Odon device for instrumental vaginal deliveries: results of a medical device pilot clinical study.

BACKGROUND: A prolonged and complicated second stage of labour is associated with serious perinatal complications. The Odon device is an innovation intended to perform instrumental vaginal delivery presently under development. We present an evaluation of the feasibility and safety of delivery with early prototypes of this device from an early terminated clinical study. METHODS: Hospital-based, multi-phased, open-label, pilot clinical study with no control group in tertiary hospitals in Argentina and South Africa. Multiparous and nulliparous women, with uncomplicated singleton pregnancies, were enrolled during the third trimester of pregnancy. Delivery with Odon device was attempted under non-emergency conditions during the second stage of labour. The feasibility outcome was delivery with the Odon device defined as successful expulsion of the fetal head after one-time application of the device. RESULTS: Of the 49 women enrolled, the Odon device was inserted successfully in 46 (93%), and successful Odon device delivery as defined above was achieved in 35 (71%) women. Vaginal, first and second degree perineal tears occurred in 29 (59%) women. Four women had cervical tears. No third or fourth degree perineal tears were observed. All neonates were born alive and vigorous. No adverse maternal or infant outcomes were observed at 6-weeks follow-up for all dyads, and at 1 year for the first 30 dyads. CONCLUSIONS: Delivery using the Odon device is feasible. Observed genital tears could be due to the device or the process of delivery and assessment bias. Evaluating the effectiveness and safety of the further developed prototype of the BD Odon Device™ will require a randomized-controlled trial. TRIAL REGISTRATION: ANZCTR ACTRN12613000141741 Registered 06 February 2013. Retrospectively registered.

Short Maternal Stature Increases Risk of Small-for-Gestational-Age and Preterm Births in Low- and Middle-Income Countries: Individual Participant Data Meta-Analysis and Population Attributable Fraction.

BACKGROUND: Small-for-gestational-age (SGA) and preterm births are associated with adverse health consequences, including neonatal and infant mortality, childhood undernutrition, and adulthood chronic disease. OBJECTIVES: The specific aims of this study were to estimate the association between short maternal stature and outcomes of SGA alone, preterm birth alone, or both, and to calculate the population attributable fraction of SGA and preterm birth associated with short maternal stature. METHODS: We conducted an individual participant data meta-analysis with the use of data sets from 12 population-based cohort studies and the WHO Global Survey on Maternal and Perinatal Health (13 of 24 available data sets used) from low- and middle-income countries (LMIC). We included those with weight taken within 72 h of birth, gestational age, and maternal height data (n = 177,000). For each of these studies, we individually calculated RRs between height exposure categories of < 145 cm, 145 to < 150 cm, and 150 to < 155 cm (reference: ≥ 155 cm) and outcomes of SGA, preterm birth, and their combination categories. SGA was defined with the use of both the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) birth weight standard and the 1991 US birth weight reference. The associations were then meta-analyzed. RESULTS: All short stature categories were statistically significantly associated with term SGA, preterm appropriate-for-gestational-age (AGA), and preterm SGA births (reference: term AGA). When using the INTERGROWTH-21st standard to define SGA, women < 145 cm had the highest adjusted risk ratios (aRRs) (term SGA-aRR: 2.03; 95% CI: 1.76, 2.35; preterm AGA-aRR: 1.45; 95% CI: 1.26, 1.66; preterm SGA-aRR: 2.13; 95% CI: 1.42, 3.21). Similar associations were seen for SGA defined by the US reference. Annually, 5.5 million term SGA (18.6% of the global total), 550,800 preterm AGA (5.0% of the global total), and 458,000 preterm SGA (16.5% of the global total) births may be associated with maternal short stature. CONCLUSIONS: Approximately 6.5 million SGA and/or preterm births in LMIC may be associated with short maternal stature annually. A reduction in this burden requires primary prevention of SGA, improvement in postnatal growth through early childhood, and possibly further intervention in late childhood and adolescence. It is vital for researchers to broaden the evidence base for addressing chronic malnutrition through multiple life stages, and for program implementers to explore effective, sustainable ways of reaching the most vulnerable populations.

Challenges and opportunities for implementing evidence-based antenatal care in Mozambique: a qualitative study.

