Association of Preterm Singleton Birth With Fertility Treatment in the US

IMPORTANCE: Preterm birth is a global health issue. The association between fertility treatment and preterm singleton births has not been clarified. OBJECTIVE: To examine the association between fertility treatment and preterm birth. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used birth data that were submitted by 50 states and the District of Columbia to the National Vital Statistics System database. All mothers in the database who had a singleton live birth from January 1, 2016, to December 31, 2019, were included. Those who had preexisting hypertension or diabetes were excluded. EXPOSURES: Fertility treatment categorized as assisted reproductive technology (ART) or non-ART treatment. MAIN OUTCOMES AND MEASURES: The main outcome was a diagnosis of preterm birth, which was defined as birth before 37 complete weeks (<259 days) of gestation. Gestational age was calculated by obstetric estimation at delivery and was collected from the database. RESULTS: The final sample consisted of 14 370 920 mothers (mean [SD] age, 28.79 [5.79] years) with singleton live births. Of these women, 122 944 (0.9%) conceived by ART and 71 176 (0.5%) received non-ART treatment. The prevalence of preterm birth was 7.6% (n = 1 071 994) in natural conception, 10.7% (n = 13 205) in ART, and 9.3% (n = 6629) in non-ART groups. Compared with neonates who were naturally conceived, newborns who were conceived with ART (adjusted risk difference [aRD], 3.10% [95% CI, 2.93%-3.27%]; adjusted odds ratio [aOR], 1.49 [95% CI, 1.46-1.52]; P < .001) and non-ART treatment (aRD, 2.22% [95% CI, 2.00%-2.44%]; aOR, 1.35 [95% CI, 1.31-1.38]; P < .001) had significantly higher risk for preterm birth after full adjustment. These associations were similar in subgroups of participants as defined by baseline characteristics. CONCLUSIONS AND RELEVANCE: This study found that singleton neonates who were conceived by fertility treatment had higher rates of preterm birth. Further investigations are warranted into the association between ART or non-ART treatment and the risk of preterm birth in singleton neonates.