Impact of prenatal triclosan exposure on gestational age and anthropometric measures at birth: A systematic review and meta-analysis
Mehri Khoshhali1, Mohammad Mehdi Amin2, Ali Fatehizadeh2, Afshin Ebrahimi2, Ensiyeh Taheri2, Roya Kelishadi1
1 Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
2 Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease; Department of Environmental Health Engineering, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||11-Dec-2019|
|Date of Decision||27-Jan-2020|
|Date of Acceptance||19-Feb-2020|
|Date of Web Publication||30-Jun-2020|
Department of Environmental Health Engineering, School of Health, Isfahan University of Medical Sciences, Hezar Jarib Ave, Azadi Squre, Isfahan 73461-81746
Pediatrics Department, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Hezar Jarib Ave, Azadi Squre, Isfahan 73461-81746
Source of Support: None, Conflict of Interest: None
Background: Exposure to endocrine disrupting chemicals such as triclosan (TCS) leads to disrupting the endocrine system and consequently effect on the birth outcomes. The findings of studies in this field are controversial. Materials and Methods: This systematic review and meta analysis was conducted based on the identified published papers in Scopus, Web of Science, and PubMed up to November 2019. All steps, including searching, screening, data extracting, and quality assessment, were done by two independent researchers. Results: Finally 15 published papers selected. The number of participants in whom the association of TCS exposure was assessed with birth weight, birth length, birth head circumference, and gestational age were 9112, 4311, 2854, and 3181 mother infant pairs, respectively. The pooled analysis showed that TCS exposure during pregnancy leads to increasing the birth weight for boys with β= 3.97 and 95% confidence interval (CI) (−3.98, 11.92), and girls with β= 5.37, 95% CI (−6.00, 16.75), but the association was not statistically significant. In addition, according to fixed effects models, the TCS exposure was not significantly associated with birth length (−0.008, 95% CI [−0.049, 0.034]), birth head circumference (−0.01, 95% CI [−0.08, 0.06]), and gestational age (−0.005, 95% CI [−0.017, 0.006]). Likewise, analysis for data segregated by gender of infants revealed similar results. Conclusion: The obtained results depicted that the TCS exposure during pregnancy period was associated with higher birth weight for boys and girls. No significant association was observed for TCS exposure with variation of birth length, head circumference, and gestational age duration. In fact, the results showed the evidence of null associations between maternal TCS exposure and birth outcomes.
Keywords: Birth length, birth weight, gestational age, head circumstance, triclosan
|How to cite this article:|
Khoshhali M, Amin MM, Fatehizadeh A, Ebrahimi A, Taheri E, Kelishadi R. Impact of prenatal triclosan exposure on gestational age and anthropometric measures at birth: A systematic review and meta-analysis. J Res Med Sci 2020;25:61
|How to cite this URL:|
Khoshhali M, Amin MM, Fatehizadeh A, Ebrahimi A, Taheri E, Kelishadi R. Impact of prenatal triclosan exposure on gestational age and anthropometric measures at birth: A systematic review and meta-analysis. J Res Med Sci [serial online] 2020 [cited 2020 Jul 5];25:61. Available from: http://www.jmsjournal.net/text.asp?2020/25/1/61/288703
| Introduction|| |
Birth outcomes, such as birth weight, birth length, birth head circumference, abdominal circumference, and gestational age, have been associated with an increase in newborn's morbidity and mortality and the risk of disability, cerebral palsy, visual problems, learning disabilities, and respiratory problems.,,
The causes of adverse birth outcomes such as low birth weight and small for gestational age are multifactorial and are not clear yet. Exposures to chemicals with estrogenic and/or antiandrogenic effects can disrupt the endocrine system functions, i.e., endocrine-disrupting chemicals (EDCs) such as phenolic compounds might affect birth outcomes through different hormone-related mechanisms.,
Phenolic compounds include various classes of chemicals including parabens, triclosan (TCS), and bisphenols. They are the common components used in consumer products that have tendency to cause hormonal disturbances during in utero and ex utero development., Exposure to these compounds usually occurs using personal care products in adults. The presence of these compounds in blood, milk, and amniotic fluid can be the exposure route for embryo and infants.,
In several consumer products including toothpaste, mouthwash, disinfectants, and soaps, the TCS is used as a bactericide and fungicide agent. Due to the widespread usage of consumer products, the people are broadly exposed to TCS through both ingestion and dermal route. Conducted studies on the US and China national population reported that in 74% and 98.2% of urine samples, TCS was detected., In addition, TCS was detected in other biological fluids such blood and breast milk. The endocrine-disrupting properties of TCS include the influence of the antiandrogenic activity and thyroid hormone function.,
From 2008 up to now, numerous studies have been conducted to investigate the likelihood relationship of prenatal TCS exposure and birth outcomes. Different results were reported for the associations of TCS concentrations with birth outcomes such as birth weight and length, as well as gestational age.,,
Taken together, exposure to TCS during intrauterine life may influence fetal growth and consequently birth outcomes; however, controversial findings led to uncertainty in this regard.
