2773 The Journal of Maternal-Fetal and Neonatal Medicine, 2012; 25(12): 2773–2777 © 2012 Informa UK, Ltd. ISSN 1476-7058 print/ISSN 1476-4954 online DOI: 10.3109/14767058.2012.715219 Objective: To evaluate lymphocyte subpopulations’ change and impact on the pregnancy outcome in fetal growth restriction (FGR) through a prospective cohort study. Methods: Sixty singleton pregnancies with FGR and 20 normal pregnant women were enrolled at the third trimester of pregnancy in this study. FGR was defined according to fundal height and abdominal circumference through obstetric examination and ultrasound examination. Third trimester peripheral blood and umbilical cord blood lymphocyte subpopulations were analysed by flow cytometry. The cytotoxic activity of lymphocytes using umbilical cord blood mononuclear activated kill cells as the effector cells, K562 cells as the target cells was measured by MTT deoxidation assay. Results: There were no significant differences about the age, parity, gestational age enrolled, BMI before pregnancy between the FGR and control group. The birth weight, length and head circumference of the neonates from FGR group were less than that from normal control. The percentages of B-lymphocytes in peripheral blood at the third trimester were significantly increased in FGR group compared to that in control group (P < 0.05). In umbilical cord blood, FGR group had a higher percentage of both CD3 and CD4 lymphocyte, lower absolute cell counts and percentage of B-lymphocyte, and higher CD4/CD8 ratio than control group (P < 0.05). Most importantly, the kill cell activity of the lymphocytes in cord blood from FGR group was significantly higher than that from control group (P < 0.05). The significant positive correlations were also found that the percentage and number of B lymphocytes in umbilical cord blood with birthweight, birthlength and birth head circumference, but CD4/CD8 ratio, the kill cell activity in umbilical cord blood had negative correlations with that. The percentage of B lmyphocyte in third trimester and CD4/CD8 ratio, kill cell activity in umbilical cord blood are associated with an increased risk of prematurity and SGA birth, but contrary result was found with the percentage and number of B lmyphocyte in cord blood. Conclusions: Fetal immunological rejection could be involved in the pathogenesis of FGR. The changes of T lymphocyte subpopulations and B-cells, enhanced kill cell activity might cause FGR and preterm birth. Keywords: Cohort study, fetal growth restriction, lymphocyte subpopulation, pregnancy, umbilical cord blood Introduction Fetal growth restriction (FGR) supposes that the fetus is retarded in its growth and development by a pathological process during fetal life. FGR is an important clinical problem [1]. Te prevalence is about 8% in the general population. It has been shown that 52% of stillbirths are associated with FGR [2] and 10% of perinatal mortality are a consequence of FGR [3]. Seventy-two percentage of unexplained fetal deaths are associated with FGR [4]. When FGR is suspected or diagnosed, it is necessary to examine the maternal condition (chronic hypertension, pre-gestational diabetes, cardiovascular disease, substance abuse, autoimmune conditions etc.), the fetal condition (infection, malformation, chromosomal aberration etc.), or placental condition (chorio- angioma, infarction, circumvallate placenta, confned placental mosaicism, obliterative vasculopathy of the placental bed etc.) [5,6]. However, the cause of 50–60% FGR is not clear [7]. During pregnancy, the fetal “allograf” is not rejected by the maternal host. It has been recognized that the systemic maternal immune system is altered in normal pregnancy. Maternal T cells acquire a transient state of tolerance specifc for paternal allo- antigens during pregnancy. Enhanced cellular immunity which leads to a failure of placentation, is involved in the pathogenesis of several pathologic pregnancy, such as spontaneous abortion, preeclampsia and FGR [8,9]. Terefore, some studies proposed the possibility that FGR might have an immunological etiology, representing a partial rejection of the fetal allograf. Many research study the immunological mechanisms of FGR, however, mainly involve cross-sectional study, without cohort study. Te aim of this study was to investigate changes in lymphocyte subpopulations and the kill activity of lymphocytes in pregnant women’s peripheral blood and umbilical cord blood with FGR and normal pregnancy through prospective cohort study, moreover, we analyse the change of immunity function impacting on the pregnancy outcome. Subjects and methods A prospective study was carried out at the West China Second University Hospital, Chengdu, China. Eighty pregnant women in Prospective cohort study about the lymphocyte subpopulations’ change and impact on the pregnancy outcome in fetal growth restriction Fei Xiong 1,2 , Yu Tong 2,3 , Yong You 4 , Ping Li 2,3 , Tingzhu Huo 2,3 , Wenwei Tu 5,6 & Meng Mao 2,3,7 1 Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, PR China, 2 Laboratory of Early Developmental and Injuries, West China Institute of Woman and Children’s Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, PR China, 3 Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, PR China, 4 Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, PR China, 5 Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, PR China, 6 The Joint Research Center of West China Second University Hospital of Sichuan University and the University of Hong Kong, Faculty of Medicine, Chengdu, Sichuan, PR China, and 7 Chengdu Women’s and Children’s Central Hospital, Chengdu, Sichuan, PR China Correspondence: Meng Mao, Department of Pediatrics, West China Second University Hospital, Sichuan University, No. 17, People’s South Road, Chengdu, Sichuan Province, PR China 610041. Tel: +86 13608088613. Fax: +86 28 85559065. E-mail: dfmmao@126.com