First name
Michele
Middle name
R
Last name
Hacker

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

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

Pregnancy-associated changes in cervical noncoding RNA.

Year of Publication

2020

Number of Pages

1013-1025

Date Published

2020 06

ISSN Number

1750-192X

Abstract

<p>To identify pregnancy-associated changes in cervical noncoding RNA (ncRNA), including miRNA and long noncoding RNA (lncRNA), and their potential effects on biologic processes. We enrolled 21 pregnant women with term deliveries (≥37&nbsp;weeks' gestation) in a prospective cohort and collected cervical swabs before 28&nbsp;weeks' gestation. We enrolled 21 nonpregnant controls. We analyzed miRNA, lncRNA and mRNA expression, applying a Bonferroni correction. Five miRNA and three lncRNA were significantly differentially (&gt;twofold change) expressed. Putative miRNA targets are enriched in genes mediating organogenesis, glucocorticoid signaling, cell adhesion and ncRNA machinery. Differential cervical ncRNA expression occurs in the setting of pregnancy. Gene ontology classification reveals biological pathways through which miRNA may play a biologic role in normal pregnancy physiology.</p>

DOI

10.2217/epi-2019-0231

Alternate Title

Epigenomics

PMID

32808540

Title

Adverse psychosocial factors in pregnancy and preterm delivery.

Year of Publication

2021

Date Published

2021 Mar 05

ISSN Number

1365-3016

Abstract

<p><strong>BACKGROUND: </strong>Mental health symptoms, stress, and low psychosocial resources are associated with preterm delivery. It is unknown if there are groups of women who experience similar patterns of these adverse psychosocial factors during pregnancy and if the risk of preterm delivery differs among these groups.</p>

<p><strong>OBJECTIVE: </strong>To identify groups of women with similar patterns of adverse psychosocial factors during pregnancy and determine whether the risk of preterm delivery differs among these groups.</p>

<p><strong>METHODS: </strong>Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) is a prospective cohort study of pregnant women, aged 18 and older. In this analysis, we included women who enrolled after 24 August 2014 and delivered by 20 January 2019. As women could enrol more than once, our cohort included 774 women with 787 pregnancies. We conducted a latent class analysis to identify groups of women with similar patterns of adverse psychosocial factors during pregnancy based on their responses to measures assessing depression, perceived stress, anxiety (pregnancy-related and generalised), stressful life events, resilience, and social support (partner and friend/family). After identifying the latent classes, we used log-binomial regression to compare the incidence of preterm delivery among the classes.</p>

<p><strong>RESULTS: </strong>The median age among participants was 33.2&nbsp;years (interquartile range 30.3-36.3), and the majority were non-Hispanic white (56.9%). We identified three classes of adverse psychosocial factors (few, some, and many factors). In total, 63 (8.0%) pregnancies resulted in a preterm delivery. Compared to participants with few factors, the risk of preterm delivery was no different among participants with some (RR 1.23, 95% CI 0.68, 2.25) and many adverse factors (RR 1.62, 95% CI 0.73, 3.62).</p>

<p><strong>CONCLUSIONS: </strong>We identified three groups of pregnant women with similar patterns of adverse psychosocial factors. We did not observe a difference in the risk of preterm delivery among the classes.</p>

DOI

10.1111/ppe.12756

Alternate Title

Paediatr Perinat Epidemiol

PMID

33666948

Title

Maternal psychosocial functioning, obstetric health history, and newborn telomere length.

