Anna Franca Cavaliere

Gadolinium periconceptional exposure: pregnancy and neonatal outcome

Background. Gadolinium derivatives are ionic paramagnetic contrast agents used to enhance magnetic resonance images, labeled as a pregnancy category C by the Food and Drug Administration because of a lack of epidemiological studies concerning first‐trimester exposure. Methods. Prospective cohort study to determine whether gadolinium derivatives exposure in periconceptional period is a risk factor for pregnancy or fetal development. Results. We report the outcome of 26 pregnant women exposed to gadolinium derivatives in the first trimester without adverse effect on pregnancy and neonatal outcome. Conclusions. Currently, this study represents the only prospective investigation of gadolinium derivatives in pregnancy, but more data are necessary to exclude a teratogenic risk.

Congenital cystic adenomatoid malformation of the lung: antenatal ultrasound findings and fetal-neonatal outcome. Fifteen years of experience

Seventeen cases of congenital cystic adenomatoid malformation of the lung (CCAM) are reported. They were followed up over a period of 1 month to 15 years. Diagnosis was made by prenatal ultrasound. Our purpose was to evaluate the fetal-neonatal outcome and the prognostic elements observable through ultrasound techniques, and to compare all types of CCAM. The outcome observed ranged from total prenatal resolution to postnatal spontaneous regression of the lesion, to complications due to the presence of nonimmune fetal hydrops (NIFH), intrauterine death and the necessity of surgical intervention. In our experience only hydrops represented a negative predictor of outcome since death occurred in all cases with this pathology. In the absence of NIFH, counselling should stress the prevalence of a positive outcome, even in cases of surgical intervention.

Helicobacter pylori infection contributes to placental impairment in preeclampsia: basic and clinical evidences.

Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality. Epidemiological association between Helicobacter pylori (Hp) infection and PE onset has been widely shown. The aim of this study was to analyze a possible correlation between Hp infection and the severity of clinical presentation of PE and to identify an immunologic mechanism triggered by Hp infection potentially contributing to the pathogenesis of PE.

A Novel Route of Transplantation of Human Cord Blood Stem Cells in Preimmune Fetal Sheep: The Intracelomic Cavity

The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40–45 days) received intracelomic transplants of human CD3‐depleted (50 × 106 per lamb) or CD34‐selected (1–2 × 105 per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human β2‐microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3‐depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%‐22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34‐selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45+ cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human β2‐microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.

Early first-trimester Sibutramine exposure. Pregnancy outcome and neonatal follow-up.

AbstractBackground: Sibutramine is a drug that is used in the treatment of obesity. There are currently no epidemiological studies relating to sibutramine exposure in pregnancy. The objective of our study was to determine whether sibutramine exposure during pregnancy constitutes a risk factor to the mother and developing fetus. Methods: Fifty-two pregnant women who were exposed to sibutramine in the first trimester of pregnancy, when they were unaware of being pregnant, contacted our Teratology Information Service. We recorded the prospective outcomes of this case series between May 2001 and September 2004 with a complete neonatal follow-up up to 1 month after delivery. Results: Seven cases of hypertensive complications were observed during pregnancies. No cases of congenital anomalies in neonates were observed. Conclusion: Although many more cases are necessary to demonstrate that sibutramine is not teratogenic in pregnancy, our experience improves the counseling of pregnancies occurring involuntarily during sibutramine therapy.

Recombinant erythropoietin in the prevention of late anaemia in intrauterine transfused neonates with Rh-haemolytic disease.

Objective: To evaluate the efficacy of recombinant human erythropoietin (rHuEPO) in prevention of late anaemia due to Rh-haemolytic disease in neonates subjected to one or more intrauterine transfusions (IUTs). Study Design: Six neonates (GA 28–38 weeks, BW 980–3,360 g), subjected to one or more IUTs for Rh-haemolytic disease, were treated for 3 weeks with rHuEPO (200 U/kg/day, s.c.) after the second week of life to prevent late anaemia and consequently reduce the need for blood transfusions. All treated neonates were supplemented weekly with iron, vitamin E and folinic acid, intramuscularly. Results: Of the 6 patients studied, 4 preterm neonates, after commencement of rHuEPO treatment, showed a decrease in Hct values with persistent reticulocytopenia, and consequent need for one or more transfusions with packed and filtered red cells (PFRC). These 4 neonates had received a greater blood volume with IUTs than the 2 other term neonates, who, after starting rHuEPO treatment, showed an increase in Hct values and in reticulocyte count, with no transfusion requirements after birth (247 ± 47 vs. 84 ± 76 ml). Conclusions: Our results seem to correlate the efficacy of erythropoietin treatment in prevention of late anaemia resulting from Rh-haemolytic disease to the severity of intrauterine anaemia and to gestational age. Erythropoietin, in fact, was less effective in cases of severe intrauterine anaemia requiring a high volume of PFRC; it was also less effective in the preterm babies, because of the simultaneous presence of anaemia of prematurity and other major diseases.

Drug-induced congenital defects: strategies to reduce the incidence.

