Original Paper Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
Received: May 25, 2013 Accepted after revision: September 23, 2013 Published online: November 29, 2013
Should We Measure Fetal Omphalocele Diameter for Prediction of Perinatal Outcome? Marina Y. Kiyohara a Maria L. Brizot a Adolfo W. Liao a Rossana P.V. Francisco a Ana C.A. Tannuri b Vera L.J. Krebs c Marcelo Zugaib a Departments of a Obstetrics and Gynaecology, b Pediatric Surgery, and c Pediatrics, Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil
Key Words Fetal omphalocele · Abdominal wall defect · Ultrasound · Prenatal diagnosis · Pregnancy outcome
Abstract Objective: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. Methods: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. The OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. Results: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio ≥0.26. In pregnancies with the first ultrasound evaluation performed before 31 weeks’ gestation and an OD/AC ≥0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2–5.7), needing twostep surgery or use of mesh was 4.9 (95% CI: 1.9–14.4), and
© 2013 S. Karger AG, Basel 1015–3837/13/0351–0044$38.00/0 E-Mail [email protected] www.karger.com/fdt
postnatal death was 4 (95% CI: 1.9–7.5). Conclusion: A fetal ultrasound OD/AC ratio ≥0.26 is associated with increased postnatal morbidity and mortality. © 2013 S. Karger AG, Basel
Introduction
Omphalocele is a congenital anterior abdominal wall defect characterized by herniation of abdominal viscera into the umbilical cord. Herniated structures are covered by the peritoneum and amnion. Prenatal diagnosis by ultrasound is possible as early as the first trimester of pregnancy [1, 2], and reported detection rates vary from 25 to 100%, depending on screening policies, ultrasound equipment and operator experience [3]. An abnormal karyotype, additional malformations and genetic syndromes can be found in up to 80% of the cases [4, 5]. As a matter of fact, a large study describing the outcome of cases diagnosed antenatally showed that less than 10% reach operative repair [4]. Likewise, other series have reported poor perinatal outcome, due to associated anomalies, and highlight the importance of careful antenatal assessment and appropriate counseling for the parents [6, 7]. When omphalocele is an isolated finding, survival rates following surgical repair are over 90% [8–10]. NevMaria L. Brizot Department of Obstetrics and Gynecology, Instituto Central, suite 10037, 10th floor Av Dr Enéas de Carvalho Aguiar 255 Sao Paulo, SP, 05403-000 (Brazil) E-Mail mlbrizot @ uol.com.br
ertheless, increased postnatal morbidity and surgical pitfalls are related to the size of the herniated content and giant defects, which include the liver [11]. The definition of big or giant omphalocele published in previous studies is heterogeneous and include presence of the liver in the omphalocele sac [11], more than 75% of the liver in the omphalocele sac [12] or the entire liver in the omphalocele sac [10]. Therefore, comparison of results across different studies that have evaluated prognosis in cases diagnosed antenatally is difficult. Moreover, gestational age at the time of diagnosis was not adjusted and the reported results are not necessarily applicable to all periods of gestation. Recently, three studies have demonstrated increased neonatal morbidity according to different ratios that adjusted omphalocele size to the fetal abdomen: omphalocele diameter/abdominal circumference (OD/AC) [13], omphalocele circumference/AC [7] and OD/abdominal diameter [14]. The present study further evaluates postnatal morbidity and mortality in isolated fetal omphalocele and reviews the literature to discuss additional methodological adjustments that are needed during prenatal omphalocele ultrasound evaluation. Material and Methods This was a retrospective analysis of a prospectively applied protocol involving singleton pregnancies with prenatal diagnosis of isolated fetal omphalocele seen at a tertiary referral center for fetal medicine (Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil) between January 1997 and December 2011. The study protocol was registered and approved by the hospital’s ethics committee (CAPPESQ 0768/10). Pregnant women with a prenatal diagnosis of fetal omphalocele are referred to our center for specialist care. Detailed fetal anomaly and echocardiography scans are performed to confirm the abnormality and investigate associated malformations. Fetal karyotype determination is offered and surveillance includes follow-up scans every 4–6 weeks. An elective cesarean section is usually scheduled at around 39 weeks’ gestation. After birth, surgical correction is planned according to the size of herniated sac and extent of the defect; options include primary closure, with or without the use of a synthetic mesh, or secondary closure after silastic reduction as previously described [8]. In women with regular menstrual cycles and certain of the date of their last menstrual period (LMP), gestational age was calculated from the first day of the LMP, and confirmed by ultrasound examination. When there was discrepancy between the LMP and scan dates of more than 7 days in the first trimester, 10 days in the second trimester or if the LMP was uncertain, gestational age was defined according to the earliest ultrasound findings (fetal crown-rump length measurement during the first trimester, or biparietal diameter and head circumference measure-
Fetal OD and Perinatal Outcome
Fig. 1. Ultrasound image demonstrating a transverse section at the
fetal abdomen at the level of omphalocele insertion. Diameters are demonstrated by calipers 1 and 2 (fetal abdomen), and calipers 3 and 4 (omphalocele).
