Ultrasound safety in early pregnancy: reduced energy setting does not compromise obstetric Doppler measurements.

OBJECTIVES: We hypothesized that first-trimester Doppler ultrasonography can be carried out at lower output energies than the currently advocated limits without compromising clinically important information. METHODS: We recruited 42 pregnant women for an ultrasound examination at 12 weeks' gestation. Twenty-one women were examined with a transvaginal transducer, the rest with a transabdominal transducer. We used pulsed Doppler to measure pulsatility index (PI) and peak systolic velocity (PSV) in five clinically relevant fetal and maternal blood vessels. The energy indicator thermal index for bone (TIb) was set at 1.0, 0.5 and 0.1. Each measurement was repeated three times. A mixed linear regression model accounting for correlation between measurements was used to assess the effect of different TIb levels and transducers. RESULTS: We were able to visualize the vessels by color Doppler and measure PI and PSV in all vessels at all energy levels in all the participants with the exception of the ductus venosus in two participants, yielding 1872 recordings for statistical analysis. A reduction in TIb from 1.0 to 0.5 and 0.1 had no effect on the PI or PSV values, nor was there any trend towards higher parameter variance with decreasing TIb. There was no difference between measured values of PI and PSV between the transducers, but the transabdominal technique was associated with a greater parameter variance. CONCLUSION: Reliable first-trimester Doppler data can be obtained with output energy reduced to a TIb of 0.5 or 0.1.

IFPA Meeting 2011 workshop report II: Angiogenic signaling and regulation of fetal endothelial function; placental and fetal circulation and growth; spiral artery remodeling.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

Preterm elective caesarean section and early enteral feeding in gastroschisis.

AIMS: To evaluate the effect of elective caesarean section (CS) before term and early enteral nutrition on length of parenteral nutrition and hospital stay in infants with gastroschisis. METHODS: Retrospective review of all infants with gastroschisis treated in a regional level III hospital from 1993 to 2008. During 1993-97, there was no established standard for management of pregnancy or delivery while a protocol on close foetal monitoring and early elective CS was adhered to for 1998-2008. Introduction of human milk on the first day after complete closure of the abdominal wall and rapid increase was the policy during the whole period. RESULTS: With early elective CS, no foetal deaths occurred after 28-week gestational age (GA). Ten infants were born during the first period and 20 during the second period at a median GA (range) of 36.5 (34-40) and 35 (34-37) weeks (p = 0.013). Seven and 20, respectively, were born by CS. Median (range) days before full enteral feeds and hospital stay were 11.5 (7-39) and 13.0 (7-46) (p = 0.85), and 17.5 (12-36) and 22.5 (13-195) (p = 0.67), respectively. One child died of volvulus after discharge. CONCLUSION: Close surveillance of pregnancy, elective preterm caesarean section, early surgery and active approach to primary closure and early enteral feeds appears to be a safe and effective line of management in gastroschisis.

The left portal vein as an indicator of watershed in the fetal circulation: development during the second half of pregnancy and a suggested method of evaluation.

OBJECTIVES: The left portal vein represents a watershed area in the fetal circulation and the change of flow direction is a suggested marker of circulatory compromise. Our aim was to study the left portal vein of uncompromised human pregnancies and establish reference ranges. METHODS: One hundred and sixty low-risk pregnant women were recruited to a longitudinal study that included four to five Doppler measurements at monthly intervals during the second half of pregnancy. RESULTS: Based on 554 Doppler recordings we found time-averaged maximum flow velocities increasing from a mean of 10.6 cm/s to 14.2 cm/s during 21-31 weeks of gestation, remaining stable until 37 weeks and decreasing towards term. Intermittent flow reversal occurred during fetal respiratory movements, and continuous flow reversal was seen in 2/160 fetuses close to delivery. CONCLUSIONS: We propose time-averaged maximum blood velocity measurement for quantification of the watershed phenomenon in the left portal branch, and have provided reference ranges for single observations and serial measurements.

Hormone replacement therapy, body mass index and asthma in perimenopausal women: a cross sectional survey.

