Invited Commentary: Rare Side Effects of Obstetric Interventions: Are Observational Studies Good Enough?

Pierre Buekens

From the Department of Maternal and Child Health, School of Public Health, Rosenau Hall, CB#7400, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599–7400 (e-mail: Pierre_Buekens{at}unc.edu).

Abbreviations: FDA, Food and Drug Administration.


    INTRODUCTION
 TOP
 INTRODUCTION
 REFERENCES
 
In this issue of the Journal, Wen et al. (1Go) used an observational design to compare the side effects of vacuum extraction and forceps among babies in Quebec, Canada, who weighed between 2,500 and 4,000 g. The use of case-control and cohort designs for the general purpose of studying side effects has been recommended for more than 2 decades (2Go). The sample size of randomized trials is often not large enough to evaluate uncommon side effects of therapy. Observational studies of side effects of drugs are generally considered to be appropriate because the side effects often are not related to the indication for the therapy (3Go). For example, patients who received chloramphenicol are probably not predisposed to aplastic anemia. Another example is the development of retroperitoneal fibrosis induced by some beta-blockers (4Go). The retroperitoneal fibrosis is unrelated to the disease for which the beta-blockers were prescribed, and an observational study can thus provide an unbiased estimate of the risk of the side effect.

Unfortunately, side effects are not always independent of the indication of the intervention. Wen et al. found an increased risk of subarachnoid hemorrhage associated with vacuum extraction. The key issue here is to determine whether vacuum extraction might have been used more often in situations that would increase the risk of intracranial hemorrhage. Risk factors for intracranial hemorrhage may include a long, dysfunctional labor and the position of the fetal head in the maternal pelvis when the intervention was performed (5Go). Vacuum extraction might be associated with such risk factors because there is a tendency to attempt vacuum deliveries at stations higher than are usually attempted with forceps (6Go, 7Go). Thus, there is a possibility of residual confounding by indication.

It is also possible that vacuum extraction was used more often in hospitals with high-risk patients or by less experienced personnel. The authors acknowledge that the use of vacuum extraction or forceps may have varied substantially among institutions. They suggest that the similarity of the effects for perineal lacerations and infant cephalhematoma as estimated in their study and in randomized trials lends validity to their results. However, the risk factors for subarachnoid hemorrhage might not be identical to the risk factors for perineal tears and cephalhematoma. An analysis stratified by institution would be a first step toward adjusting the data for differences in case mix.

Another difficulty is that the diagnosis of intracranial hemorrhage is not blinded. Side effects might be reported more often if the reporting clinician were aware of a potential risk. This awareness will probably increase because the Food and Drug Administration (FDA) has recommended watching for the signs of complications in any infant in whom a vacuum-assisted delivery device was used (8Go). There is no easy solution to this problem because all babies delivered by vacuum extraction have a visible caput succedaneum, or "chignon" (8Go). The treatment thus cannot be concealed. Case-control studies are an alternative for studying side effects of interventions (2Go). They might allow more details to be collected on the diagnoses of intracranial hemorrhages and on the delivery.

It is reassuring that Wen et al. did not find any difference in neonatal in-hospital mortality between vacuum and forceps deliveries. In the United States, the FDA reported that the frequency of deaths or serious injuries among newborns on whom vacuum-assisted delivery devices were used increased from less than one per year before 1989 to an average of five per year between 1989 and 1995 (8Go). The FDA said that part, but probably not all, of the increase can be explained by an increase in usage. They based their calculation on the report of 12 deaths and nine serious injuries in 4 years. The average number of deaths was thus three per year, or about one per 100,000 vacuum deliveries. The risk is too low to be studied adequately in one state or province. Countrywide surveillance will continue to be needed.

A California study of babies weighing between 2,500 and 4,000 g found similar risks of intracranial hemorrhage with vacuum extraction, forceps, and cesarean sections performed during labor (5Go). This suggested that the morbidity associated with operative vaginal delivery was due to an underlying abnormality of labor rather than to the procedure. In the California study, subarachnoid hemorrhages were not more frequent among vacuum extractions compared with forceps. The difference in results between the California and Quebec studies is puzzling. Frequencies of subarachnoid hemorrhages among babies who delivered spontaneously were similar in the two studies, suggesting that differences in measurement were limited. One possible explanation of the difference between the California and the Quebec studies could be that, in Quebec, vacuum extractions were used more often at high pelvic stations. Data are not available to prove or disprove this hypothesis. However, it should remind us of the recommendation that when vacuum extraction is used, the same indications and prerequisites be adhered to as for any forceps delivery (7Go).

The questions raised by these studies also suggest that the use of observational designs to study uncommon side effects might be more difficult for obstetric interventions than for drugs because the side effects of such interventions are less likely to be independent of their indications and of the conditions of their use.


    NOTES
 
(Reprint requests to Dr. Pierre Buekens at this address).


    REFERENCES
 TOP
 INTRODUCTION
 REFERENCES
 

  1. Wen SW, Liu S, Kramer MS, et al. Comparison of maternal and infant outcomes between vacuum extraction and forceps deliveries. Am J Epidemiol 2001;153:103–7.[Abstract/Free Full Text]
  2. Jick H. The discovery of drug-induced illness. N Engl J Med 1977;296:481–5.[Abstract]
  3. Weiss NS. Clinical epidemiology. In: Rothman KJ, Greenland S, eds. Modern epidemiology. Philadelphia, PA: Lippincott-Raven, 1998:519–28.
  4. Vandenbroucke JP. Observational research and evidence-based medicine: what should we teach young physicians? J Clin Epidemiol 1998;51:467–72.[ISI][Medline]
  5. Towner D, Castro MA, Eby-Wilkems E, et al. Effect of mode of delivery in nulliparous women on neonatal intracranial injury. N Engl J Med 1999;341:1709–14.[Abstract/Free Full Text]
  6. Broekhuizen FF, Washington JM, Johnson F, et al. Vacuum extraction versus forceps delivery: indications and complications, 1979 to 1984. Obstet Gynecol 1987;69:338–42.[Abstract]
  7. Cunningham FG, MacDonald PC, Gant NF, et al. Williams obstetrics. 20th ed. Stamford, CT: Appleton & Lange, 1997.
  8. Office of Surveillance and Biometrics. FDA public health advisory: need for caution when using vacuum-assisted delivery devices. Rockville, MD: Food and Drug Administration, 1998.
Received for publication September 25, 2000. Accepted for publication October 2, 2000.


Related articles in Am. J. Epidemiol.:

Comparison of Maternal and Infant Outcomes between Vacuum Extraction and Forceps Deliveries
Shi Wu Wen, Shiliang Liu, Michael S. Kramer, Sylvie Marcoux, Arne Ohlsson, Reg Sauvé, and Robert Liston
Am. J. Epidemiol. 2001 153: 103-107. [Abstract] [FREE Full Text]  




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