Beena D. Kamath-Rayne

Antenatal Steroids for Treatment of Fetal Lung Immaturity After 34 Weeks of Gestation: An Evaluation of Neonatal Outcomes

OBJECTIVE: To estimate whether antenatal corticosteroids given after fetal lung immaturity in pregnancies at 34 weeks of gestation or more would improve neonatal outcomes and, in particular, respiratory outcomes. METHODS: We compared outcomes of 362 neonates born at 34 weeks of gestation or more after fetal lung maturity testing: 102 with immature fetal lung indices were treated with antenatal corticosteroids followed by planned delivery within 1 week; 76 with immature fetal lung indices were managed expectantly; and 184 were delivered after mature amniocentesis. Primary outcomes were composites of neonatal and respiratory morbidity. RESULTS: Compared with corticosteroid-exposed neonates those born after mature amniocentesis had lower rates of adverse neonatal (26.5% compared with 14.1%, adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.27–0.96) and adverse respiratory outcomes (9.8% compared with 3.3%, adjusted OR 0.33, 95% CI 0.11–0.98); newborns born after expectant management had significantly less respiratory morbidity (1.3% compared with 9.8%, adjusted OR 0.11, 95% CI 0.01–0.92) compared with corticosteroid-exposed newborns. CONCLUSION: Administration of antenatal corticosteroids after immature fetal lung indices did not reduce respiratory morbidity in neonates born at 34 weeks of gestation or more. Our study supports prolonging gestation until delivery is otherwise indicated. LEVEL OF EVIDENCE: II

Resuscitation and Obstetrical Care to Reduce Intrapartum-Related Neonatal Deaths: A MANDATE Study

To evaluate the impact of neonatal resuscitation and basic obstetric care on intrapartum-related neonatal mortality in low and middle-income countries, using the mathematical model, Maternal and Neonatal Directed Assessment of Technology (MANDATE). Using MANDATE, we evaluated the impact of interventions for intrapartum-related events causing birth asphyxia (basic neonatal resuscitation, advanced neonatal care, increasing facility birth, and emergency obstetric care) when implemented in home, clinic, and hospital settings of sub-Saharan African and India for 2008. Total intrapartum-related neonatal mortality (IRNM) was acute neonatal deaths from intrapartum-related events plus late neonatal deaths from ongoing intrapartum-related injury. Introducing basic neonatal resuscitation in all settings had a large impact on decreasing IRNM. Increasing facility births and scaling up emergency obstetric care in clinics and hospitals also had a large impact on decreasing IRNM. Increasing prevalence and utilization of advanced neonatal care in hospital settings had limited impact on IRNM. The greatest improvement in IRNM was seen with widespread advanced neonatal care and basic neonatal resuscitation, scaled-up emergency obstetric care in clinics and hospitals, and increased facility deliveries, resulting in an estimated decrease in IRNM to 2.0 per 1,000 live births in India and 2.5 per 1,000 live births in sub-Saharan Africa. With more deliveries occurring in clinics and hospitals, the scale-up of obstetric care can have a greater effect than if modeled individually. Use of MANDATE enables health leaders to direct resources towards interventions that could prevent intrapartum-related deaths. A lack of widespread implementation of basic neonatal resuscitation, increased facility births, and emergency obstetric care are missed opportunities to save newborn lives.

Stillbirths and neonatal mortality as outcomes

Several recent studies in low‐resource countries have claimed that training in—and increased use of—newborn resuscitation resulted in reduced stillbirth rates. In the present article, we explore the ability of various types of birth attendant in some low‐resource country locations to gather data that accurately differentiate a stillbirth from a live birth/early neonatal death. We conclude that, in many situations, it cannot be determined whether the infant was a stillbirth or a live birth/early neonatal death, and therefore the least‐biased description of study outcomes includes a combined stillbirth and live birth/neonatal death outcome. However, because defining the burden of stillbirth and neonatal death is important from a public health perspective, every effort should be made, in low‐income countries and elsewhere, to distinguish between stillbirths and live births/neonatal deaths and to report the results independently.

Subtypes of preterm birth and the risk of postneonatal death.

OBJECTIVE To examine the differences in postneonatal death risk among 3 clinical subtypes of preterm birth: preterm premature rupture of membranes (PROM), indicated preterm birth, and spontaneous preterm labor. STUDY DESIGN We analyzed the 2001-2005 US linked birth/infant death (birth cohort) datasets. The preterm birth subtypes were classified using information on the birth certificate: reported PROM, induction of labor, cesarean section, and complications of pregnancy and labor. Cox proportional hazard models were used to estimate covariate-adjusted hazard ratios and 95% CIs for postneonatal death (from days 28 to 365). Estimation was given for preterm birth subtypes in a week-by-week analysis. Causes of death were analyzed by preterm birth subtype and then separately at 24-27, 28-31, and 32-36 weeks of gestation. RESULTS For the total of 1895350 singleton preterm births who survived the neonatal period, the postneonatal mortality rate was 1.11% for preterm PROM, 0.78% for indicated preterm birth, and 0.53% for spontaneous preterm labor. Preterm PROM was associated with significantly higher risk of postneonatal death compared with spontaneous preterm labor in infants born at 27 weeks gestation or later. Similarly, indicated preterm birth was associated with a significantly higher risk of postneonatal death than spontaneous preterm labor in infants born at 25 weeks gestation or later. Preterm PROM and indicated preterm birth were associated with greater risk of death in the postneonatal period compared with spontaneous preterm labor, irrespective of the cause of death. CONCLUSION Subtypes of preterm birth carry different risks of postneonatal mortality. Prevention of preterm-related postneonatal death may require more research into the root causes of preterm birth subtypes.

