Intrauterine Fetal Growth Retardation Research Articles

Pemphigoïde gestationis et syndrome vasculorénal : association fortuite ?

Pemphigoid gestationis is a gestational skin disease usually appearing between the 28th and the 32nd week of amenorrhea. It is a rare vesiculobullous skin disease and the eruption is located around the umbilicus. The diagnosis is made with clinical symptoms but mainly on histologic examination (after skin biopsy) and direct immunofluorescence. One of the main complications is the rate of recurrence. The main treatment is based on topical corticosteroids. The effects of the pemphigoid gestationis are maternal (preterm labor), fetal (intrauterine growth retardation) and neonatal (bullous disease). We report a case of pemphigoid gestationis associated to a gestational hypertensive disorder and we try to rely on both entities.

Prothrombin Gene Variants in Non-Caucasians with Fetal Loss and Intrauterine Growth Retardation

Thrombotic predisposition may affect pregnancy outcome, but in non-Caucasians the contributing genetic factors are poorly characterized. Two recently identified prothrombin gene mutations (20209C>T and 20221C>T) have been observed in non-Caucasian patients with thrombosis. The mutations are located near the commonly identified variant 20210G>A and have not been reported in Caucasian patients. The authors report a novel connection with pregnancy complications. The identification of sequence variants other than 20210G>A in the 3'-untranslated region of the prothrombin gene suggests that additional nucleotide substitutions may contribute to the development of thrombotic events and adverse pregnancy outcomes, especially in less well-characterized populations.

Assessment of fetal distress based on magnetic resonance examinations: preliminary report 1

Rationale and Objectives. Hypoxia is the main cause of injuries and intrauterine death of the fetus. Therefore, the main aim of monitoring and assessment of the fetus should be diagnosis of fetal distress before irreversible changes occur. Besides the fetal condition assessment methods used so far, in recent years in obstetrics new non-invasive imaging methods were introduced such as magnetic resonance (MR). This method enables morphologic evaluation of brain and brain tissue metabolism using magnetic resonance spectroscopy (MRS). Materials and Methods. Twenty pregnant women with pregnancy-induced hypertension (11 cases, including 3 with coexisting diabetes mellitus and 2 with intrauterine growth retardation), chronic hypertension (2 cases), gestational diabetes mellitus (6 cases), and suspected intrauterine fetal growth retardation (IUGR) participated in the study. Cardiotocography (CTG) and Doppler ultrasound examination of the blood flow in the umbilical artery and in the middle cerebral artery were performed. Results. In case of abnormal CTG and Doppler study records that indicated fetal hypoxia, MR studies showed the existence of ischemic focus in 5 patients and abnormal spectral images in 6 patients. Conclusion. The results of the preliminary study suggests that the use of MR in prenatal diagnosis may revolutionize the early detection of fetal injury in fetal distress. It is a valuable component of the diagnostic process, supplementing other examinations. The use of MR to assess fetal condition gives additional information and helps to make decisions about therapeutic actions.

Persistent short stature, other potential outcomes, and the effect of growth hormone treatment in children who are born small for gestational age.

Persistent short stature, other potential outcomes, and the effect of growth hormone treatment in children who are born small for gestational age.

The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture.

Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). We found in previous studies that sera from SLE/APS patients when used as a culture medium for rat embryos were found to reduce embryonic growth and development, induce a high rate of embryonic anomalies and death and damage the yolk sac morphologically and functionally. In order to investigate the direct effect of IgG purified from women with SLE/APS on the growth and viability of embryos, we cultured 11.5-day-old rat embryos in their yolk sacs in the presence of IgG purified from SLE/APS patients with recurrent pregnancy loss (RPL). The IgG affected directly the embryo and yolk sac, reducing their growth. The purified IgG positive for anticardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies but positive for antiphosphatydilserine and for antilaminin. Monoclonal antiphosphatydilserine reduced yolk sac growth but the embryos remained intact. Following the observed damage to the yolk sac we cultured human placental explants at 5.5-8 weeks of pregnancy in sera from SLE/APS patients for 96 hours and found that these sera reduced placental trophoblastic cell growth, reduced their proliferation rate and increased their rate of apoptosis. Successful treatment of the women resulted in a correction of the damage induced in the cultured rat embryos and in the cultured placental explants.

