Validation of gestational age determination from ultrasound or a metabolic gestational age algorithm using exact date of conception in a cohort of newborns conceived using assisted reproduction technologies.
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ABSTRACT:
SUBMITTER: Hawken S
PROVIDER: S-EPMC9758343 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Validation of gestational age determination from ultrasound or a metabolic gestational age algorithm using exact date of conception in a cohort of newborns conceived using assisted reproduction technologies.
Hawken Steven S Olibris Brieanne B Ducharme Robin R Bota A Brianne AB Murray Jeffrey C JC Potter Beth K BK Walker Mark M Chakraborty Pranesh P Wilson Kumanan K
AJOG global reports 20220826 4
<h4>Background</h4>Accurate estimates of gestational age in pregnancy are important for the provision of optimal care. Although current guidelines generally recommend estimating gestational age via first-trimester ultrasound measurement of crown-rump length, error associated with this method can range from 3 to 8 days of gestation. In pregnancies resulting from assisted reproductive technology, estimated due date can be calculated on the basis of the age of the embryo and the date of embryo tran ...[more]
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Project description:BackgroundGestational age is a useful proxy for assessing developmental maturity, but correct estimation of gestational age is difficult using clinical measures. DNA methylation at birth has proven to be an accurate predictor of gestational age. Previous predictors of epigenetic gestational age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC). Our aims here were to build an epigenetic gestational age clock specific for the EPIC array and to evaluate its precision and accuracy using the embryo transfer date of newborns from the largest EPIC-derived dataset to date on assisted reproductive technologies (ART).MethodsWe built an epigenetic gestational age clock using Lasso regression trained on 755 randomly selected non-ART newborns from the Norwegian Study of Assisted Reproductive Technologies (START)-a substudy of the Norwegian Mother, Father, and Child Cohort Study (MoBa). For the ART-conceived newborns, the START dataset had detailed information on the embryo transfer date and the specific ART procedure used for conception. The predicted gestational age was compared to clinically estimated gestational age in 200 non-ART and 838 ART newborns using MM-type robust regression. The performance of the clock was compared to previously published gestational age clocks in an independent replication sample of 148 newborns from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restrictions (PREDO) study-a prospective pregnancy cohort of Finnish women.ResultsOur new epigenetic gestational age clock showed higher precision and accuracy in predicting gestational age than previous gestational age clocks (R2 = 0.724, median absolute deviation (MAD) = 3.14 days). Restricting the analysis to CpGs shared between 450 K and EPIC did not reduce the precision of the clock. Furthermore, validating the clock on ART newborns with known embryo transfer date confirmed that DNA methylation is an accurate predictor of gestational age (R2 = 0.767, MAD = 3.7 days).ConclusionsWe present the first EPIC-based predictor of gestational age and demonstrate its robustness and precision in ART and non-ART newborns. As more datasets are being generated on the EPIC platform, this clock will be valuable in studies using gestational age to assess neonatal development.
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Project description:Research questionStudies in rodents have shown that paternal folate intake prior to conception is associated with pregnancy and offspring outcomes. The aim of this study was to assess whether those associations might apply to humans as well.DesignBetween 2007 and 2017, the study prospectively analysed data from 108 couples participating in a preconception cohort of couples undergoing fertility treatment using their own gametes, whose treatment resulted in 113 pregnancies during the course of the study. Paternal and maternal preconception folate intake was assessed using a validated food frequency questionnaire. Linear mixed models were used to assess whether paternal preconception folate intake was associated with gestational age at delivery and gestational age-specific birthweight, while accounting for correlated data and potential confounders.ResultsIn a multivariable-adjusted model, a 400 μg/day increase in preconception paternal folate intake was associated with a 2.6-day longer gestation (95% confidence interval 0.8-4.3) after adjusting for potential confounders, including maternal folate intake. Similar associations were found for folate from food and supplements. Maternal folate intake was not associated with gestational age at delivery. Neither paternal nor maternal folate intake was associated with gestational-age-specific birthweight.ConclusionsHigher paternal preconception folate intake was associated with slightly longer gestation among live births achieved through assisted reproduction. The results suggest that preconception exposures of the father may have an impact on the health of his offspring, and therefore that preconception care should shift from a woman-centric to a couple-based approach.
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Project description:Genome wide DNA methylation profiling of whole blood at birth (Guthrie blood spots) and adulthood of individuals conceived by assisted reproductive technology (ART) and matched non-ART controls. The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in guthrie cards and whole adult blood.
2019-07-29 | GSE131433 | GEO
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Project description:MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression playing a key role in organogenesis. MiRNAs are studied in tracheal aspirates (TA) of preterm infants. However; this is difficult to obtain in infants who are not intubated. This study examines early salivary miRNA expression as non-invasive early biomarkers in extremely low gestational age newborns (ELGANs). Saliva was collected using DNA-genotek swabs, miRNAs were analyzed using RNA seq and RT PCR arrays. Salivary miRNA expression was compared to TA using RNA seq at 3 days of age, and longitudinal changes at 28 days of age were analyzed using RT PCR arrays in ELGANs. Approximately 822 ng of RNA was extracted from saliva of 7 ELGANs; Of the 757 miRNAs isolated, 161 miRNAs had significant correlation in saliva and TA at 3 days of age (r = 0.97). Longitudinal miRNA analysis showed 29 miRNAs downregulated and 394 miRNAs upregulated at 28 days compared to 3 days of age (adjusted p < 0.1). Bioinformatic analysis (Ingenuity Pathway Analysis) of differentially expressed miRNAs identified organismal injury and abnormalities and cellular development as the top physiological system development and cellular function. Salivary miRNA expression are source for early biomarkers of underlying pathophysiology in ELGANs.
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Project description:In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA), small for gestational age (SGA) and adequate for gestational age/Control (AGA/Ctl) newborns. We found several differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) between LGA, SGA and AGA groups. A system biology approach identified several biological processes significantly enriched with genes in association with DMCs including Regulation of transcription, Regulation of epinephrine secretion, Norepinephrine biosynthesis, Receptor transactivation, Forebrain regionalization and several terms related with kidney and cardiovascular development. Gene ontology analysis of the genes in association with the DMRs identified several significantly enriched biological processes related with kidney development including Mesonephric duct development and Nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched at gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys and metabolism. Our study identified several DMCs/DMRs in association with fetal growth patterns. The use of cord blood as material for the identification of DNA methylation biomarkers gives us the possibility to perform follow up studies on the same patients as they enter childhood and puberty. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness.
2023-07-26 | GSE238155 | GEO
Project description:Assisted reproductive technology (ART) may affect fetal development through epigenetic mechanisms as the timing of ART procedures coincides with the extensive epigenetic remodeling occurring between fertilization and embryo implantation. However, it is unknown to what extent ART procedures alter the fetal epigenome. Underlying parental characteristics and subfertility may also play a role. Here we identify differences in cord blood DNA methylation, measured using the Illumina EPIC platform, between 962 ART conceived and 983 naturally conceived singleton newborns. We show that ART conceived newborns display widespread differences in DNA methylation, and overall less methylation across the genome. There were 607 genome-wide differentially methylated CpGs. We find differences in 176 known genes, including genes related to growth, neurodevelopment, and other health outcomes that have been associated with ART. Both fresh and frozen embryo transfer show DNA methylation differences. Associations persist after controlling for parents' DNA methylation, and are not explained by parental subfertility.
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