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Maternal Cancer During Pregnancy and Risks of Stillbirth and Infant Mortality

Publication: Journal of Clinical Oncology

Abstract

Purpose

To examine whether maternal cancer during pregnancy is associated with increased risks of stillbirth and infant mortality.

Methods

On the basis of nationwide health registers, we conducted a study of 3,947,215 singleton births in Sweden from 1973 through 2012. Exposure was defined as maternal cancer diagnosed during pregnancy (number of births = 984) or during the year after pregnancy (number of births = 2,723). We calculated incidence rate ratios (IRRs) for stillbirth and infant mortality, comparing exposed births to unexposed births. Small-for-gestational-age (SGA) and preterm births were examined as secondary outcomes.

Results

Maternal cancer diagnosed during pregnancy was positively associated with stillbirth (IRR, 2.5; 95% CI, 1.2 to 5.0), mainly stillbirths assessed as SGA (IRR, 4.9; 95% CI, 2.2 to 11.0), and with preterm SGA births (relative risk 3.0; 95% CI, 2.1 to 4.4). Positive associations of maternal cancer diagnosed during pregnancy or the year after pregnancy were noted for both neonatal mortality (deaths within 0 to 27 days; IRR, 2.7; 95% CI, 1.3 to 5.6 and IRR, 2.0; 95% CI, 1.2 to 3.2, respectively) and preterm birth (IRR, 5.8; 95% CI, 5.3 to 6.5 and IRR, 1.6; 95% CI, 1.4 to 1.8, respectively). The positive association with preterm birth was due to iatrogenic instead of spontaneous preterm birth. Preterm birth explained 89% of the association of maternal cancer during pregnancy with neonatal mortality.

Conclusion

Maternal cancer during pregnancy is associated with increased risks of rare but fatal outcomes, including stillbirth and neonatal mortality. This may be due to conditions associated with fetal growth restriction and iatrogenic preterm birth. Careful monitoring of fetal growth and cautious decision making on preterm delivery should therefore be reinforced.

Introduction

Cancer during pregnancy is a rare event.1 Whether prenatal exposure to a maternal malignancy and its treatment during pregnancy impair fetal development and neonatal health is, however, of great clinical concern.2 Detrimental effects of maternal cancer on fetal and infant health may include malnutrition, hypoxia, chronic inflammation, and toxic or teratogenic effects of cancer treatment.3-7 Management of cancer during pregnancy therefore poses major challenges for clinicians as well as for the expecting mothers and their families.
The limited evidence to date has mostly refuted the hypothesis that maternal cancer during pregnancy leads to adverse birth outcomes apart from preterm birth1,3,8-10 or that it would affect the offspring’s physical or intellectual development in early childhood.11,12 Reduction in stillbirth rate, especially in cases related to intrauterine growth restriction, and preterm birth, the leading cause of infant mortality, are still of paramount importance.13-16 The risks of fatal outcomes such as stillbirth and infant mortality, however, have rarely been successfully explored in pregnancies complicated with cancer, in either clinical or population-based studies.9,10,17-24
Pregnancy may mask cancer symptoms and delay the cancer diagnostic process.25 A cancer diagnosed soon after pregnancy may therefore already be prevalent during pregnancy. Using a Swedish nationwide cohort study, we aimed to examine the hypothesis that maternal cancer during pregnancy (diagnosed during pregnancy or shortly thereafter) increases the risks of stillbirth and infant mortality. We also assessed potential reasons for such associations, including small-for-gestational-age birth (SGA, used as a proxy for fetal growth restriction) and preterm birth, as secondary outcomes.

Methods

Study Population

Since 1973, the Swedish Medical Birth Register (MBR) has collected information on > 98% of deliveries in Sweden, starting from women’s first visit to prenatal care, through delivery and neonatal care.26 Information includes maternal age, country of birth, parity, height, weight, smoking, mode of delivery, and pregnancy complications. Information about the newborns includes single or multiple birth, sex, gestational age, birth weight, and stillbirth or live birth. In this study, we included 3,947,215 single births (including 14,441 stillbirths) among 2,032,912 mothers from 1973 through 2012. Because multiple births with a maternal cancer diagnosed during pregnancy are potentially exposed to different treatment modalities compared with single births,27 and multiple births have higher risks of adverse birth outcomes,28 we excluded multiple births from the study (n = 99,403). We also excluded births without information on infant sex (n = 169).

