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An association between preterm delivery and long-term maternal cardiovascular morbidity

      Objective

      The purpose of this study was to investigate whether a history of preterm delivery (PTD) poses a risk for subsequent maternal long-term cardiovascular morbidity.

      Study Design

      A population-based study compared the incidence of cardiovascular morbidity in a cohort of women who delivered preterm (<37 weeks' gestation) and those who gave birth at term at the same period. Deliveries occurred during the years 1988-1999 with follow up until 2010. Kaplan-Meier survival curves were used to estimate cumulative incidence of cardiovascular hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios for cardiovascular hospitalizations.

      Results

      During the study period 47,908 women met the inclusion criteria; 12.5% of the patients (n = 5992) delivered preterm. During a follow-up period of >10 years, patients with PTD had higher rates of simple and complex cardiovascular events and higher rates of total cardiovascular-related hospitalizations. A linear association was found between the number of previous PTD and future risk for cardiovascular hospitalizations (5.5% for ≥2 PTDs; 5.0% for 1 PTD vs 3.5% in the comparison group; P < .001). The association remained significant for spontaneous vs induced PTD and for early (<34 weeks) and late (34 weeks to 36 weeks 6 days' gestation) PTD. In a Cox proportional hazards model that adjusted for pregnancy confounders such as labor induction, diabetes mellitus, preeclampsia, and obesity, PTD was associated independently with cardiovascular hospitalizations (adjusted hazard ratio, 1.4; 95% confidence interval, 1.2–1.6).

      Conclusion

      PTD is an independent risk factor for long-term cardiovascular morbidity in a follow-up period of more than a decade.

