Niranjana S. Mahantshetti

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

BACKGROUND Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Biofortification of Pearl Millet with Iron and Zinc in a Randomized Controlled Trial Increases Absorption of These Minerals above Physiologic Requirements in Young Children

Millet is unusually drought resistant and consequently there is a progressive increase in the use of these grains as a human food staple, especially in large areas of India and sub-Saharan Africa. The purpose of this study was to determine the absorption of iron and zinc from pearl millet biofortified with 2 micronutrients that are typically deficient in nonfortified, plant-based diets globally. The study was undertaken in 40 children aged 2 y in Karnataka, India (n = 21 test/19 controls). Three test meals providing ∼84 ± 17 g dry pearl millet flour were fed on a single day for zinc and 2 d for iron between 0900 and 1600 h. The quantities of zinc and iron absorbed were measured with established stable isotope extrinsic labeling techniques and analyses of duplicate diets. The mean (± SD) quantities of iron absorbed from test and control groups were 0.67 ± 0.48 and 0.23 ± 0.15 mg/d, respectively (P < 0.001). The quantities of zinc absorbed were 0.95 ± 0.47 and 0.67 ± 0.24 mg/d, respectively (P = 0.03). These data did not include absorption of the modest quantities of iron and zinc contained in snacks eaten before and after the 3 test meals. In conclusion, quantities of both iron and zinc absorbed when iron and zinc biofortified pearl millet is fed to children aged 2 y as the major food staple is more than adequate to meet the physiological requirements for these micronutrients.

Brain Research to Ameliorate Impaired Neurodevelopment - Home-based Intervention Trial (BRAIN-HIT)

BackgroundThis randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia.Methods/DesignThis trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors.DiscussionThe trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.Trial RegistrationClinicaltrials.gov NCT00639184

ENC training reduces perinatal mortality in Karnataka, India

Objective: To evaluate the effect of World Health Organization Essential Newborn Care course and the American Academy of Pediatrics Neonatal Resuscitation Program training on perinatal mortality in rural India. Methods: This study was part of a multi-country prospective, community-based cluster randomized controlled trial. Birth, 7-day and 28-day neonatal outcomes for all women with pregnancies greater than 28 weeks in the 26 study communities in Karnataka, India were included. Mortality rates pre- and post-Essential Newborn Care training were collected prospectively and then communities randomized to either receive neonatal resuscitation or refresher newborn care training in the control clusters. Results: Consent was obtained on 99% of the 25,096 births. Perinatal mortality for infants ≥500 g decreased from 52 to 36/1000 after newborn care training (RR 0.7; 95% CI 0.5, 0.9); stillbirth decreased from 23 to 14/1000 (RR 0.62; 95% CI 0.46, 0.83) and early neonatal mortality decreased from 29 to 22/1000 (RR 0.74; 95% CI 0.53, 1.03). Mortality was not reduced further with resuscitation training. Conclusions: Using a pre–post design, World Health Organization Essential Newborn Care community birth attendant training resulted in a significant reduction in perinatal mortality. In low-resource settings, the newborn care training package appears to be an effective intervention to decrease perinatal mortality.

Consanguinity, prematurity, birth weight and pregnancy loss: a prospective cohort study at four primary health center areas of Karnataka, India.

Objective:To determine whether consanguinity adversely influences pregnancy outcome in South India, where consanguinity is a common means of family property retention.Study Design:Data were collected from a prospective cohort of 647 consenting women, consecutively registered for antenatal care between 14 and 18 weeks gestation, in Belgaum district, Karnataka in 2005. Three-generation pedigree charts were drawn for consanguineous participants. χ 2-Test and Students t-test were used to assess categorical and continuous data, respectively, using SPSS version 14. Multivariate logistic regression adjusted for confounding variables.Result:Overall, 24.1% of 601 women with singleton births and outcome data were consanguineous. Demographic characteristics between study groups were similar. Non-consanguineous couples had fewer stillbirths (2.6 vs 6.9% P=0.017; adjusted P=0.050), miscarriages (1.8 vs 4.1%, P=0.097; adjusted P=0.052) and lower incidence of birth weight <2500 g (21.8 vs 29.5%, P=0.071, adjusted P=0.044). Gestation <37 weeks was 6.2% in both the groups. Adjusted for consanguinity and other potential confounders, age <20 years was protective of stillbirth (P=0.01), pregnancy loss (P=0.023) and preterm birth (P=0.013), whereas smoking (P=0.015) and poverty (P=0.003) were associated with higher rates of low birth weight.Conclusion:Consanguinity significantly increases pregnancy loss and birth weight <2500 g.

Helping Babies Breathe (HBB) training: What happens to knowledge and skills over time?

