Repeated Measurements of Paraben Exposure during Pregnancy in

Subscriber access provided by The Libraries of the | University of North Dakota

Ecotoxicology and Human Environmental Health

Repeated measurements of paraben exposure during pregnancy in relation to fetal and early-childhood growth Chuansha Wu, Wei Xia, Yuanyuan Li, Jiufeng Li, Bin Zhang, Tongzhang Zheng, Aifen Zhou, Hongzhi Zhao, Wenqian Huo, Jie Hu, Minmin Jiang, Chen Hu, Jiaqiang Liao, Xi Chen, Bing Xu, Shi Lu, Zongwei Cai, and Shunqing Xu Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.8b01857 • Publication Date (Web): 14 Nov 2018 Downloaded from http://pubs.acs.org on November 14, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 42

Environmental Science & Technology

Xu, Shunqing; Tongji Medical College, Huazhong University of Science and Technology, State Key Laboratory of Environmental Health , School of Public Health

ACS Paragon Plus Environment


1

Repeated measurements of paraben exposure during pregnancy in

2

relation to fetal and early-childhood growth

3

Chuansha Wu,†,# Wei Xia,†,# Yuanyuan Li,† Jiufeng Li,‡ Bin Zhang,§ Tongzhang Zheng,‖

4

Aifen Zhou,§ Hongzhi Zhao,‡ Wenqian Huo,⊥ Jie Hu,† Minmin Jiang,† Chen Hu,† Jiaqiang

5

Liao,† Xi Chen,† Bing Xu,† Shi Lu,¶ Zongwei Cai,*,‡ and Shunqing Xu*,†

6

†

7

Environmental Protection, and State Key Laboratory of Environmental Health, School of

8

Public Health, Tongji Medical College, Huazhong University of Science and Technology,

9

Wuhan, Hubei, People’s Republic of China

Key Laboratory of Environment and Health, Ministry of Education & Ministry of

10

‡

11

Chemistry, Hong Kong Baptist University, Hong Kong, SAR, People’s Republic of China

12

§ Women

13

Republic of China

14

‖ Department

15

⊥

16

Zhengzhou University, Zhengzhou, Henan, People's Republic of China

17

¶

18

Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of

19

China

State Key Laboratory of Environmental and Biological Analysis, Department of

and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People’s

of Epidemiology, Brown University, Providence, RI, USA

Department of Occupational and Environmental Health, College of Public Health,

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College,

20

21

* Corresponding author: Prof. Shunqing Xu, E-mail: [email protected], School of Public

22

Health, Tongji Medical College, Huazhong University of Science and Technology, 13


Page 2 of 42

Page 3 of 42


23

Hangkong Road, Wuhan 430030, China; Tel: 86-27-83657705; Fax: 86-27-83657781 or

24

Prof. Zongwei Cai, E-mail: [email protected], Department of Chemistry, Hong Kong

25

Baptist University, Hong Kong, SAR, People’s Republic of China; Tel: 852-34117070.

26 27

# Both

authors contributed equally to this work.

28



29

Abstract

30

Parabens are potential endocrine disruptors with short half-lives in the human body. To

31

date, few epidemiological studies regarding repeated paraben measurements during

32

pregnancy associated with fetal and childhood growth have been conducted. Within a

33

Chinese prenatal cohort, 850 mother-infant pairs from whom a complete set of maternal

34

urine samples were acquired during three trimesters were included, and the levels of five

35

parabens were measured. We assessed the associations of both average and trimester-

36

specific urinary paraben levels with weight and height z-scores at birth, 6 months, 1, and 2

37

years of age. In all infants, each doubling increase in average ethyl paraben (EtP) was

38

associated with -2.82% (95% CI: -5.11%, -0.53%) decrease in weight z-score at birth,

39

whereas no significant age-specific associations were identified. After stratifying by sex,

40

we further observed age-specific association of average EtP with -3.96% (95% CI: -7.03%,

41

-0.89%) and -3.38% (95% CI: 6.72%, -0.03%) reduction in weight z-scores at 1 and 2 years

42

in males, respectively. Third-trimester EtP was negatively associated with weight z-scores

43

at birth, 1 and 2 years in males. Our results suggested negative associations between

44

prenatal paraben exposure and fetal and childhood growth, and the third trimester may be

45

the window of susceptibility.

