Biochemical profile of fetal blood sampled by cordocentesis in 35 pregnancies complicated by growth retardation

AIM OF THE STUDY: Intra-uterine growth retardation (IUGR) is a frequent pathology in obstetrics characterized by high heterogeneity. Fetal smallness is sometimes constitutional, but can also be accompanied by fetal distress and vital risks for the infant. In 35 pregnancies complicated by IUGR of different etiologies, we measured on fetal blood obtained by cordocentesis, biochemical variables characteristic of the fetuses' respiratory and metabolic status. The aim of the study was to identify the discriminative biological alterations, related to growth retardation and fetal distress. PATIENTS AND METHODS: The studied population includes 27 cases of severe IUGR, of gestational age 30,2+/-4,6 weeks of gestation (WG) (divided into 20 cases of isolated IUGR and 7 cases of IUGR associated with malformative syndrome), as well as 8 cases of moderate IUGR, of gestational age 26+/-4,5 WG; all fetuses had normal karyotypes. A group of 73 normal fetuses, of gestational age 26,3+/-5,7 WG, constituted a reference population. PH, pCO(2), bicarbonate concentration, pO(2) and SaO(2), as well as glucose, pyruvate, lactate, free fatty acids, aceto-acetate, beta-hydroxybutyrate and cholesterol concentrations were measured on umbilical venous blood (UVB). RESULTS: In case of severe but isolated growth retardation, UVB analysis showed the frequency of acid-base and gasometric disturbances: acidemia and hypoxemia (65% of cases), hypercapnia (60% of cases). Metabolic abnormalities were shown: decrease in glycemia (35% of cases), increase in pyruvatemia and lactatemia (40% of cases), increased free fatty acids serum concentration; a diminution of umbilical venous cholesterol level, the most frequent abnormality, can be seen in 70% of fetuses. In case of severe IUGR associated with malformative syndrome, UVB acid-base and metabolic changes were rarely seen; however, UVB cholesterol level is low in some cases. In case of growth retardation classified as moderate, modifications are relatively not frequent and essentially gasometric. CONCLUSION: In about 60% of cases of severe and isolated IUGR, there is a risk of fetal distress, related to an alteration of the transplacental transfer of respiratory gases and nutritional substrates; chronic fetal malnutrition can be involved, with an impact on the growth of the fetus. In case of IUGR associated with malformative syndrome, fetal smallness is probably a result of intrinsic fetal damage, without nutritional origin.     

Spiral artery blood volume in normal pregnancies and those compromised by pre-eclampsia

The aim of this work was to use intravoxel incoherent motion (IVIM) to provide a non-invasive in vivo assessment of the function of the maternal spiral arteries that feed the placenta in normal pregnancy and in pre-eclampsia. Eleven normal pregnant women were scanned at 16, 22, 29 and 35 weeks gestation in a longitudinal study. Nine normal pregnant women and six women with pre-eclampsia were scanned in a cross-sectional study, within 10 days of delivery. The MRI IVIM technique was used to measure the moving blood fraction (f%) at the basal plate. There was no evidence that f% changed with gestational age (P = 0.84), but considering the cross-sectional groups, f% in women with pre-eclampsia was reduced compared with normal pregnancy (mean +/- SD: 36 +/- 5% and 27 +/- 5%; P < 0.005). In conclusion, pregnancies complicated by pre-eclampsia exhibit a reduced fraction of moving blood within the region of the spiral arteries. IVIM performed in the mid-trimester may provide an early means of predicting those pregnancies with an increased likelihood of being complicated by pre-eclampsia.     

Identification of messenger RNA of fetoplacental source in maternal plasma of women with normal pregnancies and pregnancies with intrauterine growth restriction

Objective:

to quantify placenta-specific RNA in plasma of women carrying foetuses with intrauterine growth restriction and pregnant women with normal pregnancies.

