Granulocyte Colony-Stimulating Factor Use in Pregnant Women with Cancer Requiring Chemotherapy

Granulocyte Colony-Stimulating Factor Use in Pregnant Women with Cancer Requiring Chemotherapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Granulocyte Colony-Stimulating Factor Use in Pregnant Women with Cancer Requiring Chemotherapy Amy Bordogna, John Dibato, John Gaughan, Elyce Cardonick This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8842062/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Cancer complicates approximately 1 in 1,000 pregnancies. Chemotherapy can be safely administered after the first trimester; however, limited safety data on in utero exposure to granulocyte-colony stimulating factors (G-CSF) may influence chemotherapy regimens offered during pregnancy. This study evaluates neonatal and maternal outcomes following G-CSF exposure during pregnancy and examines the incidence of maternal neutropenia among women receiving chemotherapy. Methods We conducted a prospective cohort study using data from the Cancer and Pregnancy Registry (1997–2023). Outcomes were compared between pregnant women receiving chemotherapy with G-CSF and those receiving chemotherapy alone. Primary neonatal outcomes included birthweight, fetal growth restriction (FGR), neutropenia or leukopenia at birth, congenital anomalies, and pediatric medical conditions. Maternal outcomes included neutropenia and pregnancy complications. Results Among 367 pregnant women receiving chemotherapy, 85 received G-CSF. Mean maternal age at diagnosis was 32.7 years, and mean gestational age at diagnosis was 14 weeks. Breast cancer was the most common diagnosis, and patients with breast cancer were more likely to receive G-CSF than those with other malignancies (p = 0.04). No significant differences were observed between exposed and unexposed groups in birthweight (2,610 g vs 2,720 g; p = 0.13), FGR (29% vs 20%; p = 0.06), neonatal complications (16% vs 18%; p = 0.73), congenital anomalies (13% vs 8%; p = 0.15), neonatal leukopenia (2% vs 2%; p = 1.00), neutropenia (6% vs 5%; p = 0.73), or pediatric medical conditions (31% vs 27%; p = 0.47). Maternal neutropenia occurred in 7.7% of women overall, with no significant difference between those receiving G-CSF and those who did not (p = 0.59). Conclusion Exposure to G-CSF during chemotherapy in pregnancy was not associated with adverse maternal, neonatal, or pediatric outcomes. Trial Registration ClinicalTrials.gov (NCT02749474), registered April 21, 2016. Retrospectively registered. Pregnancy Cancer Chemotherapy Granulocyte colony-stimulating factors Neonatal outcomes Pregnancy complications Background Approximately 1 in 1,000 pregnancies are complicated by cancer. Oncologists and obstetricians face the challenge of providing maternal treatment while minimizing fetal risks [ 1 ]. In many cases, delaying chemotherapy until after childbirth is not optimal for the mother’s health, and instead choosing an elective premature birth can pose additional health risks to the newborn [ 1 ]. Fortunately, long-term follow up of children exposed in utero to chemotherapy for maternal cancer have been reassuring [ 2 – 5 ]. Whenever possible, treatment should mimic regimens offered to non-pregnant patients [ 6 , 7 ]. Granulocyte-colony stimulating factors (G-CSF), such as Neupogen (Filgrastim) or Neulasta (Pegfilgrastim), are commonly prescribed to non-pregnant patients receiving chemotherapy to enhance immunity, lower the risk of infection, or for prophylaxis against febrile neutropenia [ 8 , 9 ]. When chemotherapy is given during pregnancy, G-CSF may be important for the treatment or prevention of neutropenic fever and susceptibility to infections, which can potentially affect the fetus in utero [ 10 ]. Concerns about using G-CSF mobilizers during pregnancy may affect chemotherapy regimen choice or treatment intervals offered during pregnancy. The findings herein will better support clinical decision-making for obstetricians, oncologists and patients when discussing chemotherapy choices for a particular cancer during pregnancy. This is especially helpful for physicians who would otherwise offer dose-dense regimens to patients with breast cancer. The use of dose dense chemotherapy to treat breast cancer in pregnancy has been reported in small numbers without maternal or fetal complications [ 10 ], but if more safety data were published regarding the use of G-CSF in pregnancy we believe this option could be offered to more women in pregnancy if clinically indicated. In a previous study by the senior author in 2012, the use of G-CSF agents was reported in 34 of 176 patients receiving chemotherapy during pregnancy [ 11 ]. There were no significant differences in neonatal outcomes or anomalies in newborns born to pregnant patients receiving G-CSF with chemotherapy versus chemotherapy alone. In 2020 we surveyed 273 oncologists treating pregnant women with chemotherapy in the Cancer and Pregnancy Registry about their views on prescribing G-CSF during pregnancy. We learned that 20% of oncologists withheld G-CSF due to pregnancy alone. Given the increasing use of dose-dense chemotherapy for breast cancer in non-pregnant women, we aim to publish safety data on the use of G-CSF in pregnancy so that pregnant women with breast cancer could also be offered this option if clinically indicated. We have accumulated more than double the number of mother/infant pairs exposed to G-CSF from our prior study. Methods Data and Study Design The Cancer and Pregnancy Registry was created in 1997 to collect multicenter information about the diagnosis and treatment of cancer during pregnancy, the survival of women diagnosed with cancer while pregnant, and the long-term neurodevelopment and medical health of their newborns. The Cancer and Pregnancy Registry is a Clinical Trials.gov study (NCT 02749474 || 2016-04-13). A unique factor about the Cancer and Pregnancy Registry is the prospective nature of the data collection from multiple centers. Additionally, pregnant women enroll at the time of a cancer diagnosis, before the outcome of the pregnancy is known, reducing bias that only optimal or only suboptimal pregnancy and neonatal outcomes are reported. The researchers maintain annual communication with the pediatricians for each child's follow-up. As of June 2023, 583 patients consented to be enrolled in the Registry from four different world continents. This created a prospective cohort beginning in 1997 and this current study includes data through June 2023. Study Variables Researchers identified patients treated with chemotherapy during pregnancy and classified patients into two groups: those receiving granulocyte colony-stimulating factors (G-CSF) with at least one of their chemotherapy courses (exposed). Primary outcomes of this study include newborn health in the neonatal period and early childhood. Specifically, variables include neutropenia or leukopenia at birth, birthweight percentile and incidence of fetal growth restriction or anomalies