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Fetal Nuchal Translucency Thickness at 10–14 Weeks’ Gestation and Congenital Diaphragmatic Hernia
Fetal Nuchal Translucency Thickness at 10 –14 Weeks’ Gestation and Congenital Diaphragmatic Hernia N. J. SEBIRE, MD, R. J. M. SNIJDERS, PhD, M. DAVENPORT, MD, A. GREENOUGH, MD, AND K. H. NICOLAIDES, MD Objective: To examine the possible association between increased fetal nuchal translucency thickness at 10 –14 weeks and congenital diaphragmatic hernia. Methods: This was a multicenter ultrasound screening study for chromosomal defects in singleton pregnancies by a combination of maternal age and fetal nuchal translucency at 10 –14 weeks’ gestation. The prevalence of diaphragmatic hernia diagnosed prenatally or postnatally was calculated in the chromosomally normal group and in those pregnancies resulting in live births with no dysmorphic features suggestive of a chromosomal abnormality. We calculated the sensitivity of nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia and the possible prognostic value of increased nuchal translucency in the prediction of outcome. Results: There were 78,639 pregnancies presumed to be normal chromosomally, including 19 with diaphragmatic hernia. In four cases, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) cases of diaphragmatic hernia. The translucency was increased in five of the six cases that resulted in neonatal death, compared with two of the nine survivors (Z 5 2.32, P < .05). Conclusion: The prevalence of diaphragmatic hernia in chromosomally normal fetuses is about one in 4000, and nearly 40% of affected fetuses have increased nuchal translucency at 10 –14 weeks’ gestation. Increased nuchal translucency may be a marker of intrathoracic compression–related pulmonary hypoplasia. (Obstet Gynecol 1997;90:943– 6. © 1997 by The American College of Obstetricians and Gynecologists.) From the Harris Birthright Research Centre for Fetal Medicine and the Departments of Neonatology and Paediatric Surgery, King’s College Hospital Medical School, London, United Kingdom. This study was supported by a grant from the Fetal Medicine Foundation (Charity no. 1037116).
VOL. 90, NO. 6, DECEMBER 1997
Diaphragmatic hernia can be diagnosed during the second and third trimesters of pregnancy by the ultrasonographic demonstration of stomach, intestines, or liver in the thorax and the associated mediastinal shift to the opposite side. In about 50% of affected fetuses there are associated chromosomal abnormalities or other defects.1 In those with isolated diaphragmatic hernia, survival after postnatal surgery is about 50%, but the remainder die because of pulmonary hypoplasia and pulmonary hypertension.2 We3 have noted that diaphragmatic hernia is one of the conditions that may be associated with increased nuchal translucency thickness at 10 –14 weeks’ gestation. The aim of this multicenter study was to examine the possible association between increased nuchal translucency and diaphragmatic hernia and to examine the possible prognostic value of this finding in the prediction of neonatal death from pulmonary hypoplasia.
Materials and Methods As part of an ongoing multicenter ultrasound study, begun in September 1992 and coordinated by the Fetal Medicine Foundation,4 women in London and the surrounding areas are offered screening for chromosomal defects by a combination of maternal age and fetal nuchal translucency at 10 –14 weeks’ gestation. The pregnancy is examined for the number of live fetuses, crown-rump length, nuchal translucency thickness, and major defects, such as anencephaly. An ultrasound scan also is offered routinely at 16 –22 weeks for determination of fetal growth and systematic examination of fetal anatomy. Demographic details and ultrasound findings are entered into a computer database at the time of the scans, and pregnancy outcome is obtained from the patients themselves or the referring hospitals.
0029-7844/97/$17.00 PII S0029-7844(97)00483-3
943
A computer search was performed to identify all singleton pregnancies with live fetuses at the 10- to 14-week scan, crown-rump length of 38 – 84 mm, and estimated date of delivery before April 1, 1997. Excluded were pregnancies with chromosomal defects, those terminated for psychosocial indications or fetal abnormalities other than diaphragmatic hernia, perinatal deaths that did not have postmortem examinations, and pregnancies in which no follow-up details were obtained. The sensitivity of fetal nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia was calculated, and its possible prognostic value was examined by comparing outcome in cases of diaphragmatic hernia with and without increased nuchal translucency by comparison of proportions.
