Therapeutic fetal surgical procedures are predicated upon the ability to make an accurate fetal diagnosis. The earliest open fetal surgical procedures were introduced in the 1960s to treat Rh isoimmunisation. They were introduced when it became possible to predict impending fetal demise. Open procedures were abandoned when percutaneous approaches proved superior. The introduction of fetal ultrasound allowed the diagnosis of other congenital anomalies, some being amenable to fetal interventions. Open fetal surgical procedures were initially utilised, with significant maternal morbidity. For some anomalies, percutaneous approaches became favoured. In general, all of these procedures involved significant risks to the mother, to save a baby that was likely to die before or shortly after birth without fetal intervention. Fetal repair for myelomeningocele was a “sea change” in approach. The same maternal risks were taken to improve the quality of life of the affected fetus, not save its life. The completion of the “MOMs Trial” has occasioned a “tsunami” of centres in North America applying this approach. Others are attempting percutaneous repairs, with mixed results. This paper reviews the history of fetal surgery, focusing on the themes of the tension between accurate diagnosis and prognosis and open versus “minimally invasive” approaches.

To investigate roles of short peptides in gastroschisis (GS), we comprehensively analyzed peptides in amniotic fluid (AF), creating a fetal lamb model of GS. We created GS in 4 fetal lambs at 60 days of gestation. Three GS and 4 normal fetuses were delivered at term (145 days) by cesarean section, when AF samples were collected. Short peptides in the AF samples were detected and identified by mass spectrometry. One of the identified peptides was synthesized and it’s functions were investigated. In total, 77 peptide peaks were detected in the AF samples. Of these, 12 peptides showed significantly different intensity between the GS and control groups. Three of the 12 peptides were identified. One of the identified peptides with high intensity in the GS group was amino acids (AA) 135-185 of lamb annexin 7 (ANX7). A synthesized peptide for AA168-211 of human ANX7, which corresponded to AA135-185 of lamb ANX7, decreased anti-inflammatory cytokine secretion from mesothelial cells by an cytokine array study. We report a unique AF peptide profile in a GS model. One of the peptides increased in GS was suggested to possess pro-inflammatory potential. These peptides would be related to the pathophysiology of GS.

We outline the development of a reliable model of obstructive uropathy in fetal lambs highlighting our understanding of the critical time points for interventions and the variability of any such model. We identify some discoveries that may have clinical implications.

To present a case with overlapping diagnosis of prune belly and megacystitis-microcolon-intestinal hypoperistalsis. A G2P0 woman with a previous pregnancy loss at 19 weeks gestation complicated by fetal urethral atresia was referred at 20 weeks gestation for the finding of fetal megacystis on morphology scan. On ultrasound examination, the fetal bladder was grossly distended with bilateral hydronephrosis, flappy abdomen and oligohydramnios. The fetal urine components reflected satisfactory renal function. Prune belly syndrome was suspected. Due to an extensive anteriorly-lying placenta, the insertion of a vesico-amniotic shunt was not possible. Repeated fetal bladder tapping and amnioinfusion were performed till elective delivery at 29 weeks gestation. The baby was born in good condition by Caesarean section. Prune belly was noted. The renal and lung function were satisfactory. Vesicotomy was performed postnatally. The baby could not tolerate oral requiring parenteral nutrition and died neonatally. Megacystitis-microcolon-intestinal hypoperistalsis was diagnosed at post-mortem examination. Prune belly and megacystitis-microcolon-intestinal hypoperistalsis could co-exist and the prognosis may be more guarded.

To report the sonographic features of placenta accreta in relation to the extent of the condition Patients with placenta accreta confirmed at the time of delivery in 2004–2007 were identified from hospital records and a perinatal database. The sonographic appearance at the time of antenatal diagnosis was compared with the clinical findings at delivery. The features useful for the assessment of the extent of the condition will be presented. Nine patients had placenta accreta confirmed at the time of delivery clinically and/or histologically. There were 1 case of placenta percreta, 1 minor partial increta and 7 extensive increta. Observation of the extent of placental-myometrial interface disruption and the vascular pattern were useful in assessing the extent of the involvement of placenta accreta. In addition, bulging of the uterine wall could be seen in placenta percreta. The extent of placenta accreta could be mapped sonographically at the time of antenatal diagnosis.

To present the use of oblique planes in assessing fetal cleft palate and to compare the findings with normal fetal palates in stored 3D ultrasound volumes of fetal face. Stored 3D ultrasound volumes of fetal faces with confirmed cleft palates were reviewed. The facial clefts were assessed in the orthogonal planes and the oblique axial, sagittal and coronal planes. The appearance of the fetal cleft palate in various oblique planes were compared with that in fetuses with confirmed normal palates at delivery. The extent of fetal cleft palate could be assessed with the combination of various oblique planes. A combination of oblique planes is useful in the assessment of the extent of fetal cleft palate.

