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ORIGINAL ARTICLE Prevalence of conception and outcomes after hematopoietic cell transplantation: report from the transplant survivor study

A Carter1, LL Robison2, L Francisco1, D Smith1, M Grant1, KS Baker3, JG Gurney4, PB McGlave3, DJ Weisdorf3, SJ Forman5 and S Bhatia1,5

1Population Sciences, City of Hope Center, Duarte, CA, USA; 2Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, TN, USA; 3Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA; 4General , University of Michigan, Ann Arbor, MI, USA and 5Hematology and Hematopoietic Cell Transplantation, City of Hope Cancer Center, Duarte, CA, USA

We conducted a retrospective study to describe the malignant disorders, with over 45 000 transplants per- magnitude of compromise in reproductive function and formed worldwide annually.1 The widespread use of HCT investigate pregnancy outcomes in 619 women and can be attributed to its improved treatment efficacy, wider partners of men treated with autologous (n ¼ 241) or variety of stem cell sources, and improved transplantation allogeneic (n ¼ 378) hematopoietic cell transplantation strategies and supportive care, and has resulted in a (HCT) between 21 and 45 years of age, and surviving 2 or growing number of long-term survivors.1,2 Most pre- more years. Median age at HCT was 33.3 years and transplant conditioning regimens for HCT include alkylat- median time since HCT 7.7 years. Mailed questionnaires ing agents and/or irradiation, both of which may cause captured and their outcomes (, germ cell injury, gonadal dysfunction and .3,4 The , ). Thirty-four patients reported 54 risk of gonadal damage is higher with increasing doses of pregnancies after HCT (26 males, 40 pregnancies; eight alkylating agents, total body irradiation (TBI), and older females, 14 pregnancies), of which 46 resulted in live age in women at the time of transplant.5 births. Factors associated with reporting no conception Although successful pregnancies after HCT have been included older age at HCT (X30 years: odds ratio reported previously,6–11 the evidence suggests that female (OR) ¼ 4.8), female sex (OR ¼ 3.0), and total body survivors may be at an increased risk of spontaneous irradiation (OR ¼ 3.3). Prevalence of conception and and , pre-term delivery and low pregnancy outcomes in HCT survivors were compared to birth weight babies.12,13 To further investigate pregnancy those of 301 nearest-age siblings. Although the risk for not outcomes and describe the magnitude of compromise in reporting a conception was significantly increased among reproductive function, as indicated by prevalence of self- HCT survivors (OR ¼ 36), survivors were not significantly reported pregnancy occurrence and pregnancy outcomes, more likely than siblings to report miscarriage or stillbirth we utilized the cohort of survivors participating in the Bone (OR ¼ 0.7). Although prevalence of conception is dimin- Marrow Transplant Survivor Study (BMTSS) and com- ished after HCT, if pregnancy does occur, outcome is pared their experience with a sibling comparison group. likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve . Bone Marrow Transplantation (2006) 37, 1023–1029. Materials and methods doi:10.1038/sj.bmt.1705364; published online 10 April 2006 Keywords: late effects; conception; pregnancy outcomes; The BMTSS, a collaborative effort between the City of hematopoietic cell transplantation Hope Cancer Center and the University of Minnesota, examines the long-term outcomes of individuals who have survived 2 or more years after undergoing HCT, as well as Introduction similar outcomes in a cohort of siblings with a similar age and gender distribution. The aim of the current study was Hematopoietic cell transplantation (HCT) is being increas- to determine the prevalence of post-HCT conception, and ingly used for the treatment of malignant and non- outcome of pregnancy in 619 adult women and partners of men previously treated with autologous or allogeneic HCT. The present report from BMTSS is restricted to individuals who met the following eligibility criteria: (i) HCT between Correspondence: Dr S Bhatia, City of Hope Cancer Center, 1500 East 1974and 1998 at the City of Hope or University of Duarte Road, Duarte, CA 91010-3000, USA. E-mail: [email protected] Minnesota; (ii) age at transplant 21–45 years; and, (iii) Received 24February 2006; revised 8 March 2006; accepted 9 March survival of at least 2 years from HCT, irrespective of 2006; published online 10 April 2006 disease status. The Human Subjects Committees at the Pregnancy after hematopoietic cell transplantation A Carter et al 1024 participating institutions approved the BMTSS protocol. presence of chronic graft-vs-host disease (cGVHD), im- Informed consent was provided according to the Declara- munosuppressive agents used for GVH prophylaxis (yes vs tion of Helsinki. Data collection included completion of a no) and report of pre-transplant pregnancy ending in live 255-item mailed questionnaire designed to capture a wide birth (yes vs no). Patients considered being at standard risk range of demographic characteristics and health informa- for relapse included those in first or second complete tion. Specific to