Intrapartum Surveillance of IUGR Fetuses with Cardiotocography and Fetal Pulse Oximetry

Objective: To investigate the efficacy and safety of intrapartum fetal pulse oximetry, as a predictor of metabolic acidosis at birth of fetuses with intrauterine growth retardation (IUGR). Study Design: We studied 18 IUGR fetuses (group I) and a control group of 30 appropriate for gestational age (AGA) fetuses (group II) during labor. Both groups had abnormal fetal heart rate tracings and were monitored simultaneously throughout labor with cardiotocography and fetal pulse oximetry. Apgar scores, pH and base excess of fetal blood obtained from the umbilical artery after delivery were compared in both groups. Setting: The Fetal Surveillance Unit of the 2nd Department of Obstetrics and Gynecology, Aretaieion Hospital, Medical School, Athens University. Results: In IUGR fetuses, when their oxygen saturation value (FSPO₂) was less than 34%, cord artery pH was 7.10 ± 0.04, base excess –13 ± –1 mmol/l and Apgar scores ≤5 at the 5th min, and when FSPO₂ was over 35%, artery pH was 7.29 ± 0.08, base excess –8 ± –2 mmol/l and Apgar scores ≧7 at the 5th minute. In cases of drops of FSPO₂below 30% for more than 2 min, labor was completed operatively and cord pH was 7.00 ± 0.04, base excess –15 ± –2 mmol/l and Apgar scores ≤5 at the 5th minute. In AGA fetuses, when FSPO₂ was over 30%, artery pH was over 7.20, base excess <–11 mmol/l and Apgar scores ≧9 at the 5th minute; in contrast, when FSPO₂ was <30% for 2 min, a cesarean section was performed and cord pH was ≤7.02, base excess ≧–13 mmol/l and Apgar scores ≤4 at the 5th minute. Conclusions: In IUGR fetuses, FSPO₂ values less than 34% represent an acidotic status, while values of ≧35% are well tolerated. Fetal pulse oximetry proved reliable, according to umbilical cord blood measurements and Apgar scores, reducing cesarean deliveries in cases of nonreassuring cardiotocographic patterns in IUGR fetuses.

The effects of IgG purified from women with SLE and associated pregnancy loss on rat embryos in culture.

Recurrent fetal loss occurs in approximately 1% of women. Autoimmune causes have been suggested as a factor in some of these cases. High rates of intrauterine fetal growth retardation and increased incidence of prematurity is associated with systemic lupus erythematosus (SLE) and the anti-phospholipid syndrome (APS). Autoantibodies from sera of SLE/APS patients affect reproductive outcome in pregnant mice, as was studied in vivo, where injection of immunoglobulin (Ig)G purified from patients with APS to mice caused fetal resorptions and growth retardation. In order to investigate the direct effect of IgG purified from women with SLE or APS on the growth and viability of embryos, we cultured 11.5-day old-rat embryos in their yolk sacs in the presence of IgG purified from SLE and APS patients. IgG purified from SLE and recurrent pregnancy loss (RPL) patients affected directly the embryo and yolk sac reducing their growth. The purified IgG positive for anti-cardiolipin/anti-DNA antibodies reduced yolk sac and embryonic growth more than sera negative for these antibodies. Various antiphospholipid antibodies affect differently the growth and development of the embryo and the placenta.

Persistent chlorinated pesticides and intra-uterine foetal growth retardation: a possible association.

To examine the association between DDT (dichlorodiphenyl trichloroethane) and HCH (hexachlorocyclohexane) exposure and intra-uterine growth retardation (IUGR, <10th percentile of birth weight for gestational age). We detected p,p'-DDT, o,p'-DDT, p,p'-DDD, p,p'-DDE and alpha-HCH, beta-HCH, gamma-HCH, delta-HCH in maternal blood, placenta and cord blood, collected at parturition, from mothers with IUGR babies ( n=30) and from those with babies of normal weight ( n=24), using gas-liquid chromatography equipped with electron capture detector ((63)Ni). The adjusted odds ratios (ORs) for these pesticides in mothers and infants were determined by multiple logistic regression. There were statistically significant associations ( P<0.05) between maternal blood levels of alpha-HCH (OR=1.22; 95% CI: 1.02-1.46), gamma-HCH (OR=1.38; 95%CI: 1.05-1.80), delta-HCH (OR=1.61; 95% CI: 1.01-2.54), total HCH (OR=1.07; 95% CI: 1.01-1.13) and p,p'-DDE (OR=1.21; 95%CI:1.03-1.42) and IUGR after adjustment for potential confounders. Also, significant association (P<0.05) between cord blood levels of gamma-HCH (OR=1.14; 95% CI: 1.00-1.31), delta-HCH (OR=1.31; 95% CI: 1.00-1.75), total HCH (OR=1.07; 95% CI: 1.00-1.14) and IUGR were found after adjustment for potential confounders. A significant negative correlation between body weight of newborn babies and p,p'-DDE in maternal blood (r= -0.25; P<0.05) and delta-HCH and p,p'-DDE in the cord blood (r= -0.27 and -0.26; P<0.05) was noticed after gestational age had been accounted for. Exposure of pregnant women to organochlorine pesticides may increase the risk of IUGR, which is a contributing factor for infant mortality in India.

