EFFECT OF ETHANOLIC EXTRACT OF OCIMUM GRATISSIMUM LEAVES ON PLACENTAL AND BIRTH WEIGHT AND EARLY POSTNATAL GROWTH OF THE OFFSPRING OF DIABETIC PREGNANT RATS

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CHAPTER ONE
1.0     INTRODUCTION
1.1 Background of the Study
There is evidence that the diabetic intrauterine milieu has adverse consequences for fetal life. Maternal diabetes is characterized by an increased placental transport of glucose and other nutrients from the mother to the fetus, resulting in macrosomia (Freinkel, 1980). However, in severe maternal diabetes complicated by vasculopathy and nephropathy, intra-uterine growth restriction can be present (Van and Holemans, 1998).
Maternal diabetes mellitus can be pregestational or gestational. For pregestational diabetes, type 1 DM can result from the body’s failure to produce enough insulin (WHO, 2014) while type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin’s action (WHO, 2014). Gestational diabetes occurs when pregnant women without a previous history of diabetes develop a high blood glucose level (WHO, 2014).
As with diabetes mellitus in pregnancy, babies born to mothers with untreated gestational diabetes are typically at increased risk of problems such as being large-for-gestational-age (which may lead to delivery complications), low blood sugar, and jaundice (Thomas and Moore, 2005). It can also lead to seizures or stillbirth (Thomas and Moore, 2005).
Maternal diabetes is also associated with concentration changes of various hormones, cytokines and metabolites in the maternal as well as fetal circulation. Hence, these diabetic-associated changes are likely to affect the placenta, because receptors, transporters and enzymes, the primary targets of circulating molecules, are expressed often asymmetrically, on both placental surfaces (Desoye and Hauguel-de-Mouzon, 2007). Altered placental function in gestational diabetes may include changes in invasion ultimately leading to an enhanced risk of early pregnancy loss, growth restriction and pre-eclampsia, as well as a long-term stimulatory effect on placental growth leading to placentomegaly, which is frequently associated with diabetic pregnancies (Kaufmann et al., 2003).
Gestational diabetes mellitus (GDM) poses a risk to mother and child. The two main risks GDM imposes on the baby are growth abnormalities and chemical imbalances after birth, which may require admission to a neonatal intensive care unit (Metzger et al., 2008). Infants born to mothers with GDM are at risk of being both large-for-gestational-age (Metzger et al., 2008) in unmanaged GDM, and small-for-gestational-age and intrauterine growth retardation in managed GDM (Setjiet al., 2005). Macrosomia in turn increases the risk of instrumentation deliveries (e.g forceps, ventouse and caesarean section) or problem during vaginal delivery (such as shoulder dystocia) (Kelly et al., 2005). Neonates born from women with consistently high blood sugar levels are also at an increased risk of low blood glucose, jaundice,  high blood cell mass (polycythemia) and low blood calcium (hypokalemia) and magnesium (hypomagnesemia) (Jones, 2001).
Untreated GDM also interferes with maturation, causing immature babies prone to respiratory distress syndrome due to incomplete lung maturation and impaired surfactant synthesis (Jones, 2001).
1.2 Statement of the Problem/ Justification
It is well established that the diabetic intrauterine environment has adverse consequences for fetal life.These adverse consequences include neural tube defects, cognition deficit, and malformation of fetal brain to mention but a few(Freinkel, 1980).
The treatment of GDM is somehow problematic as care has to be taken to avoid low blood sugar levels due to excessive insulin injections. More injections can result in better control but requires more effort and there is no consensus that it has large benefits (Nahum, 1999; Kelly et al., 2005; Walkinshaw, 2006). With the advent of modern obstetric care, the incidence of congenital malformations and neural tube defects have drastically reduced, but macrosomic babies and associated complications remain high (Combs et al., 1992; Irene et al, 2015).
Ocimumgratissimumis widely consumed locally by pregnant women in the form of herbal tea in some part of Nigeria as it has been found to reduce birth weight which invariably makes delivery easy (Aizenabor, 2012). Studies have equally shown that extract of Ocimumgratissimum has been used to treat diabetes mellitusand its hypoglycemic effect has been confirmed in vivo(Casanova et al,2014). Unlike most anti diabetic drugs, a study revealed that aqueous extract of O. gratissimumleaf can significantly reduce postprandial hyperglycaemia in type-2 diabetic model rats, without the risk of hypoglycemia (Oguanobiet al. 2012).  However, there is paucity of data on the effect of the extract of OG on diabetic pregnancies, and fetal outcome. This study was therefore undertaken to investigate whether Ocimumgratissimum, a confirmed anti-diabetic agent, would have any effect on placentomegaly and macrosomia, which are usual complications of diabetic pregnancy.
1.3 AIM

This study was carried out to investigatethe effect of ethanolic extract of ocimumgratissimumleaves on placental and birth weight and early postnatal growth of the offspringsof diabetic pregnant rats....

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