pregnancy rates and outcomes in women with and without ms ... · and without ms in the united...

ARTICLE OPEN ACCESS

Pregnancy rates and outcomes in women withand without MS in the United StatesMaria K Houtchens MD Natalie C Edwards MSc Gary Schneider ScD Kevin Stern BA

and Amy L Phillips PharmD

Neurologyreg 201891e1559-e1569 doi101212WNL0000000000006384

Correspondence

Dr Houtchens

mhoutchens

bwhharvardedu

AbstractObjectiveTo compare pregnancy prevalence and complications in women with and without multiplesclerosis (MS)

MethodsThis retrospective US administrative claims study used data from January 1 2006 to June 302015 All data for women with MS were included A nationally representative 5 randomsample from approximately 58 million women without MS was used to compute the datasetAnnual pregnancy rates identified via diagnosisprocedure codes and adjusted for covariateswere estimated via logistic regression Claims for pregnancy and labordelivery complicationswere compared using propensity score matching

ResultsFrom 2006 to 2014 the adjusted proportion of women with MS and pregnancy increased from791 to 947 the adjusted proportion without MS and with pregnancy decreased from883 to 775 The difference in linear trend (017 increase and 015 decrease in per-annum pregnancy rates) was significant (t statistic = 78 p lt 00001) After matching (n = 2115per group) a higher proportion of womenwithMS than without had claims for premature labor(314 vs 274 p = 0005) infection (133 vs 109 p = 0016) cardiovascular disease(30 vs 19 p = 0028) anemiaacquired coagulation disorders (25 vs 13 p = 0007)neurologic complications (16 vs 06 p = 0005) sexually transmitted diseases (04 vs01 p = 0045) acquired fetal damage (278 vs 235 p = 0002) and congenital fetalmalformations (132 vs 103 p = 0004)

ConclusionsPregnancy rates in this population of women with MS have been increasing High rates ofclaims for several peripartum complications were observed in women with and those withoutMS Claims data provide knowledge of interactions patients have with the health care systemand are valuable initial exploratory analyses

RELATED ARTICLE

EditorialPregnancy in multiplesclerosis Data from anadministrative claimsdatabase

Page 771

MORE ONLINE

CME CourseNPuborgcmelist

From the Partners MS Center (MKH) Brigham and Womenrsquos Hospital Harvard Medical School Boston Health Services Consulting Corporation (NCE) Boxborough formerly withBoston Health Economics Inc (GS) Waltham Boston Health Economics (KS) Waltham and EMD Serono Inc (ALP) Rockland MA

Go to NeurologyorgN for full disclosures Funding information and disclosures deemed relevant by the authors if any are provided at the end of the article

The Article Processing Charge was funded by EMD Serono Inc Rockland MA (a business of Merck KGaA Darmstadt Germany)

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 40 (CC BY-NC-ND) which permits downloadingand sharing the work provided it is properly cited The work cannot be changed in any way or used commercially without permission from the journal

Copyright copy 2018 The Author(s) Published by Wolters Kluwer Health Inc on behalf of the American Academy of Neurology e1559

Multiple sclerosis (MS) is 3 times more common in womenthan in men1 and clinical onset often occurs as women areconsidering a family2 MS is more frequently diagnosed inwomen of childbearing age than in any other group3 Moreevidence is needed in order to support decision-making and toimprove care of women with MS who are of childbearingage4ndash7

No studies reporting the rates of pregnancy in women withMS were identified in the published literature Pregnancyoutcomes of women with MS have been evaluated in severalstudies outside the United States8ndash20 however only 3 USstudies have been published21ndash23 Mueller et al (2002)21 usedWashington statendashlinked birth certificatehospital dischargerecords for 198 women with MS and 1584 women withoutMS Pregnancy or delivery complications low birth weight orpreterm infants or infants with malformations were not morelikely in women with MS Women with MS were howevertwice as likely to be rehospitalized 3 months after deliverycompared with women without MS Kelly et al (2009)22

compared pregnancy outcomes of 10055 women with MSwith the general obstetric population using 2003ndash2009Nationwide Inpatient Sample data MS was associatedwith mildly increased odds of antenatal hospitalization in-trauterine growth restriction and cesarean delivery Fonget al (2018)23 used 2001ndash2009 hospital discharge data fromCalifornia (1185 deliveries in patients with MS out of4424049 total deliveries) and found that rates of urinary tractinfection cesarean delivery and induction of labor wereslightly increased in patients with MS however antepartumand peripartum morbidities were not increased

The objectives of this study were to use administrative claimsdata to (1) evaluate the annual prevalence of pregnancy inwomen with and without MS during the 2006ndash2014 intervaland (2) compare pregnancy-related complications in womenwith and without MS

MethodsData sourceThis was a retrospective administrative claims database studyusing data from the IQVIA Real-World Data AdjudicatedClaimsndashUS database from January 1 2006 to June 30 2015This database comprises fully adjudicated health plan claimsdata and enrollment information for individuals in commer-cial plans and contains information from health plans andself-insured employer groups throughout the United Statesfor more than 150 million unique enrollees collected since2006 This anonymous patient-centric database includes all

medical and pharmacy claims data (costs and descriptiveservices) for the enrollees Claims represent payments toproviders for services rendered to covered individuals Dataalso include patient-level enrollment which is a record ofdemographic variables including eligibility status (birth yearsex US Census region eligibility by month) The enrolleepopulation in the database is generally representative of theyounger than 65 years commercially insured population inthe United States regarding both age and sex The averagelength of enrollment is ge39 months and more than 30 millionpatients have 3 or more years of continuous enrollment(medical and pharmacy coverage) Each contributing planrsquosdata undergo rigorous data quality review by IQVIA prior toits addition into the Real-World Data Adjudicated ClaimsndashUSdatabase The database is deidentified and compliant with theHealth Insurance Portability and Accountability Act of 1996As such no institutional review board approval was required

