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Please cite this paper as: Fabbri E, Revello M, Furione M, Zavattoni M, Lilleri D, Tassis B, Quarenghi A, Rustico M, Nicolini U, Ferrazzi E, Gerna G. Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood. BJOG 2011;118:448–456. Objective To identify fetal cord blood prognostic markers of symptomatic congenital human cytomegalovirus infection (HCMV). Design Retrospective observational study. Setting Fetal medicine unit in Milan and Medical virology unit in Pavia, Italy. Population HCMV-infected and -uninfected fetuses of mothers with primary HCMV infection during the period 1995–2009. Methods Overall, 94 blood samples from as many fetuses of 93 pregnant women experiencing primary HCMV infection were examined for multiple immunological, haematological and biochemical markers as well as virological markers. Congenital HCMV infection was diagnosed by detection of virus in amniotic fluid, and symptomatic/asymptomatic infections were determined by ultrasound scans, nuclear magnetic resonance imaging, histopathology or clinical examination at birth. Blood sample markers were retrospectively compared in symptomatic and asymptomatic fetuses with congenital infection. Main outcome measures A statistical analysis was performed to determine the value of each parameter in predicting outcome. Results Univariate analysis showed that most nonviral and viral markers were significantly different in symptomatic (n = 16) compared with asymptomatic (n = 31) fetuses. Receiver operator characteristics analysis indicated that, with reference to an established cutoff for each marker, the best nonviral factors for differentiation of symptomatic from asymptomatic congenital infection were β2-microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. β2-Microglobulin alone or the combination of these four markers reached the optimal diagnostic efficacy. Conclusions The determination of multiple markers in fetal blood, following virus detection in amniotic fluid samples, is predictive of perinatal outcome in fetuses with HCMV infection.

Objectives The aim of this study was to evaluate the efficacy of the test for the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 (phIGFBP-1) in endocervical secretions in predicting preterm delivery in women with uterine contractions. Methods The study included 210 women with a singleton pregnancy with documented uterine contractions and intact membranes at between 24 and 34 weeks' gestation who underwent the cervicovaginal phIGFBP-1 test and transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point for cervical length. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for preterm delivery following univariate analysis. Results ROC curves indicated that 26 mm was the optimal cut-off value for cervical length in predicting preterm delivery. A cervical length of < 26 mm and the presence of phIGFBP-1 were statistically significant in univariate logistic regression analyses (P < 0.0001) with odds ratios of 16.18 and 9.29 for preterm delivery, respectively. Multivariate analysis of cervical length and phIGFBP-1 showed that they were independent and therefore useful in combination for predicting preterm delivery. Conclusions Cervical length and the phIGFBP-1 test are independent variables that can be used together to predict preterm delivery in women with uterine contractions. A sonographically measured cervical length of > 26 mm with a negative phIGFBP-1 test in a patient with regular uterine contractions before 37 weeks' gestation seems to indicate a low risk of preterm delivery and may therefore allow avoidance of unnecessary therapies. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Objective The technique used to perform transabdominal chorionic villus sampling (CVS) is not standardized, but aspiration of villi is generally obtained by discontinuous vacuum created in a syringe, manually or by a hand-grip device. We evaluated the feasibility of a new method of performing CVS which employs a 4-mL Vacutainer® connected to the needle, producing a continuous negative pressure. Methods Two hundred pregnant women, whose gestational age ranged from 10 + 2 to 16 + 2 (mean, 12 + 1) weeks, entered the randomized study, which was powered to detect with 90% probability the absence of any difference in the size of chorionic samples obtained by using a 20-mL syringe with the vacuum obtained by a hand-grip device (Group 1) or by a vacutainer (Group 2). Four operators with different levels of experience performed all the procedures, which were done transabdominally using a freehand technique with a 20-gauge needle under ultrasound guidance. Results Maternal age, body mass index, gestational age and the way the needle was inserted within the chorion were similar in the two groups. The median amount of villi sampled was 20 mg, with no differences between the two groups. The rate of fetal loss was 1.7%. All losses occurred in women of Group 1 who had only one needle insertion. A second needle insertion was required more frequently while using the vacutainer. Conclusion This new technique for performing transabdominal CVS uses a readily available device and is as effective as traditional sampling systems to aspirate villi. It has the advantage of being a one-operator procedure. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

The evaluation of renal function in fetuses with lower urinary tract obstruction by analysis of electrolytes and beta2-microglobulin in fetal urine has limitations. We measured fetal serum beta2-microglobulin before and after bladder shunting to evaluate renal function.A total of 12 fetuses with lower urinary tract obstruction underwent vesicoamniotic shunting. In addition to the standard evaluation of urinary electrolytes and beta2-microglobulin, fetal renal status was assessed by pre-shunt and post-shunt fetal serum beta2-microglobulin.At 2 to 4 weeks after shunting 2 of the 12 fetuses had persistent oligohydramnios, demonstrated increased values of serum beta2-microglobulin and were confirmed to have renal dysplasia. In the remaining 10 fetuses there was reaccumulation of amniotic fluid for a minimum of 4 weeks after shunting. Serum beta2-microglobulin values increased after shunting in 4 fetuses, all of which developed renal failure, whereas serum beta2-microglobulin did not change or was decreased after shunting in 6, of which 4 had normal renal function at latest followup.Urinary electrolytes, urinary beta2-microglobulin and pre-shunt serum beta2-microglobulin, whether increased or normal, failed to be predictive of potential response to prenatal intervention. Serial samples of fetal blood may provide distinction between patients who do and do not respond to prenatal treatment of lower urinary tract obstruction.