Methods:

8 pregnant women with foetuses with intrauterine growth restriction were studied as well as 18 women with uncomplicated pregnancies in the third pregnancy trimester. Total free RNA was quantified in maternal plasma by spectrophotometry and the gene expression of hPL (Human Placental Lactogen) at the messenger RNA level through technical Real Time-Chain Reaction Polymerase.

Results:

plasma RNA of fetoplacental origin was successfully detected in 100% of pregnant women. There were no statistically significant differences between the values of total RNA extracted from plasma (p= 0.5975) nor in the messenger RNA expression of hPL gene (p= 0.5785) between cases and controls.

Conclusion:

messenger RNA of fetoplacental origin can be detected in maternal plasma during pregnancy.     

Genital flora in pregnancy and its association with intrauterine growth retardation.

A study of risk factors for intrauterine growth retardation (IUGR) was conducted among a cohort of 13,914 pregnant women enrolled in the multicenter Vaginal Infections and Prematurity Study. From 23 through 26 weeks of gestational age, cultures of specimens from the vagina and cervix were done for group B streptococci, Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Candida albicans, Gardnerella vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, and anaerobic gram-negative rods belonging to the genera Bacteroides, Porphyromonas, and Prevotella. Newborns who were small for their gestational age were delivered by 1,251 women, and infants of the appropriate weight for their gestational age were delivered by 10,332 women. When controlling for ethnicity and smoking and excluding women treated with antibiotics, the Mantel-Haenszel adjusted relative risk of IUGR was 1.16 for Bacteroides, Prevotella, and Porphyromonas spp. (95% confidence interval [95% CI], 1.01 to 1.33), 1.16 for M. hominis (95% CI, 1.04 to 1.29), 1.20 for U. urealyticum (95% CI, 1.05 to 1.38), and 1.22 for T. vaginalis (95% CI, 1.05 to 1.42). There was also a strong and significant trend for an increasing risk of IUGR with the number of these four microbes recovered. Among women colonized with all four isolates, the adjusted odds ratio of IUGR was 1.79 (95% CI, 1.27 to 2.52) in comparison with women not colonized with any of these microorganisms. Group B streptococci, N. gonorrhoeae, C. trachomatis, and C. albicans were not significantly associated with IUGR. These results suggest that infection is associated with some cases of IUGR and that specific microorganisms, alone or in combination, are involved. Since genital isolates are highly correlated with each other, the relative contribution of each microbe is difficult to determine.     

Hypocomplementemia correlates with intrauterine growth retardation in systemic lupus erythematosus.

PROBLEM: The aim of this study was to elucidate fetomaternal risks in systemic lupus erythematosus (SLE)-complicated pregnancy. METHOD OF STUDY: Pregnancy course, complications, and fetal outcome in 82 pregnancies of 55 patients with SLE were investigated. RESULTS: These 82 pregnancies resulted in 14 fetal losses and 66 live births. Without clinical manifestation of SLE-flare, 4 of 8 patients who had low serum complement activity during the pregnancies delivered small-for-date neonates. The rate of the intrauterine growth retardation was significantly higher than that observed in pregnancies with normal complement activity. The frequency of premature deliveries (60%) in patients who received more than 15 mg/day of prednisolone was significantly high when compared with pregnancies maintained by 0-15 mg/day (13.1%). CONCLUSIONS: These data demonstrate the preconceptional and perinatal management necessary in SLE and suggest that the pregnancy with hypocomplementemia, the disease activity, and/or a relatively high maintenance dose of corticosteroid should be carefully managed and monitored.     

Distinction between early normal intrauterine pregnancies and pathological pregnancies by means of a logistic model.

The probability of an unclear very early pregnancy being a normal intrauterine pregnancy was estimated using a logistic model. Five diagnostic measures of prognostic value were identified in the model: (i) daily change in human chorionic gonadotrophin (HCG), (ii) results of transvaginal ultrasound, (iii) vaginal bleeding, (iv) serum progesterone level and (v) risk score for ectopic pregnancy. With the use of this model, the probability of a normal intrauterine pregnancy has been estimated as 96.7%.     

