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AIDS), Was Reported in 1981 in the United States (CDC, 2006) CHAPTER ONE INTRODUCTION 1.1 Background of study The first case of what was later called acquired immunodeficiency syndrome (AIDS), was reported in 1981 in the United States (CDC, 2006). Since then, the human immunodeficiency virus (HIV) epidemic expanded world-wide with varying prevalence in different regions of the world. In the United States; at the end of 2003, approximately 1,039,000-1,185,000 persons in the United States were living with HIV/AIDS, an estimated 24%-27% of whom were unaware of their infection. There has been various global interventions with varying outcomes including the decrease in overall AIDS incidence, the substantial increase in survival after AIDS diagnosis (especially since highly active antiretroviral therapy [HAART] became the standard of care in 1996), and the continued disparities among racial/ethnic minority populations. Comprehensive national surveillance system, expanding the use of new HIV-testing technologies, promoting knowledge of HIV sero-status, and improving access to care and prevention interventions have also been strongly advocated (CDC, 2006). Since the beginning of the epidemic, almost 78 million people have been infected with the HIV virus and about 39 million people have died of HIV. Globally, 35.0 million [33.2–37.2 million] people were living with HIV at the end of 2013. An estimated 0.8% of adults aged 15–49 years worldwide are living with HIV, although the burden of the epidemic continues to vary considerably between countries and regions. Sub-Saharan Africa remains most severely affected, with nearly 1 in every 20 adults living with HIV and accounting for nearly 71% of the people living with HIV worldwide (WHO, 2015). 1 In Nigeria, according to UNAID report (2015), about 3.4million Nigerians are living with HIV. In 2013 Nigeria continued her commitment towards meeting the vision of Millennium Development Goal (MDG) to halt and reverse HIV and AIDS epidemic in the country and promote the achievement of universal access to HIV/AIDS prevention, treatment, care and support in line with global commitments. With the valuable support of local and international partners, the country has seen the epidemic profile change significantly from HIV prevalence of 5.8% in 2001 to 4.1% in 2010. (Nigeria GARPR, 2014). HIV infection in pregnancy can be very challenging. The current prevalence rate of HIV infection among pregnant women in Nigeria ranges from 3% to 8% in different regions of the country (Sagay, et al., 2005; Egesie and Mbooh, 2008; FMOH-PMTCT Guideline, 2010; Umeononihu, et al., 2013) The HIV prevalence following repeat testing in late pregnancy in Nnewi-Nigeria is 3.91% (Umeononihu et al., 2013). HIV infection has been reported to have little effect on pregnancy outcome or complications in the developed world. Adverse pregnancy outcomes have, however, been reported more commonly in a number of African studies including complications of both early and late pregnancy. HIV may be the direct cause or a marker of a complex interaction of related medical and social conditions that affect pregnancy (WHO/UNAID, 1998) HIV infection has been linked to a higher rate of spontaneous abortion. Higher rates of ectopic pregnancy have been reported in HIV-positive women than in uninfected women, which may be related to the effects of other concurrent sexually transmitted diseases. Preterm labour may be more common in HIV-positive women, with rates as high as double those rates seen in uninfected women (WHO/UNAID, 1998). Preterm rupture of membranes may also be increased in HIV-positive women and abruptio placentae has been described as more common in HIV-positive women. There 2 is little difference in the birth weight of babies born to HIV-positive mothers in developed countries. In contrast, low birth weight has been reported in some studies in developing countries (WHO/UNAID,1998). High rates of infant and maternal mortality have been reported world-wide (Uzoigwe and John, 2004; Oladapo et al., 2006; Hill et al., 2007; Rasch, 2007). Considerable efforts in assessing fetal mortality are being made in certain parts of the developed countries (MacDorman and Kirmeyer, 2009). In the contrary, assessment of fetal mortality in Nigeria is far below expectation. Little is known about the biochemical investigation of intra-uterine fetal demise (IUFD), and threatened abortions in Nigeria in spite of their obvious occurrences (Oladapo et al., 2007; Chigbu et al., 2009). Pregnancy loss admittedly occurring at various health care levels at various stages of pregnancy in Nigeria are often unexplained, and at best grossly under investigated. This leaves a lot of information gap that need to be explored and will be very helpful if provided. The determination of