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OBSTETRICS

Occupational exposures among nursesand risk of spontaneous abortionChristina C. Lawson, PhD; Carissa M. Rocheleau, PhD; Elizabeth A. Whelan, PhD; Eileen N. Lividoti Hibert, MA;Barbara Grajewski, PhD; Donna Spiegelman, ScD; Janet W. Rich-Edwards, ScD

OBJECTIVE: We investigated self-reported occupational exposure toantineoplastic drugs, anesthetic gases, antiviral drugs, sterilizingagents (disinfectants), and X-rays and the risk of spontaneous abortionin US nurses.

STUDY DESIGN: Pregnancy outcome and occupational exposuresere collected retrospectively from 8461 participants of the Nurses’ealth Study II. Of these, 7482 were eligible for analysis using logistic

egression.

RESULTS: Participants reported 6707 live births, and 775 (10%) spon-
taneous abortions (�20 weeks). After adjusting for age, parity, shift
2012;206:327.e1-8.

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work, and hours worked, antineoplastic drug exposure was associatedwith a 2-fold increased risk of spontaneous abortion, particularly withearly spontaneous abortion before the 12th week, and 3.5-fold in-creased risk among nulliparous women. Exposure to sterilizing agentswas associated with a 2-fold increased risk of late spontaneous abor-tion (12-20 weeks), but not with early spontaneous abortion.

CONCLUSION: This study suggests that certain occupational exposurescommon to nurses are related to risks of spontaneous abortion.

Key words: antineoplastic agents, health personnel, occupational
exposure, pregnancy
Cite this article as: Lawson CC, Rocheleau CM, Whelan EA, et al. Occupational exposures among nurses and risk of spontaneous abortion. Am J Obstet Gynecol

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Over 3 million women are employedas nurses,1 representing 4% of all

mployed women in the US.2 Nurses arepotentially exposed to several suspectedreproductive hazards, including anes-thetic gases, antineoplastic (chemother-apy) drugs, antiviral drugs, sterilizingagents (disinfectants), and X-rays (ion-izing radiation).3-9 Though the nursing

rofession is a critical component of theealth care system, the effect of com-

From the National Institute for Occupational SafPrevention, Cincinnati, OH (Drs Lawson, RocheLaboratory, Department of Medicine (Ms LividotHealth and Gender Biology (Dr Rich-Edwards), aSpiegelman and Rich-Edwards) and BiostatisticHealth, Boston, MA.

Received Aug. 19, 2011; revised Nov. 7, 2011;

This work was partially funded by contract no. 2Control/National Institute for Occupational Safet

The findings and conclusions in this report are threpresent the views of the National Institute for O

The authors report no conflict of interest.

Presented at the 3rd North American Congress21-24, 2011, and the National Occupational ReCincinnati, OH, July 12-13, 2011.

Reprints: Christina C. Lawson, PhD, CDC/NIOSOhio 45226. [email protected].

0002-9378/$36.00 • Published by Mosby, Inc. • doi:

only encountered occupational expo-ures on reproductive health remainsnclear within this predominantly fe-ale occupation.Many previous studies of nursing ex-

osures and spontaneous abortion lackdequate numbers of exposed cases to al-ow adjustment for confounders. Evenhough awareness of hazardous drug ex-osure has increased, protocols to re-uce exposure of health care personnel

and Health, Centers for Disease Control and, Whelan, and Grajewski); Channingert), and the Connors Center for Women’sthe Departments of Epidemiology (Drsr Spiegelman), Harvard School of Public

epted Dec. 27, 2011.

2001-08007 from the Centers for Diseased Health.

of the author(s) and do not necessarilyupational Safety and Health.

pidemiology, Montreal, QC, Canada, Junerch Agenda (NORA) Symposium 2011,

676 Columbia Parkway, R-15, Cincinnati,

016/j.ajog.2011.12.030

APRIL 2012 Americ

o these chemicals have been insufficiento eliminate the exposure.10,11 To clarifyrevious study results, we investigatedhe association between reported occu-ational exposures and risk of spontane-us abortion among participants of theurses’ Health Study II.

MATERIALS AND METHODSThe Nurses’ Health Study II was estab-lished in 1989 as a prospective cohortstudy of 116,430 U.S. nurses, aged 25 to42, in 14 states. Participants completedmailed questionnaires regarding theirmedical and reproductive history atbaseline and were sent follow-up ques-tionnaires every 2 years. In the 2001questionnaire, participants were asked ifthey had experienced at least 1 preg-nancy since 1993 and had worked as anurse during the most recent of thosepregnancies. If so, participants were askedwhether they would be willing to completea mailed supplemental questionnaire re-garding occupational activities duringtheir most recent pregnancy.

