Fetal Neural Tube Research Articles

Oxidative–Antioxidative Markers in Pregnant Women with Fetal Neural Tube Defects

Objective We compared markers of oxidative stress (OS) in mothers with and without fetal neural tube defects (NTDs). Methods: Pregnant mothers in the second trimester with NTD-affected fetuses and age, gestational age, and body mass index-matched control mothers with unaffected fetuses were included. Maternal serum thiol-disulfide homeostasis parameters and ischemia-modified albumin (IMA) were measured. Results: In 30 affected mothers compared to 31 controls, disulfide levels, disulfide/native thiol, and disulfide/total thiol ratios were higher; native and total thiol levels and native thiol/total thiol ratios were lower (p < 0.001). Mothers with NTD-affected fetuses had higher levels of IMA than controls (p = 0.025). Conclusion: The thiol-disulfide homeostasis balance was shifted in favor of disulfide, suggesting increased thiol oxidation and OS in the second trimester of NTD-affected pregnancies. Maternal levels of IMA, an oxidatively altered form of albumin, thus a measure of OS, were higher in NTD-affected second trimester pregnancies compared to controls.

Environmental Complex Exposure and the Risk of Fetal Neural Tube Defects in North China

Environmental Complex Exposure and the Risk of Fetal Neural Tube Defects in North China

Folic Acid for the Prevention of Fetal Neural Tube Defects

The use of folic acid supplements before and during the first three months of pregnancy significantly reduces the risk of fetal neural tube defects (NTDs). This study assessed knowledge and factors that influence the use of folic acid, the actual use of folic acid and its relationship with socio-demographic factors among women of childbearing age in the Ife Central Local Government, Ile-Ife, Osun State, Nigeria. A cross-sectional descriptive design was adopted to select 400 women of childbearing age who participated in the study using a self-structured questionnaire. Results from this study showed that 39.8 per cent of the study participants had good knowledge about the benefits of folic acid, 64.6 per cent of the participants reported to have used folic acid at one time in their lives, while 55.5 per cent of them reported not to have taken folic acid before their pregnancy. This study also revealed a significant association between the respondents’ socio-demographic factors and the use of folic acid with a p-value of .000 (p-value &lt; 0.05). The study concluded that knowledge about the use of folic acid for the prevention of NTDs among women of childbearing age is not adequate and that very few of them used folic acid at the appropriate time.

Burak – właściwości prozdrowotne i nie tylko

According to available data, beetroot (Beta vulgaris) has been known and used in Poland since the XVth century. It has edible both root and leaves. Beet is often used in Polish kitchen, raw and heat-treated, pasteurized, pickled, and its low calorific value is conducive to a varied diet, because it contains micro- and macroelements and vitamins necessary to keep our body function well. Beet is a source of fiber, which has a positive effect impact on the intestinal function and regulates the level of cholesterol in the blood. Also high content of potassium supports the prevention of heart diseases. It consists betanin to improve liver’s function, as well as large amounts of vitamin C, which has positive influence on the immune system and both with flavonoids, strengthen the capillary walls. What is more the carotene contained in it prevents cataracts and macular degeneration. Consumption of beets is especially recommended to pregnant women, because beet is a source of B vitamins, which have a positive effect on the development of the fetal neural tube. The studies on effectiveness of betacyanine in preventing the development of skin, lung, colon, breast and prostate cancer has been proven. A large amount of nitrates present in raw beetroot juice contributes to the increase of endurance during physical activity, and high carbohydrate content supports effective training. A less known fact is that beet is also considered a natural aphrodisiac. Unfortunately, it is dangerous for patients with a history of kidney or gallbladder stones. By analyzing the above examples, we are trying to prove that beetroot is not only delicious vegetable but also really healthy diet composition. The aim of the article is to present the health-promoting properties of beetroot and its preserves, also to introduced the history of beetroot and subject of using the word beetroot as a negative human term.

Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons

ABSTRACT5-Hydroxymethylcytosine (5hmC), a distinct epigenetic marker that plays a role in DNA active demethylation, has been reported to be important for embryonic development and may respond to environmental exposure. No studies have evaluated the association between DNA hydroxymethylation and the risk for fetal neural tube defects (NTDs), with consideration of prenatal exposure to polycyclic aromatic hydrocarbons (PAHs), a risk factor for NTDs.We measured the global levels of 5hmC% in neural tissue from 92 terminated NTD cases and 33 terminated non-malformed fetuses. A lower level of 5hmC% was found in the NTD cases (median [interquartile range]: 0.25 [0.12–0.39]) compared to the controls (0.45 [0.19–1.00]). After adjusting for periconceptional folate supplementation, risk for NTDs increased with decreasing tertiles of 5hmC% (odds ratio: 7.89, 95% confidence interval: 2.32, 26.86, for the lowest tertile relative to the top tertile; pfor trend = 0.002). Linear regression revealed that concentrations of high-molecular-weight PAHs (H_PAHs) in fetal liver tissue were negatively associated with log2-transformed 5hmC%. Superoxide dismutase activity and 5hmC% were positively correlated in fetal neural tissue (rs = 0.64; p < 0.05). A mouse whole-embryo culture model was used for further validation. Decreased levels of 5hmC% and increased levels of reactive oxygen species were found in mouse embryos treated with BaP, a well-studied PAH. Taken together, levels of 5hmC% in fetal neural tissue were inversely associated with the risk for NTDs, and this association may be related to oxidative stress induced by exposure to PAHs.

Gangliosidome of human anencephaly: A high resolution multistage mass spectrometry study

Widely dispersed throughout the entire body tissues, gangliosides (GGs) are essential components of neuronal cell membranes, where exhibit a vital role in neuronal function and brain development, directly influencing the neural tube formation, neurogenesis, neurotransmission, etc. Due to several factors, partial or complete closing faults of the fetal neural tube may occur in the first trimester of pregnancy, generating a series of neural tube defects (NTD), among which anencephaly. The absence in anencephaly of the forebrain and skull bones determines the exposure to the amniotic fluid of the remaining brain tissue and the spinal cord, causing the degeneration of the nervous system tissue. Based on the previously achieved information related to the direct alteration of neural development with deficient concentration of several GGs, a systematic and comparative mass spectrometry (MS) mapping assay on GGs originating from fetuses in different intrauterine developmental stages, i.e. the 29th (denoted An29), 35th (An35) and the 37th (An37) gestational weeks was here conducted. Our approach, based on Orbitrap MS under high sensitivity, resolution and mass accuracy conditions, enabled for the first time the nanoelectrospray ionization, detection and identification of over 150 glycoforms, mainly novel, polysialylated species. Such a pattern, specific for incipient developmental stages reliably documents the brain development stagnation, characteristic for anencephaly. Further, the fragmentation MS2-MS3 experiments by collision induced dissociation (CID) confirmed the incidence in all three samples of GT2(d18:1/16:2) as a potential biomarker. Therefore, this fingerprinting of the anencephalic gangliosidome may serve in development of approaches for routine screening and early diagnosis.

The Importance of Maternal Folate Status for Brain Development and Function of Offspring

The importance of an adequate periconceptional maternal folate status to prevent fetal neural tube defects has been well demonstrated and resulted in the recommendation for women to use folic acid supplements during the periconception period. The importance of maternal folate status for offspring neurodevelopment and brain health is less well described. We reviewed the current evidence linking maternal folate status before conception and during pregnancy with neurodevelopment and cognition of the offspring. We discuss both animal and human studies. Preclinical research revealed the importance of maternal folate status for several key processes required for normal neurodevelopment and brain functioning in the offspring, including DNA synthesis, regulation of gene expression, synthesis of phospholipids and neurotransmitters, and maintenance of healthy plasma homocysteine concentrations. Human observational studies are inconclusive; about half have shown a positive association between maternal folate status and cognitive performance of offspring. Whereas some studies suggest a positive association between maternal folate intake and cognition of offspring during childhood, data from interventional studies are too limited to conclude that there is a direct effect. Future preclinical studies are needed to help us characterize the behavioral effects, understand the underlying mechanisms, and to establish an optimal dosage and time window of folate supplementation. Moreover, more conclusive data from well-designed human observational studies and randomized controlled trials are needed to determine whether current recommendations for folic acid supplementation during pregnancy cover the needs for normal cognitive development in the offspring.

