Summary of Use during Lactation

Immune globulin G (IgG) 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 intravenous immunoglobulin (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,[1-4] although one retrospective study failed to find a decrease in relapse rate among mothers who received IgG postpartum.[5] Rare cases of transient rash have been reported in breastfed infants during maternal IVIG therapy. No special precautions are required during breastfeeding.

Drug Levels

Maternal Levels. Colostrum (3 days postpartum) and milk (7 days postpartum) samples from 2 mothers who were receiving 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. 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.[6]

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 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.[7]

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.[8]

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.[9]

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.[10]

In a study comparing the timing of IVIG on the relapse of relapsing-remitting multiple sclerosis, 24 patients were treated with IVIG starting in the first 24 hours after delivery and during lactation. The authors concluded that IVIG is effective in reducing the frequency of postpartum-related relapses. No adverse effects were noted. Further details were not provided in the published abstract.[11]

A mother with pemphigus vulgaris received three cycles of IVIG 120 grams intravenously for 5 days during pregnancy along with daily prednisolone 30 mg orally. She gave birth to a normal, healthy infant with no skin lesions and breastfed her infant (extent not stated). About 21 days after delivery, she began her fourth cycle of IVIG. On the second day of IVIG therapy, the neonate developed an erythematous, purpuric macular rash all over the body with no clinical or laboratory indication of systemic infection. The rash resolved within a few days without any intervention.[12] The rash was possibly caused by IVIG.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Multiple Sclerosis) Glatiramer, Interferon Beta, Methylprednisolone

References

1.

Dudesek A, Zettl UK. Intravenous immunoglobulins as therapeutic option in the treatment of multiple sclerosis. J Neurol. 2006;253 Suppl 5:V50–8. [PubMed: 16998754]

2.

Ferrero S, Pretta S, Ragni N. Multiple sclerosis: Management issues during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2004;115:3–9. [PubMed: 15223156]

3.

Ringel I, Zettl UK. Intravenous immunoglobulin therapy in neurological diseases during pregnancy. J Neurol. 2006;253 Suppl 5:V70–4. [PubMed: 16998758]

4.

Götestam 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. [PubMed: 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. [PubMed: 25187102]

6.

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. [PubMed: 19220771]

7.

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. [PubMed: 15372259]

8.

Haas J. High dose IVIG in the post partum period for prevention of exacerbations in MS. Mult Scler. 2000;6 Suppl 2:S18–20. [PubMed: 11188773]

9.

Haas J, Hommes OR. A dose comparison study of IVIG in postpartum relapsing-remitting multiple sclerosis. Mult Scler. 2007;13:900–8. [PubMed: 17881400]

10.

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. [PubMed: 22309336]

11.

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 (1 Suppl):P06.185. Abstract.

12.

Bostan E, Gülseren D, Ersoy Evans S, et al. Efficacious treatment of pemphigus vulgaris by intravenous immunoglobulin during pregnancy and postpartum period. Dermatol Ther. 2020;33:e13187. [PubMed: 31830346]

Substance Name

Immune Globulin

CAS Registry Number

9007-83-4

Drug Class

Breast Feeding

Lactation

Milk, Human

Antibodies

Immunoglobulin G

Immunoglobulins