Hans Ekelund

Coagulation in the human fetus. Comparison with term newborn infants.

Coagulation factors as well as platelet counts were examined in 61 human fetuses with crown-heel lengths of 9 to 30 cm.All values of coagulation factors except factor V were lower in the fetuses than in term newborn infants, and the clottability of fetal plasma was somewhat reduced. The findings may be of importance for the understanding and management of bleeding in the preterm infant. Hemophilia factors were readily detected in small fetuses, and factor VIII antigen was demonstrated as early as in a 9 cm fetus. Prenatal diagnoses of hereditary hemorrhagic diseases may thus be possible.

MAJOR AND MINOR MALFORMATIONS IN NEWBORNS AND INFANTS UP TO ONE YEAR OF AGE

Numerous statistics on the frequency of malformations in the human population have been published-a recent review is given by Kennedy (1). The material selected for study varies considerably in the different reports. Some have utilized birth certificates and other official records, e.g., national registers of malformed children; some have used hospital and clinical records, not specifically prepared for the investigation; others have intensely studied consecutively born children within a limited population, most recently Stewart et al. (5). The first two methods yield larger groups for study than does the last-mentioned, which however, probably gives a much better recording of the malformations present in the children. One of us recently took part in a study on malformation frequencies in a Swedish national register of malformed children (3, 4), where mainly major malformations were analysed. In the present study, minor malformations were included too, as well as other developmental defects that can hardly be called malformations. Besides making it possible to estimate the incidence of such abnormalities, the present study permits an evaluation of the significance of various abnormalities in discussions on teratogenic mechanisms. From experimental teratology, it has long been known that one and the same teratogenic

α-FOETOPROTEIN, ALBUMIN AND TOTAL PROTEIN IN SERUM FROM PRETERM AND TERM INFANTS AND SMALL FOR GESTATIONAL AGE INFANTS

Blood serum levels of fetoprotein albumin and total protein were measured for infants of various gestational ages and with various birth weights. Laboratory assays used electrophoresis in agarose gel containing specific antibodies. The alpha fetoprotein levels for boys were numerically higher than for girls; these differences did not show up for either albumin or total protein. Results of the study show alpha fetoprotein levels to be a good indicator of gestational age. This is true because the levels did not differ between groups of infants of the same gestational age but different body weights; the levels did differ for groups of infants with the same birth weight but different gestational ages. In this study alpha fetoprotein levels were higher in preterm than in term infants. Albumin and total protein levels varied according to weight rather than gestational age.

Phospholipid Composition of Human Amniotic Fluid During Gestation and at Term

The concentration, composition and fatty acid components of amniotic fluid phospholipids were determined in samples obtained at term and during the second trimester of gestation. The mean concentration of total phospholipids was significantly higher at term than during the second trimester. There was also a highly significant increase in the ratio phosphatidylcholine/sphingomyelin at term. Concomitantly the proportion of palmitic acid in the phosphatidylcholines rose to very high levels. Changes in the same direction were recorded in the fatty acid composition of the phosphatidylethanolamines. The present results indicate that analysis of amniotic fluid phospholipids may be of clinical significance in determining the pulmonary maturity of the foetus.

POSTNATAL CHANGES OF ALPHA-FOETOPROTEIN, ALBUMIN AND TOTAL PROTEIN IN HUMAN SERUM

Alpha fetoprotein albumin and total protein levels were determined in 330 infants whose gestational age was 25-44 weeks. The relationship of these levels to gestational age was examined in a subgroup of 171 newborns and postnatal changes were studied in the remaining 159. Infants with 25-30 weeks gestational age had high alpha fetoprotein levels and these levels decreased successively in infants with increasing gestational age until they were 8 times lower at term than 25-30 weeks gestation. Albumin and total protein levels on the other hand increased with gestational age until term when they were double those at 25-30 weeks. Albumin and total protein levels were lower in infants delivered at 43 weeks than in term infants whereas alpha fetoprotein levels were the same. Postnatal alpha fetoprotein levels decreased from .10-.02 ng/ml in the 1st 20 hours after birth remained constant for 24 days and then decreased to .0006 ng/ml at 2 weeks. Albumin decreased from 50-30 ng/ml and total protein from 70-50 ng/ml in the 1st 5 days postpartum and remained constant for 40-150 days. Alpha fetoprotein was shown to have a higher coefficient or correlation with gestational age than did birth weight or albumin and total rotein levels but there was a high correlation between albumin and total protein.

