Prostaglandin production and contractile response of umbilical arteries in preeclamptic pregnancies with and without intrauterine growth retardation

Biochemical and biophysical properties of umbilical arteries from normotensive and preeclamptic pregnancies were examined. The production of prostaglandins E and F, 6-keto-PGF1 alpha, and thromboxane B2 by umbilical arteries from normotensive, mildly preeclamptic, and severely preeclamptic pregnancies were measured in incubation media at baseline and after addition of arachidonic acid. The initial baseline values of 6-keto-PGF1 alpha were decreased in the severely preeclamptic patients with intrauterine growth retardation (IUGR) but not in any of the other groups. Addition of arachidonic acid resulted in a significant increase in 6-keto-PGF1 alpha production over initial baseline in all groups except in the severely preeclamptic pregnancies without IUGR. These results suggest a differential defect in the 6-keto-PGF1 alpha metabolic pathway in severely preeclamptic patients with IUGR compared with those without IUGR. The stretch response curve to serotonin was decreased in the severely preeclamptic group with IUGR compared with the control group. The contractile response to individual vasoactive agents (serotonin, prostaglandin F2, norepinephrine, angiotensin II, and arachidonic acid) showed no significant difference between the normotensive and preeclamptic groups.     

Fetal blood flow in pregnancies complicated by intrauterine growth retardation

A noninvasive pulsed Doppler ultrasound technique was used to characterize blood flow in the descending thoracic aorta and the intra-abdominal part of the umbilical vein in 159 fetuses suspected of intrauterine growth retardation (IUGR) on the basis of ultrasound fetometry. From this group, 74 infants with IUGR (defined as gestational age-related birth weight of 2 standard deviations [SD] or more below the population mean) were born. The blood flow results were not available to the clinicians managing the pregnancies. Blood flow mean velocity in the fetal aorta was lower, pulsatility index and rising slope higher, and umbilical volume flow and umbilical flow per 100 g placental tissue were lower in the pregnancies with IUGR than in 21 normal pregnancies. The waveform of the maximum aortic velocity envelope was related to operative delivery for fetal distress, Apgar score, and umbilical cord blood pH. The pulsatility index and the configurational assessment of the diastolic part of the waveform were combined to form a new concept, the blood flow class. The blood flow class was abnormal in 57% of the fetuses classified as having IUGR at birth and in 93% of those growth-retarded fetuses who subsequently developed signs of fetal distress requiring operative delivery. Waveform analysis, in terms of blood flow class, seems to be a useful tool in the surveillance of fetuses when IUGR is suspected. Abnormal blood flow class is a marker of fetal distress and probably gives an earlier indication than antenatal nonstressed cardiotocography. The results of this study point to a strong association between IUGR and impaired fetal blood flow. The aortic volume blood flow, unlike waveform analysis, does not seem to be a variable sensitive enough to predict fetal outcome in the individual pregnancy.     

Determination of the intervillous perfusion index in pregnancies with intrauterine growth retardation

The authors developed a new radioisotope technique to measure placental blood flow for early detection of placental insufficiency. Using this method placental perfusion has been measured in 20 healthy pregnant women and in 15 pregnancies complicated with intrauterine growth retardation (IUGR). The T-maximum pictures obtained made it possible to differentiate between the vascular and intervillous phases of placental blood flow. The time period of intervillous phase calculated as the percent of the whole placental T-maximum was given as the intervillous perfusion index (IPI). It has been demonstrated that IPI is significantly longer in IUGR pregnancies (67.0 +/- 14.6) than in the control group (31.6 +/- 10.7). These data suggest that the first sign of placental insufficiency is the prolongation of IPI, which is likely to precede the quantitative reduction of placental perfusion.     

Essential fatty acids in pregnancies complicated by intrauterine growth retardation.

The relative fatty acid composition of lecithin was measured in maternal and cord blood serum in human pregnancies at risk for intrauterine growth retardation (IUGR) (n = 28) as compared to controls (n = 20). In the IUGR cases (n = 13) linoleic acid was lower in maternal samples but higher in cord blood, oleic acid was elevated in both whereas docosohexaenoic acid was lower. Essential fatty acid composition of lecithin was found to be different in IUGR.     

