Bo Strömberg

Neurological sequelae in children born after in-vitro fertilisation: a population-based study

BACKGROUNDnThere is an absence of population-based long-term studies on the risk of neurological sequelae in children born after in-vitro fertilisation (IVF). Our aim was to compare the frequency of such problems between IVF-born children and controls.nnnMETHODSnWe did a population-based retrospective cohort study in which we compared development of neurological problems in 5680 children born after IVF, with 11360 matched controls. For 2060 twins born after IVF, a second set of controls (n=4120), all twins, were selected. We obtained data on neurological problems from the records of the Swedish habilitation centres.nnnFINDINGSnChildren born after IVF are more likely to need habilitation services than controls (odds ratio 1.7, 95% CI 1.3-2.2). For singletons, the risk was 1.4 (1.0-2.1). The most common neurological diagnosis was cerebral palsy, for which children born after IVF had an increased risk of 3.7(2.0-6.6), and IVF singletons of 2.8 (1.3-5.8). Suspected developmental delay was increased four-fold (1.9-8.3) in children born after IVF. Twins born after IVF did not differ from control twins with respect to risk of neurological sequelae. Low-birthweight and premature infants were more likely to need habilitation than fullterm babies. Maternal age did not affect risk.nnnINTERPRETATIONnOur study suggests that children born after IVF have an increased risk of developing neurological problems, especially cerebral palsy. These risks are largely due to the high frequency of twin pregnancies, low birthweight, and prematurity among babies born after IVF. To limit these risks, we recommend that only one embryo should be transferred during IVF.

Stroke in Swedish children II: long-term outcome

Aim:u2002 To evaluate the long‐term outcome of childhood stroke in a population‐based cohort of Swedish children.

Structured Observation of Motor Performance (SOMP-I) applied to preterm and full term infants who needed neonatal intensive care. A cross-sectional analysis of progress and quality of motor performance at ages 0–10 months

A new protocol for Structured Observation of Motor Performance in Infants, SOMP-I, designed to describe both progress and quality of motor performance, was evaluated concerning its ability to describe and to discriminate between the motor performance observed in different groups of infants. Sixty-eight infants born at < 32 completed weeks (c.w.) of gestation formed group I, 81 infants born at 32-37 c.w. group II and 77 infants born at > 37 c.w. group III. Seventy-two neonatally healthy full term infants served as controls (group IV). The detailed assessment of level (progress) of motor development at 0, 2, 4, 6 and 10 months of age corrected for preterm birth disclosed few differences in mean level between the groups. Most were found between group I and the control group. In contrast, the quality of motor performance, expressed as proportion of infants with deviations, type of deviation, and total number of deviations per infant, showed many differences, especially between groups I and III, respectively, and the control group. Thus, the SOMP-I protocol permits a detailed assessment both of the level of motor development and the quality of motor performance but has a better discriminative ability for the latter.

Childhood stroke in Sweden I: incidence, symptoms, risk factors and short-term outcome

Aim:u2002 To evaluate the incidence, presenting symptoms, diagnostic delay, risk factors and short‐term outcome of childhood stroke in a population‐based cohort of Swedish children.

Neurological dysfunction above cele level in children with spina bifida cystica : a prospective study to three years

The aim of this study was to characterize the neurological dysfunction above the cele level in children with spina bifida cystica. 22 neonates were investigated prospectively to a median age of three years. Before primary closure of the spinal malformation and at three and 18 months of age, MRI and inspection of vocal cord function were performed. The children were also assessed by a physical therapist at 12 and 24 months. 19 children had a Chiari malformation. 18 children developed neurological dysfunction above the cele level. Children with signs of isolated motor impairment stabilized or improved during the second year. Six children developed severe functional impairment of respiration, feeding and motor performance within the first three months of life. Severe neurological signs/symptoms were associated with myeloschisis, clinical signs of a tethered cord and recurrent periods of shunt dysfunction.

