Ductus arteriosus flow velocity modulation by fetal breathing movements as a measure of fetal lung development Jim van Eyck, PhD, Karin van der Mooren, MD, and Juriy W. Wladimiroff, PhD Rotterdam, The Netherlands A test is needed that would accurately predict favorable neonatal lung performance in the presence of prolonged severe oligohydramnios caused by ruptured membranes so that optimal obstetric care can be provided. We propose such a test that is based on the degree of modulation of fetal ductal blood flow velocity by fetal breathing movements after maternal glucose loading. In a prospective cross-sectional study of 49 normal pregnancies (50 fetuses) between 25 and 38 weeks an exponentional increase in breathing-related ductal blood flow velocity modulation was observed with advancing gestational age, reflecting the developing pulmonary vascular bed. Fetal ductal flow velocity waveforms were also recorded in 13 cases of prolonged severe oligohydramnios after ruptured membranes before 28 weeks' gestation. Normal ductal blood flow velocity modulation values were associated with normal neonatal lung performance, whereas reduced ductal blood flow velocity modulation values were associated with pulmonary hypoplasia. Fetal breathing-related ductal flow velocity modulation appears to be a promising predictor of neonatal lung performance. (AM J OBSTET GVNECOL 1990;163:558-66.)
Key words: Ductus arteriosus, Doppler flow velocity, fetal breathing movements, lung development Rupture of membranes resulting in prolonged severe oligohydramnios during the second trimester of pregnancy may result in stillbirth or severe neonatal respiratory failure as a result of pulmonary hypoplasia. However, under these circumstances fetal outcome is not uniformly poor. I There is therefore a need for a test to accurately predict a favorable fetal outcome so that optimal obstetric care can be provided for these particular pregnancies. In cases of prolonged severe oligohydraminos, contradictory findings have been reported with regard to the association between fetal breathing movements and lung performance after birth. According to Blott et aP the predictive value of the presence of fetal breathing movements for continuing lung growth is 100%, and the predictive value of the absence of fetal breathing movements for pulmonary hypoplasia is 100%; however, Moessinger et al.' reported that the observation of fetal breathing activity is not helpful in identifying those fetuses with pulmonary hypoplasia at birth. Ductal blood flow in the fetal lamb is modulated by lung expansion.' This effect results from an opening
of the pulmonary vascular bed with subsequent reduced shunting of right ventricular output through the ductus arteriosus. Furthermore, increased pulmonary perfusion has been established with advancing gestational age, reflecting developing pulmonary vasculature.' In pulmonary hypoplasia the development of fifth- and sixth-generation vessels is impaired with a resultant reduction in development of the pulmonary vascular bed. 6 Moreover, pulmonary vascular resistance is raised and is associated with medial muscular hypertrophy of lung arterioles. 6 It may be speculated that fetal breathing-related modulation of ductal flow will be reduced in this situation. Recently a pulsed Doppler method was introduced for recording blood flow velocity waveforms in the human fetal ductal arteriosus. 7 In this study the following questions were addressed. Does breathing-related modulation of ductal flow occur in the human fetus? If so, is this modulation age dependent and is the presence of breathing-related ductal flow modulation in prolonged severe oligohydramnios caused by ruptured membranes indicative of absent pulmonary hypoplasia? Material and methods
From the Department of Obstetrics and Gynecology, Academic Hospital Rotterdam-Dijkzigt, Erasmus University. Receivedfor publication October 3, 1989; revised February 14, 1990; accepted May 1, 1990. Reprint requests: Juriy W. Wladimiroff MD, PhD, Professor of Obstetrics and Gynecology, Academic Hospital Rotterdam-Dijkz.igt, Erasmus University Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. 611122086
558
All women gave informed consent for the study, which was approved by the Ethics Review Board of the University Hospital. The gestational age was calculated from a reliable menstrual history and ultrasonographic measurement of fetal crown-rump length or biparietal diameter. All women were nonsmokers. The study population consisted of two groups. The
Volume 163 Number 2
