IS PREGNANCY ASSOCIATED WITH BIOCHEMICAL AND HAEMATOLOGICAL CHANGES IN HIV-INFECTED NIGERIAN WOMEN?

The rate of HIV infection in pregnancy is high. There is evidence that HIV infection in pregnant women is associated with adverse maternal and fetal outcomes. The effects of HIV infection include severe anaemia, infectious morbidities and vertical transmission. In a Malawian study, AIDS and anaemia were the leading causes of maternal mortality, and in Zaire maternal mortality rates in HIV-infected women were 10 times those of HIV-negative women. A personal communication revealed that in a recent unpublished report from a Nigerian Teaching Hospital, HIV/AIDS accounted for 20.2% of maternal deaths.

2][3][4][5][6][7] There is evidence that HIV infection in pregnant women is associated with adverse maternal and fetal outcomes. 2,5,6][10][11][12][13][14] In a Malawian study, AIDS and anaemia were the leading causes of maternal mortality, 15 and in Zaire maternal mortality rates in HIV-infected women were 10 times those of HIV-negative women. 16A personal communication revealed that in a recent unpublished report from a Nigerian Teaching Hospital, HIV/AIDS accounted for 20.2% of maternal deaths.
However, the effect of pregnancy on HIV disease progression remains contentious.Evidence from developed countries suggests that pregnancy does not accelerate the progression of HIV disease, [17][18][19][20][21] while reports from low-resource settings imply otherwise, indicating that pregnancy may influence the rate of disease progression. 2It has been suggested that other factors, including genetics, nutritional status and intercurrent infections, may be responsible for the rate of HIV disease progression in low-resource settings. 2,22,23John and colleagues report an association between CCR5 promotor polymorphism and increased maternal mortality in a Kenyan cohort. 23e objectives of the present study were to determine the association between pregnancy and biochemical and haematological changes in HIV-infected Nigerian women as a possible indicator of disease severity.

METHODOLOGY
This study was conducted in Central Hospital, Benin City, Nigeria, which provides tertiary care to patients in Benin City and its environs.It was a prospective study of two demographically similar cohorts of HIV-seropositive women, 154 pregnant and 151 non-pregnant.The cases were pregnant women attending the antenatal clinics of the hospital from October 2005 to October 2007.Once a pregnant case was identified, the next non-pregnant HIV-seropositive patient presenting to the HIV treatment, control and prevention programme unit of the hospital and matched for social class (patient's educational status and husband's occupation, 24 location of residence, size of apartment, average weekly income, number and types of cars if any, types of electronic and electrical gadgets at home) was selected as a control.Any patient who experienced repeated attacks of malaria or other intercurrent infections was excluded from the study.
Upon recruitment, both pregnant and non-pregnant women had a data sheet completed that elicited information on socio-demographic variables, time since diagnosis of seropositive status, duration of antiretroviral therapy, and biochemical and haematological parameters.Specifically, the following biochemical measurements were done: serum electrolyte, urea and creatinine levels, serum fasting blood sugar (FBS), serum aspartate aminotransferase (AAT)/ glutamic oxaloacetic acid transaminase (SGOT), alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT), total bilirubin, serum amylase, serum cholesterol, very low-density lipoprotein (VLDL) and lactate dehydrogenase (LH).In addition, a full blood count (FBC -packed cell volume (PCV), white blood cell (WBC) count, platelet count and differentials) and CD4 cell count were performed.
The study was approved by the hospital's Human Ethics Committee and was carefully explained to the patients, and only those who gave informed written consent were recruited into the study.
The Statistical Package for Social Sciences (SPSS) version 13 was used for the data management and statistical analysis, with Fisher's exact test, the chi-square test or Student's t-test (as appropriate) being used for comparison of the mean absolute values and standard deviations (SDs).The level of significance was 0.05.

