Association Between Delivery of a Small-for-Gestational-Age Neonate and Long-Term Maternal Cardiovascular Morbidity

Abstract

The predisposing factors of small-for-gestational-age (SGA), intrauterine growth restriction, and hypertensive disorders have led to the concept of a “placenta-associated syndrome.” The probable risk factors for placenta-associated syndrome, such as chronic hypertension, dyslipidemia, obesity, and insulin resistance, are independent predictors of subsequent cardiovascular disease. An association has been reported between women who deliver an SGA neonate and later cardiovascular morbidity and mortality. This retrospective, population-based cohort study was undertaken to investigate the risk of later cardiovascular events among women who delivered an SGA neonate. Delivery and follow-up data were collected on pregnant women who delivered during 1988–1998. All included women had a follow-up period of 10 or more years after the index delivery. Clinical characteristics evaluated included ethnicity (Jewish or Bedouin Arab), maternal age, parity, gestational age, and birth weight. The association between delivery of an SGA neonate and maternal morbidity was assessed by comparing the incidence of morbidity and mortality between those who did or did not deliver an SGA neonate. Statistical significance was calculated using the χ2 or t test for differences in qualitative and continuous variables, respectively. Odds ratios (ORs) and confidence intervals (CIs) were calculated. A Cox proportional hazards model was used to estimate the adjusted hazard ratios and 95% CIs for long-term cardiovascular mortality with controls for known confounders. Kaplan-Meier survival curves were used to estimate the cumulative incidence of cardiovascular mortality. P < 0.05 indicated statistical significance. Of 47,612 deliveries meeting inclusion criteria, 4411 resulted in SGA neonates. Women who had an SGA neonate were younger than those who did not (mean age, 26.8 ± 6.1 and 29.9 ± 6.2 years, respectively; P < 0.001) and had fewer pregnancies (P < 0.001). A total of 54.0% of Bedouin women and 46.0% of Jewish women delivered an SGA neonate (P < 0.001). Delivery of an SGA neonate was a risk factor for long-term complex cardiovascular events (OR, 2.4; 95% CI, 1.3–4.4; P = 0.006) and cardiovascular mortality (OR, 3.4; 95% CI, 1.5–7.7; P = 0.006). No significant differences were noted between the groups regarding invasive cardiovascular procedures (OR, 1.2; 95% CI, 0.8–2.0; P = 0.329), and no significant differences were apparent in subsequent long-term hospitalization due to cardiovascular causes during 10 or more years of follow-up (OR, 1.0; 95% CI, 0.9–1.2; P = 0.777). After controlling for recognized confounders associated with the risk for cardiovascular disease, delivery of an SGA neonate was independently associated with cardiovascular mortality (adjusted hazard ratio 3.5; 95% CI, 1.5–8.2) and a significantly higher risk of cardiovascular mortality over the whole follow-up period (log-rank test, P = 0.002). Delivering an SGA neonate is a risk factor for long-term complex cardiovascular events and cardiovascular mortality and an independent risk factor for maternal long-term hospitalization for cardiovascular events. Prospective studies are needed to evaluate whether risk stratification and preventive interventions should be recommended based on a woman’s obstetric history.