Alison M. Stuebe

Duration of Lactation and Risk Factors for Maternal Cardiovascular Disease

OBJECTIVE: To examine dose–response relationships between the cumulative number of months women lactated and postmenopausal risk factors for cardiovascular disease. METHODS: We examined data from 139,681 postmenopausal women (median age 63 years) who reported at least one live birth on enrolling in the Women’s Health Initiative observational study or controlled trials. Multivariable models were used to control for sociodemographic (age, parity, race, education, income, age at menopause), lifestyle, and family history variables when examining the effect of duration of lactation on risk factors for cardiovascular disease, including obesity (body mass index [BMI] at or above 30), hypertension, self-reported diabetes, hyperlipidemia, and prevalent and incident cardiovascular disease. RESULTS: Dose-response relationships were seen; in fully adjusted models, women who reported a lifetime history of more than 12 months of lactation were less likely to have hypertension (odds ratio [OR] 0.88, P<.001), diabetes (OR 0.80, P<.001), hyperlipidemia (OR 0.81, P<.001), or cardiovascular disease (OR 0.91, P=.008) than women who never breast-fed, but they were not less likely to be obese. In models adjusted for all above variables and BMI, similar relationships were seen. Using multivariate adjusted prevalence ratios from generalized linear models, we estimate that among parous women who did not breast-feed compared with those who breast-fed for more than 12 months, 42.1% versus 38.6% would have hypertension, 5.3% versus 4.3% would have diabetes, 14.8% versus 12.3% would have hyperlipidemia, and 9.9% versus 9.1% would have developed cardiovascular disease when postmenopausal. Over an average of 7.9 years of postmenopausal participation in the Women’s Health Initiative, women with a single live birth who breast-fed for 7–12 months were significantly less likely to develop cardiovascular disease (hazard ratio 0.72, 95% confidence interval 0.53–0.97) than women who never breast-fed. CONCLUSION: Among postmenopausal women, increased duration of lactation was associated with a lower prevalence of hypertension, diabetes, hyperlipidemia, and cardiovascular disease. LEVEL OF EVIDENCE: II

Associations of diet and physical activity during pregnancy with risk for excessive gestational weight gain.

OBJECTIVE We sought to identify modifiable risk factors for excessive gestational weight gain (GWG). STUDY DESIGN We assessed associations of diet and physical activity with excessive GWG among 1388 women from the Project Viva cohort study. RESULTS Three hundred seventy-nine women (27%) were overweight (body mass index >or= 26 kg/m(2)) and 703 (51%) experienced excessive GWG, according to Institute of Medicine guidelines. In multivariable logistic regression models, we found that intake of total energy (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.00-1.22, per 500 kcal/d), dairy (OR, 1.08; 95% CI, 1.00-1.17, per serving per day), and fried foods (OR, 3.47; 95% CI, 0.91-13.24, per serving per day) were directly associated with excessive GWG. First trimester vegetarian diet (OR, 0.46; 95% CI, 0.28-0.78) and midpregnancy walking (OR, 0.92; 95% CI, 0.83-1.01, per 30 minutes per day) and vigorous physical activity (OR, 0.76; 95% CI, 0.60-0.97, per 30 minutes per day) were inversely associated with excessive GWG. CONCLUSION A healthful diet and greater physical activity are associated with reduced risk for excessive GWG.

A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia

CONTEXT Vitamin D may be important in the pathogenesis of severe preeclampsia. Given the few effective preventive strategies for severe preeclampsia, studies establishing this link are needed so that effective interventions can be developed. OBJECTIVE Our objective was to assess whether midgestation vitamin D deficiency is associated with development of severe preeclampsia. DESIGN AND SETTING We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between January 2004 and November 2008. PATIENTS Participants included women with singleton pregnancies in the absence of any chronic medical illnesses. From an overall cohort of 3992 women, 51 cases of severe preeclampsia were matched by race/ethnicity with 204 women delivering at term with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. MAIN OUTCOME MEASURE The main outcome was severe preeclampsia. RESULTS Midgestation maternal 25(OH)D concentration was lower in women who subsequently developed severe preeclampsia compared with controls [median (interquartile range), 75 (47-107) nmol/liter vs. 98 (68-113) nmol/liter; P = 0.01]. Midgestation maternal 25(OH)D of less than 50 nmol/liter was associated with an almost 4-fold odds of severe preeclampsia (unadjusted odds ratio, 3.63; 95% confidence interval, 1.52-8.65) compared with midgestation levels of at least 75 nmol/liter. Adjustment for known confounders strengthened the observed association (adjusted odds ratio, 5.41; 95% confidence interval, 2.02-14.52). CONCLUSION Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia.

Maternal-recalled gestational weight gain, pre-pregnancy body mass index, and obesity in the daughter.

