Early Pregnancy Gene Expression Profiling of Women with Preeclampsia: The “Vitamin D Antenatal Asthma Reduction Trial” (VDAART) Study
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85307 | GEO | 2017/08/24
SECONDARY ACCESSION(S): PRJNA338151
REPOSITORIES: GEO
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Project description:BACKGROUND:Maternal asthma, uncontrolled asthma, and low vitamin D levels during pregnancy have been individually linked to increased risk of preeclampsia. OBJECTIVE:To investigate the association of history of physician-diagnosed asthma and uncontrolled asthma status during pregnancy with the risk of preeclampsia and the effects of early pregnancy vitamin D concentrations on this relationship. METHODS:A total of 816 subjects with available pregnancy outcome data and risk factors of interest were analyzed. A group of experienced obstetricians and gynecologists from 3 study centers validated the preeclampsia diagnoses. Vitamin D was measured using the DiaSorin method at 10 to 18 weeks of gestation. The Pregnancy-Asthma Control Test was used to assess asthma control during pregnancy. Criterion-based stepwise variable selection algorithm was applied to investigate the relationships of risk factors of interest (history of asthma diagnosis, uncontrolled asthma during pregnancy, and vitamin D) to preeclampsia. RESULTS:The incidence of preeclampsia was not related to the presence of asthma diagnosis (8.9% with vs 7.4% without). The adjusted odds of preeclampsia controlled for maternal serum 25-hydroxyvitamin D (25OHD) concentrations was higher for women with a higher proportion of uncontrolled asthma months per visit during pregnancy (adjusted odds ratio, 3.55; 95% CI, 1.15-13.0). Adjusting for asthma control status during pregnancy, an additional decrease in the associated preeclampsia risk by 7% was observed for a 10-unit (ng/mL) increase in early pregnancy 25OHD levels (adjusted odds ratio10-unit, 0.60; 95% CI, 0.43-0.82) as compared with the previous risk estimate of preeclampsia associated with low maternal 25OHD unadjusted for asthma control status. CONCLUSIONS:Uncontrolled asthma during pregnancy is associated with an increased risk of preeclampsia. Early pregnancy 25OHD contributes to the association of uncontrolled asthma status with preeclampsia.
| S-EPMC5843492 | biostudies-literature
Project description:BackgroundWe previously reported the results of a trial of prenatal vitamin D supplementation to prevent asthma and recurrent wheeze in young children, which suggested that supplementation provided a protective effect at the age of 3 years. We followed the children through the age of 6 years to determine the course of asthma and recurrent wheeze.MethodsIn this follow-up study, investigators and participants remained unaware of the treatment assignments through the children's sixth birthday. We aimed to determine whether, when maternal levels of 25-hydroxyvitamin D were taken into account, children born to mothers who had received 4400 IU of vitamin D3 per day during pregnancy (vitamin D group) would have a lower incidence of asthma and recurrent wheeze at the age of 6 years than would those born to mothers who had received 400 IU of vitamin D3 per day (control group). Time-to-event methods were used to compare the treatment groups with respect to time to the onset of asthma or recurrent wheeze. Multivariate methods were used to compare longitudinal measures of lung function between the treatment groups.ResultsThere was no effect of maternal vitamin D supplementation on asthma and recurrent wheeze in either an intention-to-treat analysis or an analysis with stratification according to the maternal 25-hydroxyvitamin D level during pregnancy. There was no effect of prenatal vitamin D supplementation on most of the prespecified secondary outcomes. We found no effects of prenatal supplementation on spirometric indexes. Although there was a very small effect on airway resistance as measured by impulse oscillometry, this finding was of uncertain significance.ConclusionsVitamin D supplementation during the prenatal period alone did not influence the 6-year incidence of asthma and recurrent wheeze among children who were at risk for asthma. (Funded by the National Heart, Lung, and Blood Institute; VDAART ClinicalTrials.gov number, NCT00920621.).
