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1.  Impact of Scotland's Smoke-Free Legislation on Pregnancy Complications: Retrospective Cohort Study 
PLoS Medicine  2012;9(3):e1001175.
An analysis of pregnancy data for the whole of Scotland demonstrates a reduction in small-for-gestational-age births and preterm delivery since the introduction of legislation banning smoking in enclosed public spaces.
Background
Both active smoking and environmental tobacco smoke exposure are associated with pregnancy complications. In March 2006, Scotland implemented legislation prohibiting smoking in all wholly or partially enclosed public spaces. The aim of this study was to determine the impact of this legislation on preterm delivery and small for gestational age.
Methods and Findings
We conducted logistic regression analyses using national administrative pregnancy data covering the whole of Scotland. Of the two breakpoints tested, 1 January 2006 produced a better fit than the date when the legislation came into force (26 March 2006), suggesting an anticipatory effect. Among the 716,941 eligible women who conceived between August 1995 and February 2009 and subsequently delivered a live-born, singleton infant between 24 and 44 wk gestation, the prevalence of current smoking fell from 25.4% before legislation to 18.8% after legislation (p<0.001). Three months prior to the legislation, there were significant decreases in small for gestational age (−4.52%, 95% CI −8.28, −0.60, p = 0.024), overall preterm delivery (−11.72%, 95% CI −15.87, −7.35, p<0.001), and spontaneous preterm labour (−11.35%, 95% CI −17.20, −5.09, p = 0.001). In sub-group analyses, significant reductions were observed among both current and never smokers.
Conclusions
Reductions were observed in the risk of preterm delivery and small for gestational age 3 mo prior to the introduction of legislation, although the former reversed partially following the legislation. There is growing evidence of the potential for tobacco control legislation to have a positive impact on health.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The risks of smoking during pregnancy, both on mother and fetus, are well established: women who smoke during pregnancy are more likely to have a miscarriage. Smoking can cause placental problems, such as placental abruption, which can result in heavy bleeding during pregnancy, which is dangerous for both mother and baby. Other dangers of smoking during pregnancy include the baby being born too early (premature birth), the baby being below average weight (small for gestational age), birth defects, and infant death. Because of the serious damage to health caused by smoking, in 2005, under the auspices of the World Health Organization, countries adopted the Framework Convention on Tobacco Control to protect present and future generations from the devastating health, social, environmental, and economic consequences of tobacco consumption and exposure to tobacco smoke. Article 8 of the treaty obliges member states who have ratified the treaty—168 so far—to protect all people from exposure to tobacco smoke in indoor workplaces, public transport, and indoor public places. As a result, many countries around the world have banned smoking in public places.
Why Was This Study Done?
Scotland was the first country in the United Kingdom to ban smoking in public places, which was implemented as part of the Smoking, Health and Social Care (Scotland) Bill on 26 March 2006. Previous studies have shown that the introduction of the legislation led directly to a reduction in smoking and also a reduction in environmental tobacco smoke exposure in adults and children. Furthermore, the Scottish legislation has been accompanied by significant reductions in both cardiovascular and respiratory disease. Because of the known risks of smoking during pregnancy, the researchers wanted to investigate whether the change in policy on smoking in public places had positive benefits on the health of mothers and babies. They evaluated this by measuring the rates of preterm delivery and small for gestational age before and after the Scottish legislation went into effect.
What Did the Researchers Do and Find?
The researchers collected information on preterm delivery and small for gestational age in all single babies born live at 22–44 weeks gestation between 1 January 1996 and 31 December 2009 by using the Scottish Morbidity Record (SMR2), which collects relevant information on all women discharged from Scottish maternity hospitals, including maternal and infant characteristics and pregnancy complications. The researchers categorized preterm delivery into mild, moderate, and extreme depending on how much before 37 weeks the baby was born. They defined small for gestational age as the smallest 10% (below the 10th centile) for sex-specific birth weight at delivery, and very small for gestational age as the smallest 3% (below the 3rd centile), for all deliveries in Scotland over the study period. As some people may have stopped smoking in anticipation of the smoking ban, in their statistical model, the researchers included two possible breakpoints for the effect of the legislation—the actual date of implementation and 1 January 2006.
The researchers found that of the 716,968 pregnancies (the number eligible for inclusion in the study), 99.9% of women had their smoking status recorded, and among these 23.9% were current smokers, 57.6% never smokers, and 8.7% former smokers. However, following implementation of the legislation the researchers noted that there was a significant reduction in current smokers to 18.8%. In their statistical model, the researchers found that following 1 January 2006, there was a significant drop in overall preterm deliveries, which remained after adjustment for potential confounding factors. Likewise, there was a significant decrease in the number of infants born small, and very small, for gestational age after 1 January 2006. Furthermore, the researchers found that these significant reductions occurred in both mothers who smoked and those who had never smoked.
What Do These Findings Mean?
These findings suggest that the introduction of national, comprehensive smoke-free legislation in Scotland was associated with significant reductions in preterm delivery and babies being born small for gestational age. These findings are plausible and add to the growing evidence of the wide-ranging health benefits of smoke-free legislation, and support the adoption of such legislation in other countries that have yet to implement smoking bans.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001175.
More information is available on the World Health Organization's Framework Convention for Tobacco Control
More information on the Smoking, Health and Social Care (Scotland) Bill is available
The US Centers for Disease Control and Prevention has more information about the risks of smoking in pregnancy, as does the UK National Health Service's smokefree web page
NHS Health Scotland has a website that summarises all the studies to date evaluating the Scottish smoke-free legislation
doi:10.1371/journal.pmed.1001175
PMCID: PMC3295815  PMID: 22412353
2.  Birthweight Centile Charts for South Asian Infants Born in the UK 
Neonatology  2011;100(4):398-403.
Background
UK-born infants of South Asian ethnic origin are known to have lower birthweights than their White British counterparts. When plotted on currently used birthweight charts they can be misclassified as small for gestational age. Similarly, large for gestational age infants can be missed. This has important clinical implications in their management.
Objective
To create birthweight centile charts for the UK-born South Asian infants to identify true small and large for gestational age infants.
Methods
A retrospective cross-sectional analysis of infants born 1 January 2003 to 31 December 2006 was undertaken. The birthweights of the South Asian and White British infants were compared. The LMS method was used to construct centile charts for the South Asian infants.
Results
24,274 White British and 7,190 South Asian infants were included in the analysis. Overall, the South Asian males were 9–15% lighter than the White British males and the South Asian females were 9–13% lighter than the White British females. At term, the median birthweight for South Asian males was 329 g lower than that for White British males and for South Asian females 295 g less than the White British females.
Conclusion
There are significant differences in the birthweights of White British and UK-born South Asian infants. Hence the standard birthweight centile charts which were designed using the birthweight data of White British infants appear to misclassify a proportion of South Asian infants. Use of ethnic specific birthweight charts would allow better detection of truly growth-restricted and macrosomic South Asian infants.
doi:10.1159/000325916
PMCID: PMC3217051  PMID: 21791931
Birthweight; Centile; Ethnicity
3.  New birth weight reference standards customised to birth order and sex of babies from South India 
Background
The foetal growth standards for Indian children which are available today suffer due to methodological problems. These are, for example, not adhering to the WHO recommendation to base gestational age on the number of completed weeks and secondly, not excluding mothers with risk factors. This study has addressed both the above issues and in addition provides birthweight reference ranges with regard to sex of the baby and maternal parity.
