First Report of a Successful Pregnancy in an Everolimus-Treated Heart-Transplanted Patient: Neonatal Disappearance of Immunosuppressive Drugs.

The use of everolimus (EVL) as primary immunosuppression is steadily increasing in heart transplantation (HTx) patients. Limited data currently exist in kidney transplantation, but there is no report of EVL use during pregnancy after HTx and its pharmacokinetics in the newborn. We report a case of an unplanned pregnancy discovered at 21 weeks of gestation in a female HTx patient aged 40 years treated with EVL and cyclosporine (CyA). Because pregnancy was advanced, immunosuppression therapy was left unchanged. At 36 weeks, a healthy infant was delivered. At birth, CyA blood levels were lower in the neonate, but EVL concentrations in maternal and neonatal umbilical blood were similar. Amniotic fluid concentrations were undetectable for both drugs. In the newborn, EVL was measurable at 5 days after birth, whereas CyA disappeared within 2 days. Cord blood displayed a normal count of B and T cells and CD4, CD8 and natural killer cell populations. At birth, both mother and newborn displayed the same blood levels of EVL; therefore, a filter effect of the placenta may be hypothesized for CyA but not for EVL. No immediate complications were observed with this pregnancy.

Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin?

We evaluated the efficacy and safety of nimesulide (100 mg orally twice daily for > 48 hours) in a pilot series of five women (two with twin pregnancies) at 24(+6) weeks (range 21(+3) - 27(+2)) in preterm labour which was unresponsive to intravenous ritodrine. Nimesulide therapy was continued for eight days (5-16) and was associated with a prolongation of pregnancy of 27 days (6-69). Oligohydramnios occurred in all seven fetuses after three to nine days of therapy, and in the five pregnancies that continued after discontinuation of nimesulide, it resolved within four days (2-7). None of the babies manifested permanent renal damage.

Fertility after ectopic pregnancy. Effects of surgery and expectant management.

OBJECTIVE: To evaluate the effects of different management strategies for ectopic pregnancy on fertility. STUDY DESIGN: Retrospective cohort study of 180 consecutive patients who were diagnosed with ectopic pregnancy between September 1988 and December 1995. The fertility rate after ectopic pregnancy treated with surgery was compared with that after expectant treatment. Statistical analysis took into consideration the following confounding variables: history of sterility, infertility, ectopic pregnancy, use of intrauterine device, endometriosis, pelvic inflammatory disease or pelvic surgery prior to ectopic pregnancy, and type of therapy for ectopic pregnancy. RESULTS: Of the 180 women enrolled in the study, 97 desired conception. The intrauterine conception rate was similar in those initially treated expectantly as in those allocated to primary surgery (63% [31/49] vs. 51% [19/37], P = .37). Successful completion of expectant management was associated with rates of subsequent intrauterine pregnancy similar to those of surgical treatment (including primary surgery and surgery after failure of expectant management) (65% [22/34] vs. 54% [28/52], P = .44). Women undergoing delayed surgery due to failure of expectant management had rates of subsequent intrauterine conception similar to those who underwent primary surgery (9/15 vs. 19/37, P = .79). Several anamnestic factors had a significant and adverse effect on reproductive outcome: history of infertility (P = .01), history of ectopic pregnancy (P = .02) and previous pelvic surgery (P = .001). CONCLUSION: Expectant and surgical management of ectopic pregnancy had similar subsequent intrauterine conception rates, even when failure of expectant management led to secondary surgery. Gynecologic history can identify the subgroup of patients at higher risk of a poor reproductive outcome.

Isolated fetal choroid plexus cysts: role of ultrasonography in establishment of the risk of trisomy 18.

