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1.  Prevention and Management of Neonatal Hypothermia in Rural Zambia 
PLoS ONE  2014;9(4):e92006.
Background
Neonatal hypothermia is increasingly recognized as a risk factor for newborn survival. The World Health Organization recommends maintaining a warm chain and skin-to-skin care for thermoprotection of newborn children. Since little is known about practices related to newborn hypothermia in rural Africa, this study's goal was to characterize relevant practices, attitudes, and beliefs in rural Zambia.
Methods and Findings
We conducted 14 focus group discussions with mothers and grandmothers and 31 in-depth interviews with community leaders and health officers in Lufwanyama District, a rural area in the Copperbelt Province, Zambia, enrolling a total of 171 participants. We analyzed data using domain analysis. In rural Lufwanyama, community members were aware of the danger of neonatal hypothermia. Caregivers' and health workers' knowledge of thermoprotective practices included birthplace warming, drying and wrapping of the newborn, delayed bathing, and immediate and exclusive breastfeeding. However, this warm chain was not consistently maintained in the first hours postpartum, when newborns are at greatest risk. Skin-to-skin care was not practiced in the study area. Having to assume household and agricultural labor responsibilities in the immediate postnatal period was a challenge for mothers to provide continuous thermal care to their newborns.
Conclusions
Understanding and addressing community-based practices on hypothermia prevention and management might help improve newborn survival in resource-limited settings. Possible interventions include the implementation of skin-to-skin care in rural areas and the use of appropriate, low-cost newborn warmers to prevent hypothermia and support families in their provision of newborn thermal protection. Training family members to support mothers in the provision of thermoprotection for their newborns could facilitate these practices.
doi:10.1371/journal.pone.0092006
PMCID: PMC3979664  PMID: 24714630
2.  Umbilical Cord Milking Improves Transition in Premature Infants at Birth 
PLoS ONE  2014;9(4):e94085.
Background
Umbilical cord milking (UCM) improves blood pressure and urine output, and decreases the need for transfusions in comparison to immediate cord clamping (ICC). The immediate effect of UCM in the first few minutes of life and the impact on neonatal resuscitation has not been described.
Methods
Women admitted to a tertiary care center and delivering before 32 weeks gestation were randomized to receive UCM or ICC. A blinded analysis of physiologic data collected on the newborns in the delivery room was performed using a data acquisition system. Heart rate (HR), SpO2, mean airway pressure (MAP), and FiO2 in the delivery room were compared between infants receiving UCM and infants with ICC.
Results
41 of 60 neonates who were enrolled and randomized had data from analog tracings at birth. 20 of these infants received UCM and 21 had ICC. Infants receiving UCM had higher heart rates and higher SpO2 over the first 5 minutes of life, were exposed to less FiO2 over the first 10 minutes of life than infants with ICC.
Conclusions
UCM when compared to ICC had decreased need for support immediately following delivery, and in situations where resuscitation interventions were needed immediately, UCM has the advantage of being completed in a very short time to improve stability following delivery.
Trial Registration
ClinicalTrials.gov NCT01434732
doi:10.1371/journal.pone.0094085
PMCID: PMC3978008  PMID: 24709780
3.  Stillbirth and early neonatal mortality in rural Central Africa 
Objective
To develop a prospective perinatal registry that characterizes all deliveries, differentiates between stillbirths and early neonatal deaths (ENDs), and determines the ratio of fresh to macerated stillbirths in the northwest Democratic Republic of Congo.
Method
Birth outcomes were obtained from 4 rural health districts.
Results
A total of 8230 women consented, END rate was 32 deaths per 1000 live births, and stillbirth rate was 33 deaths per 1000 deliveries. The majority (75%) of ENDs and stillbirths occurred in neonates weighing 1500 g or more. Odds of stillbirth and END increased in mothers who were single or who did not receive prenatal care, and among premature, low birth weight, or male infants. The ratio of fresh to macerated stillbirths was 4:1.
Conclusion
Neonates weighing 1500 g or more at birth represent a group with a high likelihood of survival in remote areas, making them potentially amenable to targeted intervention packages. The ratio of fresh to macerated stillbirths was approximately 10-fold higher than expected, suggesting a more prominent role for improved intrapartum obstetric interventions.
doi:10.1016/j.ijgo.2008.12.012
PMCID: PMC3972762  PMID: 19201402
Africa; Early neonatal death; Fresh and macerated stillbirth; Low-income country
4.  Randomized Trial of Early Developmental Intervention on Outcomes in Children after Birth Asphyxia in Developing Countries 
The Journal of pediatrics  2012;162(4):705-712.e3.
Objective
To determine if early developmental intervention (EDI) improves developmental abilities in resuscitated children.
