Peripartum considerations and challenges in the management of type IV Ehlers-Danlos syndrome

Abstract

Ehlers-Danlos syndrome (EDS) is an uncommon heterogenous autosomal dominant multisystemic connective tissue disorder, which may potentially present with life-threatening emergencies. The prevalence of EDS of all subtypes is from 1 in 10 000 to 1 in 20 000. Pregnancy in women with type IV EDS poses significant challenges, necessitating the care of multidisciplinary team. Potential complications of type IV EDS include arterial dissection, arterial aneurysm, visceral rupture, excessive bleeding, tissue fragility and delayed wound healing. We present an interesting case of a pregnant woman with type IV EDS who had previous cerebrovascular complications and had a successful delivery in our tertiary centre following a collaborative approach to her care.

Background

Pregnancy in type IV Ehlers-Danlos syndrome (EDS) can be associated with significant challenges and complications. Our case report, aims to illustrate some of the peripartum and anaesthetic implications of type IV EDS.

Case presentation

A 25-year-old woman (G1, P0) was seen in the maternal medicine clinic at 12 weeks of gestation. She was diagnosed with vascular or type IV EDS due to COL3A1 gene mutation at the age of 24, following a dissection of the right vertebral artery and internal carotid artery. Her other comorbidities consisted of elastosis perforans serpiginosa, migraine and stroke 8 years previously, following left internal carotid artery and left vertebral artery dissection. She also had a history of postural orthostatic tachycardia syndrome (POTS). There was a family history of ventricular septal defects and arrhythmias in her first-degree relatives. Her partner had no comorbidities of significance.

Investigations

Recent colposcopy revealed mild dyskaryosis. Haematology investigations showed no evidence of coagulopathy and was rhesus negative. Cerebral angiography revealed right internal carotid artery dissection, 4 mm right vertebral artery aneurysm, persistent left vertebral artery dissection flap and left internal carotid artery narrowing following the previous dissection. Obstetric consultant-led multidisciplinary care was commenced after the dating scan at 13 weeks of gestation.

We held detailed discussions regarding the potential vascular complications during pregnancy and the postpartum period in EDS—that is, increased risk of aortic dissection, intestinal rupture, uterine rupture, uterine artery dissection and considerable bleeding during pregnancy and postpartum period were held. At genetic counselling, mortality and morbidity due to EDS during pregnancy and its inheritance risks, ie, 5% risk of mortality due to vascular type of EDS, risk of uterine rupture, cervical and vaginal tears, prematurity and the 50% chance of inheritance of EDS to the baby were discussed. Amniocentesis was offered, but declined by the patient. Genetic counselling for the family members was offered. Information about EDS support groups was provided. Termination of pregnancy was offered, but the patient wished to continue the pregnancy.

Obstetric plans in the foetal medicine clinic included the need for prophylactic steroids at 28 weeks due to increased risk of premature rupture of membranes (PROM). She was booked for an elective caesarean section (CS) at 36 weeks in a tertiary cardiothoracic and vascular centre, and if spontaneous labour occurred prior to this, she was to have an emergency CS.

Her regular medications, aspirin 75 mg once daily and labetalol 100 mg two times per day, were continued during the pregnancy. Serial growth scans once in every 4 weeks from 28 weeks of gestation were within normal limits and reassuring. A third trimester CT of the abdomen showed fusiform aneurysmal dilatation of the infrarenal abdominal aorta (2.5 cm) and left common iliac artery (1.8 cm) (figure 1). Therefore, at 34⁺² weeks of gestation, the patient had a planned CS under general anaesthesia. She had an uneventful lower segment CS (LSCS). Aggressive methods to minimise intraoperative blood loss was achieved by the administration of a bolus of oxytocin five international units followed by 10 international units per hour of oxytocin infusion for 4 hours and two doses of carboprost 250 microgramsintramuscularly were given 15 min apart. In addition, 1 gof intravenous tranexamic acid was administered. These measures resulted in an estimated intraoperative blood loss of 800 mL. The patient was transferred to the Intensive care unit (ICU) postoperatively. A healthy male infant weighing 2.28 kg with an APGAR Score of 9 at 1 min and 9 at 5 min was delivered. The baby was kept in special care baby unit for 4 days due to prematurity.