Study populations

Pregnancy rates over timeNine cohorts of patients with and without MS werecreatedmdashone for each year from 2006 to 2014mdashto estimatethe prevalence of pregnancy over time Within each respectiveyear included patients were required to be enrolled for at least30 days be female and be between the ages of 18 and 64 yearsas of the first day of the year Patients with MS were alsorequired to have at least one encounter with a diagnosis of MS(ICD-9-CM code 340xx) Those included in the numeratorof the pregnancy prevalence calculation (ie pregnantwomen) were required to have at least one encounter witha diagnosis of pregnancy (table e-1 linkslwwcomWNLA712) or a pregnancy-related procedure (table e-2) duringtheir respective year

Pregnancy outcomesFor the pregnancy outcomes evaluation patients were initiallyrequired to have any eligibility from January 1 2006 to June30 2015 to be female to have at least one encounter witha diagnosis of pregnancy (table e-1 linkslwwcomWNLA712) or a pregnancy-related procedure (table e-2) to bebetween the ages of 18 and 64 as of the date of the pregnancydiagnosis and to have a live birth procedure code (table e-3)The focus of this analysis on women with a live birth was toidentify a maximally homogeneous sample for comparativepurposes

The date of the live birth procedure was used to estimate thedate of conception and the pregnancy periods13 Continuouseligibility for 1 year before estimated conception and 1 yearafter the live birth with no gaps in coverage were additional

GlossaryCCI =Charlson Comorbidity IndexDMD = disease-modifying drug ICD-9-CM = International Classification of Diseases NinthRevision Clinical Modification MS = multiple sclerosis

e1560 Neurology | Volume 91 Number 17 | October 23 2018 NeurologyorgN

inclusion criteria Patients with MS were required to have atleast one encounter with a diagnosis of MS (ICD-9-CM code340xx) Only the first pregnancy from an individual woman inthe dataset was included in the analysis

Data analyses

Pregnancy rates over timeAnnual pregnancy rates (identified via applicable diagnosis orprocedure codes) adjusted for age region payer andCharlson Comorbidity Index (CCI) score (a measure ofoverall comorbidity based on diagnosis codes in administra-tive data) were estimated separately among women with andwithout MS via logistic regression (tables 1 and 2 present thefull logistic regression models) Estimates were conductedusing all women with MS and on a nationally representative5 random sample of all women without MS provided theymet the inclusion criteria described above This randomsample was used as a subset of the general database because ofthe size of the original patient sample (approximately 58million unique enrollees) and the logistics associated withanalyzing data for such a large number of patients Statisticalcomparison of the year-over-year pregnancy rates (ie slopeof best fit line estimated via linear regression) among women

with and without MS during the 2006ndash2014 study intervalwas conducted

Pregnancy outcomesPropensity score matching24 matched patients with MS 11 toa nationally representative 5 random sample from the ap-proximately 58 million women without MS present in thedataset A priori based on a literature review25 we includedage payer region and year of pregnancy as covariates in themodel In addition we used regression modeling to determineother comorbidities associated with the outcome of interestThe comorbidities evaluated in the regression modeling werealcohol abuse anxiety arthritis chronic lung disease de-pression diabetes gastrointestinal disease hyperlipidemiahypertension hypothyroidism obesity other female genitaltract disorders ovarian dysfunction and thyroid diseaseBased on regression modeling results we also includedovarian dysfunction other female genital tract disordersobesity hypothyroidism and hypertension as covariates

Demographic characteristics evaluated included age at preg-nancy diagnosis region at pregnancy diagnosis and payertype during the 1 year prepregnancy Clinical characteristics

Table 1 Adjusted model for annual pregnancy rates in women without MS (assumptions were an age of 30 yearsMidwest region of the United States a commercial payer and a CCI score of 025)

Adjusted MS model (age region payer CCI)

Name Estimate SE OR Lower CI Upper CI z Value Pr (gt|z|)

(Intercept) 028 003 132 124 141 832 lt00001a

Age minus009 0 092 091 092 minus12982 lt00001a

CCI minus003 001 097 095 1 minus205 00404a

Cohort MS 2007 minus002 003 098 092 104 minus064 05209



Cohort MS 2010 minus008 003 093 087 098 minus249 00128a

Cohort MS 2011 minus012 003 089 083 094 minus393 lt00001a




Payer Medicaid 072 003 205 194 216 2632 lt00001a

Payer Medicare 016 018 117 08 166 088 03814

Payer Other 008 002 108 105 111 508 lt00001a

Region Northeast minus003 002 097 094 101 minus149 01371

Region South minus01 002 09 087 094 minus566 lt00001a

Region West 006 002 106 101 11 243 00149a

Abbreviations CCI = Charlson Comorbidity Index CI = confidence interval MS = multiple sclerosis OR = odds ratio SE = standard errora Statistical significance

NeurologyorgN Neurology | Volume 91 Number 17 | October 23 2018 e1561

evaluated during the 1 year prepregnancy included overallcomorbidity as measured by the CCI and the individual ratesof the most common comorbidities in MS (ie alcohol abuseanxiety arthritis [rheumatoid arthritis or osteoarthritis]chronic lung disease depression diabetes [type 1 and type 2]gastrointestinal disease hyperlipidemia hypertension andthyroid disease) These comorbidities were selected as theyare among the most common in MS based on the publishedliterature17

We evaluated pregnancy outcomes which included compli-cations during pregnancy labor and delivery and the puer-perium period Clinically relevant ICD-9-CM codesindicating pregnancy complications were selected and cate-gorized (tables e-4 to e-6 linkslwwcomWNLA712) Thebroad inclusion of ICD-9-CM codes was intended to en-compass all potentially relevant diagnoses to capture anypossible differences in outcomes for women with MS vs thosewithout MS

Sample selection and creation of analytic variables were per-formed using the Instant Health Data Platform (BostonHealth Economics Inc Boston MA) Statistical analyseswere undertaken with R version 321 (R Foundation for