Thrombophilias are inherited or acquired conditions that predispose the affected individual to thromboembolism. Several studies have demonstrated that the presence of thrombophilic defects is a risk factor for adverse pregnancy outcome. Preeclampsia (PE) is associated with vascular and endothelial damage and thrombophilias may play an important role in this pathology. Most studies have found an association between early-onset PE and thrombophilia. Early recognition of PE is essential for optimal treatment but, at present, specific markers of the disease are lacking. Therapy must address the prevention of maternal complications and improvement of neonatal outcome. There is no clear evidence to support the use of heparin prophylaxis for PE. A high dose of antithrombin concentrate may represent a possible therapy in early-onset PE. Preventive and conservative treatment of PE with early diagnosis and a new therapeutic approach will allow the prolongation of pregnancy with fewer maternal and fetal complications.

To evaluate the accuracy of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions to predict premature delivery in symptomatic and asymptomatic pregnant women.The study included 332 pregnant women: 109 symptomatic patients (study group) and 223 asymptomatic women (control group). For all women, qualitative and quantitative assessment of the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 in endocervical secretions was carried out, but the quantitative assay was finally performed in 282 of 332. Student's test, the chi2 test, and Fisher's exact test were used as appropriate.The phosphorylated insulin-like growth factor binding protein-1 qualitative test was positive in 35 of 301 women (11.6%) and 11 (31.4%) of them delivered before 37 weeks; in the remaining 266 women with a negative test, there were 11 (4.7%) premature deliveries (relative risk = 5.8; 95% CI = 3.3-10.3). The mean values of quantitative phosphorylated isoform of insulin-like growth factor binding protein-1 were 56.9 microg/l (95% CI = 40.7-73.1) in cases of a positive qualitative test and 6.1 microg/l (95% CI = 4.0-8.3; p = 0.0001) in women with a negative result. The sensitivity, specificity, positive predictive value, and negative predictive value for phosphorylated isoform of insulin-like growth factor binding protein-1 test in symptomatic patients were 69.2%, 90.5%, 50%, and 95.6% respectively, while in the asymptomatic patients they were 22.2%, 91.8%, 11.8%, and 96% respectively.The phosphorylated isoform of insulin-like growth factor binding protein-1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. This test may have an important role in the management of women presenting with symptoms suggestive of preterm labour.

Ballantyne syndrome (also called mirror syndrome or triple edema) describes the unusual association of fetal and placental hydrops with maternal preeclampsia. This is a case report illustrating a 37-year-old patient who was referred to our clinics at 28 weeks of gestation (wg) because of fetal hydrothorax. On examination, the woman did not show signs of preeclampsia. The fetal ultrasound examination revealed bulky hydrothorax, generalized subcutaneous edema, placental edema, and polyhydramnios. It was not possible to find the cause of the fetal hydrops. At 29 weeks and 4 days of gestation, the fetal hydrothorax was removed by two pleuro-amniotic shunts, but at the moment of our intervention anasarca was already present. In the following 3 days, despite observing bed rest, the mother developed edema of hands and face, while blood pressure remained normal. At 30 wg the patient underwent cesarean section because fetal movements ceased and the fetal heart rate monitoring showed loss of variability and decelerations. Before dying, the neonate lived for 20 days in a state of deep hypotension.

Objective To assess whether the addition of four-dimensional (4D) ultrasound to a conventional two-dimensional (2D) scan in the second/third trimester of pregnancy facilitates maternal recognition of specific fetal structures and movements and causes an emotional impact, as subjectively perceived by the woman. Methods Fifty-two women were randomly assigned to 2D ultrasound only (Group 1), while 48 women underwent 2D plus 4D ultrasound (Group 2). All the women completed two questionnaires. One questionnaire listed the fetal structures and movements that the women had recognized during the 2D scan or, for those women who also underwent a 4D scan, during the combination of the two; the other questionnaire required the women to score on an analog scale whether they had seen all the fetal parts and movements that they wished to see, whether they were satisfied with the scan, and if the scan had changed for the better their perception of the fetus. A subgroup of 46 women completed the Maternal Antenatal Attachment Scale (MAAS) designed to measure antenatal emotional attachment. Results Similar percentages of women in the two groups visualized fetal structures and movements, but facial expressions and hand-to-mouth movements were twice as likely to be seen with 4D ultrasound, although this difference did not reach statistical significance. The percentage of women who reported that they had seen all the fetal parts and movements that they wished to see, and of those who were satisfied overall with the scan, were similar in the two groups. There was no difference in the percentage of women who felt that the scan had changed for the better their perception of the fetus. Although the MAAS scores were similar in the two groups, there were more women with positive quality, intensity and global attachment among those who had undergone a 4D scan. Women who had seen all the fetal parts and movements they wished to see (whether with 2D or 2D plus 4D) answered more frequently that the scan had changed for the better their perception of the fetus. Conclusion This randomized study indicates that the addition of 4D ultrasound does not change significantly the perception that women have of their baby nor their antenatal emotional attachment compared with conventional 2D ultrasound. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.

