New definition of small for gestational age based on fetal growth potential

Accurate definition of small for gestational age (SGA) is essential for antenatal as well as postnatal care. SGA is associated with significant antenatal and postnatal pathology. The term, however, includes constitutional smallness, and it is essential to adjust for physiological variation in order to identify those babies who are pathologically small. Maternal height, weight, parity, ethnic origin and the baby's gender have all been found to be significantly associated with normal variation in birth weight. These variables need to be adjusted for to calculate the true growth potential, which can be represented as individually customized fetal growth curves and birth weight percentiles (www.gestation.net). This method for calculating growth potential has been validated in a number of international studies. 'Customized SGA' defines neonates with intrauterine growth restriction, while 'small-normal' does not represent increased risk. Currently, coefficients are being developed for more ethnic groups, to broaden the international applicability of individualized standards. Work is also underway to incorporate the customized birth weight percentile as the starting point of infant growth curves.     

Maternal influenza immunization and reduced likelihood of prematurity and small for gestational age births: a retrospective cohort study

Background

Infections during pregnancy have the potential to adversely impact birth outcomes. We evaluated the association between receipt of inactivated influenza vaccine during pregnancy and prematurity and small for gestational age (SGA) births.

Methods and Findings

We conducted a cohort analysis of surveillance data from the Georgia (United States) Pregnancy Risk Assessment Monitoring System. Among 4,326 live births between 1 June 2004 and 30 September 2006, maternal influenza vaccine information was available for 4,168 (96.3%). The primary intervention evaluated in this study was receipt of influenza vaccine during any trimester of pregnancy. The main outcome measures were prematurity (gestational age at birth <37 wk) and SGA (birth weight <10th percentile for gestational age). Infants who were born during the putative influenza season (1 October–31 May) and whose mothers were vaccinated against influenza during pregnancy were less likely to be premature compared to infants of unvaccinated mothers born in the same period (adjusted odds ratio [OR] = 0.60; 95% CI, 0.38–0.94). The magnitude of association between maternal influenza vaccine receipt and reduced likelihood of prematurity increased during the period of at least local influenza activity (adjusted OR = 0.44; 95% CI, 0.26–0.73) and was greatest during the widespread influenza activity period (adjusted OR = 0.28; 95% CI, 0.11–0.74). Compared with newborns of unvaccinated women, newborns of vaccinated mothers had 69% lower odds of being SGA (adjusted OR = 0.31; 95% CI, 0.13–0.75) during the period of widespread influenza activity. The adjusted and unadjusted ORs were not significant for the pre-influenza activity period.

Conclusions

This study demonstrates an association between immunization with the inactivated influenza vaccine during pregnancy and reduced likelihood of prematurity during local, regional, and widespread influenza activity periods. However, no associations were found for the pre-influenza activity period. Moreover, during the period of widespread influenza activity there was an association between maternal receipt of influenza vaccine and reduced likelihood of SGA birth. Please see later in the article for the Editors'' Summary     

Risk for schizophrenia and schizophrenia-like psychosis among patients with epilepsy: population based cohort study

Objectives To investigate whether age at onset of epilepsy, type of epilepsy, family history of psychosis, or family history of epilepsy affect the risk of schizophrenia or schizophrenia-like psychosis among patients with epilepsy.Design Comparison of population based data.Setting Danish longitudinal registers.Subjects The cohort comprised 2.27 million people.Main outcome measures Epilepsy, psychosis, personal birth data.Results We found an increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20 to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a history of epilepsy. The effect of epilepsy was the same in men and in women and increased with age. Family history of psychosis and a family history of epilepsy were significant risk factors for schizophrenia and schizophrenia-like psychosis, and the effect of epilepsy, both in cases and families, was greater among people with no family history of psychosis. In addition, the increased risk for schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy but increased with increasing number of admissions to hospital and, particularly, was significantly greater for people first admitted for epilepsy at later ages.Conclusions There is a strong association between epilepsy and schizophrenia or schizophrenia-like psychosis. The two conditions may share common genetic or environmental causes.     

Sequelae of syndrome X in children born small for gestational age

OBJECTIVE: Low birth weight is associated with the presence of syndrome X in adults. We studied the components of this syndrome in prepubertal children born SGA (small for gestational age) and children born AGA (appropriate for gestational age). METHODS: Twenty-nine SGA children, age (mean +/- SD) 9.1 +/- 1.1 years and 24 AGA children, age 9.0 +/- 1.1 years were studied. Fasting serum lipid concentrations were determined. A hyperinsulinemic euglycemic clamp was performed to measure insulin sensitivity. Ambulatory monitoring was performed to obtain 24-hour recordings of blood pressure. RESULTS: Prepubertal SGA children are less insulin sensitive and have a higher nighttime systolic blood pressure (SBP) after correction for BMI than children born AGA. No differences were found in lipid concentrations between the 2 groups. CONCLUSIONS: Not all components of syndrome X can yet be found in 9-year-old children born SGA; follow-up of this cohort is required.     

