R. M. Santana

Reversible constriction of the fetal ductus arteriosus after maternal use of topical diclofenac and methyl salicylate

A 33-year-old physician in her second pregnancy underwent fetal echocardiography at 35 weeks’ gestation. She decided to present at this late gestational age due to anxiety. Cardiac anatomy was normal, as were color Doppler velocimetry assessments of the foramen ovale, mitral valve, pulmonary artery and aortic arch. Slight tricuspid regurgitation was observed (Figure 1) and systolic and diastolic ductal velocities were 2.2 m/s and 0.42 m/s, respectively (Figure 2), indicating ductal constriction (normal values being < 1.40 m/s and 0.35 m/s). The patient did not smoke, had no history of preterm labor requiring prostaglandin inhibitors or steroids and denied use of any medication throughout her pregnancy. However, she did mention that for the last two nights, due to severe musculoskeletal pain, she had been massaging her shoulders and neck with a diclofenac gel (Cataflam Emulgel @ Novartis, São Paulo, Brazil). After rubbing in the gel she covered the painful area overnight with an adhesive patch containing methyl salicylate, l-menthol and dl-camphor (Salonpas @ Hisamitsu, São Paulo, Brazil). On the second night she repeated both topical treatments and also took a 50-mg tablet of tramadol (Tramal @ Searle, São Paulo, Brazil), a centrally acting synthetic analgesic, analogous to codeine. All medication was self-prescribed and purchased by the patient, without the knowledge of her obstetrician. She was advised to discontinue all medication and return within a week. Five days later repeat echocardiography (Figure 3) revealed normal ductal velocities (systolic, 1.1 m/s; diastolic, 0.27 m/s). An uneventful delivery occurred 1 month later and, after a neonatal echocardiogram showed no abnormalities, the infant was discharged on the 3rd day. The fetal ductus arteriosus is patent throughout gestation due to low oxygen tension and circulating prostaglandins. This patency allows the majority of right ventricular output to bypass the high-resistance pulmonary vessels. Rare cases of spontaneous ductus arteriosus constriction have been reported and some have been attributed to an anatomical distortion of the ductal arch2. More frequently, ductal constriction is caused by maternal use of non-steroidal anti-inflammatory drugs (NSAIDs) that enter the fetal circulation, block cyclooxygenase enzymes and inhibit prostaglandin synthesis. Fetuses become more susceptible to NSAIDs with advancing gestational age. Individual susceptibility also influences fetal response. Demandt et al.3 reported a case in which only one twin developed ductal constriction after maternal exposure to indomethacin. Although specific Figure 1 Echocardiography at 35 weeks’ gestation revealed slight tricuspid regurgitation (TR). RA, right atrium; RV, right ventricle.

Valor preditivo do resultado fetal da dopplervelocimetria de ducto venoso entre a 11ª e a 14ª semanas de gestação

PURPOSE: to study the value of Doppler velocimetry of the ductus venosus, between the 11th and 14th weeks of pregnancy, associated to the nuchal translucency thickness measurement, in the detection of adverse fetal outcome. METHODS: a transversal and prospective study in which a total of 1,268 fetuses were studied consecutively. In 56 cases, a cytogenetic study was performed on material obtained from a biopsy of the chorionic villus and, in 1,181 cases, the postnatal phenotype was used as a basis for the result. In addition to the routine ultrasonographic examination, all the fetuses were submitted to measurement of the nuchal translucency thickness and to Doppler velocimetry of the ductus venosus. Aiming at prevalence and accuracy indices, sensitivity, specificity, positive predictive value, negative predictive value, probability of false-positive, probability of false-negative, reason of positive probability and reason of negative probability were calculated and analyzed. RESULTS: from the total of 1,268 fetuses, 1,183 cases were selected for analysis. From this number, 1,170 fetuses were normal (98.9%) and 13 fetuses presented adverse outcome at birth (1.1%), including fetal death (trisomy 21 and 22) in two cases; genetic syndrome (Nooman) in one case; two cases of polymalformed fetuses; cardiopathy in three cases; and other structural defects in five cases. The prevalence of the modified ductus venosus (wave A zero/reverse) in the studied population was of 14 cases (1.2%), with a false-positive rate of 0.7%. CONCLUSIONS: there is a significant correlation between the alteration of the ductus venosus Doppler velocimetry and the thickness of the nuchal translucency as an ultrasonographic marker for the first trimester of gestation, in the detection of adverse fetal outcome, especially serious malformations. The ductus venosus was able to diminish the false-positive result in comparison to the isolated use of the nuchal translucency thickness, improving considerably the positive predictive value of the test.

