Reproduction and Pregnancy

Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia

This report, conducted by 13 multidisciplinary international experts intends to outline the best practices in prenatal evaluation and delivery of patients with skeletal dysplasia.

Depending on inheritance characteristics, adults with skeletal dysplasia may pass the trait on to their offspring, requiring special precautions. In addition, pregnant women with skeletal dysplasia may face physical limitations due to their own condition where there is potential for increased risk.

These issues, combined with the individual rarity of these conditions, make it paramount that pregnancies are uniformly assessed and managed in facilities that are aware of these potential complications, and have the capacity and resources to anticipate and manage them effectively. These guidelines aim to raise awareness of these risks among relevant perinatal health professionals, and assist them in optimising healthy pregnancies for both mother and child.

This report, conducted by a panel of 13 multidisciplinary international experts intends to outline the best practices in prenatal evaluation and delivery of patients with skeletal dysplasia.

Increased Risk of Pregnancy

The increased risk of pregnancy in these situations is related to multiple factors, such as cardiopulmonary and musculoskeletal considerations in pregnant women with skeletal dysplasia, and potential instability of the cervical spine in suspected fetal skeletal dysplasia.

Guidelines for Prenatal Evaluation and Delivery of Patients with Skeletal Dysplasia

A group of international experts participated in a Delphi process (a study method based on the results of multiple rounds of questionnaires sent to a panel of experts), which comprised consideration of thorough literature review and a list of 54 possible care recommendations subject to 2 rounds of anonymous voting and a face-to-face meeting. After the first round and meeting, consensus was reached to support 42 recommendations (see Table 1). These recommendations are guidelines for the evaluation and treatment of pregnant women with skeletal dysplasia and for the unborn child with or suspected skeletal dysplasia. Recommendations with more than 80% agreement were considered as consensual and are presented in Table 1:

Table 1 - Second-round statements with ≥80% of agreement – Recommended Guidelines	Strongly agree	Agree	Neutral	Disagree	Strongly disagree
1. Preconception genetic counseling is recommended for individuals and/or partners who have skeletal dysplasia or are at increased chance of having fetus with skeletal dysplasia	84.6%	15.4%	0	0	0
2. Preconception medical evaluation is recommended to consider factors that may impact safety of pregnancy, mode of delivery, and anesthetic management (eg, airway, cardiopulmonary status, and neuraxial and musculoskeletal structure and function)	84.6%	15.4%	0	0	0
3. Standard recommendations for weight gain during pregnancy are not applicable to women with skeletal dysplasia	38.5%	61.5%	0	0	0
4. Women with skeletal dysplasia are not at higher risk for preterm labor (24–37 wk of gestation), but may need delivery prior to term	50%	50%	0	0	0
5. Careful attention to fluid management in women with skeletal dysplasia is required to avoid fluid overload in peripartum period	69.3%	30.7%	0	0	0
6. In women with skeletal dysplasia, standard management of preterm labor may need to be modified	53.8%	38.5%	7.7%	0	0
7. Anatomical differences in women with skeletal dysplasia increase risk of general and regional anesthesia during pregnancy and delivery, and require advanced planning when possible	100%	0	0	0	0
8. Management of delivery should be discussed early in pregnancy, including location, mode of delivery, anesthetic options, and perinatal care to optimize maternal and fetal outcomes	92.3%	7.7%	0	0	0
9. Newborns with skeletal dysplasia may require immediate specialized medical management	69.2%	30.8%	0	0	0
10. Women with skeletal dysplasia characterized by short trunk should be identified as they are at higher risk during pregnancy for cardiopulmonary complications, maternal complications, and preterm delivery	92.3%	7.7%	0	0	0
11. In pregnant women with skeletal dysplasia, vigilance is required as increasing fundal height may adversely affect maternal cardiopulmonary and musculoskeletal status	84.6%	15.4%	0	0	0
12. Pelvic anatomy in most women with skeletal dysplasia precludes vaginal delivery, and cesarean delivery is recommended	69.2%	30.7%	0	0	0
13. Woman with skeletal dysplasia can have cesarean delivery with Pfannenstiel skin incision and low transverse uterine incision	61.5%	38.5%	0	0	0
14. Prenatal diagnosis of suspected fetal skeletal dysplasia is important in terms of pregnancy management and counseling	84.6%	15.38%	0	0	0
15. Pregnancies in which there is suspected fetal skeletal dysplasia should be referred to appropriate centers with high-level ultrasound expertise and expert evaluation	76.9%	23.1%	0	0	0
16. Pregnancies in which there is suspected fetal skeletal dysplasia should be referred to appropriate high-risk maternal fetal medicine/perinatal medicine specialists for management or recommendations for management	76.9%	23.1%	0	0	0
17. Counseling of couple with suspected skeletal dysplasia should include discussion of possible therapies/new treatments	38.5%	61.5%	0	0	0
18. If possible, instrumentation during delivery should be avoided when fetal skeletal dysplasia is suspected due to increased risk of intracranial and cervical spine complications	69.2%	23.1%	7.7%	0	0
20. Incidence of fractures in children with prenatal diagnosis of osteogenesis imperfecta is not decreased by cesarean delivery	30.8%	69.3%	0	0	0
21. As modes of inheritance vary among skeletal dysplasias, establishing correct diagnosis and individualized preconception genetic counseling are important	92.3%	7.7%	0	0	0
22. Prenatal genomic test results need to be ordered and interpreted by qualified expert and must be correlated with clinical findings	92.3%	7.7%	0	0	0
23. Increased nuchal translucency at 10–14 wk of gestation can be sign of severe skeletal dysplasia	15.4%	84.6%	0	0	0
24. Most likely time in pregnancy to detect features of skeletal dysplasia is 18–20 wk of gestation	0	100%	0	0	0
26. Most severe skeletal dysplasias are detected at routine ultrasound performed at 18–20 wk of gestation	23.1%	76.9%	0	0	0
27. Nonlethal skeletal dysplasia may not be evident by ultrasound until ≥28 wk of gestation	92.3%	7.7%	0	0	0
28. Some types of skeletal dysplasia may not be evident until birth	92.3%	7.7%	0	0	0
29. Ultrasonography remains main imaging modality to diagnose suspected prenatal skeletal dysplasias	76.9%	23.1%	0	0	0
30. Plain radiographs are not helpful refining diagnosis of suspected skeletal dysplasias	30.8%	69.2%	0	0	0
31. Low-dose CT scanning can be helpful refining diagnosis of suspected skeletal dysplasias	0	92.3%	7.7%	0	0
32. 3D ultrasonography can be helpful refining diagnosis of suspected prenatal skeletal dysplasias	30.8%	69.2%	0	0	0
33. Prenatal MRI scanning can be helpful refining diagnosis of suspected skeletal dysplasias	23.1%	76.9%	0	0	0
34. Determining predictive factors of lethality is important in assessment of prenatal suspected skeletal dysplasia	92.3%	7.7%	0	0	0
35. Key predictors of lethality at 18–20 wk of gestation ultrasound are: – Chest to abdomen ratio <0.6; – Femur length to abdominal circumference ratio <0.16; – Femur length to biparietal diameter – Micromelia 3 SD below mean – Hydrops – Severely decreased mineralization of axial skeleton	100%	0	0	0	0
36. Finding of femur length 5th percentile for gestational age during 18- to 22-wk ultrasound warrants further evaluation	92.3%	7.7%	0	0	0
37. Fetal DNA obtained for genetic testing should be retained for further evaluation until correct diagnosis is established	69.3%	30.7%	0	0	0
38. Postmortem evaluation is recommended for fetuses from pregnancies terminated due to suspected skeletal dysplasia	61.5%	38.5%	0	0	0
39. All newborns with suspected skeletal dysplasia should be evaluated as soon as practical after delivery, regardless of previous diagnosis or prognosis	69.3%	30.7%	0	0	0
40. If fetal skeletal dysplasia is suspected but specific diagnosis is not known at birth, referral to specialist center for diagnostic assessment and management is recommended	92.3%	7.7%	0	0	0
41. If specific skeletal dysplasia diagnosis is known at birth, then appropriate management should be instituted	76.9%	15.4%	7.7%	0	0
42. Postnatal skeletal surveys are helpful in diagnosis of skeletal dysplasia	69.3%	30.7%	0	0	0

Considerations for newborns with skeletal dysplasia:

• All newborns with suspected skeletal dysplasia should be evaluated as soon as practical after delivery, regardless of previous diagnosis or prognosis.

• If fetal skeletal dysplasia is suspected but a specific diagnosis is not known at birth, referral to a specialist center for diagnostic assessment and management is recommended.

• If a specific skeletal dysplasia diagnosis is known at birth, then appropriate management should be instituted.

• Postnatal skeletal surveys are helpful in the diagnosis of skeletal dysplasia.

Conclusions

• Consensus-based best practice guidelines are provided as a minimum of standard care to minimize associated health risks, and improve clinical outcomes for patients with skeletal dysplasia.

• Pregnant women and unborn foetuses with skeletal dysplasia present unique concerns. Due to the relative rarity of these conditions individually, many centers have little or no experience with the pitfalls that may exist when caring for this group.

• In general, prenatal evaluation and delivery care should be performed by appropriately experienced personnel.

• For the pregnant mother with skeletal dysplasia, thorough preconception genetic counseling, pregnancy evaluation, and discussion of management of delivery are recommended.

• For the foetus with suspected skeletal dysplasia, this panel recommends diagnostic assessment through prenatal genomic tests and imaging through ultrasonography and MRI imaging, parental counseling, and appropriate postnatal management

For the full report click here:

Source: 
Savarirayan R, et al; Skeletal Dysplasia Management Consortium. Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia. Am J Obstet Gynecol. 2018 Dec;219(6):545-562. doi: 10.1016/j.ajog.2018.07.017. Epub 2018 Jul 23. PMID: 30048634.