Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy.

BACKGROUND AND PURPOSE: Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody. METHODS: Patient 1 was an 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti-MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84-year-old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1-6. RESULTS: Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M-protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti-MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved. CONCLUSIONS: In our patients, obinutuzumab was effective as a first-line treatment of anti-MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Genetic landscape of ultra-stable chronic lymphocytic leukemia patients.

Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical course. Beside patients requiring immediate treatment, others show an initial indolent phase followed by progression and others do not progress for decades. The latter two subgroups usually display mutated IGHV genes and a favorable FISH profile. Patients and methods: Patients with absence of disease progression for over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL). Forty US-CLL underwent extensive characterization including whole exome sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis to define their unexplored genetic landscape. Microarray analysis, comparing US-CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were found, including ATM and other potential progression driving mutations. CNA analysis identified 31 lesions, none with known poor prognostic impact. No novel recurrent lesion was identified: most cases showed no lesions (38%) or an isolated del(13q) (31%). The expression of 6 genes, selected from a gene expression profile analysis by microarray and quantified by droplet digital PCR on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision-tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The genetic landscape of US-CLL is characterized by the absence of known unfavorable driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients with favorable immunogenetics, a decision-tree based on the expression of 6 genes may identify at diagnosis patients who are likely to maintain an indolent disease for decades.

Anti-sulfatide/galactocerebroside antibodies in immunoglobulin M paraproteinemic neuropathies.

BACKGROUND AND PURPOSE: Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. METHODS: Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. RESULTS: Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy (P < 0.0001). Patients with known anti-sulfatide antibodies also showed anti-Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti-Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti-MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. CONCLUSIONS: Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy.

Personal exposure to particulate matter is associated with worse health perception in adult asthma.

BACKGROUND: Epidemiological studies have shown positive associations between particulate matter (PM) air pollution and short-term mortality and morbidity for asthma. The hypothesis that lung inflammation is responsible for these effects has been tested in panel and controlled exposure studies in asthmatic adults, with inconsistent results. OBJECTIVES: We investigated whether personal exposure to PM10 and PM2.5 were related to changes in the clinical course of asthma and to lung inflammatory responses in adult asthmatics. METHODS: A cohort of 32 asthmatic patients was followed for 2 years. Asthma control test (ACT) and St George's Respiratory Questionnaire (SGRQ) scores, forced expired volume in the first second (FEV1), exhaled nitric oxide (Fe(NO)), and pH of exhaled breath condensate (EBC) were determined on 6 occasions during different seasons. Personal exposure to PM was measured for 24 hours prior to clinical assessments. RESULTS: A 10 microg/m3 increase in PM10 personal exposure was associated with an increase in SGRQ scores (regression coefficient beta = 0.22; 95% confidence interval [CI], -0.005 to 4.451; P =.055) and with a decrease in ACT scores (beta = -0.022; 95% CI, -0.045 to 0.001; P = .060), whereas no associations were found between PM10 and FEV1, Fe(NO), or EBC pH. A positive association was detected between Fe(NO) and outdoor O3 (P = .042) and SO2 (P = .042) concentrations in the subgroup of nonsmoking asthmatics. CONCLUSIONS: We concluded that increments in personal exposure to PM10 are associated with a decrease in asthma control and health-related quality of life. However, this study does not provide evidence that 24-hour exposures to PM are associated with short-term changes in lung function or inflammatory responses of the lung.

Carbon monoxide pollution is associated with decreased lung function in asthmatic adults.

The aim of the present study was to test the effects of exposure to air pollutants on lung function. A panel of 19 adult asthmatics living in Padua (Italy) was followed for five 30-day periods during 2 yrs consecutively (1,492 morning and 1,434 evening measures analysed). Peak expiratory flow (PEF) and forced expiratory volume in 1 s (FEV(1)) were measured using a pocket electronic meter. Daily levels of air pollutants and meteorological variables were collected at outdoor city monitoring sites. Significant inverse associations were observed between morning and evening PEF and carbon monoxide level (p = 0.01-0.03), without clear differences between lags (0-3 days). An increment of 1 mg.m(-3) CO was associated with a PEF variation ranging -2.6- -2.8%. All effect estimates on PEF for CO remained significant and even increased after controlling for particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide and sulphur dioxide in single and multi-pollutant models. A similar trend was observed for FEV(1), but the associations were nonsignificant. A nonsignificant inverse relationship between evening PEF and SO(2) was also detected. PEF and FEV(1) were not related to PM(10) and NO(2) concentrations. The present results indicate that, in this panel of adult asthmatics, the worsening of lung function is associated with exposure to gaseous pollutants and occurs at levels of CO and SO(2) lower than current European standards.