Study design
This was a parallel group, randomized controlled trial of infants unresponsive to stimulation who received bag and mask ventilation as part of their resuscitation at birth and infants who did not require any resuscitation born in rural communities in India, Pakistan, and Zambia. Intervention infants received a parent-implemented EDI delivered with home visits by parent trainers every other week for 3 years started the first month after birth. Parents in both intervention and control groups received health and safety counseling during home visits on the same schedule. The main outcome measure was the Mental Development Index (MDI) of the Bayley Scales of Infant Development, 2nd edition, assessed at 36 months by evaluators unaware of treatment group and resuscitation history.
Results
MDI was higher in the EDI (102.6±9.8) compared with the control resuscitated children (98.0±14.6, one-sided p=0.0202) but there was no difference between groups in the non-resuscitated children (100.1±10.7 vs. 97.7±10.4, p=0.1392). The Psychomotor Development Index (PDI) was higher in the EDI group for both the resuscitated (p=0.0430) and non-resuscitated children (p=0.0164).
Conclusions
This trial of home-based, parent provided EDI in children resuscitated at birth provides evidence of treatment benefits on cognitive and psychomotor outcomes. MDI and PDI scores of both non-resuscitated and resuscitated infants were within normal range, independent of early intervention.
doi:10.1016/j.jpeds.2012.09.052
PMCID: PMC3582821  PMID: 23164311
Early intervention; resuscitation; intellectual disability; low and middle income countries; neonatal mortality; infant mortality; developmental outcome
5.  Assessing the Elimination of User Fees for Delivery Services in Laos 
PLoS ONE  2014;9(3):e89784.
A pilot eliminating user fees associated with delivery at the point of services was introduced in two districts of Laos in March 2009. Following two years of implementation, an evaluation was conducted to assess the pilot impact, as well as to document the pilot design and implementation challenges. Study results show that, even in the presence of the substantial access and cultural barriers, user fees associated with delivery at health facilities act as a serious deterrent to care seeking behavior. We find a tripling of facility-based delivery rates in the intervention areas, compared to a 40% increase in the control areas. While findings from the control region suggest that facility-based delivery rates may be on the rise across the country, the substantially higher increase in the pilot areas highlight the impact of financial burden associated with facility-based delivery fees. These fees can play an important role in rapidly increasing the uptake of facility delivery to reach the national targets and, ultimately, to improve maternal and child health outcomes. The pilot achieved important gains while relying heavily on capacity and systems already in place. However, the high cost associated with monitoring and evaluation suggest broad-scale expansion of the pilot activities is likely to necessitate targeted capacity building initiatives, especially in areas with limited district level capacity to manage funds and deliver detailed and timely reports.
doi:10.1371/journal.pone.0089784
PMCID: PMC3954553  PMID: 24632592
6.  A Comparative Analysis of Prenatal Care and Fetal Growth in Eight South American Countries 
PLoS ONE  2014;9(3):e91292.
There has been little work that comprehensively compared the relationship between prenatal care and infant health across multiple countries using similar data sources and analytical models. Such comparative analyses are useful for understanding the background of differences in infant health between populations. We evaluated the association between prenatal care visits and fetal growth measured by birth weight (BW) in grams or low birth weight (<2500 grams; LBW) adjusted for gestational age in eight South American countries using similarly collected data across countries and the same analytical models. OLS and logistic regressions were estimated adjusting for a large set of relevant infant, maternal, and household characteristics and birth year and hospital fixed effects. Birth data were acquired from 140 hospitals that are part of the Latin American Collaborative Study of Congenital Malformations (ECLAMC) network. The analytical sample included 56,014 live-born infants (∼69% of total sample) with complete data born without congenital anomalies in the years 1996–2011 in Brazil, Argentina, Chile, Venezuela, Ecuador, Colombia, Bolivia, and Uruguay. Prenatal care visits were significantly (at p<.05) and positively associated with BW and negatively associated with LBW for all countries. The OLS coefficients ranged from 9 grams per visit in Bolivia to 36 grams in Uruguay. The association with LBW was strongest for Chile (OR = 0.87 per visit) and lowest for Argentina and Venezuela (OR = 0.95). The association decreased in the recent decade compared to earlier years. Our findings suggest that estimates of association between prenatal care and fetal growth are population-specific and may not be generalizable to other populations. Furthermore, as one of the indicators for a country’s healthcare system for maternal and child health, prenatal care is a highly variable indicator between countries in South America.
doi:10.1371/journal.pone.0091292
PMCID: PMC3953331  PMID: 24625630
7.  Economic Analysis of Delivering Primary Health Care Services through Community Health Workers in 3 North Indian States 
PLoS ONE  2014;9(3):e91781.
Background
We assessed overall annual and unit cost of delivering package of services and specific services at sub-centre level by CHWs and cost effectiveness of Government of India’s policy of introducing a second auxiliary nurse midwife (ANM) at the sub-centre compared to scenario of single ANM sub-centre.
