Tissue distribution of morphine in the newborns of addicted monkeys and humans. Clinical implications.

The distribution of morphine in various tissues of 6 addicted monkey fetuses and in 2 infants of drug-dependent mothers (IDDM) show that significant concentrations of the drug are in the gastrointestines (tissue plus content), liver, cerebellum, lungs, heart, spleen and thymus. The high concentration of morphine in the gastrointestinal tract may be secondary to the excretion of the drug through the bile or by the repeated swallowing by the fetus of amniotic fluid which contains morphine (1.9 +/- 1.0 micrograms/dl). Meconium, taken from 2 IDDMs show a significant concentration of morphine for up to 2-3 days after birth. Thus, meconium is a useful material to analyze postnatally for the diagnosis of neonatal narcotic addiction.

Children of methadone-treated women at five years of age.

Infants of methadone-treated and matched non-drug dependent women were found to differ in psychomotor development at one year of age. A follow-up of these groups at age five revealed no differences in cognitive or perceptual performance as assessed by the McCarthy Scales, although both groups performed below normative expectations. Groups did not differ in observed characteristics of home environments or patterns of child or caregiver behavior in a playroom observation, although children who had been transplacentally exposed to narcotics behaved less maturely and were more inappropriately active during psychological testing.

Behavioural concomitants of prenatal addiction to narcotics.

Behavioral characteristics of infants of methadone-treated and nonaddicted women were studied during the neonatal period and at three, six, and 12 months of age. Several Brazelton Neonatal Behavioral Assment Scale measures differentiated between groups. Major differences occurred in irritability of the central nervous system, and these measures appeared able to predict severity of withdrawal. The increased tremulousness of addicted infants remained through at least the first month of life. Mental and motor development was within normal limits in both groups throughout the year. However, the addicted infants showed a progressive decline in psychomotor performance whereas nonaddicted infants' scores remained stable.

Effect of oral contraceptives on nutrients. III. Vitamins B6, B12, and folic acid.

The interactions of oral contraceptive agents (OCA's) with vitamins were studied in a large population of women. In the upper socioeconomic groups, higher incidences of abnormal clinical signs related to vitamin deficiencies were seen in OCA users than in the control subjects. Plasma pyridoxal phosphate and red cell and serum folate were lower in subjects using OCA's in the upper socioeconomic group as compared to levels in the control subjects. Reduction in erythrocyte glutamic oxalacetic transaminase (EGOT) activity and elevation in the EGOT-stimulation test were observed in subjects using OCA's in both upper and lower socioeconomic groups. These observations suggest a relatively deficient state with respect to vitamins B6 and folic acid in OCA users. No significant effect on serum vitamin B12 was observed as a result of OCA administration.

PIP: The effect of oral contraceptives (OCs) on Vitamins-B6, -B12, and folic acid metabolism was studied in a large population of women. The OCs Norinyl (1 mg norethindrone plus 50 mcg mestranol) and Ovral (.5 mg norgestrel and 50 mcg ethinyl estradiol) were administered for 3 or more months. Higher incidences of abnormal clinical signs related to vitamin deficiency were seen in the upper socioeconomic OC users then in the control subjects. Plasma pyridoxal phosphate and red cell and serum folate were lower in OC users in the upper socioeconomic group as compared with levels in control subjects. A reduction in erythrocyte gl utamic oxalacetic transaminase (EGOT) activity and an elevation in the EGOT-stimulation test were observed in OC users in both upper and lower socioeconomic groups. These results suggest a relatively deficient state with respect to Vitamin-B6 and folic acid in OC users. No marked effects were seen with respect to Vitamin-B12 levels. These data are consistent with the hypothesis that the subjects in lower socioeconomic groups were already marginally deficient in Vitamin-B6 and folic acid and further reduction due to OCs could not be detected.

Relationship of neonatal withdrawal to maternal methadone dose.

Neonatal withdrawal is described for a sample of 70 infants born to addicted women treated with methadone and comprehensive prenatal care. Although symptoms were manifested by over 90% of the infants, those born to women receiving near-term average doses of less than or equal to 20 mg/day had significantly less symptomatology, weight loss, and need for pharmacologic treatment than those of mothers still on higher doses. Reduction of methadone dose levels during the last 6 weeks of pregnancy to less than or equal to 20 mg/day appears to reduce the severity of neonatal withdrawal.

Effect of oral contraceptive agents on nutrients: II. Vitamins.

