DOI: 10.1002/pd.4595
ORIGINAL ARTICLE
Retrospective analysis of prenatal ultrasound of children with Hirschsprung disease Ariella Jakobson-Setton1,2†, Alina Weissmann-Brenner1,2*†, Reuven Achiron1,2, Jacob Kuint3 and Liat Gindes1,2 1
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel Sackler School of Medicine, Tel Aviv University, Tel-Hashomer, Israel 3 Department of Neonatology Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel-HashomerRamat Gan, Israel *Correspondence to: Alina Weissmann-Brenner. E-mail: [email protected] † Both authors equally contributed to this work. 2
ABSTRACT Objective Hirschsprung disease (HD) is a rare gastrointestinal disorder. Our aim was to study the prenatal ultrasound findings of children who were diagnosed with HD after birth. Methods The study population included children who suffered from HD between 1990 and 2008. Data of anomaly scan findings in prenatal ultrasound, demographic and post-natal physical abnormalities and treatment were retrieved from medical files and interviews with the parents. Results Twenty-two patients confirmed histopathological diagnosis of HD at age of 1 day to 15 months. Nineteen fetuses had anomaly scan during pregnancy, which revealed minor sonographic abnormalities in three fetuses; two of them had hyperechogenic bowel. One fetus with hyperechogenic bowel had polyhydramnion, and another had a family history of three brothers with HD. A third fetus had dilated pelvic kidney. None of them had sonographic evidence of bowel dilatation. After birth, six patients (31%) were found to have other structural anomalies: ventriculoseptal defect, atriseptal defect, atrio-ventricular septal defect, and pyloric stenosis.
Conclusions Abnormal sonographic findings of fetal bowel are absent in the vast majority of fetuses who are diagnosed with HD after birth. In women with a family history of HD, a third trimester anomaly scan may be warranted. © 2015 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Hirschsprung disease (HD) is the main genetic cause of functional intestinal obstruction, with an incidence of 1 : 5000–10 000 live births, and accounts for about 33% of all neonatal intestinal obstructions.1,2 It is characterized by the absence of ganglion cells from the anorectum for a variable length up to the duodenum, both in the Meissner’s and Auerbach’s plexuses. HD may be associated with several syndromes such as Down syndrome, Smith–Lemli–Opitz syndrome, Mowat–Wilson syndrome, and congenital central hypoventilation syndrome.3,4 The disease usually presents in infancy mainly in the first 48 h of life, although some patients present with persistent, severe constipation later in life. Symptoms in infants include absence of first meconium (94%), difficult bowel movements, vomiting, diarrhea, poor feeding, poor weight gain, and progressive abdominal distention. When suspicion is raised, a barium enema is performed and an over distention of part of the colon is demonstrated. The definitive diagnosis is made by a rectal biopsy that demonstrates hypertrophic nerve trunks and absence of Prenatal Diagnosis 2015, 35, 1–4
ganglion cells in the colonic submucosa. Early diagnosis is important to prevent complications such as enterocolitis and colonic rupture that may cause severe morbidity and mortality.5–9 Prenatal detection of HD has an important implication for pregnancy follow-up and early post-natal diagnosis and treatment. Scarce data exist on the in-utero manifestation and prenatal detection. Until now, only a few case reports of sonographic prenatal diagnosis have been described and reported. The ultrasonic features that brought up the suspicion of bowel disease were fetal abdominal cystic areas, increased abdominal circumference, polyhydramnions, and echogenic bowel.1,6–9 Our goal was to study the prenatal ultrasound findings of children who had post-natal diagnosis of HD.
METHODS A retrospective study was performed between 1990 and 2008. The study was approved by the Institutional Review Board of the Chaim Sheba Medical Center. © 2015 John Wiley & Sons, Ltd.
A. Jakobson-Setton et al.
Data were collected from medical files from the prenatal ultrasound unit, neonatal intensive care unit, gastro and surgery clinics, and pathological exams. Additional information was collected by phone interviews with the patients’ parents. Definitive diagnosis of HD was confirmed only after the pathological analysis. The variables assessed in the study were the following: 1. maternal age and pregnancy complications such as preeclampsia and diabetes mellitus;
2. data regarding pregnancy including nuchal translucency, screening blood tests such as triple test, amniocentesis, genetic counseling, anomaly scan, and estimated growth along the pregnancy, anatomical findings at the prenatal ultrasound, and gestational age at diagnosis;
3. information about delivery: gestational age at delivery, mode of delivery, birth weight, gender, Apgar score, and cord pH; and
4. post-natal information included age at diagnosis, symptoms, diagnostic modalities, treatment, and hospitalization in the neonatal intensive care unit.