Methods
Data from the labour room register from 1996 to 2010 was obtained. A rotational sampling scheme was used i.e. the 12 months of the year were divided into 4 quadrants. All deliveries in January were considered to represent the first quadrant. Similarly all deliveries in April, July and October were considered to represent 2nd, 3rd and 4th quadrants. In each successive year different months were included in each quadrant. Only those mothers aged 20–39 years and delivered between 24 to 42 weeks gestational age were considered. Those mothers with obstetric risk factors were excluded. The reference standards were fitted using the Generalized Additive Models for Location Scale and Shape (GAMLSS) method for Box – Cox t distribution with cubic spline smoothing.
Results
There were 41,055 deliveries considered. When women with risk factors were excluded 19,501 deliveries could be included in the final analysis. The male babies of term firstborn were found to be 45 g heavier than female babies. The mean birthweights were 2934 g and 2889.5 g respectively. Similarly, among the preterm babies, the first born male babies weighed 152 g more than the female babies. The mean birthweights were 1996 g and 1844 g respectively.
In the case of later born babies, the term male babies weighed 116grams more than the females. The mean birth weights were 3085 grams and 2969 grams respectively. When considering later born preterm babies, the males outweighed the female babies by 111 grams. The mean birthweights were 2089 grams and 1978 grams respectively. There was a substantial agreement range from k=.883, (p<.01) to k=.943, (p<.01) between adjusted and unadjusted percentile classification for the subgroups of male and female babies and first born and later born ones.
Birth weight charts were adjusted for maternal height using regression methods. The birth weight charts for the first born and later born babies were regrouped into 4 categories, including male and female sexes of the babies. Reference ranges were acquired both for term and preterm babies.
With economic reforms, one expects improvement in birthweights. The mean (sd) birthweights of the year 1996 was 2846 (562) as compared to year 2010 (15 years later) which was 2907 (571). There was only a difference of 61 grams in the mean birthweights over one and a half decade.
Conclusion
New standards are presented from a large number of deliveries over 15 years, customised to the maternal height, from a south Indian tertiary hospital. Reference ranges are made available separately for first born or later born babies, for male and female sexes and for term and preterm babies.
doi:10.1186/1471-2393-13-38
PMCID: PMC3583685  PMID: 23409828
Reference; Foetal growth; Birth weight; Gestational age; Preterm; Modelling; Box–Cox t; Cubic spline smoothing
4.  The association of maternal ACE A11860G with small for gestational age babies is modulated by the environment and by fetal sex: a multicentre prospective case–control study 
Molecular Human Reproduction  2013;19(9):618-627.
We aimed to determine whether the ACE A11860G genotype is associated with small for gestational age babies (SGA) and to determine whether the association is affected by environmental factors and fetal sex. Overall, 3234 healthy nulliparous women with singleton pregnancies, their partners and babies were prospectively recruited in Adelaide, Australia and Auckland, New Zealand. Data analyses were confined to 2121 Caucasian parent–infant trios, among which 216 were pregnancies with SGA infants and 1185 were uncomplicated pregnancies. Women with the ACE A11860G GG genotype in the combined and Adelaide cohorts had increased risk for SGA [odds ratios (OR) 1.5, 95% confidence interval (CI) 1.1–2.1 and OR 2.0, 95% CI 1.3–3.3, respectively) and delivered lighter babies (P = 0.02; P = 0.007, respectively) compared with those with AA/AG genotypes. The maternal ACE A11860G GG genotype was associated with higher maternal plasma ACE concentration at 15 weeks' gestation than AA/AG genotypes (P < 0.001). When the Adelaide cohort was stratified by maternal socio-economic index (SEI) and pre-pregnancy green leafy vegetable intake, the ACE A11860G GG genotype was only associated with an increased risk for SGA (OR 4.9, 95% CI 1.8–13.4 and OR 3.3, 95% CI 1.6–7.0, respectively) and a reduction in customized birthweight centile (P = 0.006 and P = 0.03) if superimposed on maternal SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day. Furthermore, the associations of maternal ACE A11860G with customized birthweight centile observed among Adelaide women with SEI <34 or pre-pregnancy green leafy vegetable intake <1 serve/day were female specific. The current study identified a novel association of maternal ACE A11860G with SGA. More interestingly, this association was modified by environmental factors and fetal sex, suggesting ACE A11860G–environment–fetal sex interactions.
Trial Registry Name: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.
URL: http://www.anzctr.org.au.
Registration number: ACTRN12607000551493.
doi:10.1093/molehr/gat029
PMCID: PMC3749805  PMID: 23615722
ACE A11860G; small for gestational age; socio-economic index; pre-pregnancy green leafy vegetable intake; fetal sex
5.  Customised birthweight standards accurately predict perinatal morbidity 
Objective
Fetal growth restriction is associated with adverse perinatal outcome but is often not recognised antenatally, and low birthweight centiles based on population norms are used as a proxy instead. This study compared the association between neonatal morbidity and fetal growth status at birth as determined by customised birthweight centiles and currently used centiles based on population standards.
Design
Retrospective cohort study.
Setting
Referral hospital, Barcelona, Spain.
Patients
A cohort of 13 661 non‐malformed singleton deliveries.
Interventions
Both population‐based and customised standards for birth weight were applied to the study cohort. Customised weight centiles were calculated by adjusting for maternal height, booking weight, parity, ethnic origin, gestational age at delivery and fetal sex.
Main outcome measures
Newborn morbidity and perinatal death.
Results
The association between smallness for gestational age (SGA) and perinatal morbidity was stronger when birthweight limits were customised, and resulted in an additional 4.1% (n = 565) neonates being classified as SGA. Compared with non‐SGA neonates, this newly identified group had an increased risk of perinatal mortality (OR 3.2; 95% CI 1.6 to 6.2), neurological morbidity (OR 3.2; 95% CI 1.7 to 6.1) and non‐neurological morbidity (OR 8; 95% CI 4.8 to 13.6).
Conclusion
Customised standards improve the prediction of adverse neonatal outcome. The association between SGA and adverse outcome is independent of the gestational age at delivery.
doi:10.1136/adc.2006.108621
PMCID: PMC2675427  PMID: 17251224
fetal growth restriction; neonatal morbidity; birthweight
6.  Normal ranges of heart rate and respiratory rate in children from birth to 18 years: a systematic review of observational studies 
Lancet  2011;377(9770):1011-1018.
Summary
Background
Although heart rate and respiratory rate are routinely measured in children in acute settings, current reference ranges are not evidence-based. The aim of this study is to derive new centile charts for heart rate and respiratory rate using systematic review data from existing studies, and to compare these with existing international ranges.
Methods
We searched MEDLINE, EMBASE, and CINAHL to April 2009, and reference lists to identify studies which had measured heart rate and/or respiratory rate in normal children between birth and 18 years of age. We used a non-parametric kernel regression method to create centile charts for heart rate and respiratory rate with respect to age. We compared existing reference ranges with those derived from the centile charts.
