.02 (95% CI: 1.00, 1.04) cm/mo for the meat and cereal groups, respectively (P = 0.39). From baseline to 18 mo, stunting [length-for-age z score (LAZ) <-2.0] rates increased from ~33% to nearly 50%. Years of maternal education and maternal height were positively associated with linear growth velocity (P = 0.0006 and 0.003, respectively); LAZ at 6 mo was negatively associated (P < 0.0001). Anemia rates did not differ by group; iron deficiency was significantly lower in the cereal group. CONCLUSION: The high rate of stunting at baseline and the lack of effect of either the meat or multiple micronutrient-fortified cereal intervention to reverse its progression argue for multifaceted interventions beginning in the pre- and early postnatal periods.

Home birth attendants in low income countries: who are they and what do they do?

BACKGROUND: Nearly half the world's babies are born at home. We sought to evaluate the training, knowledge, skills, and access to medical equipment and testing for home birth attendants across 7 international sites. METHODS: Face-to-face interviews were done by trained interviewers to assess level of training, knowledge and practices regarding care during the antenatal, intrapartum and postpartum periods. The survey was administered to a sample of birth attendants conducting home or out-of-facility deliveries in 7 sites in 6 countries (India, Pakistan, Guatemala, Democratic Republic of the Congo, Kenya and Zambia). RESULTS: A total of 1226 home birth attendants were surveyed. Less than half the birth attendants were literate. Eighty percent had one month or less of formal training. Most home birth attendants did not have basic equipment (e.g., blood pressure apparatus, stethoscope, infant bag and mask manual resuscitator). Reporting of births and maternal and neonatal deaths to government agencies was low. Indian auxilliary nurse midwives, who perform some home but mainly clinic births, were far better trained and differed in many characteristics from the birth attendants who only performed deliveries at home. CONCLUSIONS: Home birth attendants in low-income countries were often illiterate, could not read numbers and had little formal training. Most had few of the skills or access to tests, medications and equipment that are necessary to reduce maternal, fetal or neonatal mortality.

Evaluation of meat as a first complementary food for breastfed infants: impact on iron intake.

The rationale for promoting the availability of local, affordable, non-fortified food sources of bioavailable iron in developing countries is considered in this review. Intake of iron from the regular consumption of meat from the age of 6 months is evaluated with respect to physiological requirements. Two major randomized controlled trials evaluating meat as a first and regular complementary food are described in this article. These trials are presently in progress in poor communities in Guatemala, Pakistan, Zambia, Democratic Republic of the Congo, and China.

Epidemiology of stillbirth in low-middle income countries: a Global Network Study.

OBJECTIVE: To determine population-based stillbirth rates and to determine whether the timing and maturity of the stillbirths suggest a high proportion of potentially preventable deaths. DESIGN: Prospective observational study. SETTING: Communities in six low-income countries (Democratic Republic of Congo, Kenya, Zambia, Guatemala, India, and Pakistan) and one site in a mid-income country (Argentina). POPULATION: Pregnant women residing in the study communities. METHODS: Over a five-year period, in selected catchment areas, using multiple methodologies, trained study staff obtained pregnancy outcomes on each delivery in their area. MAIN OUTCOME MEASURES: Pregnancy outcome, stillbirth characteristics. RESULTS: Outcomes of 195,400 deliveries were included. Stillbirth rates ranged from 32 per 1,000 in Pakistan to 8 per 1,000 births in Argentina. Three-fourths (76%) of stillbirth offspring were not macerated, 63% were ≥ 37 weeks and 48% weighed 2,500 g or more. Across all sites, women with no education, of high and low parity, of older age, and without access to antenatal care were at significantly greater risk for stillbirth (p<0.001). Compared to those delivered by a physician, women delivered by nurses and traditional birth attendants had a lower risk of stillbirth. CONCLUSIONS: In these low-middle income countries, most stillbirth offspring were not macerated, were reported as ≥ 37 weeks' gestation, and almost half weighed at least 2,500 g. With access to better medical care, especially in the intrapartum period, many of these stillbirths could likely be prevented.

Reduced perinatal mortality following enhanced training of birth attendants in the Democratic Republic of Congo: a time-dependent effect.

BACKGROUND: In many developing countries, the majority of births are attended by traditional birth attendants, who lack formal training in neonatal resuscitation and other essential care required by the newly born infant. In these countries, the major causes of neonatal mortality are birth asphyxia, infection, and low-birth-weight/prematurity. Death from these causes is potentially modifiable using low-cost interventions, including neonatal resuscitation training. The purpose of this study was to evaluate the effect on perinatal mortality of training birth attendants in a rural area of the Democratic Republic of Congo (DRC) using two established programs. METHODS: This study, a secondary analysis of DRC-specific data collected during a multi-country study, was conducted in two phases. The effect of training using the WHO Essential Newborn Care (ENC) program was evaluated using an active baseline design, followed by a cluster randomized trial of training using an adaptation of a neonatal resuscitation program (NRP). The perinatal mortality rates before ENC, after ENC training, and after randomization to additional NRP training or continued care were compared. In addition, the influence of time following resuscitation training was investigated by examining change in perinatal mortality during sequential three-month increments following ENC training. RESULTS: More than two-thirds of deliveries were attended by traditional birth attendants and occurred in homes; these proportions decreased after ENC training. There was no apparent decline in perinatal mortality when the outcome of all deliveries prior to ENC training was compared to those after ENC but before NRP training. However, there was a gradual but significant decline in perinatal mortality during the year following ENC training (RR 0.73; 95% CI: 0.56-0.96), which was independently associated with time following training. The decline was attributable to a decline in early neonatal mortality. NRP training had no demonstrable effect on early neonatal mortality. CONCLUSION: Training DRC birth attendants using the ENC program reduces perinatal mortality. However, a period of utilization and re-enforcement of training may be necessary before a decline in mortality occurs. ENC training has the potential to be a low cost, high impact intervention in developing countries. TRIAL REGISTRATION: This trial has been registered at http://www.clinicaltrials.gov (identifier NCT00136708).