Structured observation of motor performance (SOMP-I) applied to neonatally healthy fullterm infants at the ages of 0–10 months

A new protocol for structured observation of motor performance in infants, SOMP-I, was applied to 72 neonatally healthy fullterm infants at 0, 2, 4, 6 and 10 months of age. It contains 13 items, formed as ascending scales, consisting of detailed descriptions of motor performance in different body positions and body parts. The observed motor performance is assessed regarding level of development (progress), and degree and type of deviation from the described performance (quality). When observed according to the new protocol, the infants motor performance corresponded to higher levels of motor development with increasing age and agreed with descriptions in other standardized developmental scales. With age, the motor performance observed was distributed over more levels in the different scales and the number of infants with deviations from the described performance increased in most positions, but decreased in the prone position. The item for the head, at 2 months, showed the largest number of infants with deviations. The total number of deviations in each infant was small. In conclusion, the SOMP-I protocol can describe motor performance in a group of infants who were healthy at birth and is detailed enough to identify differences regarding progress of motor development and quality of motor performance. The assessment is easily performed.

Clinical characteristics and late effects in CNS tumours of childhood: Do not forget long term follow-up of the low grade tumours

AIMnTo investigate clinical characteristics and late effects of CNS tumours in childhood with a special focus on low-grade tumours, especially low-grade astrocytoma and glioneuronal tumours.nnnMETHODSnA retrospective population based study was performed at Uppsala University Childrens Hospital, a tertiary referral centre for children with CNS tumours. Patients were identified from the National Brain Tumour Registry and the National Epilepsy Surgery Registry. Hospital medical records were analysed for patients with a follow up of ≥5 years after diagnosis. A re-evaluation of the neuro-pathological diagnosis was performed.nnnRESULTSnA total of 193 patients (age 0-17.99 years) during a twelve-year period (1995-2006) were included; 149 survived ≥5 years. Three larger subgroups could be identified: astrocytic, embryonal and glioneuronal tumours. A supratentorial location was found in 52%. Medical late effects were mainly neurological and endocrinological, affecting 81% and 26% of surviving patients. Cognitive late effects were a frequent finding in the whole group but also in low-grade astrocytoma and glioneuronal tumours (53% and 67%). Thirty per cent had some kind of pedagogic support in school.nnnCONCLUSIONnLate effects are common in long-term survivors of CNS tumours in childhood. Low-grade astrocytoma and glioneuronal tumours are no exception, and the findings support the need for long-term follow up.

Neurological sequelae in in-vitro fertilisation babies

Sir—Bo Stromberg and colleagues (Feb 9, p 461), in their populationbased study of long-term neurodevelopmental consequences of birth after in-vitro fertilisation (IVF), suggest that IVF is a risk factor for neurological abnormality even among singletons. However, they conclude that the real way to reduce the risk of neurological abnormality is to lower the multiple pregnancy rate. If IVF is an independent risk factor for neurological abnormality, further important questions arise: is infertility the underlying causal factor or the process of multifollicular ovarian stimulation, or do these disorders occur because of the artificial culture media used in the earliest stages of embryonic development? However, we think several additional factors may have been overlooked in the analyses and interpretation. Stromberg and colleagues’ data Sir—Robin Biellik and colleagues report a reduction in measles mortality and morbidity in southern Africa. In Japan, routine measles immunisation with one dose of measles vaccine has been used since 1978. However, measles epidemics have still occurred, and unvaccinated young adult cases of measles have risen in number. Furthermore, measles cases have been exported to the USA. The relation between measles coverage and number of children with measles was studied in Niigata Prefecture, Honshu Island, Japan. The total population of Niigata Prefecture is around 2·5 million. Vaccine had been administered to children aged 12–70 months until 1994, and 12–90 months thereafter. At the same time, recommended immunisation age was changed from 18–36 to 12–24 months. Routine vaccination coverage has been more than 90% by age 48 months since 1989, but cases of measles continued to occur in high numbers until 1995, after which the number of cases fell because of coverage of more than 60% by age 24 months after the change in immunisation age. High coverage has now controlled measles in Niigata Prefecture. Thus, we emphasise that routine administration of single-dose measles vaccine to children as soon as possible after their first birthday is essential for measles control, as reported in Canada. However, implementation of a two-dose schedule as a next step would be also required for measles elimination in Japan. *Hiroshi Suzuki, Takatsugu Sakai, Reiko Saito, Nao Seki