RESULTS Between 1990 and 2008, 26 children were suspected to have HD at the neonatal intensive care unit or at the gastro clinic. In three out of the 26 newborns, biopsy was not taken because of clinical improvement. Another newborn had a biopsy that showed microvillus inclusion disease. All those four children were excluded from the study. Twenty-two patients had confirmed pathological diagnosis of HD and comprised the study population. In 14 cases, we retrieved maximal information from medical files and interviews with the parents. In eight cases, data were collected only from medical files. Those patients do not live in Israel, and we could not get in touch with them. The characteristics of the study population are presented in Table 1. There was a male predominance with a male : female ratio of 2.66 : 1. Most patients (90.9%) were born at term (≥37 weeks’ gestation), while two patients were born at 32 weeks’ gestation. Only one patient was small for gestational age (seventh
percentile), and 18.2% were large for gestational age (>90th percentile). Most had normal vaginal deliveries. The only complications during deliveries were lack of spontaneous breathing at the first minute in the two patients with premature deliveries. No other major complication took place during deliveries. Fifteen out of the 22 patients (68.2%) completed at least one of the screening exams for genetic abnormalities. Two patients (13.3%) had abnormal screening tests: One had abnormal nuchal translucency test and was also diagnosed with hyperechogenic bowel at the first trimester anatomical scan. His second trimester scan was normal. He was diagnosed with hepatitis after birth. This patient had a positive family history of HD. Another fetus had abnormal biochemical test with normal amniocentesis. His second trimester anatomical scan was normal. He was diagnosed with ventriculoseptal defect and necrotizing enterocolitis after birth. Second trimester fetal sonographic anatomical screening was performed in 21/22 mothers during the pregnancy. One mother did not perform any level 2 ultrasound during pregnancy. Third trimester ultrasound evaluation of fetal weight was performed in 12 patients. No patient underwent third trimester anatomical scan. Suspicious sonographic findings included hyperechogenic bowel in two patients, one of them was the fetus with the abnormal nuchal translucency exam. The second fetus had also polyhydramnions, was born at 32 weeks’ gestation, and suffered from complications of prematurity such as respiratory distress syndrome and intraventricular hemorrhage. This patient also had a family history of HD. Another patient had dilated pelvic kidney. This patient also had a family history of HD. Almost all patients were diagnosed in the neonatal period: 20 (91%) of them in the first week of life, one at the age of 2 months, and one at the age of 15 months. Two of the patients with abnormal screening findings during pregnancy were diagnosed at the first week, and one was diagnosed at the age of 2 months. Rectal biopsies performed in all patients diagnosed HD in all patients.
Table 1 Characteristics of the study population Frequency (percentage) Gender
Mean (SD)
Male = 16 (72.7%)Female = 6 (27.3%)
Family history of HD
History of HD = 3/21 (14.2%)Missing = 1/22 (4.5%)
Gestational age at delivery
≥37 weeks = 18 (81.8%)
ORIGINAL ARTICLE
Retrospective analysis of prenatal ultrasound of children with Hirschsprung disease Ariella Jakobson-Setton1,2†, Alina Weissmann-Brenner1,2*†, Reuven Achiron1,2, Jacob Kuint3 and Liat Gindes1,2 1
Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Israel Sackler School of Medicine, Tel Aviv University, Tel-Hashomer, Israel 3 Department of Neonatology Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel-HashomerRamat Gan, Israel *Correspondence to: Alina Weissmann-Brenner. E-mail: [email protected] † Both authors equally contributed to this work. 2
ABSTRACT Objective Hirschsprung disease (HD) is a rare gastrointestinal disorder. Our aim was to study the prenatal ultrasound findings of children who were diagnosed with HD after birth. Methods The study population included children who suffered from HD between 1990 and 2008. Data of anomaly scan findings in prenatal ultrasound, demographic and post-natal physical abnormalities and treatment were retrieved from medical files and interviews with the parents. Results Twenty-two patients confirmed histopathological diagnosis of HD at age of 1 day to 15 months. Nineteen fetuses had anomaly scan during pregnancy, which revealed minor sonographic abnormalities in three fetuses; two of them had hyperechogenic bowel. One fetus with hyperechogenic bowel had polyhydramnion, and another had a family history of three brothers with HD. A third fetus had dilated pelvic kidney. None of them had sonographic evidence of bowel dilatation. After birth, six patients (31%) were found to have other structural anomalies: ventriculoseptal defect, atriseptal defect, atrio-ventricular septal defect, and pyloric stenosis.
Conclusions Abnormal sonographic findings of fetal bowel are absent in the vast majority of fetuses who are diagnosed with HD after birth. In women with a family history of HD, a third trimester anomaly scan may be warranted. © 2015 John Wiley & Sons, Ltd.