OBJECTIVE: The significance of isolated choroid plexus cysts found by ultrasonographic scan during the second trimester as a marker for trisomy 18 is still debated. We analyzed our data and reviewed the series published in the English-language literature to calculate the likelihood ratio of trisomy 18 in the presence of isolated choroid plexus cysts; that is, the factor by which the individual risk of trisomy 18 is increased in the presence of isolated choroid plexus cysts. STUDY DESIGN: Likelihood ratios were calculated as ratio of the sensitivity to the false-positive rate. Sensitivity was defined as the rate of isolated choroid plexus cysts detected at midgestation among fetuses with trisomy 18. False-positive rate was defined as the rate of choroid plexus cysts detected at midgestation in the population without trisomy 18. The sensitivities of all published series reporting rates of choroid plexus cysts at the time of the first ultrasonographic examination between 14 and 24 weeks' gestation in populations with trisomy 18 and in low-risk populations were included in the analysis. To these we added all cases of trisomy 18 diagnosed at our institution during the period January 1, 1988, through June 30, 1998, in which prenatal ultrasonographic examination was performed between 14 and 24 weeks' gestation. RESULTS: The prevalence of second-trimester ultrasonographic detection of isolated choroid plexus cysts among fetuses with trisomy 18 was 6.7% (13/194), whereas that in the population without trisomy 18 was 0.9% (752/79,583). The likelihood ratio associated with isolated choroid plexus cysts was therefore 7.09 (95% confidence interval, 3.97-12.18). CONCLUSION: The presence of isolated second-trimester choroid plexus cysts increases the base risk of trisomy 18 by a factor of 7.09. This likelihood ratio can be multiplied by the risk calculated according to maternal age to obtain the individual risk of trisomy 18 and thus permit more accurate counseling of the patient.

Critical reappraisal of the utility of sonographic fetal femur length in the prediction of trisomy 21.

Measurement of femur length (FL) has been advocated as part of a genetic sonogram for the prediction of Down syndrome (DS). However its predictive ability has been inconsistent. We have studied the diagnostic value of this sonographic parameter in a prospective cohort of women with singleton gestations undergoing genetic sonogram between 14 and 22 weeks because of advanced maternal age or family history of aneuploidies. Genetic sonograms were performed at a mean gestational age of 17.0 weeks (range 14-22). DS was diagnosed in 30 fetuses, while 888 were euploid. Mean+/-SD observed/expected (O/E) values of FL (1.00+/-0.10 versus 0.97+/-0.01, p=0.07) were not significantly different between euploid and DS fetuses. Comparison of the regression equations of FL versus biparietal diameter revealed that while the intercepts were not significantly different between euploid and DS fetuses, the difference in slopes reached significance (p=0.04) suggesting that the predictive ability of FL may increase with advancing gestational age. In addition, a MEDLINE search (National Library of Medicine) was conducted for articles published between 1985 and 1998 on fetal femur length in the prediction of trisomy 21. Review of the published literature on the subject suggests that FL is not a consistent or reliable sonographic predictor of DS. Published thresholds of FL should not be used outside of the Institution from which they originated, and each Institution should establish whether this parameter has predictive ability in its own population.

Amnioreduction in emergency cerclage with prolapsed membranes: comparison of two methods for reducing the membranes.

To evaluate the effectiveness of amnioreduction in pregnancies requiring emergency cerclage placement, we performed a retrospective case-control study of all consecutive pregnant women with cervical dilation and effacement with prolapse of the fetal membranes in vagina between 16 and 26 weeks' gestation, who required placement of a McDonald emergency cerclage during the period January 1991-December 1997. Duration of pregnancy prolongation, rate of delivery before 32 weeks, and duration of neonatal hospital stay were compared between women in whom amniochorionic membranes were reduced at the time of cerclage placement using only intracervical Foley balloon catheter (controls; n = 7) and those who in addition underwent amnioreduction to facilitate cerclage placement (n = 9). Statistical analysis utilized Fisher's exact test and Wilcoxon rank sum test. A p value <0.05 was considered significant. There were no procedure-related ruptures of membranes. Gestational age at cerclage and rate of positive cervico-vaginal cultures were not different between the two groups. Gestation was prolonged for a median of 100 days (range 4 to 144 days) in the amnioreduction group and 10 days (2 to 133) among controls (p = 0.3). The rate of delivery before 32 weeks was significantly lower (1/7 vs. 6/8, p = 0.03) and the duration of neonatal hospital admission significantly shorter (median 3 vs. 37 days, p = 0.001) in the amnioreduction group than among controls. The amount of amniotic fluid withdrawn ranged from 220 to 340 mL. These findings suggest that amnioreduction at the time of emergency cerclage placement is associated with a lower rate of extreme prematurity and related neonatal morbidity.

