Pregnancy outcome following in utero exposure to bisphosphonates.
OBJECTIVE
The safety of bisphosphonates in human pregnancy has not been well established. To characterize pregnancy outcome in women receiving bisphosphonates, we conducted a multi-centre, prospective cohort study with a comparison group.


METHODS
Patients were recruited through 3 teratogen information centres in Canada and South Korea. We followed 21 women exposed to bisphosphonates during or <3 months before pregnancy, and 21 matched-comparison group women without exposure to known teratogens. Pregnancy/neonatal outcome data were collected by interview. The primary endpoint was neonatal outcome including major birth defects. The secondary endpoints included other pregnancy outcomes such as spontaneous abortions.


RESULTS
Indication of the therapy was osteoporosis in all patients. There was no difference in the maternal demographics between the 2 groups. In the bisphosphonate group, there were 18 live births, 2 spontaneous abortions and 1 therapeutic abortion, which were not significantly different from the comparison group. The mean gestational age (mean+/-SD) of the bisphosphonate group was 38.7+/-1.9 weeks (comparison group: 39.3+/-1.9 weeks; P=0.42), and the mean birth weight was 3.1+/-0.3 kg (comparison group: 3.3+/-0.5 kg; P=0.11). In the bisphosphonate group, there was a child diagnosed with Apert syndrome, an autosomal dominant acrocephalosyndactyly, with a fibroblast growth factor 2 mutation.


CONCLUSIONS
Coupled with existing data in the literature, our findings suggest that preconceptional and first-trimester use of bisphosphonates may not pose substantial fetal risks.
Levy
Shirley
S
The Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Fayez
Ibrahim
I
Taguchi
Nobuko
N
Han
Jung-Yeol
JY
Aiello
Jennifer
J
Matsui
Doreen
D
Moretti
Myla
M
Koren
Gideon
G
Ito
Shinya
S
D000014:Abnormalities, Drug-Induced; D000328:Adult; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005333:Fetus / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies
D050071:Bone Density Conservation Agents; D004164:Diphosphonates