Ultrasound-guided umbilical cord occlusion using bipolar diathermy for Stage III/IV twin-twin transfusion syndrome.

OBJECTIVES: To evaluate bipolar diathermy as a technique for selective fetocide in the treatment of advanced (Stage III/IV) twin-twin transfusion syndrome (TTTS). METHODS: A prospective observational study in two tertiary referral fetal medicine centres: Queen Charlotte's Hospital, London, UK and Haemek Hospital, Afula, Israel. Fifteen cases of TTTS (14 twins and one triplet pregnancy) were treated by selective occlusion of either the donor (n=8) or recipient's (n=7) umbilical cord using ultrasound-guided bipolar diathermy. Following each procedure, patients were scanned serially for fetal growth, liquor volume and umbilical Doppler measurements. Procedural complications and obstetric outcome were recorded. Postnatal placental injection studies were performed. RESULTS: Overall co-twin survival in Stage III/IV TTTS was 13/14 (93%). There were no treatment failures. The incidence of preterm prelabour rupture of membranes (PPROM) within 3 weeks of the procedure was 3/15 (20%). In those cases where pre-procedure umbilical artery Dopplers were abnormal, the Doppler findings normalised post-procedure in all non-cord-occluded fetuses. Growth velocities of surviving donors were similar to those of surviving recipients. CONCLUSIONS: Bipolar diathermy appears an effective technique for the selective reduction of monochorionic twins complicated by severe as well as preterminal TTTS, with recipient and donor fetuses being equally appropriate choices for fetocide. We suggest that for advanced-stage disease where the parents can contemplate this option, cord occlusion as a single preemptive procedure maximises the opportunity for intact survival of a single survivor.

Transvaginal sonography for fetal crown-rump length measurement in a Thai population.

A prospective descriptive cross-sectional study was undertaken at the Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University to establish a reference interval for fetal crown-rump length (CRL) in a Thai population using transvaginal ultrasound. This study was performed on normal pregnant women registered at the antenatal clinic in their first trimester. All had a good menstrual history. CRL measurement was obtained by a 5 MHz vaginal probe. All of the newborns were proved to be normal at birth. We constructed and compared CRL (mm) relating to gestational age (GA) (days). Five hundred and forty seven cases were enrolled into the study. CRL was correlated with gestational age. The best fit regression equation was the quadratic model: CRL (mm) = -13.872 - 0.014 GA (day) + 0.0097 GA (day)2, R = 0.92, p < 0.0001). Centiles and a chart for CRL derived from the regression equation are presented. In conclusion, a reference interval for fetal crown-rump length in a Thai population has been established. This data may be useful in the early detection of genetic or environmental disorders affecting fetal growth in the first trimester of pregnancy.

Evaluation of fetal femur length to detect Down syndrome in a Thai population.

OBJECTIVE: To assess the value of femur length shortening for prenatal detection of Down syndrome in a Thai population. METHOD: A prospective study was performed by experienced perinatologists on 3137 women undergoing second-trimester amniocentesis, between 16 and 24 weeks of gestation, for the indications of advanced maternal age and past history of chromosomal abnormality. Biparietal diameter and femur length measurements were obtained before the procedures. Regression equations relating biparietal diameter to femur length were used to calculate observed femur length/expected femur length ratio in the chromosomally normal and Down syndrome fetuses. Sensitivity, specificity, false-positive rate and likelihood ratio of a positive test result at various observed femur length/expected femur length ratios for detection of Down syndrome were calculated. A receiver-operator characteristic curve was used to determine threshold screening ratio. RESULTS: There were 3084 chromosomally normal pregnancies, 26 fetuses with Down syndrome (1:118), and 27 other chromosomal abnormalities. The relationship between femur length and biparietal diameter (BPD) was: expected femur length=-7.631+0.814 BPD, R(2)=0.78, P<0.001). Femur length in Down syndrome fetuses was significantly shorter than in normal fetuses (P<0.001). A ratio of 0.91 for observed femur length/expected femur length yielded a sensitivity of 42.3%, specificity of 86.2%, false positive rate of 13.8% and likelihood ratio of a positive test result of 3.07 (95% CI 1.94-4.84) for detection of Down syndrome. CONCLUSIONS: In this study, femur length shortening in the second trimester appears to be a useful screening parameter for fetal Down syndrome in a Thai population.

