Cytokines in human colostrum and neonatal jaundice

Breast-fed infants have higher bilirubin levels than formula-fed infants, possibly because of variations in the composition of the breast milk. The aim of this study was to investigate whether there is a relationship between cytokine levels in the colostrum of nursing mothers and neonatal jaundice (NJ). Breast milk samples were collected from breast-feeding mothers of healthy full-term neonates, 32 with NJ and 29 without jaundice. The concentrations of IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha were measured by chemiluminescence enzyme immunometric assays. Mothers of infants with NJ had a higher concentration of IL-1beta in colostrum, compared with those feeding neonates without NJ, and similar trends were seen for IL-6, IL-8, IL-10, and for TNF-alpha. The concentrations of IL-1beta significantly correlated with IL-6, IL-8, IL-10, and TNF-alpha concentrations, but not with serum bilirubin levels of infants with NJ. In conclusion, the concentrations of IL-1beta were increased in colostrum from breast-feeding mothers whose infants had NJ. The correlation between the concentrations of cytokines involved in the function of hepatic uptake and excretory systems and in the enterohepatic circulation of bilirubin provides additional data to the delineation of the cascade of pathophysiological events that can lead to NJ.     

Parathormone and perinatal calcium homeostasis.

Plasma parathormone (PTH) and calcium concentrations were measured in 309 specimens collected from 190 newborns during the first 7 days of life. The patient material consisted of 51 preterm, 130 term, and 9 postterm infants, including 22 infants of diabetic mothers (IDM), 38 infants with hypocalcemia, and 25 asphyxiated infants. PTH was detectable, although in low concentrations, in cord blood samples despite the presence of elevated calcium concentrations. Postpartum, PTH concentrations in term, appropriate for gestational age (AGA) infants remained low during the first 2 days of life; a significant (P less than 0.05) and sustained increase in plasma hormone levels was noted starting on day 3. PTH concentrations in IDM and preterm infants remained low for 3 days and a significant hormone increase did not occur until day 4. Hypocalcemia was common in IDM and asphyxiated infants; these infants accounted for two-thirds of all hypocalcemic infants. The profile of plasma calcium in IDM during the first week of life was different than that of any other group of infants. Plasma calcium concentrations remained depressed over this period of time and exhibited a temporary drop on day 4 accompanied by an increase in plasma PTH levels. Asphyxiated infants exhibited low plasma calcium concentrations, despite PTH levels that were significantly (P less than 0.007) higher than those of age-matched term AGA newborns.     

Cigarette smoke exposure and development of infants throughout the first year of life: influence of passive smoking and nursing on cotinine levels in breast milk and infant''s urine

The effects of smoke exposure via mothers' milk and/or via passive smoking during the first year of life were investigated in a prospective longitudinal matched-pair study. The somatic and mental development of 69 infants whose mothers smoked more than five cigarettes per day throughout pregnancy and continued smoking after childbirth were compared with 69 children of non-smoking mothers. At birth, mean body weight of neonates from smoking mothers was significantly lower than the weight of neonates from non-smoking mothers. This weight difference between the two groups was no longer significant in infants at 12 months of age. With the methods employed by the authors, neither psychomotor nor mental development was affected by smoke exposure during pregnancy and early infancy. Infections of the lower respiratory tract were more frequent in the children of smoking mothers. These mothers weaned their babies earlier than non-smokers, but the different feeding behaviour did not influence any of the clinical parameters that were investigated in this study. In order to evaluate the extent of smoke exposure, cotinine was measured in children's urine and in breast milk once a month throughout the first year of life. Cotinine in the urine was significantly dependent on feeding behaviour: infants breast fed showed concentrations 10-fold higher than those who were bottle fed. Cotinine excretion in urine of infants from smoking mothers, who were not breast fed (nicotine exposure via passive smoking only) was even higher than that of adult passive smokers. If infants from smoking mothers were breast fed, their urinary cotinine excretion was in the range of adult smokers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breast milk jaundice in preterm infants

A retrospective study was performed comparing bilirubin levels in 40 preterm newborns with uncomplicated courses fed a combination of premature breast milk and formula to those of 60 comparable preterm newborns fed formula only. A significantly higher bilirubin level was noted in the group fed the combined diet on the 6th day of life and on the day of discharge. Seventy-six and seven tenths percent of the preterm infants fed breast milk and formula met the criteria for phototherapy, whereas only 45 percent were treated in the group fed formula alone. Our findings indicate that premature breast milk might cause early and late increase in bilirubin levels in healthy preterm newborns.     

