Prognostic markers of symptomatic congenital human cytomegalovirus infection in fetal blood.

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 ß(2) -microglobulin and platelet count, and the best virological markers were immunoglobulin M antibody and DNAaemia. ß(2) -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.

Phosphorylated insulin-like growth factor binding protein-1 in cervical secretions and sonographic cervical length in the prediction of spontaneous preterm delivery.

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.

A randomized study to assess two different techniques of aspiration while performing transabdominal chorionic villus sampling.

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.

Transcutaneous electrical nerve stimulation to treat vestibulodynia: a randomised controlled trial.

OBJECTIVE: To assess the efficacy of transcutaneous electrical nerve stimulation (TENS) in the treatment of vestibulodynia. DESIGN: Double-arm randomised placebo-controlled trial. SETTING: An outpatient department for vulval disease. POPULATION: Forty women with vestibulodynia, a vestibular discomfort mostly reported as a burning pain, occurring in the absence of relevant visible findings or a specific, clinically identifiable, neurological disorder. METHODS: Twice a week active TENS or sham treatment were delivered through a vaginal probe via a calibrated dual channel YSY-EST device. Women of both groups underwent 20 treatment sessions. MAIN OUTCOME MEASURES: Visual analogue scale (VAS), the short form of the McGill-Melzack Pain Questionnaire (SF-MPQ), the Marinoff Scale for dyspareunia and the Female Sexual Function Index questionnaire (FSFI) were assessed at baseline, at the end of treatment and at follow up 3 months after the end of treatment. RESULTS: The VAS and SF-MPQ scores (6.2 +/- 1.9 and 19.5 +/- 11.9 before treatment, respectively) improved significantly in the active TENS group (2.1 +/- 2.7, P= 0.004 and 8.5 +/- 10.7, P= 0.001, respectively), but not in the placebo group. The Marinoff dyspareunia scale and the FSFI also showed a significant improvement. CONCLUSIONS: TENS is a simple, effective and safe short-term (3 months) treatment for the management of vestibulodynia.

Circadian rhythm of maternal blood pressure and fetal growth.

This study aimed at examining any relation between the circadian variation in blood pressure (BP) in human pregnancy and fetal growth. A prospective study included 52 pregnant women monitored during the third trimester of pregnancy. There were 33 uncomplicated pregnancies with normal fetal growth (Group 1) and 19 pregnancies complicated by intrauterine growth retardation (IUGR), confirmed at birth (Group 2). Ten women (five in each group) had pregnancy-induced hypertension. All women were hospitalized and followed a similar daily routine. BP was recorded with an automatic wearable device. Measurements were obtained every 20 min for 24 +/- 1 h. BP profiles were analyzed by conventional statistical methods and by cosinor, involving the least squares fit of cosine curves with an anticipated period (24 h) to the data. BP parameters, fetal outcome, demographic and obstetric characteristics were compared between the two groups. Logistic regression and multivariate analyses were used to assess factors putatively associated with fetal outcome. The circadian amplitude of diastolic BP was found to be larger in normotensive women with IUGR. As gauged by odds ratios (OR), the circadian amplitude of diastolic BP (OR = 1.7, 95% CI: 1.1-2.8; P = 0.03) and hematocrit (OR = 1.4, 95% CI: 1.0-1.9; P = 0.04) were the only variables positively and independently associated with IUGR. In the presence of maternal hypertension, the circadian amplitude of systolic BP was negatively associated with IUGR (OR = 0.7, 95% CI: 0.5-1.0; P = 0.03). A larger circadian variation in diastolic BP, rather than a difference in the mean value of systolic or diastolic BP, was found to be statistically significantly associated with IUGR. This study adds another condition in which the circadian BP amplitude constitutes a harbinger of elevated risk, apart from an association with a shortened lifespan in the absence or presence of malignant hypertension and with an increased risk of stroke and nephropathy reported earlier.

Managing twins discordant for fetal anomaly.

An excess of structural anomalies is observed in twins compared to singletons. Approximately 1-2% of twin pregnancies may face the dilemma of expectant management versus selective termination following diagnosis of an anomaly affecting only one fetus. If the option of selective fetocide is considered, the main variable determining the technique to achieve this aim is chorionicity. In a dichorionic pregnancy, passage of substances from one twin into the circulation of the co-twin is unlikely due to the lack of placental anastomoses, hence KCl can be injected safely into the circulation of the affected twin to produce fetal asystole. In monochorionic twin pregnancies, selective termination needs to be performed by ensuring complete and permanent occlusion of both the arterial and venous flows in the umbilical cord of the affected twin, in order to avoid acute haemorrhage from the co-twin into the dying fetus, which may lead to death or organ damage. Bipolar cord coagulation under ultrasound guidance is associated with approximately 70-80% survival rates.

Maternal/paternal antenatal attachment and fourth-dimensional ultrasound technique: a preliminary report.