Quoi de neuf en nutrition infantile ?

As main current topics in pediatric nutrition we have considered the results of the continuing research on the long term consequences of fetal malnutrition and intra-uterine growth retardation with the concept of metabolic imprinting leading to chronic disease in adulthood, the progresses of knowledge in the fields of iron metabolism and regulatory mechanisms of satiety, hunger and energetic balance, a better determination of recommended docosahexanoic and arachidonic acids intake in the first months of life for premature and term infants, and the studies on probiotics and prebiotics utilization for preventive and curative purposes. The concerns about vitamin D insufficiency in France have markedly decreased with the generalization ten years ago of cholecalciferol supplementation of infant formula, and more recently the authorization of dairy products supplementation. On the contrary the problem of iron deficiency in young children remains, as well as two major nutritional concerns : the very low percentage of breast-fed infants and the dramatic increase of childhood obesity which affects presently 14% of 10 year old children versus 5 % in 1980.

Maternal Nitric Oxide Supplementation Decreases Cord Blood S100B in Intrauterine Growth-retarded Fetuses

Intrauterine growth retardation (IUGR) is thought to reflect suppression of genetic growth potential by decreased supplies of oxygen and substrate (1). NO supplementation may be useful in IUGR to increase uteroplacental circulation (2)(3)(4)(5). The use of biochemical markers to assess the extent of brain distress associated with NO treatment could be appropriate. S100B is an acidic calcium-binding protein of the EF-hand family concentrated in the nervous system (6). The appearance of S100B in biological fluids is an indicator of brain distress in both infants and adults (7)(8)(9)(10). Recently, blood S100B concentrations in the perinatal period have been shown to correlate with brain maturation and damage (11)(12)(13)(14). We investigated the effect of maternal NO supplementation on brain distress in IUGR fetuses as assessed by cord blood S100B. We selected 51 pregnant women (gestational age, 27–35 weeks) with IUGR fetuses and impaired uteroplacental blood flow. Exclusion criteria included multiple pregnancies, gestational and type 1 diabetes, maternal infections and fever, fetal malformations and chromosomal abnormalities, metabolic diseases, and maternal diseases of the central nervous system. Patients were assigned, by use of computer-generated random numbers, to receive either placebo (n = 25) or transdermal glyceryl trinitrate (Nitroderm TTS; Ciba-Geigy) at a dose of 5 mg/16 h daily until delivery (n = 26). Placebo and glyceryl trinitrate patches were indistinguishable and were numbered and contained in identical envelopes so that patients did not know the group to which they were recruited. Similarly, neither the physicians nor the investigators who analyzed the samples knew which patients were treated with placebo and which with glyceryl trinitrate patches. The local ethics committee approved the study, and written informed consent was obtained from all participants. Two patients in the glyceryl …

Effect of maternal diet rich in docosahexaenoic acid on intrauterine fetal growth retardation in spontaneously hypertensive rats

The aim of this study was to determine the effect of maternal diet rich in docosahexaenoic acid (DHA) on intrauterine fetal growth retardation in spontaneously hypertensive rats (SHR). SHRs were fed purified diet containing either a safflower/soybeans oil mixture or a DHA-enriched oil during pregnancy. Systolic blood pressure was measured before and during pregnancy. The weights of the fetal body, organs and placenta were measured at day 20 of gestation in SHRs and were compared with those in normotensive Wistar Kyoto (WKY) control strain. In SHRs, the dietary DHA significantly decreased the systolic blood pressure by 10–15% after day 18 of gestation. The weights of fetal body, brain, and liver in the SHRs without DHA were significantly lower than those in the WKY rats. This growth retardation was prevented by the dietary DHA. The results demonstrated that maternal dietary DHA decreased the blood pressure during late gestation and prevented the fetal growth retardation in SHRs.