BACKGROUND: Hormone replacement therapy (HRT) and obesity both appear to increase the risk of asthma. A study was undertaken to investigate the association of HRT with asthma and hay fever in a population of perimenopausal women, focusing on a possible interaction with body mass index (BMI). METHODS: A postal questionnaire was sent to population based samples in Denmark, Estonia, Iceland, Norway, and Sweden in 1999-2001, and 8588 women aged 25-54 years responded (77%). Pregnant women, women using oral contraceptives, and women <46 years were excluded. Analyses included 2206 women aged 46-54 years of which 884 were menopausal and 540 used HRT. Stratified analyses by BMI in tertiles were performed. RESULTS: HRT was associated with an increased risk for asthma (OR 1.57 (95% CI 1.07 to 2.30)), wheeze (OR 1.60 (95% CI 1.22 to 2.10)), and hay fever (OR 1.48 (95% CI 1.15 to 1.90)). The associations with asthma and wheeze were significantly stronger among women with BMI in the lower tertile (asthma OR 2.41 (95% CI 1.21 to 4.77); wheeze OR 2.04 (95% CI 1.23 to 3.36)) than in heavier women (asthma: p(interaction) = 0.030; wheeze: p(interaction) = 0.042). Increasing BMI was associated with more asthma (OR 1.08 (95% CI 1.05 to 1.12) per kg/m2). This effect was only found in women not taking HRT (OR 1.10 (95% CI 1.05 to 1.14) per kg/m2); no such association was detected in HRT users (OR 1.00 (95% CI 0.92 to 1.08) per kg/m2) (p(interaction) = 0.046). Menopause was not significantly associated with asthma, wheeze, or hay fever. CONCLUSIONS: In perimenopausal women there is an interaction between HRT and BMI in the effects on asthma. Lean women who were HRT users had as high a risk for asthma as overweight women not taking HRT. It is suggested that HRT and overweight increase the risk of asthma through partly common pathways.

Venous pulsation in the fetal left portal branch: the effect of pulse and flow direction.

OBJECTIVE: To determine whether the waveform in the left portal branch is reciprocal to the waveform found in the ductus venosus and umbilical vein due to difference in pulse direction compared to flow. METHODS: Ten fetuses (gestational age, 18-33 weeks), six with intrauterine growth restriction, three with non-immune hydrops and one with sacrococcygeal teratoma, were examined using ultrasound imaging and pulsed Doppler. Techniques were adjusted to record simultaneously the waveform from neighboring sections of the veins, relate wave components to each other and determine degree of pulsatility. The corresponding vessel diameters were determined. ANOVA with t-test or Wilcoxon signed rank test was used to compare paired measurements. RESULTS: Pulsation in the left portal branch was noted in all fetuses. The pulsatility index was higher than in the umbilical vein (P = 0.005) and the diameter smaller (P = 0.001). In the left portal branch the atrial contraction wave appeared as a velocity peak while there was a nadir during ventricular systole. Simultaneous recordings showed that the waveform was reciprocal to that found in the ductus venosus and umbilical vein. In three cases an augmented pulsatility represented a pendulation of blood in the left portal branch with time-averaged velocity near zero. CONCLUSIONS: The velocity waveform recorded in the left portal vein is an inverse image of that in the ductus venosus, proving that pulse wave and blood flow run in the same direction in the left portal vein. Low compliance (i.e. small diameter) is probably a main reason for the high incidence of pulsation in this vein. Time-averaged velocity near zero recorded in three fetuses indicates that this area acts also as a watershed.

Amniotic gas values and acid-base status during acute maternal hyperoxemia and hypoxemia in the early fetal sheep.

OBJECTIVE: This study was undertaken to determine amniotic fluid gas values and acid-base balance during maternal hyperoxemia and hypoxemia in early pregnancy. STUDY DESIGN: Anesthetized sheep (n = 12) in early and mid pregnancy (0.3 to 0.5 gestation) were subjected to hyperoxemia followed by hypoxemia. Amniotic fluid PO (2), pH, PCO (2), bicarbonate concentration, and base excess were monitored continuously with a multiparameter Paratrend (Diametrics Medical Inc, St Paul, Minn) sensor and compared between 0.3 and 0.5 gestation. RESULTS: During maternal normoxemia all parameters were constant. At all gestational ages maternal hyperoxemia caused no changes apart from a rapid increase in amniotic fluid PO (2) (P <.001). Maternal hypoxemia led to a reduced amniotic fluid PO (2) (P <.001), whereas the PCO (2) and the bicarbonate concentration increased (P <.001). Changes in amniotic fluid gas values and acid-base balance were more pronounced at 0.3 gestation than at 0.5 gestation. Amniotic fluid Po(2) responded earlier to maternal hyperoxemia than to hypoxemia (9. 5 vs 14.3 minutes; P <.001). During hypoxemia maternal PaCO (2) changed faster than did amniotic fluid PCO (2) (P <.001). CONCLUSIONS: Acute maternal hypoxemia during early pregnancy was quickly reflected in amniotic fluid gas values and acid-base balance, whereas hyperoxygenation induced the quickest changes in amniotic fluid PO (2). The metabolic effects of maternal hyperoxemia and hypoxemia were also more pronounced during early pregnancy than at mid pregnancy.

Successful expression of beta-galactosidase and factor IX transgenes in fetal and neonatal sheep after ultrasound-guided percutaneous adenovirus vector administration into the umbilical vein.

