Influence of cancer in pregnancy on obstetric and neonatal outcomes: An observational retrospective cohort study

Influence of cancer in pregnancy on obstetric and neonatal outcomes: An observational retrospective cohort study | 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 Influence of cancer in pregnancy on obstetric and neonatal outcomes: An observational retrospective cohort study Xuan Huang, Chen Zhang, Jialei Zhu, Yueyan Li, Jing Tang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1638132/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Thus far, no large-scale clinical study on pregnancy with cancer has been conducted in China. Therefore, the present study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers, and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management in pregnancy-associated cancer. Methods: We conducted an observational retrospective cohort study among pregnant patients with cancer in 7 Chinese tertiary A hospitals during 2003–2021. We conducted multiple logistic regression to determine the influence of various factors on preterm birth and small-for-gestational-age infants, log-binomial regression to analyze temporal changes, and chi-square tests to explore the effects of cancer type/treatment. Results: Of 204 women, 17% terminated their pregnancies; 59% received pre-delivery treatment. Every 6 years, the rates of pregnancy termination ([RR]: 0.48, 95% confidence interval [CI]: 0.35–0.67) and iatrogenic preterm births (RR: 0.73, 95% CI: 0.54–0.98) reduced, and that of pre-delivery treatment increased, mainly due to increased rates of surgery (RR: 1.87, 95% CI: 1.31–2.67). Maternal systemic diseases were related to a higher risk of small-for-gestational-age infants ([OR]: 12.02, 95% CI: 1.82–79.43). Chemotherapy with taxanes plus platinum-based agents was related to adverse obstetric outcomes (OR: 1.87, 95% CI: 1.42–2.46, P < 0.05). Thyroid (OR: 0.36, 95% CI: 0.22–0.57) and ovarian cancer (OR: 0.70, 95% CI: 0.50–0.98) were associated with fewer cesarean sections. Thyroid cancer was associated with fetal growth restriction (OR: 5.21, 95% CI: 1.21–22.55). Conclusions: Rates of pregnancy termination in cancer have declined. Taxane plus platinum-based chemotherapy was associated with adverse obstetric outcomes. Cancer type influenced outcomes. Retrospective Studies Cohort Studies Pregnancy Complications Neoplastic Antineoplastic Agents Figures Figure 1 Figure 2 1 Introduction It has been estimated that one in every one thousand women will be diagnosed with cancer during pregnancy. 1 In recent years, with the postponement of childbirth to later ages, the adjustment of the fertility policy in China, and the onset of cancer at younger ages, the incidence of cancer during pregnancy has increased. 2 The diagnostic work-up for cancer, such as the detection of tumor markers, may be affected by the physiology of pregnancy. 3 Furthermore, the implementation of diagnostic surgical procedures during pregnancy is often rendered challenging due to safety concerns. Approximately 20–30% of cancer cases in women occur prior to the age of 45, which has a severe impact on future fertility and pregnancy management. 4 The most common malignant tumors during pregnancy are breast cancer, melanoma, hematological cancers, and cervical cancer; 1 among these, breast cancer has the highest incidence, 5 and accounts for 39% of all malignant tumors during pregnancy. The type of cancer can also have an impact on obstetric and neonatal outcomes; for example, patients diagnosed with melanoma have a significantly increased risk of death during pregnancy, while patients diagnosed with breast or ovarian cancer have a significantly increased risk of death during lactation. 6 – 8 The treatment of cancer in pregnancy complicates clinical decision-making. 2 For instance, pregnant women with cancer may need to choose between continuing or terminating the pregnancy. In general, cancer and its treatment are considered to have adverse effects on women’s fertility. Current medical practice attempts, where possible, to retain reproductive function. 9 Fortunately, the oncological and obstetric prognoses of patients who receive cancer treatment during pregnancy are relatively good, though termination of pregnancy is usually recommended for such patients. Up to 44% of gynecologists tend to terminate the pregnancy, and 37% of women do not undergo chemo- or radiotherapy during pregnancy. 10 Therefore, iatrogenic preterm birth is the most common obstetric complication of cancer in pregnancy. 11 , 12 With advances in research and the optimization of therapeutic regimens for cancer, it is increasingly becoming possible to treat cancer during pregnancy as well as protect the fetus and the mother from adverse effects as much as possible. Although life-saving cancer treatments for pregnant women seem to conflict with the interests of the developing fetus, termination of pregnancy has not been shown to improve the prognosis of pregnant women in any type of cancer. 13 Several recent studies have recommended that cancer treatment during pregnancy should be as similar as possible to the treatment of non-pregnant women and that preterm birth should be avoided; however, radiotherapy is still recommended to be postponed until after delivery, and chemotherapy should be postponed until the second trimester. 14 With the continual improvements in cancer therapy during pregnancy, the rates of survival and iatrogenic premature births have been observed to improve every 5 years. 15 Currently, it is accepted that surgery and chemotherapy are relatively safe during pregnancy, while radiotherapy is relatively contraindicated. The existing research shows that chemotherapy from the second trimester does not impact the growth and development of newborns or cause obvious long-term complications. 13 , 16 , 17 However, other studies have reported that chemotherapy during pregnancy is associated with fetal adverse events. 15 Many organizations have provided recommendations on conception for women with cancer, but warn that more evidence is needed, 17 as the precise impact of different tumors and anti-tumor treatment regimens on the mother and fetus remains to be elucidated. Due to this gap in clinical evidence, oncological management during pregnancy remains challenging for both patients as well as gynecologists, oncologists, and obstetricians. Thus far, no large-scale clinical study on pregnancy with cancer has been conducted in China. Therefore, the present study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers, and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management in pregnancy-associated cancer. 2 Patients And Methods 2.1 Study design and participants This descriptive retrospective cohort study analyzed data from pregnant women who were diagnosed with cancer and registered in 11 centers from 7 provinces of China. The core study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100044292; ongoing), and approved by the ethics committee of the Obstetrics & Gynecology Hospital of Fudan University (approval number: 2020 − 130). The inclusion criteria were pregnant patients aged 18–45 years with primary invasive cancer or borderline ovarian cancer who were admitted to one of the 11 centers between 1st January 2003 and 2nd February 2021. All subjects voluntarily participated in the study and provided written informed consent. All participants were diagnosed on the basis of pathological evidence. Patients with pre-invasive disease or postpartum diagnosis, those with primary invasive cancer or borderline ovarian cancer diagnosed after delivery, and those who had received high-dose scatter radiation to the pelvis or brain before delivery were excluded. We designed a questionnaire to collect detailed oncological, obstetric, and neonatal data. All participating centers received an online electronic questionnaire, and each center collected the required data from its electronic medical record system. The data from all centers were then consolidated and aggregated by the authors. 2.2 Definitions Systemic disease was defined as maternal hypertensive disorders, cardiac disease, hypothyroidism, gestational diabetes, and gestational anemia. Pre-delivery surgery was defined as any therapeutic or palliative surgical procedure for cancer performed after the diagnosis of cancer and prior to delivery (or termination of pregnancy). Similarly, pre-delivery chemotherapy was defined as chemotherapy administered at any time from the cancer diagnosis to the delivery (or termination of pregnancy). Miscarriage was defined as the loss of a baby before the 20th week of gestation, while stillbirth was defined as the loss of a baby at or after 20 weeks of gestation. Preterm pre-labor rupture of membranes (PPROM) was defined as the preterm rupture of membranes without contractions, and was diagnosed by the local centers. Small for gestational age (SGA) was defined as a birth weight less than the 10th percentile, as calculated according to the Chinese neonatal birth weight curve for different gestational ages. 18 Preterm birth was defined as delivery before 37 completed weeks of gestation. Iatrogenic preterm birth was defined as preterm cesarean delivery without labor. Low birth weight (LBW) and fetal macrosomia were defined as birth weights of 4000 g, respectively. 2.3 Statistical analysis We aggregated the oncological, obstetric, and neonatal data, and provided descriptive statistics for these data. Age at pregnancy was grouped into 8-year intervals as follows: 21–28, 29–36, and 37–45 years. Multiple logistic regression models were used to analyze the effects of the following factors on premature birth and birth of SGA infants: maternal age, year of last menstrual period (LMP), gestational period (in terms of trimesters) at the time of cancer diagnosis, cancer type, treatment method, and maternal complications during pregnancy. The results were reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). P values were used to measure the strength of the evidence against the null hypothesis of no relationship. The study data spanned an 18-year period, and were divided into the following three 6-year intervals according to the year in which the LMP occurred: 2003–2008, 2009–2014, and 2015–2020. Log-binomial regression models were used to analyze the average changes in patient characteristics, tumor types, treatment before delivery, and maternal complications, with year of diagnosis as a continuous predictor. The results were presented as relative risks (RRs) and 95% CIs. Considering the limited sample size, the number of independent variables, and the limited correlation between independent variables, we chose to use chi-square tests to directly study the relationship between two variables. Chi-square tests (one-tailed) were performed to assess the influence of cancer type and pre-delivery chemotherapy on maternal complications, and obstetric and neonatal outcomes. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM, Armonk, NY, USA). P values of less than 0.05 were considered statistically significant. 