Haemoglobin electrophoresis patterns in Barbados

Despite the extensive data on haemoglobinopathies and their widespread geographic distribution, the number of prospective Caribbean studies which document the prevalence of haemoglobinopathies from birth are few. The purpose of this cohort study was to document the prevalence of haemoglobinopathies in newborn infants in Barbados. One thousand successively collected cord bloods of newborn infants were screened for haemoglobinopathies using the Paragon acid electrophoresis technique. Seventeen infants were retested at 1 year of age to confirm the diagnosis. Three mothers could not be located so their infants' diagnoses could not be confirmed. From the 997 blood samples with conclusive results, a haemoglobinopathy was found in 72 (7 percent) samples. Laboratory analysis revealed: 925 patients (93 percent) with Hb AA, 41 (4 percent) with Hb AS, 27 (2.7 percent) with Hb AC, 2 (0.2 percent) with Hb SS, 1 (0.1 percent) with Hb CC and 1 (0.1 percent) with Hb SC. The prevalence of sickle gene and number of cases of Sickle Cell anaemia in the Barbadian population is less than has been reported from other regional territories.(AU)

Little evidence of HLA-G mRNA polymorphism in Caucasian or Afor-Caribbean populations

HLA-G is a nonclassical class I MHC molecule of unknown function expressed on human trophoblast. The level of polymorphism at the HLA-G locus is of considerable importance, since the paternally inherited gene product is exposed to the maternal immune system during pregnancy. However, previous studies of HLA-G polymorphism using genomic DNA samples have produced conflicting results. Our aim was to investigate polymorphism in trophoblast HLA-G mRNA from pregnancies in ten Caucasian and twelve Afro-Caribbean women by RT-PCR. A similar PCR protocol was also applied to umbilical cord blood genomic DNA from two Caucasian and two Afro-Caribbean neonates. Caucasian cDNA yielded only two different sequences: G*01011, and one containing a previously reported synonymous substitution. Afro-Caribbean samples yielded these sequences as well as one previously reported conservative (leucine-to-isoleucine) substitution. PCR amplification from genomic DNA samples from both populations using previously published primer pairs generated sequences containing multiple substitutions, many of which were nonsynonymous. More than two sequences were produced from genomic DNA from each individual. In contrast, amplification from the same genomic DNA using new primers compleentary to exons of the HLA-G gene yielded the same few sequences generated from cDNA. These results suggest that polymorphism at the HLA-G locus is extremely limited in Caucasian and Afro-Caribbean populations. This suggests that spurious polymorphism has been reported in African Americans due to the use of intron-complementary PCR primers on genomic DNA samples. The monomorphic nature of HLA-G may allow trophoblast to carry out the immunological functions of class I-bearing tissues without compromising successful pregnancy.(Au)

Indicators of long chain polyunsaturated fatty acid status of exclusively breastfed infants at delivery and after 20-22 days

The fatty acid composition of plasma cholesterol esters (CE), erythrocytes (RBC) and mature milk from seven lactating women and their exclusively breastfed newborns, living on Dominica, were studied. Blood samples were taken from umbilical cord and mother at birth. A sample of breastmilk was collected on day 20-22 postpartum, together with a blood sample from the baby. At birth, cord blood plasma CE and RBC total long chain polyunsaturated fatty acid (LC-PUFA) contents were higher, and linoleic (18:2c, omega 6) and alpha-linolenic (18:3c, omega 3) acid contents lower, than in corresponding maternal compartments. Cord blood RBC LC-PUFA omega 3 content was lower and LC-PUFA omega 6 content higher than in maternal RBC. After birth, feeding with human milk led to a drop in LC-PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remained virtually constant. Current understanding of the origin and relative affinity of fatty acids incorporated in plasma CE and RBC suggests that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than plasma CE LC-PUFA content. The RBC LC-PUFA data suggest therefore that at birth the newborn has a lower LC-PUFA omega 3 status than the mother, and that this does not change during three weeks of exclusive breastfeeding (AU)

Screening of cord blood for haemoglobinopathies and thalassaemia by high-performance liquid chromatography - abstract

