Both pre-eclampsia and intrauterine growth restriction are associated with abnormal placentation. For successful placentation, tolerance against partner alloantigens is necessary(1). Several, but not all(2), epidemiological studies suggest that an increased risk of pre-eclampsia and of small-for gestational-age (SGA), may be transmitted through the father.

Large registry based studies from Norway and the USA have shown that men born to a pre-eclamptic pregnancy had a higher risk of fathering a pre-eclamptic pregnancy themselves, compared to men unexposed to maternal pre-eclampsia(3-4). Using data from the Norwegian registers, Lie et al. have shown that the increase in risk of a second pre-eclamptic pregnancy was somewhat greater when both pregnancies were fathered by the same individual, though an increased risk of a second pre-eclamptic pregnancy following a first pre-eclamptic pregnancy was observed regardless of the father's identity(5). Furthermore, the risk of pre-eclampsia in any pregnancy was 1.8-fold higher (95%CI: 1.2, 2.6) when the father had previously fathered a pre-eclamptic pregnancy in another woman(5). Similar results were reported in a study in California, that also reported that an increase in the risk of pre-eclampsia was associated with a change in partner amongst women without pre-eclampsia in a first pregnancy(6). In contrast, a similar analysis using data from the Swedish national registers found no important paternal influence on the risk of pre-eclampsia(2). A more recent study using the Norwegian registers found that partner change was associated with a reduced risk of preterm pre-eclampsia and SGA recurrence, and with an increased risk of SGA in a second pregnancy among women who did not deliver a SGA baby in their first pregnancy. However the risk of term pre-eclampsia was not affected by partner change(1).

Using data from the Norwegian registers once more, Irgens et al, found that fathering a first pregnancy complicated by pre-eclampsia pregnancy was not associated with an increased risk of paternal death from cardiovascular causes (term preeclampsia vs term non-preeclampsia HR=1.01, 95%CI: 0.81 & preterm preeclampsia HR=1.07 & 1.03; 95%CI: 0.55, 1.92). In contrast, women with pre-eclampsia had increased CVD mortality (HR=1.65; 1.01, 2.70 and HR=8.12; 95%CI: 4.31, 15.33 for term and pre-term pre-eclampsia versus term non pre-eclamptic women respectively). Authors concluded that whilst paternal genes in the fetus may increase the risk of pre-eclampsia in a particular pregnancy, such genes are probably not related to CVD risk(7). Similarly, Mylestad et al. found no association between fathering a pregnancy complicated by a hypertensive disorder of pregnancy (HDP) and a range of CVD risk factors measured some 18 years post pregnancy using data from the Norwegian HUNT study(8). The findings of these two studies are in sharp contrast with a consistent body of evidence suggesting that women with a history of pre-eclampsia and gestational hypertension (the hypertensive disorders of pregnancy, HDP) are at increased risk of CVD later in life(9).

To the best of our knowledge the study by Irgens et al. is the only one to have examined the association of fathering a pre-eclamptic pregnancy with future CVD risk in men. Our aim is to assess whether men who fathered a pregnancy complicated by HDP, prematurity or SGA have more adverse cardiometabolic health 18 years post-pregnancy compared to men who fathered a normotensive, term non-SGA pregnancy.

Exposures: HDP (normotensive, gestational hypertension, preeclmpsia), preterm delivery and SGA in the ALPSAC index pregnancy;

Potential confounders and mediators: Maternal & paternal age at pregnancy, maternal & paternal prepregnancy BMI, maternal & paternal smoking in pregnancy, parity, household occupational social class, alcohol consumption, physical activity, pregnancy diabetes, birthweight, gestational age.

Outcomes: Paternal adiposity, blood pressure, lipids, glucose, insulin, inflammatory markers, pulse wave velocity.

References

1. Wikstrom AK, Gunnarsdottir J, Cnattingius S. The paternal role in pre-eclampsia and giving birth to a small for gestational age infant; a population-based cohort study. BMJ Open 2012;2(4).

2. Cnattingius S, Reilly M, Pawitan Y, Lichtenstein P. Maternal and fetal genetic factors account for most of familial aggregation of preeclampsia: a population-based Swedish cohort study. Am J Med Genet A 2004;130A(4):365-71.

3. Skjaerven R, Vatten LJ, Wilcox AJ, Ronning T, Irgens LM, Lie RT. Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort. BMJ 2005;331(7521):877.

4. Esplin MS, Fausett MB, Fraser A, Kerber R, Mineau G, Carrillo J, et al. Paternal and maternal components of the predisposition to preeclampsia. N Engl J Med 2001;344(12):867-72.

5. Lie RT, Rasmussen S, Brunborg H, Gjessing HK, Lie-Nielsen E, Irgens LM. Fetal and maternal contributions to risk of pre-eclampsia: population based study. BMJ 1998;316(7141):1343-7.

6. Li DK, Wi S. Changing paternity and the risk of preeclampsia/eclampsia in the subsequent pregnancy. Am J Epidemiol 2000;151(1):57-62.

7. Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 2001;323(7323):1213-7.

8. Mykelstad K, Vatten LJ, Salvesen KA et al. Hypertensive disorders of pregnancy and paternal cardiovascular risk: a population based study. Ann Epidemiol. 2011; 21:407-12.

9. Rich-Edwards JW FA, Lawlor DA, Catov JM. Pregnancy characteristics and women's future cardiovascular health: an underused opportunity to improve women's health? Epidemiologic Reviews In Press.