Breastfeeding duration and reduced risk of NAFLD in midlife of parous women

1Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy 2Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgical Sciences, Dentistry, and Pediatrics, and Gynaecology, University Hospital of Verona, 37126 Verona, Italy 3Section of General Medicine, Hypertension and Liver Unit, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy

independent of age, BMI, waist circumference, dyslipidemia, T2DM, hypertension, education levels, smoking status, age at menarche, age at the first delivery and age at the last delivery [adjusted odds ratio 0.67 (95% CI 0.48-0.94) for women with ≥ 6 to < 12 months of breastfeeding duration and adjusted odds ratio 0.64 (95% CI 0.46-0.89) for women with ≥ 12 months of breastfeeding duration, when compared to women with < 1 month of breastfeeding duration].
With the aim to assess the magnitude of the effect of breastfeeding duration on the risk of NAFLD (as diagnosed by imaging techniques or indirect biomarkers) in later life of parous women, we have meta-analyzed the data of the aforementioned studies [4,5]. More specifically, for both studies, we have obtained the adjusted odds ratios for the effect of breastfeeding duration longer than 6 months on the risk of NAFLD in later life of parous women, when compared to the breastfeeding that lasted less than 1 month. These odds ratios were pooled and an overall estimate of effect size was computed using the random-effects restricted maximum likelihood (REML) model. All statistical tests were two sided and used a significance level of P < 0.05. We used STATA® software v16.1 (StataCorp, College Station, Texas, USA) for statistical analyses.
As reported in Figure 1, compared to the breastfeeding that lasted less than 1 month, breastfeeding longer than 6 months was independently associated with a 37% lower risk of NAFLD in later life of parous women (random-effects odds ratio 0.63, 95% CI 0.51-0.79, I 2 = 0%). Despite the limitations of this analysis (including the number of the eligible studies and the choice to take the adjusted odds ratio of model 8 in the study by Ajmera et al. [4]), this result corroborates the maternal benefit of breastfeeding longer than 6 months against NAFLD and provides the magnitude of the effect. It is known that breastfeeding, especially when it lasts more than 6 months, helps to promote healthy maternal metabolism [6]. However, to date, the biological mechanisms underpinning the association between breastfeeding duration and reduced risk of NAFLD in parous women remain uncertain. That said, as also discussed elsewhere [4][5][6][7], some epidemiological studies currently indicate that women who breastfeed have a reduced risk of some chronic disease [6], such as T2DM, hypertension and metabolic syndrome; all conditions strongly and frequently associated with NAFLD and its advanced forms [1]. Moreover, experimental studies have also reported that breastfeeding may improve insulin sensitivity and mobilize fat stores, thereby reducing the risk of NAFLD [6].
Collectively, the observational studies available so far and the result of our analysis reinforce the assertion that breastfeeding is relevant for the long-term health of the mother, with a protective effect on the risk of NAFLD. However, despite this evidence, along with other Authors [4][5][6][7], we believe that future observational studies on this issue are timely needed and that other aspects should be considered, such as the complexity of the pathogenesis of NAFLD (evaluating also the genetic variants linked to hepatic steatosis), intensity of breastfeeding, various socioeconomic and cultural factors, pre-conception background and pre-natal care for the duration of pregnancy. A qualitative leap in understanding the role of breastfeeding and its relationship with the risk of NAFLD should require a multidisciplinary approach across different medical disciplines.

Supplementary materials
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Declarations
Author contributions AM conceived and designed the study. AM, GB, CZ, and AD researched data and reviewed/edited the manuscript. AM analyzed the data and wrote the manuscript draft. All Authors approved the final version of the manuscript.

Conflicts of interest
The authors have no potential conflicts of interest to disclose.

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