at birth, and a diagnosis of asthma, eczema, allergies, or other medical conditions and any behavioral conditions identified during childhood follow up. Neutropenia was defined as an absolute neutrophil count (ANC) of < 1000 per microliter from a complete blood count (CBC) obtained at the time of delivery or on day one of life. Leukopenia was defined as WBC < 5,000 cells/L. Birth percentile was determined using gestation.net centile calculator which accounts for the infant’s sex, gestational age at birth, maternal parity, height and weight at first prenatal visit, and ethnicity. Intrauterine growth restriction is defined as birth percentile < 10% for gestational age. Reportable Congenital Anomalies were determined by the Metropolitan Atlanta Congenital Defects Program. Pediatricians were contacted annually to inquire about any medical conditions, or behavioral issues (attention deficit disorder, attention deficit hyperactivity disorder, anxiety, Asperger’s or autism spectrum disorder, obsessive compulsive disorder, oppositional defiant disorder, tic disorder or social skill impairment). Secondary outcomes concern the mothers’ complications during pregnancy. As only two patients in the database to date have received Udenyca (Pegfilgrastim-cbqv) and Zarxio (Filgrastim-sndz), we limited this current report to only those who received either Filgrastim or Pegfilgrastim during pregnancy. Oncologic and obstetric variables collected for the mothers include the type of cancer, gestational age at first chemotherapy treatment and at delivery; the incidence of any pregnancy complications, and the presence of maternal neutropenia during treatment. Researchers noted whether G-CSF were used prophylactically or as treatment after the development of maternal neutropenia. Statistical Analysis All the above-mentioned variables were summarized as count (%) and mean (SD) and compared between the exposed and unexposed groups using two sample t-test or Wilcoxon rank sum test for continuous variables and chi-square test or Fisher exact test for categorical variables. All analyses were done using SAS 9.4 (SAS Institute, Inc., Cary, NC). A two-sided p value < 0.05 was considered statistically significant. Results Study participants Of 583 women enrolled in the Cancer and Pregnancy Registry, 367 pregnant patients with singleton gestations received chemotherapy during pregnancy and were included in this analysis. Most were diagnosed with a primary cancer during pregnancy, most commonly breast cancer; 11 were diagnosed with recurrent disease.Eighty-five women, including the original 34 reported previously, received Filgrastim or Pegfilgrastim (G-CSF) during pregnancy. Demographic characteristics are summarized in Table 1 . Mean maternal age, race, and country of origin did not differ significantly between exposed and unexposed groups, with the exception of the “other” race category, which was less frequent in the unexposed group (p = 0.02). For the overall cohort, mean (± SD) maternal age at cancer diagnosis was 32.7 ± 10.9 years, and mean gestational age at diagnosis was 14.0 ± 8.1 weeks. Table 1: Demographic characteristics of pregnant women receiving chemotherapy with or without G-CSF Characteristic Overall (n=367) Exposed (G-CSF n=85) Unexposed (n=282) p value Age at diagnosis, Mean ± SD 34 ± 7.4 34 ± 5.0 34 ± 5.0 0.69 Race/Ethnicity, n (%) White African American Asian Other Unknown 279 (76) 22 (6) 23 (6) 30 (8) 13 (4) 58 (68) 5 (6) 2 (2) 12 (14) 8 (9) 216 (77) 16 (6) 20 (7) 17 (6) 13 (5) 0.12 0.94 0.11 0.02 0.96 Country United States Canada Other (Eng, Aus, Thai)* Unknown 348 (95) 13 (4) 5 (1) 1 (0.2) 77 (91) 1 (1) 0 7 (8) 264 (94) 11 (4) 4 (1) 3 (1) 0.34 0.22 0.27 0.07 *Eng = England, Aus = Australia, Thai = Thailand G-CSF– granulocyte colony-stimulating factors SD – standard deviation Table 2 summarizes cancer types and G-CSF use. Breast cancer was the most common diagnosis, including 47 women treated with dose-dense chemotherapy. Patients with breast cancer were more likely to receive G-CSF compared with patients with other cancer types (80% vs 20%, p = 0.04). Other malignancies included Hodgkin and non-Hodgkin lymphoma, acute leukemia, choriocarcinoma, and cancers of the cervix, bladder, bone, colon, gallbladder, nasopharynx, rectum, lung, ovary, and pancreas. Table 2 Cancer types and G-CSF use among pregnant women receiving chemotherapy Cancer Diagnosis #Patients receiving Chemotherapy (n = 367) #Patients receiving Filgrastim/Pegfilgrastim (85) Breast (premenopausal) Dose-dense ● Prophylactic ● Therapeutic Conventional ● Prophylactic ● Therapeutic ● Unclear 261 47 214 68 (42 F, 22 P, 4 Both) 30 (9F, 19P, 2 Both) 25 5 38 (13F, 23P, 2 Both) 20 16 2 Hodgkin’s Lymphoma ● Prophylactic ● Therapeutic 31 4 (2F, 2P) 3 1 Non-Hodgkin’s Lymphoma ● Prophylactic ● Therapeutic ● Unclear 20 8 (4F, 4P) 2 5 1 Ovarian 13 0 Cervical 11 0 Acute Leukemia ● Prophylactic ● Therapeutic 4 3 (2F, 1P) 2 1 Lung ● Prophylactic ● Therapeutic 3 1 (1P) 1 0 Miscellaneous ● Unclear 24 1 (P – Bone cancer) Total : 367 85 (34F, 45P, 4 Both) F = Filgrastim, P = Pegfilgrastim, Both = combination of Filgrastim and Pegfilgrastim Maternal outcomes Pregnancy outcomes and maternal complications are presented in Table 3 . Overall, 70/367 (19%) pregnancies resulted in spontaneous preterm delivery or preterm premature rupture of membranes (PPROM), with no significant difference between groups (20% exposed vs 19% unexposed, p = 0.80). Elective iatrogenic preterm births were excluded from this comparison.Gestational diabetes mellitus and preeclampsia were the most common maternal complications. Less frequent complications included placenta previa, placental abruption, pyelonephritis, chorioamnionitis, oligohydramnios, and thromboembolism. The overall incidence of maternal complications did not differ between exposed and unexposed groups (31% vs 28%, p = 0.69). Table 3 Pregnancy and Delivery Data Variable Overall (n = 367) G-CSF exposed (n = 85) G-CSF not given (n = 282) p value Gestational age at first treatment, Mean ± SD weeks 20.6 ± 5.5 19.6 ± 5.7 20.9 ± 5.4 0.07 Gestational age at delivery, Mean ± SD weeks 36.6 ± 2.3 36.4 ± 2.3 36.7 ± 2.4 0.38 Maternal pregnancy complications, n(%) 106 (29) 26 (31) 80 (28) 0.69 Preterm delivery from spontaneous rupture or PPROM, n(%) 70 (19) 17 (20) 53 (19) 0.80 G-CSF – granulocyte colony-stimulating factors SD – standard deviation PPROM – preterm premature rupture of membranes Fifteen women developed an infection during chemotherapy. Two were receiving G-CSF at the time of infection; only one of these patients was neutropenic when infection was diagnosed. Overall, maternal neutropenia occurred in 28/367 (7.7%) women receiving chemotherapy. Three women receiving prophylactic G-CSF developed neutropenia (3/57, 5%), compared with 25 women who did not receive prophylactic G-CSF (25/310, 8%); this difference was not statistically significant (p = 0.59). Fetal and neonatal outcomes Mean gestational age at delivery for the cohort was 36.6 ± 2.3 weeks and did