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Pathological changes were studied by light and electron microscopy on term placentas collected in Malawi from 20 P. falciparum infected women (11 primiparas and 9 multiparas). One placenta from an uninfected term primipara and 4 from multiparas were studied as controls. Changes included the presence of parasitized erythrocytes and malarial pigment particles in the intervillous space, excessive syncytial knotting, chronic basal villitis, malarial pigment deposits in the trophoblasts, trophoblastic damage with focal necrosis, partial loss of microvilli, and thickening of the trophoblastic basement membrane. Infected erythrocytes were not seen in the fetal circulation. Severity appeared to correlate with the level of maternal and placental parasitemias, regardless of infant birth weight or placental weight. Differences in the severity of pathological changes between primiparas and multiparas could not be demonstrated. Immunohistochemistry revealed that 45% of the placentas stained strongly for IgG and 15% stained for C3 and for P. falciparum antigens in the trophoblastic cytoplasm and basement membrane.

In the present study we report results concerning 5-hydroxytryptamine (5-HT) metabolism in two groups of small for date (SFD) human babies (gestational age 36 and 3 weeks), who suffered intrauterine nutritional restriction. A complementary study in the brain of rat fetuses with two types of intrauterine deprivation, in which brain L-tryptophan (L-Trp), tryptophan-5-hydroxylase (T5-H) activity and 5-HT content were determined on days 17, 19 and 21 of gestation. The same parameters studied prenatally were followed in both species during the immediate postnatal period. In the SFD babies the results were: (a) the free fraction of plasma L-Trp was significantly elevated; (b) plasma neutral amino acids were not substantially modified; (c) the bound fraction of L-Trp and plasma proteins were significantly low, as compared to controls. In the fetal brain of intrauterine malnourished rats, L-Trp, activity of T5-H and 5-HT content, were significantly elevated, since day 17, as related to normal littermates. These alterations in 5-HT metabolism persisted during the early postnatal period in both species. Elevation of the free fraction of plasma L-Trp in early malnourished SFD human babies suggest an increased transport of this amino acid to the brain with a possible enhancement of serotonin synthesis, during a critical period of brain differentiation.

Methadone, injected subcutaneously into Wistar rats during the last trimester of gestation, significantly retarded offspring body and brain growth and the ontogeny of brain catecholamines. On postnatal days 1 and 20, the endogenous content and high affinity uptake of norepinephrine and dopamine were significantly lower in the forebrains of methadone-treated pups than in those of saline or pair-fed control offspring. On day 40, regional norepinephrine levels and uptake were similar in the brains of all three groups. However, the striata of methadone pups remained significantly lower in dopamine content and uptake than did those of saline pups at this age. Hindbrain norepinephrine and dopamine were not altered at any time point. These data indicate that prenatal exposure to methadone more severely retarded body and brain growth than did prenatal undernutrition alone. Furthermore, biochemical indices of the maturation of central catecholamine pathways suggest that prenatal methadone may retard catecholaminergic axonal growth from the hindbrain to the forebrain in rats.

We perfused in vitro the placentas of the mothers of 3 small for gestational age (SGA) and 3 adequate for gestational age (AGA) infants. After a systemic injection of 10 mg of dehydroepiandrosterone sulfate (DHEA-S), we measured the time course of the levels of DHEA-S, unconjugated DHEA, delta 4-androstenedione (delta 4-A), testosterone (T), estrone (E1) and estradiol (E2) in perfusate. We observed a significant accumulation of delta 4-A + T and a concomitant low increase of E1 + E2 in the placental fluid of SGA infants. We conclude that the aromatase activity could be decreased in some cases of placental insufficiency. This could, at least in part, explain the accumulation of circulating androgens in the mothers of some SGA infants following DHEA-S loading test observed in vivo.

The effect of protein-calorie malnutrition during gestation on the brain amino acids of rat pups was studied following nutritional recovery during lactation. The brain amino acids of rat pups born to dam rats malnourished during gestation were studied after these rat pups received proper nutrition during lactation. Pregnant rats were fed a 1% protein diet with total caloric intake restricted to half that of controls. After birth, the offspring of rats fed on deficient diets were nurtured up to the 28th day postpartum by foster mothers receiving adequate diets. At this time, the offspring were killed. The control group consisted of offspring from pregnant rats fed a diet with adequate protein (21%) and calories during the entire gestation and lactation period. Quantitation of brain amino acids in the pups at 28 days postpartum showed lower concentrations of essential and nonessential amino acids in the rats malnourished during gestation. Concentrations of histidine, glycine, and alpha-aminobutyric acid were all reduced. These findings demonstrate that the brains of rat pups malnourished during gestation show persistent decreases in specific brain amino acids after adequate postpartum nutrition.

Free amino-acids in the fetal and maternal compartments towards the end of normal and pathologic pregnancies were examined with gas chromatography. Blood was obtained from the cubital and uterine veins and the femoral artery of the mother, from the umbilical artery and vein and the amniotic fluid during Caesarean section. There were only minor differences of concentration of free amino-acid between normal and pathologic pregnancies. Since it is possible in principle that there is mutual balance between maternal and fetal compartments, assessment of changes in amino-acid concentration during dia- and paraplacentar exchanges is usable only with reservations.

Ovine placental lactogen levels in the maternal circulation are significantly reduced after single umbilical artery ligation in pregnant sheep. We report the ovine placental lactogen response to high-dose amino acid stimulation in four ewes with fetuses that underwent single umbilical artery ligation and six control ewes with fetuses that underwent sham operation. After maternal infusion with 50 gm of arginine in 350 ml of distilled water, mean ovine placental lactogen levels in ewes with fetuses that underwent single umbilical artery ligation increased by 170%, while mean levels in control ewes increased by 294%. Maternal infusions with hypertonic saline solution of osmolality and volume equal to those of the arginine solutions failed to increase maternal ovine placental lactogen levels. Fetal well-being, both during and after the maternal arginine infusions, was confirmed by unchanged fetal arterial blood gases and catecholamines. The ovine placental lactogen levels in the fetal circulation were not altered by maternal arginine infusion. These data suggest that the correlation between maternal ovine placental lactogen levels and functioning placental mass may be enhanced by arginine stimulation. The possible use of this provocation of placental lactogen levels as a test of placental function in clinical practice is discussed.