Congenital toxoplasmosis: efficacy of maternal treatment with spiramycin alone.

PROBLEM: The evidence supporting an additional benefit of a combined regimen of pyrimethamine-sulfonamides compared with spiramycin alone in the secondary prevention of congenital toxoplasmosis was critically evaluated. METHOD OF STUDY: We reviewed the series of cases published in the English literature on antiparasitic treatment of acute toxoplasmosis infection in pregnancy, using spiramycin until fetal infection is documented, then using cycles of spiramycin alternated with combined pyrimethamine-sulfonamide therapy. We then compared the occurrence of overt disease among infected offspring (both severe, represented by ophthalmologic or cerebral abnormalities, and mild occurrences, represented by asymptomatic intracranial calcifications and retinal scars without visual impairment) between the published case series and our consecutive series of cases treated during a 10-year period (January 1986-December 1995) with spiramycin alone. RESULTS: The prevalence of fetal infection in our series was 7.8% (12/154), similar to that reported after alternated regimens (7.0%). The rate of overt disease among infected fetuses is not different after treatment with alternated regimens than after continuous antibiotic spiramycin therapy [23% (19/82) vs. 10% (1/10); relative risk, 2.3; 95% confidence interval, 0.4, 47.0]. The pharmacokinetics of the drugs used may account for this finding. CONCLUSION: The treatment of acute toxoplasmosis in pregnancy with an alternated antibiotic regimen of pyrimethamine-sulfonamide is not more efficacious at preventing overt neonatal disease than treatment with continuous spiramycin alone.

Clinical outcome of mild fetal ventriculomegaly.

OBJECTIVE: Our purpose was to evaluate the outcome of fetuses with mild cerebral ventriculomegaly. STUDY DESIGN: We prospectively collected all cases of mild cerebral ventriculomegaly (transverse diameter of the atrium of the cerebral lateral ventricles between 10 and 15 mm) diagnosed antenatally between January 1990 and December 1996. Associated ultrasonographic abnormalities including markers of aneuploidy, presence of chromosomal anomalies, structural malformations detected at birth, and neurologic outcome were recorded. Outcome information was available on all cases. In addition, published series of cases of fetal mild cerebral ventriculomegaly were reviewed to identify prognostic indicators. RESULTS: Eighty-two cases fulfilled the inclusion criteria: 48 were isolated and 34 were associated with other ultrasonographic markers or anomalies. Among the 45 surviving euploid isolated cases, neurologic follow-up was normal at a mean age of 28 months (range 3 to 72 months). Male fetuses and those with a transverse atrial size <12 mm had a good prognosis. Ventricular atria > or =12 mm were more often associated with other anomalies (56% vs 6%) and, when isolated, with abnormal postnatal neurodevelopment (23% vs 3%). Aneuploidy was present in two cases of isolated mild cerebral ventriculomegaly, both of which were associated with advanced maternal age, and in seven cases associated with other anomalies. CONCLUSIONS: Mild cerebral ventriculomegaly should prompt targeted ultrasonographic examination, inclusive of markers of aneuploidies, visualization of the corpus callosum, and echocardiogram as well as serologic evaluation for congenital infections. In isolated mild cerebral ventriculomegaly genetic counseling should take into account clinical, laboratory, and ultrasonographic findings. A review of the published series suggests that cognitive or motor delay is predominantly mild and that it occurs in about 9% of cases of isolated mild cerebral ventriculomegaly.

Amnioinfusion for prevention of pulmonary hypoplasia in second-trimester rupture of membranes.