Intrauterine rescue transfusion in monochorionic multiple pregnancies with recent single intrauterine death.

To assess the role of fetal blood sampling and intrauterine transfusion in monochorionic (MC) multiple pregnancy complicated by single intrauterine death (IUD), we reviewed ten cases over a 4-year period in a tertiary referral centre which underwent fetal blood sampling within 24 h of death of its MC co-twin. Intrauterine rescue transfusion was performed in all seven anaemic fetuses (hematocrit; Hct < 30%) to raise the fetal Hct to > or = 40%. The rationale was to prevent death and/or brain injury. Two fetuses, which were severely acidaemic at blood sampling, died in utero within 24 h of the procedure. In two cases, the surviving twins manifested abnormal sonographic findings of the fetal brain 2-5 weeks later and underwent late termination. In two cases, the pregnancies continued uneventfully until delivery at 35 and 40 weeks' gestation with good neonatal outcome. In one case the co-twin delivered 1 week later at 29 weeks but died within 12 h. Fetuses without anaemia were not transfused and had normal clinical outcomes. We suggest that intrauterine rescue transfusion before the development of severe acidaemia in anaemic surviving MC co-twins may prevent fetal death, but does not necessarily prevent brain injury. Until its role becomes clearer, we recommend that its use be restricted to situations in which the parents and the local jurisdiction allow late termination as an option if brain injury subsequently manifests on ultrasound.

Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application.

The accuracy of in-vivo detection of arterio-arterial anastomoses (AAA) in monochorionic (MC) twins and its predictive value for twin-twin transfusion syndrome (TTTS) was assessed in 105 consecutive MC twins scanned at fortnightly intervals. AAA were sought using spectral and colour energy Doppler and ultrasound findings were compared with placental injection studies. AAA were identified in vivo in 59 (56%) pregnancies and at injection study in 68 (65%). The overall sensitivity and specificity was 85 and 97.3% respectively for the detection of AAA. Detection rates were higher at later gestations, with anterior placentae and with larger diameter AAA. The median insonation time to detect an AAA was 10 min (range 1-30). Where an AAA was identified, 15% of pregnancies (nine of 59) developed TTTS compared to 61% (28 of 46) when no AAA was seen (odds ratio 8.6). We conclude that AAA can be detected in vivo with high sensitivity and specificity without undue prolongation of scanning times and have a role in risk stratification in the antenatal assessment of MC twins.

Parvovirus B19 DNA in kidney tissue of patients with focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) represents a clinicopathological syndrome with diverse causes. We examined the possibility that some cases of FSGS are associated with parvovirus B19 infection. We studied renal biopsy tissue from 40 patients, including those with idiopathic FSGS, collapsing FSGS, membranous nephropathy, and minimal change disease, as well as normal renal tissue removed at the time of nephrectomy from 4 patients. DNA was extracted from frozen blocks of kidney tissue and amplified using nested polymerase chain reaction. Parvovirus B19 DNA was amplified from 8 of 10 patients with idiopathic FSGS, 9 of 10 patients with collapsing FSGS, 6 of 10 patients with membranous nephropathy, 5 of 10 patients with minimal change disease, and 2 of 4 cancer nephrectomy samples. The prevalence of parvovirus B19 DNA was greater among patients with idiopathic FSGS and collapsing FSGS compared with patients with other diagnoses (P = 0.05). In situ hybridization studies using digoxigenin-labeled DNA probes failed to detect parvovirus B19 nucleic acid in any of the kidney tissue samples. These results suggest that parvovirus B19 DNA is commonly found in the kidneys of patients with a range of renal diagnoses, possibly representing latent DNA from past infection. The failure to localize parvovirus B19 nucleic acid within kidney argues against ongoing, high-level viral replication. Nevertheless, the increased prevalence of B19 DNA in patients with idiopathic FSGS and collapsing FSGS could indicate a pathogenic role for the virus in the cause of FSGS in certain patients.

