Strengths and Limitations
Using the validated and weighted Maternal Comorbidity Index30,45, capture of the range of maternal comorbidities was a distinct advantage of using health claims data, as these data capture utilization before, during and post-delivery as well as across multiple health care delivery sites accessed by each patient.46 In comparison, prior studies used self-report, birth certificate and/or hospital discharge data for birth outcomes and related morbidity and were limited in identifying the full range of comorbidities that precede and occur during pregnancy.3,4 Results of our mediation analysis helps explain why AYA cancer survivors have more adverse perinatal outcomes, and illustrates potential use of this analytic approach for future research aimed at improving outcomes in cancer survivors.
We note several limitations. First, prior cancer remained associated with adverse outcomes in singleton births, after adjusting for broad chemotherapy or radiation exposures and comorbidities, leaving unanswered why cancer itself would be related to these outcomes. One potential reason is iatrogenic delivery, which cannot be accurately captured in administrative data. Restricting to commercial insurance enrollees due to the nature of the dataset excludes women with Medicaid (which provides coverage for large proportions of cancer survivors and pregnant individuals in the U.S.47), limiting generalizability. As we relied on billing codes (ICD, CPT, DRG, etc.) to identify exposures, covariates, and outcomes, misclassification could have occurred but anticipated to be non-differential by cancer status. While both severity of preterm births (<28 weeks, <32 weeks) and spontaneous versus iatrogenic preterm births are outcomes of interest, claims cannot accurately capture them. Due to using both ICD-9 and ICD-10-CM/PCS codes, potential disruptions in observed rates relating to the coding transition and coding errors could contribute to misclassification bias. Confounders including smoking, obesity, and prior preterm birth are not reliable in health claims data and thus could not be included. Finally, there may be detection bias of comorbidities and outcomes in AYA cancer survivors that contributed to our findings.