Dexamethasone stimulation of fetal rat lung antioxidant enzyme activity in parallel with surfactant stimulation

It has recently been determined that fetal lung antioxidant enzyme activity markedly increases late in gestation. A test was made of whether this normal late-in-gestation change in O2-protective enzymes would be responsive to the maturing effect of hormonal (glucocorticoid) treatment. Pregnant rats received 0.2 mg/kg of dexamethasone (or saline) at 48 and 24 hours prior to delivery of their fetuses on gestational days 19, 20, 21, and 22 (newborn). Lung disaturated phosphatidylcholine showed an expected response to prenatal dexamethasone exposure with significant elevations of surfactant lipid at gestational days 20 and 21. A similar effect of prenatal dexamethasone treatment on the lung antioxidant defensive system was found. Superoxide dismutase, catalase, and glutathione peroxidase--enzymes protective against hyperoxia-induced lung injury--showed an accelerated pattern of maturation with significant increases in the dexamethasone-treated fetal lungs compared with control fetal lung enzyme levels at gestational days 20 and 21. The results suggest that prenatal dexamethasone treatment may have dual benefits when used in impending premature deliveries--that is, it may stimulate maturation of both the surfactant system and also the antioxidant enzyme system, and this maturation can help protect the premature newborn's lungs from the toxic complications of hyperoxic therapy that may be required because of immaturity.     

Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation

Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.     

PITUITARY-ADRENAL AND TESTICULAR FUNCTION IN PRETERM INFANTS AFTER PRENATAL DEXAMETHASONE TREATMENT

ABSTRACT. Pituitary-adrenal and testicular function was monitored by plasma ACTH and testosterone (T) measurements in preterm newborns (gestational age below 36 weeks), exposed in utero to dexamethasone treatment for prevention of respiratory distress syndrome. A group of age-matched premature newborns and full-term infants served as controls. The cord-blood ACTH level was high in each group (logarithmic means 65-75 ng/l), but decreased within the first 2 days of life to mean levels between 20-30 ng/l on days 3 to 10 inclusive. Dexamethasone treatment had no effect on the postnatal ACTH concentrations when compared with preterm or full-term controls. Similarly, no differences in plasma ACTH were found between untreated preterm and full-term infants during the first 10 days of life. T levels in mixed cord blood were on average 2-3 nmol/l in the preterm male infants. An increase to a mean level of 10 nmol/l was seen in 1 h and 1d samples. Thereafter, the concentration of T decreased to 2-3 nmol/l on days 3-10 postnatally. No effect of dexamethasone treatment was seen on the postnatal pattern of plasma T. When preterm male and full-term male infants were compared, no difference was seen in the T peak in the first day of life. However, the 1-3, and 60-90 day concentrations of T were 2-fold ( p <0.01–0.05) higher in the preterm group. It is concluded that prenatal dexamethasone treatment of the mother does not influence the postnatal pituitary-adrenal function as monitored by ACTH measurements. Likewise, no effect of this treatment was observed on the postnatal testicular activity of preterm male infants. The immediate postnatal peak in plasma T levels persisted longer in the preterm than in the full-term male infants.     

Pituitary-adrenal and testicular function in preterm infants after prenatal dexamethasone treatment

