Heart Sci J 2022; 3(4): 35-39
Contents list available at www.heartscience.ub.ac.id

Heart Science Journal
Journal Homepage : www.heartscience.ub.ac.id

Case Report

Idiopathic Pulmonary Arterial Hypertension Newly Diagnosed in
Pregnancy with Anemia and Threatened Preterm Labor
Stefani Harumsari1*, Bambang Rahardjo2, Nugrahanti Prasetyorini2, Pande Made Dwijayasa2,
Valerinna Yogibuana Swastika Putri3, Mohammad Saifur Rohman3
Resident of Obstetrics and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.
3
Brawijaya Cardiovascular Research Center, Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia..
1
2

ARTI C LE I NFO

AB STR A C T

Keywords:
Idiopathic Pulmonary Arterial
Hypertension;
Pulmonary Hypertension;
Pregnancy;
Anemia;
Preterm Premature Rupture of Membrane.

Background: Pulmonary hypertension (PH) is a rare cardiovascular disorder that leads to right heart
failure (RHF). Although most PH occurs secondary to congenital heart disease (CHD), PH can occur
primarily due to pulmonary arterial vasculature abnormalities, known as Idiopathic pulmonary
arterial hypertension (IPAH). In addition, the physiologic changes during pregnancy can potentially
lead to worsening PAH and confer a poor prognosis. Therefore, when the mother refuses termination,
a multidisciplinary team should manage the pregnancy and delivery to improve maternal and fetal
outcomes.
Objectives: This case report aimed to describe the importance of early diagnosis and treatment in PAH.
Case reports: We reported a case of a 24-year-old woman with idiopathic pulmonary arterial hypertension (IPAH) that was newly diagnosed at 25 weeks of pregnancy and previously misdiagnosed with
patent ductus arteriosus (PDA). This pregnancy was complicated with anemia and threatened preterm
labor. Sildenafil was used as a vasodilator to reduce the symptoms of PAH. Unfortunately, the
pregnancy was terminated at 29 weeks because of PPROM after considering giving lung maturation
and neuroprotectant to the fetus. The patient was discharged without complication, but the baby died
after eight days of intensive care due to HMD II, which led to respiratory failure.
Conclusion: PAH in pregnancy is a life-threatening condition if untreated. Continuous treatments can
help control the symptoms and avoid further complications for both mother and baby.

1. Introduction
Pulmonary hypertension (PH) is a rare heart defect and can
be fatal, causing maternal and fetal death. The most frequent causes of
PH during pregnancy (64%) are congenital heart diseases (CHD) such
as ventricular septal defect (VSD), atrial septal defect (ASD), or patent
ductus arteriosus (PDA).1 The incidence of pregnancy with PH is scarce
for approximately 1.1:100,000 women (Obican et al., 2014). PH group
1 or known as primary Pulmonary arterial hypertension (PAH), is a
condition that is rarely found, with an average survival rate of only 2.8
years if not treated.2 Therefore, a woman with PH is not advised to get
pregnant. The physician should offer termination when pregnancy
occurs. Nevertheless, some mothers cannot accept the decision to
terminate the pregnancy and choose to continue their pregnancy.3

due to malnutrition underlies cardio-intestinal syndrome, which can
worsen hypoxic conditions in pregnant women with PAHs.4 Both
anemia and decreased CO due to PH can increase morbidity in the
mother and fetus. Pregnant women with PH and anemia require
intensive, multidisciplinary treatment during pregnancy and
childbirth.2
We will report cases of pregnancy with Idiopathic Pulmonary
Arterial Hypertension (IPAH), which was newly diagnosed during
pregnancy. The PAH condition is exacerbated by anemia in pregnancy
which causes symptoms of acute shortness of breath and causes complications of preterm labor. Pregnancy management with PAH is carried
out by a multidisciplinary team at Dr. Saiful Anwar Hospital Malang so
that it can add insight to handling pregnancy cases with PAH. However,
establishing a diagnosis that is not easy can lead to misdiagnosis and
increase the risk of complications that occur in the mother and fetus.
Therefore, the management of pregnancy with PAH is complicated and
makes it a big challenge.

