Lourens R. Pistorius

Fetal Neuroimaging : Ultrasound, MRI, or Both?

Much has been written recently about the relative merits and demerits of fetal imaging with ultrasound and magnetic resonance imaging (MRI). Unfortunately, the arguments often generate more heat than light. We attempted to identify the strengths and weaknesses of each modality from the literature, and to arrive at some practical recommendations on when to use which imaging modality. In conclusion, combining neurosonography and MRI is mostly redundant, but occasionally complementary. Both are operator dependant and neither technique obviates the need for a thorough knowledge of normal and abnormal neuroanatomy. In early pregnancy, and where repeated assessment is needed, ultrasound has the obvious advantage. Where ultrasound is difficult, as in the obese patient or a patient with severe oligohydramnios, better images might be obtained by MRI examination, although a special MR system is required for patients weighing more than 150 kg. MRI might also identify fetal ischemic lesions early after an insult such as severe maternal trauma or death of a monochorionic co-twin. There is a synergy between ultrasound and MRI for the diagnosis of certain conditions, such as congenital cytomegalovirus infection or cerebellar telangiectasis. Local conditions and expertise obviously influence the accuracy of both modalities. Both ultrasound and MRI should be performed to the highest possible standard, and the final diagnosis should be made in a multidisciplinary setting. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to summarize the limitations of ultrasound and MRI in fetal CNS imaging, appropriately prepare and counsel patients regarding the best choice of imaging modality, and modify utilization of resources.

Disturbance of Cerebral Neuronal Migration following Congenital Parvovirus B19 Infection

Objective: We describe the clinical course of an infant who presented with severe fetal anemia and fetal hydrops following congenital parvovirus B19 infection before 16 gestational weeks. The fetus was treated by cordocentesis and intrauterine transfusion at 18 weeks. Results: The infant demonstrated mild unilateral ventriculomegaly on antenatal magnetic resonance imaging, and polymicrogyria and heterotopia on postnatal magnetic resonance imaging. Conclusion: This adds to the evidence in recent literature of central nervous system damage associated with congenital parvovirus B19 infection.

Prenatal genetic confirmation of a COL4A1 mutation presenting with sonographic fetal intracranial hemorrhage

While the antenatal onset of intracranial lesions associated with COL4A1 has been reported by us and others, this diagnosis has always been made after birth1–3 (Table S1). This is the first report of the diagnosis of a mutation in the COL4A1 gene in a fetus. A 35-year-old woman was referred after detection of a cystic lesion in the fetal posterior cranial fossa during ultrasound screening. She had no family history of anomalies or recent history of maternal or fetal trauma. Screening for TORCH and alloimmune antithrombocyte antibodies in maternal plasma, and polymerase chain reaction (PCR) for cytomegalovirus and quantitative fluorescent (QF)PCR for trisomies 13, 18 and 21 in amniotic fluid were negative. Fetal neurosonography at 21 + 6 weeks’ gestation revealed hyperechogenic walls of the lateral ventricles and left-sided periventricular echogenicity. A large germinal matrix hemorrhage extended with a wedgeshaped echogenic lesion into the left thalamus. The left cerebellar hemisphere was replaced by an echolucent area with displacement of the right cerebellar hemisphere (Figure 1a). At 23 + 4 weeks, fetal MRI confirmed the ultrasound findings. The posterior fossa mass had expanded and had the appearance of an organizing hematoma with destruction of the left cerebellar hemisphere (Figures 1b and c). Repeat ultrasound scans showed mild progressive dilatation, more obvious echogenicity of the lateral ventricles and wedge-shaped cystic evolution of the left thalamus (Figure S1a). By 30 weeks’ gestation the results of sequence analysis of the COL4A1 gene using fetal DNA isolated from amniotic fluid became known, showing a de-novo pathogenic missense mutation (G1103R). At 41 + 6 weeks a female infant was delivered vaginally with normal Apgar scores, birth weight (3355 g) and head circumference (34 cm). Neonatal MRI confirmed a wedge-shaped area of cavitation in the left basal ganglia. There was lack of myelination of the posterior limb of the internal capsule and absence of the left cerebellar hemisphere (Figures S1b and c). Ophthalmological investigation showed sporadic small retinal hemorrhages. Renal sonography was normal. The infant developed a hemiplegia. Rates of fetal intracranial hemorrhage of 0.46 per 1000 deliveries and 0.9 per 1000 pregnancies have been reported at referral centers4. In an unknown proportion of fetuses, a Mendelian genetic disorder, associated with an increased risk for cerebral arteriopathy, can be detected. The COL4A1 gene encodes for the alpha-1 chain of type IV collagen, a basement membrane protein, which is expressed widely in all tissues, including the vasculature5. Mutations in the COL4A1 gene lead to an altered COL4A1 protein, which compromises the basement membrane of the vasculature, thus predisposing to hemorrhage. In 2005 Gould et al.6 were the first to report COL4A1 mutations in mice with perinatal hemorrhage and in human families with porencephaly. Since then COL4A1 mutations have been reported in association with a wide spectrum of symptoms, including familial porencephaly, intracranial aneurysms, muscle cramps, hemorrhagic stroke, infantile hemiparesis7–9 and intraventricular hemorrhage in preterm infants with parenchymal hemorrhage of antenatal onset2,3,10. More extensive supratentorial lesions, in combination with cerebellar injury, have recently been reported2. In our case, the combination of a supratentorial hemorrhage and a cerebellar lesion led to prenatal diagnosis of a