Results The selection criteria were fulfilled by 78,639 pregnancies, including 19 (prevalence of one per 4139) with diaphragmatic hernia. The median maternal age was 31 years (range 15– 49), the median gestational age at the first trimester scan was 12 weeks (range 10 –14), and the median crown-rump length was 58 mm (range 38 – 84). The diagnosis of diaphragmatic hernia was made at the first-trimester scan in one case (Figure 1), at the second-trimester scan in 14 cases, and at birth in four cases; in the latter four cases, the diagnosis was missed at the second-trimester scan (Table 1). In 17 cases the diaphragmatic hernia was an isolated finding, and in two there were additional abnormalities; in one there was a large sacrococcygeal teratoma and in the other there were also severe scoliosis and multicystic dysplastic kidneys. In four cases, including the two with additional defects, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) of 19 cases of diaphragmatic hernia, including five (83%) of six of those resulting in neonatal death. Thus, neonatal death occurred in five (71%, 95% confidence interval [CI] 30, 95%) of seven cases with increased nuchal translucency, compared with one (13%, 95% CI 1, 53%) of eight cases with normal nuchal translucency (Z 5 2.32, P , .05).
Discussion This study suggests that the prevalence of diaphragmatic hernia in chromosomally normal fetuses is about
944 Sebire et al
Hernia and Nuchal Translucency
Figure 1. Ultrasound photographs of congenital diaphragmatic hernia in a fetus at 13 weeks’ gestation demonstrating increased fetal nuchal translucency thickness (top) and the presence of stomach in the thorax (bottom).
one in 4000, nearly 40% of affected fetuses have increased nuchal translucency at 10 –14 weeks, and increased nuchal translucency is a marker of intrathoracic compression–related pulmonary hypoplasia. The reported prevalence of diaphragmatic hernia in live births is about one in 40005 but the prevalence of associated chromosomal abnormalities is only about 5%,6 which is lower than in prenatal studies. Thus, the combined data from seven studies on a total of 173 fetuses with diaphragmatic hernia diagnosed at 14 – 41 weeks’ gestation indicated that there were chromosomal abnormalities, most commonly trisomies 18 and 13, in 18% of cases.7 More than 80% of fetuses with trisomies 18 and 13 are identified through screening by nuchal translucency at 10 –14 weeks,4 and the pregnan-
Obstetrics & Gynecology
Table 1. Fetal Crown-Rump Length, Nuchal Translucency Thickness, Gestational Age at Diagnosis, and Outcome of 19 Fetuses With Diaphragmatic Hernia
Case
CRL (mm)
NT (mm)
Gestational age at diagnosis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
54 47 59 68 65 65 53 54 71 50 50 72 58 49 56 60 40 76 44
5.1* 4.7* 4.6* 3.6* 3.3* 3.1* 2.8* 2.3 2.2 2.1 1.7 1.7 1.6 1.5 1.5 1.4 1.1 1.0 0.8
13 wk 18 wk 20 wk 20 wk 16 wk 20 wk 18 wk 20 wk 16 wk 20 wk 21 wk Birth 19 wk 21 wk 20 wk Birth 19 wk Birth Birth
Outcome Neonatal death Neonatal death Neonatal death Neonatal death Survival Survival Neonatal death Termination Survival Neonatal death Survival Survival Termination Termination Survival Survival Termination Survival Survival
CRL 5 crown-rump length; NT 5 nuchal translucency thickness. In case 2 the hernia was right-sided, but in all other cases it was left-sided. * Fetal nuchal translucency above the 95th centile of the normal range for gestation.4
cies usually are terminated during the first trimester. Consequently, in our study of fetuses with diaphragmatic hernia that were identified either in the second trimester or at birth, there were no cases with chromosomal abnormalities. Because our observed prevalence of diaphragmatic hernia is similar to that in live births, the data suggest that chromosomally normal fetuses with diaphragmatic hernia are not at increased risk for intrauterine death. The prenatal diagnosis of diaphragmatic hernia by ultrasonography usually is made during the second trimester of pregnancy by the demonstration of intrathoracic viscera and the associated mediastinal shift. There are also case reports8,9 of the sonographic diagnosis during the late first trimester. In our study, the sonographers were not instructed specifically to look for diaphragmatic hernia at 10 –14 weeks, and therefore the sensitivity of direct ultrasonographic examination in the detection of this abnormality has not been investigated. However, in nearly 40% of the affected cases there was increased nuchal translucency, and it is likely that targeted examination in such cases will lead to first-trimester diagnosis. In a previous study10 investigating the sensitivity of second-trimester scanning, only about 20% of affected fetuses were identified.
