Hyperlipoproteinemia in newborn infants. A study of 1025 families.

As part of a screening study for the detection of hyperlipoproteinemia in 10,000 newborns, cord serum lipids and lipoproteins were measured in detail in 1025 infants. Elevated cord serum VLDL-LDL-cholesterol could easily be identified by a rapid turbidimetric estimation of cord serum VLDL-LDL. Cord serum VLDL-LDL-cholesterol was found to be significantly higher than normal in premature, asphyxiated and beta-methasone-phenobarbital-ritodrine treated infants. Other obstetric complications, however, were not associated with hyperlipoproteinemia. Furthermore all 2050 parents had their serum cholesterol determined. 3 parents had familial hypercholesterolemia (FH). One child also had FH, though her cord serum total cholesterol and VLDL-LDL-cholesterol were normal. The 2 other children of the 3 FH parents, had normal lipids and lipoproteins both at birth and follow-up.     

Neonatal diagnosis of familial type II hyperlipoproteinemia.

Cord serum prebeta-beta-lipoprotein concentration was measured in a radial immunodiffusion assay in 303 randomly selected, full-term infants whose parental phenotypes were unknown. Six infants had elevated concentrations, that is above a cut-off limit of 197 mg/100 ml (97.5th percentile). Three of these infants suffered from classic type II hyperlipoproteinemia, and this diagnosis was confirmed by family studies at follow-up. The three other infants and their parents were shown to be normolipemic at follow-up. The elevated cord serum prebeta-beta-lipoprotein in these three infants could be explained by highly elevated cord serum triglyceride and/or cholesterol. The 297 infants with normal cord serum prebeta-beta-lipoprotein and their parents were all shown to be normalipemic at follow-up. It is concluded that the measurement of prebeta-beta-lipoportein in cord serum allows the identification of children with familial type II hyperlipoproteinemia, if infants with transient neonatal hypertriglyceridemia and hypercholesterolemia are excluded.     

SERUM CHOLESTEROL CONCENTRATIONS IN EARLY INFANCY

Abstract. Ginsburg, B.-E. and Zetterstrom, R. (Department of Paediatrics, Karolinska Institute, St. Goran's Children's Hospital, Stockholm, Sweden). Serum cholesterol concentrations in early infancy. Acta Paediatr Scand, 69: 581, 1980.—Sixteen healthy term infants were followed from birth to the age of 3–6 months. Total cholesterol, VLDL-LDL-cholesterol and HDL-cholesterol were determined in cord serum, in serum obtained 3–10 days after birth (mean age 4.6 days) and at the age of 3–6 months (mean 4.1 months). Mean total cholesterol increased by 1.5 mmol/l during the first 3–10 days and by an additional 1.1 mmol/l during the following 3–6 months. Mean VLDL-LDL-cholesterol increased by 1.0 mmol/l and 0.9 mmol/l, respectively, and mean HDL-cholesterol by 0.4 mmol/l and 0.3 mmol/l, respectively, during the same periods. The HDL-cholesterol: VLDL-LDL-cholesterol ratio thus fell from 1.5 at birth to 0.8 at the age of 3–10 days and to 0.6 at 3–6 months. In eight breast-fed infants, the mean total cholesterol level increased by 2.9 mmol/l from birth to the age of 3–6 months. This increase was significantly higher than the increase found in eight infants who received a cow's milk formula—i.e. 2.3 mmol/l. Free and esterified cholesterol were determined in 10 infants. Free cholesterol accounted for about one-third of the total cholesterol from birth to the age of 3–6 months.     

