Abstract
Background: We evaluated subclinical cardiovascular disease in relation to lactation history among women with normotensive pregnancies and women with hypertensive pregnancies, a distinction not previously examined.
Materials and Methods: The POUCHmoms study included 678 women from a pregnancy cohort who were followed 7–15 years after delivery. We measured blood pressure, lipid levels, carotid intima-media thickness (CIMT), and lactation duration for each live birth (LB) at follow-up. We categorized lactation as never, <6 months/LB, or ≥6 months/LB. We analyzed associations between lactation and cardiometabolic risk factors and CIMT by using analysis of variance and multivariable linear regression (adjusted for age, race, socioeconomic status, smoking, time from last pregnancy, and total parity), which produced adjusted least square mean differences (LSMdiff) between groups.
Results: In the normotensive pregnancies group with women who never lactated as the referent (n = 157): Women with some lactation but <6 months/LB (n = 284) had higher high density lipoprotein (HDL) (LSMdiff = +4.47 mg/dL, p = 0.013), lower triglycerides (LSMdiff = −38.1 mg/dL, p = 0.02), and thinner mean CIMT (LSMdiff = −0.03 mm, p = 0.005); women who lactated for ≥6 months/LB (n = 133) also had higher HDL (LSMdiff = +7.59 mg/dL, p < 0.001), lower triglycerides (LSMdiff = −41.6 mg/dL, p = 0.01), and thinner mean CIMT (LSMdiff = −0.03 mm, p = 0.003). After further adjustment for body mass index, associations between lactation and HDL, triglycerides, and mean CIMT persisted. These associations were not detected in women with prior hypertensive pregnancies.
Conclusions: Women with a history of normotensive pregnancies and lactation for any duration had a more favorable cardiometabolic profile and were at decreased risk of subclinical atherosclerosis compared with those who never lactated.
Keywords: lactation, hypertensive disorders of pregnancy, carotid intima-media thickness, subclinical atherosclerosis
Introduction
Hypertensive disorders of pregnancy are increasingly common in the United States, complicating 5%–10% of pregnancies.1–3 Women who develop preeclampsia or gestational hypertension are at increased risk of hypertension and cardiovascular disease (CVD) in later life.4–6 The American Heart Association (AHA) Guidelines for Prevention of CVD in women suggest that women with hypertensive disorders of pregnancy should receive ongoing postdelivery and lifelong care from a primary care physician or cardiologist to monitor and control risk factors for CVD such as hypertension, diabetes, and hyperlipidemia.7 Women with a history of preeclampsia may also benefit from lifestyle interventions such as exercise, changes in dietary habits, and smoking cessation.8 Less attention has been given to the role that lactation may play in improving women's cardiovascular health.
Increased lifetime duration of lactation has been associated with reduced CVD risk in women and lower rates of hypercholesterolemia, diabetes, and the metabolic syndrome.9,10 Lactation affects multiple hormones that impact blood pressure (BP), including oxytocin,11 prolactin,12 cortisol,13 estrogen, and progesterone. Numerous studies have examined the association between lactation and maternal BP after menopause, which have consistently shown that mothers who do not breastfeed are more likely to develop hypertension.10,14–21 Lactation has been associated with lower postpartum BP among women with gestational hypertension,22 but it has not been well studied in women with a history of hypertensive disorders of pregnancy up to a decade after delivery.
Carotid intima-media thickness (CIMT) is a robust marker of subclinical atherosclerosis23 as well as a predictor of future cardiovascular events such as myocardial infarction and stroke.24 Women with a history of preeclampsia have increased CIMT compared with normal pregnancy women in the postpartum period,25,26 but it remains unclear if in women with gestational hypertension or preeclampsia CIMT is increased in later life.27,28 It has been suggested that women with longer lifetime duration of lactation have thinner CIMT9,29; however, little is known about lactation associations with CIMT among women with a history of hypertensive disorders of pregnancy.
In this study, we characterize the relationship between lactation, cardiometabolic risk factors, and subclinical atherosclerosis measured by CIMT 7 to 15 years after pregnancy among women with or without a history of hypertensive disorders of pregnancy.
Materials and Methods
Participants
The Pregnancy Outcomes and Community Health (POUCH) study was designed to examine pathways leading to preterm delivery and enrolled 3,019 pregnant women from 52 clinics in 5 Michigan communities from 1998 through 2004. Eligibility criteria were English-speaking women at least 15 years of age with a singleton pregnancy. Women with diabetes or any fetal abnormalities were excluded. Women provided written informed consent at enrollment. Detailed medical record abstraction provided information on pregnancy complications and comorbid conditions in a subcohort of 1,371 POUCH women for all those with preterm delivery (<37 weeks gestation), those with higher risk of preterm delivery (African American race or those with elevated concentrations of maternal alpha-fetoprotein screening), and a random sample of those delivering at term (≥37 weeks' gestation).30 In all analyses, the use of sampling weights accounts for this subcohort sampling strategy.
From this POUCH subcohort, 678 participants returned for a follow-up visit 7 to 15 years after delivery (2010–2014) as part of the POUCHmoms study. POUCHmoms was designed to examine the association between pregnancy factors and long-term CVD risk. Women who attended the follow-up visit compared with those who did not were older, had higher levels of education, were less likely to have received Medicaid insurance at pregnancy, and were more likely to be of white or other race/ethnicity (all p < 0.05; Supplementary Table S1). Women who were pregnant or within 6 months of delivery were excluded. Both the Michigan State University and University of Pittsburgh institutional review boards approved the POUCHmoms study, and the University of Pittsburgh institutional review board approved this analysis.
Study protocol
Study visits included an initial screening visit during pregnancy for enrollment in the POUCH study and then a follow-up visit at 7 to 15 years after delivery of the POUCH pregnancy. Data collected during the POUCH pregnancy visit included baseline demographics by a detailed survey questionnaire and physical measurements (height, weight, BP). We obtained pregnancy data (gestational age, delivery type, and pregnancy complications) through a combination of maternal report and postdelivery medical record abstraction. Data collected at the POUCHmoms follow-up visit included physical measurements (height, weight, BP), biomarkers of inflammation and lipid metabolism, and CIMT.
