Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

Effects of Maternal Carbohydrate and Fat Intake on Fetal Telomere Length.

OBJECTIVES: Telomere length can be affected by dietary factors in adults. We investigated the association between maternal carbohydrate and fat intake during pregnancy and telomere length in neonatal cord blood leukocytes. We hypothesized that high fat consumption and high carbohydrate consumption would be associated with shortened fetal telomere length. METHODS: We collected umbilical cord blood at delivery from women admitted for labor and delivery in a university hospital (N = 62) and extracted genomic DNA using quantitative polymerase chain reaction. We quantified telomere length using the telomere-to-single copy gene ratio method (T:S ratio). High carbohydrate intake was defined as consumption of >175 g/day and high fat intake as >35 g/day. We performed generalized linear regression modeling and bootstrap statistical analyses to derive precise estimates of association. RESULTS: Of the 62 maternal-fetal dyads included in this study, 79% were classified as high carbohydrate consumers and 37% were classified as high fat consumers. High fat consumption had a significant negative effect on T:S ratio (P < 0.05). Although high carbohydrate consumption was associated with a decreased T:S ratio, this relation did not attain statistical significance. CONCLUSIONS: To our knowledge, this study is the first evidence of an association between maternal high fat consumption and shortened fetal telomere length. These findings could enhance our understanding of the role of maternal diet in fetal programming.

Evidence of altered brain regulatory gene expression in tobacco-exposed fetuses.

AIM: We sought to determine the association between prenatal smoking status and expression of fetal brain regulatory genes. METHODS: At delivery, we collected information from parturient women on prenatal smoking habits and analyzed salivary cotinine levels. We obtained neonatal umbilical cord blood and extracted total RNA. We then employed the quantitative polymerase chain reaction (QPCR) analyses and the comparative CT method to calculate the relative gene expression of selected fetal brain regulatory genes responsible for (1) brain growth (brain-derived neutrotrophic factor, BDNF), (2) myelination (proteolipidic protein 1, PLP1 and myelin basic protein, MBP), and (3) neuronal migration and cell-cell interactions during fetal brain development or RLN. The χ2-test, analysis of variance (ANOVA), and the Grubb test were used to evaluate the relationship between prenatal smoking status and relative gene expression levels. Further analysis using bootstrapping was performed to assess the precision of our estimates. RESULTS: Of the 39 maternal-infant dyads included in this study, 25.6% were non-smokers, 43.6% were passive smokers and 30.8% were active smokers. The results showed down-regulation of the selected fetal brain regulatory genes among active smokers. CONCLUSIONS: These findings represent preliminary evidence in humans that intrauterine tobacco exposure impacts fetal brain programming. Future studies are warranted to examine whether our findings represent potential mechanisms through which adverse childhood/adult-onset cognitive and behavioral outcomes that have been previously linked to intrauterine exposure occur.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.

Association Between Maternal-Perceived Psychological Stress and Fetal Telomere Length.

OBJECTIVE: Our study aimed to investigate the association between maternal-perceived psychological stress and fetal telomere length. METHODS: We recruited women in labor upon hospital delivery admission. Based on responses to the Perceived Stress Scale, we categorized participants as having "high," "normal," or "low" perceived stress. We collected umbilical cord blood samples (N = 71) and isolated genomic DNA from cord blood leukocytes using quantitative polymerase chain reaction. We used a ratio of relative telomere length derived by telomere-to-single-copy gene ratio (T/S ratio). We applied analysis of variance and bootstrapping statistical procedures. RESULTS: Sixteen (22.5%) women were classified as having low perceived stress, 42 (59.2%) were classified as having normal perceived stress, and 13 (18.3%) were classified as having high perceived stress. Fetal telomere length differed significantly across the three stress groups in a dose-response pattern (T/S ratio of those with low perceived stress was greater than those with normal perceived stress, which was greater than those with high perceived stress [P < 0.05]). CONCLUSIONS: Our findings support our hypothesis that maternal-perceived psychological stress during pregnancy is associated with shorter fetal telomere length and suggest maternal stress as a possible marker for early intrauterine programming for accelerated chromosomal aging.

National trends in maternal use of opioid drugs among pregnancy-related hospitalizations in the United States, 1998 to 2009.

