Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas.

OBJECTIVES: To observe the effect of the antioxidant lycopene on the occurrence of pre-eclampsia and intrauterine growth retardation in primigravida women. METHODS: A total of 251 primigravida women were enrolled in this prospective, randomized controlled study in the second trimester. A total of 116 women were given oral lycopene (Group I) in a dose of 2 mg twice daily while 135 women were given a placebo (Group II) in the same dose until delivery. The criteria for recruitment included gestational age of 16-20 weeks, singleton pregnancy, absence of any medical complication and willingness on the part of the women to participate in the study. The women were followed-up until delivery for development of pre-eclampsia, mode of delivery and fetal outcome. RESULTS: The two groups were comparable in their maternal characteristics. Pre-eclampsia developed in significantly less women in the lycopene group than in the placebo group (8.6% vs. 17.7%, P=0.043 by chi-square test). Mean diastolic blood pressure was significantly higher in the placebo group (92.2+/-5.98 mmHg vs. 86.7+/-3.80 mmHg, P=0.012). Mean fetal weight was significantly higher in the lycopene group (2751.17+/-315.76 g vs. 2657+/-444.30 g, P=0.049). The incidence of intrauterine growth retardation was significantly lower in the lycopene group than in the placebo group (12% vs. 23.7%, P=0.033). CONCLUSIONS: The results of the present study suggest that the antioxidant lycopene reduces the development of pre-eclampsia and intrauterine growth retardation in primigravida women.     

Platelets and intrauterine growth retardation in pre-eclampsia.

In pre-eclampsia, but not essential hypertension of pregnancy, reduced maternal levels of circulating platelets were found to correlate with intrauterine growth retardation. This suggests that disseminated intravascular coagulation and fibrin deposition contribute to the placental damage of pre-eclampsia.     

Fetal heart block, anti-SSA and anti-SSB antibodies. Association with intra-uterine growth retardation, fetal death and lupus anticoagulant

A case of complete fetal heart block associated with intra-uterine growth retardation, SSA- and SSB-antibodies is presented. The fetus died in utero. Autopsy revealed damage to the fetal cardiac conducting system together with severe placental fibrosis and recent infarctions. These findings and a slightly prolonged activated partial thromboplastin time indicated also the presence of the lupus anticoagulant.     

Doppler ultrasound of the uteroplacental circulation as a screening test for severe pre-eclampsia with intra-uterine growth retardation

Two hundred primiparae underwent continuous-wave Doppler investigation of the uteroplacental circulation at 18-20 weeks gestation as a possible screening test for hypertension in pregnancy. Seventy-five women with abnormal waveforms suggestive of high uteroplacental resistance were tested again at 24 weeks when 21 demonstrated a persistent abnormality. Only nine (43%) of these went on to have an uncomplicated pregnancy, as compared with 150 (84%) of the remainder. Seventeen (8.5%) of the women in the study developed a hypertensive disorder of pregnancy, five of whom had abnormal waveforms at 18-20 weeks and at 24 weeks. These five women had a more severe degree of hypertension with proteinuria or intra-uterine growth retardation, and two required clinical intervention before term. The remaining 12 women were delivered at term of average, or heavier than average babies. Doppler investigation of the uteroplacental circulation at 24 weeks may prove to be a sensitive screening test for later severe pre-eclampsia with intra-uterine growth retardation.     

Ultrasound screening for detection of intra-uterine growth retardation

Intra-uterine growth retardation (IUGR) is a major problem in contemporary obstetrics. Early antenatal diagnosis is important if morbidity and mortality are to be minimized. We present the results of one years ultrasound fetometric screening for IUGR of the pregnant population in the city of Malm?. All pregnancies were dated by early biparietal diameter (BPD) measurement. From findings at 32 weeks of gestation, an IUGR risk-group (n = 436) was selected on the basis of predicted birthweight deviations with reference to standard curves, established at the Department, for BPD, abdominal diameter, femur length, and intra-uterine weight, all plotted against gestational age. The risk-group, which included 60 (77%) of the 78 IUGR infants eventually born, was subjected to additional fetometry examinations at 34, 36 and 38 weeks of gestation, in the total pregnant population of 2,068, each pregnancy was the subject of 2.3 examinations. Other fetometry variables were evaluated for their efficacy as IUGR markers, but were not found to be superior to the current screening procedure in which BPD and abdominal diameter are combined in a simple formula to assess intra-uterine growth. Overall, the screening procedure currently used at Malm? had a sensitivity of 64.1% and a specificity of 96.5%, the prevalence for IUGR being 3.8%.     