Pituitary-adrenal and testicular function was monitored by plasma ACTH and testosterone (T) measurements in preterm newborns (gestational age below 36 weeks), exposed in utero to dexamethasone treatment for prevention of respiratory distress syndrome. A group of age-matched premature newborns and full-term infants served as controls. The cord-blood ACTH level was high in each group (logarithmic means 65-75 ng/l), but decreased within the first 2 days of life to mean levels between 20-30 ng/l on days 3 to 10 inclusive. Dexamethasone treatment had no effect on the postnatal ACTH concentrations when compared with preterm or full-term controls. Similarly, no difference in plasma ACTH were found between untreated preterm and full-term infants during the first 10 days of life. T levels in mixed cord blood were on average 2-3 nmol/l in the preterm male infants. An increase to a mean level of 10 nmol/l was seen in 1 h and 1 d samples. Thereafter, the concentration of T decreased to 2-3 nmol/l on days 3-10 postnatally. No effect of dexamethasone treatment was seen on the postnatal pattern of plasma T. When preterm male and full-term male infants were compared, no difference was seen in the T peak in the first day of life. However, the 1-3, and 60-90 days concentrations of T were 2-fold (p less than 0.01-0.05) higher in the preterm group. It is concluded that prenatal dexamethasone treatment of the mother does not influence the postnatal pituitary-adrenal function as monitored by ACTH measurements. Likewise, no effect of this treatment was observed on the postnatal testicular activity of preterm male infants. The immediate postnatal peak in plasma T levels persisted longer in the preterm than in the full-term male infants.     

Formation of bilirubin conjugates in human newborns

Bilirubin conjugates in the serum of newborn human infants were investigated using the alkaline methanolysis-high-performance liquid chromatography method, a specific and sensitive method for measurement of unconjugated bilirubin and bilirubin mono- and diester conjugates. Serum samples were analyzed from 13 premature infants, 11 full term newborns, 22 healthy adults, seven pregnant women at term and their corresponding infants cord blood at delivery, 46 cord blood specimens obtained at unselected deliveries, three cord bloods from infants with maternal-fetal blood group incompatibility, and two cord bloods from infants with intrauterine hypoxia. Bilirubin conjugates were not detectable in the healthy adults, maternal blood, or in the cord blood specimens except from infants with blood group incompatibility or intrauterine hypoxia. The two isomeric monoconjugates of bilirubin appeared in serum during the first 24 to 48 postnatal h in both premature and full term infants, followed by the diconjugate on the 3rd day. Conjugated esters accounted for 2 to 5% of the total bilirubin, with the diconjugate constituting 21% of total conjugated pigment (day 3). In all instances, the unconjugated serum bilirubin concentration had increased to at least 2 mg/dl in the course of physiologic neonatal hyperbilirubinemia before bilirubin conjugates became detectable. Both premature and full term human infants displayed the identical pattern of bilirubin conjugation in serum.     

Intrauterine growth-retarded rat pups show increased susceptibility to pulmonary O2 toxicity

We used a nutritional deprivation model to produce intrauterine growth-retarded (IGR) rat pups (birth weight = approximately 75% of normal). The IGR newborns evidenced a marked reduction in tolerance to greater than 95% O2 exposure: 10-day survival = 10/47 (21%) versus 18/36 (50%) for control pups, and LT50 = 7.2 days versus 10 days for controls (p less than 0.01). Various lung parameters at birth and during O2 exposure were examined to try to define why prenatal undernutrition should compromise the survival of IGR rats in hyperoxia. We found decreased lung glutathione peroxidase and glucose-6-phosphate dehydrogenase activity (with normal superoxide dismutase and catalase levels) in the IGRs at birth; decreased lung disaturated phosphatidylcholine content (even more markedly decreased in 1-day premature pups); and decreased lung surface area/body weight. These factors and other features of newborn IGRs reported in the literature may help to explain how prenatal undernutrition compromises postnatal tolerance to prolonged high-O2 exposure.     

Digoxin intoxication in newborns correlation with digoxin plasma concentration (author's transl)

During childhood digitalis glycosides are most frequently used during the newborn period. Within two years, we found evidence of digoxin intoxication in eight newborns. This was suspected when specific electrocardiographic signs developed under digoxin treatment and disappeared either after discontinuation of digoxin alone, or in combination with specific treatment. These eight newborns had plasma digoxin concentrations of 5 ng/ml or more, while the concentrations in unaffected newborns averaged 2.4 ng/ml (premature newborns) and 2.2 ng/ml, (mature newborns). The clinical and pathophysiological features of digoxin intoxication specific to the newborn period are discussed. Despite certain limitations it seems reasonable to check plasma digoxin concentrations during the newborn period, since clinical and electrocardiographic manifestations of a digoxin intoxication are frequently unspecific at this age. A digoxin intoxication is very likely with plasma digoxin concentrations of 5 ng/ml or more, but unlikely with concentrations below 3 ng/ml.     