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.

Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. A retrospective cohort study. Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.

Subacute oral administration of folic acid elicits anti-inflammatory response in a mouse model of allergic dermatitis

Folic acid (FA) deficiency is associated with several health problems, including megaloblastic anemia and fetal neural tube defects. Therefore, supplementation with FA is strongly recommended by governments worldwide. Recent published reports indicate that FA functions in immune system maintenance. The main objective of this study is to examine possible anti-inflammatory and antipruritic effects of FA using a mouse model of allergic dermatitis. The mouse model was developed by repetitive sensitization to the Th2-type hapten toluene-2,4-diisocyanate (TDI). During the development of allergic dermatitis, FA was orally administered to the mice at doses of 8, 160, 1000 or 10,000 μg/day for 5 weeks. The ear swelling response and scratching behavior were monitored after the TDI challenge. Serum, ear tissue and auricular lymph node samples were isolated for further analysis 24 h after the TDI challenge. The ear swelling response was reduced in a dose-dependent manner by FA administration, and a significant change was observed at a concentration of 10,000-μg/day group. Comparable results were obtained through histological evaluation and cytokine level measurement in the ear tissue samples. Oral administration of FA exhibited the inhibitory effect on T-cell infiltration and T-cell-related cytokine production in auricular lymph nodes. Scratching behavior was not altered by FA administration. The in vivo evidence was corroborated by in vitro results, which showed that FA treatment significantly interfered with T-cell proliferation in a dose-dependent manner. Our findings imply that subacute oral administration of FA elicits an anti-inflammatory response, mainly through inhibition of T-cell proliferation.

Complex Nature of Neural Tube Defects: A Regional Experience

Objective: The underlying gene-environment interaction of fetal neural tube defects is affected by several factors including geography, ethnicity and time. Local features of fetal neural tube defects were described.Study Design: A prospective cohort study of 48 fetal neural tube defects in a single tertiary medical center at the northwestern region of Turkey (2013-2015) was done via ultrasound, magnetic resonance imaging (MRI), conventional karyotyping, maternal methylenetetrahydrofolate reductase c.677C&gt;T (rs1801133) single-nucleotide polymorphism and maternal serum levels of folic acid, vitamin B12 and zinc. For comparison of means, a Student’s T-Test was used.Results: The prevalence of neural tube defects was 11.4 per 10000 births (48/42000) in northwestern Turkey. The defects on the cranium (n=23; 47.9%) and spine (n=25; 52.1%) were ultrasonographically detected. MRI did not give additional benefit over the ultrasonography. The ratio of associated anomalies in neural tube defect group was 25%. Two fetal neural tube defects with Down syndrome were remarkable. The rate of homozygous methylenetetrahydrofolate reductase c.677C &gt; T SNPs among the mothers of neural tube defect fetuses (n=20) was 15%. Comparing with gestationally matched healthy pregnancies, although maternal BMIs and periconceptional folate intake of neural tube defect group were significantly different, maternal serum folic acid, vitamin B12 and zinc levels were similar.Conclusion: The northwestern region appeared to be a relatively low prevalence area of Turkey for fetal neural tube defects. Any association with maternal serum folic acid, vitamin B12 and zinc levels could not be shown in this region.

