4.2.1. Associations of Maternal Serum Adiponectin and Leptin Levels during Pregnancy with Infant Adiposity Development during the First Year of Life
The inverse relationship of maternal serum adiponectin during pregnancy with foetal birth weight was documented in several studies [12
]. In contrast, one study reported a positive association [39
], while several studies failed to find any association between maternal serum adiponectin and birth weight [24
]. The discrepancy between these studies and our findings might be attributable to the differences in subjects and the stages of pregnancy studied.
Apart from that, there might be a significant link between maternal and infant adiposity. A cohort study revealed that infants who were born to overweight and obese mothers had a higher birth weight and a greater increase in weight gain during the first year of age than infants of normal weight mothers [21
]. Moreover, a significantly positive association between gestational weight gain and birth size was also reported in previous studies [41
]. However, considering that the aim of the study was to examine the role of adipokine levels in the development of infant adiposity, the maternal pre-pregnancy BMI and total gestational weight gain were controlled as confounders in this study.
Pregnancy is described as a state of insulin resistance that results from changes in the maternal circulating levels of inflammatory mediators [43
] and increased adiposity [44
]. During the first trimester, a pregnant mother starts to accumulate adipose tissues, followed by increased insulin resistance and lipolysis in later trimesters [45
]. The changes in the hormonal milieu during pregnancy that enhance fat tissue storage may reduce sensitivity to insulin [46
]. TNF-α, as a predictor of insulin resistance in pregnancy [47
], may suppress the function of peroxisome proliferator-activated receptor in adipocytes, thus inhibiting the secretion of adiponectin [48
As pregnancy progresses, maternal insulin resistance is heightened and the adiponectin level is reduced, which may increase the supply of glucose to the foetus [49
]. In addition, increased insulin resistance is shown to suppress the inhibition of lipolysis and amino acid turnover, which leads to elevated free fatty acids and amino acids. Subsequently, the oversupply of nutrients together with increased foetal insulin resistance as a response to intrauterine hyperinsulinism may result in the overgrowth of the foetus [50
]. Adiposity and the possible existence of impaired glucose intolerance among the mothers in the current study might be related to the decreased serum adiponectin level. It was demonstrated in this study that mothers with a lower adiponectin level had heavier and larger infants. An intrauterine environment stressed by insulin resistance and molecular intermediates such as adiponectin might have programmed the infants through changes in the metabolic and/or appetite-regulating pathways that would predispose them to develop adiposity in the first year of life [50
Within the first six months after birth, the infant builds more fat mass (fat cells rapidly increase in size), then over the next six months the size of fat cells is slightly decreased. The number of adipocytes only starts to increase from the end of the first year of life [51
]. Until six months of age, the infant accumulates fat mass up to 25–30% of the total body weight, while over the second six months the fat-free mass comprises a large percentage of total infant body weight [52
]. A study reported that higher intake of protein between nine and 12 months of age was associated with increased BMI among boy infants at the age of six years [53
]. Taken together, the inverse relationship between maternal adiponectin and infant adiposity in this study might reflect the protective role of maternal adiponectin on reducing weight gain within the critical period of the first six months of infant life, at which fat mass is actively built up.
On the other hand, the period in the latter half of the first year is when the infant diet changed with the introduction of complementary food, which was not explored in the current study. That might explain the absence of a significant association between maternal serum adiponectin and infant abdominal circumference at 12 months of age. Yet, it is suggested that the higher maternal adiponectin during pregnancy might slow down the catch-up growth of infants within the first 12 months of life, when prevention of childhood obesity should begin.
4.2.2. Associations of Maternal Breast Milk Adiponectin Levels within Two Months Postpartum with Infant Adiposity Development during the First Year of Life
Thus far, there is a dearth of scientific data regarding the associations between these parameters. A study by Woo et al. [11
] demonstrated an inverse association between maternal breast milk adiponectin and infant WAZ and WLZ at 0, one and three months of age, in which the stronger cross-sectional association between breast milk adiponectin and infant weight suggested that the effects may rely on current consumption of breast milk. Since the breast milk samples were only collected at birth and two months postpartum in the current study, the association with infant adiposity at six and 12 months of age could not be finalised. The underlying mechanisms and pathways for such an inverse association remain to be elucidated.