BACKGROUND: Maternal mortality remains a daunting problem in Mozambique and many other low-resource countries. High quality antenatal care (ANC) services can improve maternal and newborn health outcomes and increase the likelihood that women will seek skilled delivery care. This study explores the factors influencing provider uptake of the recommended package of ANC interventions in Mozambique. METHODS: This study used qualitative research methods including key informant interviews with stakeholders from the health sector and a total of five focus group discussions with women with experience with ANC or women from the community. Study participants were selected from three health centers located in Maputo city, Tete, and Cabo Delgado provinces in Mozambique. Staff responsible for the medicines/supply chain at national, provincial and district level were interviewed. A check list was implemented to confirm the availability of the supplies required for ANC. Deductive content analysis was conducted. RESULTS: Three main groups of factors were identified that hinder the implementation of the ANC package in the study setting: a) system or organizational: include chronic supply chain deficiencies, failures in the continuing education system, lack of regular audits and supervision, absence of an efficient patient record system and poor environmental conditions at the health center; b) health care provider factors: such as limited awareness of current clinical guidelines and a resistant attitude to adopting new recommendations; and c) Users: challenges with accessing ANC, poor recognition amongst women about the purpose and importance of the specific interventions provided through ANC, and widespread perception of an unfriendly environment at the health center. CONCLUSIONS: The ANC package in Mozambique is not being fully implemented in the three study facilities, and a major barrier is poor functioning of the supply chain system. Recommendations for improving the implementation of antenatal interventions include ensuring clinical protocols based on the ANC model. Increasing the community understanding of the importance of ANC would improve demand for high quality ANC services. The supply chain functioning could be strengthened through the introduction of a kit system with all the necessary supplies for ANC and a simple monitoring system to track the stock levels is recommended.

A risk prediction model for the assessment and triage of women with hypertensive disorders of pregnancy in low-resourced settings: the miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) multi-country prospective cohort study.

BACKGROUND: Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. METHODS AND FINDINGS: From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735-0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658-0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. CONCLUSIONS: The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive disorders of pregnancy. It could be used in LMICs to identify women who would benefit most from interventions such as magnesium sulphate, antihypertensives, or transportation to a higher level of care.

Assessment of cesarean delivery availability in 26 low- and middle-income countries: a cross-sectional study.

OBJECTIVE: We sought to assess the capacity to provide cesarean delivery (CD) in health facilities in low- and middle-income countries. STUDY DESIGN: We conducted secondary analysis of 719 health facilities, in 26 countries in Africa, the Pacific, Asia, and the Mediterranean, using facility-based cross-sectional data from the World Health Organization Situational Analysis Tool to Assess Emergency and Essential Surgical Care. RESULTS: A total of 531 (73.8%) facilities reported performing CD. In all, 126 (17.5%) facilities did not perform but referred CD; the most common reasons for doing so were lack of skills (53.2%) and nonfunctioning equipment (42.9%). All health facilities surveyed had at least 1 operating room. Of the facilities performing CD, 47.3% did not report the presence of any type of anesthesia provider and 17.9% did not report the presence of any type of obstetric/gynecological or surgical care provider. In facilities reporting a lack of functioning equipment, 26.4% had no access to an oxygen supply, 60.8% had no access to an anesthesia machine, and 65.9% had no access to a blood bank. CONCLUSION: Provision of CD in facilities in low- and middle-income countries is hindered by a lack of an adequate anesthetic and surgical workforce and availability of oxygen, anesthesia, and blood banks.

WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component.

BACKGROUND: In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. METHODS: This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. DISCUSSION: The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.

Implementation of evidence-based antenatal care in Mozambique: a cluster randomized controlled trial: study protocol.

