| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Departments of Pathology, Obstetrics and Gynecology, and Medicine (Medical Genetics), University of Washington, Seattle, Washington.
Address reprint requests to: Edith Y. Cheng, MD Department of Obstetrics and Gynecology University of Washington Box 356460 1959 NE Pacific Street Seattle, WA 98195-6460 E-mail: chengels{at}u.washington.edu
 |
Abstract |
|---|
Top
 Abstract Materials and MethodsResultsDiscussionReferences |
|---|
Methods: We reviewed medical records of 1016 individuals whose cells were sent to the University of Washington Collagen Diagnostic Laboratory between 1987 and 1994 for confirmation of diagnoses of osteogenesis imperfecta. Information and neonatal records were available for 167 of those pregnancies. From those we identified method(s) of prenatal detection, delivery method, and neonatal complications, including survival and acquisition of new fractures, and related them to type of delivery.
Results: The cesarean delivery rate was 54%, most of them (53%) for nonvertex presentation and fewer than 15% because of an antenatal diagnoses of osteogenesis imperfecta. There was an unusually high rate of breech presentation at term (37%). In infants with nonlethal forms of osteogenesis imperfecta, 24 of 59 (40%) delivered by cesarean and 17 of 53 (32%) delivered vaginally had new fractures (
2 = .89; P = .3). Among 55 infants with the most severe form, 24 of 31 delivered by cesarean and 21 of 24 delivered vaginally died within 2 weeks of birth.
Conclusion: Cesarean delivery did not decrease fracture rates at birth in infants with nonlethal forms of osteogenesis imperfecta nor did it prolong survival for those with lethal forms. Prenatal diagnosis did not influence mode of delivery in most instances. Most cesarean deliveries were done for usual obstetric indications.
Osteogenesis imperfecta is a group of inherited connective-tissue disorders in which synthesis or structure of type I collagen, the major protein constituent of bone and many other connective tissues, is defective and causes osseous fragility.1,2 The clinical phenotype is broad and ranges from a mild form in which there is a moderate increase in fracture frequency, to a severe form that is lethal in the perinatal period. Based on the pattern of inheritance, age at presentation, radiologic features, and natural history, Sillence et al3 described four types of osteogenesis imperfecta, which provide the clinical framework for diagnosis. The incidence of all types is about one in 10,000 to one in 12,000, whereas the incidence of each specific type is between one in 28,500 and one in 60,000.3–5 Since the early 1980s, antenatal detection of fetuses with severe skeletal dysplasias has increased through routine ultrasound monitoring of pregnancies.6–10 Prenatal diagnosis using biochemical and molecular approaches is now available for families at increased risk for osteogenesis imperfecta.11,12
Few data-based guidelines exist for obstetric management of fetuses affected with any form of osteogenesis imperfecta. Recommendations in the literature have been based on the experience of a single or few cases, often with the nonlethal or less severe forms. In the largest published series of 16 cases of nonlethal autosomal dominant osteogenesis imperfecta, Young and Gorstein13 reported that 15 were delivered vaginally and one by cesarean. Twelve of those infants, including the one delivered by cesarean, had old and new fractures at birth. Kuller et al14 suggested that assessment of calvarial mineralization in the third trimester would help in planning the mode of delivery. Others advocated elective cesarean delivery of fetuses suspected to have more severe types or for fetuses suspected of having mild disease who had fractures in utero,15 based on the hypotheses that cesarean is more controlled and less traumatic than vaginal delivery, improves survival, and decreases morbidity. When fetuses are known to have a lethal or extremely severe form, cesarean delivery is discouraged because of increased maternal morbidity without definitive evidence of improved outcome for the neonate.16
We retrospectively assessed pregnancy characteristics, modes of delivery, and neonatal outcome for 167 pregnancies in which the diagnoses of osteogenesis imperfecta were made perinatally.
|
Materials and Methods |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Biochemical studies of cultured dermal fibroblasts or cells cultured from chorionic villi were performed as previously described.17,18 Diagnoses of osteogenesis imperfecta type I were made when cultured cells produced half the amount of normal type I collagen and no abnormal molecules. Diagnoses of types II, III, and IV were made when cultured cells synthesized structurally abnormal and normal type I collagen molecules.18 No specific biochemical or molecular findings reliably distinguish among these three types, so the disease was categorized on clinical grounds.