Chorioangiomas of intermediate size and intrauterine growth retardation

Very large chorioangiomas are a rare but well recognized cause of neonatal morbidity, while small ones are clinically insignificant. This study emphasizes that some chorioangiomas of intermediate size may be causally related to intrauterine growth retardation, and that they may be surprisingly difficult to detect in the unfixed placenta.     

Placental morphometry in pregnancies complicated by intrauterine growth retardation with absent or reversed end diastolic flow in the umbilical artery

The aim of this study was to assess any possible correlation between villous tree architecture and its vascularization, and absent or reversed end-diastolic flow velocity (ARED) in the umbilical artery. The study group included seven pregnancies complicated by IUGR (estimated fetal weight < 10th percentile) and absent end-diastolic flow velocity in the umbilical artery. A gestational-age matched group of seven normally grown pregnancies was selected as control group. At delivery, the placenta was weighed and immersed in 10% neutral buffered formalin. A stratified random sampling procedure was used to obtain 12 blocks of full-thickness tissue per organ. A single random section was cut from each block. The following morphometric parameters were evaluated in each section: mean vessel diameter, volume density of the villous tissue, stem villi and terminal villi. Measurements were performed using a computerized Video Image Analysis system. No significant difference in mean vessel diameter was found between the two groups (37.1 microns versus 36.1 microns; p = 0.1). There was a significant reduction in the proportion of total villous tissue in the ARED group (43% versus 52%): this was due to a significant reduction in the volume of tissue occupied by the terminal villi (14.1% versus 18.4%). No significant difference was found in the proportion of villous tissue occupied by the stem villi (42% versus 40%). Several studies have investigated the anatomical and/or vasomotor bases of absent end diastolic flow velocity in the umbilical artery of fetuses with severe IUGR. Our observations of a significant reduction in the proportion of villous tissue occupied by the peripheral villi are consistent with the theory that failure of normal development of the terminal villous is responsible for the increased vascular resistance in IUGR pregnancies with ARED.     

Nicotine-induced prenatal overexposure to maternal glucocorticoid and intrauterine growth retardation in rat

Overexposure to glucocorticoid during fetal development can result in intrauterine growth retardation (IUGR) as well as other diseases after birth. The purpose of this study is to investigate the possibility of glucocorticoid disturbance-mediated nicotine-induced IUGR after chronic prenatal exposure. Nicotine at 1.0mg/kg twice a day was administered subcutaneously to pregnant rats from gestational day (GD) 8 to GD 15 (mid-gestation) or GD 21 (late-gestation). Placental weights and fetal developmental parameters were recorded. Corticosterone levels were determined by radioimmunoassay. The mRNA expressions of adrenal steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side chain cleavage (P450scc) and placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD-2) were determined using real-time quantitative RT-PCR. The results showed that prenatal chronic nicotine exposure causes IUGR in rats (P<0.01); in response to nicotine exposure, maternal serum corticosterone levels were elevated at mid- and late-gestations (P<0.05); mRNA expressions of StAR and P450scc increased in maternal adrenals (P<0.05 or 0.01) but decreased in fetal adrenals (P=0.16 or 0.11). Furthermore, the mRNA levels of placental 11 beta-HSD-2 were reduced at mid- and late-gestations (P<0.05). These results suggest that nicotine-induced IUGR is associated with the disturbances of glucocorticoid homeostasis in maternal and fetal rats. A possible underlying mechanism is that long term nicotine administration leads to fetal overexposure to maternal glucocorticoid by the combined effect of increased maternal glucocorticoid level and impaired placental barrier to it, all of which eventually leads to the fetal adrenocortical dysfunction and IUGR.     

