Preterm birth, or birth before 37 completed weeks of pregnancy, is now the greatest single cause of mortality in children less than 5 years old and is associated with long-term morbidity in survivors. It has been estimated that approximately 15 million babies are born prematurely every year, accounting for 11% of births worldwide. Numerous interventions to prevent preterm birth have been tried, including progesterone, Arabin pessaries, cervical cerclage and tocolytic agents. However, the results of trials assessing the effectiveness of these and other interventions are generally mixed, principally because it has long been recognised that preterm birth is a syndrome, caused by a number of different conditions. Much less well-described is how the conditions and pathways to early delivery interact with each other.
Different causes of preterm birth are known to be associated with differing risks of poor outcomes for the newborn. This has led to the hypothesis that interventions for preterm birth might be more effective if only they could be targeted at women with specific clinical presentations, or phenotypes, rather than at preterm birth as a whole as occurs at present. In 2012, researchers from the INTERGROWTH-21st Consortium, working together with GAPPS, developed a ‘phenotypic classification system’ for preterm birth, which was published in the American Journal of Obstetrics & Gynecology. The authors proposed a paradigm shift, which involves thinking about preterm birth comprehensively using three different assessments:
- The patterns of associated fetal, maternal and placental conditions
- Signs of initiation of parturition (i.e. contractions, ruptured membranes)
- Events leading up to delivery
Published today in JAMA Pediatrics is the first application of this novel phenotypic approach, which identified 12 distinct preterm birth phenotypes with very different morbidity and mortality rates. Eleven of these clusters were associated with at least one severe fetal, maternal or placental condition. However, the largest phenotype, 22% of preterm births, was not associated with any of these conditions and also had the best outcomes.
This paper presents a new approach to the problem of preterm birth. It moves us away from thinking about preterm birth in terms of specific diagnoses (e.g. preeclampsia, sepsis etc) to considering the whole clinical picture (i.e. all the conditions affecting the woman and her baby) as well as decisions made by healthcare providers that result in preterm birth. It is hoped this approach will be used in future therapeutic trials to better characterise women and babies and their associated outcomes. The goal is eventually to be able to tailor the most effective therapy for every individual mother and baby to reduce the terrible burden of preterm birth.
This study used data gathered from the multinational, population-based INTERGROWTH-21st Project, which was established to study fetal and newborn growth and development in eight populations around the world: Beijing, China; Pelotas, Brazil; Nagpur, India; Turin, Italy; Nairobi, Kenya; Muscat, Oman; Oxford, UK and Seattle, USA. Within these study sites there were 60,058 births over an approximately 12 month period: 53,871 of these babies had ultrasound confirmation of gestational age and 5828 (10.8%) were born preterm.
For more information about the INTERGROWTH-21st Project and access to all publications and study documents please go to intergrowth21.org.