Normal Neurological Development Research Articles

Evaluation of fetal ventriculomegaly

Objective: To evaluate the prenatal and postnatal follow up, treatment and the outcome of the patients with ven­triculomegaly. Methods: Patients with lateral cerebral ventricle size 10mm and higher were included. 69 patients were con­sidered but 8 patients refused to join our study. The pa­tients were divided into two groups as they had additional anomalies (combined ventriculomegaly) or not (isolated ventriculomegaly). Each group was divided into three subgroups according to their lateral cerebral ventricle size as mild (10-12 mm), moderate (12.1-4.9 mm), severe (15 mm and more) ventriculomegaly. Results: 10 fetuses with isolated ventriculomegaly and combined ventriculomegaly died after birth. Neurosurgi­cal operations were performed for ten patients. We per­formed chromosomal analysis for 16.7% of our patients. Caesarian delivery was higher (91.7%) in combined ven­triculomegaly groups and all newborns went to NNICU. In isolated ventriculomegaly group 18 patients showed nor­mal neurological development at sixth month. None of the patients with combined ventriculomegaly group showed normal neurological development at sixth month. In se­vere ventriculomegaly group termination ratio was higher (64.7%) than isolated ventriculomegaly group (11%). The survival rate was 90% in mild ventriculomegaly group and 42.9% in severe ventriculomegaly group. Conclusion: Termination is more often in isolated severe ventriculomegaly than mild and moderate ventriculomeg­aly group because the prognosis is worse. Because the prognosis of the patients with mild ventriculomegaly is good decision for termination will be well evaluated with the family.

Management of breast cancer during pregnancy: Results of a large registry from a single institution.

589 Background: Given the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer during pregnancy. Management is still controversial and relies on expert guidelines. Thus the experience of single centres with high patients’ volume remains of interest. Methods: All breast cancer patients (pts) diagnosed at the European Institute of Oncology (IEO) in Milan were included in a specific registry since 1995. Results: Out of 8340 patients < 47 y/o registered up to Dec 2012, 167 were diagnosed during pregnancy (2%). Median age was 36 years (24-47y). Median gestational age was 18 weeks (1-38 w). 73 % pts had a pT1-2 tumor, with positive nodes in 48%. 9,6% had luminal A, 38% luminal B, 26% basal like and 16% HER2+ tumors, according to St Gallen criteria. 29/167 pts (17%) opted for an induced abortion. Of the remaining 97 pts, 81 (84%) underwent definitive surgery during pregnancy; 58 (72%) and 23 pts (28%) had quadrantectomy and mastectomy, respectively. Immediate breast reconstruction was performed in 13 cases. Sentinel node procedure (SLN) was performed in 42 pts (52%), with positive axilla in 10 pts. 41 pts (51%) received chemotherapy during pregnancy. Regimens included weekly epirubicin (24 pts), EC/AC (12 pts), FAC/FEC (3 pts), q21 epirubicin (2 pts). No G3-G4 toxicities were reported. No pregnancy complications were observed, with the exception of 1 case of premature delivery at 28 weeks. Median gestational age at delivery was 36 weeks (29-40 w). No major malformations were observed. Gestational age at birth and birth-weight were similar in babies who received chemotherapy in-utero (36 w and 2555g) and in babies who did not receive gestational chemotherapy (37w and 2600g). At a median follow-up of 42 months (range: 1-178 m), all children had normal neurological and physical development with no late adverse effects observed. Conclusions: Managing breast cancer during pregnancy should follow standard practice as in non-pregnant pts. Surgeries like SLN and breast reconstruction were performed with no serious complications. Our results further emphasize the safety of anthracycline-based gestational chemotherapy without major effects on pregnancy course or fetal health.

Four-dimensional HDlive rendering image of fetal facial expression: a pictorial essay.

Our objective was to present our experience of fetal facial expressions reconstructed employing the four-dimensional (4D) HDlive rendering mode. A total of 23 normal fetuses at 18-36weeks' gestation were studied using the 4D HDlive rendering mode. The 4D HDlive rendering mode provided extraordinarily realistic features of the fetal face. In particular, blinking, mouthing, swallowing, yawning, tongue expulsion, and sucking were clearly noted. Moreover, various realistic fetal emotional expressions such as smiling-like and crying-like movements were recognized. The 4D HDlive rendered images of fetal facial expressions seem to be more readily discernible than those obtained by conventional 4D ultrasonography. Observation of facial expressions using the 4D HDlive rendering mode is considered to reflect the normal and abnormal neurological development of the fetus. Therefore, the 4D HDlive rendering mode may assist in evaluation of fetal brain function, and offer potential advantages relative to conventional 4D ultrasonography.