3 Results 3.1 General information In all, 204 women (Fig. 1 ) registered in 7 tertiary A hospitals were eligible for this study. A tertiary A hospital is the highest classification grade for hospitals in mainland China and represents a large general hospital. Some tertiary A hospitals have more than 20,000 outpatient visits per day. 19 Of these, 35 (17%) women chose to terminate their pregnancies by surgery or drugs, and 119 (59%) women received antenatal treatment for cancer. The baseline characteristics of the patients are shown in Table 1 , and the distribution of cancer types is shown in Fig. 2 . Patient characteristics stratified by cancer type are shown in Supplementary Table S1 . Table 1 Patient characteristics Patient characteristic n (%) Age at the time of pregnancy, median (IQR, range), years 28 (28–35, 21–43) Timing of cancer diagnosis Before pregnancy 88/204 (43) First trimester 20/204 (10) Second trimester 40/204 (20) Third trimester 45/204 (22) Unknown 11/204 (5) Year of LMP 2003–2008 15/204 (7) 2009–2014 36/204 (18) 2015–2020 153/204 (75) Pre-delivery treatment No treatment 83/202 (41) Surgery 112/202 (55) Chemotherapy 28/202 (14) Taxanes 15/202 (7) Platinum 12/202 (6) Anthracyclines 6/202 (3) Non-platinum alkylating agents 6/202 (3) Antimetabolites 5/202 (2) Other 1/202 (0) Radiotherapy 4/202 (2) Targeted therapy and hormone therapy 7/202 (3) Obstetric complications Any 118/201 (59) Hypertensive disorders 16/201 (8) Gestational diabetes 18/201 (9) Gestational anemia 16/201 (8) Maternal cardiac disease 6/201 (3) Intestinal obstruction 3/201 (1) Liver disease 5/201 (2) Maternal infection 18/201 (9) PPROM 18/201 (9) Fetal distress 6/201 (3) Fetal growth restriction 7/201 (3) Oligohydramnios 6/201 (3) Neonatal outcomes Iatrogenic preterm delivery 49/144 (34) Spontaneous preterm delivery 7/144 (5) Apgar score < 7 at 5 min 5/137 (4) Small-for-gestational-age 17/143 (12) Low birth weight 43/143 (30) Macrosomia 7/143 (5) Neonatal complications NICU admission 18/143 (13) Neonatal acidosis 10/143 (7) Respiratory acidosis 8/143 (6) Congenital malformations 6/143 (4) Neonatal respiratory distress syndrome 27/143 (19) Neonatal infection 7/143 (5) Neonatal hyperbilirubinemia 28/143 (20) Neonatal hypoglycemia 4/143 (3) Neonatal hyperglycemia 4/143 (3) IQR, interquartile range; LMP, last menstrual period; PPROM, preterm pre-labor rupture of membranes; NICU, neonatal intensive care unit 3.2 Obstetric and neonatal complications and neonatal outcomes Of the 204 eligible women, 201 patients had records of pregnancy-related complications. In total, 118 (59%) women developed pregnancy-related complications. The most common complications were gestational diabetes (9%), gestational maternal infection (9%), and PPROM (9%). The most common obstetric outcome was preterm birth (39%), and the most common neonatal comorbidity was neonatal hyperbilirubinemia (19%). Congenital defects were observed in 6 (4%) newborns or aborted fetuses (Supplementary Table S2 ). Of the 204 patients included in the study, the majority (147, 72%) were from the Obstetrics & Gynecology Hospital of Fudan University. We recorded the total number of pregnant women who received antenatal care at this hospital between January 1, 2003 and December 31, 2021. We also noted the incidence of pregnancy-related complications, neonatal complications, and obstetric events, such as caesarean section, among these patients, as provided by the Information Department of the hospital (Supplementary Tables S3 and S4 ). We performed chi-square analyses (one-tailed) of the data of all 204 pregnant women with cancer included in this study and the data of all pregnant women from the Obstetrics & Gynecology Hospital of Fudan University. All pregnant women from the Obstetrics & Gynecology Hospital of Fudan University during the study period were taken as the reference group. Compared with all pregnant women, pregnant women with cancer had a significantly higher risk of maternal hypertension (OR: 2.18, 95% CI: 1.37–3.46, P < 0.05), heart disease (OR: 35.72, 95% CI: 14.87–85.81, P < 0.05), intestinal obstruction (OR: 105.68, 95% CI: 32.56–342.99, P < 0.001), and liver damage (OR: 4.19, 95% CI: 1.77–9.92, P < 0.05) during pregnancy as well as fetal intrauterine growth restriction (OR: 17.23, 95% CI: 8.31–35.71, P < 0.001). Compared to women without cancer, those with cancer had with a significantly higher incidence of cesarean section (OR: 4.54, 95% CI: 4.02–5.12, P < 0.001), preterm birth (OR: 8.28, 95% CI: 6.75–10.18, P < 0.001), LBW (OR: 6.39, 95% CI: 4.98–8.19, P < 0.001), and fetal macrosomia (OR: 5.2, 95% CI: 2.54–10.64, P < 0.001). Cancer in pregnancy was also associated with a significantly increased likelihood of neonatal acidosis (OR: 2.85, 95% CI: 1.57–5.18, P < 0.05), birth defects (OR: 3.83, 95% CI: 1.75–8.4, P < 0.01), and neonatal respiratory distress (OR: 10.26, 95% CI: 7.29–14.45, P < 0.001). The results of this chi-square analysis are shown in Supplementary Table S5 . Since only the pregnancy data from the Obstetrics & Gynecology Hospital of Fudan University were used instead of data from all centers, these results are for reference only. 3.3 Cancer treatments Of the 204 women, 119 (59%) women received treatment for cancer before the termination of pregnancy, and of these 121 women, 73 (60%) women were treated using a single treatment modality, 53 (42%) women underwent surgery alone, and 5 (2%) women were treated using chemotherapy alone (Supplementary Table S6 ). Among the 28 patients who received a combination of different treatment modalities, 19 (9%) patients received a combination of surgery and chemotherapy, and 2 (1%) received a combination of surgery, chemotherapy, and targeted therapy. Twelve patients received paclitaxel plus platinum-based chemotherapy (TP regimen), and seven patients received epirubicin plus cyclophosphamide chemotherapy (EC regimen). 3.4 Obstetric outcomes Among the 35 women who chose to undergo termination of pregnancy, 19 (53%) terminated their pregnancy in the first trimester, 12 (34%) terminated it in the second trimester, and 2 (6%) terminated in the third trimester; the time of termination of pregnancy was unknown in 2 cases. All 35 women who chose to terminate the pregnancy were between the ages of 24 and 43 years, and 31 of these women were aged 28 years or above. In total, 8 of these women had had a previous pregnancy, and 6 of these 8 had had a previous live birth. Among the 169 women who chose to continue the pregnancy, the pregnancy outcomes of 13 patients were missing. Among the 156 patients with recorded pregnancy outcomes, 144 live births were reported, of which 3 cases (2%) were twin pregnancies, and the others were singleton pregnancies. Among these 156 patients, 10 (6%) had a miscarriage before 20 weeks of gestation, and 2 (1%) patients had a stillbirth after 20 weeks of gestation. The obstetric outcomes stratified by cancer type are shown in Supplementary Table S7 . 3.5 Impact of cancer type on complications and outcomes Univariate analysis using chi-square tests revealed that cancer type significantly affected the obstetric outcome (Table 2 ). Compared with pregnant women with cervical cancer, pregnant women with thyroid cancer (OR: 0.16, 95% CI: 0.06–0.42, P < 0.001), breast cancer (OR: 0.3, 95% CI: 0.13–0.68, P < 0.05), or other cancer types (OR: 0.64, 95% CI: 0.41–1, P < 0.05) had a significantly lower probability of premature delivery of the fetus. No significant relationship was found between cancer type and the occurrence of other obstetric complications. Taking the patients with cervical cancer as the reference group, we found that significantly fewer proportions of patients with thyroid cancer (OR: 0.36, 95% CI: 0.22–0.57, P < 0.001) or ovarian cancer (OR: 0.70, 95% CI: 0.50–0.98, P < 0.05) underwent cesarean section. Among pregnant women with thyroid cancer, the proportion of those who chose fetal preservation was significantly increased relative to the reference group (OR: 1.28, 95% CI: 1.03–1.58, P < 0.05), but the risk of fetal intrauterine growth restriction was also significantly increased (OR: 5.21, 95% CI: 1.21–22.55, P < 0.05). Pregnancy with thyroid cancer (OR: 0.25, 95% CI: 0.09–0.68, P < 0.05), ovarian cancer (OR: 0.33, 95% CI: 0.11–1.02, P < 0.05), or breast cancer (OR: 0.28, 95% CI: 0.09–0.87, P < 0.05) was associated with a lower risk of neonatal respiratory distress syndrome than pregnancy with cervical cancer (Supplementary Table S8 ). Table 2 Chi-square tests (one-tailed) of the most common obstetric outcomes. Premature delivery Small for gestational age OR (95% CI) P OR (95% CI) P Cervical cancer Reference Reference Thyroid cancer 0.16 (0.06–0.42) 0.000 3.22 (0.38–27.28) 0.252 Ovarian cancer 0.87 (0.56–1.34) 0.364 5.8 (0.7–48.13) 0.082 Breast cancer 0.3 (0.13–0.68) 0.001 3.63 (0.4–32.64) 0.237 Other cancer types 0.64 (0.41–1) 0.042 4.26 (0.53–34.45) 0.139 Cases of pregnancy complicated with cervical cancer were taken as the reference group. OR, odds ratio; CI, confidence interval 3.6 Impact of chemotherapy According to the use of chemotherapy drugs before the end of pregnancy (including delivery, miscarriage, and stillbirth), the patients were divided into those who did not receive chemotherapy, those who received treatment with the TP regimen, and those who received treatment with the EC regimen (Table 3 ). Chi-square analyses showed that compared with no chemotherapy before delivery (or miscarriage or stillbirth), the use of the TP regimen during pregnancy was associated with adverse pregnancy outcomes (i.e., preterm birth, miscarriage, stillbirth, and SGA; OR: 1.87, 95% CI: 1.42–2.46, P < 0.05). Table 3 Chi-square tests (one-tailed) of most common obstetric and neonatal complications and obstetric outcomes. TP regimen EC regimen OR (95% CI) P OR (95% CI) P Obstetric complications: any 0.66 (0.41–1.07) 0.142 0.74 (0.38–1.44) 0.344 Preterm birth 0.43 (0.3–0.6) 0.007 1.54 (0.78–3.04) 0.252 Cesarean section delivery 0.74 (0.55–0.99) 0.174 1.13 (0.59–2.17) 0.491 Low birth weight 0.32 (0.21–0.47) 0.001 0.48 (0.24–0.98) 0.112 Small for gestational age 1.09 (0.16–7.27) 0.636 2.49 (0.7–8.87) 0.209 Neonatal complications: any 0.61 (0.29–1.28) 0.221 0.71 (0.29–1.75) 0.379 Adverse obstetric outcomes a 1.87 (1.42–2.46) 0.010 1.78 (1.25–2.53) 0.058 Patients who did not receive chemotherapy before termination of pregnancy were taken as the control group. TP regimen, paclitaxel + platinum; EC regimen, epirubicin + cyclophosphamide. a Adverse obstetric outcomes included miscarriage, stillbirth, preterm birth, and small for gestational age. OR, odds ratio; CI, confidence interval 3.7 Factors influencing obstetric outcomes The results of the multiple logistic regression models are shown in Table 4 . Both the outcome variables and the covariates in these models were prespecified. The key covariates in the models were as follows: patient’s age at admission (stratified into three 8-year ranges), timing of cancer diagnosis (relative to the pregnancy), cancer type, pre-delivery surgery or chemotherapy, year in which the LMP occurred, maternal reproductive system complications (including uterine, placenta, and umbilical cord problems), maternal digestive system complications, and maternal systemic disease. The regression coefficients