Prof. Ella Ophie

Are macrosomic offsprings prone to higher incidence of atherosclerotic assocaited diseases in their later life?

Background: Established risk factors for cardiovascular diseases and diabetes mellitus are more prevalent in maternal diabetes and increased BMI. It has long been postulated that pathogenic events during fetal development influence atherosclerosis-related diseases later in life. A new paradigm for prevention of obesity has emerged in recent years, evolved from the notion that environmental factors in early life and in utreo can have a profound influence on lifelong health. The etiological factors underlying the links between birth weight and later obesity, or other chronic diseases associated with atherosclerosis and cardiovascular diseases (CVD) are not known and, thus, cannot be quantified. Peripheral polymorphonuclear leukocytes (PMNLs) are primed in chronic diseases associated with metabolic syndrome and in clinical states associated with atherosclerosis. These PMNLs induce vascular endothelial damage, which accompanies these clinical states.

Working hypothesis and aims: We suggest that the higher birth weight which is associated with higher attained BMI, predisposing the offspring to future chronic atherosclerotic and cardiovascular diseases. Since we have shown that primed/activated PMNLs are the culprit in such clinical states at adulthood, we imply that biomarkers related to PMNL activation, will appear in macrosomic children, regardless if their mothers are diabetic or not. The specific aims of the study are: 1. Characterization of mothers BMI in relation to offspring BMI/weight; 2. characterization of PMNL activation   3. assaying PMNL-related constituents in blood of mothers and offspring, such as myeloperoxidase (MPO); 4. Determination of sera oxidative stress and inflammatory markers in mothers and offspring, to establish an early marker that can predict the later high risk factors for developing atherosclerosis and CVD.

Study design:

Study groups will include 60 diabetic and 60 non-diabetic, healthy mothers as a control group. In this study will be included only mothers who will undergo cesarean section for obstetric indications.

All babies will be divided according to birth weight to macrosomic (³4Kg.) and normal weight (>  X < 4Kg), and according to their mother BMI or diabetes. 4 groups of newborns: 1.Macrosomic babies of diabetic mothers.

2. Macrosomic babies of nondiabetic mothers. 3. Normal weight babies of diabetic mothers. 4. Normal weight babies of non-diabetic mothers.

 Clinical parameters and peripheral venous blood will be drawn from each mother and baby. Blood will be drawn from mothers and from the umbilical vein for the determination of biochemical and hematological parameters,  for CD11b on  PMNLs as measures of cell priming, plasma MPO as a marker for PMNL degranulation, and the levels of IL-6 as an inflammatory marker.

Expected results: After delivery, the extent of increased PMNL priming is expected concomitantly with increased MPO levels in the macrosomic babies. Women and babies whose levels of PMNL priming and MPO counts will be higher than normal, may probably belong to the high risk group to develop cardiovascular complications and atheroscleriosis.

Importance:The preponderance of epidemiological evidence indicates that higher birth weigth is associated with increased risk of adiposity (5) and metabolic syndrome - risk factors for adult CVD and atherosclerosis. Understanding the relationships between PMNL priming and risk of future CVD will enable tracing the fetal origin of adult diseases, identifying the population at risk to develop CVD.

Probable implications to Medicine: Early diagnosis will enable clinical intervention, to reduce oxidative stress and inflammation, possibly preventing future complications.