An EPIC predictor of gestational age and its application to newborns conceived by assisted reproductive technologies.
An EPIC predictor of gestational age and its application to newborns conceived by assisted reproductive technologies.
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DOI：
10.1186/s13148-021-01055-z
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发表时间：
2021-04-19
影响因子：
5.7
通讯作者：
Bohlin J
中科院分区：
文献类型：
--
作者：
Haftorn KL;Lee Y;Denault WRP;Page CM;Nustad HE;Lyle R;Gjessing HK;Malmberg A;Magnus MC;Næss Ø;Czamara D;Räikkönen K;Lahti J;Magnus P;Håberg SE;Jugessur A;Bohlin J
胎龄是评估发育成熟度的有用指标，但使用临床测量很难正确估计胎龄。出生时 DNA 甲基化已被证明可以准确预测胎龄。之前的表观遗传胎龄预测因子基于 Illumina HumanMmethylation 27 K 或 450 K 阵列的 DNA 甲基化数据，该数据随后被 Illumina MmethylationEPIC 850 K 阵列 (EPIC) 取代。我们的目标是建立一个专门针对 EPIC 阵列的表观遗传胎龄时钟，并使用迄今为止辅助生殖技术 (ART) 上最大的 EPIC 衍生数据集中的新生儿胚胎移植日期来评估其精度和准确度。我们使用 Lasso 回归建立了一个表观遗传胎龄时钟，该回归对来自挪威辅助生殖技术研究 (START)（挪威母亲、父亲和儿童队列研究 (MoBa) 的子研究）中随机选择的 755 名非 ART 新生儿进行了训练。对于 ART 受孕的新生儿，START 数据集包含有关胚胎移植日期和用于受孕的特定 ART 程序的详细信息。使用 MM 型稳健回归将预测胎龄与 200 名非 ART 和 838 名 ART 新生儿的临床估计胎龄进行比较。该时钟的性能与之前发表的胎龄时钟进行了比较，该样本来自于先兆子痫和宫内生长受限的预测和预防 (PREDO) 研究（芬兰妇女的前瞻性妊娠队列）中的 148 名新生儿的独立复制样本。我们新的表观遗传胎龄时钟在预测胎龄方面比以前的胎龄时钟表现出更高的精度和准确度（R2 = 0.724，中位绝对偏差 (MAD) = 3.14 天）。将分析限制为 450 K 和 EPIC 之间共享的 CpG 并不会降低时钟的精度。此外，对已知胚胎移植日期的 ART 新生儿的时钟进行验证证实，DNA 甲基化是胎龄的准确预测因子（R2 = 0.767，MAD = 3.7 天）。我们提出了第一个基于 EPIC 的胎龄预测器，并证明了其在 ART 和非 ART 新生儿中的稳健性和精确性。随着 EPIC 平台上生成更多数据集，该时钟对于使用胎龄评估新生儿发育的研究将非常有价值。在线版本包含可在 10.1186/s13148-021-01055-z 获取的补充材料。
Gestational 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age were based on DNA methylation data from the Illumina HumanMethylation 27 K or 450 K array, which have subsequently been replaced by the Illumina MethylationEPIC 850 K array (EPIC).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). We 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. Our 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). We 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. The online version contains supplementary material available at 10.1186/s13148-021-01055-z.
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出生时胎龄对3岁和5岁时健康结果的影响：基于人群的队列研究。
DOI：
10.1136/bmj.e896
发表时间：
2012-03-01
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Boyle EM;Poulsen G;Field DJ;Kurinczuk JJ;Wolke D;Alfirevic Z;Quigley MA
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作者：
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Fisher, RA
DOI：
10.1111/j.1742-7843.2007.00186.x
发表时间：
2008-02-01
影响因子：
3.1
作者：
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通讯作者：
Gluckman, Peter D.
影响因子：
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