Interpretation
GWG has been associated with subsequent risks of adverse pregnancy
outcomes, such as preterm birth, pre-eclampsia and caesarean section,
has been suggested[18,19], but evidence to clarify
the relationship between gestational weight gain and maternal VTE have
been sporadic[13,20]. A Norwegian hospital-case
control study reported that large weight gains (>p90 or
>21.0kg) were associated with 60% increased odds of
postpartum VTE, while small maternal weight gain is an independent
antenatal risk factor for VTE[13]. In a Washington
State, USA population-based, case-control study, women with large weight
gains during pregnancy (>22kg), independently of BMI, were
more likely to have VTE (1.5, 95%CI 1.2-2.1)[20].
In line with these studies, we observed that higher GWG in whole
pregnancy was associated with higher risk of PE. Over weight gain during
pregnancy accompanied with increased intraabdominal pressure can
encourage blood stasis through iliac vessels compression. Furthermore,
elevated inflammatory cytokines and adipokines with increased fat
deposition promote endothelial dysfunction and platelet hyperreactivity.
Fat deposition also skews the hemostatic-fibrinolytic balance through
elevation of procoagulant factors including von Willebrand factor,
fibrinogen, factor VII, factor VIII, issue factor, and impairment of
fibrinolysis by elevation of plasminogen activator
inhibitor[21]. On top of differential inflammatory
responses, women with high weight have longer durations of labor,
greater rates of chorioamnionitis, postpartum hemorrhage and surgical
complications, which may all lead to the observed greater risk of VTE
after delivery[22].
There is growing recognition that the impacts of gestational
stage-specific weight gain on pregnancy outcomes may
vary[23-27]. GWG in early pregnancy largely
reflects maternal fat deposition, whereas GWG in mid and late pregnancy
is also attributed to maternal and amniotic fluid expansion, and growth
of the fetus, placenta and uterus[28]. In this
study, we found that higher GWG in early pregnancy was associated with
higher risks of PE in normal-weight women. As for underweight and
overweight women, results from the categorical model for early pregnancy
weight gain indicated an increased risk at both low and high weight gain
for PE. Studies have found that mothers with increased fat deposition
during early pregnancy may involve the multifactorial engagement of
alterations to blood flow, hypercoagulability, chronic low-grade
inflammation and endothelial dysfunction, which may lead to
PE[21,29]. Therefore, GWG in early pregnancy,
prior to the development of pregnancy outcomes, might be as or more
important than GWG in late pregnancy with respect to pregnancy outcomes.
GWG below average in overweight and obese mothers were also at an
increased risk of PE in our analysis. This finding, if true, could
result from low amniotic fluid volume and fetal weight by ischemic
placental disease (including preeclampsia, intrauterine growth
retardation, stillbirth, and placental abruption), perhaps a potential
for embolism, leading to PE[1]. Blondon et al
found that the delivery of a newborn with low birth weight is associated
with a 3-fold increased risk of maternal postpartum
VTE[1]. In another Norwegian hospital-based,
case–control study, mothers of newborns with IUGR were at 3.8-fold risk
of postpartum VTE[13]. Moreover, hypertension
during pregnancy and preeclampsia are also associated with an increased
VTE risk during pregnancy and postpartum
period[9,30]. However, a randomized clinical trial
indicated that pre-pregnancy weight loss intervention has favorable
effects on the early intrauterine environment[31].
Lifestyle intervention during pregnancy could to some extent limit GWG
and improve maternal and infant health[32].
Therefore, pre-pregnancy weight interventions integrated into intensive
weight management that continues through pregnancy may be indispensable
to decrease the risks of PE.
There was no statistical association between maternal weight gain and
DVT or all VTE across all BMI categories. Similarly, Matthew et al
retrospectively analyzed a large database from American found that only
the risk of PE is elevated in patient classification as heavier
categories after surgery, whereas there was no positive association
between DVT and BMI[33,34]. Explanations for this
observed association exist, of which anticoagulation used for VTE
prophylaxis during pregnancy is most plausible. All pregnant women in
Shanghai are managed based on RCOG Green-top
Guidelines[35] and Quensland Clinical
Guidelines[36,37]. Briefly, they will undergo a
documented assessment of risk factors for VTE throughout pregnancy,
intrapartum and the puerperium. Any woman with risk factors shown in
Table S2 should be considered for prophylactic low-molecular-weight
heparin (LMWH). Previous studies have evaluated the efficacy of LMWH for
thromboprophylaxis, revealed that LMWH probably results in little to no
difference in the incidence of PE in patients undergoing knee
arthroscopy, but reduce the risk of asymptomatic
DVT[38]. Similarly, eight RCTs showed no clear
differences between the LMWH and no prophylaxis or placebo groups in
patients with lower-limb immobilization for PE, but less DVT in the LMWH
groups[39]. Therefore, aggressive pharmacologic
anticoagulation regimens during pregnancy can decrease the DVT rate but
have not been shown to affect the rate of PE. Meanwhile, common risk
factors for DVT, like history of multiple deliveries, smoking, and
obesity are less frequently observed in
China[15,40]. These may be the reasons for the
higher incidence of PE in this study. However, the evidence is very
uncertain, and further high-quality very large-scale randomized trials
are needed to determine effects of currently used treatments in women
with different VTE risk factors.