First name
Rachel
Last name
Ledyard

Title

Cervical microRNA expression and spontaneous preterm birth.

Year of Publication

2023

Number of Pages

100783

Date Published

01/2023

ISSN Number

2589-9333

Abstract

BACKGROUND: Preterm birth remains a major public health issue affecting 10% of all pregnancies and increases risks of neonatal morbidity and mortality. Approximately 50% to 60% of preterm births are spontaneous, resulting from preterm premature rupture of membranes or preterm labor. The pathogenesis of spontaneous preterm birth is incompletely understood, and prediction of preterm birth remains elusive. Accurate prediction of preterm birth would reduce infant morbidity and mortality through targeted patient referral to hospitals equipped to care for preterm infants. Two previous studies have analyzed cervical microRNAs in association with spontaneous preterm birth and the length of gestation, but the extent to which microRNAs serve as predictive biomarkers remains unknown.

OBJECTIVE: This study aimed to examine associations between cervical microRNA expression and spontaneous preterm birth, with the specific goal of identifying a subset of microRNAs that predict spontaneous preterm birth.

STUDY DESIGN: We performed a prospective, nested, case-control study of 25 cases with spontaneous preterm birth and 49 term controls. Controls were matched to cases in a 2:1 ratio on the basis of age, parity, and self-identified race. Cervical swabs were collected at a mean gestational age of 17.1 (4.8) weeks of gestation, and microRNAs were analyzed using a quantitative polymerase chain reaction array. Normalized microRNA expression was compared between cases and controls, and a false discovery rate of 0.2 was applied to account for multiple comparisons. Histopathologic analysis of slides of cervical swab samples was performed to quantify leukocyte burden for adjustment in conditional regression models. We explored the use of Relief-based unsupervised identification of top microRNAs and support vector machines to predict spontaneous preterm birth. We performed microRNA enrichment analysis to explore potential biologic targets and pathways in which up-regulated microRNAs might be involved.

RESULTS: Of the 754 microRNAs on the polymerase chain reaction array, 346 were detected in ≥75% of participants' cervical swabs. Average cervical microRNA expression was significantly higher in cases of spontaneous preterm birth than in controls (P=.01). There were 95 significantly up-regulated individual microRNAs (>2-fold change) in cases of subsequent spontaneous preterm birth compared with term controls (P<.05; q<0.2). Notably, miR-143, miR-30e-3p, and miR-199b were all significantly up-regulated, which is consistent with the 1 previous study of cervical microRNA and spontaneous preterm birth. A Relief-based, novel variable (feature) selection machine learning approach had low-to-moderate prediction accuracy, with an area under the receiver operating curve of 0.71. Enrichment analysis revealed that identified microRNAs may modulate inflammatory cell signaling.

CONCLUSION: In this prospective nested case-control study of cervical microRNA expression and spontaneous preterm birth, we identified a global increase in microRNA expression and up-regulation of 95 distinct microRNAs in association with subsequent spontaneous preterm birth. Larger and more diverse studies are required to determine the ability of microRNAs to accurately predict spontaneous preterm birth, and mechanistic work to facilitate development of novel therapeutic interventions to prevent spontaneous preterm birth is warranted.

DOI

10.1016/j.ajogmf.2022.100783

Alternate Title

Am J Obstet Gynecol MFM

PMID

36280145

Title

Benzene and NO Exposure during Pregnancy and Preterm Birth in Two Philadelphia Hospitals, 2013-2017.

Year of Publication

2022

Date Published

08/2022

ISSN Number

1660-4601

Abstract

Infants born preterm are at risk of neonatal morbidity and mortality. Preterm birth (PTB) can be categorized as either spontaneous (sPTB) or medically indicated (mPTB), resulting from distinct pathophysiologic processes such as preterm labor or preeclampsia, respectively. A growing body of literature has demonstrated the impacts of nitrogen dioxide (NO) and benzene exposure on PTB, though few studies have investigated how these associations may differ by PTB subtype. We investigated the associations of NO and benzene exposure with sPTB and mPTB among 18,616 singleton live births at two Philadelphia hospitals between 2013 and 2017. Residential NO exposure was estimated using a land use regression model and averaged over the patient's full pregnancy. Benzene exposure was estimated at the census tract level using National Air Toxics Assessment (NATA) exposure data from 2014. We used logistic mixed-effects models to calculate odds ratios for overall PTB, sPTB, and mPTB separately, adjusting for patient- and tract-level confounders. Given the known racial segregation and PTB disparities in Philadelphia, we also examined race-stratified models. Counter to the hypothesis, neither NO nor benzene exposure differed by race, and neither were significantly associated with PTB or PTB subtypes. As such, these pollutants do not appear to explain the racial disparities in PTB in this setting.

DOI

10.3390/ijerph191610365

Alternate Title

Int J Environ Res Public Health

PMID

36012001

Title

Spatially and Temporally Resolved Ambient PM in Relation to Preterm Birth.