      Key words

      For Editors' Commentary, see Contents
      Preterm delivery (PTD; <37 weeks' gestation) complicates 5-12.7% of deliveries worldwide.
      • Gotsch F.
      • Romero R.
      • Erez O.
      • et al.
      The preterm parturition syndrome and its implications for understanding the biology, risk assessment, diagnosis, treatment and prevention of preterm birth.
      In 2007, the rate of PTD in the United States was 12.7%; this is an increase of 20% from the 1990s and 36% from the 1980s. This increase is due to an increase in the number of indicated PTD rather than spontaneous PTD.
      • Goldenberg R.L.
      • Culhane J.F.
      • Iams J.D.
      • Romero R.
      Epidemiology and causes of preterm birth.
      A similar increase can be seen in other industrial countries.
      • Conde-Agudelo A.
      • Romero R.
      • Kusanovic J.P.
      Nifedipine in the management of preterm labor: a systematic review and metaanalysis.
      PTD is the leading cause of perinatal morbidity and death.
      • Goldenberg R.L.
      • Culhane J.F.
      • Iams J.D.
      • Romero R.
      Epidemiology and causes of preterm birth.
      The link between pregnancy complications and future risk for cardiovascular disease (CVD) has been studied previously,
      • Irgens H.U.
      • Reisaeter L.
      • Irgens L.M.
      • Lie R.T.
      Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study.
      • Shalom G.
      • Shoham-Vardi I.
      • Sergienko R.
      • Wiznitzer A.
      • Sherf M.
      • Sheiner E.
      Is preeclampsia a significant risk factor for long-term hospitalizations and morbidity?.
      • Mangos G.J.
      • Spaan J.J.
      • Pirabhahar S.
      • Brown M.A.
      Markers of cardiovascular disease risk after hypertension in pregnancy.
      • Vrachnis N.
      • Augoulea A.
      • Iliodromiti Z.
      • Lambrinoudaki I.
      • Sifakis S.
      • Creatsas G.
      Previous gestational diabetes mellitus and markers of cardiovascular risk.
      with a specific focus on preeclampsia and gestational diabetes mellitus. Irgens et al
      • Irgens H.U.
      • Reisaeter L.
      • Irgens L.M.
      • Lie R.T.
      Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study.
      studied a registry of 626,727 births and compared mothers with and without a history of preeclampsia. They found women with a history of preeclampsia to be at higher risk for cardiovascular-related death. Recently, Shalom et al
      • Shalom G.
      • Shoham-Vardi I.
      • Sergienko R.
      • Wiznitzer A.
      • Sherf M.
      • Sheiner E.
      Is preeclampsia a significant risk factor for long-term hospitalizations and morbidity?.
      found preeclampsia to be a significant risk factor for long-term morbidity such as chronic hypertension and hospitalizations. Likewise, Mangos et al
      • Mangos G.J.
      • Spaan J.J.
      • Pirabhahar S.
      • Brown M.A.
      Markers of cardiovascular disease risk after hypertension in pregnancy.
      studied patients with a history of preeclampsia or gestational hypertension and found biochemical evidence predisposing them to later cardiovascular complications.
      A similar trend was noted for gestational diabetes mellitus. Vrachnis et al
      • Vrachnis N.
      • Augoulea A.
      • Iliodromiti Z.
      • Lambrinoudaki I.
      • Sifakis S.
      • Creatsas G.
      Previous gestational diabetes mellitus and markers of cardiovascular risk.
      reviewed studies regarding gestational diabetes mellitus and future risk for CVD and concluded that these patients should be considered a population at risk for future CVD. This evidence led to recent recommendations published by the American Heart Association, which included preeclampsia and gestational diabetes mellitus in the guidelines for the preliminary risk evaluation for CVD in women.
      • Mosca L.
      • Benjamin E.J.
      • Berra K.
      • et al.
      Effectiveness-based guidelines for the prevention of cardiovascular disease in women-2011 update: a guideline from the American Heart Association.
      Data regarding other pregnancy complications such as PTD and future risk for CVD are not well established. The underlining cause and mechanism of PTD delivery is not yet completely understood. The main mechanisms that have been suggested are inflammation, infection, and vascular diseases.
      • Romero R.
      • Espinoza J.
      • Kusanovic J.P.
      • et al.
      The preterm parturition syndrome.
      • Romero R.
      • Kusanovic J.P.
      • Chaiworapongsa T.
      • Hassan S.S.
      Placental bed disorders in preterm labor, preterm PROM, spontaneous abortion and abruptio placentae.
      • Siddiqui N.
      • Hladunewich M.
      Understanding the link between the placenta and future cardiovascular disease.
      Several studies have investigated the association between PTD and subsequent risk for cardiovascular morbidity.
      • Smith G.C.
      • Pell J.P.
      • Walsh D.
      Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.
      • Hastie C.E.
      • Smith G.C.
      • Mackay D.F.
      • Pell J.P.
      Maternal risk of ischemic heart disease following elective and spontaneous pre-term delivery: retrospective cohort study of 750,350 single tone pregnancies.
      • Bonamy A.K.
      • Parikh N.I.
      • Cnattingius S.
      • Ludvigsson J.F.
      • Ingelsson E.
      Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth.
      • Catov J.M.
      • Wu C.S.
      • Olsen J.
      • Sutton-Tyrrell K.
      • Li J.
      • Nohr E.A.
      Early or recurrent preterm birth and maternal cardiovascular disease risk.
      • Catov J.M.
      • Newman A.B.
      • Roberts J.M.
      • et al.
      Preterm delivery and later maternal cardiovascular disease risk.
      Nevertheless, it is not yet understood clearly whether there is a direct association between PTD and future risk for CVD or whether this increased risk is due to other comorbidities such as hypertensive disorders or growth restriction.
      • Hastie C.E.
      • Smith G.C.
      • Mackay D.F.
      • Pell J.P.
      Maternal risk of ischemic heart disease following elective and spontaneous pre-term delivery: retrospective cohort study of 750,350 single tone pregnancies.
      The objective of the present population- based study was to investigate whether PTD is an independent risk factor for subsequent long-term cardiovascular morbidity during a follow-up period of more than a decade. We also wanted to investigate the association between spontaneous vs induced PTD, early vs late PTD, and the number of PTDs to long-term cardiovascular hospitalizations.

      Materials and Methods

      Setting

      The study was conducted at the Soroka University Medical Center, the sole hospital of the Negev, the southern region of Israel, that serves the entire population in this region. Thus, the study is based on a nonselective population data. The institutional review board (in accordance with the Helsinki declaration) approved the study.