Metabolic aspects of insulin resistance in individuals born small for gestational age

Numerous studies have shown an association between low weight at birth and being born small for gestational age (SGA) on the one hand and risk of developing insulin resistance and type 2 diabetes on the other. Our studies in twins have indicated a non-genetic age-dependent origin of insulin resistance and type 2 diabetes associated with being born SGA. In order to gain insight into the molecular metabolic defects and mechanisms linking SGA with insulin resistance and type 2 diabetes, we performed a series of experiments in young and elderly twins, and, in particular, in young men (aged 19-23 years) with a weight at birth at term in the lowest 10th percentile with no family history of diabetes. The control group included age-matched men with birth weights at term in the upper normal range. While body mass index and waist-to-hip ratios were similar in the individuals born SGA and controls, dual-energy X-ray absorptiometry studies documented a higher degree of abdominal obesity in the men who had a low weight at birth. Using the gold standard hyperinsulinaemic-euglycaemic clamp technique combined with glucose tracers and studies of forearm glucose uptake, we found an impairment of insulin-stimulated glycolytic flux and reduced forearm (muscle) glucose uptake in the face of normal whole-body glucose uptake. In addition, we found a significantly decreased insulin secretion rate during oral glucose ingestion after correction for insulin action (disposition index), a paradoxical enhanced insulin suppression of hepatic glucose production and lower fasting plasma glycerol levels, suggesting impaired lipolysis. Finally, analysis of skeletal muscle biopsies showed reduced muscle expression of several key proteins involved in insulin signalling and glucose transport, including protein kinase C-zeta, the two subunits of phosphoinositol 3-kinase (i.e., p85alpha and p110beta) and the insulin-sensitive glucose transporter, Glut-4, in individuals of low birth weight. In conclusion, being born SGA and of low birth weight is associated with type 2 diabetes in a non-genetic manner, and programming of muscle insulin action and signalling represents an early mechanism responsible for this association.     

Early onset of renal oxidative stress in small for gestational age newborn pigs

Objective: Oxidative stress, a common feature in cardiovascular and renal disease is associated with the causes and consequences of fetal growth restriction. Hence, renal redox status is likely an early determinant of morbidity in small-for-gestational-age (SGA) infants. In this study, we examined renal oxidative stress in naturally-farrowed SGA newborn pigs.

Methods: We studied SGA newborn pigs with 52% less body weight and 59% higher brain/liver weight ratio compared with their appropriate-for-gestational-age (AGA) counterparts.

Results: The kidneys of the SGA newborn pigs weighed 56% less than the AGA group. The glomerular cross-sectional area was also smaller in the SGA group. SGA newborn pigs exhibited increased renal lipid peroxidation, reduced kidney and urine total antioxidant capacity, and increased renal nitrotyrosine immunostaining. Whereas the protein expression level of NADPH oxidase (NOX)2 was unchanged, NOX4 expression was significantly higher in SGA kidneys. The level of serum potassium was lower, but serum sodium and creatinine were similar in SGA compared with AGA newborn pigs. The serum concentrations of C‐reactive protein and NGAL, the biomarkers of inflammation and early acute kidney injury were significantly elevated in the SGA group.

Conclusion: Early induction of oxidative stress may contribute to the onset of kidney injury in growth-restricted infants.     

Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study

Objective To examine the effect of cardiovascular risk factors before pregnancy on risk of pre-eclampsia.Design Population based prospective study.Setting Linkage between a Norwegian population based study (Nord-Trøndelag health study, HUNT-2) and Norway''s medical birth registry.Participants 3494 women who gave birth after participating in the Nord-Trøndelag health study at baseline; of whom 133 (3.8%) delivered after a pre-eclamptic pregnancy.Main outcome measure Odds ratio of developing pre-eclampsia.Results After adjustment for smoking; previous pre-eclampsia; parity; maternal age, education, and socioeconomic position; and duration between baseline measurements and delivery, positive associations were found between prepregnancy serum levels of triglycerides, cholesterol, low density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and blood pressure and risk of pre-eclampsia. The odds ratio of developing pre-eclampsia for women with baseline systolic blood pressures greater than 130 mm Hg (highest fifth) was 7.3 (95% confidence interval 3.1 to 17.2) compared with women with systolic blood pressures less than 111 mm Hg (lowest fifth). Similar results were found for nulliparous and parous women. Women who used oral contraceptives at baseline had half the risk of pre-eclampsia compared with never or former users (0.5, 0.3 to 0.9).Conclusion Women with cardiovascular risk factors may be predisposed to pre-eclampsia.     