Objective To evaluate the effects of serial intravascular transfusions on RhD-alloimmunized fetuses with ascites/ hydrops at the time of the first transfusion by measuring multiple hematological/biochemical blood variables. Methods Thirty-one singleton pregnancies were referred for management of RhD alloimmunization. Seven fetuses had hydrops on presentation and were transfused immediately. The remainder underwent weekly ultrasound examinations, and fetal blood sampling and transfusion were performed on development of ascites. In the 104 samples collected overall from the 31 fetuses, glucose, uric acid, urea, creatinine, total protein, total and directbilirubin,aspartateaminotransferase(AST),alanine aminotransferase (ALT), γ-glutamyltransferase, alkaline phosphatase, lactic dehydrogenase, amylase, pseudocholinesterase (PCHE), creatine kinase, triglycerides and cholesterol were measured and compared with a reference range for non-anemic fetuses. Results The median gestational age at first transfusion was 26 (range, 18‐34) weeks. There were three fetal losses after the first transfusion, two of which were due to procedure-related complications; one further loss occurred. At the first transfusion fetal hematocrit, pO2, total protein, PCHE, creatinine and urea concentrations were significantly decreased compared to reference data, while total and direct bilirubin, AST, ALT, amylase, triglyceride and uric acid concentrations were increased. In all surviving fetuses ascites/hydrops had disappeared by the second transfusion. Fetal pO2, total protein, AST, ALT and PCHE concentrations had normalized by the third transfusion. Correction of fetal anemia did not affect the other variables. Conclusions RhD-alloimmunized fetuses with ascites/hydrops at the time of the first transfusion had a survival rate of 87%. Alterationsof several biochemicalfetal blood indices are present at the first sampling/transfusion, but most variables normalize with intravascular transfusions. Copyright  2005 ISUOG. Published by John Wiley & Sons, Ltd.

Rhombencephalosynapsis (RES) is a rare congenital abnormality characterized by vermian agenesis and fusion of the cerebellar hemispheres. In the 3 cases reported here, prenatal magnetic resonance imaging clearly depicted cerebellar features characteristic of RES, allowing a definite diagnosis.

Quantitative fluorescent polymerase chain reaction (QF-PCR) has recently entered the field of prenatal diagnosis to overcome the need to culture fetal cells, hence to allow rapid diagnosis of some selected chromosomal anomalies. We reviewed the studies on the accuracy of QF-PCR in detecting chromosomal anomalies at prenatal diagnosis. Overall, 22 504 samples have been analysed. The detection rate of aneuploidies of the selected chromosomes (13, 18 and 21, and X and Y) was 98.6% (95% confidence interval 97.8-99.3). QF-PCR might play a major role and be considered a valid alternative to the full karyotype. Being less expensive, and almost entirely automated, more women could undergo invasive prenatal diagnosis without significant increase in health expenditure. By using QF-PCR as a stand-alone test, the chances of non diagnosing the commonest, and the only chromosome anomalies which do increase in frequency with maternal age, are approximately one in 150 abnormal karyotypes, or one in 10-30 000 samples, based on the age distribution. These error rates might be deemed acceptable, although most structural chromosomal anomalies will be missed. At present, women are rarely informed about the full spectrum of the conditions which might be diagnosed via amniocentesis or chorionic villous sampling. Some of these anomalies might be acceptable, in view of their limited or uncertain clinical relevance, and decision analysis might, in the majority of cases, confine the full karyotype to selected women who have specific indications.

Objectives Fetal face malformations represent one of the most challenging prenatal diagnoses mainly because of the wide range of morphological features involved. We tested an approach based on a combination of conventional two-dimensional ultrasound with the more recent three-dimensional technique plus magnetic resonance imaging, in order to improve parents' understanding of fetal face anomalies, thereby facilitating parent counselling. Methods Two cases of fetal facial anomaly were studied using these combined techniques; one had severe micrognathia and malformation of the ears with preauricular tags, while the other had bilateral dacryocystocele and severe hypertelorism. Results The images generated by three-dimensional ultrasound enabled the parents to visualize their child immediately and helped them to adjust to the diagnosis of facial defects and its clinical consequences. Conclusions An approach based on combined use of different imaging techniques was found useful in both cases. Copyright © 2004 John Wiley & Sons, Ltd.

Vein of Galen aneurysmal malformations are rarely seen intracranial malformations. They represent less than 1% of the cerebral arteriovenous malformations. Prenatal diagnosis of an arteriovenous fistula malformation may be achieved by real-time and Doppler sonography with color flow imaging, by identifying dilated veins and arteriovenous shunts with turbulent flow. In addition, an elevated cardiac output may be observed and correlated with the magnitude of the cerebral arteriovenous shunt. The high incidence of cardiomegaly in neonates with arteriovenous malformations also suggests that high-output cardiac failure is already present in a significant number of cases during the 3rd trimester, and, therefore, treatment in utero may need to be considered to improve the hemodynamic status. In our case, all the above cardiovascular features were present during prenatal ultrasonography. The information on outcome compiled from the literature suggests that when an arteriovenous malformation is large enough to be detected prenatally, as in our case, it is likely to lead to cardiac failure either during the antenatal period or soon after birth. In this paper, we present the management of a case of 3rd-trimester diagnosis of a vein of Galen aneurysm associated with cardiac decompensation.

