
==== Front
Perm J
tpj
tpj
The Permanente Journal
1552-5767
1552-5775
The Permanente Press

38980766
10.7812/TPP/23.168
TPJ-23-168
Evidence-Based Case Report
Multidisciplinary Management of Pregnancy in Patients With Osteogenesis Imperfecta Type 3
https://orcid.org/0009-0001-7798-1367
Partani Ekta MD 1
Stephenson Megan L MD 2
1 Department of Obstetrics and Gynecology, Kaiser Permanente, Santa Clara, CA, USA
2 Department of Maternal-Fetal Medicine, Kaiser Permanente, Santa Clara, CA, USA
Ekta Partani, MD ekta.x.partani@kp.org
2024
24 6 2024
28 3 190193
© 2024 The Authors.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Published by The Permanente Federation LLC under the terms of the CC BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.

Keywords:

obstetrics
osteogenesis imperfect
antepartum
intrapartum
==== Body
pmcIntroduction

Osteogenesis imperfecta (OI), also known as “brittle bone” disease, is a genetic disorder that affects the production of type 1 collagen.1 The genes involved in most cases are the COL1A1 and COL1A2 genes, which code for type 1 collagen alpha chains.1,2 However, mutations in 18 other genes have also been associated with OI.1,2 A common classification system based on phenotypic characteristics and mode of inheritance has been described by Sillence et al and Shapiro et al,1,3,4 classifying OI from type 1 through 6.1 Type 3 is considered the most severe form of OI in those who survive past infancy and is characterized by severe bone fragility, early onset scoliosis, frontal bossing, and extremely short stature. Inheritance can be autosomal dominant, autosomal recessive, or dominant negative and involves both qualitative and quantitative defects in type 1 collagen.1,5 Although the overall incidence of OI is 1 in 15,000 to 20,000 births, the incidence of type 3 is noted to be 1 in 70,000.5,6

Pregnancies complicated by maternal OI are associated with increased maternal and neonatal risks. Compared to the general population, pregnant patients with OI are at increased risk of postpartum hemorrhage, need for blood transfusion, antenatal and postpartum fractures, diabetes mellitus, need for cesarean delivery, Neonatal Intensive Care Unit admissions, and neonatal morbidity.7 Although patients with OI type 3 often survive to adulthood, and fertility is preserved in these patients, very few reports have been published about pregnancies complicated by maternal OI type 3.6

The authors present the case of a 36-year-old primigravid patient with OI type 3 who was managed via a multidisciplinary approach involving maternal-fetal medicine, anesthesiology, general obstetrics and gynecology, and genetics during her pregnancy. Her pregnancy resulted in a live-born female infant, unaffected by OI, who was delivered via cesarean section at term.

Case Presentation

The authors present the case of a 36-year-old primigravida with OI type 3 (heterozygote for COL1A2 c.1378G < A/ p.Gly460Ser) who presented to prenatal care at 9 weeks 4 days with a spontaneously conceived pregnancy. At the time of presentation, the patient was noted to be 119.38 cm tall and 33.1 kg with a body mass index of 22.

Her past medical history was notable for multiple fractures, including femur fractures, during her childhood and adolescence for which she has had multiple orthopedic surgical procedures and severe thoracolumbar scoliosis status post placement of Harrington rods and spinal fusion to L4. She denied any active pulmonary or cardiac issues. Her medications at the time of presentation included alendronate 40 mg daily. Baseline transthoracic echo done a year prior to conception was notable for dextrocardia but was otherwise within normal limits, with a left ventricular ejection fraction of 60%–65%. Baseline pulmonary function testing demonstrated normal lung volume with mildly decreased diffusion capacity. Several months prior to presenting for prenatal care, the patient had undergone preconception counseling with a maternal-fetal medicine physician.

Treatment

The patient was followed throughout her pregnancy by both a general obstetrics-gynecology and a maternal-fetal medicine physician. At 12 weeks 2 days, patient underwent chorionic villus sampling that was negative for familial COL1A2. Detailed anatomy ultrasound at 20 weeks 2 days revealed an appropriately grown singleton fetus (estimated fetal weight 13th percentile and abdominal circumference 22nd percentile) with normal anatomy. The patient was followed throughout the remainder of her pregnancy with serial growth scans every 4 weeks. At 32 weeks 6 days, growth ultrasound revealed fetal growth restriction with an estimated fetal weight and abdominal circumference in the 6th percentile with normal umbilical artery Dopplers and amniotic fluid volume. Thus, fetal surveillance was increased to weekly fetal nonstress testing, umbilical artery Doppler, and amniotic fluid measurement and growth ultrasounds every 3 weeks. The patient was counseled about delivery at 38–39 weeks in the setting of fetal growth restriction with normal umbilical artery Dopplers. She was also counseled that given her diagnosis of OI type 3 the recommended mode of delivery would be via cesarean section. During the third trimester, the patient also underwent a preoperative consultation with anesthesiology where the possibility of attempting a spinal prior to her cesarean section was discussed. However, given the patient’s surgical history and severe scoliosis, it was also discussed that if unable to achieve neuraxial anesthesia, the patient would require general endotracheal intubation.

