Sunni L. Mumford

A systematic review of outcomes of maternal weight gain according to the Institute of Medicine recommendations: birthweight, fetal growth, and postpartum weight retention.

This systematic review focuses on outcomes of gestational weight gain, specifically birthweight, fetal growth, and postpartum weight retention, for singleton pregnancies with respect to the 1990 Institute of Medicine weight gain recommendations. A total of 35 studies met the inclusion criteria and were reviewed. There was strong evidence to support associations between excessive gestational weight gain and increased birthweight and fetal growth (large for gestational age) as well as inadequate gestational weight gain and decreased birthweight and fetal growth (small for gestational age). There was moderate evidence to support the association between excessive gestational weight gain and postpartum weight retention. Clear clinical recommendations based on this review are challenging because of several limitations in the literature. Improvements in future research include the use of consistent definitions of gestational weight gain and outcomes of interest, assessment of confounders, and better collection of weight and weight gain data.

Effect of daily fiber intake on reproductive function: the BioCycle Study

BACKGROUND High-fiber diets have been associated with decreased breast cancer risk, likely mediated by the effect of fiber on lowering circulating estrogen concentrations. The influence of fiber on aspects of reproduction, which include ovulation, has not been well studied in premenopausal women. OBJECTIVE The objective was to determine if fiber consumption is associated with hormone concentrations and incident anovulation in healthy, regularly menstruating women. DESIGN The BioCycle Study was a prospective cohort study conducted from 2004 to 2006 that followed 250 women aged 18-44 y for 2 cycles. Dietary fiber consumption was assessed < or =4 times/cycle by using 24-h recall. Outcomes included concentrations of estradiol, progesterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which were measured < or =8 times/cycle, and incident anovulation. RESULTS Dietary fiber consumption was inversely associated with hormone concentrations (estradiol, progesterone, LH, and FSH; P < 0.05) and positively associated with the risk of anovulation (P = 0.003) by using random-effects models with adjustment for total calories, age, race, and vitamin E intake. Each 5-g/d increase in total fiber intake was associated with a 1.78-fold increased risk (95% CI: 1.11, 2.84) of an anovulatory cycle. The adjusted odds ratio of 5 g fruit fiber/d was 3.05 (95% CI: 1.07, 8.71). CONCLUSIONS These findings suggest that a diet high in fiber is significantly associated with decreased hormone concentrations and a higher probability of anovulation. Further study of the effect of fiber on reproductive health and of the effect of these intakes in reproductive-aged women is warranted.

Endogenous Reproductive Hormones and C-reactive Protein Across the Menstrual Cycle The BioCycle Study

C-reactive protein (CRP) is one of the most commonly used markers of acute phase reaction in clinical settings and predictors of cardiovascular risk in healthy women; however, data on its physiologic regulation in premenopausal women are sparse. The objective of this study was to evaluate the association between endogenous reproductive hormones and CRP in the BioCycle Study (2005-2007). Women aged 18-44 years from western New York were followed prospectively for up to 2 menstrual cycles (n = 259). Serum levels of CRP, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to 8 times per cycle, timed by fertility monitors. CRP levels varied significantly across the cycle (P < 0.001). More women were classified as being at elevated risk of cardiovascular disease (CRP, >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%; P < 0.001). A 10-fold increase in estradiol was associated with a 24.3% decrease in CRP (95% confidence interval: 19.3, 29.0). A 10-fold increase in luteal progesterone was associated with a 19.4% increase in CRP (95% confidence interval: 8.4, 31.5). These results support the hypothesis that endogenous estradiol might have antiinflammatory effects and highlight the need for standardization of CRP measurement to menstrual cycle phase in reproductive-aged women.

Age at Menarche and Metabolic Markers for Type 2 Diabetes in Premenopausal Women: The BioCycle Study

CONTEXT Early age at menarche has been linked to an elevated risk of type 2 diabetes. However, the underlying mechanism is unclear. OBJECTIVE Our objective was to examine associations between age at menarche and type 2 diabetes risk factors. DESIGN, PARTICIPANTS, AND SETTING The BioCycle Study followed 253 healthy premenopausal women from the general population (Buffalo, NY) for one to two menstrual cycles. MAIN OUTCOME MEASURES Age at menarche was self-reported. Body mass index and waist circumference were measured by trained personnel. Total body and trunk fat were measured by dual-energy x-ray absorptiometry. Fasting glucose, insulin, highly sensitive C-reactive protein, and SHBG levels were measured up to eight times per cycle. Insulin resistance (IR) and β-cell function were evaluated using the homeostasis model assessment (HOMA)-IR and HOMA-β. RESULTS The mean age at menarche was 12.5 ± 1.2 yr. After adjustment for age, race, education, and physical activity, early menarche (≤12 yr) was significantly associated with an increase of 1.35 kg/m(2) in body mass index (P = 0.01), 2.52% in percent total body fat (P = 0.004), 3.02% in percent trunk fat (P = 0.004), 0.15 μIU/ml in (log)insulin (P = 0.02), 0.15 U in (log)HOMA-IR (P = 0.03), and 0.16 U in (log)HOMA-β (P = 0.01) compared with average menarche (12-14 yr). No associations were found for SHBG or highly sensitive C-reactive protein. CONCLUSIONS Early onset of menarche is associated with unfavorable metabolic phenotypes compared with average onset of menarche in healthy premenopausal women, including reduced insulin sensitivity and β-cell function and greater total and trunk fat.

Longitudinal Study of Insulin Resistance and Sex Hormones over the Menstrual Cycle: The BioCycle Study

CONTEXT Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity. OBJECTIVE The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns. DESIGN The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes. SETTING The study was conducted in the general community of the University at Buffalo (Buffalo, NY). PARTICIPANTS A total of 257 healthy, premenopausal women (age, 27±8 yr; body mass index, 24±4 kg/m2) participated in the study. MAIN OUTCOME MEASURES We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR). RESULTS Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (β=0.082; P<0.001) and progesterone (β=0.025; P<0.001), and inversely associated with FSH (adjusted β=-0.040; P<0.001) and SHBG (β=-0.085; P<0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (β=-0.057; P=0.06) but did not affect other associations. CONCLUSION Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women.

Biological variability in serum anti-Müllerian hormone throughout the menstrual cycle in ovulatory and sporadic anovulatory cycles in eumenorrheic women

STUDY QUESTION Does serum anti-Müllerian hormone (AMH) vary significantly throughout both ovulatory and sporadic anovulatory menstrual cycles in healthy premenopausal women? SUMMARY ANSWER Serum AMH levels vary statistically significantly across the menstrual cycle in both ovulatory and sporadic anovulatory cycles of healthy eumenorrheic women. WHAT IS KNOWN ALREADY Studies to date evaluating serum AMH levels throughout the menstrual cycle have conflicting results regarding intra-woman cyclicity. No previous studies have evaluated an association between AMH and sporadic anovulation. STUDY DESIGN, SIZE, DURATION We conducted a prospective cohort study of 259 regularly menstruating women recruited between 2005 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18-44 years were followed for one (n = 9) or two (n = 250) menstrual cycles. Anovulatory cycles were defined as any cycle with peak progesterone concentration ≤5 ng/ml and no serum LH peak on the mid or late luteal visits. Serum AMH was measured at up to eight-time points throughout each cycle. MAIN RESULTS AND THE ROLE OF CHANCE Geometric mean AMH levels were observed to vary across the menstrual cycle (P < 0.01) with the highest levels observed during the mid-follicular phase at 2.06 ng/ml, decreasing around the time of ovulation to 1.79 ng/ml and increasing thereafter to 1.93 (mid-follicular versus ovulation, P < 0.01; ovulation versus late luteal, P = 0.01; mid-follicular versus late luteal, P = 0.05). Patterns were similar across all age groups and during ovulatory and anovulatory cycles, with higher levels of AMH observed among women with one or more anovulatory cycles (P = 0.03). LIMITATIONS, REASONS FOR CAUTION Ovulatory status was not verified by direct visualization. AMH was analyzed using the original Generation II enzymatically amplified two-site immunoassay, which has been shown to be susceptible to assay interference. Thus, absolute levels should be interpreted with caution, however, patterns and associations remain consistent and any potential bias would be non-differential. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrates a significant variation in serum AMH levels across the menstrual cycle regardless of ovulatory status. This variability, although statistically significant, is not large enough to warrant a change in current clinical practice to time AMH measurements to cycle day/phase. STUDY FUNDING/COMPETING INTERESTS This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD (Contracts # HHSN275200403394C, HHSN275201100002I Task 1 HHSN27500001). The authors have no conflicts of interest to declare.

Dietary Restraint and Gestational Weight Gain

OBJECTIVE To determine whether a history of preconceptional dieting and restrained eating was related to higher weight gains in pregnancy. DESIGN Dieting practices were assessed among a prospective cohort of pregnant women using the Revised Restraint Scale. Women were classified on three separate subscales as restrained eaters, dieters, and weight cyclers. SUBJECTS Participants included 1,223 women in the Pregnancy, Infection, and Nutrition Study. MAIN OUTCOME MEASURES Total gestational weight gain and adequacy of weight gain (ratio of observed/expected weight gain based on Institute of Medicine recommendations). STATISTICAL ANALYSES PERFORMED Multiple linear regression was used to model the two weight-gain outcomes, while controlling for potential confounders including physical activity and weight-gain attitudes. RESULTS There was a positive association between each subscale and total weight gain, as well as adequacy of weight gain. Women classified as cyclers gained an average of 2 kg more than noncyclers and showed higher observed/expected ratios by 0.2 units. Among restrained eaters and dieters, there was a differential effect by body mass index. With the exception of underweight women, all other weight status women with a history of dieting or restrained eating gained more weight during pregnancy and had higher adequacy of weight gain ratios. In contrast, underweight women with a history of restrained eating behaviors gained less weight compared to underweight women without those behaviors. CONCLUSIONS Restrained eating behaviors were associated with weight gains above the Institute of Medicines recommendations for normal, overweight, and obese women, and weight gains below the recommendations for underweight women. Excessive gestational weight gain is of concern because of its association with postpartum weight retention. The dietary restraint tool is useful for identifying women who would benefit from nutritional counseling prior to or during pregnancy with regard to achieving targeted weight-gain recommendations.

