Dissertation
Pregnancy complications and outcomes among women with a history of leukemia and lymphoma
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2020
DOI: 10.17077/etd.005507
Abstract
Leukemia and lymphoma are cancers that affect the blood, bone marrow, and lymph nodes. These are two of the top cancers affecting children, adolescents, and young adults and have high survival rates. The five-year survival rates have doubled for those with lymphoma quadrupled for leukemia from 1960 to 2014. However, with the longer survival, there are concerns regarding the late-effects of cancer including pregnancy complications and pregnancy outcomes. Our study evaluated the risk of gestational hypertension and preterm birth among women with a history of leukemia or lymphoma and metabolic vulnerability in the newborns of mothers with a prior history of leukemia or lymphoma. To evaluate these aims, a cross-sectional study was conducted on over a million California women included in a unique, population-based dataset with linkages between hospital discharge data and birth certificate data provided by the California Office of Statewide Health Planning and Development. We also performed a similar analysis in an Iowa-based cohort created through linkages of birth certificates and Surveillance, Epidemiology, and End Results (SEER) cancer registry data.
In aim one, we examined the relationship between history of leukemia and lymphoma prior to pregnancy with gestational hypertension. In Iowa, we found an increased risk of gestational hypertension among women with a history of leukemia/lymphoma (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.07-3.23). The result in California was directionally similar but statistically insignificant (OR 1.12; 95% CI 0.87-1.43). Only two prior studies addressed hypertension during pregnancy in women with a cancer history and had similar results. Our results suggest the need for further studies assessing this relationship as well as increased monitoring of hypertension during pregnancy among those with a history of leukemia/lymphoma.
In aim 2, we evaluated the risk of preterm birth with history of leukemia/lymphoma prior to pregnancy. We found an increased risk of preterm birth in both California (OR 1.89; 95% CI 1.56-2.28) and Iowa (OR 1.61; 95% CI 1.10-2.37) among women with a history of leukemia/lymphoma compared to women without a history of cancer. Additionally, there was no evidence of mediation through gestational hypertension as the odds ratio did not change in either Iowa (1.61 vs 1.56) or California (1.89 vs. 1.89) after controlling for gestational hypertension. The increased risk indicates the necessity of increased monitoring throughout pregnancy and counseling of risks prior to pregnancy among women with a history of leukemia or lymphoma.
Aim 3 explored metabolite levels among newborns born to mothers with a history of leukemia/lymphoma and compared them to the levels of newborns born to mothers without a history of cancer using only the California population. We found several acylcarnitines were significantly (p<0.001) increased compared to newborns of mothers without cancer history: C3-DC (mean difference (MD) = 0.006), C5-DC (MD = 0.009), C8:1 (MD = 0.008), C14 (MD = 0.010), and C16:1 (MD = 0.011), (p<0.001). Additionally, citrulline levels were lower (MD = -0.581) among newborns born to mothers with history of leukemia/lymphoma compared to newborns of mothers without cancer. Our results indicate there is a metabolic impact on the newborns of mothers with a history of leukemia/lymphoma. These altered metabolites can potentially lead to health complications in the newborns such as urea cycle enzyme disorders, necrotizing enterocolitis (NEC), and respiratory distress syndrome.
Overall, if confirmed our findings could have substantial impact; the odds ratios reported above correspond to risk differences of about 1% in California and 2% in Iowa for gestational hypertension and about 6% in California and 4% in Iowa for preterm birth, and the metabolite findings could be a marker for risk of other adverse outcomes among offspring. Findings from each of the aims indicate the importance of increased surveillance and monitoring of mothers with a history of leukemia/lymphoma throughout their pregnancy and delivery. Additionally, newborns should be monitored for any future metabolic consequences. Future studies using cancer characteristics data and longer follow-up times for offspring should be conducted to further investigate metabolic vulnerability in newborns and risk of gestational hypertension and preterm birth among women with a history of leukemia or lymphoma.
Details
- Title: Subtitle
- Pregnancy complications and outcomes among women with a history of leukemia and lymphoma
- Creators
- Sonia Anand
- Contributors
- Elizabeth Chrischilles (Advisor)Kelli Ryckman (Committee Member)Mary Charlton (Committee Member)Patrick Breheny (Committee Member)William Terry (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Epidemiology
- Date degree season
- Summer 2020
- DOI
- 10.17077/etd.005507
- Publisher
- University of Iowa
- Number of pages
- xv, 129 pages
- Copyright
- Copyright 2020 Sonia Anand
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 121-124).
- Public Abstract (ETD)
Leukemia and lymphoma are top cancers affecting children, adolescents, and young adults, with 5-year survival rates up to about 90%. However, with the high survival, there are concerns about the late-effects of these cancers including pregnancy complications and outcomes. In this dissertation, we used two large diverse population-based datasets from California and Iowa to evaluate pregnancy complications and outcomes that were theorized to potentially be affected by having had leukemia or lymphoma.
We found an increased risk of gestational hypertension among women with a history of leukemia/lymphoma compared to women without a history of cancer in Iowa and similar risk, but not significant results, in California. Only two prior studies addressed hypertension during pregnancy in women with a cancer history and had similar results.
We found an increased risk of preterm birth among women with a prior history of leukemia/lymphoma compared to women without a cancer history in both California and Iowa. The strong findings indicate the necessity of increased monitoring of mothers with a history of cancer from preconception through delivery.
Finally, we examined metabolite levels in newborns born to mothers with a history of leukemia/lymphoma in California. We found altered levels of certain acylcarnitines and citrulline, which is an amino acid, compared to newborns of mothers without a prior cancer history, raising questions about the long-term health of offspring.
Further studies are needed with information about cancer characteristics such as time from cancer diagnosis to pregnancy. Closer attention to reproductive health of leukemia and lymphoma survivors is warranted.
- Academic Unit
- Epidemiology
- Record Identifier
- 9983988098602771
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