KLandry_Thesis_2015

ONCOLOGY NURSES' WORK ENVIRONMENT AND THE
RISK OF SPONTANEOUS ABORTION
BY
KELLY ANNE LANDRY
A THESIS
Submitted in partial fulfillment of the requirement for the degree of
Master of Science in Occupational and Environmental Health and Safety
Anna Maria College
Paxton, MA
May 2015

This thesis submitted by
Kelly Anne Landry
In partial fulfillment of the requirements for the
MASTER OF SCIENCE (M.S.) DEGREE
In
OCCUPATIONAL AND ENVIRONMENTAL HEALTH AND SAFETY
Is accepted.
_______________________________ ______________________________
Susan Swedis, PhD Judith Kenary, Ed.D, MBA, RN
May 2015

i
DEDICATION
For my friend, Jessica Maskell –
You have always been my role model. You showed me the power of an educated woman.
I always hoped to follow in your footsteps.

ii
ACKNOWLEDGEMENTS
I would like to offer my sincere appreciation to my professors for instructing me to take a
piece of knowledge and push it one step further to develop a new contribution to my field of
study.
I would also like to Edward, for being my rock, forcing me to push on when I wanted to
give up and always loving me.
I would like to thank my Mother and Father for their loving support, belief in my ability to
pursue further education and giving me the confidence to follow all of my dreams.

iii
ABSTRACT
This exploratory study of health outcomes, risk factors, and protective strategies for
oncology nurses who handle chemotherapeutic agents in a changing work environment
juxtaposed three standards of research: the epidemiology of the occurrence of spontaneous
abortion, changes in cancer treatments, and occupational safety and health strategies for
handling chemotherapy agents. The study describes the experience of reproductive health issues
in oncology nurses, anticipates changes in health risks to this population due to workplace
conditions, establishes recommendations for enhanced protection for this employment sector,
and suggests future research directions.

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TABLE OF CONTENTS
CHAPTER 1. INTRODUCTION …………………………………………………… 1
Oncology Nurses
Cancer
Chemotherapy as a Cancer Treatment
Cancer Treatments Other than Standard Chemotherapy
Oncology Nurses’ Exposure to Chemotherapy Agents
Health Outcomes in Oncology Nurses
CHAPTER 2. METHODS …………………………………………………………… 11
Reproductive Health of Oncology Nurses
Chemotherapy Agents in Use
Occupational Hygiene Strategies in Oncology Nursing
CHAPTER 3. RESEARCH…………………………………………………………... 14
Reproductive Health Outcomes in Oncology Nurses
Finland, 1972 to 1980
France, 1978
Canada, 1974 to 2000
United States, 1988 to 1989
Netherlands, 1990 to 1997
United States, 1993 to 2001
Egypt, 2006
Summary of the Reproductive Outcome Studies
Prevalence Studies
Case Control and Cohort Studies
Trends in Chemotherapeutic Agents of Concern
History of OSH Practices to Protect Health of Oncology Nurses
1970s to 2014
CHAPTER 4. DISCUSSION ………………………………………………………… 34
Nurses’ Reproductive Health Effects
Cancer Treatment Changes
Occupational Health and Safety
Anticipating Oncology Nurses’ Health
Enhancements to Occupational Health and Safety
Future Research Needs
REFERENCES ……………………………………………………………………… 40

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LIST OF FIGURES
Figure Page
Figure 1 Prevalence of spontaneous abortion by age group in the United States,
2014
9
Figure 2 Studies of oncology nurses’ reproductive health outcomes, by time
period of exposure
15
Figure 3 Frequency of spontaneous abortions in oncology nurses in France (1978) 17
Figure 4 Dose-response analysis of reproductive outcomes in nurses exposed to
chemotherapy agents in the Netherlands, 1990 to 1997
21
Figure 5 Prevalence of spontaneous abortion reported in oncology nurses 1978-
2006
23
Figure 6 Prevalence of spontaneous abortion in the general population of U.S.
Women
24
Figure 7 Results of case-control and cohort studies of reproductive outcomes in
oncology nurses for three time periods
25
Figure 8 Breakthrough events in cancer treatments 26

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CHAPTER 1
Introduction
Oncology Nurses
Nurses are a large and valued segment of the health care field. They obtain high levels
of education and earn premium salaries because of their extensive training and the hazards
associated with their workplaces. In 2012, the U.S. Bureau of Labor Statistics reported that
2,711,500 registered nurses were employed in the United States. The registered nurse
population for 2022 is projected increase to 3,238,400 people, in part due to the increase in
the elderly population and their need for nurses. Women have a strong presence in the
nursing field. In 2013 in the United States there were 3.2 million of those employed as nurses
were female compared to 330,000 male nurses employed (United States Bureau of Labor
Statistics, 2014).
Oncology nursing is an area of specialization in nursing. Oncology nurses’ work setting is
varied and the largest number of oncology nurses work in outpatient and ambulatory work
settings (Quinn, 2008). Oncology nurses’ duties include administering cancer treatments,
checking vital signs, managing symptoms and pain, and in general tending to the patient
(Polovich, 2004).
Oncology nurses encounter many health risks in the course of their duties. Some risks are
common to most nurses, but some stem directly from the duties of oncology nursing. A
particular threat comes from working with chemotherapeutic agents. To put this in context,
the next section provides information about the nature of cancer, its treatment, and the health
hazards encountered by oncology workers.

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Cancer
Cancer is abnormal, uncontrolled cell growth resulting in tumorous masses and altered
genetic material (Connor, McLaughlan, & Vandenbroucke. 2007). It is estimated that half of
men and a third of women in the United States will be diagnosed with an invasive cancer
within their lifetime (National Institute of Health, 2015b). According to the American Cancer
Society, cancer is the second leading cause of death in the United States. Worldwide, cancer
is responsible for 13% of deaths (Connor et al., 2007).
Knowledge of cancer as a disease dates to about 460 to 370 BC, when Hippocrates
identified non-ulcer forming and ulcer forming tumors as carcinomas. Research in cancer has
been most prominent within the last 20 years (Bristow, Harrington, Hill, & Tannock, 2013, p.
147).
Modern research has shown that cancer involves alterations to DNA. Genetic research in
the 1960s helped scientists understand how genes function and are damaged or mutated.
Genes are inherited by offspring. Damaged or mutated genes due to exposure to carcinogens
may also be inherited, if germ cells are involved. In the 1970s, scientists identified oncogenes
that prompt cells to grow out of control and promote the spread of cancer. Tumor suppressor
genes were also identified as genes that either slow down cell growth in order to repair DNA
or regulate the life of cells. If these genes are not functioning properly, abnormal cell growth
can occur and cancer can develop. Modern knowledge within the past 150 years has linked
repeated exposures to carcinogens to the development of cancer (Bristow et al., 2013, p. 73).
In 2014 the World Health Organization identified over 100 human carcinogens. As research
continues, more information is being obtained about causes of cancer and how to prevent it.