Statistical tests for significance using 2 (or Fisher exact test where appropriate) were made for comparisons between type of delivery and prenatal diagnosis of osteogenesis imperfecta, and differences in fracture rate between infants delivered vaginally and by cesarean. For the prevalence of breech presentation and cesarean frequencies, 95% confidence intervals were constructed using binomial distribution.
|
Results |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
). Infants with the most severe types were most likely to be recognized prenatally because the morphologic changes to the bones were apparent by 20 weeks’ gestation. The only infant with osteogenesis imperfecta type I recognized prenatally had bowing of both femurs on a routine ultrasound at 24.5 weeks. For infants delivered at or near term, gestational age at prenatal diagnosis ranged from 14–38 weeks. Although 90 of 167 infants were delivered by cesarean, only 22 of 90 were known to be affected before delivery, suggesting that prenatal diagnosis of affected fetuses was only one reason for cesarean delivery. Osteogenesis imperfecta type II was the only diagnosis in which prenatal diagnosis appeared to diminish the likelihood of delivery by cesarean delivery, but that relationship was not statistically significant.
|
). About one third were delivered by cesarean for obstetric indications such as fetal distress, failure to progress, or previous cesarean, but the most common indication for surgical delivery was nonvertex presentation (Table 2). Overall frequency of malpresentation at term was 46 of 120 (38%) of which 44 infants (37%, Table 3) were breech.
|
|
2 = .89; P = .3). There was only one case in which prenatal suspicion of osteogenesis imperfecta did not lead to cesarean delivery, but there was no neonatal information about fractures. In other cases delivered by cesarean in which there was prenatal suspicion of osteogenesis imperfecta, all but one infant was delivered because of breech presentation, and all but two infants (one in type I and one in type III) had new and multiple fractures at delivery. Among infants with the most severe form of osteogenesis imperfecta, 31 were delivered by cesarean and 24 vaginally. Ten of the infants delivered surgically died within 24 hours of birth, seven died within the first week of life, seven within the second week of life, and one each after 3 and 4 weeks. Information was not available on four infants. Of the 24 infants delivered vaginally, 15 died during the first day, three more within the first week, three more within the second week, and one at 2.5 months. Information was not available on two infants. All infants received some form of ventilatory support. |
Discussion |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Several studies reported a high incidence of breech presentation (corrected for gestational age) for infants with congenital anomalies or neuromuscular disorders.18,19 The high rate of malpresentation in this study underscores the importance of excluding congenital anomalies in fetuses with malpresentation at term. The reasons are not clear for failure of anomalous fetuses to rotate from nonvertex to vertex in the third trimester. In osteogenesis imperfecta, particularly the more severe types, failure to rotate might be related to accommodation of the uterus to the disproportionately larger head, small thorax, and short, bowed extremities of an already breech fetus or to decreased mobility of fetuses with small fractured extremities.
Malpresentation at labor, rather than diagnosis, was the major indication for cesarean delivery. One limitation in the assessment of the frequency of nonvertex presentation of these affected infants was the extent to which the 167 pregnancies analyzed are representative of the entire cohort. There were an additional 295 individuals for whom we had no pregnancy-related data. However, even if all infants had been delivered vaginally and had vertex presentations, the rates of cesarean delivery and breech presentation would still be higher than the normal population rates.
One of the most important issues in counseling parents of fetuses suspected of having osteogenesis imperfecta is whether cesarean delivery improves survival and decreases morbidity for the infant. In this study, we did not find that cesarean delivery decreased new fractures for infants with the nonlethal forms of osteogenesis imperfecta. Our analysis was limited by the small number of cases with adequate neonatal information, lack of neonatal details regarding fractures, and the difficulty in diagnosing old fractures versus new fractures in the immediate neonatal period. There might be reporting bias in that physicians might be more likely to chart and report the severe cases in which cesarean delivery would have had little impact in reducing the number of fractures. In the mild forms, where fractures are infrequent, cesarean delivery might give little protection against fractures. Antenatal knowledge of osteogenesis imperfecta was the least common indication for cesarean delivery, so a protective effect of cesarean delivery could be masked by the maneuvers of a routine cesarean, which is not without forceful pushing and squeezing of the infant out of the uterus in a very short period of time; physicians might be more cautious if they suspected an affected fetus.