Statistical Computing Vienna Austria) and SAS version94 (SAS Institute Inc Cary NC) For descriptive(ie unadjusted) analyses categorical variables were sum-marized using frequencies and percentages and continuousvariables were summarized using means (with confidenceintervals) SDs and medians (with interquartile ranges) Forthe analyses of thematched datasets of patients with and thosewithout MS pairwise χ2 tests evaluated differences betweencategorical variables and paired t tests evaluated differences incontinuous variables

Data availabilityThe data utilized for this study were obtained througha license agreement with IQVIA

ResultsPregnancy rates over time

Sample selectionThe number of women without MS from the 5 nationallyrepresentative random sample who were included in the an-nual study cohorts from 2006 to 2014 ranged from 735974 to1144868 The number of women with anMS encounter who

Table 2 Adjusted model for annual pregnancy rates in women with MS (assumptions were an age of 30 years Midwestregion of the United States a commercial payer and a CCI score of 025)



(Intercept) 138 005 396 356 439 2576 lt00001a


CCI minus007 001 093 09 095 minus581 lt00001a

Cohort MS 2007 005 005 105 095 115 098 03291

Cohort MS 2008 009 005 109 1 119 187 00616

Cohort MS 2009 012 005 113 103 124 27 0007a

Cohort MS 2010 016 005 117 107 128 341 00007a

Cohort MS 2011 016 005 117 107 128 349 00005a

Cohort MS 2012 012 005 113 103 123 254 00112a

Cohort MS 2013 016 005 117 107 128 331 00009a

Cohort MS 2014 018 005 12 11 132 391 lt00001a

Payer Medicaid 006 007 107 092 122 09 03703

Payer Medicare minus027 016 077 055 103 minus167 00945

Payer Other 004 002 104 099 108 166 00961

Region Northeast 006 003 106 101 112 239 00168a


Region West minus007 004 093 087 1 minus191 00564



were included in the annual study cohorts from 2006 to 2014ranged from 36361 to 58218

Baseline characteristicsThere was little year-to-year variation in age the mean age ofthe 9 annual cohorts of women with MS and a pregnancy-related claim ranged from 292 to 296 years (table e-7 linkslwwcomWNLA712) The highest proportion of womenwithout MS and with a pregnancy diagnosis were between theages of 25 and 29 years (range 299ndash318) lived in theSouth (range 270ndash376) and had commercial healthinsurance (range 894ndash932) The mean age of pregnantwomen with MS was somewhat greater than that of pregnantwomen without MS (approximately 325 vs 293 years) withlittle year-to-year variation (table e-8) The mean age ofwomen with MS and a pregnancy-related claim ranged from322 to 330 years and the highest proportion of women withMS and a pregnancy diagnosis were between the ages of 30and 34 (range 328ndash393) lived in the Northeast (range300ndash369) and had commercial health insurance (range953ndash990)

The mean CCI score of women without MS and a pregnancydiagnosis ranged from 014 to 016 (table e-9 linkslwwcomWNLA712) Common comorbidities in this groupwere gastrointestinal diseases (range 71ndash102) thyroiddisease (range 65ndash88) hypertension (range47ndash56) and anxiety (range 44ndash91) The meanCCI score of women with MS and a pregnancy diagnosisranged from 028 to 037 (table e-10) Common comor-bidities in this group were gastrointestinal diseases (range123ndash172) thyroid disease (range 108ndash149) hy-pertension (range 80ndash110) and anxiety (range80ndash157)

Pregnancy ratesThe unadjusted proportion of women without MS who hada pregnancy-related claim decreased from 555 in 2006 to515 in 2014 (table e-11 linkslwwcomWNLA712) Theunadjusted proportion of women with MS who had a preg-nancy-related claim increased from 240 in 2006 to 257 in2014 (table e-12)

The difference between the 2 groups remained after adjustingfor age region payer and CCI score The adjusted pro-portion of women without MS who had a pregnancy de-creased from 883 in 2006 to 775 in 2014 (figure 1) Theadjusted proportion of women with MS who had a pregnancyincreased from 791 in 2006 to 947 in 2014 (figure 1)Comparing women with and without MS the difference inlinear trend (017 increase and 015 decrease in per-annum pregnancy rates respectively) was statistically signifi-cant (t statistic = 78 p lt 00001) The model assumptionswere an age of 30 years Midwest region of the United Statesa commercial payer and CCI score of 025 (assumptionsapproximated the median values) The adjusted models areshown in tables 1 and 2

Pregnancy outcomes

Sample selectionA total of 5374616 patients without a diagnosis of MS and274501 patients with a diagnosis of MS were identified fromthe IQVIA Real-World Data Adjudicated Claimsndash US data-base from 2006 to 2015 A total of 39377 patients withoutMSand 2176 patients with MS had a pregnancy diagnosis werebetween the ages of 18 and 64 years as of the date of thepregnancy diagnosis had a live birth procedure code and had1-year insurance eligibility before and after the estimatedpregnancy period

Baseline characteristicsA total of 39377 women with a live birth without MS and2176 women with a live birth with MS met the inclusioncriteria Demographics of women with a live birth withoutand with MS are presented in table 3 Among women whohad a live birth mean and median ages were higher in thosewith MS than in those without MS Most women who hada live birth had commercial health insurance (985 with MSvs 947 without MS) Among women with MS more werefrom the Midwest (313) than any other region whereasamong women without MS more were from the South(321) The mean prepregnancy CCI score was statisticallysignificantly higher in women with MS than in womenwithout MS (p lt 00001) Common comorbidities (presentin ge10 of women with MS who had a live birth) weregastrointestinal disease anxiety thyroid disease and de-pression The proportion of women with all of the comor-bidities except alcohol abuse was statistically significantlyhigher in women with MS than in women without MS(p lt 005)