Maternal Cancer

Through the unique personal identity numbers assigned to all Swedish residents, we linked all mothers to the nationwide Cancer Register.29 Births with a maternal cancer diagnosed during pregnancy (n = 984) or the year after pregnancy (n = 2,723) were classified as exposed to maternal cancer during pregnancy. The former represents cancers that were diagnosed and potentially also treated during pregnancy, whereas the latter represents cancers that were likely present but untreated during pregnancy. Start of pregnancy was estimated as the date of birth minus gestational age, and end of pregnancy was determined by delivery date.
Similar to reports from other Nordic countries,30,31 malignant melanoma, cervical cancer, and breast cancer were the most common types (Appendix Fig A1, online only). Appendix Table A1 (online only) provides diagnostic codes.
In average, maternal cancers diagnosed during pregnancy were diagnosed in 23.0±10.9 gestational weeks, including 220 (22.4%) diagnosed during the first trimester (≤ 14 completed gestational weeks), 387 (39.3%) during the second trimester (15-28 weeks), and 377 (38.3%) during the third trimester (≥ 29 weeks). Births without a maternal cancer diagnosed during pregnancy or the year after pregnancy were classified as unexposed (n = 3,943,508). Births of women with a cancer diagnosed before pregnancy (n = 12,405) were excluded from the study, because the majority of these cancers were most likely in remission during pregnancy, and we aimed to study the impact of active cancer and its treatment.

Primary Outcomes

Stillbirths are identifiable in the MBR from 28 completed gestational weeks (1973 to 2008) or from 22 completed gestational weeks (2009 onward). Causes of stillbirth are not reported to the MBR, but fetal growth restriction is assessed as a main cause of stillbirth, especially in stillbirth occurring preterm.32 Stillbirths were therefore categorized by birth weight as < 10th or ≥ 10th percentiles for gestational age, and were called SGA and non-SGA stillbirths, respectively. In this analysis, we followed every pregnancy from 28 (1973 to 2008) or 22 (2009 to 2012) completed weeks to date of birth.
Infant mortality (death at 0-364 completed days of life) was identified by linking to the Cause of Death Register. In this analysis, we followed all live births from date of birth to infant death, 1 year of age, or December 31, 2012, whichever came first. Infant mortality was classified as neonatal or postneonatal mortality (deaths within 0 to 27 or 28 to 364 days, respectively).

Secondary Outcomes

We assessed three common pregnancy complications: antepartum hemorrhage, hypertension, and diabetes. Information on these complications was available since 1987 and was identified through diagnostic codes and checkbox (Appendix Table A1).
Gestational age was determined by early second trimester ultrasound (55%), last menstrual period (41%), or through a postnatal assessment (4%). SGA was defined as having a birth weight < 10th percentile for gestational age, according to the sex-specific Swedish reference curve for normal fetal growth,33 and was further classified as birth weight less than the third percentile or from the third to 10th percentile as well as preterm (< 37 weeks) or term (≥ 37 weeks) SGA births.
Preterm birth was defined as a live birth before 37 completed gestational weeks and was subclassified as an extremely (22 to 27 weeks), very (28 to 31 weeks), or moderately (32 to 36 weeks) preterm birth. From 1992 onward, preterm birth was categorized as spontaneous or iatrogenic (ie, induction of labor or caesarean section before labor onset).

Statistical Analyses

Because cancer diagnosed during pregnancy may or may not be treated during pregnancy, and cancer diagnosed after pregnancy is inevitably untreated during pregnancy, we separately analyzed these two exposed groups. The exceptions were analyses of cause-specific infant mortality and neonatal mortality by calendar periods, when for power concerns we combined these two groups.

