Fetal sex may determine type of pregnancy complication in mother: Cambridge Study

The risks of some diseases in the pregnancy may be attributed to the sex of the child the mother is carrying, according to a new study published in the journal JCI Insight. This can be explained by the presence of small molecules known as metabolites in the pregnant mother's blood being controlled by sex of a baby.

Gordon Smith, professor, the University of Cambridge, and colleagues tested the hypothesis that fetal sex would be associated with an altered placental function using multiomic and targeted analyses.

Preeclampsia and fetal growth restriction (FGR) are major causes of the more than 5 million infant and perinatal deaths occurring globally each year, and both are associated with placental dysfunction. The mechanisms of increased risk of infant and perinatal death are still unclear.

The findings of the study, help to explain, for example, why male babies in the womb may be more vulnerable to the effects of poor growth, and why being pregnant with a girl may lead to an increased risk of severe pre-eclampsia for the mother.

For the study, a team of researchers from the Department of Obstetrics and Gynaecology, NIHR Cambridge Biomedical Research Centre, performed detailed analysis of more than 4,000 first time mothers and analyzed samples of the placenta and maternal blood.

• The genetic profile of the placentas of male and female babies were very different in relation to the baby's sex. Many of the genes that differed according to the sex of the baby in the placenta had not previously been seen to differ by sex in other tissues of the body.


• One of these uniquely sex-related placental genes controlled the level of a small molecule called spermine. Spermine is a metabolite -- a substance involved in metabolism -- that plays an important role in all cells and is even essential for the growth of some bacteria.


• Female placentas had much higher levels of the enzyme that makes spermine, and mothers pregnant with baby girls had higher levels of a form of spermine in their blood compared to mothers pregnant with baby boys.


• Placental cells from boys were also found to be more susceptible to the toxic effects of a drug that blocked spermine production. This provided direct experimental evidence for sex-related differences in the placental metabolism of spermine.


• The form of spermine which was higher in mothers pregnant with a girl was also predictive of the risk of pregnancy complications: high levels were associated with an increased risk of pre-eclampsia (where the mother develops high blood pressure and kidney disease), whereas low levels were associated with an increased risk of poor fetal growth.


• The patterns observed were all consistent with previous work which has shown that boys may be more vulnerable to the effects of fetal growth restriction and that being pregnant with a girl may lead to an increased risk of severe preeclampsia.