Figure 1.

CT of the abdomen showing fusiform aneurysmal dilatation of the infrarenal abdominal aorta.

On day 2 following the CS, the patient was transferred back to the postnatal unit. On the 3rd and 4th day after CS, she started showing signs of abdominal sepsis, with spiking temperatures, generalised abdominal pain, abdominal distension and sluggish bowel sounds. Blood cultures were taken and 1 g of intravenous meropenem was administered on an 8-hourly basis. SARS-CoV-2 PCR swabs were negative. X-ray of the chest was normal. Inflammatory markers were raised with a C reactive protein of 139, white blood cells of 18.2×10⁹/L and a normal platelet count (285×10⁹/L). Arterial blood gas on room air was normal. CT of the abdomen and pelvis showed findings suggestive of postoperative ileus. A repeat CT of the abdomen and pelvis performed on the 5th postoperative day, performed in view of failure of resolution of the abdominal signs despite the conservative management, revealed entrapment and distension of large bowel in the abdominal wall due to the dehiscence of rectus abdominis muscle. She was taken to the operating room for an emergency laparotomy and underwent a right hemicolectomy and ileostomy as the right hemicolon showed gross signs of ischaemia. Preoperative blood cultures did not show growth of any micro-organism.

Histology of the right hemicolon suggested acute ischaemic necrosis. Her postoperative stay on the ICU was complicated by hospital acquired pneumonia, wound infection, non-drainable hepatic and subhepatic abscesses and non-occlusive venous thrombus in right internal jugular and brachiocepahlic vein, which were treated conservatively with 1 g of intravenous meropenem administered 8 hourly and prophylactic enoxaparin 40 mg subcutaneously once a day was administered during her 9 days of stay on the ICU.

Outcome and follow-up

She was discharged home 14 days after the emergency laparotomy with intravenous ertapenem 1 g once a day and prophylactic enoxaparin 40 mg subcutaneously once a day for 2 weeks, to be administerd at home.

Follow-up blood investigations were normal and ultrasonography of the abdomen revealed no focal hepatic or subhepatic abscess, 2 weeks after discharge from the hospital. In addition, MRI of the heart and aorta revealed a normal heart function without any change in the aortic dimensions. Virtual outpatient consultations, due to the ongoing pandemic, were reassuring and the patient showed signs of convalescence in the community.

Discussion

EDS is a benign multisystemic autosomal dominant connective tissue disorder, which is caused by defective collagen formation.^1–3 Type IV EDS may be associated with easy bruising, arterial dilatation, aneurysm, arterial dissection/rupture, visceral perforation, poor wound healing, excessive bruising/haematomas, vascular rupture, intestinal perforation, uterine rupture and postpartum haemorrhage (PPH) requiring hysterectomy.^{4 5} Patients may pose airway challenges to the anaesthetic team due to temporomandibular joint (TMJ) dysfunction, premature spondylosis and atlanto-occiptal joint instability or subluxation.⁶

Although there are several case reports that have been published about pregnancy and type IV EDS, the majority of them have been about intra-abdominal vascular complications in these patients. We outline the salient management steps for patients with type IV EDS from preconception to the postpartum period below.

Preconception

Recognition of the type of EDS and familial genetic counselling should commence prior to conception.⁷ In patients with type IV EDS, the risk–benefits of conception and pregnancy should be weighed. These consultations provide an excellent opportunity to build rapport, enable understanding about the risks of type IV EDS such as easy bruising, arterial dilatation, aneurysm, arterial dissection/rupture, visceral perforation, visceral infarct,⁸ provide information leaflets and support groups’ information. Multiple preconception consultations may be required to ascertain the above, and therefore clinicians ought to exercise a great degree of empathy during these consultations.

