Twin pregnancies: impact of infertility treatments and postpartum lifestyle on maternal heart health.

This commentary refers to ‘Hospitalization for cardiovascular disease in the year after delivery of twin pregnancies’, by R. Lin et al., https://doi.org/10.1093/eurheartj/ehaf003 and the discussion piece ‘Key points for analysing cardiovascular disease after delivery of twin pregnancies’, by X. Li et al., https://doi.org/10.1093/eurheartj/ehaf335. We appreciate the thoughtful comments raised by Li et al.1 on our manuscript on twinning and the risks of maternal cardiovascular disease (CVD) hospitalizations in the USA, 2010–20.2 They raised three issues regarding our study, including (i) not specifying the reasons for infertility treatment; (ii) the lack of adjustment for other confounders, including lifestyle, socioeconomic stress, and physical activity levels post-delivery; and (iii) the exclusion of patients diagnosed with chronic hypertension. We address all three of their concerns. We agree with Li et al.’s point that the study did not specify the underlying reasons for infertility treatment, which can be linked to CVD. Conditions like advanced maternal age, polycystic ovary syndrome, and endometriosis, which are associated with infertility and, thus, the need for assisted reproductive technology (ART), are also connected to an increased risk of CVD.3 They claim that failure to adjust for these factors may confound the relationship between twin pregnancy and CVD, leading to inflated or deflated estimates of risk. We contend that adjustment for any infertility treatment will minimize confounding bias. Extensive database studies and meta-analyses have found mixed evidence on the association between infertility treatment and CVD.4 Assisted reproductive technology may increase cardiovascular demand due to ovarian stimulation and higher rates of multifetal gestation. There have been case reports of strokes in the setting of ovarian hyperstimulation syndrome, a well-known complication of ovarian stimulation used during ART.5 Preeclampsia risk appears higher with frozen rather than fresh embryo transfers.6 We acknowledge that due to limitations of the inpatient database, we did not specify the type of infertility treatment the patient received, which may have left our risk estimates affected by residual confounding. We excluded chronic hypertensive patients from the definition of hypertensive disease during pregnancy to avoid reverse causal associations; this may have slightly underestimated the absolute rates of CVD for all four groups (twins with and without hypertensive disease and singletons with and without hypertensive disease). We disagree with Li et al.’s1 assertion that excluding chronic hypertensive patients may underestimate the risk of maternal cardiovascular disease among twins compared to singleton pregnancies, which was the paper’s objective. We do not anticipate that pre-existing chronic hypertension would predispose a patient to have twins or singletons, so this should not affect the risk estimates we report in the manuscript. Confounding bias remains central to ensuring the robustness of findings in observational studies.7 We appreciate Li et al.’s1 suggestion that lifestyle, socioeconomic stress, and post-delivery physical activity levels be evaluated as potential confounders. However, we were limited to the availability of confounders in the Nationwide Readmissions Database. To overcome this, we assessed the role of unmeasured confounding in our study and discovered that the associations were robust and less likely to be affected by unmeasured confounders. We appreciate the opportunity to respond to Li and colleagues. Contributor Information Ruby Lin, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA. Cande V Ananth, Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA; Cardiovascular Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA; Department of Medicine, Rutgers Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901, USA; Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 683 Hoes Lane, Piscataway, NJ 08854, USA. Declarations Disclosure of Interest All authors declare no disclosure of interest for this contribution. Funding C.V.A. is supported by the National Heart, Lung, and Blood Institute (grant R01-HL150065) and by the National Institute of Environmental Health Sciences (grant R01-ES033190), the National Institutes of Health. However, these funds were not directly utilized in this study. References - 1. Li X, Yu S-Q, Yang Z-G. Key points for analysing cardiovascular disease after delivery of twin pregnancies. Eur Heart J 2025;46:3387. 10.1093/eurheartj/ehaf335 [DOI] [PubMed] [Google Scholar] - 2. Lin R, Fields JC, Lee R, Rosenfeld EB, Daggett EE, Sharma R et al. Hospitalization for cardiovascular disease in the year after delivery of twin pregnancies. Eur Heart J 2025;46:1219–28. 10.1093/eurheartj/ehaf003 [DOI] [PMC free article] [PubMed] [Google Scholar] - 3. Wekker V, van Dammen L, Koning A, Heida KY, Painter RC, Limpens J, et al. Long-term cardiometabolic disease risk in women with PCOS: a systematic review and meta-analysis. 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