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Biomedical subjects

D M Becroft

Publications and source records attributed to D M Becroft.

At least 19 recordsLinked to original sources

Proportion of cells with paternal 11p15 uniparental disomy correlates with organ enlargement in Wiedemann-beckwith syndrome.

"Genetic mosaicism" describes the presence of two or more populations of cells within a single individual that differ in their genomic constitution. Although the occurrence of asymmetric overgrowth in Wiedemann-Beckwith syndrome (WBS) suggests that mosaicism has some role in the WBS phenotype, no direct evidence for this has been published. WBS is a congenital overgrowth syndrome with variable phenotype linked to the imprinted gene cluster on chromosome region 11p15. We have performed a molecular survey of multiple organs and tissues in a case of WBS with a high degree of mosaic paternal 11p15 uniparental disomy (UPD). The organs most severely affected were those with the highest percentage of cells with UPD. In particular there was a striking difference in the degree of mosaicism for 11p15 UPD between the extremely enlarged left adrenal and non-enlarged right adrenal gland. This result indicates that the proportion of paternal 11p15 UPD cells correlates with the tissue phenotype of WBS. Our results suggest that high proportions of abnormal cells result from a combination of stochastic events and cell selection. Mosaicism may explain the variable phenotypes including hemihyperplasia and predisposition to childhood cancers in WBS patients.

Adrenal Glands↗

Previous breastfeeding does not alter thymic size in infants dying of sudden infant death syndrome.

The relationship between thymic weights and previous feeding histories was examined in 294 infants of 37 wk gestation or more dying of sudden infant death syndrome (SIDS). One hundred and sixty-five infants had been breastfed exclusively, 89 had been partially breastfed and 40 had never been breastfed. We found no relationship between thymic weight and type of previous feeding. The difference between these findings in SIDS and the substantially greater thymic size previously reported in 4-mo-old breastfed living infants deserves further study.

Age Factors↗

Water fluoridation and the sudden infant death syndrome.

AIMS: To determine whether exposure to fluoridated water supplies prenatally or postnatally at the time of death increases the risk of sudden infant death syndrome (SIDS). METHODS: A nationwide, case-control study, with infant's water fluoridation status determined from census area unit information for mother's usual address at the time of the infant's birth, infant's usual address at the time of death / nominated sleep and address where infant died / was at nominated sleep. SIDS risk associated with fluoride exposure postnatally was assessed according to method of infant feeding (breast or reconstituted formula), for the two days prior to infant's death / nominated sleep. RESULTS: Infants exposed to fluoridated water supplies during pregnancy were not at increased risk for SIDS, adjusted odds ratio (OR) 1.19 (95% confidence interval (CI) 0.82, 1.74). For breast-fed infants at the time of death / nominated sleep, fluoridated water exposure was not associated with an increased risk for SIDS, adjusted OR 1.09 (95% CI 0.66, 1.79). Similarly, 'fluoridated' formula feeding, when compared with 'unfluoridated' formula feeding, showed no increased risk of SIDS, adjusted OR 1.25 (95% CI 0.73, 2.13). There was no evidence of an interaction between fluoridation and infant feeding for the last two days (chi2 = 0.171, df = 1, p = 0.68). CONCLUSION: Exposure to a fluoridated water supply prenatally or postnatally at the time of death did not affect the relative risk for SIDS.

Analysis of Variance↗

Infections, vaccinations, and the risk of childhood leukaemia.

A nationwide case-control study was conducted in New Zealand, to test hypotheses about the role of infections in the aetiology of childhood leukaemia. Children aged 0-14 years with leukaemia were matched on age and sex to controls selected from birth records. Case ascertainment was virtually complete and 121 (92%) of 131 eligible case families took part. The participation rate among the 303 first-choice eligible controls was 69%. Home interviews and serological tests were conducted. Adjusted relative risks were estimated by logistic regression. There was an increased risk of leukaemia in relation to reported influenza infection of the child during the first year of life (adjusted odds ratio 6.8, 95% confidence interval 1.8-25.7). This could be a chance finding due to multiple comparisons, and it should be tested elsewhere. Some key variables relevant to Greaves' hypothesis were not associated with B-cell precursor acute lymphoblastic leukaemia (numbers of infections and vaccinations, firstborn status, attendance at preschool groups), although a small effect could not be ruled out with a study of this size. Leukaemia risk was higher among children in poorer social circumstances, and this was true for all eligible children as well as for the participants.

