Eighty-one term delivery mothers were selected as research subjects in the colostrum group; 52 were healthy, 16 were diagnosed with GDM, and 13 were diagnosed with GHD in the second trimester of pregnancy. A total of 67 lactating women were included in this study, including 31 normal mothers who came for a follow-up assessment during lactation, and the mothers breastfed their infants for at least 3 months. The participants' clinical characteristics are shown in Table 1.
Clinical characteristics Clinical data Colostrum Mature Number of case 81 67 Maternal age (year) 29.51 (27.00, 31.00)1 28.06±3.43 Pregnancy duration (week) 39.35±1.09 39.26±1.08 Lactation period 2 days 3.24 (2.93, 5.75) months2 Infant sex (male/female) 37/44 37/30 Pre-pregnancy weight (kg) 57.04±10.19 56.88±10.22 Pre-pregnancy BMI (kg/m2) 22.08±3.75 21.80±3.86 Weight late in pregnancy (kg) 72.38±10.89 71.88±10.69 BMI late in pregnancy (kg/m2) 27.96±3.64 27.47±3.76 BMI during lactation (kg/m2) - 23.44±3.28 Pregnancy-associated complication mother with GDM (case) 16 0 Mothers with GHD (case) 13 0 1Kolmogorov-Smirnov test: P=0.024. Skewed data are indicated with medians and quartiles. 2Kolmogorov-Smirnov test: P=0.015. Skewed data are indicated with medians and quartiles.
Table 1. Participant characteristics
The average BSSL level was lower in colostrum [(71.49±40.61) μg/mL] than mature milk [(236.90±52.75) μg/mL] in 31 paired samples (Fig. 1A). Additionally, in the non-paired samples, the BSSL level was lower in colostrum [(96.35±55.66) μg/mL, n=52] than in mature milk [(208.03±66.99) μg/mL, n=67] in healthy mothers (Fig. 1B). However, the BSSL level in mature milk decreased after 6 months (Fig. 2).
As shown in Table 2, the BSSL level in colostrum was positively correlated with pregnancy weeks and negatively correlated with maternal BMI pre-pregnancy and in late pregnancy in 52 mothers. Moreover, the BSSL level in mature milk was negatively correlated with the lactation period and positively correlated with BMI increase during pregnancy.
Charcteristics Colostrum (n=52) r/ F P Maternal age −0.084 0.563 Gestational week 0.379 0.006 Pre-pregnancy weight −0.267 0.056 Pre-pregnancy BMI −0.397 0.004 Weight late in pregnancy −0.146 0.301 BMI late in pregnancy −0.292 0.036 Weight gain during pregnancy 0.239 0.088 BMI gain during pregnancy 0.172 0.224 Charcteristics Mature milk (n=67) Maternal age 0.068 0.592 Lactating period −0.254 0.041 Pre-pregnancy weight −0.222 0.071 Pre-pregnancy BMI −0.188 0.128 Weight late in pregnancy −0.047 0.706 BMI late in pregnancy 0.020 0.875 Weight gain during pregnancy 0.236 0.057 BMI gain during pregnancy 0.256 0.038 BMI during lactation −0.064 0.616
Table 2. Bivariate associations between BSSL level in breast milk and maternal characteristics
There was no difference in the BSSL concentration in colostrum milk between preterm and term milk (Table 3).
Group n BSSL (μg/mL) Full-term 52 96.35±55.66 Preterm 24 103.73±43.22 T=0.574, P=0.568; Data on the BSSL concentration in full-term and preterm colostrum milk are shown as the average and SD; The differences were calculated using independent-samples tests.
Table 3. Comparison of BSSL levels between preterm and term colostrum milk
There was a significant difference in the BSSL concentration in colostrum milk among normal mothers and mothers with GHD or GDM (P<0.01, Table 4). The BSSL concentration in colostrum milk was lower in GDM mothers compared with normal mothers, even after adjusting for maternal pre-pregnancy BMI and pregnancy week (P<0.05).
Group n BSSL (μg/mL) Normal 52 96.35±55.66 GHD 13 69.59±42.86 GDM 16 41.63±27.58a P=0.001; One-way ANOVA was used to compare the normal, GHD, and GDM mothers with full-term infants; aP<0.05 vs. normal.
Table 4. Comparison of BSSL levels in colostrum milk between normal, GHD, and GDM mothers
Many clinical trials and animal models have indicated that milk-borne BSSL can compensate for the low expression of pancreatic lipases during infancy and is believed to be important for the healthy growth and development of infants, particularly preterm infants. To the best of our knowledge, this is the first report to indicate that BSSL is abundantly present in both colostrum and mature milk of Chinese women. The BSSL concentration in mature milk was higher than that in colostrum milk, and the high BSSL level in human milk persisted until 6 months after birth. These results were in agreement with those of previous reports from Oklahoma, which have revealed that BSSL concentrations in human milk reach 100–300 μg/mL and that BSSL levels increase significantly from the 3rd to the 60th postpartum day. The BSSL secretion pattern was similar to the pattern that has been reported for the fat content of human milk; that is, it was higher in mature milk and lower in colostrum. It has been reported that mouse pancreatic BSSL expression increases after the first 4 days of life and peaks on day 7, whereas pancreatic lipase secretion in humans remains mature for two years after parturition. Therefore, milk-borne BSSL enhancement may improve fat absorption and compensate for the poor exocrine pancreatic function in infancy, whereas BSSL declines when infants develop a mature digestive capability.