After 11 matching 2115 women without MS and 2115women with MS (mean [SD] age 3131 [493] years withoutMS and 3138 [476] years with MS) were matched Most hadcommercial insurance (9872ndash9891) and the highest

Figure 1 Adjusted proportion of women with and withoutMS and with a pregnancy by year

Model assumptions were age = 30 years region = Midwest payer = com-mercial and Charlson Comorbidity Index score = 025 (assumptions ap-proximated the median values) MS = multiple sclerosis


proportions resided in the Midwest (3220ndash3281) South(3088ndash3102) or Northeast (2846ndash2875) regions ofthe United States (figure e-1 [linkslwwcomWNLA711]

presents propensity score balance for the 2 groups and tablee-13 [linkslwwcomWNLA712] presents balance statisticsfor the covariates in each group)

Table 3 Baseline characteristics of women with a live birth without and with MS

Statistic Patients without MS Patients with MS p Value

No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)

Median (IQR) 29 (26ndash33) 31 (28ndash35)

Age grouping y n () lt00001a

18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)

Region n () lt00001a

Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)

Prepregnancy CCI score lt00001a

Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a

Chronic lung disease 1848 (47) 123 (57) 00457a

Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a

Gastrointestinal disease 3216 (82) 286 (131) lt00001a

Hyperlipidemia 1915 (49) 169 (78) lt00001a

Hypertension 1387 (35) 122 (56) lt00001a

Thyroid disease 2455 (62) 235 (108) lt00001a

Abbreviations CCI = Charlson Comorbidity Index IQR = interquartile range MS = multiple sclerosisa Significant p values (p lt 005)


Pregnancy labor and delivery and puerperiumcomplicationsPregnancy complications of matched women with and with-out a diagnosis of MS who had a live birth are presented infigure 2 There was a statistically significantly higher pro-portion of women with a live birth with MS who had a claimfor premature labor (p = 0005) infection in pregnancy (p =0016) maternal cardiovascular disease (p = 0028) anemia oracquired coagulation disorder (p = 0007) neurologic com-plications in pregnancy (p = 0005) and sexually transmitteddiseases in pregnancy (p = 0045) compared with women with

a live birth without MS Women with a live birth without MShad a higher rate of postterm pregnancy (p lt 0001) com-pared with women with a live birth with MS

Figure 3 presents complications during labor and delivery formatched women with and without a diagnosis of MS who hada live birth There was a statistically significantly higher pro-portion of women with a live birth with MS who had a claimfor acquired damage to the fetus (p = 0002) and congenitalfetal malformations (p = 0004) compared with women witha live birth without MS

Figure 2 Complications during pregnancy in matched women with and without MS who had a live birth

Significant p values (p lt 005) are shown in bold italic text C-section = cesarean section MS = multiple sclerosis STD = sexually transmitted disease


Complications during the puerperium period were not ascommon as complications during pregnancy and labor anddelivery in both patients with and those without MS Themost common complication for both groups was failed dis-ordered or suppressed lactation (35 for patients withoutMS and 30 for patients with MS) There were no significantdifferences in puerperium complications between the 2groups (figure 4)

DiscussionPregnancy in women with MS can be complex both from thepatient and the provider perspective4 yet few detailed eval-uations of specific issues of pregnancy in MS have beenreported in North American populations Approximatelythree-quarters of patients with MS are women and clinicalonset typically occurs during their childbearing years betweenthe ages of 20 and 40 years3 It is estimated that between one-fifth and one-third of women with MS deliver a child afterdisease onset1820 making pregnancy in women with MSrelevant to patients their family members and health careprofessionals19 A better understanding of the ldquoreal-worldrdquo

outcomes of women with MS and pregnancy is important forproviding quality care to women withMSwho are consideringa family4

An increase in the prevalence of pregnancy was observed inwomen with MS from 2006 to 2014 in contrast to a decreasein the prevalence of pregnancy observed in women withoutMS The finding of decreased rates of pregnancy in womenwithout MS is consistent with Centers for Disease Controland Prevention data that show steadily declining pregnancyrates for all women in the United States since 199026 Thecontrasting increase in pregnancy for women with MS mayreflect a change in perceptions and adoption of a positiveoutlook and improved counseling for patients and providersregarding pregnancy risks in this patient population Over thelast 2 decades there have been significant efforts on the part ofMS neurologists to educate the public and the general neu-rology community of the reciprocal effects between preg-nancy and MS346

Women with MS tended to be somewhat older than thegeneral population at the time of pregnancy diagnosis This isconsistent with findings in other previously published

Figure 3 Labor and delivery complications in matched women with and without MS and a live birth

Significant p values (p lt 005) are shown in bold italic text C-section = cesarean section MS = multiple sclerosis


data8ndash102123 The decision to start or enlarge a family can becomplicated by chronic conditions such as MS Concernsabout the health of a child societal attitudes unpredictabilityof neurologic symptoms during or after pregnancy and issuesregarding the appropriate time to discontinue disease-modifying drugs (DMDs) in order to become pregnant canall delay pregnancy in women with MS1927ndash30 A conceptiondelay could be related to the need to stabilize a newly di-agnosed patient before conception attempts4 In additionthere is some evidence of a possible decrease in fertility inwomen with MS3132 although no final conclusions can bemade on this subject

Both groups of patients had higher rates of labor and de-livery complications than generally reported in the litera-ture33 Compared with women without MS and a live birthwomen with MS and a live birth in the current study weresignificantly more likely to have claims for premature laborinfection during pregnancy acquired damage to the fetusand congenital hereditary fetal malformations These datawhich are derived from reimbursement information or thepayment of bills for health care services and commoditiescan improve our knowledge of the interactions that patientswith pregnancy and MS have with the health care systembut they should be interpreted with caution323435 Theremay be biases in coding and billing associated with thisspecific analysis For example there may be increasedhealth care resource utilization in women with MS becauseof increased vigilance of clinicians caring for these patientsThe data do not include Expanded Disability Status Scalescore disease duration or the numbers or outcomes of

prior pregnancies Other data sources or study designscould provide additional clinical details however thefindings of the current study suggest important hypothesesfor exploration