Índices veno-arteriais para predição da acidemia fetal ao nascimento em gestações com insuficiência placentária

OBJECTIVE: to investigate whether it is possible to predict acidemia at birth in pregnancies with placental insufficiency using venous-arterial indices: pulsatility index for vein (PIV) of the ductus venosus (DV) over PI of the middle cerebral artery (MCA) and PIV of the DV over PI of the umbilical artery, and establish cut-off values for this prediction. PATIENTS AND METHODS: this was a prospective cross-sectional study involving forty-seven patients with placental insufficiency (umbilical artery resistance and pulsatility indices above the 95th percentile for gestational age) who were submitted to Dopplervelocimetry in the last 24 hours before delivery. All pregnancies were singleton, over 26 weeks of age and without structural or chromosome anomalies. Arterial cord blood was obtained for gasometry immediately after birth. Acidemia was defined as umbilical arterial pH < 7.20 in the absence of uterine contractions and pH < 7.15 in the presence of contractions. Metabolic or mixed acidemia at birth were considered pathological. A ROC curve was calculated for the venous-arterial indices: PIV DV/PI umbilical artery (UA) and PIV DV/PI MCA. A cut-off value was established and sensitivity, specificity, accuracy, positive and negative predictive values and positive and negative likelihood ratios were calculated. RESULTS: The DV/UA PI index was not a good predictor of acidemia at birth. The DV/MCA PI index was related to acidemia at birth (area under the curve 0,785, p = 0,004). The cut-off value was: 0,582, sensitivity 66,7%, specificity 77,1 and accuracy 74,5%. CONCLUSION: the PIV DV/PI MCA ratio is adequate for predicting acidemia at birth in pregnancies with placental insufficiency. The cut-off value was: 0,582.

Prediction of acidemia at birth by Doppler assessment of fetal cerebral transverse sinus in pregnancies with placental insufficiency.

To evaluate the prediction of acidemia at birth using cerebral transverse sinus (CTS) Doppler velocimetry and to determine the best parameter and cut‐off values for its prediction in pregnancies complicated with placental insufficiency.

P02.32: Spinal muscular atrophy and increased nuchal translucency—case report

congenital contractural syndrome type 2 (LCCS2) (OMIM 607598) which is also associated with renal and cardiac malformations. A genome-wide linkage analysis, demonstrating linkage to approximately 6 cM homozygosity region on chromosome 12q13 between markers D12S1604 and D12S83, was found. Therefore, early genetic detection of this syndrome is possible. However, many patients known to be carriers of this genes deny an invasive procedure and in others this genetic diagnosis is not found. Thus, sonographic detection may be the sole tool for early detection of this abnormality. The sonographic appearance of LCCS2 in our area may appear late in second trimester and early sonographic diagnosis may be important in counseling these patients, Lately, we have sonographically diagnosed 3 patients in the fetal malformation clinic at 13–14 weeks gestation. The main sonographic symptom was myoclonic jerks of hands and feet of these fetuses. Hands were flexed in the elbow joints and the jerks were from the shoulder girdle. Jerks were from the hip joint. At that time no joint contractures were apparent. These appeared only at 17 weeks gestation. In summary, tonic myoclonic jerks are demonstrated sonographically and can be an early neurologic sign for hypokynesia/akinesia syndrome. Future sonographic observations in first trimester should be offerred to high risk patients prone to neurological accidents and congenital malformations.

O tratamento da insuficiência istmocervical com protrusão de membranas

Nas gestantes com insuficiencia istmocervical (IIC) nas quais ja houve cervicodilatacao e prolabamento das membranas existe dificuldade tecnica para realizar-se a circlagem para conseguir o prolongamento da gravidez ate que haja maturidade fetal suficiente para garantir a sobrevida do concepto. Descrevemos um caso de IIC com prolabamento de membranas na 21a semana, em que se realizou a diminuicao da pressao intra-uterina por amniocentese com drenagem de liquido amniotico ate a reintroducao das membranas para o interior da cavidade uterina, o que permitiu a tracao dos labios do colo e a realizacao da circlagem com menor trauma mecânico. Esta medida proporcionou a evolucao da gravidez por 12 semanas e a sobrevida do concepto.

Ductus venosus versus cerebral transverse sinus Doppler velocimetry for predicting acidemia at birth in pregnancies complicated by placental insufficiency.