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Cancer is diagnosed most frequently in the United Sates population in those 65 to 74
years old. The median age at diagnosis is 66 years old. In 2014, it was estimated that there
were 1,665,540 new diagnoses of cancer in the United States and 585,720 deaths from cancer
occurred. Because of advances in cancer detection and treatment as of 2011, there were
13,397,159 people living in the United States with cancer (National Institute of Health,
2015b). The most common types of cancer in 2014 in the United States were prostate, female
breast, lung/bronchus, and colon/rectum cancer. Between 2004 and 2014, new cancer
diagnoses decreased by 0.7% per year (National Cancer Institute, 2014a). Cancers originate
in one area of the body, but the cells may spread and cancer can metastasize to other areas
via the blood or lymphatic systems. The severity of the cancer or staging is based on how far
the abnormal cell growth has metastasized (Bristow et al., 2013, p. 3).
Screening and early detection is most notable for breast, colon, and cervical cancer based
on mammograms, colonoscopies and Pap smears. More recently, tests also have been
developed to detect cancers of the skin, endometrium, lung, mouth, testes, ovaries, prostate
and lymphatic system (Polovich, 2004).
Chemotherapy as a Cancer Treatment
Treatments for cancer include surgery, radiation, chemotherapy, hormone therapy, and
immunotherapy. These treatments may be used singly or in combination. There is no one
approach for all cancers, rather treatment plans are developed for each person and cancer
(Bristow et al., 2013, p. 2).
Chemotherapy is a medication used to treat cancer. Chemotherapy agents, or
antineoplastic drugs, are considered to be cytotoxic drugs, meaning the agents are toxic to

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cells (National Institute of Health, 2015a). Chemotherapy treatment works by destroying
cells that are reproducing. Many chemical agents are not able to differentiate between normal
cells and cancer cells, but because cancer cells usually reproduce faster than normal cells,
these agents can be effective, but cause side effects. Chemotherapy agents can be injected
into an artery or a tumor, or it can be infused into a local area such as the bladder, chest
cavity, or abdomen. Treatments can also be applied topically in a prescription cream or lotion
(Polovich, 2011).
Chemotherapy treatments are provided in multiple settings including the home, hospital,
doctor’s office, outpatient clinic and workplace. Chemotherapy can be prepared and
administered as a liquid, tablets, capsules, intravenously, subcutaneously and
intramuscularly. Chemotherapy administered intravenously may involve using a catheter
attached to the patient’s arm or chest (National Institute of Occupational Safety and Health,
2004).
There are side effects linked to chemotherapy because it targets healthy cells as well as
cancerous ones. It kills bone marrow, cells lining the digestive tract, hair follicle cells, and
cells that line the reproductive tract (Polovich, 2004). Chemotherapy also has carcinogenic,
mutagenic and teratogenic effects (National Institutes of Health, 2015a).
The first successful chemotherapy agent was introduced in 1940s, and cancer research
was being conducted on nitrogen mustard around the time of World War II. This compound
fought against cancer of the lymph nodes. By the 1960s, many cancers could be controlled or
ended with the use of chemotherapy. In the twentieth century chemotherapy was used to
target tumors unreachable or unaffected by surgery or radiation (Bristow et al., 2013, p. 373).

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There are numerous types of chemotherapy drugs, classified by the way they work.
Knowing the classification can give knowledge of the risks and side effects that affect the
exposed individual. In the early twenty-first century some more targeted agents are in use
that have more limited side effects.
Cancer Treatments Other than Standard Chemotherapy
Cancer treatment prior to the 1950s mostly consisted of surgery to remove the site of the
cancer and/or the use of radiation (Bristow et al., 2013, pp 393). These treatments are in use
today. Less invasive surgeries have been developed, and there are more targeted, effective
radiation techniques (Polovich, 2011). The use of radiation to diagnose and treat cancer was
first discovered in 1899. By the twentieth century, it was also established that over-using
radiation can lead to the development of cancer. Further developments led to advanced
radiation techniques such as conformal radiation, conformal proton beam radiation, and
stereotactic radiation therapy. Radiation therapy uses high-energy radiation in the form of X-
rays, gamma rays, charged particles to kill cancer cells and shrink tumors. Radiation can also
damage normal cells. Radiation is administered from an external-beam machine or having a
radioactive material placed on or in the body near the site of cancer. Radiation can directly
damage the DNA of cancer cells or create charged particles within the calls that can damage
DNA (National Cancer Institute, 2010).
Alternatives to cytotoxic chemotherapy agents have been developed to lessen the side
effects of treatments and improve effectiveness. Hormone therapy prevents the development
of new hormones or the spreading of cancers in hormonally sensitive tissues.
Immunotherapy, one alternative strategy, empowers a person’s immune system to combat
cancer cells and prevent the spread of cancer. Targeted therapies attack the products of

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altered genes that cause cells to over-duplicate, as well as some mutated genes. From 1949 to
2004 there have been over 200 medications developed and approved by the Food and Drug
Administration (FDA) for cancer treatment (Polovich, 2011).
The effects of hormones were better understood by the late 1800s after the discovery that
a rabbit’s ability to produce breast milk ended after the animal’s ovaries were removed. The
use of hormones was tested in in breast cancer patients. The result was that their cancer did
not continue to spread once their ovaries were removed. In the mid-1900s, a link was
established between the removal of the testes and prevention of the spread of prostate cancer.
Hormone therapy slows down or stops the growth of tumors that are sensitive to hormone
levels. Hormone therapy, thus, prevents the production of hormones or interferes with the
growth of cancers that are sensitive to hormones. Hormone therapy is approved by the FDA
for use in treating breast and prostate cancer (National Cancer Institute, 2014c).
Immunotherapy was initially used in the 1970s to develop antibodies to attack the cancer
cells. A patient’s body may not be able to detect or defend itself against the cancer cells.
Differentiating agents target the cancer cells and help to develop them into healthy cells.
Immunotherapy usually is aimed at blocking certain proteins. These proteins limit the body’s
immune response. Immunotherapy agents prompt the body to respond accurately based on
the defense needed. Lifting the limits of these proteins can enable the immune system to fight
against cancerous cells. In 2010, the FDA approved a preventative immunotherapy vaccine
that boosts a person’s immune system to help fight cancer cells. These vaccines consist of the
patient’s tumor cells and treat cancers that have developed previously by strengthening the
ability of the immune response to stop the growth of cancer cells, cause the tumor to shrink,

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prevent cancer from coming back, and eliminate cancer cells not killed by other cancer
treatments (National Cancer Institute, 2014b).
Targeted therapies are drugs that block the growth or spread of cancer. These agents
interfere with molecules that are the products of faulty genes. Targeted therapy works on
specific molecules and leaves the normal molecules alone. Instead of killing both normal and
cancerous cells, which happens in standard chemotherapeutic use, targeted therapies are
cytostatic because they retard cellular activity and multiplication (National Institute of
Health, 2015a). Targeted therapies include hormone therapies, signal transduction inhibitors,
gene expression modulators, apoptosis inducers, angiogenesis inhibitors, immunotherapy,
and monoclonal antibodies that deliver toxic molecules. Cancer cells can become resistant to
the targeted therapies overtime (National Cancer Institute, 2014c).
Cancer cells also can send signals that prompt the growth of new blood supply to the
tumor. In 2004, anti-angiogenesis agents were approved by the FDA to stop tumors from
forming more blood vessels (National Cancer Institute, 2014c).
Oncology Nurses’ Exposure to Chemotherapy Agents
Because nurses administer chemotherapy to patients, they also may be exposed to the
agents they work with, and thus may be subject to health effects. Exposure to cytotoxic
agents is a special concern. Nurses’ main routes of exposure to chemotherapeutic agents are
injection, ingestion, dermal absorption, and inhalation (American Society of Health-System
Pharmacists, 2002). A time of high risk of exposure in health care workers is during the
administration of the drug. There can be droplets of the medication in the air and in the
patient’s bodily waste, including blood, mucus, semen, urine, feces and vomit. As many as

