David M. O. Becroft

Infections, vaccinations, and the risk of childhood leukaemia.

SummaryA 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.

Risk factors for obesity in 7-year-old European children: the Auckland Birthweight Collaborative Study

Objective: To identify risk factors associated with obesity in primary school children, with a particular focus on those which can be modified. To identify critical periods and growth patterns in the development of childhood obesity. Methods: 871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5 and 7 years of age. Data collected at 7 years included weight, height, bioelectrical impedance analysis (BIA), television viewing time and a 24 h body movement record (actigraphy). The outcome measure was percentage body fat (PBF), which was calculated at 3.5 and 7 years using BIA. Univariate and multiple regression analyses were carried out using PBF as a continuous variable. Results: Multivariable analysis found maternal overweight/obesity, maternal age, female gender, sedentary activity time and hours of television viewing to be independently associated with PBF at 7 years. Growth variables (birth weight, rapid weight gain in infancy, early (1–3.5 years) and middle childhood (3.5–7 years)) were also independently associated with adiposity at 7 years. There was a strong correlation between PBF at 3.5 years and PBF at 7 years. Conclusions: Many primary school aged children start on the trajectory of obesity in the preschool years, which suggests interventions need to start early. Maternal overweight/obesity, television watching, sedentary activity time and rapid weight gain in infancy, early and middle childhood are risk factors for childhood obesity, and are all potentially modifiable.

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.

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

Summary 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.

Perinatal Visceral Fibrosis Accompanying the Megakaryoblastic Leukemoid Reaction of Down Syndrome

Two infants with Down syndrome, one 4 weeks old and the other stillborn, at necropsy showed hepatic and pancreatic fibrosis, which was very severe in the liver of the liveborn infant and in the pancreas of the stillbirth. The liveborn infant had typical hematological features of the transient congenital leukemoid reaction of Down syndrome, and the identification of a megakaryoblastic component was consistent with recent opinion that this is a spontaneously-remitting congenital megakaryoblastic leukemia. The hydropic stillborn infant had intense extramedullary megakaryocytosis. The visceral fibrosis may have had a pathogenesis similar to that postulated for the myelofibrosis of megakaryoblastic leukemia in older children.Two infants with Down syndrome, one 4 weeks old and the other stillborn, at necropsy showed hepatic and pancreatic fibrosis, which was very severe in the liver of the liveborn infant and in the pancreas of the stillbirth. The liveborn infant had typical hematological features of the transient congenital leukemoid reaction of Down syndrome, and the identification of a megakaryoblastic component was consistent with recent opinion that this is a spontaneously-remitting congenital megakaryoblastic leukemia. The hydropic stillborn infant had intense extramedullary megakaryocytosis. The visceral fibrosis may have had a pathogenesis similar to that postulated for the myelofibrosis of megakaryoblastic leukemia in older children.

Nasal and intrapulmonary haemorrhage in sudden infant death syndrome

BACKGROUND Fresh intrapulmonary and oronasal haemorrhages in cases of sudden infant death syndrome (SIDS) might be markers for accidental or intentional smothering inappropriately diagnosed as SIDS. AIM To compare the incidence, epidemiological association, and inter-relation of nasal haemorrhage, intrapulmonary haemorrhage, and intrathoracic petechiae in infant deaths certified as SIDS. METHODS In SIDS cases from a large nationwide case–control study, a wide range of variables were compared in cases with and without reported nasal haemorrhage and, in a subgroup of cases, in those with and without pathologically significant intrapulmonary haemorrhage. RESULTS Nasal haemorrhage was reported in 60 of 385 cases (15%) whose parents were interviewed. Pathologically significant intra-alveolar pulmonary haemorrhage was found in 47% of 115 cases studied, but was severe in only 7%. Infants with nasal haemorrhage had more haemorrhage into alveoli and air passages than age matched cases without nasal haemorrhage. In multivariate analysis, nasal haemorrhage was associated with younger infant age, bed sharing, and the infant being placed non-prone to sleep. Intrapulmonary haemorrhage was associated with the same three factors in univariate analysis, but in multivariate analysis only younger infant age remained statistically significant. There was no significant association between nasal or intra-alveolar haemorrhages and intrathoracic petechiae. CONCLUSIONS Nasal and intrapulmonary haemorrhages have common associations not shared with intrathoracic petechiae. Smothering is a possible common factor, although is unlikely to be the cause in most cases presenting as SIDS.

Falling asleep: the determinants of sleep latency.

Background: Difficulty falling asleep (prolonged sleep latency) is a frequently reported problem in school-aged children. Aims: This study aimed to describe the distribution of sleep latency and factors that influence its duration. Methods: 871 children of European mothers were recruited at birth. 591 (67.9%) children took part in the follow-up at 7 years of age. Sleep and daytime activity were measured objectively by an actigraph worn for 24 h. Results: Complete sleep data were available for 519 children (87.8%) with a mean age of 7.3 years (SD 0.2). Median sleep latency was 26 minutes (interquartile range 13–42). Higher mean daytime activity counts were associated with a decrease in sleep latency (−1.2 minutes per 102 movement count per minute, p = 0.05). Time spent in sedentary activity was associated with an increase in sleep latency (3.1 minutes per hour of sedentary activity, p = 0.01). Conclusions: These findings emphasise the importance of physical activity for children, not only for fitness, cardiovascular health and weight control, but also for promoting good sleep.

Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic? Observations in a four-generation kindred

Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal multiple congenital anomalies, but recurrence of this phenotype within one family has not been reported. Males with oto-palato-digital syndrome type II (OPD II) also demonstrate a multiple congenital anomalies phenotype that includes skeletal dysplasia but the maternal phenotype includes only mild craniofacial anomalies. These two syndromes have been suggested as being allelic despite differences in the described maternal phenotypes. We present a four-generation kindred in which four males had a consistent multiple congenital anomalies phenotype. The females in this family have skeletal changes characteristic of MNS but have only mild craniofacial anomalies and also deafness attributable to ossicular deformity, traits more commonly found in OPD II. The expression of manifestations of MNS and OPD II in males and females in this kindred further suggest that these syndromes are allelic.

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 separateChildren‘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 t o 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.

Head covering and the risk for SIDS: findings from the New Zealand and German SIDS case-control studies

OBJECTIVES. The aim of this investigation was to identify risk factors for being found with the head covered in sudden infant death syndrome cases and determine whether head covering was likely to be an agonal event or potentially part of the causal pathway in some cases. By using the data from 2 sudden infant death syndrome case-control studies, consistency of the findings could be assessed. METHODS. Two case-control studies were assessed: (1) the New Zealand Cot Death Study (1987–1990, 393 sudden infant death syndrome cases) and (2) a German SIDS case-control study (1998–2001, 333 sudden infant death syndrome cases). RESULTS. The proportion of sudden infant death syndrome cases in which infants were found with their head covered was 15.6% in the New Zealand study and 28.1% in the German study. Being found with head covering was associated with older infant age. In both studies, being found with head covering was associated with being very sweaty when found. Head covering was also associated with the incidence and severity of thymic petechiae in both studies. Both the position in which the child was placed to sleep and the position in which the child was found were not associated with head covering. CONCLUSIONS. The finding that sudden infant death syndrome cases in which infants were found with their heads covered were often very sweaty suggests that head covering was not an agonal event and that it preceded the death and may have been causally related to the death. Infants who were found with their head covered were older, which probably reflects motor development.