The purpose of the present research was to investigate the role of the fourth dimensional (4D) ultrasound scanning on the antenatal attachment development, in pregnant women (19-23 weeks of gestation) and their partners. A total of 44 couples were asked to complete questionnaires about maternal and paternal antenatal attachment, before the two-dimensional (2D; control group) and 4D (experimental group) ultrasound scanning and 2 weeks later. In the groups of women, our findings underline the progressive increase in antenatal attachment throughout gestation: the mean level of antenatal attachment was significantly different between the first and the second assessment. No significant differences are shown between 2D and 4D ultrasound scanning groups. We do not eliminate the possibility that ultrasound scanning practice would be a helpful and crucial means of investigation for a complete explanation of prenatal attachment (Ainsworth, Blehar, Waters, & Wall, 1978; Fivaz-Depeursinge & Corboz-Warney, 2000) and parental mental representations (Stern, 1987, 1997).

Two-dimensional vs. two- plus four-dimensional ultrasound in pregnancy and the effect on maternal emotional status: a randomized study.

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.

The effects of serial intravascular transfusions in ascitic/hydropic RhD-alloimmunized fetuses.

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 direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-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%. Alterations of several biochemical fetal blood indices are present at the first sampling/transfusion, but most variables normalize with intravascular transfusions.

[Vaginal swab in pediatric age]. / II tampone vaginale in età pediatrica.

Vaginal secretion sampling in young patients. The aim of the study was to evaluate whether different instrumental tools (the classical cotton swab, the urethral cotton swab, the balloon shape cotton swab and cyto-brush) yield different sampling success in young patients presenting with suspected vulvovaginitis. The study was conducted in a randomised prospective way on 100 children with symptoms of vulvovaginal infection (age range: 4 months -8 years ) seen at the Clinic of Paediatric Gynaecology of the Department of Obstetric and Gynaecology, "V.Buzzi" Children's Hospital, Milano (Italy). Children's compliance and the number of samples which had to be discontinued, because of children's intolerance have allowed the evaluation of each tools. Each of these tools was tested on 25 young patients. The vaginal secretion sampling was not possible on 8 patients out of 25 with cyto-brush (32%), on 7 out of 25 with the balloon shape cotton swab (28%), on 4 out of 25 with the classical cotton swab (16%) and only 1 out of 25 with the urethral cotton swab (4%). In conclusion all the instruments tested allow sampling of vaginal secretion in young children, but the reaction and compliance of the patients has been best with the otologic cotton swab.

The role of integrated imaging techniques for prenatal prediction of phenotype in two cases of facial anomalies.

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.

Biochemical markers for the prediction of spontaneous pre-term birth.

OBJECTIVES: The aim of this study was to identify predictive biochemical markers for preterm labor. METHODS: In this prospective study we included 225 asymptomatic Caucasian women consecutively enrolled at 24 weeks of gestation. The following data were collected only once at 24 weeks of gestation: vaginal pH, vaginal fFN, cervical and serum concentration of IL-6, IL-8 and TNFalpha, maternal blood serum, ferritin. Student's t-test, the chi(2)-test and multiple linear regression were used as statistical methods. RESULTS: There were no differences between the age of patients, parity and gestational age at sampling between women who delivered at term and those who delivered pre-term (<37 weeks' gestation). There was a significant increase of cervical IL-6 (pre-term 608+/-1595 pg/l vs. at term 58.9+/-112 pg/l) and serum ferritin (pre-term microg/l 74.4+/-1.1 vs. at term 26.3+/-56.5 microg/l) in pregnant women who delivered pre-term (P<0.05). No differences in cervical IL-8 and cervical TNFalpha between pre-term and term deliveries were found. Multiple linear regression confirmed that the vaginal pH value and cervical fFN test were the best predictive biochemical markers of pre-term birth (standardized coefficient Beta=0.33 and 0.22, respectively). CONCLUSIONS: In order to evaluate pregnancies for pre-term labor, the presence of pH>4.5 and a positive fFN test seems to be predictive of subsequent pre-term delivery.

Invasive assessment of fetal renal abnormalities: urinalysis, fetal blood sampling and biopsy.

There are a number of potential biochemical markers that may have some role in predicting renal function postnatally. These include urinary sodium, calcium and beta2-microglobulin. The latter may also be measured in fetal serum. However, the accuracy of these parameters at a point in time is far from perfect as urinary tract obstruction is a progressive disease which may be best defined by repeated observations throughout pregnancy.

Fetal and maternal white cells and B- and T-lymphocyte subpopulations in pregnant women with recent infection.