46 47

Keywords: Parabens; Repeated measurements; Birth size; Early-childhood growth

48


Page 4 of 42

Page 5 of 42


49

TOC Art

50



52

Introduction

53

Parabens are comprised of a family of antimicrobial preservatives that are added to

54

personal care products, pharmaceuticals, foods, and beverages.1 Due to the extensive

55

application of parabens, especially the combined utilization of methyl and propyl paraben

56

(MeP and PrP, respectively), humans are widely exposed to these chemicals, mainly

57

through dermal absorption, ingestion, and inhalation.2-4

58

Parabens have long been regarded as endocrine disruptors and exhibit very weak

59

estrogen activity both in vitro and in vivo.5 From 1984 to 2008, the US Food and Drug

60

Administration (FDA) and the Cosmetic Ingredient Review (CIR) reviewed the toxicity of

61

parabens and concluded that they were safe for use in cosmetic products.6, 7 However, based

62

on recent accumulating evidence from experimental animal studies, prenatal exposure to

63

different kinds of parabens in utero is associated with increased mortality rate, damaged

64

social cognition, impaired sexual behavior, and decreased semen quality (count and

65

motility), and also suggested that the aforementioned developmental toxic effects caused

66

by parabens are related to their endocrine disrupting properties.8-11

67

Prenatal development is a sensitive and vulnerable stage of human life, and disruptions

68

during this special period may cause lifetime adverse consequences. Paraben levels in

69

maternal blood are highly correlated with concentrations of parabens in cord blood or

70

amniotic fluid, indicating that parabens pass through the placental barrier and thus probably

71

influence the developing fetus.12-14 Moreover, the adverse impacts of exposure to

72

environmental factors in utero may proceed to influence offspring growth in childhood.15-


Page 6 of 42

Page 7 of 42


73

17

74

associated with delivery measures of fetal growth and postnatal growth have been

75

performed. In a French population of mother-son pairs, Philippat et al.18 did not observe

76

significant associations between maternal paraben levels in a single spot urine collected

77

during the early first to early third trimester and size at birth in 2012 (n = 191). Two years

78

later, they enlarged the sample size to 520 pairs and still did not observe significant

79

associations of prenatal paraben exposure, as measured in urine samples collected during

80

22-29 gestational weeks, with anthropometric measurements at birth and in early-

81

childhood.19 However, Geer et al.20 reported associations of cord blood butyl paraben (BuP)

82

and PrP levels with decreased birth weight and birth length, respectively, in an immigration

83

cohort study in Brooklyn, New York.

So far, few epidemiological studies concerning paraben exposure during pregnancy

84

Parabens have comparatively short half-lives in the human body.18 After being

85

absorbed into the body, these compounds are rapidly hydrolyzed by esterases without

86

accumulation, and then mainly excreted through urine.5, 21 Thus, urinary excretion levels

87

of parabens can be used as valid biomarkers of recent exposure.22 A person’s daily

88

exposure level can be represented by maternal urinary paraben concentrations measured in

89

a single spot urine, since medium to strong reproducibility of paraben levels were found in

90

24 h urine.23 However, some previous studies reported that assessing prenatal paraben

91

exposure by using a single spot urine sample may result in exposure misclassifications,18,

92

19, 24

93

variability during pregnancy (intraclass correlation coefficients ranged from 0.32-0.39).25,

since parabens were reported as chemicals with high within-subject temporal



94

26

95

the prenatal paraben exposure levels.18

Repeatedly measured urinary paraben concentrations over trimesters may better reflect

96

In this study, 850 pregnant women were repeatedly measured for urinary paraben levels

97

in biospecimens collected at the early, middle, and late stage of pregnancy to further

98

evaluated whether prenatal paraben exposure affected fetal as well as early-childhood

99

growth; we also identified the critical window of susceptibility in which prenatal paraben

100

exposure affected the growth of fetuses and children.