Onset of adolescent eating disorders: population based cohort study over 3 years

ObjectiveTo study the predictors of new eating disorders in an adolescent cohort.DesignCohort study over 3 years with six waves.SubjectsStudents, initially aged 14-15 years, from 44 secondary schools in the state of Victoria, Australia.ResultsAt the start of the study, 3.3% (29/888) of female subjects and 0.3% (2/811) of male subjects had partial syndromes of eating disorders. The rate of development of new eating disorder per 1000 person years of observation was 21.8 in female subjects and 6.0 in male subjects. Female subjects who dieted at a severe level were 18 times more likely to develop an eating disorder than those who did not diet, and female subjects who dieted at a moderate level were five times more likely to develop an eating disorder than those who did not diet. Psychiatric morbidity predicted the onset of eating disorder independently of dieting status so that those subjects in the highest morbidity category had an almost sevenfold increased risk of developing an eating disorder. After adjustment for earlier dieting and psychiatric morbidity, body mass index, extent of exercise, and sex were not predictive of new eating disorders.ConclusionsDieting is the most important predictor of new eating disorders. Differences in the incidence of eating disorders between sexes were largely accounted for by the high rates of earlier dieting and psychiatric morbidity in the female subjects. In adolescents, controlling weight by exercise rather than diet restriction seems to carry less risk of development of eating disorders.

Key messages

• Adolescent females who diet at a severe level are 18 times more likely to develop an eating disorder than those who do not diet, and those who diet at a moderate level are five times more likely to develop an eating disorder
• High levels of psychiatric morbidity in females increase the risk of developing eating disorders by sevenfold
• Around two thirds of new cases of eating disorder arise in females who have dieted moderately
• The predominance of eating disorders in females is largely explained by the higher rates of earlier dieting and psychiatric morbidity
• Daily exercise seems to be a less risky strategy for controlling weight in adolescents

     

Changing patterns of teenage pregnancy: population based study of small areas

ObjectivesTo measure the impact of socioeconomic deprivation on rates of teenage pregnancy and the extent of local variation in pregnancy rates in Scotland, and to examine how both have changed over time.Design Population study using routine data from hospital records, aggregated for small areas.Subjects Female teenagers resident in Scotland who were treated for pregnancy in an NHS hospital in either 1981-5 (62 338 teenagers) or 1991-5 (48 514) and who were aged 13-19 at the time of conception.Results From the 1980s to the 1990s pregnancy rates increased differentially according to levels of local deprivation, as measured by the Carstairs index. Among teenagers aged less than 18 the annual pregnancy rate increased in the most deprived areas (from 7.0 to 12.5 pregnancies per 1000 13-15 year olds and from 67.6 to 84.6 per 1000 16-17 year olds), but there was no change, on average, among teenagers in the most affluent areas (3.8 per 1000 13-15 year olds and 28.9 per 1000 16-17 year olds). Among 18-19 year olds the pregnancy rate decreased in the most affluent areas (from 60.0 to 46.3 per 1000) and increased in the most deprived areas (from 112.4 to 116.0 per 1000). The amount of local variation explained by deprivation more than doubled from the 1980s to the 1990s. The proportion of pregnancies resulting in a maternity was positively associated with level of deprivation, but the effect remained similar over time.Conclusion From the 1980s to the 1990s the difference in rates of teenage pregnancy between more affluent and more deprived areas widened. This has implications for allocating resources to achieve government targets and points to important social processes behind the general increase in the number of teenage pregnancies in Scotland.

What is already known on this topic

Rates of teenage pregnancy are considerably higher in the United Kingdom than in other western European countriesIn the United Kingdom rates of teenage pregnancy are known to be higher in areas of greater socioeconomic deprivation, although local variation may also reflect differential access to family planning services

What this study adds

From 1981-5 to 1991-5 rates of teenage pregnancy in Scotland increased more rapidly in areas of greater socioeconomic deprivationIn the 1990s socioeconomic deprivation explained more than 50% of local variation in rates of teenage pregnancy, more than double the amount explained by it in the 1980s     

Incidence of myocardial infarction in elderly men being treated with antihypertensive drugs: population based cohort study.

OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: Malmŏ, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in Malmŏ during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.     

Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

ObjectivesTo evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer''s disease and dementia.DesignThree year population based cohort study.SettingKungsholmen cohort, Stockholm, Sweden.Participants1435 people aged 75-95 years without dementia.AssessmentsSingle question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.ResultsNone of the three instruments was sufficiently predictive of Alzheimer''s disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer''s disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.ConclusionThis three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.

What is already known on this topic

Alzheimer''s disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer''s disease and dementia

What this study adds

This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer''s disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer''s disease and dementia do not report problems with their memory three years before diagnosis     

Chemerin concentrations in infants born small for gestational age: correlations with triglycerides and parameters related to glucose homeostasis

Journal of Physiology and Biochemistry - Infants born small for gestational age (SGA) are known to have increased risk of developing several pathologies, including the metabolic syndrome, when they...