Evaporation rate and skin blood flow in full term infants nursed in a warm environment before and after feeding cold water

Earlier results have shown that some infants born by elective Caesarean section start to sweat in a warm environment while others do not, and that sweating can be inhibited by feeding cold glucose. To determine whether these earlier observations, indicating a difference in postnatal temperature adaptation, could be reproduced in vaginally born infants, we measured the rate of evaporation from the skin surface, body and skin temperatures from several sites, skin blood flow and respiratory rate in newborn infants nursed in a warm environment, before and after feeding cold water. In all infants the body and skin temperatures increased in the warm environment (p < 0. 01), with a decreasing difference between oesophageal and leg skin temperature (p < 0. 01). Visible sweating occurred in 9/14 infants at a rectal temperature of 37.5°C. In the infants who started to sweat, evaporation rate increased from 5.6 ± 2. 8 (SD) g/m2/h 15min before sweating to 15.7 ± 10.6 g/m2/h (p < 0.05) when sweat became visible and the infants were fed cold water. After feeding of cold water the evaporation rate decreased and within 10min returned to a value not significantly different from the pre‐sweating value. Interscapular skin blood flow had increased by 42% (p < 0. 01) at the time of sweating and decreased by 22% (p < 0. 01) after feeding cold water. In the infants who did not start to sweat, no increase in evaporation rate was noted and the changes in skin blood flow were not statistically significant. The infants who started to sweat did not differ from those who did not regarding maternal medication during delivery. We conclude that some, but not all, newborn infants start to sweat at a body temperature of 37.5°C. In the infants who start to sweat, sweating and an increase in skin blood flow can be inhibited by feeding cold water. There seem to be individual differences in the regulation of body temperature in newborn infants, possibly due to a delayed change in the central temperature set‐point in some infants.

Neurological sequelae in children born after in-vitro fertilisation: A population-based study

It is recognized that the risk of multiple births, preterm birth, and low birth weight is magnified after in vitro fertilization (IVF), but little is known of the long-term outcome for children born after IVF. This retrospective study, using a population-based cohort of 5680 children born after IVF, sought to clarify the risk of severe neurological disorder, mental retardation, and visual defects. The study children, aged 18 months or older at follow-up, were matched for gender, year of birth, and hospital of birth with 11,360 control children. A second set of control subjects, 4120 twins, was chosen for 2060 of the 5680 study children who were twins born after IVF. Children born after IVF were more likely to require rehabilitation for neurological problems than were control subjects; the odds ratio was 1.7. The risk was 1.4 for singleton infants, whereas for post-IVF twins the risk was not greater than in the control twins. The commonest diagnoses were cerebral palsy (most often spastic diplegia or spastic hemiplegia), suspected developmental delay, congenital malformation, mental retardation, chromosomal aberration, and behavioral disorder. The risk of cerebral palsy was increased nearly 4-fold in post-IVF children. The risk remained after adjusting for gestational age and birth weight. Suspected delayed development also was increased 4-fold in the IVF group; singleton infants had about double the risk of control children. Maternal age did not influence the overall risk of neurological sequelae. The eight post-IVF children with severe visual disorders had an approximately 2-fold increase in risk. Although most children born after IVF are perfectly healthy, they nevertheless are at increased risk for neurological disability or handicap, particularly cerebral palsy. A high rate of twin births is part of the explanation, as are low birth weight and low gestational age. It is estimated that having a single embryo would lower the prematurity rate by approximately 60%. The authors believe that, as a practical clinical matter, only one IVF embryo should be transferred in most cases.