| S-EPMC7444088 | biostudies-literature
Project description:The in utero environment during pregnancy has important implications for the developing health of the child. We aim to examine the potential impact of maternal metabolome at two different timepoints in pregnancy on offspring respiratory health in early life. In 685 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial, we assessed the prospective associations between maternal metabolites at both baseline (10-18 weeks gestation) and third trimester (32-38 weeks gestation) and the risk of child asthma or recurrent wheeze by age three using logistic regression models accounting for confounding factors. Subgroup analyses were performed by child sex. Among 632 metabolites, 19 (3.0%) and 62 (9.8%) from baseline and third trimester, respectively, were associated with the outcome (p-value < 0.05). Coffee-related metabolites in the maternal metabolome appeared to be of particular importance. Caffeine, theophylline, trigonelline, quinate, and 3-hydroxypyridine sulfate were inversely associated with asthma risk at a minimum of one timepoint. Additional observations also highlight the roles of steroid and sphingolipid metabolites. Overall, there was a stronger relationship between the metabolome in later pregnancy and offspring asthma risk. Our results suggest that alterations in prenatal metabolites may act as drivers of the development of offspring asthma.
| S-EPMC7910853 | biostudies-literature
Project description:Peripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
2020-02-10 | GSE142974 | GEO
Project description:BackgroundLow levels of circulating 25-hydroxy-vitamin D [25(OH)D] have been shown to associate with prevalent attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the association between 25(OH)D during fetal development and risk of childhood ADHD.MethodsMaternal plasma 25(OH)D was measured at 10-18 and 32-38 weeks of gestation, with sufficiency defined as 25(OH)D ≥ 30 ng/ml. Offspring ADHD status between ages 6-9 years was measured by parent report of clinical ADHD diagnosis among 680 mother-child pairs from the Vitamin D Antenatal Asthma Reduction Trial. Association between maternal 25(OH)D and child ADHD was assessed using logistic regression, adjusting for maternal age, race and ethnicity. Effect modification by offspring sex was also assessed.ResultsNo associations between maternal 25(OH)D at 10-18 weeks of gestation and offspring ADHD were observed. In the third trimester, we observed associations between maternal vitamin D sufficiency and offspring ADHD [odds ratio (OR) 0.47, 95% confidence interval (CI) 0.26-0.84], in addition to maternal 25(OH)D sufficiency category, comparing the deficient (OR 0.34, 95% CI 0.12-0.94), insufficient (OR 0.41, 95% CI 0.15-1.10) and sufficient (OR 0.20, 95% CI 0.08-0.54) categories against highly deficient 25(OH)D, respectively. Stratified analyses revealed a protective association for sufficient maternal 25(OH)D and child ADHD among males (OR 0.47, 95% CI 0.23-0.94); the synergy index for additive effect modification of risk was 1.78 (95% CI 0.62-5.08).ConclusionsHigher levels of maternal vitamin D in the third trimester are associated with lower risk of ADHD in offspring, with modest evidence for a stronger effect among male offspring. However, larger studies will be necessary to confirm these findings.
| S-EPMC9189969 | biostudies-literature
Project description:Peripheral whole blood transcriptome profiles of pregnant women enrolled in the “Vitamin D Antenatal Asthma Reduction Trial” (VDAART) at enrollment during early pregnancy, and again at 32-38 weeks of gestation. Mothers were enrolled in 2 treatment groups: Intervention group with 4400 IU vitamin D supplementation and Control group with 400 IU vitamin D supplementation. Comparing the whole blood (PAXgene) transcriptome profile of 30 mothers at enrollment during early pregnancy versus their matching individual profile at 32-38 weeks of gestation.