Adherence to a Mediterranean diet and plasma concentrations of lipid peroxidation in premenopausal women

BACKGROUND A Mediterranean diet has been associated with a reduced risk of cardiovascular disease and mortality. A possible mechanism is through a decrease in lipid peroxidation (LPO); however, evidence linking the Mediterranean diet with lower LPO in premenopausal women is sparse. OBJECTIVE We investigated whether adherence to a Mediterranean diet was associated with lower LPO concentrations in premenopausal women. DESIGN Two hundred fifty-nine healthy women aged 18-44 y were followed for ≤ 2 menstrual cycles. Plasma concentrations of F(2)-isoprostane (8-iso-PGF2α), 9-hydroxyoctadecadieneoic acid (9-HODE), and thiobarbituric acid reactive substances (TBARS) were measured ≤ 8 times per cycle at visits scheduled by using fertility monitors. Diet was assessed ≤ 4 times per cycle by using 24-h dietary recalls. The alternate Mediterranean Diet Score (aMED) (range: 0-9) was calculated on the basis of intake of vegetables, legumes, fruit, nuts, whole grains, red and processed meat, fish, and alcohol and the ratio of monounsaturated to saturated fat. RESULTS A 1-unit increase in aMED was associated with a 4.50% decrease in 8-iso-PGF2α concentrations (95% CI: -6.32%, -2.65%) and a 14.01% decrease in 9-HODE concentrations (95% CI: -17.88%, -9.96%) after adjustment for energy intake, age, race, body mass index, plasma ascorbic acid, and serum cholesterol. No significant association was observed between aMED and TBARS. A 1-unit increase in aMED was associated with a 1.39% increase (95% CI: 0.07%, 2.72%) in plasma ascorbic acid concentrations. CONCLUSIONS Adherence to a Mediterranean diet is associated with lower LPO and higher ascorbic acid concentrations. These results confirm that decreased LPO is a plausible mechanism linking a Mediterranean diet to reduced cardiovascular disease risk.

Whole Grains Are Associated with Serum Concentrations of High Sensitivity C-Reactive Protein among Premenopausal Women

In premenopausal women, elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of negative reproductive outcomes. Whole grain consumption has been associated with lower CRP concentrations in older women; however, less is known about this relationship in younger women. We investigated whether whole grain intake was associated with serum high sensitivity CRP (hs-CRP) concentrations in young women. BioCycle was a prospective cohort study conducted at the University of Buffalo from 2005 to 2007, which followed 259 healthy women aged 18-44 y for <or= 2 menstrual cycles. hs-CRP concentrations were measured longitudinally <or= 8 times/cycle with visits standardized to menstrual cycle phase. Whole grain intake was estimated by 24-h recalls <or= 4 times/cycle. Servings were defined as 16 g or 125 mL of a 100% whole grain food. Whole grain intake was inversely associated with hs-CRP concentrations after adjusting for age, race, BMI, illness, and antiinflammatory drug use. Consumers of between 0 and 1 serving/d of whole grains had, on average, 11.5% lower hs-CRP concentrations (P = 0.02) and consumers of >or= 1 serving/d had 12.3% lower hs-CRP concentrations (P = 0.02) compared with nonconsumers. Women who consumed >or= 1 serving/d of whole grain had a lower probability of having moderate (P = 0.008) or elevated (P = 0.001) hs-CRP according to the AHA criteria compared with nonconsumers. Given that elevated concentrations of hs-CRP have been linked to adverse reproductive outcomes and pregnancy complications, interventions targeting whole grain consumption may have the potential to improve health status among young women.

Influence of endogenous reproductive hormones on F2-isoprostane levels in premenopausal women: the BioCycle Study.

Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F(2)-isoprostanes in the BioCycle Study. Women aged 18-44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005-2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F(2)-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F(2)-Isoprostane levels had an independent positive association with estradiol (beta = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (beta = -0.04, 95% confidence interval: -0.07, -0.003; beta = -0.02, 95% confidence interval: -0.03, -0.002, respectively) after adjustment for age, race, age at menarche, gamma-tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F(2)-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.