Barbara V. Parilla

Amiodarone Therapy for Drug-Refractory Fetal Tachycardia

Background—Fetal tachycardia complicated by ventricular dysfunction and hydrops fetalis carries a significant risk of morbidity and mortality. Transplacental digoxin is effective therapy in a small percentage, but there is no consensus with regard to antiarrhythmic treatment if digoxin fails. This study evaluates the safety, efficacy, and outcome of amiodarone therapy for digoxin-refractory fetal tachycardia with heart failure. Methods and Results—Fetuses with incessant tachycardia and either hydrops fetalis (n=24) or ventricular dysfunction (n=2) for whom digoxin monotherapy and secondary antiarrhythmic agents (n=13) were not effective were treated transplacentally with a loading dose of oral amiodarone for 2 to 7 days, followed by daily maintenance therapy for <1 to 15 weeks. Digoxin therapy was continued throughout gestation. Newborns were studied by transesophageal pacing or ECG monitoring to determine the mechanism of tachycardia. Three fetuses were delivered urgently in tachycardia during amiodarone loading, and 3 required additional antiarrhythmic agents for sustained cardioversion. Amiodarone or amiodarone combinations converted 14 of 15 (93%) with reentrant supraventricular tachycardia, 2 of 2 with ventricular or junctional ectopic tachycardia, and 3 of 9 (33%) with atrial flutter. Amiodarone-related adverse effects were transient in 5 infants and 8 mothers. Mean gestational age at delivery was 37 weeks, with 100% survival. Conclusions—Orally administered amiodarone is safe and effective treatment for drug-refractory fetal tachycardia, specifically reentrant supraventricular tachycardia, junctional ectopic, or ventricular tachycardia, even when accompanied by hydrops fetalis or ventricular dysfunction.

The clinical significance of a single umbilical artery as an isolated finding on prenatal ultrasound

Objective To evaluate the perinatal outcome in fetuses with single umbilical artery detected on targeted prenatal ultra-sound without other anomalies. Methods During a 3.5-year period, an isolated single umbilical artery was suspected on prenatal ultrasound examination in 57 fetuses evaluated at two referral centers. Targeted imaging to rule out concurrent fetal anomalies was normal in all cases. Pregnancy and perinatal outcome data were retrieved by review of the medical records or from conversations with referring physicians. Complete follow-up was available in 50 cases. Results A two-vessel umbilical cord was confirmed at birth in 50 neonates. The mean gestational age at delivery was 38.6 ± 2.8 weeks; the mean birth weight was 3202.8 ± 835.8 g. Seventeen patients (34%) underwent genetic amniocentesis, and all fetuses had a normal karyotype. The only neonate ascertained to have a congenital anomaly after birth was diagnosed with total anomalous pulmonary venous return. This neonate underwent a corrective surgical procedure and is thriving with no apparent problems at 3.5 years of age. There were no perinatal deaths. Conclusion In the absence of additional sonographically detectable anomalies, an isolated single umbilical artery does not seem to affect clinical outcome and therefore should not alter routine obstetric management.

Isolated choroid plexus cyst(s): An indication for amniocentesis

OBJECTIVE Our purpose was to prospectively evaluate the risk of chromosomal abnormalities associated with isolated choroid plexus cyst(s) in gravid women undergoing second-trimester ultrasonographic examination. STUDY DESIGN During a 24-month period 9100 pregnant women underwent midtrimester ultrasonographic evaluation. Women with a fetal diagnosis of choroid plexus cyst(s) were offered amniocentesis and a repeat examination in 4 to 6 weeks. RESULTS A diagnosis of choroid plexus cyst(s) was made in 102 fetuses (1.1%). In four of these fetuses multiple congenital anomalies were noted. Three of the four fetuses had a chromosomal abnormality, two trisomy 18 and one unbalanced translocation, t(3;13). In the remaining 98 fetuses the choroid plexus cysts were isolated findings, that is, there were no other ultrasonographically detected anomalies. Seventy-five of these 98 fetuses underwent amniocentesis. An abnormal karyotype was identified in four fetuses: three had Down syndrome (two trisomy 21 and one unbalanced translocation, t[14;21]), and one trisomy 18. The offspring of the 23 patients in which amniocentesis was declined were phenotypically normal. CONCLUSIONS In our prospective study the risk of chromosomal abnormality with isolated choroid plexus cyst(s) was 1:25, a risk that exceeds the 1:200 risk of pregnancy loss after amniocentesis and the 1:126 and 1:260 risk for aneuploidy and Down syndrome, respectively, in a 35-year-old pregnant women during the midtrimester. These findings indicate that amniocentesis should be offered to pregnant women in the presence of isolated fetal choroid plexus cyst(s).