OBJECTIVE: The aim of this study is to describe national trends for opioid use among pregnancy-related hospitalizations from 1998 to 2009. STUDY DESIGN: Using the Nationwide Inpatient Sample, we identified hospital discharge records associated with the diagnoses codes for the use of opioids for all eligible pregnancy-related inpatient admissions between 1998 and 2009. Joinpoint regression modeling was used to describe changes in trend of pregnancy-related opioid use. The main outcome measure was the annual percent change for opioids use among pregnancy-related hospitalizations. RESULTS: From 1998 to 2009, opioid use was documented in 138,224 of 55,781,966 pregnancy-related inpatient hospitalizations (25 cases per 10,000 discharges). A statistically significant downward trend occurred from 1998 to 2001, whereas from 2002 to 2009 there was a statistically significant upward trend. The increasing trend in opioid use from 2002 to 2009 is notably higher for whites compared with blacks and Hispanics. CONCLUSIONS: Our findings highlight the continuous need to monitor opioids use and to revise prescription guidelines, practices, and regulatory mechanisms to curtail the progression of the increasing opioids use during pregnancy. It is critical that health care providers weight the benefits of these medications along with their potential risks when discussing analgesic treatment options with pregnant women.

Association between reproductive cancer and fetal outcomes: a population-based study.

PURPOSE: This study aimed to evaluate the impact of maternal reproductive cancer diagnosis on fetal birth outcomes. MATERIALS AND METHODS: We conducted a retrospective population-based cohort study among women with a singleton live birth and diagnosed with reproductive cancer in the state of Florida (cases). We matched cases to cancer-free controls using selected sociodemographic and pregnancy-related clinical conditions. We applied logistic regression with correction for intracluster correlation using generalized estimating equations. RESULTS: Overall, 3212 (0.21%) of pregnant women had a diagnosis of reproductive cancer. Affected women had a 24% and 33% elevated risk for low birth weight (LBW) and preterm birth (PTB) infants, respectively. Compared to their white counterparts, black women with reproductive cancer had a greater risk for LBW [odds ratio (OR), 1.83; 95% confidence interval (CI), 1.37-2.44], small for gestational age (SGA) [OR, 1.64; 95% CI, 1.23-2.17], and PTB (OR, 1.47; 95% CI, 1.12-192) infants. Black women with breast cancer demonstrated significantly higher risks of LBW [adjusted odds ratio (AOR), 2.37; 95% CI, 1.56-3.60], PTB (AOR, 1.71; 95% CI, 1.15-2.56), and SGA (AOR, 1.72; 95% CI, 1.12-2.64) when compared to women of their racial group with no reproductive cancer. CONCLUSIONS: Diagnosis of reproductive cancer before or during pregnancy and within 30 days after birth is associated with adverse fetal outcomes (LBW, PTB, and SGA). These results highlight the importance of preconception and intraconception care of women with reproductive cancer diagnosis.

Systematic review on sleep disorders and obstetric outcomes: scope of current knowledge.

OBJECTIVE: To assess the current state of knowledge regarding sleep disorders and their relationship to obstetric outcomes. STUDY DESIGN: A systematic literature review of the previous two decades (1991 to 2010) was conducted. The exposure was sleep disorders during pregnancy, and the outcomes of interest were feto-infant morbidity and maternal complications. RESULTS: Sleep apnea, snoring, and sleep quantity/duration were identified as the most frequently examined sleep disorders among pregnant women. Although our review found that studies examining the impact of sleep disorders on feto-infant outcomes were lacking, previous research indicates that such disorders may enhance the risk of preterm birth. Additionally, the current body of evidence suggests that sleep disorders adversely impact maternal health, increasing the likelihood of preeclampsia, and gestational diabetes. CONCLUSION: Existing research points to the potentially harmful effects of sleep disorders on obstetric outcomes. The limited research in this arena highlights the need for further studies regarding the nature and strength of this relationship. Given the multiple dimensions of sleep and pregnancy, multivariate research approaches that incorporate biological and psychosocial factors are warranted.

De novo translocation t(5;9)(q11.2;p22) associated with hydrops fetalis and cystic hygroma.

We report on a case of a prenatally diagnosed non-immune hydrops fetalis and cystic hygroma associated with the balanced translocation t(5;9)(q11.2;p22), an association that to our knowledge has not been reported previously. Both parents had normal karyotypes. The infant was born prematurely at 33 and 3/7 weeks gestation and expired 12 h after delivery.

Interpregnancy body mass index changes and risk of stillbirth.

