There were slight differences in the characteristics of women who returned for follow-up versus the original birth cohort (). Compared with the original birth cohort, the women who returned for follow-up tended to be those who were slightly older at the time of enrollment. However, the racial/ethnic mix, educational attainment, marital status, and median urinary concentrations of the metabolites of low and high molecular phthalates were similar. Among the children followed up, 54% were boys, 75% of the children spoke only English at home, and 83% of mothers were the child’s primary caretaker. Those with other caretakers generally reported either father or grandmother.
HMWP were not associated with most of the BASC or BRIEF domains, except that increased log-HMWP was associated with poorer scores on the adaptability scale of the BASC [β = −1.33; 95% confidence interval (CI), −2.53 to −0.14].
Low molecular weight phthalate (LMWP) concentrations were strongly related to a number of clinical and composite scales (). In multivariate adjusted models, each log-unit increase in LMWP metabolite concentrations was associated with a 1.24-point increase on the aggression scale [95% confidence interval (CI), 0.15–2.34], a 1.29-point increase on the attention problems scale (95% CI, 0.16–2.41), a 2.4-point increase on the conduct problems scale (95% CI, 1.34–3.46), and a 1.18-point increase on the depression scale (95% CI, 0.11–2.24). Although the associations between urinary concentrations of phthalate metabolites and the adaptive scales did not reach conventional levels of statistical significance, there was a consistent pattern of poorer adaptive profiles with increasing metabolite concentrations. This pattern was also evident in the composite Adaptive Skills Index (β = −0.98; 95% CI, −2.05 to 0.09). However, the associations were stronger between phthalate metabolite concentrations and externalizing problems (β = 1.75; 95% CI, 0.61–2.88) and the BSI (β = 1.55; 95% CI, 0.39–2.71). These effects were not modified by the child’s sex. Using creatinine-corrected tertiles of phthalate exposure, we plotted the tertile-specific adjusted mean T-score at the median micromolar concentration of metabolites of LMWP to examine the shape of the dose–response relationship (). Consistent with the log-linear models, the strongest linear trends were demonstrated for conduct problems and externalizing problems; however, all scales demonstrated monotonically increasing LSMEANS, with the exception of the attention scale, which seemed to suggest a threshold effect at approximately 2 μM.
Prenatal metabolite concentrations of LMWP and the BASC in a multiethnic birth cohort, Mount Sinai Medical Center, New York, New York, USA, 1998–2008.a
Even restricting our analyses to BASC surveys with F-scores < 2 (n = 161), most associations between phthalate exposure and behavior remain among boys. Significant sex–phthalate interactions (i.e., significant differences in the slope of the association between log-LMWP and behavior between girls and boys) were found for the aggression, conduct problems, hyperactivity, externalizing problems, and BSI. There were few significant associations among the girls; however, among boys, increasing log-LMWP metabolite concentrations were associated with poorer T-scores for aggression (β = 1.46; 95% CI, 0.17–2.76), attention problems (β = 1.55; 95% CI, 0.22–2.88), and conduct problems (β = 2.79; 95% CI, 1.55–4.03), which was also significant in girls but with a smaller effect magnitude and less precision, externalizing problems (β = 2.08; 95% CI, 0.74–3.42), and for the BSI (β = 1.60; 95% CI, 0.23–2.97) ().
Prenatal metabolite concentrations of LMWP and the BASC among boys in a multiethnic birth cohort, Mount Sinai Medical Center, New York, New York, USA, 1998–2008.a
Few surveys met the threshold scores for at risk or clinically significant (T-scores ≥ 60 for the clinical and composite scales or ≤ 40 for the adaptive scales) in this population. However, in a sensitivity analysis, we examined whether greater than the median metabolite concentration was associated with increased risk of scoring in the at-risk or clinically significant range on the scales identified in . In general, we found that the effects were in the same direction, although only attention problems (n = 27 at-risk or clinically significant surveys) reached statistical significance (relative risk = 2.66; 95% CI, 1.06–6.66).
We also examined the metabolite-specific effects on the BASC domains (). In general, we found consistency between the LMWP sum effects and the metabolite-specific models.
Comparison of betas from metabolite-specific models to the LMWP molar sum for the BASC among boys in a multiethnic birth cohort, Mount Sinai Medical Center, New York, New York, USA, 1998–2008.
Except for aggression and conduct problems, the LMWP molar sum significance was replicated in at least two of the individual metabolite models for that scale. Although for monobutyl phthalate (MBP) only aggression and externalizing problems were statistically significant, the magnitude of the MBP associations were very similar to the LMWP sum effects for attention problems, adaptability, and the BSI.
There were fewer consistent associations between LMWP metabolite concentrations and executive functioning as measured with the BRIEF. However, similar to what was observed for the BASC, increased loge-LMWP metabolite concentrations was associated with poorer scores on the emotional control scale (β = 1.33; 95% CI, 0.18–2.49) and on the GEC index (β = 1.23; 95% CI, 0.09, 2.36) (). There were no interactions between phthalate exposure and the child’s sex for the BRIEF scales. We also compared the metabolite-specific models with the total LMWP molar sum (). There were a number of significant associations for monomethyl phthalate (MMP), however, this metabolite has the lowest concentration among all metabolites measured. MBP was associated with poorer scores on working memory (β = 1.53; 95% CI, −0.01 to 3.07), but in general, the molar sum effects were consistent in direction and magnitude with the metabolite specific effects.
Prenatal metabolite concentrations of LMWP and the BRIEF in a multiethnic birth cohort, Mount Sinai Medical Center, New York, New York, USA, 1998–2008.a
Comparison of betas from metabolite-specific models to the LMWP molar sum for the BRIEF in a multiethnic birth cohort, Mount Sinai Medical Center, New York, New York, USA, 1998–2008.