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An evaluation of fetal growth in human immunodeficiency virus infected women at Khayelitsha and Gugulethu midwifery obstetric units in the Western Cape
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A prospective cohort study was done on Human Immunodeficiency Virus (HIV) infected and uninfected women attending Khayelitsha Midwifery Obstetric Unit (MOU) and Gugulethu MOU from June 2003 to December 2004, primarily to establish whether there is an association between HIV infection and Intra-uterine growth restriction (lUGR). B-Mode real time ultrasound imaging was used to monitor fetal growth from ±22 weeks to 36 weeks gestational age. Birth weight, gestational age at delivery, gender, placental weight, and maternal complications were also included. Maternal factors considered included age, weight parity, singleton versus multiple pregnancy, previous IUGR or preterm delivery, previous fetal abnormality, social habits viz. cigarette smoking, alcohol and drug use, and vascular disease viz. Diabetes, hypertension, renal disease, cardiac disease and collagen disease. A secondary objective was to establish whether the CD4 T-lymphocyte count possibly modulated the presence of IUGR. All HIV infected women were given antiretroviral therapy according to the standard Protocol of the Provincial Government of Western Cape (2002). The research questions were: • Does maternal HIV infection increase the risk of intrauterine growth restriction and associated preterm delivery? • Does the immune status of (CD4 T-lymphocyte count) of HIV infected pregnant women modulate fetal growth? The primary objective of this study was to establish whether there is an association between HIV infection and IUGR, and hence that HIV infection leads to an adverse perinatal outcome. Ultrasound was used as a diagnostic tool to establish normal or abnormal fetal growth patterns. Anecdotal reports from health workers in the obstetric field suggested that IUGR and preterm delivery may be associated with low birth weight infants in HIV infected pregnant women. However, preterm delivery is associated with various other factors including low socio-economic status (poor nutrition), cigarette smoking, drug and alcohol abuse, previous history of preterm delivery, over distention of the uterus (hydramnios, multiple gestation), premature rupture of membranes, cervical incompetence, vaginal infections (bacterial vaginosis) and maternal disease e.g. hypertension, heart disease (Lizzi, 1993: Symmonds, 1992; Odendaal et aI, 2002). HIV is now thought to be an added factor. Afier doing a systematic review and meta-analysis of 31 studies, Brocklehurst and French (1998) reported that there is an association (although not strong) between HIV infection and adverse perinatal outcome in developed countries; but in developing countries, there is an increased risk of infant death. By excluding or controlling for confounding variables that could affect fetal growth, this study aimed to determine whether there is a significant association between HIV and fetal growth by comparing fetal growth in HIV infected and uninfected women from midsecond trimester to the time of delivery. A secondary objective was to establish whether there is an association between the immune status (CD4 T-lymphocyte count) of the mother and IUGR. The immune status of the mother is probably one of the most important factors affecting the fetus and perinatal outcome. As the mother's viral load increases, her immune system is increasingly compromised, resulting in the occurrence of HIV-related diseases, and a concurrent increase in fetal complications. In this study a CD4 T-lymphocyte count was used to assess the level of immunodeficiency of all the HIV infected participants. Ideally the test should have been done each time the participant was scanned so that the CD4 T-lymphoc)1e count could be monitored simultaneously with the fetal growth parameters, however due to financial constraints and ethical considerations, one test was done on each HIV infected women. This study was based at two MOU's where different antiretroviral therapy (ARVT) regimens were used. The one MOU offered Zidovudine (ZDV) to mothers from 34 weeks gestation to the onset of labour, and the other MOU offered Nevirapine (NVP) as a single dose to the mother at the onset of labour and to the neonate within 72 hours of birth (Provincial Government Western Cape, 2002). This presented an opportunity to compare two groups of HIV infected women on different regimes. The intention was to establish whether ZDV had an adverse effect on fetal growth and resulted in low birth weight. However, 6 months after the study started a revised Prevention of Mother to Child Transmission (PMTCT) Protocol was implemented where women at both MOU's received the same ARVT i.e. ZDV and NVP. This objective was therefore abandoned due to a change in the PMTCT Protocol in the Western Cape. The study was based at two Midwife Obstetric Units (MOU) in the Western Cape where the prevalence of HIV in pregnant women is relatively high i.e. 20 - 24 % (Mother-to-child transmission Monitoring Team, 2001), viz. Gugulethu MOU and Khayelitsha MOU. A prospective cohort study was done with the intention of recruiting a sample of 400 pregnant women, 200 HIV infected and 200 uninfected. The actual sample size was 415. The study group was 194 HIV infected women and the control group was 221 uninfected women. Confounding variables such as cigarette smoking, alcohol and drug abuse. multiple gestation. grand multipara pregnancy, history of IUGR or preterm delivery. fetal abnormality detected at the time of the first scan in the current pregnancy, and maternal vascular disease - were excluded. Confounding variables such as maternal age, maternal weight and gestational age were controlled. Ultrasound imaging was used as a diagnostic tool to establish normal and abnormal fetal growth patterns. A B-mode real time ultrasound unit was used to confirm the gestation age and rule out any obvious fetal abnormalities at 20-24 weeks gestation. Fetal growth scans were done at 28 weeks, 32 weeks and 36 weeks gestation to compare fetal growth patterns in the study and control groups. Fetal biometry used to monitor fetal growth included biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW). Amniotic fluid index (AFI), placental thickness & placental grading were also included. The following variables were analyzed post delivery: • Gestation age at delivery: Normal term delivery is considered to be at 37 - 42 weeks and premature delivery is considered to be less than 37 weeks gestation. The HIV infected and uninfected groups were compared to assess if there \vas a significant difference in the number of preterm deliveries. • Birth weight: The HIV infected and uninfected groups were compared to assess if there was a significant difference in the number of infants with low birth weight. • Perinatal complications: The HIV infected and uninfected groups were compared to assess if there was a significant difference in the number of perinatal complications and to assess if there was an association between the immune status (CD4 T-lymphocyte count) of HIV infected women and perinatal complications. Appropriate ethical principles in medical research were applied. The participant's autonomy, rights and best interests were always considered a priority. Informed consent was obtained from all the participants. Strict confidentiality was adhered to regarding any data collected throughout the study. The Research Ethics Committees at Cape Peninsula University of Technology and University of Cape Town granted ethics approval for the study. Statistical analysis was performed using the statistical package SPSS 12.0.