In utero somatic gene therapy in the later stages of pregnancy may allow targeting of organ systems which are difficult to reach later in life and to prevent the development of tissue damage otherwise caused by the early onset of inherited diseases. We report here on the percutaneous delivery of two adenoviral vectors, containing the beta-galactosidase reporter gene and the human Factor IX gene respectively, to the fetal liver and circulation by ultrasound-guided umbilical vein puncture similar to procedures used in human pregnancy. Vector spread, as detected by PCR analysis for the beta-galactosidase encoding vector, was found in almost all fetal and neonatal organs and in the maternal liver. Expression of the beta-galactosidase transgene was detected in many fetal tissues by RT-PCR. High beta-galactosidase production was shown by immuno-histochemistry predominantly in the liver, where about 30percent of the hepatocytes stained positive, and in the adrenal cortex. Production of factor IX was determined by ELISA in the plasma of treated fetuses and newborn lambs and reached at birth up to 80percent of the normal human plasma concentration. This demonstrates a very hopeful proof of principle for the development of prenatal treatment of many genetic diseases but also requires more detailed investigations with respect to the observed systemic spread of the vector.

Evaluation of a risk of malignancy index based on serum CA125, ultrasound findings and menopausal status in the pre-operative diagnosis of pelvic masses.

OBJECTIVE: To evaluate the ability of a risk of malignancy index (RMI), based on a serum CA125 level, ultrasound findings and menopausal status, to discriminate a benign from a malignant pelvic mass and to discriminate early stage (Figo Stage I) from Stages II, III and IV of ovarian cancer. DESIGN: A prospective study. SETTING: Department of Gynaecology, Trondheim University Hospital, Trondheim, Norway. PARTICIPANTS: One hundred and seventy-three women, 30 years or older, consecutively admitted between February 1992 and February 1994 for primary laparotomy of a pelvic mass. MAIN OUTCOME MEASURES: The sensitivity, specificity and positive predictive value of serum CA125 level, ultrasound findings and menopausal status, separately and combined into the RMI, to diagnose ovarian cancer. RESULTS: The RMI was more accurate than any individual criterion in diagnosing cancer. Using a RMI cut-off level of 200 to indicate malignancy, the RMI derived from this dataset gave a sensitivity of 80%, specificity of 92% and positive predictive value of 83%. Applying RMI criteria developed by others, the following test performance was found: sensitivity 71%, specificity 96% and positive predictive value 89%. For the Stages II, III and IV of ovarian cancer the sensitivity increased to approximately 90% without any substantial loss in specificity. CONCLUSIONS: The risk of malignancy index is able to correctly discriminate between malignant and benign pelvic masses. It is a scoring system which can be introduced easily into clinical practice to facilitate the selection of patients for primary surgery at an oncological unit.

Lack of evidence of permanent engraftment after in utero fetal stem cell transplantation in congenital hemoglobinopathies.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.

Prenatal diagnosis of osteogenesis imperfecta.

The lethal perinatal types (II A-C) of osteogenesis imperfecta are reported to occur in approximately 1:55000 births. We here present three cases in three unrelated families, diagnosed by antenatal ultrasound within one year. A reliable diagnosis of the lethal perinatal type of osteogenesis imperfecta can be made by ultrasound examination during the second trimester, by identification of fractures of the long bones. The compression of the fetal head by the ultrasound probe and the low echogeneity of the cranium, should raise the suspicion of skeletal dysplasia, but is not diagnostic for osteogenesis imperfecta. The diagnosis is confirmed by postmortem examination including radiography and biochemical studies of cultivated fibroblasts from the fetus. Although rare, this lethal condition should be recognized when an ultrasound examination is performed, to prevent unnecessary obstetric intervention. In families with a previously affected fetus, prenatal diagnosis by first trimester transvaginal ultrasound investigation or chorionic villus sampling should be discussed.

[Preoperative identification of malignancy among women with a pelvic mass. Evaluation of a risk index based on ultrasound findings. CA 125 in serum and menopausal status]. / Preoperativ identifisering av malign tilstand blant kvinner med oppfylning i bekkenet. Evaluering av risikoindeks basert på ultralydfunn, CA 125 i serum og menopausestatus.

A risk of malignancy index (RMI) based on vaginal ultrasound, the tumour marker CA 125 level in serum, and menopausal status was calculated in 134 consecutive patients with a pelvic mass. 41 patients harboured a malignancy, while in 93 the condition was benign. The specificity according to the presence of a malignancy was 95% using the risk of malignancy index, compared with 78% when ultrasound was used alone, and 78% when CA 125 was used alone. The corresponding sensitivities were 73, 71 and 83% respectively. The majority of patients with a false negative index score had early stage ovarian cancer. Only one of the 21 patients with advanced ovarian cancer had a score below the limit of 200. The use of the risk malignancy index is a convenient method for pre-operative identification of cases of advanced ovarian cancer.