BACKGROUND/AIMS: To examine the association between interpregnancy body mass index (BMI) change and stillbirth. METHODS: Retrospective study using Missouri maternally linked cohort files (1978-2005). A total of 218,389 women were used in the analysis. BMI was classified as: underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), or obese (≥30.0). Weight change was defined based on BMI category (i.e. normal-normal, normal-obese, etc.). Cox proportional hazard regression models were used to generate adjusted hazard ratios (HR) and 95% CI for the risk of stillbirth in the second pregnancy. RESULTS: Significant findings were associated with interpregnancy BMI changes involving overweight mothers becoming obese (HR = 1.4, 95% CI 1.1-1.7), normal-weight mothers becoming overweight (HR = 1.2, 95% CI 1.0-1.4) or obese (HR = 1.5, 95% CI 1.1-2.1), or obese mothers maintaining their obesity status across the two pregnancies (HR = 1.4, 95% CI 1.2-1.7). Other weight change categories did not show significant risk elevation for stillbirth. CONCLUSIONS: BMI change appears to play an important role in subsequent stillbirth risk.

Changes in prepregnancy body mass index between pregnancies and risk of preterm phenotypes.

We examined whether the risk of preterm birth and its subtypes (medically indicated and spontaneous preterm) are influenced by changes in prepregnancy body mass index (BMI) between the first and second pregnancies. A population-based, retrospective cohort analysis was performed using the Missouri (1978 to 2005) longitudinally linked cohort data sets. Women with their first two successive singleton live births ( N = 436,502) were analyzed. The risks for preterm birth and its subtypes were evaluated using multivariate logistic regression modeling. Compared with women who maintained normal interpregnancy BMI, women who lowered their weight from normal to underweight were more likely to experience preterm and spontaneous preterm birth (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.4 to 1.6). Women with BMI changes from normal weight to obese (OR 1.4, 95% CI 1.2 to 1.6) and normal weight to overweight (OR 1.2, 95% CI 1.1 to 1.3) were at increased risk of medically indicated preterm birth. A decrease in prepregnancy BMI from normal to underweight is associated with increased risk of spontaneous preterm birth, and prepregnancy BMI increases from normal to overweight or to obese BMI are associated with increased risk of medically indicated preterm birth.

Changes in prepregnancy body mass index between pregnancies and risk of gestational and type 2 diabetes.

INTRODUCTION: We investigated whether changes in interpregnancy body mass index (BMI) influence the risk of gestational and type 2 diabetes among a cohort of women with two consecutive live, singleton births of 20-44 weeks gestation (n = 232,272). METHODS: Logistic regression models were used to examine the risk for development of gestational or type 2 diabetes during the second pregnancy. Mothers with normal weight for both pregnancies (normal-normal) served as the referent group. RESULTS: Across all BMI categories, mothers with significant weight gain (i.e., moving from a lower BMI category into a higher category) had an increased risk for the development of diabetes. Mothers who moved from normal prepregnancy weight (BMI = 18.5-24.9 kg/m²) in the first pregnancy to obese prepregnancy weight (BMI ≥ 30.0 kg/m²) in the second pregnancy showed the greatest increment in risk. These mothers exhibited a threefold risk for developing diabetes (OR = 3.21, 95% CI 2.76-3.73). Mothers who maintained their interpregnancy BMI weight category or who moved to a lower BMI category had reduced risk for gestational and type 2 diabetes. The risk associated with mothers who moved to a lower BMI category was approximately half that of the normal-normal BMI category. CONCLUSION: Interpregnancy weight gain is associated with a dose-response increase in risk of diabetes. Establishing a normal interpregnancy BMI may reduce the risk of diabetes.

Association between tobacco use in pregnancy and placenta-associated syndromes: a population-based study.

INTRODUCTION: Cigarette smoking is an established risk factor for adverse perinatal outcomes. The purpose of this study is to examine the association between maternal smoking in pregnancy and the occurrence of placental-associated syndromes (PAS). METHODS: We analyzed data from a population-based retrospective cohort of singleton deliveries that occurred in the state of Missouri from 1989 through 2005 (N = 1,224,133). The main outcome was PAS, a composite outcome defined as the occurrence of placental abruption, placenta previa, preeclampsia, small for gestational age, preterm or stillbirth. We used logistic regression models to generate adjusted odd ratios and their 95 percent confidence intervals. Non-smoking gravidas served as the referent category. RESULTS: The overall prevalence of prenatal smoking was 19.6%. Cigarette smoking in pregnancy was associated with the composite outcome of placental syndromes (odds ratio, 95% confidence interval = 1.59, 1.57-1.60). This association showed a dose-response relationship, with the risk of PAS increasing with increased quantity of cigarettes smoked. Similar results were observed between smoking in pregnancy and independent risks for abruption, previa, SGA, stillbirth, and preterm delivery. CONCLUSION: Maternal smoking in pregnancy is a risk factor for the development of placenta-associated syndrome. Smoking cessation interventions in pregnancy should continue to be encouraged in all maternity care settings.