ments during the second trimester), performed in our own hospital or in other units. At each ultrasound examination, fetal growth, amniotic fluid volume and umbilical artery Doppler examinations were performed. Additionally, herniated contents in the omphalocele sac were described and measurements of the sac were obtained in a transverse section of the fetal abdomen at the level of the omphalocele. The calipers were positioned externally to the peritoneum membrane (fig. 1). All of these measurements were described in the patients’ reports and entered into a computer database system. All examinations were carried out by two fetal medicine specialists (M.L.B. and A.W.L.) using the following equipment: Corevision (Toshiba, Japan), HDI 3000 (ATL, USA), Envisor (Philips, Netherlands) and Voluson (General Electric, Austria). A database search was performed to identify all singleton pregnancies with fetal omphalocele that were referred to our unit and had at least one ultrasound examination before delivery. The abnormality was confirmed at birth, and pregnancy outcome information was retrieved from hospital records and autopsy examination. Cases in which OD measurements were not recorded or had associated major abnormalities, abnormal karyotype, intrauterine death or missing outcome were not included in the analysis. The study group was described according to maternal age, gestational age at delivery, birth weight, Apgar scores, respiratory insufficiency, type of surgical closure (primary or secondary), use of synthetic mesh, time in days to full oral feeding and length of hospital stay. Birth weight was classified according to reference ranges published by Alexander et al. [15]. Primary outcome was defined as neonatal death. Additional outcome measures included need for intubation within the first 24 h of life, need for mechanical ventilation >21 days, need for twostep surgical correction, use of synthetic mesh and reoperation, parenteral feeding >21 days, time to first oral feed, and days until hospital discharge. The mean OD was calculated as the average of the transverse and anteroposterior diameters and the OD/AC ratio was calcu-
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
45
Table 1. Clinical details of cases with fetal omphalocele and postnatal death
Case No.
OD/AC ratio
Gestational age at delivery, weeks
Birth weight, g
Age at death, days
Surgical repair
Complications
1 2 3 4 5 6 7 8 9 10
0.280 0.213 0.387 0.263 0.342 0.218 0.298 0.365 0.179 0.274
37 5/7 34 37 3/7 40 37 2/7 39 37 6/7 36 6/7 39 2/7 35 2/7
2,570 2,200 3,100 2,980 2,370 2,560 3,110 2,480 2,660 2,430
3 2 13 362 5 158 21 59 208 4
secondary primary primary + mesh secondary + mesh primary primary primary + mesh primary + mesh primary primary + mesh
bronchopneumonia hyaline membrane disease bronchopneumonia bronchodysplasia metabolic acidosis + anuria bronchodysplasia + bronchopneumonia sepsis sepsis bronchomalacia + sepsis hyaline membrane disease
lated for each examination. AC was calculated based on anteroposterior (AD1) and transverse (AD2) diameters: 3.14 × (AD1 + AD2)/2. To examine the distribution of the OD/AC ratio according to gestational age, all measurements were included and linear regression analysis was used. Prediction of neonatal death was examined according to the first measurement obtained in each case using the receiver operating characteristic (ROC) curve. The cases were classified according to the best value obtained by ROC curve and morbidity was compared using a Mann-Whitney test for continuous variables and Fisher’s exact test or a χ2 test to evaluate the proportions. Due to the retrospective analysis of the study, no sample size calculation was previously established. Statistical analysis was performed with Statsdirect (Statsdirect, UK) and the significance level was set at 0.05.
Results
Table 2. Prenatal ultrasound findings and delivery details in cases of fetal omphalocele according to perinatal outcome
Postnatal death
Alive
Cases, n 10 37 OD, mm First scan 53.3 [37.0–80.0] 37.1 [21.5–121.0] Last scan 63.4 [32.7–108.0] 58.8 [25.5–120.0] OD/AC First scan 0.28 [0.18–0.39] 0.23 [0.12–0.38] Last scan 0.27 [0.14–0.46] 0.22 [0.09–0.32] Gestational age at delivery, weeks 37.6 [34–40] 37.9 [32.6–39.7] Birth weight, g 2,565 [2,200–3,110] 2,830 [1,195–5,570] 0.62 (n = 2) OC/AC >0.66 (n = 15) OC/AC >0.57–0.75 (n = 13)
for herniation of the liver: sensitivity 87%, specificity 90% respiratory insufficiency: sensitivity 67%, specificity 78% staged surgery: sensitivity 100%, specificity 100%
Tassin et al. [14]
isolated: 54
12 (11–14)
OD/AD >0.8
hospitalization in the intensive care unit for more than 42 days; need for respiratory assistance and/or need for parenteral feeding >21 days
Present study
n = 47 isolated: 38 minor anomalies: 9
26.6 (16.6–35.8)
OD/AC ≥0.26
postnatal death: LR = 4 (1.9–7.5) need for intubation on the first day: LR = 2.6 (1.2–5.7) need for two-step surgery or mesh: LR = 5.9 (1.9–14.4)
Montero et al. [13]
n = 25 major anomalies: 4 minor anomalies: 6
25.0±5.7
GA = Gestational age; AD = abdominal diameter; OR = odds ratio; HC = head circumference; OC = omphalocele circumference; LR = likelihood ratio.
48
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
Kiyohara/Brizot/Liao/Francisco/Tannuri/ Krebs/Zugaib
tablish appropriate data for parental counseling at the time of diagnosis. Interestingly, our results show that both OD and the OD/AC ratio obtained at the first examination were significantly greater in fetuses that subsequently died compared to those that survived. Such differences were not observed when ultrasound findings of the last assessment were compared. We also observed that outcome prediction was better for cases that had the first evaluation before 31 weeks’ gestation (fig. 2). In fact, median gestational age at the first examination in our study was 26.6 weeks (16.6–35.8), which is very similar to the study of Montero et al. [13] (25.0 ± 5.7 weeks). The median gestational age at first examination was late in our study mainly due to late availability to anomaly scans in patients under the National Health System and because of the tertiary feature of this institution. On the other hand, Kleinrouweler et al. [7] had a median gestational age at the first evaluation of 13 weeks + 5 days, with 90% of the cases diagnosed prior to 24 weeks’ gestation. However, several cases in the latter study were terminated and excluded from the analysis. Therefore, the optimal gestational age at which the fetal OD/AC ratio better predicts perinatal outcome may need further investigation. No significant changes of the OD/AC ratio throughout pregnancy were observed in the present study or in the work published by Montero et al. [13]. However Kleinrouweler et al. [7] noted a significant decrease throughout pregnancy. These discrepancies could be related to differences in the median gestational age at which the studies were conducted. According to our data, prediction of adverse outcome is better before 31 weeks’ gestation, and this could be due to increased difficulties to obtain reliable measurements in late third trimester. It is possible that further series including more cases followed from the early first trimester diagnosis may help clarify the effect of gestational age on the fetal OD/AC ratio and prediction of outcome. So far, the largest early series included only 6 cases [7]. In neonates with omphalocele, respiratory insufficiency at birth has been described as one of the most relevant predictors of mortality, independent of gestational age at birth, birth weight, presence of other malformations or omphalocele size [20]. According to our data, only one quarter of the cases with an OD/AC ratio 75% of liver herniation [11, 12, 16]. Moreover, our data show that this is a useful parameter in the prediction of both mortality and morbidity. Although rates of pregnancy termination vary among different countries, with consequent severity selection, the omphalocele/abdomen ratio can still be useful due to its association with postnatal morbidity in ongoing pregnancies [19]. Although improvements have been made in order to leave behind single measurement criteria and subjective assessments, several issues remain to be investigated regarding the most appropriate method to minimize measurement errors during prenatal omphalocele assessment and best predict clinical and surgical outcome in these infants. Technical aspects that are still debatable include the use of circumference [7] instead of diameter measurements, and whether assessment should include the greatest diameter or mean diameter, due to the variability in
Fetal OD and Perinatal Outcome
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
49
the defects shape [14]. Moreover, there are questions regarding the advantages of using other fetal parts (e.g. head) during the evaluation of omphalocele size instead of the abdomen due to secondary intra-abdominal anatomy distortion and difficulties to define the exact abdominal limits [13]. It also needs to be clarified whether the presence of fluid content in the herniated sac needs to be taken into account during the evaluation.