In brief, the associations between maternal TCS exposure and newborn's birth size remain unclear. The previous studies demonstrated the positive or negative direction of association and sex-specific differences which have been not well proved. Therefore, in this study, we systematically reviewed the current literatures and conducted a meta-analysis to find the association between maternal TCS exposure and birth weight, birth length, birth head circumference, and gestational age.
| Methods|| |
This review was done based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews.
Studies with a cohort and cross-sectional design were included. No restrictions on publication date and language were applied in the search date until November 2019.
Participants, exposure, and outcome measures
To evaluate the association between TCS exposure of pregnant women and birth outcomes, the mother–infant pairs were considered. The pregnant women participating in studies were healthy women in each stage of pregnancy, without any history of specific illnesses or long-term use of medications. The maternal urinary TCS during pregnancy as a TCS exposure biomarker and also the infant characteristics including birth weight, birth length, birth head circumstance, and gestational age were targeted birth outcomes. Studies with a cohort and cross-sectional design were included only if they met the inclusion criteria and studies with any intervention were excluded. The presented data in full text of selected manuscripts and their appendices were used for meta-analysis.
Information sources and search strategy
The comprehensive search in electronic bibliographic databases including Scopus, Web of Science, and PubMed was carried out. The following terms using Medical Subject Headings (MeSH) comprise “birth outcome” OR “fetal growth” OR “birth weight” OR “birth size” OR “Fetal Macrosomia” OR “gestational age” OR “preterm birth” AND “Triclosan” and their relating terms and various words encompassing them were used as keywords for searching in database. For achieving a thorough list of all researches covering these combinations of keywords, truncations such as AND and OR were used based on Boolean logic. More details on search strategy are presented in [Supplementary Table 1 [Additional file 1]].
Data management, screening process, data extraction, and quality assessment
For data management, the EndNote software X8 (Thomson Scientific, USA) was used. After duplicates removal from EndNote library, the screening was done as follows:
- Titles and abstracts checking: Two independent researchers screened the studies based on their title and abstract. The irrelevant studies were removed, and when there is a doubt about an article, researchers decided after discussing, otherwise it was postponed to the next stage.
- Full-text checking: The full-text articles identified in the previous stage were checked based on inclusion criteria, and the data collection form was completed for each paper in this stage and contains first author's last name, year of publication, study location, sample size, and outcomes. To find additional related studies, the reference lists of included papers were checked.
The published checklist by the National Heart, Lung and Blood Institute for Quality Assessment of Observational Cohort and Cross-sectional Studies was used by two reviewers to assess the risk of bias of the included papers based on the scoring system. The checklist contains 14 questions about research question or objectives, population specification and definition, participation rate, recruitment and uniformity, sample size, priority of exposure and outcome, timeframe, exposure categorizing, independent variables, definition and assessment, outcome measures and blinding, attrition bias, and control of confounding. The studies were rated as either good, fair, or poor based on the mentioned criteria.