Single versus weekly courses of antenatal corticosteroids in preterm premature rupture of membranes

OBJECTIVE: This study was performed to evaluate the efficacy of weekly courses of antenatal corticosteroids compared with a single course in women with preterm premature rupture of membranes (PROM). METHODS: A planned secondary analysis of women with preterm PROM who participated in a multicenter, randomized trial of weekly courses of antenatal corticosteroids versus single-course therapy was performed. After their first course of standard antenatal steroid therapy, administered between 24 to 32–6/7 weeks of gestation, consenting women were randomly assigned to receive betamethasone versus placebo injections weekly until 34–0/7 weeks of gestation. Maternal and neonatal morbidities were compared between the 2 groups. RESULTS: Of the 161 women with preterm PROM, 81 women were assigned to receive weekly courses of steroids and 80 to the single-course group. There were no significant differences in composite morbidity between the groups (27 [34.2%] of 81 patients versus 33 [41.8%] of 80 patients, P = .41). Chorioamnionitis was higher in patients who received weekly courses of antenatal steroids (39 [49.4%] of 81 patients versus 25 [31.7%] of 80 patients, P = .04). CONCLUSION: Weekly courses of antenatal steroids in women with preterm PROM did not improve neonatal outcomes beyond that achieved with single-course therapy and was associated with an increased risk of chorioamnionitis. Antenatal steroid therapy should not be routinely repeated in patients with preterm PROM. LEVEL OF EVIDENCE: I

Indomethacin tocolysis and intraventricular hemorrhage.

Objective To determine the association between indomethacin tocolysis and neonatal intraventricular hemorrhage. Methods Fifty-six preterm neonates with intraventricular hemorrhage were matched by gestational age with neonates (n = 224) without this morbidity. Maternal and neonatal charts were reviewed to ascertain the type of tocolytic exposure experienced by the neonate. Other maternal and neonatal demographic and outcome data were also abstracted. Results were analyzed using the Student t test, χ2 analysis, and multivariable logistic regression. The number of studied subjects provided 80% power to determine if antenatal exposure to indomethacin was twice as likely among infants with intraventricular hemorrhage. Results Univariate analysis revealed that there were no significant differences between the study and control groups with respect to maternal age, parity, or betamethasone exposure. Infants with intraventricular hemorrhage were significantly more likely to be born at an earlier gestational age, a lower birth weight, after maternal chorioamnionitis, after vaginal delivery, and after exposure to either indomethacin alone or a combination of indomethacin and magnesium. Additionally, their neonatal course was significantly more likely to be complicated by sepsis and respiratory distress syndrome. In a multivariable logistic model, only gestational age, chorioamnionitis, vaginal delivery, and respiratory distress syndrome continued to be significantly associated with intraventricular hemorrhage. Indomethacin exposure, either as single-agent (adjusted odds ratio 1.3, 95% confidence interval 0.5, 3.3) or combination tocolytic therapy (adjusted odds ratio 2.0, 95% confidence interval 0.8, 4.8), was not significantly associated with intraventricular hemorrhage. Conclusion Indomethacin tocolysis is not associated with an increased risk of intraventricular hemorrhage.

A management strategy for fetal immune-mediated atrioventricular block

Introduction. The purpose of this study is to describe an in utero management strategy for fetuses with immune-mediated 2° or 3° atrioventricular (AV) block. Methods and results. The management strategy as applied to 29 fetuses consisted of three parts. First, using fetal echocardiography and obstetrical ultrasound, we assessed fetal heart rate (FHR), heart failure, growth and a modified biophysical profile score (BPS) assessing fetal movement, breathing and tone. Second, we treated all fetuses with transplacental dexamethasone, adding terbutaline if the FHR was <56 bpm. Digoxin and/or intravenous immune globulin (IVIG) was added for progressive fetal heart failure. Third, we delivered fetuses by cesarean section for specific indications that included abnormal BPS, maternal/fetal conditions, progression of heart failure, or term pregnancy. We assessed perinatal survival, predictors of delivery and maternal/fetal complications in 29 fetuses with 3° (n = 23) or 2° (n = 6) AV block. There were no fetal deaths. In utero therapy included dexamethasone (n = 29), terbutaline (n = 13), digoxin (n = 3) and/or IVIG (n = 1). Delivery indications included term gestation (66%), fetal/maternal condition (14%), low BPS (10%) and progression of fetal heart failure (10%). An abnormal BPS correlated with urgent delivery. Conclusion. These results suggest that applying this specific management strategy that begins in utero can improve perinatal outcome of immune-mediated AV block.

Positive predictive value of suspected growth aberration in twin gestations

OBJECTIVE Our purpose was to determine the positive predictive value of ultrasonographic surveillance for growth abnormalities in twin gestations as a function of gestational age. STUDY DESIGN Women with twin gestations and delivery between January 1992 and March 1998 who had a 20- to 24-week sonogram with normal fetal anatomic findings and who had at least 1 sonogram showing abnormal growth were identified. Abnormal growth on ultrasonography was defined as an estimated fetal weight <10th percentile, abdominal circumference <5th percentile, or twin discordance (>20% difference in twin weights as a function of the heavier twin). Birth weights were then assessed for evidence of twin discordance or growth restriction. RESULTS The positive predictive value for the occurrence of a growth abnormality at birth, after an abnormal growth finding on ultrasonography at any time during gestation, was 47.7%. The positive predictive value was greatest (85%) when suspected growth restriction was first documented at 20 to 24 weeks of gestation and decreased with increasing gestational age. Even though sonograms were obtained at a mean interval of 4.4 +/- 2.0 weeks, those gestations with normal growth at 20 to 24 weeks had an elapsed time of 10.3 +/- 3.9 weeks until a growth abnormality was subsequently detected. CONCLUSION In twin gestations the positive predictive value of a sonogram for a growth abnormality at birth is significantly decreased after normal findings on a 20- to 24-week sonogram. This finding suggests that a routine 2- to 4-week interval between sonograms for all twin gestations may be unwarranted.