BackgroundThe first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities.MethodsWe conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training.ResultsOne hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training).ConclusionsHBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills.Trial registrationClinicalTrials.gov Identifier: NCT01681017; 04 September 2012, retrospectively registered.

Infant rearing practices in South India: a longitudinal study.

Background: Rearing practices are a major determinant of nutritional and health status of infants. Therefore these practices need to be better understood. Objectives: To find out infant rearing practices in the study area. Materials and Methods: A longitudinal study was conducted on a birth cohort of 194 infants. Information on rearing practices and anthropometric measurements were recorded every month for a period of 1 year. Results: Only 67 (34.5%) newborns were breast fed within half an hour of delivery. Prelacteal feeds was given to 65 (33.5%) newborns and this was seen more among home deliveries (P=0.018). Demand feeding was practiced by 169 (87.1%) mothers. Exclusive breast feeding (EBF) for 6 months was practiced by 81 (41.7%) mothers. Bottle feeding was seen in 7 (3.6%) cases. Weight gain during infancy was found to be maximum when infants were EBF for 6 months (P<0.001) and weaned with semi-solid and solid diet alone in the following 6 months (P=0.002). Gain in all anthropometric measurements was more in the initial 6 months of infancy compared to latter. Four (2.1%) infants were malnourished. Oil massage before bath was practiced by 189 (97.4%) mothers. Over 50% mothers practiced oil application to eyes or ears of infants. Delayed initiation of bath (beyond 1week) was seen in 15 (7.7%) cases. Conclusion: Faulty rearing practices need to be corrected in order to improve the health status of infants.

Morbidity among infants in South India: A longitudinal study

To study the incidence and types of morbidity in the first year of life in a birth cohort, a longitudinal study. This study was undertaken in northern part of Karnataka state in India. Birth cohort consisted of all the children born during first six months of the study period. They were assessed at the time of enrollment and monthly follow up was done till they attained one yr of age. Out of the 194 newborns, 46.4% were boys and 53.6% were girls. 24.8% of newborns were of low birth weight and 5.1% were preterm. Four (2.1%) had congenital anomalies and 2.5% developed birth asphyxia. Diarrhea (10.8%) and skin diseases (8.2%) were the commonest morbidities in the neonatal period. The incidence of morbidity was 3.28 per infant per yr. It was more among boys and in the second half of infancy. Commonest morbidities during infancy were respiratory tract infection (62.4%), diarrhea 42.8% and skin diseases (21.6%). Incidence of disease in infancy highlights the need to improve and plan health programmes.

Development of a 12 month screener based on items from the Bayley II Scales of Infant Development for use in Low Middle Income countries

OBJECTIVES The purpose of the current study was to adapt the Bayley Scales of Infant Development II for use as a screening measure that could be used by health care professionals in Low Middle Income (LMI) countries with 12 month old infants to determine if they needed further assessment and early intervention. METHODS The adaptations were made as part of a larger study of children participating in a home-based early intervention program in India, Pakistan, and Zambia. Using Item Response Theory, a brief 12 month screener, with excellent sensitivity and specificity was identified. RESULTS The proposed 12 month screener contains 7 mental/cognitive items and 5 motor items. Children who cannot perform more than 3 items on the mental scale (sensitivity 79%, specificity 85%) and/or 3 items on the motor scale (sensitivity 96%, specificity 95%) should be referred for further assessment. CONCLUSION This screener can reliably be used to determine if a child needs further developmental assessment.

Factors associated with morbidities among infants in three sub centre areas of belgaum district of south India: A longitudinal study

Background: Health status of infants is a sensitive indicator of development and factors influencing it need to be better understood. Objectives: This study was conducted to search for factors associated with morbidity among infants and to find out their influence on weight gain during infancy. Materials and Methods: This longitudinal study was undertaken in south India from November 2004 till April 2006. A birth cohort of all children born during first 6 months of the study period were assessed at enrollment and followed up monthly till they attained 1 year of age. Results: Incidence of morbidity among infants was found to be least among those exclusively breast fed (EBF) for 6 months and most when EBF for less than 6 months (P = 0.045). It was also more when infants were weaned with a combination of animal milk, formula milk, semi-solids and solid diet and least when weaned only with semi-solids and solids (P = 0.018). Diarrheal episodes were more in infants who were bottle-fed (P < 0.001). Weight gain between 6th and 12th month of infancy was found to be significantly affected by various morbidities (P = 0.001). Incidence of morbidities was less among preterm babies and more among partially immunized (P < 0.001) babies with birth order ≥ 3 (P = 0.012), babies of mothers with low socio-economic and educational status. Delayed milestones during infancy was seen more in babies with history of birth asphyxia (P = 0.018). Conclusion: Several factors influenced incidence of morbidities and these morbidities had a negative effect on weight gain. Hence these factors need to be addressed to promote better child health.