Primary analyses.

We calculated incidence rates (IRs) of stillbirth and infant mortality and used Poisson regression to estimate the corresponding incidence rate ratios (IRRs). We separately analyzed stillbirth with or without SGA, as well as neonatal mortality, postneonatal mortality, and cause-specific mortality.

Secondary analyses.

We used Poisson regression to estimate IRRs for preterm birth, and relative risks (RRs) were estimated for maternal pregnancy complications and SGA because we had little knowledge about the precise onset of these conditions. These analyses were restricted to live births.
We separately analyzed spontaneous and iatrogenic preterm births. Because maternal pregnancy complications and prenatal suspicion of fetal growth restriction constitute the main indications for iatrogenic preterm birth,35,36 we further examined risk of iatrogenic preterm birth in the absence of such indications.
All analyses were adjusted for maternal age at childbirth, educational level, country of birth (Nordic v non-Nordic countries), parity, and calendar period of birth (1973 to 1976, every 5 years thereafter, or 2007 to 2012). Maternal educational level was retrieved from the Education Register and classified into college and above, high school, or below/unknown. We accounted for within-subject correlations using robust variance estimates.

Additional analyses.

The medical action plan for cancer during pregnancy may depend on when the cancer is diagnosed.1,8 We separated the analyses by trimesters for cancers diagnosed during pregnancy. Because cancers diagnosed immediately after pregnancy might have been suspected during pregnancy, we separately analyzed maternal cancers diagnosed within 3 months or during 4 to 12 months after pregnancy. Because cancer management during pregnancy has changed substantially during the study period, we separated the analyses by calendar periods. To alleviate concern of residual confounding, we also adjusted the analyses of SGA and preterm birth for smoking during pregnancy and body mass index in early pregnancy during 1992 to 2012. Some analyses were not conducted for stillbirth or infant mortality because of small numbers. Finally, to estimate the contribution of preterm birth to the association of maternal cancer during pregnancy with neonatal mortality, we performed a mediation analysis using Cox proportional hazards model.37
All analyses were performed using SAS 9.4 (SAS Institute, Cary, NC) and STATA 13.1 (STATA, College Station, TX). A two-sided P < .05 indicated statistical significance.

Results

Primary Outcomes

Compared with unexposed births, exposed births had higher maternal age, were less prenatally exposed to maternal smoking, and were more often delivered by caesarean section (Table 1).
Table 1. Maternal Characteristics of All Births During 1973 to 2012 in Sweden
We identified eight and nine stillbirths among births with a maternal cancer diagnosed during pregnancy (8.2 per 1,000 births) and the year after pregnancy (3.3 per 1,000 births), respectively. Maternal cancer diagnosed during pregnancy was positively associated with stillbirth (Table 2). The association was confined to stillbirths where the fetus was assessed as SGA at birth, of which five (83%) of six were preterm. Maternal cancer diagnosed during the year after pregnancy was not related to stillbirth.
Table 2. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Stillbirth and Infant Mortality: A Nationwide Study in Sweden, 1973 to 2012
We identified eight and 18 infant deaths among live births with a maternal cancer diagnosed during pregnancy (8.2 per 1,000 live births) and the year after pregnancy (6.6 per 1,000 live births), respectively. Positive association with infant mortality was noted for maternal cancer diagnosed during pregnancy and the year after pregnancy, and the associations were restricted to neonatal mortality (Table 2). Regarding causes of infant deaths, a statistically significant association was only noted for neonatal respiratory conditions (Appendix Table A2, online only).

