Body iron delocalization: the serious drawback in iron disorders in both developing and developed countries.

Over 2 billion people in both developing as well as developed countries - over 30% of the world's population - are anaemic. With the classical preconception that oral iron administration or the intake of foods rich in iron increase haemoglobin concentration and reduce the prevalence of anaemia, specific programs have been designed, but iron supplementations have been less effective than expected. Of note, this hazardous simplification on iron status neglects its distribution in the body. The correct balance of iron, defined iron homeostasis, involves a physiological ratio of iron between tissues/secretions and blood, thus avoiding its delocalization as iron accumulation in tissues/secretions and iron deficiency in blood. Changes in iron status can affect the inflammatory response in multiple ways, particularly in the context of infection, an idea that is worth remembering when considering the value of iron supplementation in areas of the world where infections are highly prevalent. The enhanced availability of free iron can increase susceptibility and severity of microbial and parasitic infections. The discovery of the hepcidin-ferroportin (Fpn) complex, which greatly clarified the enigmatic mechanism that supervises the iron homeostasis, should prompt to a critical review on iron supplementation, ineffective on the expression of the most important proteins of iron metabolism. Therefore, it is imperative to consider new safe and efficient therapeutic interventions to cure iron deficiency (ID) and ID anaemia (IDA) associated or not to the inflammation. In this respect, lactoferrin (Lf) is emerging as an important regulator of both iron and inflammatory homeostasis. Oral administration of Lf in subjects suffering of ID and IDA is safe and effective in significantly increasing haematological parameters and contemporary decreasing serum IL-6 levels, thus restoring iron localization through the direct or indirect modulation of hepcidin and ferroportin synthesis. Of note, the nuclear localization of Lf suggests that this molecule may be involved in the transcriptional regulation of some genes of host inflammatory response. We recently also reported that combined administration of oral and intravaginal Lf on ID and IDA pregnant women with preterm delivery threat, significantly increased haematological parameters, reduced IL-6 levels in both serum and cervicovaginal fluid, cervicovaginal prostaglandin PGF2α, and suppressed uterine contractility. Moreover, Lf combined administration blocked further the shortening of cervical length and the increase of foetal fibronectin, thus prolonging the length of pregnancy until the 37th-38th week of gestation. These new Lf functions effective in curing ID and IDA through the restoring of iron and inflammatory homeostasis and in preventing preterm delivery, could have a great relevance in developing countries, where ID and IDA and inflammation-associated anaemia represent the major risk factors of preterm delivery and maternal and neonatal death.

Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non-pregnant women.

Iron homeostasis in pregnancy compensates for increased iron requirements and in women of child-bearing age for iron loss in menses. Oral administration of ferrous sulfate, prescribed to cure iron deficiency (ID) and ID anemia (IDA), often fails to increase hematological parameters and causes adverse effects. Recently, we demonstrated safety and efficacy of bovine lactoferrin (bLf) in pregnant women suffering from ID/IDA. Two clinical trials were conducted on pregnant and non-pregnant women of child-bearing age suffering from ID/IDA. In both trials, women received oral administration of bLf 100 mg/twice/day (Arm A), or ferrous sulfate 520 mg/day (Arm B). Hematological parameters, serum IL-6 and prohepcidin were assayed before and after therapy. Unlike ferrous sulfate, bLf increased hematological parameters (P less than 0.0001). In pregnant women, bLf decreased serum IL-6 (P less than 0.0001), and increased prohepcidin (P=0.0007). In non-pregnant women bLf did not change the low IL-6 levels while it increased prohepcidin (P less than 0.0001). Ferrous sulfate increased IL-6 (P less than 0.0001) and decreased prohepcidin (P=0.093). bLf established iron homeostasis by modulating serum IL-6 and prohepcidin synthesis, whereas ferrous sulfate increased IL-6 and failed to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA.

Thrombotic thrombocytopenic purpura and pregnancy: a case report and a review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a severe disorder affecting the microcirculation of multiple organ systems. Plasma therapy has significantly reduced the mortality rate. Infections, pregnancy, cancers, drugs, and surgery were frequently associated with the initial episodes and relapses. Women who are either pregnant or in the postpartum period make up 10-25% of TTP patients, suggesting the interrelationship between TTP and pregnancy. The introduction of aggressive treatment with plasma transfusion or plasmapheresis improved maternal and fetal survival rates. We describe a case of a first successful pregnancy concomitant to a late relapse of TTP, in which the identification of important risk factors for both TTP and pregnancy allowed us easier hematological and obstetrical management. Proposed guidelines for pregnancy-related TTP management and a brief review of current treatment options for this rare condition are also included.

Low levels of natural killer cells in pregnant women transmitting Toxoplasma gondii.

