Preeclampsia was increased in women with Marfan
syndrome, however only significantly in women not yet diagnosed with
Marfan syndrome. The increased risk was also present among women
diagnosed with Marfan syndrome, although this result did not reach
significance. Reports of preeclampsia in a woman diagnosed with Marfan
syndrome has been published previously.14Reassuringly, we found no association between having Marfan syndrome and
experiencing preterm births. However, this is unexpected since
insufficiency of connective tissue is associated with preterm birth.15
Foetal death was significantly increased among the undiagnosed Marfan
syndrome women, however as none of the registrations were among women
diagnosed with Marfan syndrome, the consequences of this finding in
relation to Marfan syndrome is limited. We could not find any further
information of this result in the registries.
In Denmark, legal abortion is a possibility until 12th week of gestation
on mother’s request and after 12th week of gestation if permission is
granted from the regional abortion council. Indications for a late
abortion are for instance mother’s health, congenital malformations, and
genetic indications including Marfan syndrome. The significantly
increased proportion of late abortion in the diagnosed Marfan syndrome
women suggests that a diagnosis of MFS in a foetus is followed by
application of legal late abortion in pregnant Marfan women. This could
be a contributing cause of the reduced birth rate among diagnosed Marfan
syndrome women.
The level of cardiac surveillance of the diagnosed Marfan women during
pregnancy in Denmark seems appropriate. It is even likely that some
women with Marfan syndrome, perhaps unnecessarily when scrutinizing the
present data, refrain from becoming pregnant, or choose abortion, due to
careful guidance from the clinical and cardiac Marfan syndrome
centres16. However, we do not have detailed
information concerning the clinical status of the women with diagnosed
Marfan syndrome that chose not to be become pregnant, and it may
therefore be possible that some of these individuals, choosing not to
become pregnant, and then voluntarily infertile, indeed are very high
risk patients17. We anticipate that no cardiac
surveillance program was instituted for the previously undiagnosed women
with Marfan syndrome.
The difference in outcome shows the importance of a pre-pregnancy
diagnosis. Whether some of the associations identified during pregnancy
are driven by historical reports, thus emphasising the clinicians’ need
to observe and register the complications, can only be considered among
the women diagnosed with Marfan syndrome, and not among those not yet
diagnosed. However, there is a possibility that the musculo-skeletal
symptoms, known to be present in Marfan syndrome, are already present in
the undiagnosed women, and as such, the clinicians have an increased
awareness and register these complications.
Whether affected connective tissue because of FBN1 mutations in the
uterine system, also can explain the findings with cervical
complications, remains to be determined. The understanding of the
association of an increased risk of preeclampsia in the women not yet
diagnosed, remains to be elucidated, and clinical vigilance is
recommended. It is possible that the pregnant women diagnosed with
Marfan syndrome are treated medically with antihypertensive drugs, thus
reducing the risk of preeclampsia.