Secondary Outcomes

Pregnancy complications were not more common in pregnancies with a maternal cancer diagnosed during pregnancy or the year after pregnancy than in the reference population (Table 3 and Appendix Table A3, online only). A positive association of maternal cancer diagnosed during pregnancy was found for preterm SGA but not term SGA (Table 3). Maternal cancer diagnosed during pregnancy was also positively associated with preterm birth, especially very preterm birth (28 to 31 weeks). Positive but weaker associations were also found for maternal cancer diagnosed during the year after pregnancy.
Table 3. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Pregnancy Complications, SGA, and Preterm Birth: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Preterm SGA was more common among births with a maternal hematopoietic cancer or ovarian cancer diagnosed during pregnancy but not among those with a maternal breast cancer, malignant melanoma, or cervical cancer diagnosed during pregnancy (Table 4). Positive associations with preterm birth were noted for all cancer types (except malignant melanoma) diagnosed during pregnancy, and the strongest associations were found in hematopoietic, cervical, and breast cancers. Among hematopoietic cancers, the associations were more pronounced for leukemia compared with lymphoma or myeloma.
Table 4. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Preterm SGA and Preterm Birth, by Common Types of Maternal Cancer: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Maternal cancer during pregnancy was not significantly related to spontaneous preterm birth (Fig 1). Maternal cancer diagnosed during pregnancy was positively associated with iatrogenic preterm birth, even in the absence of pregnancy complications or SGA. Iatrogenic preterm birth appeared twice as often in maternal cancer diagnosed during the year after pregnancy as in the unexposed births, although the association was only statistically significant for moderately preterm birth (32 to 36 weeks).
Fig 1. Maternal cancer diagnosed during pregnancy or the first year after pregnancy and the risks of spontaneous or iatrogenic preterm birth, by gestational age: a nationwide study of all live births in Sweden, 1992 to 2012. Iatrogenic preterm birth without pregnancy complication or small for gestational age birth (SGA) denotes the iatrogenic preterm birth in absence of maternal antepartum hemorrhage, hypertension, diabetes, or SGA. No women with cancer diagnosed during pregnancy had spontaneous preterm birth at 22 to 27 weeks, and no women with cancer diagnosed during the year after pregnancy had iatrogenic preterm birth without pregnancy complication or SGA at 28 to 31 weeks. All models were adjusted for maternal age at childbirth, maternal educational level, maternal country of birth, maternal parity, and calendar period of birth and accounted for within-subject correlations using robust variance estimates.

Additional Analyses

The IRRs of stillbirth, neonatal mortality, preterm SGA, and preterm birth seemed to be higher for maternal cancer diagnosed during the second trimester compared with cancers diagnosed during other trimesters (Appendix Table A4, online only). The IRR of preterm birth was higher for maternal cancer diagnosed during the first 3 months after pregnancy compared with cancers diagnosed thereafter; a similar pattern was not noted, however, for neonatal mortality or preterm SGA (Table 5). Among the 30 iatrogenic preterm births with maternal cancer diagnosed during the first 3 months after pregnancy, 16 (53%) had a maternal pregnancy diagnosis suggestive of cancer, whereas none of the 25 iatrogenic preterm births with maternal cancer diagnosed during 4 to 12 months after pregnancy had such maternal diagnoses.
Table 5. Maternal Cancer Diagnosed During the First 3 Months or 4 to 12 Months After Pregnancy and the Risks of Neonatal Mortality, Preterm SGA and Preterm Birth: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Among births with a maternal cancer diagnosed during pregnancy, the IRs and IRRs of stillbirth seemed to decline over time, although numbers were small (Appendix Table A5, online only). In contrast with the clearly declined IRs over time among both the exposed and unexposed births, the IRRs of neonatal mortality remained constant (Appendix Table A6, online only). For maternal cancers diagnosed during pregnancy, the risk and RRs of preterm SGA tended to be smaller, whereas the IRs and IRRs of preterm birth were greater, comparing 2002 to 2012 to previous years (Appendix Table A7, online only). Adjustment for smoking and body mass index hardly changed the results for SGA and preterm birth (Appendix Table A8, online only). Preterm birth was estimated to account for 89% of the association of maternal cancer during pregnancy with neonatal mortality.