BACKGROUND: Antenatal care (ANC) reduces maternal and perinatal morbidity and mortality directly through the detection and treatment of pregnancy-related illnesses, and indirectly through the detection of women at increased risk of delivery complications. The potential benefits of quality antenatal care services are most significant in low-resource countries where morbidity and mortality levels among women of reproductive age and neonates are higher.WHO developed an ANC model that recommended the delivery of services scientifically proven to improve maternal, perinatal and neonatal outcomes. The aim of this study is to determine the effect of an intervention designed to increase the use of the package of evidence-based services included in the WHO ANC model in Mozambique. The primary hypothesis is that the intervention will increase the use of evidence-based practices during ANC visits in comparison to the standard dissemination channels currently used in the country. METHODS: This is a demonstration project to be developed through a facility-based cluster randomized controlled trial with a stepped wedge design. The intervention was tailored, based on formative research findings, to be readily applicable to local prenatal care services and acceptable to local pregnant women and health providers. The intervention includes four components: the provision of kits with all necessary medicines and laboratory supplies for ANC (medical and non-medical equipment), a storage system, a tracking system, and training sessions for health care providers. Ten clinics were selected and will start receiving the intervention in a random order. Outcomes will be computed at each time point when a new clinic starts the intervention. The primary outcomes are the delivery of selected health care practices to women attending the first ANC visit, and secondary outcomes are the delivery of selected health care practices to women attending second and higher ANC visits as well as the attitude of midwives in relation to adopting the practices. This demonstration project is pragmatic in orientation and will be conducted under routine conditions. DISCUSSION: There is an urgent need for effective and sustainable scaling-up approaches of health interventions in low-resource countries. This can only be accomplished by the engagement of the country's health stakeholders at all levels. This project aims to achieve improvement in the quality of antenatal care in Mozambique through the implementation of a multifaceted intervention on three levels: policy, organizational and health care delivery levels. The implementation of the trial will probably require a change in accountability and behaviour of health care providers and we expect this change in 'habits' will contribute to obtaining reliable health indicators, not only related to research issues, but also to health care outcomes derived from the new health care model. At policy level, the results of this study may suggest a need for revision of the supply chain management system. Given that supply chain management is a major challenge for many low-resource countries, we envisage that important lessons on how to improve the supply chain in Mozambique and other similar settings, will be drawn from this study. TRIAL REGISTRATION: Pan African Clinical Trial Registry database. Identification number: PACTR201306000550192.

Recurrence of adverse perinatal outcomes in developing countries.

OBJECTIVE: To evaluate the risk of recurrence of adverse perinatal outcomes in second pregnancies in developing countries. METHODS: Data from the 2004-2008 Global Survey on Maternal and Perinatal Health were used to determine the outcomes of singleton second pregnancies for 61 780 women in 23 developing countries. The mother-infant pairs had been followed up until discharge or for 7 days postpartum. FINDINGS: At the end of their second pregnancies, women whose first pregnancy had ended in stillbirth (n = 1261) or been followed by neonatal death (n = 1052) were more likely than women who had not experienced either outcome to have given birth to a child with a birth weight of < 1500 g (odds ratio, OR: 2.52 and 2.78, respectively) or 1500-2499 g (OR: 1.22 and 1.60, respectively), or to an infant requiring admission to an intensive care unit (OR: 1.64 and 1.68, respectively). At the end of their second pregnancies, those whose first pregnancy had ended in a stillbirth were at increased risk of another stillbirth (OR: 2.35) and those whose first infant had died as a neonate were at increased risk of having the second infant die within the first 7 days of life (OR: 2.82). These trends were found to be largely unaffected by the continent in which the women lived. CONCLUSION: In the developing world, a woman whose first pregnancy ends in stillbirth or is followed by the death of the neonate is at increased risk of experiencing the same outcomes in her second pregnancy.

The effectiveness of birth plans in increasing use of skilled care at delivery and postnatal care in rural Tanzania: a cluster randomised trial.

OBJECTIVES: To determine the effectiveness of birth plans in increasing use of skilled care at delivery and in the postnatal period among antenatal care (ANC) attendees in a rural district with low occupancy of health units for delivery but high antenatal care uptake in northern Tanzania. METHODS: Cluster randomised trial in Ngorongoro district, Arusha region, involving 16 health units (8 per arm). Nine hundred and five pregnant women at 24 weeks of gestation and above (404 in the intervention arm) were recruited and followed up to at least 1 month postpartum. RESULTS: Skilled delivery care uptake was 16.8% higher in the intervention units than in the control [95% CI 2.6-31.0; P = 0.02]. Postnatal care utilisation in the first month of delivery was higher (difference in proportions: 30.0% [95% CI 1.3-47.7; P < 0.01]) and also initiated earlier (mean duration 6.6 ± 1.7 days vs. 20.9 ± 4.4 days, P < 0.01) in the intervention than in the control arm. Women's and providers' reports of care satisfaction (received or provided) did not differ greatly between the two arms of the study (difference in proportion: 12.1% [95% CI -6.3-30.5] P = 0.17 and 6.9% [95% CI -3.2-17.1] P = 0.15, respectively). CONCLUSION: Implementation of birth plans during ANC can increase the uptake of skilled delivery and post delivery care in the study district without negatively affecting women's and providers' satisfaction with available ANC services. Birth plans should be considered along with the range of other recommended interventions as a strategy to improve the uptake of maternal health services.

