Globulin, Immune use while Breastfeeding
Medically reviewed on April 2, 2018.
Globulin, Immune Levels and Effects while Breastfeeding
Summary of Use during Lactation
Immune globulin is a normal component of breastmilk. Data from 2 mothers indicate that IgG concentrations in milk are normal or higher and IgM levels in milk are normal or lower during IVIG therapy. The antibacterial activity of milk in these women was normal. There appears to be an emerging consensus that intravenous immune globulin is the treatment of choice for postpartum mothers with multiple sclerosis who are breastfeeding, although one retrospective study failed to find a decrease in relapse rate among mothers who received IgG postpartum.
Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous immunoglobulin G by up to 79%. A flash heating pasteurization reduced decreased the concentration of endogenous immunoglobulin G by 33%. A continuous flow, high-temperature short-time (HTST) pasteurizer at temperatures ranging from 71 to 74 degrees C retained from about 38 to 79% of IgG activity depending on the temperature and exposure time. A study of 67 colostrum samples that underwent Holder pasteurization found that IgG amounts decreased by 34 to 40%. Immunoreactivity against ovalbumin decreased by 4 to 18% and immunoreactivity against tetanus toxoid decreased by 8 to 20%. Specific IgG subclasses decreased by different amounts, with IgG4 retaining all of its activity and IgG1 ans 2 decreasing by about 40 to 50%.
Maternal Levels. Colostrum (3 days postpartum) and milk (7 days postpartum) samples from 2 mothers who were receiving intravenous immunoglobulin (IVIG) for the treatment of common variable immunodeficiency were studied. One mother was receiving 400 to 500 mg/kg of IVIG monthly and the other received 600 to 700 mg/kg of IVIG monthly. The time of the last dose before sample collection was not reported. Immune globulin G (IgG) concentrations were normal in the first mother's colostrum and milk and higher than normal in the colostrum of the second mother. IgM levels were normal in the colostrum and milk first mother and low in the second. The colostrum and milk of both mothers strongly inhibited adhesion of enteropathogenic Escherichia coli in vitro.
Infant Levels. Relevant published information was not found as of the revision date.
Effects in Breastfed Infants
In a retrospective study of 108 women with relapsing-remitting multiple sclerosis, 69 received intravenous immunoglobulin (IVIG) postpartum. Those who received IVIG received either 0.4 g/kg daily for 5 days plus additional doses of 0.4 g/kg at 6 and 12 weeks postpartum (n = 41), or IVIG 0.4 g/kg daily for 5 days during the first 6 to 8 weeks of pregnancy, then 0.4 g/kg every 6 weeks until 12 weeks postpartum. Seventy-three percent of the 108 infants were breastfed until 3 to 12 weeks postpartum. No serious adverse event occurred in any of the infants and the mothers who breastfed had outcomes as good as those who did not.
A case series reported 43 women with multiple sclerosis who received 60 grams of IVIG within 3 days of delivery and 10 grams monthly. All of the women breastfed their infants for at least 4 weeks. The only adverse effect reported in infants was a transient rash one day after a maternal dose of IVIG which was possibly caused by the IVIG. The relapse rate was lower than with historical controls who did not receive IVIG.
A European double-blind, randomized trial compared two IVIG regimens in 168 postpartum mothers with multiple sclerosis to observe the relapse rate. One group received 150 mg/kg within 24 hours of delivery and monthly for 6 months. The other group received 450 mg/kg within 24 hours of delivery, 300 mg/kg on day 2 and 150 mg/kg on day 3 postpartum followed by monthly doses of 150 mg/kg until 6 months postpartum. More mothers who breastfed for 3 months or longer were relapse free during the study than those who did not breastfed or who breastfed less than 3 months. In all, 91 mothers breastfed for 3 months or longer and 48 mothers breastfed for less than 3 months. No mention was made of adverse effects in breastfed infants.
A woman with pemphigoid gestationis was treated with several courses of intravenous immune globulin 2 grams/kg over 3 days during pregnancy as well as at 4, 9 and 13 weeks postpartum. She was also receiving prednisolone in a dosage tapering from 0.7 mg/kg daily to 1 mg daily. She breastfed her infant (extent not stated) for 3 months with no problems noted.
In a study comparing the timing of intravenous immune globulin on the relapse of relapsing-remitting multiple sclerosis, 24 patients were treated with intravenous immune globulin starting in the first 24 hours after delivery and during lactation. The authors concluded that intravenous immune globulin is effective in reducing the frequency of postpartum-related relapses. No adverse effects were noted. Further details were not provided in the published abstract.
Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Alternate Drugs to Consider
1. Dudesek A, Zettl UK. Intravenous immunoglobulins as therapeutic option in the treatment of multiple sclerosis. J Neurol. 2006;53 Suppl 52:v50-v58. PMID: 16998754
2. Ferrero S, Pretta S, Ragni N. Multiple sclerosis: management issues during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2004;115:3-9. PMID: 15223156
3. Ringel I, Zettl UK. Intravenous immunoglobulin therapy in neurological diseases during pregnancy. J Neurol. 2006;v70-v74. PMID: 16998758
4. Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810. PMID: 26888948
5. Fragoso YD, Adoni T, Alves-Leon SV et al. Postpartum treatment with immunoglobulin does not prevent relapses of multiple sclerosis in the mother. Health Care Women Int. 2015;36:1072-80. PMID: 25187102
6. Koenig A, de Albuquerque Diniz EM, Barbosa SF, Vaz FA. Immunologic factors in human milk: the effects of gestational age and pasteurization. J Hum Lact. 2005;21:439-43. PMID: 16280560
7. Adhisivam B , Vishnu Bhat B, Rao K et al. Effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk. J Matern Fetal Neonatal Med. 2018;1-4. PMID: 29587541
8. Chantry CJ, Israel-Ballard K, Moldoveanu Z et al. Effect of flash-heat treatment on immunoglobulins in breast milk. J Acquir Immune Defic Syndr. 2009;51:264-7. PMID: 19421069
9. Dhar J, Fichtali J, Skura BJ et al. Pasteurization efficiency of a HTST system for human milk. J Food Sci. 1996;61:569-73. DOI: doi:10.1111/j.1365-2621.1996.tb13160.x
10. Rodriguez-Camejo C, Puyol A, Fazio L et al. Antibody profile of colostrum and the effect of processing in human milk banks: Implications in immunoregulatory properties. J Hum Lact. 2018;34:137-47. PMID: 28586632
11. Palmeira P, Costa-Carvalho BT, Arslanian C et al. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin. Pediatr Allergy Immunol. 2009;20:528-35. PMID: 19220771
12. Achiron A, Kishner I, Dolev M et al. Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis. J Neurol. 2004;251:1133-7. PMID: 15372259
13. Haas J. High dose IVIG in the post partum period for prevention of exacerbations in MS. Mult Scler. 2000;6 (Suppl 2):S18-20. PMID: 11188773
14. Haas J, Hommes OR. A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis. Mult Scler. 2007;13:900-8. PMID: 17881400
15. Gan DC, Welsh B, Webster M. Successful treatment of a severe persistent case of pemphigoid gestationis with antepartum and postpartum intravenous immunoglobulin followed by azathioprine. Australas J Dermatol. 2012;53:66-9. PMID: 22309336
16. Winkelmann A, Benecke R, Zettl U. Effect of intravenous immunoglobulin treatment on pregnancy and postpartum-related relapses in multiple sclerosis: A prospective, rater-blinded analysis. Neurology. 2012;78. Abstract.
Globulin, Immune Identification
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