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Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

ABSTRACT: The current study examined micro RNA (miRNAs) clusters from the maternal plasma to determine their association with preterm birth (PTB) and infant birth outcomes. A subsample of 42 participants who spontaneously delivered either preterm (?37 weeks) or term was selected from a parent sample of 515 pregnant Mexican American women. Plasma samples and prenatal data were collected at a single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were obtained from medical records after delivery. Circulating miRNAs were analyzed by qPCR. When miRNAs were grouped according to chromosomal cluster rather than expression level, individual miRNAs correlated strongly with other individual miRNAs within their respective genomic locus. miRNAs from the c19mc cluster negatively correlated with c14mc miRNAs, and this relationship was more pronounced in PTB. Clusters c14mc was negatively associated with length of gestation; while the c19mc was positively associated with length of gestation and infant head circumference. Together, these findings suggest that groups of miRNAs from common chromosomal clusters, rather than individual miRNAs, operate as co-regulated groups of signaling molecules to coordinate length of gestation and infant outcomes. From this evidence, differences in cluster-wide expression of miRNAs are involved in spontaneous PTB.

SUBMITTER: Wommack JC

PROVIDER: S-EPMC6021076 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

Wommack Joel C JC Trzeciakowski Jerome P JP Miranda Rajesh C RC Stowe Raymond P RP Ruiz R Jeanne RJ

PloS one 20180627 6

The current study examined micro RNA (miRNAs) clusters from the maternal plasma to determine their association with preterm birth (PTB) and infant birth outcomes. A subsample of 42 participants who spontaneously delivered either preterm (≤37 weeks) or term was selected from a parent sample of 515 pregnant Mexican American women. Plasma samples and prenatal data were collected at a single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were obtained from medical records after ...[more]

PMID: 29949620

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Project description:BACKGROUND: Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls. PRINCIPAL FINDINGS: Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the IL1RL1 mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (?32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p?=?0.00056). CONCLUSION: We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the IL1RL1 mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.

Project description:IntroductionHuman anelloviruses, including torque teno virus (TTV) and torque teno mini virus (TTMV), are ubiquitous in the general population and have no known pathogenicity. We investigated the prevalence and viral load of TTV and TTMV in plasma and saliva over pregnancy, and assessed their association with spontaneous or medically indicated preterm birth.MethodsThis is a secondary analysis of the Measurement of Maternal Stress (MOMS) study, which recruited 744 individuals with singleton pregnancies from 4 US sites (Chicago, Pittsburgh, San Antonio, and rural Pennsylvania). Baseline outpatient visits took place in the second trimester (between 12'0 and 20'6/7 weeks' gestation), and follow-up visits in the third trimester (between 32'0 and 35'6/7 weeks' gestation). In a case-control study design, participants who delivered preterm (<37 weeks) resulting from spontaneous labor and/or preterm premature rupture of membranes ("sPTB") were compared with participants experiencing medically indicated preterm birth ("iPTB"), or delivery at term ("controls"). Plasma and saliva samples obtained during the second and third trimesters were tested for the presence and quantity of TTV and TTMV using real-time PCR. Demographic data were obtained via self-report, and clinical data via medical record review by trained research personnel.ResultsTTV was detected in plasma from 81% (second trimester) and 77% (third trimester) of participants, and in saliva from 64 and 60%. Corresponding detection rates for TTMV were 59 and 41% in plasma, and 35 and 24% in saliva. TTV and TTMV concentrations were similar between matched plasma and saliva samples. TTV prevalence and concentrations were not significantly different between groups (sPTB, iPTB, and controls). However, plasma TTMV in the third trimester was associated with sPTB and earlier gestational age at delivery. The iPTB group was not different from either the sPTB or the control group. In saliva, concentrations of TTV and TTMV were similar among the three groups. Both TTV and TTMV were more prevalent with increasing parity and were more common in Black and Hispanic participants compared to non-Hispanic White participants.ConclusionAnellovirus presence (specifically, TTMV) in the third trimester may be associated with preterm birth. Whether this association is causative remains to be determined.

Dataset Information

Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

Publications

Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

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