Findings
We included 69 studies, 59 of which provided data on the heart rate of 143,346 children, and 20 on the respiratory rate of 3,881 children. Our new centile charts demonstrate the decline in respiratory rate from birth to early adolescence, with the steepest decline apparent in infants under two years; decreasing from a median of 44 breaths/minutes at birth to 26 breaths/minute at the age of two. The heart rate centile chart demonstrates a small peak at one month of age. The median heart rate increases from 127 beats/minute at birth to a maximum of 145 beats/minute at approximately one month of age, before decreasing to 113 beats/minute by the age of two. Comparison of the centile charts with existing published reference ranges for heart rate and respiratory rate show marked disagreement with the centile charts, with limits from published ranges frequently exceeding the 99th and 1st centiles, or crossing the median.
Interpretation
Our review shows that existing international guidelines for heart rate and respiratory rate in children are not based on evidence. We have created new centile charts based on a systematic review of studies which have measured these vital signs in normal children. Clinical and resuscitation guidelines should be updated in the light of these evidence-based reference ranges.
Funding
Research funded by the National Institute for Health Research programme grant for applied research ‘Development and implementation of new diagnostic processes and technologies in primary care’. SF was funded by the Engineering and Physical Sciences Research Council and the National Institute for Health Research Biomedical Research Centre Programme.
doi:10.1016/S0140-6736(10)62226-X
PMCID: PMC3789232  PMID: 21411136
children; heart rate; respiratory rate; normal; centiles; ranges
7.  Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth 
PLoS Medicine  2010;7(5):e1000284.
Ken Ong and colleagues genotyped children from the ALSPAC birth cohort and showed an association between greater early infancy gains in weight and length and genetic markers for adult obesity risk.
Background
Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity.
Methods and Findings
Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an “obesity-risk-allele score” comprising the total number of risk alleles (range: 2–15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00–0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023–0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004–0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032–0.284) and with reduced risk of early infancy failure to thrive (odds ratio  = 0.92 per allele; 0.86–0.98; p = 0.009).
Conclusions
The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The proportion of overweight and obese children is increasing across the globe. In the US, the Surgeon General estimates that, compared with 1980, twice as many children and three times the number of adolescents are now overweight. Worldwide, 22 million children under five years old are considered by the World Health Organization to be overweight.
Being overweight or obese in childhood is associated with poor physical and mental health. In addition, childhood obesity is considered a major risk factor for adult obesity, which is itself a major risk factor for cancer, heart disease, diabetes, osteoarthritis, and other chronic conditions.
The most commonly used measure of whether an adult is a healthy weight is body mass index (BMI), defined as weight in kilograms/(height in metres)2. However, adult categories of obese (>30) and overweight (>25) BMI are not directly applicable to children, whose BMI naturally varies as they grow. BMI can be used to screen children for being overweight and or obese but a diagnosis requires further information.
Why Was This Study Done?
As the numbers of obese and overweight children increase, a corresponding rise in future numbers of overweight and obese adults is also expected. This in turn is expected to lead to an increasing incidence of poor health. As a result, there is great interest among health professionals in possible pathways between childhood and adult obesity. It has been proposed that certain periods in childhood may be critical for the development of obesity.
In the last few years, ten genetic variants have been found to be more common in overweight or obese adults. Eight of these have also been linked to childhood BMI and/or obesity. The authors wanted to identify the timing of childhood weight changes that may be associated with adult obesity. Knowledge of obesity risk genetic variants gave them an opportunity to do so now, without following a set of children to adulthood.
What Did the Researchers Do and Find?
The authors analysed data gathered from a subset of 7,146 singleton white European children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) study, which is investigating associations between genetics, lifestyle, and health outcomes for a group of children in Bristol whose due date of birth fell between April 1991 and December 1992. They used knowledge of the children's genetic makeup to find associations between an obesity risk allele score—a measure of how many of the obesity risk genetic variants a child possessed—and the children's weight, height, BMI, levels of body fat (at nine years old), and rate of weight gain, up to age 11 years.
They found that, at birth, children with a higher obesity risk allele score were not any heavier, but in the immediate postnatal period they were less likely to be in the bottom 5% of the population for weight gain (adjusted for birthweight), often termed “failure to thrive.” At six weeks of age, children with a higher obesity risk allele score tended to be longer and heavier, even allowing for weight at birth.
After six weeks of age, the obesity risk allele score was not associated with any further increase in length/height, but it was associated with a more rapid weight gain between birth and age 11 years. BMI is derived from height and weight measurements, and the association between the obesity risk allele score and BMI was weak between birth and age three-and-a-half years, but after that age the association with BMI increased rapidly. By age nine, children with a higher obesity risk allele score tended to be heavier and taller, with more fat on their bodies.
What Do These Findings Mean?
The combined obesity allele risk score is associated with higher rates of weight gain and adult obesity, and so the authors conclude that weight gain and growth even in the first few weeks after birth may be the beginning of a pathway of greater adult obesity risk.
A study that tracks a population over time can find associations but it cannot show cause and effect. In addition, only a relatively small proportion (1.7%) of the variation in BMI at nine years of age is explained by the obesity risk allele score.
The authors' method of finding associations between childhood events and adult outcomes via genetic markers of risk of disease as an adult has a significant advantage: the authors did not have to follow the children themselves to adulthood, so their findings are more likely to be relevant to current populations. Despite this, this research does not yield advice for parents how to reduce their children's obesity risk. It does suggest that “failure to thrive” in the first six weeks of life is not simply due to a lack of provision of food by the baby's caregiver but that genetic factors also contribute to early weight gain and growth.
The study looked at the combined obesity risk allele score and the authors did not attempt to identify which individual alleles have greater or weaker associations with weight gain and overweight or obesity. This would require further research based on far larger numbers of babies and children. The findings may also not be relevant to children in other types of setting because of the effects of different nutrition and lifestyles.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000284.
Further information is available on the ALSPAC study
The UK National Health Service and other partners provide guidance on establishing a healthy lifestyle for children and families in their Change4Life programme
The International Obesity Taskforce is a global network of expertise and the advocacy arm of the International Association for the Study of Obesity. It works with the World Health Organization, other NGOs, and stakeholders and provides information on overweight and obesity
The Centers for Disease Control and Prevention (CDC) in the US provide guidance and tips on maintaining a healthy weight, including BMI calculators in both metric and Imperial measurements for both adults and children. They also provide BMI growth charts for boys and girls showing how healthy ranges vary for each sex at with age
The Royal College of Paediatrics and Child Health provides growth charts for weight and length/height from birth to age 4 years that are based on WHO 2006 growth standards and have been adapted for use in the UK
The CDC Web site provides information on overweight and obesity in adults and children, including definitions, causes, and data
The CDC also provide information on the role of genes in causing obesity.
The World Health Organization publishes a fact sheet on obesity, overweight and weight management, including links to childhood overweight and obesity
Wikipedia includes an article on childhood obesity (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1000284
PMCID: PMC2876048  PMID: 20520848
8.  No improvement in socioeconomic inequalities in birthweight and preterm birth over four decades: a population-based cohort study 
BMC Public Health  2013;13:345.
