SERUM HOMOCYSTEINE, VITAMIN B12 AND FOLATE IN GHANAIAN WOMEN WITH HYPERTENSIVE DISORDERS OF PREGNANCY

ABSTRACT
Hypertensive disorders of pregnancy are common complication occurring during pregnancy, and are associated with maternal and fetal mortality and morbidity. Hyperhomocysteinaemia, a known risk factor for vascular disease, could play a significant role in the aetiopathogenesis of pregnancy-induced hypertension (PIH). This study, therefore, evaluated the maternal serum concentrations of homocysteine, vitamin B12 and folate in normal pregnancy (NP) and pregnant women presenting with preeclampsia (PE) and gestational hypertension (GH). This randomized case-control study involved 30 PE patients, 30 GH patients and 30 age-matched normotensive uncomplicated pregnant women (control group) in the third trimester of pregnancy. After obtaining an informed consent from each participant, information on socio-demographic characteristics, medical history and previous obstetric history was obtained. Blood pressure, anthropometric measurements and blood sample were taken for the estimation of homocysteine, vitamin B12, folate and lipid profile of each woman. Mean levels of maternal serum homocysteine was significantly higher in PIH, PE and GH patients when compared with NP women (p < 0.05). Although mean vitamin B12 and folate were decreased in the PIH, PE and GH patients when compared with the normal pregnant women, it was only in the PIH and the PE patients that the differences were significant (p < 0.05). In the PIH patients, there was a statistically significant negative correlation between homocysteine and folate (r=-0.283, p < 0.05). While none of the normal pregnant women had intrauterine growth restriction (IUGR) or low birthweight (LBW), thirty-five percent (35%) and twenty-eight percent (28%) of the participants with PIH demonstrated IUGR and LBW respectively. Except for the GH patients where estimated foetal weight (EFW) was insignificantly lower, EFW and birthweight were significantly lower in the PIH (PE and GH) patients when compared with the NP women. The use of the contraceptive Depo-Provera prior to pregnancy was significantly associated with about thirty-fold (30) increase in the odds of developing preeclampsia (OR=29.71, p < 0.001). There was a significant (p < 0.01) positive correlation between homocysteine and blood pressure (systolic and diastolic blood pressure) in the PIH patients. Maternal serum concentration of homocysteine is altered in PIH (PE and GH) when compared with normal pregnancy, and this imbalance is depicted by an elevated serum concentration of homocysteine with a correspondingly decreased serum concentrations of vitamin B12 and folate. Hyperhomocysteinaemia in pregnancy could play a significant role in the aetiopathogenesis of pregnancy induced hypertension, intrauterine growth restriction and low birthweight. Furthermore, the use of the contraceptive Depo-Provera by women prior to pregnancy predisposes them to a high risk of developing preeclampsia.


CHAPTER 1
INTRODUCTION
1.1 BACKGROUND
Hypertensive disorders are among the common complications during pregnancy and contributes significantly to maternal and perinatal morbidity and mortality worldwide Leveno (2013). Pregnancy-induced hypertension (PIH) is a generic term used to define significant rise in blood pressure (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) during pregnancy, occurring after 20 weeks of gestation in a woman without prior hypertension. When accompanied by significant proteinuria, the disorder is termed preeclampsia and when it is without significant proteinuria, it is termed gestational hypertension (Leeman & Fontaine, 2008; Leveno, 2013; Owiredu et al., 2012).

Gestational hypertension is generally characterized by good maternal and foetal outcomes. Gestational hypertension is referred to as transient hypertension if preeclampsia does not develop and the blood pressure has returned to normal by 12 weeks postpartum. Importantly, women with gestational hypertension may develop other signs associated with preeclampsia - for example, headaches, epigastric pain, or thrombocytopenia - which influences management (Leeman & Fontaine, 2008; Leveno, 2013).

Although pathophysiology of preeclampsia is poorly understood, endothelial dysfunction is most popularly hypothesized to be a central pathophysiological feature of preeclampsia leading to altered vascular reactivity, loss of vascular integrity and activation of the coagulation cascade (Sangeeta et al., 2013; Var et al., 2003).

The incidence of preeclampsia is commonly cited to be about 5% although remarkable variations are reported (Leveno, 2013). The incidence is influenced by parity, with nulliparous women having a greater risk when compared with multiparous women. Other risk factors associated with preeclampsia include multiple pregnancy, history of chronic hypertension, maternal age over 35 years, excessive maternal weight (Leveno, 2013). Intrauterine growth restriction (IUGR), pre-term delivery, low birth weight, foetal death and neonatal death due to complications of pre-term delivery are common perinatal outcomes associated with pregnancy-induced hypertension (Lehrer et al., 1993; Leveno, 2013; Mahal et al., 2009).

