Neurologic Disease and Pregnancy
* Pergolide was withdrawn fromthe US market on March 29, 2007, becauseof heart valve damage resulting in cardiac valve regurgitation. It is important notto stop pergolide abruptly. Healthcare professionals should assess patients’ needfor dopamine agonist therapy and consider alternative treatment. If continued treatment witha dopamine agonist is needed, another dopamine agonist shouldbe substituted for pergolide.
Because RLS hasa benign prognosis and often resolves after pregnancy, most women are reluctant to receive pharmacologic treatment. Increased supplementation of iron and folate may bethebest approach. In addition, becausethe serum ferritin level may not directly reflect the availability of iron inthe CNS, iron supplementation to achieve a ferritin level above the minimal normal level shouldbe considered. Additional folate intake beyond the recommended daily allowance of 400 µg may alsobe warranted.
Although elderly men havethe risk of obstructive sleep apnea , sleep-disordered breathing may also occur in pregnant women. [ 31 ] The prevalence of loud snoring is reported to increase during the late months of pregnancy. Women who gain excessive weight or develop fluid retention may beat particular risk for reduced airflow (ie, apneic and hypopneic events). Such irregularities in breathing degrade the quality of nighttime sleep and may lead to daytime sleepiness.
Possible nocturnal oxygen desaturation isanother issue for pregnant women, especially during rapid eye movement (REM) sleep. REM sleep typically produces a generalized loss of muscle tone (except inthe diaphragm). Consequently, patients with restrictive lung disease may breathe at abnormally low lung volumes during REM sleep. When lung volumes are low, blood may be shunted through underventilated lung tissue, and oxygen desaturation may result. The abdominal distention caused bya gravid uterus may produce or add toa preexisting restriction.
Sleep apnea isa recognized risk factor for hypertension. It may cause recurrent activation ofthe sympathetic nervous systemin response to airway obstruction and hypoxemia. Women with preeclampsia aremost likely tohave narrow upper airways andtobe snorers; this observation suggests that increased upper airway resistance orthe resultant snoring or apneas may contribute to pregnancy-induced hypertension. A greater degree of sleep-disordered breathing is seen in in preeclamptic women thanin nonpreeclamptic women. [ 32 ]
Pregnant women whohavean elevated apnea-hypopnea index canbe successfully treated with nasal continuous positive airway pressure (NCPAP) therapy, andtheir blood pressure canbe decreased.
Daytime sleepiness isanother common symptom during pregnancy, but its severity and effect on well-being havenotbeen thoroughly studied. Hormonal changes are suspected tobea contributing factor inthefirst trimester. After this period, disrupted nighttime sleep may bea substantial factor. Sleep apnea may bethe cause inan obese woman who snores.
Particularly inthe presence of hypertension, nocturnal polysomnography (multichannel sleep study) may be warranted to diagnose the disorder. NCPAP therapy may be started if indicated, depending onthe severity ofthe condition.
Patients with previously diagnosed narcolepsy or idiopathic CNS hypersomnia may become pregnant and require changes intheir treatment. Commonly used stimulants havenotbeen shown tobe safe in pregnancy, andthese agents shouldbe withdrawn frommost patients before conception. An inability todrive safely andan overall decline in functional status may result. For the stimulants dextroamphetamine , methylphenidate , and modafinil , the level of risk tothe fetus is category C.
Since 2002, sodium oxybate (gamma-hydroxybutyrate; GHB) hasbeenavailableto treat narcolepsy. It isa highly sedating compound thatis known asa drug of abuse. Sodium oxybate is taken onlyat night and reduces both cataplexy and daytime sleepiness through unknown mechanisms. The absence of teratogenicity in animal studies has led toitbeing classified as category B.
Thus, sodium oxybate mightbe preferable to stimulants during pregnancy, but whether thisissohasnotbeen established in clinical trials. Because of its potential for respiratory suppression, sodium oxybate couldbe harmful to pregnant women with sleep apnea, hypoxemia, or hypoventilation. The maximum recommended dosage isa daily sodium load of 1.6 g, which may be undesirable in pregnant women with edema or hypertension.