Discussion

To our knowledge, this is the first population-based study to systematically address the impact of maternal cancer during pregnancy, diagnosed either during or shortly after pregnancy, on stillbirth and infant mortality risks. Maternal cancer diagnosed during pregnancy was associated with an increased risk of stillbirths that were assessed as SGA. Maternal cancer diagnosed during pregnancy or the year after pregnancy were both associated with an increased risk of neonatal mortality, mainly due to iatrogenic preterm birth.
We used maternal cancer diagnosed shortly after pregnancy as a proxy for incipient yet untreated cancer during pregnancy and found it to be associated with neonatal mortality, but not with stillbirth. We used maternal cancer diagnosed during pregnancy as a proxy for a cancer that might have in part been treated during pregnancy and found it to be linked to increased risks of both SGA stillbirth and neonatal mortality. That the increased stillbirth risk was confined to maternal cancer diagnosed during pregnancy coincides with the stronger association of maternal cancer diagnosed during pregnancy with preterm SGA live birth, compared with maternal cancer diagnosed thereafter. This is not surprising, because SGA and stillbirth share etiological factors, including intrauterine malnourishment,38,39 and SGA is by itself a major determinant of stillbirth, especially preterm stillbirth.32
The increased risk of SGA stillbirth in maternal cancer diagnosed during pregnancy might be due to cancer treatment. Although information on cancer treatment was unavailable in the current study, previous studies have reported that > 50% of cancers are treated during pregnancy,8 and SGA was particularly common among those who received treatment.8,10,18 The fact that leukemia diagnosed during pregnancy—a cancer requiring intensive chemotherapy in its acute forms3—showed the greatest risk increase for preterm SGA supports such a possibility. Similarly, maternal cancers diagnosed during the second trimester, which are more likely treated than cancers diagnosed during other trimesters, seemed to have stronger associations with stillbirth and preterm SGA.8 According to the clinical guidelines, chemotherapy might be administered beyond the first trimester without terminating pregnancy.1,3 The less pronounced impact of maternal cancer diagnosed during the first trimester might be explained by iatrogenic abortion.8 The weaker associations noted for cancers diagnosed during the third trimester might suggest that cancer treatments are less harmful during late pregnancy.1,18
Cancer treatment might not be the sole explanation for the increased risk of SGA stillbirth, however. The fact that maternal cancers diagnosed during the year after pregnancy, especially the first 3 months, brought about a two-fold increased risk of preterm SGA suggests that cancer itself might also lead to fetal growth restriction and its subsequent stillbirth. Leukemia40 and solid tumors4,5 have both been suggested to alter fetal supplies of oxygen and nutrition. Among the eight stillbirths with a maternal cancer diagnosed during pregnancy, there were both hematopoietic (one leukemia and one lymphoma) and solid cancers (three cervical, one ovarian, one CNS, and one unspecified site). Similarly, both hematopoietic and solid cancers diagnosed during pregnancy led to increased risk of preterm SGA. A local inflammatory environment might also impair the growth and viability of the fetus,41 potentially explaining the commonness of cervical cancer—a cancer commonly managed with conservative treatments during pregnancy1—in stillbirths and the increased risk of preterm SGA in cervical cancer diagnosed during pregnancy (although not statistically significant). Severe psychological distress induced by cancer diagnosis or treatment might also contribute to the increased risks of SGA and stillbirth.42,43
