Fetal middle cerebral artery Doppler to time intrauterine transfusion in red-cell alloimmunization: a randomized trial.

OBJECTIVES: To evaluate whether Doppler measurement of middle cerebral artery peak systolic velocity (MCA-PSV) for timing subsequent intrauterine transfusions (IUTs) in fetuses that had undergone one IUT for anemia secondary to red-cell alloimmunization is non-inferior to timing based on expected decrease in fetal hematocrit (Hct) or fetal hemoglobin level, without compromising infant hemoglobin at birth. METHODS: This was an international, pragmatic multicenter randomized controlled trial. Women with a pregnancy complicated by fetal anemia secondary to red-cell alloimmunization (due to any antibody alone or in combination), as indicated by the need to undergo a single IUT, were eligible for inclusion. Women were randomized to the determination of timing of further transfusion(s) by Doppler measurement of MCA-PSV (MCA-PSV Group), with a serial upward trend of values >1.5 multiples of the median considered indicative of the need for another IUT, or timing of transfusion by a decrease in fetal Hct (fetal Hct Group), with subsequent IUTs timed according to an estimated fall in fetal Hct of 1% per day or fetal hemoglobin of 0.3 g/dL per day, to maintain fetal hemoglobin level between 7 and 10 g/dL. The primary outcome was infant hemoglobin level measured at birth. RESULTS: A total of 71 women were randomized, 36 to the MCA-PSV Group and 35 to the fetal Hct Group. Median gestational age at randomization was 30.3 weeks, the majority of women were Caucasian and non-smokers, 9.9% of women had Kell alloimmunization, and 14% of fetuses were hydropic at their first IUT. No statistically significant differences between the two treatment groups were observed with regard to mean hemoglobin levels at birth (MCA-PSV Group, 10.36 ± 3.82 g/dL vs fetal Hct Group, 12.03 ± 3.14 g/dL; adjusted mean difference -1.56 g/dL (95% CI, -3.24 to 0.13 g/dL); P = 0.070), or the number of IUTs performed after randomization (MCA-PSV Group, 1.75 ± 1.79 vs fetal Hct Group 1.80 ± 1.32; adjusted relative risk 0.88 (95% CI, 0.61-1.26); P = 0.474). There was no statistically significant difference between the two groups with respect to the risk of adverse infant outcomes related to alloimmunization or procedure-related complications. CONCLUSION: Both Doppler measurement of MCA-PSV and estimation of the decrease in fetal Hct or hemoglobin can be used to determine the timing of second and subsequent IUTs in fetuses with red-cell alloimmunization. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose-finding pilot study.

The antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache).

Noninvasive ambulatory blood pressure control in normotensive pregnant women.

Twenty-four hour noninvasive, automatic and ambulatory control of blood pressure (BP) was carried out on 11 normotensive pregnant women in the third trimester of pregnancy with a Del Mar Avionics Model 1978 Pressurometer III System at 7.5 min intervals during 24 h. The patients kept a detailed record of their activities during those 24 h. BP increased from 9 AM to a peak between 7 and 10 PM. Mean (+/- SD) waking and sleeping values were 110.56 +/- 6.68 mm Hg and 96.5 +/- 10.01 mm Hg, respectively, for systolic BP, and 71.41 +/- 5.35 mm Hg and 62.82 +/- 5.47 mm Hg, respectively, for diastolic BP. There was a significant difference in systolic and diastolic BP between sleeping hours and waking hours. We believe that 24-h control of BP behavior in normotensive pregnant women allows us to adequately diagnose hypertensive disease in pregnancy.

Behavior of diluted activated partial thromboplastin time in pregnant women with a lupus anticoagulant.

The present study was developed to verify whether a reduction in phospholipid concentration could increase the activated partial thromboplastin time (APTT) sensitivity to detect lupus anticoagulant (LA) during pregnancy. The authors studied 38 pregnant women (10 normal subjects and 28 patients with associated clinical complications) and 40 nonpregnant control subjects. Tests to detect LA, including APTT, platelet neutralization procedure (standard APTT), the kaolin clotting time, the diluted Russell viper venom test neutralized by lysed platelets, and factor assays, were performed. Positive results were found in 5 of 28 pregnant women with associated clinical complications. The APTT, using three different phospholipid concentrations (standard and more diluted cephalin), was performed on plasma samples and on its 1:1 mixture with normal plasma. The behavior of standard and diluted APTT was similar in negative LA pregnant women and nonpregnant control subjects. The mean values showed nonsignificant differences. Four of five pregnant women with positive LA findings had a prolonged APTT, which was not corrected by the addition of normal plasma using standard conditions. When diluted phospholipids were used, only one of them had a prolonged APTT that was corrected by the addition of normal plasma. Therefore, the highest sensitivity (80%) and specificity (100%) of the APTT to detect LA in pregnant women were obtained using the standard conditions.