      Study population

      The study population was composed of all patients who delivered in the years 1988-1998; the follow-up period was until 2010. Patients with multiple pregnancies and with known CVD before or during the index pregnancy were excluded from the study.

      Study design

      We conducted a population-based retrospective cohort study. The primary exposure was having had at least 1 PTD. Patients who for the entire period of follow up did not experience PTD comprised the comparison group; the last delivery was used as the index birth. A retrospective follow up of hospitalizations because of cardiovascular morbidity 10-20 years after the index birth was preformed. Cardiovascular morbidity was defined as hospitalizations for any cardiovascular reasons at the first cardiovascular hospitalization at Soroka University Medical Center. Cardiovascular morbidity was divided into 4 categories according to severity and type that included simple and complex cardiovascular events (eg, angina pectoris and congestive heart failure, respectively), and invasive and noninvasive cardiac procedures (eg, insertion of a stent and a treadmill stress test, respectively). The exact International Classification of Diseases, 9th edition (ICD-9) codes for each subtype of cardiovascular morbidity are presented in the Appendix (Supplementary Table).
      Data were collected from 2 databases that were cross-linked and merged: the computerized perinatal database and the computerized hospitalization database of the Soroka University Medical Center. The perinatal database consists of information recorded directly after delivery by an obstetrician. Skilled medical secretaries routinely review the information before entering it into the database. Coding was performed after assessment of medical prenatal care records together with the routine hospital documents. The hospitalization database includes demographic information and ICD-9 codes for all medical diagnoses made during hospitalizations.

      Statistical analysis

      Statistical analysis was performed with the SPSS software (version 17; SPSS Inc, Chicago, IL). Statistical significance was calculated with the χ2 test for differences in qualitative variables and the Student t test for differences in continuous variables. Stratified analysis was performed (the pooled odds ratio was calculated with the Mantel-Haenszel test) to investigate the association between spontaneous vs induced PTD, early vs late, PTD with and without preterm premature rupture of membranes, PTD with and without preeclampsia, and long-term CVD. The association between the number of PTDs and the risk for subsequent cardiovascular hospitalizations and morbidity was evaluated with the χ2 test for trends (the linear-by-linear association test).
      Kaplan-Meier survival curve was used to compare cumulative incidence of cardiovascular hospitalizations. Cox proportional hazards models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for long-term cardiovascular hospitalizations. A probability value of < .05 was considered statistically significant.