a consistent biochemical index will elucidate potential threats to normal pregnancy, and will suggest precautionary obstetric measures in Nigeria. Already several mortality indices fail to favour the developing countries compared to the developed countries (Murray and Lopez, 1997). In addition, perinatal mortality has been shown to occur at a higher rate among black Americans than their white counterparts (MacDorman and Kirmeyer, 2009). Pregnancy usually runs a course of about 40 weeks in human starting with the fertilization of the ovum by spermatozoa in the fallopian tube of the woman. This is followed by implantation, sequential, rapid and systematic cell division, differentiation, specialization, and maturation usually resulting to a foetus. In obstetrics and gynaecology, normal pregnancy has been divided into three stages as first, second and third trimesters (Andelman, 1973; Ndububa, 2010). In normal pregnancy, the integrity of the foetus and its ability to develop normally is often dependent in part or in whole on certain physiological, biochemical, physical, and psychological state of the mother. At certain stage of gestation, the 3 mother undertakes some basic functions of life such as respiration, nutrition, excretion, and thermoregulation etc for the foetus. It is a common finding that the mothers nutritional, and biochemical needs are often compromised in favour of the foetus (Anetor et al., 2003; Ikaraoha et al., 2005; Idowu et al., 2005).The journey from conception to birth is fraught with danger. Pregnancy is often associated with some level of stress on the mother which invariably transcends to the foetus (Ndububa, 2010). In maternal distress, foetal life is however threatened in varying degrees commensurate with the nature and extent of maternal distress. It has also been noted that in some situations, certain deleterious responses of the mother could pose a serious threat to the foetus. Pregnancy constitutes a major challenge to the maternal immune system, which must tolerate foetal alloantigens encoded by paternal genes. Local factors at the maternal-foetal interface are required to maintain such tolerance and to assure foetal survival (Salmon, 2004). Some serum autoantibodies have association with pregnancy outcomes. The anti-phospholipid antibodies (aPLa) are known to have pathogenic effects on pregnancy outcome. They may react with foetal trophoblast as well as with maternal decidual cells directly inducing a defective placentation. In addition, the thrombogenic effect of aPL may cause placental infarctions with the consequent impairment of the blood exchange between maternal and foetal circulation (Vinatier, et al., 2001). There is evidence that thyroid autoimmunity is an important risk factor for miscarriage and preterm birth (Girardi, 2008).The presence of thyroid autoantibodies is relatively common in women of reproductive age. The prevalence ranges from 6% to 20%,(Girard, 2008) Studies have reported an association between the presence of thyroid autoantibodies, particularly thyroid peroxidase antibodies and adverse pregnancy outcomes, including miscarriage, preterm birth, and adverse neurodevelopmental sequelae in children (Surgi et al., 2004). It is thought that the presence of 4 thyroid autoantibodies could be associated with a subtle deficiency of thyroid hormones required in pregnancy (McIntyre, 2003) Cubillos et al., (1997) found that the incidence of ANAs was 31.8% in patients with a history of miscarriages , but only 5.7% in 35 healthy patients with proven fertility and no history of pregnancy loss or autoimmune disease. Pregnancy associated plasma protein-A (PAPP-A) can be very useful indicator of present pathology or future complications of pregnancy. PAPP-A is a 400kDa secreted homodimeric glycoprotein that belong to the metzincin superfamily of metalloproteases. It is best known as a regulator of insulin- like growth factor II (IGF-II) activity and plays a crucial role in placental development (Qin et al., 2007). The cells most associated with PAPP-A expression are endometrial stromal fibroblasts and extravillous trophoblasts (Glerup et al., 2007). During placental growth, IGF-II seems to be the dominant insulin-like growth factor. It promotes steroidogenesis, glucose transport, and trophoblast (foetal tissue) invasion of the uterine endometrium (decidua). Pregnancy associated plasma protein- A is raised in pre-eclamptic toxaemia, antepartum haemorrhage and premature labour. Pregnancy involves a lot of hormonal interplay. Variations in the levels of these hormones might imply pregnancy risk of varying degree. For instance, total estriol is lowered in foetal growth retardation and the unconjugated steroid rise in pre-eclampsia and lowered in retarded foetal growth (Lin, 1977; Lin and Halbert, 1978; Hughes
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