SERUM CHOLESTEROL CONCENTRATIONS IN NEWBORN INFANTS WITH GESTATIONAL AGES OF 28–42 WEEKS

Abstract. Ginsburg, B.-E. and Zetterström, R. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden). Serum cholesterol concentrations in newborn infants with gestational ages of 28–42 weeks. Acta Paediatr Scand, 69: 587, 1980.—Serum total cholesterol, HDL-cholesterol and VLDL-LDL-cholesterol were determined in 53 newborn infants with gestational ages of 28–42 weeks. In pre-term infants (gestational age < 37 weeks) the total cholesterol concentration in cord blood was higher than in term infants. Mean values were 2.4 and 1.7 mmol/l, respectively. The HDL-cholesterol/ VLDL-LDL-cholesterol ratio was 1.8 in pre-term and term infants. In 11 pre-term and 17 term infants a second determination was made 3–4 days after birth. Total cholesterol had increased more in term than in pre-term infants and the difference found at birth had already levelled out. Mean value was 3.0 mmol/I in pre-term and term infants. The HDL-cholesterol/ VLDL-LDL-cholesterol ratio had changed to 0.6 in pre-term and term infants. Six pre-term infants who received intravenous fluids only were also studied. Their values did not differ from those in pre-term infants fed orally. Free and esteritied cholesterol were determined in 26 infants of varying gestational ages. About one-third of the total cholesterol was in the free form in pre-term and term infants at birth and during the first days of life.     

SERUM LIPIDS AND LIPOPROTEINS IN 157 INSULIN DEPENDENT DIABETIC CHILDREN AND ADOLESCENTS IN RELATION TO METABOLIC REGULATION, OBESITY AND GENETIC HYPERLIPOPROTEINEMIA

ABSTRACT. Serum lipids and lipoproteins were measured in 157 insulin dependent diabetic children and adolescents (IDDM) and in 350 healthy reference individuals. Serum triglyceride values were lower and total cholesterol and high density lipoprotein cholesterol higher in IDDM. Metabolic regulation reflected by glucosuria, postprandial blood glucose, number of hypoglycemic episodes and hemoglobin AIC all correlated strongly with serum triglyceride and very low density lipoprotein cholesterol but not with serum low density lipoprotein cholesterol or high density lipoprotein cholesterol. Serum lipids and lipoproteins did not correlate with obesity. Three children had genetic hyperlipoproteinemia.
In IDDM measurement of serum lipids and lipoproteins can thus be used to further assess metabolic regulation. Measurement of serum lipids and lipoproteins seems warranted for future evaluation of the risk of cardiovascular disease in IDDM.     

Serum cholesterol concentrations in newborn infants with gestational ages of 28-42 weeks

Serum total cholesterol, HDL-cholesterol and VLDL-LDL-cholesterol were determined in 53 newborn infants with gestational ages of 28-42 weeks. In pre-term infants (gestational age less than 37 weeks) the total cholesterol concentration in cord blood was higher than in term infants. Mean values were 2.4 and 1.7 mmol/l, respectively. The HDL-cholesterol/VLDL-LDL-cholesterol ratio was 1.8 in pre-term and term infants. In 11 pre-term and 17 term infants a second determination was made 3-4 days after birth. Total cholesterol had increased more in term than in pre-term infants and the difference found at birth and already levelled out. Mean value was 3.0 mmol/l in pre-term and term infants. The HDL-cholesterol/VLDL-LDL-cholesterol ratio had changed to 0.6 in pre-term and term infants. Six-pre-term infants who received intravenous fluids only were also studied. Their values did not differ from those in pre-term infants fed orally. Free and esterified cholesterol were determined in 26 infants of varying gestational ages. About one-third of the total cholesterol was in the free form in pre-term and term infants at birth and during the first days of life.     

Serum lipids and lipoproteins in 157 insulin dependent diabetic children and adolescents in relation to metabolic regulation, obesity and genetic hyperlipoproteinemia

Serum lipids and lipoproteins were measured in 157 insulin dependent diabetic children and adolescents (IDDM) and in 350 healthy reference individuals. Serum triglyceride values were lower and total cholesterol and high density lipoprotein cholesterol higher in IDDM. Metabolic regulation reflected by glucosuria, postprandial blood glucose, number of hypoglycemic episodes and hemoglobin A1c all correlated strongly with serum triglyceride and very low density lipoprotein cholesterol. Serum lipids and lipoproteins did not correlate with obesity. Three children had genetic hyperlipoproteinemia. In IDDM measurement of serum lipids and lipoproteins can thus be used to further assess metabolic regulation. Measurement of serum lipids and lipoproteins seems warranted for future evaluation of the risk of cardiovascular disease in IDDM.     

