Elizabeth Butrick

Associations between Cognitive Function, Blood Lead Concentration, and Nutrition among Children in the Central Philippines

OBJECTIVE Because little is known about its effects on cognitive function among children in less-developed countries, we determined the impact of lead exposure from other nutritional determinants of cognitive ability. STUDY DESIGN Data were from a cross-sectional population-based stratified random sample of 877 children (age 6 months-5 years) participating in the Quality Improvement Demonstration Study we are conducting in the Philippines. With data from validated psychometric instruments, venous blood samples, and comprehensive survey instruments, we developed multi-stage models to account for endogenous determinants of blood lead levels (BLLs) and exogenous confounders of the association between BLLs and cognitive function. RESULTS A 1 microg/dL increase in BLL was associated with a 3.32 point decline in cognitive functioning in children aged 6 months to 3 years and a 2.47 point decline in children aged 3 to 5 years olds. BLL was inversely associated with hemoglobin and folate levels. Higher folate levels mitigated the negative association between BLL and cognitive function. CONCLUSIONS These population-based data suggest greater lead toxicity on cognitive function than previously reported. Our findings also suggest that folate and iron deficient children are more susceptible to the negative cognitive effects of lead. Folate supplementation may offer some protective effects against lead exposure.

Elevated blood-lead levels among children living in the rural Philippines

OBJECTIVE Generally, lead poisoning is not considered a significant environmental hazard for children in rural areas of developing countries. With a prospectively designed policy experiment, the research community and the government are conducting a broad-based investigation to introduce and evaluate the impact of health policy reforms on children in a rural area of the Philippines - the Quality Improvement Demonstration Study (QIDS). As part of this study, we researched lead exposure in children under the age of five. METHODS We sampled a population of children from the Visayas region in the central Philippines, covering approximately one third of the countrys geographical area. From December 2003 to September 2004, the survey collected blood lead levels (BLL) together with demographic, socioeconomic and child health data points. Supplemental field-testing among a sub-sample of the most exposed children assessed the sources of environmental lead exposure. FINDINGS Among children in this study, 21% (601 of 2861 children) had BLL greater than 10 microg/dl. BLL were associated independently with age, haemoglobin concentration, water source, roofing material, expenditures and history of breastfeeding. A follow-up assessment of possible environmental exposures among the sub-sample of children with elevated BLL revealed no single or predominant exposure source. Instead, there appear to be multiple potential sources, such as fossil-fuel combustion, lead paint (in or around 38% of homes) and household items. CONCLUSION Elevated BLL are common among children in the Visayas, and may signify an under-recognized threat to children living in rural areas of other developing nations. This setting has varied environmental sources of lead. Observed correlates of BLL may be of clinical, environmental and public health utility to identify and mitigate the consequences of lead toxicity.

Shock index: an effective predictor of outcome in postpartum haemorrhage?

To compare the predictive value of the shock index (SI) with conventional vital signs in postpartum haemorrhage (PPH), and to establish ‘alert’ thresholds for use in low‐resource settings.

Obstetric hemorrhage and shock management: using the low technology Non-pneumatic Anti-Shock Garment in Nigerian and Egyptian tertiary care facilities