Physiological changes that occur in pregnancy can aggravate
the burden on the heart, especially in PAH conditions. The condition of
anemia can also worsen the work of the heart in pregnant women with
PAHs. Iron deficiency is one of the most frequent causes of anemia in
pregnancy and also affects the pathogenesis of PAHs. Iron deficiency

*Corresponding author at: Resident of Obstetrics and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
E-mail address: dr.stefanisari@gmail.com (S. Harumsari).
https://doi.org/10.21776/ub.hsj.2022.003.04.7
Received 9 July 2022; Received in revised form 30 August 2022; Accepted 15 September 2022
Available online 1 October 2022

35

S. Harumsari, et al.

Heart Sci J 2022; 3(4): 35-39

(A)

(B)

(C)

(D)
2. Case Report
A 24-years-old woman, primigravid, was referred to our
emergency department by an Obstetrician at a private hospital with a
chief complaint of shortness of breath after two times of PRC transfusions. The patient was hospitalized for two days and diagnosed with
threatened preterm labor and anemia. The patient felt a frequent
uterine contraction at 25 weeks of gestation, a day before being
hospitalized. The hemoglobin level at visiting that private hospital was
7.4 gr/dL. Patient planned for dexamethasone-induced fetal lung
maturation and PRC transfusion twice a day. After the second transfusion, the patient felt dyspnoea and palpitation. The patient was consulted by the Cardiologist and given digoxin 1x0,25 mg. The patient was
diagnosed with ASD based on clinical appearance and electrocardiograph examination. After 24 hours of observation, the patient did not
get better. Because lack of facilities, the Obstetrician referred the
patient to our hospital.

(E)

The patient did antenatal care with the midwife and never
came to Obstetrician. She did a triple elimination test in Public Medical
Centre Jatisari, and the results were non-reactive. On admission, the
patient's vital sign was blood pressure of 120/81 mmHg, heart rate of
107 bpm, respiratory rate of 28 breaths/min, pulse oxygenation of 99%
on nasal cannula three L/min, and temperature of 36.2°C. Head and
neck examination found conjunctiva anemia and JVP +1. Cor examination found murmur systolic 3/6 continuous at ICS II left parasternal
line. The abdominal examination determined the fundal height of 18
cm, single intrauterine baby head below, fetal heart rate of 147 bpm,

Figure 1. Echocardiographic of idiopathic pulmonary arterial hypertension
A. Parasternal Long Axial image: RV dimension enlarged with LV
geometric change; B. LV D-shaped in Parasternal short Axis (PSAx)
image; C. PSAx- great artery level shows there is no interatrial shunt; D.
Pulmonary Artery Enlargement; E. There is no interatrial shunt from
sub-costal view

36

S. Harumsari, et al.

Heart Sci J 2022; 3(4): 35-39

and uterine contraction (+). In addition, we found two cm cervical
dilatation, 50% effacement, head presentation at Hodge I, and no
amniotic fluid leakage from the vaginal examination.

young patients. PH can occur in connective tissue diseases such as lupus
or systemic sclerosis.1 This patient showed an ANA test examination
result was negative. Clinical findings did not show any criteria consistent with the American College of Rheumatology (ACR) for lupus and
systemic sclerosis.5

Her hemoglobin level at admission was 8.5 mg/dL. Patient
has hypercoagulability condition that showed from increased D-dimer
1.32 mg/L FEU (normal range < 0.5 mg/L FEU) and fibrinogen 502
mg/dL (normal range 154.3-397.9 mg/dL). The patient was hospitalized in the Obstetrics High Care Unit for preterm delivery observation.
Her shortness of breath was due to suspect congenital heart disease
with a high probability of PH. The transfusion was continued with one
PRC daily. Tocolytic ketoprofen suppositories were given to relieve
uterine contraction. Treatment of pulmonary hypertension with oral
sildenafil 20 mg daily improved the shortness of breath.

Based on the WHO functional class, this case is included in
WHO FC II, characterized by mild physical activity limitations but no
complaints when the patient is resting.2 The patient is suspected of
having an Atrial Septal Defect (ASD) due to the presence of RBBB
images and "crochetage" signs on all three inferior leads on the electrocardiogram. Crochetage signs obtained in all inferior leads showed
100% specificity, 73.1% sensitivity, and 69% PPV to ASD diagnosis.6
Nevertheless, the transthoracic echocardiogram did not indicate the
presence of intracardiac shunt in these patients.