High-dose intravenous IgG for the treatment of severe rhesus alloimmunization.

The value of intravenous immunoglobulin (IVIG) in the treatment of 24 severely Rh-sensitized pregnant women was studied. IVIG was infused at a daily dose of 0.4 g/kg maternal body weight for 4-5 consecutive days, and was administered again 15-21 days later until delivery, depending on the evolution of the hemolytic disease. Our population was divided into 3 groups according to the time of onset of therapy: group 1 (n = 8), before 20 weeks' gestation; group 2 (n = 7), 20-28 weeks, and group 3 (n = 9), after 28 weeks. Initial mean anti-D level was significantly higher in group 1 (25.9 +/- 12.9 IU/ml) than in the other 2 groups, whose mean values were, however, higher than 10 IU/ml. Amniotic-fluid total bilirubin levels before the onset of therapy were pathologic, and in 55% of the cases they coincided with zone 3 of Liley's chart. Hydrops fetalis at the onset of treatment accounted for the only 3 fetal deaths in groups 1 and 2. None of the fetuses developed hydrops during treatment. Six of the 9 neonates in group 3 were depressed at birth (1-min Apgar below 7). However, at 5 min only 1 newborn showed an Apgar below 7. Mean birth weight was over 2,500 g in all the cases. Neonatal hematological condition in group 2 (50% of the babies required only phototherapy) was better than in the other 2 groups (transfusional therapy). There was a significant fall in maternal anti-D titers and intrauterine hemolysis after IVIG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of fetal and maternal atrial natriuretic peptide concentrations at delivery in man.

Matched maternal venous (MV), umbilical artery (UA) and umbilical vein (UV) concentrations of atrial natriuretic peptide [ANP] were measured in 36 normotensive women at term delivery (23 vaginal, 13 caesarean) and 17 non-pregnant women in the first half of the menstrual cycle. MV [ANP] at caesarean section was similar to that in non-pregnant women, but UA and UV [ANP] were higher (P less than 0.01 for both). UA, but not UV, [ANP] was markedly raised after vaginal delivery. Plasma concentrations of aldosterone [ALD] were measured in 16 of the matched sets of samples. No statistically significant association was found between [ANP] and [ALD] in either maternal or fetal samples. Neither maternal nor fetal [ANP] correlated with serum Na+ or osmolality, haematocrit, blood pressure or heart rate.

Uric acid levels: a useful index of the severity of preeclampsia and perinatal prognosis.

Maximum serum uric acid (SUA) levels during the third trimester of pregnancy were selected in 215 hypertensive pregnant women: 100 with mild preeclampsia (PE), 25 with severe PE, 70 with essential hypertension (EH) and 20 with EH with superimposed PE (EH + PE). The increase in SUA levels was statistically significant in women with severe PE (6.22 mg% +/- 1.30 mg%) and with EH + PE (6.09 mg% +/- 1.53 mg%) when compared with values in mild PE and EH women (4.85 mg% +/- 1.34 mg% and 4.95 mg% +/- 1.22 mg%, respectively). A significant decrease in average gestational age at delivery and a greater percentage of small-for-gestational age newborns were observed in women with severe PE and EH + PE, compared with patients with mild PE and EH. No correlation within the groups was found between SUA levels and fetal weight. To conclude, the determination of SUA concentration for the clinical screening of a pregnancy complicated by hypertension is an easy and inexpensive method for the prediction of perinatal results associated with severe PE.

[Misoprostol--a PGE1 analog for induction of labor at term: comparative and randomized study with oxytocin]. / Misoprostol--un análogo de la PGE1--para la induccíon de parto a término: estudio comparativo y randomizado con oxitocina.

