Placental pathology, corticotropin-releasing hormone, timing of parturition, and fetal growth in the pregnancy outcomes and community health study

Background: Identification of vascular pathologies in delivered placentas and their associations with biomarkers measured during pregnancy may elucidate mechanisms of adverse pregnancy outcomes and inform early detection and intervention strategies. Objectives: To examine associations of placental vascular pathology with birth size and timing of parturition, and to evaluate maternal midpregnancy serum corticotropin-releasing hormone (CRH) levels as a marker of the above associations. Study design: The pregnancy outcomes and community health (POUCH) Study enrolled women at 16–27 weeks of pregnancy from five Michigan communities. Histological assessments of delivered placentas and assays of CRH in maternal blood sampled at enrollment were performed in a subcohort of 1152 participants. Five placental vascular pathology constructs were formulated: Maternal–Vascular-Obstructive (MVO), Fetal Vascular–Obstructive (FVO), Maternal Vascular–disturbance of Integrity (MVI), Fetal Vascular–disturbance of Integrity (FVI), and Maternal Vascular–Developmental (MVD). A four-level outcome variable combined small for gestational (SGA) yes/no and delivery timing preterm/term; the non-SGA/term served as the referent group. In multinomial logistic regression models, the five vascular pathology groups were evaluated in relation to the outcome variable and effect sizes were compared before versus after exclusion of participants with high CRH (top quartile). Results: Adjusted odds ratios (aOR) for MVO among SGA/term and SGA/preterm were 4.1 (95% CI: 2.2, 7.9) and 8.8 (95% CI: 3.3, 23.5) respectively. Among SGA/preterm births, the aOR was attenuated by ∼40%, i.e. 5.4 (95% CI: 1.1, 26.2) after removing high CRH pregnancies. MVI and FVO were each associated with SGA/preterm, aOR = 3.7 (95% CI: 1.3, 10.3) and 10.5 (95% CI: 3.6, 30.8) respectively. Removal of high CRH pregnancies reduced the OR estimates by nearly half, i.e. MVI aOR = 1.9 (95% CI: 0.34, 10.9), FVO aOR = 6.0 (95% CI: 1.3, 28.6). MVI, FVI and MVD were each associated with greater odds of non-SGA/preterm, but the aORs showed little change after removing high CRH pregnancies. Conclusions: Obstructive placental vascular pathologies in maternal or fetal vessels are associated with SGA. High CRH levels coincided with a portion of pregnancies that share these complications, particularly among pregnancies that also ended prematurely.</p

Supplemental Table 1 from Applications of conceptual models from lifecourse epidemiology in ecology and evolutionary biology

Select additional examples of study systems for testing lifecourse conceptual models

Change in height-for-age in 553 school-age children from Bogotá, Colombia, according to quartiles of LINE-1 DNA methylation¹.

1<p>Height-for-age Z-scores were determined using the World Health Organization growth reference for children 5–19 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-deOnis2" target="_blank">[30]</a>.</p>2<p>For a test of linear trend when a variable that represented quartiles was introduced into a linear regression model as a continuous predictor (Wald test).</p>3<p>Values are mean ± SD.</p>4<p>Values are mean ± SE.</p>5<p>Adjusted for baseline age and socioeconomic status.</p

Change in adiposity indicators in 299 school-age girls from Bogotá, Colombia, according to quartiles of LINE-1 DNA methylation.

1<p>For a test of linear trend when a variable that represented the median value of each quartile was introduced into a linear regression model as a continuous predictor (Wald test).</p>2<p>According to the World Health Organization growth reference for children 5–19 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-deOnis2" target="_blank">[30]</a>.</p>3<p>Values are means ± SD.</p>4<p>Values are means ± SE.</p>5<p>Adjusted for baseline age and socioeconomic status.</p>6<p>Age-standardized using the LMS method with data for boys 5–16 years of age in NHANES III <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-1" target="_blank">[32]</a>.</p>7<p>Subscapular-to-tricipital skinfold thickness ratio.</p

Characteristics of 553 school-age children from Bogotá, Colombia by quartiles of LINE-1 methylation¹.

