PubMed Health⌕ Search

Biomedical subjects

S W D'Souza

Publications and source records attributed to S W D'Souza.

At least 19 recordsLinked to original sources
PubMed2006

Taurine transporter in fetal T lymphocytes and platelets: differential expression and functional activity.

Transplacental transfer of taurine, a beta-amino acid essential for fetal and neonatal development, constitutes the primary source of taurine for the fetus. Placental transport of taurine is compromised in pregnancies complicated by intrauterine growth restriction, resulting in a reduced concentration of taurine in cord plasma. This could impact on fetal cellular metabolism as taurine represents the most abundant intracellular amino acid in many fetal cell types. In the present study, we have used pure isolates of fetal platelets and T lymphocytes from cord blood of placentas, from normal, term pregnancies, as fetal cell types to examine the cellular uptake mechanisms for taurine by the system beta transporter and have compared gene and protein expression for the taurine transporter protein (TAUT) in these two cell types. System beta activity in fetal platelets was 15-fold higher compared with fetal T lymphocytes (P < 0.005), mirroring greater TAUT mRNA expression in platelets than T lymphocytes (P < 0.005). Cell-specific differences in TAUT protein moieties were detected with a doublet of 75 and 80 kDa in fetal platelets compared with 114 and 120 kDa in fetal T lymphocytes, with relatively higher expression in platelets. We conclude that greater system beta activity in fetal platelets compared with T lymphocytes is the result of relatively greater TAUT mRNA and protein expression. This study represents the first characterization of amino acid transporters in fetal T lymphocytes.

Blood Platelets↗
PubMed2006

Isolated parenchymal lesions on cranial ultrasound in very preterm infants in the context of maternal infection.

AIM: To explore the associations between a clinical diagnosis of maternal infection (CDMI) and findings on the initial cranial ultrasound scan in very preterm infants. METHODS: Among infants born at less than 32 weeks gestation, cases of CDMI and controls were identified on the basis of routinely available obstetric data. Neonatal cranial ultrasound scans carried out soon after birth were retrospectively reviewed for evidence of parenchymal echodensity (PED), intraventricular haemorrhage (IVH) or PED contiguous with IVH. RESULTS: Any PED was identified in 20/40 (50%) cases of CDMI and 9/30 (30%) of controls. Logistic regression was used to adjust for differences between the two study groups. When compared with normal scans, isolated PED was more likely with CDMI odds ratio, OR (95% confidence interval, CI), 41.8 (2.64, 662) and lower Apgar score at 5 min 2.89 (1.05, 7.98). IVH was more likely with lower gestational age, OR for each completed week of gestation 0.64 (0.46, 0.88) and a protective effect of female sex, OR 0.25 (0.063, 0.98), PED contiguous with IVH was more likely with lower gestational age OR 0.59 (0.336, 1.04). CONCLUSIONS: CDMI may be associated with isolated PED in very preterm infants. We speculate that isolated PED (including "flares") identify infants who have sustained early brain injury because of intrauterine infection. Isolated PED may be a useful intermediate outcome in perinatal cohort studies.

Apgar Score↗
PubMed2004

Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta.

We investigated the polarization of l-lactate transport in human syncytiotrophoblast by measuring uptake of [(14)C] l-lactate by both microvillous (maternal-facing; MVM) and basal (fetal-facing; BM) plasma membranes. [(14)C] l-lactate uptake by MVM and BM was stimulated in the presence of an inwardly directed H(+)gradient, with a significantly higher uptake in MVM than in BM at initial rate (15.4+/-2.3 vs 5.6+/-0.6 pmol/mg protein/20 sec). Stereospecific inhibition was observed in MVM, with a higher affinity for l-lactate compared with d-lactate. In BM, there was no difference in the inhibition by these two stereoisomers. Inhibition of lactate uptake in both MVM and BM by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of monocarboxylate transporter (MCT) activity, indicated MCT-mediated mechanisms across both membranes. Kinetic modelling supported a two-transporter model as the best fit for both MVM and BM, the K(m)of the major component being 6.21 mm and 25.01 mm in MVM and BM respectively. Western blotting and immunolocalization examining the distribution of MCT1 and MCT4, showed that MCT expression was polarized, MCT1 being predominantly localized to BM and MCT4 showing greater abundance on MVM. CD147, a chaperone protein for MCT1 and MCT4, was equally expressed by both membranes. These studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both MCT activity and expression.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2003

Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells.