4D ultrasound evaluation of fetal facial expressions during the latter stages of the second trimester

ObjectiveTo assess the frequency of fetal facial expressions at 25–27weeks of gestation using 4D ultrasound. MethodsTwenty-four normal fetuses were examined using 4D ultrasound. The face of each fetus was recorded continuously for 15minutes. The frequencies of tongue expulsion, yawning, sucking, mouthing, blinking, scowling, and smiling were assessed and compared with those observed at 28–34weeks of gestation in a previous study. ResultsMouthing was the most common facial expression at 25–27weeks of gestation; the frequency of mouthing was significantly higher than that of the other 6 facial expressions (P<0.05). Yawning was significantly more frequent than the other facial expressions, apart from mouthing (P<0.05). The frequencies of yawning, smiling, tongue expulsion, sucking, and blinking differed significantly between 25–27 and 28–34weeks (P<0.05). ConclusionThe results indicate that facial expressions can be used as an indicator of normal fetal neurologic development from the second to the third trimester. 4D ultrasound may be a valuable tool for assessing fetal neurobehavioral development during gestation.

Fetal megacystis as a prenatal challenge: megacystis–microcolon–intestinal hypoperistalsis syndrome in a male fetus

The prenatal detection of megacystis is only the first step towards identifying the etiology and deciding on suitable treatment for this condition. Here we present a report highlighting the difficulties in the prenatal diagnosis of this severe fetal anomaly. A 28-year-old healthy primigravida was referred at 24 weeks' gestation to a tertiary hospital after an ultrasound scan at 18 weeks revealed megacystis and unilateral hydronephrosis in a male fetus with normal karyotype. On referral, a further ultrasound examination revealed a large bladder with a dilated posterior urethra (the ‘keyhole sign’) and normal wall thickness. Based on these findings, posterior urethral valves (PUV) syndrome was first suspected. Following weekly clinical and ultrasound surveillance, a progressive and unexpected increase in the amniotic fluid index (AFI) was observed in the third trimester, with polyhydramnios and grade IV hydronephrosis (Figures 1 and 2). These findings were suggestive of the rare megacystis–microcolon–intestinal hypoperistalsis syndrome (MMIHS). At 32 weeks' gestation, fetal magnetic resonance imaging (MRI) showed a dilated bladder measuring 135 × 111 × 86 mm that was compressing the abdominal organs, and severe bilateral hydronephrosis (21 mm right and 18 mm left); in addition, the stomach was clearly visible, but not the intestines (Figure 3). Vesicocentesis was performed for fetal urinalysis (sodium, potassium, calcium, phosphorus, creatinine, urea, total proteins and β2-microglobulin), and amniocentesis for evaluation of digestive enzymes (including γ-glutamyl transferase, alkaline phosphatase and biliary salts); findings from these tests were consistent with MMIHS. A Cesarean section was performed at 33 weeks, after spontaneous rupture of membranes. The neonate weighed 2950 g and had Apgar scores of 8 and 8 at 1 and 5 min, respectively. During the neonatal period the diagnosis was confirmed, and vesicostomy and total parenteral nutrition were needed. At 12 months, the infant had normal physical and neurological development, but still needed parenteral nutrition and vesicostomy. MMIHS is a rare congenital disease with fewer than 200 cases described in the literature, most of whom died in the first year of life1-4. It is characterized by a functional neonatal bowel obstruction with dilated small bowel, microcolon and non-obstructive urinary bladder distension. The etiology of the disease is unknown1-3. The prenatal sonographic features of MMIHS include megacystis, hydronephrosis, hydroureters, normal or decreased AFI in the second trimester, and polyhydramnios, intestinal and/or stomach dilatation in the third trimester1, 5-9. The fetal sex should also be considered, because MMIHS occurs 3–4 times more frequently in females2-5, 8, 9, although, as our case shows, the diagnosis should not be ruled out in male fetuses. The presence of oligohydramnios, progressive bladder wall thickening, hydronephrosis, echogenic kidneys and dilated posterior urethra are more suggestive of obstructive uropathy caused by a distal urethral obstruction such as PUV5, 9-11. For this reason, amniotic fluid analysis and fetal urinalysis are also helpful in the prenatal diagnosis of MMIHS6, 9, 12, as elevated digestive enzymes and high calcium levels, respectively, can be indicative of the disease6. Fetal MRI may also improve the diagnosis, especially when upper gastrointestinal tract distension (esophagus, stomach or small bowel) and microcolon are observed13. Despite the absence of pathognomonic findings of this rare syndrome, prenatal diagnosis is mandatory for optimal counseling and postnatal treatment.

