Contributions to prematurity of maternal health conditions, subfertility, and assisted reproductive technology

Subfertility and assisted reproductive technology (ART) increased both late and early preterm birth; placental problems are on the pathway to late preterm birth and early preterm birth for ART and subfertile deliveries.

VOLUME 114, ISSUE 4, P828-836


Judy E. Stern, Ph.D., Chia-ling Liu, Sc.D., M.P.H., Sunah S. Hwang, M.D., M.P.H., Ph.D., Dmitry Dukhovny, M.D., M.P.H., Hafsatou Diop, M.D., M.P.H., Howard Cabral, Ph.D., M.P.H.



To determine the maternal demographic, health, and fertility variables underlying prematurity.


Retrospective: Society for Assisted Reproductive Technology Clinic Outcome Reporting System data linked to Massachusetts birth certificates and hospital stays.


Not applicable.


We included 166,963 privately insured, singleton, first births to women ≥18 years of age between 2004 and 2013. Deliveries were as follows: assisted reproductive technology (ART) when linked to Society for Assisted Reproductive Technology Clinic Outcome Reporting System, medically assisted reproduction (MAR) when fertility treatment was indicated on the birth certificate, unassisted subfertile (USF) when there were indications of subfertility but no treatment, and fertile if none of the above.



Main Outcome Measures

Late preterm birth (LPTB; 34–36 weeks) and early preterm birth (EPTB; <34 weeks) were compared with term deliveries (≥37 weeks). Covariates that statistically significantly influenced prematurity in binary analysis were modeled by using multinomial logistic regression. Backward elimination and mediation analysis were used to determine the influence of single parameters on outcomes of others.


LPTB was increased in the USF (adjusted odds ratio [AOR] 1.32, 95% confidence interval [CI] 1.06–1.65) and ART (AOR 1.42, 95% CI 1.30–1.56) but not MAR (AOR 1.16, 95% CI 0.98–1.37). ETPB was increased in all (USF: AOR 1.67, 95% CI 1.21–2.31; MAR: AOR 1.67, 95% CI 1.31–2.12; ART: AOR 1.40, 95% CI 1.21–1.61). The strongest effectors of prematurity were placental problems (LPTB: AOR 4.02; EPTB: AOR 10.28), pregnancy hypertension (LPTB: AOR 2.14; EPTB: AOR 2.88), and chronic hypertension (LPTB: AOR 1.85; EPTB: AOR 2.79). Mediation analysis demonstrated a statistically significant indirect effect of placental problems for ART and subfertility.


The greatest effectors of prematurity were placental problems and hypertensive disorders. ART and, to a lesser extent, subfertility were both associated with preterm birth directly and indirectly mediated by placenta problems.

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