In conclusion, the ratio between OD and AC is an additional parameter useful for the prediction of adverse perinatal outcome in isolated omphalocele and can be used for antenatal counseling. In the presence of an OD/ AC ratio ≥0.26, parents should be alerted that the chances of intubation on the first day of life, need for secondary surgery or mesh closure, and risk of death are increased by about 2.5, 6 and 4 times, respectively.
References 1 Snijders RJ, Brizot ML, Faria M, Nicolaides KH: Fetal exomphalos at 11 to 14 weeks of gestation. J Ultrasound Med 1995; 14: 569– 574. 2 Khalil A, Arnaoutoglou C, Pacilli M, Szabo A, David AL, Pandya P: Outcome of fetal exomphalos diagnosed at 11–14 weeks of gestation. Ultrasound Obstet Gynecol 2012; 39: 401– 406. 3 Barisic I, Clementi M, Häusler M, Gjergja R, Kern J, Stoll C, Euroscan Study Group: Evaluation of prenatal ultrasound diagnosis of fetal abdominal wall defects by 19 European registries. Ultrasound Obstet Gynecol 2001; 18: 309–316. 4 Lakasing L, Cicero S, Davenport M, Patel S, Nicolaides KH: Current outcome of antenatally diagnosed exomphalos: an 11 year review. J Pediatr Surg 2006;41:1403–1406. 5 Stoll C, Alembilk Y, Dott B, Roth MP: Omphalocele and gastroschisis and associated malformations. Am J Med Genetic A 2008; 146A:1280–1285. 6 Brantberg A, Blaas HGK, Haugen SE, Eik-Nes SH: Characteristics and outcome of 90 cases of fetal omphalocele. Ultrasound Obstet Gynecol 2005;26:527–537. 7 Kleinrouweler CE, Kuijper CF, van ZalenSprock MM, Mathijssen IB, Bilardo CM, Pajkrt E: Characteristics and outcome and the omphalocele circumference/abdominal circumference ratio in prenatally diagnosed fetal omphalocele. Fetal Diagn Ther 2011; 30: 60– 69. 8 Maksoud-Filho JG, Tannuri U, da Silva MM, Maksoud JG: The outcome of newborns with abdominal wall defects according to the method of abdominal closure: the experience of a single center. Pediatr Surg Int 2006; 22: 503–507.
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9 Rijhwani A, Davenport M, Dawrant M, Dimitriou G, Patel S, Greenough A, Nicolaides K: Definitive surgical management of antenatally diagnosed exomphalos. J Pediatr Surg 2005; 40:516–522. 10 Patel G, Sadiq J, Shenker N, Impey L, Lakhoo K: Neonatal survival of prenatally diagnosed exomphalos. Pediatr Surg Int 2009; 25: 413– 416. 11 Kamata S, Ishikawa S, Usui N, Kitayama Y, Sawai T, Okuyama H, Fukui Y, Kubota A, Imura K, Okada A: Prenatal diagnosis of abdominal wall defects and their prognosis. J Pediatr Surg 1996;31:267–271. 12 Biard JM, Wilson RD, Johnson MP, Hedrick HL, Schwarz U, Flake AW, Crombleholme TM, Adzick NS: Prenatally diagnosed giant omphaloceles: short- and long-term outcomes. Prenat Diagn 2004;24:434–439. 13 Montero FJ, Simpson LL, Brady PC, Miller RS: Fetal omphalocele ratios predict outcomes in prenatally diagnosed omphalocele. Am J Obstet Gynecol 2011;205:284.e1–e7. 14 Tassin M, Descriaud C, Elie C, Houfflin Debarge V, Dumez Y, Perrotin F, Benachi A: Omphalocele in the first trimester: prediction of perinatal outcome. Prenat Diagn 2013; 33: 497–501. 15 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M: A United States national reference for fetal growth. Obstet Gynecol 1996; 87:163–168. 16 Nicholas SS, Stamilio DM, Dicke JM, Gray DL, Macones GA, Odibo AO: Predicting adverse neonatal outcomes in fetuses with abdominal wall defects using prenatal risk factors. Am J Obstet Gynecol 2009; 201: 383.e1– e6. 17 Kumar HR, Jester AL, Ladd AP: Impact of omphalocele size on associated conditions. J Pediatr Surg 2008;43:2216–2219.
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
18 Heider AL, Strauss RA, Kuller JA: Omphalocele: Clinical outcomes in cases with normal karyotypes. Am J Obstet Gynecol 2004; 190: 135–141. 19 Hughes MD, Nyberg DA, Mack LA, Pretorius DH: Fetal omphalocele: prenatal US detection of concurrent anomalies and other predictors of outcome. Radiology 1989;173:371–376. 20 Tsakayannis DE, Zurakowski D, Lillehei CW: Respiratory insufficiency at birth: a predictor of mortality for infants with omphalocele. J Pediatr Surg 1996; 31: 1088–1090, discussion 1090–1091. 21 Vachharajani A, Rao R, Keswani S, Mathur A: Outcomes of exomphalos: an institutional experience. Pediatr Surg Int 2009;25:139–144. 22 Kamata S, Usui N, Sawai T, Nose K, Fukuzawa M: Prenatal detection of pulmonary hypoplasia in giant omphalocele. Pediatr Surg Int 2008;24:107–111. 23 Prendergast M, Rafferty GF, Davenport M, Persico N, Jani J, Nicolaides K, Greenough A: Three-dimensional ultrasound fetal lung volumes and infant respiratory outcome: a prospective observational study. BJOG 2011;118: 608–614. 24 Danzer E, Victoria T, Bebbington MW, Siegle J, Rintoul NE, Johnson MP, Flake AW, Adzick NS, Hedrick HL: Fetal MRI-calculated total lung volumes in the prediction of short-term outcome in giant omphalocele: preliminary findings. Fetal Diagn Ther 2012;31:248–253. 25 Hershenson MB, Brouillette RT, Klemka L, Raffensperger JD, Poznanski AK, Hunt CE: Respiratory insufficiency in newborns with abdominal wall defects. J Pediatr Surg 1985; 20:348–353. 26 Argyle JC: Pulmonary hypoplasia in infants with giant abdominal wall defects. Pediatr Pathol 1989;9:43–55.
Kiyohara/Brizot/Liao/Francisco/Tannuri/ Krebs/Zugaib
Copyright: S. Karger AG, Basel 2014. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.
Received: May 25, 2013 Accepted after revision: September 23, 2013 Published online: November 29, 2013
Should We Measure Fetal Omphalocele Diameter for Prediction of Perinatal Outcome? Marina Y. Kiyohara a Maria L. Brizot a Adolfo W. Liao a Rossana P.V. Francisco a Ana C.A. Tannuri b Vera L.J. Krebs c Marcelo Zugaib a Departments of a Obstetrics and Gynaecology, b Pediatric Surgery, and c Pediatrics, Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil
Key Words Fetal omphalocele · Abdominal wall defect · Ultrasound · Prenatal diagnosis · Pregnancy outcome
Abstract Objective: To evaluate the fetal omphalocele diameter/abdominal circumference ratio (OD/AC) as a predictor of adverse perinatal outcome. Methods: Analysis involving 47 singleton pregnancies with fetal omphalocele, normal karyotype and absence of other major abnormalities. The OD/AC ratio was determined antenatally by ultrasound and the best cutoff for the prediction of neonatal death was determined by receiver operating characteristic curve analysis. Additional secondary outcomes included need for oral intubation in the first 24 h of life, two-step surgery or use of synthetic mesh, reoperation, parenteral feeding and need for respiratory assistance >21 days, time to first oral feed, and time to hospital discharge. Results: Fetal OD/AC did not change significantly with gestational age. Postnatal death occurred in 10 (21.3%) cases and the best cutoff for prediction was an OD/AC ratio ≥0.26. In pregnancies with the first ultrasound evaluation performed before 31 weeks’ gestation and an OD/AC ≥0.26, the likelihood ratio for needing intubation in the first 24 h of life was 2.6 (95% CI: 1.2–5.7), needing twostep surgery or use of mesh was 4.9 (95% CI: 1.9–14.4), and
© 2013 S. Karger AG, Basel 1015–3837/13/0351–0044$38.00/0 E-Mail [email protected] www.karger.com/fdt
postnatal death was 4 (95% CI: 1.9–7.5). Conclusion: A fetal ultrasound OD/AC ratio ≥0.26 is associated with increased postnatal morbidity and mortality. © 2013 S. Karger AG, Basel
Introduction
