Infants With Excessive Weight Gain During Exclusive Breastfeeding - An Exploratory Study

TY - BOOK

T1 - Infants With Excessive Weight Gain During Exclusive Breastfeeding - An Exploratory Study

AU - Larsson, Melanie Wange

N1 - CURIS 2019 NEXS 075

PY - 2018

Y1 - 2018

N2 - Background: There is convincing evidence from several meta-analyses that a high weight gain during the first 6 months of life is associated with an increased risk of overweight, obesity and metabolic complications later in childhood and adulthood. Compared to formula fed infants, breastfed infants have an overall slower growth. However, breastfed infants have a more rapid growth in the first 1-2 months, but then it becomes slower for the rest of the first year. Nevertheless, some exclusively breastfed infants experience excessive weight gain during the first 6 months of life. Breastfeeding has been suggested to reduce the risk of later overweight and obesity, but not all studies find a protective effect. Human milk composition varies between women and there is emerging evidence that different components have an effect on growth. Only few studies have investigated infants with excessive weight gain. Two case-reports examined exclusively breastfed infants with excessive weight gain and suggestedhigh protein content in human milk as a potential cause. Both cases experienced a slowdown in weight gain velocity when well into the complementary period. A cohort study examined 65 infants with excessive weight gain during the first year. However, the growth velocity in this cohort continued to be high, also after introduction to complementary foods. Since the literature on excessive weight gain in exclusively breastfed infants is sparse, health personnel lack evidence on which to base advice to parents of these infants.Objective: The main objectives of this PhD thesis were to explore factors which could have a role in the excessive weight gain observed in some breastfed infants, to describe the growth and body composition pattern of these infants and to discuss potential consequences.Design and methods: Paper I reports two cases of infants with excessive weight gain during exclusive breastfeeding with information on 24h human milk intake and macronutrient concentration measured at 5.5 (Case 1) and 4 months (Case 2). Paper II-III are based on a cohort study, SKOT-III, which includes two groups of exclusively breastfed infants examined from January 2016 to October 2017. Eligible infants for the high weight-gain (HW) group were exclusively breastfed infants with excessive weight gain of at least +1 increment in weight-for-age z-scores (WAZ) during the first 5-6 months, and at 5-6 months a WAZ > 2.0or a BMI-for-age z-score (BAZ) > 2.0 according to the WHO Growth Standards. Infants with a WAZ at age 4-6 months between -1.0 and +1.0 were qualified for the normal weight-gain (NW) group. Anthropometry, body composition, milk and blood samples, and milk intakewere measured at 5 and 9 months in both groups, and in the HW group anthropometry andbody composition were also measured at 18 months. Human milk samples were analysed formacronutrients, energy, hormones, specific proteins, and oligosaccharides, and blood sampleswere analysed for appetite- and growth hormones and metabolic parameters. Information onbreastfeeding characteristics, infant eating behaviour, and family history were obtained byinterviews of the parents. Results: In Paper I, we reported two exclusively breastfed infants with an increase in WAZuntil they were well into complementary feeding (7 and 9 months, respectively) after whichboth cases had a rapid decline in WAZ. Case 1 weighed 13.0 kg at 7 months (WAZ +4.2) andCase 2 weighed 18.4 kg at 9 months (WAZ +7.5). The 24 hour milk intake was high, 1132and 1421 grams, respectively. Fat and lactose concentration in their milk were within normalrange for both mothers, whereas protein concentration in the milk was below reference values.In Paper II, 13 infants were included in the HW group with a mean WAZ of +3.02 at the 5months visit and 17 infants were included in the NW group with a mean WAZ of +0.39 at the5 months visit. All anthropometric measures and body composition were significantlydifferent between the groups at the 5 months visit. The HW group had a mean weight gain of6.6 kg and a mean WAZ increase of 1.71 from birth to 5 months of age, compared to 4.4 kgand 0.15 unit increase in the NW group. The HW group had 70% more fat mass at 5 monthsthan the NW group. After introduction to complementary foods, weight velocity decreased inthe HW group and they had a marked catch-down in WAZ of 1.1 units from 5 to 18 months.Human milk intake and breastfeeding patterns at 5-6 months did not differ between thegroups. Milk leptin was lower in the HW group at 5 months and serum leptin wasconsiderably higher at 5 and 9 months compared to the NW group. In Paper III we founddifferences in several human milk oligosaccharides (HMOs) between the HW and the NWgroup at 5 and 9 months. Lacto-N-neotetraose (LNnT) was low in the HW group compared tothe NW group at 5 months, and further at 9 months. When combining the two groups totalHMO concentrations, total HMO-bound fucose, and 2´-fucosyllactose at 5 months werepositively associated with both fat mass index and weight velocity 0-5 months. LNnT wasnegatively associated with length-for-age z-score, weight velocity 0-5 months, and fat massindex. Discussion and conclusion: All infants in the case study and the SKOT-III cohort hadmarked catch-up growth during exclusive breastfeeding compared to the NW group andWHO growth standards. Further, they all showed catch-down growth when complementaryfoods were introduced and the majority of the infants reached the normal range of WAZ andBAZ the following year, which suggest that the excessive weight gain is caused by humanmilk composition and intake. Low milk leptin in the HW group may have stimulated appetiteand milk intake when weight gain was high. Unfortunately, human milk intake was measuredwhen most infants were introduced to complementary foods and when weight velocity wasdecreasing, and although the intake was 130 g higher in the HW group, the difference was notsignificant. High serum leptin in the HW group is likely to reflect the high body fat mass, andsince energy intake was likely to be high, the infants were likely to be leptin resistant whichcould impact cerebral regulation of energy balance, but this is speculative. Our findings oflower values of the HMO LNnT in the HW group compared to the NW group, and negativeassociation of LNnT with fat mass index is in line with a previously published study findingnegative association of LNnT with percentage fat mass. The differences in HMO patternbetween the two groups and the associations with weight gain and body composition suggestthat the HMO composition could play a role in the excessive weight gain. There were nodifferences in macronutrient concentration in human milk between the HW group and the NWgroup, which contradicts the suggestions in the two previously published case-reports, that ahigh protein concentration was a possible explanation for the high weight gain. Unfortunatelywe did not measure human milk intake, composition and blood parameters during the periodwith excessive catch-up growth, which would probably have given us a better understandingof why these infants had this special growth pattern. There is a need to confirm the findingsfrom this thesis in larger studies with longer follow-up. Even though recent data from a largeDanish cohort show that the majority of infants with high WAZ at 5 months are not becomingoverweight or obese later in childhood, the evidence for the association of early rapid weightgain and later obesity is strong. Therefore, it is important for health personnel to be aware of apossible increased risk of later obesity. We do not suggest intervening in the breastfeedingpattern of infants with excessive weight gain during exclusive breastfeeding, but we find itimportant to emphasize that the growth of these infants should be monitored closely and whencomplementary feeding is introduced it is according to current recommendations.