We defined gestational hypertension and preeclampsia during the POUCH pregnancy based on American College of Obstetrics and Gynecology definitions at the time of enrollment.31 Self-reported responses to a survey questionnaire provided data on hypertensive disorders of pregnancy during subsequent or prior pregnancies. Due to potential errors and crossover in self-reporting, we combined gestational hypertension and preeclampsia into one exposure variable.
We assessed lactation duration at the 7- to 15-year follow-up visit based on self-reported responses to a survey questionnaire. Participants reported if they breastfed for each live birth (LB) and reported the age of each infant in whole months when they stopped nursing. Lifetime duration of lactation was calculated as the sum of lactation duration for all LBs. Lactation duration per pregnancy was then calculated by lifetime lactation duration divided by number of LBs. Aligned with previous approaches, we divided lactation duration into three categories: never lactated, lactated <6 months per LB, or lactated ≥6 months per LB.9,32
Trained research personnel measured BP three times, each 1 minute apart after participants had been sitting for 5 minutes at rest. Mean BP was calculated by averaging the second and third BP measurements. A Panasonic EW3109W (Panasonic Corp., Newark, NJ) or an Omron Hem-907 (Omron Healthcare, Inc., Lake Forest, IL) monitor obtained automatic BP measurements by using appropriately sized cuffs. A participant qualified for a diagnosis of stage 1 hypertension if they had systolic BP between 130 and 140 mmHg or diastolic BP between 80 and 90 mmHg and stage 2 hypertension if they were on any antihypertensive medications or if their systolic BP was greater than 140 mmHg or diastolic BP greater than 90 mmHg per ACC/AHA 2017 guidelines.33 We designated a participant as having a diagnosis of diabetes by self-report or if they were on diabetes medications.
We measured CIMT at the 7- to 15-year follow-up visit via B-mode ultrasound using the Terason t3000 Ultrasound System (TeratechCorp, Burlington, MA) and a high-resolution 8 MHz frequency linear array transducer. The participant's head was positioned at a 45° angle opposite to the side imaged and the carotid artery was interrogated in the anterior, posterior, and lateral angles. Bilateral carotid images were obtained at the angle yielding the thickest IMT at end-diastole from eight locations (four locations on both left and right carotid arteries): the distal common carotid artery (CCA), the carotid bulb, and the first centimeter of the internal carotid artery (ICA). Semi-automated edge-detection software (Artery Measurement System, Gothenburg, Sweden) was used to identify the lumen–intima and media–adventitia interfaces across 1-cm segments of the near and far walls of the CCA and the far wall of the bulb and ICA. CIMT values across these eight sites were averaged to obtain mean CIMT. Site-specific mean CIMT (CCA IMT, bulb IMT, ICA IMT) was also evaluated. CCA adventitial diameter was measured directly as the distance from the adventitial–medial interface on the near wall to the medial–adventitial interface on the far wall at end-diastole. Reproducibility of the CIMT measures was excellent, with an intra-class correlation coefficient between sonographers of ≥0.87 based on 20 participants scanned by both sonographers and an intra-class correlation coefficient between readers of 0.92 based on annual ultrasound research lab quality control checks.
Statistical analysis
We assessed differences in maternal characteristics by lactation duration category using analysis of variance (ANOVA) for continuous variables, Kruskal–Wallis tests for variables with skewed distributions, and chi-squared tests for categorical variables. Continuous variables are presented as mean ± standard deviation (median and interquartile range for variables with skewed distributions); categorical variables are presented as frequency and percentage. We examined the relationship between lactation duration and differences in measures of BP, biomarkers of lipid metabolism, and CIMT stratified according to the presence or absence of hypertensive disorders of pregnancy. Test for interaction suggested that the relationship between lactation and overall IMT was modified by history of hypertensive disorder of pregnancy (Supplementary Table S2). Differences in mean BP, lipid levels, glucose levels, and CIMT across lactation duration categories were assessed by using ANOVA analyses. Multivariable linear regression models were used to test for differences in continuous cardiometabolic and subclinical CVD endpoints by lactation duration category, adjusting for maternal age, race, income, education, smoking history, lifetime parity, and time since last delivery in our first model. A second model further adjusted for body mass index (BMI), as it may be a confounder or in the causal pathway linking lactation with CVD outcomes.34 We chose covariates based on differences across lactation groups and known associations with primary outcomes. Multivariable analyses are reported as least square mean differences (LSMdiff) between groups. Analyses were performed with SAS 9.4 (SAS Institute, Inc., Cary, NC).
Results
Of the 678 women in the POUCHmoms study, 184 women never lactated, 333 lactated for some duration, and 161 lactated ≥6 months per pregnancy (Table 1). In comparison to women who never lactated, women who lactated for longer durations were less likely to be African American and more likely to be older, nonsmokers, married, have lower BMI, and have lower parity (all p-values <0.001). In addition, women who lactated for a longer duration had higher socioeconomic status with more advanced education, higher income, and non-Medicaid insurance (all p-values <0.001). At the follow-up visit, 104 (15.3%) women reported a history of a hypertensive disorder of pregnancy (preeclampsia or gestational hypertension) during any pregnancy. The prevalence of hypertensive disorders of pregnancy was similar in each of the breastfeeding groups (p = 0.71).
Table 1.
