Protease Inhibitor Therapy and Fetal Growth Potential in HIV-Positive Women

ABSTRACT

Our objective was to test if protease inhibitors (PIs) increase the incidence of fetal growth restriction (FGR). Human immunodeficiency (HIV)-seropositive women were studied. At birth the neonatal weight percentile was assigned by predicted growth potential (GP), accounting for race, parity, weight, height, gestational age, birthweight, and gender (Gardosi, 1992). FGR was defined as GP < 10% percentile. Maternal age, CD4 count, viral load, weight gain, prenatal care, tobacco, alcohol, substance abuse, and PI use were related to FGR using chi-square and multiple regression analysis. Ninety-three of 191 women received PI. In these, FGR occurred in 27 (29%) compared with 15 (15.3%) in the non-PI group (p = 0.02). Maternal CD4 count (p < 0.0001) was the primary determinant, and smoking (p = 0.037) was an independent cofactor for FGR (Nagelkerke r² = 0.24). Twenty-six of 82 (31.7%) smokers had FGR, versus 16 of 109 (14.7%) of nonsmokers (odds ratio, 2.69; 95% confidence interval, 1.33 to 5.46; p = 0.005). After exclusion of the CD4 count, PI became a cofactor for FGR (p = 0.021 and Nagelkerke r² = 0.104). We concluded that maternal HIV status and smoking determine the risk for FGR. Although PIs increase the risk for FGR, this effect appears to depend on maternal disease severity.

KEYWORDS

Antiretroviral therapy - fetal growth restriction - pregnancy - HIV

REFERENCES

• 1 Centers for Disease Control and Prevention .Cases of HIV infection and AIDS in the United States and Dependent Areas, 2005 HIV/AIDS Surveillance Report, Volume 17, Revised Edition, June 2007. http://www.cdc.gov/hiv/topics/surveillance/resources/slides/pediatric/index.htm http://www.cdc.gov/hiv/topics/surveillance/resources/reports/2005report/table4.htm
• 2 Tuomala R E, Watts D H, LI D. Improved obstetric outcomes and few maternal toxicities are associated with ART, including HAART during pregnancy.  J Acquir Immune Defic Syndr. 2005;  38 449-460
• 3 Fiscus S A, Adimora A A, Funk M L et al.. Trends in interventions to reduce perinatal human immunodeficiency virus type 1 transmission in North Carolina.  Pediatr Infect Dis J. 2002;  21 664-668
• 4 Cotter A M, Garcia A G, Duthly M L, Luke B, O'Sullivan M J. Is antiretroviral therapy during pregnancy associated with an increased risk of preterm delivery, low birth weight, or still-birth?.  J Infect Dis. 2006;  193 1195-1201
• 5 Thorne C, Rudin C, Newell M et al.. The European Collaborative Study and The Swiss Mother + Child HIV Cohort study. Combination antiretroviral therapy and duration of pregnancy.  AIDS. 2000;  14 2913-2920
• 6 Hankin C, Thorne C, Peckham C, Newell M. Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women.  J Acquir Immune Defic Syndr. 2003;  32 380-387
• 7 Tuomala R E, Shapiro D E, Mofenson L M et al.. Antiretroviral therapy during pregnancy and the risk of an adverse outcome.  N Engl J Med. 2002;  346 1863-1870
• 8 Morris A B, Dobles A R, Cu-Uvin S et al.. Protease inhibitor use in 233 pregnancies.  J Acquir Immune Defic Syndr. 2005;  40 30-33
• 9 Szyld E G, Warley E M, Freimanis L et al.. Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth.  AIDS. 2006;  20 2345-2353
• 10 Gardosi J. Customized fetal growth standards: rationale and clinical application.  Semin Perinatol. 2004;  28 33-40
• 11 Bukowski R, Burgett A D, Geui A, Saade G R, Hankins G D. Impairment of fetal growth potential and neonatal encephalopathy.  Am J Obstet Gynecol. 2003;  188 1011-1015
• 12 Covington D L, Conner S D, Doi P A, Swinson J, Daniels E M. Risk of birth defects associated with nelfinavir exposure during pregnancy.  Obstet Gynecol. 2004;  103 1181-1189
• 13 Beckerman K, Watts H, Covington D et al.. Assessing the risk of birth defects and other poor pregnancy outcomes associated with antiretroviral exposure during pregnancy. Poster presentation at the 16th International AIDS conference, Toronto, Canada, August 2006 Available at: http://www.aids2006.org/mainpage
• 14 Lorenzi P, Spicher V M, Laubereau B et al.. Antiretroviral therapies in pregnancy: maternal, fetal and neonatal effects. Swiss HIV Cohort study, the Swiss Collaborative HIV and Pregnancy Study, and the Swiss Neonatal HIV study.  AIDS. 1998;  12 241-247
• 15 Goldstein P J, Smit R, Stevens M, Sever J L. Association between HIV in pregnancy and antiretroviral therapy, including protease inhibitors and low birth weight infants.  Infect Dis Obstet Gynecol. 2000;  8 94-98
• 16 Beckerman K, Covington D L, Garcia P et al.. Association between antiretroviral therapy during pregnancy and prematurity/low birth weight. Oral presentation at the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, 2004 Available at: http://www.retroconference.org/AbstractSearch