Breast milk feeding and cognitive ability at 7-8 years

OBJECTIVE: To examine the association between duration of breast milk feeding and cognitive ability at 7-8 years in a birth cohort of very low birthweight infants. DESIGN: 280 survivors from a national birth cohort of 413 New Zealand very low birthweight infants born in 1986 were assessed at age 7-8 years on measures of verbal and performance intelligence quotient (IQ) using the WISC-R. At the same time mothers were questioned as to whether they had elected to provide expressed breast milk at birth and the total duration of breast milk feeding. RESULTS: Some 73% of mothers provided expressed breast milk and 37% breast fed for four months or longer. Increasing duration of breast milk feeding was associated with increases in both verbal IQ (p < 0.001) and performance IQ (p < 0.05): children breast fed for eight months or longer had mean (SD) verbal IQ scores that were 10.2 (0.56) points higher and performance IQ scores that were 6.2 (0.35) points higher than children who did not receive breast milk. These differences were substantially reduced after control for selection factors associated with receipt of breast milk. Nevertheless, even after control for confounding, there remained a significant (p < 0.05) association between duration of breast milk feeding and verbal IQ: children breast fed for eight months or longer had adjusted mean (SD) verbal IQ scores that were 6 (0.36) points higher than the scores of those who did not receive breast milk. CONCLUSIONS: These findings add to a growing body of evidence to suggest that breast milk feeding may have small long term benefits for child cognitive development.     

Trends in breastfeeding: it is not only at the breast anymore

The past characterisations of breastfeeding as being only at the breast of the mother may no longer be applicable in the United States as mothers now frequently express their milk. We conducted a retrospective cohort study with women who visited the Cincinnati Children's Breastfeeding Medicine Clinic to understand breast milk feeding behaviours of healthy mothers and infants, which included questions specifically about breast milk expression. All 40 mothers in the cohort expressed their milk and all 40 infants were fed expressed milk. One infant was fed another mother's milk for 30 days. Two‐thirds (13/40) of infants received their mother's expressed milk at least a week after it was first expressed and 25% (10/40) of infants continued to be fed expressed breast milk after mothers had stopped expressing milk. There were 14 sequences of breast milk production by the mothers and 16 sequences of consumption by the infants. Early in the post‐partum period, mothers started expressing milk even though their infants were consuming all of the breast milk that they needed at the breast. As a result of breast milk expression by all mothers in this cohort, we observed highly variable patterns of maternal breast milk production and infant breast milk consumption, which were not necessarily synchronous within a dyad. It is now time to develop appropriate ways to characterise the production and consumption of breast milk more accurately and investigate whether these behaviours have consequences for the health of mothers and infants.     

Breast vs bottle feeding-impact on growth in urban infants

The growth of 50 infants given breast milk during the first 3 months was compared with 50 infants given bovine milk prior to this age. Growth parameters of infants between 9–15 months of age were measured. Fifty percent of the sample in each group represented educated and uneducated mothers. The feeding pattern was similar in the two groups although the practice of diluting milk was more common (28%) in bovine milk fed group as compared to breast fed (10%). Morbidity from diarrhea and upper respiratory infection was higher in the bovine milk group than the breast fed (P<0.05). All the growth parameters were significantly better in the breast fed group (P<0.05) than the artifically fed. The growth paramethrs of artificially fed infants from uneducated mothers were poor when compared to all other groups. This study emphasizes the critical importance of promoting breast feeding during the first 3–4 months of life irrespective of maternal educational status.     

Breast milk jaundice in premature infants.

In randomised study of 186 preterm infants those fed on maternal or banked breast milk had a significantly higher peak bilirubin concentration and a more prolonged jaundice than infants fed an artificial preterm formula and were over four times more likely to achieve plasma bilirubin values above 200 mumol/l (11.7 mg/100 ml). This dietary effect was seen even in a high risk subgroup of sick ventilated infants below 1500 g who were receiving restricted enteral intakes. We suggest that breast milk jaundice in preterm infants may increase clinical intervention. Our findings are discussed in the light of epidemiological data suggesting an association between moderate hyperbilirubinaemia (greater than 170 mumol/l) and neurodevelopmental outcome.     