[Follow-up of latex-induced occupational asthma]. / Follow up dell'asma professionale da latice.

We studied 29 subjects with latex-induced occupational asthma in a follow-up of 5 +/- 3 years. Initial and follow-up visits included a questionnaire and measurement of lung volumes, bronchial responsiveness to methacholine (PD20FEV1), and latex-specific serum IgE levels. At follow-up, 17 subjects were no longer exposed to latex, whereas 12 subjects had reduced exposure. Asthma and rhinitis symptoms, use of steroids and bronchial hyperresponsiveness improved significantly at follow-up, whereas mean FEV1% and FVC% decreased (p < 0.05). Multiple regression analysis showed that the main determinant of FEV1 and PD20FEV1 at follow up were the values of these variables at diagnosis. Complete recovery of occupational asthma was observed in 7 subjects (24%), all in the non-exposed group. Latex-specific IgE did not exhibit significant changes. In conclusion latex-induced occupational asthma improves after a follow-up of 5 +/- 3 years, but a complete recovery occurs in a minority of subjects and is associated with cessation of exposure. Lung function measurements at follow up depend from their impairment at the time of diagnosis.

[Statistics on 123 children with febrile convulsions from 1976 to 1981 with possible advantages of continuous prophylaxis with valproic acid and/or phenobarbital]. / Rilievi statistici condotti dal 1976 al 1981 sulle convulsioni febbrili in 123 bambini e sui possibili vantaggi della profilassi continua con dipropilacetato e/o fenobarbital.

All children (6 months to 5 years of age) presenting with febrile seizures have been followed for 3-5 years. Analysis of the data of 123 children gave the following results: -in 20 cases the duration of the convulsions was longer than 20 minutes; -males were prevalent (60,2%) and characterised by a longer duration of convulsive manifestations (20,2% of cases); -valproic acid (20-30 mg/kg/die) or phenobarbital (3-5 mg/kg/die) prophylaxis for a minimum of I year protect against recurrence of convulsions (26,6% of new episodes in non treated vs 10,2% in treated patients); -irrespective of drug prophylaxis, recurrence is minimal and approaches zero, when the first episode occurs in children older than 3 years; -only one case (0,8%) had recurrence not associated with fever, during valproic acid treatment two years after the first episode.

Analysis and improvement of organizational models for the management of patients with type 2 diabetes mellitus: a case study in north-east Italy.

PURPOSE: The study aimed to establish whether the organization for the management of type 2 diabetes mellitus at 9 diabetic units (DUs), in 5 neighboring local health authorities (LHAs), was able to (a) comply with the organizational model prescribed by specific regional standards; (b) ensure adequate clinical management of diabetic patients; (c) assess whether the relationship between primary care physicians (PCPs) and diabetologists (SDs) was instrumental to the needs of patients; (d) optimize specialist treatment at the DUs; (e) optimize drug management; and (f) check whether organizational changes led to variations in clinical results. METHODS: This 6-stage study analyzed procedures, precoded actions, and recordable processes. Stage (1) Defining clinical and organizational endpoints; (2) Drafting flowcharts to describe the actions and work procedures implemented within each LHA; (3) Comparing the flowcharts with the data obtained from related literature; (4) Establishing a protocol shared with PCPs for the management and treatment of patients with type 2 diabetes; (5) Changing the procedures at the DUs; and (6) Evaluating the results. The data were assessed before and after establishing a shared protocol for SDs and PCPs (year 2009 vs 2011). RESULTS: The study shows inconsistencies in the organization of work in the 5 LHAs; however, collaboration with PCPs has guaranteed: (a) unchanged hemoglobin A1C values before and after applying the protocol; (b) a percentage increase in the number of patients with type 2 diabetes who were identified thanks to these protocols; (c) an increase in the use of biguanides compared to the preprotocol period; and (d) no change in the number of patients hospitalized because of acute complications from type 2 diabetes mellitus. CONCLUSIONS: This study confirms how adequate collaboration between SDs and PCPs keeps the risk of complications stable. Nevertheless, shared protocols and clearly defined roles are required.

Open reduction and internal fixation of radial head fractures.

