Rates of congenital anomalies and other adverse birth outcomes in an offspring cohort of registered nurses from British Columbia, Canada.
Arbour, Laura T. ; Beking, Kris ; Le, Nhu D. 等
A variety of chemicals inherent to occupational environments have
the potential to influence prenatal development, resulting in such
adverse birth outcomes as congenital anomalies, stillbirths, low birth
weight, and prematurity. (1-4) A congenital anomaly is any structural
(most common), functional, or biochemical abnormality that is present at
birth. (5) Approximately 15-25% of congenital anomalies are due to known
genetic conditions (e.g., chromosomal anomalies) and the remaining cases
are suspected to have some degree of environmental influence. (5)
Health care workers are exposed to a variety of workplace hazards
that can result in adverse reproductive outcomes. (6) There are more
than 2.5 million registered nurses employed in the US (7) and 250,000 in
Canada, (8) who are potentially exposed to suspected reproductive
hazards including anaesthetic gases, antineoplastic drugs, ionizing
radiation, sterilizing agents, disinfectants, and infectious agents.
(9,10)
There are numerous case reports describing individual occupational
health hazards in the nursing professions, but epidemiological evidence
of reproductive risks related to occupational hazards for nurses is
relatively scarce. A registry-based cohort study of nurses in Norway
during 1970-1973 showed that first-born children of mothers who were
nurses had an elevated relative risk of malformations compared to
non-working mothers. (11) A data linkage study completed in Atlanta,
Georgia comparing cases of birth defects with geographic and race
matched healthy controls showed that offspring of mothers employed
within the nursing field had a modest increased risk of birth defects.
(12) Conversely, two studies noted a lower proportion of birth defects
in offspring of nurses compared to reference populations. (13,14)
The aims of our study were to determine: a) if a cohort of female
RNs in the province of British Columbia (BC), in comparison to the
general BC population, had an elevated prevalence of congenital
anomalies, stillbirths, low birth weight and prematurity in their
offspring and b) whether certain maternal and infant characteristics
were associated with these outcomes.
METHODS
The design of the study involved linking administrative data to a
retrospective cohort of RNs in BC. In 2003, we obtained data on 56,176
RNs who were registered for at least one year with their provincial
regulatory body between 1974 and 2000, inclusive. (15) Work histories,
based on yearly registration renewals completed by the nurses, contained
data about the date of initial registration, educational level, and
employment-specific information on place, position, and field of
employment for each year the subjects were registered as practicing RNs.
The offspring cohort was established by linking the RN cohort
database to live and stillbirth records from the BC Vital Statistics
Agency marriage and birth files (approximately 670,000 files).
Identifiers available in the RN database for linkage included
mother's names, birth date, location of maternal residence (city,
postal codes, local health area). Relevant vital statistics records
included child's birth date, sex, gestational age, birth weight,
multiplicity (twins, triplets), and live or stillbirth status. Rules for
scoring agreement and disagreements on surname, given names and day,
month and year of birth were based upon the generalized iterative record
linkage system. (16)
Birth registration records were linked to the BC Health Status
Registry (HSR) in order to obtain information on the presence and type
of congenital anomalies. The HSR was established in 1952 to ascertain,
record and classify "handicapping" conditions and congenital
anomalies in BC. The HSR receives health information about children up
to the age of 20 years from over 80 registering sources, including
government agencies concerned with health and human resources,
hospitals, treatment and rehabilitation centres, voluntary agencies,
physicians, and the vital registration system. Because recording
practices were less consistent in earlier periods of surveillance, BC
Vital Statistics limited data from the HSR to the 1986 to 2000 time
period to ensure consistency in data quality.
The disease conditions obtained from the HSR were coded according
to the 9th edition of the World Health Organization's
International Classification of Disease (ICD-9: codes 740 to 759)
with the year 2000 cases recoded according to the ICD-10 classification.
The four-digit ICD-9 codes were categorized into congenital anomaly
groupings used by BC Vital Statistics, as shown in Table 3. Elective
termination data were unavailable for the years studied.