Balanced Essential Micronutrients during Pregnancy: High Concern

Nutrition and epigenetic changes is the emerging topic of interest in the present scenario to understand the effects of increased supplementation of micronutrients like Folic Acid (FA). The study is taken up in the public health interest, to evaluate the importance of balancing the different micronutrients in the diet to avoid unbalanced nutritional disorders and other health complications later in life. It has been hypothesized that disease risks after birth or later in life can be determined by paternal or maternal diet. This raised an interest to study in-utero effects of environmental exposures like air pollution, toxins, nutrition, etc. It had been assumed that during embryonic period most of the dividing tissues get exposed to the environmental insults and that change results in predisposition of cancer or other health outcomes. There could be the possibility of maternal exposures like nutrition may alter the intrauterine one-carbon metabolism or the precursor milieu and may be involved in the disruption of one-carbon metabolism in developing offspring. Modification in methyl me of offspring with subsequent changes in phenotypes has been noted in the preliminary studies with increased folic acid (FA) supplementation during pregnancy. Maternal folate deficiency has been implicated as a cause of prematurity and both folate deficiency and cobalamin deficiency have been implicated in recurrent fetal loss and neural tube defects. Folic acid supplementation at the time of conception and in the first 12 weeks of pregnancy is expected to reduce by 70% the incidence of neural tube defects (NTDs) (meningomyelocele, encephalocele and spina bifida) in the fetus. Most of the protective effect can be achieved by taking folic acid, 0.4 mg daily at the time of conception. However there is no clear relationship between maternal folatestatus and the fetal abnormalities. It has been observed that, the lower the maternal folate, the greater the risk to the fetus. On the other hand maternal cobalamin status is a strong predictor of vitamin B12 in breastfed infants up to at least 6 months of age. Because of the transfer from mother to offspring during pregnancy and lactation, maternal requirements during this period are increased and deficiency may occur. The influence of low vitamin B12 during pregnancy may have cognitive ability of children later in life. Hypothyroidism is caused by insufficient production of thyroid hormones by the thyroid gland. In females, hypothyroidism is associated mainly with oligomenorrhea.

Using Hair Analysis to Assess the Exposure Level of Rare Earth Elements among Rural Housewives

Several studies have observed that population living near coal mining areas may have higher exposure level of rare earth elements (REEs). However, it is still a challenge to assess their exposure level of REEs, and the adverse effects of REEs on human health were also rarely investigated by an epidemiological study. Our study aimed to use hair analysis to assess their exposure level of REEs among women in Shanxi Province, which has the leading coal production around the world. In addition, we investigated the associations between hair concentrations of REEs and risk of hypertension among female adults and fetal neural tube defects (NTDs). About 14 concerned REEs in the specific hair sections were analyzed including lanthanum, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, yttrium, cerium, praseodymium, and neodymium. Population exposure level to indoor air pollution from coal combustion (IAPCC) was evaluated by the questionnaires of energy usage characteristics and life style. It was observed that hair concentrations of 13 REEs were overall positively correlated with the exposure level of IAPCC, except for europium. For the rural women, our study results revealed that the hair concentrations of the 14 REEs, except for europium, in hypertensive case women were higher than those in controls. The univariate odds ratios (ORs) of the 14 REEs were systematically &amp;gt; 1, of which four REEs (i.e. dysprosium, thulium, ytterbium, and yttrium) had adjusted ORs &amp;gt; 1. In addition, we found that hair REEs concentrations grown during the early preganancy had potential adverse effect on NTD risk. It was concluded that hair REEs could be used as a marker to indicate population exposure level to REEs and may be a risk factor of the development of hypertension and fetal NTDs.

Associations between Typical Environmental Factors and the Risk of Fetal Neural Tube Defects in North China

Background: The relationship between the levels of various environmental chemicals and the high prevalence of neural tube defects (NTDs) in north China remains unclear. This study aimed to classify the associations of maternal exposure to polycyclic aromatic hydrocarbons (PAHs), passive smoking, and widely concerned trace metal elements with NTD risk. Methods: Our case-control study recruited a total of 828 subjects: 285 women who delivered a fetus with NTDs (cases) and 543 women a healthy newborn without NTDs (controls). We measured the concentrations of PAHs, nicotine/cotinine, and various trace metal elements in two hair sections grown near the early pregnancy. Findings: Overall, no significant associations were found between the risk of any NTD subtypes and the hair levels of PAHs, nicotine/cotinine, and some metals (i.e., Cd, Sb, Pb, Cr, Mn, Fe, Ni, Co, and Cu). According to the cross-validation results for the two hair sections, hair concentrations of Mo and Sn were inversely associated with anencephaly risk, and the hair concentration of Zn was inversely associated with the risk of spina bifida. Interpretation: We concluded that maternal exposure to either PAHs or passive smoking was not a significant risk factor for NTDs, whereas the maternal less intake of certain trace metal elements may contribute to the high NTD prevalence in north China. It suggested that much effort should be spent to improve the dietary quality of various essential trace metal elements to reduce NTD risk for population living in North China. Funding: This research was supported by grants from the National Key Research and Development Program, P.R. China (Grant No. 2016YFC1000501) and the National Natural Science Foundation of China (No. 41771527 and 81373014). Conflict of Interest: The authors declare they have no actual or potential competing financial interests. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of Peking University (PU-IRB) and the signed consent was obtained from all subjects.