This study examines 32 patients operated for radial head fractures, mean age 48.7 years (range 26-76 years), Mason type II in 25 cases and Mason type III with 3 main fragments in 7 cases. Fractures were surgically reduced and fixed with Herbert's (12 cases) or Osteomed (20 cases) cannulated screws. The latter have a head that is <1 mm high and are only threaded distally. Both types of screw provide compression across the fracture. In Mason type II cases, the mean MEPS score was 98.4 and the DASH score 6.8. In Mason type III cases, MEPS was 99.3 and DASH 9.5. We believe that fixation can be carried out with screws alone, which are less invasive, and that the screw heads should preferably be completely buried, to avoid stiffness in prono-supination. In addition, suturing of the annular ligament and the joint capsule is made easier by the reduced invasiveness of screws. Screw treatment is effective in non-comminuted fractures of the radial head.

The transfrontal view: a new approach to the visualization of the fetal midline cerebral structures.

The objective of this study was to assess the feasibility of using the frontal suture as an acoustic window to visualize sonographically the midline cerebral structures (transfrontal view) in midtrimester fetuses. The study design was prospective and observational. In 124 healthy fetuses and in 2 fetuses with agenesis of the corpus callosum at 19 to 24 weeks' gestation, an attempt was made to obtain a transfrontal view by using transabdominal sonography. The transfrontal view was successfully and rapidly obtained in 110 (89%) of the healthy fetuses; it always provided detailed visualization of the entire corpus callosum, cavum septi pellucidii, third ventricle, brain stem, fourth ventricle, vermis cerebelli, and cisterna magna. The anatomic information was comparable with that obtained from a median sagittal scan obtained through the anterior fontanelle. In both fetuses with agenesis of the corpus callosum, the transfrontal view provided clear evidence of the anomaly. The transfrontal view is feasible in midtrimester fetuses and allows rapid demonstration of the cerebral midline structures and the corpus callosum in particular. It may be helpful in the diagnosis or exclusion of cerebral anomalies, and at least in some cases, it may obviate the need for a transvaginal examination. The transfrontal view may also be used to standardize the scanning plane for the evaluation of the fetal facial profile.

Transabdominal sonography of the cavum septum pellucidum in normal fetuses in the second and third trimesters of pregnancy.

OBJECTIVES: To assess the visualization rate and size of the cavum septum pellucidum (CSP) by transabdominal sonography in normal fetuses throughout pregnancy. METHODS: The CSP was prospectively researched and measured using an axial transventricular plane in 286 consecutive uncomplicated singleton pregnancies between 15 and 41 weeks of gestation. RESULTS: The CSP was seen in 40% of cases at 15 weeks, 82% at 16-17 weeks, 100% at 18-37 weeks and 79% at 38-41 weeks. Compared to biparietal diameter (BPD), the visualization rate was 33% between 31 and 32 mm, 45% between 33 and 34 mm, 84% between 35 and 43 mm, 100% between 44 and 88 mm and 86% between 89 and 99 mm. Mean CSP width was 5.3 +/- 1.7 mm (range 2-9 mm). The CSP width increased with gestational age and BPD but with a slight decrease around term. CONCLUSIONS: In normal fetuses the CSP should always be visualized between 18 and 37 weeks, or with a BPD of 44-88 mm. Failure to observe the CSP in this interval, or possibly the presence of a large CSP, may indicate abnormal cerebral development and warrant further investigation. Conversely, absence of the CSP prior to 18 weeks, or later than 37 weeks, is a normal finding.

Insulin dependent diabetes mellitus epidemiology: HLA genotype study in 12 north eastern Italian families with two siblings affected by type I diabetes.

The purpose of our study was to evaluate the relationship between the histocompatibility antigens and type I diabetes mellitus in families living in the north-eastern part of Italy. In each family two siblings were affected by diabetes. HLA-antigens were determined with the lymphocytotoxicity test, utilizing antisera of the series A-B-C-DR. The phenotypic frequencies were compared with those observed in controls. We showed that diabetes has a strong association with HLA DR 3 and/or DR 4 antigens. In particular we registered high frequency of compound heterozygous DR 3 - DR 4 subjects, and this fact supports the hypothesis of the existence of two different genes for diabetes associated with these HLA antigens. Moreover we observed a particular haplotype segregation with a very high percentage of HLA identity between patients belonging to the same family, confirming the association between HLA and genetic susceptibility to insulin dependent diabetes. These results confirm data in the literature and, completed by other data from other patients' families living in our area, will be useful in providing reliable genetic counselling.

Ultrasound of the fetal central nervous system.

