A Population-Based Study of Pregnancy Outcomes in Female Cancer Survivors Open Access

Hartnett, Kathleen (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/tm70mv92s?locale=en
Published

Abstract

Although some cancer treatments reduce fertility, it is unclear whether they increase the risk of adverse pregnancy outcomes. The aims of this study were to examine whether cancer survivors have higher risks of preterm birth, fetal growth restriction, low birth weight, and pregnancy complications than women without a history of cancer, and whether these risks differ by cancer type, treatment, or timing of conception. Data from cancer registries was linked to pregnancy outcomes from birth certificates in three U.S. states. Analyses were limited to the first, live singleton birth conceived after diagnosis. Births to comparison women without a previous cancer diagnosis in the registry were matched on age at delivery, parity, race/ethnicity, and education. Infants born after cervical cancer had sharply higher risks of preterm birth than comparison women, with a 36% risk of delivery before 37 weeks in pregnancies conceived ≤1 year after diagnosis and 25% for >1 year. The risks of preterm birth were slightly higher among infants born to survivors of invasive breast cancer, but only in women who conceived ≤1 year after starting chemotherapy alone (RR=2.4, 95% CI: 1.4, 4.0) or ≤2 years after chemotherapy with radiation. We observed a higher risk of infants born small for gestational age in survivors of brain cancer and extranodal non-Hodgkin lymphoma. Thyroid cancer survivors had higher risks of gestational diabetes (RR=1.8, 95% CI: 1.2, 2.6) and possibly gestational hypertension, but not other adverse outcomes. We did not see an increased risk of adverse outcomes in pregnancies conceived after ductal carcinoma in situ, melanoma, nodal non-Hodgkin lymphoma, or Hodgkin lymphoma. This research supports the recommendation that women delay pregnancy for a year after starting chemotherapy for breast cancer and slightly longer if they receive both chemotherapy and radiation. Cervical cancer patients might also have better outcomes if they delay pregnancy, and thyroid cancer survivors may need closer monitoring gestational diabetes and hypertension. Given that chemotherapy might increase the risk of preterm birth through mechanisms including immunosuppression and anemia, future studies should focus on biomarkers that may better pinpoint when patients have recovered from treatment and can safely conceive.