Background
Birthweight and gestational age are associated with socioeconomic deprivation, but the evidence in relation to temporal changes in these associations is sparse. We investigated changes in the associations between socioeconomic status (SES) and birthweight and gestational age in Newcastle upon Tyne, North of England, during 1961–2000.
Methods
We used population-based data from hospital neonatal records on all singleton births to mothers resident in Newcastle (births with complete covariate information n = 113,182). We used linear regression to analyse the associations between neighbourhood SES and birthweight over the entire 40-year period and by decade, and logistic regression for associations with low birthweight (LBW) and preterm birth, adjusting for potential confounders.
Results
There was a significant interaction between SES and decade of birth for birthweight (p = 0.028) and preterm birth (p < 0.001). Socioeconomic gradients were similar in each decade for birthweight outcomes, but for preterm birth, socioeconomic disparities were more evident in the later decades [for 1961–70, odds ratio (OR) was 1.1, 95% CI 0.9, 1.3, for the most deprived versus the least deprived quartile, while for 1991–2000, the corresponding OR was 1.5, 95% CI 1.3, 1.7]. In each decade, there was a significant decrease in birthweight adjusted for gestational age for the most deprived compared to the least deprived SES group [1961–1970: –113.4 g (95% CI–133.0, –93.8); 1991–2000: –97.5 g (95% CI–113.0, –82.0)], while there was a significant increase in birthweight in each SES group over time.
Conclusions
Socioeconomic inequalities did not narrow over the four decades for birthweight and widened for preterm birth. Mean birthweight adjusted for gestational age increased in all socioeconomic groups, suggesting an overall increase in fetal growth.
doi:10.1186/1471-2458-13-345
PMCID: PMC3651338  PMID: 23587186
Low birthweight; Preterm birth; Socioeconomic status; Townsend deprivation score; Temporal trends
9.  Primary Prevention of Gestational Diabetes Mellitus and Large-for-Gestational-Age Newborns by Lifestyle Counseling: A Cluster-Randomized Controlled Trial 
PLoS Medicine  2011;8(5):e1001036.
In a cluster-randomized trial, Riitta Luoto and colleagues find that counseling on diet and activity can reduce the birthweight of babies born to women at risk of developing gestational diabetes mellitus (GDM), but fail to find an effect on GDM.
Background
Our objective was to examine whether gestational diabetes mellitus (GDM) or newborns' high birthweight can be prevented by lifestyle counseling in pregnant women at high risk of GDM.
Method and Findings
We conducted a cluster-randomized trial, the NELLI study, in 14 municipalities in Finland, where 2,271 women were screened by oral glucose tolerance test (OGTT) at 8–12 wk gestation. Euglycemic (n = 399) women with at least one GDM risk factor (body mass index [BMI] ≥25 kg/m2, glucose intolerance or newborn's macrosomia (≥4,500 g) in any earlier pregnancy, family history of diabetes, age ≥40 y) were included. The intervention included individual intensified counseling on physical activity and diet and weight gain at five antenatal visits. Primary outcomes were incidence of GDM as assessed by OGTT (maternal outcome) and newborns' birthweight adjusted for gestational age (neonatal outcome). Secondary outcomes were maternal weight gain and the need for insulin treatment during pregnancy. Adherence to the intervention was evaluated on the basis of changes in physical activity (weekly metabolic equivalent task (MET) minutes) and diet (intake of total fat, saturated and polyunsaturated fatty acids, saccharose, and fiber). Multilevel analyses took into account cluster, maternity clinic, and nurse level influences in addition to age, education, parity, and prepregnancy BMI. 15.8% (34/216) of women in the intervention group and 12.4% (22/179) in the usual care group developed GDM (absolute effect size 1.36, 95% confidence interval [CI] 0.71–2.62, p = 0.36). Neonatal birthweight was lower in the intervention than in the usual care group (absolute effect size −133 g, 95% CI −231 to −35, p = 0.008) as was proportion of large-for-gestational-age (LGA) newborns (26/216, 12.1% versus 34/179, 19.7%, p = 0.042). Women in the intervention group increased their intake of dietary fiber (adjusted coefficient 1.83, 95% CI 0.30–3.25, p = 0.023) and polyunsaturated fatty acids (adjusted coefficient 0.37, 95% CI 0.16–0.57, p<0.001), decreased their intake of saturated fatty acids (adjusted coefficient −0.63, 95% CI −1.12 to −0.15, p = 0.01) and intake of saccharose (adjusted coefficient −0.83, 95% CI −1.55 to −0.11, p  =  0.023), and had a tendency to a smaller decrease in MET minutes/week for at least moderate intensity activity (adjusted coefficient 91, 95% CI −37 to 219, p = 0.17) than women in the usual care group. In subgroup analysis, adherent women in the intervention group (n = 55/229) had decreased risk of GDM (27.3% versus 33.0%, p = 0.43) and LGA newborns (7.3% versus 19.5%, p = 0.03) compared to women in the usual care group.
Conclusions
The intervention was effective in controlling birthweight of the newborns, but failed to have an effect on maternal GDM.
Trial registration
Current Controlled Trials ISRCTN33885819
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed during pregnancy. Like other types of diabetes, it is characterized by high levels of sugar (glucose) in the blood. Blood-sugar levels are normally controlled by insulin, a hormone that the pancreas releases when blood-sugar levels rise after meals. Hormonal changes during pregnancy and the baby's growth demands increase a pregnant woman's insulin needs and, if her pancreas cannot make enough insulin, GDM develops. Risk factors for GDM, which occurs in 2%–14% of pregnant women, include a high body-mass index (a measure of body fat), excessive weight gain or low physical activity during pregnancy, high dietary intake of polyunsaturated fats, glucose intolerance (an indicator of diabetes) or the birth of a large baby in a previous pregnancy, and a family history of diabetes. GDM is associated with an increased rate of cesarean sections, induced deliveries, birth complications, and large-for-gestational-age (LGA) babies (gestation is the time during which the baby develops within the mother). GDM, which can often be controlled by diet and exercise, usually disappears after pregnancy but increases a woman's subsequent risk of developing diabetes.
Why Was This Study Done?
Although lifestyle changes can be used to control GDM, it is not known whether similar changes can prevent GDM developing (“primary prevention”). In this cluster-randomized controlled trial, the researchers investigate whether individual intensified counseling on physical activity, diet, and weight gain integrated into routine maternity care visits can prevent the development of GDM and the occurrence of LGA babies among newborns. In a cluster-randomized controlled trial, groups of patients rather than individual patients are randomly assigned to receive alternative interventions, and the outcomes in different “clusters” are compared. In this trial, each cluster is a municipality in the Pirkanmaa region of Finland.
What Did the Researchers Do and Find?
