This proposal responds to HRSA-22-086: 'Autism Longitudinal Data Project'. Our overarching goals are to address major knowledge gaps in the understanding of autism spectrum disorders (ASD)/associated developmental disabilities (DD) and co-occurring medical conditions using a life course framework. Specifically this project will leverage the well-established Boston Birth Cohort and multi-level multi-dimensional longitudinal databases to (1) characterize ASD/DD heterogeneous manifestations and developmental trajectories across the life stages; (2) identify upstream risk and protective factors of ASD/DD; conduct comparative risk assessment to important and modifiable risks and evaluate various intervention strategies via computer simulations that are safe and time and cost efficient; and (3) integrate maternal and child multi-omics data (genome epigenome metabolome) to gain a deep understanding of molecular pathways by which early life factors drive or shape the developmental trajectories of ASD/DD. Finally we will harness the big data and machine learning to improve early risk prediction of ASD/DD. The new knowledge gained will provide critically needed evidence to inform clinical and public health practice and policies. For example it will help advance early risk assessment prediction and primary prevention of ASD/DD when interventions may have the greatest life-long benefits. It may transform how maternal and child health care and educational services are organized and delivered to better meet the needs of individuals with ASD/DD and improve their wellbeing across the lifespan
"Cao T, Zhao J, Hong X, Wang G, Pearson C, Adams WG, Hu FB, Wang X, Liang L. Cord Blood Plasma
Metabolome-wide Associations With Height From Birth to Adolescence. J Bone Miner Res. 2023 Feb 20.
doi: 10.1002/jbmr.4790. Epub ahead of print. PMID: 36805685. " DOI:doi: 10.1002/jbmr.4790 February 2023 36805685 J Bone Miner Res.
Chen Y,�Zhang M,�Wang G,�Hong X,�Wang X,�Mueller NT.�Mother's age at menarche is associated with odds of preterm delivery: A case�control study.�BJOG.�2023;�(00):1�9.�doi: 10.1111/1471-0528.17648 DOI:�doi: 10.1111/1471-0528.17648 September 2023
Che X, Gross SM, Wang G, Hong X, Pearson C, Bartell T, Wang X. Impact of consuming a Mediterranean-style diet during pregnancy on neurodevelopmental disabilities in offspring: results from the Boston Birth Cohort. Precision Nutrition. 2023;2(3):e00047. doi: 10.1097/PN9.0000000000000047 DOI:doi: 10.1097/PN9.0000000000000047 February 2023 Precision Nutrition.
Garrison-Desany HM, Ladd-Acosta C, Hong X, Wang G, Burd I, Sanchez Zvd M, Wang X, Surkan P. Addressing the smoking-hypertension paradox in pregnancy: insight from a multiethnic US birth cohort. Precision Nutrition 2(2):p e00035, June 2023. | DOI: 10.1097/PN9.0000000000000035. DOI: DOI: 10.1097/PN9.0000000000000035 June 2023
Hong X, Rosenberg AZ, Heymann J, Yoshida T, Waikar SS, Ilori TO, Wang G, Rebuck H, Pearson C, Wang MC, Winkler CA, Kopp JB, Wang X. Joint Associations of Pregnancy Complications and Postpartum Maternal Renal Biomarkers With Severe Cardiovascular Morbidities: A US Racially and Ethnically Diverse Prospective Birth Cohort Study. J Am Heart Assoc. 2023 Nov 10:e029311. https://doi.org/10.1161/JAHA.122.029311 DOI: https://doi.org/10.1161/JAHA.122.029311 November 2023 J Am Heart Assoc.
"Hu J, Xu X, Li J, Jiang Y, Hong X, Rexrode KM, Wang G, Hu FB, Zhang H, Karmaus WJ, Wang X, Liang L.
