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.

Maternal and perinatal outcomes in pregnant women with confirmed severe and mild COVID-19 at one large maternity hospital in Chile.

OBJECTIVE AND METHODS: We conducted a prospective observational cohort study in 458 pregnant and puerperal women, with confirmed COVID-19 at Hospital San Jose, Santiago, Chile, to determine the impact of COVID-19 on pregnancy and confirm safety and feasibility of a management protocol based on clinical presentation of the disease. RESULTS: 25.5% (117/458) of women were severe and 74.4% (341/458) mild presentation. Three percent (9/341) of mild presentations required a subsequent hospitalization. Overall, 26/458 women (5.6%) were admitted to ICU, and 13/458 (2.8%) required mechanical ventilation. One maternal death occurred at 49-days postpartum. Severe presentation, infection above 24 weeks, and comorbidities were associated with an adverse maternal outcome. Of total deliveries, 16.5% (36/217) were <37 weeks. Perinatal mortality was 6/226 (2.7%), mostly due to the fetal component. CONCLUSIONS: A quarter of the women had severe COVID-19 that, combined with occurrence of disease in the second half of pregnancy, resulted in substantial maternal compromise. Perinatal morbidity and mortality in women with severe disease were high and warrant consideration. Outpatient management was safe for mild cases.

Simulation for intrapartum care: from training to novel device innovation.

Improving maternal and perinatal care is a global priority. Simulation training and novel applications of simulation for intrapartum care may help to reduce preventable deaths worldwide. Evaluation studies have published details of the effectiveness of simulation training for obstetric emergencies, exploring clinical and non-clinical factors as well as the impact on patient outcomes (both maternal and neonatal). This review summarized the many uses of simulation in obstetric emergencies from training to assessment. It also described the adaption of training in low-resource settings and the evidence behind the equipment recommended to support simulation training. The review also discussed novel applications for simulation such as its use in the development of a new device for assisted vaginal birth and its potential role in Cesarean section training. This study analyzed the financial implications of simulation training and how this may impact the delivery of such training packages, considering that simulation should be developed and utilized as a key tool in the development of safe intrapartum care in both emergency and non-emergency settings, in innovation and product development.

Lessons from a multidisciplinary partnership involving women parliamentarians to address the overuse of caesarean section in Italy.

The increase of caesarean sections (CS) represents a global concern. Interventions tested to reduce unnecessary caesareans have shown limited success to date, partly because they have focused on medical perspectives or on single faceted interventions targeting only one group of stakeholders. Limited attention has been given to examining multidisciplinary and advocacy activities that could reduce unnecessary CS by raising awareness and engaging the media, advocacy groups, healthcare professionals and politicians. In 2009 in Italy, the national CS rate was the highest in Europe and momentum was building for action. This case study includes a description of the activities conducted in Italy during 2009-2012 by a partnership that included the non-governmental organisation Osservatorio Nazionale sulla Salute della Donna, a bipartisan group of Italian women parliamentarians and the WHO. The objectives were to generate awareness about the increase and overuse of CS in Italy, to foster political actions to reverse this trend, to engage with the media and journalists and to better understand women's birth preferences and needs. A reduction of the CS rate has been observed in Italy following the activities of the initiative from 38.4% in 2009 to 34.2% in 2015 according to the Ministry of Health. Although we cannot infer a casual association between the Partnership and the CS decrease, it did contribute to political momentum and specific actions that should, in theory, have contributed to this reduction. These include the engagement of women parliamentarians for policy change, improved understanding of the local drivers of increases of CS including women's needs and preferences, raising awareness and working with the media to convey appropriate information and an inclusive strategy giving the opportunity to local stakeholders to make their voices heard. This partnership initiative illustrates a model for generating dialogue, reflection and action in countries showing signs of readiness to address escalating CS.

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.

Provision of medical supply kits to improve quality of antenatal care in Mozambique: a stepped-wedge cluster randomised trial.

