First name
Chris
Last name
Gennings

Title

Bacterial and cytokine mixtures predict the length of gestation and are associated with miRNA expression in the cervix.

Year of Publication

2017

Number of Pages

33-45

Date Published

2017 01

ISSN Number

1750-192X

Abstract

<p><strong>AIM: </strong>Bacterial vaginosis may lead to preterm birth through epigenetic programming of the inflammatory response, specifically via miRNA expression.</p>

<p><strong>METHODS: </strong>We quantified bacterial 16S rRNA, cytokine mRNA and 800 miRNA from cervical swabs obtained from 80 women at 16-19 weeks' gestation. We generated bacterial and cytokine indices using weighted quantile sum regression and examined associations with miRNA and gestational age at delivery.</p>

<p><strong>RESULTS &amp; DISCUSSION: </strong>Each decile of the bacterial and cytokine indices was associated with shorter gestations (p &lt; 0.005). The bacterial index was associated with miR-494, 371a, 4286, 185, 320e, 888 and 23a (p &lt; 0.05). miR-494 remained significant after false discovery rate correction (q &lt; 0.1). The cytokine index was associated with 27 miRNAs (p &lt; 0.05; q &lt; 0.01).</p>

<p><strong>CONCLUSION: </strong>Future investigation into the role of bacterial vaginosis- and inflammation-associated miRNA and preterm birth is warranted.</p>

DOI

10.2217/epi-2016-0095

Alternate Title

Epigenomics

PMID

27936911

Title

Prenatal Stress, Methylation in Inflammation-Related Genes, and Adiposity Measures in Early Childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study.

Year of Publication

2018

Number of Pages

34-41

Date Published

2018 01

ISSN Number

1534-7796

Abstract

<p><strong>OBJECTIVE: </strong>Maternal stress during pregnancy may influence childhood growth and adiposity, possibly through immune/inflammatory programming. We investigated whether exposure to prenatal stress and methylation in inflammation-related genes were associated with childhood adiposity in 424 mother-child pairs in Mexico City, Mexico.</p>

<p><strong>METHODS: </strong>A stress index was created based on four prenatally administered stress-related scales (Exposure to Violence, Crisis in Family Systems, State-Trait Anxiety Inventory, and Edinburgh Postnatal Depression Scale). We measured weight, height, body fat mass (BFM), percentage body fat (PBF), and waist circumference in early childhood (age range, 4-6 years). Body mass index (BMI) z scores were calculated according to World Health Organization standards. DNA methylation in gene promoters of tumor necrosis factor α, interleukin 8, and interleukin 6 (IL6) in umbilical cord blood were determined by pyrosequencing.</p>

<p><strong>RESULTS: </strong>An interquartile range increase in stress index (27.3) was associated with decreases of 0.14 unit in BMI z score (95% confidence interval [CI] = -0.28 to -0.005), 5.6% in BFM (95% CI = -9.7 to -1.4), 3.5% in PBF (95% CI = -6.3 to -0.5), and 1.2% in waist circumference (95% CI = -2.4 to -0.04) in multivariable-adjusted models. An interquartile range increase in IL6 methylation (3.9%) was associated with increases of 0.23 unit in BMI z score (95% CI = 0.06-0.40), 8.1% (95% CI = 2.3-14.3) in BFM, 5.5% (95% CI = 1.7-9.5) in PBF, and 1.7% (95% CI = 0.2-3.3) in waist circumference.</p>

<p><strong>CONCLUSIONS: </strong>Prenatal stress was associated with decreased childhood adiposity, whereas cord blood IL6 methylation was associated with increased childhood adiposity in Mexican children.</p>

DOI

10.1097/PSY.0000000000000517

Alternate Title

Psychosom Med

PMID

28787364

Title

Prenatal lead exposure modifies the effect of shorter gestation on increased blood pressure in children.

Year of Publication

2018

Number of Pages

464-471

Date Published

2018 Aug 23

ISSN Number

1873-6750

Abstract

<p><strong>BACKGROUND: </strong>High blood pressure (BP) in childhood is frequently renal in origin and a risk factor for adult hypertension and cardiovascular disease. Shorter gestations are a known risk factor for increased BP in adults and children, due in part to a nephron deficit in children born preterm. As nephrogenesis is incomplete until 36 weeks gestation, prenatal lead exposure occurring during a susceptible period of renal development may contribute to programming for later life renal disease. The relationship between shorter gestation and children's BP has not yet been explored to identify i) critical windows using nonlinear piecewise models or ii) combined with other early life risk factors such as prenatal lead exposure.</p>

<p><strong>OBJECTIVES: </strong>(1) To evaluate the nonlinear relationship between lower gestational age and childhood BP measured at 4-6 years of age, and (2) to investigate modification by prenatal lead exposure.</p>

<p><strong>METHODS: </strong>In a prospective longitudinal birth cohort, we assessed 565 children between 4 and 6 years of age (mean: 4.8 years) in the PROGRESS cohort in Mexico City, Mexico. Gestational age at delivery was calculated using maternal report of last menstrual period (LMP) and confirmed with Capurro physical examination at birth. We measured pregnant women's blood lead levels (BLLs) in the second trimester via inductively coupled plasma-mass spectrometry and children's BP using an automated device. We performed both linear and nonlinear piecewise regression analyses to examine associations of gestational age with children's BP adjusting for children's age, sex, height, prenatal exposure to smoke, and maternal socioeconomic status. We stratified to assess modification by prenatal lead exposure, and used a data-adaptive approach to identify a lead cutpoint.</p>

<p><strong>RESULTS: </strong>Maternal second trimester BLLs ranged from 0.7 to 17.8 μg/dL with 112 (20%) women above the CDC guideline level of 5 μg/dL. In adjusted linear regression models, a one week reduction in gestational age was associated with a 0.5 mm Hg (95%CI: 0.2, 0.8) increase in SBP and a 0.4 mm Hg (95%CI 0.1, 0.6) increase in DBP. Our nonlinear models suggested evidence for different magnitude estimates on either side of an estimated join-point at 35.9 weeks' gestation, but did not reach statistical significance. However, when stratified by prenatal lead exposure, we identified a cutpoint lead level of concern of 2.5 μg/dL that suggested an interaction between gestational age and blood lead. Specifically, for BLLs ≥ 2.5 μg/dL, SBP was 1.6 (95%CI: 0.3, 2.9) mm Hg higher per each week reduction in gestational age among children born before 37.0 weeks; and among children born after 37.0 weeks, this relationship was attenuated yet remained significant [β: 0.9, 95%CI (0.2, 1.6)]. At BLLs below 2.5 μg/dL, there was no appreciable association between lower gestational age and SBP.</p>

<p><strong>CONCLUSIONS: </strong>Our findings suggest that shorter gestation combined with higher prenatal lead exposure contributes to a higher risk of increased SBP at 4-6 years of age, particularly among infants born &lt;37 weeks gestation. Our results underscore the importance of preventing prenatal lead exposure - even levels as low as 2.5 μg/dL - especially among pregnant women at risk for preterm birth. Given that high BP in childhood is a risk factor for adult hypertension and cardiovascular disease later in life, these results may have implications that extend across the life span.</p>

DOI

10.1016/j.envint.2018.08.038

Alternate Title

Environ Int

PMID

30145310

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