Methods
We undertook an economic costing of health services delivered by CHWs, from a health system perspective. Bottom-up costing method was used to collect data on resources spent in 50 randomly selected sub-centres selected from 4 districts. Mean unit cost along with its 95% confidence intervals were estimated using bootstrap method. Multiple linear regression model was used to standardize cost and assess its determinants.
Results
Annually it costs INR 1.03 million (USD 19,381), or INR 187 (USD 3.5) per capita per year, to provide a package of preventive, curative and promotive services through community health workers. Unit costs for antenatal care, postnatal care, DOTS treatment and immunization were INR 525 (USD 10) per full ANC care, INR 767 (USD 14) per PNC case registered, INR 974 (USD 18) per DOTS treatment completed and INR 97 (USD 1.8) per child immunized in routine immunization respectively. A 10% increase in human resource costs results in 6% rise in per capita cost. Similarly, 10% increment in the ANC case registered per provider through-put results in a decline in unit cost ranging from 2% in the event of current capacity utilization to 3% reduction in case of full capacity utilization. Incremental cost of introducing 2nd ANM at sub-centre level per unit percent increase ANC coverage was INR 23,058 (USD 432).
Conclusion
Our estimates would be useful in undertaking full economic evaluations or equity analysis of CHW programs. Government of India’s policy of hiring 2nd ANM at sub-centre level is very cost effective from Indian health system perspective.
doi:10.1371/journal.pone.0091781
PMCID: PMC3953597  PMID: 24626285
8.  Poor Thermal Care Practices among Home Births in Nepal: Further Analysis of Nepal Demographic and Health Survey 2011 
PLoS ONE  2014;9(2):e89950.
Introduction
Hypothermia is a major factor associated with neonatal mortality in low and middle income countries. Thermal care protection of newborn through a series of measures taken at birth and during the initial days of life is recommended to reduce the hypothermia and associated neonatal mortality. This study aimed to identify the prevalence of and the factors associated with receiving ‘optimum thermal care’ among home born newborns of Nepal.
Methods
Data from the Nepal Demographic and Health Surveys (NDHS) 2011 were used for this study. Women who reported a home birth for their most recent childbirth was included in the study. Factors associated with optimum thermal care were examined using Chi-square test followed by logistic regression.
Results
A total of 2464 newborns were included in the study. A total of 57.6 % were dried before the placenta was delivered; 60.3% were wrapped; 24.5% had not bathing during the first 24 hours, and 63.9% were breastfed within one hour of birth. Overall, only 248 (10.7%; 95% CI (8.8 %, 12.9%)) newborns received optimum thermal care. Newborns whose mothers had achieved higher education (OR 2.810; 95% CI (1.132, 6.976)), attended four or more antenatal care visits (OR 2.563; 95% CI (1.309, 5.017)), and those whose birth were attended by skilled attendants (OR 2.178; 95% CI (1.428, 3.323)) were likely to receive optimum thermal care.
Conclusion
The current study showed that only one in ten newborns in Nepal received optimum thermal care. Future newborn survival programs should focus on those mothers who are uneducated; who do not attend the recommended four or more attend antenatal care visits; and those who deliver without the assistance of skilled birth attendants to reduce the risk of neonatal hypothermia in Nepal.
doi:10.1371/journal.pone.0089950
PMCID: PMC3938557  PMID: 24587145
9.  High Mortality Rates for Very Low Birth Weight Infants in Developing Countries Despite Training 
Pediatrics  2010;126(5):e1072-e1080.
OBJECTIVE
The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants.
METHODS
Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP.
RESULTS
A total of 1096 VLBW (500–1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training.
CONCLUSIONS
Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected.
doi:10.1542/peds.2010-1183
PMCID: PMC3918943  PMID: 20937655
neonatal mortality; perinatal mortality; stillbirth; developing countries; health care systems; very low birth weight; prematurity
10.  Meat consumption is associated with less stunting among toddlers in four diverse low-income settings 
Food and nutrition bulletin  2011;32(3):185-191.
Background
Early growth faltering is common but is difficult to reverse after the first 2 years of life.
Objective
To describe feeding practices and growth in infants and young children in diverse low-income settings prior to undertaking a complementary feeding trial.
Methods
This cross-sectional study was conducted through the Global Network for Women’s and Children’s Health Research in Guatemala, Democratic Republic of Congo, Zambia, and Pakistan. Feeding questionnaires were administered to convenience samples of mothers of 5- to 9-month old infants and 12- to 24-month-old toddlers. After standardized training, anthropometric measurements were obtained from the toddlers. Following the 2006 World Health Organization Growth Standards, stunting was defined as length-for-age < −2SD, and wasting as weight-for-length < −2SD. Logistic regression was applied to evaluate relationships between stunting and wasting and consumption of meat (including chicken and liver and not including fish).
