Literature Scan
hormonal contraception:
• use within 3 to 6 months prior to
pregnancy: HR=1.38 (95% CI 1.03-
1.85; p=0.031)
• use within 6 to 12 months prior to
pregnancy: HR=1.22 (95% CI 0.90-
1.65; p=0.159)
• use more than 1 year prior to
pregnancy: HR=1.24 (95% CI 0.96-
1.60; p=0.108)
The unadjusted incidence of leukemia was
4.33 cases per 100,000 person-years for no
maternal hormonal contraception use and
6.45 for recent use. These incidence rates
translated to approximately one additional
leukemia case per 47,170 exposed chil-
dren, or approximately 25 leukemia cases
during the study follow-up period.
Limitations of the study include the
possibility that some women may not
have used the prescribed contraceptives
or used them at a different time, which
may have led to a misclassification of
exposure. The authors also acknowl-
edged missing information, like expo-
sure to radiation in utero and perinatal
infections, that may have confounded
the study’s findings.
“Further large, valid studies with
registry-based information of hormonal
contraception and childhood cancer –
including a substantially larger study
cohort and more cases – will help to
either firmly establish or refute the pos-
sible link between prenatal exposure to
sex hormones and the risk of childhood
cancer,” Dr. Hargreave added.
She noted that her team is conduct-
ing a similar study that will include
a total of four Nordic countries with
“[Further research] will help to
either firmly establish or rebuke
the possible link between prenatal
exposure to sex hormones and the
risk of childhood cancer.”
—MARIE HARGREAVE, PhD
“The results were almost unchanged
when sex and perinatal factors were
included in the analyses, when children
with unknown or other leukemia were
excluded, [and] when children with Down
syndrome were excluded,” the authors
reported. However, after adjustment
for maternal smoking, the association
with childhood leukemia was no longer
statistically significant, suggesting that
maternal smoking status may also play a
role in the risk of childhood leukemia.
Previous and recent use of combined oral
products (estrogen and progestin) increased
the risk of any type of leukemia, compared
with no use, but no specific type of hor-
monal contraception was associated with an
increased risk for lymphoid leukemia.
registry-based data on maternal use of
contraception and childhood cancer.
“We are exploring the risk of other
childhood cancer types with respect to
maternal hormonal contraception and
with respect to different types of fertil-
ity drugs, as we previously found an
increased risk of leukemia and neuro-
blastomas in children born to women
after fertility treatments involving the
steroid hormone progesterone,” she said.
Corresponding authors reported fi-
nancial relationships with Jazz Pharma-
ceuticals and Shire.
REFERENCE
Hargreave M, Mørch LS, Andersen KK, et al. Maternal use of hormonal
contraception and risk of childhood leukaemia: a nationwide, population-
based cohort study. Lancet Oncol. 2018 September 6. [Epub ahead of print]
Risk of Childhood Leukemia According to Maternal
Hormonal Contraception Use
Rivaroxaban Fails to
Prevent VTE and
VTE-Related Mortality
After Hospital
Discharge
Patients hospitalized for an acute medical illness are at an increased
risk for developing venous thromboembolism (VTE) in the six weeks
after discharge, but treatment with rivaroxaban after discharge did
not reduce VTE or VTE-related mortality risk, according to results
from a placebo-controlled study published in The New England
Journal of Medicine.
“The role of extended thromboprophylaxis in this population is un-
clear, as it has shown either excess bleeding or beneficial effects mainly
from reducing asymptomatic deep vein thrombosis (DVT),” lead author
Alex C. Spyropoulos, MD, of Northwell Health in Chicago, told ASH
Clinical News. Although rivaroxaban did not appear to increase bleed-
ing risk in this study, the authors noted, “the usefulness of extended
thromboprophylaxis remains uncertain.”
In the MARINER (Medically Ill Patient Assessment of Rivaroxaban
versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism
Risk) trial, researchers enrolled 12,019 patients (median age = 69.7
years; range not provided) who had been hospitalized for three to 10
consecutive days with heart failure, respiratory insufficiency, stroke, or
infectious or inflammatory disease.
All participants were required to have risk factors for VTE (de-
fined as a score of ≥4 on the 10-point modified IMPROVE model)
and to have previously received low-molecular-weight heparin or
unfractionated heparin during their hospital stay.
On the day of hospital discharge, investigators randomized
patients to receive either once-daily rivaroxaban 10 mg (n=6,007) or
placebo (n=6,012) for a total of 45 days. Patients with renal insuffi-
ciency received a lower dose of rivaroxaban (7.5 mg).
“The role of extended
thromboprophylaxis in this
population is unclear, as it has
shown either excess bleeding
or beneficial effects.”
—ALEX C. SPYROPOULOS, MD
TABLE 1.
Any Leukemia
Hazard ratio
p Value
Lymphoid Leukemia
Hazard ratio
p Value
Hazard ratio
p Value
No use 1.00
(reference) Previous use 1.25
(1.01–1.55) 0.039 1.23
(0.97–1.57) 0.089 1.33
(0.83–2.11) 0.232
Recent use 1.46
(1.09–1.96) 0.011 1.27
(0.90–1.80) 0.167 2.17
(1.22–3.87) 0.008
≤3 months
of pregnancy 1.42
(1.05–1.93) 0.025 1.28
(0.90–1.83) 0.173 1.95
(1.05–3.60) 0.033
During
pregnancy 1.78
(0.95–3.31) 0.070 1.22
(0.53–2.81) 0.635 3.87
(1.48–10.15) 0.006
44
ASH Clinical News
1.00
(reference)
Nonlymphoid Leukemia
1.00
(reference)
During the 45-day follow-up, the authors observed fewer instances
of symptomatic VTE with rivaroxaban than with placebo, but there
was no significant difference in the rates of the composite endpoint of
symptomatic VTE (including DVT and nonfatal pulmonary embolism)
or VTE-related mortality: 0.83 percent for rivaroxaban and 1.10 per-
cent for placebo (hazard ratio [HR] = 0.76; 95% CI 0.52-1.09; p=0.14).
Rates of VTE-related mortality (secondary endpoint) were also
similar between the two treatment groups: 0.72 percent for rivar-
oxaban and 0.77 percent for placebo (HR=0.93; 95% CI 0.62-1.42; p
value not provided).
Rates of other efficacy outcomes are presented in TABLE 2 .
In addition, there were no significant differences between the
rivaroxaban and placebo groups in the safety analyses (p values
November 2018