The magnitude of the rates of complications also requiresfurther investigation The high rates of complications may beattributable to the comprehensiveness of the included ICD-9-CM codes Any nonspecific ICD-9-CM codes (unspecifiedor other) from 9 of the pregnancy and labor and deliveryoutcome categories were removed to determine whetherthere was an effect on findings The differences observed inthe absolute rates of complications were small and there wasno statistically significant change in the original findingsMore detailed analyses of subsets of the coding lists mightprovide additional insight into the specific origin of theobserved differences Other important areas of additionalresearch include clinical outcomes that were not included inthis dataset such as the occurrence of spontaneous abor-tions This information would likely not be adequatelycaptured in administrative claims data given that these dataare based on the payment information for medical care andservices

A large retrospective cohort study using hospital dischargedata from California from 2001 to 2009 which described theprevalence sociodemographic features and antenatalperipartum outcomes of MS was published recently23 A to-tal of 1185 of 4424049 deliveries were in women with MSSimilar to findings in the current study patients with MS inthis study were shown to be older were more likely to have

Figure 4 Puerperium complications in matched women with and without MS who had a live birth

MS = multiple sclerosis


private insurance and were more likely to have preexistingmedical conditions such as asthma chronic hypertensionthyroid disease or cardiac disease Urinary tract infectioncesarean delivery and induction of labor were slightly in-creased in patients with MS however antepartum and peri-partum morbidities (gestational diabetes preeclampsiaeclampsia preterm rupture of membranes fetal growth re-striction oligohydramnios abruption placenta previa op-erative vaginal delivery shoulder dystocia chorioamnionitisendometritis or postpartum hemorrhage) were not found tobe increased in patients with MS The differences observedin this study compared with the current findings may beattributable to the different sources of data used The Cal-ifornia study used statewide hospital discharge data re-flective of all patients with all types of insurance whereas ournationally representative sample primarily evaluatedpatients with commercial insurance Hospital discharge datareflect resources that were charged for by hospitals whereasclaims data reflect health care resources reimbursed byinsurers

There are some additional limitations of this retrospectiveclaims database analysis It is possible that patients were givena diagnosis or had a pregnancy prior to the selected indexdiagnosis Only the first identified pregnancy was included inthe analysis Furthermore the date of the live birth procedurewas used to estimate the date of conception and the preg-nancy periods9 It is possible that there was a misclassificationof the prepregnancy period and the following trimesters insome cases however it is not expected that this would alterthe results fundamentally Matching factors were determineda priori based on a literature review however unknown orunmeasured variables may result in residual confoundingFinally these administrative claims data are derived mostlyfrom patients with commercial health insurance These datamay not be generalizable to patients who pay for health careout of pocket or for patients who do not have health insurancefrom their employers

The knowledge gaps regarding pregnancy and MS are sub-stantial and many well-designed studies are needed ExistingMS pregnancy registries and adverse event databases areincomplete as data are not collected in a standardizedmanner36 There is a need for collection of detailed in-formation such as family history ethnicity pregnancy his-tory drug and environmental exposures and motherrsquos healthstatus with respect to MS and other illnesses36 The MultipleSclerosis Centre of Excellence on Reproduction and ChildHealth an international collaborative multidisciplinary re-search consortium was convened in order to address theneed for evidence-based current information regardingchildbearing in MS4 Prospective disease-specific pregnancyregistries such as PREG-MS a US data repository that fol-lows women with MS from pregnancy planning through anystage of pregnancy to 3 years postpartum collects clinicallyrelevant data that can support pregnancy-related decision-making37

Pregnancy rates in women with MS have been increasing overthe past 10 years It is tempting to suggest that recent DMDshave helped more patients with MS achieve disease stabilitythus increasing the comfort level with family planningHowever based on our recent findings approximately 25 ofpatients with MS are exposed to a DMD at any time duringthe year prior to pregnancy38 Therefore the increase inpregnancy rates among patients with MS may suggest thatclinicians are becoming more comfortable managing thecomplex reciprocal effects of MS and pregnancy and thatsignificant efforts on the part of theMS neurology communityto educate the public and general neurologists are allowingmore women with MS to experience motherhood Theseanalyses of claims data of women with MS and pregnancyshowed high rates of several comorbidities and complicationssimilar to those seen in women without MS Despite thenoted limitations claims data reflect real-world use patternsand can improve knowledge of the interactions patients withMS have with the health care system and are a valuable re-source for initial exploratory analyses of a variety of healthservices research questions More real-world evidence to in-form decision-making in women with MS of childbearing ageis needed

Author contributionsAll authors contributed to the study concept and design ac-quisition analysis or interpretation of data drafting manu-script or revising it critically and the approval of the versionfor submission

AcknowledgmentThe authors thank Michele Springer (Caudex New YorkNY) for assistance with editing and revising the manuscriptfor nonintellectual content

Study fundingStudy funded by EMD Serono Inc Rockland MA (a busi-ness of Merck KGaA Darmstadt Germany) The authorsreceived no funding for their authorship responsibilities in thedevelopment of this manuscript

DisclosureM Houtchens funding support from EMD Serono Inc(a business of Merck KGaA Darmstadt Germany) supportfor service on scientific advisory boards from Biogen Gen-zyme Sanofi Teva Neuroscience and Novartis and receivedresearch support from Genzyme Sanofi N Edwards em-ployee of Health Services Consulting Corporation HealthServices Consulting Corporation received funding fromEMD Serono Inc (a business of Merck KGaA DarmstadtGermany) to run the analysis G Schneider is a former em-ployee of Boston Health Economics Inc (BHE) BHE re-ceived consulting fees from EMD Serono Inc (a business ofMerck KGaA Darmstadt Germany) K Stern is a currentemployee of Boston Health Economics Inc (BHE) BHEreceived consulting fees from EMD Serono Inc (a businessof Merck KGaA Darmstadt Germany) A Phillips


employee of EMD Serono Inc Rockland MA (a business ofMerck KGaA Darmstadt Germany) Go to NeurologyorgN for full disclosures