and standard errors determined using this analysis can be found in Supplementary Table S9 . Pregnant women with cancer as well as systemic diseases (such as hypertension, hyperlipidemia, diabetes, heart disease, and anemia) were more likely to give birth to SGA infants (OR: 12.02, 95% CI: 1.82–79.43). Table 4 Multiple logistic regression analysis of the most common obstetric outcomes Premature delivery Small for gestational age OR (95% CI) P OR (95% CI) P Age at admission (per 8 years) 0.83 (0.23–2.99) 0.772 1.18 (0.3–4.59) 0.811 Timing of cancer diagnosis ·· 0.183 ·· 0.784 Before pregnancy Reference ·· Reference ·· First trimester - ·· - ·· Second trimester 0.05 (0–0.65) ·· 0.73 (0.02–23.99) ·· Third trimester 0.08 (0–1.2) ·· 0.27 (0.02–4.39) ·· Unknown - ·· 0.03 (0–7.88) ·· Cancer type ·· 0.184 0.425 Cervical cancer Reference ·· Reference ·· Thyroid cancer 1.75 (0.19–16.57) ·· 0.08 (0–3.04) ·· Ovarian cancer 128.65 (2.6–6371.76) ·· 2.19 (0.05–105.52) ·· Breast cancer 2.27 (0.15–34.64) ·· 1.02 (0.05–22.18) ·· Other cancer types 5.64 (0.55–57.46) ·· 0.21 (0.01–4.87) ·· Surgery 4.22 (0.4–44.26) 0.230 4.59 (0.5–42.24) 0.179 Chemotherapy 1.13 (0.07–18.11) 0.933 0.08 (0.01–1.23) 0.071 Year of LMP ·· 0.226 ·· 0.741 [2003, 2008] Reference ·· Reference ·· [2009, 2014] - ·· 2.1 (0.02–246.39) ·· [2015, 2020] - ·· 3.52 (0.05–260.03) ·· Reproductive system complications 0.3 (0.06–1.41) 0.126 1.05 (0.21–5.37) 0.952 Digestive system complications - 0.999 0.06 (0–0.9) 0.042 Systemic disease 0.23 (0.05–1.12) 0.068 12.02 (1.82–79.43) 0.010 LMP, last menstrual period; OR, odds ratio; CI, confidence interval 3.8 Changes in cancer treatments and obstetric outcomes over the study period This study reviewed data collected over an 18-year period. We divided the patients into the following 3 subgroups according to the year in which they had their LMP: 2003–2008, 2009–2014, and 2015–2020. The LMP was used as a continuous predictor in the log-binomial regression model. The results are shown in Supplementary Table S10 . Every 6 years, we observed a decrease in the proportion of patients choosing to terminate the pregnancy (RR: 0.48, 95% CI: 0.35–0.67). The proportions of patients who chose termination of pregnancy stratified by cancer type are shown in Supplementary Table S11 . Every 6 years, the likelihood of receiving cancer treatment before delivery was found to increase, mainly due to the increase in the rate of surgery (RR: 1.87, 95% CI: 1.31–2.67). Every 6 years, we observed fewer iatrogenic preterm births on average (RR: 0.73, 95% CI: 0.54–0.98) and more term births (RR: 1.46, 95% CI: 1.00–2.13). 4 Discussion Of the 204 pregnant women with cancer who were eligible for the present study, 35 women decided to terminate their pregnancy. These 35 women were aged between 24 and 43 years, and 31 (89%) of them were aged 28 years or older; in addition, 77% of these women had previously been pregnant and given birth to a live infant. A Chinese population study has reported that the age of Chinese women at first childbirth has gradually increased from 24 years to nearly 28 years between 2006 and 2017. 20 Therefore, it can be inferred that the age of the patients and the previous live birth were important reasons driving the decision to terminate the pregnancy. Preterm birth was the most common obstetric outcome for pregnant women with cancer. Moreover, of the 56 (30%) women who gave birth prematurely in our study, only 7 (12%) gave birth vaginally; the remaining 49 (88%) women underwent cesarean section. This shows that in addition to spontaneous preterm delivery, iatrogenic preterm delivery and artificial early termination of pregnancy are common outcomes among pregnant women with cancer. Nevertheless, it remains to be determined whether the artificial shortening of pregnancy benefits pregnant women or affects the health of their newborns. The timing and specific conditions under which early termination of pregnancy is maximally beneficial to the pregnant woman and her newborn remain a thorny problem of clinical decision-making. In the present study, the incidence of congenital defects among cases of abortions, stillbirths, and live births was approximately 4%, and among live births, the incidence of congenital malformations was 3.5%. According to the China Birth Defect Prevention Report (2012) issued by the National Health Commission of the People’s Republic of China, the incidence of birth defects is significantly higher in rural and remote areas than in urban areas. Compared with the 2012 national report, the present study did not find a high proportion of birth defects among babies born to women with cancer; this is probably because our patients were all from tertiary A hospitals in capital cities, while the national report included women from across the country. We used the birth defect data obtained from all cases of pregnancy in the Obstetrics & Gynecology Hospital of Fudan University as a reference, and found that pregnant women with cancer were more likely to have babies with birth defects (OR: 3.83, 95% CI: 1.75–8.4, P < 0.01). These data may put greater pressure on women with cancer to continue their pregnancies. Further research is required to determine whether it is the physiological changes caused by the cancer itself or the treatments that affect the rate of birth defects. Every 6 years, the proportion of pregnant women with cancer who choose to continue their pregnancy increased. More patients chose to undergo treatment for cancer before delivery, but this was mainly attributable to an increase in pre-delivery surgery rather than pre-delivery chemotherapy, which is not consistent with the results of a European study. 8 The majority of our patients (86%) did not receive chemotherapy prenatally. This indicates that currently, Chinese clinicians may be relatively conservative in regards to chemotherapy during pregnancy. In this study, all of the 10 cervical cancer patients who received chemotherapy before delivery were treated with the TP regimen. In addition, 63% of the 11 breast cancer patients who received chemotherapy before delivery were treated with the EC regimen. This suggests that multidrug regimens are used in the majority of pregnant patients with cancer. However, current studies on the toxicity of chemotherapeutic drugs during pregnancy focus on single-drug chemotherapy. Thus, more research is required to investigate the effects of multi-drug chemotherapeutic regimens during pregnancy. Our study supports the findings that adriamycin, cyclophosphamide, and 5-fluorouracil are relatively safe for fetuses and newborns. 21 We did not find any significant impact of the EC regimen on obstetric outcomes. In previous studies, platinum-based therapy with or without taxanes was recommended for advanced or high-risk cancer during pregnancy. 22 Taxanes have a low potential for placental transfer 21 and low toxicity, and their use is considered feasible in the second and third trimesters. 23 This may partially explain the high proportion of patients treated with the TP regimen before delivery in this study. Our data in this cohort study suggested a relationship between the TP regimen and adverse obstetric outcomes. Another study has also shown that the use of platinum-based chemotherapy drugs is statistically associated with the birth of SGA babies, and taxane chemotherapy is associated with NICU admission. 15 In future studies, increased monitoring may be needed during the use of the TP regimen during pregnancy, especially monitoring for long-term developmental defects in newborns. Our results showed that cisplatin is more widely used than carboplatin in China. However, carboplatin is recommended as a priority drug when using the TP regimen, considering the safety issues. 23 , 24 A few studies have provided theoretical suggestions for oncological management during pregnancy, especially for cancer treatment and termination of pregnancy. 25 , 26 In clinical practice, however, whether to terminate the pregnancy, when to terminate the pregnancy, whether to carry out surgery and drug treatment, and which drug to administer at what dosage remain perplexing questions. The existing research is insufficient for the formulation of comprehensive oncological management guidelines for cancer during pregnancy. 27 We suggest strengthening the clinical research and conducting follow-up assessments of pregnant patients with cancer; we also recommend coordination among the obstetrics, oncology, neonatology, and clinical pharmacy departments in clinical practice to balance maternal benefits, fetal benefits, and possible risks for the offspring. 28 Careful multidisciplinary management is required for pregnant women with cancer. Declarations Ethics approval and consent to participate The core study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100044292; ongoing), and approved by the ethics committee of the Obstetrics & Gynecology Hospital of Fudan University (approval number: 2020-130). We confirm that all methods were carried out in accordance with relevant guidelines and regulations. We confirm that all experimental protocols were approved by a named institutional and/or licensing committee. We confirme that informed consent was obtained from all subjects and/or their legal guardian(s). Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to the reseaon that the data obtained relate to another unpublished article, but are available from the corresponding author on reasonable request. Competing interest: The authors declare that they have no competing interests. Fundings This work was supported by grants from the Special Project for clinical Research in health industry of Shanghai Municipal Health Commission (201940153) and Shanghai Science and Technology Commission (19401900900) of Jing Tang. No financial disclosures were reported by the authors of this paper. Authors' contributions X H: study design, data analysis and interpretation, manuscript writing C Z: critical manuscript revision JL Z: manuscript writing YY L: data abstraction J T: study design, critical manuscript revision Acknowledgements We thank information department and medical history room of the hospital for helping data collection. References Berends C, Maggen C, Lok CAR, van Gerwen M, Boere IA, Wolters V, et al. Maternal and Neonatal Outcome after the Use of G-CSF for Cancer Treatment during Pregnancy. Cancers (Basel). 2021; 13 (6):1214 doi 10.3390/cancers13061214 . McCormick A, Peterson E. Cancer in Pregnancy. Obstet Gynecol Clin North Am. 2018; 45 (2):187–200 doi https://doi.org/10.1016/j.ogc.2018.01.009 . Botha MH, Rajaram S, Karunaratne K. Cancer in pregnancy. Int J Gynaecol Obstet. 2018; 143 (S2):137–42 doi https://doi.org/10.1002/ijgo.12621 . Puzzi-Fernandes C, Surita FG, Schettini CS, Parpinelli MA, Guida JP, Costa ML. Awareness towards an increasing concern during pregnancy: maternal and perinatal outcomes of women with cancer. Am J Obstet Gynecol MFM. 2020; 2 (3):100168 doi 10.1016/j.ajogmf.2020.100168 . Becker S. Breast cancer in pregnancy: A brief clinical review. Best Pract Res Clin Obstet Gynaecol. 