Detection of interferon-gamma-inducible chemokines in human milk

AIM: To assess the immunological role of human milk by analysing the concentrations of interferon-gamma-inducible protein of 10 kda (IP-10) and monokine induced by interferon-gamma (MIG) in human milk from mothers of preterm and term infants. METHODS: IP-10 and MIG levels of colostrum, early milk, mature milk and sera were measured by enzyme-linked immunosorbent assay (ELISA). IP-10 and MIG mRNA expression levels in cellular components of human milk were determined by RT-PCR. IP-10 and MIG protein expression in mammary gland tissues was analysed by immunohistochemistry. RESULTS: Significant amounts of IP-10 and MIG were detected in human milk. The concentrations of IP-10 and MIG in colostrum and early milk were significantly higher than those of sera from healthy controls or lactating mothers. These chemokine concentrations in colostrum and early milk were significantly higher than those of mature milk. Premature delivery or pregnancy complications of mothers had no significant correlation with these chemokine concentrations in breast milk. There were significant correlations between MIG and interferon-gamma (IFN-gamma) or IP-10 levels (p < 0.001) in human milk. Expression of IP-10 and MIG genes and proteins in the milk cells as well as in mammary gland epithelial tissues was detected by RT-PCR and immunohistochemistry. CONCLUSION: IP-10 and MIG in human milk, probably derived from milk cells and mammary gland epithelial cells, may contribute to the migration and activation of intestinal T lymphocytes to enhance mucosal immunity during the early neonatal period.     

Is high protein milk beneficial for SGA-terms?

A three months longitudinal followup of SGA term babies was done for their response to feeding of high protein milk (3.1 g/100 ml) and they were compared with their breast fed counterparts. The formula fed infants had no advantage over the breast fed when weight was compared. However, blood urea and serum creatinine levels were higher in the formula fed infants, than the breast fed ones. The serum valine concentrations, indicative of protein nutritional status, increased with increasing postnatal age in all the infants. Formula fed had higher serum valine than breast fed ones. Serum phenylalanine and serum tyrosine levels, which may hamper CNS development, were higher in the formula fed infants than the breast fed ones.     

Effect of milk feeding on intestinal bilirubin absorption in the rat

The hypothesis that the etiologic mechanism of the late-onset, prolonged, unconjugated hyperbilirubinemia of the breast-fed infant, known as the breast milk jaundice syndrome, results from exaggeration of intestinal bilirubin absorption has been investigated in an adult rat model, which permits quantitative measurement of the enterohepatic circulation of bilirubin. After instillation of unconjugated bilirubin in buffer into the duodenum, 25% of the dose was absorbed and appeared in bile. Administration of bilirubin in human milk or cow milk formula resulted in a marked reduction in absorption to 2%. Administration of bilirubin in milk from mothers of infants with breast milk jaundice syndrome not only failed entirely to prevent the absorption of bilirubin, but enhanced late absorption, to produce a total absorption of 60% of the bilirubin dose. Thus, although normal milk significantly retarded intestinal bilirubin absorption and diminished the bilirubin load to the liver, milk from mothers of infants with breast milk jaundice syndrome appeared to enhance the enterohepatic circulation of bilirubin and to increase the total hepatic bilirubin load. This exaggeration of the enterohepatic circulation of bilirubin may be related to the increased concentrations in these milks of long-chain nonesterified fatty acids.     

Bone mineralization in preterm infants fed human milk with and without mineral supplementation

The bone mineral status of healthy preterm infants fed maternal milk was compared with that of similar infants fed maternal milk with mineral supplementation. Fifty infants with birth weight less than 1600 g were fed human milk for 1 week until reaching an intake of 120 kcal/kg/d. Thereafter, infants were assigned randomly to one of three diets: (1) continued unsupplemented human milk, providing an intake of 40 to 50 mg/kg/d calcium and 23 to 30 mg/kg/d phosphorus; (2) human milk mixed with a high mineral containing formula, providing total intakes of 130 mg/kg/d calcium and 68 mg/kg/d phosphorus; or (3) human milk alone for 1 additional week, followed by human milk mixed with a powdered fortifier, providing total intakes of 160 mg/kg/d calcium and 90 mg/kg/d phosphorus. Infants fed human milk with formula supplementation, but not those fed human milk with fortifier, had significantly higher serum phosphorus concentrations and significantly lower serum alkaline phosphatase concentrations than did those fed unsupplemented human milk (P less than 0.01). Bone mineral content of the humerus, determined by photon absorptiometry, however, was similar in all three groups; values averaged 0.104 g/cm at the beginning of the study, and remained unchanged irrespective of mineral supplementation. Shortly before hospital discharge, study diets were discontinued and infants were fed standard proprietary formula or were nursed by their mothers. At 44 weeks postconceptional age (7 to 10 weeks after change in diet), infants were reexamined. Serum phosphorus concentrations increased, serum alkaline phosphatase concentrations decreased, and bone mineral content more than doubled to values comparable with those in term infants. Results at follow-up were comparable for all three initial diet groups and for infants who were formula-fed or breast-fed after hospital discharge. The lack of any significant effect of early maternal milk supplementation on bone mineralization by 44 weeks postconceptional age suggests that these methods of supplementation of maternal milk may not be warranted for healthy preterm infants.     