Among the 101,681 respondents to the2001 biennial questionnaire, 11,177 (11%)had a pregnancy since 1993 during whichthey worked as a nurse. Willingness to

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dicated by 9547 (85%) participants; 8461(89%) of these women completed and re-turned the supplemental survey they weremailed, resulting in an overall participa-tion rate of 76% for the supplement. Be-cause multiple pregnancies per woman arenot independent events, we asked onlyabout the most recent pregnancy.

Pregnancies ending in an inducedabortion (n � 147), ectopic pregnancyn � 57), molar pregnancy (n � 13), orultiple pregnancy (n � 235), as well aspregnancies with a missing pregnancyutcome, were excluded. Stillbirths, de-ned as a pregnancy loss after 20 weeks’estation, were also excluded (n � 42).regnancies were excluded if the partic-

pant reported that the pregnancy wasot confirmed by a clinical or over-the-ounter pregnancy test (n � 130), as wells pregnancies without data on the yearhe pregnancy ended (n � 31) or theength of the pregnancy (n � 22).

omen who reported working less thanhour per week as a nurse during the

rst trimester of pregnancy (n � 65), orho did not provide information on

hift work (n � 24), anesthetic gasesn � 19), sterilizing agents (n � 91), an-ineoplastic drugs (n � 14), antiviralrugs (n � 33), or X-rays (n � 49) werelso excluded. In total, 979 (11.6%)omen were excluded, leaving data on482 women in the analysis.For each trimester of pregnancy, the

ollowing questions were asked: “On av-rage how many hours per day did youork with the following agents:” and the

ollowing categories, with examples, wereiven “a. Anesthetic gases (eg, nitrous ox-de, halothane, enflurane, isoflurane),” “b.nticancer drugs (eg, Cytoxan, Fluroplex,drucil, Etoposide, 5-FU),” “c. Antiviralrugs (eg, gancyclovir or the interfer-ns),” “d. Sterilizing agents (eg, ethylenexide, formaldehyde, glutaraldehyde),”nd “e. X-ray radiation.” Data on workchedule, night work, average hours workeder week, frequency of lifting 25 pounds orore at work, hours per day of standing oralking at work, smoking, alcohol con-

umption, and caffeine consumption werelso collected for each trimester of preg-ancy. From the main biennial question-aires, data were also available on age,
ace/ethnicity, body mass index (BMI), m
327.e2 American Journal of Obstetrics & Gynecolo

edication use, parity, and prior sponta-eous abortion.Participants reported the outcome of

he index pregnancy as a single live birth,tillbirth, twins, triplets�, induced abor-ion, tubal/ectopic pregnancy, miscar-iage, or molar pregnancy. Categoricalnformation on pregnancy duration waseported on the supplemental survey aseeks since last menstrual period (�8,-11, 12-19, 20-23, 24-27, 28-31, 32-36,7-41 [full-term], and �42 weeks).regnancies ending involuntarily before0 weeks’ gestation were classified aspontaneous abortions.

Completion of the self-administereduestionnaire was considered implied

nformed consent. The study and in-ormed consent procedure were ap-roved by the institutional review boardf the Brigham and Women’s Hospital.Descriptive statistics (frequency, range,

nd age-adjusted means) were calculatedor selected maternal characteristics. Theelationship between spontaneous abor-ion and first-trimester exposure to anes-hetic gases, antineoplastic agents, steriliz-ng agents, antiviral drugs, and X-rays wasxamined in univariable and multivariablenalyses. We modeled age as a continuousariable. Because the risk of spontaneousbortion rose exponentially with age, welso included a quadratic age term (age-quared) in the models. Exposure catego-ies were dichotomized as 1� hour per days �1 hour per day for all reportedxposures.

For univariable and multivariable anal-ses, we used logistic regression to com-ute the odds ratio (OR) using SAS soft-are (SAS Institute, Cary, NC). Covariates

hat changed the estimate by 10% or moreere retained in the final multivariableodel.We first considered the associations of

hese individual exposures with risk ofpontaneous abortion, adjusted for age.ur full multivariable model included

ll 5 work exposures of interest, age, par-ty, and work schedule. The addition ofifestyle and other factors, such as ciga-ette smoking, caffeine consumption, al-ohol consumption, BMI, race/ethnic-ty, lifting at work, and standing at workid not change the estimated effects by
ore than 10%. Because previous occur-
gy APRIL 2012

ence of spontaneous abortion couldave been due to the same environmen-al or occupational exposures studied inhe index spontaneous abortion, and tovoid possible bias, we did not adjust forrevious spontaneous abortion in thesenalyses.12 Our primary analysis lookedt all spontaneous abortions as the out-ome. In our secondary analysis, we strat-fied by the timing of the spontaneousbortion, because early and late spontane-us abortion may be controlled by differ-nt mechanisms, and the percentage ofpontaneous abortions caused by chromo-omal abnormalities decreases as gesta-ional age increases.13 For this analysis,

early spontaneous abortion is modeledas �12 weeks’ gestation, and late sponta-neous abortion as 12-20 weeks. For theanalysis of late spontaneous abortions,early spontaneous abortions were ex-cluded (n � 575). To assess statisticallyignificant differences between earlynd late models, we calculated P valuesor common effects with a �2 test sta-istic using the maximum likelihoodstimates from the logistic regression.

e also assessed interactions betweenarity and each exposure by modelingcross-product interaction term in aodel containing the main effects of

arity and the exposure, as well asther covariates.

RESULTSAmong 7482 eligible participants, thepregnancies of 775 (10%) ended in spon-taneous abortion. Seventy-four percentof those ended before the 12th week ofpregnancy (n � 575). The year of thepregnancies ranged from 1993-2002 (themean year was 1996), with 82% occur-ring between 1993 and 1998. The spon-taneous abortion rate varied by specialtyarea; the lowest rates were for medical/surgical and critical care (8.4% and8.8%, respectively), and the highest ratesfor home health/community and oncol-ogy (13.1% for each). However, 32% ofnurses specified “other” as their specialtyarea (11.0% spontaneous abortion rate).

Table 1 shows age-adjusted prevalenceof selected characteristics of eligible partic-ipants by pregnancy outcome. Women
whose pregnancies ended in spontaneous

www.AJOG.org Obstetrics Research

TABLE 1Demographic and lifestyle factorsa by pregnancy outcome

Study subject characteristics

Spontaneous abortion<20 weeks’ gestationn � 775 (10.4%)

Live birthn � 6707 (89.6%)

Maternal prepregnancy BMIb Mean, range, (SD) 25.3,16.1–50.0 (5.7) 24.3,15.0–50.0 (4.9)................................................................................................................................................................................................................................................................................................................................................................................

Maternal age (y) Mean, range, (SD) 39.5, 30–51 (3.8) 36.4, 29–50 (3.4)................................................................................................................................................................................................................................................................................................................................................................................

Maternal age category n % n %.......................................................................................................................................................................................................................................................................................................................................................................

�30 6 0.8 175 2.6.......................................................................................................................................................................................................................................................................................................................................................................

31-35 112 14.5 2609 38.9.......................................................................................................................................................................................................................................................................................................................................................................

36-40 (referent) 344 44.4 3113 46.4.......................................................................................................................................................................................................................................................................................................................................................................

41� 313 40.4 810 12.1................................................................................................................................................................................................................................................................................................................................................................................

Race.......................................................................................................................................................................................................................................................................................................................................................................

African Americanc 5 0.4 42 0.7.......................................................................................................................................................................................................................................................................................................................................................................

Asian 12 1.1 119 1.9.......................................................................................................................................................................................................................................................................................................................................................................

White 719 92.5 6229 92.8.......................................................................................................................................................................................................................................................................................................................................................................

Hispanic 11 1.3 101 1.5.......................................................................................................................................................................................................................................................................................................................................................................

Other 15 2.2 100 1.5.......................................................................................................................................................................................................................................................................................................................................................................

Missing 13 2.5 116 1.7................................................................................................................................................................................................................................................................................................................................................................................

Parous 535 68.2 5698 84.6................................................................................................................................................................................................................................................................................................................................................................................

Previous spontaneous abortion 394 44.9 2296 34.9................................................................................................................................................................................................................................................................................................................................................................................

First-trimester lifestyle factors................................................................................................................................................................................................................................................................................................................................................................................

Caffeinated coffee servingsd

.......................................................................................................................................................................................................................................................................................................................................................................

None (reference) 412 55.1 4151 61.6.......................................................................................................................................................................................................................................................................................................................................................................

�1 cup per day 232 28.8 1874 28.1.......................................................................................................................................................................................................................................................................................................................................................................

�2 cups per day 130 15.8 676 10.2.......................................................................................................................................................................................................................................................................................................................................................................

Missing 1 0.4 6 0.1................................................................................................................................................................................................................................................................................................................................................................................

Caffeinated soda/tea servingsd

.......................................................................................................................................................................................................................................................................................................................................................................

None (reference) 379 45.7 3191 47.9.......................................................................................................................................................................................................................................................................................................................................................................

�1 serving per day 284 38.4 2781 41.2.......................................................................................................................................................................................................................................................................................................................................................................

�2 servings per day 112 15.9 720 10.7.......................................................................................................................................................................................................................................................................................................................................................................

Missing 0 0.0 15 0.2................................................................................................................................................................................................................................................................................................................................................................................

Alcoholic beverage servingsd

.......................................................................................................................................................................................................................................................................................................................................................................

None (reference) 584 76.8 5459 81.2.......................................................................................................................................................................................................................................................................................................................................................................

�1 drink per week 120 14.8 926 13.9.......................................................................................................................................................................................................................................................................................................................................................................

�1 drink per week 70 8.3 315 4.8.......................................................................................................................................................................................................................................................................................................................................................................

Missing 1 0.1 7 0.1................................................................................................................................................................................................................................................................................................................................................................................

Smoked cigarettes per day.......................................................................................................................................................................................................................................................................................................................................................................

None (reference) 710 92.2 6316 94.2.......................................................................................................................................................................................................................................................................................................................................................................

�1 cigarette per day 65 7.6 389 5.8.......................................................................................................................................................................................................................................................................................................................................................................

Missing 0 0.0 2 0.0................................................................................................................................................................................................................................................................................................................................................................................

BMI, body mass index.a Percentages for all variables except maternal age are directly standardized by year of age at current pregnancy; b BMI (kg/m2) recorded on the most recent questionnaire before the current pregnancy;

c 101 participants were missing data on race; d Servings of caffeinated/alcoholic beverages � 8 oz coffee, 12 oz soda, 8 oz hot tea, 16 oz iced tea, 12 oz beer, 6 oz wine, 1 oz liquor.

Lawson. Spontaneous abortion risk in nurses. Am J Obstet Gynecol 2012.

APRIL 2012 American Journal of Obstetrics & Gynecology 327.e3


TABLE 2Occupational factorsa by pregnancy outcome

Variable

Spontaneousabortion <20weeks’ gestationn � 775 (10.4%)

Live birthn � 6707 (89.6%)

Self-reported occupational exposuresb

................................................................................................................................................................................................................................................................................................................................................................................

“On average, how many hours per day did you work with the following agents:”................................................................................................................................................................................................................................................................................................................................................................................

“Anesthetic gases (eg, nitrous oxide, halothane, enflurane, isoflurane)?”.......................................................................................................................................................................................................................................................................................................................................................................

�1 (reference) 706 90.6 6133 91.5.......................................................................................................................................................................................................................................................................................................................................................................

1-4 30 3.9 234 3.5.......................................................................................................................................................................................................................................................................................................................................................................

4-8 29 4.3 274 4.1.......................................................................................................................................................................................................................................................................................................................................................................

9� 10 1.2 66 1.0................................................................................................................................................................................................................................................................................................................................................................................

“Anticancer drugs (eg, Cytoxan, Fluroplex, Adrucil, etoposide, 5-FU)?”.......................................................................................................................................................................................................................................................................................................................................................................

�1 (reference) 727 92.8 6453 96.2.......................................................................................................................................................................................................................................................................................................................................................................

1-4 39 5.8 202 3.0.......................................................................................................................................................................................................................................................................................................................................................................

4-8 8 1.3 45 0.7.......................................................................................................................................................................................................................................................................................................................................................................

9� 1 0.1 7 0.1................................................................................................................................................................................................................................................................................................................................................................................

“Antiviral drugs (eg, gancyclovir) or the interferons?”.......................................................................................................................................................................................................................................................................................................................................................................

�1 (reference) 724 93.1 6333 94.5.......................................................................................................................................................................................................................................................................................................................................................................

1-4 45 6.2 354 5.2.......................................................................................................................................................................................................................................................................................................................................................................

4-8 6 0.8 16 0.2.......................................................................................................................................................................................................................................................................................................................................................................

9� 0 0.0 4 0.1................................................................................................................................................................................................................................................................................................................................................................................

“Sterilizing agents (eg, ethylene oxide, formaldehyde, glutaraldehyde?)”.......................................................................................................................................................................................................................................................................................................................................................................

�1 (reference) 699 90.7 6210 92.7.......................................................................................................................................................................................................................................................................................................................................................................

1-4 68 8.5 435 6.4.......................................................................................................................................................................................................................................................................................................................................................................

4-8 8 0.7 51 0.7.......................................................................................................................................................................................................................................................................................................................................................................

9� 0 0.0 11 0.2................................................................................................................................................................................................................................................................................................................................................................................

“X-ray radiation?”.......................................................................................................................................................................................................................................................................................................................................................................

�1 (reference) 650 81.5 5781 86.3.......................................................................................................................................................................................................................................................................................................................................................................

1-4 116 17.1 852 12.6.......................................................................................................................................................................................................................................................................................................................................................................

4-8 8 1.2 61 0.9.......................................................................................................................................................................................................................................................................................................................................................................

9� 1 0.2 13 0.2................................................................................................................................................................................................................................................................................................................................................................................

Work scheduleb

................................................................................................................................................................................................................................................................................................................................................................................

“What schedule did you usually work? If most of work hours are between 8 AM-4 PM, then it is day”; if 4 PM-midnight, then it is “evening”; ifmidnight-8 AM, then it is “night.”................................................................................................................................................................................................................................................................................................................................................................................

Shift.......................................................................................................................................................................................................................................................................................................................................................................

Days only (reference) 536 66.7 4573 68.6.......................................................................................................................................................................................................................................................................................................................................................................

Nights only 89 12.7 575 8.5.......................................................................................................................................................................................................................................................................................................................................................................

Rotating shifts including nights 54 7.4 433 6.4.......................................................................................................................................................................................................................................................................................................................................................................

Day/evening rotating; no nights 96 13.2 1126 16.5................................................................................................................................................................................................................................................................................................................................................................................

Hours worked, h/wk.......................................................................................................................................................................................................................................................................................................................................................................

1-20 158 24.7 1707 25.2.......................................................................................................................................................................................................................................................................................................................................................................

21-40 397 49.0 3846 57.4.......................................................................................................................................................................................................................................................................................................................................................................

41� 220 26.2 1154 17.4................................................................................................................................................................................................................................................................................................................................................................................

Cytoxan; Baxter Healthcare Corporation, Deerfield, IL. Fluoroplex; manufactured for Allergan, Inc., Irvine, CA, by Contract Pharmaceuticals Limited, Mississauga, Ontario, Canada. Adrucil; TevaParenteral Medicines, Inc., Irvine, CA. 5-FU and etoposide are generic.a Percentages for all variables except maternal age are directly standardized by year of age at current pregnancy; b Trimester-specific occupational exposures and work schedule were collected by questionnaire.

Lawson. Spontaneous abortion risk in nurses. Am J Obstet Gynecol 2012.

327.e4 American Journal of Obstetrics & Gynecology APRIL 2012

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abortion were older and less likely to beparous than those with live births. Priorspontaneous abortion, higher consump-tion of caffeinated beverages and alcohol,and cigarette smoking were also morecommon among pregnancies ending inspontaneous abortion. Occupational ex-posures were reported more often in spon-taneously aborted pregnancies, particu-larly exposure to antineoplastic drugs,which was reported nearly twice as oftencompared with live births (Table 2). Aspreviously reported,14 women whose preg-

ancies failed were more likely to haveorked the night shift and to have worked

ong hours during the first trimester thanomen with live births.Table 3 provides estimated odds ratios

nd 95% confidence intervals (CIs) forhe associations between occupationalxposures and spontaneous abortion in 3odels. First, we evaluated the associa-

ions between each individual exposurend spontaneous abortion (adjusted forge), showing increasedrisks for spontane-us abortion with reported exposure tontineoplastic drugs, sterilizing agents,nd X-rays. When simultaneously adjust-ng for age and all 5 work exposures, these 3xposures were still associated with spon-aneous abortion, though X-ray exposureas of borderline statistical significance.urther adjustment for parity, shift work,nd hours worked per week had modestmpact, and showed that nurses reportingccupational exposure to antineoplasticrugs had a 94% increased risk of sponta-eous abortion, whereas exposure to ster-

lizing agents had a 39% increased risk. Tovaluate if exclusion of pregnancies notonfirmed by a pregnancy test resulted inny bias, we analyzed the final model with-ut this exclusion, and the results wereearly identical.Because nulliparous women might have

nderlying subfertility that may makehem more susceptible to effects of repro-uctive hazards, we conducted a second-ry analysis by parity. We evaluated theultiplicative interaction between each

xposure and parity (yes/no), adjusted forge, shift work, hours worked, and eachf the occupational exposures. Thereere 240 (19.2%) spontaneous abortions

mong the 1249 nulliparous women and
35 spontaneous abortions among the
233 parous women (8.9%). Only anti-eoplastic drugs appeared to interact witharity (interaction P � .04), with stronger

associations among nulliparous women(3.50; 95% CI, 1.79–6.87) than amongparous women (1.44; 95% CI, 0.88–2.36).

Because early spontaneous abortionsmay have different causes than later preg-nancy loss,13 we conducted a subanalysisstratified by gestational age of the preg-nancy for early loss (�12 weeks’ gestation,n � 575) vs late loss (12-20 weeks’ gesta-tion, n � 200). The results—adjusted forall work exposures, age, parity, shift work,andhoursworkedperweek—areshowninTable 4. The stratified analysis shows thatreported exposures to antineoplastic drugs(OR, 2.13; 95% CI, 1.39–3.27) and, to alesser extent, X-rays (OR, 1.31; 95% CI,1.01–1.71) were associated with an in-creased risk for early pregnancy loss. Re-ported exposure to sterilizing agents wasassociated with later pregnancy loss (OR,2.10;95%CI,1.29–3.41)butnotwithearly

TABLE 3Association between occupationalthe first trimester and spontaneous

Occupational exposures

Odds ratio (

Age-adjustemodelsa

Anesthetic gases..........................................................................................................

�1 h per day (reference) 1.0..........................................................................................................

1� h per day 1.07 (0.81–1...................................................................................................................

Antineoplastic agents..........................................................................................................


1� h per day 1.97 (1.41–2...................................................................................................................

Antiviral agents..........................................................................................................


1� h per day 1.28 (0.93–1...................................................................................................................

Sterilizing agents..........................................................................................................


1� h per day 1.46 (1.12–1...................................................................................................................

X-ray radiation..........................................................................................................


1� h per day 1.31 (1.05–1...................................................................................................................a The age-adjusted model evaluated each exposure independe

each work exposure with all work exposures, adjusting for ageparity, shift work, and hours worked.

Lawson. Spontaneous abortion risk in nurses. Am J Obstet

spontaneous abortion; the difference be-

APRIL 2012 Americ

tween the 2 models was statistically signif-icant (P value � .04).

COMMENTWe found that exposure to some of theagents commonly used by health careworkers, including antineoplastic drugs,sterilizing agents, and X-rays, were asso-ciated with an increased risk of sponta-neous abortion. Antineoplastic drugs arehandled by nurses, pharmacists, physi-cians, operating room personnel, work-ers in veterinary practices, and manufac-turers; exposures can occur duringmanufacture, preparation, administra-tion, and contact with patient wasteproducts.15 Recognized as teratogenicand mutagenic, antineoplastic agents acton rapidly proliferating cells and aretherefore of particular concern for a de-veloping fetus.16-18 Previous studies havehad mixed results, and many suffer fromlimited sample sizes. The 3 largest stud-ies19-21 showed increased risks for sponta-

osures duringbortion

confidence interval)

Combinedexposuresb Full modelc

..................................................................................................................

1.0 1.0..................................................................................................................

) 0.85 (0.63–1.17) 0.88 (0.65–1.21)..................................................................................................................

..................................................................................................................

1.0 1.0..................................................................................................................

) 2.03 (1.39–2.97) 1.94 (1.32–2.86)..................................................................................................................

..................................................................................................................

1.0 1.0..................................................................................................................

) 0.93 (0.65–1.34) 0.92 (0.64–1.32)..................................................................................................................

..................................................................................................................

1.0 1.0..................................................................................................................

) 1.46 (1.09–1.95) 1.39 (1.03–1.87)..................................................................................................................

..................................................................................................................

1.0 1.0..................................................................................................................

) 1.27 (1.01–1.60) 1.22 (0.97–1.55)..................................................................................................................

adjusting for age; b The combined exposures model testede full model includes all work exposures, adjusting for age,

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mester exposure through handling ormixing, mostly among oncology nurses orpharmacists (ORs ranging from 1.5–2.3)in samples that included from 18 to 223exposed cases. Other studies did not findstatistically significant associations22-27

with ORs ranging from 0.7–2.8, and lim-ited sample sizes (3 to 34 exposed cases). Ametaanalysis pooled the results of 5 stud-ies19-21,24,25 and found an overall adjustedncreased risk of 46% (95% CI, 11–92%).28

Only 1 of these studies25 occurred after safehandling measures were first recom-mended in 1985.29,30 However, since 1985,several exposure studies still report drugcontamination on work surfaces in phar-macies and patient rooms.31 The NationalInstitute for Occupational Safety andHealth recently updated the recommenda-tions for safe handling of antineoplasticdrugs.32

Our findings regarding exposure tosterilizing agents is consistent with ourpreviously reported association of steril-izing agents with risk of preterm birth

TABLE 4Association between occupational

Occupational exposures

Odds rat

Early sp(<12 wk

Anesthetic gases..........................................................................................................


1� h per day 0.94 (0.6...................................................................................................................

Antineoplastic agents..........................................................................................................


1� h per day 2.13 (1.3...................................................................................................................

Antiviral agents..........................................................................................................


1� h per day 0.76 (0.5...................................................................................................................

Sterilizing agents..........................................................................................................


1� h per day 1.13 (0.8...................................................................................................................

X-ray radiation..........................................................................................................


1� h per day 1.31 (1.0...................................................................................................................a Adjusted for all work exposures, age, parity, shift work cate

significant differences between early and late spontaneous alogistic regressions.

Lawson. Spontaneous abortion risk in nurses. Am J Obste

(relative risk, 1.9; 95% CI, 1.1–3.4).33


Glutaraldehyde, formaldehyde, ethyleneoxide, orthophthalaldehyde, peraceticacid, and hydrogen peroxide are used todisinfect medical equipment and surgi-cal instruments. Ethylene oxide andformaldehyde are recognized as carcino-genic and mutagenic, but there havebeen few studies in humans to evaluatetheir reproductive toxicity,3,23,34,35 and

ost had limited sample sizes. Informa-ion regarding safe exposure levels forregnant women is lacking. Future stud-

es should build on these findings to clar-fy which specific sterilizing agents mayose risks to pregnant nurses, the specificontext in which they are being used, andhe efficacy of safe handling practices.

Though it is well-known that an acuteose of ionizing radiation is a reproduc-ive hazard, the reproductive risks asso-iated with occupational exposure to X-ays during pregnancy are not wellefined.36 The current occupational ex-

posure limit for ionizing radiation to thefetus of a pregnant worker is 5 mSv (0.5

posures during the first trimester an

95% confidence interval)

aneous abortionn � 575

Late spontaneous abo(12-20 wk)a,b n � 20

.........................................................................................................................

1.0.........................................................................................................................

.33) 0.79 (0.44–1.42).........................................................................................................................

.........................................................................................................................

1.0.........................................................................................................................

.27) 1.39 (0.68–2.84).........................................................................................................................

.........................................................................................................................

1.0.........................................................................................................................

.18) 1.35 (0.75–2.44).........................................................................................................................

.........................................................................................................................

1.0.........................................................................................................................

.60) 2.10 (1.29–3.41).........................................................................................................................

.........................................................................................................................

1.0.........................................................................................................................

.71) 0.98 (0.63–1.53).........................................................................................................................

s, and hours worked per week; b Excludes the 575 pregnancieson models, we calculated P values for common effects with a �2

ecol 2012.

rem) cumulative during the course of the

gy APRIL 2012

pregnancy, with a monthly equivalentdose limit of 0.5 mSv.37 Factors associ-ted with the level of radiation includehe source, distance from the source, usef a shielded control booth or leadedpron, and gestational age at the time ofxposure. Health care workers, dentalssistants, and veterinarians can be ex-osed via X-rays, CT scans, fluorosco-ies, radioactive isotopes, and radioac-ive implants; these are listed in order ofncreasing relative biologic effectiveness.

recent study found a 3-fold higher spon-aneous abortion rate among womenccupationally exposed to radioiso-opes compared to X-rays,38 suggesting a

dose-response relationship. In addition,staff who use mobile X-ray machinesmay find it difficult to follow guidelinesto reduce exposure.7 A radiation safetyofficer can advise workers on atypical ornonstandard procedures where radia-tion exposure is unavoidable.

Anesthetic gases have long been ofconcern to nurses, dental workers, and

arly vs late spontaneous abortion

n Difference of effect estimatesbetween early and latec P value

..................................................................................................................

..................................................................................................................

.6..................................................................................................................

..................................................................................................................

..................................................................................................................

.3..................................................................................................................

..................................................................................................................

..................................................................................................................

.1..................................................................................................................

..................................................................................................................

..................................................................................................................

.04..................................................................................................................

..................................................................................................................

..................................................................................................................

.3..................................................................................................................

g in early spontaneous abortion; c To assess statisticallystatistic using the maximum likelihood estimates from the

ex d e

io (

ont)a

rtio0

......... .........

......... .........

6–1......... .........

......... .........

......... .........

9–3......... .........

......... .........

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0–1......... .........

......... .........

......... .........

0–1......... .........

......... .........

......... .........

1–1......... .........

gorie endinborti test

veterinarians, though our study did not

ofagcpt


show an association with spontaneousabortion.6,39A metaanalysis of studiesthat were conducted in the absence ofscavenging systems reported increasedrisks for spontaneous abortion.40 Studies

f dental and veterinary offices haveound increased risks of spontaneousbortion in practices where anestheticases were not scavenged.41,42 More re-ent studies show inconsistent results,ossibly because of sample size limita-ions42-44 or because of the heterogeneity

of exposure. Although appropriate engi-neering controls are commonplace inmany hospital operating rooms, smallermedical facilities (such as dental, veteri-nary, or pediatric offices) may be less vig-ilant in controlling exposures. In addi-tion, reduced ability of pediatric patientsand veterinary animals to voluntarily co-operate during gas administration pro-cedures could hamper the effectivenessof scavenging. Therefore, though ourstudy supports the idea that the use ofengineering controls has reduced the riskof spontaneous abortion, it does not ruleout possible effects on pregnancy insmaller facilities.

We could find no previous studies ofoccupational exposure to antivirals andspontaneous abortion. Because certainantivirals are considered to be terato-genic to animals, and are contraindi-cated during pregnancy according to theFDA, pregnant health care workersshould be advised of potential risks whenadministering aerosolized antivirals.45

Though recall error is a potential lim-itation of our study, we attempted tominimize it by keeping the recall periodrelatively short (�8 years, mean of 5years).46 In addition, Nurses’ HealthStudy participants have been shown toself- report health data accurately forseveral medical conditions.47-49 More-over, self-report of the duration of drughandling by pharmacists has been shownto be valid.50

However, there is still potential for recallbias, because the pregnancy outcomeswere reported on the same instrument thatcollected occupational exposures. Thoughwe cannot directly measure recall bias, wedo not believe it is likely to explain ourfindings. First,weobservedsubstantiallydif-
ferent odds ratios for early vs late spontane-
ous abortions for antineoplastic agents andsterilizing agents. This observation is consis-tent with biologic mechanisms, and it is notexpected that recall bias would be differentialbased on whether the spontaneous abortionwas early or late. In addition, we would ex-pect recall bias to be highest for agents withthe most awareness of potential hazard,51

such as X-rays52; however, we noted only asmall excess risk associated with exposure toX-rays.

An important limitation of our studyis that we were not able to collect infor-mation on measures to control expo-sures, such as use of gloves, respirators,lead aprons, ventilation, or scavengingsystems, nor did we collect informationon types of agents being used, forms ofadministration, or sources of radiation.Future studies could improve on the cur-rent study with a more detailed exposureassessment instrument; such data arecurrently being collected in the Nurses’Health Study III.

The large sample size, narrow recallperiod, and ability to control for multi-ple exposures are improvements overprevious studies. Though the homoge-neity of the nurses in our study with re-spect to socioeconomic status and edu-cation may decrease generalizability, italso likely reduced confounding. Unlikeprevious studies, we were also able to dis-tinguish between early and late sponta-neous abortions, which likely follow dif-ferent mechanisms and causes, withearly spontaneous abortions having ahigher likelihood of being caused bychromosomal abnormalities.13 There-fore, it is possible that earlier spontane-ous abortions could be due to exposuresthat are mutagenic, whereas later spon-taneous abortion may be the result ofteratogenic exposures or exposures thataffect the mother’s ability to carry the in-fant to term. Further research is indi-cated to explore the differences we see inour data.

In conclusion, we found increased risksfor spontaneous abortion with reportedexposures to antineoplastic drugs, steriliz-ing agents, and X-rays. Although antineo-plastic drugs and X-rays are known repro-ductive hazards, US nurses are still reportingexposurestotheseduringpregnancy.Ween-
courage nurses who are pregnant, or who
APRIL 2012 Americ

wish to become pregnant, to work with theiremployers and their health care providers toreduce exposures during pregnancy andlactation. f

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