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Reply to: Preterm premature rupture of membranes: A continuing dilemma
LETTERS TO T H E E D I T O R S Morbidity caused by terbutaline infusion pump therapy To the Editors: Hudgens and Conradi reported a case of sudden death in a patient being treated with a terbutaline infusion pump for preterm labor (Hudgens DR, Conradi SE. Sudden death associated with terbutaline sulfate administration. A~I J O~s'r~T GYNECOL1993;169: 120-1). During the past several months, here at a regional perinatal center we have seen three serious, yet not fatal, complications of terbutaline infusion pump therapy. Two involved twin gestations where the patients had acute pulmonaly edema while hospitalized. Both responded to supportive treatment after the terbutaline pump was discontinued. The third case concerned a woman with a 25-week triplet gestation who had been using the pump since 18 weeks. She had recently been increasing the frequency of bolus injections of 0.25 mg superimposed on a basal rate of 0.07 rag/hr. On admission she was found to be having fair contractions every 3 to 4 minutes. The pump was stopped, and she was begun on magnesium sulfate with a 4 gm bolus followed by 3 grn/hr in an intravenous infusion. Shortly after this she was found to have atrial fibrillation with a ventricular rate that varied between 110 and 155 beats/min. The magnesium was discontinued, and several hours after rapid digitalization she converted to a normal sinus rhythm. She is currently undelivered, on a regimen of bed rest without tocolytics. This patient had no history of heart disease. This letter is to alert others to additional cases of untoward events relating to terbutaline infusion pump therapy. Donald L. Levy, MD Eastern Virginia Medical School, Department of Obstetrics and Gynecology, 721 Fairfax Ave., Norfolk, VA 23507-1912
Preterm premature rupture, of membranes: A continuing dilemma To the Editors: We read with interest the recent paper by Mercer et al. (Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial. AM J O~sTm GYNECOL1993; 169:775-82). This is a very hnportant article, both from a medical and an economic perspective. Their data, although intriguing, is also somewhat disturbing. The authors suggest that with mature amniotic fluid index values delivery may be recommended after 32 weeks' gestation. Interestingly, however, their median gestatioual age at admission was approximately 34 weeks in both groups, and the median age at delivery was approximately 34 weeks in both
groups. We submit that delivery after 34 weeks with mature index values is not a new suggestion and in fact is protocol at many institutions. We would ask the authors to present data on those infants delivered between 32 and 33 weeks and between 33 and 34 weeks to see if their justification for intervention would still apply. Clearly, the maturity of other organ systems has to be included in this analysis, and a very crude estimate of this maturity would be comorbidides and length of stay. We think that a more critical look at the outcomes of only those infants born between 32 and 34 weeks is warranted before the authors' recommendation can be justified. John T. Rephe, MD, and DavidJ. Berck, MD Department cf Obstetrics and Gynecology, Ha~vard Medical School, Brigham and Women'sHospital, 75 Francis St., Boston, MA 02115
Reply To the Editors: We are pleased with the interest Repke and Berck have shown in our recent publication. Their comments refer to the ability to apply a subset of results to their obstetric populations. As stated in our paper, this study was designed subsequent to a review demonstrating low infant morbidity at 32 to 36 weeks' gestation in our clinical setting. T h e subanalysis requested by Repke and Berck is limited in its ability to detect significant differences and limited in power because of small sample size. Forty-five patients were recruited at -<34 weeks 0 days. No infants had intraventricular hemorrhage, hyaline membrane disease, other pulmonary complications, including pneumonia, bronchopulmonary dysplasia, or retinopathy of prematurity. This was anticipated given the study design. In spite of the smaller sample size, expectant management was associated with prolonged latency from membrane rupture to delivery (median 1.9 vs 0.8 day, p = 0.0002), randomization to delivery (median 1.4 vs 0.7 day, p = 0.01), and prolonged maternal hospitalization (median 3.4 vs 2.5 days, p = 0.03) and with threefold increase in the incidence of chorioamnionitis (17.9% vs 5.6%). With expectant management chorioamnionifis occurred before labor in 7.1% of patients (vs 10.7% intrapartum), and fetal distress was diagnosed before the onset of labor in 10.7% of patients (vs 3.6% intrapartum). Although not statistically significant in this subpopulation, these prevalences and proportions are similar to those of the overall study group. Neonatal sepsis was confined to one infant subsequent to expectant management. A diagnosis of suspected sepsis was made in 60.7% of expectantly m a n a g e d infants and 37.5% of infants randomized to immediate induction. Again the prevalences and proportions were similar to that o f the overall study. In this population 78.6% of infants received antimicrobial therapy subsequent to expectant management, whereas just 29.4% received such 1835
1836
Letters
June 1994
Am J Obstet Gynecol
