Prolonged in utero meconium exposure impairs spatial learning in the adult rat Central Prize Award Sean C. Blackwell, MD, a, * Mordechai Hallak, MD, MPA, b John W. Hotra, BS, a Jerrie Refuerzo, MD, a Robert J. Sokol, MD, a Yoram Sorokin, MD a Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Wayne State University, Detroit, Mich a ; Division of Maternal-Fetal Medicine and the Department of Obstetrics and Gynecology, Ben Gurion University/Beer-Sheva, Israel b – Objective: The purpose of this study was to examine the effects of prolonged in utero meconium exposure on adult learning and memory, as measured by the Morris water maze. Study design: Timed pregnant Long-Evans rats were studied. On gestational day 20 (term, 21 days of gestation), laparotomy was performed, and each maternal animal received an injection of clear amniotic fluid or meconium-stained amniotic fluid into each gestational sac. The laparot- omy incision was closed, and the animals received postoperative monitoring through delivery. On postnatal days 145 to 148, the offspring underwent Morris water maze testing. The mean (GSEM) for the latency time was reported for each day’s trial and compared between groups. Results: There were significant differences between meconium-stained amniotic fluid group and clear amniotic fluid group in the mean time to platform on day 1 (82.7 G 1.8 seconds vs 75.9 G 3.0 seconds; P = .04), day 2 (60.5 G 3.5 seconds vs 47. 8 G 4.6 seconds; P = .03), and day 3 (56.5 G 4.5 seconds vs 34.7 G 4.4 seconds; P = .001). However, there were no differences on days 4 and 5. There were also no differences between recall and response learning trials that were done after a 12-day retention period. Conclusion: In the absence of hypoxia or infection, prolonged in utero meconium exposure is as- sociated with a delay of spatial learning in the adult rat. Ó 2004 Elsevier Inc. All rights reserved. KEY WORDS Meconium Amniotic fluid Morris water maze – Although most clinical and research interests that are associated with meconium-stained amniotic fluid (MSAF) and meconium aspiration syndrome is directed at the respiratory morbidities, both conditions are asso- ciated with an increased risk of adverse neurologic out- comes. Naeye et al 1 state that, in the analysis of data from the Collaborative Perinatal Study, 14% of the risk for quadriplegic cerebral palsy was associated with MSAF. MSAF has been linked to cerebral palsy in both term 2 and preterm 3 pregnancies. Survivors of severe Presented at the Seventieth Annual Meeting of the Central Association of Obstetricians and Gynecologists, October 1-4, 2003, La Jolla, California. Supported by a grant from the Children’s Research Center of Michigan. * Reprint requests: Sean C. Blackwell, MD, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Hutzel Hospital/Wayne State University, 4707 St. Antoine Blvd, Detroit, MI 48201. E-mail: sblackwe@med.wayne.edu www.elsevier.com/locate/ajog American Journal of Obstetrics and Gynecology (2004) 190, 1551e6 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.ajog.2004.03.048