Prostaglandins in Human Milk

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Prostaglandins

in Human

Milk

870 PEDIATRICS Vol. 66 No. 6 December 1980

Barbara Reid, MD, Harilyn Smith, BS, and

Zvi Friedman,

MD,

FRCP

(C)

From the Department of Pediatrics, Division of Neonatology and Perinatal Research, Baylor College of Medicine, Houston

ABSTRACT. Levels of prostaglandin E2 and prostaglan-din F,, were measured by radioimmunoassay in aliquots of foremilk and hindmilk obtained at different stages of lactation (colostrum, transitional, and mature milk) from six healthy nursing mothers who delivered at term. Im-munoreactive prostaglandin E2 and prostaglandin F, were detected in all fresh human milk samples, but not in

cows’ milk-based formulas. Further studies are necessary

to investigate the role of these hormones in the physio-logic function, the extrauterine adaptation, and the cy-toprotective effect on the gastrointestinal tract in the breast-fed human infant. Pediatrics 66:870-872, 1980; human milk, prostaglandins, cytoprotection.

glandins are distributed throughout the

gastrointes-tinal tract and affect a variety of physiologic func-tions including gastric acid and mucous secretion,’#{176} smooth muscle contraction,’ ‘local circulation,’2 wa-ter, glucose, and ion the release of brush border enzymes,’4 zinc absorption,’5 and

cytoprotec-tion.’6’

Because of the possible beneficial effect of

pros-taglandins on the gastrointestinal tract of the hu-man infant, levels of immunoreactive PGE2 and

PGF2a were measured in fresh human milk and in cows’ milk-based formulas.

MATERIALS AND METHODS

In recent years, there has been a renewed interest in the use of human milk in preference to modified cows’ milk for the nutrition of newborns, including

low-birth-weight infants.’ This trend is due

princi-paily to the realization that, while both are

nutri-tionaily adequate, human milk contains numerous

antibacterial, immunologic, and other protective

and beneficial components which are not present in modified cows’ mild.2 The protective effect of fresh breast milk against necrotizing enterocolitis in new-born rats colonized with Kiebsiella and rendered hypoxic was suggested.3 Moreover, there is evidence to suggest that breast milk may protect infants from viral and bacterial gastroenteritis4 and may lower the incidence of neonatal sepsis.5 Fresh breast milk has also been used therapeutically to stop an epi-demic of Escherichia coli 0111 neonatal enteritis.6

Prostaglandins (PG) E2 and F2, derivatives of dietary essential fatty acids linoleate and arachi-donate, are formed by many different tissues in man including the mammary 78 macrophages, and polymorphonuclear cells.9 In addition,

prosta-Received for publication June 16, 1980; accepted Aug 14 1980.

Reprint requests to (Z.F.) Department of Pediatrics, Baylor

American Academy of Pediatrics.

Six healthy nursing mothers, who delivered term infants, donated milk samples obtained by manual expression for the study. The composition of milk is known to change with time elapsed after partu-ntion, with the time of day,’8 and from beginning to end of a single feeding.’9 Therefore, samples were collected at the beginning (foremilk) and at the end (hindmilk) of a midday feeding on three occasions post partum: (1) days 1 to 3 (colostrum), (2) days 6

to 9 (transitional milk), and (3) beyond day 14 of lactation (mature milk).

Immediately after collection, PGs were extracted from 1-mi aliquots of milk according to the method described by Green et al.2#{176}The PG fractions were separated by siicic acid colum chromatography and measured by radioimmunoassay according to the

method of Dray et al.21 Cross-reactivity in the ra-dioimmunoassay between PGE2 and PGF2a is less than 1%. Blanks and control samples to which PGs were added were run through the same procedure.

Recovery was monitored with [3H]-PGE2 and [3H]

PGF2a and averaged 90% and 62%, respectively. The results were corrected for recovery and ex-pressed as picograms of PGs per milliliter of milk.

Informed consent for these studies was obtained from each mother and the experimental protocol

was approved by the Clinical Investigation

at Viet Nam:AAP Sponsored on September 7, 2020 www.aappublications.org/news

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TABLE 1. Prostaglandins in Human Milk5

ARTICLES 871

Prostaglandins Colostrum Transitio nal Milk Matur e Milk

Foremilk Hindmilk Foremilk Hindmilk Foremilk Hindmilk

PGE2 92±60 6±5 128±57 75±33 97±50 130±53

PGF2,, 584 ± 138 637 ± 331 696 ± 325 793 ± 375 221 ± 70 534 ± 350

S Values are means ± SEM; prostaglandins are measured in picograms per milliliter.

mittee of Baylor College of Medicine and St Luke’s Episcopal Hospital, Houston.