Prenatal thyroid releasing hormone and thyroid releasing hormone plus dexamethasone lessen the survival of newborn rats during prolonged high O2 exposure.

Newborn rats prenatally treated with TRH or the combination of TRH + DEX have lower lung antioxidant enzyme activities at birth than control newborns but are able to induce an adaptive antioxidant enzyme response to hyperoxic exposure of similar or even greater magnitude compared to O2 control offspring. Because of this greater antioxidant enzyme response, we hypothesized that the hormonally pretreated newborns might demonstrate superior tolerance to prolonged high O2 exposure. However, when placed in greater than 95% O2 at birth, the survival rates were consistently lower in the TRH- and TRH + DEX-treated pups at all time periods in hyperoxia from 9 d [control = 74 of 92 (80%); TRH + DEX = 32 of 47 (68%); TRH = 29 of 48 (60%); p less than 0.05] to 14 d [control = 43 of 92 (47%); TRH + DEX = 11 of 47 (23%); TRH = nine of 48 (19%); (p less than 0.05)]. Other evidence of poorer O2 tolerance in the prenatal hormone-treated pups included a greater incidence of intraalveolar edema and elevated lung conjugated dienes, an index of lipid peroxidation, at 3, 5, and 7 d of O2 exposure. There was also a persistent elevation in 3,5,3'-triiodo-L-thyronine and thyroxine serum levels in the 10-d-old TRH-treated offspring. We conclude that prenatal TRH treatment, possibly working through the secretion of 3,5,3'-triiodo-L-thyronine and thyroxine, has some important lasting postnatal effect (not completely reversed by dexamethasone) that predisposes newborn rats to greater O2 radical-induced lung sequelae of prolonged hyperoxic exposure.     

Effect of antenatal dexamethasone treatment on Ca2+-dependent nitric oxide synthase activity in rat lung

We investigated the effects of dexamethasone on nitric oxide synthase activity, nitrate/nitrite concentration, and cGMP concentration in the lungs of premature and full-term neonate rats. Dexamethasone or vehicle alone was administered to the mother (1 mg/kg/d, s.c., 2 d), and the neonate was killed 24 h after birth. Ca2+-dependent nitric oxide synthase activity and nitrate/nitrite and cGMP concentrations in lungs of dexamethasone-treated neonates, both premature and full-term, were significantly higher than those in the lungs of the control rats. Ca2+-dependent nitric oxide synthase activity, nitrate/nitrite concentration, and cGMP concentration in the lungs of control rats showed developmentally associated increases during late gestation and in the early postnatal period. The activation of the nitric oxide synthasenitric oxide-cGMP system by antenatal dexamethasone treatment may be related to the improvement of pulmonary function by antenatal glucocorticoid therapy to minimize respiratory distress syndrome.     

Growth of premature infants fed own mother's milk supplied with two milk formulas

The purpose of the authors in this article was to evaluate the effects of supplementing maternal milk with two different caloric formulas on the growth of premature newborns until they reached 40 weeks of post-conceptional age. Seventy premature infants weighing < 1750g at birth were randomized: 35 adequate for gestational age (AGA) and 35 small for gestational age received maternal milk and either a special preterm formula or a modified formula. Anthropometric measurements and clinical evaluations were used to determine the nutritional status and the postnatal growth of these infants, who were analyzed in six different moments: at maximum weight loss, at return to birth weight, at definite weight gain, when exclusively fed with formula, at 2000g, and when they reached 40 weeks of post-conceptional age. The AGA premature newborns on preterm formula had greater daily weight gain, cephalic circumference increase and growth. The SGA premature newborns on preterm formula had greater daily weight gain and cephalic circumference increase observed from the third week of life onward. The AGA premature newborns on modified formula had less weight gain and smaller increments in the cephalic circumference. The SGA premature on modified formula had the worst anthropometric results. The preterm formula was more efficient than the modified formula in promoting postnatal growth of AGA and SGA premature infants. We believe that, due to their special characteristics, SGA premature should receive individualized nutritional caloric planning     