Endothelial nitric oxide synthase in placental villous tissue from normal, pre-eclamptic and intrauterine growth restricted pregnancies

Nitric oxide (NO) regulates blood flow in the human placenta. As increased resistance to blood flow is seen in the fetal-placental vasculature in pregnancies complicated by pre-eclampsia and/or intrauterine growth restriction (IUGR), we examined expression of endothelial nitric oxide synthase (eNOS) in these placentas. Placental villous tissue sections were obtained from normotensive control (n = 5), IUGR alone (n = 5) or pre-eclamptic (with or without IUGR (n = 9) patients, immunostained for eNOS and scored for localization, type (punctate or diffuse) and intensity of eNOS staining in syncytiotrophoblast and placental vessels. The significance of differences was calculated using the Mann-Whitney U-test. No differences in intensity or type of immunostaining in syncytiotrophoblast were seen. Placentas from patients with pre- eclampsia with or without IUGR had a significantly more basal distribution of eNOS in syncytiotrophoblast. eNOS immunostaining was absent in terminal villous capillary and faint in stem villous vessel endothelium of normal placentas, but was intense in the endothelium of both of these types of vessels in the IUGR and pre-eclampsia groups, with significantly greater staining seen in stem vessels of patients with IUGR alone. This increased eNOS expression and hence increased NO production in the fetal-placental vasculature may be an adaptive response to the increased resistance and poor perfusion in these pathological pregnancies.      

A further patient with the Pitt-Rogers-Danks syndrome of mental retardation, unusual face, and intrauterine growth retardation

A further case of a syndrome of pre- and postnatal growth retardation, characteristic face, and unusual palmar creases is described. This child also had hypoplasia of labia majora and minora, deafness, and head nodding. Apparently sporadic occurrence in this family does not rule out autosomal recessive inheritance of this syndrome first described by Pitt, Rogers, and Danks in 1984.     

Two familial cases with a lethal gracile bone dysplasia and intrauterine growth retardation

A number of more or less distinct entities with low birth weight and abnormal radiographic appearances have been identified. We studied two sisters who were unusual because of severe intrauterine growth restriction, absence of growth after birth, decrease of pre- and postnatal spontaneous mobility, and early fatal outcome. The chondro-osseous morphology documented a distinctive osteochondrodysplasia. The radiographic examination was superficially similar to gracile bone dysplasias but was inconsistent with any known types of this group. These two patients appear to have a unique gracile bone dysplasia.     

A study of interferon-gamma and interleukin-2 production in premature neonates and neonates with intrauterine growth retardation.

Mononuclear cells from aborted fetuses, preterm infants, intrauterine growth retardation (IUGR) fetuses, and mature infants were stimulated with OK432 and PHA to study their effect on the production of interferon gamma (IFN-gamma) and interleukin-2 (IL-2), respectively. IFN-gamma production was reduced in the mature delivery group, while its production in preterm delivery and IUGR groups was markedly reduced compared to those in adults and the mature delivery group. Reduced IFN-gamma production in preterm delivery and IUGR groups was attributable neither to a decrease in T-cells nor to enhanced sensitivity of T-cells to prostaglandins. Unlike IFN-gamma production, IL-2 production in preterm delivery groups was higher than that in adults; its production in the IUGR group was comparable to that in adults. In addition, both IFN-gamma and IL-2 production in premature delivery cases was enhanced when these cases were exposed to the stress of infection.     

Severe intrauterine growth retardation with increased mitomycin C sensitivity: a further chromosome breakage syndrome.

We report an infant with pre- and postnatal microcephaly and growth retardation, a distinctive face, and developmental delay. The initial diagnosis was of Seckel syndrome. He became pancytopenic at 16 months and died soon after. His bone marrow was of normal cellularity but had a small lymphocyte infiltration. Increased spontaneous chromosome breakage was seen in blood and fibroblasts. Mitomycin C induced chromosome damage was increased and comparable to that seen in Fanconi anaemia. Reports of similar patients are reviewed. This entity of severe intrauterine growth retardation and increased mitomycin C sensitivity is hypothesised to be a distinct chromosome breakage syndrome.     