Sleep walking, night terrors, andother parasomnias may occur in women of childbearing age. A few systematic studies havebeen conducted to investigate the effect of pregnancy onthese disorders. Data on whether symptoms may increase or decrease during pregnancy are conflicting. Because benzodiazepines are often given to treat parasomnias andbecausethey may be harmful tothe fetus, an attempt shouldbemadeto withdraw these agents before conception or, in unplanned pregnancies, early inthefirst trimester.
Complications of pregnancy are generally thought to affect women with multiple sclerosis (MS) nomore often thanthey affect women inthe general population. This belief extends as far backas 1948 [ 33 ] and is supported by data from numerous subsequent studies of fertility, pregnancy, and delivery. [ 34 ] Data also suggest thatthe risk of spontaneous abortions, congenital malformations, stillbirths, and complications of pregnancy (eg, preeclampsia, premature delivery) isnot increased. [ 35 ]
Although many findings weigh against the idea thatthereisa higher risk of low birth weight in infants of mothers with MS, a retrospective study ofthe Norwegian national registry showed an increased rate of neonates beingsmallfortheir gestational age (SGA). [ 36 ] These neonates hada reduced mean birth weight and length but normal head circumference. The etiology was unclear, thoughthe subtle morphologic changes inthe pelvic organs of women with MS may result in suboptimal intrauterine conditions that influence fetal development.
The data also suggested an effect on deliveries. [ 36 ] Although thenumberof planned cesarean deliveries increased, women delivering vaginally hadan increased incidence of slow labor progression necessitating interventions. This result may havebeen partly due to perineal weakness and spasticity and fatigue related to MS.
These findings were countered bythoseofa 3-year prospective study that reported normal distributions of weight and head circumferences in babies born to mothers with multiple sclerosis. [ 37 ] Rates of infant death, congenital anomalies, and cesarean deliveries werealso similar tothoseofthe general population.
The reasons forthe discrepancies inthese studies are unclear. It is certainly possible that differences inthe severity and localization of disease inthe patient populations ofeach study could play a role inthe outcomes, particularly if perineal and bladder involvement differed. Factors increasing the frequencies of pelvic infections may also play a role.
Although MS is unlikely tohavea serious effect on pregnancy, each patient shouldbe evaluated onan individual basis. Patients with clinically significant bladder and perineal involvement and excessive fatigue shouldbe counseled about possible interventions that may help facilitate delivery.
An Israeli study of 338 women conducted to evaluate the MS relapse rate during each trimester of pregnancy and 6 months after delivery reported thatof 199 completed pregnancies in 66 women, 85 were accompanied by relapses (20 during pregnancy, 65 post partum). [ 38 ] The relapse rate was definitely reduced inthe third trimester.
In a later study, Salemi et al reported a significant reduction inthe relapse rate during pregnancy. [ 39 ] Using a questionnaire, the investigators collected information concerning patient age atthe onset of MS, duration of disease, numberof relapses during the prepregnancy period, numberof relapses during pregnancy, andnumberof relapses during thefirst 3 months after delivery. Out of 350 patients, 70 had 98 pregnancies.
The Pregnancy in Multiple Sclerosis (PRIMS) study wasthefirst multicenter prospective study of MS in pregnant women. [ 40 ] In this study, the relapse rate declined by approximately 70% during the third trimester as compared withthe rate inthe year before conception. The researchers evaluated 254 women with relapsing-remitting MS during andafter 269 pregnancies. Patients were examined at 20, 28, and 36 weeks’ gestation to determine the relapse rate ineach trimester.
Roullet et al reported that MS relapses occurring during pregnancy tended tobe mild, resulting in minimal orno residual deficits. [ 41 ] They examined the severity of relapses in 125 French women whowere followed via an MS clinic over 10 years andwhohada total of 32 full-term pregnancies.