Sotalol as first-line treatment for fetal tachycardia and neonatal follow-up

In fetal tachycardia, pharmacological therapy with digoxin, flecainide and sotalol has been reported to be effective. In a recent retrospective multicenter study, sotalol was considered to be less effective than the other drugs in treatment of fetal supraventricular tachycardia (SVT). The aim of this study was to re‐evaluate the efficacy and safety of maternally administered sotalol in the treatment of fetal tachycardia.

The value of umbilical artery Doppler velocimetry in the antenatal surveillance of uncomplicated monochorionic twin pregnancies

To investigate the predictive value of abnormal umbilical artery Doppler findings on outcome in uncomplicated monochorionic (MC) twin pregnancies.

Fetal Heart Disease: Severity, Associated Anomalies and Parental Decision

Objective: This study describes the association between the complexity of congenital cardiac and extracardiac malformations, and the parental decision of pregnancy continuation or termination. Methods: Congenital heart defects (CHD) was diagnosed by ultrasound in 251 fetuses before the 24th week (23 + 6 weeks) of gestation during the four year period from 2007 to 2010. All fetuses from the Utrecht region were referred to our center due to a strict referral pattern. The complexity and severity of the cardiac and possible extracardiac malformations were retrospectively categorized by a pediatric cardiologist and a perinatologist who were blinded to the pregnancy outcome. The groups with and without termination of pregnancy were compared using a univariate analysis and multivariate logistic regression. Results: In 119 (47%) of the 251 fetuses, parents opted for termination of pregnancy. In 103 of these cases (87%) there was a high complex or lethal cardiac, or a major or lethal extracardiac malformation. Of the 132 continued pregnancies, 42 fetuses (32%) had a high complex or lethal cardiac, or a major or lethal extracardiac malformation. There were significantly more terminations of pregnancy in case of a high or lethal complex cardiac or extracardiac anomaly (71 vs. 15%, p <0.001). Conclusion: Parents opted for termination of pregnancy significantly more often in cases with high complex cardiac and extracardiac malformations. It was rare for parents to opt for pregnancy termination in the absence of a severe cardiac or extracardiac malformation.

'Tobacco pipe' sign in the fetus: patent left superior vena cava with absent right superior vena cava.