Introduction: Placenta accreta is a life threatening condition associated with severe maternal haemorrhage at placental delivery. Methods: The maternal outcome was analysed in 16 cases of confirmed placenta accreta identified from our perinatal database and hospital records in 2000-6. Results: Seven women with antenatal diagnosis had Caesarean delivery, without placental separation in 5 cases of extensive accreta, and elective placental separation in 2, including I case of partial accreta. When an antenatal diagnosis was not made (n = 9), placental separation was attempted at delivery in all, resulting in a higher mean blood loss (3.6L vs. 1.4 L, p = 0.003) and emergency hysterectomy (p = 0.001). Conclusion: In extensive placenta accreta, antenatal diagnosis and topographic assessment allow avoidance of placental separation at delivery, resulting in less blood loss and improved maternal outcomes.

Objective: To present and discuss the sonographic and clinical findings in one twin of a monochorionic pair affected by amyoplasia. Methods: On ultrasound examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller, hydropic, with multiple contractures consistent with amyoplasia and oligohydramnios. Twin II was anatomically normal with polyhydramnios. Results: The twins were delivered at 28 weeks’ gestation. The clinical findings were consistent with twin-twin transfusion syndrome (TTTS). Conclusion: It is postulated that TTTS may be a causative factor in the excessive incidence of amyoplasia in monozygotic twin pregnancy.

Objectives To examine the use of oblique planes from stored three-dimensional (3D) ultrasound volumes of the fetal face for viewing the secondary palate at various gestational ages.Methods 3D ultrasound volumes of the fetal face acquired with surface rendering at 15-35 weeks' gestation in 31 fetuses with confirmed normal secondary palates were reviewed. The secondary palate was viewed in three oblique planes targeted at the uvula: the oblique axial, the oblique sagittal and the reverse face view. The detection and appearance of the secondary palate, including the soft palate, with these views at various gestational ages were compared.Results The various surfaces of the secondary palate could be viewed ill all 31 fetuses in the oblique axial and the reverse face views, and in all except two fetuses in the oblique sagittal view. Both of these were < 19 weeks' gestation, at which age the uvula could not be identified clearly in this plane.Conclusions The oblique axial, the oblique sagittal and the reverse face view targeted at the uvula allow visualization of the various aspects of the fetal secondary palate on 3 0 ultrasound in the second and third trimesters of pregnancy. The uvula could be used as a landmark for viewing the soft palate, but was not always easily identifiable before 19 weeks' gestation. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.

To describe the use of 3D ultrasound including the reverse face view in the antenatal diagnosis of 2 cases of anophthalmia. Two cases of isolated anophthalmia with suggestive sonographic features will be presented. The first patient was referred for abnormal orbital contents on fetal morphology scan at 20 weeks gestation. Bilateral absence of the lenses suggestive of anophthalmia was noted on 2D ultrasound examination. Additional sonographic features were detected on 3D ultrasound. The patient requested termination of pregnancy and the diagnosis was confirmed on pathological examination. The second patient was referred for detailed ultrasound scan because of a past history of recurrent miscarriages. The fetal face (and the lenses) could not be well seen on 2D ultrasound due to unfavorable fetal head position. On 3D ultrasound examination, there were features suggestive of right anophthalmia. The diagnosis was confirmed after birth. In these 2 cases of anophthalmia, additional 3D sonographic features could be observed, including sunken eyelid(s), hypoplastic orbit(s), and in the second case of unilateral anophthalmia, facial asymmetry and the demonstration of unilateral absence of lens and eyeball on the reverse face view. 3D ultrasound is a useful adjunct to 2D in the antenatal diagnosis and assessment of anophthalmia. The reverse face view is helpful in the demonstration of the diagnostic features of the absence of the lens and eyeball, especially when the fetal head position is unfavorable for 2D ultrasound examination. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

To present the Doppler ultrasound findings and to correlate with histology in confirmed cases of placenta accreta. The Doppler findings in 3 cases of confirmed placenta accreta are presented and correlated with the histology. The Doppler findings include placental lacuna flow, prominent subplacental venous complex, vessels bridging from placenta to margin of uterus and vessels crossing tissue interface-disruption sites. Vessels crossing the interface between the “invading” trophoblastic villi and the immediate adjacent myometrium are noted in cases of placenta accreta on histology, representing the vessels crossing tissue interface-disruption sites on Doppler. Some of these vessels are large and extending deep into the myometrium towards the serosa, corresponding to the placental lacunae, prominent subplacental venous plexus and vessels bridging from placenta to margin of uterus. Histologically, in placenta accreta, vessels could be observed running across the interface between the “invading” trophoblastic villi and the myometrium, extending deep into the latter. These vessels could explain the Doppler signs reported for placenta accreta, including vessels crossing interface-disruption sites, placental lacunar flow, prominent subplacental venous plexus and vessels bridging from placenta to margin of uterus.