Maternal Characteristics at Enrollment, Pregnancy, and 7–15 Years After Delivery by Lactation Duration
| Overall (n = 678) | Never lactated (n = 184) | Some lactation (n = 333) | Lactation ≥6 months (n = 161) | p | |
|---|---|---|---|---|---|
| POUCH pregnancy | |||||
| Maternal age at delivery (years) | 26.6 ± 6.67 | 25.2 ± 6.35 | 26.1 ± 6.61 | 28.7 ± 6.39 | <0.001 |
| Prepregnancy BMI (kg/m2) | 27.2 ± 9.07 | 28.7 ± 9.18 | 27.5 ± 9.64 | 25.4 ± 7.38 | 0.001 |
| Race | |||||
| White or other | 75.4% | 59.6% | 75.0% | 89.7% | <0.001 |
| African American | 24.6% | 40.4% | 25.0% | 10.3% | |
| Nulliparous before POUCH | 44.1% | 36.6% | 41.2% | 55.7% | 0.005 |
| Hypertensive disorders | |||||
| None | 89.6% | 92.8% | 90.7% | 84.7% | 0.126 |
| Gestational hypertension | 4.4% | 2.3% | 3.0% | 8.6% | |
| Preeclampsia | 2.8% | 1.2% | 3.5% | 3.1% | |
| Chronic hypertension | 3.2% | 3.7% | 2.8% | 3.6% | |
| Gestational diabetes | 6.7% | 6.7% | 5.0% | 9.8% | 0.272 |
| Gestational age at delivery, weeks | 39.1 ± 2.00 | 38.9 ± 2.16 | 39.0 ± 1.99 | 39.4 ± 1.84 | 0.025 |
| Preterm birth | 10.7% | 14.3% | 11.1% | 7.0% | 0.015 |
| POUCHmoms follow-up visit | |||||
| Time since last pregnancy (years) | 7.96 ± 4.03 | 8.16 ± 4.41 | 7.73 ± 4.10 | 8.17 ± 3.55 | 0.371 |
| Age | 38.0 ± 6.88 | 36.6 ± 6.89 | 37.6 ± 6.56 | 39.7 ± 6.91 | <0.001 |
| BMI (kg/m2) | 31.3 ± 10.4 | 33.8 ± 10.9 | 31.5 ± 10.6 | 28.6 ± 8.47 | <0.001 |
| Change in BMI (kg/m2) | 4.08 ± 6.41 | 5.04 ± 7.54 | 4.05 ± 6.32 | 3.29 ± 5.45 | 0.043 |
| Smoking history | |||||
| Never smoker | 54.8% | 37.7% | 55.2% | 69.0% | <0.001 |
| Former smoker | 13.8% | 6.8% | 15.5% | 16.9% | |
| Current smoker | 31.4% | 55.6% | 29.3% | 14.2% | |
| Insurance | |||||
| Never on Medicaid | 49.8% | 29.3% | 44.9% | 76.1% | <0.001 |
| Medicaid ever | 50.2% | 70.7% | 55.1% | 23.9% | |
| Education | |||||
| <12 years | 6.7% | 15.6% | 4.9% | 2.2% | <0.001 |
| High school diploma | 12.8% | 28.9% | 10.8% | 2.3% | |
| Some college | 50.1% | 45.6% | 58.1% | 40.0% | |
| College graduate | 30.4% | 9.8% | 26.2% | 55.5% | |
| Income | |||||
| <$20,000 | 10.9% | 22.3% | 11.0% | 1.0% | <0.001 |
| $20,000–49,999 | 19.9% | 32.0% | 19.0% | 10.8% | |
| $50,000–89,999 | 18.5% | 17.3% | 19.2% | 18.5% | |
| $90,000+ | 50.7% | 28.4% | 50.8% | 69.7% | |
| Marital status | |||||
| Married | 56.2% | 32.9% | 59.7% | 70.4% | <0.001 |
| Divorced or separated | 21.3% | 23.7% | 20.8% | 20.1% | |
| Never married | 22.5% | 43.4% | 19.5% | 9.5% | |
| Parity | |||||
| 1 | 7.9% | 9.5% | 5.1% | 11.4% | <0.001 |
| 2 | 41.5% | 45.1% | 31.7% | 55.3% | |
| 3 | 31.0% | 28.6% | 37.2% | 22.5% | |
| 4+ | 19.6% | 16.9% | 26.0% | 10.8% | |
| Hypertensive pregnancy ever | 14.5% | 12.0% | 13.7% | 18.0% | 0.364 |
| Menopause | |||||
| None | 89.8% | 88.1% | 90.2% | 90.5% | 0.676 |
| Menopause (nonsurgical) | 0.9% | 0.8% | 0.4% | 2.1% | |
| Menopause (surgical) | 7.2% | 7.8% | 7.5% | 6.2% | |
| Cannot determine status | 2.1% | 3.3% | 1.9% | 1.2% | |
Continuous variables presented as mean ± SD or median (interquartile range); categorical variables presented as percentages.
BMI, body mass index; POUCH, Pregnancy Outcomes and Community Health.
Among participants with normotensive pregnancies, unadjusted analyses suggested that those who lactated for a longer duration had lower systolic and diastolic BP, higher high density lipoprotein (HDL), lower triglycerides, lower glucose levels, thinner ICA IMT, thinner mean CIMT, and smaller adventitial diameter (Table 2). Participants who had a history of a hypertensive disorder of pregnancy during any pregnancy did not have any improvement in BP, lipid levels, or CIMT with lactation (Table 3). Analyses for normotensive women stratified by insurance status showed that those who were never on Medicaid and lactated had thinner ICA IMT, mean CIMT, and smaller adventitial diameter (Supplementary Table S3). Those who had been on Medicaid insurance had attenuated results, but with a similar trend in thinner IMT with longer lactation duration (Supplementary Table S4).
Table 2.
Cardiometabolic Risk Factors and Carotid Subclinical Cardiovascular Disease Measures by Lactation Duration Among Women with Normotensive Pregnancies
| Never lactated (n = 157) | Some lactation (n = 284) | Lactation ≥6 months (n = 133) | p | |
|---|---|---|---|---|
| Cardiometabolic risk factors | ||||
| Systolic BP (mmHg) | 117 ± 18.9 | 113 ± 14.9 | 111 ± 13.4 | 0.005 |
| Diastolic BP (mmHg) | 77.3 ± 13.3 | 74.6 ± 13.2 | 72.6 ± 11.9 | 0.006 |
| Hypertension (%) | ||||
| No hypertension | 54.3% | 66.5% | 70.6% | 0.062 |
| Stage 1 | 21.1% | 19.5% | 17.4% | |
| Stage 2 | 24.6% | 14.0% | 12.0% | |
| Total cholesterol (mg/dL) | 185 ± 44.9 | 177 ± 40.0 | 185 ± 39.0 | 0.072 |
| LDL (mg/dL) | 109 ± 34.0 | 102 ± 34.3 | 106 ± 33.7 | 0.111 |
| HDL (mg/dL) | 49.6 ± 15.8 | 54.4 ± 17.3 | 59.5 ± 17.1 | <0.001 |
| Triglycerides (mg/dL) | 144 ± 233 | 102 ± 71.8 | 97.0 ± 60.9 | 0.050 |
| Glucose (mg/dL) | 103 ± 50.4 | 92.7 ± 15.9 | 95.1 ± 47.5 | 0.042 |
| Diabetes (%) | 9.0% | 3.3% | 3.6% | 0.113 |
| Carotid ultrasound | ||||
| CCA (mm) | 0.61 ± 0.09 | 0.59 ± 0.10 | 0.59 ± 0.08 | 0.061 |
| ICA (mm) | 0.55 ± 0.22 | 0.50 ± 0.12 | 0.50 ± 0.11 | 0.048 |
| Bulb (mm) | 0.62 ± 0.19 | 0.58 ± 0.14 | 0.58 ± 0.15 | 0.081 |
| Overall mean IMT (mm) | 0.60 ± 0.11 | 0.57 ± 0.08 | 0.57 ± 0.08 | 0.006 |
| AD (mm) | 6.76 ± 0.69 | 6.65 ± 0.53 | 6.51 ± 0.56 | 0.003 |
Continuous variables presented as mean ± standard deviation or median (interquartile range); categorical variables presented as percentages.