2017-02-09 | GSE86200 | GEO
Project description:There is intense interest in the role of vitamin D in the development of asthma and allergies. However, studies differ on whether a higher vitamin D intake or status in pregnancy or at birth is protective against asthma and allergies. To address this uncertainty, the Vitamin D Antenatal Asthma Reduction Trial (VDAART) was developed. VDAART is a randomized, double-blind, placebo-controlled trial of vitamin D supplementation in pregnant women to determine whether prenatal supplementation can prevent the development of asthma and allergies in women's offspring. A secondary aim is to determine whether vitamin D supplementation can prevent the development of pregnancy complications, such as preeclampsia, preterm birth, and gestational diabetes. Women were randomized to the treatment arm of 4000IU/day of vitamin D3 plus a daily multivitamin that contained 400IU of vitamin D3 or the placebo arm of placebo plus a multivitamin that contained 400IU daily of vitamin D3. Women who were between the gestational ages of 10 and 18 weeks were randomized from three clinical centers across the United States - Boston Medical Center, Washington University in St. Louis, and Kaiser Permanente Southern California Region (San Diego, CA). Supplementation took place throughout pregnancy. Monthly monitoring of urinary calcium to creatinine ratio was performed in addition to medical record review for adverse events. Offspring are being evaluated quarterly through questionnaires and yearly during in-person visits until the 3rd birthday of the child. Ancillary studies will investigate neonatal T-regulatory cell function, maternal vaginal flora, and maternal and child intestinal flora.
| S-EPMC4086903 | biostudies-literature
Project description:Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic, highly fluorinated aliphatic compounds, commonly utilised in a wide variety of consumer products with diverse applications. Since the genesis of these compounds, a growing body of evidence has demonstrated adverse health effects associated with PFAS exposure. In a racially diverse cohort of 459 pregnant mothers, demographically weighted towards minority representation (black 44.4%, white 38.4%, other 17.2%), across three major populous cities of the US, PFAS profiling was performed. Nine distinct PFAS species were quantified using mass spectrometry in plasma samples collected during the third trimester. Multivariable logistic and linear regression analyses were conducted to interrogate the associations of PFAS with gestational and birth outcomes: gestational diabetes, preeclampsia, gestational age at delivery, low birth weight, birth weight-, birth length- and head circumference-for-gestational-age. Detectable levels for eight out of nine profiled PFAS species were found in the plasma of pregnant mothers with a median range of 0.1-2.70 ng ml-1. Using a mixtures approach, we observe that increased quantile-based g-computation (Qg-comp) "total" PFAS levels were associated with increased newborn birth-weight-for-gestational-age (β 1.28; 95% CI 1.07-1.52; FDR p 0.006). In study centre-stratified analyses, we observed a similar trend in Boston pregnant mothers, with Qg-comp total PFAS associated with higher newborn birth-weight-for-gestational-age (β 1.39; 95% CI 1.01-1.92, FDR p 0.05). We additionally found elevated PFUA concentrations were associated with longer gestational terms in San Diego pregnant mothers (β 0.60; 95% CI 0.18-1.02, FDR p 0.05). In this multi-city study, we detected lower levels of PFAS than in many previous US environmental studies, concordant with current US trends indicating environmental PFAS levels are falling, and we note geographical variation in the associations between PFAS levels and birth outcomes.
| S-EPMC11328948 | biostudies-literature
Project description:Background: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. We want to study the lncRNAs profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent demonstrating that the placenta is sufficient to cause the condition. So we analyze the lncRNAs profiles in preeclampsia placentas. In this study, we described the lncRNAs profiles in 6 preeclampsia placentas (T) and 5 matched normal pregnancy placentas (N) tissues by microarray. Methodology/Principal Findings: With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 28,443. From the data we found there were 738 lncRNAs that differentially expressed (M-bM-^IM-%1.5 fold-change) among preeclampsia placentas compared with matched controls. Up to 18,063 coding transcripts could be detected in placenta samples through 30,215 coding transcripts probes. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differential expressed lncRNAs and mRNAs. According to the GO-Pathway analysis of differential expressed lncRNAs/mRNAs, we choose three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, CEACAMP8 were evaluated by qPCR in 40 of preeclampsia placentas and 40 of controls. The results showed three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. Conclusions/Significance: Our study is the first one to determine genome-wide lncRNAs expression patterns in preeclampsia placenta by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which revealed that lncRNAs differentially expressed in preeclampsia placenta may exert a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, CEACAMP8 might be associated with preeclampsia. Taken together, this study may provide potential targets for future treatment of preeclampsia and novel insights into preeclampsia biology. LncRNAs/mRNAs profiles in 6 preeclampsia placentas and 5 matched normal pregnancy placentas tissues by microarray using Arraystar v2.0.
2013-09-12 | E-GEOD-50783 | biostudies-arrayexpress
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO