Informed consent rates for neonatal randomized controlled trials in low- and lower middle-income versus high-income countries: A systematic review.

OBJECTIVE: Legal, ethical, and regulatory requirements of medical research uniformly call for informed consent. We aimed to characterize and compare consent rates for neonatal randomized controlled trials in low- and lower middle-income countries versus high-income countries, and to evaluate the influence of study characteristics on consent rates. METHODS: In this systematic review, we searched MEDLINE, EMBASE and Cochrane for randomized controlled trials of neonatal interventions in low- and lower middle-income countries or high-income countries published 01/01/2013 to 01/04/2018. Our primary outcome was consent rate, the proportion of eligible participants who consented amongst those approached, extracted from the article or email with the author. Using a generalised linear model for fractional dependent variables, we analysed the odds of consenting in low- and lower middle-income countries versus high-income countries across control types and interventions. FINDINGS: We screened 3523 articles, yielding 300 eligible randomized controlled trials with consent rates available for 135 low- and lower middle-income country trials and 65 high-income country trials. Median consent rates were higher for low- and lower middle-income countries (95.6%; interquartile range (IQR) 88.2-98.9) than high-income countries (82.7%; IQR 68.6-93.0; p<0.001). In adjusted regression analysis comparing low- and lower middle-income countries to high-income countries, the odds of consent for no placebo-drug/nutrition trials was 3.67 (95% Confidence Interval (CI) 1.87-7.19; p = 0.0002) and 6.40 (95%CI 3.32-12.34; p<0.0001) for placebo-drug/nutrition trials. CONCLUSION: Neonatal randomized controlled trials in low- and lower middle-income countries report consistently higher consent rates compared to high-income country trials. Our study is limited by the overrepresentation of India among randomized controlled trials in low- and lower middle-income countries. This study raises serious concerns about the adequacy of protections for highly vulnerable populations recruited to clinical trials in low- and lower middle-income countries.

Ethiopian Pediatric Society Quality Improvement Initiative: a pragmatic approach to facility-based quality improvement in low-resource settings.

OBJECTIVES: To describe critical features of the Ethiopian Pediatric Society (EPS) Quality Improvement (QI) Initiative and to present formative research on mentor models. SETTING: General and referral hospitals in the Addis Ababa area of Ethiopia. PARTICIPANTS: Eighteen hospitals selected for proximity to the EPS headquarters, prior participation in a recent newborn care training cascade and minimal experience with QI. INTERVENTIONS: Education in QI in a 2-hour workshop setting followed by implementation of a facility-based QI project with the support of virtual mentorship or in-person mentorship. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome-QI progress, measured using an adapted Institute for Healthcare Improvement Scale; secondary outcome-contextual factors affecting QI success as measured by the Model for Understanding Success in Quality. RESULTS: The dose and nature of mentoring encounters differed based on a virtual versus in-person mentoring approach. All QI teams conducted at least one large-scale change. Education of staff was the most common change implemented in both groups. We did not identify contextual factors that predicted greater QI progress. CONCLUSIONS: The EPS QI Initiative demonstrates that education in QI paired with external mentorship can support implementation of QI in low-resource settings. This pragmatic approach to facility-based QI may be a scalable strategy for improving newborn care and outcomes. Further research is needed on the most appropriate instruments for measuring contextual factors in low/middle-income country settings.

Association of parity with birthweight and neonatal death in five sites: The Global Network's Maternal Newborn Health Registry study.

BACKGROUND: Nulliparity has been associated with lower birth weight (BW) and other adverse pregnancy outcomes, with most of the data coming from high-income countries. In this study, we examined birth weight for gestational age z-scores and neonatal (28-day) mortality in a large prospective cohort of women dated by first trimester ultrasound from multiple sites in low and middle-income countries. METHODS: Pregnant women were recruited during the first trimester of pregnancy and followed through 6 weeks postpartum from Maternal Newborn Health Registry (MNHR) sites in the Democratic Republic of Congo (DRC), Guatemala, Belagavi and Nagpur, India, and Pakistan from 2017 and 2018. Data related to the pregnancy and its outcomes were collected prospectively. First trimester ultrasound was used for determination of gestational age; (BW) was obtained in grams within 48 h of delivery and later transformed to weight for age z-scores (WAZ) adjusted for gestational age using the INTERGROWTH-21st standards. RESULTS: 15,121 women were eligible and included. Infants of nulliparous women had lower mean BWs (males: 2676 gr, females: 2587 gr, total: 2634 gr) and gestational age adjusted weight for age z-scores (males: - 0.73, females: - 0.77, total: - 0.75,) than women with one or more previous pregnancies. The largest differences were between zero and one previous pregnancies among female infants. The associations of parity with BW and z-scores remained even after adjustment for maternal age, maternal height, maternal education, antenatal care visits, hypertensive disorders, and socioeconomic status. Nulliparous women also had a significantly higher < 28-day neonatal mortality rate (27.7 per 1,000 live births) than parous women (17.2 and 20.7 for parity of 1-3 and ≥ 4 respectively). Risk of preterm birth was higher among women with ≥ 4 previous pregnancies (15.5%) compared to 11.3% for the nulliparous group and 11.8% for women with one to three previous pregnancies (p = 0.0072). CONCLUSIONS: In this large sample from diverse settings, nulliparity was independently associated with both lower BW and WAZ scores as well as higher neonatal mortality compared to multiparity.

