Table 1.
Summary of studies included in the systematic review.
| ID | First author | Year | Study design | Country | Sample Size | Study | Exposure assessment | Measured metabolites and range | Timing of outcome assessment | Outcome variables |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Agay-Shay24 | 2015 | Cohort study | Spain | 470 | INMA Spanish Birth cohort | Maternal urine in the 1st and 3rd trimester of pregnancy |
GM of MECPP, MEHHP, MEOHP, and MEHP (40.8 µg/g Cr, 28.6 µg/g Cr, 27.8 µg/g Cr, and 14.6 µg/g Cr, respectively) ‘GM of MnBP and MiBP (32.4 µg/g Cr, 32.6 µg/g Cr, respectively) |
7 y | BMI z-scores |
| 2 | Berman25 | 2020 | Cohort study | Australia | 410 | Maternal urine in the 2nd and 3rd trimester of pregnancy | Median of ∑DEHP metabolites, and ∑DBP metabolites (9.34 µg/L, 4.10 µg/L, respectively) | 1, 2, 3, 5, 8, 10, 14, 17 and 20 y | Height, BMI, DXA (total fat %, total fat mass [g], total lean mass [g]) | |
| 3 | Botton26 | 2016 | Cohort study | France | 520 | EDEN mother–child cohort | Maternal urine in the 2nd trimester | Median of molar ∑DEHP metabolites, MnBP and MiBP (0.32 µM/L, 43 µg/L, and 39 µg/L, respectively) | 5 y | BMI |
| 4 | Buckley27 | 2016 | Cohort study | U.S | 707 | MSSM + CCCEH + HOME Study | Prenatal maternal urine | GM of molar ∑DEHP metabolites, MnBP and MiBP (0.277 µM/L, 30.6 µg/L, and 6.45 µg/L, respectively) | 4–9 y | BMI z-score and overweight/obese (BMI > = 85th percentile) |
| 5 | Buckley10 | 2016 | Cohort study | U.S | 180 | MSSM Study | Prenatal maternal urine | GM of molar ∑DEHP metabolites, MnBP and MiBP (0.284 µM/L, 32.9 µg/L, and 5.83 µg/L, respectively) | 4 and 9 y | Body composition (total fat %) |
| 6 | Buser28 | 2014 | Cross-sectional study | U.S | not described | NHANES 2007–2010 | Urine of the participants |
(Children and adolescent aged 6–19) GM of molar ∑DEHP metabolites, MnBP and MiBP (0.24 µM/L, 23.0 µg/L, and 10.43 µg/L, respectively) (adults > = 20 y) GM of ∑DEHP metabolites, MnBP and MiBP (0.18 µM/L, 15.21 µg/L, and 6.75 µg/L, respectively) |
Children and adolescent aged 6–19, adults > = 20 y |
(Children and adolescent) obese 95th percentile > = BMI z-score; overweight, 95th percentile > BMI z-score > = 85th percentile (adults) obese, BMI > = 30 kg/m2; overweight, 30 kg/m2 > BMI > = 25 kg/m2 |
| 7 | Chang29 | 2020 | Cross-sectional study | Taiwan | 152 | RAPIT program | Urine of the participants | GM of ∑DEHP metabolites, MnBP and MiBP (59.29 µg/g Cr, 49.44 µg/g Cr, and 28.85 µg/g Cr, respectively) | 5 y | BMI, total fat (%) |
| 8 | Deierlein30 | 2016 | Cohort study | U.S | 1,239 | The Breast Cancer and Environment Research Program | Urine of the participants at the baseline (6–8 y) | GM of ∑DEHP metabolites (182 µg/g Cr [6 y], 152 µg/g Cr [7 y], and 152 µg/g Cr [8 y]) and LMWH (184 µg/g Cr [6 y], 136 µg/g Cr [7 y], and 163 µg/g Cr [8 y]) | 3 times until the last visit when girls were on average 14 y old (11–16 y) | BMI |
| 9 | Heggeseth31 | 2019 | Cohort Study | U.S | 335 | CHAMACOS cohort study | Prenatal maternal urine | Median of MECPP, MEHHP, MEOHP, MnBP, and MiBP (24.05 µg/L, 14.8 µg/L, 10.75 µg/L, 20.7 µg/L, and 2.8 µg/L, respectively) | 11 follow-up visits between ages 2 and 14 y | BMI |