Echocardiographic evaluation was done after three days of
hospitalization by a senior Cardiologist (Figure 1). Dilatation of the
pulmonary artery was consistent with the prior echocardiogram with a
diameter of MPA 3.26 cm, RPA 1.61 cm, and LPA 2.12 cm. The intracardiac shunt did not detect either an atrium or ventricle. Dilatation of the
right heart, including atrium (RA length 7.25 cm and RA width 6.14
cm) and ventricle (RVDB 5.99 cm, RV mid 5.77 cm), were found.
Moderate pulmonary regurgitation and moderate to severe tricuspid
regurgitation were consistent with a high probability of pulmonary
hypertension. Additional laboratory workup was done for lung disease,
thromboembolic, and autoimmune disorders. The patient was
counseled about her idiopathic pulmonary arterial hypertension and
refused to terminate the pregnancy. A multidisciplinary team, including
Obstetrician, Cardiologist, Pulmonologist, Anaesthesiologist, and
Neonatologist, collaborated for comprehensive management. The
patient showed improvement in symptoms and was discarded from the
hospital after ten days of hospitalization.

Pregnancy with a PAH is contraindicated because it causes
serious heart failure that could result in morbidity and mortality.7
Pregnancy causes physiological changes in all body organs, including
the cardiovascular system. The volume of blood plasma increases by
approximately 6-8L by the time of approaching labor.8 Hormonal
changes in pregnancy, progesterone, and estrogen, also play a role in
causing a decrease in systemic vascular resistance (SVR) by up to 40%.9
The physiologic process in pregnancy causes an increase in the heart
size by up to 30% to increase cardiac output up to 30-50%, especially in
the first trimester of pregnancy. Mothers with IPAH have idiopathic
dilatation of the pulmonary artery as compensation for the high
pressure. In this condition, the heart cannot increase CO and potentially
cause right heart failure.3 Physiological pregnancy hypercoagulability
conditions increase the risk of thromboembolism which can worsen the
condition of the patient with PAH.7
Anemia in pregnancy is still a major problem for maternal
health in Indonesia. Anemia in pregnancy increases the risk of premature delivery, low birth weight babies, perinatal mortality, and post-partum bleeding.10 Anemia in pregnant women can occur physiologically
as a response to an increased plasma volume with a peak at 30-34
weeks of gestation.11 Iron deficiency is the main cause of anemia in
pregnancy.12 The incidence of iron deficiency anemia in pulmonary
hypertension is quite high, around 40-60%.13 Iron is needed for
hemoglobin synthesis in erythrocytes and myoglobin in the heart
muscle and skeletal muscle to facilitate the diffusion and storage of
oxygen.14 Impaired iron homeostasis contributes to pulmonary vascular
endothelial dysfunction. Hemoglobin scavenger transporter CD163 is a
regulator of cellular function and proliferation of pulmonary arterial
endothelial cells (PAECs), and pulmonary artery smooth muscle cells
(PASMCs) needed for pulmonary vascular remodeling.13 The management of anemia and iron deficiency in pregnancy can reduce vasoconstriction of the vascular lung and improve pulmonary hypertension.4

Unfortunately, after two weeks of being discarded from the
hospital, the patient got a water break. The patient visited the obstetrics
outpatient unit at 28 weeks of gestation. Vital sign examination was
blood pressure of 113/70 mmHg, heart rate of 101 bpm, respiratory
rate of 20 breaths/min, pulse oxygenation of 98% on room air, and
temperature of 36.3°C. Amniotic fluid flow was visible at the uterine
external os on sterile speculum examination. The patient was planned
for hospitalization, and antenatal dexamethasone 6 mg twice a day for
two days was given for lung maturation of the fetus. Neuroprotectant
with MgSO4 20% 4 gr IV slowly bolus continued with syringe MgSO4
40% 10 gr 1 gr/hours was given 24 hours before termination.
At 29 weeks of pregnancy, the patient delivered a male infant
with Apgar scores of 6 in the first minute and 9 in the 5th minute by
cesarean section under low-dose spinal anesthesia block (SAB). The
infant's birth weight was 1126 gr, and birth length was 37 cm. Mechanic contraceptive with IUD T380A was inserted into the uterus post-placental delivery. A preventive B Lynch procedure was done to minimize
the risk of hemorrhagic post-partum. The postoperative observation
was done in the intensive care unit. The patient condition post-operation was good, without any complaints. The patient was allowed to
pump her breast milk because her condition was not a complication.
The patient was discarded three days after the cesarean section.
Unfortunately, her baby died after eight days of intensive care due to
HMD II, which led to respiratory failure.

