Eva Alberman

Cerebral Palsy Epidemiology: Where are We Now and Where are We Going?

OVER the past decade, regular international meetings devoted to the state of the art in the epidemiology of cerebral palsy have been held: in California in 1987, in Cambridge in 1989 and in Brioni, Yugoslavia, in 1990. Among the longstanding problems considered have been those of case definition, case-finding, reported changes in prevalence, the bases on which distinctions between different clinical types and meaningful classification can be achieved, and the crucial question of the timing and nature of the original insult. Reports of the meetings have not been published, however, so this annotation is intended to document some of the recurrent questions that have been considered.

Intergenerational studies of human birthweight from the 1958 birth cohort. 1. Evidence for a multigenerational effect

Objective To investigate possible multigenerational influences on birthweight.

Trends in Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008: analysis of data from the National Down Syndrome Cytogenetic Register

Objectives To describe trends in the numbers of Down’s syndrome live births and antenatal diagnoses in England and Wales from 1989 to 2008. Design and setting The National Down Syndrome Cytogenetic Register holds details of 26488 antenatal and postnatal diagnoses of Down’s syndrome made by all cytogenetic laboratories in England and Wales since 1989. Interventions Antenatal screening, diagnosis, and subsequent termination of Down’s syndrome pregnancies. Main outcome measures The number of live births with Down’s syndrome. Results Despite the number of births in 1989/90 being similar to that in 2007/8, antenatal and postnatal diagnoses of Down’s syndrome increased by 71% (from 1075 in 1989/90 to 1843 in 2007/8). However, numbers of live births with Down’s syndrome fell by 1% (752 to 743; 1.10 to 1.08 per 1000 births) because of antenatal screening and subsequent terminations. In the absence of such screening, numbers of live births with Down’s syndrome would have increased by 48% (from 959 to 1422), since couples are starting families at an older age. Among mothers aged 37 years and older, a consistent 70% of affected pregnancies were diagnosed antenatally. In younger mothers, the proportions of pregnancies diagnosed antenatally increased from 3% to 43% owing to improvements in the availability and sensitivity of screening tests. Conclusions Since 1989, expansion of and improvements in antenatal screening have offset an increase in Down’s syndrome resulting from rising maternal age. The proportion of antenatal diagnoses has increased most strikingly in younger women, whereas that in older women has stayed relatively constant. This trend suggests that, even with future improvements in screening, a large number of births with Down’s syndrome are still likely, and that monitoring of the numbers of babies born with Down’s syndrome is essential to ensure adequate provision for their needs.

Is the prevalence of Klinefelter syndrome increasing

The birth prevalence of sex chromosome trisomies (SCT), that is individuals with an XYY, XXY or XXX sex chromosome constitution, is traditionally based on six surveys of unselected newborns carried out in the 1960s and early 1970s. All three SCTs had a prevalence of 1 in 1000 same sex births. We re-examined these prevalences based on additional cytogenetic studies of newborn surveys, spontaneous abortions, perinatal deaths and prenatal diagnoses. The more recent newborn surveys suggest there has been an increase in the prevalence of XXYs, but not of the other two SCTs since the original newborn series. The prevalence of XXYs has risen from 1.09 to 1.72 per 1000 male births (P=0.023). We suggest that such an increase, in the absence of an increase in the prevalence of XXX, is unlikely to be due to increased maternal age. As XXY is the only chromosome abnormality known where a substantial proportion (∼50%) arise as the result of non-disjunction at the first paternal meiotic division, we speculate that some factor may be interfering with pairing and/or recombination of the sex bivalent at the paternal MI division.

Intergenerational studies of human birthweight from the 1958 birth cohort.

OBJECTIVE To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.Objective To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants.

Cerebral palsy: effects of twinning, birthweight, and gestational age.

AIMS: To determine the effects of birthweight and gestational age on the risk of cerebral palsy for multiple and singleton births. METHODS: Children on the North East Thames Regional Health Authority Interactive Child Health System, born between 1 January 1980 and 31 December 1986, and notified as having cerebral palsy, were included. Cases of postneonatal onset, of known progressive, or non-cerebral pathology and with only mild signs were excluded. Rates and relative risks were calculated using the most complete data, which related to 1985-86, and comprised 102,059 singletons and 2367 twins. Logistic regression was used to examine the associations between being a twin, gestational age, and birthweight. RESULTS: The crude rate per 1000 survivors at 1 year of age was 1.0 in singletons and 7.4 in twins. The relative risk was greatest in twins weighing more than 2499 g (4.5). However, after adjusting for reduced birthweight of twins it was the relative risk of twins weighing less than 1400 g that was significantly increased. Logistic regression confirmed that lower fetal growth, lower gestational age, and being a twin are all independent risk factors for cerebral palsy. CONCLUSION: The increased risk to twins of cerebral palsy is not entirely explained by their increased risk of prematurity and low birthweight.

Reported Influenza in Pregnancy and Subsequent Cancer in the Child

A longitudinal study of 1,959 infants born in the first week of March 1958 to mothers who were reported to have had influenza during pregnancy revealed an incidence of cancer of 4·1 per 1,000 compared with only 0·8 per 1,000 among the 14,791 infants of mothers who had not had influenza. This increase was caused by cases of leukaemia and other neoplasms of lymphatic and haematopoietic tissue (I.C.D. 200-209) (P <0·0001). Data from the reports of the Registrar General for England and Wales were used to estimate the number of infants born in each year from 1955 to 1964 who subsequently died of cancer before 5 years of age. The rates for each year were compared with an estimate of the prevalence of influenza during the preceding winter. After allowing for the overall trend in the cancer death rate, a highly significant correlation was shown with deaths attributed to causes classified as I.C.D. 200-209 (P <0·005), but not with deaths attributed to other cancers. The increase in the risk of developing these neoplasms among children whose mothers had influenza is estimated to be not less than fourfold. Even so the risk remains small (3 to 4 per 1,000).

Alpha-fetoprotein levels in amniotic fluids from spontaneous abortions.

Alpha-fetoprotein (A.F.P.) levels in the amniotic fluid were determined in 54 cases of spontaneous abortion in which the amniotic sac remained intact. These levels were correlated with the morphological and cytogenetic status of the fetus. Of the 29 fetuses with no apparent abnormality 22 had A.F.P. levels below 50 μg/ml, while 10 of the 11 fetuses with severe neural tube defects had raised levels (50-305 μ/ml). Seventeen fetuses had chromosome anomalies of various types. Three out of four which were 45, X had considerably raised A.F.P. levels (78-210 μg/ml) but fetuses with other chromosome constitutions and no neural tube defects had levels no higher than 32 μg/ml.

National Confidential Enquiry into counselling for genetic disorders by non‐geneticists: general recommendations and specific standards for improving care

Objectives To assess genetic counselling by non‐geneticists and to improve clinical practice.

Medical causes on stillbirth certificates in England and Wales: distribution and results of hierarchical classifications tested by the Office for National Statistics

Objective To produce a classification of stillbirths registered in England and Wales compatible with a previously described classification for neonatal deaths; to compare national data for intrapartum stillbirths with those for the remaining stillbirths; and to report on stillbirths with a gestational age of 24 to 27 completed weeks first made registrable on 1 October 1992.