this report, participants provided a remission after acute or , those with complete pregnancy history by supplying details about all severe aplastic , and first chronic phase of CML. All pregnancies and outcomes both before and subsequent to other patients were placed into the high-risk category. HCT. Data collected included age at beginning of each pregnancy, weeks the pregnancy lasted, date of delivery and Pregnancy outcomes outcome of each pregnancy (i.e. whether the pregnancy Risk factors were analyzed for the occurrence of a live birth resulted in a livebirth, stillbirth, spontaneous miscarriage or or the occurrence of an adverse pregnancy outcome medical ). Only post-HCT pregnancies were used (stillbirth or miscarriage). for the purpose of the current analysis. The two primary outcomes of interest were inability to conceive after Comparison with siblings. Potential risk factors for transplant, and pregnancy outcomes (i.e. livebirths, still- adverse pregnancy outcomes (miscarriage or stillbirth) births and spontaneous miscarriages). Pregnancies in included age at study participation (younger than 45 years were not included in outcome analyses. We vs 45 years or older), sex, race, annual household income, compared the information obtained from the HCT availability of health insurance and highest level of survivors to that obtained from 301 closest-age siblings education. w2 tests were performed to determine whether who completed an identical BMTSS questionnaire. Ana- the rate of pre-term delivery (p37 weeks gestation) differed lyses were restricted to pregnancies occurring between the with respect to the sibling controls.16 ages of 21 and 45 for both survivors and the sibling In order to account for multiple pregnancies in or by one comparison group. survivor or one sibling (within person correlation), we used generalized estimating equations with a binominal distribu- Statistical analysis tion and a logit link to estimate the relative odds of Standard parametric and non-parametric tests were used to pregnancy outcomes among survivors compared to sib- lings. Our models also included a variance component for report descriptive analyses. To test for associations between 14,17–19 ordinal and categorical end points, we applied w2 tests for within family correlation. independence. The primary outcomes of interest were inability to conceive (yes vs no) and pregnancy outcomes (live births, miscarriages and spontaneous abortions). Data Results were analyzed with SAS version 9.1 (SAS Institute, Cary, NC, USA).14 Of the 978 patients eligible for participation in this study, 897 were successfully contacted with 619 (69%) agreeing to participate (Table 1). The median age at study participation Conception was 42.6 years (range 23.3–60.4 years), median age at Comparison with siblings. Potential risk factors for not transplant 33.3 years (range 21.0–45.0) and median length reporting a conception were analyzed using unconditional of follow-up 7.7 years (2.0–24.4 years). Twenty-nine logistic regression and included age at study participation, percent of participants had received HCT for CML, sex, race, annual household income (o$20 000 vs $20 000– 22.9% for AML, and 29.9% for HD or NHL. $60 000 vs 4$60 000), availability of health insurance, and Comparison of study participants with the potentially highest level of education (high school or less vs high school eligible non-participants showed that participants were degree with or without some college or training after high more likely to be female (47 vs 39%, P ¼ 0.02), and have school, vs college graduate). Odds ratio15 was used to received a conditioning regimen containing TBI (81 vs estimate magnitude of association between the risk of not 73%, P ¼ 0.003). Participants did not differ statistically reporting a conception and the potential risk factors. from non-participants in other conditioning agents re- ceived, race/ethnicity, primary diagnosis and length of Within survivor comparison. Potential risk factors for not follow-up, age at survey, age at transplant, risk of relapse at reporting a conception were analyzed within the survivor HCT, type of HCT, presence of cGVHD or the receipt of cohort, using unconditional logistic regression and included immunosuppressive agents. age at HCT (younger than 30 years vs 30 years or older), sex, race, annual household income (as above), availability Conception of health insurance, highest level of education (as above), A total of 34(5.5%) survivors reported 54post-HCT primary diagnosis (chronic myelogenous leukemia (CML), conceptions; these included 26 (8%) male survivors and (AML), Hodgkin disease (HD), eight (3%) female survivors (Table 2). Among the non- (NHL), acute lymphoblastic autologous transplant recipients, eight males (7%) reported leukemia (ALL), aplastic anemia (AA) and other mis- nine post-transplant conceptions, had a median age at cellaneous diagnoses (other)), type of transplant (auto- HCT of 29.7 years, a median age at first post-transplant logous vs allogeneic), disease status at transplant (standard delivery of 34.2 years and 25% had received a conditioning vs high risk of relapse at HCT), preparative regimens, regimen including TBI. Four female autologous transplant