Patients with MS appear to fare betterwhentheyare pregnant (particularly inthe third trimester) thanwhentheyare not, witha decrease inthenumberand severity of relapses. Some authors claim thatthe suppression of MS seen during pregnancy may bemore potent thanthat achieved with currently available treatments. [ 42 ]
Nevertheless, the decision whether to forgo treatment with immunomodulatory agents must bemadeonan individual basis. Given the potential risks these treatments pose for pregnant women, the decision to treat shouldbe reserved onlyfor exceptional cases (see Treatments during pregnancy).
In thefirst 3 months after delivery, MS relapses appear to increase in frequency and severity, thoughthey return totheir prepregnancy level afterward. Because this increase is offset bythe decrease in MS activity during pregnancy, pregnancy does not seem to change the overall courseofthe disease fromthe perspective of disability.
Patients with relatively severe disease before and during pregnancy appear tobeat greatest risk for relapses inthe postpartum period. No other single predictor was identified. In these patients, therapies that may reduce the likelihood of relapses shouldbe considered.
In an early study, Millar et al evaluated 45 pregnancy-associated relapses in 170 pregnancies and reported that 39 women experienced relapses inthe postpartum period. [ 43 ]
Worthington et al observed that relapses weremost frequent during thefirst 6 months after pregnancy andthat fewer relapses than expected occurred in postpartum months 6-24. [ 37 ] The investigators conducted a 3-year prospective study ofthe level of disability, severity, and distribution of relapses in 15 women with MS diagnosed before pregnancy, using 22 nulliparous women withthe disease ascontrol subjects.
Salemi et al retrospectively determined thatthe relapse rate increased inthefirst 3 months after delivery, thoughthe change wasnot statistically significant. [ 39 ]
In a study of 338 women, Korn-Lubetzki et al foundthat postpartum exacerbations of MS were 3 times more common in patients thanincontrol subjects. [ 38 ]
In the Pregnancy in Multiple Sclerosis (PRIMS) study, the postpartum relapse rate increased by approximately 70% andthen returned tothe prepregnancy rate. [ 40 ] Neither breastfeeding nor epidural analgesia affected the rate of relapse or progression of disability.
In a study of 227 women enrolled inthe PRIMS study foran additional 2 years after delivery, Vukusic et al reported that women with increased disease activity inthe year before pregnancy andthosewhohad additional relapses during pregnancy weremost likely tohave postpartum relapses. [ 44 ] The investigators didnotfinda single predictor (including breastfeeding or epidural anesthesia) that helped in accurately identifying women with MS whowouldhave relapses inthefirst 3 months after delivery.
In the second postpartum year, the relapse rate was similar tothatofthe year before pregnancy. [ 44 ] In addition, pregnancy, delivery, andthe postpartum period didnot ultimately increase overall disability from MS.
Roullet et al alsofoundthat relapses weremost severe during the postpartum period, as reflected bya change ofmorethan 1 pointinthe Expanded Disability Status Scale (EDSS) score. [ 41 ] Worthington et al confirmed this result, finding that relapses weremost severe during thefirst 6 months after pregnancy. [ 37 ] No overall significant differences inthe severity of relapses werefound between patients andcontrol subjects, as measured byusingthe median EDSS score afterthe pregnant and postpartum periods.
Epidural anesthesia didnot appear to affect the rate of relapse or progression of disability in either the PRIMS trial [ 40 ] or its 2-year extension. [ 44 ] This finding suggests that despite anecdotal reports suggesting otherwise, epidural analgesia is safe and does not carry a significant risk whenitisusedfor deliveries in patients with MS.
Breastfeeding does not appear tohavea notable effect onthe activity of MS. However, it does lower the incidences of infantile illnesses, which suggests thatit confers some protection onthe infant. This finding potentially supports the consideration of breastfeeding andthe delay of immunomodulating therapy until breastfeeding is stopped in patients with MS. These potential benefits shouldbe weighed against the risks of delaying treatment ona case-by-case basis.
