Browsing by Author "Hinkle, Stefanie N."

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    Lactation Duration and Long-Term Thyroid Function: A Study among Women with Gestational Diabetes
    (MDPI, 2018-07-21) Panuganti, Pranati L.; Hinkle, Stefanie N.; Rawal, Shristi; Grunnet, Louise G.; Lin, Yuan; Liu, Aiyi; Thuesen, Anne C.B.; Ley, Sylvia H.; Olesen, Sjurdur F.; Zhang, Cuilin; Epidemiology, School of Public Health
    Lactation is associated with reduced postpartum weight retention and a lower risk of several cardiometabolic disorders in population-based studies. We examined the association between lactation and long-term thyroid function among women with history of gestational diabetes mellitus (GDM), a high-risk population for subsequent metabolic complications. The study included 550 women who developed GDM in the Danish National Birth Cohort (1996⁻2002) and followed-up in the Diabetes & Women's Health Study (2012⁻2014). We assessed adjusted associations between cumulative lactation duration and concentrations of thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) measured at follow-up. Women with longer cumulative lactation duration tended to have higher fT3 levels (adjusted β and 95% confidence interval (CI) for ≥12 months vs. none: 0.19 (0.03⁻0.36); p-trend = 0.05). When restricted to women with a single lifetime pregnancy to control for parity (n = 70), women who lactated for >6 months (vs. none) had higher fT3 levels (0.46 pmol/L (0.12⁻0.80); p-trend = 0.02) and a higher fT3:fT4 ratio (0.61 (0.17⁻1.05); p-trend = 0.007). Our findings suggested that a longer duration of lactation may be related to greater serum fT3 levels and fT3:fT4 ratio 9⁻16 years postpartum among Danish women with a history of GDM. The association was particularly pronounced among women who only had one lifetime pregnancy.
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    Longitudinal Plasma Metabolomics Profile in Pregnancy—A Study in an Ethnically Diverse U.S. Pregnancy Cohort
    (MDPI, 2021-09-01) Mitro, Susanna D.; Wu, Jing; Rahman, Mohammad L.; Cao, Yaqi; Zhu, Yeyi; Chen, Zhen; Chen, Liwei; Li, Mengying; Hinkle, Stefanie N.; Bremer, Andrew A.; Weir, Natalie L.; Tsai, Michael Y.; Song, Yiqing; Grantz, Katherine L.; Gelaye, Bizu; Zhang, Cuilin; Epidemiology, School of Public Health
    Amino acids, fatty acids, and acylcarnitine metabolites play a pivotal role in maternal and fetal health, but profiles of these metabolites over pregnancy are not completely established. We described longitudinal trajectories of targeted amino acids, fatty acids, and acylcarnitines in pregnancy. We quantified 102 metabolites and combinations (37 fatty acids, 37 amino acids, and 28 acylcarnitines) in plasma samples from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n = 214 women at 10-14 and 15-26 weeks, 107 at 26-31 weeks, and 103 at 33-39 weeks). We used linear mixed models to estimate metabolite trajectories and examined variation by body mass index (BMI), race/ethnicity, and fetal sex. After excluding largely undetected metabolites, we analyzed 77 metabolites and combinations. Levels of 13 of 15 acylcarnitines, 7 of 25 amino acids, and 18 of 37 fatty acids significantly declined over gestation, while 8 of 25 amino acids and 10 of 37 fatty acids significantly increased. Several trajectories appeared to differ by BMI, race/ethnicity, and fetal sex although no tests for interactions remained significant after multiple testing correction. Future studies merit longitudinal measurements to capture metabolite changes in pregnancy, and larger samples to examine modifying effects of maternal and fetal characteristics.