Elevated serum homocysteine has been claimed as a risk factor for vascular endothelial cell injury in preeclampsia and its consequences (Mahal et al., 2009). Experimental studies revealed that moderately elevated homocysteine concentrations may induce cytotoxic and oxidative stress, leading to endothelial cell impairment. Additionally, exposure of trophoblast cells to homocysteine (20 µmol/L) may increase cellular apoptosis and lead to inhibition of trophoblastic function (Bergen et al., 2012; Mahal et al., 2009)

Homocysteine (Hcy), a sulfur-containing amino acid, is formed by the demethylation of the essential amino acid methionine. It can be recycled into methionine or converted into cysteine with the aid of B-vitamins. Elevated serum homocysteine beyond the normal reference range (5-15 µmol/L) is traditionally referred as hyperhomocysteinaemia. Hyperhomocysteinaemia is further subcategorized into moderate (15-30 µmol/L), intermediate (30-100 µmol/L), and severe (>100) µmol/L (Ciaccio et al., 2008; Selhub & Mayer, 1999). High serum homocysteine levels could result from a genetic defect in enzymes involved in homocysteine metabolisms (defects in cystathionine β synthase, methionine synthase, or methelenetetrahydrofolate reductase); nutritional deficiency in vitamins (vitamins B6, vitamins B12 and folate), renal failure for effective amino acid clearance and drug interactions (Lawrence-de-Koning et al., 2003).

The mean homocysteine levels normally decrease with gestation either due to physiological response to the pregnancy, increase in estrogen, hemodilution from increased plasma volume or increased demand for methionine by both the mother and fetus. The levels are the lowest during second trimester of pregnancy and increase in the second half of the third trimester of pregnancy (Mahal et al., 2009; Mukhopadhyay et al., 2014). Dyslipidemia also plays a role in the aetiopathogenesis of pregnancy-induced hypertension. Human gestation is associated with an atherogenic lipid profile that is further enhanced in preeclampsia. Such profile may also be a potential contributor to endothelial cell dysfunction, which is a central feature in the pathophysiology of preeclampsia (Mahal et al., 2009).

Some studies have indicated that the complications of preeclampsia are low birth weight, intrauterine growth restriction (IUGR) and fetal loss (Ghike et al., 2011; Mukhopadhyay et al., 2014). However, data on such study in Ghana and the sub-Saharan region remain scarce.

1.2 PROBLEM STATEMENT
Despite the numerous strategies devised by the international community to curb maternal mortality, it still remains a major Public Health challenge (UN, 2009). Globally, maternal mortality is the leading cause of death among females aged 15-49 years old. More than 1500 women die each day from pregnancy related causes resulting in an estimated 550 000 maternal deaths annually (UN, 2009). Preeclampsia is a pregnancy specific disorder, which complicates 7-10% of all gestations. Approximately 10-15% of maternal deaths in developing countries are associated with preeclampsia (Mahal et al., 2009). Pregnancy-induced hypertension causes a number of problems, including intrauterine growth restriction, fetal loss, and low birth weight, for both mother and baby (Ghike et al., 2011; Leeman & Fontaine, 2008; Sangeeta et al., 2013). Some studies have linked maternal homocysteine levels to pregnancy-induced hypertension and pregnancy outcomes such as intrauterine growth restriction, fetal loss, and low birth weight (Ghike et al., 2011; Mukhopadhyay et al., 2014). However, evidence on this is conflicting with some studies stating that serum homocysteine values have no correlation to maternal and fetal outcome (Infante-Rivard et al., 2003). Also, data on this in sub-Saharan Africa remain scarce.

1.3 JUSTIFICATION
Hyperhomocysteinemia, a known risk factor for vascular disease, was incriminated as one of the predisposing risk factors for pregnancy-induced hypertension (Ghike et al., 2011; Mukhopadhyay et al., 2014). Serum homocysteine levels were found to be significantly high in preeclamptic patients, with several studies relating hyperhomocysteinaemia to preeclampsia and other adverse pregnancy outcomes such as IUGR and low birth weight (Ghike et al., 2011; Mukhopadhyay et al., 2014). If this study establishes a significant association between maternal homocysteine levels and pregnancy complications such as preeclampsia, IUGR and low birth weight, then maternal serum homocysteine could be a predictive marker well ahead of blood pressure changes and ultimately provide scope for prevention and treatment by supplementation of B12 and folic acid.

1.4 AIM
The aim of this study therefore was to investigate maternal concentrations of serum homocysteine, vitamin B12, folate and lipids in pregnancies complicated by pregnancy-induced hypertension and to determine whether these parameters were associated with intrauterine growth restriction (IUGR) and low birth weight.

1.5 OBJECTIVE
Specifically, this study sought:

To assess the serum concentrations of homocysteine, vitamin B12, folate and lipid profile in pregnancy induced hypertension (gestational hypertension and preeclampsia) and normal uncomplicated pregnancies.

To determine the IUGR and infant body weight in study participants.

To determine the correlation between the studied parameters.

1.6 HYPOTHESIS
Elevated serum homocysteine concentration is significantly correlated with pregnancy-induced hypertension, intrauterine growth restriction and infant body weight.

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Item Type: Ghanaian Project Material  |  Attribute: 127 pages  |  Chapters: 1-5
Format: MS Word  |  Price: GH50  |  Delivery: Within 30Mins.
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