**6.2. Role of lipid metabolism in pathogenesis of intrauterine growth restriction (IUGR)[17]**

It was proposed that the abnormal lipid metabolism noted in pre-eclampsia was in an attempt to compensate for the placental insufficiency [97], given the physiological role of gestational hyperlipidaemia in supplying both cholesterol and triglycerides to the rapidly developing fetus [98]. In contrast Dabi[17], et al demonstrated that concentration of total cholesterol (TC), TGs, LDL and VLDL observed to increase with increasing gestational age in normal pregnancies, these lipids and lipoproteins decreased with increasing gestational age in pregnancies with IUGR. HDL did not change significantly. These findings certainly indicated that pregnancies complicated by IUGR are associated with an abnormal lipid profile, particularly decreased levels of TC, TGs, LDL and HDL(Dabi [17],et al Sattar[18], et al), see table 7


transport TGs and other esterified lipid to the fetus (23)

receptors are decreased in the placenta of women with PE.

clinical follow-up later in life.

**(IUGR)[17]** 

metabolism can be affected due to an altered placental transfer of lipids. Maternal TGs does not cross the placenta. It has to be hydrolyzed by human placental LPL into FFAs which is then transported to the fetus. Fetal TG levels are therefore dependent on maternal TGs. Moreover, the placenta also contains receptors for VLDL, LDL and HDL which also

Catarino[16],et al observed that lipid levels observed in umbilical cord blood (UCB) from normal pregnancy were significantly lower than those found in maternal blood except for HDL, which was similar. In addition, LDL:HDL ratio in neonates of normal pregnancies are much lower than the values in normal pregnant mothers. In contrast, lower values of HDL and ApoA-1 and higher TG levels were noted in neonates of PE mothers. In addition, higher LDL:HDL ratio, a decreased HDL which is more pronounced than ApoA-1, suggest that fetal loading of ApoA-1 with cholesterol is significantly less in PE. Hence fetal HDL composition is likely to be altered due possibly to enrichment with the enhanced hypertriglyceridaemia. Also observed in the PE is a significantly higher value of TGs in UCB which is parallel with significant increased TGs in maternal blood. Since hypertriglyceridaemia is considered a maternal adaptation in order to assure fetal growth in normal pregnancy, the exaggerated hypertriglycedaemia noticed in PE mothers could be a compensation pathway to face the uteroplacental hypoperfusion in order to enhance FAs transfer to the fetus. In line with this, it seems LPL expression is also enhanced in PE as was observed in IUGR [94]. Taken together, it appears lipid transfer from maternal side in PE mothers to their fetus are altered in both quantity and quality and does not seems to be protective as noticed in neonates of normal pregnancies. In support of this PE has been associated with reduced fetal birth weight [95, 96] and the expression of lipoprotein

PE pregnancies is associated with an enhanced hypertriglyceridaemia, which seems to have a negative impact on fetal lipid profile, as reflected by a higher atherogenic LDL:HDL ratio, decreased HDL, disproportionate decreased in HDL and ApoA-1 and enhanced hypertriglycedaemia, children born in pregnancies associated with PE deserve a closer

**6.2. Role of lipid metabolism in pathogenesis of intrauterine growth restriction** 

It was proposed that the abnormal lipid metabolism noted in pre-eclampsia was in an attempt to compensate for the placental insufficiency [97], given the physiological role of gestational hyperlipidaemia in supplying both cholesterol and triglycerides to the rapidly developing fetus [98]. In contrast Dabi[17], et al demonstrated that concentration of total cholesterol (TC), TGs, LDL and VLDL observed to increase with increasing gestational age in normal pregnancies, these lipids and lipoproteins decreased with increasing gestational age in pregnancies with IUGR. HDL did not change significantly. These findings certainly indicated that pregnancies complicated by IUGR are associated with an abnormal lipid profile, particularly decreased

levels of TC, TGs, LDL and HDL(Dabi [17],et al Sattar[18], et al), see table 7

**Table 7.** Lipid and Lipoprotein changes with advancing gestational age(Group A=Pts with IUGR and Group B=Pt with normal pregnancy)

It is well known that normal fetal development needs the availability of both essential fatty acids and long chain polyunsaturated fatty acids (LCPUFAs), thus making a persuasive case indicating a relationship between nutritional status of mother during gestation reflecting her lipid profile and fetal growth. From observations in study by Dabi[17], *et al* and similar findings in other studies, it is possible that the decreased concentrations of TC, TGs, VLDL and LDL may have decreased availability of glycerol, LCPUFAs and essential fatty acids to the fetuses of mothers with otherwise normal pregnancy ultimately leading to IUGR. In addition to above findings, Sattar[18], *et al* observed a decreased in levels of VLDL-2 and IDL in IUGR pregnancies, which are precursors of LDL. Taken together, the decreased cholesterol levels (mainly reflected as decrease LDL) may be due to decreased synthesis of LDL in women with IUGR. The HDL: apoA and apoB:apoA ratios were found to be higher in the IUGR and was suggested that blood lipid modifications in the IUGR group are partly secondary to changes in HDL metabolism and the competitive inhibition of fibrinolysis by apoB which is increased in pregnancy with IUGR. This indicated that apoA: apoB ratio could be a good marker for the early detection of IUGR. Taken together also, these findings definitely generated considerable interest in certain aspects of fetal growth and its relationship to blood lipid levels during pregnancy. However, more study is recommended aiming at analyzing the otherwise normal pregnancies associated with IUGR, particularly to elucidate the hypothesis that the decrease in TGs(and particularly LDL and VLDL-2) compromises the supply of substrates for energy production to the growing fetus resulting in IUGR. The effect of the changes in lipid profile and its translation in changes in blood viscosity needs more extensive research including detailed analyses of apoA and apoB levels in these patients.

#### **6.3. Pregnancy-induced Supraphysiologic hyperlipidaemia**

It is well known in literature that hyperlipidaemia is a normal metabolic adjustment in pregnancy benefiting both mother and the fetus. However, some women may not be able to adapt to the hyperlipidaemic stress of pregnancy. In addition, in similarity with other gestational metabolic syndromes such as gestational diabetes mellitus (GDM), pregnancyinduced hypertension (PIH), pre-eclampsia, eclampsia, etc, some of them may develop a state of Supraphysiologic hyperlipidaemia, defined as lipid levels greater than 95th percentile for the corresponding gestational age, because of failed adaptation to requirement of pregnancy. Supraphysiologic hyperlipidaemia may serve as a marker for what is cited by Montes[99], et al, a 'prelipaemia' in the same way that GDM is a marker for pre-diabetes.

The characteristics of Supraphysiologic hyperlipidaemia, as observed by Montes[99], et al, are that, the antepartum hyperlipidaemia may return to normal levels postpartum more slowly than normal, the presence of HDL cholesterol concentrations that are persistently low antepartum and postpartum, and the patients do have hyperlipidaemic family members. In contrast, hypercholesterolemia is not greatly exaggerated in pregnancy among these women. Are there future consequences of the pregnancy-induced Supraphysiologic hyperlipidaemia? Long-term follow-up studies of women with genetically wellcharacterized disorders of lipoprotein metabolism are required to determine if an abnormal lipoprotein response in pregnancy can identify prelipaemic subjects and distinguish among the major disorders of lipoprotein metabolism. Identification of the prelipaemia will provide an opportunity to study prospectively the natural progression, potential for atherosclerosis, and possible treatment of hyperlipidaemia from early adulthood.