not differ between the exposed (36.4 ± 2.3 weeks) and unexposed groups (36.7 ± 2.4 weeks; p = 0.38). Mean birthweight was also similar between groups (2,610 ± 539 g exposed vs 2,720 ± 588 g unexposed; p = 0.13).Fetal growth restriction occurred in 81/367 (22%) neonates: 25/85 (29%) in the exposed group and 56/282 (20%) in the unexposed group (p = 0.06; Table 4 ). Table 4 Newborn and Pediatric Follow-Up Data Variable Overall (n = 367) G-CSF exposed (n = 85) G-CSF not given (n = 282) p value Newborn Data Birth weight, Mean ± SD grams 2694 ± 578.4 2610 ± 539.1 2720 ± 588.3 0.13 Fetal Growth restriction n (%) 81 (22) 25 (29) 56 (20) 0.06 Complications at birth, n (%) 65 (18) 14 (16) 51 (18) 0.73 Birth defects, n (%) 33 (9) 11 (13) 22 (8) 0.15 Neonatal Leukopenia, n (%) 4 (2) 1 (2) 3 (2) 1.00 Neonatal Neutropenia, n (%) 10 (6) 3 (6) 7 (5) 0.73 Pediatric Follow-Up Total, n (%) 101 (28) 26 (31) 75 (27) 0.47 Behavioral 31 (8) 8 (9) 23 (8) 0.72 Asthma 30 (8) 10 (12) 20 (7) 0.17 Eczema 44 (12) 13 (15) 31 (11) 0.28 Allergic Rhinitis 28 (8) 3 (4) 25 (9) 0.10 G-CSF – granulocyte colony-stimulating factors; SD – standard deviation A neonatal complete blood count at birth or on day 1 of life was available for 178 neonates (47 exposed, 131 unexposed). Neutropenia was present in 3/47 (6%) exposed neonates and 7/131 (5%) unexposed neonates (p = 0.73). Leukopenia occurred in 1/47 (2%) exposed and 3/131 (2%) unexposed neonates (p = 1.00). Among the 10 neonates with neutropenia, the mean interval between the final chemotherapy cycle and delivery was 3.9 ± 2.0 weeks, with half born within four weeks of maternal chemotherapy. Immediate neonatal complications, most commonly hyperbilirubinemia, apnea, hypoglycemia, and respiratory distress, occurred in 14/85 (16%) exposed neonates and 51/282 (18%) unexposed neonates (p = 0.73). Congenital anomalies were identified in 11/85 (13%) exposed and 22/282 (8%) unexposed neonates (p = 0.15). Ureteropelvic junction obstruction was the most common anomaly (four exposed, four unexposed). Multiple hemangiomas were the second most frequent anomaly and occurred only in the unexposed group. No patients received chemotherapy during the first trimester (Supplemental Table 1). Pediatric follow-up data are summarized in Table 4 . Medical conditions, most commonly asthma, eczema, and allergic rhinitis, were reported in 26/85 (31%) exposed children and 75/282 (27%) unexposed children (p = 0.47). Behavioral diagnoses did not differ significantly between groups. Discussion When cancer is diagnosed during pregnancy, termination has not been shown to improve maternal survival [ 12 – 16 ]. Studies comparing pregnant women with cancer to age- and stage-matched non-pregnant controls demonstrate similar oncologic outcomes when comparable therapies are administered [ 6 , 7 , 17 – 20 ]. Long-term follow-up studies of children exposed in utero to chemotherapy administered after the first trimester have been reassuring, with neurodevelopmental outcomes largely influenced by gestational age at delivery rather than chemotherapy exposure itself [ 2 – 5 ]. Despite these data, chemotherapy regimens offered during pregnancy may differ from those used in non-pregnant patients, particularly with respect to dose-dense protocols requiring G-CSF support. Anecdotal reports from patients with breast cancer in our cohort suggest that dose-dense chemotherapy would have been offered outside of pregnancy, highlighting ongoing clinician hesitancy regarding G-CSF use during gestation. Our findings provide additional evidence to inform discussions surrounding chemotherapy optimization during pregnancy. In this prospective cohort of 85 pregnancies exposed to G-CSF during chemotherapy, no statistically significant differences were observed in maternal, obstetric, neonatal, or pediatric outcomes compared with women treated with chemotherapy alone. Outcomes evaluated included gestational age at delivery, birthweight, fetal growth restriction, preterm delivery, neonatal complications, congenital anomalies, and hematologic abnormalities. Neonatal neutropenia and leukopenia were uncommon and occurred at similar rates in both exposure groups. Consistent with prior literature, neonates with hematologic abnormalities were more frequently delivered within three to four weeks of the final maternal chemotherapy cycle [ 21 ]. Maternal complications, including infection and neutropenia, were also comparable between groups. Although neutropenia occurred in a small proportion of women receiving prophylactic G-CSF, the overall incidence did not differ significantly from women who did not receive prophylactic support. These findings align with prior reports describing the safety of G-CSF use during pregnancy, including smaller retrospective studies and registry-based analyses [ 10 , 22 , 23 ]. Our study expands on existing literature by including a larger number of exposed pregnancies, a prospectively collected control group, and long-term pediatric follow-up. The prospective design of the Cancer and Pregnancy Registry minimizes selection bias and allows for systematic longitudinal assessment of offspring health. Several limitations warrant consideration. Neonatal complete blood counts were not uniformly obtained across all participating centers, limiting the assessment of neonatal hematologic outcomes. Additionally, the relatively low incidence of many outcomes restricts statistical power to detect small differences. While this study focused on Filgrastim and Pegfilgrastim, continued data collection is ongoing for biosimilar G-CSF. Abbreviations ANC absolute neutrophil count CBC complete blood count FGR fetal growth restriction G CSF-granulocyte colony-stimulating factors GDM gestational diabetes mellitus PPROM premature rupture of membranes Declarations Ethics approval Creation and maintenance of the Registry was approved by the Office of Research & Sponsored Programs – Division of Research Integrity, Institutional Review Board at Cooper University Healthcare. The IRB approval/reference number is 15-028. All enrolled patients provided informed consent. Consent for publication Not Applicable Data availability The data supporting the findings of this study are available from the corresponding author, AB, upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author contributions EC conceived and designed the study. AB collected the data, and JD and JG performed statistical analysis and interpreted the results. EC and AB drafted the manuscript, and all authors critically revised it for important intellectual content. All authors approved the final version of the manuscript. Acknowledgements The authors thank Audrey Ross, research assistant, for assistance with the article submission process. References Cardonick E. Pregnancy-associated breast cancer: optimal treatment options. Int J Womens Health. 2014;6:935–43. https://doi.org/10.2147/IJWH.S52381 . Amant F, Van Calsteren K, Halaska M, Gziri M, Hui W, Lagae L, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged ≥ 18 months: an observational study. Lancet Oncol. 