Omphalocele is a congenital anterior abdominal wall defect characterized by herniation of abdominal viscera into the umbilical cord. Herniated structures are covered by the peritoneum and amnion. Prenatal diagnosis by ultrasound is possible as early as the first trimester of pregnancy [1, 2], and reported detection rates vary from 25 to 100%, depending on screening policies, ultrasound equipment and operator experience [3]. An abnormal karyotype, additional malformations and genetic syndromes can be found in up to 80% of the cases [4, 5]. As a matter of fact, a large study describing the outcome of cases diagnosed antenatally showed that less than 10% reach operative repair [4]. Likewise, other series have reported poor perinatal outcome, due to associated anomalies, and highlight the importance of careful antenatal assessment and appropriate counseling for the parents [6, 7]. When omphalocele is an isolated finding, survival rates following surgical repair are over 90% [8–10]. NevMaria L. Brizot Department of Obstetrics and Gynecology, Instituto Central, suite 10037, 10th floor Av Dr Enéas de Carvalho Aguiar 255 Sao Paulo, SP, 05403-000 (Brazil) E-Mail mlbrizot @ uol.com.br
ertheless, increased postnatal morbidity and surgical pitfalls are related to the size of the herniated content and giant defects, which include the liver [11]. The definition of big or giant omphalocele published in previous studies is heterogeneous and include presence of the liver in the omphalocele sac [11], more than 75% of the liver in the omphalocele sac [12] or the entire liver in the omphalocele sac [10]. Therefore, comparison of results across different studies that have evaluated prognosis in cases diagnosed antenatally is difficult. Moreover, gestational age at the time of diagnosis was not adjusted and the reported results are not necessarily applicable to all periods of gestation. Recently, three studies have demonstrated increased neonatal morbidity according to different ratios that adjusted omphalocele size to the fetal abdomen: omphalocele diameter/abdominal circumference (OD/AC) [13], omphalocele circumference/AC [7] and OD/abdominal diameter [14]. The present study further evaluates postnatal morbidity and mortality in isolated fetal omphalocele and reviews the literature to discuss additional methodological adjustments that are needed during prenatal omphalocele ultrasound evaluation. Material and Methods This was a retrospective analysis of a prospectively applied protocol involving singleton pregnancies with prenatal diagnosis of isolated fetal omphalocele seen at a tertiary referral center for fetal medicine (Hospital das Clínicas, São Paulo University Medical School, São Paulo, Brazil) between January 1997 and December 2011. The study protocol was registered and approved by the hospital’s ethics committee (CAPPESQ 0768/10). Pregnant women with a prenatal diagnosis of fetal omphalocele are referred to our center for specialist care. Detailed fetal anomaly and echocardiography scans are performed to confirm the abnormality and investigate associated malformations. Fetal karyotype determination is offered and surveillance includes follow-up scans every 4–6 weeks. An elective cesarean section is usually scheduled at around 39 weeks’ gestation. After birth, surgical correction is planned according to the size of herniated sac and extent of the defect; options include primary closure, with or without the use of a synthetic mesh, or secondary closure after silastic reduction as previously described [8]. In women with regular menstrual cycles and certain of the date of their last menstrual period (LMP), gestational age was calculated from the first day of the LMP, and confirmed by ultrasound examination. When there was discrepancy between the LMP and scan dates of more than 7 days in the first trimester, 10 days in the second trimester or if the LMP was uncertain, gestational age was defined according to the earliest ultrasound findings (fetal crown-rump length measurement during the first trimester, or biparietal diameter and head circumference measure-
Fetal OD and Perinatal Outcome
Fig. 1. Ultrasound image demonstrating a transverse section at the
fetal abdomen at the level of omphalocele insertion. Diameters are demonstrated by calipers 1 and 2 (fetal abdomen), and calipers 3 and 4 (omphalocele).