Umbilical artery Doppler waveform in pregnancies with uncomplicated intra-uterine growth retardation

Seventy-four pregnancies with uncomplicated intra-uterine growth retardation were assessed at the time of diagnosis by Doppler ultrasound umbilical artery flow velocity waveform. The results were not disclosed to the clinicians. Only those pregnancies with a complete absence of pre-existing disease or pregnancy complications were included. Ten patients showed evidence of fetal compromise due to asphyxia either before or during labour. In all cases the umbilical artery flow velocity waveform had been abnormal, and this abnormality always preceded cardiotocogram abnormality by up to 5 weeks. Though the resistance index was significantly associated with birth weight (p less than 0.001), this relationship was clearly dependent on the compromised fetuses who tended to be very small, and the true association is probably between resistance index and compromise, with birth weight being an intervening variable.     

Fetal ponderal index as an instrument for further classification of intra-uterine growth retardation.

Perinatal morbidity and mortality are still high in cases of intra-uterine growth retardation. Present screening methods select large risk groups and have a low positive predictive value. Instruments which could be used as indicators for those cases within the risk group needing close fetal monitoring would be valuable. The aim of this prospective study was to evaluate fetal ponderal index with respect to signs of fetal distress and neonatal outcome. By means of a risk scoring system, 73 pregnancies with increased risks of intra-uterine growth retardation were compared with 61 controls. By means of ultrasound, fetal weight was estimated and the fetal femur measured. The fetal ponderal index was calculated by dividing the estimated fetal weight in grams by the third power of the femur length. In the control group, 5/61 showed signs of distress and in the risk group, 43/73. The mean fetal ponderal index of the controls was 8.60 (SD 0.84) and in the risk group 7.72. The groups were compared with each other with respect to signs of distress. The fetuses showing signs of distress had a mean FePI of 7.45 (p less than 0.001). Those (30/73) in the risk group not showing signs of fetal distress had a mean value of 8.14 and differed significantly (p less than 0.001) from the distress group. Fetal ponderal index would seem to be a valuable adjunct for the differentiation of the more susceptible fetuses in an intra-uterine growth retardation risk group.     

Screening for detection of intra-uterine growth retardation by means of ultrasound

In a two-stage ultrasound screening program the gestational age was assessed by measurement of the fetal crown-rump length in early pregnancy. At an adjusted gestational age between 32 and 35 completed weeks the biparietal diameter, the abdominal circumference, the abdominal area and the ratio between fetal head area and abdominal area were estimated by means of ultrasound measurement. 'Acute' fetal weight was estimated by calculations from biparietal diameter and abdominal diameters. Percentile curves were constructed for these parameters and cut-off limits were tested for the predictability of intra-uterine growth retardation of the fetus. The abdominal circumference and area estimations were equally good for the detection of intra-uterine growth retardation. The biparietal diameter alone is of limited value for the detection of intra-uterine growth retardation but the combination with abdominal diameters in 'acute' fetal weight estimation can well be used. The ratio between the skull and abdominal areas seems to be of little use for the detection of intra-uterine growth retardation of two reasons: difficulty in measurement and low sensitivity. We consider that the assessment of gestational age in early pregnancy is a necessity both for the identification of suspected IUGR by means of ultrasound and the diagnosis of IUGR by measurement of fetal weight at birth. It is concluded that if the gestational age has been assessed by crown-rump length measurement in early pregnancy, a single estimation of the fetal abdominal circumference between 32 and 35 completed gestational weeks and a cut-off limit at the 15th percentile offers a detection rate of about 90% of the growth retarded infants.     