First trimester

Planning for the peripartum care of the parturient should commence in the first trimester of pregnancy. A multidisciplinary referral should be made to the various stakeholders involved in the care of the patient at this stage. Careful antenatal assessment at booking will enable appropriate management during pregnancy and delivery.⁹ Routine haematological investigations including clotting profile are mandatory to ascertain the baseline parameters. However, one must be aware that the laboratory results may be within normal limits and may not be reliable at predicting the bleeding risk.¹⁰

Second trimester

Cervical incompetence and connective tissue weakness can lead to miscarriage, preterm labour (10% of pregnancies) and PROM.¹¹ Transvaginal cervical assessment to assess the cervical length would be beneficial during the second trimester. Serial growth scans once in 4 weeks from 28 weeks of gestation would be prudent in view of potential foetal growth restriction resulting from poor placental perfusion.

Third trimester and delivery

There is a high risk of having a precipitous labour with an increased risk of perineal lacerations due to increased tissue fragility in the third trimester. Attempts to minimise difficult instrumental delivery should be considered and balanced against the risk of perineal injury.^{12 13} Vaginal delivery with prompt and early episiotomy should be aimed in the absence of obstetric, vascular or musculoskeletal contraindications. Delivery should be planned in a tertiary consultant led maternity unit. Ensuring the attendance of the most senior obstetrician, anaesthetist and neonatologist is important during labour. PPH can result from defective connective tissue and capillary fragility. Robust and aggressive plans to minimise PPH should be in place.¹⁴ Ensuring the presence of large bore venous access on arrival in the delivery suite, availability of cross-matched blood and aggressive use of uterotonics could allow the clinicians to mitigate PPH.

Wound healing may be delayed and complicated by wound dehiscence. Pelvic organ prolapse can complicate the postpartum period and has been reported to occur in 15% of women.¹⁴

Anaesthetic planning and concerns

Antenatal high-risk anaesthetic assessment is essential to allow better perioperative planning and outcome in patients with type IV EDS due to the vascular complications and risk of POTS. A thorough assessment with a particular focus on the previous anaesthetic history, airway assessment, discussion about various analgesic options during labour and an anaesthetic plan for an LSCS should be discussed. Although neuraxial blockade has been used for labour and CS in some cases, there appears to be no clear recommendations about the use of neuraxial blockade during labour or CS and the specific risks of neuraxial blockade, ie, spinal and epidural haematomas in these patients’ could preclude their use.¹⁵ Operative delivery should be planned in a tertiary cardiothoracic and vascular centre which have expertise and facilities to deal with major haemorrhage.

Airway management could be challenging, particularly in women with a history of TMJ dysfunction and instability of cervical spine. Use of video laryngoscopy and fibreoptic intubation to minimise repeated airway manipulation and airway trauma should be considered. Intraoperative near patient coagulation testing or point of care testing allows appropriate management of major haemorrhage.

Preoperative cardiac imaging to assess the aortic dimensions, myocardial function and valvular pathology should be undertaken in the antenatal period. Detailed discussion about intraoperative airway management and invasive arterial±venous monitoring established under ultrasound guidance should be discussed due to increased vascular fragility,^{16 17} Intraoperative fluid loading and early use of vasopressor to minimise the possible excessive deleterious effects of vasodilatation and POTS should be done. Careful positioning intraoperatively with use of adequate padding is important to minimise any inadvertent injuries. In addition, the use of adhesive tapes and dressings requires special attention due to the skin fragility.

Need for postoperative ICU admission should form an important part of the perioperative discussions and planning.

Conclusion

The clinical management of childbearing women with EDS can be complex and challenging. A thorough preconception consultation coupled with genetic counselling, provision of access to support groups and information leaflets about the condition would allow the patients to make an informed decision. The involvement of a multidisciplinary team is crucial in formulating an individualised care plan for these patients. Provision of care should be in a tertiary cardiothoracic and vascular healthcare centre with expertise in managing sudden major blood loss.

Patient’s perspective.