SERUM LIPIDS IN MATERNAL/CORD BLOOD PAIRS FROM NORMAL AND LOW BIRTHWEIGHT INFANTS IN DAR ES SALAAM, TANZANIA

Abstract. Boersma, E. R. (Department of Child Health, Muhimbili Medical Centre, incorporating the Faculty of Medicine, University of Dar es Salaam, Tanzania). Serum lipids in maternal/cord blood pairs from normal and low birthweight infants in Dar es Salaam, Tanzania. Acta Paediatr Scand, 69:747, 1980.—Serum total cholesterol and triglyceride were determined in the cord blood of 54 term appropriate for gestational age, 14 preterm appropriate for gestational age and 17 small-for-dates infants and their mothers immediately after delivery in Dar es Salaam, Tanzania. The mean serum level of total cholesterol in cord blood of term appropriate for gestational age infants was 1.9 mmol/l, whereas that from their mothers 6.3 mmol/l. Cord serum triglyceride values in term appropriate for gestational age infants were 0.29 mmol/l and from their mothers 1.91 mmol/l. Results of these maternal cord serum lipids in the normal and low birthweight groups are similar to those of Western countries.     

SCREENING OF CORD BLOOD LOW-DENSITY-LIPOPROTEIN CHOLESTEROL IN THE DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLAEMIA: A STUDY OF 2000 INFANTS

Abstract. A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l ± S.D.): TC, 1.83 ± 0.56; LDL-C, 0.90 ± 0.49; HDL-C, 0.70 ± 0.33; TG, 0.38 ± 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C >95th percentile, and 373 control group children (cord TC and/or LDL-C >95th percentile) were followed up at age 3–12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate ≥0.05%; false positive rate ≥3.7%. Four control-group children were HC and had an HC parent; false negative rate ≥1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH.     

Screening of cord blood low-density-lipoprotein cholesterol in the diagnosis of familial hypercholesterolaemia: a study of 2000 infants.

A prospective follow-up study of infants selected by cord blood total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels from 2000 consecutive live births was undertaken to reassess the role of cord blood screening in the diagnosis of familial hypercholesterolaemia (FH). Mean values for serum cholesterol were (mmol/l +/- S.D.): TC, 1.83 +/- 0.56; LDL-C, 0.90 +/- 0.49; HDL-C, 0.70 +/- 0.33; TG, 0.38 +/- 0.16. Seventy-three of 117 infants who had had a cord TC and/or LDL-C greater than 95th percentile, and 373 control group children (cord TC and/or LDL-C less than 95th percentile) were followed up at age 3--12 months. Six of the 117 were hypercholesterolaemic (HC), and one child had an HC parent: positive detection rate greater than or equal to 0.05%; false positive rate greater than or equal to 3.7%. Four control-group children were HC and had an HC parent; false negative rate greater than or equal to 1.1%. With the possible exception of detecting FH in a child with a known affected parent, cord blood screening appears to be unreliable for the diagnosis of FH.     

Separation and characterization of cord serum lipoproteins.

Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.     

SCREENING FOR HYPERLIPOPROTEINEMIA IN 10 000 DANISH NEWBORNS Follow-up Studies in 522 Children with Elevated Cord Serum VLDL-LDL-Cholesterol

Abstract. Among 10440 newborns, 522 with upper 5 percentile values for very low-low density lipoprotein cholesterol in cord serum were selected for follow-up studies. Follow-up was possible in 446 of these 522 families (85%) and familial hypercholesterolemia (FH) was diagnosed in 11. In 273 of the 522 children, serum lipids were determined between the ages of 1 and 2 years and were now found to be normal, except in the 11 children with FH. Furthermore the serum lipids were compared in subgroups of these 273 children divided according to obstetric complications (i.e. low birth-weight, perinatal asphyxia and antepartum betamethasone treatment), which may cause a rise in serum lipids at birth. No differences were found between these subgroups at the age of 1–2 years.     