101 102

Materials and Methods

103

Study population

104

The pregnant women in this study was recruited between March 2014 and March 2015 at

105

Wuhan Women and Children Medical and Healthcare Center in Hubei Province, China.

106

Pregnant women who came to have the first prenatal care visit (before 16 weeks) were

107

asked to join in the study. Eligible participants were those who were in accordance with all

108

the following criteria: (1) with a singleton pregnancy; (2) living in the city of Wuhan at the

109

time of enrollment and plans to reside in the region continually for the foreseeable future;

110

(3) willing to donate their biospecimen during regular prenatal care; (4) giving birth at the

111

study hospital. With prenatal consent, we recruited the newborns at birth and asked them

112

to come back to the Department of Children’s Health at the hospital for follow-up study.

113

Eight hundred and fifty six mother-infant pairs from whom a complete set of maternal urine

114

samples were collected at the 1st, 2nd, and 3rd trimesters during pregnancy (13.0 ± 1.1 weeks,


Page 8 of 42

Page 9 of 42


115

23.6 ± 3.2 weeks, and 35.9 ± 3.4 weeks, respectively) were included in the present study

116

and urinary paraben levels were measured. Women who delivered neonates with a birth

117

defect (n = 5) and continued to smoke during pregnancy (n = 1) were excluded. Thus, 850

118

mother-infant pairs were examined in subsequent analyses (446 males and 404 females).

119

Follow-up visits were consecutively conducted at the ages of 0.5, 1, and 2 years as

120

described elsewhere.27 All mothers in this study signed written informed consent at

121

enrollment. The research protocol was authorized by the ethics committee of Tongji

122

Medical College, Huazhong University of Science and Technology, and the study hospital.

123

Assessment of prenatal paraben exposure

124

Maternal urine samples collected at the 1st, 2nd, and 3rd trimesters during pregnancy were

125

divided into the 5-mL polypropylene bottles and instantly reserved in -20°C freezers until

126

further analysis of the concentrations of MeP, ethyl paraben (EtP), PrP, BuP, and benzyl

127

paraben (BzP).

128

The liquid chromatography tandem mass spectrometry parameters and sample

129

pretreatment procedure were detailed in a previous study from our group by Zhao et al..28

130

Briefly, the target analytes were extracted from 1-mL of urine sample using liquid-liquid

131

extraction, separated by ultra-high performance liquid chromatography system, and

132

detected by tandem mass spectrometry. Each batch of samples included the quality control

133

samples and procedural blanks. The limits of detection (LODs) were 0.01 ng/mL for EtP,

134

BzP, and 0.05 ng/mL for MeP, PrP and BuP. The mean recoveries of all target analytes

135

ranged from 99.6% to 108.0%. We analyzed the selected duplicate samples to acquire the



136

between-assay and within-assay variation coefficients, which were both less than 10%.

137

Urinary paraben concentration was adjusted for the specific gravity (SG), as measured by

138

a refractometer (Atago Co., Ltd., Tokyo, Japan), to reduce the variations in urine dilution.

139

Anthropometric assessments

140

Within one hour after delivery, experienced obstetrical nurses measured the birth weight

141

and length of infants (in grams and centimeters, respectively) using standardized

142

procedures. Weight and height in early-childhood were measured by nurses in the

143

Department of Children’s Health when children were 6 months (mean ± SD: 0.51 ± 0.03),

144

1 (1.03 ± 0.05), and 2 (2.03 ± 0.06) years of age. Birth and early-childhood weights and

145

heights were normalized to z-scores by applying WHO child growth standards specified by

146

sex and age.29 The z-score for a birth size indicator or an early-childhood growth parameter

147

represents the percentile of neonatal or infant size at a certain gestational age or month age.