2016; 33 :79–85 doi 10.1016/j.bpobgyn.2015.10.013 . Stensheim H, Møller B, van Dijk T, Fosså SD. Cause-Specific Survival for Women Diagnosed With Cancer During Pregnancy or Lactation: A Registry-Based Cohort Study. J Clin Oncol. 2009; 27 (1):45–51 doi 10.1200/JCO.2008.17.4110 . Cottreau CM, Dashevsky I, Andrade SE, Li DK, Nekhlyudov L, Raebel MA, et al. Pregnancy-Associated Cancer: A U.S. Population-Based Study. J Womens Health (2002). 2019; 28 (2):250–7 doi 10.1089/jwh.2018.6962 . Metcalfe A, Cairncross ZF, Friedenreich CM, Ray JG, Nelson G, Fell DB, et al. Incidence of Pregnancy-Associated Cancer in Two Canadian Provinces: A Population-Based Study. Int J Environ Res Public Health. 2021; 18 (6):3100 doi 10.3390/ijerph18063100 . Wolters V, Heimovaara J, Maggen C, Cardonick E, Boere I, Lenaerts L, et al. Management of pregnancy in women with cancer. Int J Gynecol Cancer. 2021; 31 (3):314–22 doi 10.1136/ijgc-2020-001776 . Cordeiro CN, Gemignani ML. Gynecologic Malignancies in Pregnancy: Balancing Fetal Risks With Oncologic Safety. Obstet Gynecol Surv.2017; 72 (3):184–93 doi 10.1097/ogx.0000000000000407 . Barrois M, Anselem O, Pierga JY, Goldwasser F, Bouscary D, Alessandrini V, et al. Cancer during pregnancy: Factors associated with termination of pregnancy and perinatal outcomes. Eur J Obstet Gynecol Reprod Biol. 2021; 261 :110–5 doi 10.1016/j.ejogrb.2021.04.020 . Albright CM, Wenstrom KD. Malignancies in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2016; 33 :2–18 doi 10.1016/j.bpobgyn.2015.10.004 . Cardonick EH, Gringlas MB, Hunter K, Greenspan J. Development of children born to mothers with cancer during pregnancy: comparing in utero chemotherapy-exposed children with nonexposed controls. Am J Obstet Gynecol. 2015; 212 (5):658.e1-8 doi 10.1016/j.ajog.2014.11.032 . Loibl S, Schmidt A, Gentilini O, Kaufman B, Kuhl C, Denkert C, et al. Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients. JAMA Oncol. 2015; 1 (8):1145-53 doi 10.1001/jamaoncol.2015.2413%J JAMA Oncology. de Haan J, Verheecke M, Van Calsteren K, Van Calster B, Shmakov RG, Mhallem Gziri M, et al. Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients. Lancet Oncol. 2018; 19 (3):337–46 doi https://doi.org/10.1016/S1470-2045(18)30059-7 . Korakiti AM, Zografos E, van Gerwen M, Amant F, Dimopoulos MA, Zagouri F. Long-Term Neurodevelopmental Outcome of Children after in Utero Exposure to Chemotherapy. Cancers. 2020; 12 (12):3623 doi 10.3390/cancers12123623 . Hartnett KP, Mertens AC, Kramer MR, Lash TL, Spencer JB, Ward KC, et al. Pregnancy after cancer: Does timing of conception affect infant health? Cancer. 2018; 124 (22):4401–7 doi 10.1002/cncr.31732 . Zhu L, Zhang R, Zhang S, Shi W, Yan W, Wang X, et al. [Chinese neonatal birth weight curve for different gestational age]. Zhonghua er ke za zhi. 2015; 53 (2):97–103. Li Y, Gong W, Kong X, Mueller O, Lu G. Factors Associated with Outpatient Satisfaction in Tertiary Hospitals in China: A Systematic Review. Int J Environ Res Public Health. 2020; 17 (19):7070 doi 10.3390/ijerph17197070 . Chen W, Duan YY. Recent Levels and Trends of Fertility in China. Popul Res. 2019; 43 (01):3–17. Oliveira MMS, Salgado CM, Viana LR, Gomes-Marcondes MCC. Pregnancy and Cancer: Cellular Biology and Mechanisms Affecting the Placenta. Cancers. 2021; 13 (7):1667 doi 10.3390/cancers13071667 . Peccatori FA, Azim HA, Jr., Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6 :vi160-70 doi 10.1093/annonc/mdt199 . Benoit L, Mir O, Vialard F, Berveiller P. Cancer during Pregnancy: A Review of Preclinical and Clinical Transplacental Transfer of Anticancer Agents. Cancers. 2021; 13 (6):1238 doi 10.3390/cancers13061238 . Eliesen GAM, van Hove H, Meijer MH, van den Broek PHH, Pertijs J, Roeleveld N, et al. Toxicity of anticancer drugs in human placental tissue explants and trophoblast cell lines. Arch Toxikol. 2021; 95 (2):557–71 doi 10.1007/s00204-020-02925-w . Kim Y, Kang M, Jung J, Cho EK, Park HK, Chun Y-S. Subsequent pregnancy and long-term safety from breast cancer patients. J Clin Oncol. 2020; 38 (15_suppl):e13575-e doi 10.1200/JCO.2020.38.15_suppl.e13575 . Maggen C, Wolters V, Cardonick E, Fumagalli M, Halaska MJ, Lok CAR, et al. Pregnancy and Cancer: the INCIP Project. Curr Oncol Rep. 2020; 22 (2):17 doi 10.1007/s11912-020-0862-7 . Michalczyk K, Cymbaluk-Płoska A. Fertility Preservation and Long-Term Monitoring of Gonadotoxicity in Girls, Adolescents and Young Adults Undergoing Cancer Treatment. Cancers. 2021; 13 (2):202 doi 10.3390/cancers13020202 . Linkeviciute A, Buonomo B, Fazio N, Spada F, Peccatori FA. Discussing motherhood when the oncological prognosis is dire: ethical considerations for physicians. ESMO open. 2020; 5 (6):e000956 doi 10.1136/esmoopen-2020-000956 . Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-1638132","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":109041154,"identity":"623dd266-66b8-4396-a608-7ad4927d0f05","order_by":0,"name":"Xuan Huang","email":"","orcid":"","institution":"Obstetrics \u0026 Gynecology Hospital of Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xuan","middleName":"","lastName":"Huang","suffix":""},{"id":109041155,"identity":"5a2187cd-1e7f-435a-8365-f938456fa572","order_by":1,"name":"Chen Zhang","email":"","orcid":"","institution":"Obstetrics \u0026 Gynecology Hospital of Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chen","middleName":"","lastName":"Zhang","suffix":""},{"id":109041156,"identity":"11ebacf2-536f-47a8-984b-e9c61f91e780","order_by":2,"name":"Jialei Zhu","email":"","orcid":"","institution":"Obstetrics \u0026 Gynecology Hospital of Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jialei","middleName":"","lastName":"Zhu","suffix":""},{"id":109041157,"identity":"589d7036-ecc6-4b0f-a0b9-f19b921cd333","order_by":3,"name":"Yueyan Li","email":"","orcid":"","institution":"Obstetrics \u0026 Gynecology Hospital of Fudan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yueyan","middleName":"","lastName":"Li","suffix":""},{"id":109041160,"identity":"dc9ec335-b93d-4817-9af2-fc76111cc0b2","order_by":4,"name":"Jing Tang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYBACNvbG9h8fbBgMiNfCx3O4QXJGGila5CTSG6R5SNLCxnOwwdgmwc7Y4EYC4+OKXwzy5gS1sDc2JOckJJsBtTAbnu1jMNzZQIQth3N/HLABamGTbOxhSDA4QEiLRGJjs0UCiVqamRkSDpiBtTT8IEYLz8E2xp6EZGPJMw+bDRsbJAw3ENIi397+jOFHgp1h3/Hkgw8b/tjIE7QFDhQuJDYwMLZJEKseZF0/yPQ/JOgYBaNgFIyCEQMAspRCq64pjnAAAAAASUVORK5CYII=","orcid":"","institution":"Obstetrics \u0026 Gynecology Hospital of Fudan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2022-05-09 12:14:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1638132/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1638132/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22079649,"identity":"4dbe421d-62c7-4187-bc14-c1565db0815d","added_by":"auto","created_at":"2022-05-31 15:58:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":69434,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePatients included in this study\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1638132/v1/757c3dfec743f04cf90650a1.png"},{"id":22079648,"identity":"8e5bcc80-a82d-47c8-97fb-5f59d62dcd3a","added_by":"auto","created_at":"2022-05-31 15:58:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":110696,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDistribution of cancer types\u003c/strong\u003e\u003c/p\u003e\u003cp\u003e*Ovarian cancers include borderline ovarian tumors. †Other cancers consisted of 6 different cancer types.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1638132/v1/d5c1a79393c67b5b43d10d96.png"},{"id":24575555,"identity":"e8c1f20b-aa39-4e3b-b049-7ee555ea1663","added_by":"auto","created_at":"2022-08-01 05:29:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":704767,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1638132/v1/e3be8f54-54ca-4aa5-99c1-186cf92239e8.pdf"},{"id":22079650,"identity":"abcbb174-b929-4a88-908f-7257bab40671","added_by":"auto","created_at":"2022-05-31 15:58:01","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":40365,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-1638132/v1/e96082075a35d033faa0275f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Influence of cancer in pregnancy on obstetric and neonatal outcomes: An observational retrospective cohort study","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eIt has been estimated that one in every one thousand women will be diagnosed with cancer during pregnancy. \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e In recent years, with the postponement of childbirth to later ages, the adjustment of the fertility policy in China, and the onset of cancer at younger ages, the incidence of cancer during pregnancy has increased. \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The diagnostic work-up for cancer, such as the detection of tumor markers, may be affected by the physiology of pregnancy. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Furthermore, the implementation of diagnostic surgical procedures during pregnancy is often rendered challenging due to safety concerns. Approximately 20\u0026ndash;30% of cancer cases in women occur prior to the age of 45, which has a severe impact on future fertility and pregnancy management. \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The most common malignant tumors during pregnancy are breast cancer, melanoma, hematological cancers, and cervical cancer; \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e among these, breast cancer has the highest incidence, \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e and accounts for 39% of all malignant tumors during pregnancy. The type of cancer can also have an impact on obstetric and neonatal outcomes; for example, patients diagnosed with melanoma have a significantly increased risk of death during pregnancy, while patients diagnosed with breast or ovarian cancer have a significantly increased risk of death during lactation. \u003csup\u003e\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe treatment of cancer in pregnancy complicates clinical decision-making. \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e For instance, pregnant women with cancer may need to choose between continuing or terminating the pregnancy. In general, cancer and its treatment are considered to have adverse effects on women\u0026rsquo;s fertility. Current medical practice attempts, where possible, to retain reproductive function. \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Fortunately, the oncological and obstetric prognoses of patients who receive cancer treatment during pregnancy are relatively good, though termination of pregnancy is usually recommended for such patients. Up to 44% of gynecologists tend to terminate the pregnancy, and 37% of women do not undergo chemo- or radiotherapy during pregnancy. \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Therefore, iatrogenic preterm birth is the most common obstetric complication of cancer in pregnancy. \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWith advances in research and the optimization of therapeutic regimens for cancer, it is increasingly becoming possible to treat cancer during pregnancy as well as protect the fetus and the mother from adverse effects as much as possible. Although life-saving cancer treatments for pregnant women seem to conflict with the interests of the developing fetus, termination of pregnancy has not been shown to improve the prognosis of pregnant women in any type of cancer. \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Several recent studies have recommended that cancer treatment during pregnancy should be as similar as possible to the treatment of non-pregnant women and that preterm birth should be avoided; however, radiotherapy is still recommended to be postponed until after delivery, and chemotherapy should be postponed until the second trimester. \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e With the continual improvements in cancer therapy during pregnancy, the rates of survival and iatrogenic premature births have been observed to improve every 5 years. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Currently, it is accepted that surgery and chemotherapy are relatively safe during pregnancy, while radiotherapy is relatively contraindicated. The existing research shows that chemotherapy from the second trimester does not impact the growth and development of newborns or cause obvious long-term complications. \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e However, other studies have reported that chemotherapy during pregnancy is associated with fetal adverse events. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eMany organizations have provided recommendations on conception for women with cancer, but warn that more evidence is needed, \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e as the precise impact of different tumors and anti-tumor treatment regimens on the mother and fetus remains to be elucidated. Due to this gap in clinical evidence, oncological management during pregnancy remains challenging for both patients as well as gynecologists, oncologists, and obstetricians. Thus far, no large-scale clinical study on pregnancy with cancer has been conducted in China. Therefore, the present study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers, and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management in pregnancy-associated cancer.\u003c/p\u003e"},{"header":"2 Patients And Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study design and participants\u003c/h2\u003e \u003cp\u003eThis descriptive retrospective cohort study analyzed data from pregnant women who were diagnosed with cancer and registered in 11 centers from 7 provinces of China. The core study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100044292; ongoing), and approved by the ethics committee of the Obstetrics \u0026amp; Gynecology Hospital of Fudan University (approval number: 2020\u0026thinsp;\u0026minus;\u0026thinsp;130). The inclusion criteria were pregnant patients aged 18\u0026ndash;45 years with primary invasive cancer or borderline ovarian cancer who were admitted to one of the 11 centers between 1st January 2003 and 2nd February 2021. All subjects voluntarily participated in the study and provided written informed consent. All participants were diagnosed on the basis of pathological evidence. Patients with pre-invasive disease or postpartum diagnosis, those with primary invasive cancer or borderline ovarian cancer diagnosed after delivery, and those who had received high-dose scatter radiation to the pelvis or brain before delivery were excluded. We designed a questionnaire to collect detailed oncological, obstetric, and neonatal data. All participating centers received an online electronic questionnaire, and each center collected the required data from its electronic medical record system. The data from all centers were then consolidated and aggregated by the authors.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Definitions\u003c/h2\u003e \u003cp\u003eSystemic disease was defined as maternal hypertensive disorders, cardiac disease, hypothyroidism, gestational diabetes, and gestational anemia. Pre-delivery surgery was defined as any therapeutic or palliative surgical procedure for cancer performed after the diagnosis of cancer and prior to delivery (or termination of pregnancy). Similarly, pre-delivery chemotherapy was defined as chemotherapy administered at any time from the cancer diagnosis to the delivery (or termination of pregnancy). Miscarriage was defined as the loss of a baby before the 20th week of gestation, while stillbirth was defined as the loss of a baby at or after 20 weeks of gestation. Preterm pre-labor rupture of membranes (PPROM) was defined as the preterm rupture of membranes without contractions, and was diagnosed by the local centers. Small for gestational age (SGA) was defined as a birth weight less than the 10th percentile, as calculated according to the Chinese neonatal birth weight curve for different gestational ages. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Preterm birth was defined as delivery before 37 completed weeks of gestation. Iatrogenic preterm birth was defined as preterm cesarean delivery without labor. Low birth weight (LBW) and fetal macrosomia were defined as birth weights of \u0026lt;\u0026thinsp;2500 g or \u0026gt;\u0026thinsp;4000 g, respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Statistical analysis\u003c/h2\u003e \u003cp\u003eWe aggregated the oncological, obstetric, and neonatal data, and provided descriptive statistics for these data. Age at pregnancy was grouped into 8-year intervals as follows: 21\u0026ndash;28, 29\u0026ndash;36, and 37\u0026ndash;45 years. Multiple logistic regression models were used to analyze the effects of the following factors on premature birth and birth of SGA infants: maternal age, year of last menstrual period (LMP), gestational period (in terms of trimesters) at the time of cancer diagnosis, cancer type, treatment method, and maternal complications during pregnancy. The results were reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs). \u003cem\u003eP\u003c/em\u003e values were used to measure the strength of the evidence against the null hypothesis of no relationship. The study data spanned an 18-year period, and were divided into the following three 6-year intervals according to the year in which the LMP occurred: 2003\u0026ndash;2008, 2009\u0026ndash;2014, and 2015\u0026ndash;2020. Log-binomial regression models were used to analyze the average changes in patient characteristics, tumor types, treatment before delivery, and maternal complications, with year of diagnosis as a continuous predictor. The results were presented as relative risks (RRs) and 95% CIs. Considering the limited sample size, the number of independent variables, and the limited correlation between independent variables, we chose to use chi-square tests to directly study the relationship between two variables. Chi-square tests (one-tailed) were performed to assess the influence of cancer type and pre-delivery chemotherapy on maternal complications, and obstetric and neonatal outcomes. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26.0 (IBM, Armonk, NY, USA). \u003cem\u003eP\u003c/em\u003e values of less than 0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 General information\u003c/h2\u003e \u003cp\u003eIn all, 204 women (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) registered in 7 tertiary A hospitals were eligible for this study. A tertiary A hospital is the highest classification grade for hospitals in mainland China and represents a large general hospital. Some tertiary A hospitals have more than 20,000 outpatient visits per day. \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e Of these, 35 (17%) women chose to terminate their pregnancies by surgery or drugs, and 119 (59%) women received antenatal treatment for cancer. The baseline characteristics of the patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, and the distribution of cancer types is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Patient characteristics stratified by cancer type are shown in Supplementary \u003cb\u003eTable S1\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003ePatient characteristics\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient characteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at the time of pregnancy, median (IQR, range), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (28\u0026ndash;35, 21\u0026ndash;43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTiming of cancer diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88/204 (43)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20/204 (10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40/204 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45/204 (22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/204 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eYear of LMP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2003\u0026ndash;2008\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/204 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2009\u0026ndash;2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36/204 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2015\u0026ndash;2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e153/204 (75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePre-delivery treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83/202 (41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112/202 (55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/202 (14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaxanes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15/202 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatinum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/202 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnthracyclines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/202 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-platinum alkylating agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/202 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntimetabolites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/202 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1/202 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/202 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted therapy and hormone therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/202 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eObstetric complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118/201 (59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertensive disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/201 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational diabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/201 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16/201 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal cardiac disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/201 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal obstruction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/201 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/201 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/201 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePPROM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/201 