Circulating S100beta protein is increased in intrauterine growth-retarded fetuses.

To determine whether S100beta, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n = 10) or abnormal (n = 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100beta protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100beta proteins in umbilical plasma levels were higher (p < 0.05) in IUGR patients (121.8 +/- 70.4 fmol/mL) than in control patients (54.7 +/- 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 +/- 55.2 fmol/mL). Fetal S100beta concentrations correlated with middle cerebral artery pulsatility index (r = -0.536, p < 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r = 0.469, p < 0.03). No difference in the localization or intensity of S100beta staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period.

Endocrine pancreas development in growth-retarded human fetuses.

Glucose intolerance in adults born with intrauterine growth retardation (IUGR) may involve peripheral insulin resistance and/or abnormal endocrine pancreas development during fetal life. We quantified insulin-containing cells in deceased human fetuses with IUGR (<10th percentile, n = 21) or normal growth (control fetuses, n = 15). Paraffin-embedded pancreatic tissues from fetuses older than 32 weeks were obtained from two fetopathology departments. Mean gestational age was 36 weeks in both groups. Tissues with lysis and those fetuses with defects, aneuploidy, or genetic abnormalities were excluded. For each subject, six pancreatic sections spaced evenly throughout the organ were immunostained with anti-insulin antibody. Total tissue and insulin-positive areas were measured by computer-assisted quantitative morphometry. Results were expressed in percentages. To evaluate islet morphogenesis, the percentages of beta-cells inside and outside islets were determined. Islet density was similar in the two groups (P = 0.86). The percentage of pancreatic area occupied by beta-cells (beta-cell fraction) was not correlated with gestational age (r = 0.06 and P = 0.97 in IUGR fetuses; r = 0.12 and P = 0.67 in control fetuses) or body weight (r = 0.16 and P = 0.47 in IUGR fetuses; r = 0.24 and P = 0.39 in control fetuses). Mean beta-cell fraction was 2.53% in the IUGR fetuses and 2.86% in the control fetuses (P = 0.47). The percentage of beta-cells located within islets was identical in the two groups (mean 35%). Our data militate against a primary developmental pancreatic abnormality in human IUGR, leaving peripheral insulin resistance as the most likely mechanism of glucose intolerance in adults born with IUGR.

Does Thrombin Activatable Fibrinolysis Inhibitor (TAFI) Contribute to Impairment of Fibrinolysis in Patients with Preeclampsia and/or Intrauterine Fetal Growth Retardation?

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a relatively recently described glycoprotein (MM 55 KDa) that can be converted into its active form by the thrombin/thrombomodulin complex and potentially inhibits fibrinolysis. Since it represents a link between coagulation and fibrinolysis, TAFI can be expected to play a part in various clinical conditions associated with a thrombotic tendency. Preeclampsia (PE) and intrauterine fetal growth retardation (IUFGR) are fairly common complications of pregnancy that are characterized by hemostatic abnormalities. TAFI antigen and its influence on hemostasis was investigated in 46 women with PE and/or IUFGR and in 16 normal pregnancies. We found a significant decrease of TAFI antigen in the patient group. Using the recently described method Overall Hemostatic Potential (OHP) in plasma we measured clot lysis time (CLT) and overall fibrinolytic potential (OFP). We found that CLT is prolonged and OFP decreased in patients with PE and/or IUFGR. Since OFP did not increase after addition of the specific inhibitor of TAFI (potato tuber carboxypeptidase inhibitor), it seems that TAFI does not contribute to the impairment of fibrinolysis in these patients. Since serum albumin was decreased together with presence of proteinuria and aminotransferases were increased in the patients, it seems that one explanation for the decrease in TAFI could be reduced hepatic synthesis and an increased loss in urine. It an be speculated that this mechanism can prevent more serious thrombotic complications in patients with PE and/or IUFGR.

Intrauterine growth retardation index.

