Doppler in Obstetrics by Nicolaides, Rizzo, Hecker & Ximenes
The 11-14 weeks scan by Nicolaides, Sebire, Snijiders & Ximenes
The 18-23 weeks scan by Pilu, Nicolaides, Ximenes & Jeanty
 
PATHOPHYSIOLOGY

Preterm delivery occurs in less than 10% of pregnancies but accounts for more than 70% of all neonatal deaths. Approximately one-third of preterm deliveries are associated with preterm prelabor amniorrhexis and, in a high proportion of such cases, the underlying cause may be ascending infection from the lower genital tract. Thus, positive amniotic fluid cultures, with organisms commonly found in the vagina, are present in about one-third of cases with preterm prelabor amniorrhexis and in one-third of these there is fetal bacteremia.

In a study of 69 pregnancies with preterm prelabor amniorrhexis, the diagnosis of intrauterine infection was based on the results of culture of amniotic fluid and fetal blood obtained by amniocentesis and cordocentesis, respectively 1. In patients with fetal bacteremia, there was spontaneous delivery within 5 days of amniorrhexis, whereas, in those with negative fetal blood and amniotic fluid cultures, the interval between amniorrhexis and delivery was prolonged by up to 5 months and subsequent cultures of blood obtained from the umbilical cord at delivery or from the neonates were negative 1. These findings suggest that, first, infection is one of the causes rather than the consequence of amniorrhexis, and, second, in preterm prelabor amniorrhexis, infection may be the cause of subsequent preterm labor and delivery. The likely mechanism for the link between infection and labor is infection-mediated release of cytokines which stimulate the production of prostaglandins that induce uterine contractions 2,3.

In pregnancies complicated by preterm prelabor amniorrhexis, there are essentially two causes of perinatal death: prematurity and pulmonary hypoplasia. In cases with intrauterine infection, delivery occurs within a few days and therefore survival depends on the gestation at amniorrhexis 1. Postnatal survival increases from less than 10% before 24 weeks to more than 90% by 30 weeks. In those patients with no infection, pregnancy may be prolonged by several weeks and, in these cases, there is a risk of postnatal death due to pulmonary hypoplasia 4. The risk of death is inversely related to the gestation at amniorrhexis and decreases from approximately 50% for those with amniorrhexis before 20 weeks, to 20% for those with amniorrhexis at 20–24 weeks and to less than 5% for amniorrhexis after 24 weeks. Consequently, in the management of pregnancies complicated by amniorrhexis, the major issue is prediction of intrauterine infection and pulmonary hypoplasia.

Fetal blood gases
Cordocentesis in pregnancies with preterm prelabor amniorrhexis has demonstrated that the mean umbilical venous blood pO2 and pH are not significantly different from the appropriate normal mean for gestation, and there are no significant differences between those with positive or negative fetal blood and amniotic fluid cultures 5. These findings suggest that, in the presence of intrauterine infection, fetal oxygenation is not impaired.
DOPPLER STUDIES
Prediction of intrauterine infection

The rationale for the use of Doppler in pregnancies with preterm prelabor amniorrhexis is that infection of the amniotic fluid and choriodecidua causes constriction of the  umbilical cord and chorionic vessels and may consequently impair fetal perfusion6-12.

Doppler studies of the umbilical arterial circulation in pregnancies with chorioamnionitis have provided conflicting results, with some reporting an increase and others no change in impedance to flow. Thus, in two cross-sectional studies, involving a total of 35 patients with clinical chorioamnionitis, impedance to flow in the umbilical arteries was always normal 13,14. In a longitudinal study of 22 patients with preterm prelabor amniorrhexis and umbilical vasculitis, although there was an increase of impedance in the umbilical arteries 24 hours before delivery compared to previous measurements, impedance had remained within the normal range 15. In another longitudinal study of uterine and umbilical arteries in 60 patients with amniorrhexis, including 12 who developed clinical chorioamnionitis, there was no significant increase in impedance, even in measurements taken within 24 hours before delivery 16.

Carroll et al. performed Doppler studies immediately before cordocentesis and amniocentesis for bacteriological studies in 69 pregnancies with preterm prelabor amniorrhexis 5. The mean pulsatility indices in the uterine and umbilical arteries and in the fetal middle cerebral arteries and thoracic aorta were not significantly different from the appropriate normal mean for gestation and there were no significant differences in these values between those with and without intrauterine infection 5

These findings suggest that chorioamnionitis is not associated with a major degree of vasoconstriction in the uteroplacental or fetoplacental circulation. Consequently, Doppler does not provide a clinically useful distinction between infected and noninfected cases. However, Doppler studies in pregnancies with suspected amniorrhexis may be useful in the differential diagnosis from oligohydramnios due to uteroplacental insufficiency and intrauterine growth restriction. In the latter, there is an increase in impedance to flow in the uterine and/or umbilical arteries with decreased pulsatility index in the fetal cerebral vessels and increased pulsatility index (PI) in the descending thoracic aorta (see Chapter 4 ).
Prediction of pulmonary hypoplasia

Amniorrhexis before 25 weeks of gestation is associated with the development of pulmonary hypoplasia and hypertension. Suggested mechanisms for the development of pulmonary hypoplasia include: >

(1) Extrinsic compression of the fetal lungs, which interferes with normal development;

(2) Excessive loss of lung fluid, either due to extrinsic compression of the fetal thorax or decrease in intra-amniotic pressure and increase in the alveolar–amniotic pressure gradient 17; and

(3) Cessation of fetal breathing movements, because, in animal studies, transection of the cervical spinal cord and consequent interruption of breathing movements result in pulmonary hypoplasia 18.

