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臍帯血内のアセトアミノフェン濃度とADHD、自閉症との関連(前向き研究)

重要性:過去の研究により、妊娠中の母親のアセトアミノフェンの使用に関する懸念が高まり、子供の注意欠陥 / 多動性障害ADHD)および自閉症スペクトラム障害(ASD)のリスクが増加しています。しかし、ほとんどの研究は母体の自己報告に依存している。目的:臍帯 血漿 のアセトアミノフェン代謝産物と、医師が診断したADHDASDADHDASDの両方、および小児期の発達障害(DD)の前向きな関連性を調べる。設計、設定、および参加者:この前向きコホート研究では、出生時に登録され、1998101日から2018630日までボストンメディカルセンターで前向きに追跡調査された、ボストン出生コホートのサブセットである996組の母子ペアを分析しました。露出:3つの臍帯 アセトアミノフェン代謝産物(変化しないアセトアミノフェン、アセトアミノフェングルクロニド、および3- [N-アセチル-l-システイン-S-イル]- アセトアミノフェン)は、出生時に収集された保存臍帯血 血漿サンプルで測定されました。主な結果と対策:子供の医療記録に記載されている、医師が診断したADHDASD、およびその他のDD結果:参加者996人(平均[SD]年齢、9.8 [3.9]; 548 [55.0]男性)の中で、最終サンプルには257人の子供(25.8%)がADHDのみ、66人(6.6%)がASDのみ、42人(4.2 %)がADHDASDの両方、304人(30.5%)は他のDD327人(32.8%)は神経学的機能が正常でした。変化しないアセトアミノフェンレベルは、すべての臍帯血 血漿サンプルで検出可能でした。第一の三分位と比べると、第二及び第三の三分位は臍帯血のアセトアミノフェン濃度は、ADHD診断(2番目の三分位のオッズ比[OR]2.26; 95CI1.40-3.69;3番目の三分位のOR2.86; 95CI1.77-4.67)およびASD診断(2番目の三分位のOR2.14; 95CI0.93-5.13; 3番目の三分位のOR 3.62; 95CI1.62-8.60)のオッズが高いことと関連していた。感度分析とサブグループ分析により、アセトアミノフェン濃度とADHD、およびアセトアミノフェン濃度とASDの一貫した関連性が、母体の適応、物質使用、早産、および子供の年齢と性別を含む潜在的な交絡因子の層全体で見つかり、ADHDの場合は2.3から3.5まで、ASDの場合は1.6から4.1までと推定。結論と関連性:アセトアミノフェンへの胎児暴露の臍帯バイオマーカーは、用量反応様式で小児 ADHDおよびASDの有意なリスク増加と関連していた。私たちの調査結果は、出生前および周産期のアセトアミノフェン曝露と小児神経発達リスクとの関連に関する、以前の研究を支持し、追加の調査が必要です。

JAMA Psychiatry. 2019 Oct 30:1-11. doi: 10.1001/jamapsychiatry.2019.3259.[Epub ahead of print]

Association of Cord PlasmaBiomarkers of In Utero Acetaminophen ExposureWith Risk of Attention-Deficit/Hyperactivity Disorder and Autism SpectrumDisorder in Childhood.

Ji Y1, Azuine RE2, Zhang Y3, Hou W4, Hong X1, Wang G1, Riley A1, Pearson C5, Zuckerman B5, Wang X1,6.

1

Center on the EarlyLife Origins of Disease, Department of Population, Family and ReproductiveHealth, Johns Hopkins University Bloomberg School of Public Health, Baltimore,Maryland.

2

Division ofResearch, Office of Epidemiology and Research, Maternal and Child HealthBureau, Health Resources and Services Administration, US Department of Healthand Human Services, Rockville, Maryland.

3

Department ofBiostatistics, Johns Hopkins University Bloomberg School of Public Health,Baltimore, Maryland.

4

Department of ComputerScience, Johns Hopkins University Whiting School of Engineering, Baltimore,Maryland.

5

Department ofPediatrics, Boston University School of Medicine and Boston Medical Center,Boston, Massachusetts.

6

Division of GeneralPediatrics & Adolescent Medicine, Department of Pediatrics, Johns HopkinsUniversity School of Medicine, Baltimore, Maryland.

Abstract

Importance:

Prior studies have raised concern aboutmaternal acetaminophen use during pregnancy and increased risk ofattention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder(ASD) in their children; however, most studies have relied on maternalself-report.

Objective:

To examine the prospective associationsbetween cord plasmaacetaminophen metabolites and physician-diagnosed ADHD, ASD, both ADHD and ASD,and developmental disabilities (DDs) in childhood.

Design, Setting,and Participants:

This prospective cohort study analyzed 996mother-infant dyads, a subset of the Boston Birth Cohort, who were enrolled atbirth and followed up prospectively at the Boston Medical Center from October 1,1998, to June 30, 2018.

Exposures:

Three cordacetaminophen metabolites (unchanged acetaminophen, acetaminophen glucuronide,and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen) were measured in archived cord plasma samplescollected at birth.

Main Outcomes andMeasures:

Physician-diagnosed ADHD, ASD, and other DDsas documented in the child's medical records.

Results:

Of 996 participants (mean [SD] age, 9.8 [3.9]years; 548 [55.0%] male), the final sample included 257 children (25.8%) withADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304(30.5%) with other DDs, and 327 (32.8%) who were neurotypical. Unchangedacetaminophen levels were detectable in all cord plasma samples. Compared with being in the firsttertile, being in the second and third tertiles of cordacetaminophen burden was associated with higher odds of ADHD diagnosis (oddsratio [OR] for second tertile, 2.26; 95% CI, 1.40-3.69; OR for third tertile,2.86; 95% CI, 1.77-4.67) and ASD diagnosis (OR for second tertile, 2.14; 95%CI, 0.93-5.13; OR for third tertile, 3.62; 95% CI, 1.62-8.60). Sensitivityanalyses and subgroup analyses found consistent associations betweenacetaminophen buden and ADHD and acetaminophen burden and ASD across strata ofpotential confounders, including maternal indication, substance use, pretermbirth, and child age and sex, for which point estimates for the ORs vary from2.3 to 3.5 for ADHD and 1.6 to 4.1 for ASD.

Conclusions andRelevance:

Cord biomarkers of fetal exposure to acetaminophen were associatedwith significantly increased risk of childhood ADHD and ASD in a dose-responsefashion. Our findings support previous studies regarding the association between prenatal and perinatalacetaminophen exposure and childhood neurodevelopmental risk and warrantadditional investigations.




by fibromyalgia11 | 2019-11-16 23:05 | アセトアミノフェン、NSAID
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世界標準の線維筋痛症を専門家が説明します


by fibromyalgia11
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