We investigated the expression and activity of arginine transporters and endothelial nitric oxide synthase (eNOS) in human placental microvascular endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1, CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light chain dimers were indicated by a shift in molecular mass detected under nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine. The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic analysis supported a two-transporter model attributed to system y+L and system y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h, either as the basal production of nitric oxide (NO) or as the accumulation of intracellular cGMP was not detectable. We conclude that HPMEC transport cationic amino acids by systems y+ and y+L and that basal eNOS expression and activity in these cells is low.

Amino Acid Transport Systems, Basic↗
PubMed2003

Absence of leukaemic fusion gene transcripts in preterm infants exposed to diagnostic x rays.

BACKGROUND: Childhood leukaemias express novel, clonotypic fusion genes that may already be present at birth before the clinical manifestation of leukaemia. Exposure of the fetus to diagnostic x rays is reported to increase the risk of childhood leukaemia, and may do so by generating leukaemic fusion genes. Advances in neonatal medicine in the past decade that have extended the limits of viability of preterm babies down to 23 weeks of gestation have resulted in the increased use of diagnostic x rays to monitor neonatal progress. AIM: To investigate whether exposure of very preterm infants to diagnostic x rays in the neonatal period leads to the development of leukaemic fusion genes. METHODS: Peripheral blood samples were collected at birth from very preterm infants (23-30 weeks gestation) and following exposure to diagnostic x rays at intervals of two weeks, until discharge. Cord blood samples from normal full term infants served as controls. Total RNA was extracted from the blood and the expression of the fusion genes TEL-AML1, MLL-AF4, and BCR-ABL, characteristic of three subtypes of childhood leukaemia, was investigated in the preterm and full term infant samples using a nested reverse transcriptase polymerase chain reaction method. Serial pre- and post-x ray samples from 42 preterm babies, pre-x ray samples from an additional 46 preterm infants, and cord blood samples from 100 normal full term infants were screened for fusion gene transcripts. RESULTS: No leukaemic fusion gene transcripts were detected in preterm infants following exposure to diagnostic x rays. A BCR-ABL transcript was identified in a single preterm infant prior to x ray exposure. TEL-AML1 transcripts were detected in cord blood samples from two full term infants. MLL-AF4 transcripts were not detected in any of the pre- or full term infants tested. CONCLUSIONS: Exposure of the preterm infants to x rays in this small series and at the doses used for diagnostic purposes did not induce leukaemic fusion gene expression, but we cannot exclude the possibility that a small proportion of preterm infants may be unusually sensitive to x rays.

Cell Line↗
PubMed2003

L-Arginine transport across the basal plasma membrane of the syncytiotrophoblast of the human placenta from normal and preeclamptic pregnancies.

Cord blood levels of nitrate/nitrite, as a measure of nitric oxide (NO), are generally increased in preeclampsia. As L-arginine is the precursor for NO synthesis, we hypothesized that L-arginine transport across the syncytiotrophoblast basal plasma membrane (BM) of placentas from preeclamptic patients is also increased. Glutamine-sensitive and -insensitive [(3)H]L-arginine uptakes into BM vesicles were measured and expressed as femtomoles per milligram of protein per minute. Total L-arginine uptake was 418 +/- 15 (mean +/- SEM; n = 9) in BM from control placentas (CBM) and 495 +/- 27 (n = 7) in BM from preeclamptic placentas (PE BM; P < 0.05, by two-tailed t test). Glutamine insensitive (system y(+)) uptake was 45 +/- 3 (n = 6) in CBM, with a significantly higher uptake of 97 +/- 23 (n = 5) into PE BM (P < 0.05, by two-tailed t test). There was no significant difference in glutamine-sensitive uptake between the two groups. The expression of mRNA for human cationic amino acid transporter (hCAT) 1, 2, and 4 (system y(+) genes) and 4F2hc (heavy chain of system y(+)L) was not different in homogenates of whole placenta from the two groups. Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM. These data suggest increased activity of the BM system y(+) cationic amino acid transporter in preeclampsia. If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS.