first group represented 55 uncomplicated pregnancies with a mean gestational age of 32.3 weeks (range, 25 to 38 weeks) randomly selected at the outpatient clinic between August 1988 and March 1989 for a crosssectional study of normal breathing-related fetal ductal peak systolic flow velocity modulation. Recordings were performed from 25 weeks of gestation because at approximately this stage there is an increase in the total number of pulmonary vessels and vasomotor activity, reflecting the developing pulmonary vasculature during the late canalicular phase of lung development. 8 Fetal breathing activity also becomes more regular. 9 Each subject was included in the study once. One woman had a twin gestation. Mean maternal age was 28.3 years (range, 18 to 42 years); maternal parity ranged from 0 to 5. No medications were prescribed. On ultrasonographic examination there was a normal amount of amniotic fluid. Measurements of the fetal biparietal diameter, upper abdominal and head circumference, and femur length revealed a normal-sized fetus without gross structural anomalies. The second group consisted of 32 women who were admitted during the study period either from our own outpatient clinic or were referred from other centers because of premature rupture of membranes before 28 weeks' gestation. Mean gestational age was 22.9 weeks (range, 16 to 27 weeks). Fetal ductal flow velocity measurements were begun at 25 weeks' gestation. Premature rupture of membranes must have resulted in severe oligohydramnios and had to be present over a period of 3 weeks or more before delivery. Severe oligohydramnios was defined as the absence of an amniotic fluid pool of more than 1 cm, measured in two planes on ultrasound examination. Mean maternal age in this group was 27.9 years (range, 22 to 35 years); maternal parity varied from 0 to 4. Fetal biparietal diameter, upper abdominal, and head circumference revealed a normal-sized fetus without gross structural defects. In all women with premature rupture of membranes, tocolysis was established by intravenous administration of fenoterol. No corticosteroids were prescribed, and only cases with no signs of amnionitis were studied. Fetal ductal flow velocity measurements were performed with a combined two-dimensional real-time and continuous-wave Doppler system (Diasonics CV 400). A 3.0 MHz transducer was used. The sector scanner operated at power outputs < 100 m WI cm 2 in both imaging and Doppler modes by manufacturer's specifications. All women were studied while in the semirecumbent position. A longitudinal cross-section of the fetal ductus arteriosus was obtained on a short-axis view of the fetal heart parallel to the fetal spine as first described by Huhta et aJ.7 The aortic arch was distinguished from the ductal arch by visualization of the
Fetal ductal flow and lung development 559
carotid arteries. The cursor line was placed in the ductus near the junction of the ductus and the descending aorta. The angle of insonation was maintained below 5 degrees. On the same short-axis view, movements of the fetal thoracic wall and diaphragm reflecting breathing movements can be observed, while the Doppler flow velocity measurements in the ductus arteriosus are performed parallel to the ductal flow direction without changing the position of the transducer. Fetal breathing activity was defined as periodic inward movements of the fetal chest wall with downward movements of the fetal diaphragm. Continuous fetal breathing was considered present when the interval between two consecutive breathing movements was 0
Q)
~
0
'to~
CO
Q)
c.
1 sec
Fig. 1. Blood flow velocity waveforms obtained from the fetal du ctus arteriosus during fetal breathing activity.
p 99 p 95
:;-
0.35
a..
August 1990 Am J Obstet Gynecol
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a..
Key words: Ductus arteriosus, Doppler flow velocity, fetal breathing movements, lung development Rupture of membranes resulting in prolonged severe oligohydramnios during the second trimester of pregnancy may result in stillbirth or severe neonatal respiratory failure as a result of pulmonary hypoplasia. However, under these circumstances fetal outcome is not uniformly poor. I There is therefore a need for a test to accurately predict a favorable fetal outcome so that optimal obstetric care can be provided for these particular pregnancies. In cases of prolonged severe oligohydraminos, contradictory findings have been reported with regard to the association between fetal breathing movements and lung performance after birth. According to Blott et aP the predictive value of the presence of fetal breathing movements for continuing lung growth is 100%, and the predictive value of the absence of fetal breathing movements for pulmonary hypoplasia is 100%; however, Moessinger et al.' reported that the observation of fetal breathing activity is not helpful in identifying those fetuses with pulmonary hypoplasia at birth. Ductal blood flow in the fetal lamb is modulated by lung expansion.' This effect results from an opening
of the pulmonary vascular bed with subsequent reduced shunting of right ventricular output through the ductus arteriosus. Furthermore, increased pulmonary perfusion has been established with advancing gestational age, reflecting developing pulmonary vasculature.' In pulmonary hypoplasia the development of fifth- and sixth-generation vessels is impaired with a resultant reduction in development of the pulmonary vascular bed. 6 Moreover, pulmonary vascular resistance is raised and is associated with medial muscular hypertrophy of lung arterioles. 6 It may be speculated that fetal breathing-related modulation of ductal flow will be reduced in this situation. Recently a pulsed Doppler method was introduced for recording blood flow velocity waveforms in the human fetal ductal arteriosus. 7 In this study the following questions were addressed. Does breathing-related modulation of ductal flow occur in the human fetus? If so, is this modulation age dependent and is the presence of breathing-related ductal flow modulation in prolonged severe oligohydramnios caused by ruptured membranes indicative of absent pulmonary hypoplasia? Material and methods