The study was approved by the University of British Columbia's
Clinical Research Ethics Board. All files were stripped of identifying
information. Following data accuracy verification and re-linkage of the
files, the final offspring cohort totalled 23,222 births, among 12,855
RN mothers. Multiple adverse reproductive outcomes were treated as
independent outcomes. All continuous variables were categorized:
gestational age (premature <37 weeks, mature/normal 37-41 weeks, and
post-mature >41 weeks); birth weight (low birth weight <2500g,
normal birth weight 2500-4499g, and high birth weight >4500g); year
of birth (1986-1990, 1991-1995, and 19962000); mother's age at
birth (<30 years, 30-34 years, >35 years); and RN mother's
educational attainment (diploma, undergraduate degree, and graduate
degree). Missing values resulted in the case being excluded from
analyses involving that variable.
The rates of each birth outcome for each variable, calculated for
each year of birth category (see above) from Vital Statistics and
published BC general population data, (17,18) were then applied to the
respective birth count for that year category from the RN offspring
cohort and summed to derive an expected count adjusted by year of birth.
To compare the rates of reproductive outcomes and maternal
characteristics between the RN offspring cohort and the BC population,
odds ratios (OR) with 95% confidence intervals (CI) were calculated,
representative of relative risk. The chi-square statistic was used to
compare cross-tabulations of the observed and expected counts among the
RN offspring cohort for each predictor. Further cross-tabulations with
OR and CI were calculated for the distribution of each predictor by
congenital anomalies among the RN offspring cohort. Observed and
expected frequencies were then calculated for each category of
congenital anomalies. To compare the rates between the RN cohort and the
BC population, standard incidence ratios (SIR) of observed over expected
frequencies, with 95% confidence intervals, were calculated. For all
analyses, a two-sided significance level of p<0.05 was used.
RESULTS
Table 1 shows the distribution of reproductive outcomes, and
variables, among the RN offspring cohort, as well as expected
frequencies for each variable derived from rates among the BC general
population. The prevalence of low birth weight and congenital anomalies
were significantly lower in the RN offspring cohort, while high birth
weight and multiplicity (twins) were significantly higher. The average
number of diagnoses per case for the RN cohort was 1.44 compared with
1.51 among the BC general population.
Within the RN cohort (Table 2), births that were premature or low
in birth weight, stillbirths, as well as twins and triplets, had a
higher prevalence of congenital anomalies. There were more cases of
congenital anomalies in males (7.4% vs. 6.1%; OR 1.23, 95% CI
1.11-1.36), accounted for by an increased prevalence of genital
anomalies. The sex ratios were the same (1.05) for the RN cohort and the
BC population. A greater proportion of RNs gave birth in the older age
group compared to the BC population. The majority of RNs had a diploma
(74%), 24% had an undergraduate degree and 1.6 % had a graduate degree,
but there was no statistical difference in congenital anomalies between
the groups.
Table 3 shows the distribution of categorized congenital anomalies
cases with comparisons to expected frequencies based on the BC general
population. The number of total cases (with at least one congenital
anomaly) and number of specific congenital anomalies (diagnoses) were
lower than expected. Apart from chromosomal anomalies, for each of the
ICD-9 categories, there were fewer con genital anomalies than expected.
The most notable reductions were seen in heart defects (SIR 0.52; 95% CI
0.45-0.61), cleft lip and palate (SIR 0.47; 95% CI 0.34-0.65) and the
number of cases with multiple anomalies (SIR 0.43; 95% CI 0.26-0.67).
DISCUSSION
Record linkage between the RN offspring cohort with the BC Vital
Statistics birth registry effectively enabled the assessment of
suspected reproductive health risks inherent to the nursing profession.
Offspring from this cohort had a lower prevalence of congenital
anomalies and low birth weight than those of the BC population.
Stillbirths and prematurity were comparable to the BC general
population, while the prevalence of twins and high birth weight were
higher. Within the RN offspring cohort, stillbirths, male infants, those
with low birth weight, prematurity and twins were significantly more
likely to have at least one birth defect.
The prevalence of congenital anomalies was 6.7% among the offspring
RN cohort which is higher than the prevalence observed in other
large-scale studies, ranging from 3.8% (11) to 5.2%. (14) Our higher
incidence may be accounted for by a longer period of ascertainment
(until 20 years of age for the HSR) and perhaps inclusion of more minor
diagnoses (e.g., some integumentary anomalies) compared to most studies.
For the same time period in the general BC population, the prevalence of
birth defects was 7.9%, which is also higher than estimates seen in
other general populations. For example, the prevalence of birth defects
was 5.8% and 4.8% respectively for the years 1986-2000 in the Alberta
Congenital Anomalies Surveillance System, (19) and the Canadian
Congenital Anomalies Surveillance System (Personal Communication:
Jocelyn Rouleau, Canadian Congenital Anomalies Surveillance System,
Public Health Agency of Canada, April 6, 2009), both data bases using
information, at that time, collected on births until one year of age.
