Diffusion tensor imaging (DTI) was performed on 15 fresh spontaneously or therapeutically aborted normal fetuses and five term infants at different gestational ages. Regional cortical fractional anisotropy (FA) values were observed to increase with gestational age (GA) from 15 to 28 weeks, followed by a decrease through 36 weeks. The early increase in the cortical FA value, which has never been reported before, is consistent with neuronal migration from the germinal matrix. A statistically significant inverse correlation between GA and the FA values in the germinal matrix was observed (r = -0.81, P = 0.004). In addition, there was a significant difference in the FA values in the right and left frontal cortices (P = 0.007, sign test), suggesting cortical lateralization during the early stage of development. Our studies suggest that the DTI-estimated anisotropy could be useful in following neuronal migration, cortical maturation, and associated changes in the germinal matrix during early brain development.

We assessed the effect of vitamin D supplementation on related biochemistry, infection and dentition of the infant. In a double-blind, placebo-controlled trial conducted in Lucknow, India (latitude 26°N), 230 mother -newborn pairs were randomised to receive, for 9 months, 3000 µg/month oral vitamin D 3 by the mother (group A) or 10 µg/d by the infant (group B) or double placebo (group C). All babies received 15 min of sun exposure (unclothed) during massage. Infants' median 25-hydroxyvitamin D (25(OH)D) was lower in group C (median 45·3; interquartile range (IQR) 22-59·5 nmol/l) than in groups A (median 60·8; IQR 41·3-80·5 nmol/l (P < 0·01)) and B (median 61·3; IQR 41·3-75·3 nmol/l (P < 0·05)) at 3·5 months. Infant 25(OH)D correlated negatively with infant parathyroid hormone (r −0·46, P < 0·01). Elevated alkaline phosphatase (>7.5 µkat/l) was significantly more frequent in group C babies (16 %) than in group A (4 %) or group B (0 %) babies. The number of days with respiratory or diarrhoeal infection by 9 months of age was higher in group C (median 46·5; IQR 14·8-73·3 d) than in group A (median 18·5; IQR 8·8-31·0 d (P < 0·01)) or group B (median 13·0; IQR 7·0-28·5 (P < 0·05)). We conclude that monthly maternal or daily infant supplementation with vitamin D along with sun exposure is superior to sun exposure alone in maintaining normal infant 25(OH)D at 3·5 months, and provide protection from elevated alkaline phosphatase and infectious morbidity.Key words: Vitamin D: Lactation: Infants: Sunshine Hypovitaminosis D is highly prevalent in India despite adequate sunshine. Factors responsible for this include inadequate exposure to sunshine, atmospheric pollution and skin pigmentation. Serious consequences of vitamin D deficiency include cardiac failure and hypocalcaemic seizures (1) . Transplacental transfer and breast milk concentration of vitamin D are low in mothers with poor vitamin D status during pregnancy and lactation (2)(3)(4) . Studies from India have shown 84-96 % of mothers and infants at birth and at 3 months to have serum 25-hydroxyvitamin D (25(OH)D) < 20 ng/ml (50 nmol/l), with winter mean 25(OH)D in women being as low as 5·9 ng/ml (14·75 nmol/l) (2,5) . High-dose (160 µg or 6400 IU/d) vitamin D 3 administered to the lactating mother was found to safely and significantly improve maternal 25(OH)D and mean milk antirachitic activity (6) . Ala-Houhala et al. (7) showed that a regimen of 50 (but not 25) μg/d to the mother improved the nursing infant's serum 25(OH) D significantly. In the only study from India on postnatal supplementation of term infants, Kumar et al. (8) did not find any differences between the placebo and supplemented groups (receiving 35 µg vitamin D 3 /week) in mortality or hospital admissions (their primary outcomes) or referral to the outpatient clinic for moderate morbidity, although serum 25(OH)D was higher in the treated group. Current international recommendations mention 10 µg/d as routine supplementation for breastfeeding infants (3,4,9) . However, no study from tropic...

The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain.

Transient early cerebral laminar organization resulting from normal developmental events has been revealed in human beings through histology and imaging studies. DTI studies have postulated that the fractional anisotropy (FA)-based differentiation of different laminar structures reflects both differing cellular density over the glial fibers and fiber alignment in respective regions. The aim of this study was to correlate FA values in these transient zones with histology. Brain DTI was performed on 50 freshly aborted human fetuses with gestational ages (GA) ranging from 12 to 42 weeks. Regions of interest were placed on the cortical plate, subplate, intermediate and germinal matrix (GMx) zones of the frontal lobe to quantify FA values. Glial fibrillary acidic protein (GFAP), neurofilament (NF) and neuron-specific enolase (NSE) immunohistochemical analyses were performed for the cortical plate, intermediate zone and GMx. In the cortical plate, a significant positive correlation was observed between FA values and percentage area of GFAP expression in fetuses ≤28 weeks of GA (r = 0.56, p = 0.01). FA values showed a significant positive correlation with the percentage area of NF expression in the intermediate zone (r = 0.54, p = 0.05). A significant positive correlation was also observed between FA and the number of NSE-positive cells per mm² in the GMx (r = 0.76, p < 0.01) and subplate (r = 0.59, p = 0.03) zones. The results of our study suggest that the FA can be used as noninvasive marker of neurodevelopmental events in the frontal lobe of human fetal brain.

Diffusion tensor imaging was performed on 24 freshly aborted human fetuses with gestational age ranging from 20 to 37 weeks to observe age-related fractional anisotropy changes in cerebellar cortex and cerebellar white matter. Quantitative immunohistochemical analysis was performed for glial fibrillary acidic protein in each fetus molecular layer of cerebellar cortex and myelin basic protein expression was quantified in myelinated areas of the middle cerebellar peduncles. The cerebellar cortical fractional anisotropy reached its peak value at 28 weeks, and then decreased gradually until 37 weeks. The time course of glial fibrillary acidic protein expression paralleled that of fractional anisotropy in the cerebellar cortex from 20 weeks of gestation upto the gestational age at which the fractional anisotropy reached its peak value (28 weeks). In the middle cerebellar peduncles, the fractional anisotropy increased continuously upto 37 weeks of gestational age and showed a significant positive correlation with myelin basic protein immunostained fibers. The fractional anisotropy quantification can be used to assess the migrational and maturation changes during the development of the human fetal cerebellum supported by the immunohistochemical analysis.