Lupus (2016) 0,
1–7
http://lup.sagepub.com
PAPER
Breastfeeding in mothers with systemic lupus erythematosus M Noviani1,2, S Wasserman1 and MEB Clowse1 1
Department of Rheumatology, Duke University Medical Center, Durham, NC, USA; and 2Duke-National University of Singapore Graduate Medical School, Singapore
Introduction: Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. Methods: Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. Results: A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n ¼ 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. Conclusion: Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding. Lupus (2016) 0, 1–7. Key words: Breastfeeding; lactation; antirheumatic drugs; systemic lupus erythematosus; pregnancy
Introduction Breastfeeding offers many benefits to a mother and her infant.1 The American Academy of Pediatrics (AAP) recommends six months of exclusive breastfeeding, followed by another six months of breastfeeding complemented with food, to improve infant and maternal health.1 In the general population, the rate of breastfeeding in infants up to age 6 months is 49%.2 Prior studies have demonstrated that breastfeeding is influenced by several factors, such as maternal ethnicity, education level, intention to breastfeed and support during pregnancies.3,4 It is unknown how often women with systemic lupus erythematosus M.N. and S.W. contributed equally to this work. Megan E. B. Clowse, Department of Rheumatology, Duke University Medical Center, Box #3535 DUMC, Durham, NC 27710, USA. E-mail: [email protected] Received 5 August 2015; accepted 5 January 2016
(SLE; lupus) are interested in breastfeeding or engaged in breastfeeding. In addition to the influencing factors seen in healthy women, we hypothesize that disease activity and concerns about medication harm to infants will lead to less breastfeeding among women with lupus. Hydroxychloroquine is on the list of acceptable medications for breastfeeding maintained by the AAP, and the majority of lupus experts advise breastfeeding in lupus patients taking antimalarial drugs.5,6 Low-dose prednisone and ibuprofen are also generally accepted as compatible with pregnancy, but information on other lupus medications is not well known.7 In the present study, we sought to determine the rate of breastfeeding, as compared to formula feeding, among lupus patients. We also investigate the factors affecting infant feeding choice among these mothers. To further support breastfeeding in lupus patients, we used the United States (US) National Institutes of Health (NIH) TOXNET LactMed
! The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at University of York on February 17, 2016
10.1177/0961203316629555
Breastfeeding in SLE M Noviani et al.
2
database to summarize the safety profile of the most common medications used to treat lupus.8
significant. All statistical analyses were performed using Stata/IC 10.10 (College Station, TX). Safety considerations of lupus medications
Methods Study participants We prospectively collected data from lupus patients enrolled in a Duke Autoimmunity in Pregnancy Registry (DAP) from 2008 to 2013. All patients were seen by one rheumatologist (MEBC). Patients who met the 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria and provided complete information postpartum were included in the present study. This study was approved by the Institutional Review Board at the Duke University. At initial entry to the registry, pregnant women complete a questionnaire that includes information about breastfeeding intention, demographic character and socioeconomic status. Data are collected to assess socioeconomic profile including the education level, social support, marital status, annual household income, health insurance status and intention to work postpartum. At each visit during pregnancy and a single postpartum visit, medications are recorded, and lupus disease activity is measured by Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI) and Physician Global Assessment (PGA). The postpartum visit was scheduled about six weeks after delivery, but varied according to the degree of illness and schedule of the new mother. During a postpartum visit further information is obtained on infant feeding, as well as obstetric outcomes, including gestational age at delivery, mode of delivery, and infant intensive care stay. This information was obtained by administering a structured questionnaire and a chart review. Statistical analysis The study participants were divided into two groups based on postpartum lactation. Those not breastfeeding at the six-week follow-up visit were classified as ‘‘formula feeding,’’ and those who were either exclusively breastfeeding or breastfeeding and supplementing with formula were classified as ‘‘breastfeeding.’’ Data were presented as the mean SD or number (%), as appropriate. Categorical variables were compared using Fisher’s exact tests. The comparison of mean SD values was performed by student’s ttest. All hypotheses were tested two sided, and outcomes with p 0.05 were considered statistically