Sex differences in the intergenerational link between maternal and neonatal whole blood DNA methylation:
a genome-wide analysis in 2 birth cohorts. Clin Epigenetics. 2023 Mar 25;15(1):51. doi: 10.1186/s13148-
023-01442-8. PMID: 36966332; PMCID: PMC10040137." DOI:doi: 10.1186/s13148-
023-01442-8 March 2023 36966332 Clin Epigenetics
"Huang W, Meir, Anat Yaskolka; Olapeju, Bolanle; Wang, Guoying; Hong, Xiumei; Venkataramani, Maya;
Cheng, Tina L.; Igusa, Tak; Liang, Liming; Wang, Xiaobin. Defining longitudinal trajectory of body mass
index percentile and predicting childhood obesity: methodologies and findings in the Boston Birth Cohort.
Precision Nutrition 2(2):p e00037, June 2023. | DOI: 10.1097/PN9.0000000000000037" DOI:DOI: 10.1097/PN9.0000000000000037 June 2023
Precision Nutrition
"Makker K*, Zhang M, Wang G, Hong X, Zhang C, Aziz K, Wang X: Longitudinal Trajectory and Early Life
Determinant of Childhood Adipokines: Findings from a Racially Diverse Birth Cohort. J Clin Endocrinol
Metab. 2023 Jan 7: dgad005. doi: 10.1210/clinem/dgad005. " DOI:. doi: 10.1210/clinem/dgad005 January 2023 J Clin Endocrinol
Meta
Makker K. Early Life Origins of Cardio-Metabolic Outcomes in Boston Birth Cohort: Review of Findings and Future directions. Precision Nutrition; 2(3):p e00050, September 2023. DOI: 10.1097/PN9.0000000000000050. DOI:DOI: 10.1097/PN9.0000000000000050. September 2023 Precision Nutrition
Meir AY, Huang W, Cao T, et al. Umbilical cord DNA methylation is associated with body mass index trajectories from birth to adolescence. EBioMedicine. 2023;91:104550. doi:10.1016/j.ebiom.2023.104550 DOI:doi:10.1016/j.ebiom.2023. May 2023 Ebiomedicine
Raghavan R, Wang G, Hong X, Pearson C, Xie H, Adams WG, Augustyn M, Wang X. Independent and joint association of cord plasma pantothenate and cysteine levels with autism spectrum disorders and other neurodevelopmental disabilities in children born term and preterm. Precision Nutrition 2(2):p e00036, June 2023. | DOI: 10.1097/PN9.0000000000000036 DOI:DOI: 10.1097/PN9.0000000000000036 June 2023 Precision Nutrition
"Rusk SA, DiBari J, Mason DM, Li M, Hong X, Wang G, Pearson C, Mirolli G, Cheng TL, Kogan MD,
Zuckerman B, Wang X. The impact of COVID-19 on psychiatric clinical encounters among low-income
racially diverse children. J Child Psychol Psychiatry. 2023 Apr 23. doi: 10.1111/jcpp.13809. Epub ahead of
print. PMID: 37088737." DOI: doi: 10.1111/jcpp.13809 April 2023 3708873 . J Child Psychol Psychiatry
Si J, Yaskolka Meir A, Hong X, Wang G, Huang W, Pearson C, Adams WG, Wang X, Liang L. Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.�BMC Med. 2023;21(1):1-13. doi: 10.1186/s12916-023-03003-5 DOI:doi: 10.1186/s12916-023-03003-5 0 BMC Med
Wang G, Buckley JP, Bartell TR, Hong X, Pearson C, Wang X. Cord Blood Insulin Concentration and Hypertension Among Children and Adolescents Enrolled in a US Racially Diverse Birth Cohort. Hypertension. 2023 May;80(5):1092-1101. Epub 2023 Mar 13. PMID: 36912156; PMCID: PMC10133182. https://doi.org/10.1161/HYPERTENSIONAHA.122.20347 DOI:https://doi.org/10.1161 May 2023 36912156 Hypertension