Adult↗
PubMed2002

Antenatal steroids are associated with a reduction in the incidence of cerebral white matter lesions in very low birthweight infants.

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.

Analysis of Variance↗
PubMed2002

L-arginine transport by the microvillous plasma membrane of the syncytiotrophoblast from human placenta in relation to nitric oxide production: effects of gestation, preeclampsia, and intrauterine growth restriction.

Nitric oxide (NO) is an important regulator of placental perfusion, and its production is dependent on the activity of substrate (L-arginine) transporters. In the light of evidence for altered NO production in the feto-placental unit in preeclampsia and intrauterine growth restriction (IUGR), we investigated gestational changes in human placental L-arginine transport by systems y(+) and y(+)L in purified microvillous plasma membrane vesicles. We also examined the effect of preeclampsia and IUGR on the activity of these transport systems and the relationship between transporter activity and NO production (nitrate/nitrite concentrations) in the feto-placental unit. Between first trimester and term, there was a significant positive correlation between system y(+) activity and gestational age (r = 0.36; P = 0.013; n = 47), but a significant negative correlation between system y(+)L activity and gestational age (r = -0.6; P < 0.0001; n = 47). The activity of these transport systems was not altered in preeclampsia or IUGR. In placentas from normal term pregnancies, there was no correlation between the activity of microvillous plasma membrane L-arginine transporters and nitrate/nitrite concentrations in umbilical venous plasma or placental homogenate.

Arginine↗
PubMed2000

Activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane of the syncytiotrophoblast in relation to gestation and small for gestational age birth.

The effect of gestational age, low birth weight, and umbilical plasma pH on the activity and expression of the Na(+)/H(+) exchanger in the microvillous plasma membrane (MVM) of the placental syncytiotrophoblast was investigated. MVM were isolated from placentas of fetuses delivered in the first and second trimesters and from appropriately grown for gestational age (AGA) and small for gestational age (SGA) babies born at term. Na(+)/H(+) exchange activity (amiloride-sensitive Na(+) uptake) was higher (p<0.05) in second trimester and term AGA MVM versus first trimester MVM (median [range]: 1.80 [1.01-3.03], 1.72 [1.16-3.15] versus 1.48 [0.92-1.66] nmol/mg protein/30s, respectively, n = 6, 12, and 9). As regards exchanger isoforms, Western blotting showed that NHE1 expression did not change across gestation, but NHE2 and NHE3 expression were lower (p<0.01) in the first and second trimesters than in term AGA MVM. There were no differences in Na(+)/H(+) exchanger activity or in NHE1-3 expression in term AGA MVM versus SGA (n = 11) MVM. There was no correlation between exchanger activity and umbilical artery or vein plasma pH, although with a relatively small number of samples (n = 12 and 15, respectively). We conclude that there is differential regulation of the activity and expression of Na(+)/H(+) exchanger isoforms in the MVM over the course of gestation in normal pregnancy; this is not affected in pregnancies resulting in SGA babies at term.

Female↗
PubMed2000

Discordant amino acid profiles in monochorionic twins with twin-twin transfusion syndrome.

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.

Amino Acids↗
PubMed1998

Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain.

AIM: To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate. METHODS: The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains. RESULTS: Neonatal brains had the least [3H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 microM) and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains. CONCLUSION: Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.

Adult↗
PubMed1998

Increased survival and deteriorating developmental outcome in 23 to 25 week old gestation infants, 1990-4 compared with 1984-9.