Results
Data were obtained from 1,500 infants with a mean (± SD) age of 6.9 ± 1.4 months and 1,658 toddlers with a mean age of 17.2 ± 3.5 months. The majority of the subjects in both age groups were breastfed. Less than 25% of the infants received meat regularly, whereas 62% of toddlers consumed these foods regularly, although the rates varied widely among sites. Stunting rate ranged from 44% to 66% among sites; wasting prevalence was less than 10% at all sites. After controlling for covariates, consumption of meat was associated with a reduced likelihood of stunting (OR = 0.64; 95% CI, 0.46 to 0.90).
Conclusions
The strikingly high stunting rates in these toddlers and the protective effect of meat consumption against stunting emphasize the need for interventions to improve complementary feeding practices, beginning in infancy.
PMCID: PMC3918945  PMID: 22073791
Complementary feeding; infant growth; infant nutrition; stunting
11.  Knowledge about Obstetric Danger Signs and Associated Factors among Mothers in Tsegedie District, Tigray Region, Ethiopia 2013: Community Based Cross-Sectional Study 
PLoS ONE  2014;9(2):e83459.
Background
In many developing countries including Ethiopia, maternal morbidity and mortality still pose a substantial burden and thus progress towards the fifth Millennium Development Goal (MDG) remains slow. Raising awareness of women about the danger signs of pregnancy and childbirth is the first essential step in accepting appropriate and timely referral to obstetric care. However, in Ethiopia little is known about the knowledge level of mothers about obstetric danger signs. The objective of this study was to assess the status of knowledge of danger signs of pregnancy and childbirth among mothers who gave birth in the past two years prior to the survey in Tsegedie district, Tigray regional state, Ethiopia.
Methods
A Community based cross-sectional study was conducted from November 20, 2012 to June 30, 2013 on a randomly selected sample of 485 women who had at least one delivery in the past two years. Multistage sampling technique was employed to select the study participants. A pre-tested structured questionnaire was used to collect quantitative data. Focus group discussion and in-depth interviews were utilized to supplement the Quantitative data. Bivariate and multivariate data analysis was performed using SPSS version 17.0 software.
Result
Four hundred eighty five mothers participated in the study making a response rate of 100%. Vaginal bleeding was the most commonly mentioned danger signs of pregnancy (49.1%) and childbirth (52.8%). Two hundred eighty five (58.8%) and 299 (61.6%) of respondents mentioned at least two danger signs of pregnancy and childbirth respectively. One hundred seventy (35.1%) and 154 (31.8%) of respondents didn't know any danger signs of pregnancy and childbirth respectively. Educational status of the mother, place of delivery and having functional radio were found to be independent predictors of knowledge of women about the danger signs of pregnancy and childbirth.
Conclusion
Educational status of the mother, place of delivery and having functional radio were independently associated with knowledge of women about obstetric danger signs. Thus, provision of information, education and communication targeting women, family and the general community on danger signs of pregnancy and childbirth and associated factors was recommended.
doi:10.1371/journal.pone.0083459
PMCID: PMC3916287  PMID: 24516516
12.  Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions 
Pediatrics  2013;131(2):e635-e646.
Herpes simplex virus (HSV) infection of the neonate is uncommon, but genital herpes infections in adults are very common. Thus, although treating an infant with neonatal herpes is a relatively rare occurrence, managing infants potentially exposed to HSV at the time of delivery occurs more frequently. The risk of transmitting HSV to an infant during delivery is determined in part by the mother’s previous immunity to HSV. Women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants than are women with recurrent HSV infection who are shedding virus at delivery. With the availability of commercial serological tests that reliably can distinguish type-specific HSV antibodies, it is now possible to determine the type of maternal infection and, thus, further refine management of infants delivered to women who have active genital HSV lesions. The management algorithm presented herein uses both serological and virological studies to determine the risk of HSV transmission to the neonate who is delivered to a mother with active herpetic genital lesions and tailors management accordingly. The algorithm does not address the approach to asymptomatic neonates delivered to women with a history of genital herpes but no active lesions at delivery.
doi:10.1542/peds.2012-3216
PMCID: PMC3557411  PMID: 23359576
newborn; herpes simplex virus; acyclovir; pregnancy
13.  Challenges to the Programmatic Implementation of Ready to Use Infant Formula in the Post-Earthquake Response, Haiti, 2010: A Program Review 
PLoS ONE  2013;8(12):e84043.
Background and Objectives
Following the 2010 earthquake in Haiti, infant and young child feeding was identified as a priority nutrition intervention. A new approach to support breastfeeding mothers and distribute ready-to-use infant formula (RUIF) to infants unable to breastfeed was established. The objective of the evaluation was to assess the implementation of infant feeding programs using RUIF in displaced persons camps in Port-au-Prince, Haiti during the humanitarian response.
