Genetic conflict with the fetus influences when women give birth

When it comes to the length of pregnancy, fetuses and those carrying them may have slightly different interests. Now, the largest study into how genes affect the timing of childbirth suggests that the two parties reached an evolutionary compromise.

Gene variants that, in women, promote a shorter pregnancy, also encourage faster fetal growth when present in fetuses. “They have reached some kind of a deal, with the mother saying: ‘I’m going to allow you to grow a little bit more, but I’m going to deliver a little bit earlier’,” says Pol Solé Navais at the University of Gothenburg, Sweden.

Premature birth – defined as delivery before 37 weeks of pregnancy – is one of the leading causes of death in newborns globally, but the causes are poorly understood.

To explore the genetic influences of pregnancy length, Solé Navais’s team pooled the results of previous studies that together included around 200,000 women who started giving birth at various stages of pregnancy without being medically induced. Transgender people weren’t included.

These studies sequenced the DNA of both the women and their babies, as well as noting aspects such as how long the pregnancies lasted and the babies’ birth weight.

Solé Navais’s team found 22 sites within the genome that each had a small influence on the timing of birth, of which five had opposite effects when present in the mother or the fetus. In other words, if a certain variant were present in the mother, it was linked with a shorter pregnancy, while if present in the fetus, it was associated with a longer pregnancy.

This supports the idea that fetuses and those carrying them have opposing interests, because the longer a pregnancy lasts, the bigger a fetus typically grows, which makes birth riskier for the mother, says Solé Navais. Within limits, the fetus therefore has more of an interest in growing bigger than the mother has, he says.

But when fetal birth weight was considered, the picture got more complicated. When the effects of all the gene variants were aggregated, those linked to a shorter pregnancy were also linked to a higher birth weight if inherited by the fetus.

If some genetic variants in the fetus are associated with an increased birth weight, then the mother’s genome counters that by using the same variants to reduce pregnancy length, says John Perry at the University of Cambridge. “The fetus is pushing in one direction and the mother is pushing in the other direction.”

The team also found that some of the variants that influence how long a pregnancy lasts may also prevent labour from starting. Previous studies in rats suggest the proteins they encode could be involved in regulating contractions of the uterus.

Understanding more about how they have this contraction-regulating effect could lead to new medicines that trigger or prevent labour, says Solé Navais.