Chronic villitis of unknown aetiology and intrauterine growth-retarded infants of normal and low ponderal index.

Placentae from 211 term pregnancies were studied. The placentae were divided into three groups: group I, 57 placentae from neonates with birthweight over the 25th centile of the normal birthweight curve; group II, 49 placentae from neonates whose birthweight fell between the 10th and 25th centiles of this curve, and group III, 105 placentae from neonates whose birthweights were below the 10th centile of the curve. Each of the studied groups were divided into two subgroups, one comprising those infants with a normal Ponderal Index (PI) and the other comprising those with a low PI. A higher incidence of chronic villitis and of inflamed villi was observed as the average birthweight decreased in cases with normal PI as well as in cases with low PI, the highest incidence being found in placentae from infants with harmonic intrauterine growth retardation (normal PI). The same was observed with respect to the presence of maternal vascular lesions in all groups studied. It is suggested that an infant's birthweight and crown-heel length may be affected as a consequence of the extension and severity of the placental lesions and the timing of their appearance in gestation.

Chronic villitis of unknown aetiology in recurrent intrauterine fetal growth retardation.

Although recurrent chronic villitis of unknown aetiology (CVUA) has been documented in a few instances, placental lesions in recurrent intrauterine growth retardation have not, to the best of our knowledge, been reported. In the present study ten cases of recurrent intrauterine growth retardation have been described; a high incidence of severe CVUA was found in both first and successive pregnancies. If, as has been proposed, CVUA is due to a maternal immune response to placental antigens, subsequent pregnancies with the same father might be similarly affected.

Chronic villitis of unknown aetiology in placentae of idiopathic small for gestational age infants.

Placentae from 63 term pregnancies were studied. Of these, 19 were from normal pregnancies in which the neonates were within the normal weight range for their gestational age. The remaining 44 placentae were from pregnancies in which the infants were small for their gestational age (SGA). A chronic villitis was found in 68 per cent of all placentae. In the control group this lesion was present in 26 per cent but a mean of only 1.2 per cent of villi in these cases was inflamed. In the SGA group 86 per cent of placentae showed a chronic villitis and in these an average of 10 per cent of the villi were inflamed. Lymphocytic infiltrates in basal plate anchoring villi were observed in 48 of the 63 placentae and there were no differences among the various groups. Vascular lesions were found, similar to those described in placental bed arteries in preeclampsia and more recently in biopsies of the placental bed of SGA infants and in the decidua of mothers with systemic lupus erythematosus: this type of vasculopathy has also been described in rejection of renal transplants. It is suggested that the cellular infiltrate around and inside anchoring villi and free villi in cases of chronic villitis may represent the histological hallmark of an immunological reaction between mother and fetus rather than a response to infection.

Maternal vascular lesions in placentae of small-for-gestational-age infants.

Placentae from 140 term pregnancies were studied. Seventy-four were from uncomplicated pregnancies in which the neonates were within the normal weight range for their gestational age. The remaining 66 placentae were from pregnancies whose infants were small for gestational age (SGA). In eight cases of this latter group a curettage of placental bed was performed during caesarean section. Maternal arterial vessels with absence of trophoblastic migration were observed in basal decidua and basal plate, and acute atherosis in parietal decidua, basal decidua and basal plate, all of them in cases of the SGA group. Furthermore, chronic vasculitis-like lesions were observed in the parietal decidua of three cases from the SGA group and in two others of the control group. No vascular lesions were found in cases of the control group when an infant's birthweight was above the 25th percentile of the normal ponderal range. Atheromatous-like lesions have been described in placental bed arteries in pre-eclampsia, systemic lupus erythematosus and SGA infants: this type of vasculopathy has also been described in rejection of renal transplants. Moreover, lesions similar to those found in chronic vasculitis were also described in the latter pathological entity. It is suggested that these vasculopathies may represent different steps of the same lesion. On the other hand, they may also be the expression of a maternal immunological attack on placental tissues causing a deficit of placentation, low birthweight being the consequence of this deficit.

A nodule of adrenocortical tissue within a human placenta: light microscopic and immunocytochemical findings.