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal distress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/201 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal growth restriction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/201 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOligohydramnios\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/201 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeonatal outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIatrogenic preterm delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49/144 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous preterm delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/144 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eApgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5/137 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmall-for-gestational-age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17/143 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43/143 (30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrosomia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/143 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeonatal complications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18/143 (13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal acidosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10/143 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory acidosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/143 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCongenital malformations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6/143 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal respiratory distress syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27/143 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7/143 (5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hyperbilirubinemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/143 (20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hypoglycemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/143 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal hyperglycemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4/143 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eIQR, interquartile range; LMP, last menstrual period; PPROM, preterm pre-labor rupture of membranes; NICU, neonatal intensive care unit\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Obstetric and neonatal complications and neonatal outcomes\u003c/h2\u003e \u003cp\u003eOf the 204 eligible women, 201 patients had records of pregnancy-related complications. In total, 118 (59%) women developed pregnancy-related complications. The most common complications were gestational diabetes (9%), gestational maternal infection (9%), and PPROM (9%). The most common obstetric outcome was preterm birth (39%), and the most common neonatal comorbidity was neonatal hyperbilirubinemia (19%). Congenital defects were observed in 6 (4%) newborns or aborted fetuses (Supplementary \u003cb\u003eTable S2\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eOf the 204 patients included in the study, the majority (147, 72%) were from the Obstetrics \u0026amp; Gynecology Hospital of Fudan University. We recorded the total number of pregnant women who received antenatal care at this hospital between January 1, 2003 and December 31, 2021. We also noted the incidence of pregnancy-related complications, neonatal complications, and obstetric events, such as caesarean section, among these patients, as provided by the Information Department of the hospital (Supplementary \u003cb\u003eTables S3 and S4\u003c/b\u003e). We performed chi-square analyses (one-tailed) of the data of all 204 pregnant women with cancer included in this study and the data of all pregnant women from the Obstetrics \u0026amp; Gynecology Hospital of Fudan University.\u003c/p\u003e \u003cp\u003eAll pregnant women from the Obstetrics \u0026amp; Gynecology Hospital of Fudan University during the study period were taken as the reference group. Compared with all pregnant women, pregnant women with cancer had a significantly higher risk of maternal hypertension (OR: 2.18, 95% CI: 1.37\u0026ndash;3.46, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), heart disease (OR: 35.72, 95% CI: 14.87\u0026ndash;85.81, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), intestinal obstruction (OR: 105.68, 95% CI: 32.56\u0026ndash;342.99, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and liver damage (OR: 4.19, 95% CI: 1.77\u0026ndash;9.92, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) during pregnancy as well as fetal intrauterine growth restriction (OR: 17.23, 95% CI: 8.31\u0026ndash;35.71, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Compared to women without cancer, those with cancer had with a significantly higher incidence of cesarean section (OR: 4.54, 95% CI: 4.02\u0026ndash;5.12, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), preterm birth (OR: 8.28, 95% CI: 6.75\u0026ndash;10.18, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), LBW (OR: 6.39, 95% CI: 4.98\u0026ndash;8.19, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and fetal macrosomia (OR: 5.2, 95% CI: 2.54\u0026ndash;10.64, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Cancer in pregnancy was also associated with a significantly increased likelihood of neonatal acidosis (OR: 2.85, 95% CI: 1.57\u0026ndash;5.18, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), birth defects (OR: 3.83, 95% CI: 1.75\u0026ndash;8.4, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and neonatal respiratory distress (OR: 10.26, 95% CI: 7.29\u0026ndash;14.45, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The results of this chi-square analysis are shown in Supplementary \u003cb\u003eTable S5\u003c/b\u003e. Since only the pregnancy data from the Obstetrics \u0026amp; Gynecology Hospital of Fudan University were used instead of data from all centers, these results are for reference only.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Cancer treatments\u003c/h2\u003e \u003cp\u003eOf the 204 women, 119 (59%) women received treatment for cancer before the termination of pregnancy, and of these 121 women, 73 (60%) women were treated using a single treatment modality, 53 (42%) women underwent surgery alone, and 5 (2%) women were treated using chemotherapy alone (Supplementary \u003cb\u003eTable S6\u003c/b\u003e). Among the 28 patients who received a combination of different treatment modalities, 19 (9%) patients received a combination of surgery and chemotherapy, and 2 (1%) received a combination of surgery, chemotherapy, and targeted therapy. Twelve patients received paclitaxel plus platinum-based chemotherapy (TP regimen), and seven patients received epirubicin plus cyclophosphamide chemotherapy (EC regimen).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Obstetric outcomes\u003c/h2\u003e \u003cp\u003eAmong the 35 women who chose to undergo termination of pregnancy, 19 (53%) terminated their pregnancy in the first trimester, 12 (34%) terminated it in the second trimester, and 2 (6%) terminated in the third trimester; the time of termination of pregnancy was unknown in 2 cases. All 35 women who chose to terminate the pregnancy were between the ages of 24 and 43 years, and 31 of these women were aged 28 years or above. In total, 8 of these women had had a previous pregnancy, and 6 of these 8 had had a previous live birth. Among the 169 women who chose to continue the pregnancy, the pregnancy outcomes of 13 patients were missing. Among the 156 patients with recorded pregnancy outcomes, 144 live births were reported, of which 3 cases (2%) were twin pregnancies, and the others were singleton pregnancies. Among these 156 patients, 10 (6%) had a miscarriage before 20 weeks of gestation, and 2 (1%) patients had a stillbirth after 20 weeks of gestation. The obstetric outcomes stratified by cancer type are shown in Supplementary \u003cb\u003eTable S7\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Impact of cancer type on complications and outcomes\u003c/h2\u003e \u003cp\u003eUnivariate analysis using chi-square tests revealed that cancer type significantly affected the obstetric outcome (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Compared with pregnant women with cervical cancer, pregnant women with thyroid cancer (OR: 0.16, 95% CI: 0.06\u0026ndash;0.42, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), breast cancer (OR: 0.3, 95% CI: 0.13\u0026ndash;0.68, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), or other cancer types (OR: 0.64, 95% CI: 0.41\u0026ndash;1, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) had a significantly lower probability of premature delivery of the fetus. No significant relationship was found between cancer type and the occurrence of other obstetric complications. Taking the patients with cervical cancer as the reference group, we found that significantly fewer proportions of patients with thyroid cancer (OR: 0.36, 95% CI: 0.22\u0026ndash;0.57, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) or ovarian cancer (OR: 0.70, 95% CI: 0.50\u0026ndash;0.98, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) underwent cesarean section. Among pregnant women with thyroid cancer, the proportion of those who chose fetal preservation was significantly increased relative to the reference group (OR: 1.28, 95% CI: 1.03\u0026ndash;1.58, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), but the risk of fetal intrauterine growth restriction was also significantly increased (OR: 5.21, 95% CI: 1.21\u0026ndash;22.55, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Pregnancy with thyroid cancer (OR: 0.25, 95% CI: 0.09\u0026ndash;0.68, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), ovarian cancer (OR: 0.33, 95% CI: 0.11\u0026ndash;1.02, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), or breast cancer (OR: 0.28, 95% CI: 0.09\u0026ndash;0.87, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was associated with a lower risk of neonatal respiratory distress syndrome than pregnancy with cervical cancer (Supplementary \u003cb\u003eTable S8\u003c/b\u003e).\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\u003eChi-square tests (one-tailed) of the most common obstetric outcomes.\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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePremature delivery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eSmall for gestational age\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \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\u003eThyroid cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.16 (0.06\u0026ndash;0.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.22 (0.38\u0026ndash;27.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.252\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvarian cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.87 (0.56\u0026ndash;1.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.8 (0.7\u0026ndash;48.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.082\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.13\u0026ndash;0.