On the contrary, a study by Weyermann et al. [54
] found that mothers with large-for-gestational age (LGA) infants had a significantly higher level of breast milk adiponectin as compared to mothers with adequate-for-gestational age (AGA) or small-for-gestational age (SGA) infants. Bronsky et al. [55
] reported that breast milk adiponectin levels throughout the first year postpartum were not significantly associated with infant body weight. The discrepancy in the results among these studies might be attributable to the differences in subjects, stages of study, methods of breast milk sample collection and assay, or breast milk adiponectin pattern throughout the respective studied periods.
Studies with a duration longer than 12 months postpartum also reported controversial findings. Weyermann et al. [33
] documented that a higher level of breast milk adiponectin at six weeks postpartum was associated with higher odds of infant overweight at two years of age, particularly among those who were breastfed for at least six months. Yet, its underlying mechanism and pathway were not further explored. Another study also indicated that breast milk adiponectin at six weeks postpartum was positively associated with weight gain and the sum of skin-folds up to the age of two years [56
]. Woo et al. [57
] found that infants exposed to higher breast milk adiponectin experienced a significant increase in weight-for-age Z
scores (WAZ) between 12 and 24 months of age as compared to those exposed to lower adiponectin. This finding conflicted with their previous work, which reported an inverse relationship between breast milk adiponectin and infant growth in the first six months of life [11
]. However, since WAZ was consistently below the median, and overweight at 24 months of age was uncommon in the latter study, Woo et al. [57
] also concluded that the greater weight gain in the latter half of the second year might not reflect the pathology of obesity but rather the positive catch-up growth after a less evident weight gain within six months postpartum. It was suggested that delayed catch-up growth within the first half of the second year represented the protective effect of higher breast milk adiponectin against adiposity, since more fat mass depositions occur during the period.
In contrast, preliminary results from a prospective follow-up study reported that colostrum adiponectin was inversely associated with children’s BMI at 10 years old [58
]. Findings from the study were described with regards to the innate immune system regulation. The alteration in the composition of gut microbiota could influence energy homeostasis, in which glucose is rapidly absorbed and lipid is excessively stored [59
]. Thus, it was proposed that the higher colostrum adiponectin among normal-weight children might suppress the proinflammatory response in the infant’s intestines due to the changes in gut microbiota and impaired gut barrier. Adiponectin as an anti-inflammatory adipokine may downregulate the deleterious immune response (the secretion of pro-inflammatory cytokines that are likely to modulate the pathogenesis of obesity and metabolic diseases), thus could prevent excessive weight gain in later life [58
]. Findings from this study support the protective effect of breastfeeding on the future growth and development of infants. However, since the study only included the postnatal period up to 12 months, the effect of breastfeeding on infant growth trajectory beyond that age could not be finalized in the current study.
At 12 months of age, infants who were breastfed had a significantly lower body weight compared to infants who were not breastfed; however, the weight is still within the normal range. The duration of breastfeeding was shown to be related to decreased childhood overweight in a wide range of studies of weight status during the first year of age [60
] or beyond [62
]. The mechanisms regarding the effect of breastfeeding on the risk of overweight remain inconclusive. In contrast, several studies failed to establish a significant association between breastfeeding and childhood overweight [67
]. A potential explanation for the discrepancy in the findings might be the difference in sample size, population age, proportion of breastfeeding, study design or diverse population (genetic and environmental background).
The presence of adiponectin in breast milk may be involved in the programming of energy balance in the early, critical period of infant growth and metabolic homeostasis development [72
]. As a signaling molecule that regulates energy intake and expenditure, adiponectin is suggested to play a significant role in the regulation of appetite control in breastfed infants [73
]. Short-term appetite control through breastfeeding on demand may influence infant metabolic programming, wherein it would enhance the infant’s ability to self-regulate nutrient intake [74
]. Additionally, breastfed infants were shown to have greater satiety responsiveness compared to formula-fed infants [76
], which subsequently may prevent excessive energy intake and lead to positive future weight trajectory [77
Therefore, it is suggested that plausible underlying mechanisms for the protective effect of breastfeeding against adiposity may relate to the sufficient nutrients in breast milk and the presence of hormones and growth factors not found in infant formula [74
]. Breastfed infants may absorb the right amount of nutrients according to the body’s needs, while unique bioactive compounds in breast milk may be involved in the inhibition of adipocyte differentiation [78
]. Consequently, the optimal regulation or dysregulation of metabolic programming in early infancy may have an impact on the development of adiposity in later life.