The regression (β) coefficient values of selected studies were applied for pooled analysis. The potential heterogeneity across studies was evaluated using the Cochran's Q-test and expressed using the I2 index. The pooled results were calculated by the fixed-effects model (for I2< 50%) or the random-effects model (for I2 > 50%). Publication bias was evaluated by the Egger's and Begg's tests. All statistical analyses were conducted using software Stata 12.0 (StataCorp, College Station, Texas, USA).
| Results|| |
From 149 identified studies, 15 studies were included in the meta-analysis after title, abstract, and full-text checking [Figure 1]. All these studies had evaluated the effect of prenatal TCS exposure on at least one of the birth outcomes including birth weight, birth length, birth head circumference, and gestational age and were conducted in different countries without any geographical restriction. From 15 selected studies, 12 studies were cohort and 3 studies were cross-sectional studies. The number of studies that reported the association of TCS exposure with birth weight, birth length, birth head, and gestational age was 13,,,,,,,,,,,,, 9,,,,,,,,, 8,,,,,,,, and 6,,,,,, respectively. All studies had evaluated the prenatal exposure to TCS and growth in both male and female neonates, except 2 studies that investigated it in male infants.,
More details related to the included studies are available in [Table 1]. The results (after the agreement between both independent researchers) of the quality assessment for included studies are summarized in [Table 2] and showed that all included studies had good quality and low risk of bias.
Effect of prenatal triclosan exposure on birth weight
Of the 13 studies that have reported the relationship of TCS exposure and birth outcomes,,,,,,,,,,,,, two studies have included only male infants, and the remaining studies have investigated both male and female infants. Moreover, 4 studies reported the birth weight Z-score.,,, The total population from 13 included studies was 9112 mother–infant pairs. The pooled analysis of TCS exposure was associated with the increased birth weight for boys and girls, 3.97, 95% confidence interval (CI) (−3.98, 11.92), and 5.37, 95% CI (−6.00, 16.75), respectively, and decreased birth weight for both − 0.032, 95% CI (−11.59, 11.53), using the random-effects models. However, none of these effects were significant. A significant heterogeneity was detected for the meta-analysis of effect TCS exposure on birth weight for total (I2 = 54.0%, P = 0.043) [Figure 2]. In addition, the pooled effect of TCS exposure on birth weight Z-score was not also significant for girls, boys, and total. The heterogeneity was not significant for them (P > 0.05) [Figure 3]. The P values for Begg's test and Egger's test for birth weight were 0.538 and 0.419, respectively, that revealed no obvious publication bias among these studies. However, Begg's test and Egger's test for birth weight Z-score suggested publication bias, P < 0.001, respectively. Trim-and-fill analysis was conducted, but no study was filled. This showed that the publication bias had a nonsignificant effect on the results.
|Figure 2: Forest plot of beta-coefficients for the effect of triclosan exposure on birth weight by gender|
Click here to view
|Figure 3: Forest plot of beta-coefficients for the effect of triclosan exposure on birth weight Z-score by gender|
Click here to view
Effect of prenatal triclosan exposure on birth length
Birth length association with prenatal TCS exposure was investigated in 9 studies.,,,,,,,, Except Philippat et al.'s study, all other studies survived both genders of infants and contain 4311 mother–infant pairs.
The pooled analysis of TCS exposure was not significantly associated with the birth length for boys (0.016, 95% CI [−0.029, 0.062]), girls (−0.02, 95% CI [−0.062, 0.022]), and total (−0.008, 95% CI [−0.049, 0.034]) based on fixed-effects models. Furthermore, there was no significant heterogeneity for them [Figure 4]. Begg's test and Egger's test revealed no obvious publication bias among these studies; the P values for these tests were >0.05 (P = 0.558 and 0.124, respectively).