We used the NIH TOXNET LactMed database to calculate a range for the relative infant dose (RID) based on the highest and lowest results reported in the database.8 RID was calculated by dividing the estimated infant dose (mg/kg/day) by the maternal dose (mg/kg/day).9 Based on lactation norms, we assumed an estimated infant intake of 150 ml of milk/kg/day and maternal body weight of 70 kg.9 In addition, the overall assessment of the safety of the drug in LactMed and the assessment of safety in Medications and mother’s milk by Thomas Hale, PhD, were included in the evaluation. We designated a recommendation for safety in breastfeeding by weighing each of these factors.8,10
Results Study population The present study recruited 84 pregnant women with lupus who met the 2012 SLICC criteria. A total of 12 pregnancies had miscarriages or terminations, 11 pregnancies were lost to follow-up and 10 women did not provide information on infant feeding. The postpartum visit occurred 1–19 weeks after delivery, with a mean of 8.9 weeks (SD 4.5 weeks). The majority of study participants (n ¼ 34, 67%) planned to breastfeed and about half (n ¼ 25, 49%) actually did breastfeed. The rate of breastfeeding in lupus patients did not seem to be affected by socioeconomic factors such as maternal education level or household income (Table 1). However, there was a trend toward less breastfeeding in women who planned to work for pay after delivery. While SLE activity during pregnancy did not appear to affect breastfeeding, fewer breastfeeding women had high lupus activity postpartum (23.1% breastfeeding vs. 76.9% formula-feeding, p ¼ 0.04). The postpartum SLEPDAI at the first rheumatology visit after delivery for women who breastfed was significantly lower than those who formulafed (2.7 2.9 breastfeeding vs. 5.5 4.8 formulafeeding p ¼ 0.03). Infants born at term were more likely to be breastfed than babies born preterm (57.9% term vs. 23.1% preterm, p ¼ 0.03). Being delivered via cesarean section and going to the neonatal intensive care unit following delivery did not statistically affect the rate of breastfeeding in this study.
Lupus Downloaded from lup.sagepub.com at University of York on February 17, 2016
Breastfeeding in SLE M Noviani et al.
3
Table 1 Sociodemographic profile and factors influencing infant feeding modality
Number of participants, n (%) Demographics Maternal age, average SD Maternal race, n (%) Caucasian African American Asian Maternal education level, n (%) College degree and above No college degree Living arrangement, n (%) Alone With spouse/partner With adults other than spouse/partner Socioeconomic status Support from spouse, n (%) Spouse support No spouse support Intention to work postpartum, n (%) Intention to work for pay No intention to work for pay Annual household income, n (%) US$50,000 SLEPDAI Intrapartum SLEPDAI (average SD) Postpartum SLEPDAI (average SD) Postpartum SLEPDAI over 4 (n (%)) Post-partum visit First visit after delivery, weeks (average SD) Early pregnancy infant feeding intention, n (%) Plan to breastfeed Plan to formula feed No plan Postpartum medications Hydroxychloroquine Prednisone Immunosuppressant (aza, mtx, mmf) Pregnancy outcomes Gestational age at delivery in weeks (average SD) Mode of delivery C-Section Vaginal Term of birth Preterm Term NICU stay NICU No NICU
BF formula
Formula alone
25 (49%)
26 (51%)
31.3 4.6
28.4 4.7
p value
0.03
16 (57%) 7 (35%) 2 (67%)
12 (43%) 13 (65%) 1 (33%)
0.35
16 (53%) 6 (33%)
14 (47%) 12 (67%)
0.18
2 (50%) 19 (50%) 1 (20%)
2 (50%) 19 (50%) 4 (80%)
0.48
16 (48%) 5 (36%)
17 (52%) 9 (64%)
0.53
13 (38%) 9 (69%)
21 (62%) 4 (31%)
0.10
9 (47%) 13 (50%)
10 (53%) 13 (50%)
1.00
2.8 2.4 2.7 2.9 3 (23%)
3.3 5.2 5.5 4.8 10 (77%)
0.71 0.03 0.04
8.7 4.3
9.2 4.9
0.74
21 (64%) 1 (12%) 2 (25%)
13 (36%) 7 (88%) 6 (75%)
0.02
19 (51%) 7 (37%) 0
18 (49%) 12 (63%) 7 (100%)
1.00 0.22 0.01
38.1 1.6
37.1 2.1
0.05
11 (52%) 14 (47%)
10 (48%) 16 (53%)
0.68
3 (23%) 21 (57%)
10 (77%) 16 (43%)
0.03
4 (33%) 21 (57%)
8 (67%) 16 (43%)
0.16
BF: breastfeeding; SLEPDAI: Systemic Lupus Erythematosus Pregnancy Disease Activity Index; US$: United States dollars; NICU: neonatal intensive care unit; aza: azathioprine; mtx: methotrexate; mmf: mycophenolate mofetil.