In a questionnaire-based retrospective study that evaluated the onset of MS, relapse frequency, and breastfeeding in 438 women, half ofthe patients breastfed their children fora mean of 6.3 months, butthe relapse rate inthe breastfeeding group wasnot significantly differentfromthatinthecontrol subjects. [ 45 ]
In addition, the mean timeto relapse wasnot delayed with breastfeeding; in fact, 69% of relapses inthe breastfeeding group occurred whilethe patient wasstill breastfeeding. [ 45 ] The study data suggested that breastfeeding didnot extend the protective effects of pregnancy on exacerbations of MS.
Indeed, Vukusic et al reported that women who chose to breastfeed had fewer relapses thanother women did. [ 44 ] However, the investigators alsofoundthatthe women who chose to breastfeed had relatively mild disease. Conversely, women with active disease (and additional relapses) chose notto breastfeed.
In a study that assessed the incidence of various infantile illnesses at age 6, 9, and 12 months inthe children of 140 breastfeeding mothers and 35 nonbreastfeeding mothers, the infants whowerenot breastfed had significantly higher incidences of otitis media, lower respiratory tract illnesses, constipation, milk intolerance, and allergies. [ 46 ]
How bestto treat pregnant women with MS remains controversial. Although some claim thatthe suppression of MS during pregnancy ismore potent thanthat achieved with currently available therapies forthe disease, [ 42 ] it isnot clear whether this claim holds true inall cases.
Interferons (category C)
Although interferon beta-1a (IFN-β1a) and interferon beta-1b (IFN-β1b) are category C agents, sufficient data areavailablefrom published reports to indicate thattheyshouldnotbeusedin pregnant patients, becausethey impose a high frequency of serious risks onthe fetus.
In a rhesus monkey model, high doses of IFN-β1a werenot teratogenic buthada dose-dependent abortive effect. [ 47 ] In a longitudinal, 3-pronged cohort study involving a group exposed to IFN-β1a and IFN-β1b, a disease-matched unexposed group, anda healthy control group, mean birth weight decreased and rates of miscarriages and stillbirths increased inthe exposed group as compared withthecontrol group (39.1% vs 5%). Two major malformations werealso identified: an X chromosomal abnormality and Down syndrome. [ 48 ]
In another study, 41 pregnancies involving IFN-β1a exposure resulted in 20 healthy full-term infants, 1 healthy premature infant, 9 induced abortions, 8 spontaneous abortions, and 1 fetal death; 1 patient had hydrocephalus, andanotherwas lost to follow-up. [ 49 ] These findings werein stark contrast tothoseofthe 22 control subjects, whowere exposed to IFN-β1a before, butnot during, pregnancy. This control group included 20 full-term healthy infants, 1 healthy premature infant, and 1 infant witha birth-related complication (Erb palsy).
Glatiramer acetate (category B)
An abstract presented ata meeting ofthe American Academy of Neurology (AAN) in 2003 suggested that glatiramer acetate imposes no substantial risks in pregnancy andhasno abortifacient or teratogenic effects. This drug isnot known tobe excreted in breast milk. Evidence suggests that glatiramer acetate mightbe safe in pregnancy and breastfeeding. However, caution shouldbe exercised ifone decides to treat patients withthis drug.
Mitoxantrone (category D)
Mitoxantrone hasbeen associated with low birth weight and abnormal fetal kidney development in animal studies. Rats treated with mitoxantrone hadan increased incidence of preterm labor. [ 50 ] Because of its known risk in pregnancy, mitoxantrone shouldnotbeusedin pregnant patients.
Intravenous immunoglobulin (category C)
Orvieto et al suggested that intravenous immunoglobulin (IVIg) hasno known teratogenic effects. [ 51 ] It also appears tohaveno effects onthe immune systemofthe fetus or newborn. If necessary, treatment with IVIg may be considered, thoughthe potential risks must be carefully assessed.
Azathioprine (category D)
Despite azathioprine’s category D rating, some believe thatthis agent is potentially useful for treating MS in pregnancy. Although azathioprine crosses the placenta, the fetus lacks the enzymes that convert the drug into its active metabolites; this lack may protect the fetus fromthe potential teratogenic effects of azathioprine. [ 52 , 53 ] Nevertheless, given the category D rating, theuseofthis drug in pregnancy shouldbe avoided ifatall possible.