VOL. 90, NO. 6, DECEMBER 1997
In 80% of our cases with isolated diaphragmatic hernia resulting in neonatal death there was increased nuchal translucency at 10 –14 weeks’ gestation. The diaphragm develops by fusion of the pleuroperitoneal membrane with the septum transversum, the dorsal mesentery of the esophagus, and the lateral body walls, and this process usually is completed by the 9th week of gestation.11 In the presence of a defective diaphragm there is herniation of the abdominal viscera into the thorax at about the 10th week of gestation, when the intestines return to the abdominal cavity from the umbilical cord. It is possible that in those cases with increased nuchal translucency, there is intrathoracic herniation of the abdominal viscera at this gestational age, and the increased nuchal translucency may be the consequence of venous congestion in the head and neck due to mediastinal compression and impedance of venous return. In such cases, prolonged intrathoracic compression of the lungs causes pulmonary hypoplasia. In the cases in which diaphragmatic hernia is associated with a good prognosis, the intrathoracic herniation of viscera may be delayed until the second or third trimester of pregnancy. An alternative hypothesis is that in all cases of diaphragmatic hernia there is intrathoracic herniation at 10 –14 weeks, but increased nuchal translucency is observed only in those with compression of the lungs sufficiently severe to cause pulmonary hypoplasia. Screening for diaphragmatic hernia at the 10- to 14-week scan will help determine which of the hypotheses is likely to be true. Studies12 in the lamb have demonstrated that intrathoracic tamponade from midgestation is associated with the development of pulmonary hypoplasia and that intrauterine decompression can prevent or reduce the severity of these complications. Such studies have encouraged the introduction of fetal surgery in the human for cases diagnosed at less than 24 weeks’ gestation13 but without evidence that such interventions are beneficial. The findings of our study suggest that, at least in some affected fetuses, the pathologic insult to lung development occurs in the first trimester and, therefore, early intervention may be required to prevent subsequent pulmonary hypoplasia and hypertension. Because survival may be as high as 80% in fetuses with normal nuchal translucency, the possible role of surgery in utero should be investigated in the group with increased nuchal translucency, in which the likelihood of survival with no prenatal surgery may be less than 30%. However, it is possible that increased nuchal translucency may be a marker of abnormal development of the lungs that cannot be reversed even by intrauterine surgery as early as 10 –14 weeks.
Sebire et al
Hernia and Nuchal Translucency
945
References 1. Thorpe-Beeston JG, Gosden CM, Nicolaides KH. Prenatal diagnosis of congenital diaphragmatic hernia: Associated malformations and chromosomal defects. Fetal Ther 1989;4:21– 8. 2. Harrison MR, Adzick NS, Estes JM, Howell LJ. A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA 1994;271:382– 4. 3. Pandya PP, Kondylios A, Hilbert L, Snijders RJM, Nicolaides KH. Chromosomal defects and outcome in 1,015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995;5:15–9. 4. Snijders RJM, Johnson S, Sebire NJ, Noble PL, Nicolaides KH. First-trimester ultrasound screening for chromosomal defects. Ultrasound Obstet Gynecol 1996;7:216 –26. 5. Wenstrom KD, Weiner CP, Hanson JW. A five-year statewide experience with congenital diaphragmatic hernia. Am J Obstet Gynecol 1991;165:838 – 42. 6. Torfs CP, Curry CJ, Bateson TF, Honore LH. A population based study of congenital diaphragmatic hernia. Teratology 1992;46:555– 65. 7. Snijders RJM, Farrias M, Von Kaisenberg C, Nicolaides KH. Fetal abnormalities. In: Snijders RJM, Nicolaides KH, eds. Ultrasound markers for fetal chromosomal defects. Casterton, UK: Parthenon Press, 1996:1–54. 8. Bronshtein M, Lewit N, Sujov PO, Makhoul IR, Blazer S. Prenatal diagnosis of congenital diaphragmatic hernia: Timing of herniation and outcome. Prenat Diagn 1995;15:695– 8. 9. Zimmer EZ, Bronshtein M. Early sonographic diagnosis of fetal midline disruption syndromes. Prenat Diagn 1996;16:65–9. 10. Dillon E, Renwick M. Antenatal detection of congenital diaphragmatic hernias: The Northern Region experience. Clin Radiol 1993; 48:264 –7.