      Results

      During the study period, there were 47,908 women who met the inclusion criteria; 5992 women (12.5%) had at least 1 PTD, the first of which was considered the index delivery.
      Table 1 presents a summary of the characteristics of the index delivery of patients with and without a diagnosis of PTD. Patients in the PTD group were significantly younger at the index birth, had a lower birth order than the comparison group, and were more likely to be Bedouin than women in the comparison group. The mean number of days from the index pregnancy to the cardiovascular hospitalization was significantly shorter in the PTD compared with the comparison group.
      Table 1Characteristics of patients with and without a history of preterm delivery
      CharacteristicPreterm delivery (n = 5992)No preterm delivery (n = 41,916)P value
      Maternal age at index birth, y
      Data are given as mean ± SD
      28.1 ± 629.9 ± 6.001
      Ethnicity, %.001
       Jewish52.670.4
       Bedouin47.429.6
      Postpartum anemia: hemoglobin (<10 g/dL), %23.818.2.001
      Diabetes mellitus: gestational and pregestational, %8.38.2.768
      Obesity: pregestational body mass index >30 kg/m2, %1.12.0.001
      Parity at index birth, n
      Data are given as median (mode).
      3 (2)3 (1).001
      Years from index pregnancy to hospitalization
      Data are given as mean ± SD
      9.3 ± 4.710.6 ± 4.8.001
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      a Data are given as mean ± SD
      b Data are given as median (mode).
      Table 2 presents a comparison of cardiovascular morbidity and hospitalizations during the follow-up period. Patients with PTD had higher rates of simple and complex cardiovascular events and total cardiovascular-related hospitalizations.
      Table 2Incidence of first hospitalizations for cardiovascular causes
      VariablePreterm delivery (n = 5992)No preterm delivery (n = 41,916)OR95% CIP value
      Cardiac noninvasive diagnostic procedures1.4%1.1%1.20.9–1.5.062
      Cardiac invasive diagnostic procedures0.5%0.4%1.10.7–1.7.610
      Simple cardiovascular events3.7%2.5%1.51.3–1.7.001
      Complex cardiovascular events0.4%0.1%3.62.1–6.1.001
      Total cardiovascular hospitalizations5.1%3.5%1.51.3–1.7.001
      CI, confidence interval; OR, odds ratio.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      Table 3 presents a comparison between the incidence of cardiovascular morbidity in women with early PTD (<34 weeks' gestation) and late preterm PTD (34-37 weeks' gestation). The risk for CVD remained significant in the early and the late PTD groups, and both groups were noted as having a risk factor for simple and complex events, and for cardiovascular hospitalizations in general. Nevertheless, the odds ratio was higher for the early PTD group.
      Table 3ORs of cardiovascular morbidity and hospitalization during the follow-up period in patients with and without a history of PTD with a subdivision of early (<34 weeks' gestation) and late (34-37 weeks' gestation) PTD, compared with term deliveries
      VariableEarly PTD: <34 weeks' gestation (n = 1396)Late PTD: 34-37 weeks' gestation (n = 4596)
      OR95% CIP valueOR95% CIP value
      Cardiac noninvasive diagnostic procedures1.30.8–2.3211.30.9–1.6.099
      Cardiac invasive diagnostic procedures1.80.9–3.4.0760.90.5–1.5.717
      Simple cardiovascular events1.81.4–2.3.0011.41.2–1.7.001
      Complex cardiovascular events5.12.3–11.5.0013.11.7–5.7.001
      Total cardiovascular hospitalizations1.71.3–2.1.0011.41.2–1.6.001
      CI, confidence interval; OR, odds ratio; PTD, preterm delivery.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      Table 4 presents a comparison between the incidence of cardiovascular morbidity in women with spontaneous PTD and women with a history of PTD after induction of labor. The risk for simple and complex cardiovascular events and total cardiovascular-related hospitalizations remained significant in both spontaneous and induced PTD.
      Table 4OR of cardiovascular morbidity and hospitalization during the follow-up period in patients with spontaneous PTD and PTD after induction of labor
      VariableInduction (n = 6239)Spontaneous (n = 41,669)
      OR95% CIP valueOR95% CIP value
      Cardiac noninvasive diagnostic procedures1.30.5–2.1.9621.31.1–1.7.044
      Cardiac invasive diagnostic procedures2.00.8–4.9.1100.90.6–1.6.971
