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Objectives:To determine the incidence of severe hyperbilirubinaemia in the newborn, and to identify associated clinical and demographic variables, and short-term outcomes.Design:Prospective, population-based study.Setting:UK and Republic of Ireland, between 1 May 2003 and 31 May 2005.Participants:Infants in the first month of life with severe hyperbilirubinaemia (maximum unconjugated serum bilirubin ⩾510 μmol/l).Results:108 infants met the case definition, 106 from the UK and 2 from the Republic of Ireland. The UK incidence of severe hyperbilirubinaemia was 7.1/100 000 live births (95% CI 5.8 to 8.6). Only 20 cases presented in hospital; 88 were admitted with severe jaundice. 64 (60.4%) cases were male, and 56 (51.8%) were of ethnic minority origin. 87 (80.5%) cases were exclusively breast fed. Co-morbidity included haemolysis, dehydration, infection and bruising. 14 infants showed evidence of bilirubin encephalopathy, of whom 3 died. The UK incidence of bilirubin encephalopathy was 0.9/100 000 live births (95% CI 0.46 to 1.5).Conclusions:This is the first large, prospective, population-based study of the incidence of severe hyperbilirubinaemia in the newborn. The clinical and demographic associations, and short-term outcomes identified, are the same as those reported recently in North America and Europe.

Cerebral palsy seems to be more common in term babies whose birthweight is low for their gestational age at delivery, but past analyses have been hampered by small datasets and Z-score calculation methods. We compared data from ten European registers for 4503 singleton children with cerebral palsy born between 1976 and 1990 with the number of births in each study population. Weight and gestation of these children were compared with reference standards for the normal spread of gestation and weight-for-gestational age at birth. Babies of 32–42 weeks' gestation with a birthweight for gestational age below the 10th percentile (using fetal growth standards) were 4–6 times more likely to have cerebral palsy than were children in a reference band between the 25th and 75th percentiles. In children with a weight above the 97th percentile, the increased risk was smaller (from 1·6 to 3·1), but still significant. Those with a birthweight about 1 SD above average always had the lowest risk of cerebral palsy. A similar pattern was seen in those with unilateral or bilateral spasticity, as in those with a dyskinetic or ataxic disability. In babies of less than 32 weeks' gestation, the relation between weight and risk was less clear. The risk of cerebral palsy, like the risk of perinatal death, is lowest in babies who are of above average weight-for-gestation at birth, but risk rises when weight is well above normal as well as when it is well below normal. Whether deviant growth is the cause or a consequence of the disability remains to be determined.

The risk of cerebral palsy, the commonest physical disability of children in western Europe, is higher in infants of very low birthweight (VLBW)—those born weighing less than 1500 g—and those from multiple pregnancies than in infants of normal birthweight. An increasing proportion of infants from both of these groups survive into childhood. This paper describes changes in the frequency and distribution of cerebral palsy by sex and neurological subtype in infants with a birthweight below 1000 g and 1000–1499 g in the period 1980–96. A group of 16 European centres, Surveillance of Cerebral Palsy in Europe, agreed a standard definition of cerebral palsy and inclusion and exclusion criteria. Data for children with cerebral palsy born in the years 1980–96 were pooled. The data were analysed to describe the distribution and prevalence of cerebral palsy in VLBW infants. Prevalence trends were expressed as both per 1000 livebirths and per 1000 neonatal survivors. There were 1575 VLBW infants born with cerebral palsy; 414 (26%) were of birthweight less than 1000 g and 317 (20%) were from multiple pregnancies. 1426 (94%) had spastic cerebral palsy, which was unilateral (hemiplegic) in 336 (24%). The birth prevalence fell from 60·6 (99%CI 37·8–91·4) per 1000 liveborn VLBW infants in 1980 to 39·5 (28·6–53·0) per 1000 VLBW infants in 1996. This decline was related to a reduction in the frequency of bilateral spastic cerebral palsy among infants of birthweight 1000–1499 g. The frequency of cerebral palsy was higher in male than female babies in the group of birthweight 1000–1499 g (61·0 [53·8–68.·2] vs 49.5 [42·8–56·2] per 1000 livebirths; p=0·0025) but not in the group of birthweight below 1000 g. These data from a large population base provide evidence that the prevalence of cerebral palsy in children of birthweight less than 1500 g has fallen, which has important implications for parents, health services, and society.