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    Metabolic Biomarkers of Mediterranean Diet in Pregnant Women
    (Elsevier, 2021) Dai, Jin; Chen, Liwei; Fei, Zhe; Liu, Xinyue; Zhu, Yeyi; Hinkle, Stefanie N.; Wu, Jing; Lu, Ruijin; Rahman, Mohammad L.; Chen, Zhen; Song, Yiqing; Zhang, Cuilin; Epidemiology, Richard M. Fairbanks School of Public Health
    Objectives: Using an untargeted approach to identify plasma metabolomics signature of the Mediterranean diet, a healthful dietary pattern related to both maternal and fetal outcomes, in pregnancy. Methods: This study included 193 pregnant women from the NICHD Fetal Growth Studies-Singletons (FGS) cohort who had habitual dietary intake in the past three months measured at 8–13 gestational weeks (GW) by the semi-quantified food frequency questionnaire. Fasting plasma metabolomics profiles at 15–26 GW were measured by the high-throughput liquid chromatography quadrupole time of-flight mass spectrometry (LC-QTOF MS/MS). Metabolites were re-scaled to a median of 1 for each batch and log transformed. Alternate Mediterranean Diet (aMED) score was calculated by eight food and nutrient components (i.e., fruits, vegetables, whole grains, nuts, fish, legumes, red and processed meats, and monounsaturated-to-saturated fat ratio), with a higher score indicating a better adherence. Prospective associations of aMED score in peri-conception and early pregnancy with individual metabolites at 15–26 GW were estimated using the linear regression adjusting for potential confounders and multiple testing. LASSO (Least Absolute Shrinkage and Selection Operator) regression with 10-fold cross-validation was performed to select metabolites that were jointly associated with high aMED score (defined as the top tertile). All statistical analyses were weighted to represent the entire FGS cohort. Results: A total of 460 known metabolites were profiled and annotated. Six metabolites were selected as the biomarkers of high aMED score by the LASSO regression (i.e., with no-zero coefficients). Among them, glutamic acid and 3-hydroxybutyric acid were negatively whereas PC (40:7), CE (20:5), TG (49:1), and TG (58:4) were positively associated with aMED score. The six biomarkers were also confirmed by the linear regression with false discovery rates < 0.1. Conclusions: Our study is the first one conducted in pregnant women using the untargeted metabolomics approach and we newly identified several biomarkers of Mediterranean diet in pregnant women. Results from this study warrant the replication by future studies.
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    Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort
    (MDPI, 2021-12-17) Song, Yiqing; Lyu, Chen; Li, Ming; Rahman, Mohammad L.; Chen, Zhen; Zhu, Yeyi; Hinkle, Stefanie N.; Chen, Liwei; Mitro, Susanna D.; Li, Ling-Jun; Weir, Natalie L.; Tsai, Michael Y.; Zhang, Cuilin; Epidemiology, School of Public Health
    As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10-14, 15-26, 23-31, and 33-39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5-DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (-475 g; 95% CI, -942, -6.79), birthweight z score (-0.39, -0.71, -0.06), and birth length (-1.38 cm, -2.49, -0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.
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    Vitamin D Status during Pregnancy and the Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort
    (Wiley, 2019) Xia, Jin; Song, Yiqing; Rawal, Shristi; Wu, Jing; Hinkle, Stefanie N.; Tsai, Michael Y.; Zhang, Cuilin; Epidemiology, School of Public Health
    Aims Emerging evidence suggests that maternal vitamin D status may be associated with gestational diabetes (GDM). However, the temporal relation remains unclear due to the lack of longitudinal data on vitamin D over pregnancy. We aimed to prospectively and longitudinally investigate vitamin D status during early to mid‐pregnancy in relation to GDM risk. Methods In a nested case‐control study of 107 GDM cases and 214 controls within the Fetal Growth Studies‐Singleton Cohort, plasma levels of 25‐hydroxyvitamin D2 and D3 (25(OH)D) and vitamin D binding protein were measured at gestational weeks 10‐14, 15‐26, 23‐31, and 33‐39; we further calculated total, free, and bioavailable 25(OH)D. Conditional logistic regression models and linear mixed‐effects models were used. Results We observed a threshold effect for the relation of vitamin D biomarkers with GDM risk. Vitamin D deficiency (<50 nmol/L) at 10‐14 gestational weeks was associated with a 2.82‐fold increased risk for GDM [odds ratio (OR) =2.82, 95% confidence interval (CI): 1.15‐6.93]. Women with persistent vitamin D deficiency at 10‐14 and 15‐26 weeks of gestation had a 4.46‐fold elevated risk for GDM compared to women persistently non‐deficient (OR=4.46, 95% CI: 1.15‐17.3). Conclusions Maternal vitamin D deficiency as early as the first trimester of pregnancy was associated with an elevated risk of GDM. The association was stronger for women who were persistently deficient through the 2nd trimester. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for improving risk stratification and developing effective interventions for the primary prevention of GDM.