Objective:Emerging evidence suggests that exposures during fetal life affect adult metabolism. We assessed the relationship between recalled maternal pre-pregnancy body mass, gestational weight gain (GWG), and adiposity in the daughter.Design:Retrospective cohort study among mother–nurse daughter dyads in the Nurses’ Health Study II and the Nurses’ Mothers’ Cohort. Mothers of participants completed questionnaires regarding their nurse daughter in 2001.Participants:26,506 mother–nurse daughter dyads born between 1946 and 1964.Main outcome measures:Body mass index (BMI) of the nurse daughter at age 18 and in 2001.Results:At age 18, 561 (2.1%) daughters were obese (BMI>30), and in 2001, 5442 (22.0%) were obese. Adjusting for covariates, women whose mothers had a recalled pre-pregnancy BMI of 29 had a 6.1-fold increased risk of obesity at age 18 and a 3.4-fold risk of obesity in 2001, compared with women whose mothers had a pre-pregnancy BMI of 21. We found a U-shaped association between recalled GWG and offspring obesity. Compared with a maternal weight gain of 15–19 lb, GWG <10 lb was associated with a significant increase in obesity risk at age 18 (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.02–2.34) and in 2001 (OR 1.27, 95% CI 1.05–1.53). High weight gain (40+lb) was also associated with obesity risk at age 18 (OR 1.81, 95% CI 1.22–2.69) and in 2001 (OR 1.74, 95% CI 1.48–2.04). These associations were stronger among mothers who were overweight before pregnancy (P for interaction=0.03), and they persisted with adjustment for birth weight.Conclusion:A high recalled pre-pregnancy BMI and extremes of recalled GWG are associated with an increased risk of adolescent and adult obesity in offspring, particularly when the mother is overweight. Pre-pregnancy weight and GWG may be modifiable fetal origins of overweight and obesity in women.

Weight gain in pregnancy and risk of maternal hyperglycemia

OBJECTIVE The purpose of this study was to examine associations of weight gain from prepregnancy to glycemic screening with glucose tolerance status. STUDY DESIGN Main outcomes were failed glycemic screening (1-hour glucose result >or= 140 mg/dL) with either 1 high value on 3-hour oral glucose tolerance testing (impaired glucose tolerance in pregnancy) or >or= 2 high values on 3-hour oral glucose tolerance testing (gestational diabetes mellitus). We performed multinomial logistic regression to determine the odds of these glucose intolerance outcomes by quartile of gestational weight gain among 1960 women in Project Viva. RESULTS Mean gestational weight gain was 10.2 +/- 4.3 (SD) kg. Compared with the lowest quartile of weight gain, participants in the highest quartile had an increased odds of impaired glucose tolerance in pregnancy (adjusted odds ratio, 2.54; 95% confidence interval, 1.25-5.15), but not gestational diabetes mellitus (odds ratio, 0.93; 95% confidence interval, 0.50-1.70). CONCLUSION Higher weight gain predicted impaired glucose tolerance in pregnancy, but not gestational diabetes mellitus.

Early Breastfeeding Experiences and Postpartum Depression

BACKGROUND: The first weeks after childbirth are a critical period for mother and newborn. Women may present with lactation failure and postpartum depression. It is unclear how a womans early breastfeeding experiences relate to postpartum depression. OBJECTIVE: We estimated the association between early breastfeeding experiences and postpartum depression at 2 months. METHODS: We modeled this association with logistic regression in a secondary analysis of data from the Infant Feeding Practices Study II. We assessed postpartum depression status with the Edinburgh Postnatal Depression Scale. RESULTS: In the neonatal period, 2,586 women reported ever breastfeeding, among whom 223 (8.6%) met criteria for major depression (Edinburgh Postnatal Depression Scale 13 or greater) at 2 months postpartum. Women who disliked breastfeeding in the first week were more likely to experience postpartum depression at 2 months (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.04–1.93) adjusting for maternal age, parity, education, ethnicity, and postnatal WIC participation. Women with severe breastfeeding pain in the first day (adjusted OR 1.96, 95% CI 1.17–3.29), the first week (adjusted OR 2.13, 95% CI 0.74–6.15 compared with no pain), and the second week (adjusted OR 2.24, 95% CI 1.18–4.26 compared with no pain) were more likely to be depressed. Breastfeeding help appeared protective among women with moderate (adjusted OR 0.22, 95% CI 0.05–0.94) or severe (adjusted OR 0.17, 95% CI 0.04–0.75) pain with nursing. CONCLUSION: Women with negative early breastfeeding experiences were more likely to have depressive symptoms at 2 months postpartum. Women with breastfeeding difficulties should be screened for depressive symptoms. LEVEL OF EVIDENCE: II

Breastmilk is a novel source of stem cells with multilineage differentiation potential

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self‐renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self‐renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC‐like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self‐renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient‐specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. STEM Cells2012;30:2164–2174

Cost Analysis of Maternal Disease Associated With Suboptimal Breastfeeding

OBJECTIVE: To estimate the U.S. maternal health burden from current breastfeeding rates both in terms of premature death as well as economic costs. METHODS: Using literature on associations between lactation and maternal health, we modeled the health outcomes and costs expected for a U.S. cohort of 15-year-old females followed to age 70 years. In 2002, this cohort included 1.88 million individuals. Using Monte Carlo simulations, we compared the outcomes expected if 90% of mothers were able to breastfeed for at least 1 year after each birth with outcomes under the current 1-year breastfeeding rate of 23%. We modeled cases of breast cancer, premenopausal ovarian cancer, hypertension, type 2 diabetes mellitus, and myocardial infarction considering direct costs, indirect costs, and cost of premature death (before age 70 years) expressed in 2011 dollars. RESULTS: If observed associations between breastfeeding duration and maternal health are causal, we estimate that current breastfeeding rates result in 4,981 excess cases of breast cancer, 53,847 cases of hypertension, and 13,946 cases of myocardial infarction compared with a cohort of 1.88 million U.S. women who optimally breastfed. Using a 3% discount rate, suboptimal breastfeeding incurs a total of

Lactation and Maternal Risk of Type 2 Diabetes: A Population-based Study

17.4 billion in cost to society resulting from premature death (95% confidence interval [CI]

Association Between Maternal Mood and Oxytocin Response to Breastfeeding

4.38–24.68 billion),