In this analysis of a large prospective cohort, we found an inverse association between long duration of lactation and myocardial infarction, independent of known risk factors for cardiovascular disease, including obesity at age 18, parental history of MI, smoking, exercise, diet, aspirin use, alcohol consumption, hormone use, and menopausal status.
Breastfeeding rates in our study population are comparable with contemporary rates in the United States. All of our study participants were registered nurses, and 63% had ever breastfed. More than 10% of the cohort reported a birth in each year from 1954 to 1968, a period during which overall rates of breastfeeding were declining, from about 70% in 1951 to about 30% in 196621
. In 2005, 73% of US women had ever breastfed, 39% were still breastfeeding at 6 months, and 20% were breastfeeding at 1 year22
. These data suggest that, at current breastfeeding rates, a substantial number of US women of childbearing age who give birth to two or more children will breastfeed for ≥ 2 years.
Our findings must be interpreted in the context of the study design. All observational studies are subject to confounding, and studies of breastfeeding are particularly challenging in this regard. Animal data and human studies have linked obesity and insulin resistance to difficulties with breastfeeding, suggesting that shortened lactation could be a marker for an aberrant metabolic profile23, 24
. Successful, prolonged breastfeeding depends on a wide range of factors, from a woman’s choice to begin nursing to the support she receives from her birth attendant, her infant’s pediatrician, her family, and her employer. A woman whose circumstances allow prolonged breastfeeding may live in a less stressful environment and thus face a lower risk of cardiovascular disease. Secular trends in breastfeeding duration, diet, exercise, and other health behaviors may also affect our results. Of note, all participants in our study are registered nurses, and 97 percent are Caucasian, so confounding by race or socio-economic status is less likely than in a more diverse cohort. Moreover, when we adjusted for parental occupation, education, partner's education and marital status, the effect was minimal, making it unlikely that other unmeasured SES variables explain the observed association.
Misclassification is also a potential concern, because lifetime lactation history was self-reported. Promislow and colleagues25
examined maternal recall of breastfeeding duration among women ages 69 to 79. The authors compared self-reported duration with prospectively recorded menstrual diaries collected between 1940 and 1966. They observed an overall correlation of 0.55, with a mean difference between recorded and recalled duration of 0 (SD 2.7) months, indicating misclassification, but no overall recall bias. Moreover, they found that women with shorter durations tended to over-report, while women with longer durations tended to underreport. If such misclassification occurred in our cohort, it would bias our results toward the null. Nevertheless, we observed a substantial, statistically significant association between more than 2 years of lifetime breastfeeding and incident myocardial infarction.
Notably, we observed a stronger protective association for women who breastfed for >23 months, suggesting either a threshold effect or substantial differences between this group and those with shorter durations of lactation. When we adjusted for multiple coronary risk and lifestyle factors, the inverse association between long duration of breastfeeding and MI was diminished, but the association remained significant, suggesting that other mechanisms also play a role.
Our findings are consistent with and extend those from earlier reports linking reproductive history to cardiovascular disease risk. Several author have reported an increased risk of coronary heart disease among women with high parity26, 27
, although results are mixed 28–30
and may be confounded by socioeconomic status 31
. Pre-eclampsia and stillbirth32, 33
have also been linked to subsequent cardiovascular risk. Both animal and human studies suggest biologically plausible mechanisms for an association between lactation and coronary heart disease. Lactation influences carbohydrate and lipid metabolism, and oxytocin has been linked to regulation of blood pressure and cardiovascular function.
Studies in animal models34, 35
and lactating women36
show that lactation is associated with decreased postpartum insulin resistance, lower insulin-glucose ratios, and increased carbohydrate utilization. Differences in lactation physiology among rodents, ruminants and humans limit extrapolation of animal data to humans37
; however, epidemiologic studies suggest that human lactation is associated with beneficial long-term changes in glucose metabolism. In a previous analysis in the Nurses’ Health Studies, we found that lifetime lactation was inversely associated with incident type 2 diabetes10
, and a recent study of middle-aged women found an inverse association between lactation and the metabolic syndrome13
. The association of lactation with incident diabetes among women with gestational diabetes is less clear38, 39
Both animal and human studies suggest that lactation affects lipid metabolism40
. In the rat, lipids accumulate in adipose tissue during pregnancy and are mobilized during lactation through local lipoprotein lipase activity41, 42
. Moreover, lactating rats have reduced visceral fat stores43
, smaller adipose cells, and reduced peripheral levels of lipoprotein lipase44
compared with nonlactating animals. Differences in regional adipose tissue activity during pregnancy and lactation have also been observed in humans45
. These data suggest that women who do not lactate may have greater difficulty mobilizing fat stores after delivery, although data linking lactation with long term adiposity in human populations are mixed46
Pregnancy is also associated with a physiologic increase in serum triglycerides and total cholesterol. These changes resolve more rapidly in women who breastfeed than in those who do not3
. Lactating women also have higher levels of HDL cholesterol and apolipoprotein AI than their nonlactating counterparts4, 38, 47
. In a recent prospective cohort study, Gunderson et al11
reported that these favorable changes in lipid metabolism persist after weaning, suggesting that lactation has a lasting effect on maternal metabolism.
Lactation may also modify cardiovascular risk through changes in stress response. A recent study found a modest protective association between lactation history and incident hypertension12
. Animal studies suggest that oxytocin, which is released during milk let-down, may affect blood-pressure regulation. Petersson et al.48
found that oxytocin administration produced decreases in blood pressure in rats that persisted for weeks after discontinuation, despite the drug’s brief half-life. The authors postulate that oxytocin administration leads to long-term changes in central regulatory pathways. Similarly, observational studies 7, 49–52
suggest that nursing mothers have diminished autonomic responses to stressors.
These observations suggest an important role for lactation in women’s health. Fat stores accumulate during pregnancy, assuring that the mother will have adequate resources to compensate for variations in local food supply during the neonatal period53
. If these resources are not mobilized during lactation, women may accumulate adipose tissue, and pregnancy-associated metabolic changes may persist for a longer period of time. We speculate that this impaired resetting of postpartum physiology may contribute to long-term disease risk. Further studies will be needed to test this hypothesis.
In conclusion, we have identified a novel association between greater than two years of lifetime lactation and myocardial infarction risk in a large, prospective cohort. This association persists after controlling for multiple lifestyle factors. Studies of metabolic risk profiles among contemporary women are needed to delineate further the relation between lactation and cardiovascular disease risk.