Year of Publication

2021

Number of Pages

105043

Date Published

2021 Jan

ISSN Number

1873-3360

Abstract

<p>There is growing interest in elucidating the determinants of newborn telomere length, given its potential as a biomarker of lifetime disease risk affected by prenatal exposures. There is limited evidence that increased maternal stress during pregnancy predicts shorter newborn telomere length. However, the few studies published to date have been conducted primarily with small samples utilizing inconsistent definitions of maternal stress. Moreover, the potential influence of fetal sex as a moderator of maternal stress effects on newborn telomere length has been largely ignored despite compelling evidence of likely impact. In a prospective cohort study of pregnant women seeking routine prenatal care, we tested whether a range of maternal measures of stressor exposures, subjective feelings of stress, and mental health (depression, anxiety) were associated with newborn telomere length assessed from cord blood among 146 pregnant women and their newborn infants. We further examined whether the pattern of associations differed by infant sex. Sociodemographic and maternal and newborn health indicators were considered as potential covariates. When examined within the whole sample, none of the maternal psychosocial measures were associated with newborn telomere length. Among potential covariates, maternal history of smoking and preeclampsia in a previous pregnancy were negatively associated with newborn telomere length. In adjusted linear regression analyses that considered potential sex-specific effects, maternal depression, general anxiety, and pregnancy-specific anxiety symptoms were positively associated with newborn telomere length among males. Overall, the findings provide some evidence for an association between maternal psychosocial wellbeing in pregnancy and newborn telomere length in males, although in the opposite direction than previously reported. Maternal smoking and obstetric history prior to conception may be associated with shorter offspring telomere length.</p>

DOI

10.1016/j.psyneuen.2020.105043

Alternate Title

Psychoneuroendocrinology

PMID

33176222

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

Title

Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.

Year of Publication

2019

Date Published

2019 Nov 25

ISSN Number

1476-5543

Abstract

<p><strong>OBJECTIVE: </strong>To evaluate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and postnatal therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.</p>

<p><strong>STUDY DESIGN: </strong>Matched case-control study of singleton deliveries at a tertiary hospital from 2010 to 2016. Cases were infants treated with therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Controls were noncase infants, matched on gestational age, maternal age, obstetric provider group, and hospital shift.</p>

<p><strong>RESULT: </strong>Prenatal SSRI exposure occurred in 18.4% of cases compared with 4.1% of controls (aOR: 5.9, 95% CI: 1.8-19.7). Among all cases, 36.8% had evidence of hypoxic ischemic encephalopathy on postnatal MRI. In addition, 28.6% of SSRI-exposed cases and 38.7% of SSRI-unexposed cases had MRI confirmation of hypoxic ischemic encephalopathy, respectively.</p>

<p><strong>CONCLUSION: </strong>Future research to disentangle signs of SSRI exposure from true hypoxic ischemic encephalopathy may facilitate targeting therapeutic hypothermia stewardship toward infants more likely to benefit.</p>

DOI

10.1038/s41372-019-0564-x

Alternate Title

J Perinatol

PMID

31767980

Title

Racial and ethnic disparities in universal cervical length screening with transvaginal ultrasound.

Year of Publication

2016

Number of Pages

4078-81

Date Published

2016 Dec

ISSN Number

1476-4954

Abstract

<p><strong>OBJECTIVE: </strong>Determine if race or ethnicity is associated with missed or late transvaginal cervical length screening in a universal screening program.</p>

<p><strong>METHODS: </strong>Retrospective cohort study of nulliparous women with singleton gestations and a fetal anatomical ultrasound from 16-24 weeks' gestation from January 2012 to November 2013. We classified women into mutually exclusive racial and ethnic groups: non-Hispanic black (black), Hispanic, Asian, non-Hispanic white (white), and other or unknown race. We used log-binomial regression to calculate the risk ratio (RR) and 95% confidence interval (CI) of missed or late (≥20 weeks' gestation) screening versus optimally timed screening between the different racial and ethnic groups.</p>

<p><strong>RESULTS: </strong>Among the 2967 women in our study population, 971 (32.7%) had either missed or late cervical length screening. Compared to white women, black (RR: 1.3; 95% CI: 1.1-1.5) and Hispanic (RR:1.2; 95% CI: 1.01-1.5) women were more likely to have missed or late screening. Among women screened, black (versus white) women were more likely to be screened late (RR: 2.2; 95% CI: 1.6-3.1).</p>

<p><strong>CONCLUSIONS: </strong>Black and Hispanic women may be more likely to have missed or late cervical length screenings.</p>

DOI

10.3109/14767058.2016.1157577

Alternate Title

J. Matern. Fetal. Neonatal. Med.

PMID

26987873

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