Uterine blood flow response to hormonal replacement therapy in asymptomatic postmenopausal women: a transvaginal Doppler study.

To evaluate the effect of continuous hormonal replacement therapy (HRT) on Doppler parameters of uterine blood flow in asymptomatic postmenopausal women. Thirty-eight asymptomatic postmenopausal women were recruited into the study from the outpatient menopause clinic, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University. The study population was divided into 20 cases without any HRT (group 1) and 18 cases using continuous conjugated equine estrogen 0.625 mg/day combined with medroxyprogesterone acetate 2.5 mg/day (group 2). The duration of HRT was 21.3 +/- 9.5 (13-56) months. A transvaginal colour flow imaging system (ALOKA SSD-2000 MultiView, Tokyo, Japan) was used to assess uterine blood flow. Quantitative data from areas of colour were evaluated by pulsed Doppler spectrum analysis. Resistance indices (RI) were measured as indicators of uterine perfusion. Both groups were statistically similar with respect to age, parity, age at menopause, height and weight. The endometrial thickness in group 1 and 2 were 3.8 +/- 0.8 and 4.1 +/- 0.6 millimetres, respectively. The left uterine artery RIs of group 1 and 2 were 0.86 +/- 0.08 and 0.84 +/- 0.07, respectively (p = 0.33). The right uterine artery RIs of group 1 and 2 were 0.87 +/- 0.07 and 0.83 +/- 0.06, respectively (p = 0.06). In conclusion, continuous HRT had a non-significant influence on uterine blood flow in the postmenopausal women.

Transvaginal hysterosalpingo-contrast sonography (HyCoSy) compared with chromolaparoscopy.

OBJECTIVE: To compare the efficacy and safety of HyCoSy with chromolaparoscopy for the diagnosis of tubal occlusion and uterine abnormalities. METHODS: Sixty infertile women in whom the cause of infertility was thought to be tubal occlusion or uterine abnormalities and who satisfied the inclusion and exclusion criteria as specified in the study protocol were included. HyCoSy was performed during the first half of the menstrual cycle at least 24 hours prior to chromolaparoscopy. The results from both HyCoSy and chromolaparoscopy were compared in assessing tubal occlusion and uterine pathology. RESULTS: For the evaluation of fallopian tubes, we found corresponding results between HyCoSy and chromolaparoscopy in 80.0%. The agreement between both procedures in assessing the uterine pathology was 80.4%. Twenty-two women experienced adverse events. The most common complaint was pelvic pain. Other events encountered were: nausea (3 women) and vaginal bleeding (2 women). All events were thought to be not related to the study drug. CONCLUSION: HyCoSy showed good diagnostic performance in the evaluation of the fallopian tubes and uterus in infertile women. The adverse events reported in this study are minor and procedure-related (catheter insertion) rather than the trial substance.

Reference intervals for first trimester embryonic/fetal heart rate in a Thai population.