8
5.5 million health care workers have the risk of exposure to hazardous chemicals in the work
environment and among them are oncology nurses (Polovich, 2004). Factors affecting a
nurse’s exposure include the amount of drug prepared, handling of drug, and potential for
absorption, personal protective equipment used, the use of biological safety cabinets, and
other work practices (National Institute of Occupational Safety and Health, 2004).
To avoid exposure and detrimental health outcomes from the use of cytotoxic
chemotherapy agents in a health care environment, safe handling practices must be used
when around the hazardous drugs. Safe handling practices were developed within the last 20
years for hazardous drugs, yet a high risk of unintended exposures still occurs (Polovich,
2004).
Health Outcomes in Oncology Nurses
Many studies have reported on health outcomes in oncology nurses, including the
incidence of cancer and reproductive outcomes such as spontaneous abortions or stillbirths
(National Institute of Occupational Safety and Health, 2004). This thesis focuses on
spontaneous abortion as a health outcome in these nurses. Up to 80% of working American
women work least eight months into their pregnancy where they can face occupational
exposures that may affect them or the developing fetus. (United States Census Bureau, 2008).
Because the vast majority of nurses are female, reproductive outcomes such as spontaneous
abortion or stillbirth are important to study in this group.
A spontaneous abortion (also known as a miscarriage) is the expulsion of a fetus before it
is viable, usually defined as occurring within the first 20 weeks of the pregnancy. It is
estimated that between 15 and 25% of all pregnancies end in a spontaneous abortion

9
(National Institute of Health, 2015a). Within the first trimester the most common cause of a
spontaneous abortion is a chromosomal abnormality in the fetus, usually caused by a
damaged sperm or egg. Maternal factors also play a role in the chances of a spontaneous
abortion occurring, such as health problems, age, lifestyle choices or trauma. Lifestyle
choices include drug use, smoking, caffeine intake, malnutrition and exposure to hazardous
substances and radiation. Women who have had a previous spontaneous abortion have a 25%
chance of having another spontaneous abortion (National Institute of Health, 2015a). As a
woman’s age increases, there is a higher rate of spontaneous abortion (Figure 1).
Figure 1
Prevalence of spontaneous abortion by age group in the United States, 2014
Women’s Age (years) Prevalence of Spontaneous Abortion
Under 35 15%-20%
35 20%
40 40%
45 80%
Source: Mayo Clinic, 2015
Warning signs of a spontaneous abortion include weight loss, severe back pain,
contractions, bleeding, and decreased signs of pregnancy. Although chromosomal
abnormalities are not preventable, there are steps that can be taken to help prevent some
causes of spontaneous abortion including managing stress levels, exercising, eating a
healthful diet, taking vitamins and avoiding smoking (Mayo Clinic, 2015).
Stillbirth is defined as an intrauterine death and delivery of a fetus beyond 20 weeks of
gestation. Factors that contribute to an increased risk of a stillbirth include age (older than 35
years old), alcohol and drug use, poor prenatal care, smoking, ethnicity, and malnutrition.
Common causes of stillbirths include birth defects, growth room restriction, infections,

10
umbilical cord accidents, mature diabetes, trauma, high blood pressure and issues with the
placenta (National Institute of Health, 2015a).
Nurses who handle chemotherapeutic agents have been studied over time. There is
epidemiological evidence that the oncology nurses experience spontaneous abortions at
elevated rates. These data are examined in detail in the course of this study

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CHAPTER 2
Methods
This is an exploratory study to examine the risk of spontaneous abortion in oncology
nurses in light of their changing work environment. The central risk factor for spontaneous
abortion in oncology nurses has been exposure to certain chemotherapy agents. Over time,
however, there have been changes in the types of chemotherapeutic agents used, their
frequency of use, and the efforts to introduce occupational safety practices to reduce risks to
nurses and other healthcare workers.
This study analyses data available for a period of approximately 30 years about three
related themes:
 oncology nurses’ reproductive health indicators
 changes over time in the mix of types of chemotherapy agents used that may
represent different health hazards; and
 occupational health strategies used by oncology nurses.
The period covered is approximately 1970 to 2013, when all three research areas are taken
into consideration.
The goals of this study are to explore possible relationships among these three areas of
inquiry, to describe and anticipate changes in health risks to oncology nurses, to develop
recommendations for enhanced protections for them in the workplace, and to suggest
recommendations for future research,

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Reproductive Health of Oncology Nurses
Studies of the occurrence of spontaneous abortion as a reproductive outcome in oncology
nurses exposed to chemotherapeutic agents were identified in the literature. Exposures
occurred between 1972 and 2006 and the studies were conducted in multiple countries.
Criteria for selecting the published studies to be analyzed included the subjects’ professions,
strength of study design, and time period and geography of the study. All participants had to
be women 45 years old or under because women over 45 years old have less of a chance to
get pregnant and have a higher risk of having a spontaneous abortion (Mayo Clinic, 2015).
The studies were published in peer reviewed journals. Many of the studies cited earlier
reports that were helpful in gaining an understanding of longer term investigations into this
problem. The studies selected varied in size and had from 60 to 50,000 participants. Both
descriptive and analytical studies were considered that used varying designs, namely
prevalence, case-control, and cohort, so outcome measures also varied (i.e., percent, odds
ratio, and rate ratio).
Studies were selected to construct an international view point, so there were examples
from the United States, Egypt, Canada, France, and Finland.
Chemotherapy Agents in Use
The types of chemotherapy agents in use may represent different health hazards. Historic,
economic and scientific data were sought to explore any changes in the classes of
chemotherapy drugs used over time. An effort was made to focus on the time period
represented by the epidemiology studies included in the description of oncology nurses’
reproductive health. A table of breakthrough events in cancer treatment strategies was
constructed covering about 100 years, from 1899 to 2004. Data were derived from published

13
research reports. This project also examined the most recent picture for treatment of common
cancers as identified by SEER to further illustrate the combination approach that is common
in the early twenty-first century (National Cancer Institute, 2014a). The statistics were based
upon research of treatment trends in 2008 and 2012-2013 conducted by the American Cancer
Society.
Occupational Hygiene Strategies in Oncology Nursing
The third analysis of this research looked at the types of occupational hygiene approach to
protecting oncology nurses’ health in use from the 1970s to 2014. Standards and
recommendations on the safe handling of chemotherapeutic drugs were the focus. This
information was obtained from numerous sources, primarily the Occupational Safety and
Health Administration (OHSA), NIOSH, and the Mount Sinai Summit meeting (Frank,
Jones, & Mass, 1983).
Finally, these three strands of research were examined together to anticipate changes in
health risks to oncology nurses, to develop recommendations for enhanced protections for
them in the workplace, and to develop recommendations for future research.