We conducted a study to evaluate the feasibility and benefits of transabdominal amnioinfusion in preterm premature rupture of membranes with persistent oligohydramnios for the prevention of pulmonary hypoplasia. To this purpose, we designed a cohort study in which the pregnancy outcome of women with rupture of membranes at < or = 25 weeks and persistent (> or = 4 days) oligohydramnios managed with serial amnioinfusions (n = 18) was compared with that of a historic cohort group (controls) with similar characteristics but managed expectantly (n = 16). Pulmonary hypoplasia was diagnosed at birth in the presence of strict radiological and pathological criteria. No amnioinfusion-related complications occurred. The prevalence of pulmonary hypoplasia was significantly lower among the amnioinfused cases compared with the controls (46% [6 of 13] vs 86% [12 of 14], odds ratio [OR] = 0.4, 95% confidence interval [CI] 0.2-0.9), despite a lower gestational age at rupture of membranes in the treated group. Within the group undergoing amnioinfusions, those in which the infused solution was rapidly lost had a higher rate of pulmonary hypoplasia compared with those in which amnioinfusion alleviated oligohydramnios for > 48 hours (considered successful) (0 of 4 vs. 6 of 9, OR = 2.3, 95% CI 1-5.5). Cases of successful amnioinfusion had a longer interval between membrane rupture and appearance of oligohydramnios than those in which the procedure failed to correct oligohydramnios, even though both groups had similar gestational age at appearance of oligohydramnios. This suggests that the rate of loss of amniotic fluid after membrane rupture may predict the rate of loss of the infused solution, and therefore identify a subset of patients who may benefit from the procedure.

Clinical significance of fetal intracranial hemorrhage.

OBJECTIVE: We reviewed our experience with six consecutive cases of fetal intracranial hemorrhage and the cases published in the English literature in an attempt to devise an original prognostic scoring system for antenatal intracranial hemorrhage. STUDY DESIGN: The series included the cases of fetal intracranial hemorrhage detected at our institution between 1992 and 1994 by transabdominal ultrasonography. In addition, we performed an English literature search (Medline computer search, National Library of Medicine) of all reported cases of a prenatal diagnosis of intracranial hemorrhage. The prenatal ultrasonographic findings were correlated with the clinical outcome, which was divided into (1) normal outcome or mild neurologic sequelae and (2) poor outcome (severe neurologic impairment and fetal or neonatal death). RESULTS: Six cases of intracranial hemorrhage were detected in a population of 6641 pregnancies (0.9/1000) at our institution. Parenchymal involvement was present in three cases. Review of the English literature revealed 35 additional cases with prenatal ultrasonographic findings and postnatal follow-up. The total cases (n = 41) were divided into three groups: (1) isolated intraventricular hemorrhage (n = 20), (2) parenchymal hemorrhage (n = 13), and (3) subdural or subarachnoid hemorrhage (n = 8). Overall, poor outcome was present in 68% of cases, including 45% (9/20) of intraventricular hemorrhage, 92% (12/13) of parenchymal hemorrhage, and 88% (7/8) of subdural or subarachnoid hemorrhage. The heterogeneity of the intraventricular hemorrhage group in both severity of antenatal findings and outcome prompted us to devise a prognostic scoring system based on prenatal ultrasonographic lesions, grouping cohorts with similar outcomes. Outcome was favorable in 100% (5/5) of grade 1 intraventricular hemorrhage cases, in 50% (6/12) of grade 2 cases, and in 0% (0/3) of grade 3 cases. CONCLUSIONS: Fetal intracranial hemorrhage can be classified on the basis of the anatomic location of the intracranial bleeding. The prognosis is poor in nearly 90% of parenchymal and subdural hemorrhages, whereas it is better in the subgroup with intraventricular hemorrhage. The prognostic scoring system we propose for intraventricular hemorrhage may assist the physician in providing patients with prognostic information.

Transabdominal amnioinfusion in oligohydramnios at term before induction of labor with intact membranes: a randomized clinical trial.