OBJECTIVE: To establish reference intervals for first trimester embryonic/fetal heart rate in a Thai population. METHODS: A prospective descriptive cross-sectional study was performed on normal pregnant women registered at the antenatal clinic in their first trimester. All had a good menstrual history and the calculated gestational age using crown-rump length (CRL) in the first trimester ultrasound was in agreement. Crown-rump length and embryonic/fetal heart rate measurements were obtained by a 5 MHz vaginal probe combined with a duplex color Doppler machine. All of the newborns were proved to be normal at birth. We constructed and compared embryonic/fetal heart rate expressed as beats/min relating to gestational age (GA) (days) and CRL. The data was analyzed and the best fit mathematical model was derived using the SPSS computer program. RESULTS: 547 cases were enrolled into the study. The median embryonic/fetal heart rate increased from 124 beats/min at GA of 40-44 days to 177 beats/min at GA 60-64 days, thereafter, embryonic/fetal heart rate gradually decreased to 159 beats/min at GA 95-99 days. The best fit regression equation was: embryonic/fetal heart rate (beats/min) = -21.666 + 5.4796 GA (day) - 0.0383 GA (day)2, R = 0.5, p < 0.0001). In addition, embryonic/fetal heart rate also correlated with CRL. The median embryonic/fetal heart rate increased from 131 beats/min at CRL of 5-9 mm to 177 beats/min at CRL 20-34 mm, thereafter, embryonic/fetal heart rate gradually decreased to 155 beats/min at CRL 75-79 mm. The best fit regression equation was: embryonic/fetal heart rate (beats/min) = 127.361 + 3.4939 CRL (mm) - 0.0749 CRL (mm)2 + 0.0004 CRL (mm)3, R = 0.58, p < 0.0001). CONCLUSION: Reference intervals for first trimester embryonic/fetal heart rate in a Thai population were established. Our reference intervals may be useful for further studies, such as the prediction of spontaneous abortion or chromosomal disorders after ultrasound-proven viability in the first trimester.

Fetal hematology.

The objective of this study was to establish normal fetal hematological parameters throughout gestation. Samples of pure fetal blood from 35 fetuses of 21-38 weeks' gestation were obtained by fetal blood sampling under continuous ultrasound guidance. The hematological parameters were determined with automated cell counter within 30 minutes after the procedures. Fetal red blood cell and granulocyte counts rose significantly with advancing gestation, whereas, the mean corpuscular volume fell. There were no significant changes in fetal hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cell distribution width, total white blood cell count, lymphocyte count, mid-cell count, platelet count, mean platelet volume, and platelet distribution width with increasing gestation. The growing application of fetal blood sampling to the prenatal diagnosis renders mandatory a knowledge of normal fetal blood values. These results may provide useful reference values for prenatal diagnoses of hematological disorders.

Cut-off criteria for second-trimester nuchal skinfold thickness for prenatal detection of Down syndrome in a Thai population.

OBJECTIVE: To evaluate the use of progressive cut-offs for nuchal skinfold thickness with advancing gestational age and the commonly applied cut-off method (> 6 mm) for prenatal detection of Down syndrome in a Thai population. METHOD: A prospective study was performed by experienced perinatologists on 2150 women undergoing second-trimester amniocentesis for the indications of advanced maternal age and past history of chromosomal abnormality. Reference ranges were established for nuchal skinfold thickness from the 16th to the 24th week, using either gestational-specific centiles or the parametric method. Assaying different cut-off criteria for both centile and the parametric methods were calculated and then compared with the commonly applied cut-off level (> or = 6 mm.). RESULTS: There were 2114 chromosomally normal pregnancies, 19 fetuses with Down syndrome (1:113), and 17 other chromosome abnormalities. In fetuses with normal karyotype the nuchal skinfold thickness increased with advancing gestational age [NF (mm) = -0.502 + 0.212 GA (week), r = 0.36, P < 0.001]. The sensitivities of an abnormal nuchal skinfold thickness using different cut-off criteria for detecting Down syndrome were low (5.3-26.3%) with the false positive rates ranging from 2.5 to 16.5%. CONCLUSIONS: In this study, measurement of second-trimester nuchal skinfold thickness was a poor and unreliable screening test for fetal Down syndrome in a Thai population.

Transvaginal hysterosalpingo-contrast sonography (HyCoSy) compared with chromolaparoscopy: a preliminary report.

Fifteen infertile women who required tubal passage evaluation by chromolaparoscopy were recruited. Those who had lower genital tract infection or abnormal uterine bleeding were excluded from the study. Transvaginal HyCoSy was performed during the first half of the menstrual cycle at least 24 hours prior to chromolaparoscopy. The results from both transvaginal HyCoSy and chromolaparoscopy were compared in assessing tubal patency and uterine pathology. A high correlation was noted regarding uterine examination using transvaginal HyCoSy compared with chromolaparoscopy (sensitivity, specificity, PPV and NPV were 91.7%, 33.3%, 84.6% and 50%, respectively). The correlation of the outcome between the two procedures in assessing tubal patency, when combining both tubes, was also high (sensitivity, specificity, PPV and NPV were 100%, 55.6%, 80% and 100%, respectively). The most common adverse event was only mild pelvic pain which did not necessitate any treatment. These preliminary results reveal the potential value of transvaginal HyCoSy as an alternative in infertility investigations. It seems to be as effective but less invasive than conventional chromolaparoscopy. The adverse events reported in this study relate more to the procedure (catheter insertion) rather than the trial substance.