Morbidity associated with nonemergent hysterectomy for placenta accreta.

OBJECTIVE: The purpose of this study was to report the morbidity of nonemergent hysterectomy for suspected placenta accreta. STUDY DESIGN: This was a retrospective study of all patients who underwent nonemergent hysterectomy for placenta accreta at Tampa General Hospital from June 1, 2003 to May 31, 2009. RESULTS: Twenty-nine patients were identified. Diagnosis was suspected on ultrasound scanning in 26 women (6 women also underwent magnetic resonance imaging) and on direct vision at repeat cesarean section delivery in 3 women. All of the women were multiparous, and 18 women had undergone > or =2 cesarean section deliveries. Twenty-one women had a placenta previa, and 8 women had a low anterior placenta. Final pathologic findings revealed accreta (20 specimens), increta (6 women), and percreta (3 women). Mean total operative time was 216 minutes; blood loss was 4061 mL. Two women had ureteral transection (1 was bilateral); 3 women had cystotomy, and 3 women had partial cystectomy. Postoperative hemorrhage occurred in 5 women; 1 hemorrhage resolved after catheter embolization, and the other 4 hemorrhage required reoperation. CONCLUSION: Nonemergent hysterectomy for placenta accreta is associated with significant morbidity in the forms of hemorrhage and urinary tract insult.

Obstetric outcomes with a false-positive one-hour glucose challenge test by the Carpenter-Coustan criteria.

OBJECTIVE: Pregnancies complicated by a false-positive one-hour glucose challenge test (GCT), as determined by the National Diabetes Data Group (NDDG) criteria, have higher rates of adverse maternal and neonatal outcomes. This study was conducted to determine if pregnancies complicated by a false-positive GCT, as determined by the Carpenter-Coustan (CC) criteria, also have higher rates of adverse maternal and neonatal outcomes. STUDY DESIGN: In this retrospective case-control study, we compared 165 patients with a false-positive GCT, as determined by the Carpenter-Coustan criteria, to a cohort of 165 pregnant controls with a normal screening GCT. Multiple variables for maternal and neonatal outcomes were compared between the two groups. RESULTS: The racial distribution and gestational age of delivery were similar in both groups. The study group had a higher one-hour GCT (148.2 mg/dl vs. 95.3 mg/dl, p < 0.001), was older (27.4 yrs vs. 23.8 years, p < 0.001), was more likely to be multiparous (71.5% vs. 58.2%, p = 0.011), and had a higher BMI (26.7 kg/m2 vs. 24.6 kg/m2, p = 0.002). There were no differences between the two groups in mode of delivery, birth weight, rates of macrosomia, shoulder dystocia, antenatal death and maternal laceration. There were also no differences between the two groups in rates of preeclampsia, chorioamnionitis, endometritis, ICN admission, neonatal hypoglycemia, Erb's palsy, clavicular fracture, neonatal sepsis, neonatal death or use of phototherapy. CONCLUSION: Women with a false-positive one-hour GCT by the Carpenter-Coustan criteria do not have higher rates of adverse perinatal outcomes. Using the Carpenter-Coustan criteria to diagnose GDM appears to be superior to NDDG criteria in terms of avoiding adverse maternal and neonatal outcomes.

Telomere length and fetal programming: A review of recent scientific advances.

We sought to synthesize a comprehensive literature review comprising recent research linking fetal programming to fetal telomere length. We also explored the potential effects fetal telomere length shortening has on fetal phenotypes. Utilizing the PubMed database as our primary search engine, we retrieved and reviewed 165 articles of published research. The inclusion criteria limited the articles to those that appeared within the last ten years, were pertinent to humans, and without restriction to language of publication. Our results showed that socio-demographic factors like age, sex, genetic inheritance, and acquired disease impact telomere length. Further, we found several maternal characteristics to be associated with fetal telomere length shortening, and these include maternal chemical exposure (eg, tobacco smoke), maternal stress during pregnancy, maternal nutritional and sleeping disorders during pregnancy as well as maternal disease status. Due to paucity of data, our review could not synthesize evidence directly linking fetal phenotypes to telomere length shortening. Although the research summarized in this review shows some association between determinants of intrauterine programming and fetal telomere length, there is still significant work that needs to be done to delineate the direct relationship of telomere attrition with specific fetal phenotypes.

Baking soda pica: a case of hypokalemic metabolic alkalosis and rhabdomyolysis in pregnancy.