AD, adventitial diameter; BP, blood pressure; CCA, common carotid artery; HDL, high density lipoprotein; ICA, internal carotid artery; IMT, intima media thickness; LDL, low density lipoprotein.
Table 3.
Cardiometabolic Risk Factors and Carotid Subclinical Cardiovascular Disease Measures by Lactation Duration Among Women with a History of Hypertensive Disorders of Pregnancy
| Never lactated (n = 27) | Some lactation (n = 49) | Lactation ≥6 months (n = 28) | p | |
|---|---|---|---|---|
| Cardiometabolic risk factors | ||||
| Systolic BP (mmHg) | 125 ± 20.7 | 119 ± 14.8 | 123 ± 19.7 | 0.432 |
| Diastolic BP (mmHg) | 84.0 ± 14.0 | 77.9 ± 12.4 | 80.7 ± 13.4 | 0.161 |
| Hypertension (%) | ||||
| No hypertension | 28.4% | 54.0% | 43.2% | 0.497 |
| Stage 1 | 30.7% | 20.5% | 17.7% | |
| Stage 2 | 40.8% | 25.5% | 39.1% | |
| Total cholesterol (mg/dL) | 180 ± 35.5 | 194 ± 31.7 | 195 ± 52.4 | 0.178 |
| LDL (mg/dL) | 104 ± 26.8 | 117 ± 31.3 | 116 ± 40.1 | 0.141 |
| HDL (mg/dL) | 53.9 ± 13.6 | 52.8 ± 11.0 | 54.6 ± 13.9 | 0.821 |
| Triglycerides (mg/dL) | 106 ± 47.1 | 120 ± 75.1 | 118 ± 83.7 | 0.556 |
| Glucose (mg/dL) | 104 ± 45.8 | 92.5 ± 10.3 | 94.1 ± 8.91 | 0.352 |
| Diabetes (%) | 13.3% | 5.1% | 6.8% | 0.573 |
| Carotid ultrasound | ||||
| CCA (mm) | 0.59 ± 0.10 | 0.63 ± 0.11 | 0.63 ± 0.12 | 0.198 |
| ICA (mm) | 0.53 ± 0.09 | 0.58 ± 0.26 | 0.55 ± 0.17 | 0.422 |
| Bulb (mm) | 0.58 ± 0.17 | 0.66 ± 0.28 | 0.67 ± 0.26 | 0.215 |
| Overall mean IMT (mm) | 0.57 ± 0.10 | 0.62 ± 0.15 | 0.62 ± 0.14 | 0.127 |
| AD (mm) | 6.92 ± 0.64 | 6.77 ± 0.48 | 6.68 ± 0.72 | 0.397 |
Continuous variables presented as mean ± standard deviation or median (interquartile range); categorical variables presented as percentages.
In models adjusting for age, race, income, education, lifetime parity, smoking, and time since last delivery, normotensive women who lactated for some duration, but less than 6 months per LB, had higher HDL (LSMdiff = +4.47 mg/dL confidence interval [CI] 0.94–8.00, p = 0.013) and lower triglycerides (LSMdiff = −38.1 mg/dL, CI −70.3 to −5.88, p = 0.02), as well as thinner CCA IMT (LSMdiff = −0.02 mm, CI −0.04 to −0.00, p = 0.02), thinner ICA IMT (LSMdiff = −0.04 mm, CI −0.07 to −0.01, p = 0.02), and thinner mean CIMT (LSMdiff = −0.03 mm, CI −0.04 to −0.01, p = 0.005) (Table 4) compared with women who never lactated. Similarly, normotensive women who lactated ≥6 months per LB had higher HDL (LSMdiff = +7.59 mg/dL, CI 3.08–12.09, p < 0.001) and lower triglycerides (LSMdiff = −41.6 mg/dL, CI −73.1 to −10.1, p = 0.01), as well as thinner CCA IMT (LSMdiff = −0.03 mm, CI −0.04 to −0.00, p = 0.02), thinner ICA IMT (LSMdiff = −0.05 mm, CI −0.08 to −0.01, p = 0.02), and thinner mean CIMT (LSMdiff = −0.03 mm, CI −0.05 to −0.01, p = 0.007) (Table 4) compared with women who never lactated. Among women with a history of hypertensive disorders of pregnancy, those who lactated for some duration, but less than 6 months per LB, had lower diastolic BP, thicker CCA IMT, and thicker mean CIMT when compared with women who never lactated (Table 5). We did not see an association with longer lactation duration ≥6 months per LB and cardiometabolic variables or CIMT among women with prior hypertensive pregnancies.
Table 4.