Chronic hypoxia and rat lung development: analysis by morphometry and directed microarray

It is unclear how sublethal hypoxia affects lung development. To investigate the effects of chronic hypoxia on postnatal lung remodeling, we treated neonatal rats with FIO2 of 0.12 for 10 d and analyzed lung development by morphometry and gene expression by DNA microarray. Our results showed the neonatal rats exposed to hypoxia reduced body weight by 42% and wet lung weight by 32% compared with the neonatal rats exposed to normoxia. In the neonatal rats exposed to hypoxia, the radial alveolar counts were decreased to 5.6 from 7.9 and the mean linear intercepts were increased to 56.5 mum from 38.2 mum. In DNA microarray analysis, approximately half of probed genes were unknown. Chronic hypoxia significantly regulated expression of genes that are involved in pathogenesis of pulmonary hypertension and postnatal lung remodeling. Chemokine ligand 12, jagged 2 were among those upregulated; c-kit, ephrin A1, and Hif-2alpha were among those downregulated. The altered expression of those genes was correlated with the lung development and remodeling.     

Lung epithelial cells undergo apoptosis in neonatal respiratory distress syndrome

For studying the presence of programmed cell death in the lungs of infants with fatal respiratory distress syndrome (RDS) and the possible contribution of postnatal glucocorticoid administration on this cell destruction, lung tissue samples from autopsies of 16 premature infants with fatal RDS were studied. The infants had neither been exposed to antenatal steroids nor received surfactant therapy, but seven of these infants had been subjected to postnatal dexamethasone treatment. Lung autopsy samples of seven term and two preterm neonates without any obvious lung disease served as controls. Lungs were studied histologically, and apoptotic cell death was identified using DNA nick end-labeling assay and caspase-related M30 antibody staining (CytoDeath). Lung tissue from the RDS infants showed elevated leukocyte infiltration, histologic injury score, and number of apoptotic cells, located mainly in the respiratory epithelium, when compared with controls. In contrast, lungs from infants who had RDS and received dexamethasone demonstrated markedly reduced tissue leukocyte accumulation and injury score and lower rates of epithelial apoptosis than the lungs of infants who had RDS and did not receive dexamethasone. These results suggest that significant epithelial apoptosis is present in the lungs of newborn infants with fatal RDS and that this apoptosis may be attenuated by steroid administration.     

Impairment of rat postnatal lung alveolar development by glucocorticoids: involvement of the p21CIP1 and p27KIP1 cyclin-dependent kinase inhibitors.

It has been shown that glucocorticoids accelerate lung development by limiting alveolar formation resulting from a premature maturation of the alveolar septa. Based on these data, the aim of the present work was to analyze the influence of dexamethasone on cell cycle control mechanisms during postnatal lung development. Cell proliferation is regulated by a network of signaling pathways that converge to the key regulator of cell cycle machinery: the cyclin-dependent kinase (CDK) system. The activity of the various cyclin/CDK complexes can be modulated by the levels of the cyclins and their CDKs, and by expression of specific CDK inhibitors (CKIs). In the present study, newborn rats were given a 4-d treatment with dexamethasone (0.1-0.01 microg/g body weight dexamethasone sodium phosphate daily on d 1-4), or saline. Morphologically, the treatment caused a significant thinning of the septa and an acceleration of lung maturation on d 4. Study of cyclin/CDK system at d 1-36 documented a transient down-regulation of cyclin/CDK complex activities at d 4 in the dexamethasone-treated animals. Analysis of the mechanisms involved suggested a role for the CKIs p21CIP1 and p27KIP1. Indeed, we observed an increase in p21CIP1 and p27KIP1 protein levels on d 4 in the dexamethasone-treated animals. By contrast, no variations in either cyclin and CDK expression, or cyclin/CDK complex formation could be documented. We conclude that glucocorticoids may accelerate lung maturation by influencing cell cycle control mechanisms, mainly through impairment of G1 cyclin/CDK complex activation.     