Bone Marrow Transplantation Pregnancy after hematopoietic cell transplantation A Carter et al 1025 Table 1 Clinical and demographic characteristics of study female siblings reported conceptions for a total of 211 participants and non-participants siblings (70%) reporting 539 pregnancies. Participants Non-participant P-value HCT survivors were at a 36-fold increased risk of not (n ¼ 619) (n ¼ 359) reporting a conception compared to siblings (OR ¼ 35.9, n (%) n (%) 95% CI: 23.2–55.8, Po0.0001). Furthermore, study participants with an annual income of o$20 000 were at Sex Male 327 (52.8) 218 (60.7) an increased risk of not reporting a conception compared Female 292 (47.2) 141 (39.3) 0.02 to those with a higher income (OR ¼ 2.9, 95% CI: 1.1–7.8, P ¼ 0.03), as were participants who were younger at the Race time of survey completion compared to older participants White 456 (73.7) 243 (67.7) (OR ¼ 1.03, 95% CI: 1.01–1.05, P ¼ 0.002). Risk did not Hispanic 112 (18.1) 84(23.4) Other 51 (8.2) 32 (8.9) 0.1 vary statistically by race/ethnicity, education, sex or health insurance status (Table 3). Diagnosis Restricting the analysis to HCT survivors demonstrated Chronic myelogenous 180 (29.1) 99 (27.6) that age at transplantation X30 years (OR ¼ 4.8, 95% CI: leukemia Acute myeloid leukemia 142 (22.9) 73 (20.3) 2.1–10.7, Po0.001), female sex (OR ¼ 3.0, 95% CI: 1.3– Hodgkin disease 73 (11.8) 47 (13.1) 6.9, Po0.001) and receipt of TBI-containing conditioning Non-Hodgkin lymphoma 112 (18.1) 68 (18.9) (OR ¼ 3.3, 95% CI: 1.5–7.3, P ¼ 0.003), were associated Aplastic anemia 29 (4.7) 20 (5.6) with an increased risk of not reporting a post-HCT Acute lymphoblastic 53 (8.6) 32 (8.9) conception. The analysis was adjusted for ethnicity, leukemia 11 (1.8) 8 (2.2) income, health insurance status, report of pre-transplant Other 19 (3.1) 12 (3.3) 0.9 live birth, immunosuppressive agents received, chemother- apeutic exposures, type of transplant, presence of cGVHD, Risk of relapse at HCT primary diagnosis, disease status at HCT and level of Standard risk 398 (64.6) 244 (68.0) High risk 218 (35.4) 115 (32.0) 0.3 education (Table 3).

