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Liquid biopsies that measure circulating cell-free RNA (cfRNA) offer an opportunity to study the development of pregnancy-related complications in a non-invasive manner and to bridge gaps in clinical care1–4. Here we used 404 blood samples from 199 pregnant mothers to identify and validate cfRNA transcriptomic changes that are associated with preeclampsia, a multi-organ syndrome that is the second largest cause of maternal death globally5. We find that changes in cfRNA gene expression between normotensive and preeclamptic mothers are marked and stable early in gestation, well before the onset of symptoms. These changes are enriched for genes specific to neuromuscular, endothelial and immune cell types and tissues that reflect key aspects of preeclampsia physiology6–9, suggest new hypotheses for disease progression and correlate with maternal organ health. This enabled the identification and independent validation of a panel of 18 genes that when measured between 5 and 16 weeks of gestation can form the basis of a liquid biopsy test that would identify mothers at risk of preeclampsia long before clinical symptoms manifest themselves. Tests based on these observations could help predict and manage who is at risk for preeclampsia—an important objective for obstetric care10,11.

Maternal morbidity and mortality continue to rise, and pre-eclampsia is a major driver of this burden1. Yet the ability to assess underlying pathophysiology before clinical presentation to enable identification of pregnancies at risk remains elusive. Here we demonstrate the ability of plasma cell-free RNA (cfRNA) to reveal patterns of normal pregnancy progression and determine the risk of developing pre-eclampsia months before clinical presentation. Our results centre on comprehensive transcriptome data from eight independent prospectively collected cohorts comprising 1,840 racially diverse pregnancies and retrospective analysis of 2,539 banked plasma samples. The pre-eclampsia data include 524 samples (72 cases and 452 non-cases) from two diverse independent cohorts collected 14.5 weeks (s.d., 4.5 weeks) before delivery. We show that cfRNA signatures from a single blood draw can track pregnancy progression at the placental, maternal and fetal levels and can robustly predict pre-eclampsia, with a sensitivity of 75% and a positive predictive value of 32.3% (s.d., 3%), which is superior to the state-of-the-art method2. cfRNA signatures of normal pregnancy progression and pre-eclampsia are independent of clinical factors, such as maternal age, body mass index and race, which cumulatively account for less than 1% of model variance. Further, the cfRNA signature for pre-eclampsia contains gene features linked to biological processes implicated in the underlying pathophysiology of pre-eclampsia.

Purpose: To assess the impact of direct-to-consumer marketing of genetic testing for risk of breast and ovarian cancer by a biotechnology company on: 1) physicians' knowledge; 2) reasons given when asking questions about the test; and 3) physicians' practice patterns in two pilot cities where the campaign took place and two control cities. Methods: Survey of randomly selected family physicians, internists, obstetrician-gynecologists, and oncologists from May 1-May 21, 2003. Results: Physicians' knowledge did not differ between pilot and control cities. Significant differences (pilot versus control cities) were seen in the reasons patients gave for asking questions about testing. More physicians in pilot cities (14%) than control cities (7%) reported an increase in the number of times they ordered genetic testing for breast and ovarian cancer risk in the previous 6 months (adjusted odds ratio 1.9, 95% confidence interval, 1.2-3.1). Awareness of professional guidelines and being in a practice with a policy on genetic testing for risk of breast and ovarian cancer were associated with physicians' behaviors and interest among patients in testing. Conclusions: Given the complexity and limitations of genetic testing for risk of breast and ovarian cancer, the development and broad dissemination of clinical guidelines and education of physicians are needed.

The purpose of this study was to assess the incidence of medical illness among members of trekking groups in the Nepal Himalaya. The design was a cohort study using interview and clinical examination by a single physician. The setting was the Manaslu area in the central Nepal Himalaya along a 22-day trekking route with elevations ranging from 487 m to 5100 m. Subjects were 155 members of commercial trekking groups: 102 Nepali porters, 31 Nepali trek staff, and 22 Western trekkers. We found that medical problems occurred in 45% of party members. The porter cohort contained the highest diversity and severity of illness. The relatively larger porter cohort experienced 77% of the medical problems recorded compared with 17% among Western trekkers and 6% among trek staff. The incidence of medical problems was not significantly different in the porter staff (52%) and Western trekkers (55%) and was significantly lower for the trek staff (13%). High-altitude pharyngitis/bronchitis was the most common illness in the party (12%) followed by acute mountain sickness (8%) and gastroenteritis (6%). Other conditions included anxiety (3%), cellulitis (3%), scabies (3%), snow blindness (3%), acute alcohol intoxication (2%), conjunctivitis (2%), fever (2%), lacerations (2%), and hemorrhoids (1%). Illness with infectious etiologies comprised 33% of the medical problems. The incidence of altitude illness was not significantly less in the Nepali porter staff than in the Western trekkers. Evacuation was required in 5% of party members, all from the porter group. This study should alert expedition medical providers and trip leaders of the need to be observant for and prepared to treat the frequent and diverse medical problems among the porter staff in their party, in addition to the Western members. Medical problems are common in remote mountainous areas, indicating that trip physicians should be experienced in primary care.

BackgroundPreterm birth is a worldwide challenge with the highest burden in low- and middle-income countries. Despite availability of low-cost interventions to decrease mortality of preterm, low birth weight, and sick newborns, these interventions are not well integrated in the health systems of low- and middle-income countries. The aim of this study was to assess, from the perspective of key stakeholders comprising leaders in the public health system, the health system readiness to support health care facilities in the care provided to preterm, low birth weight, and sick newborns in different regions of Ethiopia.MethodsA qualitative assessment using in-depth interviews with health facility leaders was conducted in health facilities in 3 regions of Ethiopia from December 2017 to February 2018. The interview guide was developed using a modified version of the World Health Organization health system building blocks.ResultsAcross the public health system, adequate and reliable space, power, and water were problematic. Human resource issues (training, staffing, and retention) were critical to being able to properly care for preterm, low birth weight, and sick newborns. Problems with functional equipment and equipment distribution systems were widespread. Funds were lacking to support preterm, low birth weight, and sick newborn needs in facilities. Data collection practices, data quality, and data utilization were all problematic. There were gaps in the availability of guidelines and protocols, specifically targeting preterm, low birth weight, and sick newborn care. Key facilitators, information disseminators, and influencers identified in the study were the Health Development Army, community and religious leaders, and mothers and families who had had positive experiences or outcomes of care.ConclusionsThe Ethiopian health system has opportunities across all 7 World Health Organization health system building blocks to strengthen readiness to support health facilities to provide quality care and improve outcomes for preterm, low birth weight, and sick newborns.

This diagnostic/prognostic study describes the use of cell-free transcriptomics, urine metabolomics, and plasma proteomics for identifying the biological measurements associated with preterm birth.

Countries have put in place some elements necessary for safe and effective antenatal corticosteroid (ACS) use, but significant challenges remain including: ensuring accurate gestational age determination, establishing clear treatment guidelines, strengthening provider capacity, incorporating obstetric indications for ACS use in national essential medicines lists, and collecting and using ACS-related data in the HMIS. Most importantly, the quality of maternal and newborn care, including specialized newborn care, needs improvement to ensure a strong foundation for the safe and effective use of ACS.