2012;13(3):256–64. https://doi.org/10.1016/S1470-2045(11)70363-1 . Esposito S, Tenconi R, Preti V, Groppali E, Principi N. Chemotherapy against cancer during pregnancy: a systematic review on neonatal outcomes. 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Supplementary Files GCSFSupplementalTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 11 May, 2026 Reviewers agreed at journal 11 May, 2026 Reviewers agreed at journal 01 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviewers invited by journal 28 Apr, 2026 Editor assigned by journal 26 Apr, 2026 Editor invited by journal 09 Apr, 2026 Submission checks completed at journal 26 Mar, 2026 First submitted to journal 26 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8842062","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":635030583,"identity":"12b95ffa-cd82-485d-905f-e5ed191714ee","order_by":0,"name":"Amy Bordogna","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYBACeyCWYGCwkeOHCx0goMWwAawlzViygVgtBgfAWg4nboCrJGhLe+/DGx9+pSVuvn34mMTPHQxyfDcS8Gux5zlubDmzz8Z427m0NMneMwzGkoS0GM5IY5Pm7UmT3XaGx+wGbxtD4gZCWgxugLUcZtzcw2N2828bQz1xWnh+HFbcwMNjdhtoS4IBQYf1HGO2nNmQZixxhi39t2ybhOHMMw/wa7Fnb2O88eEPMCp7mA8bvm2zkec7TsAWMGBsgzMliFAOBn+IVTgKRsEoGAUjEgAA42BIrb2BDA8AAAAASUVORK5CYII=","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":true,"prefix":"","firstName":"Amy","middleName":"","lastName":"Bordogna","suffix":""},{"id":635030584,"identity":"62e66c83-f2da-48b3-b68f-ee1473460fd5","order_by":1,"name":"John Dibato","email":"","orcid":"","institution":"Cooper Medical School of Rowan University","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Dibato","suffix":""},{"id":635030585,"identity":"1699b825-60c3-40a0-882e-d836ea2505b6","order_by":2,"name":"John Gaughan","email":"","orcid":"","institution":"Cooper Medical School of Rowan University","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Gaughan","suffix":""},{"id":635030586,"identity":"d24ef83a-1e23-4571-be17-963b2e56145b","order_by":3,"name":"Elyce Cardonick","email":"","orcid":"","institution":"Cooper University Health Care","correspondingAuthor":false,"prefix":"","firstName":"Elyce","middleName":"","lastName":"Cardonick","suffix":""}],"badges":[],"createdAt":"2026-02-10 14:23:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8842062/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8842062/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108635346,"identity":"27bbe0af-38c3-4fd0-8250-d0cb67a6eac5","added_by":"auto","created_at":"2026-05-06 17:44:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":307373,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8842062/v1/a562705e-d85c-4c91-8daf-e15766f16e65.pdf"},{"id":108635345,"identity":"2e32905d-3eb0-4cce-b80e-d072cc8e88d5","added_by":"auto","created_at":"2026-05-06 17:44:48","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":20009,"visible":true,"origin":"","legend":"","description":"","filename":"GCSFSupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8842062/v1/94b684aa730be15f369b2d02.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Granulocyte Colony-Stimulating Factor Use in Pregnant Women with Cancer Requiring Chemotherapy","fulltext":[{"header":"Background","content":"\u003cp\u003eApproximately 1 in 1,000 pregnancies are complicated by cancer. Oncologists and obstetricians face the challenge of providing maternal treatment while minimizing fetal risks [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In many cases, delaying chemotherapy until after childbirth is not optimal for the mother\u0026rsquo;s health, and instead choosing an elective premature birth can pose additional health risks to the newborn [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Fortunately, long-term follow up of children exposed in utero to chemotherapy for maternal cancer have been reassuring [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Whenever possible, treatment should mimic regimens offered to non-pregnant patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Granulocyte-colony stimulating factors (G-CSF), such as Neupogen (Filgrastim) or Neulasta (Pegfilgrastim), are commonly prescribed to non-pregnant patients receiving chemotherapy to enhance immunity, lower the risk of infection, or for prophylaxis against febrile neutropenia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. When chemotherapy is given during pregnancy, G-CSF may be important for the treatment or prevention of neutropenic fever and susceptibility to infections, which can potentially affect the fetus in utero [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Concerns about using G-CSF mobilizers during pregnancy may affect chemotherapy regimen choice or treatment intervals offered during pregnancy. The findings herein will better support clinical decision-making for obstetricians, oncologists and patients when discussing chemotherapy choices for a particular cancer during pregnancy. This is especially helpful for physicians who would otherwise offer dose-dense regimens to patients with breast cancer. The use of dose dense chemotherapy to treat breast cancer in pregnancy has been reported in small numbers without maternal or fetal complications [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], but if more safety data were published regarding the use of G-CSF in pregnancy we believe this option could be offered to more women in pregnancy if clinically indicated.\u003c/p\u003e \u003cp\u003eIn a previous study by the senior author in 2012, the use of G-CSF agents was reported in 34 of 176 patients receiving chemotherapy during pregnancy [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. There were no significant differences in neonatal outcomes or anomalies in newborns born to pregnant patients receiving G-CSF with chemotherapy versus chemotherapy alone. In 2020 we surveyed 273 oncologists treating pregnant women with chemotherapy in the Cancer and Pregnancy Registry about their views on prescribing G-CSF during pregnancy. We learned that 20% of oncologists withheld G-CSF due to pregnancy alone. Given the increasing use of dose-dense chemotherapy for breast cancer in non-pregnant women, we aim to publish safety data on the use of G-CSF in pregnancy so that pregnant women with breast cancer could also be offered this option if clinically indicated. We have accumulated more than double the number of mother/infant pairs exposed to G-CSF from our prior study.