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.63 (0.4\u0026ndash;32.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.237\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther cancer types\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.64 (0.41\u0026ndash;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.26 (0.53\u0026ndash;34.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eCases of pregnancy complicated with cervical cancer were taken as the reference group.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eOR, odds ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.6 Impact of chemotherapy\u003c/h2\u003e \u003cp\u003eAccording to the use of chemotherapy drugs before the end of pregnancy (including delivery, miscarriage, and stillbirth), the patients were divided into those who did not receive chemotherapy, those who received treatment with the TP regimen, and those who received treatment with the EC regimen (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Chi-square analyses showed that compared with no chemotherapy before delivery (or miscarriage or stillbirth), the use of the TP regimen during pregnancy was associated with adverse pregnancy outcomes (i.e., preterm birth, miscarriage, stillbirth, and SGA; OR: 1.87, 95% CI: 1.42\u0026ndash;2.46, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\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\u003eChi-square tests (one-tailed) of most common obstetric and neonatal complications and obstetric outcomes.\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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTP regimen\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eEC regimen\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstetric complications: any\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.66 (0.41\u0026ndash;1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.74 (0.38\u0026ndash;1.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreterm birth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.43 (0.3\u0026ndash;0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.54 (0.78\u0026ndash;3.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.252\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean section delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.74 (0.55\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.13 (0.59\u0026ndash;2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLow birth weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.32 (0.21\u0026ndash;0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.48 (0.24\u0026ndash;0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmall for gestational age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.09 (0.16\u0026ndash;7.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.49 (0.7\u0026ndash;8.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.209\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonatal complications: any\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.61 (0.29\u0026ndash;1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.71 (0.29\u0026ndash;1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.379\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse obstetric outcomes\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.87 (1.42\u0026ndash;2.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.78 (1.25\u0026ndash;2.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003ePatients who did not receive chemotherapy before termination of pregnancy were taken as the control group.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTP regimen, paclitaxel\u0026thinsp;+\u0026thinsp;platinum; EC regimen, epirubicin\u0026thinsp;+\u0026thinsp;cyclophosphamide. \u003csup\u003ea\u003c/sup\u003eAdverse obstetric outcomes included miscarriage, stillbirth, preterm birth, and small for gestational age.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eOR, odds ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.7 Factors influencing obstetric outcomes\u003c/h2\u003e \u003cp\u003eThe results of the multiple logistic regression models are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Both the outcome variables and the covariates in these models were prespecified. The key covariates in the models were as follows: patient\u0026rsquo;s age at admission (stratified into three 8-year ranges), timing of cancer diagnosis (relative to the pregnancy), cancer type, pre-delivery surgery or chemotherapy, year in which the LMP occurred, maternal reproductive system complications (including uterine, placenta, and umbilical cord problems), maternal digestive system complications, and maternal systemic disease. The regression coefficients and standard errors determined using this analysis can be found in Supplementary \u003cb\u003eTable S9\u003c/b\u003e. Pregnant women with cancer as well as systemic diseases (such as hypertension, hyperlipidemia, diabetes, heart disease, and anemia) were more likely to give birth to SGA infants (OR: 12.02, 95% CI: 1.82\u0026ndash;79.43).\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\u003eMultiple logistic regression analysis of the most common obstetric outcomes\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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003ePremature delivery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eSmall for gestational age\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eOR (95% CI)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at admission (per 8 years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.83 (0.23\u0026ndash;2.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.18 (0.3\u0026ndash;4.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTiming of cancer diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.784\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBefore pregnancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFirst trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05 (0\u0026ndash;0.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.73 (0.02\u0026ndash;23.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird trimester\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.08 (0\u0026ndash;1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.27 (0.02\u0026ndash;4.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03 (0\u0026ndash;7.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.75 (0.19\u0026ndash;16.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08 (0\u0026ndash;3.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOvarian cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128.65 (2.6\u0026ndash;6371.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.19 (0.05\u0026ndash;105.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.27 (0.15\u0026ndash;34.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02 (0.05\u0026ndash;22.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther cancer types\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.64 (0.55\u0026ndash;57.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.21 (0.01\u0026ndash;4.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.22 (0.4\u0026ndash;44.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.59 (0.5\u0026ndash;42.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.13 (0.07\u0026ndash;18.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.933\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08 (0.01\u0026ndash;1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYear of LMP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.226\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.741\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[2003, 2008]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[2009, 2014]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.1 (0.02\u0026ndash;246.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e[2015, 2020]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.52 (0.05\u0026ndash;260.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026middot;\u0026middot;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReproductive system complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.3 (0.06\u0026ndash;1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.05 (0.21\u0026ndash;5.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.952\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDigestive system complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06 (0\u0026ndash;0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystemic disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.23 (0.05\u0026ndash;1.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.02 (1.82\u0026ndash;79.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eLMP, last menstrual period; OR, odds ratio; CI, confidence interval\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.8 Changes in cancer treatments and obstetric outcomes over the study period\u003c/h2\u003e \u003cp\u003eThis study reviewed data collected over an 18-year period. We divided the patients into the following 3 subgroups according to the year in which they had their LMP: 2003\u0026ndash;2008, 2009\u0026ndash;2014, and 2015\u0026ndash;2020. The LMP was used as a continuous predictor in the log-binomial regression model. The results are shown in Supplementary \u003cb\u003eTable S10\u003c/b\u003e. Every 6 years, we observed a decrease in the proportion of patients choosing to terminate the pregnancy (RR: 0.48, 95% CI: 0.35\u0026ndash;0.67). The proportions of patients who chose termination of pregnancy stratified by cancer type are shown in Supplementary \u003cb\u003eTable S11\u003c/b\u003e. Every 6 years, the likelihood of receiving cancer treatment before delivery was found to increase, mainly due to the increase in the rate of surgery (RR: 1.87, 95% CI: 1.31\u0026ndash;2.67). Every 6 years, we observed fewer iatrogenic preterm births on average (RR: 0.73, 95% CI: 0.54\u0026ndash;0.98) and more term births (RR: 1.46, 95% CI: 1.00\u0026ndash;2.13).\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eOf the 204 pregnant women with cancer who were eligible for the present study, 35 women decided to terminate their pregnancy. These 35 women were aged between 24 and 43 years, and 31 (89%) of them were aged 28 years or older; in addition, 77% of these women had previously been pregnant and given birth to a live infant. A Chinese population study has reported that the age of Chinese women at first childbirth has gradually increased from 24 years to nearly 28 years between 2006 and 2017. \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Therefore, it can be inferred that the age of the patients and the previous live birth were important reasons driving the decision to terminate the pregnancy.