Francis Mimouni

Multiple Hamartomas Associated with Intracranial Malformation

Abstract: We examined a newborn infant with multiple hamartomas, including an epidermal nevus syndrome and a giant pigmented congenital nevocellular nevus, associated with other structural developmental abnormalities such as nevus flammeus, vascular malformation, cutis aplasia congenita of the scalp, cartilage hamartoma, and a lipodermoid of the conjunctiva. This child had a significant brain malformation, diagnosed by sonography and computerized tomography, consisting of a significant enlargement of the left hemisphere not associated with asymmetry of the skull or facial bones. We suggest a careful investigation of the intracranial structures by computerized tomography and/or ultrasonography in case of either extensive linear nevus sebaceous sequence and/or giant pigmented nevocellular nevus.

High infectious morbidity in pregnant women with insulin-dependent diabetes: an understated complication.

Patients with insulin-dependent diabetes are prone to infection, possibly related to poor metabolic control. Relative immune deficiency exists in pregnancy. We hypothesized that pregnant patients with insulin-dependent diabetes are at an increased risk for infection and that infection is related to poor glycemic control. We matched 65 pregnant women with insulin-dependent diabetes to 65 nondiabetic pregnant controls. At least one episode of infection before delivery occurred in 83% of the women with insulin-dependent diabetes (26% in control group). The rate of postpartum infection was five times higher in the group with insulin-dependent diabetes and they were susceptible to more kinds of infections. Although there was no overall difference among the indices of glycemic control, hemoglobin A1 obtained before the infection was higher than during infection. We conclude that a high rate of infection exists in pregnant women with diabetes; infection and poor glycemic control may be associated, but it is unclear whether improvement in metabolic control will reduce this high infection rate.

A role for magnesium in neonatal parathyroid gland function

Little is known of the factors regulating parathyroid function in the neonatal period. Twenty-seven term infants born after uncomplicated pregnancies, labors, and deliveries were studied to test the hypothesis that in normal newborns the amplitude of parathyroid hormone (PTH) response to decreasing serum ionized calcium (iCa) correlates with serum magnesium (Mg) concentrations. Serum iCa (ion selective electrode, Radiometer ICA 1), PTH (1-84 intact molecules, radioimmunoassay) and Mg (atomic absorption) were measured at birth (cord blood) and 24 hours of age. Repeated measures analysis of covariance showed decreasing serum iCa (p less than 0.01) and increasing serum Mg (p less than 0.01) and PTH (p less than 0.01) over time. The change in PTH over the first 24 hours was directly correlated with cord blood (r = 0.38, p less than 0.05) and 24-hr Mg concentrations (r = 0.53, p less than 0.01). We conclude that the ability of the parathyroid gland to respond to decreasing serum iCa after birth is directly related to Mg status. We speculate that neonatal hypomagnesemia may lead to a blunted PTH secretory response, thus contributing to early neonatal hypocalcemia.

Biphasic intrauterine growth in insulin-dependent diabetic pregnancies.

Early fetal growth delay (7-14 weeks of gestation) has been reported in insulin-dependent diabetic (IDD) pregnancies and in several animal models. Macrosomia is a classic feature of the infant of the IDD mother. We hypothesized therefore that a biphasic pattern of fetal growth exists in IDD pregnancies. We compared fetal growth measurements [biparietal diameter (BPD) and abdominal circumference (AC)] obtained sonographically from 106 IDD pregnancies (Class B-RT) to similar data obtained from 117 normal, nondiabetic patients. The goals for diabetic glycemic control were: fasting blood sugar less than or equal to 100 mg/dl and postprandial blood sugar less than 140 mg/dl. From one to five ultrasonographic measurements were performed at varying gestational ages in all study patients. For data analysis, one examination from each pregnancy was randomly selected by computer. Gestational age (GA) was calculated from last menstrual period and corroborated by infant physical examination (Ballard score) at birth. BPD growth pattern was biphasic in the diabetic group, described by a cubic equation: BPD = 4.99 - 0.567GA + 0.037(GA)2 - 0.0005(GA)3, R2 = 0.935. Such a biphasic pattern did not exist in the control population [BPD = -3.0323 + 0.473(gestation) - (-0.0040)(gestation)2, R2 = 0.9173]. Early growth delay was greater in fetuses that subsequently developed macrosomia (p less than 0.01). Similar results were found for AC measurements. We conclude that fetal growth delay occurs in the first half of the IDD pregnancy, followed by a phase of increased growth. The mechanism of the early growth delay is unclear. We speculate that early growth delay may be due to a toxic effect of glucose or other metabolite; and subsequent increased growth relates to fetal hyperinsulinism which develops from weeks 15 to 20 of gestation.

