Although the causes of high birthweight include both genetic and environmental factors, the rapid increase in the prevalence of large newborns has environmental causes. The evidence is extensive that maternal overweight and associated metabolic changes, including type 2 and gestational diabetes, play a central role. There is a paucity of studies of the effect of intervention before and/or during pregnancy on the risk of having an 'overweight newborn'. It appears rational, however, that preventive measures should primarily be implemented before pregnancy and should include guidance about nutrition and physical activity in order to reduce the prevalence of overweight. In pregnancy, limited weight gain, especially in obese women, seems to reduce the risk of macrosomia, as do good control of plasma glucose among those with diabetes. Prediction of fetal macrosomia remains an inaccurate task even with modern ultrasound equipment. There is little evidence that routine elective delivery (induction or caesarean section) for the mere reason of suspected macrosomia should be employed in a general population. Vaginal delivery of a macrosomic fetus requires considered attention by an experienced obstetrician and preparedness for operative delivery, shoulder dystocia and newborn asphyxia.

Human low density lipoprotein (LDL) was incubated with an established line of rabbit aortic endothelial cells. Density gradient fractionation showed a time-, concentration-, and temperature-dependent increase in the average density ofthe LDL (from about 1.036 to as high as 1.070 g/ml). Incubation without cells or with other types of cultured cells (fibroblasts, henatocytes, 3T3-L1 cells) caused no significant change in density. '2I-Labeled LDL ('25I-LDL) recovered after incubation with endothelial cells (EC-modified LDL) was taken up and degraded 3 to 4 times more rapidly than control LDL by resident mouse peritoneal macrophages and by an established tumor line of mouse macro hages (J774 cells). Macrophage degradation of EC-modified 5I-LDL exhibited saturation kinetics (>85% inhibited by excess unlabeled EC-modified LDL). Degradation was also inhibited by unlabeled acetylated LDL and, conversely, unlabeled ECmodified LDL inhibited degradation of acetylated '2'I-LDL. Incubation of LDL with conditioned medium removed from endothelial cell cultures modified neither its density nor its rate of degradation by macrophages. These studies show that endothelial cells have the potential to metabolically modify the LDL molecule, generating a form that is more rapidly degraded by macrophages and that is recognized by the macrophage receptor for acetylated LDL. This process may play a significant role in the pathogenesis of atherosclerosis.

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Even modest increases in maternal BMI were associated with increased risk of fetal death, stillbirth, and neonatal, perinatal, and infant death. Weight management guidelines for women who plan pregnancies should take these findings into consideration to reduce the burden of fetal death, stillbirth, and infant death.

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Low density lipoprotein (LDL) conditioned by incubation in the presence of rabbit aortic or human umbilical vein endothelial cells (endothelial cell-modified LDL) was degraded by macrophages three to five times more rapidly than LDL incubated in the absence of cells (control LDL). This enhanced degradation occurred mostly via a high affinity, saturable pathway related to the pathway for macrophage uptake of acetylated LDL. Conditioning LDL with cultured aortic smooth muscle cells had a qualitatively similar but smaller effect; conditioning with fibroblasts had no effect. Conditioning very low density lipoproteins or high density lipoproteins with endothelial cells did not affect subsequent metabolism of these lipoproteins by macrophages. Endothelial cell-modified LDL, while degraded more rapidly than control LDL by macrophages, was degraded more slowly by cultured smooth muscle cells and by human skin fibroblasts. Degradation of endothelial cell-modified LDL by macrophages was accompanied by stimulation of cholesterol esterification, inhibition of cholesterol synthesis, and a net increment in total cellular cholesterol content. Thus, a biologically generated modification of LDL is described that markedly alters cholesterol metabolism of macrophages and, consequently, may play a role in foam cell formation during atherogenesis. (Arteriosclerosis 3:149-159, March/April 1983) T he biological mechanisms leading to the formation of foam cells in atherosclerotic lesions have yet to be clarified. It is generally accepted that a significant fraction of foam cells is derived from cells of the mononuclear phagocyte system, 1 -3 and that the major portion of the cholesterol in atheromata is derived from plasma LDL. Yet, paradoxically, the capacity of macrophages to take up native LDL is relatively low, 4 suggesting the possibility that not LDL itself but some modified form of it is actually responsible for the delivery of cholesterol to the macrophage. Several chemically modified forms of LDL (acetylated LDL, 4 acetoacetylated LDL, 5 and malondialdehyde-conjugated LDL 6 ) are taken up by macrophages several times faster than is native LDL. There has, however, been no evidence for the occurrence of such chemically modified forms in vivo nor any evidence that they can be formed biologically. It has been reported that some malondialdehyde-conjugated LDL is formed in vitro from LDL during platelet aggregation. 6 We have previously reported that conditioning of human LDL with cultured rabbit aortic endothelial cells converts it to a form that is taken up and degraded by murine macrophages at rates three to five times the rate for control LDL. 7 The LDL conditioned by prior incubation with endothelial cells (endothelial cell-modified LDL; EC-modified LDL) was taken up by macrophages and degraded via a high affinity, saturable pathway related at least in part to the pathway for uptake of acetylated LDL. 7 The present studies show for the first time that EC-modified LDL can be produced using human umbilical vein endothelial cells....

I would consider such an increased focus on the antepartum period, not a refocusing, but an expanded focusing. We still believe there are gains to be made in the intrapartum and postpartum periods. But, we need to redouble our efforts if we are to achieve meaningful reductions in CP anytime soon.-ABC) ABSTRACTGreater maternal body mass index (BMI) before or during early pregnancy is associated with an increased risk of fetal death, stillbirth, perinatal death, neonatal death, and infant death. This systematic review and meta-analysis of cohort studies was conducted to determine the strength of these associations, the shape of the dose-response relationship, potential confounding, and potential sources of heterogeneity.

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