Adolescent↗

Childhood cancer in New Zealand 1990 to 1993.

An epidemiological study of childhood cancer in New Zealand identified 409 children aged 0 to 14 years with malignant neoplasms newly diagnosed between 1990 and 1993 inclusive. The original microscopic material on which the diagnoses were based was reviewed in 398 cases and the neoplasms were allocated into the 12 major groupings and 48 further subcategories of the International Classification of Childhood Cancer (ICCC). The pathology reviewers agreed with group and subcategory classification of the confirmed cancers in all but one case of acute leukemia and three cancers of the central nervous system. Changes were also made in the FAB classification of three cases of acute non-lymphocytic leukemia and in the further subcategorisation of three Hodgkin's lymphomas and ten astrocytomas. The results show a high level of diagnostic accuracy for confirmed childhood neoplasms in that time period. Nine of 15 cases of malignant melanoma notified to the study were not confirmed for various reasons, which included a change in the pathological diagnosis in four cases. Compared with Victoria (Australia), New Zealand has a high incidence rate of lymphomas in boys and an unusual female preponderance of Wilms' tumor cases.

Adolescent↗

Chest physiotherapy may be associated with brain damage in extremely premature infants.

OBJECTIVES: To determine whether a characteristic form of brain damage (encephaloclastic porencephaly) was associated with chest physiotherapy treatment in preterm babies. METHODS: A retrospective case-control study was undertaken among 454 infants of birth weight less than 1500 gm cared for during the 3-year period of 1992 to 1994. Thirteen babies of 24 to 27 weeks of gestation who weighed 680 to 1090 gm at birth had encephaloclastic porencephaly. Twenty-six control subjects were matched for birth weight and gestation. RESULTS: The patients received two to three times as many treatments with chest physiotherapy in the second, third, and fourth weeks of life as did control infants (median 79 vs 19 treatments in the first 4 weeks, p < 0.001). Patients also had more prolonged and severe hypotension in the first week than did control subjects (median duration of hypotension 4 vs 0.5 days, p < 0.01), and were less likely to have a cephalic presentation (31% vs 81%, p < 0.01). Since December 1994 no very low birth weight baby has received chest physiotherapy treatment in the first month of life in our nursery, and no further cases have occurred. CONCLUSIONS: Encephaloclastic porencephaly may be a previously unrecognized complication of chest physiotherapy in vulnerable extremely preterm infants.

Birth Weight↗

SIDS or murder?

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Asphyxia↗

The accuracy and completeness of childhood cancer registration in New Zealand.

The New Zealand Cancer Registry (NZCR) is the main source of data on cancer incidence in New Zealand. The accuracy and completeness of registration of childhood cancers (ages zero to 14 years) were assessed during the conduct of a case-control study. Newly diagnosed children (1990-93) were ascertained from three sources: the NZCR; the Patient Management System (hospital admissions and discharges); and the separate Children's Cancer Registry. Pathology reviews were conducted to verify the diagnoses. Capture-recapture methods were used to assess the completeness of ascertainment. During the four-year period, 409 incident cases of childhood cancer were confirmed, giving an age-standardized incidence rate of 131 per million person-years (95 percent confidence interval = 119-144). The NZCR ascertained 395 (97 percent) of these children. In addition, the NZCR notified us of 43 other 'childhood cancer' registrations which were not confirmed as new cases of childhood cancer according to our eligibility criteria. The main reasons for these were coding errors (20 registrations), duplicates (seven), and a change in the pathological diagnosis as a result of the pathology review (seven). The capture-recapture estimate of the total number of incident cases was 410. Overall, the NZCR had good completeness for childhood cancers, but the number of unconfirmed registrations was larger than expected.

Adolescent↗

Intra-alveolar pulmonary siderophages in sudden infant death: a marker for previous imposed suffocation.

Staining for iron showed previously overlooked intra-alveolar siderophages widely distributed in the lungs of two pairs of siblings, all of whom had hospital admissions for apparent life-threatening events (ALTEs) before dying suddenly at home. A mother and babysitter were convicted of their murder and manslaughter respectively. There were no siderophages in the lungs of a fifth infant whose death was included in the murder charge but who had no ALTEs. Bleeding from mouth or nose was observed during six of ten previous ALTEs suffered by these children and three unrelated infants in the same care. Such external hemorrhage is well described in imposed infant suffocation which may be one aspect of "Munchausen syndrome by proxy" child abuse. Our findings imply that there may also be intrapulmonary hemorrhage and that intra-alveolar siderophages can be a marker for previous abuse. Retrospectively we found diffusely distributed intra-alveolar siderophages in the lungs of seven of 158 infants with diagnoses of SIDS. Siderophages in such numbers demand an explanation and if this is not provided by clinical history or other necropsy findings should cause suspicion of previous imposed suffocation and infanticide and require further enquiry. The lungs should be stained for iron in all cases of sudden infant death.

