Ultrasound detection of hyaloid artery in the ... - Wiley Online Library

Ultrasound Obstet Gynecol 2012; 39: 478–481 Published online in Wiley Online Library (wileyonlinelibrary.com).

Letters to the Editor

Ultrasound detection of hyaloid artery in the third trimester of pregnancy: a pathological finding The hyaloid artery is part of the embryonic vasculature of the eye and normally regresses during the second trimester of pregnancy1 . Failure of regression of the hyaloid artery is a sign of abnormal eye development and is usually associated with a persistent hyperplastic primary vitreous (PHPV)2 . The hyaloid artery disappears between 23 and 28 weeks, and is normally not visible on ultrasound after 29 weeks of gestation3 . One report has linked the observation of cataracts and thickened hyaloid artery–lens junction on ultrasound at 23 weeks with the diagnosis of PHPV4 . Persistence of the hyaloid artery on ultrasound examination during the third trimester is a rare pathological finding. We report a case of persistence of the hyaloid artery in the third trimester of pregnancy associated with other anomalies. A 31-year-old woman, gravida 2 para 1, was referred to our prenatal diagnosis center at 27 weeks’ gestation for intrauterine growth restriction (IUGR). Her obstetric history consisted of one normal pregnancy with term delivery. The parents were not consanguineous. The firsttrimester screening ultrasound scan had found a normal nuchal translucency measurement, but maternal serum markers had not been obtained. Follow-up ultrasound confirmed IUGR at 30 weeks, with all fetometric measurements below the 3rd centile but a normal umbilical

Doppler. Ultrasound examination also showed hyperechogenic kidneys and a persistent hyaloid artery visible on a transverse view of the right fetal orbit (Figure 1a). Amniocentesis was performed revealing a normal karyotype, and no deletion of the chromosomal region 4p was found on fluorescence in-situ hybridization (FISH) analysis. Polymerase chain reaction (PCR) analysis of amniotic fluid was negative for cytomegalovirus. Fetal skeletal three-dimensional helical computer tomography and cerebral magnetic resonance imaging were performed and were found to be normal. The hyaloid artery was still present on ultrasound examination at 32 weeks. The morphological abnormalities observed, the uncertain prognosis and the suspicion of syndromic association were explained to the couple by a multidisciplinary team involving geneticists and pediatric ophthalmologists. In accordance with French legislation, termination of pregnancy was performed at the request of the parents. The woman delivered a 1175-g (< 3rd centile) male baby at 34 weeks. Postmortem examination confirmed IUGR and revealed renal microcysts. Macroscopic and microscopic examination of the eyes also confirmed the presence of the right hyaloid artery (Figure 1b). Hyperplastic primary vitreous was not visible on histological examination, but lens histology revealed a developing cataract (Figure 2). Despite the histological absence of PHPV in our case, the persistence of the hyaloid artery belongs to the same spectrum of ocular malformations and our histological examination showed a unilateral right cataract, which

Figure 1 (a) Ultrasound image of the right fetal orbit in transverse view. The hyaloid artery is indicated (arrow). (b) Macroscopic examination of the right eye; the hyaloid artery is visible as a thin white filament (arrows). The box at the bottom right of this panel is a microscopic image of the right eye showing the proximal part of the hyaloid artery at the level of the retina.

Copyright  2012 ISUOG. Published by John Wiley & Sons, Ltd.

LETTERS TO THE EDITOR


479 5. Haddad R, Font RL, Reeser F. Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature. Surv Ophthalmol 1978; 23: 123–134. 6. Hunt A, Rowe N, Lam A, Martin F. Outcomes in persistent hyperplastic primary vitreous. Br J Ophthalmol 2005; 89: 859–863.

Masked anemia due to cardiac tamponade in a hydropic fetus caused by placental chorioangioma

Figure 2 Cataract visible on histological examination of the lens. Note the moth-eaten appearance of the posterior wall of the lens.

has been described as a frequent association5 . In cases of PHPV the visual prognosis is variable; it can be very poor and depends on the extent of anterior or posterior segment involvement6 . There are no data in the literature on the visual prognosis in cases with persistence of the hyaloid artery without PHPV. In our case, the combination with IUGR and microcystic kidneys suggested a syndromic association of unknown etiology. Persistence of the hyaloid artery in the third trimester is an abnormal ultrasound finding. Management should involve collaboration with geneticists and ophthalmologists. E. Spaggiari*†‡, E. Vuillard§, C. Baumann¶, C. Dupont¶, N. Belarbi**, J.-F. Oury‡§, A.-L. Delezoide†‡ and F. Guimiot†‡ †Department of Developmental Biology, AP-HP, Robert Debré Hospital, Paris, France; ‡University Paris 7 Diderot, Paris Sorbonne-Cité, France; §Department of Gynaecology and Obstetrics, AP-HP, Robert Debré Hospital, Paris, France; ¶Department of Genetics, AP-HP, Robert Debré Hospital, Paris, France; **Department of Radiology, AP-HP, Robert Debré Hospital, Paris, France *Correspondence. (e-mail: [email protected])