The researchers enrolled 399 women, each of whom had a normal blood glucose level at 8–12 weeks gestation but at least one risk factor for GDM. Women in the intervention municipalities received intensified counseling on physical activity at 8–12 weeks' gestation, dietary counseling at 16–18 weeks' gestation, and further physical activity and dietary counseling at each subsequent antenatal visits. Women in the control municipalities received some dietary but little physical activity counseling as part of their usual care. 23.3% and 20.2% of women in the intervention and usual care groups, respectively, developed GDM, a nonstatistically significant difference (that is, a difference that could have occurred by chance). However, the average birthweight and the proportion of LGA babies were both significantly lower in the intervention group than in the usual care group. Food frequency questionnaires completed by the women indicated that, on average, those in the intervention group increased their intake of dietary fiber and polyunsaturated fatty acids and decreased their intake of saturated fatty acids and sucrose as instructed during counseling, The amount of moderate physical activity also tended to decrease less as pregnancy proceeded in the intervention group than in usual care group. Finally, compared to the usual care group, significantly fewer of the 24% of women in the intervention group who actually met dietary and physical activity targets (“adherent” women) developed GDM.
What Do These Findings Mean?
These findings indicate that intensified counseling on diet and physical activity is effective in controlling the birthweight of babies born to women at risk of developing GDM and encourages at least some of them to alter their lifestyle. However, the findings fail to show that the intervention reduces the risk of GDM because of the limited power of the study. The power of a study—the probability that it will achieve a statistically significant result—depends on the study's size and on the likely effect size of the intervention. Before starting this study, the researchers calculated that they would need 420 participants to see a statistically significant difference between the groups if their intervention reduced GDM incidence by 40%. This estimated effect size was probably optimistic and therefore the study lacked power. Nevertheless, the analyses performed among adherent women suggest that lifestyle changes might be a way to prevent GDM and so larger studies should now be undertaken to test this potential primary prevention intervention.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001036.
The US National Institute of Diabetes and Digestive and Kidney Diseases provides information for patients on diabetes and on gestational diabetes (in English and Spanish)
The UK National Health Service Choices website also provides information for patients on diabetes and on gestational diabetes, including links to other useful resources
The MedlinePlus Encyclopedia has pages on diabetes and on gestational diabetes; MedlinePlus provides links to additional resources on diabetes and on gestational diabetes (in English and Spanish)
More information on this trial of primary prevention of GDM is available
doi:10.1371/journal.pmed.1001036
PMCID: PMC3096610  PMID: 21610860
10.  Temporal changes in key maternal and fetal factors affecting birth outcomes: A 32-year population-based study in an industrial city 
Background
The link between maternal factors and birth outcomes is well established. Substantial changes in society and medical care over time have influenced women's reproductive choices and health, subsequently affecting birth outcomes. The objective of this study was to describe temporal changes in key maternal and fetal factors affecting birth outcomes in Newcastle upon Tyne over three decades, 1961–1992.
Methods
For these descriptive analyses we used data from a population-based birth record database constructed for the historical cohort Particulate Matter and Perinatal Events Research (PAMPER) study. The PAMPER database was created using details from paper-based hospital delivery and neonatal records for all births during 1961–1992 to mothers resident in Newcastle (out of a total of 109,086 singleton births, 97,809 hospital births with relevant information). In addition to hospital records, we used other sources for data collection on births not included in the delivery and neonatal records, for death and stillbirth registrations and for validation.
Results
The average family size decreased mainly due to a decline in the proportion of families with 3 or more children. The distribution of mean maternal ages in all and in primiparous women was lowest in the mid 1970s, corresponding to a peak in the proportion of teenage mothers. The proportion of older mothers declined until the late 1970s (from 16.5% to 3.4%) followed by a steady increase. Mean birthweight in all and term babies gradually increased from the mid 1970s. The increase in the percentage of preterm birth paralleled a two-fold increase in the percentage of caesarean section among preterm births during the last two decades. The gap between the most affluent and the most deprived groups of the population widened over the three decades.
Conclusion
Key maternal and fetal factors affecting birth outcomes, such as maternal age, parity, socioeconomic status, birthweight and gestational age, changed substantially during the 32-year period, from 1961 to 1992. The availability of accurate gestational age is extremely important for correct interpretation of trends in birthweight.
doi:10.1186/1471-2393-8-39
PMCID: PMC2542990  PMID: 18713457
11.  Relative risks of low birthweight in Scotland 1980-2. 
Routinely collected data for 187,000 Scottish singleton livebirths in 1980-2 were used to relate the risk of birthweight below 2500 g, 2000 g, 1500 g, and 1000 g to sex of infant and nine maternal factors. Maternal height was a major predictor of birthweight below 2500g but was less important in predicting birthweight in the lower intervals. A history of prenatal death and spontaneous abortion was important for all four intervals and was associated with most extreme risks for birthweight below 1000 g. The analysis confirms that the patterns of risk of birthweight below 2500g and 2000 g associated with social class, marital status, and maternal age and height found among the women of the 1958 cohort of British births are still applicable in the early 1980s.
PMCID: PMC1052598  PMID: 3498784
12.  Fetal growth restriction and the risk of perinatal mortality–case studies from the multicentre PORTO study 
Background
Intrauterine growth restriction (IUGR) is the single largest contributing factor to perinatal mortality in non-anomalous fetuses. Advances in antenatal and neonatal critical care have resulted in a reduction in neonatal deaths over the past decades, while stillbirth rates have remained unchanged. Antenatal detection rates of fetal growth failure are low, and these pregnancies carry a high risk of perinatal death.
Methods
The Prospective Observational Trial to Optimize Paediatric Health in IUGR (PORTO) Study recruited 1,200 ultrasound-dated singleton IUGR pregnancies, defined as EFW <10th centile, between 24+0 and 36+6 weeks gestation. All recruited fetuses underwent serial sonographic assessment of fetal weight and multi-vessel Doppler studies until birth. Perinatal outcomes were recorded for all pregnancies. Case records of the perinatal deaths from this prospectively recruited IUGR cohort were reviewed, their pregnancy details and outcome were analysed descriptively and compared to the entire cohort.
Results
Of 1,116 non-anomalous singleton infants with EFW <10th centile, 6 resulted in perinatal deaths including 3 stillbirths and 3 early neonatal deaths. Perinatal deaths occurred between 24+6 and 35+0 weeks gestation corresponding to birthweights ranging from 460 to 2260 grams. Perinatal deaths occurred more commonly in pregnancies with severe growth restriction (EFW <3rd centile) and associated abnormal Doppler findings resulting in earlier gestational ages at delivery and lower birthweights. All of the described pregnancies were complicated by either significant maternal comorbidities, e.g. hypertension, systemic lupus erythematosus (SLE) or diabetes, or poor obstetric histories, e.g. prior perinatal death, mid-trimester or recurrent pregnancy loss. Five of the 6 mortalities occurred in women of non-Irish ethnic backgrounds. All perinatal deaths showed abnormalities on placental histopathological evaluation.
Conclusions
The PNMR in this cohort of prenatally identified IUGR cases was 5.4/1,000 and compares favourably to the overall national rate of 4.1/1,000 births, which can be attributed to increased surveillance and timely delivery. Despite antenatal recognition of IUGR and associated maternal risk factors, not all perinatal deaths can be prevented.
doi:10.1186/1471-2393-14-63
PMCID: PMC3923738  PMID: 24517273
Perinatal mortality; Antepartum stillbirth; Neonatal death; Intrauterine growth restriction; PORTO Study
13.  The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study 
PLoS Medicine  2009;6(9):e1000153.