Objective: This prospective randomized trial compares the effects of a 5% glucose solution or no infusion during labor on glucose levels, pH, pO2, pCO2, and base excess (BE) of normal pregnant women in early labor and at delivery, and on fetal cord blood.Methods: Forty-three women were randomized to glucose infusion and 38 were controls.Results: Starting glucose levels were independent from the fasting state. When no glucose supplementation was given, the labor itself was associated with a reduction of mean pH (from 7.42 to 7.36, P = 0.00001), mean pCO2 (from 25.7 to 24.4 mm Hg, P = 0.04), and mean BE (from -6.3 to -9.8 mEq/L, P = 0.00001), and an increase of capillary glucose (from a mean of 83 to 105 mg/dL, P = 0.00001). Infusions of glucose did not significantly alter maternal acid–base balance at delivery. pH, pO2, pCO2, and BE were similar in arterial and venous cord blood of both groups. No variables correlated with cord blood glucose levels or with glucose vein–artery difference.Conclusions: We con...

Diagnostic advances have made it possible to use ultrasonograph to assess placentation and therefore zygosity in utero in the case of monochorionic-monozygotic twins. Foetal behaviour of 15 monozygotic and 15 unlike-sexed dizygotic twin pairs was studied serially with ultrasounds from 10 to 22 weeks gestational age. Each twin, regardless of its zygosity, showed individualised behavioural styles. One twin was found to be 'dominant' in the sense of being more active, but less reactive, possibly due to the fewer stimuli being generated by its co-twin. Monozygotic twins, as opposed to dizygotic twins, showed greater similarities in activity and reactivity levels, but were never behaviourally identical and decreased in likeness with increasing age. Our data suggest that so-called identical twins are very similar, but not behaviourally identical, from very early in pregnancy. The unequally shared intrauterine environment contributes to putting each monozygotic twin on a progressively distinct behavioural path.

Human cytomegalovirus (HCMV) load and virus-specific IgM were quantified in blood of 36 fetuses from mothers with primary HCMV infection. Nineteen fetuses were congenitally infected and 17 were uninfected as diagnosed by virus isolation from and DNA detection in amniotic fluid. Sensitivity of antigenemia was 57.9%; of viremia, 55. 5%; of leukoDNAemia, 82.3%; and of IgM, 57.9%; specificity was 100% for all assays. When amniocentesis was performed, 4 HCMV-infected fetuses (group A) showed abnormal ultrasound and biochemical/hematologic findings, 8 (group B) had elevated gamma-glutamyl transferase values, and 7 (group C) had normal ultrasound and biochemical findings. Virus loads were higher in groups A and B than in group C. In group A, no pregnancy went to term, in group B, 3 of 6 newborns were symptomatic at birth, and in group C, the 6 newborns were subclinically infected. Taken together, virologic, laboratory, and ultrasound findings may contribute to a better prognostic definition of fetal HCMV infection.

Objective: The study’s aim was to analyze the type of cardiac involvement in fetuses or infants with twin-twin transfusion syndrome. Study Design: Seventeen pairs of monochorionic diamniotic twin fetuses with twin-twin transfusion syndrome underwent serial Doppler echocardiographic studies. Repeated decompressive amniocenteses were performed in all pregnancies. Results: No specific cardiac involvement was seen in donor twins in utero or after birth. All recipient twin fetuses showed variable degrees of biventricular hypertrophy and dilation with tricuspid regurgitation. These features were also evident in 45% of the recipient twin neonates. The fluid unbalance resolved with serial amniocenteses in 9 cases and in a further 2 after the death of the donor twin; in all 11 of these recipient twin fetuses there was some degree of improvement of the cardiac involvement, which became normal in all surviving recipient twin infants within 40 days to 6 months after birth. Conclusion: Features of cardiac hypertrophy with signs of a prehydropic or hydropic state develop during fetal life in recipient twins in twin-twin transfusion syndrome; this impairment is reversible with the resolution of the fluid imbalance or after delivery. (Am J Obstet Gynecol 1998;179:1056-62.)

36 MCDA twin pregnancies with FFTS investigated by fetal blood sampling (FBS) were studied over a 10-year period (1988-1997). The haematological data obtained at FBS were compared between the donor and recipient fetuses. It was shown that the donor fetus had a significantly lower haematocrit (35.7 per cent versus 47.2 per cent; p 15 per cent, however, was found in only 25 per cent of twin pairs. There were no significant inter twin differences in the remaining indices. The study concluded that although there are significant differences in haematocrit and red cell mass between the donor and recipient fetuses, only a minority of fetuses will have degrees of discordancy suggested in the literature to be diagnostic. We suggest that FBS does not have a role in establishing the diagnosis of FFTS, although its role in determining the degree of haematocrit discordancy to assist in timing of delivery remains to be evaluated.

Forty-six pregnant women undergoing second-trimester biochemical screening for Down syndrome were asked to fill in the State–Trait Anxiety Inventory (STAI) questionnaire to assess their anxiety level at two different moments: when recruited to the study (at 11–13 weeks' gestation), and after the test result was communicated. The test result was given as a numeric value of risk (1/x), rather than as positive/negative. There were 10 women in whom the risk after biochemical screening increased (median Δrisk=+1/535; range=1/69 to 1/1083), whereas in the remainder the risk decreased (median Δrisk=−1/1576; range=−1/42 to −1/4947) compared with the baseline value calculated on maternal age alone. Although only in a minority of women the STAI score after biochemical screening exceeded the reference range, the change in the STAI score was significantly higher when the risk increased, and the change in the risk estimate correlated significantly with the change in this index of anxiety. Three out of seven women with a ‘negative’ test, but increased risk estimate and increased anxiety after biochemical screening chose to undergo amniocentesis. A policy of providing the result of biochemical screening for Down syndrome as a numeric value, even for ‘negative’ tests, may cause some women to experience anxiety and request amniocentesis. © 1998 John Wiley & Sons, Ltd.