Patient Outcome

At 38 weeks 3 days, the patient presented to labor and delivery for her scheduled cesarean section. Prior to positioning the patient for surgery, attempts were made to place spinal anesthetic but were ultimately unsuccessful. Decision was made to proceed with general endotracheal intubation. The patient was carefully placed in a dorsal supine position with a leftward tilt. General anesthesia was achieved without complications. She underwent an uncomplicated cesarean delivery of a live female infant with Apgar scores of 8 and 9 at 5 minutes and 10 minutes respectively. Total blood loss from surgery was 400 mL. Just prior to transferring the patient out of the operating room, a transverse abdominis plane block was performed by the anesthesia provider.

The patient’s inpatient postoperative course was notable for a new diagnosis of gestational hypertension for which the patient was started on nifedipine 30 mg daily initially but switched to labetalol 100 mg every 8 hours at the time of discharge due to a brief episode of hypotension and tachycardia. By postoperative day 2 the patient was meeting all postoperative milestones and was deemed stable for discharge.

Discussion

The case above is one of the few describing pregnancy in a patient with OI type 3.6,8 This case highlights the importance of multidisciplinary management of these patients with involvement from genetics, anesthesia, maternal-fetal medicine, and obstetrics.

Preconception and prenatal genetic counseling are vital parts of care for patients affected by OI. As in the case of this patient, 90% of OI tends to be a result of autosomal dominant mutations in COL1A1, COL1A2, and IFTM5 genes.9 These patients should be counseled that they have a 50% chance of having a child affected by OI. Although the patient in this case conceived spontaneously, patients with OI who are undergoing conception via in vitro fertilization should be counseled about the option of in vitro fertilization with donor germ cells/embryos and preimplantation genetic testing.9

For patients who choose to use their own embryos, preimplantation genetic testing for monogenic/single gene defects, which can be used to screen for monogenic diseases, can be performed. With this form of testing the blastocyst would undergo genetic testing for OI in the hopes that a blastocyst without the genetic mutation could be transferred during the in vitro fertilization cycle.9 Patients should be counseled that even with the estimated accuracy of preimplantation genetic testing being 95%–99.6% there is still a small chance for error.9

During the prenatal period, patients should undergo counseling about the screening and diagnostic testing that is available. Screening tests that are offered to all pregnant patients, such as noninvasive prenatal screening or cell-free DNA testing and quadruple screening tests, do not specifically look at likelihood for OI in the fetus. For patients whose primary concern is fetal risk for OI, invasive diagnostic testing can help elucidate this information. The patient in the case above met with a genetic counselor to review options for diagnostic testing with either amniocentesis or chorionic villus sampling. Both chorionic villus sampling and amniocentesis would allow for sampling of fetal DNA.9 The patient in this case opted for chorionic villus sampling with array comparative genomic hybridization and testing for familial COL1A2 to assess for fetal risk of OI.

Patients with OI are at higher likelihood for antenatal, intrapartum, and neonatal complications such as hemorrhage, intrauterine growth restriction, preterm birth, and placenta abruption.6,10 Thus this patient was followed throughout this pregnancy by a maternal-fetal medicine provider with close antenatal surveillance, which was notable for intrauterine growth restriction diagnosed at 32 weeks. A common dilemma when managing pregnancies in patients with OI type 3 is mode of delivery. The literature demonstrates that in patients with moderate to severe OI, such as the patient in this study, there are increased rates of cesarean delivery.6 Much of the data on mode of delivery focuses primarily on pregnancies that are complicated by fetuses with OI, and very little data exists for recommendations on mode of delivery in pregnancies complicated by severe maternal OI. Review of the case reports on maternal OI type 3 demonstrates that cesarean delivery is most commonly chosen due to fetal malpresentation, cephalopelvic disproportion, maternal skeletal deformities, or desire to decrease maternal fracture likelihood.8,11