Jane Norman and colleagues analyzed linked perinatal surveillance data in Scotland and find that between 1980 and 2004 increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births.
Background
Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.
Methods and Findings
There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.
Conclusions
In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (gestation is the period during which a baby develops in its mother). Nowadays in the US, for example, more than half a million babies arrive earlier than expected every year (1 in 8 babies). Although improvements in the care of newborn babies (neonatal care) mean that preterm babies are more likely to survive than in the past, preterm birth remains the single biggest cause of infant death in many developed countries, and many preterm babies who survive have long-term health problems and disabilities, particularly those born before 32 weeks of gestation. Preterm births can be spontaneous or medically induced. At present, it impossible to predict which mothers will spontaneously deliver early and there is no effective way to prevent these preterm births; medically induced early labor is undertaken when either the unborn baby or mother would be at risk if the pregnancy continued to full term.
Why Was This Study Done?
Preterm birth rates need to be reduced, but before this can be done it is important to know how the causes of preterm birth, the numbers of preterm stillbirths, and the numbers of preterm babies who die at birth (neonatal deaths) or soon after (perinatal deaths) are changing with time. If, for example, the rise in preterm births is mainly due to an increase in medically induced labor and if this change in practice has reduced neonatal deaths, it would be unwise to try to reduce the preterm birth rate by discouraging medically induced preterm births. So far, data from the US and Latin America suggest that the increase in preterm births in these countries is solely due to increased rates of medically induced preterm births. However, in Europe and Australia, the rate of spontaneous preterm births also seems to be increasing. In this study, the researchers examine the trends over time and causes of preterm birth and of neonatal death and illness in Scotland over a 25-year period.
What Did the Researchers Do and Find?
By searching a Scottish database of linked maternity records and infant health and death records, the researchers identified 1.49 million singleton births that occurred between 1980 and 2004 of which nearly 90,000 were preterm births. Over the study period, the rates of spontaneous and of medically induced preterm births per 1,000 births increased by 10.7% and 41.2%, respectively, but because there were more spontaneous preterm births than medically induced preterm births, the absolute increase in the rates of each type of birth was similar. Several maternal complications including preeclampsia (a condition that causes high blood pressure) and placenta previa (covering of the opening of the cervix by the placenta) played a decreasing role in preterm births over the study period, whereas gestational and preexisting diabetes played an increasing role. Finally, there was a decline in stillbirths and in neonatal and perinatal deaths among preterm babies, although more babies remained in the hospital longer than 7 days after birth. More specifically, after 28 weeks of gestation, stillbirths and perinatal deaths decreased among medically induced preterm births but not among spontaneous preterm births.
What Do These Findings Mean?
These findings indicate that in Scotland between 1980 and 2004, increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births. Importantly, they also show that the increase in induced preterm births helped to reduce stillbirths and neonatal and perinatal deaths, a finding that supports the criteria that clinicians currently use to decide whether to induce an early birth. Nevertheless, preterm births still account for two-thirds of all stillbirths, neonatal deaths, and extended neonatal stays in hospital and thus cause considerable suffering and greatly increase the workload in neonatal units. The rates of such births consequently need to be reduced and, for Scotland at least, ways will have to be found to reduce the rates of both spontaneous and induced preterm births to achieve this goal while continuing to identify those sick babies who need to be delivered early to give them the best chance of survival.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000153
Tommys is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy, including a section on pregnancy complications
MedlinePlus provides links to other information on premature babies and to information on pregnancy (in English and Spanish)
doi:10.1371/journal.pmed.1000153
PMCID: PMC2740823  PMID: 19771156
14.  Influence of folic acid on birthweight and growth of the erythroblastotic infant. I. Birthweight. 
The birthweights of 100 infants with erythroblastosis were carefully matched as to sex, gestational age, and parity with the birthweights of 200 control infants born during the same period. At all gestational ages the average birthweight of the affected infants was below that of the controls, the average reduction being 227 g. The more severely affected infants tended to be at a lower centile for birthweight than were the mildly affected ones. The relationships between maternal serum folate, cord blood serum folate, and centile for birthweight among affected infants were also studied. There was a strong correlation between low maternal serum folate and the incidence of small-for-dates babies among the affected infants. There was also a strong correlation between maternal and cord blood serum folate values. There was a lack of correlation between maternal serum folate and cord blood haemoglobin. It is concluded that infants with erythroblastosis are lighter than controls and that the reason for this may be a shortage of folic acid available for fetal growth.
PMCID: PMC1546211  PMID: 319765
15.  Growth and very low birth weight. 
Archives of Disease in Childhood  1989;64(3):379-382.
Information on the likelihood of catch up growth in poorly grown very low birthweight children is sparse. The centiles for weight, height, and head circumference were recorded at both 2 and 5 years of age for 135 very low birthweight children and 42 normal birthweight children. At both ages significantly more children of very low birth weight were under the 10th centile for weight and height. Children of birth weight under 1000 g were more often under the 10th centile for weight at 5 years compared with those of birth weight 1000-1500 g. Mean incremental weight gain between 2 and 5 years was significantly less for very low birthweight children. Mean increment in weight from 2 to 5 years was less for very low birthweight children who had been under the 10th centile for weight at 2 years; children who had been under the 10th centile for height also had lower mean height increments. The growth centiles achieved by 2 years of age were useful predictors of poor growth at 5 years, with perinatal data of marginal importance. Only six of 43 (14%) children with a weight at 5 years of age under the 10th centile were small for gestational age at birth. Very low birthweight children who had a weight or height under the 10th centile at 2 years of age usually remained in this category at 5 years with no evidence of catch up growth.
PMCID: PMC1791899  PMID: 2705802
16.  Low Birthweight in Relation to Placental Abruption and Maternal Thrombophilia Status: A Case-Control Study 
Objective:
To evaluate whether the association between low birthweight and placental abruption is mediated through preterm birth or restricted fetal growth, and if these associations were influenced by maternal thrombophilia status.
Study design:
Data were derived from the New Jersey-Placental Abruption Study, an ongoing, multicenter, case-control study conducted in New Jersey since August 2002. Abruption cases (n=156) were identified based on a clinical diagnosis, and controls (n=170) were matched to cases based on parity and maternal race. Low birthweight (<2500 g) was stratified based on preterm birth (<37 weeks gestation) and small for gestational age (birthweight <10th centile for gestational age). Maternal thrombophilia assessment was based on serum evaluation (Protein C and S deficiency, activated Protein C resistance ratio, and anticardiolpin antibodies) as well as genetic polymorphisms (methylenetetrahydrofolate reductase, prothrombin gene, and Factor V Leiden). Associations were expressed based on odds ratio (OR) with 95% confidence interval (CI).
Results:
Among abruption cases, 60.3% (n=94) were low birthweight in comparison to 11.2% (n=19) of controls (OR 13.7, 95% CI 7.4, 25.2). Furthermore, placental abruption had a significantly increased association with preterm birth in both SGA (OR 17.4, 95% CI 4.6, 64.9) and appropriately grown fetuses (OR 15.8, 95% CI 8.4, 29.8). However, the association between abruption and low birthweight were similar between women with and without thrombophilia.
