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 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 outcomesa | 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. aAdverse 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).