Anemia can increase the risk of infection in pregnancy. The
infection causes a 2.4-fold increase in the risk of early rupture of the
amniotic. A decrease in hemoglobin levels causes a decrease in oxygen
transport to tissues, including the membrane amnion. Hypoxia causes
an increase in serum norepinephrine which induces maternal and fetal
stress. The incidence of anxiety in pregnancy will increase corticotrophin-releasing hormone (CRH). Increased CRH can improve premature
labor, hypertension, preeclampsia, and PROM. Iron deficiency can
affect the proliferation of T and B cells and reduce phagocytic activity,
cell activity, and bactericidal ability, thereby increasing the risk of
infection. Infection is one of the risk factors for the onset of premature
labor.15

3. Discussion
PH generally occurs secondary due to underlying medical
conditions such as heart and lung disease. Primary PH is less common
and is included in a condition called pulmonary arterial hypertension
(PAH). Our patient has been diagnosed with idiopathic pulmonary
arterial hypertension (IPAH). Primary PH is very rare and often
idiopathic, with a life expectancy between 2.8-5 years, especially in

The administration of medications can control pulmonary
hypertension in pregnancy. Pharmacological therapy for HAP in
pregnancy can be divided into four groups: prostaglandins,

37

S. Harumsari, et al.

Heart Sci J 2022; 3(4): 35-39

phosphodiesterase five inhibitors (PDE-5), endothelin receptor antagonists, and soluble guanylate cyclase stimulators.9 Only the PDE-5
inhibitor group is available in our hospitals. PDE5 inhibitors as
monotherapy can be recommended in patients with functional class FC
I or II with normal right ventricular function. Sildenafil is a PDE5
inhibitor first used in pulmonary hypertension and is more widely
recommended than the newly recommended tadalafil.16 Around 2009,
PDE5 inhibitors acted on the nitric oxide (NO) pathway as competitive
inhibitors against cGMP degradation. Increased cGMP concentrations
lead to the activation of protein kinase G through the potassium
sarcolemma canal. This process triggers conditions of intracellular
hyperpolarisation and inhibition of calcium canals that cause the
relaxation of smooth muscles of pulmonary blood vessels.17 Sildenafil is
safe to use in pregnancy, as reported by a meta-analysis study in the
Netherlands. Sildenafil in obstetrics is used as a therapy for intrauterine
growth restriction (IUGR) in preeclampsia. The administration of
sildenafil also positively lowers peripheral vascular resistance and
improves uteroplacental flow, which is beneficial for fetal development.18 In this case, the patient is given therapy with sildenafil 3x20
mg. Complaints of tightness gradually improved after the patient was
given therapy with sildenafil. The administration of sildenafil is continued until the KRS patient.

the coronary arteries. Norepinephrine is an alpha and beta-agonist that
functions for inotropic augmentation while also being able to cause
systemic vasoconstriction without affecting the pulmonary vascular.
Meanwhile, milrinone is a phosphodiesterase III (PDE III) agent that
directly affects the relaxation of smooth muscles of pulmonary blood
vessels so that it can reduce vascular resistance of the lungs.23
Mothers with PAHs are recommended to use contraceptives
to prevent unplanned pregnancies. Estrogen-containing contraceptives
are not recommended because they will increase the risk of venous
thromboembolism (VTE) and negatively affect pulmonary blood
vessels. Estrogen also contributes to the pathogenesis of PAH in
pregnant patients. Copper-containing intrauterine devices (IUDs) or
progestin-releasing IUDs can be the recommended contraceptive
options in PAHs.9 In this case, the contraceptive chosen was a post-placental IUD installed during cesarean section because the patient was
still of reproductive age. The IUD installation during surgery is safer
because it does not manipulate the cervix so that it does not cause
vasovagal reflexes that can harm the patient.
4. Conclusion
We reported cases of 24-year-old women with idiopathic
pulmonary arterial hypertension newly diagnosed at 25 weeks of
pregnancy with threatened preterm labor and anemia. The patient was
diagnosed with a congenital heart defect PDA at the referring hospital.
After going through laboratory supporting examinations and echocardiography evaluations, the patient was diagnosed with IPAH. Cardiovascular physiological changes during pregnancy and conditions of anemia
compromise heart function, causing manifestations of shortness of
breath. Treatment with collaboration between divisions between
obstetricians, cardiologists, pulmonologists, anesthesiologists, and
neonatologists, in this case, is appropriate. Termination was performed
with an elective cesarean section performed to reduce the risk of perioperative mortality. The patient's current condition is good and controlled
with the administration of 20 mg of sildenafil three times daily. PAH in
pregnancy is a life-threatening condition if untreated. Continuous
treatments can help control the symptoms and avoid further complications for both mother and baby.