A case of adrenocortical tissue within a human placenta is described, this being the second example of such a phenomenon. Immunocytochemistry showed that the adrenal tissue reacted positively for DHEA-S but negatively for 17-OH progesterone and cortisol. This suggests that the heterotopic adrenal tissue resembled metabolically the fetal zone of the adrenal cortex.

Absence of Wharton's jelly around the umbilical arteries: an unusual cause of perinatal mortality.

Three cases are described in which Wharton's jelly was completely absent around the umbilical cord arteries but was present around the umbilical vein. All three instances of this anomaly were associated with perinatal death.

Passage of mannitol from mother to amniotic fluid and fetus.

Ten pregnant women and three pregnant sheep received mannitol intravenously. The results show that during late pregnancy this substance appears in amniotic fluid, and when the fetus is alive, its concentration increases with time, reaching values which are higher than those simultaneously obtained in maternal plasma. The experiments performed in sheep show that in fetal urine the concentration of mannitol reached values 10 to 20 times higher than those found in fetal plasma. This supports the hypothesis that the fetal kidney has an important role in the transference of this type of substance from the mother to the amniotic fluid.

Primary chronic abortion, preeclampsia, idiopathic intrauterine growth retardation, hydatidiform mole, and choriocarcinoma: a unifying concept.

Different degrees of maternal hyporesponse, as far as blocking activity is concerned, are proposed for primary chronic abortion, preeclampsia, and idiopathic intrauterine growth retardation. On the other hand, a maternal hyperresponse to fetal antigens with a higher production of blocking antibodies may be related to an unusual proliferation of the trophoblast in cases of hydatidiform mole and choriocarcinoma.

Intrauterine growth retardation of unknown etiology: II. Serum complement and circulating immune complexes in maternal sera and their relationship with parity and chronic villitis.

Significantly lower CH50 levels were found in women with small for gestational age (SGA) infants. The lowest values corresponded to nulliparous with placental chronic villitis (124.0 +/- 10.6). Three out of five mothers with circulating immune complexes from SGA group were nulliparous, having placental chronic villitis. An immunological derangement in women with SGA infants is proposed for the development of placental lesions, mainly in nulliparous mothers with a lower previous exposure to fetal antigens.

Deficiency of blocking factors in intrauterine growth retardation and its relationship with chronic villitis.

We tested sera from 22 women and their singleton full-term infants for inhibition in one-way mother/father mixed lymphocyte culture (MLC). Ten of these infants were small for gestational age (SGA) and 12 of them adequate for gestational age (AGA). Twenty placentas from these cases (ten from SGA infants and ten from AGA infants) were histologically studied. The results show evidence that blocking factors capable of inhibiting responses of wife's lymphocytes to husband's cells in MLC are present in sera from women with normal pregnancies but not in women with SGA infants. Sera from AGA infants showed a blocking activity on responses of husband's lymphocytes to wife's cells and this was not observed in sera from SGA infants. Lesions of chronic villitis were found in six placentas from SGA infants and in none from AGA infants. A deficit of blocking protective factors and its relationship with placental lesions is in favor of an immunological mechanism for intrauterine growth retardation.

Intrauterine growth retardation of unknown etiology. I. Serum complement and circulating immune complexes in mothers and infants.

Complement (C) and circulating immune complexes (CIC) levels were measured in 22 full-term pregnant women and 15 of their small-for-gestational-age (SGA) offspring in order to seek evidence supporting an immunological etiology for placental lesions related to idiopathic intrauterine growth retardation. We used 19 normal full-term pregnant women and 18 of their infants with birthweight above the 25th centile of the ponderal curve as a control population for this study. C levels were significantly lower in mothers of SGA infants than in controls (146.6 +/- 46.6 and 183.6 +/- 36.6 respectively, p less than 0.01). CIC were present in the sera of 5 out of 22 mothers of the SGA group and in 3 out of the 15 infants sera. No CIC were found in the sera of mothers or infants from the control group. Placental lesions were observed in 14 out of the 22 (64%) cases studied in the SGA group and in 1 of 11 (9%) of the controls. Two placentas from SGA infants showed acute atherosclerosis, and deposits of IgM and C3 were found in their vessel walls. These data are in favor of an immunological mechanism for intrauterine growth retardation of unknown etiology.