Given that many of these patients will likely deliver via cesarean section, patients should be counseled about the anesthetic complications that accompany OI type 3. As in the case above, neuraxial anesthesia may be difficult to obtain in the event of severe scoliosis or multiple spinal surgical procedures. Patients should be counseled about the likelihood of needing general anesthesia. However, it should be noted that patients with OI are at increased likelihood of mandibular fractures, odonto-axial dislocations, and malignant hyperthermia with general endotracheal intubation.11,12 Lastly, patients with OI type 3 are also at high risk for fractures due to positioning during surgery and blood pressure cuff inflation.12 Thus, great caution should be taken to ensure that the patient is well padded during the procedure and that care is taken with blood pressure measurements.12

Conclusion

The case above is one of few that describe pregnancy in a patient with OI type 3. As illustrated above, these patients are successfully able to carry a pregnancy to term, but these pregnancies carry significant risk for antenatal, intrapartum, anesthetic, and postpartum complications. Patients with OI type 3 should receive thorough counseling during the preconception period and throughout pregnancy, addressing topics such as genetic screening and diagnostic testing, antenatal fetal monitoring, intrapartum and postpartum complications, intrapartum anesthesia, and mode of delivery. These patients are best managed by a multidisciplinary approach to ensure the best maternal and fetal outcomes and appropriate management of any complications that may arise.

Author Contributions: Ekta Partani, MD, and Megan L Stephenson, MD, were responsible for the authorship, editing, and final approval of the manuscript.

Conflicts of Interest: None declared.

Funding: None declared.

Consent: Written consent for publication was obtained from the patient.

Relevancy Statement: This case report emphasizes the importance of a team-based approach to care for pregnant patients with osteogenesis imperfecta Type 3 who are at high risk for multiple anesthetic, maternal, and neonatal complications. Multidisciplinary management plays an important role in the minimizing the risks in these pregnancies and to improve outcomes.
==== Refs
References

1. Subramanian S , Viswanathan VK . Osteogenesis Imperfecta. In: StatPearls. StatPearls Publishing; 2022. Accessed February 2023. www.ncbi.nlm.nih.gov/books/NBK536957
2. Tauer JT , Robinson M-E , Rauch F . Osteogenesis imperfecta: New perspectives from clinical and translational research. JBMR Plus. 2019;3 (8 ). 10.1002/jbm4.10174
3. Shapiro F . Consequences of an osteogenesis imperfecta diagnosis for survival and ambulation. J Pediatr Orthop. 1985;5 (4 ):456–462. 10.1097/01241398-198507000-00014 4019761
4. Sillence D . Osteogenesis imperfecta: An expanding panorama of variants. Clin Orthop Relat Res. 1981;159 :11–25.7285446
5. Forlino A , Cabral WA , Barnes AM , Marini JC . New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011;7 (9 ):540–557. 10.1038/nrendo.2011.81 21670757
6. Kawakita T , Fries M , Singh J , Al-Kouatly HB . Pregnancies complicated by maternal osteogenesis imperfecta type III: A case report and review of literature. Clin Case Rep. 2018;6 (7 ):1252–1257. 10.1002/ccr3.1549 29988651
7. Rao R , Cuthbertson D , Nagamani SCS , et al. Pregnancy in women with osteogenesis imperfecta: Pregnancy characteristics, maternal, and neonatal outcomes. Am J Obstet Gynecol MFM. 2021;3 (4 ):100362. 10.1016/j.ajogmf.2021.100362 33781976
8. Sharma A , George L , Erskin K . Osteogenesis imperfecta in pregnancy: Two case reports and review of literature. Obstet Gynecol Surv. 2001;56 (9 ):563–566. 10.1097/00006254-200109000-00022 11524621
9. Zhytnik L , Simm K , Salumets A , Peters M , Märtson A , Maasalu K . Reproductive options for families at risk of osteogenesis imperfecta: A review. Orphanet J Rare Dis. 2020;15 (1 ). 10.1186/s13023-020-01404-w
10. Ruiter-Ligeti J , Czuzoj-Shulman N , Spence AR , Tulandi T , Abenhaim HA . Pregnancy outcomes in women with osteogenesis imperfecta: A retrospective cohort study. J Perinatol. 2016;36 (10 ):828–831. 10.1038/jp.2016.111 27442154
11. Porsborg P , Astrup G , Bendixen D , Lund AM , Ording H . Osteogenesis imperfecta and malignant hyperthermia: Is there a relationship? Anaesthesia. 1996;51 (9 ):863–865. 10.1111/j.1365-2044.1996.tb12619.x 8882252
12. Yan M , Knowland NP , Lien D . The anesthetic management of a parturient with osteogenesis imperfecta type I undergoing cesarean delivery. Cureus. 2021;13 (3 ). 10.7759/cureus.13849