Type of HCT Pregnancy outcomes Autologous 241 (38.9) 148 (41.2) Provided in Table 4are the outcomes of pregnancies Allogeneic (related) 312 (50.4) 177 (49.3) reported by survivors and siblings. Eighty-five percent Allogeneic (unrelated) 66 (10.7) 34(9.5) 0.7 of conceptions reported by the HCT survivors resulted in Conditioning regimen live birth, which was significantly higher than the 75% TBI 502 (81.2) 262 (73.0) 0.003 of live birth outcomes reported by siblings (P ¼ 0.05). 481 (77.8) 278 (77.4) 0.9 Thus, outcomes of the 54reported post-HCT conceptions Etoposide 317 (51.3) 184(51.3) 0.9 included 46 live births (85.2%), five miscarriages (9.2%), Busulfan 30 (4.9) 29 (8.1) 0.06 one stillbirth (1.9%) and two pregnancies in gestation Cytarabine 12 (1.9) 11 (3.1) 0.4 56 (9.1) 43 (12.0) 0.2 (3.7%) at the time of survey. In contrast, outcomes of 298 (48.2) 169 (47.2) 0.8 the 539 pregnancies reported by the siblings included 401 Cyclosporine 282 (45.6) 157 (43.9) 0.6 live births (74.4%), 89 miscarriages (16.5%), 37 medical 231 (37.4) 129 (36.0) 0.7 abortions (6.9%), six (1.1%) and six pregnancies Chronic graft vs host 226 (36.6) 127 (35.5) 0.8 disease in gestation (1.1%). This pattern was observed both in male Age at HCT in years 33.3 (21.0–45.0) 32.5 (21.2–45.0) 0.3 survivors (proportion of pregnancies resulting in livebirths: (median, range) 84.6 vs 78.5%, P ¼ 0.5), as well as female survivors (100 vs Length of follow-up in 7.7 (2.0–24.4) 8.1 (2.1–22.9) 0.3 73.5%, P ¼ 0.07) when compared with same sex siblings. years Survivors were not more likely than siblings to report pre- Age at survey in years 42.6 (23.3–60.4) 42.0 (25.8–61.5) 0.2 term deliveries (defined as p37 weeks gestation; 33.3 vs Abbreviation: HCT ¼ hematopoietic cell transplantation. 40.8%, P ¼ 0.5). Bold indicates statistically significant differences between groups. Multivariate analysis of pregnancy outcomes among study participants reporting the occurrence of pregnancy, indicated that HCT survivors were statistically as likely as survivors (3%) reported nine post-transplant conceptions, siblings to report a livebirth (OR ¼ 2.2, 95% CI: 0.8–6.2, had a median age at HCT of 27.4years, a median age at P ¼ 0.1), and that the survivors were not at an increased first post-transplant delivery of 31.3 years and 50% had risk for miscarriage or stillbirth (RR ¼ 0.7, 95% CI: 0.2– received TBI. Among the allogeneic transplant recipients, 2.1, P ¼ 0.5). This analysis was adjusted for age at survey 18 males (9%) reported 31 post-transplant conceptions in completion, race/ethnicity, income, sex, health insurance their partners, had a median age at transplant of 27.2 years, and education (Table 5). a median age at first delivery of 30.7 years and 72.2% had received TBI. Four female allogeneic transplant survivors (2%) reported five pregnancies post-HCT, had a median Discussion age at transplant of 22.0 years, a median age at first delivery of 25.7 years, and 75% received TBI. In the sibling The results of this study demonstrate that the prevalence of comparison group, 66% of male siblings and 72% of conception following HCT was significantly diminished

Bone Marrow Transplantation Pregnancy after hematopoietic cell transplantation A Carter et al 1026 Table 2 Clinical characteristics of survivors reporting pregnancies after HCT

Variables of interest Autologous (n ¼ 241) Allogeneic (n ¼ 378)

Sex Male (n ¼ 119) Female (n ¼ 122) Male (n ¼ 208) Female (n ¼ 170)

Total number of patients 8 (7%) 4(3%) 18 (9%) 4(2%) Total number of pregnancies 9 9 31 5 Age at HCT: median (range) 29.7 (23.3–36.5) 27.4(24.8–30.1) 27.2 (21.2–35.1) 22.0 (21.3–29.8) Follow-up: median (range) 7.2 (4.6–12.8) 11.2 (9.1–15.1) 13.6 (7.7–19.4) 10.2 (6.7–18.0) Age at first post-HCT pregnancy: median (range) 34.2 (26.9–39.7) 31.3 (29.4–33.1) 30.7 (24.8–43.3) 25.7 (22.6–28.0) Age at survey: median (range) 36.8 (28.4–46.8) 39.6 (37.2–40.1) 39.8 (32.3–47.4) 35.2 (29.2–40.7)

Diagnosis Chronic myelogenous leukemia — — 6 (33.3%) 1 (25.0%) Acute myeloid leukemia — — 2 (11.1%) 2 (50.0%) Hodgkin’s disease 5 (62.5%) 3 (75.0%) — — Non-Hodgkin’s lymphoma 3 (37.5%) 1 (25.0%) 1 (5.6%) — Aplastic anemia — — 5 (27.8%) 1 (25.0%) Acute lymphoblastic leukemia — — 3 (16.7%) — Other diagnoses — — 1 (5.6%) —

Conditioning agents Total body irradiation 2 (25.0%) 2 (50.0%) 13 (72.2%) 3 (75.0%) Cyclophosphamide 8 (100.0%) 4(100.0%) 14(77.8%) 3 (75.0%) Etoposide 7 (87.5%) 3 (75.0%) 5 (27.8%) 1 (25.0%) Carmustine 6 (75.0%) 2 (50.0%) — —

Graft-vs-host disease prophylaxis Methotrexate — — 12 (66.7%) 3 (75.0%) Cyclosporine — — 9 (50.0%) 3 (75.0%) Prednisone — — 9 (50.0%) 2 (50.0%) Chronic GVHD — — 12 (66.7%) 0

