Interplay between Maternal and Neonatal Vitamin D Deficiency and Vitamin-D-Related Gene Polymorphism with Neonatal Birth Anthropometry.

Vitamin D deficiency during pregnancy has been associated with poor foetal growth and neonatal birth anthropometry. However, the associations were inconsistent and could be confounded by neonatal vitamin D status and genetic factors. Until recently, limited studies have concomitantly examined the effect of maternal and neonatal vitamin D deficiency and vitamin D-related single nucleotide polymorphisms (SNPs) on neonatal birth anthropometry. This study aims to examine the independent and combined effects of maternal and neonatal vitamin D deficiency and vitamin-D-related SNPs on neonatal birth anthropometry. This cross-sectional study included 217 mother−neonate dyads recruited from Hospital Serdang, Selangor, Malaysia, between 2015 and 2017. Plasma 25-hydroxyvitamin D (25OHD) concentration was measured in maternal and umbilical cord blood using ultra-high-performance liquid chromatography (UHPLC). Maternal and neonatal vitamin D Receptor (VDR) SNP (rs2228570) genotypes were determined using high-resolution melting (HRM). Group-specific component (GC) SNPs (rs4588 and rs7041) genotypes were determined using restriction fragment length polymorphism. Our results showed that: (1) maternal vitamin D deficiency (25OHD < 30 nmol/L) was inversely associated with birth weight, head circumference and crown−heel length; (2) neonatal SNPs, VDR rs2228570 and GC rs4588, were significantly associated with birth weight and head circumference, respectively; and (3) a potential interaction was observed between maternal VDR rs2228570 with maternal vitamin D deficiency on head circumference. These findings suggest that the underlying mechanisms of vitamin D on foetal growth are likely to be localised in the maternal compartment, mediated through the placenta, rather than through cellular mechanisms within the foetus. Further large-scale studies are warranted to validate and extend these findings.

Inadequate vitamin D intake among pregnant women in Malaysia based on revised recommended nutrient intakes value and potential dietary strategies to tackle the inadequacy.

BACKGROUND/OBJECTIVES: Recently, the recommended nutrient intakes (RNI) for vitamin D for Malaysian aged 1-70 yrs has been revised from 5 µg/day to 15 µg/day. This study is aimed to assess the adequacy of vitamin D intake based on revised RNI and to recommend several dietary strategies to increase total vitamin D intake. SUBJECTS/METHODS: Vitamin D intake from both food and supplement of 217 pregnant women was assessed using a validated food frequency questionnaire. Hypothetical effect of expanded supplementation and food fortifications strategies were modelled using the consumption data. RESULTS: The results revealed that more than half (67.7%) of pregnant women had inadequate vitamin D intake (RNI < 15 µg/day). The modelling results demonstrated the potential of universal provision of 10 µg/day of multivitamins supplements in increasing vitamin D intake. Moreover, mandatory fortification of both milk and malted drink at single level of 5 µg/serving would lead to increase in vitamin D intake of Malaysians, particularly pregnant women. CONCLUSIONS: The outcome of this study can be used as a reference for public health professionals to re-evaluate the existing Malaysian food fortification policies and supplementation recommendation for vitamin D for pregnant women.

Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women.

BACKGROUND: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women. METHOD: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using a questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using an Ultra-High-Performance Liquid Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique. RESULTS: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD < 30 nmol/L). VDD (25OHD < 30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, a significant positive association was found between CC genotype for SNP GC rs7041, GC 1s-1s and GC If-2 with risk of VDD (25OHD < 30 nmol/L). CONCLUSIONS: The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state.

Indications for invasive prenatal diagnostic procedures at a dedicated fetal medicine centre: an 8 year audit 2003-2010.

OBJECTIVE: Analyze indications and type of prenatal diagnostic procedures performed. METHOD: This retrospective audit was conducted at a dedicated fetal medicine center in Petaling Jaya. All invasive prenatal diagnosis procedures performed from 2003 up until 2010 (amniocentesis, chorionic villous sampling and fetal blood sampling) were analyzed. RESULT: A total of 1560 invasive prenatal diagnostic procedures were performed during the 8 year period. Advanced maternal age is the leading indication for invasive prenatal diagnostic procedures followed by fetal abnormalities. The fetal loss rate was 0.2% for amniocentesis and 1.2% for CVS. CONCLUSION: Advanced maternal age is the leading indication for invasive prenatal diagnostic procedures at this centre but is on a declining trend. The fetal loss rates are comparable to auditable standards set by professional bodies, in this case, the Royal College of Obstetricians & Gynecologists of London.