The prenatal diagnosis of anophthalmia can be made on the demonstration of absent eye globe and lens on the affected side(s) on two‐dimensional ultrasound examination, but when the fetal head position is unfavorable three‐dimensional (3D) ultrasound may reveal additional diagnostic sonographic features, including sunken eyelids and small or hypoplastic orbit on the affected side(s). We present two cases of isolated anophthalmia diagnosed on prenatal ultrasound examination in which 3D ultrasound provided additional diagnostic information. The reverse face view provides valuable information about the orbits and the eyeballs for prenatal diagnosis and assessment of anophthalmia. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Human renal dysplasia is frequently associated with urinary tract obstruction and the abnormal expression of mitogen-activated protein kinase (MAPK). Here, we determined the renal responses and MAPK expression in developing kidneys that were obstructed in fetal lambs. Kidneys were harvested at various times after obstruction (gestation day 60) through normal term (day 145). Dilation of Bowman's capsule and proximal tubules was seen 2 days after obstruction and involved the whole cortex 18 days later, with numerous cysts present throughout the kidney at term. The proliferation marker Ki-67 and transforming growth factor-beta (TGF-beta) were detected 2 days after obstruction and progressively increased in tubules, cysts, and the interstitium. In control kidneys, p38 was expressed in tubules only during the fetal stage, whereas phosphorylated extracellular signal-regulated kinase (P-ERK) was limited to ureteric buds and collecting ducts at all stages examined. However, Jun-N-terminal kinase (JNK) was absent in the fetal kidney but present in tubules at term. In obstructed kidneys, cyst epithelia were positive for p38 and P-ERK but negative for JNK throughout all stages. These studies show that P-ERK correlated spatially and temporally with Ki-67 and TGF-beta expression, which suggests that ERK may contribute to cyst formation and fibrosis in the obstructed fetal kidney.

To examine the feasibility of viewing the fetal soft palate at various gestations on 3D ultrasound. A routine 3D sweep of the fetal face was taken at antenatal ultrasound examination at various gestations. By using the uvula as a landmark (indicated by the arrow in Fig. 1), the fetal soft palate was examined in the following planes: the oblique axial plane, the oblique sagittal plane and the reverse face views targeted at the uvula. The possibility of viewing the fetal soft palate at various gestations in these planes was analyzed. The 3D volume of the fetal face in 31 fetuses at 15–35 weeks gestation was analyzed. The mean gestational age was 23.7 weeks. The fetal soft palate could be identified in the oblique axial plane, the oblique sagittal plane and the targeted reverse face view in 100%, 96% and 100% of the fetuses respectively. There were 2 cases where the soft palate including the uvula could not be well visualized in the oblique sagittal plane, at 15 and 18 weeks gestation respectively. The fetal soft palate could be examined consistently in the oblique planes on a routine 3D ultrasound volume of the fetal face in the second and third trimesters, at or above 19 weeks gestation, by using the uvula as a landmark. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Objective: To present the early 2D and 3D ultrasound findings and the molecular confirmation in a case of thanatophoric dysplasia. Methods: On ultrasound examination, there was frontal bossing, increased nuchal translucency and short limbs at 12 weeks’ gestation and a small thorax and short and bowed long bones on 3D at 16 weeks. Amniocentesis and DNA analysis confirmed the mutation of FGFR3 gene indicating thanatophoric dysplasia. Results: After medical termination of pregnancy, the postmortem X-ray and pathology examination findings were consistent with the diagnosis. Conclusion: 3D anatomy scan and molecular confirmation may be helpful in early diagnosis and genetic counseling of thanatophoric dysplasia.

Objectives: To report a technique to view the fetal soft and hard palates, utilizing acquired routine 3-D volumes of the fetal face. Method: The axial, sagittal and coronal planes in acquired volumes of 3-D surface rendering of 5 normal fetal faces obtained at 19, 21, 23, 26 and 28 weeks, respectively, were reviewed by focusing on the uvula. Results: The surfaces of the soft and the hard palate could be viewed in oblique axial, oblique sagittal and targeted coronal planes in all fetuses. Conclusion: Rotating or tilting of the axial, sagittal and coronal planes of the fetal head allows the visualization of the various aspects of the soft and hard palates, with the uvula as a useful landmark.

To describe the use of 3D ultrasound in the antenatal diagnosis of 3 cases of skeletal dysplasia. The sonographic findings of 3 cases of skeletal dysplasia are presented, including 1 case of each of the following conditions: thanatophoric dysplasia, osteogenesis imperfecta and hypochondroplasia. The distinguishing sonographic features detected on 3D ultrasound for the antenatal diagnosis of these conditions are described in addition to the 2D ultrasound findings. Other than the finding of limb shortening on 2D ultrasound examination, the typical external and bony appearance of these conditions could be observed on 3D ultrasound. These include the small rib cage, flaring of the lower ribs and bowed long bones with abnormal ends in thanatophoric dysplasia, bowed bones with multiple fractures and callus formation in osteogenesis imperfecta, and short but otherwise normal bony appearance in hypochondroplasia. These sonographic findings allow antenatal diagnosis to be made more readily and facilitate patient counselling and management. When skeletal dysplasia is suspected antenatally, the use of 3D ultrasound in the examination of the fetal general appearance and bony structures provides additional information and facilitates antenatal diagnosis and management of the condition.