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Maternal and fetal genes both impact pregnancy duration

A new study, published in Nature Genetics, has revealed genetic mechanisms that may explain preterm birth. The work highlights the ways in which maternal and fetal genes impact the duration of pregnancy and the subsequent weight of the infant at birth.

Birth is a dangerous event

Preterm delivery is the number one cause of death in newborn infants. Subsequently, the effects of early birth can impact an individual throughout their life. Preterm delivery is defined as birth before 37 weeks gestation, and the shorter the pregnancy, the more risk of complications. Moreover, gestational duration governs birth weight, with lighter babies typically suffering from more health problems.

Both maternal and fetal genomes control preterm delivery and birth weight. However, recent studies have revealed that mother and baby have conflicting goals: a mother’s biology is more likely to favour a shorter gestation and a smaller infant, whilst the fetus expresses genes that promote a longer pregnancy and healthier birth. This is not altogether surprising – the longer the pregnancy the healthier the child, but a birthing large baby can be detrimental to the mother’s health. This is due to the fact that the human pelvis is barely big enough to pass a newborn infant.

Strong genetic signals

In the largest genome-wide association study of its kind, the genomes of nearly 200,000 women were analysed to find links between their genes and the length of their pregnancies. This part of the study revealed 22 genetic loci associated with gestational duration, 16 of which had never been previously implicated. Furthermore, a meta-analysis looking specifically into preterm delivery identified another six significant loci.

To determine whether the maternal or fetal genome is primarily responsible for gestational duration, the researchers investigated the effects of transmitted and non-transmitted alleles in the fetuses using parent-child trios or mother-child pairs. This allowed the team to assess whether an effect came from the mother or baby. They concluded that most of the genetic influence on gestational duration comes from the mother. 15 variants acted entirely through the maternal line, 7 through both genomes and 2 from the fetus alone. The research also revealed that fetal genomes independently act to increase birth weight. Conversely, maternal alleles involved in controlling pregnancy duration often additionally acted to decrease the weight of the infant.

Conflicting needs

The findings shed new light on the interplay between maternal and fetal biology during pregnancy. Given the complex nature of human birth due to our unusual bipedal stature, the impacts of pregnancy and delivery can be life-changing for mother and baby. An understanding of the mechanisms governing these processes is crucial in improving not only the health of newborns, but individuals of all ages. The results reveal the ongoing conflict between mother and child to maintain a healthy status quo, and the intricacies of this relationship.

Senior author Bo Jacobsson stated: “The results have given us more routes to understanding how labor is initiated, both at full term and in premature labor. In samples, we were able to identify numerous previously undiscovered genetic variants associated with the timing of parturition, and these provide unmatched insights into the underlying biological mechanisms.” The ongoing aim of the work is to find treatments that can lower the risk of preterm birth, keeping mother and baby safe.

More on these topics

Genetics / Pregnancy / Preterm Delivery