ments during the second trimester), performed in our own hospital or in other units. At each ultrasound examination, fetal growth, amniotic fluid volume and umbilical artery Doppler examinations were performed. Additionally, herniated contents in the omphalocele sac were described and measurements of the sac were obtained in a transverse section of the fetal abdomen at the level of the omphalocele. The calipers were positioned externally to the peritoneum membrane (fig. 1). All of these measurements were described in the patients’ reports and entered into a computer database system. All examinations were carried out by two fetal medicine specialists (M.L.B. and A.W.L.) using the following equipment: Corevision (Toshiba, Japan), HDI 3000 (ATL, USA), Envisor (Philips, Netherlands) and Voluson (General Electric, Austria). A database search was performed to identify all singleton pregnancies with fetal omphalocele that were referred to our unit and had at least one ultrasound examination before delivery. The abnormality was confirmed at birth, and pregnancy outcome information was retrieved from hospital records and autopsy examination. Cases in which OD measurements were not recorded or had associated major abnormalities, abnormal karyotype, intrauterine death or missing outcome were not included in the analysis. The study group was described according to maternal age, gestational age at delivery, birth weight, Apgar scores, respiratory insufficiency, type of surgical closure (primary or secondary), use of synthetic mesh, time in days to full oral feeding and length of hospital stay. Birth weight was classified according to reference ranges published by Alexander et al. [15]. Primary outcome was defined as neonatal death. Additional outcome measures included need for intubation within the first 24 h of life, need for mechanical ventilation >21 days, need for twostep surgical correction, use of synthetic mesh and reoperation, parenteral feeding >21 days, time to first oral feed, and days until hospital discharge. The mean OD was calculated as the average of the transverse and anteroposterior diameters and the OD/AC ratio was calcu-
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
45
Table 1. Clinical details of cases with fetal omphalocele and postnatal death
Case No.
OD/AC ratio
Gestational age at delivery, weeks
Birth weight, g
Age at death, days
Surgical repair
Complications
1 2 3 4 5 6 7 8 9 10
0.280 0.213 0.387 0.263 0.342 0.218 0.298 0.365 0.179 0.274
37 5/7 34 37 3/7 40 37 2/7 39 37 6/7 36 6/7 39 2/7 35 2/7
2,570 2,200 3,100 2,980 2,370 2,560 3,110 2,480 2,660 2,430
3 2 13 362 5 158 21 59 208 4
secondary primary primary + mesh secondary + mesh primary primary primary + mesh primary + mesh primary primary + mesh
bronchopneumonia hyaline membrane disease bronchopneumonia bronchodysplasia metabolic acidosis + anuria bronchodysplasia + bronchopneumonia sepsis sepsis bronchomalacia + sepsis hyaline membrane disease
lated for each examination. AC was calculated based on anteroposterior (AD1) and transverse (AD2) diameters: 3.14 × (AD1 + AD2)/2. To examine the distribution of the OD/AC ratio according to gestational age, all measurements were included and linear regression analysis was used. Prediction of neonatal death was examined according to the first measurement obtained in each case using the receiver operating characteristic (ROC) curve. The cases were classified according to the best value obtained by ROC curve and morbidity was compared using a Mann-Whitney test for continuous variables and Fisher’s exact test or a χ2 test to evaluate the proportions. Due to the retrospective analysis of the study, no sample size calculation was previously established. Statistical analysis was performed with Statsdirect (Statsdirect, UK) and the significance level was set at 0.05.
Results
Table 2. Prenatal ultrasound findings and delivery details in cases of fetal omphalocele according to perinatal outcome
Postnatal death
Alive
Cases, n 10 37 OD, mm First scan 53.3 [37.0–80.0] 37.1 [21.5–121.0] Last scan 63.4 [32.7–108.0] 58.8 [25.5–120.0] OD/AC First scan 0.28 [0.18–0.39] 0.23 [0.12–0.38] Last scan 0.27 [0.14–0.46] 0.22 [0.09–0.32] Gestational age at delivery, weeks 37.6 [34–40] 37.9 [32.6–39.7] Birth weight, g 2,565 [2,200–3,110] 2,830 [1,195–5,570] 0.62 (n = 2) OC/AC >0.66 (n = 15) OC/AC >0.57–0.75 (n = 13)
for herniation of the liver: sensitivity 87%, specificity 90% respiratory insufficiency: sensitivity 67%, specificity 78% staged surgery: sensitivity 100%, specificity 100%
Tassin et al. [14]
isolated: 54
12 (11–14)
OD/AD >0.8
hospitalization in the intensive care unit for more than 42 days; need for respiratory assistance and/or need for parenteral feeding >21 days
Present study
n = 47 isolated: 38 minor anomalies: 9
26.6 (16.6–35.8)
OD/AC ≥0.26
postnatal death: LR = 4 (1.9–7.5) need for intubation on the first day: LR = 2.6 (1.2–5.7) need for two-step surgery or mesh: LR = 5.9 (1.9–14.4)
Montero et al. [13]
n = 25 major anomalies: 4 minor anomalies: 6
25.0±5.7
GA = Gestational age; AD = abdominal diameter; OR = odds ratio; HC = head circumference; OC = omphalocele circumference; LR = likelihood ratio.