Funding sources: None Conflicts of interest: None declared
INTRODUCTION Hirschsprung disease (HD) is the main genetic cause of functional intestinal obstruction, with an incidence of 1 : 5000–10 000 live births, and accounts for about 33% of all neonatal intestinal obstructions.1,2 It is characterized by the absence of ganglion cells from the anorectum for a variable length up to the duodenum, both in the Meissner’s and Auerbach’s plexuses. HD may be associated with several syndromes such as Down syndrome, Smith–Lemli–Opitz syndrome, Mowat–Wilson syndrome, and congenital central hypoventilation syndrome.3,4 The disease usually presents in infancy mainly in the first 48 h of life, although some patients present with persistent, severe constipation later in life. Symptoms in infants include absence of first meconium (94%), difficult bowel movements, vomiting, diarrhea, poor feeding, poor weight gain, and progressive abdominal distention. When suspicion is raised, a barium enema is performed and an over distention of part of the colon is demonstrated. The definitive diagnosis is made by a rectal biopsy that demonstrates hypertrophic nerve trunks and absence of Prenatal Diagnosis 2015, 35, 1–4
ganglion cells in the colonic submucosa. Early diagnosis is important to prevent complications such as enterocolitis and colonic rupture that may cause severe morbidity and mortality.5–9 Prenatal detection of HD has an important implication for pregnancy follow-up and early post-natal diagnosis and treatment. Scarce data exist on the in-utero manifestation and prenatal detection. Until now, only a few case reports of sonographic prenatal diagnosis have been described and reported. The ultrasonic features that brought up the suspicion of bowel disease were fetal abdominal cystic areas, increased abdominal circumference, polyhydramnions, and echogenic bowel.1,6–9 Our goal was to study the prenatal ultrasound findings of children who had post-natal diagnosis of HD.
METHODS A retrospective study was performed between 1990 and 2008. The study was approved by the Institutional Review Board of the Chaim Sheba Medical Center. © 2015 John Wiley & Sons, Ltd.
A. Jakobson-Setton et al.
Data were collected from medical files from the prenatal ultrasound unit, neonatal intensive care unit, gastro and surgery clinics, and pathological exams. Additional information was collected by phone interviews with the patients’ parents. Definitive diagnosis of HD was confirmed only after the pathological analysis. The variables assessed in the study were the following: 1. maternal age and pregnancy complications such as preeclampsia and diabetes mellitus;
2. data regarding pregnancy including nuchal translucency, screening blood tests such as triple test, amniocentesis, genetic counseling, anomaly scan, and estimated growth along the pregnancy, anatomical findings at the prenatal ultrasound, and gestational age at diagnosis;
3. information about delivery: gestational age at delivery, mode of delivery, birth weight, gender, Apgar score, and cord pH; and
4. post-natal information included age at diagnosis, symptoms, diagnostic modalities, treatment, and hospitalization in the neonatal intensive care unit.
RESULTS Between 1990 and 2008, 26 children were suspected to have HD at the neonatal intensive care unit or at the gastro clinic. In three out of the 26 newborns, biopsy was not taken because of clinical improvement. Another newborn had a biopsy that showed microvillus inclusion disease. All those four children were excluded from the study. Twenty-two patients had confirmed pathological diagnosis of HD and comprised the study population. In 14 cases, we retrieved maximal information from medical files and interviews with the parents. In eight cases, data were collected only from medical files. Those patients do not live in Israel, and we could not get in touch with them. The characteristics of the study population are presented in Table 1. There was a male predominance with a male : female ratio of 2.66 : 1. Most patients (90.9%) were born at term (≥37 weeks’ gestation), while two patients were born at 32 weeks’ gestation. Only one patient was small for gestational age (seventh
percentile), and 18.2% were large for gestational age (>90th percentile). Most had normal vaginal deliveries. The only complications during deliveries were lack of spontaneous breathing at the first minute in the two patients with premature deliveries. No other major complication took place during deliveries. Fifteen out of the 22 patients (68.2%) completed at least one of the screening exams for genetic abnormalities. Two patients (13.3%) had abnormal screening tests: One had abnormal nuchal translucency test and was also diagnosed with hyperechogenic bowel at the first trimester anatomical scan. His second trimester scan was normal. He was diagnosed with hepatitis after birth. This patient had a positive family history of HD. Another fetus had abnormal biochemical test with normal amniocentesis. His second trimester anatomical scan was normal. He was diagnosed with ventriculoseptal defect and necrotizing enterocolitis after birth. Second trimester fetal sonographic anatomical screening was performed in 21/22 mothers during the pregnancy. One mother did not perform any level 2 ultrasound during pregnancy. Third trimester ultrasound evaluation of fetal weight was performed in 12 patients. No patient underwent third trimester anatomical scan. Suspicious sonographic findings included hyperechogenic bowel in two patients, one of them was the fetus with the abnormal nuchal translucency exam. The second fetus had also polyhydramnions, was born at 32 weeks’ gestation, and suffered from complications of prematurity such as respiratory distress syndrome and intraventricular hemorrhage. This patient also had a family history of HD. Another patient had dilated pelvic kidney. This patient also had a family history of HD. Almost all patients were diagnosed in the neonatal period: 20 (91%) of them in the first week of life, one at the age of 2 months, and one at the age of 15 months. Two of the patients with abnormal screening findings during pregnancy were diagnosed at the first week, and one was diagnosed at the age of 2 months. Rectal biopsies performed in all patients diagnosed HD in all patients.
Table 1 Characteristics of the study population Frequency (percentage) Gender
Mean (SD)
Male = 16 (72.7%)Female = 6 (27.3%)
Family history of HD
History of HD = 3/21 (14.2%)Missing = 1/22 (4.5%)
Gestational age at delivery
≥37 weeks = 18 (81.8%)