Conclusion:
The association between placental abruption and low birthweight is chiefly mediated through preterm birth, and this association does not appear to be modified by maternal thrombophilia status.
doi:10.1016/j.ajog.2007.09.011
PMCID: PMC2346588  PMID: 18191809
Placental abruption; fetal growth restriction; preterm birth; maternal thrombophilia
17.  Influence of elective preterm delivery on birthweight and head circumference standards. 
We calculated new birthweight and head circumference centiles for boys and girls between 24 and 42 weeks' gestation from 20,713 singleton live births at our hospital between 1978 and 1984. Among the 803 babies born at or before 34 weeks' gestation, 28% were delivered electively for fetal problems; they were considerably lighter than babies born after spontaneous preterm labour. In contrast, they showed only a small deficit in head circumference, possibly due to a brain sparing effect in growth retarded infants. Electively delivered preterm infants cause a bias in birthweight and head circumference centiles and we recommend that these babies should be excluded when these centiles are calculated.
PMCID: PMC1778138  PMID: 3813633
18.  Postnatal weight loss in term infants: what is "normal" and do growth charts allow for it? 
Background: Although it is a well known phenomenon, limited normative data on neonatal weight loss and subsequent gain are available, making it hard to assess individual children with prolonged weight loss.
Objective: To establish, using data from a large prospective population based cohort study, norms and limits for postnatal weight loss and its impact on current growth reference charts.
Method: A cohort of 961 term infants were recruited at birth and followed using parental questionnaires and community nursing returns. Routine weights were collected for half the cohort at 5 days and for all at 12 days and 6 weeks.
Results: Less weight loss was seen than the 3–6% suggested by previous studies, but one in five infants had not regained their birth weight by 12 days. Those lightest at birth showed least weight loss. Twenty six (3%) children had more than 10% weight loss, but none showed evidence of major organic disease. Actual weights in the first fortnight are half to one centile space lower than growth charts suggest, while birthweight centiles for children born at 37 weeks were two centile spaces lower.
Conclusions: Neonatal weight loss is brief, with few children remaining more than 10% below birth weight after 5 days. Growth charts are misleading in the first 2 weeks, because they make no allowance for neonatal weight loss.
doi:10.1136/adc.2003.026906
PMCID: PMC1721692  PMID: 15102731
19.  Distribution of Birth Weight for Gestational Age in Japanese Infants Delivered by Cesarean Section 
Journal of Epidemiology  2011;21(3):217-222.
Background
Neonatal anthropometric charts of the distribution of measurements, mainly birth weight, taken at different gestational ages are widely used by obstetricians and pediatricians. However, the relationship between delivery mode and neonatal anthropometric data has not been investigated in Japan or other countries.
Methods
The subjects were selected from the registration database of the Japan Society of Obstetrics and Gynecology (2003–2005). Tenth centile, median, and 90th centile of birth weight by sex, birth order, and delivery mode were observed by gestational age from 22 to 42 weeks among eligible singleton births.
Results
After excluding 248 outliers and 5243 births that did not satisfy the inclusion criteria, 144 980 births were included in the analysis. The distribution of 10th centile curves was skewed toward lower birth weights during the preterm period among both first live births and second and later live births delivered by cesarean section. More than 40% of both male and female live births were delivered by cesarean section at 37 weeks or earlier.
Conclusions
The large proportion of cesarean sections influenced the skewness of the birth weight distribution in the preterm period.
doi:10.2188/jea.JE20100123
PMCID: PMC3899412  PMID: 21478642
birth weight; distribution; gestational age; cesarean section; preterm
20.  Risk adjusted and population based studies of the outcome for high risk infants in Scotland and Australia 
OBJECTIVES—To compare outcomes of care in selected neonatal intensive care units (NICUs) for very low birthweight (VLBW) or preterm infants in Scotland and Australia (study 1) and perinatal care for all VLBW infants in both countries (study 2).
DESIGN—Study 1: risk adjusted cohort study; study 2: population based cohort study.
SUBJECTS—Study 1: all 2621 infants of < 1500 g birth weight or < 31 weeks' gestation admitted to a volunteer sample of hospitals comprising eight of all 17 Scottish NICUs and six of all 12 tertiary NICUs in New South Wales and Queensland in 1993-1994; study 2: all 5986infants of 500-1499 g birth weight registered as live born in Scotland and Australia in 1993-1994.
MAIN OUTCOMES—Study 1: (a) hospital death; (b) death or cerebral damage, each adjusted for gestation and CRIB (clinical risk index for babies); study 2: neonatal (28 day) mortality.
RESULTS—Study 1. Data were obtained for 1628 admissions in six Australian NICUs, 775 in five Scottish tertiary NICUs, and 148 in three Scottish non-tertiary NICUs. Crude hospital death rates were 13%, 22%, and 22% respectively. Risk adjusted hospital mortality was about 50% higher in Scottish than in Australian NICUs (adjusted mortality ratio 1.46, 95% confidence interval (CI) 1.29 to 1.63,p < 0.001). There was no difference in risk adjusted outcomes between Scottish tertiary and non-tertiary NICUs. After risk adjustment, death or cerebral damage was more common in Scottish than Australian NICUs (odds ratio 1.9, 95% CI 1.5 to 2.5). Both these risk adjusted adverse outcomes remained more common in Scottish than Australian NICUs after excluding all infants < 28 weeks' gestation from the comparison. Study 2. Population based neonatal mortality in infants of 500-1499 g was higher in Scotland (20.3%) than Australia (16.6%) (relative risk 1.22, 95% CI 1.08 to 1.39, p = 0.002). In a post hoc analysis, neonatal mortality was also higher in England and Wales than in Australia.
CONCLUSIONS—Study 1: outcome was better in the Australian NICUs. Study 2: perinatal outcome was better in Australia. Both results may be consistent, at least in part, with differences in the organisation and implementation of neonatal care.


doi:10.1136/fn.82.2.F118
PMCID: PMC1721047  PMID: 10685984
21.  The risk of obesity by assessing infant growth against the UK-WHO charts compared to the UK90 reference: findings from the Born in Bradford birth cohort study 
BMC Pediatrics  2012;12:104.
Background
The new growth charts in the UK, the UK-WHO charts, comprise prescriptive data from the WHO standard between two weeks and four years of age. Little is known about the development of obesity risk in normal UK infants, who are necessarily not fed according to the WHO recommendations and do not live in constraint-free environments (the selection criteria of the WHO standard source sample), using the new charts. Here, we investigated infant growth trajectories and traits indicative of childhood obesity using the UK-WHO charts, with the aim to clearly document the implications of adopting the new charts on UK growth monitoring practice.
Methods
Mixed effects models were applied to serial weight and length data from 2181 infants (1187 White; 994 Pakistani) in the Born in Bradford birth cohort study to produce curves from 10 days to 15 months of age. Individual monthly estimates were converted to Z-scores and were plotted by sex and ethnic group. The relative risks (RR) of traits indicative of childhood obesity, including high BMI and rapid weight gain, using the UK-WHO charts compared to the previously used UK90 reference were calculated for all infants together and for White and Pakistani infants separately.