Consistent with our study, two previous studies noted a lower
proportion of birth defects in offspring of nurses compared to those of
reference populations. The first was a study on almost 3,000,000 births
during 1980,14 and the second was a small study of nurses employed in
operating rooms from 1973 to 1975. (13) In contrast, a case-control
study of 4,915 cases and 3,027 randomly selected healthy controls
(frequency matched for geographic region, hospital of birth, race, year
of birth and quarter of year) between 1968 and 1980 found that the
offspring of mothers employed in a nursing occupation while pregnant had
a relative risk of 1.42 (95% CI 1.06-1.88) for having at least one
congenital anomaly. (12)
Many early studies tended to be cross-sectional or anecdotal case
studies, self-reported questionnaire-based, and/or of a smaller scale.
(2,20) Such studies are prone to recall biases, poor response rates,
limited statistical power to detect significant associations, and
nonstandardized ascertainment of outcomes. By comparison, our record
linkage analysis allowed for more comprehensive ascertainment in that
the large sample size enabled sufficient power for assessing outcomes
that are generally infrequent. The use of administrative records avoided
recall bias, a significant problem for questionnaire-based studies, and
having records for the total population of interest avoided selection
bias.
Working women in general tend to have more favourable demographic,
behavioural, and health-related characteristics than nonworking women.
(1) Although the BC population data included mothers in other lines of
employment, it also included those who were not working. As health care
providers, nurses may be more likely to adopt healthier practices when
preparing for pregnancy, such as folic acid supplementation, avoidance
of alcohol and smoking, and other behaviours protective of fetal health.
(21)
A weakness of examining total congenital anomalies is that they are
heterogeneous outcomes that include distinct etiologies (e.g., genetic
basis) and differential susceptibility to specific teratogenic
exposures. (4,5) Therefore, interpretations of results based on total
congenital anomalies are not as meaningful as when the congenital
anomalies are grouped into biologically relevant categories. (22) The
large cohort size afforded this investigative capacity for each category
of congenital anomaly. Although most categories were lower, the rates of
heart defects and facial cleft were substantially lower in the RN
cohort. Both anomalies may be decreased with folic acid supplementation
(23-25) and increased with exposures such as alcohol consumption and
cigarette smoking, (26-28) which may reflect the health care
providers' level of health promotion knowledge. The significantly
higher prevalence of high birth weight infants, however, is concerning
and may reflect rates of obesity or gestational diabetes. (29)
Just as variability exists across categories of congenital anomaly
cases, the degree of exposure to suspected teratogens may vary depending
on the type of work within the nursing occupation. While this study
served as an exploratory tool for investigating the risk of reproductive
outcomes among RNs, further internal analyses will allow for
investigation of the risk related to different areas of employment
within nursing, or levels of exposure to specific teratogens, as
estimated from questionnaire and work histories.
Acknowledgements: We thank the BC College of Registered Nurses, the
BC Vital Statistics Agency, the BC Health Status Registry, and the BC
Cancer Registry for their contributions to the study; the Canadian
Institutes of Health Research for providing funding for the study (grant
number: 135329); and the Michael Smith Foundation for Health Research
for research scientist awards for LA and PAR. Dr. Beatrixe Whittome
Waygood assisted in the formatting of the manuscript.
Received: July 3, 2009
Accepted: February 5, 2010
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Laura T. Arbour, MD, [1] Kris Beking, MSc, [2] Nhu D. Le, PhD, [3]
Pamela A. Ratner, PhD RN, [4] John J. Spinelli, PhD, [3] Kay Teschke,
PhD, [5] Richard P. Gallagher, MA, [3] Zenaida U. Abanto, MSc, [3] Helen
Dimich-Ward, PhD [2]
Author Affiliations
[1.] Department of Medical Genetics, and the Island Medical
Program, Faculty of Medicine, University of British Columbia, Victoria,
BC
[2.] Department of Respiratory Medicine, Faculty of Medicine, UBC,
Vancouver, BC
[3.] Cancer Control Research Program, British Columbia Cancer
Research Centre, Vancouver, BC
[4.] NEXUS--School of Nursing, UBC, Vancouver, BC
[5.] School of Population and Public Health, UBC, Vancouver, BC
Correspondence: Dr. Laura Arbour, Medical Sciences Building, University
of Victoria, PO Box 1700 STN CSC, Victoria, BC V8W 2Y2, Tel:
250-472-5544, Fax: 250-472-4283, E-mail: larbour@uvic.ca
Conflict of Interest: None to declare.