Three cases of placental chorioangiomas, from 6.5 to 10 cm in diameter, were diagnosed prenatally by ultrasound and color Doppler imaging at 21–34 weeks of gestation. In 1 case, due to fetal hydrops a

OBJECTIVE: Our purpose was to establish a reference range of fetal serum β 2 -microglobulin, an index of glomerular filtration rate, and to compare the values obtained in fetuses with urinary tract anomalies with this range. STUDY DESIGN: Serum β 2 -microglobulin was measured in 53 control fetuses at 18 to 39 weeks' gestation and in 14 fetuses with urinary tract anomalies, 9 of which had simultaneous urine sampling. RESULTS: In controls fetal serum β 2 -microglobulin had a mean value of 3.4 mg/L (95% data intervals 2.0 to 4.9) and did not correlate with gestational age. In the 14 fetuses with urinary tract anomalies β 2 -microglobulin levels were increased overall compared with controls (median Z score 1.7, range −0.1 to 9.2), and this was also the case in the five fetuses with unilateral renal disorders (median Z score 1.7, range −0.1 to 3.8) and in a fetus who underwent vesicoamniotic shunting and had normal renal function at birth. Serum β 2 -microglobulin was normal in 4 fetuses with bilateral urinary tract obstruction and normal function at postnatal follow-up and also in 1 of 5 fetuses with renal failure. In fetuses with bilateral uropathy urinary sodium correlated with serum β 2 -microglobulin levels. CONCLUSIONS: Increased values of serum β 2 -microglobulin in fetuses with urinary tract anomalies indicate an impaired glomerular filtration rate. The finding of raised concentrations in fetuses with unilateral damage suggests that the compensatory role of the normal kidney is not complete during intrauterine life. Larger series are required to ascertain whether fetal blood sampling is warranted in the antenatal investigation of renal function, especially in view of the close correlation between urinary sodium and serum β 2 -microglobulin levels in fetuses with bilateral obstruction. (Am J Obstet Gynecol 1997;176:54-7.)

Seventy-one fetal urine samples were taken from the bladder or renal pelvis of 33 fetuses at 13-36 weeks' gestation with a diagnosis of urinary tract anomaly. Severe isolated hydronephrosis in the absence of an enlarged bladder was the indication for sampling in 12/33 fetuses (26 samples), who were retrospectively classified into three groups: normal, intermediate, and dysplastic, based on the evaluation of postnatal renal function or histology. For all samples, urinary sodium (Na+), calcium (Ca2+), creatinine, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) were measured. Among the 71 fetal urine samples, both beta 2-microglobulin and NAG correlated inversely with gestational age, Na+, and Ca2+, but not with creatinine concentrations. However, the correlation of urinary beta 2-microglobulin with gestational age was dependent on the Na+ and Ca2+ concentrations, whereas urinary NAG correlated significantly with urinary Na+ and Ca2+, and also with gestational age. In fetuses with isolated hydronephrosis, only Na+, and not Ca2+, was significantly related to both beta 2-microglobulin and NAG. Only Na+ and beta 2-microglobulin were significantly, and similarly, higher in both dysplastic and intermediate kidneys when compared with fetuses with normal postnatal function. If only the last urine sampled was considered, there was overlapping of all parameters in the three groups. In isolated hydronephrosis, only the most extreme forms of renal failure might be suggested by elevated levels of Na+, Ca2+, beta 2-microglobulin, and NAG, without an obvious superiority of any of these parameters.

Essential fatty acid status of fetal plasma phospholipids: similar to postnatal values obtained at comparable gestational ages.van Houwelingen AC, Foreman-van Drongelen MM, Nicolini U, Nicolaides KH, Al MD, Kester AD, Hornstra G.Department of Human Biology, Limburg University, Maastricht, The Netherlands. A.C.Houwelingen@HB.Rulimburg.NLHardly any direct information is available on the essential fatty acid (EFA) status of the fetus during intrauterine development. Therefore, we studied 86 umbilical plasma samples obtained by trans-abdominal puncture during ongoing pregnancies (18.3-39.0 weeks of gestational age). These were compared with 51 samples of umbilical cord blood, collected immediately after birth (gestational ages, 28.5-39 weeks). The total amounts of fatty acids in fetal plasma phospholipids (mg/l) did not change during gestation. The relative amounts of linoleic acid (% of total fatty acids) showed a slight increase (P = 0.03) during fetal maturation. Arachidonic acid (20:4n-6) decreased (both absolute (mg/l) and relative (% wt/wt) P < or = 0.0001), while docosahexaenoic acid (22:6n-3) increased (absolute P < 0.003, relative P < 0.0001) when pregnancy progressed. The EFA profiles of fetal samples were in general comparable with postnatal results of infants born at similar gestational ages. However, the fetal linoleic acid status was lower than the linoleic acid status of the neonates. The same was true for the overall EFA status. The results of this study indicate that the low EFA status observed in preterm infants at birth, is a developmentally related phenomenon.

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16-30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases andor = 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.