Methods
A retrospective record review was conducted from April–July, 2010 to obtain data on infants receiving RUIF in 30 baby tents. A standardized data collection form was created based on data collected across baby tents and included: basic demographics, admission criteria, primary caretaker, feeding practices, and admission and follow-up anthropometrics.
Main Findings
Orphans and abandoned infants were the most frequent enrollees (41%) in the program. While the program targeted these groups, it is unlikely that this is a true reflection of population demographics. Despite programmatic guidance, admission criteria were not consistently applied across programs. Thirty-four percent of infants were undernourished (weight for age Z score <−2) at the time of admission. Defaulting accounted for 50% of all program exits and there was no follow-up of these children. Low data quality was a significant barrier.
Conclusions
The design, implementation and magnitude of the ‘baby tents’ using RUIF was novel in response to infant and young child feeding (IYCF) in emergencies and presented multiple challenges that should not be overlooked, including adherence to protocols and the adaption of emergency programs to existing programs. The implementation of IYCF programs should be closely monitored to ensure that they achieve the objectives set by the humanitarian community and national government. IYCF is an often overlooked component of emergency preparedness; however to improve response, generic protocols and pre-emergency training and preparedness should be established for humanitarian agencies.
doi:10.1371/journal.pone.0084043
PMCID: PMC3877141  PMID: 24391877
14.  EVALUATION OF MEAT AS A FIRST COMPLEMENTARY FOOD FOR BREASTFED INFANTS: IMPACT ON IRON INTAKE & GROWTH 
Nutrition reviews  2011;69(0 1):10.1111/j.1753-4887.2011.00434.x.
The rationale is considered for promoting the availability of local, affordable, non-fortified food sources of bioavailable iron in developing countries. Intakes of iron from the regular consumption of meat from the age of six months are evaluated with respect to physiological requirements. The paper includes a description of two major randomized controlled trials of meat as a first and regular complementary food that are currently in progress. These trials involve poor communities in Guatemala, Pakistan, Zambia, Democratic Republic of the Congo and China.
doi:10.1111/j.1753-4887.2011.00434.x
PMCID: PMC3875190  PMID: 22043884
iron; meat; complementary feeding
15.  Evaluation of the Cost Effectiveness of Vesico-Amniotic Shunting in the Management of Congenital Lower Urinary Tract Obstruction (Based on Data from the PLUTO Trial) 
PLoS ONE  2013;8(12):e82564.
Objective
To determine the cost-effectiveness of in-utero percutaneous Vesico Amniotic Shunt (VAS) in the management of fetal lower urinary tract obstruction (LUTO)
Design
Model based economic analysis using data from the randomised controlled arm of the PLUTO (percutaneous vesico-amniotic shunting for lower urinary tract obstruction) trial.
Setting
Fetal medicine departments in United Kingdom, Ireland and Netherlands.
Population or Sample
Pregnant women with a male, singleton fetus with LUTO.
Methods
Costs and outcomes were prospectively collected in the trial; three separate base case analyses were performed using the intention to treat (ITT), per protocol and uniform prior methods. Deterministic and probabilistic sensitivity analyses were performed to explore data uncertainty.
Main Outcome Measures
Survival at 28 days, 1 year and disease free survival at 1 year.
Results
VAS was more expensive but appeared to result in higher rates of survival compared with conservative management in patients with LUTO. Using ITT analysis the incremental cost effectiveness ratios based on outcomes of survival at 28 days, 1 year, or 1 morbidity-free year on the VAS arm were £15,506, £15,545, and £43,932, respectively.
Conclusions
VAS is a more expensive option compared to the conservative approach in the management of individuals with LUTO. Data from the RCT suggest that VAS improves neonatal survival but does not result in significant improvements in morbidity. Our analysis concludes that VAS is not likely to be cost effective in the management of these patients given the NICE (National Institute of Health and Clinical Excellence) cost threshold of £20,000 per QALY.
doi:10.1371/journal.pone.0082564
PMCID: PMC3869698  PMID: 24376546
16.  Platelet Content of Nitric Oxide Synthase 3 Phosphorylated At Serine1177 Is Associated with the Functional Response of Platelets to Aspirin 
PLoS ONE  2013;8(12):e82574.
Objective
To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO).
Patients/Methods
Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100).
Results
ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position −786 (T−786→C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)1177, an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser1177 phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser1177. On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser1177. During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets.
Conclusions
Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser1177.
doi:10.1371/journal.pone.0082574
PMCID: PMC3869699  PMID: 24376548
17.  Rural Clinician Scarcity and Job Preferences of Doctors and Nurses in India: A Discrete Choice Experiment 
PLoS ONE  2013;8(12):e82984.