Publication historyReceived by Neurology December 15 2017 Accepted in finalform July 23 2018

References1 National Multiple Sclerosis Society Who gets MS Available at nationalmssociety

orgWhat-is-MSWho-Gets-MS Accessed May 17 20182 Compston A Coles A Multiple sclerosis Lancet 20083721502ndash15173 National Multiple Sclerosis Society Pregnancy and reproductive issues Available at

nationalmssocietyorgLiving-Well-With-MSDiet-Exercise-Healthy-BehaviorsWom-ens-HealthPregnancy Accessed December 7 2017

4 Bove R Alwan S Friedman JM et al Management of multiple sclerosis during pregnancyand the reproductive years a systematic review Obstet Gynecol 20141241157ndash1168

5 Dreyer NA Schneeweiss S McNeil BJ et al GRACE principles recognizing high-quality observational studies of comparative effectiveness Am JManag Care 201016467ndash471

6 Wundes A Pebdani RN Amtmann D What do healthcare providers advise womenwith multiple sclerosis regarding pregnancy Mult Scler Int 20142014819216

7 Rae-Grant A Day GS Marrie RA et al Practice guideline recommendations sum-mary disease-modifying therapies for adults with multiple sclerosis report of theGuideline Development Dissemination and Implementation Subcommittee of theAmerican Academy of Neurology Neurology 201890777ndash788

8 Dahl J Myhr KM Daltveit AK Hoff JM Gilhus NE Pregnancy delivery and birthoutcome in women with multiple sclerosis Neurology 2005651961ndash1963

9 Dahl J Myhr KM Daltveit AK Gilhus NE Planned vaginal births in women with multiplesclerosis delivery and birth outcome Acta Neurol Scand Suppl 200618351ndash54

10 Dahl J Myhr KM Daltveit AK Gilhus NE Pregnancy delivery and birth outcome indifferent stages of maternal multiple sclerosis J Neurol 2008255623ndash627

11 Hellwig K BruneN Haghikia A et al Reproductive counselling treatment and courseof pregnancy in 73 German MS patients Acta Neurol Scand 200811824ndash28

12 Jalkanen A Alanen A Airas L Pregnancy outcome in women with multiple scle-rosis results from a prospective nationwide study in Finland Mult Scler 201016950ndash955

13 Knox CA Delaney JA Winterstein AG Anti-diabetic drug utilization of pregnantdiabetic women in US managed care BMC Pregnancy Childbirth 20141428

14 Lu E Zhao Y Dahlgren L et al Obstetrical epidural and spinal anesthesia in multiplesclerosis J Neurol 20132602620ndash2628

15 Lu E Zhu F van der KM et al Labor induction and augmentation in women withmultiple sclerosis Mult Scler 2013191182ndash1189

16 Lu E Zhao Y Zhu F et al Birth hospitalization in mothers with multiple sclerosis andtheir newborns Neurology 201380447ndash452

17 Marrie RA Cohen J Stuve O et al A systematic review of the incidence and prev-alence of comorbidity in multiple sclerosis overview Mult Scler 201521263ndash281

18 Runmarker B Andersen O Pregnancy is associated with a lower risk of onset anda better prognosis in multiple sclerosis Brain 1995118(pt 1)253ndash261

19 van der Kop ML Pearce MS Dahlgren L et al Neonatal and delivery outcomes inwomen with multiple sclerosis Ann Neurol 20117041ndash50

20 Weinshenker BG Hader W Carriere W Baskerville J Ebers GC The influence ofpregnancy on disability from multiple sclerosis a population-based study in Mid-dlesex County Ontario Neurology 1989391438ndash1440

21 Mueller B Zhang J Critchlow C Birth outcomes and need for hospitalization afterdelivery among women with multiple sclerosis Am J Obstet Gynecol 2002186446ndash452

22 Kelly VM Nelson LM Chakravarty EF Obstetric outcomes in women with multiplesclerosis and epilepsy Neurology 2009731831ndash1836

23 Fong A Chau CT Quant C Duffy J Pan D Ogunyemi DA Multiple sclerosis inpregnancy prevalence sociodemographic features and obstetrical outcomesJ Matern Fetal Neonatal Med 201831382ndash387

24 Schneeweiss S Gagne JJ Glynn RJ Ruhl M Rassen JA Assessing the comparativeeffectiveness of newly marketed medications methodological challenges and impli-cations for drug development Clin Pharmacol Ther 201190777ndash790

25 Wyszynski DF Carman WJ Cantor AB et al Pregnancy and birth outcomes amongwomen with idiopathic thrombocytopenic purpura J Pregnancy 201620168297407

26 Centers for Disease Control and Prevention (CDC) Trends and variations in re-production and intrinsic rates United States 1990ndash2014 Available at cdcgovnchsdatanvsrnvsr66nvsr66_02pdf Accessed December 12 2017

27 Alwan S Yee IM Dybalski M et al Reproductive decision making after the diagnosisof multiple sclerosis (MS) Mult Scler 201319351ndash358

28 Borisow N Doring A Pfueller CF Paul F Dorr J Hellwig K Expert recom-mendations to personalization of medical approaches in treatment of multiple scle-rosis an overview of family planning and pregnancy EPMA J 201239

29 PruntyMC Sharpe L Butow P Fulcher G The motherhood choice a decision aid forwomen with multiple sclerosis Patient Educ Couns 200871108ndash115

30 Giesser B Benedetto-Anzai MT Talking with your MS patients about difficulttopics talking about reproductive issues Available at nationalmssocietyorgNationalMSSocietymediaMSNationalFilesBrochuresClinical-Bulletin-Reproductive-2010pdfAccessed May 3 2018

