Drug metabolism in the human fetus and newborn infant

This is a literature review designed to present the current state of knowledge regarding drug metabolism in the human fetus. Since pharmaco-kinetic processes, i.e., absorption, distribution, metabolism, and excretion of drugs, largely determine the intensity and duration of drug action, such knowledge is useful as a guideline for drug therapy in the newborn period. Both in vitro and in vivo studies dealing with pre-and postnatal drug metabolism in humans and animal species are reviewed. The liver is considered the principle organ of drug metabolism. Animal fetuses seem to have a negligible capacity to oxidize and conjugate drugs. After birth the capacity increases at different rates, depending on the species, the type of reaction, and the type of drug. There is, on the other hand, evidence that drug metabolism occurs in human fetuses. The human fetal liver contains the drug-metabolizing enzyme system early in gestation. The data which argues for and that arguing against the concept of low drug-oxidizing capacity in the newborn is summarized. The old concepts regarding drug metabolism during the early part of life need reevaluation.     

Simultaneous choriocarcinoma in mother and newborn infant

A male infant, born following an uncomplicated pregnancy, was severely anaemic at birth following significant foeto-maternal haemorrhage. At three weeks of age a tumour was found in the liver with evidence of metastatic disease in the lungs. The infant died before treatment could be started. Postmortem revealed choriocarcinoma which led to subsequent diagnosis in the mother who also had pulmonary metastases. The mother has been successfully treated. The case is described in detail and followed by a discussion and a literature review of reported cases of simultaneous choriocarcinoma in infant and mother. © 1995 Wiley-Liss, Inc.     

Serum growth hormone-binding proteins in the human fetus and infant.

Growth hormone-binding protein (GH-BP) levels were studied in cord serum of 69 human infants born after 24 to 41 wk of gestation and in serum of 14 infants aged 1 to 3 mo. GH-BP levels were measured by HPLC-gel filtration of serum incubated overnight with 125I-hGH. The radioactive elution profile revealed two small 125I-hGH peaks of high molecular weight and a large peak, corresponding to monomeric 125I-hGH. The first peak of high molecular weight was variable, showed some of the characteristics (high molecular weight, displaceability by a large excess of unlabeled hGH) of the described low affinity, high capacity GH-BP, and did not correlate with gestational age or birth weight (peak I-BP). The second peak was identified as 125I-hGH bound to the high affinity, low capacity GH-BP (peak II-BP). Mean +/- SD specific binding of 125I-hGH to this peak was significantly (p less than 0.0001) different between preterm infants (3.1 +/- 1.1%; n = 51), term infants at birth (4.2 +/ 1.1%; n = 18), and 1- to 3-mo-old infants (8.5 +/- 1.6%; n = 14). To evaluate the effect of intrauterine nutritional state, the ponderal index (weight/lengths) was calculated. Peak II-BP levels were lower (p less than 0.05) in infants with the ponderal index less than 2.35 (2.8 +/- 1.0%; n = 20) than in those with the ponderal index between 2.35 and 2.65 (3.4 +/- 1.2%; n = 29) or greater than 2.65 (3.8 +/- 1.2%; n = 20).(ABSTRACT TRUNCATED AT 250 WORDS)     

Bone maturation in the fetus and newborn infant]

On the basis of a study of X-ray films of the lower limbs of 994 babies (included 245 hypotrophics) a "bone age" scale of the fetus between 28 and 42 weeks of gestation has been established. The Acheson's method has been used and the bone age determined by addition of notes given to different evolutive phases of the first five ossification centers of the ankle and the knee. To more practical purpose, the results of boys and girls have been joined, although the bone age is in advance among the girls and a theorical scale established with the 10th, 50th and 90th percentiles curves. The comparison with the curves established among 245 hypotrophic newborns, seems to prove that the bone age is a more resistant criteria to malnutrition than the weight and even the length. This new criteria to determine the fetal age does not escape to the criticisms given to the other existing criteria, but radiograph is an objective and fixed document. Its repetition allows to follow the growth of the child and probably to study the role of various factors, mainly nutritional, on this growth. The measure of the length of the tibia and of its increament on the same X-ray films is an other possible method of great interest for the same purpose.     

Cerebral Doppler studies in the fetus and newborn infant

The goal of developing reliable commercial Doppler systems for measuring vessel diameter and velocity changes during the cardiac cycle appears to be near. Reaching this goal would enable us to obtain volume-flow information continuously. In animal experiments, continuous measurements of Doppler velocity, pressure, and flow add important insights into hemodynamic measurements. Incorporating Doppler methods in microcirculatory research could also provide a link between the microcirculatory and the macrocirculatory hemodynamic research. Although Doppler methods have been validated, Doppler findings in clinical research (using commercial systems) must be considered at best to reflect qualitative circulatory alterations indicating directions of change. Because of inherent technologic limitations and considerable intersubject and intrasubject variability, direct extrapolation of the numeric findings from one study to the other can lead to misleading conclusions. The Doppler results are also influenced by measurement conditions and equipment settings. However, Doppler-derived information can be used as an adjunct to clinical management in many of the diseases discussed above. As with any physiologic variable, serial measurements probably are of greater value than single measurements. With continued improvement in technology, Doppler methods hold promise of becoming an important adjunct in cerebral hemodynamic monitoring in perinatal-neonatal intensive care units.     

Pharmacokinetics and protein binding of intravenous ibuprofen in the premature newborn infant

The elimination, disposition and protein binding of ibuprofen (IBU) in premature infants were studied for use in the prevention of intraventricular hemorrhage and closure of patent ductus arteriosus. The kinetic profile of i.v. IBU lysine (10 mg/kg bolus) given within the first 3 h after birth was studied in 21 premature neonates (mean birthweight = 944.7 g, range: 575–1450 g; gestational age: 26.8 weeks, range: 22–31 weeks). Blood samples (0.3 ml/sample) were obtained at time 0 and at 1, 3, 6, 12, 24, 48, and 72 h post-dose for IBU by high-performance liquid chromatography (HPLC). Kinetic analyses assumed applicability of one open-compartment model and calculations from the model-independent areas under the time concentration curve (AUC). Data (mean ± SEM) show that apparent volume of distribution (AVd) was 62.1 ± 3.9 ml/kg, plasma t _1/2 beta was 30.5 ± 4.2 h, elimination rate constant (k_el) was 0.032 ± 0.004 h^-1plasma clearance was 2.06 ± 0.33 ml/kg/h and plasma concentration (Cp) at 1 h was 180.6 ±11.1 mg/1. Gestational age and birthweight were not related to drug elimination. In 10 neonates, IBU maintenance dose of 5 mg/kg once daily on days 2 and 3 generated mean Cp of 116.6 ± 54.5 mg/1 and 113.6 ± 58.2mg/1, respectively. Protein binding by ultrafiltration and capillary electrophoresis showed that the percentage bound IBU was significantly lower in full term cord plasma (94.98 ± 0.39%, n = 26) compared to adult plasma protein (mean ± SE = 98.73 ± 0.31%, n = 8, p < 0.0001). Compared to data from adults and older children, IBU elimination is markedly prolonged in neonates and protein binding is slightly lower. Thus, investigational and clinical therapeutic regimens should be adjusted to account for decreased drug disposition to ensure safe and effective therapy.