      Simple cardiovascular events1.91.4–2.7.0011.41.2–1.7.001
      Complex cardiovascular events2.60.5–12.5.2153.82.2–6.6.001
      Total cardiovascular hospitalizations1.71.3–2.4.0011.41.2–1.6.001
      CI, confidence interval; OR, odds ratio; PTD, preterm delivery.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      Table 5 presents a comparison between the number of PTD and the risk for subsequent cardiovascular hospitalizations and morbidity. A significant linear association was found between the number of PTD and the risk for simple CVD and cardiovascular hospitalizations.
      Table 5A comparison of the incidence of cardiovascular-related hospitalizations and morbidity between patients with a history of ≥2 PTDs with patients with just 1 and no PTD (with the use of the χ2 test for trends)
      VariablePTD, %P value
      None (n = 41,916)1 (n = 5217)≥2 (n = 775)
      Cardiac noninvasive diagnostic procedures1.11.41.2.150
      Cardiac invasive diagnostic procedures0.40.40.6.582
      Simple cardiovascular events2.53.64.1.001
      Complex cardiovascular events0.10.40.3.001
      Total cardiovascular hospitalizations3.55.05.5.001
      PTD, preterm delivery.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      Table 6 presents the pooled odds ratio for cardiovascular-related hospitalizations in patients with a history of PTD; the Mantel-Haenszel test controlled for specific confounders. Stratified analysis showed a significant association between PTD and total cardiovascular hospitalizations after being controlled for premature rupture of membranes, preeclampsia, intrauterine growth restriction, and induction of labor.
      Table 6OR for cardiovascular-related hospitalizations in patients with a history of PTD with the use of the Mantel-Haenszel test to control for specific confounders
      VariableWeighted OR for PTD95% CIP value
      Preterm rupture of membranes1.51.3–1.7.001
      Intrauterine growth restriction1.51.3–1.7.001
      Preeclampsia/toxemia1.31.2–1.5.001
      Induction of labor1.51.3–1.7.001
      CI, confidence interval; OR, odds ratio; PTD, preterm delivery.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      The Figure presents a Kaplan-Meier hazard function curve for the cumulative incidence of cardiovascular hospitalizations after the index birth in both study groups (PTD or term). Patients with a history of PTD had a significantly higher risk for cardiovascular events during the whole follow-up period.
      Figure thumbnail gr1
      FigureKaplan-Meier hazard function curve for cardiovascular-associated hospitalization of patients with and without a history of PTD
      Cum, cumulative; PTD, preterm delivery.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.
      Cox proportional hazards models were used to estimate the adjusted HRs and 95% CI for long-term cardiovascular hospitalizations (Table 7). After we controlled for recognized confounders that are related to the metabolic syndrome (eg, diabetes mellitus, preeclampsia, and obesity) and that are known to be associated with higher risk for CVD, PTD remained associated independently with cardiovascular hospitalizations (adjusted HR, 1.33; 95% CI, 1.17–1.5). Even after we controlled for additional variables (eg, maternal age, labor induction, ethnicity, and anemia), PTD remained independently associated with an increased risk for subsequent cardiovascular hospitalizations (adjusted HR, 1.4; 95% CI, 1.2–1.6).
      Table 7Cox multivariable regression models for the risk of cardiovascular hospitalization
      VariableAdjusted hazard ratio95% CIP value
      Model 1
       Preterm delivery (<37 weeks' gestation)1.31.2–1.5.001
       Diabetes mellitus (gestational and pregestational)2.62.3–2.9.001
       Obesity (pregestational body mass index >30 kg/m2)2.51.9–3.2.001
       Preeclampsia2.42.1–2.8.001
      Model 2
       Preterm delivery (<37 weeks' gestation)1.41.2–1.6.001
       Diabetes mellitus (gestational and pregestational)2.01.8–2.3.001
       Obesity (pregestational body mass index >30 kg/m2)2.31.7–3.0.001
       Preeclampsia2.21.9–2.6.001
       Maternal age1.11.05–1.15.001
       Ethnicity (Bedouin vs Jewish)2.01.7–2.5.001
       Anemia (hemoglobin <10 g/dL)1.21.1–1.4.002
       Induction of labor1.21.04–1.4.004
      CI, confidence interval.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.