Table 1. Prevalence and Odds Ratios of RN Offspring Cohort Variables
and Birth Outcomes Compared to Those of the BC Population, Adjusted
for Year of Birth
Observed Expected *
n % n
Birth Outcomes
Stillbirths
No 23,075 99.4% 23,062
Yes 147 0.6% 160
Multiplicity ([double dagger])
Single 22,491 97.4% 22,579
Twin 560 2.5% 479
Triplet 24 0.1% 17
Gestational Age
[section] (weeks)
Premature (<37) 1555 6.7% 1551
Normal (37-41) 20,709 89.2% 20,634
Post mature (>41) 950 4.1% 1029
Birth Weight [section]
Low (<2500g) 1138 4.9% 1260
Normal (2500-4499g) 21,483 92.4% 21,440
High (([greater than
or equal to]) 4500g) 592 2.6% 512
Congenital Anomalies
None 21,655 93.3% 21,376
Cases (any diagnoses) 1567 6.7% 1846
Descriptive Variables
Sex [section]
Female 11,320 48.8% 11,301
Male 11,895 51.2% 11,914
Mother's Age (years)
<30 8183 35.2% 13,690
30-34 9673 41.7% 6604
[greater than or
equal to]>35 5366 23.1% 2928
Total cohort 23,222 100.0% 23,222
OR CI (95%) p-value
([dagger])
Birth Outcomes
Stillbirths
No 1.00 0.458
Yes 0.92 0.73-1.15
Multiplicity ([double dagger])
Single 1.00 0.022
Twin 1.17 1.04-1.33
Triplet 1.41 0.76-2.64
Gestational Age
[section] (weeks)
Premature (<37) 1.00 0.93-1.07 0.193
Normal (37-41) 1.00
Post mature (>41) 0.92 0.84-1.01
Birth Weight [section]
Low (<2500g) 0.90 0.83-0.98 0.002
Normal (2500-4499g) 1.00
High (([greater than
or equal to]) 4500g) 1.15 1.02-1.30
Congenital Anomalies
None 1.00
Cases (any diagnoses) 0.84 0.78-0.90 <0.001
Descriptive Variables
Sex [section]
Female 1.00 0.863
Male 1.00 0.96-1.03
Mother's Age (years)
<30 1.00 <0.001
30-34 2.45 2.35-2.55
[greater than or
equal to]>35 3.07 2.91-3.23
Total cohort
* Expected frequencies based on BC rates and adjusted for year of
birth.
([dagger]) Significance of the trend, based on chi-square analysis of
observed and expected frequencies.
([double dagger]) Prevalence of congenital anomalies among multiple
births for BC population unavailable for total births; figures based
on single births among RN cohort and BC population.
[section] Unknown values for sex (n=7), gestational age (n=8) and
birth weight (n=9) excluded; figures based on reduced frequencies.
Table 2. Prevalence and Odds Ratios for Potential Risk Factors
of Congenital Anomalies within the RN Offspring Cohort (n=23,222) *
No Congenital
Anomalies
([dagger]) Cases % Cases
Stillbirths
No 21,538 1537 6.7%
Yes 117 30 20.4%
Multiplicity
Single 21,105 1508 6.7%
Twin 525 56 9.6%
Triplet 25 3 10.7%
Gestational Age ([section]) (weeks)
<37 1347 208 13.4%
37-41 19,416 1293 6.2%
>41 884 66 6.9%
Birth weight ([section])
Low (<2500g) 951 187 16.4%
Normal (2500-4499g) 20,144 1339 6.2%
High ([greater than or equal
to] 4500g) 552 40 6.8%
Sex ([section])
Female 10,630 690 6.1%
Male 11,018 877 7.4%
Mother's Age (years)
<30 7653 530 6.5%
30-34 9029 644 6.7%
[greater than or equal to] 35 4973 393 7.3%
Mother's Education
Diploma 16,065 1188 6.9%
Undergraduate degree 5237 355 6.3%
Graduate degree 353 24 6.4%
Total cohort 21,655 1567 6.7%
p-value
([double
OR CI (95%) dagger])
Stillbirths
No 1.00 <0.001
Yes 3.59 2.40-5.38
Multiplicity
Single 1.00 0.013
Twin 1.49 1.13-1.98
Triplet 1.68 0.51-5.57
Gestational Age ([section]) (weeks)
<37 2.32 1.98-2.71 <0.001
37-41 1.00
>41 1.12 0.87-1.45
Birth weight ([section])
Low (<2500g) 2.96 2.51-3.49 <0.001
Normal (2500-4499g) 1.00
High ([greater than or equal
to] 4500g) 1.09 0.79-1.51
Sex ([section])
Female 1.00 <0.001
Male 1.23 1.11-1.36
Mother's Age (years)
<30 1.00 0.142
30-34 1.03 0.91-1.16
[greater than or equal to] 35 1.14 0.99-1.31
Mother's Education
Diploma 1.00 0.363
Undergraduate degree 0.92 0.81-1.04
Graduate degree 0.92 0.61-1.40
Total cohort
* Case defined as having one or more diagnosis of a congenital anomaly
as categorized in ICD-9.