The scarcity of rural doctors has undermined the ability of health systems in low and middle-income countries like India to provide quality services to rural populations. This study examines job preferences of doctors and nurses to inform what works in terms of rural recruitment strategies. Job acceptance of different strategies was compared to identify policy options for increasing the availability of clinical providers in rural areas. In 2010 a Discrete Choice Experiment was conducted in India. The study sample included final year medical and nursing students, and in-service doctors and nurses serving at Primary Health Centers. Eight job attributes were identified and a D-efficient fractional factorial design was used to construct pairs of job choices. Respondent acceptance of job choices was analyzed using multi-level logistic regression. Location mattered; jobs in areas offering urban amenities had a high likelihood of being accepted. Higher salary had small effect on doctor, but large effect on nurse, acceptance of rural jobs. At five times current salary levels, 13% (31%) of medical students (doctors) were willing to accept rural jobs. At half this level, 61% (52%) of nursing students (nurses) accepted a rural job. The strategy of reserving seats for specialist training in exchange for rural service had a large effect on job acceptance among doctors, nurses and nursing students. For doctors and nurses, properly staffed and equipped health facilities, and housing had small effects on job acceptance. Rural upbringing was not associated with rural job acceptance. Incentivizing doctors for rural service is expensive. A broader strategy of substantial salary increases with improved living, working environment, and education incentives is necessary. For both doctors and nurses, the usual strategies of moderate salary increases, good facility infrastructure, and housing will not be effective. Non-physician clinicians like nurse-practitioners offer an affordable alternative for delivering rural health care.
doi:10.1371/journal.pone.0082984
PMCID: PMC3869745  PMID: 24376621
18.  Maternal Education and Micro-Geographic Disparities in Nutritional Status among School-Aged Children in Rural Northwestern China 
PLoS ONE  2013;8(12):e82500.
Objectives
Prior evidence suggests geographic disparities in the effect of maternal education on child nutritional status between countries, between regions and between urban and rural areas. We postulated its effect would also vary by micro-geographic locations (indicated by mountain areas, plain areas and the edge areas) in a Chinese minority area.
Methods
A cross-sectional study was conducted with a multistage random sample of 1474 school children aged 5-12 years in Guyuan, China. Child nutritional status was measured by height-for-age z scores (HAZ). Linear mixed models were used to examine its association with place of residence and maternal education.
Results
Micro-geographic disparities in child nutritional status and the level of socioeconomic composition were found. Children living in mountain areas had poorer nutritional status, even after adjusting for demographic (plain versus mountain, β = 0.16, P = 0.033; edge versus mountain, β = 0.29, P = 0.002) and socioeconomic factors (plain versus mountain, β = 0.12, P = 0.137; edge versus mountain, β = 0.25, P = 0.009). The disparities significantly widened with increasing years of mothers’ schooling (maternal education*plain versus mountain: β = 0.06, P = 0.007; maternal education*edge versus mountain: β = 0.07, P = 0.005). Moreover, the association between maternal education and child nutrition was negative (β = -0.03, P = 0.056) in mountain areas but positive in plain areas (β = 0.02, P = 0.094) or in the edge areas (β = 0.04, P = 0.055).
Conclusions
Micro-geographic disparities in child nutritional status increase with increasing level of maternal education and the effect of maternal education varies by micro-geographic locations, which exacerbates child health inequity. Educating rural girls alone is not sufficient; improving unfavorable conditions in mountain areas might make such investments more effective in promoting child health. Nutrition programs targeting to the least educated groups in plain and in edge areas would be critical to their cost-effectiveness.
doi:10.1371/journal.pone.0082500
PMCID: PMC3858303  PMID: 24340034
19.  Reasons for Unmet Need for Child and Family Health Services among Children with Special Health Care Needs with and without Medical Homes 
PLoS ONE  2013;8(12):e82570.
Objectives
Medical homes, an important component of U.S. health reform, were first developed to help families of children with special health care needs (CSHCN) find and coordinate services, and reduce their children’s unmet need for health services. We hypothesize that CSHCN lacking medical homes are more likely than those with medical homes to report health system delivery or coverage problems as the specific reasons for unmet need.
Methods
Data are from the 2005-2006 National Survey of Children with Special Health Care Needs (NS-CSHCN), a national, population-based survey of 40,723 CSHCN. We studied whether lacking a medical home was associated with 9 specific reasons for unmet need for 11 types of medical services, controlling for health insurance, child’s health, and sociodemographic characteristics.
Results
Weighted to the national population, 17% of CSHCN reported at least one unmet health service need in the previous year. CSHCN without medical homes were 2 to 3 times as likely to report unmet need for child or family health services, and more likely to report no referral (OR= 3.3), dissatisfaction with provider (OR=2.5), service not available in area (OR= 2.1), can’t find provider who accepts insurance (OR=1.8), and health plan problems (OR=1.4) as reasons for unmet need (all p<0.05).