      Comments

      The major finding of the current study is that PTD is an independent risk factor for subsequent long-term cardiovascular morbidity and cardiovascular-related hospitalizations.
      The results of our study add to the data from other studies regarding the relationship between PTD and future risk for cardiovascular morbidity.
      • Smith G.C.
      • Pell J.P.
      • Walsh D.
      Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.
      • Hastie C.E.
      • Smith G.C.
      • Mackay D.F.
      • Pell J.P.
      Maternal risk of ischemic heart disease following elective and spontaneous pre-term delivery: retrospective cohort study of 750,350 single tone pregnancies.
      • Bonamy A.K.
      • Parikh N.I.
      • Cnattingius S.
      • Ludvigsson J.F.
      • Ingelsson E.
      Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth.
      • Catov J.M.
      • Wu C.S.
      • Olsen J.
      • Sutton-Tyrrell K.
      • Li J.
      • Nohr E.A.
      Early or recurrent preterm birth and maternal cardiovascular disease risk.
      • Catov J.M.
      • Newman A.B.
      • Roberts J.M.
      • et al.
      Preterm delivery and later maternal cardiovascular disease risk.
      Smith et al
      • Smith G.C.
      • Pell J.P.
      • Walsh D.
      Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births.
      studied data regarding 129,920 first deliveries and found that patients with a history of PTD had significantly high rates of ischemic heart disease (adjusted HR, 1.8; 95% CI, 1.3–2.5). In our study, further categorization of the cardiovascular complications was performed according to ICD-9 codes. It emphasizes the importance of a previous history of PTD as a risk factor for not only the endpoint of cardiovascular hospitalizations but also for simple and complex morbidity. Hastie et al
      • Hastie C.E.
      • Smith G.C.
      • Mackay D.F.
      • Pell J.P.
      Maternal risk of ischemic heart disease following elective and spontaneous pre-term delivery: retrospective cohort study of 750,350 single tone pregnancies.
      found a strong association between induced PTD and subsequent cardiovascular morbidity. The authors suggested that induced deliveries usually were due to suspicion of intrauterine growth restriction or preeclampsia, which might better explain the association with vascular events later in life. Therefore, the analysis in our study included an adjustment for preeclampsia, intrauterine growth restriction, premature rupture of membranes, and labor induction. PTD remained an independent risk factor for CVD, even after we controlled for these significant confounders.
      The risk for CVD was more substantial when a patient had a history of early PTD (<34 weeks' gestation). Two previous studies addressed this issue with different conclusions: Bonamy et al
      • Bonamy A.K.
      • Parikh N.I.
      • Cnattingius S.
      • Ludvigsson J.F.
      • Ingelsson E.
      Birth characteristics and subsequent risks of maternal cardiovascular disease: effects of gestational age and fetal growth.
      analyzed data from 923,686 patients in their first singleton birth. After controlling for confounders, they demonstrated an increasing risk for CVD with decreasing gestational age at birth. Catov et al
      • Catov J.M.
      • Wu C.S.
      • Olsen J.
      • Sutton-Tyrrell K.
      • Li J.
      • Nohr E.A.
      Early or recurrent preterm birth and maternal cardiovascular disease risk.
      did not find an association between the lower gestational age and cardiovascular complications.
      Interestingly, in our study, a significant linear association was documented between the number of previous PTDs and the future risk for simple CVD and cardiovascular hospitalizations. A similar “dose-response” association has been documented by only 1 previous study.
      • Catov J.M.
      • Wu C.S.
      • Olsen J.
      • Sutton-Tyrrell K.
      • Li J.
      • Nohr E.A.
      Early or recurrent preterm birth and maternal cardiovascular disease risk.
      Although some previous studies that investigated the association between PTD and cardiovascular morbidity were based on self-reports of the patients regarding PTD, birthweight, smoking, and hypertensive disorders,
      • Catov J.M.
      • Newman A.B.
      • Roberts J.M.
      • et al.
      Preterm delivery and later maternal cardiovascular disease risk.
      our study data were obtained from the computerized files and not based on self-reports, which might lead to a recall bias.
      The proportion of Bedouin parturients was significantly higher in the PTD group than in the comparison group. The Bedouins are a traditional society that tends to under-utilize the existing prenatal care services and in general have different accessibility to health services. The higher prevalence of PTD among Bedouin parturients (as compared with Jewish parturients) was noted in other studies
      • Twizer I.
      • Sheiner E.
      • Hallak M.
      • Mazor M.
      • Katz M.
      • Shoham-Vardi I.
      Lack of prenatal care in a traditional society. Is it an obstetric hazard?.
      • Melamed Y.
      • Bashiri A.
      • Shoham-Vardi I.
      • Furman B.
      • Hackmon-Ram R.
      • Mazor M.
      Differences in preterm delivery rates and outcomes in Jews and Bedouins in Southern Israel.
      ; therefore, it was considered to be a potential confounder.
      The main strength of the study lies in the fact that our hospital is the only hospital serving the entire population of southern Israel. The hospital provides both maternity services and tertiary cardiovascular medical services; thus, as long as patients live in the area, they would use this hospital. However, the ascertainment of cardiovascular events that occurred outside of the hospital could not be accomplished. It is therefore possible that some cardiovascular events were missed, but there is no reason to suspect differential rates of outcome ascertainment in the 2 study groups.
      In conclusion, in our population, PTD was noted as an independent risk factor for subsequent long-term simple and complex cardiovascular complications that require hospitalization. This risk is more substantial in patients with early PTD and patients with >1 previous PTD.
      The cardiovascular risk assessment for women is suboptimal; pregnancy could be considered a stress test to improve risk assessment for future risk of CVD. On the basis of our findings, patients after a PTD may benefit from cardiovascular risk screening, early detection, and perhaps secondary prevention of CVD.