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CHAPTER 3
Results
This chapter reports the results of the three research strands outlined in methods
section. It reviews epidemiology studies of the reproductive health outcomes in oncology
nurses, describes trends in the use of chemotherapy agents, and provides a history of
occupational hygiene practices used to protect the health of oncology nurses.
Reproductive Health Outcomes in Oncology Nurses
This section provides an analysis of seven epidemiology reports, and is organized by time
period of exposure. The studies vary in location, type of study conducted, number of subjects
and the year the study was conducted (Figure 2). These are free standing studies so this
analysis cannot produce a time trend, but does report on what is known about reproductive
outcomes. This section includes an evaluation whether the results of these studies seem
consistent among the locations and time periods represented. Although this thesis focused on
spontaneous abortion as a reproductive health outcome, some of the epidemiology studies
may have considered additional outcomes, as well.
In total, seven studies from six countries were examined. The studies represent some
populations of nurses who could have been exposed to chemotherapy agents during the years
1972 to 2006. Two were analytic studies and five were descriptive studies. Among the five
prevalence studies was a nested case-control study. The cohort and case-control studies
divided the subjects into two groups: exposed and unexposed, as did three of the five
prevalence studies. The exposed group consisted of nurses who performed various nursing
tasks that could have led to exposure to chemotherapeutic agents through preparing and

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administering treatments to cancer patients. The unexposed group consisted of nurses whose
various nursing tasks involved exposure to chemotherapy agents too low to document or no
exposure at all. These studies are reviewed separately in the sections that follow.
Sources (listed by study number):
(1) Hemminki, Hornung, Lindbohm &Selevan, 1985
(2) Caillard, Collin, Gout, Hémon, Poyen & Stücker, 1990
(3) Beking, Chow, D Le, Dimich-Ward, Gallagher, Lorenzi, Ratner, … & Teschke, 2010
(4) Steele, Valanis, & Vollmer, 1991
(5) Fransman, Roeleveld, Peelen, de Kort, Kromhout & Heederik, 2007
(6) Grajewski, Lawson, Lividoti Hibert, Spiegelman, Rich-Edwards, Rocheleau & Whelan,
2012
(7) Elshamy, El-Hadidi, El-Roby & Fouda, 2010
1. Finland, 1972 to 1980
A case-control study was conducted with nurses who had pregnancies and worked within
17 Finnish hospitals (Hemminki et al., 1985). Nurses were identified using databases that
contained information about hospitalization. To be considered for this study, a nurse had to
be 40 years of age or under as of 1980 and had their last menstrual period between late 1972
Figure 2
Studies of oncology nurses’ reproductive health outcomes, by time period of exposure
1972-
1980
1978 1974-
2000
1988-1989 1990-1997 1993-2001 2006
Study
Number
1 2 3 4 5 6 7
Nation Finland France Canada United
States
Netherlands United
States
Egypt
Type of
Study
Case-
control
Prevalence Case-
control/
Cohort
Prevalence Prevalence Prevalence/
Case-
control
Prevalence
Number of
Subjects
124 466 56,213 2,815 4,393 7,482 60

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and early 1980. Only one pregnancy per nurse was considered in this study. For each nurse
with a fetal loss, there were three matching controls. A questionnaire was sent out to all
participants asking for lifestyle and exposure information (x-rays, anesthetic gases, ethylene
oxide and chemotherapeutic agents). Nurses who had exposure to these hazards less than
once per week were considered to be unexposed for the purposes of this study. Of 650
subjects, 87.4% responded to the questionnaire. The study found 124 participants who
experienced fetal loss and 321 who experienced live births. Of the 124 participants who had
fetal loss, 14.5% had exposure to chemotherapeutic agent’s exposure within the first
trimester. Of the 321 participants who experienced live births, 8.7% had exposure to
chemotherapeutic agents within the first trimester. Participants who experienced fetal loss
were found to have had a significantly higher likelihood of exposure to chemotherapeutic
agents within the first trimester (Odds Ratio = 2.30, 95% CI: 1.20-4.39). Any bias in this
study could have stemmed from recall error by the study participants (Hemminki et al.,
1985).
2. France, 1978 (mean year of pregnancy)
Nurses from four French hospitals were recruited for a prevalence study of reproductive
outcomes with respect to exposure to chemotherapeutic agents (Caillard et al., 1990). The
study was conducted by means of interviews between 1985 and 1986, but the exposure
period was 1978. The interview consisted of three sections. The first section reviewed the
general characteristics of the nurses including age and years of working as a nurse. The
second part reviewed the pregnancy characteristics and maternal factors. The final aspect
reviewed the work performed as a nurse and the amount of exposure to chemotherapy agents.
To be considered an exposed nurse, the nurses must have administered a perfusion 10 times

17
within a week. Unexposed nurses worked in general, cardiac, and endocrinology units. The
mean length of a nurse’s work within the department was 4.6 years (SD 4.3). There was a
total of 535 women eligible to participate; however, 39 nurses were on leave and 30 refused
to respond. The mean age of the nurses at the interview was 31.2 yrs. (SD 6.5). Thus there
were 466 nurses who took part in the study, with a total of 534 pregnancies. Of the 534
pregnancies, there were 139 conceptions among exposed nurses and 357 conceptions among
unexposed nurses.
Within the constraints of this study, spontaneous abortion was considered as a pregnancy
ending before the 28th week into the pregnancy. The frequency of spontaneous abortions was
greater in exposed nurses (Figure 3). Nurses with exposure to chemotherapeutic agents had a
prevalence of 25.9% for the occurrence of spontaneous abortions, compared to 15.2% in
unexposed nurses. The prevalence of spontaneous abortions in first pregnancies was lower in
both exposed and unexposed nurses compared to all pregnancies. In all first pregnancies,
exposed nurses had a prevalence of spontaneous abortion of 22.7% compared to unexposed
nurses (10.3%). In this prevalence study a rate ratio was also calculated for all pregnancies of
1.7 (95% CI: 1.2-2.5) and first pregnancies 2.2 (95% CI: 1.2-4.1). The results were
statistically significant (Caillard et al., 1990).
Source: Caillard et al, 1990
Figure 3
Frequency of spontaneous abortions in oncology nurses in France (1978)
Exposed
Pregnancies
Unexposed
Pregnancies
Rate Ratio 95%
Confidence
Interval
All Pregnancies 25.9% 15.1% 1.7 1.2-2.5
First Pregnancies 22.7% 10.3% 2.2 1.2-4.1

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3. Canada, 1974 to 2000
A combined case-control and cohort study was conducted to examine the adverse birth
outcome in nurses with potential exposure to chemotherapeutic agents in British Columbia,
Canada (Beking et al., 2010). This study consisted of 56,213 women who worked as
registered nurses at least one year from 1974 to 2000 and who had a pregnancy occurring any
time in the period 1986 to 2000. Of the 56,213 women registered within this time period,
12,741 had live births totaling 22,491 offspring. A total of 141 women were identified as
working within the cancer unit during their pregnancy. Within the constraints of this study,
spontaneous abortion was considered as a pregnancy ending before 20 weeks into the
pregnancy. Three outcomes were evaluated in this study using different study designs and
yielding different measures: congenital anomalies (odds ratio), spontaneous abortion in
exposed nurses (relative risk), and fetal loss in the first trimester for exposed nurses (odds
ratio). Data for the study were collected by conducting phone calls asking if nurses had ever
prepared or administered chemotherapeutic agents and if care was provided to a cancer
patient. The length and amount of exposure was discussed. Protective equipment, safe
handling and location of the preparation of the agents were other factors taken into
consideration. For congenital anomalies in offspring of nurses who had exposure to
chemotherapeutic agents at least once per week, the study resulted in an odds ratio of 4.7
(95% CI: 1.2-18.1). Nurses who had exposure to antineoplastic drugs had a relative risk of
spontaneous abortion of 1.7 (95% CI: 1.0-2.8). Nurses who had a fetal loss had a higher
likelihood of exposure to chemotherapy agents in the first trimester (Odds Ratio of 2.3 (95%
CI: 1.2-4.4)). All of these results were statistically significant (Beking et al., 2010).

