Point-of-care testing and treatment of sexually transmitted infections to improve pregnancy outcomes in resource-limited, high-burden settings Women in developing countries worldwide face a high and unacceptable burden of adverse pregnancy outcomes. Curable, genital sexually transmitted infections (STIs) are major contributors to this disease burden in many resource-limited settings, but the majority of these infections go untreated.  Health services are unable to diagnose them because of limited laboratory facilities and the cost of conventional laboratory-based STI diagnostic tests. In the absence of such resources, diagnosis has relied on the clinical strategy known as 'syndromic management' that is recognised as having very poor sensitivity, particularly for women, in whom the vast majority of these STIs are asymptomatic. Newly available, highly accurate and easy to use point-of-care tests for the first time offer a real solution to this long-term health problem in developing countries.   We will undertake a world-first field trial to investigate the effectiveness of a comprehensive point-of-care testing and treatment strategy for curable STIs to improve pregnancy outcomes in resource-limited, high-burden settings. Our trial will also be the first to investigate new molecular point-of-care tests, based on the GeneXpert technology, for the routine diagnosis of chlamydia, gonorrhoea and trichomonas infections in resource-limited settings. This newly available technology will allow trained health staff to make correct diagnoses and to provide curative treatment during routine antenatal clinic visits.   Papua New Guinea is a unique environment in which to conduct this research because of the conjunction of (a) a high burden of both adverse pregnancy outcomes and curable STIs among pregnant women; and (b) recent and extensive experience by our team in the conduct of health intervention studies involving pregnant women and their children.   We will conduct a randomised trial among 4200 pregnant women attending 12 antenatal clinics in Eastern Highlands, Madang and Milne Bay Provinces. Participating clinics and their catchment communities will be randomly allocated to receive either routine antenatal care (control arm) or point-of-care STI testing and immediate treatment (intervention arm). Women in both arms of the trial will undergo an obstetric ultrasound examination to accurately estimate the duration of their pregnancy; be asked to attend a minimum of four antenatal follow-up visits; and receive a postnatal follow-up visit by the research team within 48 hours of giving birth. We will compare birth outcomes between antenatal women who were offered point-of-care STI testing and treatment with those who were not.   We will measure the difference in pregnancy outcomes among women in each arm of the trial in terms of the proportion of preterm birth (birth less than 37 weeks gestation) and low birth weight (birth weight less than 2500 grams). We will also evaluate the cost-effectiveness, health system implementation requirements, and acceptability of antenatal point-of-care STI testing and treatment compared to routine antenatal care in order to maximise the impact of our research and to inform future roll-out.  The trial will have a potentially major impact on public health policy and clinical practice in all low-resource, high-burden settings, and its findings could lead to significant gains in maternal and newborn health globally. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.