Barriers to progress in pregnancy research: How can we break through?

Abstract

Healthy pregnancies are fundamental to healthy populations, but very few therapies to improve pregnancy outcomes are available. Fundamental concepts—for example, placentation or the mechanisms that control the onset of labor—remain understudied and incompletely understood. A key issue is that research efforts must capture the complexity of the tripartite maternal-placental-fetal system, the dynamics of which change throughout gestation. Studying pregnancy disorders is complicated by the difficulty of creating maternal-placental-fetal interfaces in vitro and the uncertain relevance of animal models to human pregnancy. However, newer approaches include trophoblast organoids to model the developing placenta and integrated data-science approaches to study longer-term outcomes. These approaches provide insights into the physiology of healthy pregnancy, which is the first step to identifying therapeutic targets in pregnancy disorders.

Gut microbiota-derived trimethylamine N-Oxide: a novel target for the treatment of preeclampsia

“…Pre-eclampsia (PE) is a complex multisystem disease unique to pregnancy, with a global incidence of approximately 2%–8%. 1 PE, which is characterized by hypertension and end-organ dysfunction after 20 weeks of gestation, is associated with an increased risk of adverse pregnancy outcomes, such as preterm birth, fetal growth restriction, and stillbirth, and it is one of the main causes of maternal and perinatal mortality. 2–4 At present, the clinical treatment of PE is mainly symptomatic, including the use of antispasmodics, antihypertensives, and sedation; however, these strategies cannot fundamentally change and correct the cause of PE, and do not have a preventive effect.…”

The Vexing Problem of Preterm Birth Prevention

“…Until a better appreciation is gained of the root causes of preterm birth, simplistic, mechanical approaches such as the pessary are unlikely to succeed. In a recent interesting commentary, Stock and Aiken note that 3 key directions of research should be addressed, including identifying the early pathologies that lead to preterm birth, developing an individualized evaluation of both fetal and maternal responses to threatened preterm labor, and better understanding the timing of birth to balance the risks of continuing the pregnancy vs delivery so as to optimize both fetal and maternal outcomes. Most interventions address the end result of the pathologic process leading to preterm cervical ripening or contractions and, hence, are unlikely to be successful.…”