A high-performance liquid chromatography (HPLC) method for the screening of haemoglobins in cord blood was evaluated and the gene frequencies of the structural haemoglobin variants HbS and HbC and the synthesis variants O- and á+ -thalassaemia were studied in babies born on the Caribbean island of Curacao, the Netherlands Antilles. In 3 months, 67.2 percent of all (748) newborns were screened and 122 (24.3 percent) had an abnormal haemoglobin pattern, of which 53 (43.4 percent) had a haemoglobinopathy (HbS or HbC), 64(52.2 percent) O-thalassaemia (Hb Barts > 0.5 percent, corresponding with heterozygous or homozygous O-thalassaemia-2) and 5 (4.1 percent) a haemoglobinopathy plus O-thalassaemia. None of the newborns with heterozygous HbS and HbC had concomitant á+-thalassaemia. The population genotype frequency of heterozygous O-thalassaemia -2 remain undetected. The data are in excellent agreement with comparable published results. The HPLC method proved pre-eminently suitable for the screening of cord blood samples. (AU)

Cord blood thyrotropin screening for congenital hypothyroidism: three years' experience on the island of Saint Lucia

Cord blood thyrotropin (TSH) screening for congenital primary hypothyroidism has been in effect on the island of St. Lucia for the past three years. Umbilical cord blood samples are obtained on Guthrie filter paper and then transported 3,000 miles to Loyola University of Chicago and delivered to the Illinois State Metabolic Screening Laboratory. There TSH is measured by radioimmunoassay (RIA). After three years, 1,789 newborns have been screened, and the mean value is 6.23 +/-0.13 microIU per ml. This mean value is less than previously reported by us in 1986 (10.23 +/-0.29 microIU per ml.).13 It is concluded that this screening service continues to be possible far removed from the population under observation. No case of primary hypothyroidism has been detected. Our decreased mean TSH value is due to the new method currently used by the Illinois State Metabolic Screening Laboratory. Congenital hypothyroidism will not be missed provided internal controls are established and rigidly observed. (AU)

Durability of passive measles antibody in Jamaican children

Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum lgG so that high lgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents as an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all lgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries. (AU)

Intrapartum infusion of oxytocin and glucose water and neonatal jaundice

Two hundred and seventy-eight deliveries were studied prospectively to determine the association between the use of oxytocin during labour and the incidence of neonatal jaundice. Jaundice was seen significantly more often in neonates following maternal infusion of oxytocin in dextrose water (OT) or dextrose water alone (DW) as compared to those whose mothers did not receive either. No significant difference was seen in the incidence of jaundice between OT or DW groups. Mean umbilical cord serum sodium levels were significantly lower in the OT and DW group neonates who became jaundiced, as compared to the rest of the neonates in the same group and the control group. Sixty per cent of the jaundiced neonates in the OT as well as the DW group had frank hyponatremia as compared to only 8 percent in the control group. These findings support a probable causative association between hyponatremia at birth and neonatal jaundice in the deliveries following dextrose water and/or oxytocin infusion (AU)

Immunoglobulin and C3 levels in maternal and cord blood in Jamaica

IgG, IgM, IgA and C3 were estimated by radial immunodiffusion (RID) in one hundred paired maternal and cord blood samples. The mean maternal IgG, and IgM, and IgA were 2112 mg/dl, 118 mg/dl and 251 mg/dl, respectively, while in corresponding infants, the mean levels were 2194 mg/dl, 36 mg/dl and 19 mg/dl. Mean cord serum C3 levels was 113 mg/dl, approximately half the maternal level (203 mg/dl). Variation in the gestational age, birth weight, duration of labour and maternal pre-eclamptic toxaemia did not significantly affect the immunoglobulin levels. Seven out of 36 (16 percent) cord blood with IgM level greater than 36 mg/dl showed either fourfold rise or high antibody titres against one of the TORCH (toxoplasma, rubella, cytomegalovirus and herpes simplex virus) agents. Screening of cord serum for IgM levels can be of particular value in detection of newborn infants with clinically apparent or inapparent intrauterine infections (AU)

