Katherine C. King

Human Fetal Insulin Response to Sustained Maternal Hyperglycemia

Abstract Hyperglycemia was maintained in normal mothers before delivery both at term and early in gestation to study the fetal pancreatic response to glucose. Normal controls and gestationally diabetic mothers were infused with saline. At term the human fetal pancreas responded to elevated blood glucose levels by increasing plasma insulin, and there was a direct correlation between blood glucose and plasma insulin concentrations (r equal to 0.75, p less than 0.001). In early gestation there was an attenuated plasma insulin response. Infants of gestationally diabetic mothers had increased umbilical plasma insulin levels — 23.3 ± 6.9 μU per milliliter (mean ± S.E.M.) — as compared to those of normal controls - 6.4 ± 1.3 μU per milliliter (mean ± S.E.M.) — even though the umbilical blood glucose levels in these two groups were similar. The data support the concept that hyperglycemia leads to hyperinsulinism in infants of diabetic mothers.

Effects of Pregnancy on Hemoglobin AIc in Normal, Gestational Diabetic, and Diabetic Women

Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal ( = 6.97 per cent), pregnant nondiabetic obese ( = 6.89 per cent), and gestationally diabetic subjects ( = 8.77 per cent) above that of normal females ( = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics ( = 12.77 per cent) and the pregnant diabetics ( = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.

Factors relating to readmission of term and near term neonates in the first two weeks of life

Abstract Aims: A multisite study of term and near term infants readmitted in the first two weeks of life to 9 New York City area hospitals in 1995 was conducted to evaluate factors related to readmission, including length of newborn stay. Results: Of the 30,884 infants born at the 9 study hospitals 391 newborns were readmitted. The major admission diagnoses were infection, 40.7 %, hyperbilirubinemia, 39.1 %, and feeding and/or gastrointestinal problems, 10.5 %. In the first week, 65.1% of readmissions were for hyperbilirubinemia and 19.1% were for infection or suspected sepsis. In the second week, 67.8% of readmissions were for infection and 7.6% were for hyperbilirubinemia. Hyperbilirubinemia was the most frequent diagnosis for White and Asian infants, while infection was most frequent for African-American and Hispanic infants. Age at readmission was younger and the interval from discharge was shorter for infants with hyperbilirubinemia. Abnormalities which should have precluded early discharge included feeding difficulties, cyanotic congenital heart defects, hemolytic disease of the newborn, early jaundice or early high bilirubin levels. Conclusion: Attention to identification of infants at risk and programs such as lactation counseling and universal screening for bilirubin (with appropriate interpretation) prior to discharge could have reduced the necessity for readmission regardless of the newborn length of stay.

Role of glucose in the regulation of endogenous glucose production in the human newborn

ABSTRACT. The role of plasma glucose concentration in the regulation of endogenous glucose production in the human newborn was examined by infusing glucose at 2.6- 4.6 mg/kg · min as a continuous infusion to eight normal term appropriate for gestational age infants, five preterm, and six small for gestational age infants. All infants were healthy, had no overt clinical problems and were studied 6 h after their last feed. Glucose production rates were measured during the basal state and during glucose infusion by tracer dilution using [6,62H2]glucose. The rate of glucose production during the basal state was similar in preterm and term appropriate for gestational age infants (appropriate for gestational age 3.53 ± 0.32, preterm 3.49 ± 0.38 mg/kg · min, mean ± SD), while it was higher in the small for gestational age infants (4.25 ± 0.98, p<0.03) as compared with appropriate for gestational age. During glucose infusion, the peak glucose concentration was related to the rate of glucose infusion. The endogenous glucose production rates during glucose infusion were variable in the three groups. However, a negative correlation between peak glucose concentration and endogenous glucose production rate was observed (r=-0.59, p=0.006). The insulin response to glucose infusion was comparable in all infants. In addition, three small gestational age and one preterm infants, who had become hypoglycemic in the immediate newborn period, were studied while they were receiving parenteral glucose and their plasma glucose had stabilized at 55.5 ± 10.25 mg/dl. Tracer kinetic studies showed persistence of endogenous glucose production in these infants even though they were receiving high rates of exogenous glucose infusion. These data show that, as in human adults, the endogenous glucose production in the newborn infant is regulated by plasma glucose and that prematurity and intrauterine growth retardation do not appear to have any significant effect on this regulation. However clinical hypoglycemia, probably as a result of counter-regulatory hormonal responses, can disturb this regulation.

Should all pregnant women be screened for hepatitis B

To assess the sensitivity of historical risk factors for identification for hepatitis B surface antigen (HBsAg)-positive parturients, 4399 pregnant women were consecutively screened for HBsAg. Information regarding risk for hepatitis B infection was obtained from each HBsAg-positive parturient. Twenty-three HBsAg-positive subjects were identified (5.2/1000 deliveries). The HBsAg carrier rate (18/2231, or 8.1/1000 deliveries) was significantly higher in women of black, Asian, or Hispanic origin than in the remaining ethnic groups (non-Hispanic whites plus all others, 5/2168, or 2.3/1000 deliveries) (chi square, 5.95; p = 0.016). Risk factors for identification of HBsAg-positive women were present in 10 of 22 asymptomatic subjects (sensitivity, 45%; 95% confidence interval, 24% to 68%). Much of the information required to assess one of these risk factors, previous infection, involved detailed questioning and is unlikely to be obtained in the context of conventional obstetrical care. Routine maternal HBsAg screening programs may be needed if transmission of hepatitis B from mother to infant is to be prevented.