BackgroundObstetric hemorrhage is the leading cause of maternal mortality globally. The Non-pneumatic Anti-Shock Garment (NASG) is a low-technology, first-aid compression device which, when added to standard hypovolemic shock protocols, may improve outcomes for women with hypovolemic shock secondary to obstetric hemorrhage in tertiary facilities in low-resource settings.MethodsThis study employed a pre-intervention/intervention design in four facilities in Nigeria and two in Egypt. Primary outcomes were measured mean and median blood loss, severe end-organ failure morbidity (renal failure, pulmonary failure, cardiac failure, or CNS dysfunctions), mortality, and emergency hysterectomy for 1442 women with ≥750 mL blood loss and at least one sign of hemodynamic instability. Comparisons of outcomes by study phase were assessed with rank sum tests, relative risks (RR), number needed to treat for benefit (NNTb), and multiple logistic regression.ResultsWomen in the NASG phase (n = 835) were in worse condition on study entry, 38.5% with mean arterial pressure <60 mmHg vs. 29.9% in the pre-intervention phase (p = 0.001). Despite this, negative outcomes were significantly reduced in the NASG phase: mean measured blood loss decreased from 444 mL to 240 mL (p < 0.001), maternal mortality decreased from 6.3% to 3.5% (RR 0.56, 95% CI 0.35-0.89), severe morbidities from 3.7% to 0.7% (RR 0.20, 95% CI 0.08-0.50), and emergency hysterectomy from 8.9% to 4.0% (RR 0.44, 0.23-0.86). In multiple logistic regression, there was a 55% reduced odds of mortality during the NASG phase (aOR 0.45, 0.27-0.77). The NNTb to prevent either mortality or severe morbidity was 18 (12-36).ConclusionAdding the NASG to standard shock and hemorrhage management may significantly improve maternal outcomes from hypovolemic shock secondary to obstetric hemorrhage at tertiary care facilities in low-resource settings.

Non-pneumatic anti-shock garment (NASG), a first-aid device to decrease maternal mortality from obstetric hemorrhage: a cluster randomized trial.

Background Obstetric hemorrhage is the leading cause of maternal mortality. Using a cluster randomized design, we investigated whether application of the Non-pneumatic Anti-Shock Garment (NASG) before transport to referral hospitals (RHs) from primary health care centers (PHCs) decreased adverse outcomes among women with hypovolemic shock. We hypothesized the NASG group would have a 50% reduction in adverse outcomes. Methods and Findings We randomly assigned 38 PHCs in Zambia and Zimbabwe to standard obstetric hemorrhage/shock protocols or the same protocols plus NASG prior to transport. All women received the NASG at the RH. The primary outcomes were maternal mortality; severe, end-organ failure maternal morbidity; and a composite mortality/morbidity outcome, which we labeled extreme adverse outcome (EAO). We also examined whether the NASG contributed to negative side effects and secondary outcomes. The sample size for statistical power was not reached; of a planned 2400 women, 880 were enrolled, 405 in the intervention group. The intervention was associated with a non-significant 46% reduced odds of mortality (OR 0.54, 95% CI 0.14–2.05, p = 0.37) and 54% reduction in composite EAO (OR 0.46, 95% CI 0.13–1.62, p = 0.22). Women with NASGs recovered from shock significantly faster (HR 1.25, 95% CI 1.02–1.52, p = 0.03). No differences were observed in secondary outcomes or negative effects. The main limitation was small sample size. Conclusions Despite a lack of statistical significance, the 54% reduced odds of EAO and the significantly faster shock recovery suggest there might be treatment benefits from earlier application of the NASG for women experiencing delays obtaining definitive treatment for hypovolemic shock. As there are no other tools for shock management outside of referral facilities, and no safety issues found, consideration of NASGs as a temporizing measure during delays may be warranted. A pragmatic study with rigorous evaluation is suggested for further research. Trial Registration ClinicalTrials.gov NCT00488462

Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index.

Objective To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings. Study Design We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values. Results Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0–74.8) with negative predictive value (range 93.2–99.2), and ≥ 1.7 further improved specificity (range 80.7–90.8) without compromising negative predictive value (range 88.8–98.5). Conclusions For women with hypovolemic shock from obstetric hemorrhage, shock index was consistently a strong predictor of all adverse outcomes. In lower-level facilities in low resource settings, we recommend a shock index threshold of ≥ 0.9 indicating need for referral, ≥ 1.4 indicating urgent need for intervention in tertiary facilities and ≥ 1.7 indicating high chance of adverse outcome. The vital sign alert device incorporated values 0.9 and 1.7; however, all thresholds will be prospectively validated and clinical pathways for action appropriate to setting established prior to clinical implementation.

Assessing the role of the non-pneumatic anti-shock garment in reducing mortality from postpartum hemorrhage in Nigeria.