The efficacy of misoprostol (a PGE1 analog) for induction of labor at term was compared with oxytocin by means of an open and randomized study in 153 pregnant women. A vaginal tablet containing 50 mcg of misoprostol was placed intravaginally in 78 women, the remaining 75 patients received i.v. oxytocin (2-32 mU/min). Bishop's score at the entry of the trial was similar in both groups. Delivery within 24 hours was achieved in 85.7% of the patients induced with misoprostol and in 64% of the patients infused with oxytocin (p < 0.05). Mean induction to delivery interval was significantly shorter in the misoprostol group (552 +/- 211 min; mean =SD) in comparison with that of the oxytocin group (745 +/- 292 min; mean +/- SD) (p < 0.05). The probability of still being pregnant at 24 hours (Life table analysis) was 14% (misoprostol group) and 26% (oxitocyn group). The difference was also statistically significant (p < 0.01). No undesirable side effects were observed in any of the patients, however, polisystoly (> 5 contractions in 10 min) was more frequently observed in the patients induced with misoprostol (24.6% vs 13.3%; p = NS). Cesarean section rate was higher in the oxytocin-induced patients (25.3%) than in the misoprostol-induced women (3.8%) (p < 0.05). The main cause of cesarean section was failure to progress in labor in both groups of patients. Neonatal outcome was good in both groups and there were no differences with respect to birthweight or to Apgar scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial blood pressure standards during normal pregnancy and their relation with mother-fetus variables.

The purpose of our work was to study blood pressure variations during pregnancy in a normal Latin American population from Argentina and Uruguay; to investigate blood pressure variations according to maternal age, parity, or pregnancy weight gain; and to correlate diastolic blood pressure levels in the last trimester of pregnancy with newborn birth weight. This prospective study included follow-up throughout gestation of 249 normal pregnant women (129 nulliparous and 120 multiparous) with a weekly blood pressure control under the same experimental conditions. Our results demonstrate that there is only a low correlation between maternal age and diastolic blood pressure, but no correlation was found with systolic blood pressure; maternal weight gain correlates with blood pressure changes; no correlation was found between gestational age and blood pressure, although an increasing tendency in systolic and diastolic blood pressure was found toward the end of gestation; and a significant correlation was observed between birth weight and average diastolic blood pressure during the third trimester. These findings demonstrate the potential significance of the use of standard blood pressure data from normal pregnant women for the future clinical evaluation of our population.

Ketanserin versus alpha-methyldopa in the treatment of hypertension during pregnancy: a preliminary report.

The antihypertensive efficacy of acute treatment with the serotonin receptor antagonist, ketanserin, in women with preeclampsia has been recently documented. The purpose of this study was to determine the safety and efficacy of chronic ketanserin treatment in a group of 20 hypertensive pregnant women: 10 received daily oral doses of ketanserin (20-80 mg), and 10 were treated with oral alpha-methyldopa (500-2000 mg). This study includes (a) patients with a sustained elevation of systolic blood pressure higher than 159 mm Hg and/or diastolic blood pressure higher than 99 mm Hg at bed rest, and (b) hypertensive patients with systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg with superimposed symptoms such as headaches, stomach aches, and neurological disturbances. A significant and comparable decrease in blood pressure was noted in both groups, in relation with pretreatment levels; no adverse affects were observed in mother or fetus from the ketanserin and alpha-methyldopa groups.

Agreement between different frequencies of measurements in ambulatory blood pressure monitoring.

The purpose of this study was to determine the degree of agreement among different frequencies of blood pressure measurements (FoM) in 24-hour ambulatory blood pressure monitoring (ABPM) in their ability to obtain useful clinical information. ABPM records were obtained with a Del Mar IV Avionics device from 49 hospitalised preeclamptic women with a FoM of 7 per hour (high-FoM). With these records, we simulated two sets of data as if measurements had been recorded at a rate of 1 measurement per hour (low-FoM) and of 2 per hour (medium-FoM). Diastolic blood pressure > 89 mmHg defined hypertension and > 109 mmHg, severe hypertension The median and 25th and 75th centiles for the differences in hypertensive rate detected (expressed as percentage points) between lowFoM vs. high-FoM was 0.00 (- 3.4-3.00) and between medium-FoM vs. high-FoM,- 1.04 (- 3.7-1.5). The agreement in the detection of severely affected patients was 85% (CI 95%: 74-96) between low-FoM and high-FoM and 87% (CI 95%: 77-98), between medium-FoM and high-FoM. Average blood pressure was similar in the three FoMs studied at day-time and night-time. We did not find any strong argument to perform ABPM at a high-FoM. Lower FoM are more comfortable for the patient and could reduce equipment deterioration, while providing equivalent information to that supplied by high-FoM.

Prolactin, estriol and progesterone levels in frequent blood samples throughout normal pregnancy (lack of prolactin pulsatile secretion).