The prevalence and timing of cervical cerclage placement in multiple gestations

Objectives: To investigate the prevalence and timing of cervical cerclage placement in multiple gestations. Methods: Our perinatal database was queried for all multiple gestations delivered at Evanston Hospital from 12/95 through 12/00. This list was then cross‐matched with billing and medical records for ‘incompetent cervix’ and ‘cerclage.’ The medical records of all deliveries ≤26 weeks were reviewed in order to ascertain if cervical incompetence was responsible for the preterm delivery. Results: There were 802 deliveries of multiple gestations ≥14 weeks over a 5‐year period. The number of patients that underwent cerclage placement was 29 or 3.6%. The mean gestational age at cerclage placement was 18.6±4.5 weeks (range 11–24.6). Twelve were elective or prophylactic while 17 were ‘urgent’ or ‘emergent.’ The mean gestational age for the 17 emergent cerclages was 21.4±2.2 weeks (range 16.6–24.6). When compared with those patients who did not undergo cerclage placement, there was no difference in maternal demographics including age, parity, or previous full‐term delivery. There was a significant difference in the gestational age at delivery for the cerclage vs. no cerclage group; 29.3±5.6 vs. 34.4±4.6 weeks, respectively, and in the frequency of losses at ≤26 weeks; 8/23 (38%) vs. 48/707 (6.8%), P<0.001. Ten of the losses in the no cerclage group appeared consistent with incompetent cervix for a total of 39/802 or 4.9% rate of cervical incompetence in our multiple gestation population. Conclusions: The relatively low prevalence of cervical incompetence in our multiple gestations does not justify prophylactic cervical cerclage placement. Expectant management with serial cervical examinations starting at 16–18 weeks appears more prudent.

Ghrelin levels in cord blood from concordant and discordant twin pairs: association with birth weight and postnatal catch-up growth

Objective. To determine whether cord blood ghrelin levels in discordant and concordant twins predict postnatal catch-up growth. Methods. After obtaining parental consent, cord blood samples were collected at delivery for total ghrelin analysis. Infant weight, length and head circumference were obtained at birth, 2, 4, and 6 months of age. Data points post-discharge were obtained from the pediatricians office or via parent contact. Pearson correlation evaluated the relationship between cord blood ghrelin levels and postnatal catch-up growth. Results. There was a statistically significant correlation between cord blood ghrelin levels and birth weight among concordant twins, but not among the discordant twins. Cord blood ghrelin levels did not predict postnatal growth at 6 months of age overall, but did so in the subset of monochorionic, discordant pairs. Conclusion. Cord blood ghrelin levels did not correlate overall with birth size or postnatal catch-up growth in concordant and discordant twin pairs, but did so in selected subsets. Further studies are needed.

Cervical incompetence in multiple gestations

Objective: To investigate the prevalence and timing of cervical incompetence in multiple gestations. Materials and Methods: Our perinatal database was queried for all multiple gestations delivered at Evanston Hospital from December 1995 through August 2000. This list was then crossmatched with billing and medical records for ‘incompetent cervix‘ and ‘cerclage placement.‘ The medical records of all deliveries at 26 weeks of gestation or earlier were reviewed in order to find out whether cervical incompetence was responsible for the preterm delivery. Results: There were 730 deliveries of multiple gestations greater than or equal to 14 weeks over a 57-month period. The number of patients who underwent cerclage placement was 23 (3.2%). The mean gestational age (GA) at cerclage placement was 18.6 ± 4.5 weeks (range 11–24.6). Eight cerclage placements were elective or prophylactic, whereas 15 were ‘urgent‘ or ‘emergent.‘ The mean GA for the 15 emergent cases was 21.4 ± 2.2 weeks (range 17–24.6). When patients who underwent cerclage placement were compared with patients who did not undergo cerclage placement, there was no difference in maternal demographics, including age, parity, previous full-term deliveries, or number of fetuses. There was a significant difference in the GA at delivery for the cerclage versus no-cerclage group: 29.3 ± 5.6 versus 34.4 ± 4.6 weeks, respectively, and in the frequency of losses at 26 weeks or earlier: 8/23 (38%) versus 48/707 (6.8%), P = <0.001. Six of the losses in the no-cerclage group appeared consistent with incompetent cervix, for a 4% rate of cervical incompetence (29/730) in our multiple-gestation population. Conclusion: The relatively low incidence of cervical incompetence in our multiple gestations does not justify prophylactic cervical cerclage placement. Expectant management with serial cervical examinations starting at 16–18 weeks of gestation appears more prudent.