| 10 | Hou32 | 2015 | Cross-sectional study | Taiwan | 308 | 270 normal adolescents (6.5–15 y) and 38 complainants (6.5–8.5 y) | Urine of the participants | GM of ∑DEHP, MnBP and MiBP (193.73 µg/L, 75.42 µg/L, and 47.06 µg/L, respectively) | When assessing phthalate exposure (6.5–8.5 y) | Obese (BMI), waist-to-hip ratio, Subcutaneous fat thickness |
| 11 | Kim33 | 2016 | Cohort Study | South Korea | 128 | 128 healthy pregnant women and their infants in 2012 | Umbilical cord blood, newborns’ first urine | GM of MEHHP in maternal blood, maternal urine, cord blood, placenta, and newborns’ urine (0.31 µg/L, 18.23 µg/L, 0.,33 µg/L, 0.10 µg/L, and 5.83 µg/L, respectively), GM of MEOHP in maternal urine and newborns’ urine (15.88 µg/L, and 3.02 µg/L, respectively) | Perinatal | BMI z-score change during 3 months (Evaluation criterion for relative body mass increase was BMI z-score change over the 50th percentile) |
| 12 | Kim34 | 2018 | Cross-sectional study | South Korea | 137 | 65 overweight children (6–13 y) and 72 controls | Urine of the participants | GM OF MECPP, MEOHP, and MEHHP (87.3 µg/g Cr, 29.5 µg/g Cr, and 36.8 µg/g Cr, respectively) | When assessing phthalates exposure (6–13 y) | BMI percentile |
| 13 | Lee35 | 2020 | Cohort study | South Korea | 481 | EDC cohort | Prenatal maternal urine and urine of the participants |
GM of molar ∑DEHP in prenatal maternal urine and children’s urine at 6 years of age (0.11 µM/L, and 0.33 µM/L, respectively) GM of ∑MnBP in prenatal maternal urine and children’s urine at 6 years of age (39.68 µg/L, and 70.00 µg/L, respectively) |
6 y | BMI z-score, percentage of fat mass, fat mass index, percentage of skeletal muscle mass, skeletal muscle index |
| 14 | Maresca36 | 2016 | Cohort study | U.S | 424 | CCCEH cohort | Prenatal maternal urine | GM of molar ∑DEHP metabolites, MiBP, and MnBP (0.29 µM/L, 8.81 µg/L, 37.58 µg/L) | 5 y and 7 y | BMI z-score at 5 y and 7 y, percent of fat mass at 7 y, FMI at 7 y, WC at 7 y |
| 15 | Harley37 | 2017 | Cohort study | U.S | 219 | CHAMACOS cohort study | Prenatal maternal urine, two times | GM of ∑DEHP, MECPP, MEHHP, MEOHP, MnBP, and MiBP in each measurement (0.2 and 0.2 nmol/mL, 25.9 and 32.4 µg/L, 15.1 and 18.8 µg/L, 11.2 and 13.8 µg/L, 22.8 and 28.5 µg/L, and 2.7 and 3.4 µg/L, respectively) | 12 y | BMI z-score, WC |
| 16 | Saengkaew38 | 2017 | Cross-sectional study | Thailand | 155 | Children aged 7–18 y | Urine of the participants | Median of MBP (216.47 µg/g Cr), detection rate 82.58% | When assessing phthalate exposure | BMI z-score, WC |
| 17 | Shoaff39 | 2017 | Cohort study | U.S | 219 | HOME study | up to two times prenatally and six times from 1 to 8 y | GM of ∑DEHP, MiBP, and MnBP for children (86 µg/L, 4.8 µg/L, and 25 µg/L, respectively) | 8 y | BMI z-score, WC, body fat percent |
| 18 | Smerieri40 | 2015 | Cross-sectional study | Italy | 72 |
41 obese children and 31 controls (mean age 12 y) |
Urine of the participants | Detection rates of MECPP, MEOHP, and MEHHP were 80.5%, 87.8%, and 80.5% among obese group, and 38.7%, 74.2%, and 8.39% among control group, respectively | When assessing phthalate exposure | WC |