BACKGROUND: We report a case of baking soda pica in a woman at 31 weeks of pregnancy causing severe hypokalemic metabolic alkalosis and rhabdomyolysis. CASE: A multigravida at 31 weeks of gestation presented with weakness and muscle pain. She was found to have severe hypokalemic metabolic alkalosis and rhabdomyolysis, with elevation in serum transaminases and hypertension. We initially thought the patient had an atypical presentation of preeclampsia until it was realized that she was ingesting 1 full box of baking soda (454 g sodium bicarbonate) per day. Symptoms and abnormal laboratory findings resolved with discontinuation of the patient's pica practices. CONCLUSION: Pica is a common but often overlooked practice that can potentially lead to life-threatening disorders. A thorough evaluation of a patient's dietary intake is extremely important, especially in the setting of atypical presentations of disease in pregnancy.

Recent trends in placenta accreta in the United States and its impact on maternal-fetal morbidity and healthcare-associated costs, 1998-2011.

OBJECTIVE: To describe the prevalence, trends, adverse maternal-fetal morbidities and healthcare costs associated with placenta accreta (PA) in the United States (US) between 1998 and 2011. METHODS: A retrospective, cross-sectional analysis of inpatient hospital discharges was conducted using the National Inpatient Sample (NIS). We used International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify both cases of PA and of selected comorbidities. Survey logistic regression was used to assess the association between PA and various maternal-fetal outcomes. Joinpoint regression modeling was used to estimate annual percent changes (APCs) in PA prevalence during the study period. RESULTS: The prevalence of PA from 1998 to 2011 was 3.7 per 1000 delivery-related discharges. After adjusting for known or suspected confounders, PA conferred between a 20% to over a 19-fold increased odds of experiencing an adverse outcome. This resulted in a higher mean, per-hospitalization, cost of inpatient care after adjustment for inflation ($5561 versus $4989), translating into over $115 million dollars in additional inpatient expenditures relative to non-PA affected deliveries from 2001 to 2011. CONCLUSIONS: This study updates recent trends in the prevalence of PA, which is valuable to clinicians and policymakers as they formulate targeted strategies to address factors related to PA.

A positive association between umbilical cord RBC folate and fetal TL at birth supports a potential for fetal reprogramming.

Telomere length (TL) has been studied extensively in adults; however, limited information exists regarding maternal influences on TL in utero. The objective of this study was to investigate the relationship between fetal red blood cell (RBC) folate levels, a surrogate measure for maternal folate levels, and TL. We hypothesized that umbilical cord RBC folate concentrations would positively correlate with fetal TL. Data for this analysis were collected as part of a prospective cohort study that recruited pregnant women upon admission into labor and delivery. Cord blood was collected for 96 maternal-fetal dyads, and DNA analysis was performed using quantitative polymerase chain reaction. The telomere to single copy gene ratio method was used to determine TL, and RBC folate levels were measured. Statistical analysis was conducted by incorporating a bootstrapping approach into generalized linear modeling-based analyses. Consistent significant positive correlations were observed between RBC folate and TL (telomere to single copy gene ratio) with 9880 of the 10000 (98.8%) iterations performed having a P value less than .05. Our study shows a positive association between umbilical cord RBC folate and fetal TL at birth. These findings may provide a pathway of understanding and preventing adult-onset disease and mortality through intrauterine reprogramming.

Socio-ecological Model as a Framework for Overcoming Barriers and Challenges in Randomized Control Trials in Minority and Underserved Communities.

BACKGROUND: Numerous barriers and challenges can hinder the successful enrollment and retention of study participants in clinical trials targeting minority populations. To conduct quality research, it is important to investigate these challenges, determine appropriate strategies that are evidence-based and continue seeking methods of improvement. METHODS: In this paper, we report such experiences in a registered clinical trial in an underserved minority population in the Southern part of United States. This research study is a randomized double-blind controlled clinical trial that tests the efficacy of higher-strength as compared to low-strength/standard of care folic acid to prevent fetal body and brain size reduction in pregnant women who smoke. A unique approach in this socio-behavioral, genetic-epigenetic clinical trial is that we have adopted the socio-ecological model as a functional platform to effectively achieve and maintain high participant recruitment and retention rates. RESULTS: We highlight the barriers we have encountered in our trial and describe how we have successfully applied the socio-ecological model to overcome these obstacles. CONCLUSIONS AND GLOBAL HEALTH IMPLICATIONS: Our positive experience will be of utility to other researchers globally. Our fi ndings have far-reaching implications as the socio-ecological model approach is adaptable to developed and developing regions and has the potential to increase recruitment and retention of hard-to-reach populations who are typically under-represented in clinical trials.