Myasthenia gravis and pregnancy

Table 1 Summary of previous studies of myasthenia gravis in pregnancy

Ref.	Number of pregnancies/patients	Treatment	MG during pregnancy	Mode of birth	TNMG	MG after birth	Other findings
Plauché[60], 1991	322/255	NA	41.0% exacerbation, 31.7% no change, 28.6 % remission	5.6% C-sec before 1963; 15.4% forceps, 13.5% C-sec after 1963	14.9%	29.8% exacerbation, 4 % death	Large literature review
Batocchi et al[10], 1999	64/47	42 underwent thymectomy before conception 36% on no treatment, 47% on pyridostigmine alone, 17 % on multi-treatments (pyridostigmine, steroids, azathioprine, IVIG or plasmapheresis)	17% relapsed (no treatment); 19% relapsed, 42% unchanged, 39% improved (on treatment)	30% C-sec (most for obstetric reasons)	9%	28% worse	No correlation between TNMG and maternal disease severity
Djelmis et al[11], 2002	69/65	23.2% on no treatment, 43.5% on pyridostigmine alone, 33.3 % on pyridostigmine and steroids 9 received plasmapheresis	14.5% exacerbation, 22.3% unchanged, 24.6% improved	8.7% vacuum extraction, 17.4 % C-sec	30.0%	15.9% exacerbation	Inverse association between incidence of TNMG and maternal disease duration
Hoff et al[42], 2003	127/79	45 underwent thymectomy (16 before the first conception), No record before 1999; 54.5% on pyridostigmine alone since 1999	NA	17.3% C-sec, 8.7% forceps/vacuum extraction	3.9%	NA	Three times higher risk of preterm rupture of amniotic membranes in MG
Hoff et al[62], 2004	49/37	6 underwent thymectomy before conception	29.7% remission	14.6% C-sec, 8.2% forceps/vacuum	NA	NA	6.1% neonatal mortality. No correlation between TNMG and maternal disease severity
Hoff et al[12], 2007	135/73	50% on treatment at the time of conception (99% on pyridostigmine, 1% on steroids), then 45% continued throughout pregnancy, 3 received plasmapheresis	10% relapsed	19% protracted labor	19%	NA	A half risk of TNMG if mother had thymectomy
Wen et al[43], 2009	163/163	NA	NA	44.8% C-sec	NA	NA	No significant difference in the risk of preterm, low birth weight, small for gestational age and C-sec between women with and without MG
Almeida et al[14], 2010	17/17 (2 abortion)	23.5% on no treatment, 5.9% on pyridostigmine alone, 5.9% on steroids alone, 5.9% on IVIG alone, 47% on multi-treatments (pyridostigmine, steroids or IVIG)	23.5 % relapsed, 47.1% unchanged	47% C-sec (most for obstetric reasons)	NA	17.6% MG crisis	C-sec only carried out if there are obstetric reasons on women with controlled MG
Ducci et al[44], 2017	35/21 (4 abortion)	5 underwent thymectomy before conception, 8.6% on no treatment, 91.4% on treatment (22.9% on pyridostigmine alone, 68.6% on multi-treatments) at the time of first trimester, then most of them continued throughout pregnancy	50% relapsed, 20% unchanged, 30% improved	66.7% C-sec, 6.7% forceps/vacuum	12.9 %	NA	Severity and duration of MG, repetitive nerve stimulation and treatment influence MG and pregnancy
Gamez et al[63], 2017	5/5	100% on monthly IVIG (switched to IVIG prior to pregnancy)	100% unchanged	60% C-sec	0 %	100% unchanged	IVIG monotherapy during pregnancy in MG women could be a good option but bigger study is required
Santos et al[64], 2018	27/13 (All MuSK MG, 4/4 for pregnancy after MG onset)	77.8% on no treatment (74.1% who was pregnant before MG onset), 7.4% on pyridostigmine and steroids, 7.4% on multi-treatments including pyridostigmine and steroids with azathioprine or IVIG	3.7 % relapsed	22.2% C-sec	3.7%	0% relapse	Pregnancy does not precipitate MuSK MG

MG: Myasthenia gravis; IVIG: Intravenous immunoglobulins; MuSK: Muscle specific tyrosine kinase; TNMG: Transient neonatal myasthenia gravis.

Table 2 Treatment options in myasthenia gravis during pregnancy

Medication	FDA category	Effects on pregnancy	Breastfeeding
Treatment of choice
Pyridostigmine	B	None reported	No limitation (Excreted in breast milk)
Steroid	C	Cleft lip or palate (rare), low birth weight	No limitation (Excreted in breast milk)
Treatment of choice for steroid-sparing agents if indicated
Azathioprine	D	Intrauterine growth retardation, prematurity, low birth weight, hematological toxicities (lymphopenia, pancytopenia) in newborn	Limited but can be considered (Excreted in breast milk)
Cyclosporine	C	Intrauterine growth retardation, prematurity, low birth weight	Limited but can be considered (Excreted in breast milk)
Contraindicated
Mycophenolate	D	Congenital anomalies	Contraindicated
Cyclophosphamide	D	Congenital anomalies	Contraindicated
Methotrexate	X	Fetal death, congenital anomalies	Contraindicated
Insufficient data
Rituximab	C	Transient B- and CD19+-cell depletion in newborns, prematurity, low birth weight	Limited data (minimally detected in breast milk)
Eculizumab	C	Limited data (prematurity)	Limited data (not detected in breast milk)
Treatment of choice for exacerbation of MG or myasthenic crisis
IVIG	C	None reported	No limitation
Plasmapheresis	N/A	Small for gestational age	No limitation

FDA: Food and Drug Administration; MG: Myasthenia gravis; IVIG: Intravenous immunoglobulins.