{"doi":"10.1093/aje/kwag060","title":"A new tool for pregnancy research: a unified definition for major congenital malformation across ICD eras","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Composite major congenital malformation (MCM) outcomes are commonly used to assess teratogenic effects of prenatal medication exposure, but this approach dilutes effect estimates when the risk is confined to a specific MCM. Tree-based scan statistics address this by screening outcomes using a hierarchical tree, enabling detection of specific risks without predefined hypotheses. To apply this method across ICD-9-CM and ICD-10-CM eras, we developed a unified hierarchical outcomes tree for MCM. We selected ICD-9-CM and ICD-10-CM codes classified as congenital anomalies, removing minor malformations, chromosomal anomalies, and single-gene conditions. A multilevel tree was built based on the Multi-level Clinical Classification Software, General Equivalence Mappings, and expert review. We validated the tree using birth cohorts from MarketScan and Medicaid databases (2011-2013; 2016-2018), assessing the balance of MCM prevalences within 1 year of birth via standardized mean differences (SMDs). The final tree included 1023 codes, organized into 244 clinical MCM groups at the most granular level. We identified 572 107 (2011-2013) and 360 167 infants (2016-2018) in MarketScan and 362 820 and 3 500 589 infants in Medicaid. All SMDs were below 0.1, indicating consistency across coding eras. This hierarchical MCM tree bridges ICD-9-CM and ICD-10-CM, enabling consistent outcome definitions and enhancing the detection of specific teratogenic risks.</jats:p>","journal":"American Journal of Epidemiology","year":2026,"id":636286,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":868641,"name":"Nicole E. Smolinski","orcid":"0000-0002-0866-4579","position":1,"is_corresponding":false},{"id":590595,"name":"Sonja A. Rasmussen","orcid":"0000-0002-0574-4928","position":2,"is_corresponding":false},{"id":1651308,"name":"Junko Nagai","orcid":"0000-0002-9069-5752","position":3,"is_corresponding":false},{"id":1651309,"name":"Thorben Kurzbach","orcid":"0009-0003-0264-9604","position":4,"is_corresponding":false},{"id":1078821,"name":"Yanning Wang","orcid":"0000-0002-4263-3944","position":5,"is_corresponding":false},{"id":316904,"name":"Almut G. Winterstein","orcid":"0000-0002-6518-5961","position":6,"is_corresponding":false},{"id":990318,"name":"Judith C. Maro","orcid":"0000-0001-9900-2142","position":7,"is_corresponding":false},{"id":870167,"name":"Thuy Nhu Thai","orcid":"0000-0003-4544-1160","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"A new tool for pregnancy research: a unified definition for major congenital malformation across ICD eras","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Composite major congenital malformation (MCM) outcomes are commonly used to assess teratogenic effects of prenatal medication exposure, but this approach dilutes effect estimates when the risk is confined to a specific MCM. Tree-based scan statistics address this by screening outcomes using a hierarchical tree, enabling detection of specific risks without predefined hypotheses. To apply this method across ICD-9-CM and ICD-10-CM eras, we developed a unified hierarchical outcomes tree for MCM. We selected ICD-9-CM and ICD-10-CM codes classified as congenital anomalies, removing minor malformations, chromosomal anomalies, and single-gene conditions. A multilevel tree was built based on the Multi-level Clinical Classification Software, General Equivalence Mappings, and expert review. We validated the tree using birth cohorts from MarketScan and Medicaid databases (2011-2013; 2016-2018), assessing the balance of MCM prevalences within 1 year of birth via standardized mean differences (SMDs). The final tree included 1023 codes, organized into 244 clinical MCM groups at the most granular level. We identified 572 107 (2011-2013) and 360 167 infants (2016-2018) in MarketScan and 362 820 and 3 500 589 infants in Medicaid. All SMDs were below 0.1, indicating consistency across coding eras. This hierarchical MCM tree bridges ICD-9-CM and ICD-10-CM, enabling consistent outcome definitions and enhancing the detection of specific teratogenic risks.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41848193","pmcid":null,"openalex_id":"https://openalex.org/W7138891256","authors":[],"funders":[{"funder_name":"National Institute of Child Health and Human Development","grant_id":"R01HD110107","title":null}],"total_grants":1,"fwci":0.0,"citation_percentile":0.25201068,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13419262/","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13419262/","host_type":"repository"},{"url":"https://academic.oup.com/aje/advance-article-pdf/doi/10.1093/aje/kwag060/67389622/kwag060.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/aje/article-pdf/195/8/2244/67389622/kwag060.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/aje/kwag060","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41848193","host_type":"repository"}],"fields_of_study":["Pregnancy and Medication Impact","Birth, Development, and Health","Pharmacological Effects and Toxicity Studies"],"mesh_terms":["Humans","Abnormalities, Drug-Induced","Pregnancy","International Classification of Diseases","Infant, Newborn","United States","Female","Congenital Abnormalities"],"keywords":["Pregnancy","Tree (set theory)","Consistency (knowledge bases)","Coding (social sciences)","MEDLINE","Congenital malformations","Medicaid","Malformation","Congenital Anomaly","Icd-9-cm","Icd-10-cm","Tree-based Scan"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T16:45:21.155429Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}