Neurological outcomes by mode of delivery for fetuses with open neural tube defects: a systematic review and meta-analysis.

Controversy exists regarding the optimal mode of delivery for fetuses with open neural tube defects. To compare neurological outcomes among infants with open neural tube defects who underwent vaginal compared with caesarean delivery. Electronic databases MEDLINE, EMBASE, Scopus, and Clinicaltrials.gov were searched from inception to November 2017. Eligible studies included observational or randomised studies comparing vaginal and caesarean delivery in pregnancies with fetal open neural tube defects who did not undergo prenatal repair. Two reviewers independently reviewed abstracts and full-text articles. Outcomes were compared between vaginal and caesarean delivery and prelabour caesarean versus exposure to labour. The primary outcome was motor-anatomic level difference. Secondary outcomes included shunt requirement, sac disruption, meningitis, and ambulation at 2years. Meta-analysis was performed and mean difference or odds ratios with 95% CI were calculated. Of 201 abstracts identified in the primary search, nine studies (672 women) met the eligibility criteria. Comparing vaginal and caesarean delivery, there was no significant difference in motor-anatomic level difference (mean difference -0.10, 95% CI -0.58 to 0.38; I2 =57%). The vaginal delivery group was less likely to require a shunt or have sac disruption [odds ratio (OR) 0.37, 95% CI 0.14-0.95 and OR 0.46, 95% CI 0.23-0.90, respectively]. Comparisons by prelabour caesarean versus exposure to labour showed no significant difference in motor-anatomic level difference (OR 1.29, 95% CI 0.63-3.21) or ambulation at 2years (OR 2.13, 95% CI 0.35-13.12). Caesarean delivery was not associated with improved neurological outcomes among fetuses with open neural tube defects. Available evidence does not support routine caesarean delivery for fetuses with open neural tube defects.

Maternal association and influence of DHFR 19 bp deletion variant predisposes foetus to anencephaly susceptibility: a family-based triad study

Objective: Previous studies have not used family-based methods to evaluate maternal-paternal genetic effects of the folate metabolizing enzyme, dihydro folate reductase (DHFR) essential during embryogenesis. Present study focuses on evaluating the association and influence of parental genetic effects of DHFR 19 bp deletion in the development of foetal neural tube defects (NTDs) using family-based triad approach.Materials and methods: The study population (n = 924) including 124 NTD case-parent trios (n = 124 × 3 = 372) and 184 healthy control-parent trios (n = 184 × 3 = 552) from Telangana, India, was genotyped for DHFR 19 bp deletion. Statistical analysis was used by SPSS and parent-of-origin effects (POE).Results: Foetuses with deletion genotype (DD) were at risk of developing anencephaly (OR = 3.26, p = 0.020). Among parents, increased maternal risk of having an anencephaly foetus (OR = 2.66, p = 0.028) was observed in mothers with DD genotype. In addition, POE analysis also demonstrated higher risk of maternal transmission of the deletion allele to anencephaly foetus compared with paternal transmission (OR = 6.00, p = 0.016). Interestingly, maternal-paternal-offspring genotype incompatibility revealed maternal deletion genotype (DD) in association with paternal heterozygous deletion genotype (WD) significantly increased risk for NTDs (OR = 5.29, p = 0.013).Conclusions: This study, using family-based case-parent and control-parent triad approach, is the first to report influence of maternal transmission of DHFR 19 bp deletion in the development of anencephaly in the foetus.