The role of cell-mediated immunity in the maternal-fetal transmission of Toxoplasma gondii was investigated in 17 pregnant women with primary T. gondii infection, in 7 of whom fetal infection occurred. 18 healthy pregnant women were followed-up as controls. Fetal outcome was uneventful in six women who were treated early in pregnancy with spiramycin, while stillbirth due to T. gondii encephalitis occurred in the offspring of one patient who started with therapy at 34 weeks' gestation. All patients who transmitted T. gondii showed significant changes in the mean levels of immune cells. The most prominent finding was a significantly lower level of natural killer (NK) cells in the mothers transmitting T. gondii to the fetus compared with non-transmitters and controls both in the number (99.7 (71.8-107.5)/microl versus 320.9 (307.9-356.4)/microl and 172.1 (122.4-213.3)/microl: median (25 degrees-75 degrees). p<0.001) and the percentage of NK cells (4.0+/-1.5 per cent versus 13.2+/-2.3 per cent and 10.2+/-3.4 per cent; mean+/-SD, p<0.001). Although limited by the small number of patients, our data suggest that the assessment of NK cells may be considered as a prognostic marker of primary T. gondii infection in pregnancy.

Hodgkin's disease during pregnancy: diagnostic and therapeutic management.

OBJECTIVES: To evaluate the possibility that women affected by Hodgkin's disease (HD) during their second or third trimester of pregnancy can safely carry their pregnancy to term. METHODS: From 1986 to 1997, 6 women came to our Center during the second trimester of pregnancy and were diagnosed as having HD. Three of these 6 patients were treated with chemotherapy before delivery and 3 of them were kept under observation and started treatment after delivery. RESULTS: All 6 women gave birth to a healthy female. CONCLUSIONS: The pregnancy does not worsen the course of the illness and does not compromise long-term clinical remission and recovery.

Obstetrical implications in multiple pregnancies.

In the present study 90 multiple pregnancies were examined. These were subdivided on the basis of the number of embryos involved (74 twins, 10 triplets, 6 quintuplets) and on whether they were followed at our clinic for the entire pregnancy or not. In each group we analysed certain variables, calculating the respective mean values and standard deviations. We used the ANOVA test to discriminate the eventual differences in the means of the variables analysed, operating a p < 0.05 significance value. In addition, significant differences were analysed by the test of Contrasts (Scheffe F-test). The concept that emerged from the data investigated is that careful management of these pregnancies, carried out in high-level structures, can reduce the incidence of complications on both the maternal and fetal side and thus prevent "minimal brain damage" in the newborn.

Autoimmune thrombocytopenic purpura in pregnancy: maternal risk factors predictive of neonatal thrombocytopenia.

Pregnancy in ATP women is not unusual. The problem of this association concerns the possibility of disease transmission to the fetus due to the crossing of maternal antiplatelet antibodies through the placenta. Maternal risk factors predictive of neonatal thrombocytopenia, can be identified as follows: severe thrombocytopenia, previous splenectomy, high titre of PA-IgG and/or SPB-IgG. In 63 pregnancies in ATP patients, we have evaluated whether the above maternal risk factors, considered in the third trimester, can provide useful criteria for the prediction of neonatal thrombocytopenia. In the third trimester, the distribution of maternal risk factors was as follows: 0 in 7 cases, 1 in 27 cases, 2 in 15 cases, 3 in 12 cases, 4 in 2 cases. From a statistical evaluation, the neonatal platelet values and the maternal risk factors seem inversely correlated (r -0.437; p = 0.0005). In particular, neonatal and maternal platelet count correlated positively (r = 0.249; p = 0.025); moreover, neonatal platelet count correlated negatively with Splenectomy (r = -0.209; p = 0.05), PA-IgG (r = -0.401; p < 0.0005) and SPB-IgG (r = -0.338; p < 0.005). We tried to apply a multiple regression model for all the above parameters which appears statistically significant (p = 0.001); the variability was about 30%. This regression model could be validated if applied to a larger number of cases, and it could represent an alternative to the invasive methods used for the diagnosis of neonatal thrombocytopenia.

Autoimmune thrombocytopenic purpura: maternal and fetal disease.

We have followed up 63 pregnancies in women with autoimmune thrombocytopenic purpura (ATP). Of these, 15 were previously splenectomized. The characteristics of the sample can be summed up as follows: average age 27 years (17-41); platelets at the beginning of pregnancy, mean 129.5 x 10(9)/l (range 16-488); platelets at delivery, mean 133 x 10(9)/l (range 8-477); PA-IgG at delivery, mean 320 ng IgG/10(7) platelets (range 10-1000); SPB-IgG at delivery, mean 262 ng IgG/10(7) platelets (range 10-1000). There were 30 spontaneous deliveries and 33 cesarean sections. Forty-two newborns had a platelet count within the normal range while nine had a platelet count less than or equal to 150 x 10(9)/l, while six had less than or equal to 100 x 10(9)/l and a further six less than or equal to 50 x 10(9)/l. The aim of this study is the evaluation of maternal risk and of possible feto-neonatal thrombocytopenia at birth. In this regard, the following parameters were considered: previous maternal splenectomy; the platelet count at the beginning of pregnancy; the platelet count and the titres of PA-IgG and SPB-IgG at delivery. Preliminary statistical evaluation of these parameters enabled us to identify a risk score. From this it was possible to obtain an optimum management of the final stage of pregnancy regarding the therapeutic approach and the timing of delivery.