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData and Study Design\u003c/h2\u003e \u003cp\u003eThe Cancer and Pregnancy Registry was created in 1997 to collect multicenter information about the diagnosis and treatment of cancer during pregnancy, the survival of women diagnosed with cancer while pregnant, and the long-term neurodevelopment and medical health of their newborns. The Cancer and Pregnancy Registry is a Clinical Trials.gov study (NCT 02749474 || 2016-04-13). A unique factor about the Cancer and Pregnancy Registry is the prospective nature of the data collection from multiple centers. Additionally, pregnant women enroll at the time of a cancer diagnosis, before the outcome of the pregnancy is known, reducing bias that only optimal or only suboptimal pregnancy and neonatal outcomes are reported. The researchers maintain annual communication with the pediatricians for each child's follow-up. As of June 2023, 583 patients consented to be enrolled in the Registry from four different world continents. This created a prospective cohort beginning in 1997 and this current study includes data through June 2023.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Variables\u003c/h3\u003e\n\u003cp\u003eResearchers identified patients treated with chemotherapy during pregnancy and classified patients into two groups: those receiving granulocyte colony-stimulating factors (G-CSF) with at least one of their chemotherapy courses (exposed). Primary outcomes of this study include newborn health in the neonatal period and early childhood. Specifically, variables include neutropenia or leukopenia at birth, birthweight percentile and incidence of fetal growth restriction or anomalies at birth, and a diagnosis of asthma, eczema, allergies, or other medical conditions and any behavioral conditions identified during childhood follow up. Neutropenia was defined as an absolute neutrophil count (ANC) of \u0026lt;\u0026thinsp;1000 per microliter from a complete blood count (CBC) obtained at the time of delivery or on day one of life. Leukopenia was defined as WBC\u0026thinsp;\u0026lt;\u0026thinsp;5,000 cells/L. Birth percentile was determined using \u003cem\u003egestation.net\u003c/em\u003e centile calculator which accounts for the infant\u0026rsquo;s sex, gestational age at birth, maternal parity, height and weight at first prenatal visit, and ethnicity. Intrauterine growth restriction is defined as birth percentile\u0026thinsp;\u0026lt;\u0026thinsp;10% for gestational age. Reportable Congenital Anomalies were determined by the Metropolitan Atlanta Congenital Defects Program. Pediatricians were contacted annually to inquire about any medical conditions, or behavioral issues (attention deficit disorder, attention deficit hyperactivity disorder, anxiety, Asperger\u0026rsquo;s or autism spectrum disorder, obsessive compulsive disorder, oppositional defiant disorder, tic disorder or social skill impairment).\u003c/p\u003e \u003cp\u003eSecondary outcomes concern the mothers\u0026rsquo; complications during pregnancy. As only two patients in the database to date have received Udenyca (Pegfilgrastim-cbqv) and Zarxio (Filgrastim-sndz), we limited this current report to only those who received either Filgrastim or Pegfilgrastim during pregnancy. Oncologic and obstetric variables collected for the mothers include the type of cancer, gestational age at first chemotherapy treatment and at delivery; the incidence of any pregnancy complications, and the presence of maternal neutropenia during treatment. Researchers noted whether G-CSF were used prophylactically or as treatment after the development of maternal neutropenia.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAll the above-mentioned variables were summarized as count (%) and mean (SD) and compared between the exposed and unexposed groups using two sample t-test or Wilcoxon rank sum test for continuous variables and chi-square test or Fisher exact test for categorical variables. All analyses were done using SAS 9.4 (SAS Institute, Inc., Cary, NC). A two-sided p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy participants\u003c/h2\u003e \u003cp\u003eOf 583 women enrolled in the Cancer and Pregnancy Registry, 367 pregnant patients with singleton gestations received chemotherapy during pregnancy and were included in this analysis. Most were diagnosed with a primary cancer during pregnancy, most commonly breast cancer; 11 were diagnosed with recurrent disease.Eighty-five women, including the original 34 reported previously, received Filgrastim or Pegfilgrastim (G-CSF) during pregnancy. Demographic characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Mean maternal age, race, and country of origin did not differ significantly between exposed and unexposed groups, with the exception of the \u0026ldquo;other\u0026rdquo; race category, which was less frequent in the unexposed group (p\u0026thinsp;=\u0026thinsp;0.02). For the overall cohort, mean (\u0026plusmn;\u0026thinsp;SD) maternal age at cancer diagnosis was 32.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.9 years, and mean gestational age at diagnosis was 14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 weeks.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1: Demographic characteristics of pregnant women receiving chemotherapy with or without G-CSF\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 90px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOverall (n=367)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eExposed\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(G-CSF\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003en=85)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 147px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnexposed\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;(n=282)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at diagnosis, Mean \u0026plusmn; SD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e34 \u0026plusmn; 7.4 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e34 \u0026plusmn; 5.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e34 \u0026plusmn; 5.0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e0.69\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRace/Ethnicity, n (%)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; White\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; African American\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Asian\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Other\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Unknown\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e279 (76)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (6)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (6)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (8)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58 (68)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (6)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (2)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (14)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e216 (77)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (6)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (7)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (6)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.12\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.94\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.11\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.02\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.96\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 204px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCountry\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; United States\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Canada\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Other (Eng, Aus, Thai)*\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Unknown\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 90px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e348 (95)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (4)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (1)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (0.