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Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
Kiyohara/Brizot/Liao/Francisco/Tannuri/ Krebs/Zugaib
tablish appropriate data for parental counseling at the time of diagnosis. Interestingly, our results show that both OD and the OD/AC ratio obtained at the first examination were significantly greater in fetuses that subsequently died compared to those that survived. Such differences were not observed when ultrasound findings of the last assessment were compared. We also observed that outcome prediction was better for cases that had the first evaluation before 31 weeks’ gestation (fig. 2). In fact, median gestational age at the first examination in our study was 26.6 weeks (16.6–35.8), which is very similar to the study of Montero et al. [13] (25.0 ± 5.7 weeks). The median gestational age at first examination was late in our study mainly due to late availability to anomaly scans in patients under the National Health System and because of the tertiary feature of this institution. On the other hand, Kleinrouweler et al. [7] had a median gestational age at the first evaluation of 13 weeks + 5 days, with 90% of the cases diagnosed prior to 24 weeks’ gestation. However, several cases in the latter study were terminated and excluded from the analysis. Therefore, the optimal gestational age at which the fetal OD/AC ratio better predicts perinatal outcome may need further investigation. No significant changes of the OD/AC ratio throughout pregnancy were observed in the present study or in the work published by Montero et al. [13]. However Kleinrouweler et al. [7] noted a significant decrease throughout pregnancy. These discrepancies could be related to differences in the median gestational age at which the studies were conducted. According to our data, prediction of adverse outcome is better before 31 weeks’ gestation, and this could be due to increased difficulties to obtain reliable measurements in late third trimester. It is possible that further series including more cases followed from the early first trimester diagnosis may help clarify the effect of gestational age on the fetal OD/AC ratio and prediction of outcome. So far, the largest early series included only 6 cases [7]. In neonates with omphalocele, respiratory insufficiency at birth has been described as one of the most relevant predictors of mortality, independent of gestational age at birth, birth weight, presence of other malformations or omphalocele size [20]. According to our data, only one quarter of the cases with an OD/AC ratio 75% of liver herniation [11, 12, 16]. Moreover, our data show that this is a useful parameter in the prediction of both mortality and morbidity. Although rates of pregnancy termination vary among different countries, with consequent severity selection, the omphalocele/abdomen ratio can still be useful due to its association with postnatal morbidity in ongoing pregnancies [19]. Although improvements have been made in order to leave behind single measurement criteria and subjective assessments, several issues remain to be investigated regarding the most appropriate method to minimize measurement errors during prenatal omphalocele assessment and best predict clinical and surgical outcome in these infants. Technical aspects that are still debatable include the use of circumference [7] instead of diameter measurements, and whether assessment should include the greatest diameter or mean diameter, due to the variability in
Fetal OD and Perinatal Outcome
Fetal Diagn Ther 2014;35:44–50 DOI: 10.1159/000355936
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the defects shape [14]. Moreover, there are questions regarding the advantages of using other fetal parts (e.g. head) during the evaluation of omphalocele size instead of the abdomen due to secondary intra-abdominal anatomy distortion and difficulties to define the exact abdominal limits [13]. It also needs to be clarified whether the presence of fluid content in the herniated sac needs to be taken into account during the evaluation.
In conclusion, the ratio between OD and AC is an additional parameter useful for the prediction of adverse perinatal outcome in isolated omphalocele and can be used for antenatal counseling. In the presence of an OD/ AC ratio ≥0.26, parents should be alerted that the chances of intubation on the first day of life, need for secondary surgery or mesh closure, and risk of death are increased by about 2.5, 6 and 4 times, respectively.
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