148

Covariates

149

Maternal age, pregnancy history (parity), maternal weight before childbirth, and delivery

150

information such as birth weight, birth length, sex, birth date, and gestational age of infants

151

were all extracted from hospital medical records. Face-to-face interviews were conducted

152

to retrieve the following information, including maternal demographic and socioeconomic

153

characteristics (education level, household income, etc.), basic personal information

154

(prepregnancy weight, parental height, etc.) and lifestyle factors (smoking and drinking,

155

etc.) by well-trained nurses. We used self-reported maternal height and prepregnancy

156

weight to compute prepregnancy body mass index (BMI). Pregnancy weight gain was


Page 10 of 42

Page 11 of 42


157

defined as the value between prepregnancy weight and weight before childbirth.

158

Gestational age was calculated based on 1st-trimester ultrasound estimates. Breastfeeding

159

duration was retrieved from the caregivers’ questionnaires during the follow-up visits.

160

Previous studies suggested that fetal and postnatal growth were associated with many

161

maternal characteristics, such as prepregnancy BMI, pregnancy weight gain, parity, and

162

breastfeeding duration.30-32 Forward stepwise model selection procedures were applied to

163

obtain the best fit for the models. We included the covariates into the final models if they

164

significantly contributed to the models (p ≤ 0.10). We adjusted models for maternal and

165

paternal height (cm), self-reported prepregnancy BMI (underweight, normal weight and

166

overweight), weight gain during pregnancy (kg), gestational age (weeks, in models

167

including birth weight and birth length), parity (primiparous and multiparous), maternal

168

age (years), maternal education level (more than high school, high school, and less than

169

high school), infant sex (male and female, in models including all infants), and

170

breastfeeding duration (except in models including birth size).

171

Statistical analysis

172

The total paraben concentration (SumP) was computed as the sum of the molar

173

concentrations (μmol/L) of the five measured parabens. The value of urinary paraben

174

concentrations below the LOD were assigned a value of the LOD/ 2.33 Paraben

175

concentrations were log2-transformed to bring down the effects of extremums on the

176

regression coefficients (βs) and to compute the Pearson’s correlation coefficients and

177

interclass correlation coefficients (ICCs). We calculated ICCs to evaluate the



178

reproducibility of urinary paraben concentrations over the three trimesters of pregnancy.

179

We also computed Pearson’s correlation coefficients between pairs of the log2-transformed

180

paraben concentrations measured in urine collected during the three trimesters.

181

MeP, EtP, PrP, and SumP (detection rate > 90%) were log2-transformed, whereas BuP

182

and BzP (detection rate < 40%) were treated as binary variables (detected vs. undetected).

183

Since parabens have relatively short biological half-lives,34 we first used the average SG-

184

adjusted paraben concentrations measured in the three trimesters of pregnancy to provide

185

reasonable estimates of exposure during pregnancy. Initially, general linear models were

186

constructed to estimate the associations of average paraben concentrations with birth size

187

(including weight and length at birth, and z-scores for weight and height at birth), as well

188

as the age-specific associations of average paraben concentrations with weight and height

189

z-scores at each time point (6 months, 1, and 2 years) in early childhood. Then, mixed linear

190

models were used to examine z-scores for weight and height on average from birth to 2

191

years of age in relation to prenatal paraben exposure. The age of infants at follow-up were

192

also added to the mixed linear models as a categorical variable in addition to the

193

confounders mentioned above. Fixed effect coefficient estimations were calculated to

194

interpret the average effects of prenatal paraben exposure on z-scores for weight and height

195

started from birth to 2 years. An interaction term of the age of infants at follow-up

196

(categorical variable: birth, 6 months, 1, and 2 years) × paraben exposure were used to

197

estimate the differences in association over time. A statistically significant interaction was

198

defined if the p-value of the interaction term was less than 0.10.