Leptin concentration in women with normal pregnancy and intrauterine growth retardation

OBJECTIVES: Leptin takes part in fat regulation and can also take part in regulation of prenatal fetal weight. DESIGN: The aim of the study was to find correlation between leptin concentration in healthy women and intrauterine growth restriction. MATERIAL AND METHODS: The study was done in Medical University in Lodz in 2000-2002. The study group consisted of 50 women with IUGR, the control group of 50 healthy pregnant women. Elisa immunoenzymatic IBL test was used. The results were expressed in microgram/l. RESULTS: In group of normal pregnancy leptin concentration was 5.347 +/- 1.098 micrograms/l. In group of intrauterine growth restriction leptin concentration was 4.617 +/- 0.949 micrograms/l. The difference between groups was statistically significant but the mean values in both groups were normal for nonpregnant women. CONCLUSIONS: Low concentration of leptin can play role in intrauterine growth restriction.     

Trophoblast apoptosis in human term placentas from pregnancies complicated with idiopathic intrauterine growth retardation

Objective.?To investigate proliferative, apoptotic, and antiapoptotic activity of placental trophoblast in pregnancies complicated with idiopathic intrauterine growth retardation (IUGR).

Methods.?Study group included data and placentas from 52 normal singleton term pregnancies with idiopathic IUGR. Records and placentas from 69 singleton pregnancies with normal fetal growth served as a control group. IUGR was defined by birth weight less than 10th percentile of standard values. Children with congenital malformations and those born with the signs of hypoxia, laboratory or clinical signs of preeclampsia or infection, children born to anemic mothers and those born from pregnancies with an increased coagulation system activity were excluded.

Results.?There was no statistically significant difference in the cytotrophoblast proliferation index value (Z?=?0.24; P?=?0.553), trophoblast expression of the Bcl-2 antiapoptotic factor (Z?=?0.47; P?=?0.634), and trophoblast apoptotic index (Z?=?0.51; P?=?0.613) between the idiopathic IUGR and control group.

Conclusion.?The proliferative and apoptotic events in the trophoblast of placentas with idiopathic IUGR did not differ from physiologic ones. Study results suggest the IUGR syndrome to have no uniform etiology or even underlying pathophysiology that would determine the possible fetal risk and subsequent long-term consequences for fetal health and life. This imposes the need of a more precise definition and unambiguous distinction between the idiopathic and other forms of IUGR.     

Management of pregnancies with suspected intrauterine growth retardation in Sweden. Results of a questionnaire

BACKGROUND: Diagnosis and management of intrauterine growth retardation during pregnancy remain a major challenge in obstetric care. The objective of this survey was to evaluate the routine clinical management of pregnancies with suspected intrauterine growth retardation at obstetric departments in Sweden. METHODS: In 1997, a questionnaire was sent to all 59 obstetric departments in Sweden. Forty-two departments, caring for 83% of all deliveries in Sweden, replied. Four major topics were addressed: definition and diagnosis of intrauterine growth retardation; magnitude of the problem; clinical management; use of Doppler ultrasound in clinical decision-making. RESULTS: Intrauterine growth retardation is diagnosed by a combination of serial fundal height measurements and ultrasonic fetal biometry at 40 departments, two departments perform routine fetal biometry at 32 weeks. The diagnosis is most often made at 32-36 gestational weeks. Five departments use 1.5 s.d. below the mean as cut-off point for diagnosis of small for gestational age fetuses; 35 departments use mean - 2 s.d. and two departments mean - 2.5 s.d. Intrauterine growth retardation is suspected in 1.6-6.3% pregnancies. About 19% of patients with suspected intrauterine growth retardation are hospitalized. On average, 63% of all small-for-gestational age babies are diagnosed prenatally. Thirty-nine out of 42 obstetric departments use formalized management protocols. All departments use cardiotocography, repeat ultrasound scans and Doppler ultrasound for antenatal surveillance. CONCLUSIONS: In Swedish obstetric units, the diagnostic procedures and methods of fetal surveillance in pregnancies suspected of intrauterine growth retardation are more or less uniform. Doppler examination of umbilical artery is used at all responding departments and is considered a valuable asset in clinical decision-making.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation

Objectives.?The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies.

Patients and methods.?The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method.

Results.?There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood.