Multivariable Linear Regression Models of Relationship Between Lactation, Cardiometabolic Risk Factors, and Carotid Intima-Media Thickness Among Women with Normotensive Pregnancies (Adjusted)
| Model 1a |
Model 2b |
|||||
|---|---|---|---|---|---|---|
| LSMdiff | 95% CI | p | LSMdiff | 95% CI | p | |
| Systolic BP (mmHg) | ||||||
| Some lactationc | −1.17 | −4.37 to 2.04 | 0.475 | −0.54 | −3.69 to 2.61 | 0.736 |
| Lactation ≥6 months | −3.07 | −6.87 to 0.73 | 0.114 | −1.25 | −4.90 to 2.50 | 0.515 |
| Diastolic BP (mmHg) | ||||||
| Some lactation | −0.34 | −2.88 to 2.21 | 0.795 | 0.27 | −2.17 to 2.72 | 0.828 |
| Lactation ≥6 months | −1.10 | −4.28 to 2.08 | 0.498 | 0.67 | −2.38 to 3.73 | 0.668 |
| Total cholesterol (mg/dL) | ||||||
| Some lactation | −6.03 | −14.6 to 2.57 | 0.170 | −5.50 | −14.0 to 3.03 | 0.207 |
| Lactation ≥6 months | −0.27 | −10.3 to 9.78 | 0.957 | 1.22 | −8.84 to 11.2 | 0.813 |
| LDL (mg/dL) | ||||||
| Some lactation | −5.44 | −12.5 to 1.71 | 0.136 | −4.76 | −11.7 to 2.27 | 0.185 |
| Lactation ≥6 months | −1.82 | −10.2 to 6.61 | 0.672 | 0.06 | −8.35 to 8.47 | 0.989 |
| HDL (mg/dL) | ||||||
| Some lactation | 4.47 | 0.936–8.00 | 0.013 | 3.59 | 0.41–6.76 | 0.027 |
| Lactation ≥6 months | 7.59 | 3.083–12.09 | 0.001 | 5.13 | 1.08–9.19 | 0.013 |
| Triglycerides (mg/dL) | ||||||
| Some lactation | −38.1 | −70.3 to −5.88 | 0.021 | −34.3 | −65.7 to −2.81 | 0.033 |
| Lactation ≥6 months | −41.6 | −73.1 to −10.05 | 0.010 | −30.9 | −61.5 to −0.41 | 0.047 |
| Glucose (mg/dL) | ||||||
| Some lactation | −8.43 | −15.8 to −1.02 | 0.026 | −7.75 | −15.0 to −0.48 | 0.037 |
| Lactation ≥6 months | −4.77 | −15.3 to 5.80 | 0.377 | −2.89 | −13.0 to 7.24 | 0.576 |
| CCA IMT (mm) | ||||||
| Some lactation | −0.02 | −0.03 to −0.00 | 0.027 | −0.02 | −0.03 to −0.00 | 0.045 |
| Lactation ≥6 months | −0.03 | −0.04 to −0.00 | 0.018 | −0.02 | −0.03 to 0.00 | 0.119 |
| ICA IMT (mm) | ||||||
| Some lactation | −0.04 | −0.07 to −0.01 | 0.019 | −0.04 | −0.07 to −0.01 | 0.022 |
| Lactation ≥6 months | −0.05 | −0.08 to −0.01 | 0.02 | −0.04 | −0.08 to −0.00 | 0.030 |
| Bulb IMT (mm) | ||||||
| Some lactation | −0.03 | −0.06 to 0.01 | 0.154 | −0.02 | −0.05 to 0.01 | 0.196 |
| Lactation ≥6 months | −0.02 | −0.07 to 0.02 | 0.285 | −0.02 | −0.06 to 0.03 | 0.469 |
| Mean IMT (mm) | ||||||
| Some lactation | −0.03 | −0.04 to −0.01 | 0.005 | −0.02 | −0.04 to −0.01 | 0.007 |
| Lactation ≥6 months | −0.03 | −0.05 to −0.01 | 0.007 | −0.02 | −0.04 to −0.00 | 0.044 |
| AD (mm) | ||||||
| Some lactation | −0.01 | −0.14 to 0.12 | 0.877 | 0.02 | −0.10 to 0.14 | 0.753 |
| Lactation ≥6 months | −0.09 | −0.24 to 0.07 | 0.292 | 0.00 | −0.14 to 0.14 | 0.952 |
Adjusted for age, race, income, education, smoking, time from last pregnancy, and total lifetime parity.
Adjusted for Model 1+BMI.
Never lactated is the reference group.
LSMdiff, least squares mean difference between groups.
Table 5.
Multivariable Linear Regression Models of Relationship Between Lactation, Cardiometabolic Risk Factors, and Carotid Intima-Media Thickness Among Women with a History of Hypertensive Disorders of Pregnancy (Adjusted)
| Model 1a |
Model 2b |
|||||
|---|---|---|---|---|---|---|
| LSMdiff | 95% CI | p | LSMdiff | 95% CI | p | |
| Systolic BP (mmHg) | ||||||
| Some lactationc | −6.65 | −13.7 to 0.47 | 0.070 | −3.69 | −10.8 to 3.44 | 0.313 |
| Lactation ≥6 months | −4.17 | −12.3 to 4.05 | 0.322 | −1.55 | −9.58 to 6.48 | 0.706 |
| Diastolic BP (mmHg) | ||||||
| Some lactation | −8.31 | −13.9 to −2.68 | 0.005 | −5.83 | −10.9 to −0.75 | 0.026 |
| Lactation ≥6 months | −4.73 | −12.0 to 2.62 | 0.210 | −2.54 | −9.49 to 4.42 | 0.476 |
| Total cholesterol (mg/dL) | ||||||
| Some lactation | 11.6 | −6.09 to 29.4 | 0.201 | 13.9 | −4.24 to 32.2 | 0.136 |
| Lactation ≥6 months | 7.15 | −16.7 to 31.0 | 0.559 | 9.19 | −15.7 to 34.1 | 0.472 |
| LDL (mg/dL) | ||||||
| Some lactation | 10.8 | −2.78 to 24.5 | 0.122 | 12.7 | −1.60 to 27.1 | 0.085 |
| Lactation ≥6 months | 6.76 | −11.8 to 25.3 | 0.477 | 8.46 | −11.0 to 27.9 | 0.398 |
| HDL (mg/dL) | ||||||
| Some lactation | −2.24 | −8.85 to 4.37 | 0.508 | −4.73 | −11.0 to 1.54 | 0.142 |
| Lactation ≥6 months | −1.85 | −9.55 to 5.86 | 0.640 | −4.05 | −11.0 to 3.54 | 0.298 |
| Triglycerides (mg/dL) | ||||||
| Some lactation | 15.3 | −18.1 to 48.7 | 0.372 | 28.7 | −10.5 to 67.9 | 0.155 |
| Lactation ≥6 months | 9.60 | −27.6 to 46.8 | 0.614 | 21.4 | −24.2 to 67.2 | 0.360 |
| Glucose (mg/dL) | ||||||
| Some lactation | −9.61 | −26.2 to 7.00 | 0.259 | −8.64 | −25.0 to 8.56 | 0.327 |
| Lactation ≥6 months | −8.67 | −25.2 to 7.89 | 0.307 | −7.80 | −24.9 to 9.30 | 0.373 |
| CCA IMT (mm) | ||||||
| Some lactation | 0.07 | 0.02–0.11 | 0.004 | 0.07 | 0.03–0.12 | 0.003 |
| Lactation ≥6 months | 0.06 | −0.00 to 0.12 | 0.053 | 0.07 | 0.01–0.13 | 0.036 |
| ICA IMT (mm) | ||||||
| Some lactation | 0.03 | −0.03 to 0.10 | 0.306 | 0.04 | −0.02 to 0.11 | 0.198 |
| Lactation ≥6 months | −0.03 | −0.11 to 0.06 | 0.507 | −0.02 | −0.10 to 0.07 | 0.676 |
| Bulb IMT (mm) | ||||||
| Some lactation | 0.09 | −0.00 to 0.18 | 0.062 | 0.10 | 0.00–0.20 | 0.043 |