The fetal humerus, radius/ulna, femur, tibia/fibula and foot were measured in 296 pregnant women at 64–108 days' menstrual age, using vaginal sonography. All limb measurements correlated significantly with gestational age and biparietal diameter independently. Ratios of limb segment lengths did not change with gestation. Reference ranges (mean and 95% data intervals) were constructed for each limb segment. These data may prove useful in prenatal diagnosis of skeletal dysplasias and in the antenatal assessment of patients at risk of chromosomal abnormalities. Copyright © 1994 International Society of Ultrasound in Obstetrics and Gynecology

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy-Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post-axial polydactyly and neuroblastoma-in-situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.

Ganciclovir was administered 'in utero' for 12 days in a 29-week-old fetus with ascertained congenital human cytomegalovirus (HCMV) infection, thrombocytopenia and elevated gamma-glutamyl transferase (gammaGT) value. Efficacy of therapy was shown by reduction in virus titer of amniotic fluid and fetal urine, disappearance of viral DNA in fetal blood, and normalization of platelet count and gammaGT value. However, stillbirth occurred at 32 weeks of gestation and HCMV inclusion bodies were detected in kidneys, lungs, heart and pancreas at autopsy. During therapy, side-effects,possibly related to ganciclovir administration, were observed.

Objectives: The assessment of fetal renal function plays a key role in the evaluation of posterior urethral valve obstruction cases. The aim of our study was to determine the value of several urinary compounds, including β 2 -microglobulin, N -acetyl-β-D-glucosaminidase, and microalbumin in the assessment of prenatal renal function in cases of posterior urethral valve and their potential role in the selection of such cases for in utero shunting. Study Design: A range of urinary compounds was measured, including β 2 -microglobulin, N -acetyl-β-D-glucosaminidase, and microalbumin in 25 cases of posterior urethral valve obstruction. These cases were divided into four groups based on outcome. The Mann-Whitney test and analysis of covariance were used. Results: Sodium, calcium, and β 2 -microglobulin were the best predictors for fetal survival. β 2 -Microglobulin values > 13 mg/L were almost invariably associated with fatal outcome. Conclusion: The estimation of β 2 -microglobulin may help in counseling parents and in selecting cases for in utero shunting.

Since time immemorial twin births have been perceived as an extraordinary, often disquieting phenomenon. Many legends and myths flourished around their origins. Twins were thought to be the result of adultery, considered as the incarnation of evil spirits and ancestors, or, as in the myth of Castor and Pollux, one was regarded as having godly origins and the other not.

To determine plasma zinc concentrations in normally and abnormally growing fetuses.Prospective observational study.Fetal Medicine Unit, Queen Charlotte's Maternity Hospital.53 pregnant women attending for fetal blood sampling at between 18 and 40 weeks gestation. 27 fetuses were normal (central group), 11 fetuses were growth retarded and 15 were malformed.Plasma zinc concentrations in maternal and fetal blood at time of fetal blood sampling.In normally growing fetuses, between 18 and 40 weeks gestation, there was no fall in maternal plasma zinc concentration; the fetal level fell by 36%. In 10 fetuses with symmetrical growth retardation, plasma zinc concentration tended to be low, but was not significantly different from that in the normal control fetuses.The results suggest that (i) placental transfer of zinc is an uphill secretory process and that it is a rate-limiting step in the accumulation of zinc by the fetus and (ii) in fetuses with symmetrical intrauterine growth retardation, a low plasma zinc is probably a parallel phenomenon and not necessarily an aetiological factor.

The suggestion that amnioinfusion improves umbilical artery Doppler indices of downstream resistance in oligohydramnios by relieving cord compression was investigated by obtaining waveforms before and immediately after amnioinfusion in 16 pregnancies with severe oligohydramnios. There was no significant difference in the change in umbilical artery pulsatility index (PI) between 11 pregnancies in which amniotic fluid volume was restored (mean delta PI = -0.07, 95% confidence interval -0.17 to +0.07), and 5 pregnancies in which immediate vaginal leakage of infused fluid prevented restitution of amniotic fluid volume. Fetal heart rate did not change significantly in either group. End-diastolic frequencies did not return with restitution of amniotic fluid volume in the 2 pregnancies in which they were absent before infusion (absent in 1, reverse in 1). This study suggests that restitution of amniotic fluid volume in human pregnancies complicated by severe oligohydramnios does not acutely alter the umbilical artery PI.

Objective To characterize amniotic pressure (AP) in pregnancies with normal amniotic fluid volume. Design Observational study, mainly cross-sectional. Setting Fetal medicine unit within a tertiary referral hospital. Subjects Patients undergoing transamniotic invasive procedures in whom amniotic fluid volume was subjectively assessed as normal on ultrasound. Those beyond 16 weeks with a deepest vertical pool on ultrasound less than 3.0 or greater than 8.0 cm were excluded. Overall 194 pregnancies were studied on 232 occasions between 7 and 38 weeks gestation. Interventions Manometry readings referenced to the top of the maternal abdomen were obtained via a fluid-filled line from the needle hub and either connected to a pressure transducer (n = 190) or held vertically against a ruler (n = 42). Main outcome measures AP in mm Hg, AP corrected for gestational age (z scores), semi-quantitative ultrasonic indices of amniotic fluid volume, clinical variables. Results AP in singleton pregnancies increased with advancing gestation (P less than 0.001), and the sigmoid-shaped regression curve plateaued in the mid-trimester. AP z scores were not influenced by volume-related phenomena such as twin gestation, the deepest vertical pool, or amniotic fluid index, nor by maternal age, parity, gravidity, fetal sex, or subsequent spontaneous preterm delivery. Conclusions These findings suggest that AP is not principally determined by intrauterine volume. We speculate that AP, which reflects change in uterine tension as a function of radius, may instead be determined by gestation-specific anatomical and hormonal influences on gravid uterine musculature. A reference range for AP has been constructed for use in amnioinfusion and amnioreduction procedures.