In other studies, black women have a lower rate of breastfeeding compared to white women.11 In this study, African American women had a nonsignificantly lower rate of intention to breastfeed (55% vs. 78%, p ¼ 0.06) and actual breastfeeding (35% vs. 57%, p ¼ 0.15). More African American
women had high lupus activity (SLEPDAI > 4) postpartum than white women (47% vs. 16%, p ¼ 0.05) and this strongly correlated with breastfeeding. As has been reported previously, a woman’s plan to breastfeed strongly affects whether she actually Lupus
Downloaded from lup.sagepub.com at University of York on February 17, 2016
Breastfeeding in SLE M Noviani et al.
4
breastfeeds her baby.4 In this cohort, 68% of the women reported that they intended to breastfeed at study enrollment. The main reasons for planning not to breastfeed were no desire to breastfeed (42%) and concerns over medications (42%). The rate of breastfeeding at six weeks postpartum was significantly higher in the patients who intended to breastfeed early in pregnancy (62% breastfed who intended to breastfeed vs. 19% breastfed who did not intend to breastfeed, p ¼ 0.005). Improved infant health was the main reason for breastfeeding in the majority of women (92%). Other contributing factors were cost effectiveness (67%), maternalinfant bonding (67%), desire for weight loss effect (58%) and convenience (33%). Half of the women who formula-fed had intended on breastfeeding. Of the 26 women who were not breastfeeding at six weeks postpartum, 10 never tried to breastfeed and 16 had already stopped. The most common reasons for not breastfeeding included medication use (54%), low milk production (27%) and difficulty coping (23%). The practice by this clinic was to allow women to breastfeed while taking hydroxychloroquine and moderate doses of prednisone, but not immunosuppressants. In this cohort, hydroxychloroquine was taken postpartum by 86.4% of women and 51.3% of them breastfed on it (Table 2). Prednisone was taken postpartum by 43.2% of women and 36.8% of them breastfed while taking it. However, 16.1% of the women did not breastfeed due to taking immunosuppressants, including azathioprine (n ¼ 1), methotrexate (n ¼ 3), or mycophenolate (n ¼ 3). Update on the safety of lupus medications in lactation Based on a review of the data in LactMed, it appears that the majority of lupus medications are likely safe in breastfeeding because of very
Table 2
Postpartum lupus medications
Medications
BF formula
Formula
Hydroxychloroquine Azathioprine Methotrexate Mycophenolate Prednisone Ibuprofen
19 (50%) 0 (0%) 0 (0%) 0 (0%) 6 (33%) 6 (66%)
19 (50%) 1 (100%) 3 (100%) 3 (100%) 12 (66%) 3 (33%)
BF: breastfeeding.
limited transfer of each medication into breast milk (Table 3). This includes hydroxychloroquine, azathioprine, methotrexate, prednisone, nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, celecoxib), acetaminophen, and anticoagulants (warfarin and enoxaparin). The medications that are not preferred for use during breastfeeding include mycophenolate and cyclophosphamide. While no data are available about the transfer of the biologics belimumab and rituximab, because these are both immunoglobulin G (IgG) antibodies it is likely that they do not cross into breast milk in significant quantities. The data available for prednisone suggest that exposure through breast milk would have very limited adverse effects in breastfed infants. In a study of woman taking prednisone 20 mg/day, an estimated prednisone dose in a breastfed infant two hours after a dose is 0.015 mg/kg, an equivalent of 0.075 mg for an average 5 kg 2-month-old infant.12 With the high maternal doses, avoiding breastfeeding two hours after a dose may further decrease infant dose. Hydroxychloroquine use during breastfeeding is advised by most experts and it is on the AAP list of compatible medications.5,6 With a maternal dose of 400 mg/day, a breastfed infant receives a small amount of hydroxychloroquine in breast milk ranging from 0.002 to 0.219 mg/kg, depending on the timing after a dose. Follow-up of a small cohort of infants to at least 1 year of age demonstrated no adverse effects on growth, hearing or vision.13 Based on the available data from lactation studies, the transfer of azathioprine into breast milk appears to be negligible. In a woman taking 100 mg of azathioprine each day, the amount transferred into breast milk ranged between 1.2 and 7.6 mg/l, which translates into a dose of
1–7
http://lup.sagepub.com
PAPER
Breastfeeding in mothers with systemic lupus erythematosus M Noviani1,2, S Wasserman1 and MEB Clowse1 1