Asphyxia↗

DNA-based diagnostics for adrenoleukodystrophy in a large New Zealand family.

AIM: To develop a DNA-based diagnostic test for adrenoleukodystrophy (ALD) in a large New Zealand family. METHODS: Mutation screening of the X chromosome-linked ALD gene was undertaken by direct sequencing of PCR amplified products encompassing defined exons of the ALD gene. The identification of a mutation led to the development of a simple restriction enzyme digestion protocol of a PCR amplified product to identify those individuals with the mutation. RESULTS: A nonsense mutation, resulting in deduced premature termination of translation of the ALD gene product, was detected in exon 4 of the ALD gene in an affected male. This mutation was found in three obligate gene carriers in the same ALD family. A DNA-based test was established to identify this mutation by Bgl II digestion of a PCR amplified product encompassing exons 3 and 4 of the ALD gene. The DNA-based test was applied to a chorionic villus sampling for prenatal diagnosis. CONCLUSIONS: A simple DNA-based test has been developed for ALD in a large New Zealand family. This test provides a rapid means of determining carrier status and for undertaking prenatal diagnosis for ALD in this family.

Adolescent↗

Somatic overgrowth associated with overexpression of insulin-like growth factor II.

Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic features of BWS. Three children showed constitutional abnormalities of H19 methylation. All four children showed nephromegaly and two developed Wilms' tumors. Gene methylation is known to be associated with gene silencing, and three children showed constitutional abnormalities of H19 gene methylation. Disruption of H19 methylation, and concomitant relaxation of IGF2 imprinting, provides another mechanism that can increase IGF2 expression in children with overgrowth. The accumulated data on normal and pathologic IGF2 expression are now sufficient to define an entity, "IGF2 overgrowth disorder," of which BWS may be one extreme manifestation. These findings have broad implications for the characterization of idiopathic overgrowth.

Base Sequence↗

Risk factors for small for gestational age infants: a New Zealand study. New Zealand Cot Death Study Group.

AIM: The aim was to identify risk factors for small for gestational age infants. METHOD: Case-control study. The study population was 1800 infants selected randomly from all babies born over a three year period over 78% of the country. Of these 1800 infants, 85 (4.8%) were classified as preterm (< 37 weeks completed gestation) and were excluded. 157 (8.9%) were classified as small for gestational age (cases) and 1519 (86.3%) were fullterm, nonsmall for gestational age infants (controls). Risk factors were investigated using data collected from obstetric records and parental interviews. RESULTS: Risk factors associated with small for gestational age after controlling for potential confounders included maternal smoking during pregnancy (Odds ratio (OR) 2.61, 95% confidence interval (CI) 1.65, 4.15), primiparity (OR 2.96, 95% CI 1.59, 5.48), lack of antenatal care in the first trimester (OR 1.83, 95% CI 1.13, 2.98) and young age when mother left school (OR 1.56, 95% CI 1.01, 2.41). Use of marijuana in pregnancy significantly increased risk of small for gestational age at the 6% level (OR = 1.86, 95% CI 0.98, 3.52). The population attributable risk for maternal smoking was 31.1% (95% CI 18.2, 41.9). CONCLUSION: Maternal smoking was the most important modifiable risk factor in this dataset for small for gestational age.

Adolescent↗

Travel and changes in routine do not increase the risk of sudden infant death syndrome.

We investigated the relationship between travel and changes in routine and the sudden infant death syndrome (SIDS) among 485 SIDS cases compared with 1800 randomly selected control infants. There was no increased risk of SIDS with travel. Special events, such as christenings, were not associated with an increased risk of SIDS. However, visits to and by friends or relatives were associated with a significantly reduced risk of SIDS after controlling for potential confounders (odds ratios = 0.70; 95% confidence interval = 0.52, 0.96). These findings may indicate less social support in SIDS cases.

Analysis of Variance↗