Shorter Time to Pregnancy With Increasing Preconception Carotene Concentrations  Among Women With 1-2 Previous Pregnancy Losses

Keewan Kim; Enrique F Schisterman; Robert M Silver; Brian D Wilcox; Anne M Lynch; Neil J Perkins; Richard W Browne; Laurie L Lesher; Joseph B Stanford; Aijun Ye; Jean Wactawski-Wende; Sunni L Mumford

doi:10.1093/aje/kwy101

Lifestyle and Environment · Nutrition and Metabolic Health

Shorter Time to Pregnancy With Increasing Preconception Carotene Concentrations Among Women With 1-2 Previous Pregnancy Losses

Kim K, Schisterman EF, Silver RM, Wilcox BD, Lynch AM, Perkins NJ, Browne RW, Lesher LL, Stanford JB, Ye A, Wactawski-Wende J, Mumford SL

Published September 2018 American Journal of Epidemiology, 187(9), 1907-1915

DOI 10.1093/aje/kwy101 PMID 29767694 PMC PMC6118073

RRM Academy Synopsis

Higher alpha-carotene was linked to faster pregnancy after 1-2 losses

In a 2018 study of 1,228 women with one or two earlier losses, higher alpha-carotene in the blood was linked to a shorter time to pregnancy. Gamma-tocopherol (a form of vitamin E) at or above the US average was linked to a longer wait.

About 2 in 10 women with one or two earlier losses became pregnant in the first cycle. Source: Kim K et al., 2018, PMID 29767694.

Study at a glance, observational cohort of 1,228 women: Higher alpha-carotene was linked to faster pregnancy after 1-2 losses. Source: Kim K et al., 2018, PMID 29767694.

Key Findings

Each log unit increase in serum alpha-carotene was linked to a shorter time to pregnancy (fecundability odds ratio (FOR) = 1.17, 95% confidence interval (CI): 1.00, 1.36) after adjustment.
In these women, alpha-carotene at or above the US average was linked to a shorter time to pregnancy than levels below it (FOR = 1.21, 95% CI: 1.02, 1.44).
In these women, gamma-tocopherol at or above the US average was linked to a longer time to pregnancy (FOR = 0.83, 95% CI: 0.69, 1.00).
After adjustment, a log unit increase in gamma-tocopherol was not associated with time to pregnancy. Lycopene and beta-carotene showed imprecise or attenuated associations. No other measured micronutrient showed a significant association.
Follow-up lasted 6 menstrual cycles. Pregnancy came in cycle 1 for 22.0% of the women, and 34.8% did not get pregnant within 6 cycles or withdrew.

Interpretation

The study is an observational cohort nested in a randomized trial. It shows association and cannot show that carotene causes faster pregnancy. Women were 18 to 40 years old, had one or two earlier losses, and used no infertility treatment. The authors limit the findings to women with one or two prior losses. Blood was drawn once at baseline, and the authors note that levels may not reflect status at conception. Diet, supplement type and dose, and the male partners' nutrition were not measured. About 10% of women withdrew early, and sensitivity analyses gave similar results. The authors describe the effect sizes as small and call for more research.

RRM Context

Restorative reproductive medicine looks for causes of delayed pregnancy in both partners. Nutrition is one possible cause among several. This study had blood measures from the women only. The male partners' role stays unexamined. An earlier study the authors cite found beta-carotene intake from supplements associated with a shorter time to pregnancy in women with unexplained (undiagnosed) infertility and a BMI of 25 or more or an age under 35.

Our editorial summary of this paper, not the article's abstract.

Abstract

Although maternal nutrition may affect fecundity, associations between preconception micronutrient levels and time to pregnancy (TTP) have not been examined. We assessed the relationship between preconception fat-soluble micronutrient concentrations and TTP among women with 1-2 prior pregnancy losses. This was a prospective cohort study of 1,228 women set within the Effects of Aspirin in Gestation and Reproduction (EAGeR) Trial (United States, 2007-2011), which assessed the association of preconception-initiated daily low-dose aspirin with reproductive outcomes. We measured preconception levels of zeaxanthin, cryptoxanthin, lycopene, α- and β-carotene, and α- and γ-tocopherol in serum. We used discrete Cox regression models, accounting for left-truncation and right-censoring, to calculate fecundability odds ratios and 95% confidence intervals. The models adjusted for age, body mass index, race, smoking, alcohol, physical activity, income, vitamin use, cholesterol, treatment arm, and study site. Serum α-carotene levels (per log unit (μg/dL) increase, fecundability odds ratio (FOR) = 1.17, 95% confidence interval (CI): 1.00, 1.36) and serum α-carotene concentrations at or above the US average (2.92 μg/dL) versus below the average (FOR = 1.21, 95% CI: 1.02, 1.44) were associated with shorter TTP. Compared with levels below the US average (187 μg/dL), γ-tocopherol concentrations at or above the average were associated with longer TTP (FOR = 0.83, 95% CI: 0.69, 1.00). The potential for these nutrients to influence fecundability deserves further exploration.

Topics

Lifestyle and Environment Nutrition and Metabolic Health Dietary Patterns

Lifestyle and Environment › Nutrition and Metabolic Health › Dietary Patterns

Keewan Kim, Enrique F Schisterman, Robert M Silver, Brian D Wilcox, Anne M Lynch, Neil J Perkins, Richard W Browne, Laurie L Lesher, Joseph B Stanford, Aijun Ye, Jean Wactawski-Wende, Sunni L Mumford

K Kim, E Schisterman, Bob Silver, Rob Silver, Bobby Silver, R Silver, B Wilcox, A Lynch, N Perkins, Rick Browne, Dick Browne, Rich Browne, R Browne, L Lesher, Joe Stanford, Joey Stanford, J Stanford, A Ye, J Wactawski-Wende, S Mumford

PMID 29767694 29767694 DOI 10.1093/aje/kwy101 10.1093/aje/kwy101 Kim et al. 2018, Kim 2018

Keywords

Micronutrients, Beta Carotene, gamma-Tocopherol