Fetal diaphragmatic hernia: Echocardiography and clinical outcome

Fetal Diaphragmatic Hernia: Echocardiography and Clinical Outcome By Karen J. VanderWall,

Thomas

Kohl, N. Scott Adzick, Norman and Michael R. Harrison San Francisco, California

l It is difficult to predict survival of fetuses diagnosed prenatally with congenital diaphragmatic hernia. Some studies suggest that left heart underdevelopment is associated with poor outcome, but fetal echocardiographic variables have not been conclusively proven to be good predictors of postnatal survival. The authors reviewed detailed fetal echocardiographic studies in twelve fetuses with congenital diaphragmatic hernia. Ten echocardiographic variables, including left and right ventricular width, left ventricular volume, and left ventricular mass, were examined from a four-chamber view, corrected for gestational age, and compared with normal data. The results of this study showed no significant differences between survivors and nonsurvivors in the ten variables analyzed. Although left heart dimensions and left ventricular volume in fetuses with congenital diaphragmatic hernia were below the expected normal range, these results did not predict postnatal outcome. Copyright o 1997 by W.6. Saunders Company INDEX WORDS: Congenital diaphragmatic cardiography, left heart hypoplasia.

hernia,

fetal

LTHOUGH cogenital diaphragmatichernia (CDH) is now frequently diagnosedbefore birth, predicting outcome after birth hasbeen difficult. Some studieshave suggestedthat the heart may be abnormal in fetuseswith CDH, and that left heart hypoplasia may predict poor outcome.‘-3 Fetal echocardiography is quite accurate in identifying associatedcardiac abnormalities, but a detailed assessmentof cardiac structure and function is usually not done. We reviewed detailed echocardiographic studies on fetuses diagnosed with CDH to identify variables that might predict outcome after birth. We then compared the echocardiographic variables from the CDH fetuses with echocardiographic variables from normal fetuses. AND METHODS

Thirty of the patients with a fetal diagnosis of CDH who were referred 10 the Fetal Treatment Center at the University of California, San Francisco (UCSF) from 1990 to 1995 had detaIled fetal echocarchographic evaluations. We excluded fetuses with other cardiac anomalies and cases mvolvmg elective termmation of pregnancy, in utero fetal demise. or fetal surgery. Of the 30 patients reviewed. twelve fetuses (range. 17 to 2.5 weeks’ gestation) had fetal echocardiographic studies that were adequate for careful measurement and analysis. One examiner (T.K.) who was unaware of clinical outcome reviewed the echocardiograpluc videotaped exams. Echocardiographic variables were examined from a four-chamber view of the heart (Fig 1). We measured the maximum length of the left and right ventricular chamber

Journal

of Pediatric

Surgery,

Vol32,

No 2 (February).

1997:

pp 223-226

Julien

I. Hoffman,

during diastole (LV length, RV length), maximum width of the left and right ventricular wall during diastole (LV width. RV width). and left ventricular wall. right ventricular wall and septal thickness during drastole (LV wall, RV wall, VS). The left-to-right ventricular width ratio (measunng the widths of the ventricles m end-diastole) and the left ventricular volume (LV volume) were also calculated. Left ventricular mass (LV mass) was calculated at end-dlastole (LV volume of muscle and cavity - LV volume of the cavity) X l.05].1 Postnatal care took place at UCSF or other appropnate tertiary centers with extracorporeal membrane oxygenation (ECMO) capability. The principal outcome vanable was survival, wluch was defined as achievmg the age of 2 months or &charge from the hospital. StatIstical analysis was performed by the paired Student’s 1 test with P values of less than .05 consldered sigmficant. Regression analysis curves with mean and confidence levels for individual pomts were constructed for each variable and data were compared with normal controls at corresponding gestatlonal ages.5 A one-sided Fisher’s exact test was used to compare the CDH group with the normal controls.

RESULTS

echo-

A

MATERIALS

H. Silverman,

The overall survival was 50% (6 of 12). All diagnoses of CDH were madeat or before 25 weeks’ gestation.The average gestational age was similar (23 weeks for survivors, 22.8 weeks for nonsurvivors). Of the ten variables evaluated, none predicted survival (Table 1). Although the LV width and LV masswere less in the nonsurvivor group, the differences were not significant (P > .5). When the echocardiographic variables from the CDH group (n = 12) were compared with fetal echocardiographic variables from normal controls, the LV width and RV width were significantly lessthan controls at the same gestational age (one-sided Fisher’s exact test, P = .034 and P = .0226, respectively; Fig 2). The LV length and RV length were not significantly different from controls (data not shown). The LV volume and LV masswere also significantly lessthan the control group (P = 0.0102 and P = 0.0137. respectively; Fig 3).