Mast cells and histamine in intrauterine growth retardation - relation to the development of placental microvessels

Objective and Design: The aim was to determine the time courses for the changes in airway function, airway reactivity, influx of inflammatory cells and levels of the pro-inflammatory cytokines, interleukin (IL)-5 and IL-8 in bronchoalveolar lavage fluid (BALF), and the plasma levels of cortisol and ACTH after antigen challenge to determine whether a temporal link could be established between these events.¶Methods: Airway function was measured as specific airway conductance (sG_sw) in conscious ovalbumin (OvA)-sensitized guinea pigs using whole body plethysmography at intervals after an inhalation challenge with ovalbumin (0.5% for 10 min). Airway responses to the inhaled spasmogen, U46619 (30 ng/ml, 60 s), were measured at 3, 6 and 24 h after challenge. In separate animals, bronchoalveolar lavage fluid (BALF) was obtained after anaesthetic overdose either before challenge or at 1, 3, 6, 12, or 24 h after OvA challenge. Total and differential cell counts of eosinophils and neutrophils were performed on BALF and levels of IL-5 and IL-8 determined by scintillation proximity assays and ELISA, respectively. Plasma cortisol and ACTH levels were determined by RIA kits in blood removed by cardiac puncture at intervals after challenge.¶Results: An early phase bronchoconstriction occurred which resolved by 3 h and was followed by a late phase between 17 and 24 h. Airway hyperresponsiveness to inhaled U46619, was evident at 3, 6 and 24 h after antigen challenge. Increased IL-5_[BALF] was observed by 60 min post challenge implicating a preformed storage site. In contrast, IL-8_[BALF] was not raised until 3 h post challenge. There was a significant infiltration of neutrophils and eosinophils by 3 and 6 h, respectively. IL-5_[BALF] further increased up to 24 h, during the appearance of the late phase of bronchoconstriction and whilst eosinophilia was maximal. Plasma cortisol levels were increased 1 and 3 hours after antigen challenge, thereafter returning to baseline levels.¶Conclusions: The hyperresponsiveness appears to be dissociated from the appearance of eosinophils in lavage fluid. The early appearance of IL-5, however, could be a trigger for the migration of eosinophils and development of hyperresponsiveness. The increased plasma cortisol levels occurring after antigen challenge were presumably due to the stress involved and these would be expected to exert an endogenous anti-inflammatory effect.     

Obstetric and perinatal outcome of pregnancies after intrauterine insemination.

The main aim of this study was to evaluate the obstetric and perinatal outcome of pregnancies after intrauterine insemination (IUI) with the partner's spermatozoa combined with ovarian stimulation. Information concerning the antenatal care and obstetric and perinatal outcome of IUI pregnancies (n = 111), spontaneous (n = 333) and in-vitro fertilization (IVF) (n = 333) was obtained from the Finnish Medical Birth Register (MBR). The multiple birth rate in the IUI group was 17% (19/111). Significantly less antenatal care was required by the IUI group than the IVF group. The frequency of Caesarean section was 25% for IUI singletons and 58% for IUI multiples, similar to the other groups. The mean (SD) gestational age for IUI singletons at birth was 39.5 (1.8) weeks, with a mean birth weight of 3285 (575) g, compared with 3448 (600) g in non-assisted singletons (P < 0.05). For IUI multiples the mean gestational age at birth was 36.0 (2.8) weeks and the mean birth weight was 2449 (678) g. The incidence of preterm birth, low birth weight or low Apgar scores and the need for neonatal care were similar in all groups. One case of major malformation and two perinatal deaths were recorded in the IUI group. In conclusion, IUI treatment did not appear to increase obstetric or perinatal risks compared with matched spontaneous or IVF pregnancies. Most problems were associated with patient characteristics and multiple pregnancy. Reduction of the high incidence of multiple pregnancies after assisted reproductive technology is essential to improve its outcome.