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4. United Sates, 1988 to 1989
A prevalence study was conducted with male and female nurses, nurse’s aides,
pharmacists and pharmacy technicians in the United States (Steele et al., 1991). A
questionnaire was used to obtain information on lifestyle choices, exposures in the workplace
and pregnancy outcomes in the years 1988 and 1989. A total of 2,815 participants were
within this study and 7,049 pregnancies were reviewed. Of the 7,049 pregnancies, 6,363 were
among female staff members and 731 occurred in the wives of male staff members. Multiple
pregnancies per participant were included as part of this study. A total of 1,434 female
workers had exposure to chemotherapeutic agents within the workplace for at least 2 years
(1988-1989). The wives of the male nurses accounted for 288 pregnancies and were
considered to have had second-hand exposure to chemotherapeutic agents within the
workplace for at least two years. For this study a spontaneous abortion was defined as a
failed pregnancy within the first 20 weeks and a stillbirth was defined as a failed pregnancy
after 20 weeks. Among the participants 82.8% of pregnancies resulted in a live birth.
Spontaneous abortion was the pregnancy outcome for 11.3% of pregnancies in those
considered to have had occupational exposure. Stillbirth was the pregnancy outcome for
0.9% of pregnancies in the unexposed. Female workers exposed to chemotherapeutic agents
within their pregnancy, therefore, were found to have an increased risk of having a
spontaneous abortion. Wives of male workers did not have an increased risk of having a
spontaneous abortion. The risk of having a still birth was not associated with exposure to
chemotherapeutic agents in this study (Steele et al., 1991).

20
5. Netherlands, 1990 to 1997
A prevalence study in the Netherlands was conducted in 121 hospitals to study the
reproductive outcomes in nurses who had dermal exposure to antineoplastic drugs (Fransman
et al., 2007). The study used a questionnaire sent to 4,393 exposed and unexposed nurses
who were between 22 and 37 years old in 2005. To be a participant in this study, a woman
must have worked as a nurse for at least two months in the period 1990 to 1997. The
questionnaire asked about nurse’s pregnancies, lifestyles, work performed, and exposure to
chemotherapeutic agents. Within this study a spontaneous abortion was considered a fetal
loss before the twentieth week of confirmed pregnancy. A stillbirth was considered a fetal
loss during or after the twentieth week of confirmed pregnancy. Of 4,393 participants, 2,426
had been pregnant or were attempting to get pregnant from 1990 to 1997. Nurses who had a
premature delivery of viable births had an elevated likelihood of exposure to
chemotherapeutic agents (Odds Ratio = 1.08, CI: 1.00-1.17). Nurses who had exposure to
chemotherapeutic agents and had a low birth weight baby had an Odds Ratio of 1.11 (CI:
1.01-1.21).
Despite finding an association between exposure and premature birth or low birth weight,
this study did not determine that spontaneous abortion and stillbirth were not seen to be
related to exposure to chemotherapeutic agents. Spontaneous abortion was prevalent in 5.5%
of unexposed births. Stillbirth was present in 0.4% of unexposed births dose-response
analysis was done to further problem and associations. In low levels of exposure to
chemotherapeutic agents, spontaneous abortions were present in 6.8% of births and stillbirths
occurred in 1.4% of pregnancies. In medium levels of exposure to chemotherapeutic agents,
spontaneous abortions were present in 5.6% of pregnancies and still births occurred in 1.4%.

21
In high levels of exposure to chemotherapeutic agents, spontaneous abortions were present in
6.9% of pregnancies and stillbirths occurred in 0.7% (Figure 4). The study design includes
the chance of recall bias. The data indicated a possible relationship between dermal exposure
to chemotherapeutic agents and some of the nurses’ reproductive outcomes. This study found
dose-response results to be irrelevant (Fransman et al, 2007).
Figure 4
Dose-response analysis of reproductive outcomes in nurses exposed to
chemotherapy agents in the Netherlands, 1990 to 1997
Levels of Exposure to
Chemotherapeutic Agents
Spontaneous Abortion Still Birth
No Exposure 5.5% 0.4%
Low Levels of 6.8% 1.4%
Medium Levels 5.6% 1.4%
High Levels 6.9% 0.7%
Source: Fransman et al., 2007
6. United States, 1993 to 2001
A study published in 2012 in the American Journal of Obstetrics and Gynecology
reviewed spontaneous abortion risks based on nurses’ occupations (Grajewski et al., 2012).
This was a retrospective prevalence study that was conducted from 1993 to 2001. Nurses
reported their exposure to anesthetic gases, disinfectants, x-rays, and chemotherapeutic
agents during each trimester of pregnancy. They estimated exposure based on how many
hours a day a nurse was exposed to the hazard. An initial study was conducted in 1989 and
then a follow-up study started in 1993. The initial study consisted of 116,430 nurses, and
then a questionnaire was used to determine if any of those nurses had experienced at least
one pregnancy and if the nurse had worked through her pregnancy. There were 7,482 nurses

22
who fit that description, and 775 nurses had any hazardous exposure experience. This
amounted to 10.5% of nurses. The age adjusted odds ratio for those who had exposure to
chemotherapeutic agents and had a spontaneous abortion was 1.97 (CI: 1.41-2.76) and thus
was statistically significant (Grajewski et al., 2012).
7. Egypt 2006
A cross-sectional prevalence study conducted in Egyptian hospitals examined health
hazards among oncology nurses with exposure to chemotherapeutic agents (Elshamy et al.,
2010). There were 35 exposed nurses working in adult and pediatric oncology units. The
control group of unexposed nurses consisted of 29 nurses within the same age bracket as the
exposed, but who worked in a surgical department, general medicine, or cardiac medicine.
The exposed group of nurses had 54.3% of participants within the age group of 30 to 40
years old, while the control group nurses had 51.7% of participants within the age group of
30 to 40 years old. All nurses had at least 10 years of work experience within their field.
The study consisted of a questionnaire, an Ames test of urine samples and a performance
checklist. The questionnaire obtained information about the nurse’s work history, exposure to
chemotherapeutic agents and safe handling practices. Of the exposed nurses, 22.6% of nurses
had experienced a spontaneous abortion, and in the control group, 10.3% of nurses had
experienced a spontaneous abortion. Of the exposed nurses, 40% of urine samples tested
positive for exposure to mutagens, compared to the control group that had 10.3% positive
tests (Elshamy et al., 2010). The results show both an association between exposure and a
health outcome, and the use of a biomarker of exposure (positive Ames test of urine
samples).

23
Summary of the reproductive outcome studies
The outcomes of the studies reviewed are not directly comparable to each other because
they use different study designs and outcome measures. The dates the studies focus on was
the time the women were pregnant. Some of the studies overlapped in time and were for a
span of years. In some studies data was also available for stillbirths, although there are not
enough data points to draw any firm conclusions.
Prevalence Studies.
As part of this research, the results of the prevalence studies were analyzed as a group.
Prevalence data were available from five of the seven studies in this thesis. The studies
involved time periods from 1978 to 2006 (Figure 5). The highest prevalence figures were
found in the earliest and latest studies, and the lowest prevalence was found in the study that
covered the years 1990 to 1997 (in the Netherlands). In the three studies where a prevalence
was reported for both exposed and unexposed nurses, exposed nurses had a higher rate of
spontaneous abortion (France, Netherlands, and Egypt).
Source: Caillard et al., 1990, Steele et al., 1991, Fransman et al., 2007, Grajewski
et al., 2012, Elshamy et al., 2010
Figure 5
Prevalence of spontaneous abortion reported in oncology nurses 1978-2006
1978 1988-
1989
1990-1997 1993-
2001
2006
Spontaneous Abortions in
exposednurses
25.9% 11.3% 6.43% 10.5% 22.6%
Spontaneous Abortions in
unexposed nurses
15.1% 5.5% 10.3%
Nation France United
States
Netherlands United
States
Egypt