Importance of Screening in 0–18 Months Infants by using INFANIB at Tertiary Hospital

Objectives: Child development is a dynamic process and is often hard to measure by its very nature. The various streams of development, including gross motor, fine motor, language, cognitive, and adaptive behaviour, are interrelated and complex within themselves. Developmental delay refers to when a child's development lags behind established normal ranges for his or her age. The prevalence of developmental delay, deviation, disability or deformity in India is 2.5%. So the objective of this study was to screen the infants at Tertiary hospital and to categorize them as normal, transiently abnormal & abnormal neurologic development according to the INFANIB score. Design: Cross sectional study Method: 639 subjects were included in this study. According to the INFANIB manual guidelines, screening test was administered and infants were categorized as normal, transiently abnormal and abnormal neurologic development. Then, the data was evaluated statistically and results were obtained. Results: In Group 1(age of less than 4 months) as per INFANIB score out of 194 samples there were 161(82.99%) normal, 24(12.37%) transiently abnormal and 9(4.64%) abnormal neurologic development infants. Group 2 (age of 4-8 month) had 162(86.63%) normal, 12(6.42%) transiently abnormal and 13(6.95%) abnormal neurologic development infants out of 187 samples. In Group 3(age of 8 months or more) out of 258 samples there were 205(79.46%) normal, 18(6.98%) transiently abnormal and 35(13.57%) abnormal neurologic development infants. When all three age groups were considered, there were 528(82.63%) normal, 54(8.45%) transiently abnormal, 57(8.92%) abnormal neurologic development infants. Conclusion: On INFANIB screening, there were 8.45% transiently abnormal and 8.92% abnormal neurologic development infants at the Tertiary hospital.

Does docosahexaenoic acid play a role in infant malnutrition in the children of Fulani nomads in Northern Nigeria?

Malnutrition is a major contributor to the death of children under 5 years of age in sub-Saharan Africa. Furthermore, poor nutrition causes stunting and underweight in infants and children while at the same time putting at risk normal neurologic and cognitive development. A recent study of rural Fulani infants up to age 2 years in northern Nigeria found that more than one-quarter were stunted and underweight. The nutritional status of these infants was relatively sound at birth but progressively declined over the following 2 years. While insufficient dietary macronutrients such as protein and carbohydrate and micronutrients such as iodine, zinc, vitamin A and iron may well have contributed to their post-natal growth retardation, in this report we raise the possibility that inadequate intake of essential long-chain ω-3 fatty acids, docosahexaenoic acid (DHA) in particular, by infants during the first few years of life may play a role in childhood malnutrition in this part of the world, especially in populations like the Fulani pastoralists who live far-removed from the ocean which would otherwise provide access to DHA-rich seafood. We conclude this piece by suggesting several approaches for improving the DHA status of pregnant and lactating Fulani women and their offspring in Nigeria.

Regional cortical development in very low birth weight infants with normal neurodevelopmental outcome assessed by 3D-ultrasound

Three-dimensional ultrasound (3D-US) offers new perspectives in cerebral imaging. This prospective study aimed to determine whether 3D-US is appropriate to assess cortical development of the premature brain, and compare it to previously established reference values assessed by magnetic resonance imaging (MRI). Preterm infants with a gestational age (GA) of <32 weeks were examined by serial 3D-US scans. Data of 30 patients with normal neurological development at the age of 5 years were included in the analysis. Cortical development was graded according to a five-point scoring system, and data were stratified into 6 age groups. Cortical developmental scores were established for various brain regions. In the frontal and frontoparietal regions, 3D-US reference values differed from published MRI reference values, but were consistent with the published data in all other regions. 3D-US reference values facilitate routine diagnostics and enable the evaluation of cortical development in preterm infants.