\u003c/p\u003e \u003cp\u003ePreterm birth was the most common obstetric outcome for pregnant women with cancer. Moreover, of the 56 (30%) women who gave birth prematurely in our study, only 7 (12%) gave birth vaginally; the remaining 49 (88%) women underwent cesarean section. This shows that in addition to spontaneous preterm delivery, iatrogenic preterm delivery and artificial early termination of pregnancy are common outcomes among pregnant women with cancer. Nevertheless, it remains to be determined whether the artificial shortening of pregnancy benefits pregnant women or affects the health of their newborns. The timing and specific conditions under which early termination of pregnancy is maximally beneficial to the pregnant woman and her newborn remain a thorny problem of clinical decision-making.\u003c/p\u003e \u003cp\u003eIn the present study, the incidence of congenital defects among cases of abortions, stillbirths, and live births was approximately 4%, and among live births, the incidence of congenital malformations was 3.5%. According to the China Birth Defect Prevention Report (2012) issued by the National Health Commission of the People\u0026rsquo;s Republic of China, the incidence of birth defects is significantly higher in rural and remote areas than in urban areas. Compared with the 2012 national report, the present study did not find a high proportion of birth defects among babies born to women with cancer; this is probably because our patients were all from tertiary A hospitals in capital cities, while the national report included women from across the country. We used the birth defect data obtained from all cases of pregnancy in the Obstetrics \u0026amp; Gynecology Hospital of Fudan University as a reference, and found that pregnant women with cancer were more likely to have babies with birth defects (OR: 3.83, 95% CI: 1.75\u0026ndash;8.4, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01). These data may put greater pressure on women with cancer to continue their pregnancies. Further research is required to determine whether it is the physiological changes caused by the cancer itself or the treatments that affect the rate of birth defects.\u003c/p\u003e \u003cp\u003eEvery 6 years, the proportion of pregnant women with cancer who choose to continue their pregnancy increased. More patients chose to undergo treatment for cancer before delivery, but this was mainly attributable to an increase in pre-delivery surgery rather than pre-delivery chemotherapy, which is not consistent with the results of a European study. \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The majority of our patients (86%) did not receive chemotherapy prenatally. This indicates that currently, Chinese clinicians may be relatively conservative in regards to chemotherapy during pregnancy.\u003c/p\u003e \u003cp\u003eIn this study, all of the 10 cervical cancer patients who received chemotherapy before delivery were treated with the TP regimen. In addition, 63% of the 11 breast cancer patients who received chemotherapy before delivery were treated with the EC regimen. This suggests that multidrug regimens are used in the majority of pregnant patients with cancer. However, current studies on the toxicity of chemotherapeutic drugs during pregnancy focus on single-drug chemotherapy. Thus, more research is required to investigate the effects of multi-drug chemotherapeutic regimens during pregnancy.\u003c/p\u003e \u003cp\u003eOur study supports the findings that adriamycin, cyclophosphamide, and 5-fluorouracil are relatively safe for fetuses and newborns. \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e We did not find any significant impact of the EC regimen on obstetric outcomes. In previous studies, platinum-based therapy with or without taxanes was recommended for advanced or high-risk cancer during pregnancy. \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Taxanes have a low potential for placental transfer \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e and low toxicity, and their use is considered feasible in the second and third trimesters. \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e This may partially explain the high proportion of patients treated with the TP regimen before delivery in this study. Our data in this cohort study suggested a relationship between the TP regimen and adverse obstetric outcomes. Another study has also shown that the use of platinum-based chemotherapy drugs is statistically associated with the birth of SGA babies, and taxane chemotherapy is associated with NICU admission. \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In future studies, increased monitoring may be needed during the use of the TP regimen during pregnancy, especially monitoring for long-term developmental defects in newborns. Our results showed that cisplatin is more widely used than carboplatin in China. However, carboplatin is recommended as a priority drug when using the TP regimen, considering the safety issues. \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA few studies have provided theoretical suggestions for oncological management during pregnancy, especially for cancer treatment and termination of pregnancy. \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e In clinical practice, however, whether to terminate the pregnancy, when to terminate the pregnancy, whether to carry out surgery and drug treatment, and which drug to administer at what dosage remain perplexing questions. The existing research is insufficient for the formulation of comprehensive oncological management guidelines for cancer during pregnancy. \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e We suggest strengthening the clinical research and conducting follow-up assessments of pregnant patients with cancer; we also recommend coordination among the obstetrics, oncology, neonatology, and clinical pharmacy departments in clinical practice to balance maternal benefits, fetal benefits, and possible risks for the offspring. \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Careful multidisciplinary management is required for pregnant women with cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe core study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2100044292; ongoing), and approved by the ethics committee of the Obstetrics \u0026amp; Gynecology Hospital of Fudan University (approval number: 2020-130). We confirm that all methods were carried out in accordance with relevant guidelines and regulations.\u0026nbsp;We confirm that all experimental protocols were approved by a named institutional and/or licensing committee.\u0026nbsp;We\u0026nbsp;confirme that informed consent was obtained from all subjects and/or their legal guardian(s).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to the reseaon that\u0026nbsp;the data obtained relate to another unpublished article, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest:\u003c/strong\u003e The authors declare that they have no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eFundings\u003c/h3\u003e\n\u003cp\u003eThis work was supported by grants from the Special Project for clinical Research in health industry of Shanghai Municipal Health Commission (201940153) and Shanghai Science and Technology Commission (19401900900) of Jing Tang. No financial disclosures were reported by the authors of this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX H: study design, data analysis and interpretation, manuscript writing\u003c/p\u003e\n\u003cp\u003eC Z: critical manuscript revision\u003c/p\u003e\n\u003cp\u003eJL Z: manuscript writing\u003c/p\u003e\n\u003cp\u003eYY L: data abstraction\u003c/p\u003e\n\u003cp\u003eJ T: study design, critical manuscript revision\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank\u0026nbsp;information department and medical history room of the hospital for helping data collection.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBerends C, Maggen C, Lok CAR, van Gerwen M, Boere IA, Wolters V, \u003cem\u003eet al.\u003c/em\u003e Maternal and Neonatal Outcome after the Use of G-CSF for Cancer Treatment during Pregnancy. 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ESMO open. 2020;\u003cb\u003e5\u003c/b\u003e(6):e000956 doi \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/esmoopen-2020-000956\u003c/span\u003e\u003cspan address=\"10.1136/esmoopen-2020-000956\" 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":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Retrospective Studies, Cohort Studies, Pregnancy Complications, Neoplastic, Antineoplastic Agents","lastPublishedDoi":"10.21203/rs.3.rs-1638132/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1638132/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Thus far, no large-scale clinical study on pregnancy with cancer has been conducted in China. Therefore, the present study aimed to review the oncological characteristics and treatment of pregnancy-associated cancers, and analyze the obstetric and neonatal outcomes to provide evidence-based recommendations for reproductive function preservation, oncological treatment, and obstetric management in pregnancy-associated cancer.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted an observational retrospective cohort study among pregnant patients with cancer in 7 Chinese tertiary A hospitals during 2003–2021. We conducted multiple logistic regression to determine the influence of various factors on preterm birth and small-for-gestational-age infants, log-binomial regression to analyze temporal changes, and chi-square tests to explore the effects of cancer type/treatment.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf 204 women, 17% terminated their pregnancies; 59% received pre-delivery treatment. Every 6 years, the rates of pregnancy termination ([RR]: 0.48, 95% confidence interval [CI]: 0.35–0.67) and iatrogenic preterm births (RR: 0.73, 95% CI: 0.54–0.98) reduced, and that of pre-delivery treatment increased, mainly due to increased rates of surgery (RR: 1.87, 95% CI: 1.31–2.67). Maternal systemic diseases were related to a higher risk of small-for-gestational-age infants ([OR]: 12.02, 95% CI: 1.82–79.43). Chemotherapy with taxanes plus platinum-based agents was related to adverse obstetric outcomes (OR: 1.87, 95% CI: 1.42–2.46, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). Thyroid (OR: 0.36, 95% CI: 0.22–0.57) and ovarian cancer (OR: 0.70, 95% CI: 0.50–0.98) were associated with fewer cesarean sections. Thyroid cancer was associated with fetal growth restriction (OR: 5.21, 95% CI: 1.21–22.55).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eRates of pregnancy termination in cancer have declined. Taxane plus platinum-based chemotherapy was associated with adverse obstetric outcomes. Cancer type influenced outcomes.\u003c/p\u003e","manuscriptTitle":"Influence of cancer in pregnancy on obstetric and neonatal outcomes: An observational retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-05-31 15:57:59","doi":"10.21203/rs.3.rs-1638132/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"13edf352-942c-4d89-973e-952a15b59428","owner":[],"postedDate":"May 31st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-08-01T05:29:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-05-31 15:57:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1638132","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1638132","identity":"rs-1638132","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}