Methotrexate (category X)
Methotrexate is known tobecapableof causing malformations and abortifacient effects. [ 54 ] It hasa category X rating andshouldnotbeusedin pregnant patients.
Cyclophosphamide (category D)
Cyclophosphamide is teratogenic in animals, but whether itisalso teratogenic in humans hasnotbeen clearly determined. [ 54 ] Nevertheless, itisa category D agent and therefore shouldbe avoided in pregnant patients.
Corticosteroids (methylprednisolone) (category C)
The PRIMS study included 16 pregnant women who received corticosteroids; no adverse effects were noted in either the patients ortheir children. [ 40 ] Corticosteroids (eg, methylprednisolone ) may be safe in pregnancy. However, useofthese drugs in pregnant patients shouldbe considered carefully and avoided unless deemed necessary.
There issome evidence to suggest that corticosteroids and IVIg mightbe beneficial inthe postpartum management of MS.
In one study, 22 patients from 1996 to 1998 who received no treatment for MS after delivery were compared with 20 patients from 1999 to 2001 whowere treated with 1 g of intravenous (IV) corticosteroids monthly forthefirst 6 months post partum. [ 55 ] Although the mean relapse rate increased during thefirst 3 months inboth groups, itwas higher inthe untreated group thaninthe treated group (2 ± 0.66 versus 0.8 ± 0.41).
The finding fromthis study suggests that prophylactic treatment with IV corticosteroids may be beneficial during thefirst 3 months after pregnancy. [ 55 ] To the authors’ knowledge, however, no studies have adequately assessed the safety ofthis approach in breastfeeding women.
IVIg treatment may be effective in reducing the incidence of pregnancy- and postpartum-related relapses. Again, the potential risks and benefits must be carefully assessed before treatment is started, especially becausethe medication falls into category C. Its safety in breastfeeding women is unknown.
In a study of 9 patients witha history of postpartum acute exacerbations of MS whowere treated with IVIg for 5 consecutive days inthefirst week after childbirth andat 6 and 12 weeks afterward, none hada relapse during the 6 months after delivery. [ 56 ]
Achiron et al retrospectively studied IVIg treatment during pregnancy andthe postpartum period in 108 pregnant patients with relapsing-remitting MS andfounda positive effect. [ 57 ] The subjects were assigned toan untreated group, a group treated with IVIg inthefirst week after delivery with booster doses after 6 and 12 weeks, oranother group treated continuously with IVIg during andafter pregnancy.
Comparison of relapse rates for patients treated with IVIg forthe entire pregnancy and relapse rates inthe untreated group revealed a positive effect forthe former, as follows [ 57 ] :
First trimester – 0.43 versus 0.72
Second trimester – 0.15 versus 0.61
Third trimester – 0.0 versus 0.41
Postpartum period – 0.28 versus 1.33
Relapse rates also decreased in patients treated with IVIg onlyafter delivery (0.58) as compared with untreated patients (1.33). No significant adverse events were associated with IVIg treatment in patients or newborns. [ 57 ]
Haas reported thatthe exacerbation rate after delivery in IVIg-treated individuals was reduced by 33%. [ 58 ] IVIg was administered within 3 days after delivery andthen monthly to patients thought tobeat high risk for exacerbations. They were compared with patients inthe PRIMS study, who, forthis study, served ascontrol subjects.