24
In the two studies conducted on nurses in the United States, a prevalence of
spontaneous abortion for unexposed nurses was not calculated. To address this gap, the
prevalence values found for exposed nurses can be compared to that for women in the
general United States population (15-20%) for 2014 (Figure 6). Oncology nurses’
prevalence of spontaneous abortion in the United States in 1988 to 1989 (Steele et al,
1991) and 1993 to 2001 (Grajewski et al, 2012) was slightly lower than in the U.S.
general population (Mayo Clinic, 2015). The lifestyle factors embraced by nurses and
their access to health care may be factors in the differences seen.
Source: Source: Caillard et al, 1990, Steele et al, 1991, Fransman et al, 2007,
Grajewski et al, 2012, Elshamy et al, 2010
Case Control and Cohort Studies.
Three of the studies analyzed for this thesis reported results as odds ratios and relative risks
(rate ratios) and represented exposures data from the time periods of 1978, 1990-1997, and 1993-
2001 (Figure 7). The ratios are all between 1.7 and 2.3. There is no way to determine if there is a
0
5
10
15
20
25
30
1978 1988-1989 1990-1997 1993-2001 2006
Prevelance
Time Period
Figure 6 Prevalence of spontaneous abortion in the general population of
U.S. Women
Oncology Nurses Prevalence of Spontaneous Abortion

25
significant difference between them because they were independent studies. Nonetheless, it is
interesting to note that rates for oncology nurses were higher in all three studies, regardless of
time period or geography.
Source: Hemminki et al., 1985; Beking, et al., 2010; Grajewski et al., 2012
Trends in Chemotherapeutic Agents of Concern
The use of chemotherapeutic agents had an early discovery and use, unlike other types of
cancer treatments (Figure 8). In 1899, radiation was used for the first time as a cancer
treatment. In 1942, nitrogen mustard was studied as a chemotherapy agent. In 1959,
cyclophosphamide was approved by the Food and Drug Administration (FDA) for use in
cancer treatment. In 1965, two types of chemotherapy treatments were combined and were
successful in putting a cancer into remission. Three types of cytotoxic chemotherapy were
administered in 1975 as a treatment. In 1992, Taxol was approved for use as a hormonal
cancer treatment option. Hormonal treatments included Taxol and Tamoxifen, agents that
target the role of estrogen receptors in cancer. In 2001, Glivec was approved by the FDA as a
targeted therapy treatment. In 2004, gefitinib was discovered to work as a cancer treatment
by targeting epidermal growth factors. In the same year, Avastin, an antiangiogenic agent,
was used to treat colon cancer (Figure 8).
Figure 7
Results of case-control and cohort studies of reproductive outcomes in oncology nurses for
three time periods
1972-1980 1986-2000 1993-2001
Spontaneous
Abortion
Odds Ratio 2.30
(95% CI 1.20-4.39)
Relative Risk 1.7
(95% CI 1.0-2.8)
Odds Ratio 1.9
(1.4-2.76)
Nation Finland Canada United States

26
The classes of chemotherapy agents include alkylating agents, antimetabolites, anti-tumor
antibiotics, corticosteroids, mitotic inhibitors, and topoisomerase inhibitors (Connor et al.,
2007). Specific agents include Temodar, Tamoxifen, Methotrexate, and Imuran (Polovich,
2011). Chemotherapy discoveries have been the most prominent treatment option besides
radiation therapy since the 1900s. Antiangiogenic and targeted therapies were only
discovered in the 2000s as viable cancer treatment options (DeVita, Jr. et al., 2008).
The oncology workplace is changing because treatments are changing. If the proportion of
treatments that involve cytotoxic agents is decreasing because of the greater variety of
treatment agents available, then exposures to oncology nurses also may be changing. The
effect of changing treatments relative to health risks for oncology nurses has not yet appeared
in the scientific literature.
Figure 8
Breakthrough events in cancer treatments
Year Agent Cancer Treated Type of Action
1899 X-ray NA Radiation Therapy
1942 Nitrogen Mustard Non-Hodgkin’s
Lymphoma
Alkylating Chemotherapy
1948 Methotrexate Childhood Leukemia Antifolates
1950 Fluoropyrimidine Colorectal Cancer Antifolates
1951 6-Thioquanine and 6-
Mercaptopurine
Acute Leukemia Alkylating Chemotherapy
1959 Cyclophosphamide NA Alkylating Chemotherapy
1965 POMP Regimen Childhood Acute
Lymphoblastic Leukemia
and Antifolates
1975 Combination of
Cyclophosphamide,
Methotrexate, and 5-Flurouracil
(CMF)
Node-Positive Breast
Cancer
and Antifolates
1992 Taxol NA Immunotherapy
2001 Glivec Chronic Myelogenous
Leukemia
Targeted Therapy
2004 Gefitinib NA Targeted Therapy
2004 Avastin Colon Cancer Antiangiogenic Agent
Source: Chabner, & Roberts, Jr., 2005; DeVita, Jr., & Chu, 2008; Polovich, 2011

27
A report conducted by the American Cancer Society in 2012, identified the most common
types of cancer, female breast and colon/rectum cancer in both men and women. The cancer
treatment types were identified by a prevalence increase or decrease throughout a time
period. The time band of this study is not comparable to the prevalence from the studies
mention above as the time periods do not intersect. However, this report examines the change
in prevalence of cancer treatments from 2008 to 2013. Alternative cancer treatments had an
increased prevalence overtime. Alternative cancer treatments in this context does not mean
new chemotherapy agents, rather, the combined use of surgery, radiation, and chemotherapy.
In some treatment plans there was a combination of multiple treatments. The
chemotherapeutic agent use decreases or increases depending on the combination of
treatments and the type of cancer. There was not a consistent prevalence change for
chemotherapeutic agents, however alternative treatments had a higher prevalence over time.
Within a narrow time point, changes in treatment are evident, but no major reductions in the
reliance on chemotherapy in colon and breast cancer are evident. This study shows that older
cancer treatments are still used today in addition to new treatments (American Cancer
Society, 2013).
History of OSH Practices to Protect Health of Oncology Nurses
1970s
In the 1970s, there was a link established between occupational exposure to chemotherapy
agents and the development of cancer (Polovich, 2011). The first study of chemotherapy
risks to health care workers in America was performed using an Ames test. Agents that
caused genetic mutations in bacteria were found in the urine of cancer patients and workers
(Polovich, 2004). This test has a 90% accuracy of finding the carcinogenic effects as long as

28
the exposure was within 48 hours, the time the toxicants could expected to be held within the
human body. Ames tests are still used to check mutation levels (Polovich, 2004). They can
identify exposed workers and contamination of work environments (National Institute of
Occupational Safety and Health, 2004).
1980s
During the 1980s, the Occupational Safety and Health Administration (OSHA) visited a
California hospital that had no preparation and protection practices for handling
chemotherapy. Ames tests were conducted on health care workers and they showed the
presence of mutagens in their systems. These findings at the hospital resulted in the
American Society of Health-Systems Pharmacists Assistance Bulletin on Handling Cytotoxic
Drugs (2002). There were no standardized safe practices in oncology medicine accepted
globally. Once the risk was identified, nurses in America prepared the cytotoxic drugs in a
medication room to lower the risk of contamination and human exposure (Polovich, 2004).
In 1981, a committee met at the Mount Sinai Medical Center to discuss the safe handling
practices and guidelines for handing of chemotherapeutic agents. At this meeting, the
hazardous effects of chemotherapeutic agents were established and federal laws were
researched. Information on exposure of healthcare workers was discussed along with means
of protection. The report produced following this meeting suggested that pregnant healthcare
workers should not be handling chemotherapeutic agents and reassigned to lower risk tasks
(Frank et al., 1983).
OSHA published safe handling practices for chemotherapeutic agents in 1986. These
practices included administration of chemotherapeutic treatments, spills, and excretions from