Results
Both ethnic groups demonstrated patterns of growth similar to the UK-WHO charts in length but not in weight. The resulting pattern for BMI was remarkable, with an average gain of 1.0 Z-score between two and 12 months of age. The UK-WHO charts were significantly (p < 0.05) more likely than the UK90 reference to classify BMI above the 91st centile after age six months (RR 1.427-2.151) and weight and BMI gain between birth (one month for BMI) and 12 months of age greater than two centile bands (RR 1.214 and 1.470, respectively).
Conclusions
The change to the UK-WHO charts means that normal UK infants risk being diagnosed as being on a trajectory toward childhood obesity. National estimates of obesity will have to be recalculated for previous years to allow longitudinal comparison. The new charts do not allow a focused prevention effort for targeting programmes at infants most at risk of becoming obese, because the use of the 91st or 98th centile on the UK-WHO charts will identify many more infants as being at risk than the same centiles on the UK90 reference. Now more than ever, research is needed to develop a large scale childhood obesity prevention programme which could ideally be integrated with routine infant growth monitoring practice.
doi:10.1186/1471-2431-12-104
PMCID: PMC3439315  PMID: 22824296
Growth charts; Postnatal growth; Infant; Obesity; Longitudinal studies
22.  Birthweight ratio and outcome in preterm infants. 
Archives of Disease in Childhood  1990;65(1 Spec No):30-34.
The association between birthweight ratio and outcome was investigated in 429 infants born before 31 weeks' gestation. Birthweight ratio was calculated in each case as birth weight divided by mean birth weight for gestation (from reference data). It was shown that a given ratio corresponded to the same birth centile across the gestational age range studied; a ratio of 0.8 corresponding to the 10th centile. There was a linear relationship between birthweight ratio and requirement for mechanical ventilation and postneonatal mortality. Birthweight ratio was also strongly and linearly related to body weight, length, and head circumference at 18 months' corrected age. Overall, there was no association between this ratio and neurodevelopmental outcome to 18 months. However, the subgroup with the largest weights for gestation (birthweight ratio greater than or equal to 1.1), had significantly higher language subscores than all the other children. Our data show that conventional dichotomous categorisation of preterm infants into small or appropriate for gestation is inadequate when exploring the association between size for gestation and outcome.
PMCID: PMC1590167  PMID: 2306131
23.  Low birthweight, preterm, and small for gestational age babies in Scotland, 1981-1984. 
STUDY OBJECTIVE--The aim was to examine the effect of maternal age, gravidity, marital status, previous perinatal deaths, and parental social class on babies born low birthweight, preterm, and small for gestational age. DESIGN--The study used data on discharge summaries from all maternity hospitals in Scotland. SETTING--The study was based on all singleton deliveries in Scotland. PARTICIPANTS--The analysis involved information on 259,462 singleton babies born during the four years 1981-84 in Scotland. MEASUREMENTS AND MAIN RESULTS--Previous perinatal death was found to be the strongest predictor for both preterm and low birthweight. Single mothers were at particularly high risk of having a small for gestational age baby and those who were previously married of having a preterm baby. Women aged less than 20 years old, those over 34 years old, nulligravidae, and those of parity 3 or more were also at increased risk of adverse pregnancy outcome. Mothers and fathers in manual social classes and those who could not be assigned a social class on the basis of their occupation were at increased risk for all three adverse outcomes studied. The babies of parents who were in manual occupations were twice as likely as those of parents in non-manual occupations to be small for gestational age and almost twice as likely to be low birthweight. CONCLUSIONS--Mother's social class is a risk factor for adverse pregnancy outcome independent of maternal age, parity, and adverse reproductive history, and also independent of father's social class. Information on both parents' occupations should be collected in maternity discharge systems.
PMCID: PMC1060759  PMID: 1757762
24.  The potential effect of the UK 1990 height centile charts on community growth surveillance. 
Archives of Disease in Childhood  1996;74(5):452-454.
The UK 1990 height charts are derived from an up to date dataset and introduce a change in the centile lines, particularly the addition of the 0.4th centile. This study examined the likely impact of these changes. Height data from London school children (1990-1993) were examined using Tanner and Whitehouse (TW) and UK 1990 charts. Numbers of children with height below TW 3rd centile were compared with numbers below the UK 1990 3rd and 0.4th centiles. The TW charts identified only 1% of children below the TW 3rd centile, while the UK 1990 charts identified 3% below the 3rd and 0.4% below the 0.4th centiles. If the 3rd centile remains as the referral 'cut off' for short stature, the introduction of the UK 1990 charts would increase current workload two- to three-fold, while a change to the 0.4th centile would reduce it by 50%. A significant number of children with abnormalities may be excluded from further assessment as a result of this latter change. In this small scale community study it is not possible to assess the consequences of this change. The heights at diagnosis of children with growth hormone (GH) deficiency (peak GH < 20 mU/l during a standard provocation test) were therefore compared to the 0.4th centile (UK 1990 charts). Sixty eight children with heights < 2nd centile (UK 1990 charts) currently receiving GH replacement (17 female, 51 male, aged 9.7, SD 3.5, years) were assessed, and of these, 28 (41%) had heights at diagnosis between 0.4th and 2nd centile, with a mean height standard deviation score of -2.32 (SD 0.21). This suggests that if the 0.4th centile were to be used as the sole criterion for referral for slow growth, a significant proportion of children with abnormality would not be referred for further assessment. The UK 1990 2nd centile should replace the TW 3rd centile. Children below this should undergo an intermediary medical assessment to confirm height measurement, to exclude from referral children with mild familial short stature and to identify concerns regarding the child.
PMCID: PMC1511551  PMID: 8669965
25.  Secular change in birthweight of Asian babies born in Birmingham. 
Archives of Disease in Childhood  1982;57(11):867-871.
We have studied changes in the birthweight of Asian babies born alive at this hospital between 1968 and 1978. In 1978 Pakistani babies were 139 g heavier but Indian babies only 25 g heavier than 10 years earlier. Contributing to these changes were significantly fewer short mothers and primiparae among Pakistanis, and non-significant increases in gestational age and intrauterine growth (that is, weight centile after allowing for gestational age, parity, and maternal height). Among Indians there were significant increases in maternal height and gestational age, but parity was reduced and intrauterine growth did not increase. In both groups there were fewer teenage mothers, but whereas among Pakinstanis birth intervals of less than one year were less common, there was no such reduction among Indian mothers. The secular change suggests that genetic factors are unlikely to be the major reason why Pakistani babies born in Birmingham are lighter than European babies, and that environmental factors play an important role. Efforts to increase birthweight need to consider both the mothers' physical environment during pregnancy and prepregnancy factors influencing growth in childhood, age at first pregnancy, and birth interval. The study shows a need to describe an 'Asian' population with details of their sub-ethnic structure. The sub-ethnic and secular differences further suggest that a single 'Asian' standard for birthweight and intrauterine growth may be inappropriate; the use of international reference data with which all infants may be compared is preferable.
PMCID: PMC1628028  PMID: 7149760

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