Department of Rheumatology, Duke University Medical Center, Durham, NC, USA; and 2Duke-National University of Singapore Graduate Medical School, Singapore
Introduction: Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. Methods: Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. Results: A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n ¼ 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. Conclusion: Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding. Lupus (2016) 0, 1–7. Key words: Breastfeeding; lactation; antirheumatic drugs; systemic lupus erythematosus; pregnancy
Introduction Breastfeeding offers many benefits to a mother and her infant.1 The American Academy of Pediatrics (AAP) recommends six months of exclusive breastfeeding, followed by another six months of breastfeeding complemented with food, to improve infant and maternal health.1 In the general population, the rate of breastfeeding in infants up to age 6 months is 49%.2 Prior studies have demonstrated that breastfeeding is influenced by several factors, such as maternal ethnicity, education level, intention to breastfeed and support during pregnancies.3,4 It is unknown how often women with systemic lupus erythematosus M.N. and S.W. contributed equally to this work. Megan E. B. Clowse, Department of Rheumatology, Duke University Medical Center, Box #3535 DUMC, Durham, NC 27710, USA. E-mail: [email protected] Received 5 August 2015; accepted 5 January 2016
(SLE; lupus) are interested in breastfeeding or engaged in breastfeeding. In addition to the influencing factors seen in healthy women, we hypothesize that disease activity and concerns about medication harm to infants will lead to less breastfeeding among women with lupus. Hydroxychloroquine is on the list of acceptable medications for breastfeeding maintained by the AAP, and the majority of lupus experts advise breastfeeding in lupus patients taking antimalarial drugs.5,6 Low-dose prednisone and ibuprofen are also generally accepted as compatible with pregnancy, but information on other lupus medications is not well known.7 In the present study, we sought to determine the rate of breastfeeding, as compared to formula feeding, among lupus patients. We also investigate the factors affecting infant feeding choice among these mothers. To further support breastfeeding in lupus patients, we used the United States (US) National Institutes of Health (NIH) TOXNET LactMed
! The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav
Downloaded from lup.sagepub.com at University of York on February 17, 2016
10.1177/0961203316629555
Breastfeeding in SLE M Noviani et al.
2
database to summarize the safety profile of the most common medications used to treat lupus.8
significant. All statistical analyses were performed using Stata/IC 10.10 (College Station, TX). Safety considerations of lupus medications
Methods Study participants We prospectively collected data from lupus patients enrolled in a Duke Autoimmunity in Pregnancy Registry (DAP) from 2008 to 2013. All patients were seen by one rheumatologist (MEBC). Patients who met the 2012 Systemic Lupus Collaborating Clinics (SLICC) criteria and provided complete information postpartum were included in the present study. This study was approved by the Institutional Review Board at the Duke University. At initial entry to the registry, pregnant women complete a questionnaire that includes information about breastfeeding intention, demographic character and socioeconomic status. Data are collected to assess socioeconomic profile including the education level, social support, marital status, annual household income, health insurance status and intention to work postpartum. At each visit during pregnancy and a single postpartum visit, medications are recorded, and lupus disease activity is measured by Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI) and Physician Global Assessment (PGA). The postpartum visit was scheduled about six weeks after delivery, but varied according to the degree of illness and schedule of the new mother. During a postpartum visit further information is obtained on infant feeding, as well as obstetric outcomes, including gestational age at delivery, mode of delivery, and infant intensive care stay. This information was obtained by administering a structured questionnaire and a chart review. Statistical analysis The study participants were divided into two groups based on postpartum lactation. Those not breastfeeding at the six-week follow-up visit were classified as ‘‘formula feeding,’’ and those who were either exclusively breastfeeding or breastfeeding and supplementing with formula were classified as ‘‘breastfeeding.’’ Data were presented as the mean SD or number (%), as appropriate. Categorical variables were compared using Fisher’s exact tests. The comparison of mean SD values was performed by student’s ttest. All hypotheses were tested two sided, and outcomes with p 0.05 were considered statistically