therapy with immediate induction (p = 0.02). As discussed in our paper, the neonatologists' practice of"prophylaxis" subsequent to p r e t e r m delivery is important in the demonstration of differential antimicrobial therapy. No difference in the incidence o f infant treatment would be identified in centers where antimicrobial prophylaxis is given routinely for p r e t e r m infants or infants o f low birth weight. In spite o f similar survival curves, analysis did not demonstrate significant differences in neonatal hospitalization or the duration of time infants remain in hospital after maternal discharge. This is not surprising given the p values o f 0.09 and 0.08 in the original study. As Repke and Berck suggest, and as we stated in our conclusions, this stt,dy should not be extrapolated to populations with significant neonatal morbidity at these gestations or be applied to gestational ages other than those evaluated. It m i g h t be hypothesized that induction of labor will reduce infectious morbidity and antepartum fetal distress at any gestational age. It might also be suggested that a policy of expectant management will not reduce gestational age-appropriate infant morbidity because of the inherently brief latency after preterm premature rupture o f membranes before 32 weeks' gestation. However, we chose not to address these questions in this study. Given the variability of infant morbidity across the country at a given gestational age, it is important that individual centers assess gestational age-appropriate infant morbidity and mortality and their ability to care for premature infants should complications arise before implementation of a protocol such as we have described. Brian M. Mercer, BA, AID Department of Obstetricsand Gynecology, Room El02, E.H. Grump Women's Hospital, 853Jefferson Ave., Memphis, TN 38103
Fetal grasping of the umbilical cord with simultaneous fetal heart rate monitoring To the Editors: Fetal behavior in utero is being defined by ultrasonic observations. How the fetus interacts with its umbilical cord is little understood. Traumatic interaction with the umbilical cord resulting in nuchal cords, torsion, and true knots can lead to stillbirth. An unusual interaction reported by Sherer et al.~ is fetal sucking of the umbilical cord. Fetal bradycardia was not recorded during the 10 minutes of observation. It was stated that "such an event [bradycardia] might result from transient occlusion of the umbilical vessels." While we were scanning a 32-week fetus as part of the Perinatal Umbilical Cord Project, the fetus was obsewed to be grasping its umbilical cord. A simultaneous fetal heart rate recording showed a baseline of 150 beats/rain and recurrent variable decelerations (Fig. 1). Spike variables and "w" sign appeared to dominate, with the fetal heart rate becoming 100 beats/min at times. The observation period was about 5 minutes, and the fetus was stimulated to release the umbilical cord. On release, fetal hiccups began and lasted for about 3 minutes: How often this happens in utero is unknown, and the degree of variable decelerations is unknown. The ability to see in vivo the effects of cord compression as it relates to the fetal heart rate pattern is intriguing. Jason H. Collins, MD Obstetrics and Gynecology, 2259 Gause Blvd., E., St. 202, Slidell, LA 70461 REFERENCES 1. Sherer DM, Eggers PC, Smith SA, Abramowicz .IS. Fetal sticking of the umbilical cord. J Ultrasound Med 1991;10: 300. 2. Collins JH. Fetal hiccups and the umbilical ring [Letter]. AM J OBS~v:r GvNtcoI. 1991;165:1161.
Fig. 1. Fetal grasping of umbilical cord with simuhaneous fetal heart rate raonitoring.
Preterm premature rupture, of membranes: A continuing dilemma To the Editors: We read with interest the recent paper by Mercer et al. (Mercer BM, Crocker LG, Boe NM, Sibai BM. Induction versus expectant management in premature rupture of the membranes with mature amniotic fluid at 32 to 36 weeks: a randomized trial. AM J O~sTm GYNECOL1993; 169:775-82). This is a very hnportant article, both from a medical and an economic perspective. Their data, although intriguing, is also somewhat disturbing. The authors suggest that with mature amniotic fluid index values delivery may be recommended after 32 weeks' gestation. Interestingly, however, their median gestatioual age at admission was approximately 34 weeks in both groups, and the median age at delivery was approximately 34 weeks in both
groups. We submit that delivery after 34 weeks with mature index values is not a new suggestion and in fact is protocol at many institutions. We would ask the authors to present data on those infants delivered between 32 and 33 weeks and between 33 and 34 weeks to see if their justification for intervention would still apply. Clearly, the maturity of other organ systems has to be included in this analysis, and a very crude estimate of this maturity would be comorbidides and length of stay. We think that a more critical look at the outcomes of only those infants born between 32 and 34 weeks is warranted before the authors' recommendation can be justified. John T. Rephe, MD, and DavidJ. Berck, MD Department cf Obstetrics and Gynecology, Ha~vard Medical School, Brigham and Women'sHospital, 75 Francis St., Boston, MA 02115