Conclusions
CSHCN without medical homes were more likely than those with medical homes to report health system delivery or coverage reasons for unmet child health service needs. Attributable risk estimates suggest that if the 50% of CSHCN who lacked medical homes had one, overall unmet need for child health services could be reduced by as much as 35% and unmet need for family health services by 40%.
doi:10.1371/journal.pone.0082570
PMCID: PMC3858312  PMID: 24340042
20.  Prediction of Severe Disease in Children with Diarrhea in a Resource-Limited Setting 
PLoS ONE  2013;8(12):e82386.
Objective
To investigate the accuracy of three clinical scales for predicting severe disease (severe dehydration or death) in children with diarrhea in a resource-limited setting.
Methods
Participants included 178 children admitted to three Rwandan hospitals with diarrhea. A local physician or nurse assessed each child on arrival using the World Health Organization (WHO) severe dehydration scale and the Centers for Disease Control (CDC) scale. Children were weighed on arrival and daily until they achieved a stable weight, with a 10% increase between admission weight and stable weight considered severe dehydration. The Clinical Dehydration Scale was then constructed post-hoc using the data collected for the other two scales. Receiver Operator Characteristic (ROC) curves were constructed for each scale compared to the composite outcome of severe dehydration or death.
Results
The WHO severe dehydration scale, CDC scale, and Clinical Dehydration Scale had areas under the ROC curves (AUCs) of 0.72 (95% CI 0.60, 0.85), 0.73 (95% CI 0.62, 0.84), and 0.80 (95% CI 0.71, 0.89), respectively, in the full cohort. Only the Clinical Dehydration Scale was a significant predictor of severe disease when used in infants, with an AUC of 0.77 (95% CI 0.61, 0.93), and when used by nurses, with an AUC of 0.78 (95% CI 0.63, 0.93).
Conclusions
While all three scales were moderate predictors of severe disease in children with diarrhea, scale accuracy varied based on provider training and age of the child. Future research should focus on developing or validating clinical tools that can be used accurately by nurses and other less-skilled providers to assess all children with diarrhea in resource-limited settings.
doi:10.1371/journal.pone.0082386
PMCID: PMC3857792  PMID: 24349271
21.  Reproductive Health Voucher Program and Facility Based Delivery in Informal Settlements in Nairobi: A Longitudinal Analysis 
PLoS ONE  2013;8(11):e80582.
Introduction
In Kenya, the maternal mortality rate had ranged from 328 to 501 deaths per 100,000 live births over the last three decades. To reduce these rates, the government launched in 2006 a means-tested reproductive health output-based approach (OBA) voucher program that covers costs of antenatal care, a facility-based delivery (FBD) and a postnatal visit in prequalified healthcare facilities. This paper investigated whether women who bought the voucher for their index child and had a FBD were more likely to deliver a subsequent child in a facility compared to those who did not buy vouchers.
Methods and Findings
We used population-based cohort data from two Nairobi slums where the voucher program was piloted. We selected mothers of at least two children born between 2006 and 2012 and divided the mothers into two groups: Index-OBA mothers bought the voucher for the index child (N=352), and non-OBA mothers did not buy the voucher during the study period (N=514). The most complete model indicated that the adjusted odds-ratio of FBD of subsequent child when the index child was born in a facility was 3.89 (p<0.05) and 4.73 (p<0.01) in Group 2.
Discussion and Conclusion
The study indicated that the voucher program improved poor women access to FBD. Furthermore, the FBD of an index child appeared to have a persistent effect, as a subsequent child of the same mother was more likely to be born in a facility as well. While women who purchased the voucher have higher odds of delivering their subsequent child in a facility, those odds were smaller than those of the women who did not buy the voucher. However, women who did not buy the voucher were less likely to deliver in a good healthcare facility, negating their possible benefit of facility-based deliveries. Pathways to improve access to FBD to all near poor women are needed.
doi:10.1371/journal.pone.0080582
PMCID: PMC3832453  PMID: 24260426
22.  The Prognostic Value of Amplitude-Integrated EEG in Full-Term Neonates with Seizures 
PLoS ONE  2013;8(11):e78960.