Counseling parents with fetuses suspected of having osteogenesis imperfecta requires information about expected outcome and the effect of mode of delivery on fetal and maternal morbidity. If a severe but nonlethal form of osteogenesis imperfecta is suspected, delivery in a tertiary center is recommended. Method of delivery should be based on obstetric considerations and risks for the fetus and mother. If vaginal delivery is chosen, instrumentation probably should be minimized with the most severely affected fetuses to avoid intracranial trauma. Cesarean delivery has a mortality rate of 6.1–22 per 100,000 live births, which is several times greater than that of vaginal delivery.20,21 Maternal morbidity includes intraoperative damage to bowel, bladder, and ureter, and infection. Subsequent pregnancies that undergo a trial of labor are subject to an approximate 1% risk of intrapartum uterine rupture.22 Cesarean delivery might not protect against fractures in infants with the mild forms of osteogenesis imperfecta, so physicians should consider reserving this procedure for the usual obstetric complications in these pregnancies.
|
Footnotes |
|---|
Received February 14, 2000. Received in revised form August 8, 2000. Accepted September 28, 2000.
|
References |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
2. Byers PH. Osteogenesis imperfecta. In: Royce PM, Steinmann B, eds. Connective tissue and its heritable disorders. Molecular, genetic and medical aspects. New York: Wiley-Liss, 1993:317–50.
3. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 1979;16:101–16.[Abstract]
4. Orioli IM, Castilla EE, Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genet 1986;23:328–32.[Abstract]
5. Andersen PE Jr, Hauge M. Osteogenesis imperfecta: A genetic, radiological, and epidemiological study. Clin Genet 1989;36:250–5.[Medline]
6. Chervenak FA, Romero R, Berkowitz RL, Mahoney MJ, Tortora M, Mayden K, et al. Antenatal sonographic findings of osteogenesis imperfecta. Am J Obstet Gynecol 1982;143:228–30.[Medline]
7. Hobbins JC, Bracken MB, Mahoney MJ. Diagnosis of fetal skeletal dysplasias with ultrasound. Am J Obstet Gynecol 1982;142:306–12.[Medline]
8. Thompson EM, Young ID, Hall CM, Pembrey ME. Genetic counselling in perinatally lethal and severe progressively deforming osteogenesis imperfecta. Ann N Y Acad Sci 1988;543:142–56.[Medline]
9. Thompson EM. Non-invasive prenatal diagnosis of osteogenesis imperfecta. Am J Med Genet 1993;45:201–6.[Medline]
10. Lachman RS. Fetal imaging in the skeletal dysplasias: Overview and experience. Pediatr Radiol 1994;24:413–7.[Medline]
11. Pepin M, Atkinson M, Starman BJ, Byers PH. Strategies and outcomes of prenatal diagnosis for osteogenesis imperfecta: A review of biochemical and molecular studies completed in 129 pregnancies. Prenat Diagn 1997;17:559–70.[Medline]
12. Raghunath M, Steinmann B, Delozier-Blanchet C, Extermann P, Superti-Furga A. Prenatal diagnosis of collagen disorders by direct biochemical analysis of chorionic villus biopsies. Pediatr Res 1994;36:441–8.[Medline]
13. Young BK, Gorstein F. Maternal osteogenesis imperfecta. Obstet Gynecol 1968;31:461–70.
14. Kuller J, Bellantoni J, Dorst J, Hamper U, Callan N. Obstetric management of a fetus with nonlethal osteogenesis imperfecta. Obstet Gynecol 1988;72:477–9.[Medline]
15. Marini JC. Osteogenesis imperfecta: Comprehensive management. Adv Pediatr 1988;35:391–426.[Medline]
16. Brons JT, van der Harten HJ, Wladimiroff JW, van Geijn HP, Dijkstra PF, Exalto N. Prenatal ultrasonographic diagnosis of osteogenesis imperfecta. Am J Obstet Gynecol 1988;159:176–81.[Medline]
17. Bonadio J, Holbrook KA, Gelinas RE, Jacob J, Byers PH. Altered triple helical structure of type I procollagen in lethal perinatal osteogenesis imperfecta. J Biol Chem 1985;260:1734–42.
18. Wenstrup RJ, Willing MC, Starman BJ, Byers PH. Distinct biochemical phenotypes predict clinical severity in nonlethal variants of osteogenesis imperfecta. Am J Hum Genet 1990;46:975–82.[Medline]
19. Braun FH, Jones KL, Smith DW. Breech presentation as an indicator of fetal abnormality. J Pediatr 1975;86:419–21.[Medline]
20. Petitti DB. Maternal mortality and morbidity in cesarean section. Clin Obstet Gynecol 1985;28:763–9.[Medline]
21. Sachs BP, Yeh J, Acker D, Driscoll S, Brown DA, Jewett JF. Cesarean section-related maternal mortality in Massachusetts, 1954–1985. Obstet Gynecol 1988;71:385–8.[Medline]
22. Leung AS, Farmer RM, Leung EK, Medearis AL, Paul RH. Risk factors associated with uterine rupture during trial of labor after cesarean delivery: A case-control study. Am J Obstet Gynecol 1993;168:1358–63.[Medline]
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