|Figure 4: Forest plot of beta-coefficients for the effect of triclosan exposure on birth length by gender|
Click here to view
Effect of prenatal triclosan exposure on birth head circumference
The extracted data from 8 studies,,,,,,, related to effect TCS exposure on birth head and covering 2854 mother–infant pairs were used. The pooled analysis of TCS exposure was associated with the decreased birth head for boys − 0.04, 95% CI (−0.10, 0.01); −0.02, 95% CI (−0.05, 0.01), for girls; and − 0.01, 95% CI (−0.08, 0.06), for both using the random-effects models. However, none of these effects were significant. A significant heterogeneity was detected for the meta-analysis of effect TCS exposure on birth head for total (I2 = 55.8%, P = 0.045) [Figure 5]. Begg's test and Egger's test revealed no obvious publication bias among these studies; the P values for these tests were >0.05 (P = 0.330 and 0.308, respectively).
|Figure 5: Forest plot of beta-coefficients for the effect of triclosan exposure on birth head by gender|
Click here to view
Effect of prenatal triclosan exposure on gestational age
The pooled analysis of extracted data from 6 studies,,,,, explained that the TCS exposure of 3181 pregnant women and gestational age of their infants showed that TCS exposure was not significantly associated with the gestational age for boys (−0.028, 95% CI [−0.068, 0.012]), girls (−0.028, 95% CI [−0.063, 0.007]), and total (−0.005, 95% CI [−0.017, 0.006]) based on fixed-effects models. Furthermore, there was no significant heterogeneity for them [Figure 6]. The P values for Begg's test and Egger's test were 0.436 and 0.534, respectively. Therefore, there was no publication bias among these studies (P > 0.05).
|Figure 6: Forest plot of beta-coefficients for the effect of triclosan exposure on gestational age by gender|
Click here to view
Effect of prenatal triclosan exposure on anogenital distance
Anogenital distance (AGD) refers to the distance from the anus to the genitals in neonatal as a sexually dimorphic was studied in 2 included studies. The prenatal TCS exposure does not have any association with AGD in girls in both studies, but its effect on reduced AGD at 3 months of age in boys was significant (P < 0.10), as reported Lassen et al.,
| Discussion|| |
The present study is focused solely on reviewing the studies that have investigated the association of prenatal exposure to TCS with birth outcomes. We performed a comprehensive search of PubMed, Web of Science, and Scopus databases using a well-defined search strategy and with no language and time restrictions applied.
After duplicates removal and studies screening, 15 remained studies were systematically reviewed to determine the association of prenatal TCS exposure with birth outcomes. In all included studies, the maternal TCS urinary concentration was considered as a biomarker of the pregnant women's exposure to TCS.
For accounting the unpublished studies, the publication bias was investigated. The Begg's and Egger's tests for birth weight, birth length, birth head circumference, and gestational age were revealed no obvious publication bias. However, the Begg's and Egger's tests for birth weight Z-score were suggested significant publication bias. In addition, trim-and-fill analysis resulted that the publication bias had no significant effect on the obtained results.
Our study revealed the association between maternal TCS exposure and increasing birth weight for boys and girls, but the association was not statistically significant. However, maternal TCS exposure does not have any significant effect on birth weight, length, head circumference, and gestational age.
TCS is a phenol derivative that, unlike other phenolic compounds, is identified as a safe and tolerable compound with low acute toxicity. The main mechanism suggested for describing how TCS can affect the fetal growth is as follows: disrupting the levels of thyroid hormones through increasing their hepatic metabolism., The mentioned mechanism is the suggested mechanism based on animal studies., The effect of TCS on thyroid hormones is inconsistent, and reported associations in human studies included the positive, negative, or nonexistent association.,,,
Thyroxin availability is an effective factor on the fetus growth and development, and the fetus is dependent on maternal thyroxin during the first trimester and the function of the fetal thyroid starts after the 12nd week of gestation. However, the fetus gain the most weight during the third trimester of pregnancy. The urine samples collected around the 28th week of pregnancy may be better for the assessment of fetal growth effects. The half-life of TCS is <24 h, and as a short-lived compound, its concentration varies during and across days. This fluctuation is higher in spot urine samples than in long-term samples.,, At all included studies in the current review, the spot urine samples that were derived dominantly in the second and third trimesters and rarely in the first trimester were used for exposure assessment. It seems that a single spot urine sample cannot clearly reflect the average of exposure to the TCS during the entire pregnancy. It can be the possible reason for controversial results reported for the association of prenatal exposure to TCS with birth outcomes.
