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Rates of congenital anomalies and other adverse birth outcomes in an offspring cohort of registered nurses from British Columbia, Canada.

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.


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.


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).


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:

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
    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

Birth Outcomes
    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

([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
                                       ([dagger])     Cases   % Cases

  No                                     21,538       1537      6.7%
  Yes                                       117         30     20.4%
  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%

                                       OR    CI (95%)    dagger])

  No                                  1.00                <0.001
  Yes                                 3.59   2.40-5.38
  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

([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

Congenital Anomaly Category ([dagger])    ([double dagger])


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

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

([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.
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Author:Arbour, Laura T.; Beking, Kris; Le, Nhu D.; Ratner, Pamela A.; Spinelli, John J.; Teschke, Kay; Gall
Publication:Canadian Journal of Public Health
Article Type:Report
Geographic Code:1CBRI
Date:May 1, 2010
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