Consequences of the composition of breast milk for the nutrition of underweight newborn infants. II. Lipids and lactose

The concentrations of fat, lactose and protein were measured in the 24 hour pooled breast milk of 37 mothers delivering preterm (PTM) and of 19 mothers delivering term (TM) from the second to the eighth postnatal day and in addition in the PTM from the third week of lactation. During the 4th week of life the nitrogen retention, the fat absorption rate as well as the energy balance were estimated in 21 very low birth weight infants appropriate for gestational age fed either native PTM (n = 11) or by heating procedures sterilized PTM (n = 10). The concentrations of fat and lactose increase within in the first week of lactation. The concentrations of fat are higher in the PTM during the first 3 days of lactation which results in a higher energy density of PTM during the first days of lactation. At the end of the first week of lactation there are no differences in the energy density between PTM and TM. The fat absorption rate was significantly lower in the infants fed sterilized PTM than in the infants fed native PTM (70.5 +/- 8.4 vs 86.3 +/- 7.4 p.c.). Thus, an energy intake of (70.5 to 8.4 vs 86.3 +/- 7.4 p.c.). Thus, an energy intake of 120-130 kcal/kg.d or an energy absorption of more than 100 kcal/kg.d; respectively, is possible by feeding native PTM as well as TM when feeding volumes of more than 180 ml/kg.d are tolerated. When sterilized breast milk is used or the feeding volume is below 160 ml/kg.d an energy supplementation of the milk is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new breast milk supplement for preterm infants

Objective : To assess the effect of a new formula (Prenan), which contains n-3 and n-6 long-chain polyunsaturated fatty acids (LC PUFA) on the fatty acid profile of preterm infants.
Methodology : Plasma fatty acids were measured in 61 preterm infants at term by gas liquid chromatography. In 20 of these infants, paired samples were collected and changes in fatty acids with time analysed.
Results : Plasma docosahexaenoic acid (DHA) levels were higher in those who had been fed expressed breast milk (EBM) ±/or Prenan compared with those fed standard formula ± EBM, P <0.05. The plasma arachidonic acid (AA) levels of infants fed Prenan were not different to those fed EBM, both groups achieving higher levels than infants fed standard formula, P <0.05. Further, paired analysis demonstrated that DHA levels increased in infants changed from standard formula to Prenan to levels equal or higher than those of fully breast-fed infants ( P <0.01), whereas DHA levels remained unchanged with time in all other groups.
Conclusions : The fatty acid composition of Prenan enables preterm infants fed formula to have plasma DHA and AA levels similar to those of infants fed breast milk and consequently different to those of infants fed standard formula. Prenan is an appropriate supplement to breast milk for preterm infants in that it provides LC PUFA as well as additional phosphorus and protein without exposing the infant to intact cows milk protein.     

Immunoglobulin concentrations and bacterial antibody titres in breast milk from mothers of 'preterm' and 'term' infants

IgA, IgM and IgG concentrations and their bacterial antibodies to E. coli, group B streptococci and Brucella abortus were measured in human breast milk collected from the 1st to 10th day post-partum from mothers delivered of 'preterm' infants (Premature Breast Milk or PBM) and from mothers delivered of term infants (Term Breast Milk or TBM). Reverse passive haemagglutination tests (RPH), rocket immuno-electrophoresis and mixed reverse passive antiglobulin haemagglutination tests (MRPAH) were employed. PBM at 2-5 days post-partum (though not beyond this period) contained higher IgA levels than did TBM, and this difference persisted even when total IgA was expressed as a proportion of total milk protein: in contrast the IgM and IgG contents of PBM and TBM were the same at both these postnatal ages. The titre of IgA antibody to E. coli, which was absorbable only by the corresponding bacteria, showed no significant difference between PBM and TBM, whereas the titres of IgA reacting with Br. abortus and, to a lesser extent group B streptococci, were higher in PBM than those in TBM. However the IgA which reacted with Br. abortus and group B streptococci was not specific to those organisms but was absorbed by all three bacteria studied. It is speculated that the high IgA content of early preterm milk and perhaps the presence of especially high titres of what appears to be a non-specific or cross-reacting bacterial IgA in such milk, may be immunologically advantageous to low birthweight infants fed on their own mother's milk.     