BACKGROUND: High levels of maternal and newborn mortality and morbidity remain a daunting reality in many low-income countries. Several interventions delivered during antenatal care have been shown to improve maternal and newborn outcomes, but stockouts of medical supplies at point of care can prevent implementation of these services. We aimed to evaluate whether a supply chain strategy based on the provision of kits could improve quality of care. METHODS: We did a pragmatic, stepped-wedge, cluster-randomised controlled trial at ten antenatal care clinics in Mozambique. Clinics were eligible if they were not already implementing the proposed antenatal care package; they served at least 200 new pregnant women per year; they had Maternal and Child Health (MCH) nurses; and they were willing to participate. All women attending antenatal care visits at the participating clinics were included in the trial. Participating clinics were randomly assigned to shift from control to intervention on prespecified start dates. The intervention involved four components (kits with medical supplies, a cupboard to store these supplies, a tracking sheet to monitor stocks, and a one-day training session). The primary outcomes were the proportion of women screened for anaemia and proteinuria, and the proportion of women who received mebendazole in the first antenatal care visit. The intervention was delivered under routine care conditions, and analyses were done according to the intention-to-treat principle. This trial is registered with the Pan African Clinical Trial Registry, number PACTR201306000550192. FINDINGS: Between March, 2014, and January, 2016, 218 277 antenatal care visits were registered, with 68 598 first and 149 679 follow-up visits. We found significant improvements in all three primary outcomes. In first visits, 5519 (14·6%) of 37 826 women were screened for anaemia in the control period, compared with 30 057 (97·7%) of 30 772 in the intervention period (adjusted odds ratio 832·40; 99% CI 666·81-1039·11; p<0·0001); 3739 (9·9%) of 37 826 women were screened for proteinuria in the control period, compared with 29 874 (97·1%) of 30 772 in the intervention period (1875·18; 1447·56-2429·11; p<0·0001); and 17 926 (51·4%) of 34 842 received mebendazole in the control period, compared with 24 960 (88·2%) of 28 294 in the intervention period (1·88; 1·70-2·09; p<0·0001). The effect was immediate and sustained over time, with negligible heterogeneity between sites. INTERPRETATION: A supply chain strategy that resolves stockouts at point of care can result in a vast improvement in quality during antenatal care visits, when compared with the routine national process for procurement and distribution of supplies. FUNDING: Government of Flanders and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction.

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.

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.

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.

Outdoor air pollution, preterm birth, and low birth weight: analysis of the world health organization global survey on maternal and perinatal health.

BACKGROUND: Inhaling fine particles (particulate matter with diameter ≤ 2.5 µm; PM2.5) can induce oxidative stress and inflammation, and may contribute to onset of preterm labor and other adverse perinatal outcomes. OBJECTIVES: We examined whether outdoor PM2.5 was associated with adverse birth outcomes among 22 countries in the World Health Organization Global Survey on Maternal and Perinatal Health from 2004 through 2008. METHODS: Long-term average (2001-2006) estimates of outdoor PM2.5 were assigned to 50-km-radius circular buffers around each health clinic where births occurred. We used generalized estimating equations to determine associations between clinic-level PM2.5 levels and preterm birth and low birth weight at the individual level, adjusting for seasonality and potential confounders at individual, clinic, and country levels. Country-specific associations were also investigated. RESULTS: Across all countries, adjusting for seasonality, PM2.5 was not associated with preterm birth, but was associated with low birth weight [odds ratio (OR) = 1.22; 95% CI: 1.07, 1.39 for fourth quartile of PM2.5 (> 20.2 µg/m3) compared with the first quartile (< 6.3 µg/m3)]. In China, the country with the largest PM2.5 range, preterm birth and low birth weight both were associated with the highest quartile of PM2.5 only, which suggests a possible threshold effect (OR = 2.54; CI: 1.42, 4.55 and OR = 1.99; CI: 1.06, 3.72 for preterm birth and low birth weight, respectively, for PM2.5 ≥ 36.5 µg/m3 compared with PM2.5 < 12.5 µg/m3). CONCLUSIONS: Outdoor PM2.5 concentrations were associated with low birth weight but not preterm birth. In rapidly developing countries, such as China, the highest levels of air pollution may be of concern for both outcomes.

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.

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

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

Maternal and perinatal outcomes of twin pregnancy in 23 low- and middle-income countries.

BACKGROUND: Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins. METHODS: We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes. RESULTS: 279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60-2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40-4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95-6.62) and stillbirth (AOR 1.22, 95% CI 0.58-2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective. CONCLUSIONS: Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.