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-á+ thalassaemia, and in sickle cell-á Thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children, Eceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin cocentration from age 2 months to 4 years. The combination of a raised MCHC and a lowered MCV is unusual and may be characteristic of SC disease. Features in sickle cell-á thalassaemaia generally differed accordingly to the type of á thalassaemia gene. Sickle cell-B degree thalassaemia had lower levels of haemoglobin, MCHC, red cell count, MCV, and higher reticulocytes, most differences being significant before 1 year. No differences between SB degree thalassaemia and Sá+ thalassaemia were apparent in HbF levels (which resembled those in SS disease) or in HbA2 levels (which exceeded those in SS disease by 1 year of age).(AU)

Intrapartum infusion of aquenous glucose solution, transplacental hyponatraemia and risk of neonatal jaundice

Cord serum sodium levels in three groups of 278 singleton infants, born vaginally at term, were correlated with the incidence of jaundice (serum bilirubin o85æmol/1) in the first 3 days of life. Of the 278 infants, 87 were born to mothers who were given infusions of 5 percent or 10 percent glucose in water during labour (group I), 90 were born to mothers who received glucose solution as a vehicle for oxytocin (group II), and 101 to mothers who did not receive any intravenous fluid therapy (control group). Jaundice was seen significantly more frequently in groups I (28/87, 32 percent) and II infants (30/90, 33 percent) than in the control group (12/101, 12 percent) (P<0.01), but when analysed in relation to cord serum sodium levels, the prevalence of jaundice in the normonatraemic infants (serum sodium o131 mmol/1) was similar in the three groups. On the other hand, in groups I and II jaundice occurred about 3.5 times more frequently in the hyponatraemic infants (group I (17/32, 53 percent) and II (20/39, 51 percent) than in the normonatraemic infants (P<0.01). The difference was not associated with any other perinatal or neonatal characteristic.(AU)

Paired maternal and umbilical cord serum cholesterol and triglyceride levels in Jamaicans: normal values and the influence of some perinatal factors

Serum total cholesterol (TCHO) and tryglyceride (TG) levels were determined in paired maternal and umbilical cord serum from 120 full-term deliveries at the University Hospital of the West Indies. The median cord serum TG level was found toPbe 0.74 mmol/l, which is much higher than the levels of 0.34-0.52 mmol/l in the studies reprted so far. On the other hand, cord serum TCHO levels of 1.91 mmol/l, and maternal TG and TCHO levels of 1.84 mmol/l and 5.60 mmol/l respectively are within the range of values reported in the literature. Cord serum hypertriglyceridaemia was seen in 7 newborns, all of whom had at least one kind of perinatal stress. A significant elevation of cord serum TG was seen in infants who suffered neonatal jaundice. Further studies are needed to confirm our findings to elucidate their significance (AU)

Neonatal screening for sickle cell disease in the Eastern Province of Saudi Arabia

Neonatal screening for sickle cell disease has been established in three hospitals in the Eastern Province of Saudi Arabia. In the first 17 months of this programme, 5630 cord blood samples were screened with the detection of 47 babies with an FS phenotype. The sickle cell trait occurred in 4.4 percent births at Al Khobar, in 6.7 percent in Dammam and in 17.9 percent in Qatif. An apparent excess of the FS phenotype over that predicted from the observed S gene frequency occurred at all three centres. The cause of this excess remains unknown although a high prevalence of sickle cell-beta-o thalassaemia and the effects of non-random mating may be contributory factors. (Summary)

Hb F Kingston (G gamma 55 (D6) Met leads to Arg)

A fetal haemoglobin variant was noted in a healthy Jamaican infant of mixed African/Chinese extration. A two-dimensional chromatogram of the soluble tryptic peptides (Tp) showed 2 'new' ones. One was composed of the last 4 residues of the usually insoluble Tpgamma41-59. To permit a tryptic split this required a change of residue gamma 55 Met to Lys or Arg. The other new Tp contained arginine and was in the position expected for a Ty gamma41-55 (55 Arg). As the material was limited it could not be analysed. When after more than 6 years no example of Hb F Kingston had become available it was decided to describe the variant on the basis of the present evidence. (AU)

