Association of Parental Preconception Exposure to Phthalates and Phthalate Substitutes With Preterm Birth
Bibliographic record
Abstract
Importance: Although phthalate exposure during pregnancy has been associated with preterm birth, the association of preconception exposure in either parent with preterm birth constitutes a knowledge gap. Objective: To examine the association of paternal and maternal preconception urinary concentrations of biomarkers of phthalates and phthalate substitutes with singleton preterm birth. Design, Setting, and Participants: This study, conducted at an academic fertility center in Boston, Massachusetts, included a prospective preconception cohort of subfertile couples comprising 419 mothers and 229 fathers and their 420 live-born singleton offspring born between January 1, 2005, and December 31, 2018. Statistical analysis was performed from August 1 to October 31, 2019. Exposures: Urinary concentrations of metabolites of phthalates and phthalate substitutes obtained before conception. Main Outcomes and Measures: Gestational age was abstracted from delivery records and validated using the American College of Obstetricians and Gynecologists guidelines for births after medically assisted reproduction. The risk ratio (RR) of preterm birth (live birth before 37 completed weeks' gestation) was estimated in association with urinary concentrations of 11 individual phthalate metabolites, the molar sum of 4 di-(2-ethylhexyl) phthalate (ΣDEHP) metabolites, and 2 metabolites of 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH, a nonphthalate plasticizer substitute) using modified Poisson regression models adjusted for covariates. Results: The mean (SD) age of the 419 mothers was 34.7 (4.0) years, the mean (SD) age of the 229 fathers was 36.0 (4.5) years, and the mean (SD) gestational age of the 420 singleton children (217 boys) was 39.3 (1.7) weeks, with 34 (8%) born preterm. In adjusted models, maternal preconception ΣDEHP concentrations (RR, 1.50; 95% CI, 1.09-2.06; P = .01) and cyclohexane-1,2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH, a metabolite of DINCH) concentrations (RR, 1.70; 95% CI, 0.89-3.24; P = .11) were associated with an increased risk of preterm birth. After additional adjustment for prenatal ΣDEHP or MHiNCH concentrations, the association of maternal preconception exposure to ΣDEHP and preterm birth remained robust (RR, 1.69; 95% CI, 1.17-2.44; P = .006), while the association of maternal preconception exposure to MHiNCH and preterm birth was attenuated (RR, 1.17; 95% CI, 0.49-2.81; P = .72). The remaining urinary metabolites examined in either parent showed no association with preterm birth. Conclusions and Relevance: In this prospective cohort of subfertile couples, maternal preconception exposure to ΣDEHP metabolites was associated with an increased risk of preterm birth. The results suggest that female exposure to select phthalate plasticizers during the preconception period may be a potential risk factor for adverse pregnancy outcomes, which may need to be considered in preconception care strategies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".