Comparison of Spin-Echo T1- and T2-Weighted and Gradient-Echo T1-Weighted Images at 3T in Evaluating Very Preterm Neonates at Term-Equivalent Age

Term-equivalent imaging can assess myelination status in very preterm infants (<30 weeks' gestational age at birth). However, myelination assessment has yet to be compared among GRE-T1WI, SE-T1WI, and SE-T2WI at 3T. We aimed to compare the rates of myelination among those 3 sequences in 11 very preterm neonates who underwent 3T MR imaging at term-equivalent age and subsequently had normal neurologic development. On each sequence, 2 neuroradiologists individually assessed 22 structures. SE-T2WI depicted a higher myelination rate (present in 58.2%-66.4% of all structures) than either GRE-T1WI (51.6%-63.9%) or SE-T1WI (20.5%-38.5%), while GRE-T1WI had the highest interobserver agreement (κ, 0.56; P < .0001). Myelination was present in 90%-100% of patients within the corpus callosum splenium, DSCP, ICP, lateral lemniscus, and spinal tract/nucleus of cranial nerve V on SE-T2WI, and in the DSCP, ICP, lateral lemniscus, medial lemniscus, pyramidal decussation, PLIC, and superior cerebellar peduncle on GRE-T1WI, occurring in similar structures as previously shown at 1.5T and 1T. However, it is not clear whether these findings represent true myelination versus precursors to myelination.

1272 Survival and Neurodevelopmental Outcome of Preterm Infants with a Gestational Age of 22 to 26 Weeks in a Regional Centre

Background and AimsCounselling parents of extremely preterm infants requires knowledge on results of large population-based cohorts and contemporaneous local data.MethodsWe assessed the outcome of all live-born infants 2006 to 2009...

Follow-Up of Tacrolimus Breastfed Babies

Tacrolimus is a calcineurin inhibitor immunosuppressant approved in the prevention of organ allograft rejection or in the treatment of acute graft rejection. The human experience of tacrolimus during pregnancy is reassuring with no specific pattern of neonatal complications, except possible transient hyperkalemia (1). Although the available data on human milk transfer indicate that only very limited amounts of tacrolimus are excreted into breast milk (2), clinical data on the safety of breast-feeding for the newborn of tacrolimus-treated patients are still very scarce. As a member of the European Network of Teratogen Information Services, our center provides advice on the safety and risk of medications for pregnant and lactating women. We report our experience regarding the safety of tacrolimus for newborns whose mother opted for breast-feeding after delivery. Since 2003, we have received advice queries concerning 14 women treated with tacrolimus. After individual assessment including the maternal treatment, dose, comedications, indication, characteristics of the neonate, and the expected type of breast-feeding (exclusive or not), clinical and biologic follow-up of the infant was systematically proposed if the mother decided to breast-feed. After oral consent, the clinical follow-up consisted of a standardized questionnaire filled during telephone interviews of the patient during and after the period of breast-feeding. To monitor the infant’s exposure to tacrolimus through breast-feeding, measurement of whole-blood tacrolimus concentration was also proposed within 2 to 3 weeks after starting breast-feeding to avoid any residual presence of tacrolimus in the newborn caused by transplacental passage and tacrolimus long half-life (up to 43 hr in healthy adults). No immunologic monitoring was proposed. Among these 14 patients, breast-feeding was initiated in 9, but 3 discontinued within 5 to 15 days (2 because of breast-feeding difficulties and 1 because of mycophenolate mofetil initiation), and they were not included in the follow-up. Data from Table 1 provide details on the mothers, the infant’s characteristics at birth, medication exposure, and follow-up of children for the remaining evaluable six patients. All six women (mean age, 32 years) had received tacrolimus throughout pregnancy for the prophylaxis of solid organ rejection. The mean daily dose was 9.6 mg/d (4.5–15 mg/d). Concomitant drugs included azathioprine in four women, diltiazem in one, and prednisolone and low-dose aspirin in one. The mean gestational age at delivery was 37.1 weeks, and four of six newborns were moderately premature (34–36 weeks). Breast-feeding was exclusive in four patients and partial in two. The median duration of breast-feeding was 3 months (range, 1.5–6 months), and the median duration of infant follow-up was 8.5 months (range, 2–30 months). Whole-blood tacrolimus concentration measured in four neonates between day 15 and day 27 after delivery were undetectable (lower limit of detection <1.9 μg/L, antibody-conjugated magnetic immunoassay; Siemens Healthcare Diagnostics, Tarrytown, NY). Clinical follow-up of the infants did not identify any adverse outcome that might be related to tacrolimus maternal treatment, and developmental milestones were within the expected ranges. In particular, no specific pattern of infection was observed. A longer follow-up of these infants is expected.TABLE 1: Details on mothers and child exposureOnly four previous reports have provided data on tacrolimus exposure of infants through breast-feeding. Jain et al. (2) measured tacrolimus concentrations in 10 colostrum samples from six mothers treated with tacrolimus during pregnancy. The highest tacrolimus concentration was 1.9 μg/L, corresponding to a maximal dose of 0.29 μg/kg per day delivered from milk to the neonate, that is, 0.1% of the lowest pediatric dose (based on an infant milk ingestion of 150mL/kg/d). None of these mothers had breast-fed. The very low tacrolimus exposure of infants during breast-feeding was documented by two other reports that included the measurement of tacrolimus levels in mature milk and, respectively, found a mean tacrolimus concentration of 0.6 and 1.8 μg/L in milk (3, 4). Chusney et al. (5) showed a similarly quick postpartum decrease in tacrolimus serum levels in neonates exposed throughout pregnancy, whether or not subsequently breast-fed, suggesting higher exposure in utero than through human milk. Finally, only one report included the clinical follow-up of an exclusively breast-fed neonate with normal physical and neurologic development at 2.5 months of age (3). To the best of our knowledge, the present study is the first one to provide relatively long-term follow-up in infants exposed to tacrolimus through breast-feeding. These results confirm previous analytical data suggesting that tacrolimus exposure in breast-fed babies is negligible and probably safe even in case of prematurity, therefore allowing the mother to breast-feed. Until more data are available, particularly regarding long-term safety, careful infant monitoring is required, especially in patients on a multiple immunosuppressant regimen. Aurore Gouraud Nathalie Bernard Anne Millaret Méri Bruel Nathalie Paret Jacques Descotes Thierry Vial Poison Center and Pharmacovigilance Department Lyon University Hospitals Lyon, France