Intrauterine therapy of fetal atrial flutter.

An increased awareness of fetal arrhythmias by obstetricians has resulted in a growing number of diagnosed cases of fetal cardiac problems. A fetus with atrial flutter diagnosed at 31 weeks of gestation was successfully converted to normal sinus rhythm in utero by maternal administration with digitalis. The fetal heart rate stayed in a normal rhythm with a maintenance dose of 0.5 mg/day. The fetus was delivered spontaneously at term and the neonatal heart rate has been in normal rhythm without any medical treatment.

Nomogram of nuchal fold thickness of Thai fetuses.

The aim of the study was to establish normal values of nuchal fold thickness during 14-21 weeks of pregnancy. Three hundred Thai pregnant women before 12 weeks of gestation were recruited. Gestational age was determined by last menstrual period and confirmed by crown-rump length. Subjects with date-size discrepancy of more than 7 days were excluded from the study. Nuchal fold thickness was measured twice, first during 14-17 weeks, and then during 18-21 weeks. Five hundred and nine measurements were obtained. Nomogram of nuchal fold thickness was constructed. Mean values of nuchal fold thickness increased steadily from 2.59 +/- 0.77 millimeters (mm) at 14 weeks to 4.12 +/- 0.98 mm at 21 weeks. Average rate of increase were 0.22 mm per week. In conclusion, nuchal fold thickness increased with advancing gestational age from 14 to 21 weeks of pregnancy. Different normal cut-off levels for each gestational week may be more appropriate for screening of fetal Down syndrome in Thai pregnant women.

Dengue hemorrhagic fever during pregnancy: antepartum, intrapartum and postpartum management.

Dengue hemorrhagic fever is a common tropical disease in Thailand that nowadays has an increasing incidence during adulthood. We managed three cases of dengue hemorrhagic fever during pregnancy which developed during the antepartum, intrapartum and postpartum periods. We diagnosed dengue hemorrhagic fever during pregnancy with clinical pictures of fever, hemoconcentration and thrombocytopenia with serological proof in all cases. All cases were treated conservatively except for the second one, in which cesarean delivery was inevitable due to severe preeclampsia with unfavorable cervix. All patients and their babies were in good condition before discharge. With increasing incidence during adulthood, more cases of dengue hemorrhagic fever in pregnancy can be found. Conservative treatment should be conducted in all cases. We believe that this is the first case report of intrapartum dengue hemorrhagic fever during pregnancy.

The canine sodium/myo-inositol cotransporter gene: structural organization and characterization of the promoter.

The sodium/myo-inositol cotransporter (SMIT) is a plasma membrane protein catalyzing transfer of myo-inositol into cells against a considerable concentration gradient using the electrochemical potential of sodium across the cell membrane. Transcription of the SMIT gene is markedly stimulated when cells are exposed to a hypertonic environment resulting in increased abundance of SMIT mRNA and increased SMIT activity. The increased accumulation of myo-inositol protects cells from the deleterious effects of hypertonicity. In an effort toward understanding transcriptional regulation, we cloned canine genomic DNA fragments containing the SMIT gene. The gene is 37 kb in size consisting of 2 exons and a large intron of 25 kb. The entire open reading frame is in the second exon. The promoter of the gene is highly active due to a GC-rich sequence. Ribonuclease protection assay using a riboprobe complementary to the 5' end of the gene confirmed that the promoter of the gene is stimulated by hypertonicity. The promoters and regulatory sequences of the SMIT gene and the betaine transporter gene, another gene regulated by hypertonicity, appear to be different.

Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy.

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.