Clinical, biochemical and nutritional data were collected from a large population of women using oral contraceptive agents. Higher incidence of abnormal clinical signs related to malnutrition were observed in the lower (B) as compared to the higher (A) socioeconomic groups, and also in the nonsupplemented groups as compared to the supplemented groups in the B subjects. As a rule the intake of oral contraceptive agent subjects of vitamin A, C, B6 and folic acid did not differ from that of the controls As expected, subjects from the supplemented groups had higher intake of vitamin A, C, B6, thiamin, riboflavin and folic acid, and A groups had higher intake of vitamin C, B6, riboflavin and folic acid. Increased plasma vitamin A and decreased carotene levels were observed in oral contraceptive agent users. In general oral contraceptive agents had little or no effect on plasma ascorbic acid. Urinary excretion of both thiamin and riboflavin in subjects using oral contraceptive agents were lower in A groups. Erythrocyte folate and plasma pyridoxal phosphate was decreased in A groups due to oral contraceptive agents. Subjects who took supplements had higher levels of plasma vitamin A, ascorbic acid and folate. But urinary thiamin and riboflavin were higher only in group A subjects who took supplements.

PIP: 18-45 year old women were tested to determine if the use of oral contraceptive agents (OCAs) affects the metabolism of vitamins. 4 different hormonal conditions and 2 socioeconomic levels in 8 groups were considered. Some of each socioeconomic level had taken Norinyl (1 mg norethisterone and 50 mcg mestranol) for 3 months or more. Others had used Ovral (.5 mg norgestrel and 5 mcg ethinyl estradiol) for equal periods. There were some in each group who had resumed use of OCAs during lactation within 5 weeks after pregnancy. Vitamins and mineral supplements were given to groups in each socioeconomic classification. They had a higher intake of Vitamins-A, C, thiamin, riboflavin, and folic acid. Incidence of clinical sings of malnutrition, such as dry skin, easily pluckable hair, angular lesions of the mouth, dental caries, bleeding gums, glossitis, and scaling of the skin, were significantly more frequently observed in the lower socioeconomic groups, and especially in nonsupplemented groups of women taking OCAs than in others. OCA administration increased plasma Vitamin-A levels but no socioeconomic effect was found. Plasma carotene levels were decreased by OCA therapy, but less so in the higher socioeconomic subjects. Plasma ascorbate was not affected by OCA use. Urinary excretion of thiamin annd riboflavin was decreased in subjects using OCAs. Erythrocyte folate and plasma pyridoxal phosphate (PLP) were also decreased. Results show a definite lowering effect of OCAs on red cell folate in subjects in the upper socioeconomic levels. There may also be a depletion of body stores of folic acid. It has been suggested that women who become pregnant soon after discontinuing OCA therapy have a high chance of developing folic acid deficiency during pregnancy. The lower socioeconomic group may be marginally deficient in folic acid. Similar results were obtained with thiamin and riboflavin. Changes due to OCA use with respect to thiamin, riboflavin, folate, and PLP were seen mainly in subjects in the upper lower socioeconomic groups may have prevented detection of smaller similar alterations due to OCA use.

Effect of oral contraceptive agents on nutrients: I. Minerals.

The epidemiological aspects of oral contraceptive agents on nutrient metabolism were studied in a large population of women. Incidence of clinical abnormalities, related to malnutrition, were more frequently observed in the lower (B) as compared to the higher (A) socioeconomic groups. In the A groups some clinical signs were more common in the nonsupplemented groups of subjects. In general, the intake of oral contraceptive agent subjects for calories, protein, calcium, magnesium, iron, copper and zinc did not differ from the controls. The intake of the above nutrients in group A subjects were higher than those of group B except for calories. The subjects who took supplements had higher intakes of calcium, iron, magnesium and copper. No effect of oral contraceptive agents was seen on hemoglobin, hematocrit and erythrocyte count. Serum iron was increased due to "Norinyl." Total iron binding capacity was increased as a result of oral contraceptive agent administration. Total iron binding capacity values were higher in group B as compared to group A and in the nonsupplemented as compared to the supplemented groups. Plasma copper was increased and plasma zinc was decreased as a result of oral contraceptive agent administration. An increase in erythrocyte zinc was observed due to "Norinyl." No effect of oral contraceptive agents on plasma calcium, magnesium and erythrocyte magnesium was observed. Although no effect of oral contraceptive agents on plasma total protein was found, serum albumin was decreased.