OBJECTIVE: Our purpose was to determine the effectiveness of transabdominal amnioinfusion before induction of labor in reducing the incidence of fetal distress in pregnancies with oligohydramnios at term. STUDY DESIGN: Between June 1991 and September 1994 primiparous women with ultrasonographic evidence of oligohydramnios at term, intact membranes, and unripe cervix (Bishop score < or = 6), candidates for induction of labor with cervical or vaginal prostaglandin E2 gel, were randomly selected to receive transabdominal amnioinfusion (amnioinfused group, n = 39) or to proceed with direct labor induction (control group, n = 40). Inclusion criteria were (1) singleton gestation, (2) vertex presentation, (3) ultrasonographic estimation of fetal weight > or = 2500 gm, and (4) reactive nonstress test. Fetoneonatal outcome variables were compared between the two groups. Statistical analysis used contingency tables, Student t test, or Wilcoxon rank-sum tests, where applicable. RESULTS: Amnioinfusion was successfully performed in 100% of the patients randomized for the procedure. The incidence of severely abnormal fetal heart rate tracings was significantly higher in the control than in the amnioinfused group (42% [17/33] vs 5% [2/37], relative risk 12.9, 95% confidence interval 2.4 to 56.4). The rate of cesarean sections performed for fetal distress was fivefold higher in the control group (25% [10/40] vs 5% [2/39], relative risk 4.9, 95% confidence interval 1.1 to 32.4). No bleeding complications or fetomaternal infectious morbidity were noticed. CONCLUSION: Transabdominal amnioinfusion is a safe, effective option for the prevention of fetal distress in pregnancies with oligohydramnios at term with intact membranes and unripe cervix.

Prognostic factors for successful expectant management of ectopic pregnancy.

OBJECTIVE: To determine the independent ability of initial hCG titers, trend of hCG titers, and ultrasonographic findings in the prediction of successful expectant management in ectopic pregnancy (EP). DESIGN: Case-control study. SETTING: University hospital. PATIENTS: Sixty-seven patients with EP managed expectantly, 49 of whom (73%) had a spontaneous resolution, whereas 3 (5%) underwent medical treatment, and 15 (22%) eventually underwent surgical treatment. RESULTS: Univariate analysis showed that the initial hCG titer, the trend in hCG titers between first and second sample, and ultrasonographic visualization of absence of an ectopic gestational sac were significant predictors of a successful expectant management. Using receiver operating characteristic curve analysis, an hCG titer < 1,000 mIU/mL was chosen as the optimal cutoff for this prediction, identifying 88% of women destined to have spontaneous resolution of the EP. Multivariate analysis showed that both initial hCG titer and trend in hCG titers but not ultrasonographic visualization of an ectopic gestational sac were independent predictors of a successful or failed expectant management. CONCLUSION: Expectant management of EP is successful in the majority of patients with initial hCG titer < 1,000 mIU/mL.

Intrauterine diagnosis and management of transient myeloproliferative disorder.

Transient myeloproliferative disorders can be associated with hydrops in Down syndrome fetuses. No cases of prenatal management of such a condition have been reported in the literature. We report a case of myeloproliferative disorder diagnosed by cordocentesis at 31 weeks in a Down syndrome fetus with pericardial effusion. A pericardiocentesis was performed at the first signs of hydrops and successfully improved fetal cardiac function, allowing for continuation of pregnancy.

Do uterine leiomyomas influence pregnancy outcome?

To evaluate the clinical significance of the presence, location, size, and number of uterine leiomyomas in pregnancy, a retrospective cohort study in which pregnancy complications and outcome of pregnant women with uterine myomas was undertaken by routine second trimester ultrasound examination. The case group consisted of 183 consecutive women with uterine myomas detected and followed during the years 1983-1989; the control group was made up of all pregnancies diagnosed and followed at the obstetric clinic during the period 1985-1987. The incidences of preterm delivery (less than 37 weeks), preterm premature rupture of membranes, in utero growth retardation (less than 5th percentile), placental abruptio, placenta previa, postpartum hemorrhage (more than 500 cc), and retained placenta were not significantly increased in the group of women with myomas compared with the general population. However, cesarean sections were more common in women with myomas (23 vs 12%; P < 0.001). Within the group of women with myomas, the incidence of cesarean section was not different in cases with multiple rather than solitary myomas, but it was significantly higher in cases of lower uterine segment compared with fundal myomas (39 vs 18%; P < 0.01) and when the mean diameter of the myoma was greater than 5 cm (35 vs 17%; P = 0.01). Stepwise logistic regression analysis showed that both myoma location and size were independent predictors of the odds of cesarean section.