| Lactation ≥6 months | 0.07 | −0.06 to 0.21 | 0.329 | 0.09 | −0.06 to 0.23 | 0.262 |
| Mean IMT (mm) | ||||||
| Some lactation | 0.07 | 0.025–0.11 | 0.002 | 0.08 | 0.03–0.12 | 0.001 |
| Lactation ≥6 months | 0.04 | −0.02 to 0.11 | 0.209 | 0.05 | −0.01 to 0.12 | 0.137 |
| AD (mm) | ||||||
| Some lactation | −0.01 | −0.24 to 0.23 | 0.937 | 0.06 | −0.19 to 0.31 | 0.634 |
| Lactation ≥6 months | −0.10 | −0.40 to 0.21 | 0.528 | −0.03 | −0.34 to 0.28 | 0.842 |
Adjusted for age, race, income, education, smoking, time from last pregnancy, and total lifetime parity.
Adjusted for Model 1+BMI.
Never lactated is the reference group.
Models were then further adjusted for BMI, as this may be a confounder or in the pathway linking lactation to CV health. Among women with normotensive pregnancies, lactation duration for both <6 months and ≥6 months per LB remained associated with higher HDL, lower triglycerides, thinner ICA IMT, and thinner mean CIMT, but only <6 months of duration of lactation remained associated with CCA IMT (Table 4). Additional adjustment for BMI among women with hypertensive pregnancies did not alter the association between some lactation and lower diastolic BP, higher low density lipoprotein (LDL), thicker CCA IMT, and thicker mean CIMT (Table 5). Further, adjusting for BP as a known CVD risk factor did not significantly change the results of the relationship between lactation and CIMT (data not shown). Sensitivity analyses limited to only patients with a hypertensive disorder of pregnancy diagnosis during the POUCH pregnancy (n = 52) showed no difference in outcomes (data not shown).
Discussion
In this study, we found that women who were normotensive across all pregnancies and who lactated for any duration had a more favorable cardiometabolic profile and markers of subclinical CVD measured by CIMT compared with those who never lactated. This relationship persisted after adjustment for age, race, socioeconomic status, smoking, time from last pregnancy, lifetime parity, and BMI. Interestingly, we did not see these same cardioprotective benefits of lactation among women with a history of hypertensive disorders of pregnancy.
Our results of the association between lactation duration and cardiometabolic profile among normotensive women support findings in other prospective cohort studies. Among 44,198 women in the Nurses Health Study II, those who did not breastfeed or breastfed for shorter durations were at increased risk of developing hypertension compared with those who breastfed their first child for ≥12 months.19 The Women's Health Initiative study showed a reduced odds of self-reported hyperlipidemia with increasing breastfeeding duration compared with women who never breastfed in models that controlled for multiple confounding variables.14 In addition, the Norwegian HUNT2 study found an inverse dose-response relationship of lifetime duration of lactation with total cholesterol, LDL cholesterol, and triglycerides and a positive association with HDL.10 Overall, these data suggest that lactation may be associated with lower triglycerides and non-LDL cholesterol concentrations and higher HDL cholesterol in later life. Mechanistically, it has been hypothesized that lactation acts to “reset” abnormal metabolic changes that occur during pregnancy through lowering postpartum lipid levels and reducing insulin resistance.35
Women with a longer duration of lactation have also been shown to have thinner CIMT compared with women who never lactated. In the Coronary Artery Risk Development in Young Adults (CARDIA) study, women had thinner CIMT as lactation duration increased.29 By comparison, in a cross-sectional analysis of a subset of women enrolled in the SWAN-Heart study, women who breastfed for ≥3 months per pregnancy were less likely to have aortic calcifications in fully adjusted models, but had no difference in distal CCA IMT.9 This lack of association with lactation and CIMT in the SWAN-Heart study may be due to a number of factors. They included women who breastfed for <6 months rather than only those who breastfed ≥6 months per LB. The SWAN study also included an older population with an average age of 50 compared with an average age of 38 in our study, who may have progressed beyond the age of perceivable benefit from lactation on IMT. Notably, in SWAN-Heart, it was not documented whether women had a history of hypertensive disorders of pregnancy. Although aortic calcification may be a stronger predictor of cardiovascular events, it is unlikely that we would be able to find arterial calcifications in our young population.36 In fact, only 12.9% of women in our study had confirmed carotid plaque. Thus, with measuring CIMT, our study provides the advantage of assessing a subclinical measure measurable in all women that is also an independent predictor of cardiovascular events in a younger population.37 The results of our study are supportive of lactation contributing to a reduction in cardiovascular risk factors, including subclinical CVD in women14,38 even after adjustment for other known risk factors such as BMI and hypertension.