Neurodevelopment evaluation in children with congenital hypothyroidism by Bayley-III

Background: Congenital hypothyroidism is the most common reason of mental retardation, and normal neurological development can be provided by early and effective treatment. In this present study, it is aimed to compare neurological developments of patients in 6–42months of age with congenital hypothyroidism and healthy controls of the same age group prospectively by Bayley III test. Methods: In this present study, neurological developments of 41 congenital hypothyroidism cases and 39 healthy controls, who applied to Pediatric Endocrinology Section of Mersin Children Hospital and Pediatric Neurology Outpatient Clinic of the Medical School at Mersin University between years 2009 and 2011, were evaluated by Bayley III test. Results: Cognitive, language and global motor scores in addition to receptive communication, expressive communication, fine motor and gross motor subscores in children with congenital hypothyroidism were statistically significantly lower than those in the control group (p<0.05). It is detected that initiation dose and day of treatments, severity of hypothyroidism and time to normalization thyroid stimulating hormone had no statistically significant effects on neurological development of the study group (p>0.05). In both groups, as the education levels of mothers are increased, language development scores are also increased (p<0.05). Additionally, statistically significant increases in Bayley III scores except cognitive scores have been observed in both groups as the level of income is increased (p<0.05). Conclusions: Despite early and effective treatment in newborns with congenital hypothyroidism, retardation in neurological developmental has been detected. This situation can be related to influences on neurodevelopment in intrauterine period. According to our present knowledge, this study is the first case–control study in the literature that neurological developments of congenital hypothyroidism patients are evaluated with Bayley-III score.