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.

Reducing maternal mortality from preeclampsia and eclampsia in low-resource countries - what should work?

Preeclampsia/eclampsia (PE/E) remains a major cause of maternal death in low‐income countries. We evaluated interventions to reduce PE/E‐related maternal mortality in sub‐Saharan Africa.

Amniotic fluid: the use of high-dimensional biology to understand fetal well-being.

Our aim was to review the use of high-dimensional biology techniques, specifically transcriptomics, proteomics, and metabolomics, in amniotic fluid to elucidate the mechanisms behind preterm birth or assessment of fetal development. We performed a comprehensive MEDLINE literature search on the use of transcriptomic, proteomic, and metabolomic technologies for amniotic fluid analysis. All abstracts were reviewed for pertinence to preterm birth or fetal maturation in human subjects. Nineteen articles qualified for inclusion. Most articles described the discovery of biomarker candidates, but few larger, multicenter replication or validation studies have been done. We conclude that the use of high-dimensional systems biology techniques to analyze amniotic fluid has significant potential to elucidate the mechanisms of preterm birth and fetal maturation. However, further multicenter collaborative efforts are needed to replicate and validate candidate biomarkers before they can become useful tools for clinical practice. Ideally, amniotic fluid biomarkers should be translated to a noninvasive test performed in maternal serum or urine.

Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity

BackgroundAmniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation.MethodsWe isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions.ResultsSample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity.ConclusionThe AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing.

Tranexamic acid to reduce postpartum hemorrhage: A MANDATE systematic review and analyses of impact on maternal mortality.

OBJECTIVE Postpartum hemorrhage (PPH) is a major cause of maternal mortality, with almost 300,000 cases and ~72,000 PPH deaths annually in sub-Saharan Africa. Novel prevention methods practical in community settings are required. Tranexamic acid, a drug to reduce bleeding during surgical cases including postpartum bleeding, is potentially suitable for community settings. Thus, we sought to determine the impact of tranexamic acid on PPH-related maternal mortality in sub-Saharan Africa. STUDY DESIGN We created a mathematical model to determine the impact of interventions on PPH-related maternal mortality. The model was populated with baseline birth rates and mortality estimates based on a review of current interventions for PPH in sub-Saharan Africa. Based on a systematic review of literature on tranexamic acid, we assumed 30% efficacy of tranexamic acid to reduce PPH; the model assessed prophylactic and treatment tranexamic acid use, for deliveries at homes, clinics, and hospitals. RESULTS With tranexamic acid only in the hospitals, less than 2% of the PPH mortality would be reduced. However, if tranexamic acid were available in the home and clinic settings for PPH prophylaxis and treatment, a nearly 30% reduction (nearly 22,000 deaths per year) in PPH mortality is possible. CONCLUSION These analyses point to the importance of preventive and treatment interventions compatible with home and clinic use, especially for sub-Saharan Africa, where the majority of births occur at home or community health clinics. Given its feasibility to be given in the home, tranexamic acid has potential to save many lives.

Neonatal resuscitation in global health settings: an examination of the past to prepare for the future

As rates of childhood mortality decline, neonatal deaths account for nearly half of under-5 deaths worldwide. Intrapartum-related events (birth asphyxia) contribute to approximately one-quarter of neonatal deaths, many of which can be prevented by simple resuscitation and newborn care interventions. This paper reviews various lines of research that have influenced the global neonatal resuscitation landscape. A brief situational analysis of asphyxia-related newborn mortality in low-resource settings is linked to renewed efforts to reduce neonatal mortality in the Every Newborn Action Plan. Possible solutions to gaps in care are identified. Building on international scientific evidence, tests of educational efficacy, and community-based trials established the feasibility and effectiveness of training in resource-limited settings and identified successful implementation strategies. Implementation of neonatal resuscitation programs has been shown to decrease intrapartum stillbirth rates and early neonatal mortality. Challenges remain with respect to provider competencies, coverage, and quality of interventions. The combination of resuscitation science, strategies to increase educational effectiveness, and implemention of interventions with high coverage and quality has resulted in reduced rates of asphyxia-related neonatal mortality. Further efforts to improve coverage and implementation of neonatal resuscitation will be necessary to meet the 2035 goal of eliminating preventable newborn deaths.