From the Department of Obstetrics and Gynecology, Academic Hospital Rotterdam-Dijkzigt, Erasmus University. Receivedfor publication October 3, 1989; revised February 14, 1990; accepted May 1, 1990. Reprint requests: Juriy W. Wladimiroff MD, PhD, Professor of Obstetrics and Gynecology, Academic Hospital Rotterdam-Dijkz.igt, Erasmus University Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. 611122086
558
All women gave informed consent for the study, which was approved by the Ethics Review Board of the University Hospital. The gestational age was calculated from a reliable menstrual history and ultrasonographic measurement of fetal crown-rump length or biparietal diameter. All women were nonsmokers. The study population consisted of two groups. The
Volume 163 Number 2
first group represented 55 uncomplicated pregnancies with a mean gestational age of 32.3 weeks (range, 25 to 38 weeks) randomly selected at the outpatient clinic between August 1988 and March 1989 for a crosssectional study of normal breathing-related fetal ductal peak systolic flow velocity modulation. Recordings were performed from 25 weeks of gestation because at approximately this stage there is an increase in the total number of pulmonary vessels and vasomotor activity, reflecting the developing pulmonary vasculature during the late canalicular phase of lung development. 8 Fetal breathing activity also becomes more regular. 9 Each subject was included in the study once. One woman had a twin gestation. Mean maternal age was 28.3 years (range, 18 to 42 years); maternal parity ranged from 0 to 5. No medications were prescribed. On ultrasonographic examination there was a normal amount of amniotic fluid. Measurements of the fetal biparietal diameter, upper abdominal and head circumference, and femur length revealed a normal-sized fetus without gross structural anomalies. The second group consisted of 32 women who were admitted during the study period either from our own outpatient clinic or were referred from other centers because of premature rupture of membranes before 28 weeks' gestation. Mean gestational age was 22.9 weeks (range, 16 to 27 weeks). Fetal ductal flow velocity measurements were begun at 25 weeks' gestation. Premature rupture of membranes must have resulted in severe oligohydramnios and had to be present over a period of 3 weeks or more before delivery. Severe oligohydramnios was defined as the absence of an amniotic fluid pool of more than 1 cm, measured in two planes on ultrasound examination. Mean maternal age in this group was 27.9 years (range, 22 to 35 years); maternal parity varied from 0 to 4. Fetal biparietal diameter, upper abdominal, and head circumference revealed a normal-sized fetus without gross structural defects. In all women with premature rupture of membranes, tocolysis was established by intravenous administration of fenoterol. No corticosteroids were prescribed, and only cases with no signs of amnionitis were studied. Fetal ductal flow velocity measurements were performed with a combined two-dimensional real-time and continuous-wave Doppler system (Diasonics CV 400). A 3.0 MHz transducer was used. The sector scanner operated at power outputs < 100 m WI cm 2 in both imaging and Doppler modes by manufacturer's specifications. All women were studied while in the semirecumbent position. A longitudinal cross-section of the fetal ductus arteriosus was obtained on a short-axis view of the fetal heart parallel to the fetal spine as first described by Huhta et aJ.7 The aortic arch was distinguished from the ductal arch by visualization of the
Fetal ductal flow and lung development 559
carotid arteries. The cursor line was placed in the ductus near the junction of the ductus and the descending aorta. The angle of insonation was maintained below 5 degrees. On the same short-axis view, movements of the fetal thoracic wall and diaphragm reflecting breathing movements can be observed, while the Doppler flow velocity measurements in the ductus arteriosus are performed parallel to the ductal flow direction without changing the position of the transducer. Fetal breathing activity was defined as periodic inward movements of the fetal chest wall with downward movements of the fetal diaphragm. Continuous fetal breathing was considered present when the interval between two consecutive breathing movements was 0
Q)
~
0
'to~
CO
Q)
c.
1 sec
Fig. 1. Blood flow velocity waveforms obtained from the fetal du ctus arteriosus during fetal breathing activity.
p 99 p 95
:;-
0.35
a..
August 1990 Am J Obstet Gynecol
0.35
a..