RESULTS

Immunoreactive PGE2 and PGF2a were detected in human colostrum, transitional, and mature milk

(see Table). On the contrary, cows’ milk-based for-mulas Enfamil (Mead Johnson Co, Evansville, IN)

and Similac (Ross Laboratories, Columbus, OH)

did

not contain PGs.

DISCUSSION

Our data showed that samples of colostrum,

tran-sitional, and mature milk contain PGE2 and PGF2a. The source of PGs in human milk is uncertain.

They could possibly be derived from local synthesis in the mammary 78 the cellular elements of

human milk,9 or from the maternal circulation. The levels of maternal serum PGs were not measured. Such values would be difficult to interpret because of the rapid catabolism of serum PGs in the lung. The elevated concentrations of PGF20 compared with PGE2 could reflect either a preferential

syn-thesis by the mammary gland and the cellular ele-ments in the milk, or the conversion of PGE2 to PGF2,,. The conversion of PGE2 to PGF2a has been

reported to occur in human breast cancer tissue.7

The presence of prostaglandins in human milk may play an important role in the physiologic

func-tion and the adaptation of the gastrointestinal tract to extrauterine life. The physiologically normal

levels of PGs in the human gastrointestinal tract

have not yet been determined. Biosynthesis and catabolism of prostaglandins, prostacycin and thromboxane, throughout the gastrointestinal tract in human fetuses and newborns have been

re-ported.22 In addition, prostaglandins have been

shown to affect gastric acid and mucous secretion,’#{176}

smooth muscle contraction,” local circulation,’2

wa-ter, glucose, and ion ans’3 the release of brush border enzymes,’4 and zinc absorption.’5 Moreover,

the prostaglandins characteristically have been shown to protect the integrity of the gastrointes-tinal epithelium against a variety of noxious sub-stances; this effect is termed cytoprotection. The potential significance of prostaglandin

cytoprotec-tion in stressed and nonstressed infants remains to

be studied. Oral administration of PGE2 in human subjects has been demonstrated to protect the gas-trointestinal mucosa from blood loss produced by indomethacin.23 Similarly, it is expected that PGs provided by human milk could have effects on the gastrointestinal tract.

Increased interest in the utilization of human milk for feeding premature infants has become ev-ident in recent years. Because premature infants exhibit greater limitations of digestive functions

and immunologic status than do full-term infants, human milk may offer particular advantages. The presence of PGE2 and PGF20 in fresh human milk may represent another way in which breast-feeding confers advantage to the infant compared with for-mula feeding.

ACKNOWLEDGMENTS

This research was supported by National Institute of

Child Health and Human Development grant

7-R01-HD-13507. The authors are indebted to Dr Buford Nichols

and to Mrs Roseland Klein from Children’s Nutrition Center at Baylor College of Medicine and Texas

Chil-dren’s Hospital for their critical review and suggestions.

REFERENCES

1. Martinez GA, Nalezienski JP: The recent trend in

breast-feeding. Pediatrics 64:686, 1979

2. Jelliffe DB, Jelliffe EFP: Current concepts in nutrition

“breast is best”: Modern meanings N Engi J Med 297:912, 1977

3. Barlow B, Santulli TV, Heird WC, et al: An experimental

study of acute necrotizing enterocolitis-The importance of

breast milk. J Pediatr Surg 9:587, 1974

4. Larsen SA Jr, Homer DR: Relation of breast versus bottle feeding to hospitalization for gastroenteritis in a middle-class

US population. J Pediatr 92:417, 1978

5. Winberg J, Wessner G: Does breast milk protect against

septicaemia in the newborn? Lancet 1:1091, 1971

6. Svirsky-Gross 5: Pathogenic strains of E coli (0,111) among

prematures and the use of human milk in controlling the

outbreak of diarrhea. Ann Pediatr 190:109, 1958 7. Rolland PH, Martin PM, Rolland AM, et al: Prostaglandins

in human breast cancer. Identification of a cytosolic prosta-glandin a-keto-reductase activity. Biomedicine 31:178, 1979 8. Bennet A, Charlier EM, McDonald AM, et al: Prostaglandins

and breast cancer. Lancet 2:624, 1977

9. Friedman Z, Berman W: Hematologic effects of prostaglan-dins and thromboxanes and inhibitors of their synthesis in the perinatal period. Semin Perinatol 4:73, 1980