Pregnant women with PH have a higher risk of post-partum
bleeding, premature delivery, and cesarean delivery.19 Childbirth is
recommended to be scheduled immediately after fetal lung maturation.
Delivery with cesarean section is highly recommended to avoid
prolonged labor and prepare for hemodynamic optimization and better
anesthesia techniques. Childbirth is associated with an extra increase in
CO by 30-50%, with a total increase of 80%. PAP increased from 53.5
mmHg in pre-pregnancy conditions to 72.8 mmHg at 31 ± three weeks.
Increased reverse blood flow from causing hemodynamic instability in
pregnancy with PAHs. A multidisciplinary team must carry out the
management of pregnancy with PAH.20 Experts consisting of obstetricians, cardiologists, anesthesiologists, pulmonologists, and neonatologists play an important role in managing this case.
Post-partum bleeding can be controlled during surgery by
administering oxytocin and the B-Lynch procedure. In addition,
oxytocin administration as a preventive therapy for post-saline bleeding
is also recommended. However, oxytocin is not allowed to be administered bolus intravenously because it can cause hypotension and reflex
tachycardia.3 The B-Lynch method has been known since 1997 as a
suturing method that accommodates mechanical compression of the
uterus during surgery to prevent and manage uterine atony.21 Oxytocin
administration, in this case, was given by intravenous drip at a dose of
20 IU in RL 500 cc at a rate of 28 drip/min to 12 hours postoperatively.
Postoperative evaluation of this patient found a stable hemodynamic
condition, no complaints of tightness were obtained, and the patient
could be transferred to the HCU treatment room 24 hours after
monitoring in the ICU.

5. Declarations
5.1. Ethics Approval and Consent to participate
This study was approved by local Institutional Review Board, and all
participants have provided written informed consent prior to involvement in the study.
5.2. Consent for publication
Not applicable.
5.3. Availability of data and materials
Data used in our study were presented in the main text.
5.4. Competing interests
Not applicable.

The preoperative management carried out by TS Anesthesia
includes the installation of a 2-lane IV line with an 18G needle, the
administration of IVFD RL fluid 40 cc/hour during fasting, the fasting of
6 hours of pre-operation, the premedication of ranitidine 50 mg and
metoclopramide 10 mg 1 hour of pre-operation and the installation of
arterial line pre-operation. The key to managing intraoperative anesthesia in patients with pulmonary hypertension is the prevention of
ischemia, especially in the right coronary artery.22 The strategy that can
be applied is to optimize the contractility of the right ventricle by
keeping the preload safe and preventing an increase in afterload caused
by mechanical, physiological, and pharmacological factors.23 The
installation of invasive arterial lines can be very useful for monitoring
coronary perfusion pressure and analyzing diastolic pressure.22 The
administration of pharmacological agents such as norepinephrine and
milrinone during surgery is recommended to maintain the perfusion of

5.5. Funding source
Not applicable.
5.6. Authors contributions
Idea/concept: SH, BR. Design: SH, BR, NP, PMD, VYSP, MSR. Control/supervision: BR, NP, PMD, VYSP, MSR. Data extraction: SH. Statistical
analysis: SH, BR, NP, PMD, VYSP, MSR. Results interpretation: SH, BR,
NP, PMD, VYSP, MSR. Critical review/discussion: SH, BR, NP, PMD,
VYSP, MSR. Writing the article: SH, BR, NP, PMD, VYSP, MSR. All
authors have critically reviewed and approved the final
draft and are responsible for the content and similarity index of the
manuscript.

38

S. Harumsari, et al.

5.7. Acknowledgements
We thank to Department of Obstetrics and Gynecology, Universitas
Brawijaya
References

1. Obican SG, Cleary KL. Pulmonary arterial hypertension in pregnancy. Semin Perinatol. 2014;38(5):289–94.
2. Afify H, Kong A, Bernal J, Elgendy IY. Pulmonary hypertension in
pregnancy: challenges and solutions. Integr Blood Press Control.
2022;15:33–41.
3. Olsson KM, Channick R. Pregnancy in pulmonary arterial hypertension. Eur Respir Rev. 2016;25(142):431–7.
4. Quatredeniers M, Mendes‐ferreira P, Santos‐ribeiro D, Nakhleh MK,
Ghigna MR, Cohen‐kaminsky S, Perros F. Iron deficiency in pulmonary arterial hypertension: A deep dive into the mechanisms. Cells.
2021;10(2):1–22.
5. Bazan IS, Mensah KA, Rudkovskaia AA, Adonteng-Boateng PK,
Herzog EL, Buckley L, Fares WH. Pulmonary arterial hypertension
in the setting of scleroderma is different than in the setting of lupus:
A review. Respir Med. 2018;134(2018):42–6
6. Raut MS, Verma A, Maheshwari A, Shivnani G. Think beyond right
bundle branch block in atrial septal defect. Ann Card Anaesth.
2017;20(4):475–6.