Social deprivation is associated with higher rates of preterm birth and subsequent infant mortality. Our objective was to identify risk factors for preterm birth in the UK's largest maternity unit, with a particular focus on social deprivation, and related factors. Retrospective cohort study of 39,873 women in Liverpool, UK, from 2002-2008. Singleton pregnancies were stratified into uncomplicated low risk pregnancies and a high risk group complicated by medical problems. Multiple logistic regression, and generalized additive models were used to explore the effect of covariates including area deprivation, smoking status, BMI, parity and ethnicity on the risk of preterm birth (34⁺⁰ weeks). In the low risk group, preterm birth rates increased with deprivation, reaching 1.6% (CI₉₅ 1.4 to 1.8) in the most deprived quintile; the unadjusted odds ratio comparing an individual in the most deprived quintile, to one in the least deprived quintile was 1.5 (CI₉₅ 1.2 to 1.9). Being underweight and smoking were both independently associated with preterm birth in the low risk group, and adjusting for these factors explained the association between deprivation and preterm birth. Preterm birth was five times more likely in the high risk group (RR 4.8 CI₉₅ 4.3 to 5.4), and there was no significant relationship with deprivation. Deprivation has significant impact on preterm birth rates in low risk women. The relationship between low socio-economic status and preterm births appears to be related to low maternal weight and smoking in more deprived groups.

Background Microbiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and CRC risk is lacking. Methods A matched case–control study (incident CRC cases and up to 5 matched controls) was conducted in the Clinical Practice Research Datalink (CPRD; 1989–2012). The CRPD is validated as 92% and 99% sensitive and specific for CRC detection (98% PPV). Antibiotic exposure [categorical and continuous terms (spline)] was investigated for risk pattern, stratified by tumor location, using conditional logistic regression and adjusting for known confounders. Results In total, 28,980 CRC cases and 137,077 controls were identified. Oral antibiotic use increased risk of colon cancer in a dose-dependent fashion (Ptrend < 0.001), but effects differed by anatomic location. Colon cancer risk was greatest in the proximal colon and with antibiotics with anti-anaerobic activity (Figure 1). In contrast, an inverse association was detected between antibiotic use and rectal cancers (Ptrend = 0.003), particularly with length of antibiotic exposure >60 days (adjusted odds ratio [AOR], 0.85, 95% CI 0.79–0.93) when compared with no antibiotic exposure. Nonlinearity models showed significantly increased colon cancer risk after minimal antibiotic use, but decreased rectum cancer risk with cumulative use of over 30 days (Figure 2). Penicillins, particularly ampicillin/amoxicillin, increased risk of colon cancer (AOR,1.09, [1.05–1.13]) whereas tetracyclines reduced risk for rectal cancer (AOR, 0.90, [0.84–0.97]). Significant interactions were detected between antibiotic use and tumor location (colon vs. rectum, Pinteraction < 0.001). The antibiotic-cancer association was found for antibiotic exposure occurring >10 years before diagnosis (AOR, 1.17, [1.06–1.31]). Conclusion We conclude that oral antibiotic use associates with increased colon cancer risk, particularly in the right colon, but a reduced risk for rectal cancer. This effect heterogeneity suggests unabsorbed antibiotics impact gut microbiota in the right colon to enhance carcinogenesis whereas antibiotic anti-inflammatory or anti-proliferative actions may yield an inverse effect on carcinogenesis in the rectum. Disclosures Sara E. Cosgrove, MD, MS, Basilea: Consultant; Theravance: Consultant.

Aim  To report the prevalence, clinical associations, and trends over time of oromotor dysfunction and communication impairments in children with cerebral palsy (CP). Method  Multiple sources of ascertainment were used and children followed up with a standardized assessment including motor speech problems, swallowing/chewing difficulties, excessive drooling, and communication impairments at age 5 years. Results  A total of 1357 children born between 1980 and 2001 were studied (781 males, 576 females; median age 5y 11mo, interquartile range 3–9y; unilateral spastic CP, n=447; bilateral spastic CP, n=496; other, n=112; Gross Motor Function Classification System [GMFCS] level: I, 181; II, 563; III, 123; IV, 82; IV, 276). Of those with ‘early‐onset’ CP (n=1268), 36% had motor speech problems, 21% had swallowing/chewing difficulties, 22% had excessive drooling, and 42% had communication impairments (excluding articulation defects). All impairments were significantly related to poorer gross motor function and intellectual impairment. In addition, motor speech problems were related to clinical subtype; swallowing/chewing problems and communication impairments to early mortality; and communication impairments to the presence of seizures. Of those with CP in GMFCS levels IV to V, a significant proportion showed a decline in the rate of motor speech impairment (p=0.008) and excessive drooling (p=0.009) over time. Interpretation  These impairments are common in children with CP and are associated with poorer gross motor function and intellectual impairment.