946 Sebire et al
Hernia and Nuchal Translucency
11. Moore KC, Persaud TVN. The developing human: Clinically oriented embryology. London: Saunders, 1993:174 – 85. 12. Harrison MR, Bressack MA, Churg AM, De Lorimier AA. Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth. Surgery 1980;88:260 – 8. 13. Harrison MR, Adzick NS, Flake AW, Jennings RW, Estes JM, MacGillivray TE, et al. Correction of congenital diaphragmatic hernia in utero. VI. Hard-earned lessons. J Pediatr Surg 1993;28: 1411– 8.
Address reprint requests to:
K. H. Nicolaides, MD Harris Birthright Research Centre for Fetal Medicine King’s College Hospital Medical School Denmark Hill London SE5 8RX United Kingdom E-mail: [email protected]
Received May 22, 1997. Received in revised form July 21, 1997. Accepted August 7, 1997.
Copyright © 1997 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology
VOL. 90, NO. 6, DECEMBER 1997
Diaphragmatic hernia can be diagnosed during the second and third trimesters of pregnancy by the ultrasonographic demonstration of stomach, intestines, or liver in the thorax and the associated mediastinal shift to the opposite side. In about 50% of affected fetuses there are associated chromosomal abnormalities or other defects.1 In those with isolated diaphragmatic hernia, survival after postnatal surgery is about 50%, but the remainder die because of pulmonary hypoplasia and pulmonary hypertension.2 We3 have noted that diaphragmatic hernia is one of the conditions that may be associated with increased nuchal translucency thickness at 10 –14 weeks’ gestation. The aim of this multicenter study was to examine the possible association between increased nuchal translucency and diaphragmatic hernia and to examine the possible prognostic value of this finding in the prediction of neonatal death from pulmonary hypoplasia.
Materials and Methods As part of an ongoing multicenter ultrasound study, begun in September 1992 and coordinated by the Fetal Medicine Foundation,4 women in London and the surrounding areas are offered screening for chromosomal defects by a combination of maternal age and fetal nuchal translucency at 10 –14 weeks’ gestation. The pregnancy is examined for the number of live fetuses, crown-rump length, nuchal translucency thickness, and major defects, such as anencephaly. An ultrasound scan also is offered routinely at 16 –22 weeks for determination of fetal growth and systematic examination of fetal anatomy. Demographic details and ultrasound findings are entered into a computer database at the time of the scans, and pregnancy outcome is obtained from the patients themselves or the referring hospitals.
0029-7844/97/$17.00 PII S0029-7844(97)00483-3
943
A computer search was performed to identify all singleton pregnancies with live fetuses at the 10- to 14-week scan, crown-rump length of 38 – 84 mm, and estimated date of delivery before April 1, 1997. Excluded were pregnancies with chromosomal defects, those terminated for psychosocial indications or fetal abnormalities other than diaphragmatic hernia, perinatal deaths that did not have postmortem examinations, and pregnancies in which no follow-up details were obtained. The sensitivity of fetal nuchal translucency above the 95th centile of the normal range in the detection of diaphragmatic hernia was calculated, and its possible prognostic value was examined by comparing outcome in cases of diaphragmatic hernia with and without increased nuchal translucency by comparison of proportions.
Results The selection criteria were fulfilled by 78,639 pregnancies, including 19 (prevalence of one per 4139) with diaphragmatic hernia. The median maternal age was 31 years (range 15– 49), the median gestational age at the first trimester scan was 12 weeks (range 10 –14), and the median crown-rump length was 58 mm (range 38 – 84). The diagnosis of diaphragmatic hernia was made at the first-trimester scan in one case (Figure 1), at the second-trimester scan in 14 cases, and at birth in four cases; in the latter four cases, the diagnosis was missed at the second-trimester scan (Table 1). In 17 cases the diaphragmatic hernia was an isolated finding, and in two there were additional abnormalities; in one there was a large sacrococcygeal teratoma and in the other there were also severe scoliosis and multicystic dysplastic kidneys. In four cases, including the two with additional defects, the parents opted for termination of the pregnancy. The other 15 pregnancies resulted in live births; nine infants survived after successful surgical repair of the hernia, but six neonates died because of pulmonary hypoplasia. At the 10- to 14-week scan, the fetal nuchal translucency was above the 95th centile for crown-rump length in seven (37%) of 19 cases of diaphragmatic hernia, including five (83%) of six of those resulting in neonatal death. Thus, neonatal death occurred in five (71%, 95% confidence interval [CI] 30, 95%) of seven cases with increased nuchal translucency, compared with one (13%, 95% CI 1, 53%) of eight cases with normal nuchal translucency (Z 5 2.32, P , .05).