1<p>Values are mean ± SD unless otherwise noted.</p>2<p>Total is <553 due to missing values.</p>3<p>According to the World Health Organization 2007 growth reference for children 5–19 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-deOnis2" target="_blank">[30]</a>.</p>4<p>Stratum 1 of a maximum of 4, according to the local government classification for tax and planning purposes.</p

Change in adiposity indicators in 254 school-age boys from Bogotá, Colombia, according to quartiles of LINE-1 DNA methylation.

1<p>For a test of linear trend when a variable that represented the median value of each quartile was introduced into a linear regression model as a continuous predictor (Wald test).</p>2<p>According to the World Health Organization growth reference for children 5–19 years <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-deOnis2" target="_blank">[30]</a>.</p>3<p>Values are means ± SD.</p>4<p>Values are means ± SE.</p>5<p>Adjusted for baseline age and socioeconomic status.</p>6<p>Age-standardized using the LMS method with data for boys 5–16 years of age in NHANES III <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0062587#pone.0062587-1" target="_blank">[32]</a>.</p>7<p>Subscapular-to-tricipital skinfold thickness ratio.</p

Additional file 3 of Association of total lifetime breastfeeding duration with midlife handgrip strength: findings from Project Viva

Additional file 3.Table S2: Associations of lifetime breastfeeding duration (BFD) with dominant and nondominant handgrip strength among N=304 women who were nulliparous at enrollment

Additional file 2 of Association of total lifetime breastfeeding duration with midlife handgrip strength: findings from Project Viva

Additional file 2. Table S1: Characteristics of Project Viva participants included vs excluded from this analysis

Metabolic trajectories across early adolescence: differences by sex, weight, pubertal status and race/ethnicity

Background: Biomarkers of cardiovascular and metabolic risk track from adolescence into adulthood, therefore characterising the direction and magnitude of these changes is an important first step to identifying health trajectories that presage future disease risk. Aim: To characterise changes in metabolic biomarkers across early adolescence in a multi-ethnic cohort. Subjects and methods: Among 891 participants in Project Viva we estimated changes in insulin resistance (HOMA-IR), adipokines, lipids, and SBP between ages 6–10 years and 11–16 years. Next, we used multivariable linear regression to examine associations of sex, baseline overweight/obesity, baseline pubertal status and race/ethnicity with change in the biomarkers during follow-up. Results: Boys exhibited a larger decrement in adiponectin (−0.66 [95% CI = −1.14, −0.18)] ng/mL) and a greater increase in SBP (3.20 [2.10, 4.30] mmHg) than girls. Overweight/obese participants experienced larger increases in HOMA-IR, leptin, and triglycerides; and a steeper decrement in HDL. Pubertal youth showed larger decrements in total and LDL cholesterol than their pre-pubertal counterparts. In comparison to White participants, Black youth experienced a larger magnitude of increase in HOMA-IR, and Hispanic youth exhibited larger decrements in adiponectin and HDL. Conclusions: Change in metabolic biomarkers across early adolescence differed by sex, weight status, pubertal status and race/ethnicity. Some of the metabolic changes may reflect normal physiological changes of puberty, while others may presage future disease risk. Future studies are warranted to link metabolic changes during adolescence to long-term health.</p

Additional file 1 of History of infertility and pregnancy outcomes in Project Viva: a prospective study

Additional file 1: Table S1. Distributions of pregnancy outcomes by history of infertility for the index pregnancy (n = 2201). Table S2. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, excluding 39 women with PCOS. Table S3. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, according to the use of MAR and excluding 39 women with PCOS. Table S4. Unadjusted and adjusted β coefficients for systolic blood pressure in women with vs. without infertility, according to the use of MAR and type of medication, excluding 39 women with PCOS. Figure S1. Conceptual Directed Acyclic Graph depicting the variables under study