Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease

Abstract

Background: Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). It is uncertain whether giving birth to SGA infant is a specific determinant of later IHD, independent of other risk factors, or a marker of general poor health. The purpose of this study was to investigate the association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors.

Methods and findings: Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999-2006), a probability sample of the U.S. population. Sequence of events was determined from age at last live birth and at diagnosis of IHD. Delivery of a SGA infant is strongly associated with greater maternal risk for IHD (age adjusted OR; 95% CI: 1.8; 1.2, 2.9; p = 0.012). The association was independent of the family history of IHD, stroke, hypertension and diabetes (family history-adjusted OR; 95% CI: 1.9; 1.2, 3.0; p = 0.011) as well as other risk factors for IHD (risk factor-adjusted OR; 95% CI: 1.7; 1.1, 2.7; p = 0.025). Delivery of a SGA infant was associated with earlier onset of IHD and preceded it by a median of 30 (interquartile range: 20, 36) years.

Conclusions: Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD.

Figure 1. Prevalence of ischemic heart disease in relation to delivery of a small for gestational age infant.

SGA, delivery of a small for gestational age infant, a term live born infant with birth weight <2500 g. No SGA, prior delivery of a term live born infant that was not small for gestational age. Population weighted proportion and 95% confidence intervals of the ischemic heart disease in women with prior live birth, adjusted for age. p-value was calculated using weighted logistic regression accounting for the sampling scheme of the survey and adjusted for age.

Figure 2. Kaplan–Meier curves of the cumulative probability of ischemic heart disease according to delivery of small for gestational age infant.

SGA, delivery of a small for gestational age infant, a term live born infant with birth weight <2500 g. No SGA, prior delivery of a term live born infant that was not small for gestational age. Number at risk, number of participants at risk of ischemic heart disease (IHD) at age 20, 40, 60 and 80 years. Age was used as the time scale, age at last live birth as time of study entry and age at IHD diagnosis was taken as the event.

Figure 3. Relative odds for breast cancer, cancer, stroke and ischemic heart disease in mothers according to history of a delivery of a small for gestational age infant.

Breast cancer, cancer, stroke and ischemic heart disease (IHD) were reported as diagnosed by a physician. Population weighted odds ratios and 95% confidence intervals of adverse outcomes in women with prior live term birth of a small for gestational age infant comparing to women with prior live term birth of an infant not small for gestational. The odds ratios and 95% confidence intervals were obtained using weighted logistic regression accounting for the sampling scheme of the survey and adjusted for age. SGA, delivery of a small for gestational age infant, a term live born infant with birth weight <2500 g. No SGA, prior delivery of a term live born infant that was not small for gestational age.

Figure 4. Risk of ischemic heart disease in relation to the traditional risk factors and delivery of a small for gestational age infant in a multivariable analysis.

Multivariable logistic regression model of preterm birth included all investigated traditional risk factors for ischemic heart disease and SGA. IHD, ischemic heart disease. SGA, delivery of a small for gestational age infant, a term live born infant with birth weight <2500 g. No SGA, prior delivery of a term live born infant that was not small for gestational age. Smoking, smoked at least 100 cigarettes in lifetime. Low fiber diet, less than 25 g of fiber consumed daily. Antihyperlipidemic med., use of antihyperlipidemic medication at the time of examination. BMI, body mass index≥30. Inactivity, number of hours spent daily watching television or in front of the computer. Income, annual household income reported in $5,000 increments. Detectable cotinine, serum cotinine concentrations ≥0.05 ng/mL. Alcohol, no alcohol use comparing to a moderate <15 g/day alcohol consumption. Total cholesterol, total serum cholesterol ≥240 mg/dl. LDL cholesterol, LDL serum cholesterol ≥160 ng/ml. HDL cholesterol, HDL serum cholesterol <35 mg/dl. Triglycerides, serum triglycerides ≥200 mg/dl. Serum CRP, serum C-reactive protein ≥1 mg/dl. Hgb A1c, concentration of Hemoglobin A 1c >5.6%. OR (95% CI), population weighted odds ratios and 95% confidence intervals of ischemic heart disease in women with prior live term birth. The odds ratios and 95% confidence intervals were obtained using weighted logistic regression accounting for the sampling scheme of the survey and adjusted for all risk factors of ischemic heart disease.