AIMS: To assess whether changes in survival over time in infants of 23 to 25 weeks of gestational age were accompanied by changes in the incidence of disability in childhood during an 11 year period. METHODS: Obstetric and neonatal variables having the strongest association with both survival to discharge from a regional neonatal medical unit and neurodevelopmental disability in 192 infants of 23 to 25 weeks of gestation, born in 1984 to 1994, were studied as a group and in two cohorts (1984 to 1989 n = 96 and 1990 to 1994 n = 96). The data collected included CRIB (clinical risk index for babies) scores and cranial ultrasound scan findings. The children were followed up at outpatient clinics. RESULTS: Between 1984 and 1989 (cohort 1) and 1990 and 1994 (cohort 2) the rate of survival to discharge increased significantly from 27% to 42% and the rate of disability in survivors increased from 38% to 68%; most of this increase was in mild disability. The proportions of survivors with cerebral palsy did not alter significantly (21% vs 18%), but more survivors with blindness due to retinopathy of prematurity (4% vs 18%), myopia (4% vs 15%) and squints (8% vs 13%) contributed to the increased rate of disability. Clinically significant cranial ultrasound findings and a high CRIB score were strongly associated with death. A high CRIB score was most strongly associated with disability. CONCLUSIONS: The rise in disability with improved survival was not due to cerebral palsy; rather the main contributors were blindness due to retinopathy, myopia, and squint. The causes of these disabilities seem to be linked to high CRIB scores. A system of regular and skilled retinal examination and access to facilities for retinal ablation should be in place in all neonatal units which undertake the care of such extremely preterm infants.

Birth Weight↗
PubMed1997

Nitric oxide does not modulate kainate receptor binding in human brain.

The ability of three nitric oxide (NO) donor compounds to modify ligand binding to kainate receptors was studied in tissue from human adult autopsy brains. Binding of [3H]kainic acid (5 nM) was measured in frontal cortex membranes made from Brodmann area 8 (BA 8) and autoradiographically using sections of frontal cortex (BA 8 and 9). None of the three donors, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitrosocysteine (Cys-NO) and 3-morpholinosydnonimine chloride (SIN-1) altered the specific binding of [3H]kainic acid. Nitrite accumulation assays confirmed that adequate amounts of NO were released by the donors under the ligand binding conditions used. The findings show that binding to the kainate receptor, in contrast to the other ionotropic glutamate receptors, is not affected by NO and strongly suggest that endogenous NO produced by NO synthase (NOS) does not modulate kainate receptors in vivo. Mechanisms whereby NOS inhibitors potentiate kainic acid-induced seizures in animal models may include altered modulation of glutamate N-methyl-D-aspartate (NMDA) receptors.

Brain↗
PubMed1997

Children conceived by in vitro fertilisation after fresh embryo transfer.

AIMS: To compare the outcome in in vitro fertilisation (IVF) children (after fresh embryo transfer) from multiple and singleton births with one another, and with normally conceived control children. METHODS: A cohort of 278 children (150 singletons, 100 twins, 24 triplets and four quadruplets), conceived by IVF after three fresh embryos had been transferred, born between October 1984 and December 1991, and 278 normally conceived control children (all singletons), were followed up for four years after birth. They were assessed for neonatal conditions, minor congenital anomalies, major congenital malformations, cerebral palsy and other disabilities. Control children, all born at term, were matched for age, sex and social class. RESULTS: The ratio of male:female births was 1.03. Forty six per cent of IVF children were from multiple births; 34.9% were from preterm deliveries; and 43.2% weighed less than 2500 g at birth. The IVF singletons were on average born one week earlier than the controls, weighed 400 g less, and had a threefold greater chance of being born by caesarean section. The higher percentage of preterm deliveries was largely due to multiple births and they contributed to neonatal conditions in 45.0% of all IVF children. The types of congenital abnormalities varied: 3.6% of IVF children and 2.5% of controls had minor congenital anomalies, and 2.5% of IVF children and none of the controls had major congenital malformations. The numbers of each specific type of congenital abnormality were small and were not significantly related to multiple births. IVF children (2.1%) and 0.4% of the controls had mild/moderate disabilities. They were all from multiple births, including two children with cerebral palsy who were triplets. CONCLUSIONS: The outcome of IVF treatment leading to multiple births is less satisfactory than that in singletons because of neonatal conditions associated with preterm delivery and disabilities in later childhood. A reduction of multiple pregnancies by limiting the transfer of embryos to two instead of three remains a high priority.