RESULTS
The socio-demographic profile and time since diagnosis and commencement of treatment are set out in Table I.The pregnant women had had their HIV diagnosis for periods ranging from 1 to 30 months (median 10 months) and had been on treatment for periods ranging from 1 to 30 months (median 8 months), while the non-pregnant women had had their HIV diagnosis for periods ranging from 14 to 29 months (median 17 months) and had been on treatment for periods ranging from 2 to 29 months (median 16 months).
The median age of the pregnant women was 29.4 years, with a range of 18 -36 years (mean 28.6, SD 4.6) and the median age of the non-pregnant women 30.2 years, with a range of 16 -42 years (mean 29.2, SD 3.9).The median parity in the pregnant women was 1.00, with a range of 0 -7 (mean 1.25, SD 1.59), and that for the non-pregnant women 2.00, with a range of 0 -13 (mean 2.10, SD 2.29).This difference was statistically significant (p<0.0001).The median estimated gestational age at booking was 26 weeks, with a range of 2 -42 weeks (mean 25.8, SD 8.13).In the pregnant group a median of 10 months had elapsed since the diagnosis of HIV, with a range of 1 -30 months (mean 10.27, SD 6.12), and in the non-pregnant group a median of 17 months had elapsed, with a range of 14 -29 months (mean 16.86, SD 1.69).This difference was statistically significant (p<0.0001).
Serum electrolyte, urea and creatinine levels in cases versus controls are set out in Table II.The mean serum urea and potassium levels, though within normal limits, were higher in non-pregnant than pregnant women, as were the mean serum aspartate aminotransferase (AAT)/ serum glutamic oxaloacetic acid transaminase (SGOT), alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) and serum amylase (Table III).However, the CD4 cell count was higher in the pregnant women than in the controls (p=0.001),while the haematological parameters were within normal limits and comparable between cases and controls (Table IV).Comparison of the mean CD4 count, total WBC count and PCV in the three trimesters of pregnancy did not reveal any statistically significant differences in the respective values.

DISCUSSION
A systematic review and meta-analysis of seven cohort studies from 1983 to 1996 suggested that there is an association between adverse maternal outcomes and pregnancy in HIV-infected women.The summary odds ratios for the risk of an adverse maternal outcome related to HIV infection and pregnancy were 1.8 (85% confidence interval (CI) 0.99 -3.3) for death, 1.41 (95% CI 0.85 -2.33) for HIV disease progression, and 1.63 (95% CI 1.00 -2.67) for progression to an AIDS-defining illness.This association appeared to be stronger in the one study in this group conducted in a resourcepoor setting. 2 The objective of the present study was to describe any biochemical and haematological differences in the plasma of pregnant and non-pregnant HIV-infected Nigerian women.In all women, the parameters assessed were within normal limits.The CD4 count was significantly higher in the pregnant compared with the non-pregnant controls, despite the fact that the non-pregnant women had been on antiretroviral drugs for longer.
Nutritional factors and intercurrent infections have been shown to play a role in disease progression in lowresource settings.These factors were controlled for in this study, as the two groups were matched for social class and women with intercurrent infections were excluded from the study.The prognosis for HIV disease in pregnancy is worse for patients with intercurrent infections such as malaria, urinary tract infections, sexually transmitted infections and parasitic infestation. 2,24alnutrition, infections and infestations are generally widespread in low resource-settings.
In conclusion, this study failed to show any independent association between pregnancy and abnormal blood parameters that may suggest disease severity in HIV-infected Nigerian women.It is reasonable to suppose that any increased morbidity and mortality of pregnancy may be modulated through the combined effects of nutritional factors, intercurrent infections and genetic factors.Efforts to address these are likely to contribute to reducing the burden of HIV morbidity in infected pregnant Nigerian women.

coMPariSon oF tHe SUMMarY StatiSticS oF tHe Socio-DeMograPHic ProFile, DUration oF DiagnoSiS anD treatMent oF caSeS v. controlS
SD = standard deviation; EGA = estimated gestational age.taBlei.