Page 12 of 42

Page 13 of 42


199

Furthermore, generalized estimating equation models with a linear link function were

200

applied to assess the associations of trimester-specific urinary parabens concentrations with

201

birth size and early-childhood growth (weight and height z-scores at birth, 6 months, 1 year

202

and 2 years), as well as to identify the windows of susceptibility. The significance of

203

interaction terms between prenatal paraben exposure and the trimester were estimated to

204

assess the differences in associations over trimester. All βs represented the percent change

205

in the z-score for each doubling increase in maternal urinary paraben concentrations and

206

the β was multiplied by 100 to become a percentage. Sex-stratified analyses were

207

conducted for prenatal exposure levels of parabens in relation to all fetal as well as early-

208

childhood anthropometric assessments due to the hormonally active property of parabens.

209

In the models including measurements of fetal and early-childhood growth as dependent

210

variables, infant sex × paraben exposure were inserted to examine the potential interactions

211

between infant sex and paraben exposure.

212

Statistical Analysis System (SAS) version 9.4 (SAS Institute Inc., Cary, NC, USA) was

213

applied to perform statistical analyses. All tests were two-sided and significance levels

214

were set at α = 0.05.

215 216

Results

217

Study population

218

Maternal baseline characteristics and infant anthropometric measurements of the study

219

population are provided in Table 1. The mothers were approximately 28.6 years of age



220

(ranged from 20 to 44 years) and were primarily primiparous (85.9%). The majority of the

221

mothers were well-educated (78.4% for more than high school) and had a normal

222

prepregnancy BMI (68.2%). The average weight gain during pregnancy was 16.5 ± 4.6

223

(4.0−33.0) kg. A large proportion of the infants (69.5%) were breastfed for more than 6

224

months.

225

Maternal urinary concentrations of parabens and their reproducibility

226

Table 2 shows the detection rate and ICCs during the three trimesters, along with the

227

distribution of average unadjusted and SG-adjusted urinary paraben concentrations of our

228

study population. Concentrations of MeP, EtP and PrP were detected in more than 90% of

229

the urine samples, whereas the detection rates of BuP and BzP were less than 40%. ICCs

230

were low (< 0.4; EtP: 0.37, PrP: 0.36, BuP: 0.38, BzP: 0.33) to moderate (0.4–0.6; MeP:

231

0.41) and of comparable magnitude for all 5 parabens and their sum (ICC = 0.38).

232

Pearson’s correlation coefficients were weak to medium (ranged from 0.26 to 0.51, see

233

Table S1), which showed the similar patterns with ICCs. Among all 5 parabens, the highest

234

concentration was observed for the short-chain alkyl paraben MeP (SG-adjusted median:

235

32.06 ng/mL), whereas EtP showed the lowest concentration (SG-adjusted median: 0.80

236

ng/mL).

237

Average prenatal exposure levels of parabens and birth size

238

For all infants, each doubling increase in average urinary EtP concentrations was associated

239

with reduction in weight [β = -9.10, 95% confidence interval (CI): -17.77, -0.44] and z-

240

score for weight at birth (percent change = -2.82%, 95% CI: -5.11%, -0.53%) (Table 3).