Autoimmune myasthenia gravis (MG) isan uncommon disease ofthe neuromuscular junction characterized by striated muscle fatigue and weakness. MG frequently affects young women of childbearing age (20-40 years of age), and pregnancy creates potential risks forboththe mother andthe fetus. [ 59 , 60 ] (See Myasthenia Gravis and Pregnancy.) During pregnancy, thecourseof disease is unpredictable. In a series of 69 pregnancies in 65 women with MG whowere treated ina single obstetrics department, 15% had deterioration during pregnancy, and 16% had deterioration during the puerperium. [ 61 ] In a report of 64 pregnancies in 47 women with MG, 39% ofthose treated improved, 42% were unchanged, 19% had deterioration, and 17% ofthosenot receiving therapy had deterioration. [ 61 ] Myasthenic symptoms of 28% of women worsened after pregnancy. Therefore, successful management necessarily involves recognizing the potential for myasthenic crisis, optimizing anticholinesterase or immunosuppressivemedicationtreatment, and preparing forthe possibility of transient neonatal MG. The challenging care ofa woman with MG whois contemplating pregnancy should begin with careful planning andthe collaboration of obstetricians and neonatal intensive care specialists. Counseling should address current knowledge, risks, andavailable treatments. Women with MG who decide to become pregnant should receive prenatal care from providers with experience in treating this disease, and delivery shouldbe performed ata hospital thatcan manage any complications that may arise. [ 59 , 62 , 63 , 64 ] Management of pregnancy and delivery The risks and benefits of continuing medication orother immunosuppressive therapy shouldbe discussed, and counseling should begin whenthe pregnancy is planned. Treatment of MG shouldbe optimized, and clinical improvement shouldbe maximized. The needfor immunosuppressant treatment depends onthe severity of illness andshouldbe modified according tothe duration andseverity of thepatient’s symptoms of MG. If possible, physicians with experience in treating patients withthis disease should perform the delivery ata hospital withthe capability to treat both women and infants with complications of MG. In the 1967-2000 Medical Birth Registry of Norway, a population-based cohort study, the potential for cesarean delivery doubled in 127 births by 79 mothers with MG (17.6%) as compared witha reference group (8.6%). [ 62 ] The numberof births requiring medication to induce labor wasnot increased. Serious birth defects occurred in 5 children of mothers with MG, butthe rate ofsuch defects wasnot significantly greater thanthatofa reference group. Preterm rupture ofthe amniotic membranes wastheonly complication that occurred more frequently inthe MG group thanina comparison group. [ 62 ] Rates of neonatal mortality, birth weight, or prematurity didnot differ. Pregnancy didnot worsen the long-term outcome of MG. [ 65 ] Cesarean delivery is recommended ifit isnecessary for obstetric reasons, and regional anesthesia is safe with correct drug selection. [ 63 ] To reduce the potential for adverse effects onthe fetus, immunosuppressive medication shouldbe discontinued if possible, orthe dose shouldbe minimized. However, little information aboutthis topic isavailableinthe literature. Some information canbe derived fromthe treatment of patients withother autoimmune disorders, but separating the effects fromthe potential risks ofthe treated illness is difficult.
Prednisone or prednisolone is associated witha slightly (<1%) increased risk of cleft palate. High-dose corticosteroids may be associated with premature rupture of amniotic membranes. [ 63 ] Methotrexate may be associated with fetal malformations and thus isnot recommended foruse during childbearing years. [ 62 ] Although women taking azathioprine have generally been advised against pregnancy, no teratogenicity or specific malformation pattern hasbeen definitively demonstrated with therapeutic doses in humans. [ 62 , 63 ]
In a retrospective review of pregnancy outcomes, infants exposed to azathioprine wereat risk forthe development of reversible leukopenia, anemia, thrombocytopenia, reduced immunoglobulin levels, infection, or thymic atrophy. [ 62 , 63 ] Babies born to mothers treated with azathioprine havean increased risk of myelosuppression and immunosuppression. [ 63 ]
Cyclosporine increases the risk of low birth weight, prematurity, and spontaneous abortions. [ 62 , 63 ] Nausea and vomiting early in pregnancy may interfere with pyridostigmine dosing. Drug schedules may havetobe altered becauseof increased renal clearance, expanded blood volume, and erratic gastrointestinal absorption. [ 66 ]
Discontinuance of maternal immunosuppressants can either worsen or improve MG. If needed, plasma exchange or human intravenous immunoglobulin (IVIg) therapy may be effective andcanbe safely administered during pregnancy. In theory, plasma exchange can induce premature delivery through large hormonal shifts. [ 62 ]
Although MG does not directly affect the uterine smooth muscle, the striated abdominal muscles that contract withthe effort of delivery during the second stage of labor may fatigue and weaken moreeasilythantheywouldifthe disease werenot present.