Heart Sci J 2022; 3(4): 35-39

18. Paauw ND, Terstappen F, Ganzevoort W, Joles JA, Gremmels H,
Lely AT. Sildenafil during pregnancy: A preclinical meta-analysis on
fetal growth and maternal blood pressure. Hypertension.
2017;70(5):998–1006.
19. Thomas E, Yang J, Xu J, Lima F V., Stergiopoulos K. Pulmonary
hypertension and pregnancy outcomes: Insights from the national
inpatient sample. J Am Heart Assoc. 2017;6(10):1–12.
20. Luo J, Shi H, Xu L, Su W, Li J. Pregnancy outcomes in patients with
pulmonary arterial hypertension: A retrospective study. Med
(United States). 2020;99(23):1–7.
21. Hall E, Djordjevic M, Mazzullo L. Modified B-Lynch Suture
Technique for Prevention of Postpartum Hemorrhage. Obstet
Gynecol. 2017;129(5):187S.
22. Price LC, Martinez G, Brame A, Pickworth T, Samaranayake C,
Alexander D et al. Perioperative management of patients with
pulmonary hypertension undergoing non-cardiothoracic, non-obstetric surgery: a systematic review and expert consensus statement.
Br J Anaesth [Internet]. 2021;126(4):774–90.
23. Steppan J, Heerdt PM. Pre-operative assessment and peri-operative
management of the patient with pulmonary vascular disease. Clin
Chest Med. 2021;42(1):133–41.

7. Terek D, Kayikcioglu M, Kultursay H, Ergenoglu M, Yalaz M,
Musayev O, Mogulkoc N, Gunusen I, Akisu M, Kultursay N. Pulmonary arterial hypertension and pregnancy. J Res Med Sci.
2013;18:73–6.
8. Krishnan S, Fricke EM, Cordoba M, Chalifoux LA, Girgis RE. Pulmonary hypertension complicating pregnancy. Curr Pulmonol Reports.
2021;10(2):71–83.
9. Anjum H, Surani S. Pulmonary hypertension in pregnancy: A
review. Medicina (B Aires). 2021;57:259.
10. Widyawati W, Jans S, Bor HH, van Dillen J, Lagro-Janssen ALM.
The effectiveness of a new model in managing pregnant women
with iron deficiency anemia in Indonesia: A nonrandomized
controlled intervention study. Birth. 2015;42(4):337–45.
11. ACOG. ACOG practice bulletin No. 212: Pregnancy and heart
disease. Obs Gynecol. 2019;133(5):e320–56.
12 Friedrisch JR, Friedrisch BK. Prophylactic iron supplementation in
pregnancy: A controversial issue. Biochem Insights. 2017;10:1–8.
13. Sonnweber T, Pizzini A, Tancevski I, Löffler-Ragg J, Weiss G.
Anaemia, iron homeostasis and pulmonary hypertension: A review.
Intern Emerg Med. 2020;15(4):573–85.
14. Ruiter G, Lankhorst S, Boonstra A, Postmus PE, Zweegman S,
Westerhof N, Van Der Laarse WJ, Vonk-Noordegraaf A. Iron
deficiency is common in idiopathic pulmonary arterial hypertension. Eur Respir J. 2011;37(6):1386–91.
15. Pratiwi PI, Emilia O, Kartini F. The effect of anemia on the incidence
of premature rupture of membrane (PROM) in Kertha Usada
Hospital, Singaraja, Bali. Belitung Nurs J. 2018;4(3):336–42.
16. Alipour MR, Lookzadeh MH, Namayandeh SM, Pezeshkpour Z,
Sarebanhassanabadi M. Comparison of tadalafil and sildenafil in
controlling neonatal persistent pulmonary hypertension. Iran J
Pediatr. 2017;27(1):10–3.
17. Henrie AM, Nawarskas JJ, Anderson JR. Clinical utility of tadalafil
in the treatment of pulmonary arterial hypertension: An
evidence-based review. Core Evid. 2015;10:99–108.

39 39