We used the NIH TOXNET LactMed database to calculate a range for the relative infant dose (RID) based on the highest and lowest results reported in the database.8 RID was calculated by dividing the estimated infant dose (mg/kg/day) by the maternal dose (mg/kg/day).9 Based on lactation norms, we assumed an estimated infant intake of 150 ml of milk/kg/day and maternal body weight of 70 kg.9 In addition, the overall assessment of the safety of the drug in LactMed and the assessment of safety in Medications and mother’s milk by Thomas Hale, PhD, were included in the evaluation. We designated a recommendation for safety in breastfeeding by weighing each of these factors.8,10
Results Study population The present study recruited 84 pregnant women with lupus who met the 2012 SLICC criteria. A total of 12 pregnancies had miscarriages or terminations, 11 pregnancies were lost to follow-up and 10 women did not provide information on infant feeding. The postpartum visit occurred 1–19 weeks after delivery, with a mean of 8.9 weeks (SD 4.5 weeks). The majority of study participants (n ¼ 34, 67%) planned to breastfeed and about half (n ¼ 25, 49%) actually did breastfeed. The rate of breastfeeding in lupus patients did not seem to be affected by socioeconomic factors such as maternal education level or household income (Table 1). However, there was a trend toward less breastfeeding in women who planned to work for pay after delivery. While SLE activity during pregnancy did not appear to affect breastfeeding, fewer breastfeeding women had high lupus activity postpartum (23.1% breastfeeding vs. 76.9% formula-feeding, p ¼ 0.04). The postpartum SLEPDAI at the first rheumatology visit after delivery for women who breastfed was significantly lower than those who formulafed (2.7 2.9 breastfeeding vs. 5.5 4.8 formulafeeding p ¼ 0.03). Infants born at term were more likely to be breastfed than babies born preterm (57.9% term vs. 23.1% preterm, p ¼ 0.03). Being delivered via cesarean section and going to the neonatal intensive care unit following delivery did not statistically affect the rate of breastfeeding in this study.
Lupus Downloaded from lup.sagepub.com at University of York on February 17, 2016
Breastfeeding in SLE M Noviani et al.
3
Table 1 Sociodemographic profile and factors influencing infant feeding modality
Number of participants, n (%) Demographics Maternal age, average SD Maternal race, n (%) Caucasian African American Asian Maternal education level, n (%) College degree and above No college degree Living arrangement, n (%) Alone With spouse/partner With adults other than spouse/partner Socioeconomic status Support from spouse, n (%) Spouse support No spouse support Intention to work postpartum, n (%) Intention to work for pay No intention to work for pay Annual household income, n (%) US$50,000 SLEPDAI Intrapartum SLEPDAI (average SD) Postpartum SLEPDAI (average SD) Postpartum SLEPDAI over 4 (n (%)) Post-partum visit First visit after delivery, weeks (average SD) Early pregnancy infant feeding intention, n (%) Plan to breastfeed Plan to formula feed No plan Postpartum medications Hydroxychloroquine Prednisone Immunosuppressant (aza, mtx, mmf) Pregnancy outcomes Gestational age at delivery in weeks (average SD) Mode of delivery C-Section Vaginal Term of birth Preterm Term NICU stay NICU No NICU
BF formula
Formula alone
25 (49%)
26 (51%)
31.3 4.6
28.4 4.7
p value
0.03
16 (57%) 7 (35%) 2 (67%)
12 (43%) 13 (65%) 1 (33%)
0.35
16 (53%) 6 (33%)
14 (47%) 12 (67%)
0.18
2 (50%) 19 (50%) 1 (20%)
2 (50%) 19 (50%) 4 (80%)
0.48
16 (48%) 5 (36%)
17 (52%) 9 (64%)
0.53
13 (38%) 9 (69%)
21 (62%) 4 (31%)
0.10
9 (47%) 13 (50%)
10 (53%) 13 (50%)
1.00
2.8 2.4 2.7 2.9 3 (23%)
3.3 5.2 5.5 4.8 10 (77%)
0.71 0.03 0.04
8.7 4.3
9.2 4.9
0.74
21 (64%) 1 (12%) 2 (25%)
13 (36%) 7 (88%) 6 (75%)
0.02
19 (51%) 7 (37%) 0
18 (49%) 12 (63%) 7 (100%)
1.00 0.22 0.01
38.1 1.6
37.1 2.1
0.05
11 (52%) 14 (47%)
10 (48%) 16 (53%)
0.68
3 (23%) 21 (57%)
10 (77%) 16 (43%)
0.03
4 (33%) 21 (57%)
8 (67%) 16 (43%)
0.16
BF: breastfeeding; SLEPDAI: Systemic Lupus Erythematosus Pregnancy Disease Activity Index; US$: United States dollars; NICU: neonatal intensive care unit; aza: azathioprine; mtx: methotrexate; mmf: mycophenolate mofetil.
