Keywords
idiopathic pulmonary fibrosis - pregnancy - respiratory failure
Idiopathic pulmonary fibrosis (IPF) is a progressive restrictive lung disease that
results from an abnormal proliferation of mesenchymal cells, varying degrees of fibrosis,
deposition of collagen and extracellular matrix, and distortion of both pulmonary
architecture and subpleural cystic airspaces.[1] Familial IPF is a rare form of chronic interstitial lung disease that is believed
to be autosomal dominant with variable penetrance.[2] The worldwide incidence of IPF is estimated to be 0.33 to 4.51 per 10,000 persons.[3]
In normal pregnancy, several changes in respiratory function occur. Functional residual
capacity decreases by approximately 20% toward the latter half of pregnancy due to
a decrease in both residual volume and expiratory reserve volume.[4] Minute ventilation at rest rises nearly 50% at term primarily due to increased tidal
volume.[5] Progesterone-induced increase in ventilation results in the “air hunger of pregnancy”
with arterial PCO2 decreasing to 27 to 32 mm Hg during pregnancy and an increase in maternal arterial
oxygen tension (PaO2) to 106 to 108 mm Hg in the first trimester and to 101 to 104 mm
Hg in the third trimester.[6]
[7] As IPF typically presents in the fourth to sixth decade of life, data on the impact
of pregnancy on IPF and maternal outcome is extremely limited.
Case
We present the case of a 35-year-old woman, gravida 1 para 0, who was referred to
the maternal fetal medicine service at our institution for management of pregnancy
with IPF. The patient's mother had previously undergone lung transplantation at the
age of 60 for IPF, thus the patient's condition was believed to be familial but without
a specific genetic etiology identified. Echocardiogram immediately prior to pregnancy
demonstrated an ejection fraction of 61% and no evidence of pulmonary hypertension.
The patient did not have an oxygen requirement and exercised 5 days per week. She
reported some shortness of breath with exertion but immediate recovery with rest.
The patient had undergone a preconception consult and was extensively counseled on
the uncertain impact of pregnancy on her pulmonary function. Her history was significant
for multiple pneumothoraces with a total of five pleurodesis procedures, a history
of a prior loop electrosurgical excision procedure of her cervix and recently diagnosed
chronic hypertension not requiring medications. Her medical and surgical history was
otherwise non-contributory. The patient's vaccination status was up to date including
three doses of the Pfizer COVID-19 vaccine.
The patient established prenatal care at 5 weeks' gestation. At that time, she had
noted the recent onset of occasional episodic desaturations but did not require oxygen
supplementation. The patient subsequently underwent a sleep study at 16 weeks' gestation
which demonstrated no requirement for supplemental oxygen. By 22 weeks' gestation,
she was taken out of work as she was requiring intermittent supplemental oxygen due
to desaturation with activity. She was placed on modified bed rest at home having
declined hospital admission at that time. Chest CT demonstrated progressive worsening
of an upper lung zone predominant parenchymal disease process with traction bronchiectasis
and fibrosis. At 26 weeks' gestation, the patient required 4 to 5 liters of oxygen
with activity but reported her oxygen requirement had been stable over several weeks.
The patient was hospitalized with acute hypoxic respiratory failure at 272/7 weeks gestation when she had an acute change in her status as evidenced by increasing
shortness of breath and episodes of oxygen desaturation as low as 80% occurring with
minimal activity.
Upon admission, the patient had a negative COVID-19 polymerase chain reaction and
viral respiratory panel. CT angiogram demonstrated a new nonspecific ground glass
lung process throughout the left and right lower lobes but no pulmonary embolism.
Betamethasone was administered for fetal lung maturity and a 2-week course of IV methylprednisolone
40 mg daily was initiated. Following multidisciplinary team review, a decision was
made to proceed with primary cesarean section at 28 weeks' gestation due to the patient's
worsening respiratory status as she then was requiring 5 L/min of oxygen at rest.
Daily fetal non-stress tests remained reassuring and the fetus was appropriately grown
with an estimated fetal weight of 1,251 g at 27 weeks + 6 days gestation, at the 66th
percentile. Magnesium sulfate was administered for fetal neuroprotection with the
approval of the patient's pulmonologist. The patient underwent an uncomplicated primary
low transverse cesarean section, and bilateral tubal ligation under epidural anesthesia.
She delivered a live born male infant weighing 1,304 g with APGARs of 4 and 8 at 1
and 5 minutes, respectively. The infant went to the NICU and had an uneventful course.
The child was discharged to home at day of life 63, intact with good prognosis. The
patient's oxygen requirement remained at 4 to 5 L/min postpartum. She received several
doses of IV furosemide postoperatively per pulmonology. The patient was discharged
home on postoperative day 6 with an oral prednisone taper. At 5 months postpartum,
she continues to be oxygen dependent with a requirement of 3 to 5 L/min despite multiple
courses of high dose prednisone. The patient's pulmonologist and lung transplant team
intend to proceed with lung transplantation if she does not demonstrate significant
improvement in the coming months.
Comment
This case report describes pregnancy in a patient with IPF, which resulted in progression
of disease and ultimate premature delivery at 28 weeks' gestation due to worsening
hypoxic respiratory failure. Delivery did not result in return of the patient's respiratory
status to baseline at 5 months postpartum and she remains oxygen dependent postpartum.