      Appendix

      Supplementary TableCardiovascular morbidity divided to 4 groups from the International Classification of Diseases 9 (ICD-9)
      GroupInvestigated diagnosesICD-9
      1: simple cardiovascular events
      Chronic ischemic heart disease, unspecified4149
      Cardiovascular disease, unspecified4292
      Acute, but ill-defined, cerebrovascular disease436
      Other and ill-defined cerebrovascular disease437
      Cerebral atherosclerosis4371
      Other specified peripheral vascular diseases4438
      Other peripheral vascular disease44389
      Mixed hyperlipidemia2722
      Other and unspecified hyperlipidemia2724
      Angina pectoris413
      Other and unspecified angina pectoris4139
      Hypertensive heart disease402
      Other acute and subacute forms of ischemic heart disease411
      Other acute and subacute forms of ischemic heart disease4118
      Acute ischemic heart disease without myocardial infarction41181
      Other forms of chronic ischemic heart disease414
      Other specified forms of chronic ischemic heart disease4148
      Heart disease, unspecified4299
      Atherosclerosis440
      Atherosclerosis of arteries of the extremities4402
      Unspecified essential hypertension4019
      Peripheral vascular disease, unspecified4439
      2: cardiac noninvasive diagnostic procedures
      Diagnostic ultrasound scanning of peripheral vascular systemZ8877
      Cardiovascular stress test with treadmillZ8941
      Cardiovascular stress test with bicycle ergometerZ8943
      Other cardiovascular stress testZ8944
      Other nonoperative cardiac and vascular diagnostic proceduresZ895
      Screening for other and unspecified cardiovascular conditionsV812
      Other cardiovascular proceduresZ005
      Other nonoperative cardiac and vascular diagnostic proceduresZ895
      Screening for ischemic heart diseaseV810
      3: complex cardiovascular events
      Acute myocardial infarction (different types)410
      Congestive heart failure4280
      Left heart failure4281
      Heart failure, unspecified4289
      Congestive heart failure, unspecified4280
      Unspecified hypertensive heart and kidney disease404
      Unspecified hypertensive heart and kidney disease without heart failure or chronic kidney disease4049
      Cardiac arrest4275
      Acute pulmonary heart disease415
      Acute cor pulmonale4150
      4: cardiac invasive diagnostic procedures
      Insertion of 1 vascular stentZ0045
      Insertion of 2 vascular stentsZ0046
      Percutaneous insertion of intracranial vascular stent(s)Z0065
      Insertion of 3 vascular stentsZ0047
      Right heart cardiac catheterization, cardiac catheterization, nosZ3721
      Cardiac catheterization, nosZ37211
      Left heart cardiac catheterizationZ3722
      Combined right and left heart cardiac catheterizationZ3723
      Angiocardiography of right heart structuresZ8852
      Angiocardiography of left heart structuresZ8853
      Combined right and left heart angiocardiographyZ8854
      Coronary arteriography with 2 cathetersZ8855
      Coronary arteriography with 2 cathetersZ8856
      Other and unspecified coronary arteriographyZ8857
      Aortocoronary bypass for heart revascularization, nosZ3610
      Other bypass anastomosis for heart revascularizationZ3619
      nos, not otherwise specified.
      Kessous. PTD and future risk for cardiovascular disease. Am J Obstet Gynecol 2013.

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