Serum immunoglobulin levels in children with homozygous sickle cell disease

Serum immunoglobulin levels (IgA, IgG, and IgM) have been assayed in a representative sample of children (aged 1-7 years) with homozygous sickle cell disease and in age/sex-matched control children with a normal haemoglobin genotype, followed from birth in a prospective cohort study. In SS disease, significant elevation of IgA occurred from the age of two years and of IgG from the age of six years. IgM levels were not significantly different in the two genotypes. The mechanisms contributing to these changes in immunoglobulins are currently unclear as is their clinical significance.(AU)

Cord blood screening for sickle hemoglobin: evidence against a female preponderance of hemoglobin S

The genes controlling á-chain synthesis in hemoglobins A, S, and C are not sex linked, and sex differences in the prevalence at birth of the various á-chain genotypes would not be expected. However, the results of a recent study in the United States appeared to conflict with this expectation. In a series of 3,976 black infants whose cord blood was examined by hemoglobin electrophoresis, electrophoretic patterns compatible with AS and SS genotypes occurred in significantly higher proportions of females than males. Moreover, the number of SS births was significantly higher than expected on the basis of the observed frequency of S genes. A similar, but much larger screening program is in progress in Jamaica; results for the first 70,000 births are presented below. There were no appreciable sex differences in the proportions with AS and SS genotypes, and the number of SS births was not significantly in excess of its expected value. It seems likely, therefore, that the findings reported previously were the result of stochastic variation. (AU)

Beta-chain variants in Jamaica newborns

In an electrophoretic study of 15,661 Jamaican cord bloods, 8 rare beta-chain variants were found in 18 subjects in addition to the common beta-chain variants, Hb S and Hb C. The heterozygote frequencies for Hb S and Hb C were 10.1 percent and 3.7 percent respectively. The most frequent of the rare beta-chain variants were Hb Korle Bu (beta 73 Asp leads to Asn) (7 cases) and Hb O su-Christiansborg (beta 52 Asp leads to Asn) (3 cases). One new beta-chain variant, Hb Caribbean (beta 91 Leu leads to Arg) was found. (AU)

Fetal steroid levels at delivery

The purpose of this study was to investigate cortisol levels in the circulation of neonates following spontaneous onset of labor. There was no significant difference of values between primagravidas and multigravidas, male and female babies, or normal and preeclamptic pregnancies. There was no significant change in mean cord plasma cortisol values with advancing gestational age, after the thirty-third week. It is conceivable that spontaneous labor in humans may be preceded by a release of cortisol into the fetal circulation and when a critical "parturient" level is reached labor becomes established (AU)

Use of blood specimens collected on filter paper in screening for abnormal hemoglobins

Both cellulose acetate electrophoresis and citrate agar electrophoresis were performed on 834 blood samples collected on filter paper in Jamaica and shipped for testing to the National Hemoglobinopathy Standardization Laboratory at the U.S. National Center for Disease Control. Additionally, 30 blood samples collected locally were stored on filter paper, in microhematocrit capillary tubes, and as whole blood specimens; at selected times the samples were tested for stability to determine the best sample-collection technique for hemoglobin electrophoresis. Results were most nearly accurate when both cellulose acetate electrophoresis and citrate agar testing were used. The methods are easy to perform, but results are unreliable if the blood samples on filter paper are stored at 4§C for longer than two weeks before they are tested (AU)

An unusual type of hemoglobinopathy resembling sickle cell-thalassemia disease in a Jamaican family

Three generations of a Jamaican family of African extraction are desribed, in several members of which an abnormal gene is carried. This gene produces high levels of fetal hemoglobin unassociated with the usual stigmata of thalassemia. It is found in all three generations of the family associated with hemoglobin A only and is also found in at least two members of the family interacting with hemoglobin S. In the latter combination little or no disability results. The mode of inheritance of this abnormal gene is discussed, and reasons are put forward for a possible protective effect of high fetal hemogobin levels due to inhibition of sickling. The findings in the cord blood of the youngest child, including an unusually high percentage of sickling, are discussed, together with follow-up studies to the age of 25 weeks.(AU)