Natural history of uterine leiomyomas in pregnancy.

A prospective study was conducted over a 6 year period to determine the natural history of uterine leiomyomas in pregnancy. All pregnant women with myomas detected during obstetric ultrasonographic examination and with three or more sonographic examinations were included; 134 patients fulfilled the inclusion criteria. Sonograms were obtained at 2 week intervals until 20 weeks of gestation, and monthly thereafter. The following observations were made: (1) the majority of myomas 5 cm or less in average diameter could no longer be seen during pregnancy; (2) the majority of myomas greater than 5 cm in diameter tended to remain stable or decrease in size during pregnancy; and (3) multiple myomas were less likely to disappear than solitary myomas.

Prognostic indicators in the prenatal diagnosis of agenesis of corpus callosum.

OBJECTIVE: Our aim was to determine the accuracy of ultrasonography in the prenatal diagnosis of agenesis of the corpus callosum and to establish whether ultrasonography can provide prognostic indicators in cases of agenesis of the corpus callosum. STUDY DESIGN: Prospective ultrasonographic study of the corpus callosum in all cases during an 8-year period in which fetal cerebral ventriculomegaly was detected. RESULTS: A total of 14 cases of agenesis of the corpus callosum are reported. In seven cases agencies of the corpus callosum was an isolated finding, and in seven cases it was associated with other abnormalities. Six cases involved mendelian syndromes (3 Lissencephaly syndrome, 2 Aicardi syndrome, and 1 Andermann syndrome), and one case was associated with trisomy 13. In 5 of 14 fetuses, all male, agenesis of the corpus callosum was an isolated benign finding. The corpus callosum could never be visualized before midgestation, but diagnosis of agenesis of the corpus callosum was very accurate after 20 weeks. CONCLUSION: Prenatal ultrasonographic findings suggestive of agenesis of the corpus callosum should be followed by a careful search for associated anomalies that may indicate genetic syndromes. Isolated agenesis of the corpus callosum is often an isolated, benign finding, particularly in male fetuses. In families at risk for mendelian syndromes associated with agenesis of the corpus callosum, lack of visualization of this structure is suggestive of the diagnosis.

Screening for congenital heart disease with the four-chamber view of the fetal heart.

OBJECTIVE: Our objective was to determine the efficacy of the four-chamber view of the fetal heart in routine ultrasonographic examination as a screening tool for congenital heart defects. STUDY DESIGN: A prospective cohort study compared the detection rate of congenital heart defects among 5336 pregnant women screened with the ultrasonographic four-chamber view of the fetal heart from 1987 through 1989 with that among 3680 patients examined ultrasonographically without the four-chamber view during the 2 preceding years (1985 through 1986). All patients were followed until delivery or termination of pregnancy, and clinical or autopsy confirmation of prenatal findings were obtained on all cases. RESULTS: The overall incidence of congenital heart diseases was 5.2 per 1000 (47/9016). During the years 1985 through 1986 15 neonates with congenital heart diseases were identified, seven of which were prenatally diagnosed (sensitivity 43%). During the period 1987 through 1989 a four-chamber view of the fetal heart was obtained in 95% of cases; 32 cases of congenital heart disease occurred, 26 of which were diagnosed antenatally (sensitivity 81%; p = 0.01). Two false-positive diagnoses were made during the second time period, giving a specificity of 99.9%. CONCLUSION: The four-chamber view of the fetal heart is easily obtained, does not significantly increase the duration of a routine ultrasonographic examination, and has an excellent sensitivity for the identification of congenital heart diseases.