The limitation related to current review are including: the urine sampling in different pregnancy stages in various study and once sampling in most of studies.
| Conclusion|| |
The present systematic review showed no significant association between maternal exposure to TCS and birth outcomes. According to obtained results, we recommend the conduction of more studies on TCS detection in diverse biological matrixes (blood, cord blood, urine, and placenta) and in diverse pregnancy stages to evaluate the effect of TCS exposure during pregnancy on birth outcomes. Due to the limitation of these studies, it is wise to limit TCS exposure in pregnancy, especially in the maternal period.
The authors would like to thank the Isfahan University of Medical Sciences of Iran (Project No. 298243 and Ethics code: IR.MUI.RESEARCH.REC.1398. 674) for the financial support of this work.
Financial support and sponsorship
This study was financially supported by the Isfahan University of Medical Sciences.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kinney MV, Lawn JE, Howson CP, Belizan J. 15 million preterm births annually: What has changed this year? Reprod Health 2012;9:28.
Setiawan C. Background Paper 6.23 Neonatal Conditions. Priority Medicines for Europe and the World a Public Health Approach to Innovation; 2013. p. 1-50.
Tough SC, Schopflocher D, Svenson L. Maternal Risk Factors in Relationship to Birth Outcome: Report: Health Surveillance. Canada: Alberta Health and Wellness; 1999.
Ding G, Wang C, Vinturache A, Zhao S, Pan R, Han W, et al
. Prenatal low-level phenol exposures and birth outcomes in China. Sci Total Environ 2017;607-608:1400-7.
Weng YH, Yang CY, Chiu YW. Risk assessment of adverse birth outcomes in relation to maternal age. PLoS One 2014;9:e114843.
Geer LA, Pycke BFG, Waxenbaum J, Sherer DM, Abulafia O, Halden RU. Association of birth outcomes with fetal exposure to parabens, triclosan and triclocarban in an immigrant population in Brooklyn, New York. J Hazard Mater 2017;323:177-83.
Lassen TH, Frederiksen H, Kyhl HB, Swan SH, Main KM, Andersson AM, et al
. Prenatal triclosan exposure and anthropometric measures including anogenital distance in danish infants. Environ Health Perspect 2016;124:1261-8.
Ley C, Pischel L, Parsonnet J. Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention. Reprod Toxicol 2017;74:143-9.
Wang X, Ouyang F, Feng L, Wang X, Liu Z, Zhang J. Maternal urinary triclosan concentration in relation to maternal and neonatal thyroid hormone levels: A prospective study. Environ Health Perspect 2017;125:067017.
Lester F, Arbuckle TE, Peng Y, McIsaac MA. Impact of exposure to phenols during early pregnancy on birth weight in two Canadian cohort studies subject to measurement errors. Environ Int 2018;120:231-7.
Huo W, Xia W, Wu C, Zhu Y, Zhang B, Wan Y, et al
. Urinary level of triclosan in a population of Chinese pregnant women and its association with birth outcomes. Environ Pollut 2018;233:872-9.
Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, et al
. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect 2008;116:1092-7.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009;151:264-9.
Basu A. How to Conduct Meta-Analysis: A Basic Tutorial; 2017.
National Heart Lung and Blood Institute. Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. National Heart Lung and Blood Institute; 2019.
Diez-Fernández A, Álvarez-Bueno C, Martínez-Vizcaíno V, Sotos-Prieto M, Recio-Rodríguez JI, Cavero-Redondo I. Total dairy, cheese and milk intake and arterial stiffness: A systematic review and meta-analysis of cross-sectional studies. Nutrients 2019;11:1-4.
