what-when-how
In Depth Tutorials and Information
calcium, the vast majority of it in the third trimester
(when fetal skeletal mineralization peaks). Calcium is
actively transported across the placenta. In pregnancy
total serum calcium levels decrease but this is a result
of reduced serum albumin and thus a lower albumin-
bound fraction of calcium. Most importantly, serum
ionized calcium fraction is unchanged.
18
Calcium is
absorbed through the small intestines, absorption
increases in the first trimester and maximal absorp-
tion occurs in the third trimester.
18,19
While most cal-
cium comes from intestinal absorption, in the third
trimester there is some absorption from the maternal
skeletal. The increased intestinal absorption of intesti-
nal calcium results from increased levels of 1,25-dihy-
droxyvitamin D in pregnancy.
18
Controversy continues
regarding proper levels of vitamin D levels (25(OH)D),
though levels of less than 32 ng/mL indicate vitamin D
deficiency and treatment should be instituted.
19
While
the effect of pregnancy on bone metabolism is com-
plex, there has been concern that pregnancy and lacta-
tion lead to an increased risk for long-term osteoporosis
and thus potentially could profoundly affect women
with OI. Pregnancy and lactation do cause some revers-
ible bone loss, but studies do not support the effect of
numerous pregnancies and osteoporosis in later life.
21
Whether these data in non-OI patients can be extrapo-
lated to OI is unknown. Maintenance of normal vita-
min D levels (25(OH)D) should be achieved in pregnant
women with OI as well as 1000 to 1300 mg/day of cal-
cium during pregnancy and lactation.
19
Beyond adaptations to bone metabolism, preg-
nancy is associated with increased ligamentous lax-
ity. Non-OI patients develop increased lordosis of the
lumbar spine which can result in lower back pain in a
significant number of pregnant women. Ligaments of
the pubic symphysis and sacroiliac joints also loosen
and can cause pain on standing and walking. The pro-
gression of kyphoscoliosis, particularly in patients
with OI, is unknown. The literature on progression of
kyphoscoliosis in pregnancy is controversial and not
recently addressed. Further, the issues of age of devel-
opment of kyphoscoliosis and whether instrumentation
has been used affect the progression of the scoliosis.
Some authors have proposed that there is increased
progression of the curve if it is initially greater than
25 degrees,
22
while others have not agreed. Probably
the severity of the curve at time of pregnancy contrib-
utes to its progression.
23
Thus, it would be prudent for
an OI pregnant patient with severe kyphoscoliosis to
have their spines evaluated throughout gestation (per-
haps each trimester) and post-delivery by an orthope-
dic team. It may be beneficial to consult with anesthesia
regarding placement of an epidural in advance of labor.
Transient osteoporosis of the hip in pregnancy or
lactation is usually a rare self-limiting disorder of
unknown etiology which has been associated with hip
fractures.
24,25
It is characterized by spontaneous, pro-
gressive pain and typical MRI findings of bone marrow
edema. The hip is the most common site, but transient
osteoporosis is seen at other sites including the knee,
ankle, shoulder, elbow and wrist. The disorder tends
to be a self-limited disease that resolves within 6-12
months. Treatments include non-weight-bearing physi-
cal therapy, passive immobilization, prostaglandin
PGI
2
analogs, bisphosphonates, vitamin D if appropri-
ate, calcium supplementation and surgical intervention
(core decompression) to reduce tissue pressure. While
the disorder is extremely rare in the non-OI pregnant
population, it has been reported in pregnancy and OI.
The combination of transient osteoporosis of the hip
and OI has only been reported in a few cases, almost
all of them in pregnancy, suggesting that pregnancy
places the OI patient at risk for this rare event.
26-30
Management of the patient should be based on a team
approach with expertise on transient osteoporosis. In
pregnancy conservative management should be initi-
ated first, noting that use of bisphosphonates is rela-
tively contraindicated (they have been used in pregnant
women with little ill effect on mothers and fetuses, but
theoretically could cause decreased mineralization in
the fetus)
31
and prostaglandin analogs are contraindi-
cated in the third trimester due to the fetal risk of pre-
mature closure of the ductus arteriosus.
32
MANAGEMENT OF PREGNANCY,
LABOR AND DELIVERY
In addition to the concomitant medical issues that
are seen in OI, which can complicate pregnancy man-
agement, routine obstetrical issues should also be
addressed. Women with OI are still at risk for fetuses
with non-OI-related congenital birth defects, gesta-
tional diabetes, preterm delivery, anemia, infection and
preeclampsia. Women with OI should receive genetic
screening and obstetrical management based on the
standards in their communities. However, the issues
surrounding both timing and mode of delivery, includ-
ing type of anesthesia, need to be considered as early in
gestation as possible.
There are no large series on the management of preg-
nancy and delivery in pregnant women with OI. To
date, there are fewer than 50 case reports on maternal
OI and outcome.
33-36
Further complicating the limited
information is that each patient can present with varia-
tions in phenotype and no comprehensive statement
can be made regarding precise management based on
mild, moderate or severe OI. The milder form of OI (OI
type I, and in some cases OI type IV, Sillence classifica-
tion)
37
is usually accompanied by near average height,