Immunohistochemical findings in acute atherosis associated with intrauterine growth retardation.

Lesions of acute atherosis in 23 placentas from pregnancies complicated by fetal growth retardation (less than tenth percentile) were studied by an immunoperoxidase staining. Twelve of them were from normotensive pregnancies, ten complicated by pregnancy induced hypertension, and the remaining associated with systemic lupus erythematosus. Twenty-three placentas with physiological changes of the spiral arteries corresponding to normal pregnancies served as controls. Six of the cases complicated by fetal growth retardation showed absence of physiological changes in basal decidua. Massive intramural granular deposits of IgM, a smaller amount of C3 and C1q, and slight deposits of IgA and IgG were found in vessels with acute atherosis. No intramural deposition of immunoglobulins or complement was observed in vessels with or without physiological changes. The presence of granular deposits of immunoglobulins and complement within the vessel walls with acute atherosis may be related to an immunological disorder, probably mediated by immune complexes.

Placental lesions in maternal autoimmune diseases.

We have investigated the presence and clinical implications of maternal vascular lesions and chronic villitis of unknown etiology (CVUE) in 18 placentas of 15 mothers with several autoimmune diseases (AD), including, for the first time, idiopathic thrombocytopenic purpura, autoimmune thyroid diseases, and multiple sclerosis. The group with AD had significantly more maternal vascular lesions and CVUE than the control group. We did not find lesions that could be attributed to any of the diseases in particular. The histopathologic picture was similar in these diseases, although there appears to be a spectrum in severity. Placental vascular damage with deposits of IgM, C3, and C1q was more prominent in systemic lupus erythematosus and in a patient with systemic sclerosis. In both of these diseases but not in the other conditions, these lesions were related to poor fetal outcome. Although the precise role of each of these autoimmune diseases in pregnancy and fetal outcome remains to be established, there appears to be at least one link between them represented by the presence of severe acute atherosis and heavy granular vascular deposits of IgM, C3, and C1q associated in some with poor fetal outcome. The role of CVUE remains speculative.

Chronic villitis of unknown etiology and maternal arterial lesions in preeclamptic pregnancies.

Placental lesions from 361 singleton full-term pregnancies were studied. These placentas were divided into two major groups: the study group consisting of 146 placentas from mothers with pregnancy-induced hypertension and a normotensive control group, which included 215 placentas from mothers with normal pregnancies. Each group was divided into three subgroups according to the allocation of infant's birthweight in the normal ponderal curve. A statistically significant higher incidence and severity of villous lesions was observed in placentas of mothers with pregnancy-induced hypertension when infants were over the 25th centile of the ponderal curve. Vascular lesions, i.e., absence of physiological changes in spiral arteries of the placental bed, acute atherosis and chronic vasculitis-like lesions were also more frequently observed in the hypertensive group than in controls. These placental lesions have been described in placentas of small for gestational age infants with or without maternal hypertension and in those of preeclamptic women with appropriate for gestational age infants. Since acute atherosis-like lesions have been reported in placentas of pregnant women with systemic lupus erythematosus and in rejected renal transplants, a possible maternal immunological reaction against fetal tissues could be responsible for the pathogenesis of these entities.

Chronic villitis of unknown aetiology and decidual maternal vasculopathies in sustained chronic hypertension.

Ninety-six full-term placentae were examined in the study. Of the 96 pregnancies, 72 were normotensive and 24 were complicated by hypertension. Of the 24 hypertensive pregnancies, 19 patients had chronic hypertension only, and 5 had chronic hypertension with superimposed preeclampsia. The birth weights of babies were over the 25th centile of our ponderal curve in all cases. Chronic villitis of unknown aetiology (CVUE) was found in 25% of control placentae and in 26% of placentae from chronic hypertension without preeclampsia. Eighty percent of placentae of chronic hypertension with superimposed preeclampsia presented the lesion. The incidence of CVUE was significantly higher in the latter than in the other groups. The same was observed about the proportion of inflamed villi. A higher frequency of maternal vascular lesions was observed in placentae of chronic hypertension with superimposed preeclampsia. Similar incidence and severity of the above-mentioned placental lesions have been recently described in preeclamptic pregnancies. These results suggest that these lesions (CVUE and maternal vasculopathies) are related to preeclampsia and not only to maternal hypertension.

