Wise LA, Mikkelsen EM, Sorensen HT, Rothman KJ, Hahn KA, Riis AH, Hatch EE. Prospective study of time to pregnancy and adverse birth outcomes. Fertil Steril. 2015 Apr;103(4):1065-73. doi: 10.1016/j.fertnstert.2015.01.024.

OBJECTIVE: To investigate the association between time to pregnancy (TTP) and adverse birth outcomes.

DESIGN: Prospective cohort study.

SETTING: Not applicable.

PATIENT(S): A total of 3521 singletons born to women aged 18-40 years at cohort entry.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Selected birth outcomes, including preterm birth (PTB,  less than 37 weeks' gestation), low birth weight (less than 2,500 g), small for gestational age, large for gestational age, and placental disorders, ascertained from the Danish Medical Birth Registry and Danish National Registry of Patients. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using log-binomial regression, with adjustment for potential confounders and fertility treatment.

RESULT(S): Multivariable RRs for PTB in relation to TTP of 3-5, 6-11, and greater than or = 12 vs. less than 3 cycles were 1.59 (95% CI 0.94-2.69), 0.85 (95% CI 0.48-1.50), and 1.57 (95% CI 0.93-2.65). The association was slightly stronger for spontaneous PTB (TTP greater than or =12 vs. less than 3 cycles: RR 1.69, 95% CI 0.84-3.42) than for medically indicated PTB (RR 1.39, 95% CI 0.62-3.12). Longer TTPs (greater than or =12 cycles) were associated with increased risks of low birth weight (RR 1.80, 95% CI 0.97-3.35), cesarean delivery (RR 1.64, 95% CI 1.27-2.12), placental disorders (RR 2.21, 95% CI 1.07-4.56), ischemic placental disease (RR 1.56, 95% CI 0.99-2.44), pre-eclampsia (RR 1.45, 95% CI 0.79-2.65), and postpartum hemorrhage (RR 1.58, CI 1.14-2.19), and decreased risks of macrosomia (greater than or = 4,500 g; RR 0.63, 95% CI 0.35-1.13) and large for gestational age (RR 0.76, 95% CI 0.58-1.00). Longer TTP showed little association with small for gestational age.

CONCLUSION(S): In a prospective cohort study of Danish pregnancy planners, delayed conception was a marker for adverse birth outcomes, after accounting for fertility treatment.

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