31 Cil AP Leventoglu A Sonmezer M Soylukoc R Oktay K Assessment of ovarianreserve and Doppler characteristics in patients with multiple sclerosis using immu-nomodulating drugs J Turk Ger Gynecol Assoc 200910213ndash219

32 Thone J Kollar S Nousome D et al Serum anti-Mullerian hormone levels inreproductive-age women with relapsing-remitting multiple sclerosis Mult Scler 20152141ndash47

33 Centers for Disease Control and Prevention (CDC) Update on overall prevalence ofmajor birth defectsmdashAtlanta Georgia 1978ndash2005 MMWR Morb Mortal Wkly Rep2008571ndash5

34 Cadarette SM Wong L An introduction to health care administrative data Can JHosp Pharm 201568232ndash237

35 Schneeweiss S Avorn J A review of uses of health care utilization databases forepidemiologic research on therapeutics J Clin Epidemiol 200558323ndash337

36 Alwan S Chambers CD Armenti VT Sadovnick AD The need for a disease-specificprospective pregnancy registry for multiple sclerosis (MS) Mult Scler Relat Disord201546ndash17

37 Mahlanza TD Sadovnick D Houtchens MK PREG-MS the New England multiplesclerosis pregnancy prospective cohort study Presented at the 32nd Congress of theEuropean Committee for Treatment and Research inMultiple Sclerosis (ECTRIMS)September 14ndash17 2016 London Abstract P863

38 Houtchens MK Edwards NC Phillips AL Disease-modifying drug treatment beforeduring and after pregnancy in women with multiple sclerosis and a live birth Pre-sented at the 31st annual Meeting of the Consortium of Multiple Sclerosis Centers(CMSC) May 24ndash27 2017 New Orleans Poster DX11


DOI 101212WNL0000000000006384201891e1559-e1569 Published Online before print September 28 2018Neurology

Maria K Houtchens Natalie C Edwards Gary Schneider et al Pregnancy rates and outcomes in women with and without MS in the United States

This information is current as of September 28 2018

ServicesUpdated Information amp

httpnneurologyorgcontent9117e1559fullincluding high resolution figures can be found at

References httpnneurologyorgcontent9117e1559fullref-list-1

This article cites 32 articles 5 of which you can access for free at

Citations httpnneurologyorgcontent9117e1559fullotherarticles

This article has been cited by 1 HighWire-hosted articles

Subspecialty Collections

httpnneurologyorgcgicollectionmultiple_sclerosisMultiple sclerosisfollowing collection(s) This article along with others on similar topics appears in the

Permissions amp Licensing

httpwwwneurologyorgaboutabout_the_journalpermissionsits entirety can be found online atInformation about reproducing this article in parts (figurestables) or in

Reprints

httpnneurologyorgsubscribersadvertiseInformation about ordering reprints can be found online

ISSN 0028-3878 Online ISSN 1526-632XWolters Kluwer Health Inc on behalf of the American Academy of Neurology All rights reserved Print1951 it is now a weekly with 48 issues per year Copyright Copyright copy 2018 The Author(s) Published by

reg is the official journal of the American Academy of Neurology Published continuously sinceNeurology

Multiple sclerosis (MS) is 3 times more common in womenthan in men1 and clinical onset often occurs as women areconsidering a family2 MS is more frequently diagnosed inwomen of childbearing age than in any other group3 Moreevidence is needed in order to support decision-making and toimprove care of women with MS who are of childbearingage4ndash7

No studies reporting the rates of pregnancy in women withMS were identified in the published literature Pregnancyoutcomes of women with MS have been evaluated in severalstudies outside the United States8ndash20 however only 3 USstudies have been published21ndash23 Mueller et al (2002)21 usedWashington statendashlinked birth certificatehospital dischargerecords for 198 women with MS and 1584 women withoutMS Pregnancy or delivery complications low birth weight orpreterm infants or infants with malformations were not morelikely in women with MS Women with MS were howevertwice as likely to be rehospitalized 3 months after deliverycompared with women without MS Kelly et al (2009)22

compared pregnancy outcomes of 10055 women with MSwith the general obstetric population using 2003ndash2009Nationwide Inpatient Sample data MS was associatedwith mildly increased odds of antenatal hospitalization in-trauterine growth restriction and cesarean delivery Fonget al (2018)23 used 2001ndash2009 hospital discharge data fromCalifornia (1185 deliveries in patients with MS out of4424049 total deliveries) and found that rates of urinary tractinfection cesarean delivery and induction of labor wereslightly increased in patients with MS however antepartumand peripartum morbidities were not increased

The objectives of this study were to use administrative claimsdata to (1) evaluate the annual prevalence of pregnancy inwomen with and without MS during the 2006ndash2014 intervaland (2) compare pregnancy-related complications in womenwith and without MS

MethodsData sourceThis was a retrospective administrative claims database studyusing data from the IQVIA Real-World Data AdjudicatedClaimsndashUS database from January 1 2006 to June 30 2015This database comprises fully adjudicated health plan claimsdata and enrollment information for individuals in commer-cial plans and contains information from health plans andself-insured employer groups throughout the United Statesfor more than 150 million unique enrollees collected since2006 This anonymous patient-centric database includes all

medical and pharmacy claims data (costs and descriptiveservices) for the enrollees Claims represent payments toproviders for services rendered to covered individuals Dataalso include patient-level enrollment which is a record ofdemographic variables including eligibility status (birth yearsex US Census region eligibility by month) The enrolleepopulation in the database is generally representative of theyounger than 65 years commercially insured population inthe United States regarding both age and sex The averagelength of enrollment is ge39 months and more than 30 millionpatients have 3 or more years of continuous enrollment(medical and pharmacy coverage) Each contributing planrsquosdata undergo rigorous data quality review by IQVIA prior toits addition into the Real-World Data Adjudicated ClaimsndashUSdatabase The database is deidentified and compliant with theHealth Insurance Portability and Accountability Act of 1996As such no institutional review board approval was required