Impaired hepatic glycogenolysis related to hyperinsulinemia in newborns from hyperglycemic pregnant rats

We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.     

Effect of maternal vitamin-A administration on fetal lung vitamin-A stores in the perinatal rat

Vitamin A (retinol) is essential for normal differentiation and integrity of developing respiratory epithelium and its deficiency has been linked to an increased susceptibility to lung injury. Because significant vitamin-A storage occurs in the fetal lung near term in the perinatal rat, prematurely born animals deprived of adequate stores in their lungs may be susceptible to the adverse effects of vitamin-A deficiency. It would be desirable if lung vitamin-A stores could be augmented with maternal administration, but the feasibility of this strategy has not been reported. We therefore conducted this study in rats to determine whether maternal administration of vitamin A could increase the lung stores of vitamin A in the offspring. Vitamin-A-sufficient pregnant rats were given a single dose of either vitamin A (50,000 IU retinyl palmitate) or 0.9% saline solution on gestational day 16 (term = 21 days) by the intragastric route. High-performance liquid chromatography was used to measure concentrations of vitamin A and its esters in fetal and neonatal lungs and livers at times ranging from gestational day 17 through 21, and from postnatal day 1 through 14. The concentrations of vitamin-A esters in the lungs of fetuses and newborn pups of the vitamin-A-treated animals were significantly (1.7- to 7.1-fold) higher than those of the control group. This increase in the lung vitamin-A ester concentrations was seen within 24 h of maternal administration and persisted throughout the 14-day postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antenatal dexamethasone administration impairs normal postnatal lung growth in rats

Our purpose was to determine the influences of antenatal dexamethasone administration on neonatal lung development in rats. Dexamethasone (0.4 mg/kg maternal body weight per day) was administered i.p. on the 21st d (group 1) or on the 20th and 21st d (group 2) of gestation in Sprague Dawley rats with timed pregnancies. After natural deliveries, the lungs of the pups 1-60 d of age were removed and processed for morphometric analysis. In 60-d-old pups, groups 1 and 2 both showed a lower numerical density of alveoli and a larger mean alveolar radius than control pups. Antenatal administration of dexamethasone to rats impairs the normal postnatal lung growth. Some aspects of the use of antenatal glucocorticoid therapy in humans may require reconsideration.     

The use of inhaled glucocorticosteroids and recovery from adrenal suppression after systemic steroid use in a VLBW premature infant with BPD: case report and literature discussion

Despite development of many prevention and treatment modalities for bronchopulmonary dysplasia (BPD), a form of chronic respiratory insufficiency in premature infants recovering from respiratory distress syndrome, BPD remains a treatment challenge and a significant cause of long-term morbidity. A ventilator-dependent very low birth weight infant in our newborn special care unit was receiving multiple courses of systemic dexamethasone for severe respiratory failure. The infant demonstrated adrenal suppression manifested by a baseline cortisol concentration below reported levels in infants of similar birth weight and postnatal age. We hypothesized that he had developed adrenal insufficiency as a result of the prolonged systemic steroid administration used to treat his respiratory problems. We further hypothesized that inhaled beclomethasone therapy would aid in the infant's recovery phase during relative adrenal insufficiency--and so substituted inhaled for systemic steroids. Inhaled corticosteroid treatment improved the clinical respiratory course and postnatal growth of this premature infant with BPD without inhibiting his recovery from adrenal insufficiency.     