The objective of the study discussed was to develop an intrauterine growth retardation (IUGR) index to detect fetuses with IUGR. The study was conducted in Australia and was based on 219 pregnant women at Wollongong Hospital in the Illawarra region in New South Wales, Australia. Overall, 21 variables, including ultrasonographic variables and risk factors for IUGR, related to IUGR were tested in the sample. The results of discriminant analysis showed that hypertension, amniotic fluid index, abdominal circumference, head circumference, head circumference-to-abdominal circumference ratio, and low maternal weight gain in pregnancy have the highest F values. That means that these parameters were the most important predictors of IUGR in fetuses. An IUGR score was developed using these parameters. The developed index in this study has a reasonably high sensitivity (89.1%) and specificity (71.8%) in detecting IUGR in fetuses, compared with the developed indices to date. The IUGR score includes both ultrasonographic and maternal risk factor variables. This combination increases the accuracy of identification of IUGR in fetuses.

Insulin-like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy.

Fetal intrauterine growth retardation (IUGR) is one of the most common obstetric problems, with a frequency of 12% in Mexico. In the past, investigations have focused on extrinsic causes of IUGR. More recent studies have examined the intrinsic factors that cause fetal intrauterine growth. Maintenance of fetal growth has been attributed to insulin-like growth factor (IGF), epidermal growth factor (EGF) and transforming growth factor beta (TGF-beta). The objective of this study was to assess the levels of these growth factors during pregnancy and to determine whether or not low concentrations are associated with IUGR. Nine women whose pregnancies were complicated by IUGR and a group of nine women whose pregnancies exhibited normal fetal intrauterine growth were studied. IUGR was determined by sonography and confirmed by weight at birth. Venous blood samples were taken from both groups of pregnant women at the end of each trimester. Enzyme-linked immunosorbent assays, immunoradiometric assays and radioimmunoassays were used to process samples, and the results were analysed by anova. IGF-I levels increased in both groups during pregnancy, but the increase was lower (p < 0.001) in the IUGR group throughout pregnancy and at delivery. EGF did not show any significant changes during pregnancy. Blood TGF-beta levels varied only during the first trimester of pregnancy. The differences were not statistically significant. However, TGF-beta concentrations were higher in the pregnancies with IUGR. Women in the IUGR group were smaller than in the control group (p < 0.05), and, using the covariance test (p < 0.05), this was found to be correlated with IGF-I levels but not with EGF or TGF-beta levels. Changes in fetal weight might be explained by the different concentrations of IGF. The structural homology between IGF-1 and insulin could mean that the presence of higher levels of IGF would result in a increased energetic metabolism that could contribute to fetal growth. EGF levels were not related to IUGR, and TGF-beta levels increased only during the first 3 months in the IUGR group. This observation correlates with the in vitro action of TGF-beta as a negative factor of growth, but as a positive support for sustaining early pregnancy. Our data illustrates that low height represents an increased risk factor for IUGR. These data also correlate with the studies involving extrinsic factors.

Delayed disaccharidase development in a rabbit model of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) affects almost 10% of infants born in the United States. It may be responsible for delayed gastrointestinal function and is an important cause of perinatal morbidity and mortality. The New Zealand White rabbit provides an optimal model for the study of naturally occurring IUGR. At term, birth weight is determined by fetal position within the bicornuate uterus. The small intestinal disaccharidase enzymes are indicators of bowel maturity and function. To examine potential differences in disaccharidase development between normal and IUGR fetuses, this rabbit model was investigated. Jejunum was harvested at multiple stages in rabbit development including the third trimester fetus, neonate, and adult. Lactase, maltase, and sucrase enzyme activity, as well as total protein content, was determined. Results were analyzed by the 2-tailed t test and ANOVA. Lactase activity appeared in the mid-third trimester, peaked in the early neonatal period, then declined to adult levels. Maltase activity appeared in the early third trimester and gradually rose to adult levels. Sucrase remained at trace levels until the mid-neonatal period, reaching adult levels by weaning. Both lactase and maltase activity were depressed in IUGR fetuses compared with their normal littermates. This pattern of disaccharidase depression continued into the neonatal period until catch-up growth occurred at 2 wk when levels equalized. This report describes differential small intestinal disaccharidase development between normal and growth-retarded rabbit fetuses in a naturally occurring model of IUGR.

The predictive value of plasma fibronectin concentration on fetal growth retardation at earlier stage of the third trimester.

