Global report on preterm birth and stillbirth (2 of 7): discovery science

Abstract

Background: Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions. PREGNANCY AND PARTURITION CONTINUUM: The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy. ETIOLOGIES: The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.

Recommendations: Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.

Conclusion: Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.

Figure 1

Phases of parturition as a continuum of pregnancy

Figure 2

Representative causes of stillbirth in high-income countries. Source: Modifi ed from [90]. Reprinted from Acta Obstetricia et Gynecologica Scandinavica, 87, Varli H, Petersson K, Bottinga R, Bremme K, Hofsjo A, Holste C, Kublickas M, Norman M, Pilo C et al, The Stockholm classifi cation of stillbirth, 10, 2008, with permission from Acta Obstet Gynecol Scand.

Figure 3

A compilation of systems biology publications and proportion relating to pregnancy, semi-logarithmic scale. Data source: Data abstracted from PubMed, 1997-2008. Key abstracting words “functional genomics, transcriptomics, proteomics… alone or + pregnancy”

Figure 4

Grading criteria for evaluation of discovery science needs in preterm birth and stillbirth