Neonatal Jaundice in Infants of Diabetic Mothers

Jährig, D., Jährig, K., Stiete, S., Beyersdorff, E., Poser, H. and Hopp, H. (Department of Paediatrics, the Data Centre of the Ernst Moritz Arndt University of Greifswald, Greifswald, and the'Gerhard Katsch'Central Research Institute for Diabetes, Karlsburg, G.D.R.). Neonatal jaundice in infants of diabetic mothers. Acta Paediatr Scand Suppl 360: 101, 1989.
357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweightllength ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphory lation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.     

Erythropoiesis in infants of diabetic mothers

Neonatal polycythemia is a well-established perinatal complication in infants of diabetic mothers (IDM). To investigate the regulation of erythropoiesis in these infants, we measured cord blood erythropoietin (EP) levels by a sensitive radioimmune assay and examined the growth of erythroid progenitor colonies in a series of IDM and control infants. Fifteen of 18 diabetic mothers were managed on a protocol emphasizing careful glycemic control throughout pregnancy; 10 had glycosolated hemoglobin values within the normal, nondiabetic range during the third trimester. Cord blood EP was elevated in one of 18 IDM and in two of 13 controls (p = NS). In IDM, cord blood EP values were higher in infants delivered following maternal labor and were inversely correlated with umbilical artery pH (r = -0.72; p = 0.006). Growth of burst forming units-erythroid was similar in IDM and controls in the presence of 0.1 to 2.0 U of exogenous EP per ml of methylcellulose medium. Individual infants tended to respond consistently over the entire range of EP doses tested. The number of burst forming units-erythroid observed did not correlate with cord blood EP, birth weight, or neonatal hematocrits. We conclude that: umbilical cord blood EP levels are generally normal in IDM delivered by mothers in whom good glycemic control is maintained throughout gestation, cord blood EP values are strongly influenced by perinatal events, and the response of erythroid progenitors to EP is intrinsically normal in IDM. These data suggest that polycythemia is an adaptive response in IDM and is not associated with a primary abnormality in erythropoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of saccharolactone on rat intestinal absorption of bilirubin in the presence of human breast milk

Beta-glucuronidase hydrolyzes glucuronic acid from bilirubin glucuronides. The unconjugated bilirubin that results is more readily absorbed from the intestine. Human breast milk has significant beta-glucuronidase activity, and it has been suggested that the milk may play an etiologic role in the hyperbilirubinemia commonly seen in breast-fed infants. To test whether breast-milk can facilitate intestinal bilirubin absorption, pairs of rats were fitted with bile duct and duodenal catheters. One rat of each pair received an intraduodenal infusion of rat bile plus breast-milk; the other rat received a similar amount of bile and milk plus the beta-glucuronidase inhibitor saccharolactone. Rats receiving saccharolactone excreted significantly less bilirubin in their bile, suggesting that inhibition of beta-glucuronidase decreased intestinal absorption of bilirubin. These findings were not seen in similar experiments when saline was substituted for human breast-milk.     

Plasma amino acids in small preterm infants fed on human milk or formula.

Plasma amino acids were measured in 35 preterm infants, of whom 11 weighed less than 1000 g and 24 weighed between 1000 g and 1500 g at the time of sampling. Repeat samples were obtained in 18 at least seven days later. Seventeen infants were fed with preterm formula milk and 18 with expressed maternal breast milk at one to two hourly intervals during the study period. Formula fed infants gained weight faster than those fed on breast milk but there was little difference in amino acid patterns. Infants fed on breast milk were more likely to have concentrations of essential amino acids below the mid trimester fetal range than formula fed infants, but few infants in either feeding group had values above the fetal range. Those that did were equally distributed between both groups. Only two samples approached toxic concentrations, both in the group fed breast milk. The ratio of branched chain to aromatic amino acids was higher in the group fed on formula after correction for post conceptional age, implying that liver maturation may be accelerated by formula feeding. No correlations were found between plasma amino acid concentrations and nitrogen retention or metabolisable energy intake.