When we examined these associations in a sub-population of women with a history of hypertensive disorders of pregnancy, we did not detect the same cardioprotective associations with lactation. To our knowledge, no other studies have looked at lactation and later life association with cardiovascular risk factors and markers of subclinical CVD in women with hypertensive disorders of pregnancy. A select few studies have looked at a history of hypertensive disorders of pregnancy and subclinical CVD in the postpartum period without examining the associations with lactation. In particular, one study reported an increased femoral IMT in the postpartum period in 22 women with early-onset preeclampsia compared with normotensive women.25 In addition, one study showed thicker intima, thinner media, and higher intima/media ratio in women with preeclampsia at diagnosis of preeclampsia with improvement, but persistent differences compared with normotensive women at 1 year postpartum.26 A limited number of studies are inconclusive about the association of preeclampsia and later-life CIMT.27 Overall, this suggests that subclinical CVD markers may be a part of the early pathophysiologic mechanism of vascular abnormalities in preeclamptic women, but it is unclear whether this persists in later life and it is unknown whether lactation plays a role in this risk.
We can only speculate regarding why women in our study with a history of hypertensive disorders of pregnancy who lactated for some duration had higher LDL, lower diastolic BP, thicker CCA IMT, and thicker mean CIMT compared with women who never lactated. The trend for thicker CIMT with some duration of lactation may be reflective of an overall increased risk of subclinical CVD in the subset of women who have a history of hypertensive disorders of pregnancy and suggests that lactation may not be cardioprotective in these women. Another possibility is that the vascular remodeling associated with hypertensive disorders of pregnancy predates the pregnancy, and thus lactation benefits may not accrue in affected women. Our study used a combined exposure group, including gestational hypertension and preeclampsia; thus, the heterogeneity in this group may have contributed to our lack of expected improvement. Further research is needed to disentangle these associations. It is worth noting that our sample size of women with a history of hypertensive disorders of pregnancy was modest and larger studies are needed to further clarify these associations.
There are additional limitations worth noting for our study. First, diagnoses of hypertensive disorders of pregnancy for pregnancies other than the initial POUCH pregnancy were obtained via self-report from participants and thus there is the potential for recall bias and inaccuracy.39 Our sample size in the hypertensive disorder of the pregnancy group is small in comparison to the normotensive group. In addition, lactation duration was assessed via self-report and may be subject to recall bias, although maternal recall of lactation is likely reliable and valid.40 Participants were also unaware of their outcome measures in this study; thus, recall bias, if present, was likely nondifferential. Lactation is a highly selective behavior and has greater potential for unmeasured confounding. Our study recruited women from multiple clinics and counties in Michigan and our cohort is representative of Michigan births in these communities30; it may, however, have limits in generalizability to other parts of the country. Also, it is worth noting that women who attended a follow-up visit tended to be older and of higher socioeconomic status, which may have contributed to selection bias.
Strengths of our study include a prospective design with participants enrolled during pregnancy, and pregnancy history information collected 7–15 years after delivery. In addition, women were asked about lactation duration for each pregnancy and we categorized lactation across all births, including identification of a group with ≥6 months of lactation. Breastfeeding for at least 6 months is recommended by the World Health Organization for optimal infant development and growth and there may be benefits for a longer duration with maternal health as well. Another strength is that we measured IMT across all visible segments, including those more likely to reflect early atherosclerotic changes and thus provide a more comprehensive picture of subclinical vascular disease burden in the carotid bed. To our knowledge, this is also the first study to look at lactation duration and association with subclinical atherosclerosis among women with a history of gestational hypertension or preeclampsia.
Conclusions
Lactation is associated with favorable lipid profiles and thinner CIMT, suggesting that it plays a role in lipid metabolism and modulates subclinical atherosclerosis. This may explain its cardioprotective benefit among women with normotensive pregnancies; however, benefits may not accrue in women with hypertensive disorders of pregnancy. Future studies should confirm these findings among larger cohorts of women with hypertensive disorders of pregnancy.
Supplementary Material
Author Disclosure Statement
No competing financial interests exist.
Funding Information
POUCHmoms Study was supported by the National Heart, Blood, and Lung Institute (R01-HL103825). The parent POUCH Study was supported by the National Institute of Child Health and Human Development and the National Institute of Nursing Research (R01 HD034543), the March of Dimes Foundation Perinatal Epidemiological Research Initiative Program (20-FY98-0697 through 20-FY04-37), the Thrasher Research Foundation (02816-7), and the Centers for Disease Control and Prevention (U01 DP000143-01).
Supplementary Material
References
- 1. Wallis AB, Saftlas AF, Hsia J, Atrash HK. Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987–2004. Am J Hypertens 2008;21:521–526 [DOI] [PubMed] [Google Scholar]
- 2. Ananth CV, Keyes KM, Wapner RJ. Pre-eclampsia rates in the United States, 1980–2010: Age-period-cohort analysis. BMJ 2013;347:f6564. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Hernandez-Diaz S, Toh S, Cnattingius S. Risk of pre-eclampsia in first and subsequent pregnancies: Prospective cohort study. BMJ 2009;338:b2255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: Systematic review and meta-analysis. BMJ 2007;335:974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Wilson BJ, Watson MS, Prescott GJ, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: Results from cohort study. BMJ 2003;326:845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Ray JG, Vermeulen MJ, Schull MJ, Redelmeier DA. Cardiovascular health after maternal placental syndromes (CHAMPS): Population-based retrospective cohort study. Lancet 2005;366:1797–1803 [DOI] [PubMed] [Google Scholar]