Conclusions.?It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

Unstressed antepartum cardiotocography in the management of pregnancies complicated by intrauterine growth retardation

A study of antenatal cardiotocographs (CTG) in 250 patients with fetal growth retardation showed that nonreactive tracings were associated with a significant increase in operative deliveries for fetal distress in labour, a high perinatal mortality rate, and fetal anomalies, and a low Apgar score of the infant, both at one and five minutes after delivery. A "ten-point" scoring system was used to evaluate the CTG tracing. A score of 6 or less was associated with a significantly higher perinatal morbidity and mortality rate compared with those who had a score of 7 or more (p less than 0.01).     

Experimental intrauterine growth retardation with indomethacin

The present study was undertaken to determine the influence of indomethacin, a potent inhibitor of prostaglandin synthetase, on the intrauterine fetal growth of rats. All experimental rats administered indomethacin on various days of gestation were sacrificed on day 22 of gestation. The following results were obtained. The intrauterine fetal growth retardation (IUGR) and maternal weight loss were found following intramuscular administration of indomethacin 2mg on day 19 of gestation. IUGR and maternal weight loss were also found after fasting from day 19 of gestation to day 22. IUGR was induced by the administration of indomethacin on days 15 to 21 of gestation, while not by that on day 10. The mean fetal weight of rats which received indomethacin on day 19 of gestation was 3.57 +/- 0.44g, which was as low as 67.9% of normal fetal weight. There seemed to be a critical period for the occurrence of IUGR in rat due to indomethacin. The possible jeopardy of fetal development due to the administration of indomethacin to pregnant women in the late pregnancy should be warned against.     

Comparative analysis of the maternal and umbilical interleukin-8 levels in normal pregnancies and in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation.

OBJECTIVES: The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies. PATIENTS AND METHODS: The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method. RESULTS: There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood. CONCLUSIONS: It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.     

Lipid peroxidation in women with gestational hypertension complicated by asymetric intrauterine growth retardation

OBJECTIVES: Hypertension in pregnancy is connected with increased rate of prematurity and perinatal morbility. 8-isoprostane and lipid peroxides are the oxidative stress indices, similar to the prostaglandins both connected with vessels restriction. DESIGN: The aim of the study was to find the correlation between concentration of lipid peroxides and 8-isoprostane and the blood pressure in pregnancy. MATERIALS AND METHODS: The study was done in Dep. of Obstetrics and Gynaecology Medical University in Lodz in 2002-2005. The study group consisted of 78 women with diagnosed hypertension in pregnancy, the control group of 50 healthy pregnant women at the same gestational age. Lipid peroxides and 8-isoprostane were measured in maternal blood. The Oxis Immunoassay for 8-epi prostaglandin and LPO 586 were used. The results were expressed in ng/ml and microM. RESULTS: The concentration of 8-isoprostane in women with hypertension was 0,0691 ng/ml, in women with hypertension and IUGR the value of 8-isoprostane was similar--0,0728 ng/ml. In women in normal pregnancy was lower--0,0541 ng/ml. Lipid peroxides and 8-isoprostane concentration in both hypertensive groups was higher than in group of normotensive pregnant women. CONCLUSIONS: In pregnancies complicated by hypertension the concentration of vasorestrictive lipid peroxidation products is higher than in normotensive women and the antioxidative treatment may be used to decrease lipid peroxidation process.     

Placenta in intrauterine growth retardation

Undernutrition and toxemia of pregnancy are considered to be important maternal causes for the fact that 15-30% of infants born at term in India are "small for date." The various changes of senescence in placenta were quantitatively studied in cases of toxemia, anemia, and unexplained growth retardation and compared with healthy controls. Placenta was studied in 100 term parturients admitted to the labor ward of the Lady Hardinge Medical College and Hospital in New Delhi, India. The parturients included the following: 1) group 1 -- 25 normal term parturients; 2) group 2 -- 25 intrauterine growth retardation, birth weight less than 2500 grams; 3) group 3 -- toxemia of pregnancy with blood pressure of 130 + 90 mm of Hg. and above with or without edema and/or proetinurea (25); and 4) group 4 -- anemia of pregnancy, Hb. less than 8.0 gm% (25). Despite extensive work no specific lesion in placental histology is found in toxemia of pregnancy and the same is true in cases of unexplained intrauterine growth retardation. The reason for this may be probable underlying multiple etiology in both conditions. The only significant finding which has been observed by many workers is decrease in size and weight of placentae in the IUGR group. Mean diameter was 15.3 cm compared to 17.54 in control cases, and mean weight was 288.0 gms compared to 466.8 in control cases.