Reply To the Editors: We are pleased with the interest Repke and Berck have shown in our recent publication. Their comments refer to the ability to apply a subset of results to their obstetric populations. As stated in our paper, this study was designed subsequent to a review demonstrating low infant morbidity at 32 to 36 weeks' gestation in our clinical setting. T h e subanalysis requested by Repke and Berck is limited in its ability to detect significant differences and limited in power because of small sample size. Forty-five patients were recruited at -<34 weeks 0 days. No infants had intraventricular hemorrhage, hyaline membrane disease, other pulmonary complications, including pneumonia, bronchopulmonary dysplasia, or retinopathy of prematurity. This was anticipated given the study design. In spite of the smaller sample size, expectant management was associated with prolonged latency from membrane rupture to delivery (median 1.9 vs 0.8 day, p = 0.0002), randomization to delivery (median 1.4 vs 0.7 day, p = 0.01), and prolonged maternal hospitalization (median 3.4 vs 2.5 days, p = 0.03) and with threefold increase in the incidence of chorioamnionitis (17.9% vs 5.6%). With expectant management chorioamnionifis occurred before labor in 7.1% of patients (vs 10.7% intrapartum), and fetal distress was diagnosed before the onset of labor in 10.7% of patients (vs 3.6% intrapartum). Although not statistically significant in this subpopulation, these prevalences and proportions are similar to those of the overall study group. Neonatal sepsis was confined to one infant subsequent to expectant management. A diagnosis of suspected sepsis was made in 60.7% of expectantly m a n a g e d infants and 37.5% of infants randomized to immediate induction. Again the prevalences and proportions were similar to that o f the overall study. In this population 78.6% of infants received antimicrobial therapy subsequent to expectant management, whereas just 29.4% received such 1835
1836
Letters
June 1994
Am J Obstet Gynecol
therapy with immediate induction (p = 0.02). As discussed in our paper, the neonatologists' practice of"prophylaxis" subsequent to p r e t e r m delivery is important in the demonstration of differential antimicrobial therapy. No difference in the incidence o f infant treatment would be identified in centers where antimicrobial prophylaxis is given routinely for p r e t e r m infants or infants o f low birth weight. In spite o f similar survival curves, analysis did not demonstrate significant differences in neonatal hospitalization or the duration of time infants remain in hospital after maternal discharge. This is not surprising given the p values o f 0.09 and 0.08 in the original study. As Repke and Berck suggest, and as we stated in our conclusions, this stt,dy should not be extrapolated to populations with significant neonatal morbidity at these gestations or be applied to gestational ages other than those evaluated. It m i g h t be hypothesized that induction of labor will reduce infectious morbidity and antepartum fetal distress at any gestational age. It might also be suggested that a policy of expectant management will not reduce gestational age-appropriate infant morbidity because of the inherently brief latency after preterm premature rupture o f membranes before 32 weeks' gestation. However, we chose not to address these questions in this study. Given the variability of infant morbidity across the country at a given gestational age, it is important that individual centers assess gestational age-appropriate infant morbidity and mortality and their ability to care for premature infants should complications arise before implementation of a protocol such as we have described. Brian M. Mercer, BA, AID Department of Obstetricsand Gynecology, Room El02, E.H. Grump Women's Hospital, 853Jefferson Ave., Memphis, TN 38103
Fetal grasping of the umbilical cord with simultaneous fetal heart rate monitoring To the Editors: Fetal behavior in utero is being defined by ultrasonic observations. How the fetus interacts with its umbilical cord is little understood. Traumatic interaction with the umbilical cord resulting in nuchal cords, torsion, and true knots can lead to stillbirth. An unusual interaction reported by Sherer et al.~ is fetal sucking of the umbilical cord. Fetal bradycardia was not recorded during the 10 minutes of observation. It was stated that "such an event [bradycardia] might result from transient occlusion of the umbilical vessels." While we were scanning a 32-week fetus as part of the Perinatal Umbilical Cord Project, the fetus was obsewed to be grasping its umbilical cord. A simultaneous fetal heart rate recording showed a baseline of 150 beats/rain and recurrent variable decelerations (Fig. 1). Spike variables and "w" sign appeared to dominate, with the fetal heart rate becoming 100 beats/min at times. The observation period was about 5 minutes, and the fetus was stimulated to release the umbilical cord. On release, fetal hiccups began and lasted for about 3 minutes: How often this happens in utero is unknown, and the degree of variable decelerations is unknown. The ability to see in vivo the effects of cord compression as it relates to the fetal heart rate pattern is intriguing. Jason H. Collins, MD Obstetrics and Gynecology, 2259 Gause Blvd., E., St. 202, Slidell, LA 70461 REFERENCES 1. Sherer DM, Eggers PC, Smith SA, Abramowicz .IS. Fetal sticking of the umbilical cord. J Ultrasound Med 1991;10: 300. 2. Collins JH. Fetal hiccups and the umbilical ring [Letter]. AM J OBS~v:r GvNtcoI. 1991;165:1161.
Fig. 1. Fetal grasping of umbilical cord with simuhaneous fetal heart rate raonitoring.