Discussion This study suggests that the prevalence of diaphragmatic hernia in chromosomally normal fetuses is about
944 Sebire et al
Hernia and Nuchal Translucency
Figure 1. Ultrasound photographs of congenital diaphragmatic hernia in a fetus at 13 weeks’ gestation demonstrating increased fetal nuchal translucency thickness (top) and the presence of stomach in the thorax (bottom).
one in 4000, nearly 40% of affected fetuses have increased nuchal translucency at 10 –14 weeks, and increased nuchal translucency is a marker of intrathoracic compression–related pulmonary hypoplasia. The reported prevalence of diaphragmatic hernia in live births is about one in 40005 but the prevalence of associated chromosomal abnormalities is only about 5%,6 which is lower than in prenatal studies. Thus, the combined data from seven studies on a total of 173 fetuses with diaphragmatic hernia diagnosed at 14 – 41 weeks’ gestation indicated that there were chromosomal abnormalities, most commonly trisomies 18 and 13, in 18% of cases.7 More than 80% of fetuses with trisomies 18 and 13 are identified through screening by nuchal translucency at 10 –14 weeks,4 and the pregnan-
Obstetrics & Gynecology
Table 1. Fetal Crown-Rump Length, Nuchal Translucency Thickness, Gestational Age at Diagnosis, and Outcome of 19 Fetuses With Diaphragmatic Hernia
Case
CRL (mm)
NT (mm)
Gestational age at diagnosis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
54 47 59 68 65 65 53 54 71 50 50 72 58 49 56 60 40 76 44
5.1* 4.7* 4.6* 3.6* 3.3* 3.1* 2.8* 2.3 2.2 2.1 1.7 1.7 1.6 1.5 1.5 1.4 1.1 1.0 0.8
13 wk 18 wk 20 wk 20 wk 16 wk 20 wk 18 wk 20 wk 16 wk 20 wk 21 wk Birth 19 wk 21 wk 20 wk Birth 19 wk Birth Birth
Outcome Neonatal death Neonatal death Neonatal death Neonatal death Survival Survival Neonatal death Termination Survival Neonatal death Survival Survival Termination Termination Survival Survival Termination Survival Survival
CRL 5 crown-rump length; NT 5 nuchal translucency thickness. In case 2 the hernia was right-sided, but in all other cases it was left-sided. * Fetal nuchal translucency above the 95th centile of the normal range for gestation.4
cies usually are terminated during the first trimester. Consequently, in our study of fetuses with diaphragmatic hernia that were identified either in the second trimester or at birth, there were no cases with chromosomal abnormalities. Because our observed prevalence of diaphragmatic hernia is similar to that in live births, the data suggest that chromosomally normal fetuses with diaphragmatic hernia are not at increased risk for intrauterine death. The prenatal diagnosis of diaphragmatic hernia by ultrasonography usually is made during the second trimester of pregnancy by the demonstration of intrathoracic viscera and the associated mediastinal shift. There are also case reports8,9 of the sonographic diagnosis during the late first trimester. In our study, the sonographers were not instructed specifically to look for diaphragmatic hernia at 10 –14 weeks, and therefore the sensitivity of direct ultrasonographic examination in the detection of this abnormality has not been investigated. However, in nearly 40% of the affected cases there was increased nuchal translucency, and it is likely that targeted examination in such cases will lead to first-trimester diagnosis. In a previous study10 investigating the sensitivity of second-trimester scanning, only about 20% of affected fetuses were identified.