The aim of this paper was to study the episodic fluctuations of circulating prolactin (PRL), estriol (E3) and progesterone (P4) concentrations throughout pregnancy. We examined 24 pregnant women; 21 were between the 28th and 40th week of gestation, and the other 3 in the 12th, 16th and 20th week of gestation. Blood samples were drawn every 5 min for half an hour, and every 15 min for one and a half hour. Blood samples were taken in two and three different weeks of gestation in 11 and 2 of the cases, respectively. Two normal non-pregnant women were also studied and used as controls. PRL, E3 and P4 were determined by radioimmunoassay in all the samples. The coefficients of variation of PRL values were 40 and 22.6%, respectively, in the two control women, 8, 12 and 9.8% in the pregnant women studied at the 12th, 16th and 20th week of gestation, respectively, while in the 21 cases studied during the third trimester the coefficient of variation was 8 +/- 3% (mean +/- SD). The coefficients of variation of the values obtained for E3 and P4 in women studied in he third trimester were 26 +/- 15 and 16 +/- 6% (Mean +/- SD), respectively. There was an increase in the average concentration of the three hormones in all the cases at two or three different weeks. We can conclude that E3 and P4 have a pulsatile secretion pattern throughout pregnancy, and that PRL looses its pulsatile secretion as from an early gestational age. Our results suggested that central mechanisms regulating PRL episodic fluctuations were altered during pregnancy.

High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease.

Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results.

Neonatal administration of high-dose intravenous immunoglobulin in rhesus hemolytic disease.

Our aim was to assess the effectiveness of neonatal treatment of Rh hemolytic disease with high-dose intravenous immunoglobulin (HDIVIG), in reducing neonatal hemolysis. A total of 40 neonates born to isoimmunized Rh negative women were studied. The population was randomized into 2 groups: Group 1 received IVIG 800 mg/kg/day for 3 days, plus phototherapy; and Group 2 received only phototherapy. No significant difference was observed between the groups in the severity of either the antenatal and neonatal disease, mode of delivery, mean birthweight, gestational age at delivery, proportion of preterm deliveries, 1 minute Apgar Score, days of phototherapy, and presence of neonatal cholestasis. Group 1 babies showed a significantly decreased duration of hospitalization, less hemolysis, and a less marked increase in bilirubin levels on the first day of life than Group 2 newborns. Therefore, Group 1 neonates received less treatment with transfusions (exchange-transfusions and/or simple blood treatment with transfusions) than those in Group 2. Our data suggest that the frequency of transfusional therapy can be reduced by combining conventional phototherapy with HDIVIG. Further studies are needed to determine the optimum timing and dosages of neonatal HDIVIG treatment.

Two-dimensional and M-mode echocardiographic findings in hypertensive pregnant women.

Two-dimensional and M-mode echocardiograms were obtained during the thirty-second week of gestation from 69 women classified as follows: group I, 22 normotensive primigravid women; group II, 16 primigravid women with pregnancy-induced hypertension; group III, 21 percent women with essential hypertension; and group IV, 10 normotensive nonpregnant control subjects. Systolic, diastolic, and mean arterial pressures were higher in groups II and III than in groups I and IV (p less than 0.001). Echocardiographic dimensions were significantly increased in group III compared with the other groups (p less than 0.01). No significant differences were observed among the other groups in the echocardiographic parameters or in the indices of ventricular performance studied. In echocardiographic studies, chronic hypertensive pregnant women are distinguished from patients with pregnancy-induced hypertension because the former have ventricular hypertrophy resulting from the pressure overload exerted for a long period of time. Our patients with essential hypertension experienced no changes in left ventricular performance because of the early stage of their hypertensive disease.

Intrathoracic alimentary tract duplication cysts treated in utero by thoracoamniotic shunting.

Alimentary tract duplication cysts are rarely diagnosed in utero. We report two fetal patients that presented with intrathoracic alimentary tract duplication cysts, mediastinal shift and hydrops. In one fetus, the cyst continued into the fetal abdomen and pelvis through a left diaphragmatic hernia. Despite successful ultrasound-guided needle aspirations in both fetuses, there was rapid reaccumulation of the fluid and recurrence of the mediastinal shift, prompting the placement of a thoracoamniotic shunt. In one fetus, there was rapid resolution of the mediastinal shift with the disappearance of the hydrops within 2 weeks. The second fetus suffered an intrauterine demise 2 days after the shunt placement. Postnatal resection in the surviving infant revealed a large cyst consistent with an intrathoracic duplication of the stomach. The autopsy of the second fetus revealed an intrathoracic duplication cyst of the stomach and proximal small intestine.