I believe that I was extremely fortunate to have survived previous episodes of stroke without any major debilitating complications at such a young age. I was always keen on starting a family : fortunately, I conceived a year later following the diagnosis of my condition. I was extremely delighted and felt over the moon at this news! However, during my antenatal visits to the hospital which consisted of multiple consultations with various specialists, I was extremely petrified and worried about the outcome of my pregnancy and the impact of pregnancy on my well-being due to the underlying condition. I was provided with a volume of information by various specialists during these visits. At first, I felt extremely overwhelmed by the information provided—gradually I started to get a grip about the information provided. I took the help of the internet to gain some more knowledge about Ehlers-Danlos syndrome (EDS) and pregnancy. It was not an easy decision for me during this phase whether to continue the pregnancy or not. I was adamant to continue with the pregnancy as I had always wanted to start a family for myself and I must confess that it was not a decision made in a haste. I was very well aware of the implications of my decisions; I felt well supported during this process by the specialists in the hospital.

The rest of my pregnancy went to plan, and I did not have any issues from the pregnancy as such. In view of my enlarged aorta, I was scheduled to have a planned caesarean section (CS) at a cardiovascular hospital which had facilities to manage any untoward complication that could arise because of EDS. Before, I was sent off to sleep for the operation, there were several doctors from various specialities to look after me and my baby in the operating suite—I was made to feel special by these fantastic doctors.

Following the operation, I woke up in a sophisticated environment, surrounded by gadgets, alarms, friendly nursing and medical team on the intensive care unit (ICU). I had good pain relief when I woke up and was extremely overjoyed when I was made aware that the operation was uncomplicated. My joy had no boundaries when I saw my beautiful and adorable baby! I was shifted to my usual hospital 2 days after my CS.

I started experiencing pain in the tummy on the third day after the CS. The moment I started getting this pain, I was extremely concerned as I thought that it could be because of my enlarged aorta. I was reassured by the doctors on the ward. I had several investigations to make sure that everything was fine with my aorta and I was not getting an infection in the tummy. However, I felt extremely devastated when I was made aware that I need another visit to the operating theatre to have a larger cut on my tummy as there was a possible obstruction in my gut. I was also told of various peculiar complications of the procedure, waking up on the ICU after the operation and that I could even end up having a bag on my abdomen to relieve my bowels. The idea of having a bag to relieve by bowels was very depressing and not dignified. I felt all my dreams of having a straightforward recovery were shattered. I was finding this news extremely difficult to come to terms with; I did not want to go back to the theatre again but I suppose there were no other options for the doctors due to what was happening in my tummy.

I was rushed to the theatre for an emergency procedure. I was extremely tearful before I was sent off to sleep. The last thing I can remember is the Anaesthetist and his team telling me that I was going to be fine and that they would take good care of me along with rest of the team. The next thing I can recall is waking up in the ICU. Unlike the last time, I was not woken up a few hours after the operation. I was woken after a few days. I was kept in a medically induced coma. When I woke up, I found myself attached to all sorts of wires, tubes and the bag on my tummy. I was informed that I need to stay in the ICU for few more days, as I had developed a chest infection and I was on antibiotics. During my stay, the physiotherapists made sure that I coughed and did deep breathing exercise to get rid of the secretions from my chest. I was finally discharged from the ICU and was reunited with my baby. I felt incredibly relieved to be discharged home from the hospital on the 14th day after my emergency operation. I was sent home with some antibiotics and blood thinners.

Being home was probably the best thing that could happen to me after a roller coaster ride in the hospital. I had virtual follow-up appointments due to the ongoing pandemic and some more investigations to make sure everything was ok with my heart, liver and the aorta. I was immensely pleased to know that the doctors were happy with my overall recovery.

I would like to thank all the members who looked after me during my stay in the hospital and hope that no other person with a similar condition like me has to go through an ordeal similar to that of mine.

Learning points.

• Peripartum management of pregnant patients with type IV/vascular Ehlers—Danlos syndrome can be extremely challenging.

• Provision of care in a tertiary cardiothoracic and vascular centre with a collaborative, multidisciplinary team should be the standard of care in managing such patients.

• Peripartum management should focus on preconception counselling, genetic assessment for the family members and availability of facilities for managing peripartum massive bleeding.

Ethics statements

Patient consent for publication

Obtained.