Effect of maternal NG-nitro-l-arginine administration on fetal growth and hypoxia-induced changes in newborn rats

BACKGROUND: Nitric oxide (NO) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in the last trimester of pregnancy caused intrauterine growth retardation and hind-limb disruptions in rats. In the present study, the effect of maternal NO inhibition with NG-nitro-l-arginine (l-NNA) on hypoxic newborn rats was investigated. METHODS: Timed-pregnant rats were obtained on gestational day 17. Four groups of rats were used: control, hypoxic, l-NNA and l-NNA + hypoxic groups. In the last two groups, l-NNA (2 mg/kg bolus, i.p.) was administered to the mothers of pups antenatally on 3 consecutive days. Hypoxia was induced in newborn rats by breathing of a mixture of 8% oxygen and 92% nitrogen for 3 h. Pups were then allowed to inhale normal atmospheric air for 30 min. All newborn rats were decapitated on the first day of life after hypoxia and reoxygenation. Brain, heart, lung, liver, kidney and intestinal tissues were studied biochemically. Hypoxia-induced biochemical changes were determined by measuring lipid peroxidation. Histopathologic examination of lung tissue was performed. RESULTS: Nitric oxide synthase inhibition in pregnancy did not cause fetal growth retardation. Hypoxia increased lipid peroxidation in all tissues except the heart; this increase was decreased by maternal l-NNA administration in brain, lung, liver and kidney tissues. However, lipid peroxidation was increased by NO synthase inhibition in the intestines. In the lungs, pulmonary hemorrhage was observed in the hypoxic group. Minimal pulmonary hemorrhage was detected in the l-NNA and l-NNA + hypoxic groups. CONCLUSIONS: These data suggest that antenatal administration of an NO synthase inhibitor acts as both a destructive and protective agent in hypoxic newborn rats.     

Maternal plasma homocysteine, placenta status and docosahexaenoic acid concentration in erythrocyte phospholipids of the newborn

The enhanced transport of long-chain polyunsaturated fatty acids, in particular docosahexaenoic acid (22:6 ω-3) (DHA), to the fetus is a placental function important for adequate membrane phospholipid formation and herewith decisive for the quality of fetal CNS myelination. A compromised placental function is correlated with signs of vascular pathology. As elevated plasma total homocysteine (tHcy) concentrations are considered an independent risk for premature occlusive vascular disease, the influence of maternal plasma tHcy concentrations on placental function was indirectly studied, determining the DHA content in erythrocyte membrane phospholipids of the newborn. A total of 60 unselected pregnant women (age range: 21 to 39 years) were investigated at delivery. Gestational age ranged from 26 to 41 weeks. Prior to delivery a placental ultrasound scan was performed. Complete sets of data could be obtained from 43 mothers and their offspring. tHcy concentrations were determined in the plasma of cord and maternal blood. The fatty acid pattern of erythrocyte membrane phospholipids was determined in the mothers and their newborns. Z-scores of the birth weights ranged from −3.4 to 2.1 and of the placental weights from −3.8 to 4.7. The mean maternal plasma tHcy concentration was 6.29 ± 3.34 μmol/l ranging from below our limit of detection up to 15 μmol/l. These maternal concentrations were correlated with those of their infants (r = 0.71; P < 0.0001). The tHcy concentrations were significantly higher in mothers with pregnancies complicated by gestosis or placental calcifications. The Z-scores of birth weights as well as placental weights showed a significant negative correlation with maternal plasma tHcy concentrations. The mean DHA percentage of total fatty acids in erythrocyte phospholipids was 3.2 ± 2.2% in the mothers and 3.4 ± 2.3% in their newborns. Most importantly the maternal plasma tHcy levels and the erythrocyte phospholipid DHA concentrations of their offspring were significantly correlated (r = −0.51; P < 0.0003). Conclusion In this study, total homocysteine concentrations were elevated in the plasma of pregnant women with signs of placental vasculopathy. Maternal plasma total homocysteine concentrations were positively correlated with erythrocyte phospholipid docosahexaenoic acid of their offspring and may be an indicator for the integrity of placental vascular function. The nutritional status as well as predisposing genetic factors of pregnant mothers need to be investigated more thoroughly. Received: 17 May 1998 / Accepted in revised form: 10 September 1998