Page 14 of 42

Page 15 of 42


241

Similarly, more evident associations were identified in males, with β values of -10.62 (95%

242

CI: -19.95, -1.29) for birth weight and a percent change of -3.61% (95% CI: -6.74%, -

243

0.48%) for birth weight z-score. In females, prenatal EtP concentrations tended to be

244

negatively associated with birth weight and birth weight z-score (β = -8.76, 95% CI: -21.62,

245

4.10, and percent change = -2.34%, 95% CI: -5.74%, 1.06%, per doubling increase in EtP

246

concentrations) (Table 3). For all infants, prenatal MeP exposure showed a nonsignificant

247

inverse association with birth length and its z-score (β = -0.03, 95% CI; -0.07, 0.01, and

248

percent change = -2.47%, 95% CI: -5.32%, 0.38%, per doubling increase in MeP

249

concentrations) (Table 3). In females, birth length reduced by -0.07 cm (95% CI: -0.13, -

250

0.01) and height z-score at birth reduced by -5.08% (95% CI: -9.12%, -1.04%) with each

251

doubling increase in MeP concentrations, whereas the associations observed for males

252

were approximately zero (Table 3).

253

Average prenatal exposure levels of parabens and early-childhood growth

254

The associations between average paraben levels and age-specific weight z-scores in early-

255

childhood were nonsignificant. (Table 4). After stratifying by sex, each doubling increase

256

in EtP concentration was associated with decrease in z-scores for weight at 1 year (percent

257

change = -3.96%, 95% CI: -7.03%, -0.89%) and 2 years (percent change = -3.38%, 95%

258

CI: -6.72%, -0.03%) in males (Table 4). However, we did not observe the same inverse

259

association among females, and evidence for a modulatory effect of sex was observed (p

260

for interaction = 0.03 and 0.06, respectively) (Table 4). We did not observe significant

261

associations between average paraben levels and age-specific z-scores for height during



262

early-childhood in all children or in sex-stratified analyses (Table S2).

263

Among all children, average urinary EtP level was inversely associated with average z-

264

score for weight over the early-childhood, where each doubling increase in exposure was

265

associated with a -2.81% (95% CI: -4.94%, -0.68%) decrease in weight z-score on average

266

throughout childhood (Table 5). Likewise, males exhibited a similar result, with a more

267

prominent percent change of -3.64% (95% CI: -6.64%, -0.64%, per doubling increase in

268

EtP concentration) (Table 5). In females, prenatal EtP tended to be associated with

269

decreased z-score for weight on average throughout early-childhood (percent change = -

270

1.80%, 95% CI: -4.86%, 1.25%, per doubling increase in EtP concentration) (Table 5). We

271

did not identify significant interactions between prenatal paraben exposure and follow-up

272

age (p > 0.10) (Table 5). Additionally, each doubling increase in MeP concentrations was

273

negatively associated with height z-score on average, with a -2.95% decrease (95% CI: -

274

5.77%, -0.13%) in all infants (Table 5). In females, height z-score on average decreased by

275

-5.24% (95% CI: -9.18%, -1.30%) in association with each doubling increase in MeP

276

concentrations, whereas the association in males was approximately zero (Table 5).

277

Significant interactions with follow-up age for prenatal MeP were found for all infants and

278

females only (p = 0.04) (Table 5).

279

Trimester-specific prenatal exposure levels of parabens and size at birth and early-

280

childhood growth

281

The 3rd-trimester EtP concentration was negatively associated with z-score for birth

282

weight in all infants, as well as male and female infants (percent change = -3.31%, 95%


Page 16 of 42

Page 17 of 42


283

CI: -5.30%, -1.33% for all infants; percent change = -3.41%, 95% CI: -6.17%, -0.66% for

284

male infants; percent change = -3.49%, 95% CI: -6.33%, -0.64% for female infants) (Figure

285

1). Moreover, each doubling increase in the 3rd-trimester EtP concentration was associated

286

with reduced weight z-scores at 1 year and 2 years in males only (percent change = -2.65%,

287

95% CI: -5.31%, -0.01% and -3.04%, 95% CI: -5.72%, -0.36%, respectively) (Figure 1).