Increased risk of preterm births is well documented among pregnancies complicated with cancer.1,2,8,10 We extended this knowledge by showing that such increased risk was not due to spontaneous but rather to iatrogenic preterm birth. Furthermore, common pregnancy complications or SGA did not seem to be the driving force, suggesting that the vast majority of the preterm births were indicated for oncologic reasons.8 This is supported by the fact that, in contrast to other cancers, malignant melanoma led to no increased risk, whereas leukemia had the highest increased risk of preterm birth.20,24 Although with a small number of outcomes, breast cancer led to no increased risk of preterm SGA but highly increased risk of preterm birth, suggesting further that the preterm deliveries were iatrogenic.1 The increased risk of preterm birth in maternal cancer diagnosed during the first 3 months after pregnancy might also suggest that some of the preterm births were indicated to speed up the diagnostic process and initiate cancer treatment. Finally, although a lower rate of preterm birth was noted among births with a maternal cancer diagnosed during pregnancy in this nationwide study, compared with the previous clinical studies,8,10 the rate increased greatly during 2002 to 2012, suggesting an increasing practice of iatrogenic preterm delivery.
Given the highly increased risk of preterm birth and the fact that preterm birth is the leading cause of neonatal death,16 it is not surprising that we found an increased risk of neonatal mortality among births exposed to maternal cancer during pregnancy. Indeed, preterm birth explained 89% of the increased neonatal mortality risk. Although multiple studies have shown elegantly various adverse health outcomes in relation to preterm birth in pregnancies complicated with cancer,10,11 we are the first, to our knowledge, to demonstrate the increased risk of neonatal mortality. In support of the present clinical guidelines,1,3 prolongation of gestation is therefore of critical importance to reduce neonatal morbidity and mortality. However, expectant obstetrical management may increase risk of fetal malnutrition and stillbirth, leading to a clinical dilemma.
Strengths of our study include the large-scale nationwide study design, enabling us to study rare exposures and outcomes. The prospectively and independently collected information on maternal cancer and neonatal outcomes together with adjustments for multiple potential confounders largely alleviate concerns of common biases and confounding, ensuring a high internal validity.
Given the register-based nature, the current study lacked detailed information on treatment modalities. Because the impact of cancer treatment on fetal health has been thoroughly documented,1,3,8,10 the novelty of the current study lies in demonstrating the risks and characteristics of rare but extreme outcomes—stillbirth and neonatal mortality—in relation to maternal cancer during pregnancy, as well as in shedding light on the potential involvement of other facts, including cancer biology and iatrogenic effect, in addition to cancer treatment in such risks. We were unable to study miscarriage or fetal death before 22 gestational weeks because of data unavailability. Given the small number of stillbirths and infant deaths, the cancer type–specific results should be interpreted with caution. That maternal cancer diagnosed during pregnancy did not influence risks of pregnancy complications might be partly explained by differential clinical management in women with and without cancer diagnosed during pregnancy. Finally, the generalizability of our findings to other populations and to more recent time periods needs to be assessed. Sweden is among the high-income countries with the lowest stillbirth and infant mortality rates, and these rates have decreased over time in many populations.44,45
In conclusion, maternal cancer diagnosed during pregnancy was associated with increased risks of stillbirths assessed as SGA and preterm SGA live birth, suggesting that cancer and its treatment during pregnancy may impair fetal growth. Maternal cancer diagnosed during or shortly after pregnancy was associated with an increased risk of neonatal mortality, largely attributable to iatrogenic preterm birth. Although stillbirth and neonatal death are rare outcomes, the absolute risks of SGA and preterm birth are not small in pregnancies complicated with cancer. Careful monitoring of fetal growth and cautious decision making on the choices as well as the timing of preterm delivery should therefore be reinforced in these pregnancies.