Indications for invasive prenatal diagnostic procedures at a dedicated fetal medicine centre: an 8 year audit 2003-2010

Analyze indications and type of prenatal diagnostic procedures performed. Method: This retrospective audit was conducted at a dedicated fetal medicine center in Petaling Jaya. All invasive prenatal diagnosis procedures performed from 2003 up until 2010 (amniocentesis, chorionic villous sampling and fetal blood sampling) were analyzed.

Nanowired drug delivery to enhance neuroprotection in spinal cord injury.

Spinal cord injury (SCI) is a serious clinical situation for which no suitable drug therapy exists. SCI often results in paraplegia or quadriplegia and, apart from the personal trauma leads to huge costs to society for rehabilitation or day-to-day life support. Sensory motor dysfunction following SCI is mainly a consequence of the slowly progressing cord pathology after primary injury that worsens over tine. Thus, almost all sensory and motor nerve control and pathways passing through spinal cord and reflexes are compromised in SCI patients. As a result their peripheral nervous system, autonomic nervous function and central nervous system regulations are adversely affected. Experiments carried out in our laboratory show that various therapeutic agents, if given within 10 to 30 minutes after primary SCI could correct morphological changes to a certain extent. In these rat models of SCI reduction in cord pathology, e.g., bloodspinal cord barrier (BSCB) breakdown, edema formation and cell injury by the neuroprotective agents that also limited sensory motor dysfunction and improved functional behavior. However, these drugs if given beyond 30 minutes after SCI showed a markedly reduced neuroprotective efficacy. Thus, new strategies are needed to enhance neuroprotection in SCI to prevent structural and functional changes over longer periods of time. To that end our laboratory has initiated a series of investigations in which nanowired delivery of various neurotherapeutic agents are applied after different time periods of SCI, that resulted in a much better outcome than with the parent compounds under identical conditions. The superior neuroprotective activity of nanowired compound delivery could be due to a reduced metabolism of active compounds in the central nervous system (CNS) or by sustained release of the drug for longer times. In addition, nanowired drugs may penetrate the CNS faster and could reach widespread areas once entering the spinal cord. Thus, nanowired drug delivery to treat SCI may have potential therapeutic value. These aspects of nanowired drug delivery to enhance neuroprotection in SCI are discussed in this review based on our own investigations.

Holoprosencephaly: an antenatally-diagnosed case series and subject review

<p><b>INTRODUCTION</b>Holoprosencephaly (HPE) is an uncommon congenital failure of forebrain development. Although the aetiology is heterogeneous, chromosomal abnormalities or a monogenic defect are the major causes, accounting for about 40% to 50% of HPE cases. At least 7 genes have been positively implicated, including SHH, ZIC2, SIX3, TGIF, PTCH1, GLI2, and TDGF1.</p><p><b>CLINICAL PICTURE</b>Twelve antenatally- and 1 postnatally-diagnosed cases are presented in this study. These comprised 6 amniotic fluid, 3 chorionic villus, 2 fetal blood, 1 peripheral blood, and 1 product of conception.</p><p><b>OUTCOME</b>The total chromosome abnormality rate was 92.3%, comprising predominantly trisomy 13 (66.7%). There was 1 case of trisomy 18, and 3 cases of structural abnormalities, including del13q, del18p, and add4q.</p><p><b>CONCLUSION</b>Despite the poor outcome of an antenatally-diagnosed HPE and the likely decision by parents to opt for a termination of pregnancy, karyotyping and/or genetic studies should be performed to determine if a specific familial genetic or chromosomal abnormality is the cause. At the very least, a detailed chromosome analysis should be carried out on the affected individual. If the result of high resolution karyotyping is normal, Fluorescence in situ hybridisation (FISH) and/or syndrome-specific testing or isolated holoprosencephaly genetic testing may be performed. This information can be useful in making a prognosis and predicting the risk of recurrence.</p>

Sonographically guided removal of a double J ureteral stent in an infant.

A 2-month-old male infant with a prenatally diagnosed obstruction of the ureteropelvic junction underwent a dismembered Anderson-Hynes pyeloplasty. A transanastomotic double J ureteral stent was placed between the renal pelvis and the urinary bladder. This report describes the subsequent removal of the double J ureteral stent from the patient's urinary bladder without the aid of a cystoscope: a rigid biopsy forceps was introduced trans-urethrally into the urinary bladder, and the stent was removed with sonographic guidance. Removal of a ureteral stent with sonographic guidance has not been previously reported in infants. This technique may be particularly useful in developing countries, where appropriate-sized cystoscopes and accessories may not be available.