Cerebral Palsy↗
PubMed1996

Longitudinal variation in the activities of mucosal enzymes in the small intestine of suckling rats.

The extent of positional variation in mucosal enzyme activity along the small intestine was investigated in 14-day-old suckling rats. Samples were taken from ten equally spaced sites along the intestine in 11 rat pups and the activities of the enzymes alkaline phosphatase, neutral aminopeptidase, gamma-glutamyl transferase, lactase and sucrase were measured. All the enzymes except sucrase were subject to considerable positional variation. Alkaline phosphatase and aminopeptidase activities were distributed throughout the intestine, with a broad maximum in the distal intestine. Lactase was also broadly distributed but with greatest activity in the mid intestine. gamma-glutamyl transferase exhibited a novel profile, with a very high proportion of the total activity (78%) present in the distal intestine. Sucrase was essentially absent throughout the intestine.

Alkaline Phosphatase↗
PubMed1995

Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos.

A total of 91 children (68 singletons, 20 twins and three triplets) who were conceived from cryopreserved embryos between 27 December 1989 and 18 January 1994, and 83 normally conceived control children (81 singletons and two twins) of a similar age, sex and social class, were assessed for minor congenital anomalies and major congenital malformations. Their development was assessed using the Griffiths Scales of Mental Development. The incidence of minor congenital anomalies (31.9% in the cryopreserved embryo group and 21.7% in the controls) and major congenital malformations (3.3 and 2.4% respectively) in our two groups of children was statistically similar. The relative risk (odds ratio and 95% confidence interval) in the cryopreserved embryo group compared with the controls was 1.7 (0.8, 3.3) for minor congenital anomalies and 1.4 (0.2, 8.5) for major congenital malformations. The minor congenital anomalies were mostly naevi and haemangiomas. The major congenital malformations included Down's syndrome, Beckwith-Wiedemann syndrome and hypophosphataemic rickets in the cryopreserved embryo group and hydronephrosis and gastroschisis in the controls. The Griffiths assessment showed that children from the cryopreserved embryo group and the controls were functioning at a similar level. The mean Griffiths quotient and subquotient values were greater than the standard 100 in children with or without congenital abnormalities. These results in the cryopreserved embryo group are reassuring in that the minor congenital anomaly and major congenital malformation rates were similar to those in normally conceived children of a similar age, sex and social class and their development was not adversely affected by cryopreservation.

Case-Control Studies↗
PubMed1995

Outcome in children from cryopreserved embryos.

A cohort of 91 children from cryopreserved embryos and 83 control children who were conceived normally had their development assessed using the Griffiths's scales of mental development. The controls (81 singletons and two twins) of a similar age, sex, and social class were selected from siblings, cousins, and peers of the cryopreserved embryo group (68 singleton, 20 twins, and three triplets). Children from cryopreserved embryos had a lower mean birth weight and mean gestational age and a higher proportion were born by caesarean section. One child from the cryopreserved embryo group had Down's syndrome, three had squints, and four had conductive hearing loss while in the control children, six had squints, and nine had conductive hearing loss. In both groups, including the child with Down's syndrome, the mean Griffiths's quotient was greater than the standard 100. In the children from cryopreserved embryos, the singleton and multiple birth subgroups had statistically similar assessment results. The mean (SD) Griffiths's quotient was 105.69 (13.55) in children from cryopreserved embryos and 108.18 (9.80) in controls at a chronological age of 25.08 (12.86) and 29.19 (14.65) months respectively. Overall, the development in children from cryopreserved embryos did not cause concern though formal testing had highlighted small differences compared with other children conceived normally and of a similar social class.

Birth Weight↗