Current ultrasound equipment allows the antenatal identification of many central nervous system anomalies from early gestation. In selected cases, special techniques (transvaginal sonography, three-dimensional ultrasound, colour Doppler) may enhance the diagnostic potential. Diagnostic accuracy, however, remains heavily dependent upon the expertise of the sonologist. Fetal ultrasound is effective in identifying neural tube defects, although alpha-fetoprotein screening seems to yield a greater sensitivity. The sensitivity in the diagnosis of central nervous system malformations other than neural tube defects remains unclear because of the ascertainment biases of the few large prospective studies that have been carried out so far. Magnetic resonance imaging may play a major role in the evaluation of cases with suboptimal ultrasound visualization, or when specific anomalies are suspected, such as intracranial haemorrhage or migrational disorders.

Amniotic fluid volume and onset of labor in physiological pregnancy.

We measure, by means of ultrasound, the amniotic fluid volume (expressed as maximal vertical pocket or MVP) in 646 normal pregnancies at the 39th gestational week. Our aim is to evaluate the possible correlation between MVP and onset of the labor. In a 2-week follow-up, the onset of the labor is considered the "event" variable in a time-dependent statistical analysis. Univariate analysis (Kaplan-Meier algorithm) describes a different trend in predicting the onset of labor when a stratification of MVP < 50 and > or = 50 mm was performed (chi2 = 7.91 p < 0.0049 with 1 df, Breslow-Gehan test). The first category was comprised of 496 fetuses with a median (min-max) MVP of 39 mm (25-49), the second category of 150 fetuses with a MVP of 57 mm (50-100). The results suggest that lower levels of MVP are associated to a higher percentage of the onset of labor. Furthermore, in our measurement, performed at the 39th gestational week, the correlation with the events is higher within the 40th gestational week. In fact, at 7 days from the amniotic fluid measurement, the onset of labor and the subsequent delivery is observed in 80.65 and 73.00% of the cases when they are stratified according to MVP < 50 and > or = 50 mm. At the end of the follow-up, instead, the percentage of "events" is similar, 88.10 and 86.67%, respectively. Adjustment for covariates (Cox analysis), as well as maternal age, neonatal weight, and obstetrics history, show an odds ratio (95% C.I.) of 2.08 (1.61-2.69) for MVP, using the above cutoff level. In physiological pregnancy, lower levels of amniotic fluid at term correlated to a higher probability of the onset of labor.

Prenatal diagnosis of thrombosis of the dural sinuses with real-time and color Doppler ultrasound.

OBJECTIVE: To assess the sonographic findings and clinical implications of fetal thrombosis of dural sinuses. DESIGN: Retrospective study of cases with a prenatal diagnosis of thrombosis of the dural sinuses. RESULTS: The diagnosis of fetal thrombosis of the dural sinuses was established in three uncomplicated pregnancies at 21, 22 and 28 weeks' gestation by transabdominal and transvaginal sonography, demonstrating a blood clot within the dilated dural sinuses, always in the region of the torcular Herophilii. The diagnosis was further confirmed by the color Doppler demonstration of absence of blood flow within the dilated dural sinuses. Upon request of the couples two pregnancies were terminated. One infant was delivered at term by Cesarean section and died during neurosurgery. CONCLUSIONS: Thrombosis of the cerebral venous circulation can occur antenatally. Accurate diagnosis can be made using fetal real-time and color Doppler ultrasound.

Absence of the ductus venosus: report of 10 new cases and review of the literature.

OBJECTIVE: To assess the clinical significance of the absence of the ductus venosus. DESIGN: A retrospective study with a review of the literature. METHODS: The archives of our ultrasound laboratory and the English literature were searched for cases with a prenatal diagnosis of absence of the fetal ductus venosus. RESULTS: Between 1985 and 2000, 10 fetuses were diagnosed in our center as having absence of the ductus venosus. The review of the literature revealed 23 cases. Three main patterns of abnormal venous circulation were documented: (1) umbilical vein bypassing the liver and connecting directly to the right atrium (46%); (2) umbilical vein bypassing the liver and connecting to the inferior vena cava mostly through one of the iliac veins (25%); (3) umbilical vein connecting to the portal circulation without giving rise to the ductus venosus (21%). Major anomalies, including chromosomal aberrations, were found in 8/33 (24%) cases. Hydrops developed in 11/33 (33%) cases. Twenty fetuses with isolated absence of the ductus venosus were delivered, and 5 (20%) died. The portal vein was found to be absent in half of the infants examined after birth. CONCLUSIONS: Our results and the review of literature suggest that absence of the ductus venosus is associated with a high incidence of fetal anomalies and adverse outcomes, including associated malformations, chromosomal aberrations, in utero heart failure and absence of the portal vein. Heart failure and absence of the portal vein seem particularly frequent when absence of the ductus venosus is associated with a connection of the umbilical vein to either the inferior vena cava or the right atrium.