VOL. 90, NO. 6, DECEMBER 1997
In 80% of our cases with isolated diaphragmatic hernia resulting in neonatal death there was increased nuchal translucency at 10 –14 weeks’ gestation. The diaphragm develops by fusion of the pleuroperitoneal membrane with the septum transversum, the dorsal mesentery of the esophagus, and the lateral body walls, and this process usually is completed by the 9th week of gestation.11 In the presence of a defective diaphragm there is herniation of the abdominal viscera into the thorax at about the 10th week of gestation, when the intestines return to the abdominal cavity from the umbilical cord. It is possible that in those cases with increased nuchal translucency, there is intrathoracic herniation of the abdominal viscera at this gestational age, and the increased nuchal translucency may be the consequence of venous congestion in the head and neck due to mediastinal compression and impedance of venous return. In such cases, prolonged intrathoracic compression of the lungs causes pulmonary hypoplasia. In the cases in which diaphragmatic hernia is associated with a good prognosis, the intrathoracic herniation of viscera may be delayed until the second or third trimester of pregnancy. An alternative hypothesis is that in all cases of diaphragmatic hernia there is intrathoracic herniation at 10 –14 weeks, but increased nuchal translucency is observed only in those with compression of the lungs sufficiently severe to cause pulmonary hypoplasia. Screening for diaphragmatic hernia at the 10- to 14-week scan will help determine which of the hypotheses is likely to be true. Studies12 in the lamb have demonstrated that intrathoracic tamponade from midgestation is associated with the development of pulmonary hypoplasia and that intrauterine decompression can prevent or reduce the severity of these complications. Such studies have encouraged the introduction of fetal surgery in the human for cases diagnosed at less than 24 weeks’ gestation13 but without evidence that such interventions are beneficial. The findings of our study suggest that, at least in some affected fetuses, the pathologic insult to lung development occurs in the first trimester and, therefore, early intervention may be required to prevent subsequent pulmonary hypoplasia and hypertension. Because survival may be as high as 80% in fetuses with normal nuchal translucency, the possible role of surgery in utero should be investigated in the group with increased nuchal translucency, in which the likelihood of survival with no prenatal surgery may be less than 30%. However, it is possible that increased nuchal translucency may be a marker of abnormal development of the lungs that cannot be reversed even by intrauterine surgery as early as 10 –14 weeks.
Sebire et al
Hernia and Nuchal Translucency
945
References 1. Thorpe-Beeston JG, Gosden CM, Nicolaides KH. Prenatal diagnosis of congenital diaphragmatic hernia: Associated malformations and chromosomal defects. Fetal Ther 1989;4:21– 8. 2. Harrison MR, Adzick NS, Estes JM, Howell LJ. A prospective study of the outcome for fetuses with diaphragmatic hernia. JAMA 1994;271:382– 4. 3. Pandya PP, Kondylios A, Hilbert L, Snijders RJM, Nicolaides KH. Chromosomal defects and outcome in 1,015 fetuses with increased nuchal translucency. Ultrasound Obstet Gynecol 1995;5:15–9. 4. Snijders RJM, Johnson S, Sebire NJ, Noble PL, Nicolaides KH. First-trimester ultrasound screening for chromosomal defects. Ultrasound Obstet Gynecol 1996;7:216 –26. 5. Wenstrom KD, Weiner CP, Hanson JW. A five-year statewide experience with congenital diaphragmatic hernia. Am J Obstet Gynecol 1991;165:838 – 42. 6. Torfs CP, Curry CJ, Bateson TF, Honore LH. A population based study of congenital diaphragmatic hernia. Teratology 1992;46:555– 65. 7. Snijders RJM, Farrias M, Von Kaisenberg C, Nicolaides KH. Fetal abnormalities. In: Snijders RJM, Nicolaides KH, eds. Ultrasound markers for fetal chromosomal defects. Casterton, UK: Parthenon Press, 1996:1–54. 8. Bronshtein M, Lewit N, Sujov PO, Makhoul IR, Blazer S. Prenatal diagnosis of congenital diaphragmatic hernia: Timing of herniation and outcome. Prenat Diagn 1995;15:695– 8. 9. Zimmer EZ, Bronshtein M. Early sonographic diagnosis of fetal midline disruption syndromes. Prenat Diagn 1996;16:65–9. 10. Dillon E, Renwick M. Antenatal detection of congenital diaphragmatic hernias: The Northern Region experience. Clin Radiol 1993; 48:264 –7.
946 Sebire et al
Hernia and Nuchal Translucency
11. Moore KC, Persaud TVN. The developing human: Clinically oriented embryology. London: Saunders, 1993:174 – 85. 12. Harrison MR, Bressack MA, Churg AM, De Lorimier AA. Correction of congenital diaphragmatic hernia in utero. II. Simulated correction permits fetal lung growth with survival at birth. Surgery 1980;88:260 – 8. 13. Harrison MR, Adzick NS, Flake AW, Jennings RW, Estes JM, MacGillivray TE, et al. Correction of congenital diaphragmatic hernia in utero. VI. Hard-earned lessons. J Pediatr Surg 1993;28: 1411– 8.
Address reprint requests to:
K. H. Nicolaides, MD Harris Birthright Research Centre for Fetal Medicine King’s College Hospital Medical School Denmark Hill London SE5 8RX United Kingdom E-mail: [email protected]
Received May 22, 1997. Received in revised form July 21, 1997. Accepted August 7, 1997.
Copyright © 1997 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc.
Obstetrics & Gynecology