In order to evaluate the predictive value of maternal plasma fibronectin (FN) concentration at 24-34 weeks on fetal intrauterine growth retardation (IUGR), a prospective double-blinded study was performed. The maternal plasma FN concentrations were measured by using a rate nephelometric procedure in the 130 initial normal nulliparous pregnant woman at 24-34 gestational weeks. The outcome of pregnancies and birth weight of their infants were followed up. IUGR was defined as that the birth weight was less than the 10th percentile for gestational age. The receiver operating characteristic curves and predictive values of FN predicting on outcome of pregnancy with IUGR were analyzed. The results showed that: (1) In a cohort of 130 initially normal nulliparous pregnant women, IUGR occurred in 14 cases during the follow-up; (2) The plasma FN levels in the women with IUGR (467.58 +/- 104.43 mg/L) were significantly higher than in the normal control group (299.44 +/- 105.55 mg/L, P < 0.01). However, there was no significant difference in the mean maternal age, gravidity, sampling gestational ages, delivering gestational ages between the two groups (P > 0.05); (3) The areas under ROC curve for predicting the outcome of pregnancy in IUGR was 0.893; (4) At the cut point of 475 mg/L FN level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index for predicting the outcomes of pregnancy in IUGR were 57.14%, 95.69%, 61.54%, 94.87%, 0.5455 respectively. It was concluded that the maternal plasma FN might be used as an earlier predictor for screening of IUGR.

Melatonin stimulates glutathione peroxidase activity in human chorion.

In preeclampsia, placental production of lipid peroxides is abnormally increased, while placental glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are decreased. Administration of melatonin, a powerful scavenger of oxygen free radicals, also may protect the placenta from free radical-induced damage by increasing the activity of antioxidant enzymes. To test this hypothesis we administered melatonin to pregnant women before they underwent voluntary interruption of pregnancy between 7 and 9 wk of gestation. Melatonin (6 mg) was administered orally at 12:00 hr, and samples of chorion and maternal blood were obtained at the time of the procedure, 1, 2 or 3 hr later. We measured the melatonin concentration in maternal serum and activities of GSH-Px and SOD and levels of melatonin in chorionic homogenates. Melatonin administration was reflected by markedly increased melatonin concentrations in maternal serum and in chorion, with peak levels achieved 1 hr after melatonin administration (serum, 46.87 +/- 10.87 nM/L; chorionic homogenate, 4.36 +/- 1.56 pmol/mg protein). Between 1 and 3 hr after melatonin administration, GSH-Px activity in chorionic homogenates increased significantly (P < 0.001), with peak levels occurring at 3 hr (51.68 +/- 3.22 mU/mg protein per min, 137.3% of GSH-Px activity in untreated control subjects). No significant changes in chorionic SOD activity occurred during the 3-hr post-administration period. These results indicate that exogenous melatonin increases GSH-Px activity in the chorion and thereby may protect indirectly against free radical injury. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excessive free radical production, such as intrauterine fetal growth retardation and fetal hypoxia.

Role of leukocytes in uterine hypoperfusion and fetal growth retardation induced by ischemia-reperfusion.

We investigated leukocyte involvement in uterine hypoperfusion and intrauterine fetal growth retardation (IUGR) induced by ischemia-reperfusion (I/R) in Sprague-Dawley rats. On day 17 of gestation, leukocyte accumulation in the uterus and placenta subjected to 30 min of ischemia, followed by reperfusion, was assessed by measuring myeloperoxidase (MPO) activity. Uterine MPO activity was significantly higher after 1 h of reperfusion than it was before ischemia (P < 0.05), without any increase in placental MPO activity. Immunohistochemical staining showed leukocyte accumulation in the uterus subjected to I/R. The effects of treatment with monoclonal antibodies against CD11a (WT1) and CD18 (WT3) at a dose of 0.8 mg/kg on uterine blood flow and IUGR were investigated. Laser-Doppler flowmetry demonstrated that uterine hypoperfusion at 2 h after ischemia (blood flow, -51.7 +/- 1.2%; P < 0.01) was inhibited by WT1 and WT3 treatment. I/R-induced IUGR at full term (P < 0.05 vs. nonischemic horn) was prevented by WT1 and WT3 treatment on day 17. These results indicate that leukocyte accumulation may play an important role in the pathogenesis of uterine hypoperfusion and IUGR induced by I/R in pregnant rats.