Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
Status:
Completed
Trial end date:
2020-01-22
Target enrollment:
Participant gender:
Summary
Intrauterine growth restriction (IUGR) is correlated to an abnormal placenta development,
with an alteration of the maternal-fetal circulation, coagulation troubles, and apparition of
placental infarcts. IUGR represents the third cause of perinatal mortality in France, and is
associated to an important morbidity. For birth-weights < 10th percentile of the gestational
age, the neonatal death risk is doubled, compared to abnormal weights. In 35% of cases, IUGR
is of vascular origin and is included in the broader framework of placental vascular
pathology (PVP).
Up to now, studies have focused on the primary or secondary prevention of PVP. Few studies
have evaluated the treatment of constituted vascular IUGR. Currently, the management of
vascular IUGR is mainly based on active surveillance, or termination of pregnancy.
Pathological findings suggest that placental pro-thrombotic phenomena play a role in the
constitution of vascular IUGR. Since aspirin is not effective in reducing this type of event,
a randomized, open-label study conducted in China compared 14-day treatment with
low-molecular-weight heparin (LMWH) versus Dan-Shen (a product not used in France) after
diagnosis of IUGR. This trial, including 73 patients, showed a significant improvement in
average growth kinetics in the LMWH group. The mean birth weight was 2877 g in the heparin
group and 2492 g in the Dan-Shen group (p <0.0001). However, no data were provided concerning
the number of newborns with a birth weight <10th percentile, i.e. the risk of morbidity and
mortality, or complications occurring. Due to the lack of reliable data, LMWH are not
included in the currently recommended therapeutic strategy for vascular IUGR.
The studies in IUGR reported to date mainly focused on primary or secondary prevention in
women at risk of PVP, assessing the value of aspirin, which showed only a modest effect. No
effective therapeutic strategy is available to treat patients with constituted vascular IUGR,
a situation where LMWH should be more effective than antiplatelets given the vascular
context.