Postnatal changes in serum osteocalcin and parathyroid hormone concentrations.

Cord clamping at birth leads to interruption of calcium (Ca) supply to the fetus. After birth, neonatal parathyroid hormone (PTH) secretion appears stimulated by hypocalcemia, with serum PTH increasing after birth and peaking at 24 hours of age. This rise in PTH presumably leads to bone resorption and Ca release. We theorize that bone formation may also be affected and that a serum marker of bone formation, serum osteocalcin (OC) concentrations, will decrease postnatally. OC is synthesized by osteoblasts and its serum concentrations are believed to reflect bone formation. We measured serum ionized Ca (iCa), PTH, and OC in cord blood and at 2 and 24 hours in 26 neonates born after uncomplicated pregnancies, labors, and deliveries. Serum iCa (mg/dl) decreased from 5.79 +/- 0.06 (cord, means +/- SEM) to 5.31 +/- 0.05 (2 hr), then to 4.89 +/- 0.05 (24 hr) (p less than 0.05). Serum PTH (microliter Eq/ml) increased from 35.9 +/- 4.3 (cord) to 41.7 +/- 4.0 (2 hr) (p = 0.1), and to 50.3 +/- 4.6 (24 hr) (p less than 0.01). Serum OC (ng/ml) decreased from 55.1 +/- 10.6 (cord), to 12.4 +/- 4.3 (2 hr) (p less than 0.01), then remained stable at 12.7 +/- 1.9 (24 hr). The change (cord minus 24 hr) in OC correlated inversely with the change in PTH over the first 24 hours of age (r = -0.42. p = 0.03). Therefore, there is a sudden decrease in an index of bone formation (i.e., serum OC) in the first 24 hours of life in which rising serum PTH may have had an impact.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan-induced diabetes mellitus in the pregnant ewe: Metabolic and cardiovascular effects on the mother and her fetus

Diabetes mellitus was acutely produced in nine pregnant sheep by the intravenous administration of alloxan 40 mg/kg in the maternal inferior vena cava. Maternal and fetal plasma concentrations of glucose, lactate, beta-hydroxybutyrate, insulin, glucagon, and PaO2, oxygen content, and pH were determined before and at days 1, 3, and 5 after the injection of alloxan. Two animals aborted between days 1 and 3 after alloxan administration. In the other animals, significant changes occurred from baseline to day 5: maternal hyperglycemia (56.8 +/- 5.2 vs. 227.3 +/- 54.6 mg/dl; p less than 0.01), maternal hypoinsulinemia (6.2 +/- 3.5 vs. 1.0 +/- 0.4 microU/ml, p = 0.016); maternal hyperketonemia (beta-hydroxybutyrate: 0.79 +/- 0.27 vs. 4.69 +/- 2.64 mmol/L, p less than 0.01); fetal hyperglycemia (17.0 +/- 2.6 vs. 86.0 +/- 16.2 mg/dl, p less than 0.001); fetal hyperinsulinemia (8.4 +/- 4.5 vs. 19.2 +/- 6.4 microU/ml, p less than 0.001); fetal hyperketonemia (beta-hydroxybutyrate: 0.03 +/- 0.03 vs. 0.06 +/- 0.02 mmol/L, p less than 0.05); fetal hypoxemia (arterial PO2: 21.6 +/- 1.8 vs. 18.0 +/- 2.8 mm Hg, p less than 0.05, and oxygen content: 7.1 +/- 0.5 vs. 4.5 +/- 1.9 vol/dl, p less than 0.02). Thus alloxan administered in the pregnant ewe can produce major metabolic and endocrine derangements acutely simulating those occurring in human insulin-dependent diabetic pregnancy.

Effect of chronic maternal dietary magnesium deficiency on placental calcium transport.