| 19 | Trasande13 | 2013 | Cross-sectional study | U.S | 2,884 | NHANES 2003–2008 (children 6–19 y) | Urine of the participants | GM of ∑DEHP metabolite (0.358 µM/L among male and 0.360 among female) and ∑LMW metabolite (0.593 µM/L among male and 0.680 µM/L among female) | When assessing phthalate exposure | BMI z-score, overweight (BMI z-score > = 85th percentile), and obesity (BMI z-score > = 95th percentile) |
| 20 | Tsai41 | 2016 | Cohort study | Taiwan | 88 | RAPIT program (6.0–10.5 y) | Estimated the total daily intake of DEHP, and urine of the participants | Mean of ∑DEHP metabolite 106.19 µg/g Cr | When participants were examined | Weight percentile and height percentile above 50th percentile (based on the standards provided by the Ministry of Health and Welfare) |
| 21 | Vafeiadi42 | 2018 | Cohort Study | Greece | 500 | Rhea Study | Prenatal maternal urine and urine of the participants |
GM of molar ∑DEHP, MiBP and MnBP in prenatal maternal urine (0.1 µM/g Cr, 33.5 µg/g Cr, and 37.1 µg/g Cr, respectively) GM of molar ∑DEHP, MiBP, and MnBP in children’s urine (0.3 µM/gCr, 41.1 µg/g Cr, and 21.7 µg/g Cr, respectively) |
4–6 y | BMI z-score |
| 22 | Valvi43 | 2015 | Cohort study | Spain | 391 | INMA Spanish birth cohort | Prenatal maternal urine at 1st and 3rd trimester | GM of ∑DEHP metabolites, MnBP and MiBP (99.6 µg/gCr, 32.7 µg/gCr, and 33.0 µg/gCr, respectively) | Birth to 6 mos., 1, 4, and 7 y of age | BMI z-score, weight gain z-score (0–6 months) |
| 23 | Vrijheid44 | 2020 | Cohort study | Europe | 1,031 | HELIX study (BiB in UK, EDEN in France, INMA in Spain, KANC in Lithuanina, MoBa and Rhea in Greece) | 77 prenatal exposure and 96 childhood exposure including air pollutants, built environments, and biomarkers of chemical pollutants | Not described | BMI z-score (age-and-sex standardized z-scores) | BMI z-score |
| 24 | Wu45 | 2020 | Cross-sectional study | U.S | 2372 | NHANES 2005–2010 (6–19 y) | Urine of the participants | GM of MiBP, 9.98 µg/L | When assessing phthalate exposure | BMI z-score |
| 25 | Xia46 | 2018 | Cross-sectional study | China | 159 | PTHEC study, 69 overweight/obese children and 80 normal weight children | Urine of the participants | Median of MEOHP, MEHHP, and MnBP among normal participants (2.97 µg/L, 7.57 µg/L, and 13.68 µg/L, respectively) and among overweight/obese participants (2.6 µg/L, 6.5 µg/L, and 18.68 µg/L, respectively) | When assessing phthalate exposure | Overweight/obese |
| 26 | Xie47 | 2015 | Case–control study | China | 167 | 57 boys with constitutional delay for growth and puberty and 110 controls (11 y) | Urine of the participants | Median of ∑DEHP metabolites and MnBP among cases (20.06 µg/L and 37.43 µg/L, respectively), and among controls (12.85 µg/L and 15.56 µg/L, respectively) | When assessing phthalate exposure | Constitutional delay of growth and puberty |
| 27 | Zettergren48 | 2021 | Cohort study | Sweden | 100 | BAMSE birth cohort | Urine of the participants at 4 years of age | GM of ∑DEHP metabolites and MnBP (331 µg/L, 296 µg/L) | 24 y | BMI, WC, Body fat %, trunk fat % (Bio-electrical impedance analysis) |