Acknowledgment

The study was approved by the Regional Ethical Review Board in Stockholm, Sweden (No. 2013/2192-32). We thank Gunnar Petersson, Karolinska Institutet, for assistance with data extraction and linkage, and Alessandra Grotta, PhD, Karolinska Institutet, for intellectual contributions to the mediation analysis.
See accompanying Editorial on page 1499

Publisher’s Note

The early release article by Lu et al, entitled "Maternal Cancer During Pregnancy and Risks of Stillbirth and Infant Mortality" (Journal of Clinical Oncology 10.1200/JCO.2016.69.9439) was published online March 6, 2017, with errors.

In the lower panel of Table 4, under "Preterm birth (37 weeks)," "Lymphoma/myeloma" and "Leukemia" should be indented by two spaces.

Also, in Table A4, a solid line should be added to the top border of the line that reads "Preterm SGA (37 weeks)."

This has been corrected as of April 6, 2017. Journal of Clinical Oncology apologizes for the errors.

Authors' Disclosures of Potential Conflicts of Interest

Maternal Cancer During Pregnancy and Risks of Stillbirth and Infant Mortality

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc.

Donghao Lu

No relationship to disclose

Jonas F. Ludvigsson

No relationship to disclose

Karin E. Smedby

Research Funding: Janssen Oncology

Katja Fall

No relationship to disclose

Unnur Valdimarsdóttir

No relationship to disclose

Sven Cnattingius

No relationship to disclose

Fang Fang

No relationship to disclose

Appendix

Fig A1. Distribution of individual cancer types that were diagnosed (A) during pregnancy, or (B) the year after pregnancy.
Table A1. Classifications of Cancer Types and Pregnancy Complications, According to the Swedish Revisions of the ICD Codes
Table A2. Maternal Cancer Diagnosed During Pregnancy or the Year After Pregnancy and the Risk of Infant Mortality, by the Underlying Cause of Death: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Table A3. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Pregnancy Complications and SGA: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Table A4. Maternal Cancer Diagnosed During Pregnancy and the Risks of Stillbirth, Neonatal Mortality, Preterm SGA, and Preterm Birth, by Trimesters
Table A5. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Stillbirth, Stratified by the Calendar Period of Birth: A Nationwide Study In Sweden, 1973 to 2012
Table A6. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risk of Neonatal Mortality, Stratified by the Calendar Period of Birth: A Nationwide Study of all Live Births in Sweden, 1973-2012
Table A7. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of Preterm SGA and Preterm Birth, Stratified by the Calendar Period of Birth: A Nationwide Study of All Live Births in Sweden, 1973 to 2012
Table A8. Maternal Cancer Diagnosed During Pregnancy or the First Year After Pregnancy and the Risks of SGA and Preterm Birth, Also Adjusted for Smoking During Pregnancy and BMI at Early Pregnancy, 1992 to 2012

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Published In

Journal of Clinical Oncology
Pages: 1522 - 1529
PubMed: 28384079

History

Published online: March 06, 2017
Published in print: May 10, 2017

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Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Jonas F. Ludvigsson
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Karin E. Smedby
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Katja Fall
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Unnur Valdimarsdóttir
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Sven Cnattingius
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.
Fang Fang
Donghao Lu, Jonas F. Ludvigsson, Katja Fall, Unnur Valdimarsdóttir, and Fang Fang, Karolinska Institutet; Karin E. Smedby and Sven Cnattingius, Karolinska University Hospital, Stockholm; Jonas F. Ludvigsson, Örebro University Hospital; Katja Fall, Örebro University, Örebro, Sweden; Jonas F. Ludvigsson, University of Nottingham, Nottingham, United Kingdom; Jonas F. Ludvigsson, Columbia University College of Physicians and Surgeons, New York, NY; and Unnur Valdimarsdóttir, University of Iceland, Reykjavík, Iceland.

Notes

S.C. and F.F. contributed equally to this work.
Corresponding author: Donghao Lu, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden; e-mail: [email protected].

Author Contributions

Conception and design: Donghao Lu, Jonas F. Ludvigsson, Sven Cnattingius, Fang Fang
Financial support: Sven Cnattingius, Fang Fang
Administrative support: Fang Fang
Provision of study materials or patients: Sven Cnattingius
Collection and assembly of data: Sven Cnattingius
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors

Funding Information

Supported by the Swedish Research Council for Health, Working Life, and Welfare Grant No. 2012-0498; Swedish Cancer Society Grant No. CAN 2014/417; Partial financing of new doctoral student (KID-funding) from the Karolinska Institutet (D.L.); Swedish Society for Medical Research and Karolinska Institutet Research Associate Award (F.F.); and by an unrestricted grant from Karolinska Institutet (Distinguished Professor Award, S.C.).

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Donghao Lu, Jonas F. Ludvigsson, Karin E. Smedby, Katja Fall, Unnur Valdimarsdóttir, Sven Cnattingius, Fang Fang
Journal of Clinical Oncology 2017 35:14, 1522-1529

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