Disappearance of para-amino-hippurate from amniotic fluid.

Eight pregnant women and three pregnant sheep received 400 mg of para-amino-hippurate (PAH) intraaminotically. Serial samples of amniotic fluid and maternal blood were obtained. In sheep samples of fetal blood were also withdrawn. PAH appeared in maternal plasma in all the cases. In all pregnant women PAH disappeared slowly from amniotic fluid (50% in 4 hours). In one ewe the study was performed as in humans and showed the same pattern of disappearance. In the other two, fetal urine was drained outside the amniotic fluid and PAH disappeared from it at a much faster rate (90% in 4 hours). PAH concentration in fetal urine was 100 times higher than in fetal plasma. Our findings in pregnant women seem to suggest that PAH disappears from the amniotic sac by a diffusion mechanism. On the other hand the results found in sheep also suggest that the fetus may have an active role in PAH concentration in amniotic fluid, eliminating part of the substance into maternal blood across the placenta but returning a major portion to the amniotic fluid with fetal urine.

[Intensified insulin therapy in the management of gestational diabetes]. / Insulinoterapia intensificada en el manejo de la diabetes pregestacional.

A total of 35 pregnancies in 28 Pregestational Diabetic Patients (PDP) were followed with the goal of achieving and maintaining near normoglycemia (as many pre-postprandial glycemias as possible between 60-140 mg/dl); 13 patients (16 pregnancies) were assigned to Subcutaneous Continuous Preprogrammed Insulin Infusion (SCII) because of high risk pregnancies (HRP) (at least one of the following: former history of spontaneous abortions, stillbirths, premature deliveries and/or sterility). The remaining 12 PDP's (15 pregnancies with no past history of the above nature) were treated with Multiple Conventional Insulin Injections (MCII). Both groups were comparable regarding the following clinical parameters: age, time of onset and class of diabetes. All patients were instructed in performing 3 to 7 daily Self Capillary Blood Glucose controls (SCBG). Mean follow-up observation period was (mean +/- SEM) 28.5 +/- 2.5 weeks for SCII and 3.2 MCII and 28.8 +/- 3.2 weeks for MCII. All the 3 PDP drop out's (4 pregnancies) belonged to the CMII group. No drop out's were recorded in the SCII group. Both insulin therapy approaches were similarly effective in improving metabolic control in that comparable levels of mean blood glucose (MBG) and HbA1 were attained by SCII and MCII (Fig. 1). Compliance, as evidenced by average of daily SCBG was also similar in both groups (Fig. 2). Such satisfactory metabolic control was achieved mostly because of an increase in the percentage (65%) of "fair" glycemias (60-139 mg/dl) and not because of an increase in hypoglycemias (< 60 mg/dl) which could have canceled out an undesirable degree of hyperglycemias thus rendering "false satisfactory" MBG's and HbA1 (Fig. 1). With the above degree of metabolic control obtained there occurred no severe hypoglycemic episodes requiring medical intervention. All newborns to the PDP's who remained under treatment showed an adequate APGAR (X +/- SEM, 9.5 +/- 0.2) regardless of the modality (SCII or MCII) of insulin delivery used (Tables 1, 2). The single malformed baby found in this series was born to a patient on SCII who happened to start on the intensified insulin treatment rather late in her pregnancy (21st week) and, in addition, the patient self medicated with high doses of chlorpromazine because of recurrent vomiting episodes. Incidence of neonatal hypoglycemia (HY) or macrosomy (MS) was comparable in both groups (Tables 1, 2). It is to be pointed out, however, that PDP's who bore the babies with no HY or MS had presented a larger number of low glycemic values than mothers who bore the babies with HY and/or MS.(ABSTRACT TRUNCATED AT 400 WORDS)