Fetal death in a twin conception during second and third trimester is associated with increased risk of cerebral injury in the surviving twin. The aim of this study is to test the hypothesis that even early fetal losses as a ‘vanishing’ twin may be associated with an increased risk of cerebral impairment in the surviving twin. The study population comprised 362 pregnant women attending Liverpool Women's Hospital recruited between 1999 and 2001. Women were classified according to the first ultrasound scan into 3 groups: vanishing twin, twin and singleton. The vanishing twin group was further subdivided into ‘definite’ and ‘probable’. Children from these pregnancies were assessed at 1 year of age for their development and neurological function using the Griffiths Mental and Developmental Scales and Optimality score. Children from 229 pregnancies (63.2%) attended the assessment. Information on children from a further 21 (5.8%) pregnancies was obtained through a review of hospital records. Cerebral impairment was found in 2 children from the vanishing twin group, 2 from the twin group and none from the singleton group. When cases with definite vanishing twin are considered there is a significant difference between the vanishing twin and singleton group (relative risk 6.1; 95% confidence interval 1.5–8.3; p = .03). An additional study with an increased sample size would enable a more robust conclusion.

BackgroundMicrobiome dysbiosis predisposes to colorectal cancer (CRC), but a population-based study of oral antibiotic exposure and risk patterns is lacking.ObjectiveTo assess the association between oral antibiotic use and CRC risk.DesignA matched case–control study (incident CRC cases and up to five matched controls) was performed using the Clinical Practice Research Datalink from 1989 to 2012.Results28 980 CRC cases and 137 077 controls were identified. Oral antibiotic use was associated with CRC risk, but effects differed by anatomical location. Antibiotic use increased the risk of colon cancer in a dose-dependent fashion (ptrend <0.001). The risk was observed after minimal use, and was greatest in the proximal colon and with antibiotics with anti-anaerobic activity. In contrast, an inverse association was detected between antibiotic use and rectal cancers (ptrend=0.003), particularly with length of antibiotic exposure >60 days (adjusted OR (aOR), 0.85, 95% CI 0.79 to 0.93) as compared with no antibiotic exposure. Penicillins, particularly ampicillin/amoxicillin increased the risk of colon cancer (aOR=1.09 (1.05 to 1.13)), whereas tetracyclines reduced the risk of rectal cancer (aOR=0.90 (0.84 to 0.97)). Significant interactions were detected between antibiotic use and tumour location (colon vs rectum, pinteraction<0.001; proximal colon versus distal colon, pinteraction=0.019). The antibiotic–cancer association was found for antibiotic exposure occurring >10 years before diagnosis (aOR=1.17 (1.06 to 1.31)).ConclusionOral antibiotic use is associated with an increased risk of colon cancer but a reduced risk of rectal cancer. This effect heterogeneity may suggest differences in gut microbiota and carcinogenesis mechanisms along the lower intestinal tract.

Early loss of one fetus in a multiple gestation as a ‘vanishing’ twin is a well recognized phenomenon. It is uncertain whether this has an impact on the development of the surviving co-twin. The aim of this study is to compare the development of singletons, twins and the surviving co-twins of a vanishing twin. The 324 children born to 229 women who were recruited into the study between 1999 and 2001 formed the study population. Children were assessed at 1 year of age with Griffiths Mental and Developmental Scales. A neurological examination was performed using an optimality score to exclude those with severe neurodisability. Three hundred and five children (92 singletons, 180 twins and 33 survivors with a vanishing twin) were included. The sub- and general quotient scores in singletons and surviving co-twins of a vanishing twin did not differ significantly. Twins had significantly lower scores than singletons in all areas of development and were more likely to be born early with lower birthweights. Following adjustment for gestation and birthweight, the difference between the two groups was nullified suggesting that the slower development of twins is related to their prematurity and lower birthweight.

Multiple births (twins or higher order multiples) are increasing in developed countries and may present higher risk for cerebral palsy (CP). However, few studies can reliably investigate trends over time because these outcomes are relatively rare.ObjectiveWe pooled data from European CP registers to investigate CP birth prevalence and its trends among single and multiple births born between 1990 and 2008.DesignPopulation cohort study.Setting12 population-based registers from the Surveillance of Cerebral Palsy in Europe collaboration.Participants4 446 125 single and multiple live births, of whom 8416 (0.19%) had CP of prenatal or perinatal origin.Main outcomesCP diagnosis ascertained in childhood using harmonised methods; CP subtype; Motor impairment severity among CP cases.ResultsThe rate of multiple births increased from 1990. Multiples displayed higher risk for CP (RR=4.27, 95% CI 4.00 to 4.57). For singletons and multiples alike, risk for CP was higher among births of lower gestational age (GA) or birth weight (BW). However, CP birth prevalence declined significantly among very preterm (<32 weeks) and very low BW (<1500 g) multiples. Singletons and multiples with CP displayed similar severity of motor impairment.ConclusionsBetween 1990 and 2008, CP birth prevalence decreased steadily among multiples with low GA or BW. Furthermore, multiples with CP display similar profiles of severe motor impairment compared with CP singletons. Improvements in management of preterm birth since the 1990s may also have been responsible for providing better prospects for multiples.