AB - Background: There is convincing evidence from several meta-analyses that a high weight gain during the first 6 months of life is associated with an increased risk of overweight, obesity and metabolic complications later in childhood and adulthood. Compared to formula fed infants, breastfed infants have an overall slower growth. However, breastfed infants have a more rapid growth in the first 1-2 months, but then it becomes slower for the rest of the first year. Nevertheless, some exclusively breastfed infants experience excessive weight gain during the first 6 months of life. Breastfeeding has been suggested to reduce the risk of later overweight and obesity, but not all studies find a protective effect. Human milk composition varies between women and there is emerging evidence that different components have an effect on growth. Only few studies have investigated infants with excessive weight gain. Two case-reports examined exclusively breastfed infants with excessive weight gain and suggestedhigh protein content in human milk as a potential cause. Both cases experienced a slowdown in weight gain velocity when well into the complementary period. A cohort study examined 65 infants with excessive weight gain during the first year. However, the growth velocity in this cohort continued to be high, also after introduction to complementary foods. Since the literature on excessive weight gain in exclusively breastfed infants is sparse, health personnel lack evidence on which to base advice to parents of these infants.Objective: The main objectives of this PhD thesis were to explore factors which could have a role in the excessive weight gain observed in some breastfed infants, to describe the growth and body composition pattern of these infants and to discuss potential consequences.Design and methods: Paper I reports two cases of infants with excessive weight gain during exclusive breastfeeding with information on 24h human milk intake and macronutrient concentration measured at 5.5 (Case 1) and 4 months (Case 2). Paper II-III are based on a cohort study, SKOT-III, which includes two groups of exclusively breastfed infants examined from January 2016 to October 2017. Eligible infants for the high weight-gain (HW) group were exclusively breastfed infants with excessive weight gain of at least +1 increment in weight-for-age z-scores (WAZ) during the first 5-6 months, and at 5-6 months a WAZ > 2.0or a BMI-for-age z-score (BAZ) > 2.0 according to the WHO Growth Standards. Infants with a WAZ at age 4-6 months between -1.0 and +1.0 were qualified for the normal weight-gain (NW) group. Anthropometry, body composition, milk and blood samples, and milk intakewere measured at 5 and 9 months in both groups, and in the HW group anthropometry andbody composition were also measured at 18 months. Human milk samples were analysed formacronutrients, energy, hormones, specific proteins, and oligosaccharides, and blood sampleswere analysed for appetite- and growth hormones and metabolic parameters. Information onbreastfeeding characteristics, infant eating behaviour, and family history were obtained byinterviews of the parents. Results: In Paper I, we reported two exclusively breastfed infants with an increase in WAZuntil they were well into complementary feeding (7 and 9 months, respectively) after whichboth cases had a rapid decline in WAZ. Case 1 weighed 13.0 kg at 7 months (WAZ +4.2) andCase 2 weighed 18.4 kg at 9 months (WAZ +7.5). The 24 hour milk intake was high, 1132and 1421 grams, respectively. Fat and lactose concentration in their milk were within normalrange for both mothers, whereas protein concentration in the milk was below reference values.In Paper II, 13 infants were included in the HW group with a mean WAZ of +3.02 at the 5months visit and 17 infants were included in the NW group with a mean WAZ of +0.39 at the5 months visit. All anthropometric measures and body composition were significantlydifferent between the groups at the 5 months visit. The HW group had a mean weight gain of6.6 kg and a mean WAZ increase of 1.71 from birth to 5 months of age, compared to 4.4 kgand 0.15 