10. Robert A, Nezamis JE, Phillips JP: Inhibition of gastric

secretion by prostaglandins. Am J Dig Dis 12:1073, 1967

11. Mukhopadhyay A, Rattan 5, Goyal RK: Effect of

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872 PROSTAGLANDINS IN HUMAN MILK glandin E2 on esophageal motility in man. J Appi Physiol 39:479, 1975

12. Bolint CA, Kiss ZS, Varkonyi T, et al: Effects of

prostaglan-din E2 and F2 on the absorption and portal transport of

sugar and on the local intestinal circulation. Prostaglandins 18:265, 1979

13. Bukhave K, Rask-Madsen J: Saturation kinetics applied to in vitro effects of low prostaglandin E2 and F2,, concentrations

on ion transport across human jejunal mucosa. Gastroenter-ology 78:32, 1980

14. Mirhom R, Eloy R, Vaultier JP, et a!: Prostaglandins E, and

E2 stimulate release of intestinal brush border enzymes.

Prostaglandins 14:463, 1977

15. Johnson PE, Evans GW: Identification of a prostaglandin

E2-zinc complex in human breast milk, and porcine and rat duodenum. Fed Proc 37:889, 1978

16. Robert A, Nezamis JE, Lancaster C, et al: Cytoprotection by prostaglandins in rats. Gastroenterology 77:433, 1979 17. Robert A, Lancaster C, Hanchar AJ, et al: Mild irritants

prevent gastric necrosis through prostaglandin formation:

Histological study. Gastroenterology 74:1086, 1978 18. Jenness R: The composition ofhuman milk. Semin Perinatol

3:225, 1979

19. Hail B: Changing composition of human milk and early development of an appetite control. Lancet 1:779, 1975 20. Green K, Hamberg M, Samuelsson B, et al: Extraction and

chromatographic procedures for purification of

prostaglan-dins, thromboxanes, prostacycin, and their metabolites, in

Frolich JC (ed): Advances in Prostaglandin and

Throm-boxane Research, New York, Raven Press, 1978, vol 5, p 15

21. Dray F, Charbonnel B, Maclouf J: Radioimmunoassay of prostaglandins F, E, and E2 in human plasma. Eur J Clin Invest 5:311, 1975

22. Reid B, Smith H, Friedman Z: Prostaglandin metabolism in

the human fetal and neonatal gastrointestinal tract. Gastro-enterology 78:1242, 1980

23. Johansson C, Kollberg B, Nordemar R, et al: Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic disease. Gastroenter-ology 78:479, 1980

‘THE RIGHT TO NOT BE BORN’

In a precedent-setting decision, an appeals court yesterday upheld the right of parents to sue for damages on behalf of a child who was born with a severe genetic defect after the parents allegedly were improperly tested for the defect. The ruling in the so-called “wrongful life” case allows the father of 2-year-old Shauna Temar Curlender to sue two laboratories on her behalf for negligence in

allegedly testing her parents for Tay-Sachs disease and erroneously telling them

they were not carriers. Shauna has the disease, which results from a genetic defect carried by some Jews. Infants born with the condition generally develop normally for the first six to nine months of life but then regress, becoming blind, losing weight and dying at age 3 or 4.

A Superior Court judge had held that no suit could be filed on behalf of the child. The suit contended that the negligence of two laboratories had resulted in her being born with the defect when she would have been better off never

having been born.

The Court of Appeal sent the case back to the lower court yesterday, and

presiding Justice Bernard S. Jefferson said “the reality of the ‘wrongful life’ concept is that such a plaintiff both exists and suffers due to the negligence of

others.”

Roland Wrinkle, the attorney for the parents, Hyam and Phiis Curlender, said today that the appellate court ruling recognized for the first time the child’s right to sue in such a case. “She had a right never to be brought into existence,” Mr. Wrinkle said.

From The New York Times, June 12, 1980.

J.F.L.

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1980;66;870

Pediatrics

Barbara Reid, Harilyn Smith and Zvi Friedman