1. Kutsche LM, Van Mierop LH. Anomalous origin of a pulmonary artery from the ascending aorta: associated anomalies and pathogenesis. Am J Cardiol 1988; 1: 850–856. 2. Carretero J, Rissech M, Mortera C, Mayol J, Caffarena J, Prada F. Aortic origin of the left pulmonary artery in an infant with Fallot’s tetralogy. Rev Esp Cardiol 2005; 58: 1124–1126. [Spanish] 3. Peng EW, Shanmugam G, Macarthur KJ, Pollock JC. Ascending aortic origin of a branch pulmonary artery – surgical management and long-term outcome. Eur J Cardiothorac Surg 2004; 26: 762–764. 4. Prifti E, Crucean A, Bonacchi M, Bernabei M, Leacche M, Murzi B, Bartolozzi F, Vanini V. Postoperative outcome in patients with anomalous origin of one pulmonary artery branch from the aorta. Eur J Cardiothorac Surg 2003; 24: 21–27. 5. Prifti E, Bonacchi M, Murzi B, Crucean A, Leacche M, Bernabei M, Bartolozzi F, Nathan NS, Vanini V. Anomalous origin of the right pulmonary artery from the ascending aorta. J Card Surg 2004; 19: 103–112. 6. Jung MJ, Yoo SJ. Prenatal diagnosis of anomalous origin of the right pulmonary artery from the ascending aorta. Cardiol Young 2002; 12: 186–188.

Effect of (minor or major) maternal trauma on fetal motility: A prospective study

BACKGROUND Fetal motility represents the spontaneous activity of the central nervous system and as such can be used to evaluate its functional integrity. Maternal mechanical trauma in pregnancy is a risk factor for hypoxic ischemic brain injury and can potentially affect the CNS and fetal motility. AIM To study motility in fetuses after maternal trauma. STUDY DESIGN Prospective study; 1-h sonographic observations at 2-8h (T1), 24-72h (T2) and >72h (T3) after trauma. SUBJECTS Fetuses exposed to trauma after 20weeks gestational age. OUTCOME MEASURES Motor aspects; differentiation into specific movement patterns, quality and quantity of general movements were compared to a normal population. Obstetrical outcome; neurological outcome at term and 1year of age. RESULTS Sixteen fetuses were examined between 2012 and 2014. Median gestational age at time of trauma was 25+6 (range 20-38) weeks. Most traumas were traffic accidents or falls, injuries were mainly minor. Motility assessment showed abnormal differentiation in 2/16; 2/14 and 0/16; abnormal quality in 2/16; 3/14 and 6/16; and abnormal quantity in 6/16, 9/14 and 9/16 at T1, T2 and T3 respectively. Preterm delivery occurred once. Neurological development was normal in 13/14 infants at term and 14/14 at one year. CONCLUSIONS This study shows that maternal trauma affected fetal motility in the majority of the fetuses. The changes in motility support the concern that even minor mechanical trauma may have influence on the functional integrity of the central nervous system, although no neurological sequelae were present at 1year.

Lactate to creatinine ratio in amniotic fluid: a pilot study

Abstract Measurement of amniotic fluid (AF) lactate concentration in complicated pregnancies may provide information on the extent of fetal acidemia. However, normalisation for AF volume may be necessary by calculating the lactate:creatinine (L:C) ratio. We measured these AF parameters and compared them to arterial cord blood lactate in 28 term and 10 preterm pregnancies. Cord blood lactate was not correlated to AF lactate, but was correlated to the L:C ratio in the complete study population (R = 0.54, p = 0.001) and the subgroups. Correlation was strongest in a preterm intrauterine growth restricted subgroup (n = 7, R = 0.83, p = 0.02). The L:C ratio is more accurate in estimating fetal lacticaemia than AF lactate.

First trimester neurosonoembryology with automated follicle tracking: Preliminary findings

We evaluated the feasibility of demonstration of the embryonic cerebral ventricles using three dimensional transvaginal ultrasonography and software which has been developed to automatically calculate the volume of ovarian follicles after ovarian stimulation. In four out of six subsequent ultrasound examinations which were done for determination of gestational age from eight to ten gestational weeks, sufficient resolution was obtained to demonstrate the embryonic cerebral ventricles with automated volume calculation software, yielding striking images of a dramatic stage of embryonic development.