Summary. In 40 cases of haemolytic disease of the fetus due to RhD immunization where the fetus required intrauterine transfusion, fetal packed cell volume was compared with the following parameters of maternal anti-D: (a) concentration, (b) IgG subclass, (c) activity in a macrophage binding assay, and (d) activity in a monocyte antibody-dependent cell mediated cytotoxicity (ADCC) assay. The anti-D concentration exceeded 4 iu/ml in all cases, correctly indicating the risk of haemolytic disease. A relationship between IgG subclass composition of the anti-D and severity of anaemia was not observed; IgGl, IgG3 and IgG 1 + 3 antibodies were all detected. The AuCC assay gave the best correlation between assay results and fetal packed cell volume: high results correctly indicated fetal anaemia in 95% of cases. Macrophage binding assay results were only considered as high in 70% of cases. Overall, these results indicate that serological tests and bioassays in highly immunized mothers may not generate any information that proves more useful than ultrasonography and their previous obstetric history.

Fetal hydrothorax and hydrops is a frequent complication of extralobar pulmonary sequestration which is associated with a high perinatal mortality and severe respiratory insufficiency in the newborn. In a 27-week-old fetus with this condition, injection of 1 ml of pure alcohol and pleuro-amniotic shunting achieved resolution of hydrops. The pregnancy progressed to term and a healthy neonate was delivered who did not require postnatal surgery.

Summary. objective In fetuses, adrenal steroids have been Implicated In organ maturation and in some species in initiation of labour. The fetal adrenal gland differs from the adult in its complement of steroid metabolizing enzymes. This study sought to examine the changes in peripheral cortisol, progesterone and dehydroepiandrosterone sulphate (DHEAS) in unstressed fetuses during pregnancy. DESIGN Paired maternal and fetal samples were collected from 47 patients. Fetal blood samples were collected by transabdominal needling. All fetuses were appropriately grown for age which ranged from 18 to 41 weeks. measurements Hormones were measured using specific, validated Immunoassays. results Fetal progesterone (mean, 822 nmol/l; 95% data Intervals 196–1449 nmol/l) varied considerably between Individuals but there was no significant change In serum concentration with gestational age, nor was there any difference between male and female fetuses. There was a small, but significant (y= 0.339x2–13.5x+ 231; r= 0.72, P= 0.0001) rise in cortisol in the fetal circulation from 32 to 41 weeks gestational age, whereas the mean fetal DHEAS concentration decreased linearly with gestational age from 4.1 μmol/l at 18 weeks to 2.6 μmol/l at 41 weeks (r=–0.41; P= 0.007). Mean progesterone concentration in the maternal serum Increased linearly from 98 nmol/l at 18 weeks to 783 nmolll at 41 weeks. In the fetus there was a significant correlation between progesterone and cortisol concentrations. conclusions These results are compatible with the proposed role of cortisol in fetal lung maturation, confirm high levels of progesterone in the fetus from an early stage of gestation, and provide further evidence for placental progesterone being the precursor of fetal cortisol.

One hundred and twelve fetuses with structural anomalies (n = 84), intrauterine growth retardation (n = 21) or amniotic fluid volume disorders (n = 7) detected by ultrasound underwent blood sampling from the intrahepatic vein for rapid karyotyping. The procedure was successful in 95.5%. 12.5% of the fetuses had an abnormal karyotype. Fetal bradycardia was observed in two fetuses (1.8%) and intraperitoneal bleeding in three (2.7%). There were three procedure-related losses but these were not due to the intrahepatic vein sampling itself. Fetal blood sampling is the method of choice for rapid karyotyping in the second and third trimesters, and the intrahepatic vein is an alternate site when access is difficult or failure to sample occurs at the placental cord insertion. Additional advantages of fetal blood sampling at the intrahepatic vein include absence of cord complications, reduced risk of fetal blood loss and fetomaternal haemorrhage, and the lack of need to confirm the fetal origin of the sample.

Fetal acid-base status was evaluated on 66 blood samples taken for rapid karyotyping from 58 growth-retarded fetuses. Before blood sampling, doppler blood flow studies of the umbilical artery showed end-diastolic frequencies to be absent in 32 fetuses (group 1) and present in 26 (group 2). Fetuses with chromosomal (n = 4) or structural (n = 8) abnormalities were excluded from subsequent analysis. Gestational age at blood sampling (27.8 [95% CI 26.5-29.1] vs 32.2 [30.4-34.1] weeks) and time from sampling to delivery (median 2 (range 0-35] vs 14 [0-77] days) were significantly lower in group 1 than group 2. There were no perinatal deaths in group 2 whereas mortality in group 1 was 65.4%. There were significant differences between the groups at blood sampling in pH, pO2, pCO2, base equivalents, and nucleated-red-cell count, but within group 1 these measurements were similar in surviving fetuses and those who died perinatally. Since acid-base determination does not predict perinatal outcome in growth-retarded fetuses, fetal blood sampling has a limited role in monitoring fetal wellbeing.