Measuring equity in utilization of emergency obstetric care at Wolisso Hospital in Oromiya, Ethiopia: a cross sectional study.

INTRODUCTION: Improving equity in access to services for the treatment of complications that arise during pregnancy and childbirth, namely Emergency Obstetric Care (EmOC), is fundamental if maternal and neonatal mortality are to be reduced. Consequently, there is a growing need to monitor equity in access to EmOC. The objective of this study was to develop a simple questionnaire to measure equity in utilization of EmOC at Wolisso Hospital, Ethiopia and compare the wealth status of EmOC users with women in the general population. METHODS: Women in the Ethiopia 2005 Demographic and Health Survey (DHS) constituted our reference population. We cross-tabulated DHS wealth variables against wealth quintiles. Five variables that differentiated well across quintiles were selected to create a questionnaire that was administered to women at discharge from the maternity from January to August 2010. This was used to identify inequities in utilization of EmOC by comparison with the reference population. RESULTS: 760 women were surveyed. An a posteriori comparison of these 2010 data to the 2011 DHS dataset, indicated that women using EmOC were wealthier and more likely to be urban dwellers. On a scale from 0 (poorest) to 15 (wealthiest), 31% of women in the 2011 DHS sample scored less than 1 compared with 0.7% in the study population. 70% of women accessing EmOC belonged to the richest quintile with only 4% belonging to the poorest two quintiles. Transportation costs seem to play an important role. CONCLUSIONS: We found inequity in utilization of EmOC in favour of the wealthiest. Assessing and monitoring equitable utilization of maternity services is feasible using this simple tool.

Do Italian women prefer cesarean section? Results from a survey on mode of delivery preferences.

BACKGROUND: About 20 million cesareans occur each year in the world and rates have steadily increased in almost all middle- and high-income countries over the last decades. Maternal request is often argued as one of the key forces driving this increase. Italy has the highest cesarean rate of Europe, yet there are no national surveys on the views of Italian women about their preferences on route of delivery. This study aimed to assess Italian women's preference for mode of delivery, as well as reasons and factors associated with this preference, in a nationally representative sample of women. METHODS: This cross sectional survey was conducted between December 2010-March 2011. An anonymous structured questionnaire asked participants what was their preferred mode of delivery and explored the reasons for this preference by assessing their agreement to a series of statements. Participants were also asked to what extent their preference was influenced by a series of possible sources. The 1st phase of the study was carried out among readers of a popular Italian women's magazine (Io Donna). In a 2nd phase, the study was complemented by a structured telephone interview. RESULTS: A total of 1000 Italian women participated in the survey and 80% declared they would prefer to deliver vaginally if they could opt. The preference for vaginal delivery was significantly higher among older (84.7%), more educated (87.6%), multiparous women (82.3%) and especially among those without any previous cesareans (94.2%). The main reasons for preferring a vaginal delivery were not wanting to be separated from the baby during the first hours of life, a shorter hospital stay and a faster postpartum recovery. The main reasons for preferring a cesarean were fear of pain, convenience to schedule the delivery and because it was perceived as being less traumatic for the baby. The source which most influenced the preference of these Italian women was their obstetrician, followed by friends or relatives. CONCLUSION: Four in five Italian women would prefer to deliver vaginally if they could opt. Factors associated with a higher preference for cesarean delivery were youth, nulliparity, lower education and a previous cesarean.

Dietary intakes of women during pregnancy in low- and middle-income countries.

OBJECTIVE: To provide a better understanding of dietary intakes of pregnant women in low- and middle-income countries. DESIGN: Systematic review was performed to identify relevant studies which reported nutrient intakes or food consumption of pregnant women in developing countries. Macronutrient and micronutrient intakes were compared by region and the FAO/WHO Estimated Average Requirements. Food consumption was summarized by region. SETTING: Developing countries in Africa, Asia, and the Caribbean and Central/South America. SUBJECTS: Pregnant women in the second or third trimester of their pregnancies. RESULTS: From a total of 1499 retrieved articles, sixty-two relevant studies were analysed. The ranges of mean/median intakes of energy, fat, protein and carbohydrate were relatively higher in women residing in the Caribbean and Central/South America than in Africa and Asia. Percentages of energy from carbohydrate and fat varied inversely across studies in all regions, whereas percentage of energy from protein was relatively stable. Among selected micronutrients, folate and Fe intakes were most frequently below the Estimated Average Requirements, followed by Ca and Zn. Usual dietary patterns were heavily cereal based across regions. CONCLUSIONS: Imbalanced macronutrients, inadequate micronutrient intakes and predominantly plant-based diets were common features of the diet of pregnant women in developing countries. Cohesive public health efforts involving improving access to nutrient-rich local foods, micronutrient supplementation and fortification are needed to improve the nutrition of pregnant women in developing countries.

