Premature fetal closure of the ductus arteriosus of unknown cause – could it be influenced by maternal consumption of large quantities of herbal chamomile tea – a case report?

Introduction

Premature fetal closure of the ductus arteriosus (DA) is rare and can result in fetal death [1], [2]. Premature closure of the DA is primarily associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) due to inhibition of cyclooxygenase-2 prostaglandins [2], [3]. The diet of pregnant women that is rich in polyphenols such as green tea, chamomile, dark chocolate, and grapefruit juice may increase the risk of premature closure of the DA by inhibition of prostaglandin synthesis [4]. A growing amount of evidence has recently shown that herbs, fruits, nuts, and a wide variety of substances commonly consumed as part of a daily diet affect the inflammatory cascade, culminating in reduced PG synthesis. It has been presumed that that maternal ingestion of polyphenol-rich beverages during pregnancy might be associated with fetal ductal constriction [5]. Premature closure of the DA in utero provides to fetal hemodynamic compromise and it has the potential for neonatal pulmonary hypertension [3], [4]. The occurrence of tricuspid and pulmonary regurgitation, dilatation of the right heart due to a condition providing to impaired flow through the pulmonary valve functionally resembling pulmonary atresia which may cause fetal death [4], [5], [6], [7]. The aim of this case report is to present a case of premature fetal closure of the DA which was associated with increased consumption of chamomile tea during pregnancy, which to our surprise, was quite unexpected possible cause of premature DA closure in the third trimester of pregnancy.

Case presentation

A 32-year-old pregnant woman, in her third uncomplicated pregnancy, at 33 weeks of gestation was referred for fetal echocardiography due to suspicion of acute fetal heart failure. The patient did not take any medication during pregnancy but has decided to stop consuming coffee, and instead she started drinking chamomile tea, considered as a healthy beverage. In the period of 2 weeks she used to drink 3 to 4 cups of tea a day – (almost 1,000 mL a day). At 34 weeks of gestation fetal ultrasound revealed normal fetal growth and biophysical profile and slightly decreased amniotic fluid index (AFI=7/4). Cardiothoracic index and heart axis were normal, while foramen ovale was slightly enlarged (5 mm), mitral valve diameter was up to 11 mm and tricuspid valve up to 12 mm. Mild non-significant tricuspid regurgitation was found (velocity 2.4 m/s, peak gradient 24 mm Hg). Diameter of the right atrium was 13 mm, slightly enlarged compared to the left atrium which had a diameter of 11 mm. The aortic root was 5 mm, with flow velocity 0.9 m/s, which were considered normal. The pulmonary artery was up to 8.2 mm, together with pulmonary artery branches of up to 4.6 mm in diameter, with high flow velocity through pulmonary valve of 1 m/s (Figures 1 and 2). An extremely dilated DA was found (5.5 mm), which was tortuous with turbulent high flow up to 2.2 m/s (Figures 3 and 4). Heart rhythm was regular with a frequency of 132 beats per minute. Hemodynamics through umbilical blood vessels (resistance index = 0.58) as well as through the middle cerebral artery (resistance index = 0.78, middle cerebral artery peak systolic velocity = 54 cm/s) were normal. The described findings indicated prenatal closure of the DA. At regular follow-up every 3 days unchanged hemodynamic findings were found, and at 36 + 1 GW the patient was hospitalized due to development of oligohydramnios (amniotic fluid index = 4.5/3). Dexamethasone was administrated in case of emergency cesarean (CS) section delivery. At37 GW due to progressive oligohydramnios and non-reassuring cardiotocography, it was decided to deliver the baby by emergency CS. A healthy appearing eutrophic baby boy was delivered (birth weight 2,830 g, birth length 49 cm and head circumference 34 cm), Apgar score of 9 after 1 and 5 min, and normal pH of 7.28 from the umbilical artery. Postnatal course of the mother and the baby was uneventful with normal postnatal neonatal check-up. Neonatal echocardiography at 12 h of live revealed mild right ventricular dysfunction, disappearing at the age of 7 days, with functionally closed DA. The baby was asymptomatic and hemodynamic changes did not indicate any intervention. The baby did well and was discharged home after 7 days and his development was normal at the age of 3 months.

Figure 1:

Three-vessels view in our patient revealed dilation of the pulmonary artery and the branches.

Figure 2:

Pulmonary artery and the branches.

Figure 3:

Depiction of dilated and tortuous ductus arteriosus (arrow) by color Doppler at 36 + 1 weeks of gestation in our patient.

Figure 4:

Dilated ductus arteriosus in our patient at 36+1 weeks of gestation (arrow).

Discussion

In normal fetal circulation, the right ventricle provides approximately 65% of cardiac output [8]. Pulmonary vascular resistance is the reason why only 12% of blood from the right ventricle enters the pulmonary circulation, while the remaining 88% passes through the DA to the descending aorta and systemic circulation [8]. The patency of the fetal DA is regulated by low oxygen saturation, and high levels of prostaglandin E2, and prostacyclin PGI2 mostly produced by placenta and fetal hemodynamics [8]. Premature closure of the DA occurs rarely in utero usually associated with the prenatal use of non-steroidal anti-inflammatory drugs (NSAID). To our surprise, in the study of 20 cases of intrauterine DA closure, NSAID use was identified in only 30% of cases, while in the significant number of patients consumption of green tea, herbal chamomile tea, dark chocolate, grape juice and other foods rich in flavonoids has been claimed as a potential cause [9]. Most commonly the causative factor for prenatal DA closure could not be identified [10], [11]. Polyphenols in green and chamomile tea, such as flavonoids or catechins have significant antioxidant and anti-inflammatory effects attenuating cyclooxygenase-2 and inducible nitric oxide synthase [11].

Increase in the afterload of the right ventricle with subsequent ventricular hypertrophy, dysfunction (systolic and diastolic impairment), dilatation, tricuspid and pulmonary valve regurgitation, papillary muscle stress or rupture with flail of valve, cardiac failure, ischemia and fetal demise are characteristics of DA constriction and closure [3, 7, 9, 12]. Increased mechanical pressure on the pulmonary vasculature may lead to the hypertrophy of tunica media, constriction of the fetal pulmonary vessels and pulmonary hypertension [13]. Parameters for intrauterine DA restrictions (diagnosis at >27 weeks) are: peak systolic velocity >1.4 m/s, diastolic peak flow velocity <0.35 m/s and pulsatility index <1.9 [13]. DA constriction will lead to blood turbulence, increased systolic flow, absent diastolic flow and reduced pulsatility index <1.9 [13]. Peak systolic velocity greater than 1.4 m/s along with persistent diastolic peak flow velocity greater than 0.35 m/s can be suggestive to DA constriction [13, 14].

All of the consequences of the premature closure of the DA should be prenatally diagnosed and possible etiology determined. In our case we excluded prenatal NSAID use and the only data revealed from the history was consumption of 1,000 mL per day of chamomile tea for more than 2 weeks. After searching the literature, we found that consumption of chamomile tea can be etiologic factor for premature closure of DA in unborn baby. Due to oligohydramnios and non-reassuring CTG at 37 GW we decided to deliver the baby, who did well postnatally without any intervention.

Conclusions

Prenatal diagnosis of premature closure of DA is the reason for the close follow-up of fetal wellbeing and in case of fetal distress the option might be delivery, as in our case. Although the cause of premature closure of DA in most of the cases will remain undetected, thorough history sometimes with unexpected events, should be taken under the consideration as possible causative factor for premature DA closure, as was drinking of high quantities of chamomile tea in our case. All other possible cases of prenatal premature DA closure were excluded.