Wang G, Buckley JP, Bartell TR, Hong X, Pearson C, Wang X. Gestational Diabetes Mellitus, Postpartum Lipidomic Signatures, and Subsequent Risk of Type 2 Diabetes: A Lipidome-Wide Association Study. Diabetes Care. 2023 Jun 1;46(6):1223-1230. doi: 10.2337/dc22-1841. PMID: 37043831. DOI:doi: 10.2337/dc22-1841 June 2023 37043831 Diabetes Care
Wang G, Radovick S, Buckley JP, Hauser R, Williams PL, Hong X, Pearson C, Adams WG, Wang X. Plasma Insulin Concentration in Newborns and Children and Age at Menarche. Diabetes Care. 2023 Jun 1;46(6):1231-1238. PMID: 37018448; PMCID: PMC10234748. https://doi.org/10.2337/dc22-2017 DOI:https://doi.org/10.2337/dc22-2017 0 37018448 Diabetes Care
Wang G, Xu R, Zhang B, Hong X, Bartell TR, Pearson C, Liang L, Wang X. Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator. Clin Epigenetics. 2023 Apr 7;15(1):59. doi: 10.1186/s13148-023-01473-1. PMID: 37029435; PMCID: PMC10082529. DOI:doi: 10.1186/s13148-023-01473-1 April 2023 37029435 Clin Epigenetics
Wang X. Prenatal Nutrition and Developmental Origins of Health and Disease. Precision Nutrition 2(2):p e00040, June 2023. | DOI: 10.1097/PN9.0000000000000040 DOI:DOI: 10.1097/PN9.0000000000000040 June 2023 Precision Nutrition
Xu R, Hong X, Ladd-Acosta C, Buckley JP, Choi G, Wang G, Hou W, Wang X, Liang L, Ji H. Contrasting Association of Maternal Plasma Biomarkers of Smoking and 1-Carbon Micronutrients with Offspring DNA Methylation: Evidence of Aryl Hydrocarbon Receptor Repressor Gene-Smoking-Folate Interaction. J Nutr. 2023 May 6:S0022-3166(23)37595-3. doi: 10.1016/j.tjnut.2023. PMID: 37156443. DOI:doi: 10.1016/j.tjnut.2023 May 2023 37156443 J Nutr.
"Yaskolka Meir A, Huang W, Cao T, Hong X, Wang G, Pearson C, Adams WG, Wang X, Liang L. Umbilical
cord DNA methylation is associated with body mass index trajectories from birth to adolescence.
EBioMedicine. 2023 Apr 21;91:104550. doi: 10.1016/j.ebiom.2023.104550. Epub ahead of print. PMID:
37088033; PMCID: PMC10141503. " DOI:doi: 10.1016/j.ebiom.2023.104550 April 2023
3708803 EBIoMedicine
" Hou W, Zhang M, Ji Y, Hong X, Wang G, Richard Xu, Liang L, Saria S, Ji H. A
prospective birth cohort study of maternal prenatal cigarette smoking (by self-report and
biomarkers) on offspring risk of obesity in childhood. Precis Nutr 2022; 1(3): e00017 doi:
10.1097/PN9.0000000000000017." DOI:doi:
10.1097/PN9.000000000000001 November 2022 Precis Nutr
"Pearson C, Bartell T, Wang G, Hong X, Rusk SA, Fu L, Cerda S, Bustamante-Helfrich B, Kuohung W, Yarrington C, Adams WG,
Wang X. Boston Birth Cohort Profile: Rationale and Study Design. Precis Nutr. 2022 Nov;1(2):e00011. Epub 2022 Aug 18.
PMID: 36660305; PMCID: PMC9844822." August 2022 3666030 Precis Nutri
Makker K, Zhang M, Wang G, Hong X, Zhang C, Wang X. Early-life determinants of childhood plasma insulin levels: implications for primordial prevention of diabetes. Pediatr Res. 2023 Jan;93(1):189-197. Epub 2022 Apr 21. PMID: 35449397; PMCID: PMC10184189. https://doi.org/10.1038/s41390-022-02070-3 DOI: https://doi.org/10.1038/s41390-022-02070-3 April 2022 35449397