Elsevier

Journal of Hepatology

Volume 70, Issue 1, January 2019, Pages 126-132
Journal of Hepatology

Research Article
Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women

https://doi.org/10.1016/j.jhep.2018.09.013Get rights and content

Highlights

  • Lactation duration >6 months was protective against NAFLD in mid-life after adjustment for confounders.

  • The benefits of increased lactation duration on weight and waist circumference mediated <1/4 of this benefit.

  • Longer lactation duration may be an important lifestyle intervention to prevent the NAFLD during mid-life.

Background & Aims

Lactation lowers blood glucose and triglycerides, and increases insulin sensitivity. We hypothesized that a longer duration of lactation would be associated with lower prevalence of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease in the United States.

Methods

Participants from the Coronary Artery Risk Development in Young Adults cohort study who delivered ≥ 1 child post-baseline (Y0: 1985–1986), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010–2011) were included (n = 844). The duration of lactation was summed for all post-baseline births, and NAFLD at Y25 was assessed by central review of CT images and defined by liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of hepatic steatosis. Unadjusted and multivariable logistic regression analyses were performed using an a priori set of confounding variables; age, race, education, and baseline body mass index.

Results

Of 844 women who delivered after baseline (48% black, 52% white, mean age 49 years at Y25 exam), 32% reported lactation duration of 0 to 1 month, 25% reported >1 to 6 months, 43% reported more than 6 months, while 54 (6%) had NAFLD. Longer lactation duration was inversely associated with NAFLD in unadjusted logistic regression. For women who reported >6 months lactation compared to those reporting 0–1 month, the odds ratio for NAFLD was 0.48 (95% CI 0.25–0.94; p = 0.03) and the association remained after adjustment for confounders (adjusted odds ratio 0.46; 95% CI 0.22–0.97; p = 0.04).

Conclusions

A longer duration of lactation, particularly greater than 6 months, is associated with lower odds of NAFLD in mid-life and may represent a modifiable risk factor for NAFLD.

Lay summary

A longer duration of breastfeeding has been associated with multiple potential health benefits for the mother including reduction in heart disease, diabetes and certain cancers. In this study we found that breastfeeding for longer than 6 months was associated with a lower risk of non-alcoholic fatty liver disease in mid-life.

Introduction

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common cause of cirrhosis and hepatocellular carcinoma and is on trajectory to become the most frequent indication for liver transplantation in the United States,[1], [2] however therapeutic options are limited. While NAFLD is recognized as the hepatic manifestation of metabolic dysfunction, it also portends an increased risk for incident diabetes mellitus (DM) and metabolic syndrome suggesting a complex bidirectional relationship.[3], [4]

We recently demonstrated that gestational DM (GDM), a condition of glucose intolerance during pregnancy, is a risk marker for NAFLD in mid-life in women.5 In addition, other perinatal factors may potentially lower the risk of NAFLD. Lactation lowers maternal blood glucose, lipids and insulin concentrations through non-insulin facilitated cellular uptake of circulating glucose for milk production.6 Furthermore, in-depth studies of glucose homeostasis in the post-partum period suggest that lactation also improves insulin sensitivity.7 Lactation may also have favorable metabolic effects that persist post-weaning. A longer duration of lactation has been associated with lower future risk of developing the metabolic syndrome and type 2 diabetes mellitus in women of childbearing age, independent of changes in lifestyle behaviors, body weight, and other risk factors.[8], [9], [10], [11], [12] The biological mechanism behind this prolonged benefit is not clear. The association between lactation and increased weight loss is equivocal, however lactation may result in metabolically beneficial changes in blood lipids, regional fat mobilization, and/or reduced insulin secretion and resistance that may prevent beta cell exhaustion.[13], [14] The impact of lactation on maternal risk of NAFLD is unknown. Therefore, we sought to evaluate if a longer lactation duration was associated with a lower prevalence of NAFLD in mid-life. Modification of the risk for NAFLD in childbearing women represents a novel opportunity to decrease disease burden on a large scale.

Section snippets

Study population

The CARDIA study is a multicenter community-based longitudinal cohort study evaluating cardiovascular disease in young black and white adults 18–30 years of age from 4 US cities (Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) in 1985–1986. Participants were not selected based on risk factors for metabolic disease and were recruited by random-digit dialing from total communities, census tract information, or from their healthcare plan. The study design has been published

Study cohort characteristics

Of the 844 women meeting inclusion criteria, 48% were black and 52% were white, with a median (IQR) age of 25 (6) years at baseline. Two-hundred and seventy-six women (32%) reported a lactation duration of 0 to 1 month, 209 (25%) reported >1 to 6 months, 359 (43%) reported >6 months. Fifty-four (6.4%) met the CT definition for NAFLD at year 25. Of the women with NAFLD, 43% breastfed for 0–1 month, 30% for >1 to 6 months and 28% for >6 months. As expected, women with NAFLD had higher BMI,

Discussion

Our findings provide evidence that longer duration of lactation, particularly >6 months compared to never or very short lactation (<1 month), is associated with approximately half the odds of prevalent NAFLD in parous women in mid-life. This association was minimally affected by other risk factors for NAFLD such as race and baseline pre-pregnancy BMI and HOMA-IR. This is the first study to evaluate the relationship between lactation duration and NAFLD and to show that lactation may be an

Financial support

The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute. The analyses were supported by grants from K01 DK059944 (Dr. Gunderson, PI), R01 DK090047 (Dr. Gunderson, PI) and T32 5T32DK060414-13 (Dr. Maher, PI) from the National Institute of Diabetes, Digestive and Kidney Diseases, and R01 HL098445 (Dr. Carr) from the National Heart, Lung, and Blood Institute. Dr. VanWagner is supported by the National

Conflicts of interest

The authors declare no conflicts of interest that pertain to this work.

Please refer to the accompanying ICMJE disclosure forms for further details.

Authors’ contributions

Veeral H. Ajmera: Study concept and design, Analysis and interpretation of data, Drafting of Manuscript, Critical Revision. Norah A. Terrault: Study concept and design, interpretation of data, Critical Revision. Lisa B. VanWagner: Interpretation of data, Critical Revision. Monika Sarkar: Interpretation of data, Critical Revision. Cora E. Lewis: Collection and interpretation of data, Critical Revision. John J. Carr: Collection and interpretation of data, Critical Revision. Erica P. Gunderson:

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