Preterm Delivery and Maternal Cardiovascular Disease in Young and Middle-Aged Adult Women.
Preterm delivery has been shown to be associated with increased risk of cardiovascular disease (CVD), but it is unknown whether this risk remains after adjustment for prepregnancy lifestyle and CVD risk factors.



We examined the association between history of having delivered an infant preterm (<37 weeks) and CVD in 70 182 parous women in the Nurses' Health Study II. Multivariable Cox proportional-hazards models were used to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) for CVD events (myocardial infarction and stroke, n=949); we also adjusted for intermediates to determine the proportion of the association between preterm and CVD accounted for by postpartum development of CVD risk factors.



After adjusting for age, race, parental education, and prepregnancy lifestyle and CVD risk factors, preterm delivery in the first pregnancy was associated with an increased risk of CVD (HR, 1.42; 95% CI, 1.16-1.72) in comparison with women with a term delivery (≥37 weeks) in the first pregnancy. When preterm delivery was split into moderate preterm (≥32 to <37 weeks) and very preterm (<32 weeks), the HRs were 1.22 (95% CI, 0.96-1.54) and 2.01 (95% CI, 1.47-2.75), respectively. The increased rate of CVD in the very preterm group persisted even among women whose first pregnancy was not complicated by hypertensive disorders of pregnancy (HR, 2.01; 95% CI, 1.38-2.93). In comparison with women with at least 2 pregnancies, all of which were delivered at term, women with a preterm first birth and at least 1 later preterm birth had a HR of CVD of 1.65 (95% CI, 1.20-2.28). The association between moderate preterm first birth and CVD was accounted for in part by the development of postpartum chronic hypertension, hypercholesterolemia, type 2 diabetes mellitus, and changes in body mass index (proportion accounted for, 14.5%; 95% CI, 4.0-41.1), as was the very-preterm-CVD relationship (13.1%; 95% CI, 9.0-18.7).



Preterm delivery is independently predictive of CVD and may be useful for CVD prevention efforts. Because only a modest proportion of the preterm-CVD association was accounted for by development of conventional CVD risk factors, further research may identify additional pathways.
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.). ltanz@mail.harvard.edu.
Lauren J
LJ
Tanz
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Jennifer J
JJ
Stuart
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Paige L
PL
Williams
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Eric B
EB
Rimm
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Stacey A
SA
Missmer
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Kathryn M
KM
Rexrode
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Kenneth J
KJ
Mukamal
From Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (L.J.T., J.J.S., P.L.W., E.B.R., S.A.M., J.W.R.-E.); Connors Center for Women's Health and Gender Biology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (L.J.T., J.J.S., J.W.R.-E.); Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (P.L.W.); Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R., K.J.M.); Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, MA (S.A.M.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (E.B.R., S.A.M., J.W.R.-E.); Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids (S.A.M.); Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (K.M.R.); and Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.).
Janet W
JW
Rich-Edwards
D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D047928:Premature Birth; D012307:Risk Factors
cardiovascular diseases; epidemiology; pregnancy; prevention & control; women