OBJECTIVE: To study maternal and fetal white cell counts, B- and T-lymphocyte subpopulations in pregnant women with evidence of recent infection. METHODS: Thirty-seven pregnant women with recent infection and 38 controls were studied. All were referred for fetal blood sampling to exclude congenital infection, or to perform fetal chromosome analysis. There were 16 infected fetuses: 9 cytomegalovirus (CMV), 4 rubella, and 3 toxoplasmosis. Maternal and fetal blood was taken and white cell counts, the percentage of CD3+, CD4+, CD8+, CD56+, HLADR+CD3+ T-lymphocyte subpopulations and CD19+ B lymphocytes were measured. RESULTS: The percentage of CD3+, CD8+, and HLADR+CD3+ lymphocytes were significantly higher in infected mothers compared to controls, while CD19+ and the CD4+/CD8+ ratio were lower. Infected mothers carrying infected fetuses had significantly lower white blood cell counts compared to those infected mothers without fetal infection. The percentage of HLADR+CD3+ T lymphocytes was significantly higher and the CD4+/CD8+ ratio lower in infected fetuses compared to controls and noninfected fetuses of infected mothers. Abnormal CD4+/CD8+ ratios and/or increased HLADR+CT3+ T lymphocytes were found in 8 of 10 fetuses with structural abnormalities and/or hematological/biochemical signs of systemic damage, and in 7 of 27 without (RR = 3.1, 95% CI = 1.5-6.3). CONCLUSION: Both infected fetuses and their mothers have significant identifiable changes in white cell counts and T-lymphocyte subpopulations compared to controls. These tests may help in diagnosing maternal and fetal infection.

Complicated monochorionic twin pregnancies: experience with bipolar cord coagulation.

OBJECTIVE: The purpose of the study was to evaluate our experience with ultrasound-guided bipolar diathermy forceps for cord occlusion in complicated monochorionic twin pregnancies. STUDY DESIGN: Seventeen consecutive cases were included: 9 cases were twin-to-twin transfusion syndrome; 2 cases were twin reversed arterial perfusion syndrome, and 6 cases were discordant for fetal abnormality. Bipolar diathermy was performed under local anesthetic with the use of 3-mm forceps with ultrasound guidance. RESULTS: Cord occlusion was successfully accomplished in all cases between 18 and 27 weeks' gestation. There were 2 deaths of the co-twin within 12 hours; 1 death was due to cord hemorrhage, and 1 death was unexplained. One neonatal death occurred after delivery at 27 weeks, and 1 woman with twin-to-twin transfusion syndrome elected termination of pregnancy when hydrocephaly was diagnosed 7 days after the procedure (probably related to the underlying pathologic condition). All other co-twins are alive and well, although 2 pregnancies were complicated by preterm delivery and premature rupture of membranes before 30 weeks' gestation. CONCLUSION: Bipolar diathermy is an effective procedure for cord occlusion, although it still has significant morbidity and mortality rates.

Intravenous glucose infusion in labor does not affect maternal and fetal acid-base balance.

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 conclude that a 5% glucose infusion does not significantly reduce maternal acidemia associated with vaginal delivery and therefore its use cannot be recommended, since maternal glucose is largely available during labor. Intrapartum glucose infusions do not alter the acid-base balance, when the fetus is well oxygenated.

A new approach to prenatal treatment of extralobar pulmonary sequestration.

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.

Fetal hydrops due to a tachyarrhythmia progressing to organic pulmonary stenosis.

We discovered supraventricular tachycardia with advanced hydrops in the setting of normal cardiac anatomy at 26 weeks of gestation which resolved successfully following administration of digoxin and flecainide to the mother. A female baby was born after a premature rupture of the membranes at 30.6 weeks. The neonate was in sinus rhythm, showed a progressive regression of right ventricular insufficiency, but developed signs of acquired pulmonary valvar and subvalvar stenosis at 2 months of age.

Is the angle of needle insertion influencing the created defect in human fetal membranes? Evaluation of the agreement between specialists' opinions and ex vivo observations.

OBJECTIVE: We sought to evaluate the agreement between the opinions of specialists in fetal medicine with ex vivo observations on the potential influence of the angle of needle insertion on the fluid leak through the created defect in human fetal membranes. STUDY DESIGN: Membranes from placentas of women who were delivered by elective cesarean were harvested, cut in pieces, and secured to the bottom of plastic tubes filled with Hartmann solution. They were punctured with 18-, 20-, or 22-gauge needles, with an angle of insertion of 90 degrees (group 1) or 45 degrees (group 2), and the flow rate (in milliliters per minute) through the created defect at a constant pressure of 150 mm H(2)O was measured. Fifty physicians performing amniocentesis at fetal medicine reference centers were interviewed about their impression and clinical attitude with respect to the angle of needle insertion at the time of amniocentesis. RESULTS: In the ex vivo study, puncture with a 45 degrees angle was associated with a significantly lower flow of fluid through the membrane defect for all needle sizes tested. Regarding survey answers, 82% of physicians try to perform amniocentesis with a given angle (ie, 90 degrees in the vast majority of cases). Among the reasons for doing so, minimizing membrane damage was mentioned in more than half of cases. CONCLUSION: These results provide evidence that the angle of needle insertion influences the type of defect and therefore the flow rate through human membranes. Membrane damage is a concern of a proportion of specialists while performing amniocentesis, but ex vivo observations do not agree with clinical assumptions on the potential influence of the angle of insertion.