Handbook of Solvents - George Wypych - ChemTech - Ventech!

20.3 Pregnancy outcome following solvent exposure 1339
that did not permit extraction of data. For subgroup analysis, we also identified and analyzed
cohort and case-control studies specifically involving solvent exposure. Major malformations
were defined as malformations which were either potentially life threatening or
a major cosmetic defect. 13 Spontaneous abortion was defined as the spontaneous termination
of pregnancy before 20 weeks gestation based upon the date of the first day of the last
normal menses. 14
To obtain an estimate of the risk ratio for major malformations and spontaneous abortion
in exposed versus unexposed infants, an overall summary odds ratio (ORs) was calculated
according to the protocol established by Einarson et al. 15 Additionally, homogeneity of
the included studies, power analysis and the extent of publication bias were also examined
as described by Einarson et al. 15
Results and discussion
The literature search yielded 559 articles. Of these, 549 in total were rejected for various
reasons. The types of papers rejected were: animal studies (298), case reports/series (28),
review articles (58), editorials (13), duplicate articles (10), not relevant (62), malformation
not specified (29), spontaneous abortion not defined (31), unable to extract data (4), no indication
of timing of exposure (16). Five papers were included into the major malformation
analysis (Table 20.3.1) and 5 papers were included into the spontaneous abortion analysis
(Table 20.3.2).
Table 20.3.1. Studies of teratogenicity of organic solvents meeting criteria for
meta-analysis [Adapted, by permission, from K.I. McMartin, M. Chu, E. Kopecky, T.R.
Einarson and G. Koren, Am. J. Ind. Med., 34, 288 (1998) Copyright 1998 John Wiley &
Sons, Inc.
Sons, Inc.]
Reprinted by permission of Wiley-Liss, Inc. a division of John Wiley &
Authors Study type Data collection Malformation described
Axelsson et al. 16
C R “serious malformations”
Tikkanen et al. 17
CC R cardiac malformations
Holmberg et al. 18
CC R CNS, oral clefts, musculoskeletal, cardiac defects
Cordier et al. 19
CC R “major malformations”
Lemasters 20
CC=Case control; C=Cohort; R=Retrospective
C R “major malformations”
A. Malformations
In total 5 studies describing results from organic solvent exposure were identified (Table
20.3.3). The summary odds ratio obtained was 1.64 (95% CI: 1.16 - 2.30) which indicates
that maternal inhalational occupational exposure to organic solvents is associated with
an increased risk for major malformations. The test for homogeneity yielded a chi square of
2.98 (df=4, p=0.56). When studies were analyzed separately according to study type, the
chi square value from the test for homogeneity of effect for cohort studies was 0.52 (df=1,
p=0.47) and for case control studies it was 0.01 (df=2, p=0.99). Their combinability remains
justified on the basis of the lack of finding heterogeneity among the results.
Meta-analysis of both the cohort studies and case-control studies produced similar results,
i.e., they demonstrate a statistically significant relationship between organic solvent
exposure in the first trimester of pregnancy and fetal malformation. The summary odds ratio