Describing and interpreting 24-hour blood pressure patterns in physiologic pregnancy.

The time course of blood pressure in clinically healthy (pregnant and nonpregnant) women was followed by automatic ambulatory monitoring. Chronobiologic methods revealed the time course of dynamic rhythm characteristics as a function of gestational age. Differences were found between nonpregnant and pregnant women with an overall lowering during pregnancy of the rhythm-adjusted midline estimating statistic of rhythm (mesor).

Psychological aspects of therapeutic abortion after early prenatal diagnosis.

The early discovery of a fetal pathology creates a "crisis" situation fraught with psychic problems for the couple who must live through it. The Authors observed a group of patients in the second trimester of pregnancy. They had all requested therapeutic abortion since serious malformation of the fetus had been confirmed. By means of a questionnaire constructed for the purpose, certain characteristics of fetal malformation and of pregnancy were evidenced, as well as the way these were experienced by the patients. The immediate and delayed reactions to the diagnosis of malformation were also studied, as was the experience lived when faced with the choice of abortion.

PIP: The psychological aspects of therapeutic abortion after early prenatal diagnosis of a fetal pathology among 50 2nd trimester (16th-22nd week) patients at the University of Rome obstetric clinic are described. A crises is experienced after discovery of a fetal pathology (e.g., chromosomic, dismetabolic, infectious, and multifactorial). An open ended questionnaire format was used to obtain information on the malformations and to solicit responses to the malformation and the choice to abort. Respondents' average age was 32, and all educational levels and job types were represented. 80% of malformations had a low recurrence risk of 2-3%, and 20% had a high risk of 25-50%. 42% were planned pregnancies and 36% were desired; 22% occurred by chance. 44% had previous healthy children. 22% were in a 1st pregnancy and 10% were in a 2nd pregnancy following an abortion. 14% had both healthy and handicapped children. Visual representation of the expected child was clear to 44%, unclear to 44%, and unimaginable to 12%. Only 26% had programmed a future for the child. 82% had a clear view of themselves as mothers, while 18% were vague. 76% had confident maternal attitudes toward child rearing. 76% considered the pregnancy to be organically easy. 16% felt it was decidedly difficult, and 8% had some difficulty. 60% felt emotionally comfortable with the pregnancy. 38% felt ambivalent, of which 80% had high-risk pregnancies. After notification of the malformation or suspicion, 90% felt emotionally aroused. 22% felt anxiety, particularly if the extent and gravity were not indicated; 18% felt amazement and 8% rejection. 14% rebelled. Examples of the exact responses are given. The reasons for choosing abortion are also given, ranging from being against abortion, but finding the malformation to be incompatible with life, to not wanting to inflict the consequences on other family members. 80% considered abortion as an option to limit the frustration and disappointment to a short period in their lives and to prevent repercussions. After the decision is made, the focus turns to the immediate aspects of the abortion.

Carrier detection and prenatal diagnosis in haemophilia A and B.

Sixty probable carriers of haemophilia from 25 families were studied by using coagulation phenotype and DNA analysis: 33 with haemophilia A and 27 with haemophilia B. Coagulation phenotype was based on factor VIII/IX assay and DNA analysis on the examination of restriction fragment length polymorphisms (RFLPs) within and closely linked to factor VIII or IX: 3 RFLP for factor VIII and 3 for factor IX. The comparison between the coagulation phenotype and RFLP analysis showed the misclassification of 15 females (6 for haemophilia A and 9 for haemophilia B). Four prenatal haemophilia A diagnosis were made by DNA analysis of chorionic villi, taken with a transcervical trophoblastic biopsy, between the 18th and the 11th week.

First-trimester prenatal diagnosis of homozygous (14;21) translocation in a fetus with 44 chromosomes.

A (14;21) homozygous Robertsonian translocation was detected by first-trimester prenatal diagnosis. The related parents were heterozygous for the same translocation. At birth the baby was physically normal and had a normal psychomotor development. Together with a few previous observations in living homozygotes for (13;14) translocations, this case corroborates the idea that these subjects with 44 chromosomes are healthy without dysmorphic features.

Prenatal exclusion of purine nucleoside phosphorylase deficiency.

We report on the prenatal exclusion of purine nucleoside phosphorylase (PNP) deficiency in a fetus whose parents were known to be heterozygotes for the enzyme defect. Prenatal investigation was performed in the 16th week of gestation on amniotic fluid and cultured amnion cells using sensitive techniques. The results suggested that the fetus was either normal or a heterozygote. PNP activity in cord red cells confirmed the heterozygous status of the baby.