Risk of relapse at HCT Standard risk 4(50%) 3 (75%) 12 (66.7%) 3 (75%) High risk 4(50%) 1 (25%) 6 (33.3%) 1 (25%)

Abbreviations: GVHD ¼ Graft-vs-host disease; HCT ¼ hematopoietic cell transplantation.

compared to siblings with a comparable age and gender the outcome of these pregnancies using a concurrent distribution. Risks for not reporting conception were comparison group. Our goal was to determine the significantly higher among survivors undergoing HCT at prevalence of conception and outcome of pregnancy in an older age, females, those exposed to TBI and those with adult women and partners of men treated with autologous a low-household income. We have, however, identified 54 or allogeneic HCT by directly surveying the survivors self-reported post-transplant conceptions in a patient rather than relying upon data abstracted from medical population that has a high prevalence of infertility. records or obtained from central registries. Moreover, our Although we have confirmed that the overall prevalence goal was to report on the outcomes after HCT, thus of pregnancy following HCT is low, as in all previous broadening the base of information available to help studies, the true magnitude of infertility following HCT will educate pre-transplant patients. always be difficult to determine, in part because of lack of Several case series have described pregnancy outcomes complete data on pre- and post-transplant fertility status, among female HCT survivors.7,12,23–30 Data from Sanders and lack of sufficiently detailed information regarding et al.12 suggest that pregnancies among female HCT desire to become pregnant after undergoing HCT.20 recipients who had received TBI were significantly more Post-pubertal recipients of high-dose cyclophosphamide likely to end in miscarriage, reporting a miscarriage rate of have a high probability of recovery of gonadal function, 38% after TBI as a 10.0 Gy single exposure or 12–14.0 Gy and exposure to TBI may also result in occasional recovery fractionated exposure. Furthermore, they reported a of normal gonadal function.21–24 Nevertheless, infertility miscarriage rate of 7% among female survivors who had following HCT is widespread, although it has been received cyclophosphamide alone, and no miscarriages established that select patients may retain or recover among the five females who had received TBI at a much fertility. Moreover, female survivors have been reported lower dose of 5–8.0 Gy. Pregnancy outcomes analyses in to be at an increased risk of spontaneous abortions and the current study indicated that 85% of the pregnancies miscarriages, pre-term delivery and resulted in live birth, compared with 75% of those reported babies.6,12,13,24 However, previous research has generally by the nearest-age siblings and 62% of those reported by not included comprehensive systematic assessments of the the Centers for Disease Control/National Center for Health prevalence of conception after both autologous and Statistics on trends in the in Pregnancy Rates allogeneic HCT, nor have the previous studies described by Outcome.31 Our study demonstrates that, after adjusting

Bone Marrow Transplantation Pregnancy after hematopoietic cell transplantation A Carter et al 1027 for key variables, the survivors were as likely as sibling that a reporting bias would be more prevalent among either controls to report a pregnancy ending in live birth, and the patient or sibling participant groups, thus indicating survivors were not more likely to report a pregnancy ending that HCT was not associated with an increased prevalence in miscarriage or stillbirth. Overall, 11% of the pregnancies of miscarriage in the current study. A recent large cohort resulted in miscarriages or stillbirths, compared with 17.6% study from the EBMT Late Effects Working Party did of those reported by the nearest age siblings and 15.7% of not find an increase in the rate of miscarriage, among those reported by the CDC/NCHS.31 Furthermore, while transplant survivors when compared with general popula- 14% of the pregnancies partnered by male HCT survivors tion rates.13 There is a possibility that the reported resulted in miscarriages, none of the pregnancies reported incidence of miscarriage underestimates the actual rate, by female survivors resulted in miscarriage. It is unlikely since successful pregnancies are more likely to be reported, and recall of events representing a spontaneous abortion have been found to be inaccurate;32 approximately one in five pregnancies as detected by human chorionic gonado- Table 3 Multivariate analysis of risk factors associated with tropin assay are clinically unrecognized.33 reporting no conception after HCT Pre-term labor and delivery may result from pre- Variables Odd ratio (95% confidence interval) P-value , multiple gestation, intrauterine and distortion of the uterine cavity due to a variety of reasons. Sibling comparison groupa Irradiation has been shown to reduce the elasticity of the Sibling 1.0 uterine musculature, probably secondary to intrauterine HCT survivors 35.95 (23.18–55.77) o0.0001 vascular damage.34 In contrast to previous studies that Age at survey completion suggested female survivors of HCT are at an increased risk Older 1.0 of delivering low birth weight and pre-term ,12,13 we Younger 1.03 (1.01–1.05) 0.002 did not find a higher reported prevalence of pre-term Yearly household income delivery after HCT when compared with the sibling X$60 000 1.0 comparison group. $20–60 000 1.16 (0.74–1.82) 0.5 The current study did not obtain information regarding o$20 000 2.91 (1.08–7.80) 0.03 assisted reproductive techniques that might have been Within survivor comparisonb utilized by the survivors. Thus, it is unclear what role the Sex use of assisted reproductive techniques, such as sperm or Male 1.0 oocyte cryopreservation, in vitro fertilization or pharma- Female 2.99 (1.30–6.91) 0.01 cological interventions, played in the current findings of rate of post-transplant pregnancy.35 The observation of the Age at HCT o30 years 1.0 present study that low income is a risk factor for not X30 years 4.78 (2.14–10.67) 0.0001 reporting a post-transplant pregnancy may suggest that lower income survivors may have limited access to medical Total body irradiation care, including assisted reproductive technologies. No 1.0 Yes 3.32 (1.50–7.32) 0.003 Pre-transplantation counseling typically includes discus- sions regarding the likelihood of post-transplant infertility, aAnalysis adjusted for sex, race/ethnicity, current health insurance, and the chance of uncomplicated pregnancy, should education. conception be achieved. This study provides encouraging bAnalysis adjusted for race/ethnicity, current health insurance, education, data for HCT survivors, indicating that although the yearly household income, primary diagnosis, type of HCT, risk of relapse prevalence of conception is significantly diminished after at HCT, presence of chronic graft-vs-host disease, history of pre-HCT live birth, myeloablative , and immunosuppressive therapy for HCT, if pregnancy occurs, the outcome is likely to be graft-vs-host disease prophylaxis. favorable. Therefore, thought should be given prior to Bold indicates statistically significant differences between groups. transplant to possible strategies to preserve fertility, such as