In this study, the BSSL level in preterm milk was higher than that in term milk, although this difference was not significant. Previous studies have shown that the BSSL in preterm milk is higher than or similar to that in term milk and that the lipolytic enzyme activity (i.e., hydrolysis of long-chain triglycerides) does not change with lactation length. However, Pamblanco et al have posited that gestational age may influence the BSSL activity. Together, these observations suggest that breastfed preterm infants may obtain the same or greater fat digestion capability compared with term neonates, thus improving energy acquisition and allowing infants to catch up in early life.
Obesity-related cytokines in breast milk, such as leptin, microRNAs, and adiponectin, dynamically change over the course of lactation and are influenced by maternal BMI. In the present study, the BSSL level in colostrum was negatively correlated with maternal pre-pregnancy BMI rather than BMI late in pregnancy. The milk BSSL level may be influenced by changes in maternal endocrine hormones (such as prolactin) during pregnancy. Prolactin regulates the nuclear factor 1-C2 (NF1-C2) protein level, which can activate and regulate the BSSL milk gene in mammary epithelial nuclei, and obese mothers have lower prolactin levels during lactation thus resulting in decreased BSSL secretion. Interestingly, the BSSL level in mature milk was positively associated with BMI gain throughout pregnancy. Being overweight and obese during pregnancy increases the risk of fetal macrosomia, and the composition of breast milk can influence the metabolism of the offspring through breastfeeding. Therefore, increased BSSL secretion in the presence of a high gestational BMI gain suggests the influence of milk-borne BSSL on the health of the offspring by promoting the efficient digestion of milk lipids, which may in turn increase infant weight. Many researchers have confirmed that prenatal nutritional exposure not only influences children's growth and development, but also affects adulthood health. Notably, early overnutrition is a risk factor for obesity and metabolic syndrome[30–31]. However, further studies are needed to determine whether the higher BSSL level in breast milk merely represents the nutritional status of overweight and obese mothers or influences the health of their children.
Moreover, GDM women had a lower BSSL concentration in colostrum than that of normal women. Increased glucose and insulin levels have been reported in human breast milk from diabetic mothers, owing to diffusion of glucose and insulin from the maternal circulation into breast milk[32–33]. Insulin is secreted by pancreatic endocrine cells and is not only involved in glycometabolism but also regulates pancreatic lipase through the islet-acinar shaft and reduces pancreatic lipase activity. However, the small sample size in this study limited our ability to discover any additional correlations between milk-borne BSSL and maternal lipid and glucose metabolic indexes. Further study is required to determine whether BSSL secretion and synthesis in the mammary gland are regulated by insulin.
In this first reported investigation on the BSSL concentration in the milk of Chinese women, we confirmed that the milk-borne BSSL level is correlated with the maternal lactation length and the BMI at pre-pregnancy, late pregnancy, and the BMI gain during pregnancy. However, we measured the BSSL level, but not activity, in the present study. Published reports have demonstrated that the activity of BSSL, instead of its level, reflects its function[9,14,35,23–24]. Moreover, the small sample size and small number of mature milk samples from mothers with GDM/GHD and preterm groups limited our ability to discover any additional effect of the BSSL level in mature breast milk on the maternal metabolic status or gestational age. Furthermore, additional research is needed to determine whether the BSSL level in offspring is regulated by the milk-borne BSSL level and facilitates weight control in breastfed infants.
In conclusion, our findings demonstrated that pancreatic BSSL, which is involved in lipid absorption, was abundantly present in human milk, particularly in mature milk. The BSSL level in human milk was mainly correlated with maternal BMI. These findings suggest that preterm milk has the same fat digesting potential as term milk. GDM may affect BSSL secretion in colostrum milk. The changes in BSSL features in this study may have clinical implications associated with the weight and metabolic changes in pregnant women with respect to the nutrition and health of the offspring.
The level of bile salt-stimulated lipase in the milk of Chinese women and its association with maternal BMI
- Received Date: 2018-10-21
- Accepted Date: 2019-02-26
Abstract: This study aimed to investigate the bile salt-stimulated lipase (BSSL) concentration in the milk of Chinese women and its correlation with maternal body mass index (BMI), gestational diabetes mellitus (GDM) and gestational hypertensive disorder (GHD). The BSSL levels in the milk samples were measured by enzyme-linked immunosorbent assay (ELISA). BSSL level in colostrum milk of mothers with full-term infants was positively correlated with pregnancy week and negatively correlated with maternal pre-pregnancy BMI and BMI late in pregnancy. Moreover, the BSSL concentration in mature milk was positively correlated with BMI gain during pregnancy. The BSSL concentration in colostrum milk was lower in GDM mothers than in normal mothers. The BSSL helps infants digest fat in early life and its level was associated with lactation. The changes in BSSL characteristics with maternal BMI and GDM in this study may have clinical implications regarding the effects of pregnancy weight and metabolism on the nutrition and health of the offspring.