Theophylline metabolism in premature infants.

The theophylline metabolite pattern in premature infants was studied with gas chromatography–mass spectrometry. The identities of metabolites were established by retention time indices and mass chromatograms. In the steady state of a multiple‐dose regimen, the urinary metabolites of theophylline identified and quantified were caffeine (9.6 ± 4.8%), theophylline (50.4 ± 6.7%), 3‐methylxanthine (1.3 ± 0.7%), 1,3‐dimethyluric acid (27.7 ± 8.8%), and 1‐methyluric acid (9.3 ± 5.4%). Those in plasma were caffeine (21.4 ± 6.1%), theophylline (73.6 ± 6.5%), 3‐methylxanthine (0.7 ± 0.4%), 1,3‐dimethyluric acid (2.6 ± 1.2%), and 1‐methyluric acid (0.6 ± 0.3%). Occasionally, theobromine, the metabolic breakdown product of caffeine, was found in urine and plasma in small quantities. The demethylation pathway occurring predominantly in adults was substituted by N‐methylation to caffeine in premature infants; the other major metabolic pathway of theophylline in adults, C‐8 oxidation to 1,3‐dimethyluric acid, was slightly diminished. We concluded that the enzyme systems responsible for the C‐8 oxidation of theophylline are relatively active in premature infants and that the development of the enzyme systems responsible for oxidative demethylation of theophylline lags behind. The oxidation and demethylation pathways of theophylline in premature infants are significant.

Glycohemoglobin (HbAIc): A predictor of birth weight in infants of diabetic mothers

Hemoglobins AIa-c (fast Hb), minor variants of HbA, are elevated in patients with diabetes mellitus. Recent studies indicate a relationship of fast hemoglobins, especially HbAIc (glycosylated form), to chronic hyperglycemia. Since infant oversize has been attributed to maternal hyperglycemia and fetal hyperinsulinemia, the hemoglobin HbAIc fraction was compared to birth weight (actual and relative to gestational age) and to maternal glucose tolerance. Normal (13), probably normal (8), gestational diabetic (10), and insulin-dependent women (14) were studied in the third trimester; women with advanced diabetic vascular disease were excluded. When corrected for gestational age, relative birth weights correlated in a significant linear regression with HbAIc (n = 45, r = 0.57, P less than 0.001). Third trimester maternal glucose tolerance (Kt) of women, not insulin dependent, correlated in a signigicant manner with both HbAIc (P less than 0.05) and birth weight for gestational age (P less than 0.01).

Developmental aspects of theophylline metabolism in premature infants

The metabolic degradation of theophylline was studied in nine premature infants with postconception ages of 28 to 42 wk. Urinary and plasma metabolites (caffeine; theobromine; 3‐methylxanthine; 1,3‐dimethyiuric acid; and 1‐methyluric acid) and unchanged theophylline were analyzed with selected ion monitoring gas chromatography–mass spectrometry. The anticipated decrease in plasma caffeine (which is absent in adult human and children) did not occur in the postconception age range studied, but the urinary percentages of unchanged theophylline decreased from 61% at a postconception age of 28 to 32 wk to 43% at 38 to 42 wk. This suggests increasing theophylline metabolism with age due to developing hepatic cytochrome P‐450 enzyme systems. The increased degradation of theophylline is largely explained by the production of 1,3‐dimethyluric acid (from 20% to 34%). In infants of an older postconception age, theobromine, a caffeine metabolite, was also detected. To explain the difference of caffeine pathway between adults and premature infants, it is hypothesized that the caffeine pathway of theophylline is equally active in both age groups. The absence of caffeine metabolite in adults is due to the maturing caffeine‐metabolizing enzymes, which degrade caffeine immediately to its metabolites.

Propoxyphene and Acetaminophen: Possible Effects on the Fetus

Propoxyphene (Darvon®) and acetaminophen (Tylenol®) are widely prescribed analgesic agents. Both can cross the placenta, and propoxyphene can produce serious withdrawal symptoms in newborns. Neither propoxyphene nor acetam inophen is considered a teratogen, yet, three malformed infants who were an tenatally exposed to propoxyphene have previously been reported. We report a fourth case of an infant, with withdrawal symptoms and cranial-facial and digital malformations, born to a woman who used propoxyphene and acetaminophen throughout her pregnancy. We suggest the possibility that the antepartum use of propoxyphene and acetaminophen, in combination, may be teratogenic.

Insulin Response to Arginine in Normal Newborn Infants and Infants of Diabetic Mothers

The effect of maternal diabetes during pregnancy on insulin release of the newborn infant was examined employing arginine infusion as stimulus. At age two hours, eight normal newborn infants, six of gestationally diabetic mothers (IGDM) and four of insulin-dependent diabetic mothers (IDM) were infused with arginine hyd-rochloride 0.5 gm. per kilogram body weight for thirty minutes. Eight additional normal newborn infants were infused with isotonic saline. A small but definite rise in plasma IRI was observed in the normal newborns receiving arginine; however, the infants of gestationally diabetic mothers responded with an enhanced blood glucose and plasma insulin rise compared with the normal newborns. It seemed that intermittent or sustained hyperglycemia in utero may have potentiated the neonatal insulin response to arginine.