Approximately 1% of congenital anomalies relate to pharmacological exposure and are, in theory, preventable. Prevention consists of controlled administration of drugs known to have teratogenic properties (e.g. retinoids, thalidomide). When possible, prevention could take the form of the use of alternative pharmacological therapies during the pre-conception period for certain specific pathologies, selecting the most appropriate agent for use during pregnancy [e.g. haloperidol or a tricyclic antidepressant instead of lithium; anticonvulsant drug monotherapy in place of multitherapy; propylthiouracil instead of thiamazole (methimazole)], and substitution with The most suitable therapy during pregnancy (e.g. insulin in place of oral antidiabetics; heparin in place of oral anticoagulants; α-methyldopa instead of ACE inhibitors). Another strategy is the administration of drugs during pregnancy taking into account the pharmacological effects in relation to the gestation period (e.g. avoidance of chemotherapy during the first trimester, avoidance of nonsteroidal anti-inflammatory drugs in the third trimester, and avoidance of high doses of benzodiazepines in the period imminent to prepartum).

Efficacy of Oral Iodide Therapy on Neonatal Hyperthyroidism Caused by Maternal Graves’ Disease

Objective: To verify the efficacy of oral iodide therapy in treating a case of early neonatal hyperthyroidism due to maternal Graves’ disease. Methods: We report a case of neonatal hyperthyroidism which occurred in a 2,650-gram, female baby, born at 39 weeks’ gestational age (GA) to a 30-year-old mother affected by Graves’ disease and treated with thionamides (propylthiouracil) from the 20th week of gestation. A fetal goiter, due to maternal therapy, had been observed by ultrasound scan at 31 and 35 weeks of gestation, with contemporary low cord thyroid hormone levels. Two intra-amniotic injections of levothyroxine were then performed at 34 and 36 weeks of gestation, which led to a significant reduction of fetal goiter and to normalization of cord thyroid hormone levels. The neonatal clinical course was characterized by symptoms of hyperthyroidism from the 2nd to 3rd days of life (irritability, tachycardia, tachypnea, hyperphagia), mostly during feeding. Oral treatment with potassium iodide (KI, 8 mg × 3 times a day) was started at 23 days of life. Results: Treatment with KI led to a significant reduction of neonatal clinical symptoms and to a normalization of hormone levels within 4 days of therapy. The treatment was discontinued in 13th week of life because of neonatal well-being and normal hormone levels. Conclusions: We believe that KI therapy is effective in treating neonatal hyperthyroidism and does not cause suppression of neonatal thyroid activity, which is possible using antithyroid drugs like thionamides.

Effect of HCV infection on glucose metabolism in pregnant women with HIV receiving HAART

Abstract Objective: A prospective study was designed to evaluate the prevalence and determinants of glucose metabolism abnormalities (GMAs) among HIV-1–infected pregnant women receiving highly active antiretroviral therapy (HAART). Methods: Blood samples were collected in fasting conditions and following a 100 g oral glucose tolerance test among HIV-infected pregnant women consecutively followed at asingle HIV reference centre in 2001–2008. GMAs were defined by glucose intolerance(IGT) or gestational diabetes (GDM), according to the National Diabetes Data Group criteria. Predictors of GMAs were assessed in univariate and multivariate analyses. Results: Overall, 78 women with no history of diabetes or GMAs were eligible for analysis. All were on stable HAART with either nevirapine or protease inhibitors (PIs) from at least 4 weeks at the time of sampling. GMAs during pregnancy were observed in 20 women (25.6%; GDM: 6, 7.7%; IGT: 14, 17.9%). In a multivariate analysis, after adjusting for age and ongoing antiretroviral treatment (PI or nevirapine), GMAs in pregnancy were significantly associated with HCV coinfection(adjusted odds ratio 4.16; 95% CI, 1.22–14.1;p = .022). No maternal or neonatalcomplications were observed. Conclusion: GMAs represent a relevant issue in the management of HIV-1–infected pregnant women. Our data suggest that these abnormalities are relatively common in this particular group. Women with HCV coinfection have an increased risk of developing GMAs during pregnancy and should be monitored for potential complications.

The morbidly adherent placenta: when and what association of signs can improve MRI diagnosis? Our experience

PURPOSE We aimed to verify whether combination of specific signs improves magnetic resonance imaging (MRI) accuracy in morbidly adherent placenta (MAP). METHODS MRI findings for MAP were retrospectively evaluated in 27 women. Histopathology was the reference standard, showing MAP in eight of 27 cases. Specificity, sensitivity, positive predictive value, and negative predictive value were calculated for all MRI signs. Two skilled radiologists analyzed MRI findings, resolving discrepancies by consensus, using three alternative diagnostic criteria during three consecutive sections. First criterion: at least one of reported MRI signs indicates MAP and the absence of any sign is normal; second criterion: at least one statistically significant sign indicates MAP and no sign or nonsignificant sign is normal; third criterion: at least two statistically significant signs indicate MAP and no sign, nonsignificant sign, or only one significant sign is normal. RESULTS Using the first criterion yielded an unacceptable rate of false positive results (78.9%). Using the second criterion there were less false positive results (31.5%), and diagnostic accuracy of the second criterion was significantly higher than the first; the third criterion correctly classified 100% of cases. CONCLUSION Only specific MRI signs can correctly predict MAP at histopathology, particularly when multiple (at least two) specific signs are observed together.