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e77 (91)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (1)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 147px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e264 (94)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (4)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (1)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.34\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.22\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.27\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.07\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Eng = England, Aus = Australia, Thai = Thailand\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eG-CSF\u0026ndash; granulocyte colony-stimulating factors\u003c/p\u003e\n\u003cp\u003eSD \u0026ndash; standard deviation\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes cancer types and G-CSF use. Breast cancer was the most common diagnosis, including 47 women treated with dose-dense chemotherapy. Patients with breast cancer were more likely to receive G-CSF compared with patients with other cancer types (80% vs 20%, p\u0026thinsp;=\u0026thinsp;0.04). Other malignancies included Hodgkin and non-Hodgkin lymphoma, acute leukemia, choriocarcinoma, and cancers of the cervix, bladder, bone, colon, gallbladder, nasopharynx, rectum, lung, ovary, and pancreas.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCancer types and G-CSF use among pregnant women receiving chemotherapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer Diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e#Patients receiving Chemotherapy (n\u0026thinsp;=\u0026thinsp;367)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e#Patients receiving Filgrastim/Pegfilgrastim (85)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreast (premenopausal)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDose-dense\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003cp\u003eConventional\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003cp\u003e● Unclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e261\u003c/p\u003e \u003cp\u003e47\u003c/p\u003e \u003cp\u003e214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (42 F, 22 P, 4 Both)\u003c/p\u003e \u003cp\u003e30 (9F, 19P, 2 Both)\u003c/p\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e38 (13F, 23P, 2 Both)\u003c/p\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHodgkin\u0026rsquo;s Lymphoma\u003c/b\u003e\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2F, 2P)\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-Hodgkin\u0026rsquo;s Lymphoma\u003c/b\u003e\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003cp\u003e● Unclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (4F, 4P)\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOvarian\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCervical\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAcute Leukemia\u003c/b\u003e\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2F, 1P)\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLung\u003c/b\u003e\u003c/p\u003e \u003cp\u003e● Prophylactic\u003c/p\u003e \u003cp\u003e● Therapeutic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1P)\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMiscellaneous\u003c/b\u003e\u003c/p\u003e \u003cp\u003e● Unclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (P \u0026ndash; Bone cancer)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e:\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e367\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (34F, 45P, 4 Both)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eF\u0026thinsp;=\u0026thinsp;Filgrastim, P\u0026thinsp;=\u0026thinsp;Pegfilgrastim, Both =\u0026thinsp;combination of Filgrastim and Pegfilgrastim\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMaternal outcomes\u003c/h2\u003e \u003cp\u003ePregnancy outcomes and maternal complications are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Overall, 70/367 (19%) pregnancies resulted in spontaneous preterm delivery or preterm premature rupture of membranes (PPROM), with no significant difference between groups (20% exposed vs 19% unexposed, p\u0026thinsp;=\u0026thinsp;0.80). Elective iatrogenic preterm births were excluded from this comparison.Gestational diabetes mellitus and preeclampsia were the most common maternal complications. Less frequent complications included placenta previa, placental abruption, pyelonephritis, chorioamnionitis, oligohydramnios, and thromboembolism. The overall incidence of maternal complications did not differ between exposed and unexposed groups (31% vs 28%, p\u0026thinsp;=\u0026thinsp;0.69).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePregnancy and Delivery Data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;367)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eG-CSF exposed (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eG-CSF not given (n\u0026thinsp;=\u0026thinsp;282)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at first treatment, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal pregnancy complications, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e106 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm delivery from spontaneous rupture or PPROM, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eG-CSF \u0026ndash; granulocyte colony-stimulating factors\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD \u0026ndash; standard deviation\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePPROM \u0026ndash; preterm premature rupture of membranes\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFifteen women developed an infection during chemotherapy. Two were receiving G-CSF at the time of infection; only one of these patients was neutropenic when infection was diagnosed. Overall, maternal neutropenia occurred in 28/367 (7.7%) women receiving chemotherapy. Three women receiving prophylactic G-CSF developed neutropenia (3/57, 5%), compared with 25 women who did not receive prophylactic G-CSF (25/310, 8%); this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.59).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFetal and neonatal outcomes\u003c/h3\u003e\n\u003cp\u003eMean gestational age at delivery for the cohort was 36.