unit increase in the NW group. The HW group had 70% more fat mass at 5 monthsthan the NW group. After introduction to complementary foods, weight velocity decreased inthe HW group and they had a marked catch-down in WAZ of 1.1 units from 5 to 18 months.Human milk intake and breastfeeding patterns at 5-6 months did not differ between thegroups. Milk leptin was lower in the HW group at 5 months and serum leptin wasconsiderably higher at 5 and 9 months compared to the NW group. In Paper III we founddifferences in several human milk oligosaccharides (HMOs) between the HW and the NWgroup at 5 and 9 months. Lacto-N-neotetraose (LNnT) was low in the HW group compared tothe NW group at 5 months, and further at 9 months. When combining the two groups totalHMO concentrations, total HMO-bound fucose, and 2´-fucosyllactose at 5 months werepositively associated with both fat mass index and weight velocity 0-5 months. LNnT wasnegatively associated with length-for-age z-score, weight velocity 0-5 months, and fat massindex. Discussion and conclusion: All infants in the case study and the SKOT-III cohort hadmarked catch-up growth during exclusive breastfeeding compared to the NW group andWHO growth standards. Further, they all showed catch-down growth when complementaryfoods were introduced and the majority of the infants reached the normal range of WAZ andBAZ the following year, which suggest that the excessive weight gain is caused by humanmilk composition and intake. Low milk leptin in the HW group may have stimulated appetiteand milk intake when weight gain was high. Unfortunately, human milk intake was measuredwhen most infants were introduced to complementary foods and when weight velocity wasdecreasing, and although the intake was 130 g higher in the HW group, the difference was notsignificant. High serum leptin in the HW group is likely to reflect the high body fat mass, andsince energy intake was likely to be high, the infants were likely to be leptin resistant whichcould impact cerebral regulation of energy balance, but this is speculative. Our findings oflower values of the HMO LNnT in the HW group compared to the NW group, and negativeassociation of LNnT with fat mass index is in line with a previously published study findingnegative association of LNnT with percentage fat mass. The differences in HMO patternbetween the two groups and the associations with weight gain and body composition suggestthat the HMO composition could play a role in the excessive weight gain. There were nodifferences in macronutrient concentration in human milk between the HW group and the NWgroup, which contradicts the suggestions in the two previously published case-reports, that ahigh protein concentration was a possible explanation for the high weight gain. Unfortunatelywe did not measure human milk intake, composition and blood parameters during the periodwith excessive catch-up growth, which would probably have given us a better understandingof why these infants had this special growth pattern. There is a need to confirm the findingsfrom this thesis in larger studies with longer follow-up. Even though recent data from a largeDanish cohort show that the majority of infants with high WAZ at 5 months are not becomingoverweight or obese later in childhood, the evidence for the association of early rapid weightgain and later obesity is strong. Therefore, it is important for health personnel to be aware of apossible increased risk of later obesity. We do not suggest intervening in the breastfeedingpattern of infants with excessive weight gain during exclusive breastfeeding, but we find itimportant to emphasize that the growth of these infants should be monitored closely and whencomplementary feeding is introduced it is according to current recommendations.

UR - https://rex.kb.dk/primo-explore/fulldisplay?docid=KGL01012003796&context=L&vid=NUI&search_scope=KGL&tab=default_tab&lang=da_DK

M3 - Ph.D. thesis

SN - 978-87-7209-242-3

BT - Infants With Excessive Weight Gain During Exclusive Breastfeeding - An Exploratory Study

PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen

CY - Copenhagen

ER -