Prenatal Neurologic Anomalies

The low prevalence of fetal CNS anomalies results in a restricted level of exposure to, and limited experience for most obstetricians involved in, prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way may increase the detection rate of fetal CNS anomalies, thus promoting correct referral to tertiary care centers offering patients a multidisciplinary approach to the condition. The aim of this review is to elaborate on the prenatal sonographic diagnosis and outcome of various CNS malformations. Detailed neurosonographic investigation has become available through high-resolution vaginal ultrasound probes and the development of a variety of 3-dimensional (3D) ultrasound modalities, such as ultrasound tomographic imaging. In addition, fetal magnetic resonance imaging is particularly helpful in the detection of gyration and neurulation anomalies, and disorders of the gray and white matter. Isolated mild ventriculomegaly is a rather common finding with good overall outcome. With an increasing diameter of the atria, however, and especially with the presence of associated malformations, long-term neurodevelopmental and behavioral outcome is disturbed in about 15% or more of cases. In view of recent developments in fetal therapy for neural tube defects, there is a clear need for a high level of ultrasound screening, work-up and counseling in tertiary care centers to identify those cases that might benefit from in utero intervention. The failure of prosencephalic midline induction and development results in midline defects ranging from alobar holoprosencephaly to isolated corpus callosum defects. The detection of callosal abnormaties is enhanced by 3D ultrasound, but counseling on neurodevelopmental outcome remains challenging. The Dandy-Walker spectrum includes isolated megacisterna magna, Blake's pouch cyst, hypoplasia of the vermis and Dandy-Walker malformation. Except for complete agenesis of the vermis associated with fourth ventricle cyst formation, data on long-term outcomes for the various conditions is largely lacking. Congenital cytomegalovirus (CMV) results in the highest incidence of children born with, or developing, long-term neurologic conditions. If proof of fetal infection has been delivered, microcephaly, cortical malformations, and intraparenchymal cysts show a strong correlation with poor outcome. Fetuses with CMV-related ultrasound abnormalities might benefit from maternal transplacental treatment. The aneurysm of the vein of Galen, a vascular malformation of the brain, often results in high cardiac output failure. After neonatal arterial embolization, survival is about 50% with normal neurologic development in 36% of cases. Over 50% of intracranial tumors are teratomata, presenting as fast-growing heterogeneous solid-cystic masses with calcifications. Most intracranial hemorrhages are related to the ventricular system, and prognosis is often poor, particularly in cases involving parenchymal and subdural bleeding. Proliferation disorders of the brain are often characterized by microcephaly. Their etiology is heterogeneous and prenatal diagnosis is often made late in gestation.

133. Survival with Normal Neurological Development of the Juvenile Lethal Urea Cycle Defect Arginase Deficient Mouse with AAV Gene Therapy

133. Survival with Normal Neurological Development of the Juvenile Lethal Urea Cycle Defect Arginase Deficient Mouse with AAV Gene Therapy

Epidural hematoma

Epidural hematomas are rare birth injuries, and spontaneous presentation is exceptional. We present 2 cases of newborns with spontaneous epidural hematomas after delivery. In both cases, cerebral hemorrhage was associated with skull fracture and cephalohematoma. One newborn presented with neurologic symptoms in the form of convulsions, whereas the other was asymptomatic. Confirmation of the diagnosis was made by cranial computed tomography. Both cases were treated surgically by craniotomy. Follow-up showed normal neurologic development.

Vein of Galen Aneurysmal Malformations: An Ultrasonographic Incidental Finding—A Case Report

Background. The Vein of Galen aneurysmal malformation (VGAM) is a rare congenital, cerebral, arteriovenous deformity. Good cross-discipline cooperation is in demand because of associated complications and high mortality. The recognition of the optimal therapeutic window is useful to allow proper management. Case Report. We report on the successful treatment of a 2-week-old, healthy girl with a VGAM, which came across in the context of the newborn ultrasonographic screening. After interdisciplinary discussion, 2 embolizations of the VGAM followed without complications—the first in the age of 6 months and the second at 12 months of life. Before and after the intervention, the patient had an age-appropriate development without neurological deficits. Conclusion. The endovascular transarterial embolization is described as the treatment of choice. Time and method of intervention depend on clinical signs of the patient. In our case the patient was asymptomatic. So the arteriovenous abnormality was an incidental finding by ultrasound. Because of the natural history of the disease, and the potential severe neurocognitive consequences at long-term followup if left untreated, it was decided to embolize the lesion. Thanks to embolization with glue, good therapeutical and clinical results could be obtained with normal neurological development.

Effect of Prolonged Discontinuation of L-Thyroxine Replacement in a Child with Congenital Hypothyroidism

When diagnosed through neonatal screening and treated promptly and adequately, infants with congenital hypothyroidism (CH) experience normal physical growth and neurological development. Here we present a 3-year-old boy diagnosed with CH as a newborn, who was subsequently left untreated and experienced significant growth failure and developmental delay. This case emphasizes the importance of a consistent adherence to treatment in preventing such complications, especially in infancy and early childhood.