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 weeks and did not differ between the exposed (36.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 weeks) and unexposed groups (36.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 weeks; p\u0026thinsp;=\u0026thinsp;0.38). Mean birthweight was also similar between groups (2,610\u0026thinsp;\u0026plusmn;\u0026thinsp;539 g exposed vs 2,720\u0026thinsp;\u0026plusmn;\u0026thinsp;588 g unexposed; p\u0026thinsp;=\u0026thinsp;0.13).Fetal growth restriction occurred in 81/367 (22%) neonates: 25/85 (29%) in the exposed group and 56/282 (20%) in the unexposed group (p\u0026thinsp;=\u0026thinsp;0.06; Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNewborn and Pediatric Follow-Up Data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;367)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eG-CSF exposed (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eG-CSF not given (n\u0026thinsp;=\u0026thinsp;282)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eNewborn Data\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD grams\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2694\u0026thinsp;\u0026plusmn;\u0026thinsp;578.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2610\u0026thinsp;\u0026plusmn;\u0026thinsp;539.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2720\u0026thinsp;\u0026plusmn;\u0026thinsp;588.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal Growth restriction n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications at birth, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth defects, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal Leukopenia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal Neutropenia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePediatric Follow-Up\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBehavioral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEczema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAllergic Rhinitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eG-CSF \u0026ndash; granulocyte colony-stimulating factors; SD \u0026ndash; standard deviation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA neonatal complete blood count at birth or on day 1 of life was available for 178 neonates (47 exposed, 131 unexposed). Neutropenia was present in 3/47 (6%) exposed neonates and 7/131 (5%) unexposed neonates (p\u0026thinsp;=\u0026thinsp;0.73). Leukopenia occurred in 1/47 (2%) exposed and 3/131 (2%) unexposed neonates (p\u0026thinsp;=\u0026thinsp;1.00). Among the 10 neonates with neutropenia, the mean interval between the final chemotherapy cycle and delivery was 3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.0 weeks, with half born within four weeks of maternal chemotherapy.\u003c/p\u003e \u003cp\u003eImmediate neonatal complications, most commonly hyperbilirubinemia, apnea, hypoglycemia, and respiratory distress, occurred in 14/85 (16%) exposed neonates and 51/282 (18%) unexposed neonates (p\u0026thinsp;=\u0026thinsp;0.73).\u003c/p\u003e \u003cp\u003eCongenital anomalies were identified in 11/85 (13%) exposed and 22/282 (8%) unexposed neonates (p\u0026thinsp;=\u0026thinsp;0.15). Ureteropelvic junction obstruction was the most common anomaly (four exposed, four unexposed). Multiple hemangiomas were the second most frequent anomaly and occurred only in the unexposed group. No patients received chemotherapy during the first trimester (Supplemental Table\u0026nbsp;1).\u003c/p\u003e \u003cp\u003ePediatric follow-up data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Medical conditions, most commonly asthma, eczema, and allergic rhinitis, were reported in 26/85 (31%) exposed children and 75/282 (27%) unexposed children (p\u0026thinsp;=\u0026thinsp;0.47). Behavioral diagnoses did not differ significantly between groups.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWhen cancer is diagnosed during pregnancy, termination has not been shown to improve maternal survival [\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Studies comparing pregnant women with cancer to age- and stage-matched non-pregnant controls demonstrate similar oncologic outcomes when comparable therapies are administered [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Long-term follow-up studies of children exposed in utero to chemotherapy administered after the first trimester have been reassuring, with neurodevelopmental outcomes largely influenced by gestational age at delivery rather than chemotherapy exposure itself [\u003cspan additionalcitationids=\"CR3 CR4\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite these data, chemotherapy regimens offered during pregnancy may differ from those used in non-pregnant patients, particularly with respect to dose-dense protocols requiring G-CSF support. Anecdotal reports from patients with breast cancer in our cohort suggest that dose-dense chemotherapy would have been offered outside of pregnancy, highlighting ongoing clinician hesitancy regarding G-CSF use during gestation. Our findings provide additional evidence to inform discussions surrounding chemotherapy optimization during pregnancy.\u003c/p\u003e \u003cp\u003eIn this prospective cohort of 85 pregnancies exposed to G-CSF during chemotherapy, no statistically significant differences were observed in maternal, obstetric, neonatal, or pediatric outcomes compared with women treated with chemotherapy alone. Outcomes evaluated included gestational age at delivery, birthweight, fetal growth restriction, preterm delivery, neonatal complications, congenital anomalies, and hematologic abnormalities. Neonatal neutropenia and leukopenia were uncommon and occurred at similar rates in both exposure groups. Consistent with prior literature, neonates with hematologic abnormalities were more frequently delivered within three to four weeks of the final maternal chemotherapy cycle [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMaternal complications, including infection and neutropenia, were also comparable between groups. Although neutropenia occurred in a small proportion of women receiving prophylactic G-CSF, the overall incidence did not differ significantly from women who did not receive prophylactic support. These findings align with prior reports describing the safety of G-CSF use during pregnancy, including smaller retrospective studies and registry-based analyses [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study expands on existing literature by including a larger number of exposed pregnancies, a prospectively collected control group, and long-term pediatric follow-up. The prospective design of the Cancer and Pregnancy Registry minimizes selection bias and allows for systematic longitudinal assessment of offspring health.\u003c/p\u003e \u003cp\u003eSeveral limitations warrant consideration. Neonatal complete blood counts were not uniformly obtained across all participating centers, limiting the assessment of neonatal hematologic outcomes. Additionally, the relatively low incidence of many outcomes restricts statistical power to detect small differences. While this study focused on Filgrastim and Pegfilgrastim, continued data collection is ongoing for biosimilar G-CSF.