Metabolisms of calcium (Ca) and magnesium (Mg) are closely interrelated in the intestine, bone, and kidney. Interaction of Ca and Mg at the placental level, however, is not well defined. The occurrence of decreased bone mineral content and hypocalcemia in infants of hypomagnesemic mothers led us to test the hypothesis that chronic dietary maternal Mg deficiency decreases placental Ca transport. On day 10 of gestation, 20 Sprague-Dawley rats were randomized to a Mg-deficient diet (3.3 mg/day, n = 10) or to a control diet (70 mg/day, n = 10). On day 20 of gestation (term = 22 days), intact placentas were perfused in situ through the umbilical artery and perfusate was collected through the umbilical vein. Calcium 45 (45Ca) and chromium 51-EDTA (51Cr-EDTA) (a diffusional marker for placental membrane integrity) were injected to the dam and steady state maternofetal clearance (Kmf45Ca, microliter/min/g placenta) of both isotopes were calculated. There was no difference in the clearance of 45Ca and 51Cr in both groups (55 +/- 10 vs 57 +/- 16 and 3.2 +/- 0.4 vs 3.6 +/- 0.4, respectively, mean +/- SEM). We conclude that, in the rat, placental Ca transfer is unaffected by chronic maternal dietary Mg deficiency. We speculate that Ca and Mg cross the placenta by independent mechanisms.

Bone mineral content: data analysis.

We reviewed the literature related to intrauterine bone mineral content (BMC) curves and the expression of BMC measurements in infants. From this review, it appears that the curves developed by Greer and by Minton for the radius are extremely similar and that both should be used as the reference curve. It also appears that expression of assessment results in terms of BMC and bone width (BW) permits an evaluation of growth of bone mass versus growth of size of the bone scanned. Although the BMC/BW ratio might be a useful but unproved conceptual adjunct, expression of photon absorptiometry results in terms of the BMC/BW ratio alone does not confer any specific advantage and theoretically could mask important specific information about bone mass and size.

Bone mineral content of infants fed soy-based formula

We compared the results of two studies that measured the bone mineral content (BMC) of 57 infants fed soy-based formula and 27 infants fed human milk or cow milk-based formula at various ages from 2 weeks to 1 year. In a study by Chan et al., the BMC of 40 white infants fed soy-based formula and 10 infants (of unstated race) fed human milk was measured at 2 weeks and at 2 and 4 months of age. The infants fed soy-based formula also had BMC measured at 6 and 12 months; the BMC of these infants was compared to the BMC of human milk-fed historical control subjects. The BMC was similar at 2 weeks in both groups but was lower in infants fed soy-based formula than in human milk-fed infants at 2 and 4 months. The BMC was similar in historical control subjects fed human milk and in soy formula-fed infants at 6 and 12 months. In the Steichen-Tsang study, the BMC of 17 soy formula-fed infants and of 17 white infants fed cow milk-based formula was measured at 6 weeks and at 3, 6, and 12 months of age. The BMC was similar at 6 weeks in both groups but was lower in infants fed soy-based formula than in those fed cow milk-based formula at 3, 6, and 12 months. The BMC of the historical control group fed human milk and of the soy formula-fed infants was also similar. In the first year of life, the BMC of infants fed soy formula and those fed human milk appears to be similar, especially after 6 months of age. However, the BMC of infants so fed may be lower than that of infants fed cow milk-based formula.

Effects of maternally administered epidermal growth factor on placental permeability

Epidermal growth factor is a well-studied modulator of epithelial membrane structure and function. Mammalian placentas are a rich source of epidermal growth factor receptors, but the role of epidermal growth factor in placental pathophysiologic conditions is unclear. To determine whether epidermal growth factor could affect mechanisms of placental transfer, we used an in situ rat placental perfusion model. Fourteen Sprague-Dawley rats that were 20 days pregnant were randomized to epidermal growth factor or placebo during placental transport experiments. We chose ethylenediaminetetraacetate tagged with chromium 51 as a marker of placental permeability. Epidermal growth factor treatment led to a dramatic increase of maternofetal clearances of chromium 51-ethylenediaminetetraacetate. We conclude that maternally administered epidermal growth factor has a potent action on placental permeability.