29
chemotherapy patients. Recommendations continued to be developed on safe handling
practices (Corelle, C., Glass, A., Labuhn, K., Valanis, B., & Vollmer, W., 1992).
A biological safety cabinet was recommended as they provided a vertical airflow that gets
filtered through a high efficiency particulate air filter. This pushes the air flow away from the
worker (Frank et al., 1983; National Institute of Occupational Safety and Health, 2004).
1990s
By 1990 the American Society of Health-System Pharmacists revised and published a
bulletin on the dangers and safe handling procedures for hazardous drugs, which prompted
OSHA to add new guidelines in 1995 (2002). In 1999, the NIOSH alert reported that 11 out
of 12 case studies showed chemotherapeutic agents within the urine of health care workers
despite the use of safety precautions. NIOSH also stated that guidelines for proper handling
of chemotherapeutics established before 1991 had sporadic adherence. Since nurses at that
time were mostly females, this brought attention to the reproductive outcomes of handling
these agents. The results of a study conducted in the 1900s, revealed that exposure to
chemotherapeutic agents resulted in menstrual cycle changes, malformation in fetuses and
spontaneous abortion (Corelle, et al., 1992
2000s
In 2001, the Oncology Nursing Society published complete guidelines for chemotherapy
and biotherapy, as well as recommendations for safe handling practices. NIH also established
safe handling recommendations and administration of cytotoxic drugs that appeared in 2002.
By 2003, the Oncology Nursing Society published Safe Handling of Hazardous Drugs.
NIOSH reported on using a closed system approach to handle chemotherapeutics for six

30
months. The result was a reduction of chemotherapeutics found within health care workers
urine samples (National Institute of Occupational Safety and Health, 2004).
The American Society of Clinical Oncology in 2004 published safety recommendations
that would at least meet the minimum safety criteria established by OSHA (Bonelli,
Cummings, Galioto, Jacobson, Lefebvre, McCorkle, McNiff, & Polovich, 2009). That same
year the NIOSH alert, Preventing Occupational Exposures to Antineoplastic and Other
Hazardous Drugs in Health Care Setting, was published. The report covered
recommendations on receiving and storing chemotherapy agents, drug preparation and
administration, use of ventilated cabinets, spill control, medical surveillance, routine
cleaning, and decontaminating, housekeeping and waste disposal. NIOSH reviewed 14
studies on the association between chemotherapy exposures and developmental and
reproductive effects, Of the 14 studies, nine showed a link. The NIOSH alert found an
increase in fetal loss, congenital malformations dependent upon the length of the exposure,
low birth weights, infertility, and congenital abnormalities. The NIOSH alert also pointed out
that there were no OSHA permissible exposure limits, American Conference of
Governmental Hygienists (ACGIH) threshold limits, or NIOSH recommended exposure
limits established for hazardous drugs. Any limits that had been established were in relation
to sensitivity to the item and not the carcinogenic effect. Some pharmaceutical manufacturers
may have occupational exposure limits used within their workplace. This information was
available upon the Standard Data Sheets SDSs (NIOSH, 2004).
NIOSH recommendations.
If a nurse was exposed to a chemotherapy patient’s bodily fluids, the nurse should clean
the area well and inform the physician. Personal protective equipment should be required for

31
anyone preparing and administrating hazardous medications. As part of a full protective
ensemble gowns and goggles must be used to provide complete protection (National Institute
of Occupational Safety and Health, 2004). Contact lenses should not be allowed in a
chemical preparation environment although, wearing eye glasses can increase the difficulty
of wearing goggles. Gowns need to be provided to protect against getting the chemicals onto
their clothing and absorbing them dermally (National Institute of Occupational Safety and
Health, 2004). The personal protective equipment needs to be offered to fit all sizes of
workers. The correct type of gloves are also important. Most health care workers use gloves
but not all gloves are designed to be used while working with chemotherapy drugs. The
hospital needs to provide chemotherapy protective gloves (Polovich, 2004).
Facemasks approved by the National Institute of Occupational Safety and Health
(NIOSH) should be available when cleaning up a spill to prevent inhalation of hazardous
chemicals. Exposure to dirty surfaces are also a risk to health care workers. Even with
engineering controls there are still the chance of spills and splash back exposure. During the
administration of an intravenous agent (IV), the IV is not designed to keep the administrator
safe; additional precautions must be taken to reduce chances of exposure (Polovich, 2004).
Symptoms may appear if exposure to the chemicals have occurred. Hospitals should be on
alert if any workers have nausea, vomiting, headache, dizziness, cough, or develop liver
damage (Polovich, 2004). In addition to the risk of developing cancer connected to
chemotherapy, there has been a link to infertility and exposure to these hazardous chemicals.
The workers have the right to know about the chemicals that are in the workplace, the risks
and ways to prevent exposure. This is important to oncology nurses, doctors, pharmacists,
dietary nutritionists and laundry services, indeed for anyone who comes in contact with the

32
chemotherapy agents, and the patient. Within 48 hours of the treatment, a patient’s bodily
fluids are contaminated with the chemotherapy agents (Polovich, 2004).
Special precautions should be taken in the disposal of materials used in the preparation
of the chemotherapeutic agents. Cleaning and disposal procedures for contaminated areas
must be set. Separate containers should be used to dispose of administrative tools such as
syringes and medicine bags. Separate laundry bags are to be used for clothing worn by
patients and protective gowns of nurses. Bags should be sealed until the laundry can be done.
Laundry should be washed with hot water twice. Spills and leaks require additional safety
procedures (Connor et al, 2007). A wide range of health effects are have been examined the
association between workplace exposures and health effects in nurses that are exposed to
chemotherapy agents.
A challenge to training nurses on the exposure precautions is linked to the fact that
nurses work varying hours, days and departments (Corelle et al., 1992). It is difficult to
conduct group training with all staff present because some nurses must be tending to patients.
In 2007, the International Society of Oncology Pharmacy Practitioners ISOPP Standards of
Practice was published on the handling of chemotherapeutic agents (Connor et al., 2007).
The 2007 ISOPP Standards of Practice stated that individuals who were planning to become
pregnant, were pregnant or were breastfeeding were advised not to handle chemotherapeutic
agents. It warned that handling hazardous drugs can result in infertility, birth defects, and
spontaneous abortion (Connor et al., 2007).

33
2010s
According to the OSHA Technical Manual, hazardous drug exposure has been linked to
reproductive outcomes (2014). Main elements of the technical manual addressed hazardous
drugs as occupational risks, prevention of employee exposure, medical surveillance, hazard
communication, training and recordkeeping. There has been a link to malformations of the
fetus and spontaneous abortions. The manual also references a study of exposures in
oncology nurses and normal pregnancy outcomes (Occupational Safety and Health
Administration, 2014). It was suggested that the suspected link to trends of spontaneous
abortions in nurses would be explored further throughout this project.