Table of Contents

Table of Contents

1. MOTIVATION AND AIMS. 1

2. BACKGROUND.. 2

2.1 Possible effects of cancer treatment 3

2.2 Studies in childhood cancer survivors. 4

2.3 Studies in adult cancer survivors. 5

2.4 Pregnancy outcomes by treatment type. 6

2.5 Pregnancy outcomes by cancer type. 9

2.6 Other limitations of existing research. 9

2.7 Possible disparities by race in pregnancy outcomes after cancer 16

2.8 Pregnancy timing after cancer 16

2.9 Biological hypotheses underlying the current pregnancy timing recommendations. 19

2.10 Previous studies analyzing pregnancy outcomes by time since diagnosis. 20

2.11 Pregnancy timing after cervical cancer 21

2.12 Pregnancy timing after thyroid cancer 22

2.13 Relevance and implications of the current study. 23

3. AIM 1: THE RISK OF PRETERM BIRTH AND FETAL GROWTH RESTRICTION IN PREGNANCY AFTER CANCER.. 26

3.1 Manuscript information. 26

3.2 Abstract 27

3.3 Introduction. 28

3.4 Material and Methods. 29

3.4.1 Study population. 29

3.4.2 Exposures. 30

3.4.3 Outcomes. 30

3.4.4 Covariates. 30

3.4.5 Statistical methods. 31

3.5 Results. 32

3.6 Discussion. 34

3.7 Acknowledgments. 38

3.8 Supplement 38

3.9 Tables. 41

3.10 Appendix Table. 46

3.11 Figure. 47

4. AIM 2: PREGNANCY OUTCOMES IN WOMEN TREATED FOR CANCER BEFORE CONCEPTION 48

4.1 Manuscript information. 48

4.2 Abstract 49

4.2.1 Background. 49

4.2.2 Methods. 49

4.2.3 Results. 49

4.2.4 Conclusions. 49

4.3 Introduction. 50

4.4 Methods. 51

4.4.1 Study populations. 51

4.4.2 Exposures. 53

4.4.3 Outcomes. 53

4.4.4 Covariates. 54

4.4.5 Statistical methods. 54

4.5 Results. 55

4.6 Discussion. 57

4.7 Acknowledgments. 60

4.8 Tables. 62

4.9 Appendix Tables. 66

5. AIM 3: PREGNANCY AFTER CANCER: DOES TIMING OF CONCEPTION AFFECT INFANT HEALTH?. 68

5.1 Manuscript information. 68

5.2 Abstract 69

5.2.1 Background. 69

5.2.2 Methods. 69

5.2.3 Results. 69

5.2.4 Conclusions. 69

5.3 Introduction. 70

5.4 Methods. 71

5.4.1 Study populations. 71

5.4.2 Exposures. 73

5.4.3 Outcomes. 74

5.4.4 Statistical analyses. 74

5.5 Results. 74

5.6 Discussion. 76

5.7 Acknowledgments. 79

5.8 Tables. 80

5.9 Appendix Tables. 83

5.10 Figures. 85

6. CONCLUSION AND FUTURE DIRECTIONS. 88

6.1 Summary of Findings. 88

6.2 Study Limitations. 89

6.3 Study Strengths. 91

6.4 Future Directions. 91

6.5 References. 93

List of Tables

Table 2.1. Overview of registry-linked studies on pregnancy outcomes after adult cancer diagnoses. 7

Table 2.2. Results of registry-linked studies on adverse pregnancy outcomes after cancer. 10

Table 2.3. Results from three studies assessing whether timing of pregnancy after cancer diagnosis or a procedure to remove abnormal cervical tissue are associated with adverse pregnancy outcomes. 24

Table 3.1. Characteristics of the first eligible live singleton birth to women ages 20-45 conceived after cancer diagnosis (N=4,203), for the most common cancer types and all cancers, compared with all eligible live, singleton births to women ages 20-45 without a previous diagnosis. 41

Table 3.2. Risk ratios for preterm birth, low birth weight and small for gestational age for the first live singleton birth conceived after diagnosis with each cancer, compared with births to matched comparison women without a previous cancer diagnosis. 43

Table 3.3. Risk ratios for pregnancy complications, admission to the neonatal intensive care unit, 5-minute Apgar score < 7, and Cesarean section for the first live singleton birth conceived after diagnosis with each cancer, compared with births to matched comparison women without a previous cancer diagnosis. 44

Table 3.4. Risks, risk differences, and risk ratios for preterm birth, low birth weight, and small for gestational age in the first live singleton birth conceived after diagnosis with breast, reproductive, and thyroid cancers, compared with births to matched comparison women. 45

Appendix Table 3.A1. Cancer type for the first eligible singleton birth conceived after a cancer diagnosis (N=4,203). 46

Table 4.1. Characteristics of the first eligible live singleton birth to women ages 20-45 conceived after cancer diagnosis (N=4,203), for different cancer treatments, compared with all live singleton births to women ages 20-45 without a previous diagnosis. 62

Table 4.2. Risk ratios comparing the risk of preterm birth, low birth weight and small for gestational age for the first pregnancy conceived after cancer treatment with the risk of adverse pregnancy outcomes in women without a previous cancer diagnosis. 64

Table 4.3. Change in estimates of the risk ratio comparing risk of preterm birth, low birth weight and small for gestational age in breast cancer survivors to matched comparison women, after bias analysis addressing misclassification of treatment in the registry. 65

Appendix Table 4.A1. N for each treatment type by cancer type, for the first eligible live singleton birth conceived after diagnosis. 66

Appendix Table 4.A2. Comparison of treatment prior to pregnancy conception in medical records from the FUCHSIA Women's Study to registry values for breast cancer survivors in Georgia. 67

Table 5.1. Characteristics of the first eligible live singleton birth to women ages 20-45 conceived after cancer diagnosis, by time between diagnosis and conception. 80

Table 5.2. Risk and risk ratios by time between treatment start date and conception of the first live birth after cancer, compared with the risk in matched women who have never had cancer. 81

Appendix Table 5.A1. Risks and risk ratios for small for gestational age births by the mother's age at cancer diagnosis and time between start of treatment and conception, for women treated with chemotherapy. 83

Appendix Table 5.A2. Risk of preterm birth, low birth weight, and small for gestational age infants by time from imputed end of treatment to conception of first pregnancy among breast cancer patients. 84

List of Figures

Figure 3.1. Exclusions and total N for first births after cancer and comparison groups. 47

Figure 5.1. Percent (and number) of cancer survivors in the FUCHSIA Women's Study who reported receiving a recommendation from a healthcare professional about how long to wait after their treatment ended before attempting pregnancy, by cancer type. 85

Figure 5.2a. Length of time that cancer survivors in the FUCHSIA Women's Study said they were told to wait after treatment before attempting pregnancy, by cancer type. 86

Figure 5.2b. Length of time that cancer survivors in the FUCHSIA Women's Study said they were told to wait after treatment before attempting pregnancy, by treatment type. *Excluding women prescribed Tamoxifen. 87


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