Neonatal Hypoglycemia Back to Basics in Diagnosis and Treatment ROBERT SCHWARTZ
Hypoglycemia continues to be found in infants of diabetic mothers, although the significance of the observation remains to be defined in terms of long-term neurodevelopment and behavior. Most follow-up studies no longer identify CNS problems. The criterion, i.e., the level of blood glucose at which the diagnosis should be made, has evolved and drifted toward the adult level. No single criterion can be used dependably to make this clinical and chemical diagnosis. Diabetes 40 (Suppl. 2):71-73,1991
H
ypoglycemia in infants of diabetic mothers was first reported in detail in 1937 by Hartmann and Jaudon (1), who developed micromethods to enable analysis of capillary blood on 200-|xl samples. They used specific techniques for protein precipitation and true sugar analysis, which provided a low blank and had results similar to those obtained today with glucose oxidase or hexokinase. They stated the following. "An analysis has been made of all cases of hypoglycemia studied in the St. Louis Children's Hospital over a period of fifteen years (286 cases). Pathogenesis and classification on an etiologic basis have been emphasized, together with data obtained particularly from three groups: (1) normal newborn infants, (2) infants born of diabetic mothers, and (3) children developing recurring attacks of very severe hypoglycemia, who seem to be insulin hypersensitive or intolerant, chiefly because of the lack of proper opposing secretions (adrenal and pituitary)."
Their conclusions regarding newborn infants of nondiabetic mothers were that "hypoglycemia during the first four or five days of life occurs quite regularly in normal newborn
From the Division of Biology and Medicine, Brown University, and the Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital, Providence, Rhode Island. Address correspondence and reprint requests to R. Schwartz, MD, Department of Pediatrics, Rhode Island Hospital, 593 Eddy Street, Providence, Rl 02903.
DIABETES, VOL. 40, SUPPL. 2, DECEMBER 1991
infants and seems due to an imperfectly developed regulatory mechanism which creates a state of relative hyperinsulinism" (1). Their observations in infants of diabetic mothers are summarized as follows (1). "A similar period of hypoglycemia with the development occasionally of such very severe manifestations as convulsions and collapse occurs in infants born of diabetic mothers. The greater fall in blood sugar in such infants (sometimes with a striking absence of symptoms) seems more often referable to an increased physiologic hyperactivity of the islands of Langerhans than to the development of islet cell hypertrophy or hyperplasia."
The latter was first observed in 1920 by Dubreuil and Anderodias (2). Hartmann and Jaudon (1) made specific recommendations for management that presaged current recommendations. "This may be prevented or controlled quite effectively by the combined use of epinephrine (now glucagon may be given) and dextrose injection as emergency measures, and the prophylactic starting of complemental milk and carbohydrate feedings immediately after birth. The most careful observation of such infants for the first four or five days of life (with special nurses, if possible) seems almost necessary."
Thus, Hartmann and Jaudon (1) predicted virtually every aspect of neonatal hypoglycemia; little was added in regard to its diagnosis or treatment in the next 50 yr. Confusion existed for the next 20 yr, in part due to inadequate attention to methodology. Thus, in 1959, Gellis and Hsia (3) reported on >600 infants from P. White's diabetic pregnant population in Boston, in which only two infants were considered hypoglycemic. Details of methodology were not given. In 1964, our group (4) found an increased incidence of hypoglycemia in both infants of insulin-dependent diabetic mothers and those of gestational diabetic mothers. The initial rate of fall of glucose was inversely related to the level observed in the umbilical plasma. Similar observations were reported by Farquhar and Isles (5) in 1968. In 20 infants observed from delivery onward, they noted that the initial cord plasma glucose level of 6.5 mM decreased to 1.9 mM
71
NEONATAL HYPOGLYCEMIA
TABLE 1 Plasma glucose concentrations in normal full-term infants Age (h)
Hypoglycemia
Intermediate
Normoglycemia
Intermediate
Hyperglycemia
0-6 6-24 >24
0-1.4 0-1.7 0-2.2
1.4-2.2 1.7-2.5 2.2-2.8
2.2-5.6 2.5-5.6 2.8-5.6
5.6-6.9 5.6-6.9 5.6-6.9
>6.9 >6.9 >6.9
Values are given in mM.