A 23-year-old woman in her third pregnancy was referred at 28 + 2 weeks because of fetal hydrops and a suspected placental tumor. Ultrasound examination confirmed severe polyhydramnios, placentomegaly and a large chorioangioma of 104 × 84 × 88 mm. The fetus had hydrops with severe bilateral hydrothorax (Figure 1), generalized skin edema, ascites and holosystolic tricuspid insufficiency. Doppler examination of the middle cerebral artery (MCA) revealed a peak systolic velocity (PSV) of 61 cm/s corresponding to 1.5 multiples of the median1 and normal pulsatility. Umbilical Doppler examination and further investigations (chromosomal analysis, TORCH serology and search for HbF cells in maternal blood) were unremarkable. At 28 + 4 weeks bilateral thoraco–amniotic shunts (Harrison fetal bladder stents) were inserted. Only a few hours after successful drainage and cardiac decompression ultrasound examination revealed an increase of MCA-PSV to 100 cm/s, indicating fetal anemia (Figure 2). Fetal blood sampling confirmed severe anemia (hemoglobin concentration, 5.8 g/dL) and intrauterine transfusion was performed. After the procedure MCAPSV normalized to 67 cm/s and signs of hydrops started to regress. One week later a second transfusion of packed erythrocytes was necessary. At 30 + 3 weeks of gestation secondary Cesarean section was performed because of preterm rupture of membranes followed by labor. The female newborn (weight, 1610 g; Apgar scores 7, 9 and 10 at 1 min, 5 min and 10 min, respectively; hemoglobin concentration, 13 g/dL) was referred to the neonatal intensive care unit. She was discharged in healthy condition at

DOI: 10.1002/uog.10123

References 1. Birnholz JC. Ultrasonic fetal ophthalmology. Early Hum Dev 1985; 12: 199–209. 2. Goldberg MF. Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 1997; 124: 587–626. 3. Achiron R, Kreiser D, Achiron A. Axial growth of the fetal eye and evaluation of the hyaloid artery: in utero ultrasonographic study. Prenat Diagn 2000; 20: 894–899. 4. Katorza E, Rosner M, Zalel Y, Gilboa Y, Achiron R. Prenatal ultrasonographic diagnosis of persistent hyperplastic primary vitreous. Ultrasound Obstet Gynecol 2008; 32: 226–228.


Figure 1 Bilateral severe hydrothorax and skin edema in a 28-week fetus.

Ultrasound Obstet Gynecol 2012; 39: 478–481.


480

¨ A. Hellmund†, C. Berg†‡, B. Rosing†, U. Gembruch† and A. Geipel*† †Department of Obstetrics and Prenatal Medicine, University Medical School Bonn, Bonn, Germany; ‡Division of Prenatal Medicine and Gynecologic Sonography, University Medical School Cologne, Cologne, Germany *Correspondence. (e-mail: [email protected]) DOI: 10.1002/uog.10105

References

Figure 2 Middle cerebral artery Doppler velocimetry following shunt insertion for bilateral hydrothorax, showing a peak systolic velocity of 100 cm/s.

6 weeks of age and development at the age of 1.5 years appeared to be normal. Placental histology confirmed a chorioangioma of 115 × 95 mm. In the presented case chorioangioma led to severe but masked anemia2,3 , which was correctly diagnosed by measuring MCA-PSV4,5 only after drainage of the severe bilateral hydrothorax. A likely explanation is cardiac compression due to the hydrothorax, leading to impaired ventricular filling and low cardiac output, resulting in relatively normal MCA-PSV despite severe anemia. After successful drainage of fluid the intrathoracic pressure decreased and the cardiac tamponade disappeared, leading to increased ventricular filling, stroke volume and cardiac output which resulted in higher MCA-PSV, correctly indicating the presence of fetal anemia. The pathomechanism of fetal cardiac compression leading to diminished cardiac output and hydrops has been investigated in the context of different thoracic anomalies6,7 . Swast et al.8 measured diminished cardiac output in fetuses with congenital cystic adenomatoid malformation of the lung. Bigras et al.9 found that fetuses with hydrothorax had smaller dimensions of the left ventricle and the peak velocity of the ascending aorta was lower than that of the normal population. Both authors hypothesized that these findings may represent lower preload of the left ventricle caused by increased intrathoracic pressure. In addition, Van Mieghem et al.10 recently found decreased MCA-PSV in fetuses with prenatally diagnosed congenital diaphragmatic hernia. The authors’ explanation was similar to our observation, with a smaller dimension of the left ventricle and decreased left ventricular output due to intrathoracic compression. In summary, elevated intrathoracic pressure may generate distinct alterations in fetal hemodynamics, which are likely to affect MCA-PSV. Therefore, evaluation of MCA-PSV to exclude associated fetal anemia should be interpreted with caution in the presence of bilateral hydrothorax. In these cases drainage of bilateral pleural effusions may normalize intrathoracic pressure and increase cardiac output.


1. Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise KJ, Dorman KF, Ludomirsky A, Gonzalez R, Gomez R, Oz U, Detti L, Copel JA, Bahado-Singh R, Berry S, MartinezPoyer J, Blackwell SC. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal redcell alloimmunization. N Engl J Med 2000; 342: 9–14. 2. Zanardini C, Papageorghiou A, Bhide A, Thilaganathan B. Giant placental chorioangioma: natural history and pregnancy outcome. Ultrasound Obstet Gynecol 2010; 35: 332–336. 3. Wehrens XH, Offermans JP, Snijders M, Peeters LL. Fetal cardiovascular response to large placental chorioangiomas. J Perinat Med 2004; 32: 107–112. 4. Hernandez-Andrade E, Scheier M, Dezerega V, Carmo A, Nicolaides KH. Fetal middle cerebral artery peak systolic velocity in the investigation of non-immune hydrops. Ultrasound Obstet Gynecol 2004; 23: 442–445. 5. Escribano D, Galindo A, Arbuès J, Puente JM, De la Fuente P. Prenatal management of placental chorioangioma: value of the middle cerebral artery peak systolic velocity. Fetal Diagn Ther 2006; 21: 489–493. 6. Mahle WT, Rychik J, Tian ZY, Cohen MS, Howell LJ, Crombleholme TM, Flake AW, Adzick NS. Echocardiographic evaluation of the fetus with congenital cystic adenomatoid malformation. Ultrasound Obstet Gynecol 2000; 16: 620–624. 7. Rice HE, Estes JM, Hedrick MH, Bealer JF, Harrison MR, Adzick NS. Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops. J Pediatr Surg 1994; 29: 692–696. 8. Swast A, Tian Z, McCann M, Donaghue D, Bebbington M, Johnson M, Wilson RD, Rychik J. Impact of altered loading conditions on ventricular performance in fetuses with congenital cystic adenomatoid malformation and twin-twin transfusion syndrome. Ultrasound Obstet Gynecol 2007; 30: 40–46. 9. Bigras JL, Ryan G, Suda K, Silva AE, Seaward PG, Windrim R, McCrindle BW. Echocardiographic evaluation of fetal hydrothorax: the effusion ratio as a diagnostic tool. Ultrasound Obstet Gynecol 2003; 21: 37–40. 10. Van Mieghem T, Sandaite I, Michielsen K, Gucciardo L, Done E, Dekoninck P, Claus F, Deprest J. Fetal cerebral blood flow velocities in congenital diaphragmatic hernia. Ultrasound Obstet Gynecol 2010; 36: 452–457.

Acute changes in the embryonic heart rate: a response to environmental challenges? Little is known about the functionality of the heart rate during early intrauterine life. Ultrasound has allowed invivo observation of normal changes of the heart rate in humans and non-human primate embryos1 . Before 10 weeks’ gestation, ultrasound-guided celocentesis has also allowed the prenatal diagnosis of genetic disorders2,3 , insights into the physiological properties of the chorionic membrane and extracelomic fluid4,5 and investigations


Letters to the Editor concerning the feasibility of in-utero cell-based therapy in the pre-immune period6,7 . We now show how this technique can be used to study in vivo the capabilities of the embryonic heart. Indeed, until this study, it was not known if the 8-week human embryo could respond to acute environmental changes. This study was performed in baboons at around 40 days after fertilization and was approved by the Animal Care Committee at the University of Oklahoma (Figure S1, equivalent to 7–8 weeks’ gestation in humans; Carnegie stages 20–23 of development). In five animals, 1 mL of a physiologic solution was injected into the extracelomic space, whereas in three animals 1 mL of extracelomic fluid was aspirated. Embryonic heart rates were recorded before, and 15 min and 24 h after celocentesis. Our findings suggest that there was a significant increase in the embryonic heart rate after the celocentesis procedure (P = 0.05) (Table S1, Figure S2). Although we cannot rule out the possibility that the observed changes are merely the reflection of a primary response to the uterine puncture procedure, this experimentally induced observation is important. Moreover, it can be used to formulate the hypothesis that there is some degree of functional regulation of the embryonic heart rate at these developmental stages: until now, the rate of the beat of the heart musculature at these gestational ages was thought to be controlled by the effect of the action potential initiated in the sinoatrial (SA) node on the cardiocytes with no true resting potential8 . Our findings, however, suggest that the intrinsic rate of the electrical impulses generated from the SA node can be modulated at the equivalent of 8 weeks’ gestation in human pregnancies. Ultrasoundguided celocentesis in the timed-pregnant baboon is therefore a valuable model for studying the effects of environmental challenges on the embryonic heart rate and also for investigating if the control of the rate of the embryonic heart beat relies primarily on the ontogenesis of the autonomic nervous system9 , the contributions of the developing adrenergic and parasympathetic nervous systems on cardiovascular function10,11 or on metabolic events induced by acute modification of the gestational sac surface tension and function. In addition, this model could be used to investigate the long-term effect on cardiovascular regulation and congenital malformation of environmental challenges occurring early in gestation.

