Fetal and maternal contributions to risk of pre-eclampsia: population based study

BMJ 1998;316:1343-1347 ( 2 May )

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Fetal and maternal contributions to risk of pre-eclampsia: population based study

Rolv Terje Lie, professor, ^a Svein Rasmussen, obstetrician, ^b Helge Brunborg, researcher, ^c Håkon K Gjessing, researcher, ^a Erik Lie-Nielsen, managing director, ^b Lorentz M Irgens, professor. ^b

^a Division for Medical Statistics, University of Bergen, Armauer Hansen's Building, Haukeland Hospital, 5021 Bergen, Norway, ^b Medical Birth Registry of Norway, Armauer Hansen's Building, Haukeland Hospital, 5021 Bergen, ^c Statistics Norway, PO Box 8131 Dep, 0033 Oslo, Norway

Correspondence to: Professor Lie rolv.lie{at}smis.uib.no

Objective: To use familial patterns of recurrence of pre-eclampsia to investigate whether paternal genes expressedin the fetus contribute to the mother's risk of pre-eclampsiaand whether mother's susceptibility to pre-eclampsia is relatedto maternal inheritance by mitochondrial DNA.
Design: Linked data on pregnancies of different women who had children with the same father, and subsequently linkeddata on pregnancies of half sisters who either had same motherand different fathers or had same father and different mothers.
Setting: Population based data from the Medical Birth Registry of Norway covering all births since 1967 (about 1.7million) and the Norwegian Central Population Register.
Main outcome measures: Relative risk of pre-eclampsia after a previous pre-eclamptic pregnancy in the family. Relativerisks approximated by odds ratios.
Results: If a woman becomes pregnant by a man who has already fathered a pre-eclamptic pregnancy in a different womanher risk of developing pre-eclampsia is 1.8 (95% confidence interval1.2 to 2.6). If the woman has a half sister who had pre-eclampsiaand with whom she shares the same mother but different fathersthe risk of pre-eclampsia is 1.6 (0.9 to2.6). If the two sistershave the same father but different mothers the risk is 1.8 (1.01to 2.9).
Conclusions: Both the mother and the fetus contribute to the risk of pre-eclampsia, the contribution of the fetus beingaffected by paternal genes. Mitochondrial genes, which are transmittedby mothers, do not seem to contribute to the risk.

Key messages

Paternal genes in the fetus may contribute substantially to a pregnant woman's risk of pre-eclampsia
The role of the fetus may be as important as that of the mother
Purely maternal inheritance (specifically by mitochondrial DNA) is probably not involved in pre-eclampsia
Search for specific genes that predispose for pre-eclampsia should include the fetus as well as the mother

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