Background/Aims: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality. The non-pneumatic anti-shock garment (NASG), a first-aid lower-body pressure device, may decrease mortality. Methods: This pre-intervention/NASG study of 288 women was conducted in four referral facilities in Nigeria, 2004–2008. Entry criteria: women with PPH due to uterine atony, retained placenta, ruptured uterus, vaginal or cervical lacerations or placenta accreta with estimated blood loss of ≧750 ml and one clinical sign of shock. Differences in demographics, conditions on study entry, treatment and outcomes were examined. t tests and relative risks with 95% confidence intervals were calculated for primary outcomes – measured blood loss and mortality. Multiple logistic regression analysis was performed to examine independent association of the NASG with mortality. Results: Mean measured blood loss decreased by 80% between phases. Women experienced 350 ml of median blood loss after study entry in the pre-intervention and 50 ml in the NASG phase (p < 0.0001). Mortality decreased from 18% pre-intervention to 6% in the NASG phase (RR = 0.31, 95% CI 0.15–0.64, p = 0.0007). In a multiple logistic regression model, the NASG was associated with reduced mortality (odds ratio 0.30; 95% CI 0.13–0.68, p = 0.004). Conclusion: The NASG shows promise for reducing mortality from PPH in referral facilities in Nigeria.

Combined analysis of the non-pneumatic anti-shock garment on mortality from hypovolemic shock secondary to obstetric hemorrhage

BackgroundObstetric hemorrhage is the leading cause of maternal mortality, particularly in low-resource settings where women face significant delays in accessing definitive treatment. The Non-pneumatic Anti-Shock Garment (NASG) is a first-aid device to stabilize women in hypovolemic shock secondary to obstetric hemorrhage. Prior studies on the effectiveness of the NASG have suffered from small sample sizes and insufficient statistical power. We sought to generate a summary effect estimate of this intervention by combining data from all previous quasi-experimental studies.MethodsFive quasi-experimental studies that tested the NASG as treatment for hypovolemic shock secondary to obstetric hemorrhage at the tertiary care facility level were included in the analysis. We evaluated heterogeneity of effect across studies and calculated pooled odds ratios. We also conducted a subgroup analysis among women in the most severe condition.ResultsParticipant characteristics were similar across studies with some variation in hemorrhage etiology. Median blood loss was at least 50% lower in the intervention group than the control group. The pooled odds ratio suggested that NASG intervention was associated with a 38% significantly reduced odds of mortality among the overall sample, and a 59% significantly reduced odds of mortality among the most severe women.ConclusionsThe results from this combined analysis suggest that NASG intervention is associated with a reduced odds of death for women with hypovolemic shock secondary to obstetric hemorrhage. Further research should focus on application of the NASG at the community or primary health care level, and utilize a more robust methodology.

Use of the Non-Pneumatic Anti-Shock Garment (NASG) for Life-Threatening Obstetric Hemorrhage: A Cost-Effectiveness Analysis in Egypt and Nigeria

Objective To assess the cost-effectiveness of a non-pneumatic anti-shock garment (NASG) for obstetric hemorrhage in tertiary hospitals in Egypt and Nigeria. Methods We combined published data from pre-intervention/NASG-intervention clinical trials with costs from study sites. For each country, we used observed proportions of initial shock level (mild: mean arterial pressure [MAP] >60 mmHg; severe: MAP ≤60 mmHg) to define a standard population of 1,000 women presenting in shock. We examined three intervention scenarios: no women in shock receive the NASG, only women in severe shock receive the NASG, and all women in shock receive the NASG. Clinical data included frequencies of adverse health outcomes (mortality, severe morbidity, severe anemia), and interventions to manage bleeding (uterotonics, blood transfusions, hysterectomies). Costs (in 2010 international dollars) included the NASG, training, and clinical interventions. We compared costs and disability-adjusted life years (DALYs) across the intervention scenarios. Results For 1000 women presenting in shock, providing the NASG to those in severe shock results in decreased mortality and morbidity, which averts 357 DALYs in Egypt and 2,063 DALYs in Nigeria. Differences in use of interventions result in net savings of

A comparison of objective biomarkers with a subjective health status measure among children in the Philippines.

9,489 in Egypt (primarily due to reduced transfusions) and net costs of