Table 4 A comparison of the prevalence of pregnancy outcomes between HCT survivors with siblings

Males Females

HCT survivors Siblings HCT survivors Siblings

Autologous Allogeneic Total Autologous Allogeneic Total

Pregnancies resulting in live birth 7 (78%) 26 (84%) 33 (83%) 146 ((78%) 9 (100%) 4 (80%) 13 (93%) 255 (72%)

Pregnancies not resulting in live birth Miscarriage 1 (11%) 4(13%) 5 (13%) 26 (14%) 0 (0%) 0 (0%) 0 (0%) 63 (18%) Medical abortion 0 (0%) 0 (0%) 0 (0%) 13 (7%) 0 (0%) 0 (0%) 0 (0%) 24(7%) Stillbirth 0 (0%) 1 (3%) 1 (2%) 1 (0.5%) 0 (0%) 0 (0%) 0 (0%) 5 (1%)

Pregnant at time of survey 1 (11%) 0 (0%) 1 (2%) 1 (0.5%) 0 (0%) 1 (20%) 1 (7%) 5 (1%) Total number of pregnancies 9 31 40 187 9 5 14 352

Bone Marrow Transplantation Pregnancy after hematopoietic cell transplantation A Carter et al 1028 Table 5 Risk Factors associated with adverse pregnancy outcomes, a comparison of HCT survivors with siblings

Variables Factors associated with live birth Risk associated with adverse pregnancy outcomes

Relative risk (95% confidence interval) P-value Relative risk (95% confidence interval) P-value

Comparison groups – HCT survivors vs siblings Sibling 1.0 HCT survivors 2.18 (0.76–6.24) 0.1 0.70 (0.24–2.08) 0.5

Age at survey completion o45 years 1.0 1.0 X45 years 1.27 (0.83–1.96) 0.3 0.68 (0.42–1.11) 0.1

Sex Males 1.0 1.0 Females 0.75 (0.48–1.16) 0.2 1.40 (0.87–2.27) 0.2

Race/ethnicity Whites 1.0 1.0 Other race/ethnicity 1.20 (0.45–3.15) 0.7 0.61 (0.18–2.12) 0.4

Annual household income X$20 000 1.0 1.0 p$19 999 1.89 (0.50–7.05) 0.3 0.79 (0.22–2.79) 0.7

Availability of current health insurance Health insurance available 1.0 1.0 No current health insurance 0.65 (0.22–1.88) 0.42.37 (0.81–6.89) 0.1

Educational status Post high school education 1.0 1.0 High school education or less 1.59 (0.76–3.32) 0.2 0.76 (0.37–1.57) 0.5

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