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eabsolute neutrophil count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecomplete blood count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFGR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efetal growth restriction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCSF-granulocyte colony-stimulating factors\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGDM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egestational diabetes mellitus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePPROM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epremature rupture of membranes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eCreation and maintenance of the Registry was approved by the Office of Research \u0026amp; Sponsored Programs \u0026ndash; Division of Research Integrity, Institutional Review Board at Cooper University Healthcare. The IRB approval/reference number is 15-028. All enrolled patients provided informed consent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author, AB, upon reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eEC conceived and designed the study. AB collected the data, and JD and JG performed statistical analysis and interpreted the results. EC and AB drafted the manuscript, and all authors critically revised it for important intellectual content. All authors approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors thank Audrey Ross, research assistant, for assistance with the article submission process.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCardonick E. Pregnancy-associated breast cancer: optimal treatment options. Int J Womens Health. 2014;6:935\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/IJWH.S52381\u003c/span\u003e\u003cspan address=\"10.2147/IJWH.S52381\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmant F, Van Calsteren K, Halaska M, Gziri M, Hui W, Lagae L, et al. 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Cancers (Basel). 2021;13(6):1214. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cancers13061214\u003c/span\u003e\u003cspan address=\"10.3390/cancers13061214\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pregnancy, Cancer, Chemotherapy, Granulocyte colony-stimulating factors, Neonatal outcomes, Pregnancy complications","lastPublishedDoi":"10.21203/rs.3.rs-8842062/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8842062/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCancer complicates approximately 1 in 1,000 pregnancies. Chemotherapy can be safely administered after the first trimester; however, limited safety data on in utero exposure to granulocyte-colony stimulating factors (G-CSF) may influence chemotherapy regimens offered during pregnancy. This study evaluates neonatal and maternal outcomes following G-CSF exposure during pregnancy and examines the incidence of maternal neutropenia among women receiving chemotherapy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a prospective cohort study using data from the Cancer and Pregnancy Registry (1997\u0026ndash;2023). Outcomes were compared between pregnant women receiving chemotherapy with G-CSF and those receiving chemotherapy alone. Primary neonatal outcomes included birthweight, fetal growth restriction (FGR), neutropenia or leukopenia at birth, congenital anomalies, and pediatric medical conditions. Maternal outcomes included neutropenia and pregnancy complications.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 367 pregnant women receiving chemotherapy, 85 received G-CSF. Mean maternal age at diagnosis was 32.7 years, and mean gestational age at diagnosis was 14 weeks. Breast cancer was the most common diagnosis, and patients with breast cancer were more likely to receive G-CSF than those with other malignancies (p\u0026thinsp;=\u0026thinsp;0.04). No significant differences were observed between exposed and unexposed groups in birthweight (2,610 g vs 2,720 g; p\u0026thinsp;=\u0026thinsp;0.13), FGR (29% vs 20%; p\u0026thinsp;=\u0026thinsp;0.06), neonatal complications (16% vs 18%; p\u0026thinsp;=\u0026thinsp;0.73), congenital anomalies (13% vs 8%; p\u0026thinsp;=\u0026thinsp;0.15), neonatal leukopenia (2% vs 2%; p\u0026thinsp;=\u0026thinsp;1.00), neutropenia (6% vs 5%; p\u0026thinsp;=\u0026thinsp;0.73), or pediatric medical conditions (31% vs 27%; p\u0026thinsp;=\u0026thinsp;0.47). Maternal neutropenia occurred in 7.7% of women overall, with no significant difference between those receiving G-CSF and those who did not (p\u0026thinsp;=\u0026thinsp;0.59).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eExposure to G-CSF during chemotherapy in pregnancy was not associated with adverse maternal, neonatal, or pediatric outcomes.\u003c/p\u003e\u003ch2\u003eTrial Registration\u003c/h2\u003e \u003cp\u003eClinicalTrials.gov (NCT02749474), registered April 21, 2016. Retrospectively registered.\u003c/p\u003e","manuscriptTitle":"Granulocyte Colony-Stimulating Factor Use in Pregnant Women with Cancer Requiring Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-06 17:44:40","doi":"10.21203/rs.3.rs-8842062/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-11T23:18:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"307358458973947408611040308430001688203","date":"2026-05-11T08:52:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299367026431483514777731605536806805350","date":"2026-05-01T23:44:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70008626415952054579461238624084433949","date":"2026-05-01T01:42:46+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-28T11:02:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-26T22:11:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-09T10:18:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-26T17:03:10+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-03-26T16:57:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4439ede8-6db1-43c7-9aa9-e2d708023bb4","owner":[],"postedDate":"May 6th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-11T23:18:07+00:00","index":70,"fulltext":""},{"type":"reviewerAgreed","content":"307358458973947408611040308430001688203","date":"2026-05-11T08:52:48+00:00","index":69,"fulltext":""},{"type":"reviewerAgreed","content":"299367026431483514777731605536806805350","date":"2026-05-01T23:44:24+00:00","index":47,"fulltext":""},{"type":"reviewerAgreed","content":"70008626415952054579461238624084433949","date":"2026-05-01T01:42:46+00:00","index":46,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T17:44:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-06 17:44:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8842062","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8842062","identity":"rs-8842062","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}