LIPIDS IN CORD SERUM AND FREE FATTY ACIDS IN PLASMA IN HEALTHY NEWBORN TERM INFANTS

ABSTRACT. Christensen, N. Chr. (Department of Obstetrics, Odense University Hospital, Odense, Denmark). Lipids in cord serum and free fatty acids in plasma in healthy newborn term infants. Acta Paediatr Scand, 63: 711, 1974.—Serum cholesterol, triglycerides, and glycerol in cord serum and plasma FFA in cord blood and at 1 1/2, 6, 12, 24 and 48 hours after birth were determined in 18 healthy term infants. Concentrations of lipids in cord blood were low; and there were no correlation between cord lipids and subsequent FFA values. A rapid increase in FFA level, with peak values at 12 hours, was seen. Significant, negative correlations were found between FFA concentration and rectal temperature at 1 1/2 hour and between total caloric intake and FFA concentration at 48 hours.     

Screening for hyperlipoproteinemia in 10,000 Danish newborns. Follow-up studies in 522 children with elevated cord serum VLDL-LDL-cholesterol.

Among 10 440 newborns, 522 with upper 5 percentile values for very low-low density lipoprotein cholesterol in cord serum were selected for follow-up studies. Follow-up was possible in 446 of these 522 families (85%) and familial hypercholesterolemia (FH) was diagnosed in 11. In 273 of the 522 children, serum lipids were determined between the ages of 1 and 2 years and were now found to be normal, except in the 11 children with FH. Furthermore the serum lipids were compared in subgroups of these 273 children divided according to obstetric complications (i.e. low birth-weight, perinatal asphyxia and antepartum betamethasone treatment), which may cause a rise in serum lipids at birth. No differences were found between these subgroups at the age of 1--2 years.     

THE PATTERN OF MAJOR SERUM APOLIPOPROTEINS DURING THE EARLY NEONATAL PERIOD

ABSTRACT. Serum triglycerides, total cholesterol, lipoproteins and apolipoprotein A-I, B and C-III were investigated in 24 normal newborns at birth (umbilical cord blood) and again 4 days after birth (venous blood). Blood samples from 95 fasted normolipidemic male and female subjects aged between 20 to 60 years were also analysed. Immunochemical studies of serum from umbilical cord blood have shown that all investigated apolipoproteins were present although at lower levels than found in adults. The concentration of lipids, lipoproteins and apolipoprotein B and C-III in the serum from blood collected 4 days after birth did not practically differ from that of adult.     

SERUM APOLIPOPROTEINS AND LIPOPROTEIN (a) DURING THE FIRST WEEK OF LIFE

ABSTRACT. The levels of apolipoproteins, A-I, A-II, B and E, lipoprotein (a) and of total cholesterol and triglycerides were determined in cord serum and in capillary serum at the fifth day of life in a group of 44 term newborns. Additionally, cord serum lipoproteins were estimated. Sera from 26 healthy adults were studied for comparison. The concentrations of lipids and lipoproteins in cord serum were diminished as compared to adult levels. The occurrence of lipoprotein (a) in cord serum in concentrations significantly lower than in adults could be established. Serum apolipoproteins A-I, A-II and B were significantly lower at birth than in the adult, whereas apolipoprotein E levels did not differ from adult concentrations. During the first five days apolipoprotein B levels more than doubled, apolipoprotein A-I increased moderately and apolipoprotein E rose slightly. In contrast, serum lipoprotein (a) and apolipoprotein A-II did not change signiflcantly. Unlike serum cholesterol, the levels of apolipoproteins B and E at day five were significantly correlated to those measured at birth in the same infants. The changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system of the newborn and may be related to the increasing utilisation of fat and to hormonal factors.     

