OBSTETRICS First-trimester maternal serum screening and the risk for fetal distress during labor Stefano Uccella, MD; Giacomo Filippo Colombo, MD; Carlo Maria Bulgheroni, MD; Maurizio Serati, MD; Giorgio Bogani, MD; Stefano Salvatore, MD; Fabio Ghezzi, MD; Pierfrancesco Bolis, MD OBJECTIVE: The purpose of this study was to assess whether low pregnancy-associated plasma protein-A (PAPP-A) levels in the first trimester are related to the risk of emergency cesarean section delivery (CS) for fetal distress during labor and fetal intrapartum acidemia. STUDY DESIGN: We prospectively studied patients who requested first-trimester biochemical screening for Down syndrome. RESULTS: Among the 1037 women who were enrolled, 152 women (14.7%) had a low first-trimester PAPP-A value, and 855 women (85.3%) had a normal first-trimester PAPP-A value. Excluding elective CS, 19 of 117 women (16.2%) with low PAPP-A values vs 59 of 749 women (7.9%) with normal PAPP-A values underwent CS for concerning fetal status during labor (P = .003; odds ratio, 2.27; 95% confidence interval, 1.30-3.97). This difference re- mained significant after correction for possible confounders (hy- pertension, preterm delivery, small for gestational age, labor induc- tion). Among these 78 women, umbilical artery pH was significantly lower in fetuses from mothers with low vs normal PAPP-A values (pH = 7.19 [range, 6.95-7.39] vs pH = 7.26 [range, 7.02-7.39]; P = .022). CONCLUSION: Low PAPP-A levels at first-trimester screening are as- sociated independently with higher rates of emergency CS for nonre- assuring fetal status during labor and lower pH. Key words: cesarean section delivery, fetal distress, first-trimester screening, nonreassuring fetal status, PAPP-A Cite this article as: Uccella S, Colombo GF, Bulgheroni CM, et al. First-trimester maternal serum screening and the risk for fetal distress during labor. Am J Obstet Gynecol 2009;201:166.e1-6. P regnancy-associated plasma pro- tein-A (PAPP-A) and free -human chorionic gonadotropin (-hCG) are placenta-derived biochemical markers that are used increasingly as a part of screening programs for the detection of fetal aneuploidies during early preg- nancy. 1-7 An obvious consequence of the wide implementation of this type of first- trimester screening is the great number of abnormal values of the biochemical analytes in the presence of a normal karyotype. Recent studies have focused especially on PAPP-A and have shown a strong association between low levels of this marker and a number of adverse ob- stetric outcomes: in particular, intra- uterine growth restriction, gestational hypertension, preeclampsia, fetal death, and preterm delivery. 8-13 These findings have been explained by the fact that PAPP-A is produced by the trophoblast; therefore, as early as in the first trimester, abnormal values of this protein could suggest abnormal placentation, which usually sustains the aforementioned pathologic conditions. 10,14 We hypothesized that abnormal pla- cental function (suspected on the basis of low levels of PAPP-A in the first trimes- ter) can imply not only a higher tendency to the development of obstetric compli- cations during pregnancy but also to a lower ability of the fetus to tolerate the stress of labor and, consequently, a higher risk of intrapartum fetal distress. The primary aim of this study has been to assess whether low PAPP-A levels at the first-trimester biochemical screening for aneuploidy are related to a higher risk of emergency cesarean section delivery for nonreassuring fetal status during la- bor. Our secondary aim was to evaluate the possible association between low PAPP-A levels and intrapartum aci- demia (ie, low umbilical artery pH) in fetuses of mothers who underwent cesar- ean section delivery for nonreassuring fetal status. MATERIALS AND METHODS All women who access the outpatient ob- stetric clinic at the University of Insubria during the first trimester of pregnancy are thoroughly counseled about the pos- sibilities of screening for aneuploidies. Between ultrasonographically confirmed 11 + 0 and 13 + 6 weeks of gestation (crown-rump length between 45-84 mm), all women undergo a fetal ultra- sound first-trimester scan for the mea- surement of nuchal translucency and are offered biochemical screening by the combination of nuchal translucency with maternal serum PAPP-A and free -hCG dosage. 15 Women who opt for invasive prenatal diagnosis (villocentesis or amniocentesis) as first line are not of- fered biochemical screening. Maternal serum-free -hCG and PAPP-A are measured with the Kryptor Analyzer From the Department of Obstetrics and Gynecology, Del Ponte Hospital, University of Insubria, Varese, Italy. Received Jan. 23, 2009; revised March 26, 2009; accepted May 10, 2009. Reprints: Stefano Uccella, MD, Dept. of Obstetrics and Gynecology, University of Insubria, Piazza Biroldi, 1, Varese, 21100, Italy. stefucc@libero.it. Authorship and contribution to the article is limited to the 8 authors indicated. There was no outside funding or technical assistance with the production of this article. 0002-9378/$36.00 © 2009 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2009.05.009 Research www. AJOG.org 166.e1 American Journal of Obstetrics & Gynecology AUGUST 2009