([dagger]) Births with no congenital anomalies.
([double dagger]) Significance of the trend, based on chi-square
analysis.
([section]) Unknown values for sex (n=7), gestational age (n=8) and birth
weight (n=9) excluded; figures based
Table 3. Distribution and Standard Incidence Ratios (SIR)
of Congenital Anomalies by Category * among Offspring of the
RN Cohort (n=23,222)
Congenital Anomaly Category ([dagger]) ICD-9 Code Observed
n %
Nervous System 740-742 69 3.6%
Eye 743 99 5.2%
Ear, Face, Neck 744 99 5.2%
Heart 745-746 164 8.5%
Circulatory System 747 155 8.1%
Respiratory System 748 65 3.4%
Cleft Palate/Lip 749 38 2.0%
Upper Alimentary Tract 750 92 4.8%
Other Digestive System 751 46 2.4%
Genital 752 239 12.4%
Urinary System 753 112 5.8%
Musculoskeletal System 754-756 510 26.5%
Integumentary System 228, 757 109 5.7%
Chromosomal Anomalies 758 79 4.1%
Multiple Anomalies 759.7-759.8 19 1.0%
Other/Unspecified Anomalies ([section]) 759.0-759.6, 27 1.4%
759.9, 237.7
Total Diagnoses 740-759.9 2258
Total Cases 740-759.9 1567
Expected
Congenital Anomaly Category ([dagger]) ([double dagger])
n
Nervous System 119
Eye 119
Ear, Face, Neck 163
Heart 313
Circulatory System 227
Respiratory System 79
Cleft Palate/Lip 80
Upper Alimentary Tract 146
Other Digestive System 71
Genital 327
Urinary System 146
Musculoskeletal System 676
Integumentary System 141
Chromosomal Anomalies 79
Multiple Anomalies 45
Other/Unspecified Anomalies ([section]) 42
Total Diagnoses 2773
Total Cases 1842
SIR
Congenital Anomaly Category ([dagger]) ([double dagger]) CI (95%)
Nervous System 0.58 0.45-0.74
Eye 0.83 0.67-1.01
Ear, Face, Neck 0.61 0.49-0.74
Heart 0.52 0.45-0.61
Circulatory System 0.68 0.58-0.80
Respiratory System 0.82 0.63-1.05
Cleft Palate/Lip 0.47 0.34-0.65
Upper Alimentary Tract 0.63 0.51-0.77
Other Digestive System 0.65 0.48-0.87
Genital 0.73 0.64-0.83
Urinary System 0.76 0.63-0.92
Musculoskeletal System 0.75 0.69-0.82
Integumentary System 0.77 0.63-0.93
Chromosomal Anomalies 1.01 0.80-1.25
Multiple Anomalies 0.43 0.26-0.67
Other/Unspecified Anomalies ([section]) 0.64 0.42-0.93
Total Diagnoses 0.81 0.78-0.85
Total Cases 0.85 0.81-0.89
* Cases are represented more than once across categories if there are
multiple anomalies present, but multiple diagnoses within a category of
the same case is only counted once in that category. Therefore, neither
total diagnoses nor total cases are summations of the cases for each
category.
([dagger]) Categories as defined by BC Vital Statistics.
([double dagger]) SIR derived from observed/expected (based on BC rates
and adjusted for year of birth).
([section]) Includes anomalies of the spleen, adrenal gland, and other
endocrine glands; situs inversus; conjoined twins; tuberous sclerosis;
other hamartoses; and unspecified diagnoses.