Attempts at antenatal prediction of pulmonary hypoplasia in pregnancies with preterm prelabor amniorrhexis have focused on ultrasonographic assessment of lung size, amniotic fluid volume and fetal breathing movements 19. Studies examining fetal thoracic circumference and lung size have reported favorable results in the prediction of pulmonary hypoplasia 20,21, whereas studies that attempted to quantify the degree of oligohydramnios or fetal breathing movements have generally reported poor prediction 19–23. Prediction of pulmonary hypoplasia has also been attempted by antenatal Doppler studies 24. Blood flow in the ductus arteriosus, as assessed by Doppler ultrasound, is altered by breathing movements. In a study of 12 cases of preterm prelabor amniorrhexis and severe oligohydramnios, the alteration in ductal blood flow by breathing movements was normal in seven cases with normal lungs, and reduced in all five cases with pulmonary hypoplasia 25. Doppler studies in fetuses with pulmonary hypoplasia, due to multicystic kidneys or obstructive uropathy, reported increased impedance to flow in the branches of the pulmonary artery, consistent with high peripheral pulmonary vascular resistance 26–29.

Rizzo et al. meaured the PI in the peripheral pulmonary arteries in 20 pregnancies complicated by amniorrhexis before 24 weeks of gestation 30. In fetuses that subsequently developed pulmonary hypoplasia, the PI was increased from as early as 2 weeks after amniorrhexis (Figure 1). The PI in the peripheral pulmonary arteries was above the 95th centile of the normal range in 62.5% of those that developed pulmonary hypoplasia 30.

Figure 1: Flow velocity waveforms (left) from the fetal peripheral pulmonary artery at 28 weeks in a non-complicated pregnancy.
CONCLUSIONS

  • Preterm prelabor amniorrhexis is associated with a high risk of preterm delivery, due to intrauterine infection, as well as neonatal death, due to pulmonary hypoplasia.

  • In pregnancies with preterm prelabor amniorrhexis, intrauterine infection is not associated with altered fetal oxygenation or a major degree of vasoconstriction in the uteroplacental or fetoplacental circulation.

  • In pregnancies with preterm prelabor amniorrhexis, Doppler assessment does not provide a clinically useful distinction between infected and non-infected cases. The pulsatility indices in the uterine and umbilical arteries and in the fetalmiddle cerebral arteries and thoracic aorta are not significantly different from normal and there are no significant differences between these values in those with and without intrauterine infection.

  • In pregnancies with preterm prelabor amniorrhexis, Doppler assessment may be useful in the prediction of pulmonary hypoplasia. Thus, in fetuses that subsequently develop pulmonary hypoplasia, impedance in the peripheralpulmonary arteries is increased from as early as 2 weeks after amniorrhexis.
 
REFERENCES

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2. Gomez R, Romero R, Mazor M, Ghezzi F, David C, Yoon BH. The role of infection in preterm labour and delivery. In Elder MG, Lamont RF, Romero R, eds. Preterm Labour. Edinburgh: Churchill Livingstone, 1997:85

3. Carroll SG, Abbas A, Ville Y, Meher-Homjii H, Nicolaides KH. Concentration of fetal plasma and amniotic fluid interleukin-1 in pregnancies complicated by preterm prelabour amniorrhexis. J Clin Pathol 1995;48:368–71

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18. Wigglesworth JS, Desai R. Effects on lung growth of cervical cord section in the rabbit fetus. Early Hum Dev 1979;3:51–65

19. Carroll SG, Papaioannou S, Nicolaides KH. Assessment of fetal activity and amniotic fluid volume in the prediction of intrauterine infection in preterm prelabor amniorrhexis. Am J Obstet Gynecol  1995;172:1427–35

20. Blott M, Greenough A, Nicolaides KH, Campbell S. The ultrasonographic assessment of the fetal thorax and fetal breathing movements in the prediction of pulmonary hypoplasia. Early Hum Dev 1990;21:143–51

21. Roberts AB, Mitchell JM. Direct ultrasonographic measurement of fetal lung length in normal pregnancies and pregnancies complicated by prolonged rupture of membranes. Am J Obstet Gynecol 1990;163:1560–6

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23. Moessinger AC, Higgins A, Fox HE, Rey HR. Fetal breathing movements are not a reliable predictor of continued lung development in pregnancies complicated by oligohydramnios. Lancet 1987;ii:1297–9

24. Wladimiroff JW. Predicting pulmonary hypoplasia: assessment of lung volume or lung function or both? Ultrasound Obstet Gynecol 1998;11:164–6

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28. Oshimura S, Masuzaki H, Miura K, Muta K, Gotoh H, Ishimaru T Diagnosis of fetal pulmonary hypoplasia by measurement of blood flow velocity waveforms of pulmonary arteries with Doppler ultrasonography. Am J Obstet Gynecol 1999;180:441–6

29. Chaoui R, Kalache K., Tennestedt C, Lenz F, Vogel M. Pulmonary arterial Doppler velocimetry in fetuses with lung hypoplasia. Eur J Obstet Gynecol Reprod Biol 1999;84:179–185

30. Rizzo G, Capponi A., Angelini E, Mazzoleni A, Romanini C. Blood flow velocity waveforms from fetal peripheral pulmonary arteries in pregnancies with preterm premature rupture of membranes: relationship with pulmonary hypoplasia. Ultrasound Obstet Gynecol 2000;in press
Doppler in Obstetrics
Copyright © 2002 by Kypros Nicolaides, Giuseppe Rizzo, Kurt Hecker and Renato Ximenes
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