Long‐term cardiovascular mortality in women with twin pregnancies by lifetime reproductive history

Abstract

Background: Women with one lifetime singleton pregnancy have increased risk of cardiovascular disease (CVD) mortality compared with women who continue reproduction particularly if the pregnancy had complications. Women with twins have higher risk of pregnancy complications, but CVD mortality risk in women with twin pregnancies has not been fully described. Objectives:We estimated risk of long-term CVD mortality in women with naturally conceived twins compared to women with singleton pregnancies, accounting for lifetime number of pregnancies and pregnancy complications.Methods: Using linked data from the Medical Birth Registry of Norway and the Norwegian Cause of Death Registry, we identified 974,892 women with first pregnancy registered between 1967 and 2013, followed to 2020. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for maternal CVD mortality were estimated by Cox regression for various reproductive history (exposure categories): (1) Only one twin pregnancy, (2) Only one singleton pregnancy, (3) Only two singleton pregnancies, (4) A first twin pregnancy and continued reproduction, (5) A first singleton pregnancy and twins in later reproduction and (6) Three singleton pregnancies (the referent group). Exposure categories were also stratified by pregnancy complications (pre-eclampsia, preterm delivery or perinatal loss).Results: Women with one lifetime pregnancy, twin or singleton, had increased risk of CVD mortality (adjusted hazard [HR] 1.72, 95% confidence interval [CI] 1.21, 2.43 and aHR 1.92, 95% CI 1.78, 2.07, respectively), compared with the referent of three singleton pregnancies. The hazard ratios for CVD mortality among women with one lifetime pregnancy with any complication were 2.36 (95% CI 1.49, 3.71) and 3.56 (95% CI 3.12, 4.06) for twins and singletons, respectively. Conclusions:Women with only one pregnancy, twin or singleton, had increased longterm CVD mortality, however highest in women with singletons. In addition, twin mothers who continued reproduction had similar CVD mortality compared to women with three singleton pregnancies.

History of multifetal gestation and long‐term maternal mortality

“…Our finding of reduced risk of all‐cause mortality before age 70 for participants with a history of multifetal gestation was unexpected, as twin pregnancy has not been found to confer either a survival disadvantage or survival benefit in prior studies of cardiovascular mortality, 17,18 and some evidence supports an increased risk of cancer 19–21 . Consistent with our results, two previous studies of cardiovascular morbidity suggest a slight benefit of multifetal gestation: history of twin versus singleton delivery was associated with 15% lower odds of cardiovascular hospitalisation over approximately 11 years of follow‐up in an Israeli cohort 14 ; and among Swedish women without preeclampsia, those with a multifetal pregnancy had 17% lower risk of later compound cardiovascular disease compared to women with a singleton pregnancy 15 .…”

“…[19][20][21] Consistent with our results, two previous studies of cardiovascular morbidity suggest a slight benefit of multifetal gestation: history of twin versus singleton delivery was associated with 15% lower odds of cardiovascular hospitalisation over approximately 11 years of follow-up in an Israeli cohort 14 ; and among Swedish women without preeclampsia, those with a multifetal pregnancy had 17% lower risk of later compound cardiovascular disease compared to women with a singleton pregnancy. 15 Unlike most prior research 14,[16][17][18] Evolutionary biology and anthropology researchers have hypothesized that a human maternal fitness benefit may be associated with spontaneous multifetal pregnancy. [11][12][13] Historical demographic data in the Utah Population Database, representing a very high-parity population of women born in the 1800s, suggests that among women who survived to age 50, those who ever had twins had a postmenopausal survival benefit compared to those who never had twins.…”

“…Five prior epidemiologic studies of long-term maternal postpartum cardiovascular health suggest that carrying a multifetal gestation does not confer additional risk compared to a singleton pregnancy. [14][15][16][17][18] However, the prior literature incompletely describes the potential relationship between multifetal gestation and longterm maternal health risks. For example, inference from the prior studies was hindered by incomplete outcome ascertainment (i.e., <5% of study participants, and in some cases <1%, developing outcomes of interest): most participants were in their 50s or younger at the end of follow-up in four of these studies, [14][15][16][17] and the fifth cohort restricted to mortality before age 70.…”

“…For example, inference from the prior studies was hindered by incomplete outcome ascertainment (i.e., <5% of study participants, and in some cases <1%, developing outcomes of interest): most participants were in their 50s or younger at the end of follow-up in four of these studies, [14][15][16][17] and the fifth cohort restricted to mortality before age 70. 18 The previous studies also focussed largely or entirely on non-Hispanic White populations, leading to questionable generalisability to the US context, which is characterised by greater racial and ethnic diversity. Finally, all prior studies focussed on cardiovascular outcomes (including mortality), capturing only some of the potential health effects of multifetal gestation, which may additionally include the risk of breast, endometrial, and cervical cancers.…”

Understanding the role of twinning for the risk of long‐term maternal health

“…The article by Basnet et al 2 in this month's Paediatric and Perinatal Epidemiology aims to address this gap. Using administrative health data in Norway from 1967 to 2020, including data from pregnancy and death registries, the authors examined the relationship between twinning and CVD‐related mortality, accounting for parity and pregnancy complications.…”