The aim of this case report is to review the outcomes of pregnancies with IPF to guide
patient counseling.
A review of the literature found few reported cases of pregnancy amongst women with
IPF, whether familial in nature or not. The first reported case of a pregnant woman
with familial IPF was in 1984.[8] The patient's pulmonary function remained unchanged until 26 weeks' gestation when
she developed progressively increasing shortness of breath ultimately requiring delivery
at 38 weeks' gestation. Similar to our case, pulmonary function did not return to
baseline and the patient remained “incapacitated by breathlessness” at 3 months postpartum.[8] Another reported case in 1985 of pregnancy in a patient with IPF diagnosed at the
age of 17 reported the patient became oxygen dependent at 15 weeks' gestation, delivered
at 37 weeks and a maternal death occurred 3 weeks postpartum following acute onset
of shortness of breath and chest pain.[9] A final cause of death was not established as the patient's family declined autopsy.
Zanutto et al also reported a maternal death in 2002 1-year postpartum following progression
of a patient's familial IPF during pregnancy.[10]
In 2020, a case was reported by Sekine et al of a pregnant woman with IPF who presented
with rapid decline in respiratory function and hypoxemia at 25 weeks' gestation.[11] Similar to our case, delivery was required at 28 weeks' gestation due to further
deterioration in the patient's pulmonary status requiring 4 L/min of oxygen not responsive
to high dose steroid therapy. The woman required lung transplantation at 26 days postpartum
due to worsening hypoxemic respiratory failure unresponsive to steroid therapy.[11] Sholapurkar et al reported a case in 1990 of pregnancy in a woman with IPF who experienced
an acute deterioration in respiratory status at 19 weeks' gestation, which also failed
to respond to steroid therapy.[12] Therefore, the decision was made to proceed with termination of pregnancy at 24
weeks due to severe maternal hypoxemia. The authors reported a marked improvement
in the patient's hypoxemic respiratory failure immediately postoperative. The patient
was treated with a prolonged 6-month course of oral steroids and she remained well
at follow-up 2.5 years later. [Table 1] summarizes the literature with regards to reported cases of IPF in pregnancy.
Table 1
Summary of reported cases of Idiopathic pulmonary fibrosis in pregnancy
|
Author
Year
|
Maternal age
|
Diagnosis
|
Gestational age at delivery
|
Outcome
|
|
Prichard and Musk
1984
|
25
|
Familial IPF
|
Increasing dyspnea noted from 26 wk, vaginal delivery at 38 wk following induction
of labor
|
The patient dialed to respond to high dose prednisolone and azathioprine postpartum
and the patient “remained incapacitated by breathlessness 3 mo later”.
|
|
Smythe et al
1985
|
31
|
IPF
|
34 wk following admission with PPROM
|
Discharged on postpartum day 6 requiring oxygen with prophylactic heparin. Maternal
death occurred at 3 wk postpartum following sudden onset of shortness of breath and
chest pain. Autopsy was declined.
|
|
Sholapurkar et al
1991
|
35
|
IPF
|
Termination of pregnancy at 24 wk gestation due to severe hypoxic respiratory failure
|
Return to near normal lung function following treatment with high dose corticosteroids.
The patient remained well with grade 1 dyspnea noted at 2.5 y postpartum.
|
|
Zanutto et al
2003
|
26
|
Familial IPF
|
Not reported[a]
|
Severe respiratory failure complicated by pulmonary arterial hypertension leading
to death 1 y postpartum.
|
|
Sekine et al
2020
|
29
|
IPF
|
Cesarean section at 28 wk following admission for worsening respiratory failure at
25 wk gestation.
|
Lung transplantation required at 26 d postpartum due to failure to respond to high
dose corticosteroids and cyclosporine with oxygen requirement of 5 L/min.
|
Abbreviations: IPF, idiopathic pulmonary fibrosis; PPROM, preterm premature rupture
of membranes.
a Unable to obtain full text for Zanutto et al.
While pregnancy does not appear to result in a rapid decline in pulmonary function
amongst patients with interstitial lung disease secondary to connective tissue disease,
our case and the few reported cases in the literature of pregnancies have demonstrated
an acute decline in respiratory status in the late second trimester of pregnancy amongst
patients with IPF.[2]
[8]
[9]
[13] Worsening hypoxemic respiratory failure amongst pregnant patients with IPF does
not appear to respond to steroid therapy based on the limited available data.[11]
[12] Unfortunately, delivery does not appear to result in return of the patient's respiratory
status to pre-pregnancy baseline.[8]
[9]
[10]
[11] The limited cases reported in the literature demonstrate a significant mortality
rate (40%) by 1 year postpartum. However, as there is only five previously published
individual case reports, we acknowledge this may be an overestimation due to publication
bias. The significant maternal morbidity and potential mortality as well as the risk
to the fetus of inheriting this condition is important information to consider when
counseling patients with IPF who are considering pregnancy. Definitive treatment of
IPF involves lung transplantation. Successful pregnancy outcome has been reported
following lung transplantation in a patient with pulmonary fibrosis.[14] However, data on pregnancy following lung transplantation is extremely limited.
To conclude, it is important for providers to be aware that data regarding pregnancy
outcomes in women with chronic interstitial lung disease due to connective tissue
disorders is not applicable to patients with IPF and that based on limited available
data, significant maternal morbidity and mortality has been reported for women with
IPF who become pregnant.