34
CHAPTER 4
Discussion
This study identified three major pieces of the puzzle of the occurrence of spontaneous
abortion in oncology nurses: epidemiology studies of oncology nurses, changes in the mix of
chemotherapy agents in the workplace, and occupational hygiene requirements for healthcare
workers. This chapter examines the results of the analyses done for this thesis and derives
from them a set of observations and recommendations.
Nurses’ Reproductive Health Effects
The epidemiologic studies indicated that the risk of spontaneous abortion in oncology
nurses was observable across several nations and time periods. Oncology nurses also were
shown to have had a greater risk of having a spontaneous abortion than other nurses. They
also indicated that nurses in the United States had a lower risk than the general population in
2014.
The studies addressed a 30 year timeframe, from 1972 to 2006. In the entire period an
association was seen between exposure in oncology nurses and spontaneous abortion. The
research measured the possible occurrence of spontaneous abortions using different study
designs. All results were statistically significant. This shows an association between
oncology nurses spontaneous abortion and exposure to chemotherapeutics that kill both
healthy and diseased cells and can mutate DNA.
In the later years of the time period studied in this thesis, the case load of hospital nurses
has been an issue. According to the American Nursing Association, two out of five units in a

35
hospital are understaffed (2014). Only 13 states have regulation related to staffing in
hospitals (American Nursing Association, 2014). Nurses have been inundated with the
number of patients they are treating. With an increase in patients and a decrease in time
available, standard safety precautions could be ignored. This may have been reflected in an
increase in spontaneous abortion occurrence. It is interesting to note that the prevalence of
spontaneous abortion in studies conducted after 1997 were higher. Additional research is
needed to determine if safe handling practices actually have changed during the same time
period.
All the data in the case studies were obtained by a questionnaire or interview. The
spontaneous abortions were self-reported and did not have medical proof. There was a
chance of recall error; however, the nature of the occurrence is a memorable event in a
woman’s life.
The nature of the nursing profession may play a role in o accounting for the discrepancy
between spontaneous abortion rates for all women compared to exposed nurses in the United
States. In general, it is reasonable to assume that nurses are more aware of prenatal health
care needs, have better access to health care, are aware of nutritional requirements, and are
less likely to use tobacco products due to their extensive studies required to become a nurse
(University of California Los Angeles, 2014). Because education is a contributing factor in
reasoned decision making, the elevated awareness of health related factors could have
resulted in lower prevalence of spontaneous abortion in nurses compared to the general
public.

36
Cancer Treatment Changes
Since the advent of chemotherapy in the 1940s, the research into what effect the various
drugs had on cancerous as well as healthy cells has continued, most significantly within the
last 20 years. This research built understanding of how these agents work, when to use which
type, and side effects on patients and health care workers. Starting in the 1990s, additional
cancer treatments that work by a different means entered use. In the same time period,
occupational hygiene strategies were established for health care workers handling and
preparing chemotherapeutic agents.
Within the American Cancer Society’s reports on usage of cancer treatments in breast
cancer, colon cancer, and rectal cancer; there is a trend from of types of treatments used in
2008 and 2012-2013. The report showed that older chemotherapeutic treatments were still
used. A combination of new and old strategies were used as treatments. The nature of cancer
strategies will continue to use old and new technologies as every type of cancer responds
differently to treatments. As old treatments are not being replaced entirely, this leaves open
the risk for continued exposure to cytotoxic agents. In the future additional targeted, less
cytotoxic therapies are expected that target only diseased cells. Whether newer agents also
are reproductive hazards remains to be discovered and reported.
Occupational Health and Safety
Safe handling practices had been in development in the 1970s. The protective strategies
from 1970s to 1990s were found to be weak or absent even in hospitals. Indicators of
exposure to health care workers, who were following safe handling procedures, was found in
their urine in the 1990s. It was noted that OHSA found no safe handling practices in

37
California hospital, and it is possible that these events prompted recommendations and
guidelines on the safe handling and administration of chemotherapeutic agents. The largest
introduction of policies by reputable agencies occurred in the 1990s to 2000s. The occurrence
of spontaneous abortion in oncology nurses was consistent within the ratio results. The
prevalence studies results started high in the first study and ended high in the last study. The
lowest prevalence of spontaneous abortion occurred from 1990-1997.
Information about the hazards associated with chemotherapy was only recognized in the
1970s. NIOSH has identified that guidelines for proper handling of chemotherapeutics
established before 1991 had sporadic adherence. This could have contributed to the initial
high occurrence of spontaneous abortion and the occurrence started to decrease once data
was more readily available about the hazards associated.
Anticipating Oncology Nurses’ Health
A change in nurses’ exposure to hazardous chemotherapy agents may not change greatly
in the short term. Old treatments are still in use and will continue to be used if they are able
to cure the disease. Hospital staffs have high patient to nurse ratios. Due to understaffing,
oncology nurses may have limited time to stop to put on personal protective equipment or
follow a safety practice. The nurses’ first concern will be to tend to their patients. In the
longer term, the addition of targeted anticancer agents may reduce the use of traditional
cytotoxic agents. Research on their hazards, if any, has yet to be done.
Enhancements to Occupational Health and Safety
Nurses who handle chemotherapeutic drugs need guidelines and safe practices in order to
prevent the occurrence of spontaneous abortions. Oncology nurses need more time to receive

38
training on safe handling, and to follow these practices in order to decrease the occurrence of
spontaneous abortions in oncology nurses. This training needs to be implemented in order to
make a difference. Informing nurses of epidemiologic studies of the negative health
outcomes associated with handling chemotherapeutics may raise awareness of the oncology
nurse’s health risks.
If more training is provided, then there will be a need for additional personal protective
equipment. The equipment needs to be comfortable, free to employees, and offered in a
variety of sizes. Medical monitoring would aid in gaining a full picture of oncology nurses’
health.
The Bloodborne Pathogen Standard can be used as a model for safe handling of
chemotherapeutics. The Bloodborne Pathogen Standard requires the employer to establish an
exposure control plan accessible to all employees. The control plan must consist of methods
of compliance, HIV and HBV research laboratories and production facilities, hepatitis B
vaccination, post-exposure evaluation and follow-up, communication of hazards to
employees, and recordkeeping. Engineering controls and work practice controls are put in
place to minimize employee exposure. Where exposure remains after of these controls,
personal protective equipment shall also be used to further reduce possible exposure. The use
of lipstick and contacts, eating, drinking, or smoking is not allowed within the work area to
prevent additional exposure (Bloodborne Pathogen Standard, 2013).
Following this model and adapting it to the problem of exposure to chemotherapy agents
could reduce exposure, keep oncology nurses safer, and reduce spontaneous abortions. There
is a need for mandated regulations on handling and administration of chemotherapeutics. By
using the existing Occupational Safety and Health Administration’s Bloodborne Pathogen

39
Standards as a model, a more streamlined route to effective strategies for chemotherapy
agents may be possible.
Future ResearchNeeds
Research should be conducted to look for other indicators of reproductive health in
oncology nurses. Infertility may be one such health outcome. Additional studies of
spontaneous abortion in oncology nurses should continue as the mix of chemotherapy agents
evolves and occupational safety and health practices improve
Future research is needed to determine if spontaneous abortion occurrence has changed
since 2006. A comparison of the occurrence of spontaneous abortion within oncology nurses
in the United States and other U.S. nurses is needed. This would provide a clearer depiction
of the oncology work environment in the United States and could be compared to the
international data used in this project. Studies in nations such as Iceland or Japan that have
complete medical record tracking of each individual and their family trees also could be
helpful.
Nurses, just as other workers, require and deserve a safe working environment. Work in
oncology creates a complex mix of chemical hazards, a population with special health
concerns (pregnancy), and uneven occupational hygiene practices. Continued care and study
are warranted.

40
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