What made you look at a sibling design to study associations between maternal and offspring preterm birth? 

Compared to term infants, preterm infants, especially those born earliest, are more likely to experience a myriad of health-related problems, from neurodevelopmental problems in childhood to cardiovascular and metabolic disorders later in life. The etiology of preterm birth is multifactorial, complex and not well understood. One poorly understood factor is the intergenerational recurrence of preterm birth. Several studies have consistently shown that women born preterm are more likely to have preterm babies. Based on this evidence, it has been recommended to include maternal birth status in risk assessment when planning pregnancy care for individual women.

The problem with most previous studies is that they were not designed to account for familial confounding. Comparing preterm delivery rates of women born preterm versus women born at term, regardless of family characteristics, does not answer the question of whether being born preterm is itself a risk factor for preterm delivery. Women born preterm may have different family characteristics than those born at term and those characteristics may account for the higher risk of preterm delivery. To answer that question appropriately and rule out familial confounding, we need to compare sisters of discordant preterm birth status using sibling designs.

Consideration of a female family history of preterm birth in risk assessments may better identify women at higher risk of preterm delivery.

Sibling designs are particularly suited to study the effect of a factor that differs between siblings; in this case, whether a woman who was born preterm is more likely to deliver preterm than her sister(s) not born preterm. If being born preterm is itself a risk factor, then preterm sisters would be more likely to deliver preterm babies than their sisters not born preterm. Conversely, if discordant siblings have a similar risk of delivering preterm, this means that being born preterm is not the cause, but something else that is shared by the sisters and puts both sister at higher risk. That is precisely what we found. Women born at term with a sister born preterm had a similarly elevated risk of delivering a preterm infant (10%) as their preterm sisters, in contrast with women born at term with sisters born at term (6.1%) or without sisters (6.0%).

What are the potential implications of your research in identifying women at higher risks of preterm delivery?

The main implication is that the focus of the risk assessment may be better shifted from the individual to the family. Our results suggest that it is not the fact of having been born preterm that puts women at higher risk of delivering preterm, but the fact of having been born to a mother who ever delivered preterm. Our findings do not support the notion of seeing maternal preterm birth status itself as an individual risk factor for preterm delivery. Rather, consideration of a female family history of preterm birth in risk assessments may better identify women at higher risk of preterm delivery and perhaps other pregnancy complications characterized by intergenerational transmission patterns, such as hypertensive disorders.