Preconception hemoglobin A1c concentration in healthy women is not associated with fecundability or pregnancy loss

Jessica R Zolton; Lindsey A Sjaarda; Sunni L Mumford; Tiffany L Holland; Keewan Kim; Kerry S Flannagan; Samrawit F Yisahak; Stefanie N Hinkle; Matthew T Connell; Mark V White; Neil J Perkins; Robert M Silver; Micah J Hill; Alan H DeCherney; Enrique F Schisterman

doi:10.1016/j.xfre.2022.01.002

Preconception hemoglobin A1c concentration in healthy women is not associated with fecundability or pregnancy loss

F S Rep. 2022 Jan 20;3(1):39-46. doi: 10.1016/j.xfre.2022.01.002. eCollection 2022 Mar.

Authors

Jessica R Zolton^{1

2}, Lindsey A Sjaarda², Sunni L Mumford², Tiffany L Holland², Keewan Kim², Kerry S Flannagan², Samrawit F Yisahak³, Stefanie N Hinkle², Matthew T Connell^{1

2}, Mark V White⁴, Neil J Perkins², Robert M Silver⁵, Micah J Hill¹, Alan H DeCherney¹, Enrique F Schisterman⁶

Affiliations

¹ Program in Reproductive Endocrinology and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
² Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
³ Office of the Director, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
⁴ Department of Medical Education, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania.
⁵ Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah.
⁶ Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

Objective: To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases.

Design: A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial.

Setting: Four US academic medical centers.

Patients: A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived.

Interventions: Not applicable.

Main outcome measures: Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth.

Results: Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss.

Conclusionss: Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes.

Clinical trial registration number: ClinicalTrials.gov: NCT00467363.

Keywords: fecundability; hemoglobin A1c; preconception care; pregnancy loss.

Associated data

ClinicalTrials.gov/NCT00467363