We describe a case of obstructive uropathy in the midtrimester, in which the antenatal recognition of the megalourethra not only allowed a specific diagnostis of PBS to be made, but also altered the prognosis offered to the parents

Aim The aim of our study was to evaluate the understanding of lower urinary tract symptom (LUTS) terminology used by patients. Materials and Methods Women attending urodynamic clinics in United Kingdom, Australia, and Italy were asked to complete a questionnaire testing the women's understanding of stress urinary incontinence, urge urinary incontinence, frequency, urgency, nocturia, and hesitancy. Five possible explanations for the meaning of each symptom were given. Results A total of 138 consecutive women were prospectively recruited. The terms of daytime frequency, nocturia, urgency, urge urinary incontinence, stress urinary incontinence, and hesitancy were defined correctly, according to the International Continence Society terminology, only by 33% (45/138), 44% (61/138), 46% (64/138), 39% (54/138), 37% (51/138), and 41% (57/138) of women, respectively. Over 20% of women were unsure about the meaning of each symptom. We did not find any statistical difference between the three groups in determining the correct definition (P = 0.5). Conclusions Our findings showed that most women do not know the correct meaning of LUTS terminology currently used by physicians. Neurourol. Urodynam. 27:368–371, 2008. © 2007 Wiley-Liss, Inc.

Fetal pleural effusion, a nonspecific accumulation of fluid in the pleural space, is an uncommon anomaly which can be associated with aneuploidy and a range of other structural malformations or genetic syndromes. Spontaneous resolution is not rare and confers a good prognosis. Perinatal outcome is better for those fetuses without hydrops than those presenting with hydrops. A detailed review of the literature indicates that, for fetuses with persistent effusions, in utero intervention (repeated thoracocentesis, intrauterine shunting and pleurodesis) may improve the chances of survival.

Objectives Prenatal diagnosis by ultrasound of fetal polymicrogyria has been reported only once. Methods We describe an additional case of polymicrogyria in a fetus from a monozygotic twin pair, probably the consequence of twin-to-twin transfusion syndrome. Results On ultrasound, there were bilateral cortical hyperechogenic spots, and prenatal magnetic resonance imaging demonstrated the typical features of bilateral focal polymicrogyria. Conclusion Polymicrogyria can be considered in the differential diagnosis of hyperechogenic brain lesions on fetal ultrasound. We also confirm the risk of brain damage in monochorionic twins pregnancies and the likely hypoxic–ischemic etiology of polymicrogyria. Copyright © 2004 John Wiley & Sons, Ltd.

Pre-eclampsia is a pregnancy-specific syndrome of unknown aetiology, observed in 3 – 5% of all pregnancies, associated with pathological vascular lesions in multiple organs, activation of the coagulation system, and maternal multisystemic and fetal complications. Clinically, pre-eclampsia is characterised by the onset of hypertension, proteinuria and oedema, usually beginning in the third trimester. Conventionally, antihypertensive agents are the main pharmacological treatment. Recently, some studies have shown that the treatment of pre-eclampsia with antithrombin concentrate corrects the hypercoagulability and improves the fetal status and the perinatal outcome. No clear evidence supports the use of heparin. A conservative treatment of moderate- to- severe pre-eclampsia, based on the administration of antithrombin concentrate, may allow a significant prolongation of pregnancy and a better neonatal outcome, as well as fewer maternal complications.

The death of 1 twin of monochorionic pairs is associated with a significant risk of brain hypoxic-ischemic damage in the survivor. Ultrasound may diagnose cerebral anomalies only a few weeks after the event. We report 3 cases of single survivors of monochorionic-twin pregnancies in which prenatal magnetic resonance imaging detected brain changes earlier and with better definition of the brain abnormalities than ultrasound.

Currently, amnioinfusion fluids used in operative fetoscopy usually are preheated to body temperature. As the complexity of procedures increases, purposed designed devices should be designed that allow control of pressure and temperature during amnioinfusion or amnioexchange. In the current study, a prototype amnio-irrigator and fluid heater were evaluated.The medical fluid heater heats fluid by conduction up to 37 degrees C. The maximum irrigation pressure and flow rates can be preset. Actual irrigation pressure (0 to 30 mm Hg) and flow rate (0 to 300 mL/min) can be read on the front panel. A series of ex vivo experiments were set up to determine the relationship between the flow rate (FR) and lumen of the instruments as well as the maximum flow rate (MFR) with and without the pressure control. Further, the relationship between FR and the irrigation pressure (IP) was determined. In an artificial pseudoamniotic sac the relationship between FR and change in temperature was measured, with and without the use of the medical fluid heater.When the IP was limited to 24 mm Hg, FR and pressure were correlated (r = 0.34; P.001). The larger the functional lumen of the fetoscopic instrumentation, the higher the flow (r = 0.43; P.001) and the lower the increase in IP (r = -0.47; P.001). A quadratic relation between flow and temperature was observed both for preheated fluid as when using the fluid heater (r(2) = 0.71 and r(2) = 0.88; P.001). However, at low flow rates, a thermal decrease of over 3 degrees C was observed when the fluid heater was not used.The current study quantifies an expected relationship between the diameter of the irrigation channel and achievable flow rates. It also shows that a medical fluid heater is needed when strict control of temperature would be desired.