From Pediatrics.

the Departments Urziversuy

of Surgery

of California,

Pedratnc San Francisco.

Echocardiography,

and

CA

Presented at tlze 27th Annual Meeting of the Amerrcan Pediatric Surgical Assoczation, San Diego, California. May 20-23. 1996. Address reprznt requests to Karen J. VanderWall. MD, The Fetal Treatment Center: 513 PurnassusAve, Room 1601 HSW San Francisco. CA 93133-0570. Copyright

o I997

by W B. Saurzders

Cornpuny

0022-3468/97/3202-0015$03.00/0

223

224

VANDERWALL

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0.5 , 4’ Fig 1. Line drawing of a four-chamber view of the fetal heart in diastole. Ventricular dimensions were measured as demonstrated by the arrows. LA, left atrium; RA, right atrium; LV, left ventricle; RV, right ventricle.

0.0

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DISCUSSION

Survivors Nonsurvivors P value NOTE.

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(n = 6) (n = 6)

measurements

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Fetal echocardiography of fetuses with CDH is often used as a screening tool to rule out associatedcardiac anomalies. Rarely is a comprehensive evaluation of the fetal heart pursuedin thesepatients. In particular, predictive variables of neonatal death would be useful as selection criteria for fetal therapy. Previous studieshave found fetal echocardiographic variables that were associated with poor outcome but were not absoluteprognostic indicators.2.3 These variables. a reduced left-to-right ventricular width ratio and cardiac ventricular disproportion, suggestthat the left heart may be underdeveloped. Our study, however, found no echocardiographic parameter that predicted survival in fetuseswith CDH. Left heart underdevelopment has previously been reported in fetuses with CDH, but the pathophysiology remains elusive. One of the proposedmechanismscausing left heart underdevelopment is mechanical compression from the herniated visceraS6Karamanoukian et al7 created a CDH model in the fetal lamb and demonstrated that the heartsin the CDH lambswere smaller.If the heart is underdevelopedas a result of mechanical compression alone, a decreasein width as well aslength (i.e. a smaller heart) might be expected. When we compared the echocardiographic variables of the CDH group with normal controls, the CDH group had a decreasein LV width and RV width. The LV volume and LV mass in the CDH group were alsoreduced, but the lengths of the ventricles were near normal. These findings support a compression Table

?+’

p= oJ343

Fig 2. Left and right ventricular width measurements from CDH fetuses compared with measurements from normal human fetuses. The graphs show the measurements of normal human fetuses at various gestational ages as a line of regression. The bold, continuous line is the mean and the dotted lines are the 95% confidence intervals. The data points are the measurements for each CDH fetus. +, survivors; l , nonsurvivors. (Al For LV width, a one-sided Fisher exact test was performed to assess CDH fetuses above and below the mean values for normal fetuses. (6) For RV width, a one-sided Fisher exact test was performed to assess CDH fetuses above and below the lower 95th percentile values for normal fetuses.

phenomenon;the left heart is compressedin width but not length, and the LV volume is reduced more than the decreasein LV mass. The cause of left heart underdevelopment in fetuses of Fetuses

Prenatally

Diagnosed

With

CDH

LV Width

LV Length

LV Wall

LV Volume

LV Mass

RV Width

RV Length

RV Wall

LV/RV Width

VS

0.74 0.61

1.76 1.69

0.23 0.22

0.57

0.5

1.38 1.03 0.16

0.84 0.78 0.5

17 1.72 0.94

0.24 0.23 0.31

0.88 0.84 0.8

0.23 0.23

0.11

1.31 0.98 0.16

are in centimeters.

0.97

CDH:

ECHOCARDIOGRAPHY

AND

CLINICAL

225

OUTCOME

4d weeks

6 4 2

Es0

weeks

Fig 3. Left ventricular volume and mass measurements from CDH fetuses compared with measurements from normal human fetuses. The graphs show the measurements of normal human fetuses at various gestational ages as a linear line of regression. The data points are the measurements for each CDH fetus. f, survivors; a, nonsurvivors. IA) For LV volume, a one-sided Fisher exact test was performed to assess CDH fetuses above and below the mean values for normal fetuses. W For LV mass, a one-sided Fisher exact test was performed to assess CDH fetuses above and below the mean values for normal fetuses.