Distribution of abnormal karyotypes among malformed fetuses detected by ultrasound throughout gestation.

A karyotype was obtained from 755 fetuses with structural anomalies detected by sonography between 13 and 40 weeks' gestation. Gestational age was found to have no influence on the prevalence of chromosomal aberrations. The incidence in the second and third trimesters of pregnancy was 15.7 and 17.5 per cent, respectively. The contribution of the different malformations to such proportions did, however, change throughout gestation. Cystic hygroma was by far predominant in the early second trimester, cardiac defects in the late second trimester, and duodenal atresia in late pregnancy. Our findings confirm that karyotyping of malformed fetuses is highly advisable; the importance of chromosomal investigation is not dependent on the gestational age at detection of the structural defect as the likelihood of finding a chromosomal anomaly during the second and third trimesters is quite similar. Spontaneous intrauterine selection of chromosomally abnormal fetuses is most likely counterbalanced by the limited accuracy of prenatal ultrasound in recognizing many fetal anomalies early in pregnancy.

Pituitary adenomas in childhood and adolescence. Clinical analysis of 10 cases.

Pituitary adenomas in childhood and adolescence constitute 2-6% of all operated pituitary adenomas. We report the clinical features, treatment and follow-up of 10 pediatric patients affected by pituitary adenomas. All patients underwent clinical evaluation, endocrine tests, magnetic resonance imaging and visual field assessment. Follow-up ranged from 8 to 132 months (median 52.6). All patients were older than 10 years of age; 60% were males. In 50% the initial complaints were headache and/or visual impairment, all except one had clear evidence of endocrine dysfunction. Ninety percent were macroadenomas. According to hormone measurements and immunostaining 50% were prolactinomas, 20% were pure GH-secreting and 30% were non-functioning adenomas. Prolactinomas in two females were successfully treated with cabergoline. The other patients underwent surgery: three prolactinomas are still being treated with dopamine agonists and a GH-secreting adenoma is being treated with octreotide LAR and cabergoline. Two patients were also treated with conventional radiotherapy. Treatments were completely successful in 50% of patients: these have normal hormone secretion, full pubertal development, no significant tumor mass and normal visual field. Hypersecretion of prolactin persists in two cases; partial or complete hypopituitarism is present in four, relevant tumor remnant in another four and impairment of visual field is present in two cases. In conclusion, pediatric adenomas occur mostly in pubertal age, are prevalently macroadenomas and clinically functioning. Medical therapy should be preferred for secreting adenomas, but in some cases, notably prolactinomas in males, surgery and eventual radiotherapy may be needed.

Uterine and fetal cerebral Doppler predict the outcome of third-trimester small-for-gestational age fetuses with normal umbilical artery Doppler.

OBJECTIVE: To assess the value of different admission tests in predicting the outcome of small-for-gestational age (SGA) fetuses with normal Doppler waveforms in the umbilical artery. METHODS: Criteria for admission into this retrospective study included: singleton pregnancy with a birth weight < 10th centile; absence of severe maternal complications; no evidence of fetal anomalies on the sonogram; normal umbilical artery Doppler; and availability of complete follow-up. At the first antenatal sonogram classifying the fetus as SGA, Doppler analysis of the uterine and middle cerebral arteries was performed and amniotic fluid volume was assessed. Outcome variables included adverse perinatal outcome (perinatal death, severe morbidity) and emergency Cesarean section for fetal distress. RESULTS: Two hundred and thirty-one pregnancies were included in the study. The mean +/- standard deviation birth weight and gestational age at delivery were 2222 +/- 502 g and 37.3 +/- 2.9 weeks, respectively. In 37 cases (16%), an emergency Cesarean section was performed. There was one intrauterine death and three fetuses delivered by emergency Cesarean section developed severe morbidity. Logistic regression demonstrated that abnormal velocimetry of the uterine arteries and fetal middle cerebral artery were independently correlated with the occurrence of Cesarean section. CONCLUSIONS: SGA fetuses with normal umbilical artery Doppler waveforms and abnormal uterine arteries and fetal middle cerebral artery waveforms have an increased risk of developing distress and being delivered by emergency Cesarean section. Particularly when both uterine and fetal cerebral waveforms are altered at the same time, the risk is exceedingly high (86%) and delivery as soon as fetal maturity is achieved seems advisable. On the other hand, when both vessels have normal waveforms, the chances of fetal distress are small (4%) and expectant management is the most reasonable choice.