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Am J Obstet Gynecol. 2013 Jun;208(6):492.e1-11. doi: 10.1016/j.ajog.2013.02.012. Epub 2013 Feb 24.

Association of early-preterm birth with abnormal levels of routinely collected first- and second-trimester biomarkers.

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Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA.



The purpose of this study was to examine the relationship between typically measured prenatal screening biomarkers and early-preterm birth in euploid pregnancies.


The study included 345 early-preterm cases (<30 weeks of gestation) and 1725 control subjects who were drawn from a population-based sample of California pregnancies who had both first- and second-trimester screening results. Logistic regression analyses were used to compare patterns of biomarkers in cases and control subjects and to develop predictive models. Replicability of the biomarker early-preterm relationships that was revealed by the models was evaluated by examination of the frequency and associated adjusted relative risks (RRs) for early-preterm birth and for preterm birth in general (<37 weeks of gestation) in pregnancies with identified abnormal markers compared with pregnancies without these markers in a subsequent independent California cohort of screened pregnancies (n = 76,588).


The final model for early-preterm birth included first-trimester pregnancy-associated plasma protein A in the ≤5th percentile, second-trimester alpha-fetoprotein in the ≥95th percentile, and second-trimester inhibin in the ≥95th percentile (odds ratios, 2.3-3.6). In general, pregnancies in the subsequent cohort with a biomarker pattern that were found to be associated with early-preterm delivery in the first sample were at an increased risk for early-preterm birth and preterm birth in general (<37 weeks of gestation; adjusted RR, 1.6-27.4). Pregnancies with ≥2 biomarker abnormalities were at particularly increased risk (adjusted RR, 3.6-27.4).


When considered across cohorts and in combination, abnormalities in routinely collected biomarkers reveal predictable risks for early-preterm birth.

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