Looking beyond the numbers: quality assurance procedures in the Global Network for Women's and Children's Health Research Maternal Newborn Health Registry.

BACKGROUND: Quality assurance (QA) is a process that should be an integral part of research to protect the rights and safety of study participants and to reduce the likelihood that the results are affected by bias in data collection. Most QA plans include processes related to study preparation and regulatory compliance, data collection, data analysis and publication of study results. However, little detailed information is available on the specific procedures associated with QA processes to ensure high-quality data in multi-site studies. METHODS: The Global Network for Women's and Children's Health Maternal Newborn Health Registy (MNHR) is a prospective population-based registry of pregnancies and deliveries that is carried out in 8 international sites. Since its inception, QA procedures have been utilized to ensure the quality of the data. More recently, a training and certification process was developed to ensure that standardized, scientifically accurate clinical definitions are used consistently across sites. Staff complete a web-based training module that reviews the MNHR study protocol, study forms and clinical definitions developed by MNHR investigators and are certified through a multiple choice examination prior to initiating study activities and every six months thereafter. A standardized procedure for supervision and evaluation of field staff is carried out to ensure that research activites are conducted according to the protocol across all the MNHR sites. CONCLUSIONS: We developed standardized QA processes for training, certification and supervision of the MNHR, a multisite research registry. It is expected that these activities, together with ongoing QA processes, will help to further optimize data quality for this protocol.

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.

Challenges in classification and assignment of causes of stillbirths in low- and lower middle-income countries.

Stillbirths account for 2.6 million deaths annually. 98% occur in low- and lower middle-income countries. Accurate classification of stillbirths in low-resource settings is challenged by poor pregnancy dating and infrequent access to electronic heart rate monitoring for both the newborn and fetus. In these settings, liveborn infants may be misclassified as stillbirths, and stillbirths may be misclassified as miscarriages. Causation is available for only 3% of stillbirths globally due to the absence of registration systems. In low-resource settings where culture and autopsy are infrequently available, clinical course is used to assign cause of stillbirth. This method may miss rare or subtle causes, as well as those with non-specific clinical presentations. Verbal autopsy is another technique for assigning cause of stillbirth when objective medical data are limited. This method requires family engagement and physician attribution of cause. As interventions to reduce stillbirths in LMICs are increasingly implemented, attention to accurate classification and assignment of causes of stillbirth are critical to charting progress.

Essential Care for Every Baby: improving compliance with newborn care practices in rural Nicaragua.

BACKGROUND: Neonatal mortality comprises an increasing proportion of childhood deaths in the developing world. Essential newborn care practices as recommended by the WHO may improve neonatal outcomes in resource limited settings. Our objective was to pilot a Helping Babies Breathe and Essential Care for Every Baby (HBB and ECEB) implementation package using HBB-ECEB training combined with supportive supervision in rural Nicaragua. METHODS: We employed an HBB-ECEB implementation package in El Ayote and Santo Domingo, two rural municipalities in Nicaragua and used a pre- and post- data collection design for comparison. Following a period of pre-intervention data collection (June-August 2015), care providers were trained in HBB and ECEB using a train-the- trainer model. An external supportive supervisor monitored processes of care and collected data. Data on newborn care processes and short-term outcomes such as hypothermia were collected from facility medical records and analyzed using standard run charts. Home visits were used to determine breastfeeding rates at 7, 30 and 60 days. RESULTS: There were 480 institutional births during the study period (June 2015-June 2016). Following the HBB-ECEB implementation package, cord care improved (pre-intervention median 66%; post-intervention shift to ≥85%) and early skin-to-skin care improved (pre-intervention median 0%; post-intervention shift to ≥56%, with a high of 92% in June 2016). Rates of administration of ophthalmic ointment and vitamin K were high pre-intervention (median 97%) and remained high. Early initiation of breastfeeding increased with a pre-intervention median of 25% and post-intervention shift to ≥28%, with a peak of 81% in June 2016. Exclusive breastfeeding rates increased short-term but were not significantly different by 60-days of life (9% pre-intervention versus 21% post-intervention). CONCLUSIONS: The implementation of the HBB-ECEB programs combined with supportive supervision improved the quality of care for newborns in terms of cord care, early skin-to-skin care and early initiation of breastfeeding. The rates of administration of ophthalmic ointment and vitamin K were high pre- intervention and remained high afterwards. These findings show that HBB-ECEB programs implemented with supportive supervision can improve quality of care for newborns.