Born too soon: care during pregnancy and childbirth to reduce preterm deliveries and improve health outcomes of the preterm baby.

Pregnancy and childbirth represent a critical time period when a woman can be reached through a variety of mechanisms with interventions aimed at reducing her risk of a preterm birth and improving her health and the health of her unborn baby. These mechanisms include the range of services delivered during antenatal care for all pregnant women and women at high risk of preterm birth, services provided to manage preterm labour, and workplace, professional and other supportive policies that promote safe motherhood and universal access to care before, during and after pregnancy. The aim of this paper is to present the latest information about available interventions that can be delivered during pregnancy to reduce preterm birth rates and improve the health outcomes of the premature baby, and to identify data gaps. The paper also focuses on promising avenues of research on the pregnancy period that will contribute to a better understanding of the causes of preterm birth and ability to design interventions at the policy, health care system and community levels. At minimum, countries need to ensure equitable access to comprehensive antenatal care, quality childbirth services and emergency obstetric care. Antenatal care services should include screening for and management of women at high risk of preterm birth, screening for and treatment of infections, and nutritional support and counselling. Health workers need to be trained and equipped to provide effective and timely clinical management of women in preterm labour to improve the survival chances of the preterm baby. Implementation strategies must be developed to increase the uptake by providers of proven interventions such as antenatal corticosteroids and to reduce harmful practices such as non-medically indicated inductions of labour and caesarean births before 39 weeks of gestation. Behavioural and community-based interventions that can lead to reductions in smoking and violence against women need to be implemented in conjunction with antenatal care models that promote women's empowerment as a strategy for reducing preterm delivery. The global community needs to support more discovery research on normal and abnormal pregnancies to facilitate the development of preventive interventions for universal application. As new evidence is generated, resources need to be allocated to its translation into new and better screening and diagnostic tools, and other interventions aimed at saving maternal and newborn lives that can be brought to scale in all countries.

Feasibility and safety study of a new device (Odón device) for assisted vaginal deliveries: study protocol.

BACKGROUND: Intrapartum complications are responsible for approximately half of all maternal deaths, and two million stillbirth and neonatal deaths per year. Prolonged second stage of labour is associated with potentially fatal maternal complications such as haemorrhage and infection and it is a major cause of stillbirth and newborn morbidity and mortality. Currently, the three main options for managing prolonged second stage of labour are forceps, vacuum extractor and caesarean section. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for caesarean section) and/or highly trained staff which are often not available in low resource settings. The specific aim of the proposed study is to test the safety and feasibility of a new device (Odón device) to effectively deliver the fetus during prolonged second stage of labour. The Odón device is a low-cost technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care and reducing maternal and perinatal morbidity and mortality in low resource settings. METHODS/DESIGN: This will be a hospital-based, multicenter prospective phase 1 cohort study with no control group. Delivery with the Odón device will be attempted under normal labour and non-emergency conditions on all the women enrolled in the study. One-hundred and thirty pregnant women will be recruited in tertiary care facilities in Argentina. Safety will be assessed by examining maternal and infant outcomes until discharge. Feasibility will be evaluated by observing successful expulsion of the fetal head after one-time application of the device under standardized conditions (full cervical dilation, anterior presentation, +2 station, normal fetal heart rate). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier: ACTRN12613000141741.

Preterm Birth Genome Project (PGP) -- validation of resources for preterm birth genome-wide studies.

We determined a series of quality control (QC) analyses to assess the usability of DNA collected and processed from different countries utilizing different DNA extraction techniques prior to genome-wide association studies (GWAS). The quality of DNA collected utilizing four different DNA extraction techniques and the impact of shipping DNA at different temperatures on array performance were evaluated. Fifteen maternal-fetal pairs were used from four countries. DNA was extracted using four approaches: whole blood, blood spots with whole genome amplification (WGA), saliva and buccal swab. Samples were sent to a genotyping facility, either on dry ice or at room temperature and genotyped using Affymetrix SNP array 6.0. QC measured included extraction techniques, effect of shipping temperatures, accuracy and Mendelian concordance. Significantly fewer (50 % ) single nucleotide polymorphisms (SNPs) passed QC metrics for buccal swab DNA (P < 0.0001) due to missing genotype data (P < 0.0001). Whole blood or saliva DNA had the highest call rates (99.2 0.4 % and 99.3 0.2 % , respectively) and Mendelian concordance. Shipment temperature had no effect. DNA from blood or saliva had the highest call rate accuracy, and buccal swabs had the lowest. DNA extracted from blood, saliva and blood spots were found suitable for GWAS in our study.