Experimental study on DEHP affect the neurodevelopment through interfering with placental thyroid hormones transport

Objective: The present study was represented by di-(2-ethylhexyl) phthalate (DEHP), to explore the role of thyroid hormones (THs) disruption in the connection of placenta and neurodevelopmental toxicity. Methods: During fetal mice neural tube closed (pregnancy 9.5 days, E9.5d) to begin synthesis of THs (E15.5 d), all pregnant mice were administered with different concentration of DEHP (0、10、50、200 mg/kg) by gavage once a day(10 mice per group). All pregnant mice were conducted with BrdU administration in E14d by subcutaneous injection. Seven pregnant mice from each group were scarified after anesthesia in E15.5 d, serum and amniotic fluid were collected to determinate the levels of THs(T(3), T(4), FT(3) and FT(4)) by the automatic biochemical analyzer, detecting fetal mice placental protein expression of monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptide 1C1 (OATP1C1) and deiodinaseⅡ&Ⅲ (DIO(2), DIO(3)) by Western blot. Each group of the remaining three pregnant mices were killed after anesthesia in E18d, take the male fetal brain, BrdU immunohistochemistry was used to detect the proliferation and migration of fetal brain cortical neurons. Results: There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiolo. Results There was no abnormalities in diet, water intake, body weight and general activity of pregnant mice in each treatment group, and there were no difference in the general physiological development status of body weight, brain weight, brain body ratio between the mice of each group. There was no statistically significant differences in serum T(3), T(4), FT(3), FT(4) and amniotic fluid FT(4) in pregnant mice of each group (P>0.05), Compared with the control group, the FT(3) levels in the amniotic fluid of the DEHP 50 and 200 mg/kg groups were significantly decreased(P<0.05). Compared with the control group, the placental MCT8 and DIO(2) protein levels of male fetal mice in the DEHP 50 and 200 mg/kg group decreased, and the level of OATP1C1 protein in 200 mg/kg group decreased(P<0.05), and there was no statistically significant difference in DIO(3) protein levels among all groups (P>0.05). Compared with the control group, the number of BrdU positive cells in the cerebral cortex of male mice in DEHP 200 mg/kg group decreased, 56.5% was distributed in VZ-SVZ layer, and the percentage of BrdU positive cells in the IZ layer of 50 mg/kg group increased (P<0.05). Conclusion: DEHP 50, 200 mg/kg may affect the proliferation and migration of neural cells in the developing brain, which may be related to its interference with thyroid hormone by placental transport.

Donor mesenchymal stem cell linetics after transamniotic stem cell therapy (TRASCET) for experimental spina bifida

PurposeWe sought to examine donor mesenchymal stem cell (MSC) kinetics after transamniotic stem cell therapy (TRASCET) in experimental spina bifida. MethodsPregnant Sprague–Dawley dams exposed to retinoic acid for the induction of fetal neural tube defects received volume-matched intra-amniotic injections on gestational day 17 (E17; term=E22): either amniotic fluid MSCs (afMSCs) labeled with a luciferase reporter gene (n=78), or luciferase protein alone (n=66). Samples from twelve organ systems from each surviving fetus with spina bifida (total n=60) were screened via microplate luminometry at term. ResultsDonor afMSCs were identified exclusively in the placenta, umbilical cord, spleen, bone marrow, hip bones, defect, and brain. Luminometry was negative in control fetuses receiving luciferase alone (p<0.001). Signal intensity in relative light units (RLUs) was moderately correlated between the defect and the hip bones (rho=0.38, p=0.048), and between the placenta and the brain (rho=0.40, p=0.038). ConclusionsAmniotic mesenchymal stem cells engraft to specific sites after concentrated intra-amniotic injection in the setting of spina bifida. A hematogenous route encompassing the bone marrow as well as distant central nervous system homing are fundamental constituents of cell trafficking. These findings must be considered during eventual patient selection for transamniotic stem cell therapy in the prenatal management of spina bifida.

