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Decrease in anogenital distance among male infants with prenatal phthalate exposure
Environmental Health Perspectives, August, 2005 by Shanna H. Swan, Katharina M. Main, Fan Liu, Sara L. Stewart, Robin L. Kruse, Antonia M. Calafat, Catherine S. Mao, J. Bruce Redmon, Christine L. Ternand, Shannon Sullivan, J. Lynn Teague
Table 1. Participants included in present analysis.
Percent Percent
potential male
No. participants babies
All pregnancy outcomes (CA, MN, and MO)
Potential participants (a) 654 100 --
Eligible for SFFII 477 72.9 --
SFFII participant 346 72.5 --
Male babies only (CA, MN, and MO)
SFFII participant 172 -- 100
With AGD, age, and weight (b) 134 -- 78
Prenatal urine sample (c) 85 -- 49
(a) A potential participant is an SFFI participant from CA, M0, or MN
who gave permission to be recontacted for future studies and for whom
all study data were entered by 17 December 2004. (b) Boys in twin
births and boys with missing data or AGD measurements considered
unreliable by pediatricians excluded. (c) Urine collection began
midway through SFFI.
Table 2. Characteristics of boys with complete physical examination.
Characteristic Mean [+ or -] SD 25th
All boys (n = 134)
Age (months) 15.9 [+ or -] 8.6 11.0
Height (cm) 79.1 [+ or -] 10.6 72.6
Weight (kg) 10.5 [+ or -] 2.7 8.7
AGD (mm) 70.3 [+ or -] 11.0 63.9
AGI (mm/kg) 7.1 [+ or -] 1.9 5.8
ASD (mm) 37.4 [+ or -] 7.5 31.2
Boys whose mother's prenatal urine was
assayed for phthalate metabolites (n = 85)
Age (months) 12.6 [+ or -] 6.9 5.0
Height (cm) 75.6 [+ or -] 9.5 66.5
Weight (kg) 9.7 [+ or -] 2.4 8.4
AGD (mm) 68.0 [+ or -] 9.7 61.7
AGI (mm/kg) 7.4 [+ or -] 1.8 6.1
ASD (mm) 35.9 [+ or -] 7.1 30.4
Percentile
Characteristic 50th 75th
All boys (n = 134)
Age (months) 15.0 23.0
Height (cm) 80.0 87.2
Weight (kg) 10.7 12.3
AGD (mm) 70.3 76.6
AGI (mm/kg) 6.7 7.8
ASD (mm) 36.8 43.4
Boys whose mother's prenatal urine was
assayed for phthalate metabolites (n = 85)
Age (months) 14.0 16.0
Height (cm) 77.6 82.0
Weight (kg) 10.0 11.1
AGD (mm) 66.7 74.4
AGI (mm/kg) 7.0 8.2
ASD (mm) 35.6 41.4
Table 3. Percentiles of phthalate monoester metabolites.
Percentile (ng/mL)
Percent >
Monoester metabolite 25th 50th 75th LOD (a)
Phthalate monoester metabolite
MBP 7.2 13.5 30.9 96.5
MBzP 3.5 8.3 23.5 94.1
MCPP 0.7 2.1 3.6 69.4
MEP 53.3 128.4 436.9 97.6
MiBP 0.7 2.5 5.1 74.1
MMP 0.7 0.7 3.2 49.4
Metabolites of DEHP
MEHHP 6.0 11.4 20.1 97.6
MEHP 1.3 3.3 9.0 77.6
MEOHP 5.1 11.1 19.0 94.1
(a) LOD for all metabolites was between 0.95 and 1.07 ng/mL.
Table 4. Regression analyses of AGI on loglo monoester metabolite
concentration, controlling for age and age squared.
[Log.sub.10] monoester metabolite concentration
Monoester metabolite Coefficient (SE) p-Value (95% CI)
MBP -0.592 (0.269) 0.031 (-1.126 to -0.057)
MBzP -0.390 (0.232) 0.097 (-0.851 to 0.072)
MCPP -0.264 (0.356) 0.461 (-0.973 to 0.445)
MEHHP -0.398 (0.270) 0.145 (-0.935 to 0.140)
MEHP -0.051 (0.241) 0.833 (-0.530 to 0.428)
MEOHP -0.412 (0.258) 0.114 (-0.925 to 0.101)
MEP -0.400 (0.164) 0.017 (-0.726 to -0.074)
MiBP -0.765 (0.274) 0.007 (-1.309 to -0.220)
MMP -0.283 (0.323) 0.383 (-0.924 to 0.359)
Phthalate score (a) -0.0951 (0.035) 0.009 (-0.165 to-0.025)
(a) Phthalate score measures joint exposure to MBP, MBzP, MEP, and
MiBP; see "Statistical analysis."
Table 5. Mean (median) phthalate monoester metabolite levels
by AGI category.
AGI category [mean (median, ng/mL)]
Long (a) Intermediate (b) Short (c)
Monoester metabolite (n=17) (n = 43) (n = 25)
MBP 13.1 (11.5) 22.2 (13.1) 38.7 (24.5)
MBzP 10.6 (6.6) 15.1 (7.7) 25.8 (16.1)
MEP 124 (47.1) 592 (112) 1,076 (225)
MiBP 2.3 (1.5) 3.3 (2.1) 7.7 (4.8)
(a) Long, AGI [greater than or equal to] 75th percentile of expected
AGI. (b) Intermediate, 25th percentile [less than or equal to] AGI
< 75th percentile of expected AGI. (c) Short, AGI < 25th percentile
of expected AGI.
Table 6. OR (95% CI) for AGI less than expected from regression
model, by monoester metabolite level.
Monoester metabolite Level (percentile) AGI < expected
MBP Low 5
Medium 24
High 17
MBzP Low 6
Medium 26
High 14
MEP Low 7
Medium 25
High 14
MiBP Low 6
Medium 23
High 17
AGI [greater than or
Monoester metabolite equal to] expected OR (95% CI)
MBP 15 Referent
19 3.8 (1.2 to 12.3)
5 10.2 (2.5 to 42.2)
MBzP 13 Referent
18 3.1 (1.002 to 9.8)
8 3.8 (1.03 to 13.9)
MEP 14 Referent
19 2.6 (0.9 to 7.8)
6 4.7 (1.2 to 17.4)
MiBP 16 Referent
18 3.4 (1.1 to 10.5)
5 9.1 (2.3 to 35.7)
Low, < 25th percentile; medium, [greater than or equal to] 25th and
< 75th percentile; high, [greater than or equal to] 75th percentile.
Table 7. Concentrations of four phthalate metabolites in three
groups of women (ng/mL).
This study
Monoester metabolite Percentile Short AGI Others NHANES (a)
MBP 50th 24.5 12.1 30.0
75th 44.8 28.0 59.5
MBzP 50th 16.1 7.2 16.0
75th 27.5 17.8 35.8
MEP 50th 225 90.4 174
75th 551 281 425
MiBP 50th 4.8 2.1 --(b)
75th 12.1 4.3 --(b)
(a) Females only (CDC 2003). (b) MBP in the NHANES analysis includes
both MBP and MiBP; in this study these metabolites were measured
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