Borenstein M, Hedges L, Higgins J Rothstein HR. Introduction to Meta-analysis. Chichester, UK: John Wiley and Sons; 2009. p. 9
Philippat C, Botton J, Calafat AM, Ye X, Charles MA, Slama R, et al
. Prenatal exposure to phenols and growth in boys. Epidemiology 2014;25:625-35.
Messerlian C, Mustieles V, Minguez-Alarcon L, Ford JB, Calafat AM, Souter I, et al
. Preconception and prenatal urinary concentrations of phenols and birth size of singleton infants born to mothers and fathers from the Environment and Reproductive Health (EARTH) study. Environ Int 2018;114:60-8.
Ouyang F, Tang N, Zhang HJ, Wang X, Zhao S, Wang W, et al
. Maternal urinary triclosan level, gestational diabetes mellitus and birth weight in Chinese women. Sci Total Environ 2018;626:451-7.
Philippat C, Heude B, Botton J, Alfaidy N, Calafat AM, Slama R, et al
. Prenatal exposure to select phthalates and phenols and associations with fetal and placental weight among male births in the EDEN cohort (France). Environ Health Perspect 2019;127:17002.
Etzel TM, Calafat AM, Ye X, Chen A, Lanphear BP, Savitz DA, et al
. Urinary triclosan concentrations during pregnancy and birth outcomes. Environ Res 2017;156:505-11.
Ferguson KK, Meeker JD, Cantonwine DE, Mukherjee B, Pace GG, Weller D, et al
. Environmental phenol associations with ultrasound and delivery measures of fetal growth. Environ Int 2018;112:243-50.
Wu C, Li J, Xia W, Li Y, Zhang B, Zhou A, et al
. The association of repeated measurements of prenatal exposure to triclosan with fetal and early-childhood growth. Environ Int 2018;120:54-62.
Aker AM, Ferguson KK, Rosario ZY, Mukherjee B, Alshawabkeh AN, Cordero JF, et al
. The associations between prenatal exposure to triclocarban, phenols and parabens with gestational age and birth weight in northern Puerto Rico. Environ Res 2019;169:41-51.
Philippat C, Mortamais M, Chevrier C, Petit C, Calafat AM, Ye X, et al
. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ Health Perspect 2012;120:464-70.
Arbuckle TE, Agarwal A, MacPherson SH, Fraser WD, Sathyanarayana S, Ramsay T, et al
. Prenatal exposure to phthalates and phenols and infant endocrine-sensitive outcomes: The MIREC study. Environ Int 2018;120:572-83.
Paul KB, Hedge JM, Devito MJ, Crofton KM. Developmental triclosan exposure decreases maternal and neonatal thyroxine in rats. Environ Toxicol Chem 2010;29:2840-4.
Paul KB, Hedge JM, Bansal R, Zoeller RT, Peter R, DeVito MJ, et al
. Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: A dynamic and kinetic evaluation of a putative mode-of-action. Toxicology 2012;300:31-45.
Skarha J, Mínguez-Alarcón L, Williams PL, Korevaar TIM, de Poortere RA, Broeren MAC, et al
. Cross-sectional associations between urinary triclosan and serum thyroid function biomarker concentrations in women. Environ Int 2019;122:256-62.
Berger K, Gunier RB, Chevrier J, Calafat AM, Ye X, Eskenazi B, et al
. Associations of maternal exposure to triclosan, parabens, and other phenols with prenatal maternal and neonatal thyroid hormone levels. Environ Res 2018;165:379-86.
Derakhshan A, Shu H, Peeters RP, Kortenkamp A, Lindh CH, Demeneix B, et al
. Association of urinary bisphenols and triclosan with thyroid function during early pregnancy. Environ Int 2019;133:105123.
Aylward LL, Hays SM, Zidek A. Variation in urinary spot sample, 24h samples, and longer-term average urinary concentrations of short-lived environmental chemicals: Implications for exposure assessment and reverse dosimetry. J Expo Sci Environ Epidemiol 2017;27:582-90.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]