by 30 min and remained < 1.1 mM for the next 1.5 h. During the 2nd h of life the mean ± SD plasma glucose level was below that of infants of nondiabetic mothers. They reported careful clinical observations and long-term follow-up of > 100 infants of nondiabetic mothers, and 8 had plasma glucose concentrations
Hypoglycemia continues to be found in infants of diabetic mothers, although the significance of the observation remains to be defined in terms of long-term neurodevelopment and behavior. Most follow-up studies no longer identify CNS problems. The criterion, i.e., the level of blood glucose at which the diagnosis should be made, has evolved and drifted toward the adult level. No single criterion can be used dependably to make this clinical and chemical diagnosis. Diabetes 40 (Suppl. 2):71-73,1991
H
ypoglycemia in infants of diabetic mothers was first reported in detail in 1937 by Hartmann and Jaudon (1), who developed micromethods to enable analysis of capillary blood on 200-|xl samples. They used specific techniques for protein precipitation and true sugar analysis, which provided a low blank and had results similar to those obtained today with glucose oxidase or hexokinase. They stated the following. "An analysis has been made of all cases of hypoglycemia studied in the St. Louis Children's Hospital over a period of fifteen years (286 cases). Pathogenesis and classification on an etiologic basis have been emphasized, together with data obtained particularly from three groups: (1) normal newborn infants, (2) infants born of diabetic mothers, and (3) children developing recurring attacks of very severe hypoglycemia, who seem to be insulin hypersensitive or intolerant, chiefly because of the lack of proper opposing secretions (adrenal and pituitary)."
Their conclusions regarding newborn infants of nondiabetic mothers were that "hypoglycemia during the first four or five days of life occurs quite regularly in normal newborn
From the Division of Biology and Medicine, Brown University, and the Division of Pediatric Endocrinology and Metabolism, Rhode Island Hospital, Providence, Rhode Island. Address correspondence and reprint requests to R. Schwartz, MD, Department of Pediatrics, Rhode Island Hospital, 593 Eddy Street, Providence, Rl 02903.
DIABETES, VOL. 40, SUPPL. 2, DECEMBER 1991
infants and seems due to an imperfectly developed regulatory mechanism which creates a state of relative hyperinsulinism" (1). Their observations in infants of diabetic mothers are summarized as follows (1). "A similar period of hypoglycemia with the development occasionally of such very severe manifestations as convulsions and collapse occurs in infants born of diabetic mothers. The greater fall in blood sugar in such infants (sometimes with a striking absence of symptoms) seems more often referable to an increased physiologic hyperactivity of the islands of Langerhans than to the development of islet cell hypertrophy or hyperplasia."
The latter was first observed in 1920 by Dubreuil and Anderodias (2). Hartmann and Jaudon (1) made specific recommendations for management that presaged current recommendations. "This may be prevented or controlled quite effectively by the combined use of epinephrine (now glucagon may be given) and dextrose injection as emergency measures, and the prophylactic starting of complemental milk and carbohydrate feedings immediately after birth. The most careful observation of such infants for the first four or five days of life (with special nurses, if possible) seems almost necessary."
Thus, Hartmann and Jaudon (1) predicted virtually every aspect of neonatal hypoglycemia; little was added in regard to its diagnosis or treatment in the next 50 yr. Confusion existed for the next 20 yr, in part due to inadequate attention to methodology. Thus, in 1959, Gellis and Hsia (3) reported on >600 infants from P. White's diabetic pregnant population in Boston, in which only two infants were considered hypoglycemic. Details of methodology were not given. In 1964, our group (4) found an increased incidence of hypoglycemia in both infants of insulin-dependent diabetic mothers and those of gestational diabetic mothers. The initial rate of fall of glucose was inversely related to the level observed in the umbilical plasma. Similar observations were reported by Farquhar and Isles (5) in 1968. In 20 infants observed from delivery onward, they noted that the initial cord plasma glucose level of 6.5 mM decreased to 1.9 mM
71
NEONATAL HYPOGLYCEMIA
TABLE 1 Plasma glucose concentrations in normal full-term infants Age (h)
Hypoglycemia
Intermediate
Normoglycemia
Intermediate
Hyperglycemia
0-6 6-24 >24
0-1.4 0-1.7 0-2.2
1.4-2.2 1.7-2.5 2.2-2.8
2.2-5.6 2.5-5.6 2.8-5.6
5.6-6.9 5.6-6.9 5.6-6.9
>6.9 >6.9 >6.9
Values are given in mM.
by 30 min and remained < 1.1 mM for the next 1.5 h. During the 2nd h of life the mean ± SD plasma glucose level was below that of infants of nondiabetic mothers. They reported careful clinical observations and long-term follow-up of > 100 infants of nondiabetic mothers, and 8 had plasma glucose concentrations