481

J. L. Santolaya†, V. Di Stefano†, J. DeLeon Luis‡ and J. Santolaya-Forgas*†‡ †The Center for Research and Mentorship, Department of Obstetrics and Gynecology, UMDNJ - Robert Wood Johnson Medical School, New Brunswick, NJ, USA; ‡The Amarillo Women’s Health Research Institute, Texas Tech University, TX, USA *Correspondence. (e-mail: [email protected]) DOI: 10.1002/uog.10134

References 1. Santolaya-Forgas J, DeLeon-Luis J, Friel LA, Wolf R. Application of the Carnegie stages of development to unify human and baboon ultrasound findings early in pregnancy. Ultrasound Med Biol 2007; 18: 1400–1405. 2. Jurkovic D, Jauniaux E, Campbell S, Pandya P, Cardy DL, Nicolaides KH. Coelocentesis: a new technique for early prenatal diagnosis. Lancet 1993; 341: 1623–1624. 3. Santolaya-Forgas J, DeLeon-Luis JA, Shen Z, McCorquodale M. Chromosomal studies on 2 mL of celomic fluid obtained during the fifth week of development in the timed-pregnant baboon model. J Reprod Med 2005; 50: 692–696. 4. Santolaya-Forgas J, Duval J, Prespin C, Vengalil S, Kushwaha A, Wilson L, Fortman J. Extracoelomic fluid osmometry and electrolyte composition during early gestation in the baboon. Am J Obstet Gynecol 1998; 179: 1124–1127. 5. Santolaya-Forgas J, DeLeon-Luis JA, Espinoza J, Goncalves L, Romero R. Solutes in maternal circulation and gestational sac compartments during early human development. Fetal Diagn Ther 2006; 21: 287–292. 6. Santolaya-Forgas J, DeLeon-Luis J, Galan I. Can the extraembryonic celomic fluid be replaced with stem cell culture medium? Ultrasound Obstet Gynecol 2006; 28: 232–233. 7. Santolaya-Forgas J, DeLeon-Luis J, Wilkins-Haug L. Celocentesis for in utero stem cell therapy: where we now stand and future directions. Am J Perinatol 2007; 24: 277–281. 8. Klabunde RE. Electrical activity of the heart. In Cardiovascular Physiology Concepts (2nd edn). Lippincott Williams & Wilkins: Philadelphia, PA, 2011; (http://cvphysiology.com/ Arrhythmias/A004.htm). 9. Crossley D, Altimiras J. Ontogeny of cholinergic and adrenergic cardiovascular regulation in the domestic chicken (Gallus gallus). Am J Physiol Regul Integr Com Physiol 2000; 279: R1091–R1098. 10. Smolen AJ. Morphology of synapses in the autonomic nervous system. J Electron Microsc Tech 1988; 10: 187–204. 11. Assali NS, Brinkman CR, Woods JR Jr, Dandavino A, Nuwayhid B. Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions. Am J Obstet Gynecol 1977; 129: 748–759.

SUPPORTING INFORMATION ON THE INTERNET The following supporting information may be found in the online version of this article: Figure S1 Endoscopic image of baboon fetus at ≈ 40 days from fertilization. Embryonic crown–rump length, heart rate, placental location and the mean of three-diameters of the gestational (GS), amniotic (AS) and yolk (YS) sac were recorded using a Sonosite 180 Plus ultrasound system prior to transabdominal ultrasound-guided celocentesis performed with a 20-gauge needle at ∼ 40 days of development (days from fertilization; term pregnancy in baboons is 178–182 days). Figure S2 Graph of embryonic heart rates recorded before and 15 min and 24 h after celocentesis in baboons. Non-parametric Friedman test for repeated measurements was used to determine heart rate differences between the three time periods. Mean heart rate increased significantly after the celocentesis procedure (P = 0.05). Table S1 Characteristics and findings in the eight baboon fetuses that underwent a celocentesis procedure. Six animals survived and delivered at term. Two animals (A and C, from the injection group) aborted within 3 days of the procedure.