A rare case of a fetal neural tube defect: Iniencephaly

Iniencephaly is characterized by severe retro flexion of the head with the absence of neck due to spinal vertebrae deformities, it is considered as uncommon anomaly. Prevalence: 0.1-10:10,000, M:F. Etiology: Unknown, but genetic, environmental factors are implicated. Pathogenesis: Unknown. Recurrence risk: 1-4%. Associated anomalies: Anencephaly, encephalocele, cyclopedia, lack of lower jaw bone, cleft palate, arthrogryposis, clubfeet, holoprosencephaly, spina bifida, lung hypoplasia, omphalocele, gastroschisis, cardiovascular disorders, Congenital diaphragmatic hernias, gastrointestinal atresia, single umbilical artery and renal abnormalities. Conclusion: Iniencephaly is a lethal congenital neural tube malformation. It is characterized by occipital bone defect, fixed retroflexion of the fetal head and severe lordosis of the cervicothoracic spine. Differential diagnosis: Include anencephaly with cervical spinal retro flexion and Klippel-Fiel syndrome

491: Neurodevelopmental assessment in patients who underwent prenatal fetoscopic and open fetal neural tube defect repair

To compare neurodevelopmental outcomes in infants who had undergone prenatal neural tube defect (NTD) repair by either a Fetoscopic or by an Open hysterotomy approach 41 infants were included (22 Fetoscopic and 19 Open) in this prospective longitudinal cohort study. Neurodevelopmental outcomes were assessed using the Developmental Profile 3 (DP-3) screening test, which evaluates 5 domains of development as documented in an interview with the patient’s parents. Results were compared to reference values. Infants were categorized as “Delayed and Below Average” if the standard score (SS) was ≤ 84 and “Average and Above average ” if the SS was ≥ 85. In addition, infants were clinically evaluated by a Developmental Pediatrician in our Spina Bifida Clinic, with a full evaluation and documented the motor development and the disparity (if any) between the anatomic and functional levels of the lesion. The Capute Scales test evaluates visual-motor problem solving (CAT Developmental Quotient -DQ-) and language abilities (CLAMS DQ). Results were categorized as “Delayed” if DQ <70, “Borderline” if DQ 70-84, and “Normal” if DQ > 84. Motor DQ scores were determined by the Gesell Developmental Scale The DP-3 test was performed on 22 infants after Fetoscopic repair and on 14 after Open repair (Table 1). Fetoscopically repaired infants were assessed at an earlier age than their Open counterparts, but no differences in neurodevelopmental outcome were detected. The Capute Scales were performed on 14 Fetoscopic and on 19 Open repair infants at a similar age (Table 2). No differences in CAT DQ, CLAMS DQ, Motor DQ or classification of developmental outcomes were detected. Improvement in functional level by 3 or more was noted in 33.3% of the Fetoscopic group and in 26.3% of the Open group (p=0.7) There were no significant differences in neurodevelopmental outcome between those infants who underwent a Fetoscopic NTD repair as compared to their Open repair counterpartsView Large Image Figure ViewerDownload Hi-res image Download (PPT)

Maternally Contributed Folate Receptor 1 Is Expressed in Ovarian Follicles and Contributes to Preimplantation Development.

Folates have been shown to play a crucial role for proper development of the embryo as folate deficiency has been associated with reduced developmental capacity such as increased risk of fetal neural tube defects and spontanous abortion. Transcripts encoding the reduced folate carrier RFC1 (SLC19A1 protein) and the high-affinity folate receptor FOLR1 are expressed in oocytes and preimplantation embryos, respectively. In this study, we observed maternally contributed FOLR1 protein during mouse and human ovarian follicle development, and 2-cell mouse embryos. In mice, FOLR1 was highly enriched in oocytes from primary, secondary and tertiary follicles, and in the surrounding granulosa cells. Interestingly, during human follicle development, we noted a high and specific presence of FOLR1 in oocytes from primary and intermediate follicles, but not in the granulosa cells. The distribution of FOLR1 in follicles was noted as membrane-enriched but also seen in the cytoplasm in oocytes and granulosa cells. In 2-cell embryos, FOLR1-eGFP fusion protein was detected as cytoplasmic and membrane-associated dense structures, resembling the distribution pattern observed in ovarian follicle development. Knock-down of Folr1 mRNA function was accomplished by microinjection of short interference (si)RNA targeting Folr1, into mouse pronuclear zygotes. This revealed a reduced capacity of Folr1 siRNA-treated embryos to develop to blastocyst compared to the siRNA-scrambled control group, indicating that maternally contributed protein and zygotic transcripts sustain embryonic development combined. In summary, maternally contributed FOLR1 protein appears to maintain ovarian functions, and contribute to preimplantation development combined with embryonically synthesized FOLR1.