- 7. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: A guideline from the American Heart Association. Circulation 2011;123:1243–1262 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Berks D, Hoedjes M, Raat H, Duvekot JJ, Steegers EA, Habbema JD. Risk of cardiovascular disease after pre-eclampsia and the effect of lifestyle interventions: A literature-based study. BJOG 2013;120:924–931 [DOI] [PubMed] [Google Scholar]
- 9. Schwarz EB, McClure CK, Tepper PG, et al. Lactation and maternal measures of subclinical cardiovascular disease. Obstet Gynecol 2010;115:41–48 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Natland ST, Nilsen TI, Midthjell K, Andersen LF, Forsmo S. Lactation and cardiovascular risk factors in mothers in a population-based study: The HUNT-study. Int Breastfeed J 2012;7:8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Gutkowska J, Jankowski M. Oxytocin revisited: Its role in cardiovascular regulation. J Neuroendocrinol 2012;24:599–608 [DOI] [PubMed] [Google Scholar]
- 12. Stamatelopoulos KS, Georgiopoulos GA, Sfikakis PP, et al. Pilot study of circulating prolactin levels and endothelial function in men with hypertension. Am J Hypertens 2011;24:569–573 [DOI] [PubMed] [Google Scholar]
- 13. Ozarda Y, Gunes Y, Tuncer GO. The concentration of adiponectin in breast milk is related to maternal hormonal and inflammatory status during 6 months of lactation. Clin Chem Lab Med 2012;50:911–917 [DOI] [PubMed] [Google Scholar]
- 14. Schwarz EB, Ray RM, Stuebe AM, et al. Duration of lactation and risk factors for maternal cardiovascular disease. Obstet Gynecol 2009;113:974–982 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Lee SY, Kim MT, Jee SH, Yang HP. Does long-term lactation protect premenopausal women against hypertension risk? A Korean women's cohort study. Prev Med 2005;41:433–438 [DOI] [PubMed] [Google Scholar]
- 16. Groer MW, Jevitt CM, Sahebzamani F, Beckstead JW, Keefe DL. Breastfeeding status and maternal cardiovascular variables across the postpartum. J Women's Health (Larchmt) 2013;22:453–459 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Ebina S, Kashiwakura I. Influence of breastfeeding on maternal blood pressure at one month postpartum. Int J Women's Health 2012;4:333–339 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Wiklund P, Xu L, Lyytikainen A, et al. Prolonged breast-feeding protects mothers from later-life obesity and related cardio-metabolic disorders. Public Health Nutr 2012;15:67–74 [DOI] [PubMed] [Google Scholar]
- 19. Stuebe AM, Schwarz EB, Grewen K, et al. Duration of lactation and incidence of maternal hypertension: A longitudinal cohort study. Am J Epidemiol 2011;174:1147–1158 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Oken E, Patel R, Guthrie LB, et al. Effects of an intervention to promote breastfeeding on maternal adiposity and blood pressure at 11.5 y postpartum: Results from the Promotion of Breastfeeding Intervention Trial, a cluster-randomized controlled trial. Am J Clin Nutr 2013;98:1048–1056 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Ram KT, Bobby P, Hailpern SM, et al. Duration of lactation is associated with lower prevalence of the metabolic syndrome in midlife—SWAN, the study of women's health across the nation. Am J Obstet Gynecol 2008;198:268..e1–e6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. Countouris ME, Schwarz EB, Rossiter BC, et al. Effects of lactation on postpartum blood pressure among women with gestational hypertension and preeclampsia. Am J Obstet Gynecol 2016;215:241..e1–e8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. de Groot E, Hovingh GK, Wiegman A, et al. Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation 2004;109:III33–III38 [DOI] [PubMed] [Google Scholar]
- 24. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation 2007;115:459–467 [DOI] [PubMed] [Google Scholar]
- 25. Blaauw J, van Pampus MG, Van Doormaal JJ, et al. Increased intima-media thickness after early-onset preeclampsia. Obstet Gynecol 2006;107:1345–1351 [DOI] [PubMed] [Google Scholar]
- 26. Akhter T, Wikstrom AK, Larsson M, Naessen T. Individual common carotid artery wall layer dimensions, but not carotid intima-media thickness, indicate increased cardiovascular risk in women with preeclampsia: An investigation using noninvasive high-frequency ultrasound. Circ Cardiovasc Imaging 2013;6:762–768 [DOI] [PubMed] [Google Scholar]
- 27. McDonald SD, Ray J, Teo K, et al. Measures of cardiovascular risk and subclinical atherosclerosis in a cohort of women with a remote history of preeclampsia. Atherosclerosis 2013;229:234–239 [DOI] [PubMed] [Google Scholar]
- 28. Haukkamaa L, Moilanen L, Kattainen A, et al. Pre-eclampsia is a risk factor of carotid artery atherosclerosis. Cerebrovasc Dis 2009;27:599–607 [DOI] [PubMed] [Google Scholar]
- 29. Gunderson EP, Quesenberry CP Jr., Ning X, et al. Lactation duration and midlife atherosclerosis. Obstet Gynecol 2015;126:381–390 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30. Holzman C, Bullen B, Fisher R, Paneth N, Reuss L; Prematurity Study Group. Pregnancy outcomes and community health: The POUCH study of preterm delivery. Paediatr Perinat Epidemiol 2001;15 Suppl 2:136–158 [DOI] [PubMed] [Google Scholar]
- 31. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–S22 [PubMed] [Google Scholar]
- 32. McClure CK, Catov JM, Ness RB, Schwarz EB. Lactation and maternal subclinical cardiovascular disease among premenopausal women. Am J Obstet Gynecol 2012;207:46..e1–e8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Whelton PK, Carey RM, Aronow WS, et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018;6:e13–e115 [DOI] [PubMed] [Google Scholar]
- 34. Snyder GG, Holzman C, Sun T, Bullen B, Bertolet M, Catov JM. Breastfeeding greater than 6 months is associated with smaller maternal waist circumference up to one decade after delivery. J Womens Health (Larchmt) 2019;28:462–472 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Stuebe AM, Rich-Edwards JW. The reset hypothesis: Lactation and maternal metabolism. Am J Perinatol 2009;26:81–88 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Kalsch H, Lehmann N, Moebus S, et al. Aortic calcification onset and progression: Association with the development of coronary atherosclerosis. J Am Heart Assoc 2017;6 pii: [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37. Eikendal AL, Groenewegen KA, Anderson TJ, et al. Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years. Hypertension 2015;65:707–713 [DOI] [PubMed] [Google Scholar]
- 38. Stuebe AM, Michels KB, Willett WC, Manson JE, Rexrode K, Rich-Edwards JW. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol 2009;200:138..e1–e8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39. Stuart JJ, Bairey Merz CN, Berga SL, et al. Maternal recall of hypertensive disorders in pregnancy: A systematic review. J Women's Health (Larchmt) 2013;22:37–47 [DOI] [PubMed] [Google Scholar]
- 40. Li R, Scanlon KS, Serdula MK. The validity and reliability of maternal recall of breastfeeding practice. Nutr Rev 2005;63:103–110 [DOI] [PubMed] [Google Scholar]
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