| 28 | Zhang11 | 2014 | Cross-sectional study | China | 497 | PTHEC study (8–13 y) | Urine of the participants | GM of ∑DEHP metabolites and MnBP; boys (8–10 y), 29.6 µg/L; boys (11–13 y), 21.9 µg/L; girls (8–10 y), 32.5 µg/L; girls (11–13 y), 16.5 µg/L | When assessing phthalate exposure | BMI z-score, body fat % (Yao’s formula) |
| 29 | Amin49 | 2017 | Cross-sectional study | Iran | 242 | Urine of the participants | Mean of MEOHP, MEHHP, MEHP, MBzP, MBP, and MMP were 257.98 µg/L, 149.44 µg/L, 104.46 µg/L, 233.01 µg/L, 218.17 µg/L, and 59.82 µg/L | 6–18 y | BMI z-score, WC | |
| 30 | Ashley-Martin50 | 2021 | Cross-sectional study | Canada | 200 | MIREC study | Urine of the participants | Twenty-two metabolites were measured. Median of ∑DEHP and ∑DiBP were 155 nmol/mL and 100 nmol/mL, respectively | 2–5 y | BMI z-score |
| 31 | Ding51 | 2021 | Cross-sectional study | China | 463 | Urine of the participants | Median of MECPP, MCMHP, MEOHP, MEHHP, MEHP, and ∑DEHP were 13.00 μg/L, 7.68 μg/L, 6.04 μg/L, 4.78 μg/L, 3.18 μg/L, and 34.56 μg/L | 16–19 y | BMI, WHR, WHtR | |
| 32 | Berger52 | 2021 | Cohort study | U.S | 309 | CHAMACOS cohort study | Prenatal maternal urine | GM of ∑DEHP (0.2 nmol/mL) | 5 y | BMI z-score |
| 33 | Li53 | 2021 | Cohort study | China | 814 | Maternal urine in the 1st, 2nd and 3rd trimester of pregnancy | Median of ∑DEHP at 1st, 2nd, and 3rd trimesters were 0.09 nmol/mL, 0.06 nmol/mL, and 0.07 nmol/mL | average BMI z-score of 6-, 12- and 24-month | BMI z-score | |
| 34 | Nidens54 | 2021 | Cohort study | Germany | 130 | Prenatal maternal urine | GM of ∑HMWP (31.31 μg/gCr) | 2 y | Weight gain (%) first 2 years of life | |
| 35 | On55 | 2021 | Cross-sectional study | South Korea | 240 | Urine of the participants | GM of MECPP, MEOHP, MEHHP, and MEHP (104.73 µg/g Cr, 33.96 µg/g Cr, and 14.54 µg/g Cr, respectively) | 5–16 y | BMI percentile, weight percentile, and height percentile | |
| 36 | Silva56 | 2021 | Panel study | Netherland | 471 | Urine of the participants | Median of MECCP, MEOHP, and MEHHP were 0.94 nmol/L, 0.14 nmol/L, and 0.27 nmol/L | 6y and 10 y | BMI z-score, Fat mass index | |
| 37 | Hatch57 | 2008 | Cross-sectional study | U.S | 1,009 (6–19 y) | NHANES 1999–2002 | Urine of the participants |
GM of MEHHP among boys in 6–11 y and 12–19y were 39.6 μg/gCr and 21.1 μg/gCr, respectively GM of MEHHP among girls in 6–11 y and 12–19y were 39.1 μg/gCr and 18.2 μg/gCr, respectively |
6–19y | BMI, WC |
| 38 | Wang58 | 2013 | Cross-sectional study | China | 259 | Urine of the participants | GM of ∑DEHP (117.3 nmol/mL) | 8–15y | BMI, WC | |
| 39 | Bowman59 | 2019 | Cohort study | Mexico | 229 | ELEMENT study | Urine of the participants |
(boys) GM of ∑DEHP at 1st, 2nd, and 3rd trimester in prenatal maternal urine were 65.07 μg/L and 63.42 μg/L, and 78.60 μg/L (girls) GM of ∑DEHP at 1st, 2nd, and 3rd trimester in prenatal maternal urine were 71.03 μg/L and 75.97 μg/L, and 76.69 μg/L |
8–14y (Visit 1) and 9–17y (Visit 2) | BMI z-score, WC, skinfold thickness |
MEHHP mono-(2-ethyl-5-hydroxy-hexyl) phthalate; MEOHP mono-(2-ethyl-5-oxo-hexyl) phthalate; MnBP mono-n-butyl phthalate (MnBP); MECCP Mono-2-ethyl-5-carboxypentyl phthalate; MBzP Monobenzyl phthalatete; BMI body mass index; WC waist circumference.