Vein of Galen Malformations in Neonates

Untreated patients with symptomatic neonatal presentation of vein of Galen aneurismal malformations (VGAMs) carry almost 100% morbidity and mortality. Medical management and endovascular techniques for neonatal treatment have significantly evolved. To evaluate the clinical and angiographic outcomes of modern management of neonates with refractory heart failure from VGAMs. From 2005 to 2010, 16 neonatal patients with VGAM presented to our institution. Medical care from the prenatal to perinatal stages was undertaken according to specified institutional guidelines. Nine patients with refractory heart failure required neonatal endovascular intervention. All patients were treated by transarterial deposition of n-butyl cyanoacrylate into fistula sites. Short- and long-term angiographic studies and clinical outcomes were reviewed. Control of heart failure was achieved in 8 patients. One premature baby died shortly after treatment. Long-term angiographic follow-up shows total or near-total angiographic obliteration in all 8 patients. One patient has a mild hemiparesis from treatment. Another has a mild developmental delay. One patient developed a severe seizure disorder and developmental delay. Overall, 66.7% patients have normal neurological development with near-total or total obliteration of the malformation. Treatment of refractory heart failure in neonatal VGAM with modern prenatal, neurointensive, neuroanesthetic, and pediatric neuroendovascular care results in significantly improved outcomes with presumed cure and normal neurological development in most.

Expression and uptake of the thyroxine-binding protein transthyretin is regulated by oxygen in primary trophoblast placental cells

Transplacental delivery of maternal thyroid hormones to the fetus, in particular thyroxine (T₄), is critical in ensuring normal fetal neurological development. The fetus relies on maternal T₄ till around 16 weeks gestation, but mechanisms of placental T₄ transport are not yet fully elucidated. Placenta produces, secretes and takes up the thyroid hormone-binding protein transthyretin (TTR). Many placental genes are regulated by oxygen levels, which are relatively low (1%) in the early first trimester, rising to 3% in the mid first trimester and 8% in the early second trimester and thereafter. We examined the expression and uptake of TTR in isolated primary human placental cytotrophoblast cells cultured under different oxygen concentrations (1, 3, 8, 21% O₂ and 200 μM desferrioxamine (DFO)) for 24 h. We observed sevenfold higher expression of TTR mRNA and protein levels at 1% O₂ than at 8 and 21% O₂. Significant increases were observed after culture at 3% O₂ and following DFO treatment. We observed significantly higher uptake of ¹²⁵I-TTR and Alexa-594-TTR when cells were cultured at 1 and 3% O₂ and in the presence of 200 μM DFO than at 8 and 21% O₂. When JEG-3 choriocarcinoma cells were transfected with TTR promoter reporter constructs, increased luciferase activity was measured in cells cultured at 1 and 3% O₂ in comparison to 8 and 21% O₂. We conclude that placental TTR expression and uptake is increased by the relative hypoxia observed in the first trimester of pregnancy, a time when materno-fetal T₄ transfer is the sole source of fetal T₄.

Preterm birth and the endocrine regulation of growth in childhood and adolescence

Poor growth during childhood is a common problem associated with preterm birth, but few studies have examined the associations between linear growth, weight and body composition with the postnatal hormonal milieu in preterm children. We aimed to define the IGF-IGFBP axis in preterm children and its association with growth. A cohort of healthy 2- to 20-year-old subjects who were born prematurely (<37 weeks gestation) and experienced normal neurological development were recruited. In total, 54 premature and 82 control subjects were included in this study. Preterm subjects were relatively shorter (P < 0·001) and leaner (P < 0·05) than their parents in contrast to the term cohort. Preterm children also appeared to fail to reach their genetic height potential (prepuberty: P < 0·01; puberty: P < 0·05). Only IGFBP-2 differed between preterm and term cohorts, with higher levels observed in prepubertal preterm subjects (P < 0·01). In the term group, height SDS was positively associated with IGF-I (P < 0·01) and IGFBP-3 (P < 0·001) concentrations, but no such associations were observed for preterm subjects. Preterm children are shorter and lighter than controls throughout childhood, remaining below their genetic height potential. Preterm birth appears to alter the endocrine regulation of postnatal growth in childhood and adolescence, so growth is no longer associated with its normal endocrine regulators.