Year of Publication

2021

Date Published

2021 Dec 14

ISSN Number

2305-6304

Abstract

<p>Growing evidence suggests that maternal exposure to ambient fine particulate matter (PM) during pregnancy is associated with preterm birth; however, few studies have examined critical windows of exposure, which can help elucidate underlying biologic mechanisms and inform public health messaging for limiting exposure. Participants included 891 mother-newborn pairs enrolled in a U.S.-based pregnancy cohort study. Daily residential PM concentrations at a 1 × 1 km resolution were estimated using a satellite-based hybrid model. Gestational age at birth was abstracted from electronic medical records and preterm birth (PTB) was defined as &lt;37 completed weeks of gestation. We used Critical Window Variable Selection to examine weekly PM exposure in relation to the odds of PTB and examined sex-specific associations using stratified models. The mean ± standard deviation PM level averaged across pregnancy was 8.13 ± 1.10 µg/m. PM exposure was not associated with an increased odds of PTB during any gestational week. In sex-stratified models, we observed a marginal increase in the odds of PTB with exposure occurring during gestational week 16 among female infants only. This study does not provide strong evidence supporting an association between weekly exposure to PM and preterm birth.</p>

DOI

10.3390/toxics9120352

Alternate Title

Toxics

PMID

34941786

Title

Maternal anxiety and depression in pregnancy and DNA methylation of the glucocorticoid receptor gene.

Year of Publication

2020

Date Published

2020 Nov 20

ISSN Number

1750-192X

Abstract

<p><strong>Aim:&nbsp;</strong>To quantify associations of anxiety and depression during pregnancy with differential cord blood DNA methylation of the glucorticoid receptor (<em>NR3C1</em>). <strong>Materials &amp; methods:&nbsp;</strong>Pregnancy anxiety, trait anxiety and depressive symptoms were collected using the Pregnancy Related Anxiety Scale, State-Trait Anxiety Index and Edinburgh Postnatal Depression Scale, respectively. <em>NR3C1&nbsp;</em>methylation was determined at four methylation sites. <strong>Results:</strong>&nbsp;DNA methylation of CpG 1 in the <em>NR3C1&nbsp;</em>CpG island shore&nbsp;was higher in infants born to women with high pregnancy anxiety (β 2.54, 95% CI: 0.49-4.58) and trait anxiety (β 1.68, 95% CI: 0.14-3.22). No significant association was found between depressive symptoms and <em>NR3C1&nbsp;</em>methylation. <strong>Conclusion:</strong>&nbsp;We found that maternal anxiety was associated with increased <em>NR3C1&nbsp;</em>CpG island shore methylation.</p>

DOI

10.2217/epi-2020-0022

Alternate Title

Epigenomics

PMID

33215541

Title

Racial and ethnic representation in epigenomic studies of preterm birth: a systematic review.

Year of Publication

2020

Date Published

2020 Dec 02

ISSN Number

1750-192X

Abstract

<p>We conducted a systematic review evaluating race/ethnicity representation in DNA methylomic studies of preterm birth. PubMed, EMBASE, CINHAL, Scopus and relevant citations from 1 January&nbsp;2000 to 30 June&nbsp;2019. Two authors independently identified abstracts comparing DNA methylomic differences between term and preterm births that included&nbsp;race/ethnicity data. 16&nbsp;studies were included. Black and non-Hispanic Black deliveries were well represented (28%). However, large studies originating from&nbsp;more than&nbsp;95% White populations were excluded due to unreported race/ethnicity data. Most studies were cross-sectional, allowing for reverse causation. Most studies were also racially/ethnically homogeneous, preventing direct comparison of DNA methylomic differences across race/ethnicities. In DNA methylomic studies, Black women and infants were well represented. However, the literature has limitations and precludes drawing definitive conclusions.</p>

DOI

10.2217/epi-2020-0007

Alternate Title

Epigenomics

PMID

33264049

Title

Resilience During Pregnancy by Race, Ethnicity and Nativity: Evidence of a Hispanic Immigrant Advantage.

Year of Publication

2020

Date Published

2020 Aug 17

ISSN Number

2196-8837

Abstract

<p>The similar socioeconomic position of black and Hispanic women coupled with better birth outcomes among Hispanic women is termed the "Hispanic Paradox." However, birth outcome disparities among Hispanic women exist by maternal nativity. Persistent unequal exposure over time to stressors contributes to these disparities. We hypothesized that variation in maternal resilience to stressors also exists by race, ethnicity, and nativity. We utilized data from the Spontaneous Prematurity and Epigenetics of the Cervix study in Boston, MA (n = 771) where resilience was measured mid-pregnancy using the Connor Davidson Resilience Scale 25. We assessed resilience differences by race/ethnicity, by nativity then by race, ethnicity, and nativity together. We also assessed the risk of low resilience among foreign-born women by region of origin. We used Poisson regression to calculate risk ratios for low resilience, adjusting for maternal age, education, and insurance. Resilience did not differ significantly across race/ethnicity or by foreign-born status in the overall cohort. US-born Hispanic women were more likely to be in the low resilience tertile compared with their foreign-born Hispanic counterparts (adjusted RR 3.52, 95% CI 1.18-10.49). Foreign-born Hispanic women also had the lowest risk of being in the low resilience tertile compared with US-born non-Hispanic white women (aRR 0.33, 95% CI 0.11-0.98). Resilience did not differ significantly among immigrant women by continent of birth. Overall, foreign-born Hispanic women appear to possess a resilience advantage. Given that this group often exhibits the lowest rates of adverse birth outcomes, our findings suggest a deeper exploration of resilience among immigrant Hispanic women.</p>

DOI

10.1007/s40615-020-00847-y

Alternate Title

J Racial Ethn Health Disparities

PMID

32808195

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