288

Additionally, the 3rd-trimester MeP exposure was inversely associated with height z-score

289

at birth (percent change = -3.32%, 95% CI: -6.23%, -0.41%) in females only (Figure S1),

290

and the 3rd-trimester SumP was inversely associated with z-score for birth weight (percent

291

change = -2.58%, 95% CI: -5.03%, -0.13%) in all infants (Figure S5). Apart from these

292

findings, no significant associations of trimester-specific prenatal PrP, BuP, or BzP

293

exposure with size at birth or early-childhood growth were observed either in overall

294

population or in sex-stratified analyses (Figures S2-4).

295 296

Discussion

297

As far as we know, our study is the first to explore repeated measurements of paraben

298

exposures during pregnancy in relation to multiple growth measures starting from birth to

299

2 years. Among all infants, inverse associations were identified between average prenatal

300

EtP exposure and weight z-score at birth and weight z-score on average throughout

301

childhood. In sex stratified analyses, the same associations were found in males, with more

302

evident estimated effect, and a nonsignificant association with consistent direction was

303

observed in females. In addition, age-specific negative associations were identified



304

between the average prenatal EtP exposure and weight z-scores in 1 year- and 2 year-old

305

males. Similarly, 3rd-trimester EtP were inversely associated with z-scores for weight at

306

birth, 1 and 2 years in males. Besides, the average prenatal MeP and 3rd-trimester MeP

307

were associated with reduced height z-score at birth among female infants.

308

More than 90% of the pregnant women in this study were detected for MeP, EtP, and

309

PrP, indicating the prevalent exposure of paraben in our study population. BuP and BzP

310

were measured at a far lower rate (less than 40%), probably because BuP and BzP are used

311

at a much lower dosage in personal care products in China.35 The patterns of detection rates

312

for different parabens were similar to those reported in the common population in Belgium

313

as well as the pregnant women in Greece.36, 37 Compared to the common population in the

314

U.S. and Denmark (LOD for EtP: 0.1 and 0.4 ng/mL, respectively), our population had a

315

higher detection rate for EtP, probably due to the lower LOD of EtP in the present study

316

(LOD for EtP: 0.01 ng/mL).22, 38 In addition, the highest paraben exposure levels occurred

317

in the first trimester, with a decreasing trend in later trimesters. Similarly, the median

318

urinary paraben concentrations observed in the 2nd and 3rd-trimesters were lower than in

319

the 1st-trimester among pregnant women in Boston.26 The explanation may involve the

320

tendency of pregnant women to reduce the consumption of cosmetic and skin care products,

321

which are the major routes of human exposure to paraben, as the pregnancy progresses.23

322

We compared the urinary paraben concentrations and ICCs in our population with

323

previous studies (Table S3). The temporal variability in urinary paraben concentrations, as

324

indicated by ICCs that were low to moderate in our study population, is probably attributed


Page 18 of 42

Page 19 of 42


325

to the rapid metabolism of parabens. In this study, the ICCs of urinary concentrations of

326

paraben were comparable to the ICCs through three trimesters in pregnant women in Puerto

327

Rico and Boston (MeP: 0.41 vs. 0.39 and 0.38, respectively; PrP: 0.36 vs. 0.32 and 0.36,

328

respectively).25, 26 However, the ICCs calculated in the present study were somewhat lower

329

than the ICCs of paraben concentrations over three trimesters among pregnant women in

330

New York (MeP: 0.41 vs. 0.61; EtP: 0.37 vs. 0.48; PrP: 0.36 vs. 0.55; BuP: 0.38 vs. 0.56),39

331

probably because of the differences in individual application of personal care products

332

containing parabens and diverse lifestyle characteristics. Our study population had

333

comparable median concentrations of unadjusted urinary parabens (ng/mL) compared with

334

the common population in developed countries, such as male and female adults in the USA

335

and female adults in Belgium (MeP: 28.4 vs. 43.9 and 32.4; EtP: 0.7 vs. 1.0 and 1.9; PrP:

336

2.2 vs. 9.1 and 3.3; BuP:

Repeated Measurements of Paraben Exposure during Pregnancy in

Recommend Documents