Acetylcholinesterase drugs shouldprobablybe given parenterally becauseoftheir unpredictable oral absorption. Neuromuscular blockers may exaggerate and prolong muscular weakness andshouldbe avoided if possible. Epidural anesthesia is considered relatively safe for vaginal and cesarean deliveries.
Magnesium sulfate isusedto prevent seizures in patients with preeclampsia, to treat eclampsia, andto prevent preterm birth in patients with preterm labor; this drug can precipitate weakness by interfering with neuromuscular transmission. Maternal deaths are reported with its useto treat MG in women with preeclampsia. [ 63 ]
Consultation withan anesthesiologist shouldbe considered forall pregnant patients with MG.
Neonatal MG may result from passive transplacental transfer of antibodies tothe nicotinic acetylcholine receptor fromthe myasthenic mother tothe fetus. However, notall infants with detectable levels of antibodies to acetylcholine receptor develop neonatal MG.
The severity of symptoms varies, ranging from mild hypotonia to respiratory distress. Clinical symptoms develop inthefirstfew hours after birth and usually resolve within 2-3 weeks. [ 63 ] In the Medical Birth Registry of Norway, 21.3% of children of mothers with MG needed transfer to intensive care units (ICUs), compared with 2% ofthe reference group. Other studies have shown a neonatal MG incidence of 10-21%, and neonatal disease was reported in 4% (but probably affected 12%) ofthe Norway registry cohort. [ 59 ]
Children of mothers with MG require careful observation inthefirstfew days after birth, and symptoms may respond to anticholinesterase medication. [ 63 ] Women with MG should deliver ina facility witha neonatal ICU.
Arthrogryposis multiplex congenita, characterized by multiple joint contractures in utero, occasionally complicates the pregnancy ofa mother with MG. Circulating antibodies may inhibit the function of fetal acetylcholine receptors, withlittle effect on adult acetylcholine receptor function, and may be responsible forthis condition. [ 67 ]
A high ratio of antifetal to antiadult muscle antiacetylcholine receptor antibodies is predictive of neonatal MG inthefirst child ofa mother withthe disease. [ 68 ] Elevated alpha-fetoprotein levels may inhibit acetylcholine antibody binding capacity, andthis may explain the delay to onset of neonatal MG symptoms after birth. [ 63 ]
Stroke isthe third leading cause of death andthe primary cause of adult disability inthe United States. It may be broadly classified as either ischemic or hemorrhagic. Although cerebrovascular disease is thought tobe uncommon in pregnancy, itisan important source of maternal and fetal morbidity and mortality, causing 3.5-26 cases of neurologic dysfunction per 100,000 deliveries, andis associated withmorethan 12% of maternal deaths. [ 69 ]
The incidence of stroke during the childbearing ages alone is 10.7 cases per 100,000 women. Some authors have questioned whether the risk of stroke increases in association with pregnancy itself [ 70 ] ; however, evidence suggests thatthe postpartum period is associated withan increased risk of ischemic stroke. [ 71 , 72 ]
Ischemic strokes account for 85% ofall strokes. [ 72 ] Causes of ischemic stroke in pregnancy may be divided into 2 general categories: pregnancy-specific etiologies and stroke-in-the-young factors.
The first category includes the following:
Preeclampsia [ 73 ] and eclampsia – These are present in 24-47% of ischemic strokes and 14-44% of intracranial hemorrhages [ 69 , 71 ]
Amniotic fluid embolism
Postpartum cerebral angiopathy – This rare and reversible condition causes narrowing ofthe blood vessels, whichcan lead to ischemia [ 65 , 69 ]
Causes of stroke ina young person include the following: