Exposure to solvents during pregnancy

Exposure to solvents during pregnancy DEFAULT

Common solvents tied to birth defects

By Reuters Health

3 Min Read

NEW YORK (Reuters Health) - Pregnant women with frequent exposure to solvents at work may be at higher risk of having babies with birth defects, French researchers have found.

Both self-reported exposure and urine samples supported the link between the chemicals and newborn malformations such as cleft palate and limb deformities, they report in the journal Epidemiology.

Specifically, urine breakdown products pointed to bleach-containing solvents and glycol ethers - a group of solvents common in paints, cleaning products and cosmetics - as potential culprits.

Concentrated fumes from both types of chemicals are toxic to humans, and glycol ethers in particular cause birth defects and developmental problems in animals.

A U.S. study published earlier this year also found a link between occupational exposure to solvents during pregnancy and several kinds of congenital heart defects.

Still, the new research is not ironclad proof the substances are to blame, and earlier research findings have been mixed. What’s more, the overall risk is not huge, with less than three percent of the more than 3, pregnant women in the study giving birth to children with deformities.

Based on questionnaires filled out by the pregnant women, 45 percent of those whose babies had major malformations reported “regular” exposure to solvents at work. These women were typically nurses, chemists, cleaners, hairdressers or beauticians.

By contrast, of the women who had babies without birth defects, only 28 percent had been in regular contact with solvents at work.

The researchers, led by Sylvaine Cordier of the National Institute of Health and Medical Research in Rennes, France, said earlier studies had not looked at urine samples.

While that part of their research is limited by low detection rates and the study’s size - one in five women had urine tests - it bolstered women’s self-reported solvent exposure with objective evidence.

“These results identify work situations that require further investigation,” Cordier and colleagues conclude.

SOURCE: bit.ly/SqkmkC Epidemiology, September 21,

Sours: https://www.reuters.com/article/us-common-solvents-birth-defects-idUSBRECY

Solvents and pregnancy

Solvents are chemicals that dissolve other substances. Solvents include alcohols, degreasers, paint thinners and stain and varnish removers. Lacquers, silk-screening inks and paints contain solvents.

You may work with solvents or use solvents in your home. But they may cause problems for you and your baby if you’re exposed to them during pregnancy. When you’re pregnant, stay away from solvents.

How can solvents affect your pregnancy?

If you inhale (breathe in) solvents, you risk liver, kidney and brain damage and even death. During pregnancy, exposure to (coming in contact with) solvents, especially if you work with them, may cause problems for you and your baby, including:

  • Miscarriage. This is when your baby dies in the womb before 20 weeks of pregnancy.
  • Slow growth in the womb
  • Premature birth. This is when your baby is born too early, before 37 weeks of pregnancy.
  • Birth defects. These are health conditions that a baby has at birth. Birth defects change the shape or function of one or more parts of the body. They can cause problems in overall health, in how the body develops, or in how the body works.

How can you protect yourself from solvents during pregnancy?

Here’s what you can do:

  • If you work with solvents at your job, talk to your boss. Tell her you’re pregnant. You may be able to change job responsibilities to help keep you and your baby safe during pregnancy.
  • Air out your work area. Open a window or use a fan. 
  • Wear safety clothes, like gloves and a face mask. 
  • Don’t eat or drink in your work area. Wash your hands before eating.


Last reviewed: September,

Sours: https://www.marchofdimes.org/pregnancy/solvents-and-pregnancy.aspx
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REPRODUCTIVE HEALTH AND THE WORKPLACE

Solvents

Exposure to some organic solvents could increase your chances of having a miscarriage, stillbirth, preterm birth, a low birth weight baby, or a baby with a birth defect. Many solvents also pass into breast milk. Here, you can learn more about what you can do to reduce your exposure for a healthier pregnancy.

What are organic solvents?

These are organic chemicals, usually liquids, that are used in many workplaces.

Solvents are chemicals, usually liquids, used to dissolve other substances.  Some common solvents that might have adverse health effects include perchloroethylene, benzene, toluene, turpentine, methyl acetate, hexane, chloroform, and xylene.

Why should I be concerned about exposure?

Not all solvents are hazardous to you or your pregnancy, but some studies have linked certain solvents with birth defects, miscarriages, low birth weight, and preterm birth. The studies linking solvents to these problems are limited and results differ because workers may use more than one solvent at a time and it is hard to know which solvent is causing a problem, but many solvents containing carbon (called organic solvents) or chlorine (called chlorinated solvents) have been linked to some level of increased reproductive risk. Many solvents also pass into breast milk.

Who is exposed to solvents?

  • Laboratory workers
  • People who work in printing shops
  • Painters
  • Dry cleaners
  • Metalworkers
  • Oil and chemical industry workers
  • Artists
  • Cosmetologists, beauticians, and nail salon technicians

What is not known?

  • We don’t know what causes most miscarriages, birth defects, and other reproductive problems. If you work with solvents and have a miscarriage or baby with a birth defect, we often can’t tell if it was caused by exposure to solvents or if it was caused by something else.
  • Guidelines for safe levels of exposure to some solvents have been developed (OSHA PELs and NIOSH RELs) but these were developed for normal adult non-pregnant workers.  Most solvents do not have guidelines for exposure limits.
  • Often we don’t know what levels of exposure to certain solvents are safe. If you work with solvents, talk to your doctor about your working conditions or contact us.

What can I do to reduce or eliminate exposure?

  • If you are pregnant, talk to your employer to find out what solvents are used in your workplace.  If the solvents you work with might be hazardous to your health or pregnancy, or you aren’t sure if they might be hazardous, talk to your doctor or contact us.
  • If you work with solvents that might be hazardous to your health or your pregnancy, see if it’s possible to avoid duties with solvent exposure during pregnancy and breastfeeding. If this is not possible, there are ways you can reduce exposure:
    • Increase ventilation as much as possible. Open a window or a door to bring in fresh air while using these products if possible.
    • Avoid breathing solvent vapors, skin contact, or splashing near your eyes or mouth.
    • Find out what solvents are in use, and wear the right personal protective equipment (PPE).
    • If you get a solvent on your skin or clothes, wash your skin or change your clothing as soon as you can.
    • If you are working with solvents in a laboratory, identify a certified ventilation hood and use it correctly for solvent work.
  • Keep in mind that smelling or not smelling a chemical doesn’t mean you are safe or not safe. Harmful levels of chemicals cannot always be smelled, and some much less hazardous chemicals have an odor.
  • Solvents can be carried into the home on shoes and clothing. Find tips on reducing take-home exposures.

Where can I get more information?

Sours: https://www.cdc.gov/niosh/topics/repro/solvents.html
Exposure To Toxins And Nutrients During Pregnancy Correlated To Autism Risk

Mother&#;s exposure to solvents while pregnant is associated with negative effects on child

CHICAGO – Children of mothers exposed to organic solvents during their pregnancies had lower scores on certain tests of language, behavior, and cognitive functioning, according to an article in the October issue of The Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

According to the article, organic solvents are some of the most common sources of workplace chemical exposure reported by pregnant women. Organic solvents are used in dry cleaning, manufacturing, jobs involving paints and plastic adhesives, nail salons and medical laboratories, and in many other industries. Organic solvents are toxic and can harm the central nervous system. There are also reports of women who abused organic solvents during pregnancy ("sniffers") delivering infants with developmental delay or birth defects, the article states.

Dionne Laslo-Baker, M.Sc., of The Hospital for Sick Children and the University of Toronto, Ontario, and colleagues compared the cognitive, language and motor skills and behavioral achievements of 32 children (age range, 3 to 9 years old) whose mothers were occupationally exposed to organic solvents during pregnancy to a matched control group of children whose mothers were not exposed to solvents during pregnancy.

Mothers in the exposed group reported being exposed to 78 organic solvents between one and 40 hours per week and between eight and 40 weeks of their pregnancies. Exposed mothers reported using protective equipment to limit exposure to organic solvents. The children in the two groups did not differ in birth weight, gestational age or age at achieving certain behavioral milestones, and none had major malformations or neurological deficits.

The researchers found that "After controlling for potential confounding because of maternal IQ and maternal education, children exposed in utero to organic solvents obtained lower scores on subtests of intellectual, language, motor and neurobehavioral functioning," write the researchers.

"The results of this study suggest some adverse fetal effects of occupational exposure to organic solvents during pregnancy as measured by neurocognitive, behavioral, and motor coordination measures," the authors write. "Exposed children performed at a lower level than control children in subtests that measure short-term auditory memory, general verbal information, and attention. Furthermore, children who were exposed to organic solvents in utero showed reduced ability in recalling sentences, even when their global scores were within the normal range."

"Reducing exposure in pregnancy is merited until more refined risk assessment is possible. Further studies that address exposure to specific solvents, dose and gestational timing of exposure are needed," the researchers conclude.

###

(Arch Pediatr Adolesc Med. ; Available post-embargo at archpediatrics.com)

Editor's Note: This study was supported by a grant from Physician Services Inc., Toronto. Dr. Laslo-Baker received a doctoral research award from the Canadian Institutes of Health Research (CIHR), Ottawa, Ontario. Dr. Kozer received a fellowship from the Research Training Centre, The Hospital for Sick Children. Dr. Koren is a senior scientist of the CIHR and holder of the Research Leadership in Better Pharmacotherapy During Pregnancy and Lactation and The Ivey Chair in Molecular Toxicology, The University of Western Ontario, London, Ontario.

For more information, contact JAMA/Archives Media Relations at JAMA () or e-mail [email protected]



Journal

Archives of Pediatrics and Adolescent Medicine

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Sours: https://www.eurekalert.org/news-releases/

To solvents during pregnancy exposure

Occupational exposure to organic solvents during pregnancy and childhood behavior: findings from the PELAGIE birth cohort (France, –)

Environmental Healthvolume 17, Article number: 63 () Cite this article

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A Correction to this article was published on 04 September

Abstract

Background

Numerous industries use organic solvents, and many workers from various occupational sectors are exposed to these known neurotoxicants, including pregnant women. Our objective is to explore whether occupational exposure of pregnant women to solvents may impair the neurodevelopment of their babies and consequently affect their behavior in childhood.

Methods

Within the French birth cohort PELAGIE, parents assessed their children’s internalizing and externalizing behaviors using items from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire at age 2, and the Strength and Difficulties Questionnaire at age 6. The occupational exposure to solvents of the pregnant women was self-reported prospectively at the beginning of their pregnancy (N = ). We applied structural equation modeling to capture the longitudinal association of prenatal exposure to solvents with children’s behavioral traits at 2 and 6 years.

Results

Increased externalizing behavior score at age 2 was associated with prenatal exposure to solvents (standardized score: (95% CI = , ) for occasional exposure and (, ) for regular exposure). This association was attenuated at age 6 ( (− , ) for occasional exposure and (− , ) for regular exposure). No association was observed for internalizing behavior.

Conclusions

Pregnant women’s occupational exposure to solvents may affect their children’s behavior in early childhood. This effect may be attenuated with aging or diluted by the effects of other postnatal predictors.

Peer Review reports

Background

Organic solvents are a group of diverse chemical compounds widely used in industry due to properties convenient for extracting, dissolving, or diluting materials. Their inclusion in numerous products such as paints, degreasers, glues, inks, pharmaceuticals, pesticides, and cosmetic and cleaning products results in exposures in diverse occupational settings. In , , tons of organic solvents were used in France [1]. A recent survey of a sample representative of French workers nationwide estimated that 13% of workers – 14% of men and 12% of women – were exposed to at least one solvent during the week before the visit with the occupational health physician [2]. As a nationally representative population study reported that 70% of French pregnant women work during their pregnancy [3], the issue of occupational solvent exposures in this population is particularly relevant in terms of public health.

Studies of populations exposed either occupationally or through contaminated environments provide compelling evidence of the neurotoxicity of organic solvents in humans [4, 5]. Lipid-soluble and low-molecular-weight solvents, such as toluene, xylene, benzene [6], and tetrachloroethylene [7], can easily cross the placental barrier and reach the fetus. Animal data suggest the possible neurodevelopmental toxicity of some solvents, such as toluene [8] and some low-molecular-weight glycol ethers [9]. Only three epidemiological studies have explored the impact of prenatal exposure to solvents on human neurodevelopment. Two of them suggested that children prenatally exposed to organic solvents have a higher level of behavioral problems than non-exposed children [10, 11], while another study found that the exposed children walked earlier and observed no association with behavioral problems [12]. These three studies, however, were based on a limited number of subjects (n = 33 to 82 children, aged 3–9 years old).

Based on data from the PELAGIE mother-child cohort’s large population-based sample with prospectively assessed exposure, we previously reported an increased level of attention deficit/hyperactivity disorders and aggression disorders among 2 year-old children whose mothers were exposed to organic solvents at work during the beginning of their pregnancy [13]. Benefiting from a longer follow-up of the children up to school age, this study examines whether the impact of prenatal occupational exposure to organic solvents on the children’s behavior persisted to age 6.

Methods

Population

The PELAGIE (Perturbateurs Endocriniens: Étude Longitudinale sur les Anomalies de la Grossesse, l’Infertilité et l’Enfance) mother-child cohort study has previously been described in detail [14]. Overall, pregnant women were included between and in Brittany, France, before the 19th week of gestation (median 10 weeks, interquartile range (IQR) 8–11). Mothers were asked at inclusion and when the child had turned 2 and 6 years old to complete self-administered questionnaires, focused on medical and social characteristics of the child and its family, including lifestyle, domestic habits, and occupation.

Among the women who gave birth to live-born singletons, were lost to follow-up before the child turned 2. Among the remaining women, responded to the 2-year-old questionnaire, and also responded to the 6-year-old questionnaire. Among these women, we restricted our sample to the women who reported working at the beginning of the pregnancy (N = ). We excluded families if the child was born before the 35th week of gestation (N = 8), had a chromosomal anomaly (N = 1), had severe head trauma during childhood (N = 1), or if a parent or sibling died during childhood (father: N = 2; sibling: N = 3), as well as children with missing behavior scores at age 2 and/or age 6 (N = 58). The eligible sample included children (see Flowchart in Additional file 1: Figure S1).

All mothers provided written informed consent, and the appropriate French ethics committees approved the study procedures.

Assessment of child behavior

At the 2-year-old follow-up, parents assessed their children’s behavior using items derived from the Child Behavior Checklist (CBCL) [15, 16] and the Preschool Social Behavior Questionnaire (PSBQ) [17]. Items were 3-point Likert scales ranging from 0 to 2 points (0 = never, 1 = sometime, 2 = often), summed into four different subscales: a score for the attention deficit/hyperactivity subscale was computed from six items, and scores for the aggression, opposition, and emotionality subscales were derived from 3 items each. The detailed list of items is presented in Additional file 1: Table S1, further details about construction of the subscales are provided elsewhere [13].

The year the children turned 6, parents assessed their behavior using four subscales of the French version of the Strengths and Difficulties Questionnaire (SDQ) [18, 19]: emotional symptoms, peer relationship problems, conduct problems, and hyperactivity-inattention. These subscales were derived from 20 items scored from 0 (not true) to 2 (certainly true). When children had two missing SDQ items or more within a subscale (N = 3), no score was calculated. In 40 children with one missing item, the corresponding subscale score was extrapolated from the remaining available items. The sample included children with available behavior subscales.

For all subscales at age 2 and 6, higher scores indicate more potential problems.

Exposure assessment

At inclusion (≤ 19 weeks of gestation), women were asked whether in their current job, they were using, producing, or exposed to one of 11 groups of products known to contain organic solvents (paints, strippers, varnishes, dyes, inks, glues, gasoline, grease remover, detergents and cleaning agents, textile treatment agents, and cosmetics) according to a 3-level scale (never, occasionally, regularly). Women reporting regular exposure to at least one group of products were considered “regularly exposed”; women reporting occasional exposure to at least one group of products were considered “occasionally exposed”; and finally, women were classified “not exposed” if they reported no exposure to any of these products [14]. The exposure status was available for % of the working women. We then excluded the 42 women who declared at the 2-year follow-up that they had changed job position in the late pregnancy. The final sample for analysis included mother-child pairs.

Statistical analysis

We addressed the relations between the multidimensional and longitudinal child’s behavior data within the structural equation modeling (SEM) framework.

To deal with the multidimensional data, we defined latent variables representing internalizing, and externalizing behaviors at age 6, as suggested by Goodman et al. [20] for the SDQ, and we applied the same rationale at age 2 (Fig. 1). The internalizing behavior trait was thus defined at age 2 by the emotional symptoms subscale, at age 6 by the emotional symptoms and peer relationship problems subscales. The externalizing behavior trait was defined at age 2 by the attention deficit/hyperactivity, aggression and opposition subscales, at age 6 by the hyperactivity/inattention and conduct problems subscales. Covariance between the two latent traits at each age was estimated.

Structural Equation Modeling of behavior traits at ages 2 and 6, raw model, PELAGIE cohort, France, – Abbreviations: Latent traits: Internal, internalizing behavior; External, externalizing behavior. Observed variables are scores from the Child Behavior Checklist (CBCL) and the Preschool Social Behavior Questionnaire (PSBQ) at age 2 and from the Strengths and Difficulties Questionnaire (SDQ) at age 6. At age 2: Emotion, “Emotional symptoms” (CBCL); Hyperactivity/Inattention, “Attention deficit/hyperactivity” (CBCL); "Aggression" (CBCL); "Opposition" (CBCL). At age 6: Emotion, “Emotional symptoms”, Peer-relation, “Peer-relationship problems”; “Hyperactivity/Inattention”; Conduct, “Conduct problems”. Arrows relating latent traits and observed variables represent standardized factor loadings. Double-headed curvilinear arrows represent covariances between latent traits at each age or residual variances of observed variables. Arrows between latent traits of different ages represent standardized regression coefficients. Each latent trait at age 6 was regressed on the two latent traits at age 2

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The longitudinal approach was considered by regressing each latent trait at age 6 linearly on the two latent traits at age 2, and by decomposing the associations between exposure and behavior latent traits at age 6 (total associations) into direct and indirect pathways. The indirect pathway represents the associations at age 6 that are determined by the associations between exposure and behavior traits at age 2 and the correlations between behavior traits at age 2 and 6. The direct pathway represents the marginal association at age 6, after adjusting for the associations at age 2.

First, a crude structural model representing the relations between latent behavior traits at ages 2 and 6 was fitted (Fig. 1). Each latent trait at age 6 was regressed linearly on all the two latent traits at age 2. All models’ parameters were estimated with a weighted least squares procedure (WLSM), which provides robust estimators and standard errors when the normality assumption is violated for observed variables [21]. Factor loadings and latent traits were standardized for easier interpretation. Parameters were considered significant if their 95% confidence intervals (95% CIs) did not include 0. A Satorra–Bentler scaled Chi-square statistic with P > , a RMSEA< , a CFI > , a GFI >  and a SRMR<  were considered to indicate good fit of the model [22].

In a second phase, we included the prenatal solvent exposure variable as a categorical variable. Both latent behavior traits at age 2 and age 6 were linearly regressed on the exposure variable. The association between exposure and each latent behavioral trait is interpreted as the mean change in the latent trait (expressed in number of standard deviations), expected for exposed compared to unexposed children.

All regression parameters were a priori adjusted for maternal age (continuous); maternal education (≤12 years, > 12 years); parity (0, ≥1); child’s sex; maternal tobacco consumption at the beginning of pregnancy (no, < 10 cig/day, ≥10 cig/day); breastfeeding (none, ≤16, > 16 weeks); mother-child interaction at age 2. This variable was based on five items collected at the 2-year follow-up on the activities shared with the child (e.g., singing, playing, and reading) (see Additional file 1: Table S2; see also Pelé et al. [13]). Missing values for covariates (< %) were imputed by the mode for categorical variables, and by the median for continuous variables.

Finally, we stratified our analyses by sex to explore possible differential pathways and associations in boys and girls. We tested the measurement invariance of the latent behavioral traits between boys and girls by comparing a restricted model constrained to estimate equal factor loadings in both sexes and the unrestricted model. The chi-square change (and associated p-value) was used to state whether measurement models were equivalent. SEM analyses were performed with the lavaan package, R software V [23].

Results

Table 1 presents the demographic characteristics and the lifestyle factors of the mother-child pairs. At the beginning of the pregnancy, most mothers were non-smokers (77%) and had completed a post-secondary degree (87%). Their mean age at delivery was  years, 42% had no previous delivery, 16% were overweight, and 21% had breastfed the child for more than 6 weeks. Fifty-three percent of children were boys. Overall, about half the pregnant women reported occupational exposure to organic solvents, either occasionally (19%) or regularly (31%) (Table 1). These exposures were mainly cleaning products and detergent (63% of the occasionally exposed women and 79% of the regularly exposed), glues, mastics, resins and adhesives (38 and 34%, respectively), inks and dyes (17 and 21%, respectively), or diluent and grease remover (10 and 24%, respectively) (see Additional file 1: Table S3). Among women classified as occasionally (respectively regularly) exposed to solvents, 63% (69%) were exposed occasionally (regularly) to one group of products, 21% (20%) to two groups and 16% (11%) to 3 groups of solvents or more. Among women classified as regularly exposed, some of them cumulated occasional exposure to other groups of solvents, so that 40% of them were exposed regularly and/or occasionally to one group of products, 27% to two groups, 33% to 3 groups of solvents or more (data not shown).

Full size table

Compared to the sample at inclusion in the cohort PELAGIE, women included in the present study tended to be older (+ 0,8 year on average), to have higher educational level (87% vs 81%), to be more often non-smokers during pregnancy (77% vs 72%), and slightly less overweight (16% vs 17%) and nulliparous (42% vs 44%). However, the distribution of prenatal exposure to solvents and behavioral scores remained very similar through the different follow-ups of the children of the cohort (see Additional file 1: Table S5).

Median behavior subscale scores at the ages of 2 and 6 are reported in Table 2, together with their loadings (λ) on their corresponding latent behavioral trait (crude model). Because the internalizing disorders latent trait was related to only one observed variable, its loading at age 2 was set to 1, by definition. At age 2, the externalizing behavior trait was highly related to the attention deficit/hyperactivity score (λ = ), then to the opposition score (λ = ) and moderately to the aggression score (λ = ). At age 6, the internalizing behavior trait was related to both emotional (λ = ) and peer-relational problems (λ = ) and the externalizing behavior trait was highly related to conduct problems (λ = ) and then to the hyperactivity score (λ = ).

Full size table

Each behavior latent trait at age 6 was significantly associated with the same latent trait at age 2 (standardized regression coefficients: (95% CI = , ) for internalizing behavior; and (95% CI = , ) for externalizing behavior) (see Additional file 1: Table S6). We also found a statistically significant relation between the externalizing behavior trait at age 2 and the internalizing behavior trait at age 6 (, 95% CI = , ). The fit statistics indicated that the model fit the data satisfactorily (RMSEA = , GFI = , CFI = , CFI = ). The adjustment of the model for covariates and exposure variable did not modify these structural relations: after adjustment, we found similar factor loadings (see Additional file 1: Table S7) and associations between behavioral latent traits at ages 2 and 6 (see Additional file 1: Table S6).

The associations between exposures and behavior traits through age 6 are presented in Table 3 and Fig. 2. Scores of externalizing behavior trait at age 2 were higher among children whose mothers reported occasional and regular occupational exposure to organic solvents during pregnancy (respectively, , 95% CI = , and , 95% CI = , ) than among unexposed mothers. No statistically significant association was observed between exposure and the internalizing behavior trait at age 2.

Full size table

Associations of occasional (a) and regular (b) prenatal self-reported exposure to solvents with behavior traits at ages 2 and 6 (N = , PELAGIE cohort, France, –), compared to non-exposure. Latent traits: Internal, internalizing behavior; External, externalizing behavior. All regression coefficients were adjusted for sex, education level, maternal age, breastfeeding duration, smoking during pregnancy, parity and mother-child interaction score. Results are presented in Table 3. Bold arrows indicate significant standardized regression coefficients (and confidence intervals). The association of latent traits at age 2 with prenatal exposure can be directly read on the graph arrows on the top of the graph. The direct association of latent traits at age 6 with prenatal exposure can be directly read on the broken arrows around the graphs. The indirect associations of each latent trait at age 6 can be derived by summing the associations through the two pathways pointing to it via internal and external traits at age 2. Each of these pathways generates an association with exposure. The intensity of the association is given by multiplying all the regression coefficients situated on the respective pathway. The total association, indicated in the shaded boxes under each latent trait at age 6, is obtained by summing the direct and indirect associations with exposure. Example of decomposition of the total association of occasional exposure to solvents with externalizing behavior at age 6: Direct association = ; Indirect association via internalizing behavior trait at age 2 = (*); via externalizing behavior trait at age 2 = (*). Indirect association = (*) + (*) =  Total association = −  +  = 

Full size image

At age 6, the associations between occasional and regular prenatal exposure and the externalizing behavior score were lower than at age 2 and statistically non-significant (respectively, , 95% CI = (− , ) and (95% CI = (− , )) compared to non-exposure. No association was observed for the internalizing behavior trait at age 6.

After adjustment for the latent behavior traits at age 2, the marginal associations (direct effect) of prenatal exposure with the latent behavior traits at age 6 were all non-significant. The fit statistics of the model were satisfactory (RMSEA = , GFI = , CFI = ).

Stratified analyses according to sex showed that the SEM model fit better in girls than in boys (Additional file 1: Tables S8-S10). The measurement invariance of the latent behavioral traits between boys and girls was rejected (P = ), meaning that latent behavior variables did not measure the behavior traits similarly (factor loadings were not strictly equal) (Additional file 1: Table S8). This is particularly true at age 6, where the peer-relationship score was predominant to define the externalized behavior in boys (factor loading =  vs in girls) and the hyperactivity-inattention score was predominant to define the internalized behavior in girls ( vs in boys). We also observed that the association between externalizing trait at age 2 and internalizing trait at age 6 was lower and not statistically significant in girls, compared to boys (Additional file 1: Table S9). Despite these structural differences which prevented us from formally concluding about differential effect prenatal exposure, we observed that the association between prenatal exposure to solvents and the externalizing behavior trait at age 2 was stronger in girls (, 95% CI: , ) than in boys (, 95% CI = − , ) (Additional file 1: Table S10).

Discussion

Higher scores of externalizing behavior disorders were seen among 2-year-old children whose mothers were exposed to organic solvents at work during their pregnancy. This association appeared strongly attenuated at age 6. No association was found between internalizing behavior at age 2 or age 6 and self-reported prenatal exposure to solvents.

As expected, the present study confirms our previous findings conducted among 2-year-old children in the PELAGIE cohort [13]. It additionally suggests that the possible role of occupational exposure to solvents during pregnancy on child externalizing behavior at age 2 may be transient. One hypothesis is that the effect may be reversible. More likely, possible compensatory mechanisms and/or the experience during childhood of different stimuli and stressors (all of them unmeasured) that may impact neuro-development, might have diluted the adverse effect of the prenatal exposure observed at age 2. To our knowledge, no similar study with repeated measurements of behavioral traits in childhood has been conducted previously to document that point.

Only a few previous studies were conducted and have suggested impaired behavior among children prenatally exposed to organic solvents. Laslo-Baker et al. found higher scores for both internalizing and externalizing disorders with the CBCL scale, based on 32 exposed and 32 unexposed children aged 3–9 years. They also observed higher levels of hyperactivity in exposed children based on the Conner’s Rating Scale-Revised [11]. Using the CBCL scale, Till et al. reported that children aged 3–7 years who had been prenatally exposed to organic solvents (n = 33) were at higher risk of both externalizing or internalizing behavioral problems, compared to unexposed children (n = 28) (P =  and P < , respectively) [10]. Both studies used self-reported exposure measurements standardized within a large-scale counseling program for pregnant women on diverse risks related to drugs, chemicals, radiation, and infections. Among the exposed groups, the main occupations were factory workers, laboratory technicians, graphic designers, and photography laboratory workers who had regular exposure (at least 5 h/week in Till et al. [10]) to multiple organic solvents including aromatic hydrocarbons (e.g., toluene, benzene, and xylene), alcohols (e.g., ethanol, methanol, and isopropanol) and aliphatic hydrocarbons (e.g., methane and ethane) and, especially in Till et al. [10], halogenated compounds (e.g., trichloroethylene and methyl chloride).

Conversely, using the Conners Parent Scale of Hyperactivity and the National Institute of Mental Health (NIHM) Childhood Personality Scale-Revised, Eskenazi et al. found no association between in utero exposure to organic solvents and behavior among  year-olds (n = 41 exposed and 41 unexposed) [12]. In this study, two independent industrial hygienists assessed exposure based on job title and industry and on the associated job description, including the material and equipment used. Occupations in the exposed group were mainly lab-workers, art-related workers, and operating room personnel, with identified exposures to aromatic hydrocarbons and halogenated solvents.

In the PELAGIE cohort, the women occasionally exposed were most frequently teachers (22%), clerical and related workers (19%), and health workers (assistant nurses, nurses, midwifes and x-ray technicians) (13%). The women regularly exposed were most frequently nurses’ aides, nurses, midwifes and x-ray technicians (29%), cleaners and helpers (13%), teachers (%), and chemists and biologists (8%) (Additional file 1: Table S4). These occupations differ from the occupations represented in the similar studies above-mentioned [10,11,12]. Teachers mainly reported exposure to glues, mastics, adhesives (42%), inks and dyes (27%), paints and lacquers (25%). Health workers reported mainly exposure to cleaning products or detergents (82%). Clerical workers reported exposure to glues, mastics, resins and adhesives (13%) or detergents (13%) and inks (7%). These groups of workers are likely to be exposed mostly to oxygenated and chlorinated solvents that may be associated with widely different potencies in regard to developmental neurotoxicity.

There were limited differences in the product types declared by women reporting occasional or regular exposures (detergents and cleaning agents, glues, dyes or inks, and diluents or grease removers) (see Additional file 1: Table S3). This suggests some exposure similarities in terms of chemical compound classes. However, the differential occupations correspond probably to different conditions and intensities of exposure, different uses of individual protection, and exposure to different (unmeasured) mixtures of compounds.

A major limitation of our study is that the exposure assessment was based on maternal self-reports and that groups were defined according to frequency and not to intensity of exposure. Nonetheless, we previously reported positive and statistically significant associations between this maternal self-report of regular occupational exposure and biomarkers of some types of solvents known to be used occupationally (e.g., glycol ethers and halogenated solvents), which supports the reliability of this self-reported exposure measurement [24].

The fact that the behavior scores at age 2 were adapted from two scales, the CBCL and the PSBQ, and were thus not strictly validated, may also be a limitation of this study. However, satisfactory Cronbach’s alpha scores for these behavioral scores were previously estimated in our cohort, which suggests good reliability [13]. Despite the use of different behavioral tools at ages 2 and 6, internalizing and externalizing behavior traits at age 2 were positively and statistically significantly correlated with their corresponding traits at age 6. This homotypic continuity for externalizing disorders is consistent with previous studies among children of similar ages or older [25, 26]. Finally, parents’ perception of their children’s behavior might depend on the sex, as shown in a validation study of the SDQ among children aged 5–6 years [27]. This may result in the lack of measurement invariance between sexes that we observed, with latent traits being differentially measured in boys and girls. This prevented us from formally concluding about the possible heterogeneous association between exposure and externalizing behavior for girls and boys.

In our analyses, we could not consider other possible sources of maternal exposure to solvents during pregnancy and postnatal exposure of the children at home or outside, except the use of products containing solvents for household renovation during childhood, which was not correlated with prenatal occupational exposure in our data.

Our study also presents strengths. The PELAGIE cohort, specifically designed to explore the possible role of prenatal exposure to various chemicals on the childhood development, assessed exposure prospectively and makes it possible to consider trajectories of different behavioral traits between ages 2 and 6 questioning the persistence of the associations observed in early childhood in previous work of the cohort. This study was conducted on a sub-sample (n =  participants to the 2 and 6-year-old follow-ups) of our previous work (n =  participants to the 2-year-old follow-up). However, behavioral scores and maternal exposure distribution at age 2 were similar between participants and non-participants at the 6-year-old follow-up (see Additional file 1: Table S11); possible selection bias is thus likely to be very minimal. Our methodological approach makes it possible to analyze different age-specific multi-item behavioral scales without aggregating them in predetermined single scores at each age, and in this sense, we better handle possible measurement errors of the behavior traits. This approach has also allowed us to avoid the multiple testing that occurs when separate regression models are fitted repeatedly for different outcomes. Finally, this is a large sample size (n = ) compared to the few previous studies conducted on this topic (n < ).

Conclusions

We confirmed the observation of higher scores of externalizing behavior at age 2 in children whose mothers have been occupationally exposed to organic solvents at the beginning of their pregnancy. Among our general-population-based cohort, this association seemed attenuated at age 6, suggesting that compensatory mechanisms may occur, and/or that many other unmeasured stimuli and stressors during childhood affecting behavior may dilute the effect of prenatal exposure to solvents. These results should encourage further studies to identify the compounds or mixtures of compounds associated for these results and increased awareness in occupational settings for preventive chemical protection of pregnant women.

Change history

    Abbreviations

    95% confidence interval

    Child Behavior Checklist

    Goodness of fit index

    Interquartile range

    National Institute of Mental Health

    Preschool Social Behavior Questionnaire

    Root Mean Square Error Approxiamtion

    Strengths and Difficulties Questionnaire

    Structural Equation Modelling

    Standardized root-mean-square residual

    Weighted least squares-mean

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    Acknowledgments

    We are grateful to the participants. We thank Jo Ann Cahn for her careful revision of the manuscript.

    Funding

    This work was supported by grant ANRPRSP from the French National Research Agency (ANR) and by grants from the Fondation de France, the National Institute for Public Health Surveillance (InVS), the Ministry of Labor, and the French Agency for Food, Environmental and Occupational Health and Safety (ANSES).

    Availability of data and materials

    The data are not freely available for duplication as they are property of our research institute. Access might be asked by contacting the corresponding author.

    Author information

    Author notes
    1. Nathalie Costet and Rémi Béranger contributed equally to this work.

    Affiliations

    1. Epidemiological Research in Environment, Reproduction and Health, Univ Rennes, Inserm, EHESP, Irset-UMR_S , 9, avenue du Prof. Léon Bernard, F, Rennes, France

      Nathalie Costet, Christine Monfort, Sylvaine Cordier & Cécile Chevrier

    2. Univ Rennes, CHU Rennes, Inserm, EHESP, Irset-UMR_S , Rennes, France

      Rémi Béranger, Ronan Garlantézec & Florence Rouget

    3. Univ Rennes, CHU Rennes, Inserm, Irset-UMR_S , CIC , F, Rennes, France

      Fabienne Pelé

    Contributions

    NC proposed and performed the statistical analyses and drafted the manuscript equally with RB and CC; RB took part to the statistical analyses and drafted the manuscript with NC and CC; RG took part to the conception of the questionnaire for occupational exposure and to the interpretation of the results; FR is the pediatrician consultant for the PELAGIE cohort and took part to the design of the study; CM was responsible for the fieldwork phase, the databases management and quality within the PELAGIE cohort; SC conceived and designed the initial PELAGIE cohort and took part to the interpretation of the results; FP took part to the interpretation of the results regarding the behavior traits; CC conceived and designed the PELAGIE follow-up at age 6, took part to the interpretation of the results and drafted the manuscript with NC and RB. All authors read and approved the final manuscript.

    Corresponding author

    Correspondence to Nathalie Costet.

    Ethics declarations

    Ethics approval and consent to participate

    All mothers provided written informed consent, and the appropriate French ethics committees approved the study procedures.

    Consent for publication

    All authors approved the manuscript and gave consent for publication.

    Competing interests

    The authors declare that they have no competing interests.

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    Additional information

    The original version of this article was revised: Table 2 has been replaced with the corrected version.

    Additional file

    Additional file 1:

    Figure S1. Flow chart of sample selection (PELAGIE Cohort, France, –). Table S1. Items used to assess the child behavior at age 2 in the PELAGIE cohort study, France, – Table S2. Items used to assess the mother-child interaction at age 2 in the PELAGIE cohort study, France, – Table S3. Groups of products related to occupational exposure to solvents (n = ) in the PELAGIE Cohort study, France, – Table S4. Distribution of maternal occupations during pregnancy in the PELAGIE Cohort, France, – Table S5. Characteristics of samples across the PELAGIE Cohort follow-ups (France, –). Table S6. Associations between behavior latent traits at 2 and 6 years (crude and adjusted models), PELAGIE Cohort, France, –, N =  Table S7. Structural Equation Modeling of behavior at ages 2 and 6 in the PELAGIE Cohort, France, – – Factor loadings for the latent traits at ages 2 and 6 (crude and adjusted model, n = ). Table S8. Structural Equation Modeling of behavior at ages 2 and 6 in the PELAGIE Cohort. France. – – Factor loadings for the latent traits at ages 2 and 6 (crude model) in boys (N = ) and girls (N = ). Table S9. Associations between behavior latent traits at age 6 and age 2 in boys (N = ) and girls (N = ) (crude model), PELAGIE Cohort, France, – Table S10. Sex-Stratified Total Associations Between Occupational Solvent Exposure During Pregnancy and Child Behavior at Age 2 and Age 6 (N =  Boys and N =  Girls, PELAGIE cohort, France, –). Table S11. Comparison of children participating at the 2 year and 6 year follow-ups with those participating only at the 2 year follow-up (PELAGIE Cohort, France, –). (DOCX kb)

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    Costet, N., Béranger, R., Garlantézec, R. et al. Occupational exposure to organic solvents during pregnancy and childhood behavior: findings from the PELAGIE birth cohort (France, –). Environ Health17, 63 (). https://doi.org//sx

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    Keywords

    • Solvents
    • Prenatal exposure delayed effects
    • Behavior
    • Cohort studies
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    MRI Exposure During Pregnancy and Offspring Outcomes

    Non-occupational exposure to paint fumes during pregnancy and risk of congenital anomalies: a cohort study

    Environmental Healthvolume 11, Article number: 54 () Cite this article

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    Abstract

    Background

    Occupational exposure to organic solvents during the 1st trimester of pregnancy has been associated with congenital anomalies. Organic solvents are also used in the home environments in paint products, but no study has investigated the effect of such exposure in a general population.

    Methods

    We studied associations between residential exposure to paint fumes during the 1st trimester of pregnancy and predefined subgroups of congenital anomalies, using data from the Danish National Birth Cohort (DNBC). During and , a total of 20 pregnant women, enrolled in the DNBC, were interviewed in the 30th week of gestation about the use of paint in their residence during pregnancy. By the end of first trimester, information about smoking habits, alcohol consumption and occupation were collected. Information on congenital anomalies was obtained from national registers. Associations were examined by estimating odds ratios (OR) using logistic regression.

    Results

    In total women (7%) had been exposed to paint fumes during the 1st trimester of pregnancy and children were diagnosed with congenital anomalies; 73 children with congenital anomalies had been exposed to paint fumes in utero. Exposure to paint fumes seemed positively associated with congenital anomalies of the nervous system (OR , 95% confidence interval (CI) to ), ear, face and neck (OR , 95% CI to ) and the renal system (OR , 95% CI to ) after adjustment for maternal age, smoking, alcohol consumption and occupational solvent exposure. Congenital anomalies in the remaining subgroups were not associated with the exposure.

    Conclusions

    Our results suggest that in the general population, exposure to paint fumes during the 1st trimester of pregnancy may increase the risk of some types of congenital anomalies, but the findings need to be confirmed.

    Peer Review reports

    Introduction

    The prevalence of congenital anomalies has been estimated to 50 per in live births in Denmark. Congenital anomalies are associated with significant societal costs related to treatment and improving quality of life with medical, social and educational services. Furthermore, congenital anomalies are of the top 20 list of leading causes of burden of disease (DALY´s) and are an important contributor to infant mortality. Also, the World Health Organisation estimated in that deaths or about 7% of all neonatal deaths were attributable to congenital anomalies.

    For a majority of the congenital anomalies, the etiology is unknown, though occupational and environmental agents are suspected to be involved[1]. Organic solvents are widely used in the work environment, e.g. the graphic industry and dry-cleaning, and in the home environment in products such as paint and cleaning agents. They represent a structurally diverse group of chemicals with low molecular weight, lipophilicity and are able to dissolve other organic substances. Chemicals in the solvent class include aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, aliphatic alcohols, glycols and glycol ethers. They are volatile liquids at room temperature and their main routes of exposure are through inhalation and skin contact.

    Epidemiological studies have indicated that women occupationally exposed to organic solvents during pregnancy may have a higher risk for congenital anomalies[2–7] than unexposed women, though the results are far from consistent[3, 5, 8]. Some studies have indicated that specific organic solvents like halogenated hydrocarbons, e.g. per- and trichloroethylene[9] and aromatic hydrocarbons, e.g. toluene and xylene[3] might be more hazardous to the fetus than other organic solvents.

    Ethanol is the most known and widely used organic solvent. Excessive intake of ethanol during pregnancy may lead to the foetal alcohol syndrome. This syndrome includes characteristic facial anomalies of the affected child, growth retardation and permanent central nervous system damage and is also associated with an increased risk of congenital anomalies in several organ systems. A suggested mechanism of action is that ethanol and the degradation product acetaldehyde may induce cell death and abnormal cell migration, which can cause a variety of congenital anomalies[10]. A similar mechanism of action, have been suggested for exposure to the organic solvents toluene or gasoline and risk of congenital anomalies[11, 12].

    To our knowledge, no studies have investigated if exposure to organic solvents in the home environment during pregnancy affects the risk for congenital anomalies in a general population. Organic solvents are used in different concentrations in all kinds of paint and many of these are liberated during painting and subsequently during drying and hardening. Many pregnant women are expected to be exposed to organic solvents from paint fumes during pregnancy due to “nesting behavior” and/or moving residence.

    The aim of the present study was to investigate the association between exposure to paint fumes in the residence during the 1st trimester of pregnancy and the risk of congenital anomalies in a prospective cohort.

    Methods

    Study population

    The study was carried out within The Danish National Birth Cohort (DNBC), which is a population based cohort of more than pregnant women and their offspring, and created to study determinants of early child health and diseases in later life[13]. From March to November pregnant women, who met the requirements of being able to speak Danish, being pregnant and intended to carry the pregnancy to term, were invited to participate in the DNBC. The invitation took place at the general practitioner, at the first antenatal visit, where the women received written information and an informed consent to sign and forward to the study secretariat. In the DNBC the women took part in two prenatal computer-assisted telephone interviews around gestational week 12 and The content of the interviews was developed in consultation with external experts and included, among others, questions related to lifestyle factors such as alcohol consumption and smoking habits and furthermore questions about occupation. The Danish ethical committee approved the DNBC.

    Paint fumes exposure assessment

    In the time period between September and May the second prenatal interview included questions about exposure to paint fumes in the residence. In total 20 pregnant women were interviewed during this time period. At first the women were asked if any painting had been done in their residence during pregnancy and if so, if they painted “furniture, floor, radiator and/or woodwork” and/or “wall and/or ceiling” and further, in exactly which gestational week(s) these two categories of painting was done.

    From these questions, we generated the variable “exposure to paint fumes in 1st trimester” (no/yes) based on painting done in th pregnancy week, regardless of the object of painting (furniture, floor, radiator and/or woodwork, wall and/or ceiling).

    Assessment of congenital anomalies

    Information on congenital anomalies in the offspring were obtained by linking the unique personal identification number of the mother and her child to the nationwide National Hospital Discharge Registry, which entails information on all hospital admissions and outpatient contacts on the individual patient[14]. All pregnancy outcomes are reported to and recorded in this register including congenital anomalies in live born children, whereas congenital anomalies in stillbirths, abortions and terminated pregnancies are not registered in the National Hospital Register. Congenital anomalies in live born children are diagnosed and assigned by physicians according to the International Classification of Diseases 10th Revision (ICD). We identified all children with ICD-codes Q to Q recorded during the first three and a half year of life.

    Congenital anomalies were grouped according to the EUROCAT recommendations[15], in specific subgroups, mainly based on organ systems and in addition genetic syndromes and other anomalies were considered as one group. EUROCAT, which is a network of population-based registries for the epidemiologic surveillance of congenital anomalies, recommend in their guideline to exclude both minor isolated anomalies and non-congenital anomalies. Since minor anomalies which include defects of smaller medical, functional or cosmetic importance, may be associated with exposure to chemical substances, such as organic solvents, we did not choose to exclude minor isolated anomalies, as purposed by EUROCAT. However, the following ICD-codes were excluded from our study: Q (pyloric stenosis), Q (plagiocephaly – head asymmetry), Q (torticollis) and Q (macrocephalus) were all excluded because they mainly occur at birth or after birth, and thus, unlikely to be associated with paint fumes exposure during the first trimester of pregnancy; Q (tongue tie – short frenum) and Q (hypoplasia of umbilical artery) were excluded because these are often not considered as congenital anomalies; Q (hiatus hernia) was excluded since it most often does not cause any symptoms and/or often disappears within the first years of life; Q (tracheomalacia) and QQ (laryngomalacia) representing weakness and floppiness of the walls of the trachea were excluded since these conditions most often disappear within 18 month of age. Furthermore, infants and children with the ICD-codes; QQ, which included chromosomal abnormalities, were not considered as events.

    The congenital anomaly subgroups used were: nervous system (QQ07), eye (QQ15), ear, face and neck (QQ18), congenital heart defects (QQ28), respiratory system (QQ34), oro-facial clefts (QQ37), digestive system (QQ45, Q), abdominal wall defects (Q, Q), renal (QQ64), genital (QQ56), limb defects (QQ, QQ74), musculo-skeletal (QQ, QQ) and other congenital anomalies (QQ85, Q87, Q89). Distribution of the specific congenital anomalies according to exposure status among the cases in the study using ICD10 is shown in Additional file1.

    Covariates

    We decided a priori to adjust for the following potential confounders: maternal smoking (no, yes), alcohol consumption (< 1, ≥ 1 drinks per week), potential occupational exposure to organic solvents and maternal age.

    Information on smoking habits, alcohol consumption and occupation came from the first (12th week) interview. An industrial hygienist defined “potentially occupationally exposed to organic solvents” as house painters, dry cleaners, employers in graphic industries, lab technicians and hairdressers. Maternal age was obtained from the National Hospital Discharge Registry.

    Statistical analyses

    We used logistic regression (proc GENMOD, SAS) and estimated odds ratios (OR) to test for associations between exposure to paint fumes in the 1st trimester of pregnancy (no/yes) and 1) all congenital anomalies and 2) congenital anomalies by subgroup. We performed crude analyses and analyses adjusted for the a priori defined potential confounders. We calculated two-sided 95% confidence intervals (CI) based on Wald’s test. All analyses were done in SAS (version , SAS Institute, Inc., Cary. NC, USA).

    Results

    Of the pregnant women, interviewed between September and May and with a singleton outcome (N = 20 ), we excluded women, who gave birth to a stillborn child (N = 57), whose children had a diagnosis of chromosomal abnormalities (N = 33), who had incomplete information on the use of paint during the 1st trimester (N = 55) and with incomplete information on any potential confounder (N = 15). Also, for women participating with two pregnancies/births within the study period, we excluded the second pregnancy/birth (N = 8). The remaining 19 mother and child pairs were eligible for the analyses.

    Characteristics of the women are shown in Table1. In total women (7%) were exposed to paint fumes in their residence in the 1st trimester. Among the children recorded in the Danish Hospital Discharge Register with congenital anomalies, 73 children had mothers, who had been exposed to paint fumes during the 1st trimester of pregnancy (Table1).

    Full size table

    There was no increased risk with exposure to paint fumes in the 1st trimester of pregnancy for all congenital anomalies combined (OR , 95% CI to ). Looking at individual subgroups, exposure to paint fumes in the 1st trimester of pregnancy was associated with a more than twofold increased risk of congenital anomalies in the nervous system (OR , 95% CI to ), ear, face and neck (OR , 95% CI to ) and in the renal system (OR , 95% CI to ) (Table2). The remaining subgroups were not persuasively associated with the exposure. Further adjustment of the analyses by the mother’s occupational status did only result in minor changes in the estimates (results not shown). In the subgroup: genital anomalies, we performed a sub-analysis in which we restricted the analysis to boys only. This only resulted on minor change in the estimate (results not shown).

    Full size table

    Discussion

    Our results indicate a positive association between exposure to paint fumes in the 1st trimester of pregnancy and the risk of congenital anomalies in the nervous system, the ear, face and neck and the renal system. Some occupational studies have indicated similar results. A case-referent study found that occupational exposure to aromatic solvents during the 1st trimester of pregnancy was associated with congenital anomalies, predominantly in the renal-urinary subgroup and in the gastrointestinal subgroup[2]. Two prospective occupational studies have found associations between maternal exposure to organic solvents and major congenital anomalies. The first study found associations between congenital anomalies in the renal system (hydronephrosis) and in the nervous system, particular neural tube defects[5]. The second study, designed as a cohort study, found occupational exposure to organic solvents to be associated with urinary anomalies, with OR of 2. Furthermore the authors described a weak association with congenital anomalies in the nervous system, in which the observed cases mainly were diagnosed with hydrocephalus[7]. Non-occupational studies have indicated a relation between prenatal alcohol consumption and risk of renal congenital anomalies, but a recent review, which investigated foetal alcohol spectrum disorders and risk of specific anomalies, did not confirm a homogenous pattern according to renal congenital anomalies[16]. Also, some environmental studies have indicated positive associations between solvents in drinking water and neural tube defects, which support our findings regarding congenital anomalies in the nervous system[17, 18]. In line with our results there are some indications from earlier occupational and environmental studies of an association between organic solvents and increased risk of congenital anomalies in the nervous system and the renal system[2, 5, 7]. However, due to small number of cases in these two congenital anomaly groups in the present study (28 and 58, respectively) the results should be treated with caution.

    Our study suggests that exposure to paint fumes might increase the risk for congenital anomalies in the ear, face and neck. One prior occupational study failed to find a positive association between exposure to organic solvents and congenital anomalies in the ear, face, and neck. In contrast, these kinds of anomalies have often and predominantly been observed in studies investigating maternal alcohol consumption or solvent abuse during pregnancy[11, 12]. Unstable findings due to the small numbers of cases may account for the inconsistent findings.

    Some studies have indicated associations between occupational exposure to organic solvents and congenital anomalies in the digestive system or cleft lip and cleft palate[5–7], for which we find no association. This can be due to different groupings of the particular congenital anomaly, but may also be explained by low power in our study to detect associations (only 39 cases) or by exposure to different organic solvents. Organic solvents are a very diverse group of chemicals with different toxicity and may therefore not be expected to create a homogenous pattern.

    In our study, estimation of exposure to paint fumes during the 1st trimester of pregnancy is based on questions in the 30th pregnancy week. This involves limitations compared with measurement of concentrations of organic solvents, as many factors affecting the actual concentrations, such as ventilation and room temperature, are not accounted for. Furthermore, paint contains different organic solvents in different concentrations depending on the type and brand of the paint, and, thus, makes it difficult to predict an actual exposure to specific organic solvents when exposure information is based on questions. Also the women had to recall exposure to paint fumes for some months, which could lead to misclassification.

    Although the overall ultrasonic examination for structural anomalies and developmental defects as a general offer to all pregnant women were first introduced in Denmark in (that is after the DNBC enrolment period), it cannot be ruled out, that some pregnant mothers may have been ultrasonic examined on indication resulting in, that they already in the 30th pregnancy week knew, that their child would be born with a congenital anomaly. This can have introduced some recall bias with regard to the questions regarding painting.

    We obtained information on congenital anomalies in the National Hospital Register, identifying all children with diagnosis of congenital anomalies from birth until the age of  year old. The applied time period allowed us to include diagnosis, such as congenital anomalies in the urinary system, which usually not are detected at birth, unless routine ultrasound during pregnancy has been used[7]. The diagnosis may however be subjects to some misclassification, as some anomalies may wrongly be classified as other anomalies. This non-differential misclassification is most likely not associated with the exposure to paint fumes in the residence and would as such, either not affect the risk estimates or bias it towards the neutral value.

    Based on EUROCAT´s recommendations, we grouped congenital anomalies in 13 subgroups. For three of these, we found exposure odds ratios higher than two, but only the estimate for the renal subgroup remained statistically significant in the adjusted analysis. Overall the subgroups used are rather large with some etiological heterogeneity. The rationale behind this grouping was that the numbers of congenital anomalies were too small to examine more specific subgroups. However, this might have diluted the effect of more specific groups of anomalies.

    In total we found no estimates of exposure ratios to be less than We have adjusted for few obvious potential confounding factors and it can be argued that other risk factors should have been included. However, the size of the data material did not allow further adjustment. The fact that the crude and adjusted results were virtually identical may indicate that our results are not largely confounded. On the other hand, information on potential important confounders such as sources of solvent exposure in the home environment including use of cleaning agents or hobbies was not available for the study[19, 20]. The consistency between our results and previous findings indicates the associations we find might be true, although it is possible that our findings may be due to chance. The fact that our study is based on small number of exposed cases may have resulted in statistical instability of our findings.

    We found congenital anomalies in % of the pregnancies included in our study and that congenital anomalies were more common in boys than in girls. Both these findings are consistent with Danish national data for live births. Furthermore, our study is based on data from a population based birth cohort, from which we only excluded 1%, mainly because of birth of stillborns and incomplete information on covariates and not the main exposure of interest, paint fumes. However, it is a limitation to the study that we were only able to include live born children with congenital anomalies. Assuming that exposure to paint fumes affects the risk of severe congenital anomalies that may result in abortion or stillbirth, the risk estimates of such anomalies would be underestimated in our study. We also excluded 33 women, whose children were diagnosed with chromosomal abnormalities. These children could not be cases despite other morphological anomalies, since children with chromosomal abnormalities (who often have anomalies) were excluded as potential cases as these conditions are founded before conception and as such, not due to paint fumes exposure during pregnancy. A previous study has shown that participants in the DNBC were somewhat healthier, according to smoking habits than the general population[21], but we have no knowledge of whether the women included in our study have painted more or less than the general population.

    Conclusions

    Our results suggested an association between exposure to paint fumes in the 1st trimester of pregnancy and risk of congenital anomalies in the nervous system, the ear, face and neck and the renal system. These results need to be confirmed.

    Abbreviations

    Danish National Birth Cohort

    Odds ratio

    Confidence interval

    International classification of diseases 10th Revision.

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    Acknowledgments

    We thank senior researcher Johnny Hansen for his help with identifying the women potentially occupationally exposed to organic solvents.The Danish Agency for Science, Technology and Innovation supported this study. The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Author information

    Affiliations

    1. Danish Cancer Society Research Centre, Copenhagen, Denmark

      Dorrit Hjortebjerg, Ole Raaschou-Nielsen & Mette Sørensen

    2. Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark

      Anne-Marie Nybo Andersen

    3. Pediatric Department, Hospital Lillebaelt, Kolding, Denmark

      Ester Garne

    Corresponding author

    Correspondence to Mette Sørensen.

    Additional information

    Competing interests

    The authors declare that they have no competing interests.

    Author contributions

    DH, MS, ANA and ORN conceived the study. ANA participated in establishing the Danish National Birth Cohort. EG participated in grouping of the congenital anomalies. DH analysed the data. MS, ANA and ORN contributed to the data analysis and data interpretation. DH drafted the paper, and all the authors critically revised it. All authors read and approved the final manuscript.

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    Hjortebjerg, D., Andersen, AM.N., Garne, E. et al. Non-occupational exposure to paint fumes during pregnancy and risk of congenital anomalies: a cohort study. Environ Health11, 54 (). https://doi.org//X

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    Keywords

    • Epidemiology
    • Organic solvent
    • Paint fumes
    • Birth cohort
    • Congenital anomalies
    • Birth defects
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