with CDH may be more complex than direct mechanical compression. Left heart underdevelopment in CDH may be secondary to reduced LV blood Ilow in utero.2 The development of cardiac chambers is related to blood flow in utero such that reduced blood flow results in underdevelopment. Possible mechanisms leading to a decrease in LV flow may be decreased flow across the patent foramen ovale,’ decreased pulmonary venous flow because of lung hypoplasia (although its contribution may be minimal), or increased left atria1 pressure from mechanical compression.2 Whether a postulated decrease in LV flow is caused by direct mechanical compression or one of the mechanisms mentioned above, clearly, the pathophysiology needs to be elucidated in fetal animal models. Echocardiographic variables and diminished left ventricular size, although documented, do not determine outcome after birth. The left ventricle in fetuses with congenital abnormalities seems to accommodate the altered hemodynamics observed even though they appear “hypoplastic.” The paradigm of this is the postoperative change in the size of the left ventricle in the case of totally anomalous pulmonary venous connection. Here dramatic changes in left ventricular volume occur as the pressure and volume are corrected. Perhaps in fetuses with CDH. the left ventricle is able to accommodate in a similar manner. The prenatal treatment of fetuses with CDH is complicated in part because we still cannot predict which fetuses will live or die. If a fetal echocardiographic parameter could predict survival in fetuses with CDH, the treatment and, ultimately, survival of these fetuses might improve.

REFERENCES 1. Schwartz SM, Vermilion RP, Hirsch1 RB: Evaluation of left ventricular mass in children with congenital diaphragmatic hernia. J Pediatr Surg 125:447-451, 1994 2. Sharland GK, Lockhart SM, Heward AJ, et al: Prognosis m fetal diaphragmatic hernia. Am J Obstet Gynecol 1669-13, 1991 3. Crawford DC, Wright VM, Drake DP, et al: Fetal diaphragmatic hernia: The value of fetal echocardtography in the prediction of postnatal outcome. Br J Obstet Gynaecol96:705-710, 1989 4. Silverman NH: Quantitative methods to enhance morphological mformation using M-mode Doppler, and cross-sectional ultrasound, in

Silverman NH (ed): Pediatric Echocardiography, chap 2. Baltimore, MD, Williams &Wilkins, 1993, p 53 5. Tan J, Silverman NH. Hoffman JI, et al: Cardiac dimenstons determined by cross-sectional echocardiography in the normal human fetus from 18 weeks to term. Am J Cardiol70: 1459-1467, 1992 6. Siebert JR, Hass JE, Beckwith JB: Left ventricular hypoplasia m congenital diaphragmatic hernia. J Pedtatr Surg 19:567-571, 1984 7. Karamanoukian HL, Glick PL, Wdcox DT, et al: Pathophysiology of congenital diaphragmatic hernia. XI: Anatomic and biochemical characterization of the heart in the fetal lamb CDH model. J Pediatr Surg 30:925-928, 1995

Discussion Dr Hirsch1 (Ann Arbor, MI): Previous studies looking at the decrease in left ventricular mass in newborns with CDH have been performed either just before delivery or after delivery. In those studies outcome appeared to be related to left ventricular mass in the perinatal period. The current study is performed in fetuses less than 25 weeks’

gestation and it is suggested that left ventricular thickness or mass is not predictive of outcome. I wonder if you have any thoughts as to the mechanism of decrease in LV mass in these newborns with CDH that explains how LV mass is relatively normal at less than 25 weeks’ gestation and yet decreased later in gestation?

226

K.J. VanderWall (response): We have the unique opportunity to study the hearts of fetuses with CDH early in gestation because of the large number of referrals that we get at UCSF. The gestational age of the fetuses that we studied ranged from 17 to 25 weeks. Let me emphasize that we compared the echo findings with age-matched controls, not with fetuses later in gestation. As I mentioned, the fetuses with CDH had significantly smaller hearts compared with the controls, but the variables that we looked at did not predict survival. I think that the changes in the heart that occur in these fetuses is much more complex than we think, and may be from not only a compression phenomenon, but from changes in blood flow in utero that ultimately cause the small left heart. These changes may take place later in gestation so that

VANDERWALL

ET AL

the small left heart becomes more significant and apparent later in gestation. J.L. Hill (Baltimore, MD): The numbers that you showed, with the limit of six fetuses in each group, show a definite trend in mass and volume. In fact, Bruce Beckwith reported this difference between two pathology autopsy groups comparing CDH patients with matched controls. Don’t you think with more numbers you might have a significantly positive relationship? K. J. VanderWall (response): Yes, I think that if we had more fetuses in our study, we would find that the decrease in mass and volume would be statistically significant for predicting survival. Unfortunately, some of the problems with these studies are that we do have such small numbers, and the examinations are quite laborious and lengthy.