EPIDEMIOLOGY AND SOCIAL SCIENCE Association of Low CD4 Cell Count and Intrauterine Growth Retardation in Thailand Johann Cailhol, MD,* Gonzague Jourdain, MD, PhD,*† Sophie Le Coeur, MD, PhD,†‡ Patrinee Traisathit, PhD,§ Kamol Boonrod, MD, k Sinart Prommas, MD,¶ Chaiwat Putiyanun, MD,# Annop Kanjanasing, MD,** and Marc Lallemant, MD, MSc*† for the Perinatal HIV Prevention Trial Group Objective: Each year, intrauterine growth retardation (IUGR) affects 20–30 million neonates worldwide, mostly in resource-limited settings. Increased perinatal and infant mortality has been associated with IUGR. Some studies have suggested that HIV infection could increase the risk of IUGR. To confirm this hypothesis, we examined the association between HIV-related factors and the risk of IUGR in Thailand. Patients and Methods: Data from a cohort of 1436 HIV-infected pregnant women enrolled in the ‘‘Perinatal HIV Prevention Trial-1’’, a clinical trial conducted from 1997 to 1999 in Thailand, were analyzed using a logistic regression, adjusting for risk factors usually associated with IUGR. Results: The rate of IUGR was 7.6%. Adjusting for a short maternal height, low body mass index, small weight gain during pregnancy, and infant female sex, a low maternal CD4 percentage was independently associated with IUGR (odds ratio 0.96, per 1% increment, 95% confidence interval 0.93 to 0.99, P = 0.03). Conclusions: The current World Health Organization recommen- dation to initiate combination antiretroviral therapy for immuno- compromised women as early as possible during pregnancy for their own health and for the prevention of HIV mother-to-child transmission is likely to also decrease the incidence of IUGR. Encouraging immunocompromised HIV-infected women who plan to become pregnant to wait until immune restoration has been achieved may help to reduce the risk of IUGR. Key Words: antiretroviral therapy, developing country, HIV, intrauterine growth retardation, immune deficiency, pregnancy (J Acquir Immune Defic Syndr 2009;00:000–000) INTRODUCTION Intrauterine growth retardation (IUGR) is defined as a birth weight below the 10th percentile of weight for the corresponding gestational age. After prematurity, IUGR is the second cause of perinatal mortality in developing countries. 1 Neonates affected by IUGR have a higher susceptibility to various diseases such as respiratory distress, ventricular hemorrhage, neonatal sepsis, and have overall a higher morbidity than non-IUGR neonates. 2 Adults born with IUGR have been shown to be at higher risk of diabetes mellitus, obesity, and hypertension. 3 In resource-limited settings, the most frequent factors of IUGR are nutritional. 4 Where malaria is endemic, it also significantly contributes to IUGR. 1 In industrialized countries, smoking is the main risk factor for IUGR, 4 followed by gravidic hypertension and preeclampsia. 5 Other factors such as female sex of the child, primiparity, and ethnicity have also been associated with the risk of IUGR. 4 In 1987, the World Health Organization (WHO) estimated the rate of IUGR at 23.8% (9.4–54.2) in resource- limited countries, affecting approximately 30 million infants per year. 1 In Thailand, the rate of IUGR was estimated to be 8.5% in 1983. 6 Because the definition of IUGR relies on the gestational age at delivery, for which an accurate measurement is often unavailable in resource-limited settings, a low birth weight (LBW), defined as below 2500 g, is often used as a proxy for IUGR. In HIV-infected women, studies have reported conflicting results with regards to IUGR due to the use of different definitions (LBW or IUGR) or the lack of adjustment for confounding factors. 7–13 Using the stringent definition of IUGR, we analyzed the HIV-specific determinants of IUGR in a cohort of HIV-infected pregnant women in Thailand. 1 Patients and Methods The Perinatal HIV Prevention Trial-1 was a randomized, double-blind, multicenter, clinical trial comparing the efficacy of zidovudine regimens of different durations in mothers and children to prevent HIV perinatal transmission in Thailand. 14 Between June 1997 and December 1999, consenting HIV- positive women meeting the selection criteria were enrolled. Women with contraindication to zidovudine or hydramnios were excluded. At baseline, sociodemographic characteristics were recorded, medical and obstetrical history taken, physical, obstetrical, and ultrasound examinations performed, and blood drawn for viral load and CD4 count. At 28-week pregnancy, Received for publication July 1, 2008; accepted November 17, 2008. From the *Institut de Recherche pour le De ´veloppement, Paris, France (UMI 174); †Harvard School of Public Health, Boston, MA; ‡Institut National d’Etudes De ´mogaphiques, Paris, France; §Faculty of Sciences, Chiang Mai University, Chiang Mai, Thailand; k Banglamung Hospital, Chonburi, Thailand; {Bhumibol Adulyadej Hospital, Royal Thai Air Force, Bangkok, Thailand; #Chiang Kham Hospital, Phayao, Thailand; and **Chachoengsao Hospital, Chachoengsao, Thailand. Correspondence to: Gonzague Jourdain, MD, PhD, Program for HIV Prevention and Treatment, Institut de Recherche pour le De ´veloppement, IRD 174, PO Box 207 Prasing Post, Muang, Chiang Mai 50205, Thailand (e-mail: gonzague@phpt.org). 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