Improving Neonatal Care: A Global Perspective.

Each year, approximately 2.7 million babies die during the neonatal period; more than 90% of these deaths occur in developing countries, largely from preventable causes. The known, evidence-based, simple, low-cost interventions that may improve neonatal survival often have low or unknown baseline coverage rates. Gaps in coverage of essential interventions and in quality of care may be amenable to improvement strategies. However, often these gaps are not easily identified. A variety of international organizations have recommended key indicators of quality and established roadmaps for improving neonatal outcomes. Quality improvement at the facility level is an area for future investment.

Transitions in Care for Infants with Trisomy 13 or 18.

Background and Objectives The scope of interventions offered to infants with trisomy 13 (T13) or trisomy 18 (T18) is increasing. We describe the spectrum of care provided, highlighting transitions in care for individual patients. Patients and Methods This is a single-center, retrospective cohort of infants with T13 or T18 born between 2004 and 2015. Initial care was classified as comfort care or intervention using prenatal counseling notes. Transitions in care were identified in the medical record. Results In this study, 25 infants were divided into two groups based on their care: neonates who experienced no transition in care and neonates who experienced at least one transition. Eleven neonates experienced no transition in care with 10 receiving comfort care. Fourteen neonates experienced at least one transition: three transitioned from comfort care to intervention and 11 from intervention to comfort care. The three initially provided comfort care were discharged home with hospice and readmitted. Among the 11 cases who transitioned from intervention to comfort care, 9 transitioned during the birth hospitalization, 6 had no prenatal suspicion for T13 or T18, and 5 experienced elective withdrawal of intensive care. Conclusion The spectrum of care for infants with T13 or T18 illustrates the need for individualized counseling that is on-going, goal directed, collaborative, and responsive.

Management of Pregnancy and Survival of Infants with Trisomy 13 or Trisomy 18.

Objective The objective of this study was to describe antenatal/intrapartum management and survival of liveborn infants with known trisomy 13 (T13) or trisomy 18 (T18) based on planned neonatal care. Study Design This is a retrospective cohort study of singleton pregnancies complicated by T13/T18 at a tertiary center from 2004 to 2015. We included pregnancies with antenatal or neonatal cytogenetic T13/T18 diagnosis and excluded those which were terminated or had a fetal demise < 20 weeks. We compared antenatal/intrapartum management and neonatal survival by planned neonatal care, defined as either neonatal intervention (INT), including neonatal cardiopulmonary resuscitative measures or comfort care (CC) without resuscitative measures. Results In this study, 32 women (10 with T13 and 22 with T18) met study criteria; 12 (38%) elected INT and 20 (62%) CC. Compared with those who elected INT, women who elected CC were more likely to undergo elective induction (40 vs. 0%, p = 0.01), have an intrapartum stillbirth (0 vs. 32%, p = 0.14), and deliver vaginally (25 vs. 63%, p < 0.01). In neonatal survival analysis (n = 26), median survival was longer in the INT group compared with CC group (64 days [interquartile range, IQR: 2, 155) vs. 3 days [IQR]: 0.3, 42), p = 0.28), but survival to hospital discharge was similar (53 vs. 57%, p = 0.95). Conclusion Regardless of desired level of neonatal INT, many women who continue pregnancies complicated by T13/18 have infants who survive beyond hospital discharge.

Reducing central line-associated bloodstream infections in North Carolina NICUs.

OBJECTIVE: Central lines in NICUs have long dwell times. Success in reducing central line-associated bloodstream infections (CLABSIs) requires a multidisciplinary team approach to line maintenance and insertion. The Perinatal Quality Collaborative of North Carolina (PQCNC) CLABSI project supported the development of NICU teams including parents, the implementation of an action plan with unique bundle elements and a rigorous reporting schedule. The goal was to reduce CLABSI rates by 75%. METHODS: Thirteen NICUs participated in an initiative developed over 3 months and deployed over 9 months. Teams participated in monthly webinars and quarterly face-to-face learning sessions. NICUs reported on bundle compliance and National Health Surveillance Network infection rates at baseline, during the intervention, and 3 and 12 months after the intervention. Process and outcome indicators were analyzed using statistical process control methods (SPC). RESULTS: Near-daily maintenance observations were requested for all lines with a 68% response rate. SPC analysis revealed a trend to an increase in bundle compliance. We also report significant adoption of a new maintenance bundle element, central line removal when enteral feedings reached 120 ml/kg per day. The PQCNC CLABSI rate decreased 71%, from 3.94 infections per 1000 line days to 1.16 infections per 1000 line days with sustainment 1 year later (P = .01). CONCLUSIONS: A collaborative structure targeting team development, family partnership, unique bundle elements and strict reporting on line care produced the largest reduction in CLABSI rates for any multiinstitutional NICU collaborative.