Apparent response of impaired mental development, minor motor epilepsy and ataxia to pyridoxine.

Impaired mental development, minor motor epilepsy, and ataxia in a 2 1/:! year old boy without cystathioninuria and with a normal reaction to the tryptophane‐loading test responded favourably to pyridoxine. Transient taurinuria and a long lasting general aminoaciduria occurred during the treatment. Certain clinical and biochemical findings and observations suggested that the childs symptoms were due to an increased pyridoxine requirement.

FIBRIN DEGRADATION PRODUCTS AND PLASMINOGEN IN NEWBORN INFANTS WITH RESPIRATORY DISTURBANCES AND POSTNATAL ASPHYXIA

Recent advances have widened our knowledge of the significance of fibrin/fibrinogen degradation products (FDP) in various diseases in adults, such as cancer, renal disorders and thrombosis (18). In newborns, interest in FDP has been centred mainly on conditions in which “disseminated intravascular coagulation” (DIC) is apt to occur e.g. in haemorrhagic diathesis, septicaemia and idiopathic respiratory distress syndrome (1, 7, 8, 9, 15, 16, 17, 23). In a previous study at this laboratory (12) it was shown that sera from healthy newborns do not contain any appreciable amounts of FDP. It was thought worthwhile to continue these studies on sick newborns and to relate the findings to events during pregnancy, delivery and the first minutes of life. This paper concerns determinations of FDP and plasminogen within the first 48 hours of life in preterm and term infants with and without certain common neonatal disorders.

THE DIAGNOSIS OF TAY‐SACHS DISEASE1

Gangliosides and neutral aminoglycolipids were determined in several organs from two subjects with classical Tay‐Sachs disease. Ganglioside GM2 was stored in all organs investigated. Of the extraneural organs, the highest concentration was found in the adrenals, spleen and liver. The rectal muscular layer had a high concentration of gangliosides. Rectal biopsy might be used for studies of the nervous ganglioside pattern.

FIBRINOLYTIC ACTIVITY IN LUNG TISSUE FROM NEONATES WITH HYALINE MEMBRANE DISEASE

The fibrinolytic activity of lung tissue was studied with Todds histochemical method in a material of 29 newborn infants containing normal lungs, hyaline membrane disease, atelectasis and massive pulmonary haemorrhage. No significant difference was found between a group of hyaline membrane lungs and a group of atelectatic lungs without hyaline membranes. In one case with massive pulmonary haemorrhage the activity was high.

Abnormal proteolysis in sick newborns.

ABSTRACT: Henriksson, P. and Ekelund, H. (Department of Paediatrics, University of Lund, Allmänna Sjukhuset, Malmö, Sweden). Abnormal proteolysis in sick newborns. Acta Paediatr Scand, 64:327, 1975–87 newborn infants were studied on their first day of life for defects in the coagulation and fibrinolytic systems. The infants were divided into two diagnostic groups, one with IRDS, the other with mixed neonatal disorders. Factor V, fibrinogen and fibrin/fibrinogen degradation products (FDP) were abnormal more often than any of the other factors examined. The presence or absence of “multiple defects” appeared to depend on the severity of the illness and its ultimate course. Thus 28% of the surviving infants or 85% of those who died had “multiple defects”. The pattern of abnormalities did not differ between the infants with IRDS and those with mixed disorders. The “multiple defects” are ascribed to the following mechanisms: (1) impaired synthesis due to vitamin K deficiency and/or liver damage, (2) abnormal proteolytic activity stimulated by tissue damage and causing (a) an activation of the coagulation process (b) activation of the fibrinolytic system, or (c) of both the coagulation and the fibrinolytic systems. Differentiation between these pathways to defective haemostasis are important when deciding upon therapeutic measures in addition to the basic treatment.