In other studies, black women have a lower rate of breastfeeding compared to white women.11 In this study, African American women had a nonsignificantly lower rate of intention to breastfeed (55% vs. 78%, p ¼ 0.06) and actual breastfeeding (35% vs. 57%, p ¼ 0.15). More African American
women had high lupus activity (SLEPDAI > 4) postpartum than white women (47% vs. 16%, p ¼ 0.05) and this strongly correlated with breastfeeding. As has been reported previously, a woman’s plan to breastfeed strongly affects whether she actually Lupus
Downloaded from lup.sagepub.com at University of York on February 17, 2016
Breastfeeding in SLE M Noviani et al.
4
breastfeeds her baby.4 In this cohort, 68% of the women reported that they intended to breastfeed at study enrollment. The main reasons for planning not to breastfeed were no desire to breastfeed (42%) and concerns over medications (42%). The rate of breastfeeding at six weeks postpartum was significantly higher in the patients who intended to breastfeed early in pregnancy (62% breastfed who intended to breastfeed vs. 19% breastfed who did not intend to breastfeed, p ¼ 0.005). Improved infant health was the main reason for breastfeeding in the majority of women (92%). Other contributing factors were cost effectiveness (67%), maternalinfant bonding (67%), desire for weight loss effect (58%) and convenience (33%). Half of the women who formula-fed had intended on breastfeeding. Of the 26 women who were not breastfeeding at six weeks postpartum, 10 never tried to breastfeed and 16 had already stopped. The most common reasons for not breastfeeding included medication use (54%), low milk production (27%) and difficulty coping (23%). The practice by this clinic was to allow women to breastfeed while taking hydroxychloroquine and moderate doses of prednisone, but not immunosuppressants. In this cohort, hydroxychloroquine was taken postpartum by 86.4% of women and 51.3% of them breastfed on it (Table 2). Prednisone was taken postpartum by 43.2% of women and 36.8% of them breastfed while taking it. However, 16.1% of the women did not breastfeed due to taking immunosuppressants, including azathioprine (n ¼ 1), methotrexate (n ¼ 3), or mycophenolate (n ¼ 3). Update on the safety of lupus medications in lactation Based on a review of the data in LactMed, it appears that the majority of lupus medications are likely safe in breastfeeding because of very
Table 2
Postpartum lupus medications
Medications
BF formula
Formula
Hydroxychloroquine Azathioprine Methotrexate Mycophenolate Prednisone Ibuprofen
19 (50%) 0 (0%) 0 (0%) 0 (0%) 6 (33%) 6 (66%)
19 (50%) 1 (100%) 3 (100%) 3 (100%) 12 (66%) 3 (33%)
BF: breastfeeding.
limited transfer of each medication into breast milk (Table 3). This includes hydroxychloroquine, azathioprine, methotrexate, prednisone, nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, celecoxib), acetaminophen, and anticoagulants (warfarin and enoxaparin). The medications that are not preferred for use during breastfeeding include mycophenolate and cyclophosphamide. While no data are available about the transfer of the biologics belimumab and rituximab, because these are both immunoglobulin G (IgG) antibodies it is likely that they do not cross into breast milk in significant quantities. The data available for prednisone suggest that exposure through breast milk would have very limited adverse effects in breastfed infants. In a study of woman taking prednisone 20 mg/day, an estimated prednisone dose in a breastfed infant two hours after a dose is 0.015 mg/kg, an equivalent of 0.075 mg for an average 5 kg 2-month-old infant.12 With the high maternal doses, avoiding breastfeeding two hours after a dose may further decrease infant dose. Hydroxychloroquine use during breastfeeding is advised by most experts and it is on the AAP list of compatible medications.5,6 With a maternal dose of 400 mg/day, a breastfed infant receives a small amount of hydroxychloroquine in breast milk ranging from 0.002 to 0.219 mg/kg, depending on the timing after a dose. Follow-up of a small cohort of infants to at least 1 year of age demonstrated no adverse effects on growth, hearing or vision.13 Based on the available data from lactation studies, the transfer of azathioprine into breast milk appears to be negligible. In a woman taking 100 mg of azathioprine each day, the amount transferred into breast milk ranged between 1.2 and 7.6 mg/l, which translates into a dose of