Study populations

Pregnancy rates over timeNine cohorts of patients with and without MS werecreatedmdashone for each year from 2006 to 2014mdashto estimatethe prevalence of pregnancy over time Within each respectiveyear included patients were required to be enrolled for at least30 days be female and be between the ages of 18 and 64 yearsas of the first day of the year Patients with MS were alsorequired to have at least one encounter with a diagnosis of MS(ICD-9-CM code 340xx) Those included in the numeratorof the pregnancy prevalence calculation (ie pregnantwomen) were required to have at least one encounter witha diagnosis of pregnancy (table e-1 linkslwwcomWNLA712) or a pregnancy-related procedure (table e-2) duringtheir respective year

Pregnancy outcomesFor the pregnancy outcomes evaluation patients were initiallyrequired to have any eligibility from January 1 2006 to June30 2015 to be female to have at least one encounter witha diagnosis of pregnancy (table e-1 linkslwwcomWNLA712) or a pregnancy-related procedure (table e-2) to bebetween the ages of 18 and 64 as of the date of the pregnancydiagnosis and to have a live birth procedure code (table e-3)The focus of this analysis on women with a live birth was toidentify a maximally homogeneous sample for comparativepurposes

The date of the live birth procedure was used to estimate thedate of conception and the pregnancy periods13 Continuouseligibility for 1 year before estimated conception and 1 yearafter the live birth with no gaps in coverage were additional

GlossaryCCI =Charlson Comorbidity IndexDMD = disease-modifying drug ICD-9-CM = International Classification of Diseases NinthRevision Clinical Modification MS = multiple sclerosis



Data analyses








(Intercept) 028 003 132 124 141 832 lt00001a


CCI minus003 001 097 095 1 minus205 00404a










Payer Medicare 016 018 117 08 166 088 03814

Payer Other 008 002 108 105 111 508 lt00001a



Region West 006 002 106 101 11 243 00149a













(Intercept) 138 005 396 356 439 2576 lt00001a



Cohort MS 2007 005 005 105 095 115 098 03291

Cohort MS 2008 009 005 109 1 119 187 00616

Cohort MS 2009 012 005 113 103 124 27 0007a

Cohort MS 2010 016 005 117 107 128 341 00007a

Cohort MS 2011 016 005 117 107 128 349 00005a

Cohort MS 2012 012 005 113 103 123 254 00112a

Cohort MS 2013 016 005 117 107 128 331 00009a

Cohort MS 2014 018 005 12 11 132 391 lt00001a

Payer Medicaid 006 007 107 092 122 09 03703


Payer Other 004 002 104 099 108 166 00961











Pregnancy outcomes











No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)



18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)


Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)


Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a


Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a




























































































Reprints





Data analyses








(Intercept) 028 003 132 124 141 832 lt00001a


CCI minus003 001 097 095 1 minus205 00404a










Payer Medicare 016 018 117 08 166 088 03814

Payer Other 008 002 108 105 111 508 lt00001a



Region West 006 002 106 101 11 243 00149a













(Intercept) 138 005 396 356 439 2576 lt00001a



Cohort MS 2007 005 005 105 095 115 098 03291

Cohort MS 2008 009 005 109 1 119 187 00616

Cohort MS 2009 012 005 113 103 124 27 0007a

Cohort MS 2010 016 005 117 107 128 341 00007a

Cohort MS 2011 016 005 117 107 128 349 00005a

Cohort MS 2012 012 005 113 103 123 254 00112a

Cohort MS 2013 016 005 117 107 128 331 00009a

Cohort MS 2014 018 005 12 11 132 391 lt00001a

Payer Medicaid 006 007 107 092 122 09 03703


Payer Other 004 002 104 099 108 166 00961











Pregnancy outcomes











No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)



18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)


Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)


Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a


Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a




























































































Reprints














(Intercept) 138 005 396 356 439 2576 lt00001a



Cohort MS 2007 005 005 105 095 115 098 03291

Cohort MS 2008 009 005 109 1 119 187 00616

Cohort MS 2009 012 005 113 103 124 27 0007a

Cohort MS 2010 016 005 117 107 128 341 00007a

Cohort MS 2011 016 005 117 107 128 349 00005a

Cohort MS 2012 012 005 113 103 123 254 00112a

Cohort MS 2013 016 005 117 107 128 331 00009a

Cohort MS 2014 018 005 12 11 132 391 lt00001a

Payer Medicaid 006 007 107 092 122 09 03703


Payer Other 004 002 104 099 108 166 00961











Pregnancy outcomes











No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)



18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)


Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)


Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a


Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a




























































































Reprints









Pregnancy outcomes











No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)



18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)


Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)


Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a


Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a




























































































Reprints








No 39377 2176

Age y lt00001a

Mean (SD) 294 (55) 314 (48)



18ndash24 7291 (185) 165 (76)

25ndash29 12634 (321) 594 (273)

30ndash34 12570 (319) 857 (394)

35ndash39 5677 (144) 464 (213)

ge40 1205 (31) 96 (44)

Payer n () lt00001a

Commercial 37300 (947) 2144 (985)

Medicaid 2042 (52) 28 (13)

Medicare 35 (01) 4 (02)


Midwest 11249 (286) 681 (313)

Northeast 8679 (220) 611 (281)

South 12646 (321) 653 (300)

West 5492 (139) 173 (80)


Mean (SD) 011 (041) 021 (060)


Comorbidities n ()

Alcohol abuse 156 (04) 6 (03) 04834

Anxiety 2487 (63) 267 (123) lt00001a

Arthritis 434 (11) 46 (21) lt00001a


Depression 2195 (56) 219 (101) lt00001a

Diabetes 613 (16) 57 (26) 00002a




























































































Reprints

























































































Reprints




pregnancy rates and outcomes in women with and without ms ... · and without ms in the united...

Documents