Neonatal seizures pose a high risk for adverse outcome in survived infants. While the prognostic value of amplitude-integrated electroencephalogram (aEEG) is well established in neonates with encephalopathy and asphyxia, neonatal seizure studies focusing on the direct correlation between early aEEG measurement and subsequent neurologic outcome are scarce. In this study, the prognostic value of aEEG features was systematically analyzed in 143 full-term neonates to identify prognostic indicators of neurodevelopmental outcome. Neonatal aEEG features of background pattern, cyclicity, and seizure activity, as well as the etiology of neonatal seizures, were significantly associated with neurodevelopmental outcome at one year of age. aEEG background pattern was highly associated with neurologic outcomes (χ2 = 116.9), followed by aEEG cyclicity (χ2 = 87.2) and seizure etiology (χ2 = 79.3). Multiple linear regression showed that the four predictors explained 71.2% of the variation in neurological outcome, with standardized β coefficients of 0.44, 0.24, 0.22, and 0.14 for the predictors of aEEG background pattern, cyclicity, etiology, and aEEG seizure activity, respectively. This clinically applicable scoring system based on etiology and three aEEG indices would allow pediatricians to assess the risk for neurodevelopmental impairment and facilitate an early intervention in newborns developing seizures.
doi:10.1371/journal.pone.0078960
PMCID: PMC3827298  PMID: 24236076
23.  Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants 
Objective
Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500g,VLBW) with and without blood stream infection (BSI) during their birth hospitalization.
Patients and Methods
Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4, and 6 months after birth with blood drawn 4–6 weeks after 3rd dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with birth-weight groups and other confounding factors identified in the primary study.
Results
244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody ≥0.35μg/mL.
Conclusions
BSI was not associated with reduced odds of WHO-defined protective PCV7 responses in VLBWs.
doi:10.1038/jp.2013.5
PMCID: PMC3722279  PMID: 23370608
VLBW; immune response; vaccine; sepsis; blood stream infection
24.  Meeting Community Health Worker Needs for Maternal Health Care Service Delivery Using Appropriate Mobile Technologies in Ethiopia  
PLoS ONE  2013;8(10):e77563.
Background
Mobile health applications are complex interventions that essentially require changes to the behavior of health care professionals who will use them and changes to systems or processes in delivery of care. Our aim has been to meet the technical needs of Health Extension Workers (HEWs) and midwives for maternal health using appropriate mobile technologies tools.
Methods
We have developed and evaluated a set of appropriate smartphone health applications using open source components, including a local language adapted data collection tool, health worker and manager user-friendly dashboard analytics and maternal-newborn protocols. This is an eighteen month follow-up of an ongoing observational research study in the northern of Ethiopia involving two districts, twenty HEWs, and twelve midwives.
Results
Most health workers rapidly learned how to use and became comfortable with the touch screen devices so only limited technical support was needed. Unrestricted use of smartphones generated a strong sense of ownership and empowerment among the health workers. Ownership of the phones was a strong motivator for the health workers, who recognised the value and usefulness of the devices, so took care to look after them. A low level of smartphones breakage (8.3%,3 from 36) and loss (2.7%) were reported. Each health worker made an average of 160 mins of voice calls and downloaded 27Mb of data per month, however, we found very low usage of short message service (less than 3 per month).
Conclusions
Although it is too early to show a direct link between mobile technologies and health outcomes, mobile technologies allow health managers to more quickly and reliably have access to data which can help identify where there issues in the service delivery. Achieving a strong sense of ownership and empowerment among health workers is a prerequisite for a successful introduction of any mobile health program.
doi:10.1371/journal.pone.0077563
PMCID: PMC3812262  PMID: 24204872
25.  Economic Impact of Maternal Death on Households in Rural China: A Prospective Cohort Study 
PLoS ONE  2013;8(10):e76624.
Objective
To assess the economic impact of maternal death on rural Chinese households during the year after maternal death.
Methods
A prospective cohort study matched 183 households who had suffered a maternal death to 346 households that experienced childbirth without maternal death in rural areas of three provinces in China. Surveys were conducted at baseline (1–3 months after maternal death or childbirth) and one year after baseline using the quantitative questionnaire. We investigated household income, expenditure, accumulated debts, and self-reported household economic status. Difference-in-Difference (DID), linear regression, and logistic regression analyses were used to compare the economic status between households with and without maternal death.
Findings
The households with maternal death had a higher risk of self-reported “household economy became worse” during the follow-up period (adjusted OR = 6.04, p<0.001). During the follow-up period, at the household level, DID estimator of income and expenditure showed that households with maternal death had a significant relative reduction of US$ 869 and US$ 650, compared to those households that experienced childbirth with no adverse event (p<0.001). Converted to proportions of change, an average of 32.0% reduction of annual income and 24.9% reduction of annual expenditure were observed in households with a maternal death. The mean increase of accumulated debts in households with a maternal death was 3.2 times as high as that in households without maternal death (p = 0.024). Expenditure pattern of households with maternal death changed, with lower consumption on food (p = 0.037), clothes and commodity (p = 0.003), traffic and communication (p = 0.022) and higher consumption on cigarette or alcohol (p = 0.014).
Conclusion
Compared with childbirth, maternal death had adverse impact on household economy, including higher risk of self-reported “household economy became worse”, decreased income and expenditure, increased debts and changed expenditure pattern.
doi:10.1371/journal.pone.0076624
PMCID: PMC3811988  PMID: 24204648

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