Lupus anticoagulant in pregnancy

In a group of 10 women with circulating lupus anticoagulant 25 intrauterine deaths were previously documented in the nine multigravidae. The presence of lupus anticoagulant activity was confirmed by showing prolongation of the activated partial thromboplastin time and kaolin clotting time with failure of correction of the prolongation on incubation with normal plasma. A clinical diagnosis of systemic lupus erythematosus (SLE) was made in four women. Three had deep vein thrombosis in pregnancy, one chorea gravidarum while two had only recurrent fetal losses. All the women had positive antinuclear antibody tests and blood platelet counts less than 175 X 10(9)/l. Anti-smooth muscle antibody and VDRL tests were each positive in half the patients; anti-DNA antibody was present in two patients with clinically active SLE. In six pregnancies correction of the activated partial thromboplastin and kaolin clotting time was attempted using prednisone (40-60 mg/day); aspirin, 75 mg/day, was added. Five live infants were obtained, four by spontaneous delivery, when the restoration of the clotting abnormalities to normal was achieved. In one woman presenting with extensive deep vein thrombosis a live infant was delivered following therapeutic doses of heparin and low dose aspirin. Maternal lupus anticoagulant activity has major implications for pregnancy and should be excluded in women with a clinical suspicion of SLE, a positive antinuclear antibody test, thrombotic episodes, biologically false-positive VDRL and unexplained late or repetitive early fetal losses.     

Lupus anticoagulant and pregnancy

A subset of women with a high rate of fetal wastage is identifiable among those with serologic but not necessarily clinical evidence of connective tissue disease. The presence of lupus anticoagulant in the plasma of a pregnant woman serves as a marker for a high rate of fetal wastage and risk of thrombosis. Lupus anticoagulant is best identified by the activated partial thromboplastin time or kaolin clotting time and can be specifically confirmed by the platelet neutralization procedure. Review of the obstetric literature indicates a total of 49 women with 160 unsuccessful pregnancies and 13 live births. Prednisone in immunosuppressive doses (40 to 60 mg/day) combined with low-dose aspirin (75 mg/day) has been demonstrated to be effective in suppressing activity of lupus anticoagulant in pregnant women and successful pregnancies have been obtained with this treatment. Lupus anticoagulant should be excluded in women with suspected collagen disease, with repeated early abortions and all unexpected late fetal losses.     

Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia

OBJECTIVE: The incidence of placental thrombotic lesions in early onset preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared between women with and without thrombophilia or hyperhomocysteinemia. STUDY DESIGN: Matched case-control study. 183 women with a history of early onset PE and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66 women with a thrombophilic factor the placental histological slides were available in 47 women. These were matched for maternal condition (PE and/or IUGR), gestational age at delivery, parity and maternal age, to 47 women with no thrombophilic factor. All slides were revised for lymphohistiocytic villitis, fetal thrombosis and fibrin depositions. RESULTS: There were no significant differences between the placentas of the matched groups with and without a thrombophilic factor. CONCLUSION: Placental thrombotic and inflammatory lesions associated with early onset PE and/or IUGR do not occur more often in women with compared to women without thrombophilia or hyperhomocysteinemia.     

New insight in physiopathology of preeclampsia and intra-uterine growth retardation: role of inflammation

Inflammatory response is a major component in physiopathology of preeclampsia and intra-uterine growth retardation. Endothelium is a main connection between placental ischemia and clinical manifestations during vascular pregnancy complications. In this review recent findings concerning inflammatory response and its links with endothelium are reported. Studies concerning isolated intra-uterine growth retardation confirm the hypothesis of a similar pathophysiology with an activation confined to utero-placental bed or at a lower level. Current information on oxidative stress, atherosclerosis, and apoptosis in vascular pregnancy complications are available in this review. These concepts offer innovative possibilities of treatment.     

Zinc in Danish women during late normal pregnancy and pregnancies with intra-uterine growth retardation

Zinc and alkaline phosphatase were examined in 41 pregnant women (gestational weeks 35-41) and in 12 women within 24 h of delivery. The serum-zinc level was reduced in all the women, though to a lesser degree in women giving birth to small for gestational age (SGA) babies than in the control mothers. The difference between the two groups was significant (p = 0.019). Erythrocyte-zinc increased during pregnancy, more in control mothers than in SGA mothers (p = 0.020). Granulocyte-zinc was not significantly reduced in pregnancy and no difference was found between SGA mothers and control mothers. Alkaline phosphatase levels in serum and granulocytes were elevated equally in the two groups. These findings show that zinc level changes occur in pregnancy, but that the changes do not appear to be a dominant cause of SGA pregnancy, in Danish women.     

Lupus anticoagulant and anticardiolipin antibodies in an obstetric population.

Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been reported to be associated with fetal loss. OBJECTIVE. Our aim was to estimate the incidence of LA and to examine the correlation between LA and ACA in pregnant women. To investigate the clinical significance of LA and ACA in an obstetric population. STUDY DESIGN. A prospective, cross sectional study of 2856 consecutive women admitted to a department of obstetrics and gynecology for delivery or due to pregnancy complications during an 11 month period. METHODS. Activated partial thromboplastin time (APTT) was determined in all patients. LA and ACA were determined if APTT > or = 35 sec. For reference ACA was determined in a group of randomly selected patients with APTT < 35 sec. The results were analyzed in relation to the obstetrical records. RESULTS. Overall incidence of APTT > or = 35 sec.: 7.0%, significantly more frequent in patients with early spontaneous abortion (18.6%) and intrauterine growth retardation (17.5%). Incidence of LA 0.07%. The patients had undetectable ACA and no clinical condition related to LA. Incidence of ACA class IgM (IgM-ACA) in patients with APTT > or = 35: 20.4%, significantly higher than in the reference group (9.6%). Uncomplicated pregnancy in 84% of patients with IgM-ACA. No cases of ACA class IgG (IgG-ACA) in patients with APTT > or = 35 but two cases in the reference group (one normal pregnancy, one spontaneous abortion). CONCLUSION. LA is a rare manifestation with uncertain significance in otherwise healthy pregnant women. IgM-ACA in low titer occurs relatively frequently during normal pregnancy.     

Histomorphometry of the human placenta in pre-eclampsia associated with severe intrauterine growth retardation

The morphological changes in the functional structure of the placenta in cases of pre-eclampsia associated with severe intrauterine growth retardation have been investigated with quantitative analyses. It has been demonstrated that in pregnancies complicated by severe pre-eclampsia, the placenta can suffer significant morphological alterations characterized by an abnormal maturation or arborization of the terminal villi. The findings of this study suggest that, among the pathogenic mechanisms responsible for the observed placental changes, uteroplacental ischaemia is probably a dominant factor, and that any ill effects on fetal growth and viability are very likely to be related not only to the inadequate maternal supply of oxygen and nutrients but also to placental ischaemic damage.     

The effect of bedrest in hospital on fetal outcome in pregnancies complicated by intra-uterine growth retardation

A prospective study was made to evaluate whether bedrest in hospital is beneficial in pregnancies where intra-uterine growth retardation (IUGR) was suspected. Diagnosis was based on routine fetometry at 32 weeks of gestation, in conjunction with general ultrasound screening. 107 patients with suspected IUGR-pregnancies were divided into two groups, 49 in a hospital bedrest group and 58 in an 'out-patient' group. Fifteen women in the bedrest group refused hospitalization, and 8 women in the out-patient group had to be hospitalized for medical reasons other than suspected growth retardation, leaving 79% of the women in their allocated group. The women in the bedrest group were hospitalized for a mean duration of 29.2 days (range 5-54). The results suggest that bedrest in hospital is not beneficial, either to fetal growth or to pregnancy outcome.     

Ultrasonic and biochemical detection and prenatal treatments of intra-uterine fetal growth retardation (author's transl)

Efficacy of three ultrasonographic and six biochemical methods for the detection of intrauterine growth retardation were assessed in prospective studies of 40 cases associated with short uterine fundal height less than -1.5 SD and/or small ultrasonographically determined total intrauterine volume (TIUV) less than -1 SD of normal populations. Prenatal treatments, consisting of bed rest, high protein diet, intravenous drip infusion of 10% maltose, 500 ml per day, for more than 12 days, etc., were administered on them. Fifteen cases (37.5%) delivered small-for-date infants, 9 of which complicated by toxemia of pregnancy. At the final determinations, small TIUV were found in all small-for-date cases (100%), short biparietal diameter 80.0%, and short longitudinal intracavital uterine length 53.3% of 15 small-for-date cases. In biochemical parameters, low maternal plasma estriol levels were found in 73.3%, low plasma human placental lactogen levels 66.7%, low urinary estriol excretion 53.3%, abnormal plasma alpha-fetoprotein levels 33.3%, and low plasma progesterone levels 20.0% of 15 small-for-date cases. Nineteen cases (47.5%) demonstrated remarkable increases in TIUV following prenatal treatments, and delivered appropriate-for-date infants. Despite of marked growth in biophysical parameters, abnormal biochemical values were mostly not improved by these treatments.