Potential association between infertility and spinal neural tube defects in offspring.
BACKGROUND
We examined the possible association between infertility and spinal neural tube defects (NTDs).


METHODS
This is a nested case-control study within the Kaiser Permanente Medical Care Program (KPMCP) in Northern California. Among a birth cohort of 110,624 singleton infants > or = 36 weeks gestation, 1994-1997, we electronically identified cases of spinal NTDs and confirmed the diagnosis by chart review. Controls (n = 1,608) were randomly selected from the birth population. History of infertility was defined as: (1) physician diagnosis of infertility; (2) prescription for an infertility medication noted in the KPMCP pharmacy; and/or (3) evaluation at 1 of 15 infertility clinics in Northern California.


RESULTS
Eighteen infants diagnosed with spinal NTDs (prevalence 1.6/10,000) included 13 with spina bifida cystica and 5 with spina bifida occulta. Case mothers were more likely to have a history of infertility (4/18 vs. 96/1,608, OR 4.3, 95% CI 1.01-14.0), and to have been prescribed clomiphene citrate within the window spanning 60 days before to 15 days after conception (3/18 vs. 32/1,608, OR 11.7, 95% CI 2.0-44.8).


CONCLUSIONS
This exploratory study suggests that infertility may be associated with an increased risk of spinal NTDs among liveborn, term infants.
Wu
Yvonne W
YW
Department of Neurology, University of California, San Francisco, California 94143-0137, USA. wuy@neuropeds.ucsf.edu
Croen
Lisa A
LA
Henning
Louis
L
Najjar
Daniel V
DV
Schembri
Michael
M
Croughan
Mary S
MS
D002140:California; D002996:Clomiphene / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007247:Infertility, Female / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D016137:Spina Bifida Cystica / Q000453:epidemiology / Q000209:etiology*; D016136:Spina Bifida Occulta / Q000453:epidemiology / Q000209:etiology*
D005300:Fertility Agents, Female; D002996:Clomiphene