The objectives of this study is to compare ductus venosus (DV) and cerebral transverse sinus (CTS) Doppler velocimetry for predicting acidemia at birth in pregnancies complicated by placental insufficiency.

P01.03: Reproducibility of the fetal nasal bone length measurement

Objective: To determine the effect of first-trimester screening on the amniocentesis rate and the detection rate of fetal aneuploidy in a high risk population. Methods: We began to offer first-trimester screening (nuchal translucency, PAPP-A, and free beta HCG) to women at increased risk for fetal aneuploidy (mainly age 35 or older) in March 2002. We retrospectively reviewed the prenatal records of women who registered to deliver at Massachusetts General Hospital and who underwent a genetic amniocentesis during two time periods: prior to, and subsequent to, offering first-trimester screening. We also reviewed the cytogenetics database to identify all cases of fetal aneuploidy during the two time periods. Results: Data were collected over 13 months from each time period. The number of deliveries were similar (3174 and 3505 in calendar years 2000 and 2003, respectively) as were both the mean (30.1 and 31.0) and median (30.8 and 31.7) maternal age. There were 531 amniocenteses in the earlier period and 344 in the later period, a 35% decrease. Detection rate for fetal aneuploidy was 14/15 in the earlier period and 16/20 in the later period. The single undetected case in the earlier period was trisomy 21 in a 36 year-old woman who was not screened. In the later period there were 3 undetected cases trisomy 21, all to women who declined amniocentesis despite age > 35 and either increased risk on second-trimester serum screen (1 case) or abnormal findings on second-trimester ultrasound (2 cases). There was also a case of Turner’s syndrome in a 40 year-old woman who had a negative second-trimester serum screen. In the later period 5 cases of fetal aneuploidy were detected based on abnormal findings at first-trimester screening. Conclusions: The institution of first-trimester screening was associated with a 35% reduction in the amniocentesis rate without a demonstrable decrease in the detection rate of fetal aneuploidy.

Valores dos parâmetros da dopplerfluxometria do ducto venoso entre a 10ª e a 14ª semana de gestações normais

PURPOSE: to analyze the values of Doppler ultrasound for blood flow velocity in the ductus venosus between the 10th and the 14th week of gestation, during the different phases of the cardiac cycle: ventricular systole (wave S), ventricular diastole (wave D), atrial systole (wave a), and angle-independent indexes. METHODS: Doppler was used in this prospective cross-sectional study to examine 276 single pregnancies. Fetus malformations, abnormal nuchal translucency, and women with clinical pathologies were excluded. A Toshiba SSH-140 ultrasound equipment was used. The derivation of Doppler frequency spectra was carried out according to standardized measurement procedures: less than 30oinsonation angle and 50-70 Hz high-pass filter. The ductus venosus was identified in a median sagittal and ventral plane with the presence of color aliasing due to increase in blood flow velocity. The sample volume (1-2 mm3) was placed immediately at the origin of the ductus venosus. At least three clearly and subsequent waves were available for measurement of standard values. The Levene test and the Bonferroni method were used for statistical analysis. RESULTS: increase in blood flow velocity from 29 cm/s to 37 cm/s (p=0.013) was observed during ventricular systole between the 10th and the 14th week of gestation. Similarly, increase in blood flow velocity was recorded during the ventricular diastole (from 25 cm/s to 32 cm/s, p=0.026). There were no changes in wave a, pulsatility index, and S/a ratio in this period. CONCLUSION: the reference ranges established by this study may serve as the basis for Doppler ultrasound follow-up in a normal patient population. Further studies are required to determine the validity of these parameters and, in particular, for the fetus at risk.

OP12.03: Fetal cardiac ventricle volumetry in the second half of gestation assessed by 4D ultrasound using STIC

Objectives: To evaluate the significance of changes in umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) in fetuses with congenital heart disease (CHD) of septal defect. Methods: Umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were retrospectively analyzed in 82 fetuses with CHD, including 25 cases of ECD, 51 cases of VSD and 6 cases of ASD. The control group comprised 660 healthy gestational agematched fetuses. Individual PI measurements were converted into Z-scores for statistical analysis. Results: When compared to controls, fetuses with ECD, VSD and all CHD had an increased UA-PI (P < 0.05), but fetuses with ASD have no significant difference (P > 0.05). There was no significant difference in the MCA-PI between fetuses with ECD, VSD, ASD, all CHD and controls (P > 0.05). Conclusions: Fetuses with CHD of septal defect might have an increased UA-PI, without remarkable change in MCA-PI.