Complementary feeding: a Global Network cluster randomized controlled trial.

BACKGROUND: Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. METHODS/DESIGN: A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. DISCUSSION: Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale for global efforts to enhance local supplies of meat as a complementary food for young children. TRIAL REGISTRATION: NCT01084109.

High mortality rates for very low birth weight infants in developing countries despite training.

OBJECTIVE: The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants. METHODS: Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP. RESULTS: A total of 1096 VLBW (500-1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training. CONCLUSIONS: Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected.

Newborn-care training and perinatal mortality in developing countries.

BACKGROUND: Of the 3.7 million neonatal deaths and 3.3 million stillbirths each year, 98% occur in developing countries. An evaluation of community-based interventions designed to reduce the number of these deaths is needed. METHODS: With the use of a train-the-trainer model, local instructors trained birth attendants from rural communities in six countries (Argentina, Democratic Republic of Congo, Guatemala, India, Pakistan, and Zambia) in the World Health Organization Essential Newborn Care course (which focuses on routine neonatal care, resuscitation, thermoregulation, breast-feeding, "kangaroo" [skin-to-skin] care, care of the small baby, and common illnesses) and (except in Argentina) in a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (which teaches basic resuscitation in depth). The Essential Newborn Care intervention was assessed among 57,643 infants with the use of a before-and-after design. The Neonatal Resuscitation Program intervention was assessed as a cluster-randomized, controlled trial involving 62,366 infants. The primary outcome was neonatal death in the first 7 days after birth. RESULTS: The 7-day follow-up rate was 99.2%. After birth attendants were trained in the Essential Newborn Care course, there was no significant reduction from baseline in the rate of neonatal death from all causes in the 7 days after birth (relative risk with training, 0.99; 95% confidence interval [CI], 0.81 to 1.22) or in the rate of perinatal death; there was a significant reduction in the rate of stillbirth (relative risk with training, 0.69; 95% CI, 0.54 to 0.88; P=0.003). In clusters of births in which attendants had been randomly assigned to receive training in the Neonatal Resuscitation Program, as compared with control clusters, there was no reduction in the rates of neonatal death in the 7 days after birth, stillbirth, or perinatal death. CONCLUSIONS: The rate of neonatal death in the 7 days after birth did not decrease after the introduction of Essential Newborn Care training of community-based birth attendants, although the rate of stillbirths was reduced. Subsequent training in the Neonatal Resuscitation Program did not significantly reduce the mortality rates. (ClinicalTrials.gov number, NCT00136708.)

Prevention of bronchopulmonary dysplasia.

Considerable effort has been devoted to the development of strategies to reduce the incidence of bronchopulmonary dysplasia (BPD), including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent BPD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia, were evaluated for the improvement of other outcomes and found to reduce BPD. Cohort studies suggest that the use of continuous positive airway pressure as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce BPD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7-11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease.

Evaluating the effectiveness of a strategy for teaching neonatal resuscitation in West Africa.

AIM: To evaluate the effectiveness of a strategy for teaching neonatal resuscitation on the cognitive knowledge of health professionals who attend deliveries in Ghana, West Africa. METHODS: Train-the-trainer model was used to train health professionals at 2-3 day workshops from 2003 to 2007. Obstetric Anticipatory Care and Basic Neonatal Care modules were taught as part of Neonatal Resuscitation Training package. American Neonatal Resuscitation Program was adapted to the clinical role of participants and local resources. Cognitive knowledge was evaluated by written pre- and post-training tests. RESULTS: The median pre-training and post-training scores were 38% and 71% for midwives, 43% and 81% for nurses, 52% and 90% for nurse anaesthetists, and 62% and 98% for physicians. All groups of the 271 professionals (18 nurse anaesthetists, 55 nurses, 68 physicians, and 130 midwives) who completed the course showed significant improvement (p<0.001) in median post-training test scores. Midwives at primary health care facilities were less likely to achieve passing post-test scores than midwives at secondary and tertiary facilities [35/53 vs. 24/26 vs. 45/51 (p=0.004)] respectively. CONCLUSION: Evidence-based neonatal resuscitation training adapted to local resources significantly improved cognitive knowledge of all groups of health professionals. Further modification of training for midwives working at primary level health facilities and incorporation of neonatal resuscitation in continuing education and professional training programs are recommended.