Serum apolipoproteins and lipoprotein (a) during the first week of life

The levels of apolipoproteins, A-I, A-II, B and E, lipoprotein (a) and of total cholesterol and triglycerides were determined in cord serum and in capillary serum at the fifth day of life in a group of 44 term newborns. Additionally, cord serum lipoproteins were estimated. Sera from 26 healthy adults were studied for comparison. The concentrations of lipids and lipoproteins in cord serum were diminished as compared to adult levels. The occurrence of lipoprotein (a) in cord serum in concentrations significantly lower than in adults could be established. Serum apolipoproteins A-I, A-II and B were significantly lower at birth than in the adult, whereas apolipoprotein E levels did not differ from adult concentrations. During the first five days apolipoprotein B levels more than doubled, apolipoprotein A-I increased moderately and apolipoprotein E rose slightly. In contrast, serum lipoprotein (a) and apolipoprotein A-II did not change significantly. Unlike serum cholesterol, the levels of apolipoproteins B and E at day five were significantly correlated to those measured at birth in the same infants. The changes of the apolipoprotein pattern during the first week of life reflect the evolution of the lipid transport system of the newborn and may be related to the increasing utilisation of fat and to hormonal factors.     

LDL RECEPTOR STUDIES IN TERM AND PRE-TERM INFANTS: MEASUREMENT OF STEROL SYNTHESIS IN CORD BLOOD LYMPHOCYTES

Abstract. Andersen, G. E. and Johansen, K. B. (The Neonatal Department, Rigshospitalet, University of Copenhagen, Denmark). LDL receptor studies in term and pre-term infants: Measurement of sterol synthesis in cord blood lymphocytes. Acta Paediatr Scand, 69: 577, 1980.—Low density lipoprotein (LDL) receptor activity was measured in lymphocytes from pre-term and term infants in order to elucidate if the hypercholesterolemia found in pre-term infants might be secondary to a block in cholesterol transport across the cell membrane, analogous to that seen in familial hypercholesterolemia (FH). LDL receptor activity was found to be fully developed in pre-term infants and no different from that of term infants and of a normal adult control.     

Serum lipids and lipoproteins at birth in a biracial population: the Bogalusa heart study.

The lipid profile, total cholesterol, triglycerides, and lipoproteins (beta-, pre-beta-, and alpha-) of cord blood, is presented for 419 black and white infants (94% of the eligible population) born during an 18-month period in Bogalusa, Louisiana. At birth, white neonates of both sexes had higher average levels than black neonates of total cholesterol and beta-lipoproteins. White girls among the four race-sex groups had the highest cord blood levels of total cholesterol, beta-lipoproteins, and alpha-lipoproteins. Neither stress at delivery, birthweight, socioeconomic status, nor season of the year had an observable effect on any of the lipid or lipoprotein levels. The magnitude and direction of the relationships between the respective lipids and lipoproteins in cord blood were similar to those we have observed in preschool and school-aged children in the same community. Total cholesterol was highly correlated with both beta- and alpha-lipoproteins; triglycerides were correlated with pre-beta-lipoproteins but inversely with alpha-lipoproteins. These observations suggest that basic biochemical relationships are already established at birth.     

THE FATTY ACID COMPOSITION OF SERUM LOW DENSITY LIPOPROTEIN- AND LYMPHOCYTE CHOLESTEROL ESTERS IN CHILDREN WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Abstract. Andersen, G. E. and Johansen, K. B. (The Neonatal Department, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark). Fatty acid composition of serum low density lipoprotein- and lymphocyte cholesterol esters in children with heterozygous familial hypercholesterolemia. Acta Paediatr Scand, 69:453, 1980.—The content of free and esterified cholesterolin serum low density lipoprotein (LDL) was measured in 19 children with heterozygous familial hypercholesterolemia (FH) and in 10 normal siblings. In FH both free and esterified cholesterol were found to be elevated. Furthermore the fatty acid composition of serum LDL- and lymphocyte cholesterol esters was determined. However, no difference was found between FH heterozygotes and normals thus indicating that LDL-hypocatabolism typically found in FH does not correlate with an abnormal fatty acid composition of LDL-cholesterol esters nor with an impaired cholesterol esterification intracellularly in lymphocytes.