The Role of Genetics in Preterm Birth.

Preterm birth (PTB), defined as the birth of a child before 37 completed weeks gestation, affects approximately 11% of live births and is the leading cause of death in children under 5 years. PTB is a complex disease with multiple risk factors including genetic variation. Much research has aimed to establish the biological mechanisms underlying PTB often through identification of genetic markers for PTB risk. The objective of this review is to present a comprehensive and updated summary of the published data relating to the field of PTB genetics. A literature search in PubMed was conducted and English studies related to PTB genetics were included. Genetic studies have identified genes within inflammatory, immunological, tissue remodeling, endocrine, metabolic, and vascular pathways that may be involved in PTB. However, a substantial proportion of published data have been largely inconclusive and multiple studies had limited power to detect associations. On the contrary, a few large hypothesis-free approaches have identified and replicated multiple novel variants associated with PTB in different cohorts. Overall, attempts to predict PTB using single "-omics" datasets including genomic, transcriptomic, and epigenomic biomarkers have been mostly unsuccessful and have failed to translate to the clinical setting. Integration of data from multiple "-omics" datasets has yielded the most promising results.

A global reference for fetal-weight and birthweight percentiles.

BACKGROUND: Definition of small for gestational age in various populations worldwide remains a challenge. References based on birthweight are deficient for preterm births, those derived from ultrasound estimates might not be applicable to all populations, and the individualised reference can be too complex to use in developing countries. Our aim was to create a generic reference for fetal weight and birthweight that overcame these deficiencies and could be readily adapted to local populations. METHODS: We used the fetal-weight reference developed by Hadlock and colleagues and the notion of proportionality proposed by Gardosi and colleagues and made the weight reference easily adjustable according to the mean birthweight at 40 weeks of gestation for any local population. For application and validation, we used data from 24 countries in Africa, Latin America, and Asia that participated in the 2004-08 WHO Global Survey on Maternal and Perinatal Health (237,025 births). We compared our reference with that of Hadlock and colleagues (non-customised) and with that of Gardosi and colleagues (individualised). For every reference, the odds ratio (OR) of adverse perinatal outcomes (stillbirths, neonatal deaths, referral to higher-level or special care unit, or Apgar score lower than 7 at 5 min) for infants who were small for gestational age versus those who were not was estimated with multilevel logistic regression. FINDINGS: OR of adverse outcomes for infants small for gestational age versus those not small for gestational age was 1·59 (95% CI 1·53-1·66) for the non-customised fetal-weight reference compared with 2·87 (2·73-3·01) for our country-specific reference, and 2·84 (2·71-2·99) for the fully individualised reference. INTERPRETATION: Our generic reference for fetal-weight and birthweight percentiles can be easily adapted to local populations. It has a better ability to predict adverse perinatal outcomes than has the non-customised fetal-weight reference, and is simpler to use than the individualised reference without loss of predictive ability. FUNDING: None.

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model.

BACKGROUND: Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS: We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS: 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION: The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING: Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Inequities in the use of cesarean section deliveries in the world.

OBJECTIVE: The purpose of this study was to describe the unequal distribution in the performance of cesarean section delivery (CS) in the world and the resource-use implications of such inequity. STUDY DESIGN: We obtained data on the number of CSs performed in 137 countries in 2008. The consensus is that countries should achieve a 10% rate of CS; therefore, for countries that are below that rate, we calculated the cost to achieve a 10% rate. For countries with a CS rate of >15%, we calculated the savings that could be made by the achievement of a 15% rate. RESULTS: Fifty-four countries had CS rates of <10%, whereas 69 countries showed rates of >15%. The cost of the global saving by a reduction of CS rates to 15% was estimated to be $2.32 billion (US dollars); the cost to attain a 10% CS rate was $432 million (US dollars). CONCLUSION: CSs that are potentially medically unjustified appear to command a disproportionate share of global economic resources.