Zhang J, Kim S, Grewal J, Albert PS. Predicting large fetuses at birth: do multiple ultrasound examinations and longitudinal statistical modelling improve prediction? Paediatric and Perinatal Epidemiology 2012; ••: ••–••.

Predicting large fetuses at birth has long been a challenge in obstetric practice. We examined whether ultrasound examinations at multiple times during pregnancy improve the accuracy of prediction using repeated, longitudinal statistical modelling, and whether adding maternal characteristics improves the accuracy of prediction. We used data from a previous study conducted in Norway and Sweden from 1986 to 1989 in which each pregnant woman had four ultrasound examinations at around 17, 25, 33 and 37 weeks of gestation. At birth, infant size was classified as large-for-gestational age (LGA, >90th centile) and macrosomia (>4000 g) or not. We used a longitudinal random effects model with quadratic fixed and random effects to predict term LGA and macrosomia at birth. Receiver–operator curves and mean-squared error were used to measure accuracy of the prediction. Ultrasound examination around 37 weeks had the best accuracy in predicting LGA and macrosomia at birth. Adding multiple ultrasound examinations at earlier gestations did not improve the accuracy. Adjusting for maternal characteristics had limited impact on the accuracy of prediction. Thus, a single ultrasound examination at late gestation close to birth is the simplest method currently available to predict LGA and macrosomia.

Vanaelst B, De Vriendt T, Huybrechts I, Rinaldi S, De Henauw S. Epidemiological approaches to measure childhood stress. Paediatric and Perinatal Epidemiology 2012; ••: ••–••.

The prevalence of childhood stress has repeatedly been shown to be high, with ‘parental separation’ and ‘being bullied at school’ as the most frequently reported stressors in the child's everyday life. This is quite alarming as children are most vulnerable to the adverse psychological and physiological health consequences of chronic stress exposure.

Despite growing research interest in this field over the last years, literature falls short in providing an overview of methods to adequately assess stress in elementary school children (6–12 years old). This review describes questionnaires and interviews, as well as laboratory measurements of cortisol in biological samples (serum, urine, saliva and hair) as stress assessment methods in children, with the emphasis on epidemiological research settings. Major characteristics, strengths and limitations of these methods are established, examples of child-specific stressor questionnaires and interviews are provided and specific recommendations with respect to epidemiological research are formulated. In addition, hair cortisol as a potential biomarker for chronic stress (in children) is discussed more thoroughly.

This review is meant to serve as a preliminary guide for health researchers new to this research area by reflecting on theoretical and methodological aspects in childhood stress assessment.

Klungsøyr K, Morken NH, Irgens L, Vollset SE, Skjærven R. Secular trends in the epidemiology of pre-eclampsia throughout 40 years in Norway: prevalence, risk factors and perinatal survival. Paediatric and Perinatal Epidemiology 2012; ••:••–••.

Pre-eclampsia is a leading complication of pregnancy, associated with maternal and neonatal morbidity. The present study describes the epidemiology of pre-eclampsia in Norway, with data from the Medical Birth Registry of Norway, covering 40 years. We aimed at describing time trends in prevalence, selected risk factors and perinatal mortality. We also analysed time trends in recurrence risk of total pre-eclampsia and pre-eclampsia with preterm delivery. A total of 2 416 501 women giving birth during 1967–2008 were included. Prevalence of pre-eclampsia increased from 1967 to 1999 and decreased thereafter, with an overall prevalence of 3%. Rates increased more over time among younger than older women, resulting in a significantly lower excess risk of pre-eclampsia associated with high maternal age in later years. For example, relative risk (RR) of pre-eclampsia among primiparae aged ≥35 relative to <25 years changed from 2.4 [95% confidence interval (CI) 2.1, 2.7] in 1967–1976 to 1.2 [95% CI 1.1, 1.3] in 1999–2008. For recurrence risk, subsequent pregnancies to a mother were linked, with the mother being the unit of analysis. Recurrence risk of pre-eclampsia was high, particularly recurrence of preterm pre-eclampsia, with overall RR close to 50 of a second pregnancy with pre-eclampsia and preterm birth compared with women without pre-eclampsia in first pregnancies. Finally, stillbirth associated with pre-eclampsia decreased more than neonatal mortality over time, and in the last 5 years only a moderate excess risk of stillbirth and neonatal death was observed.

Tvinnereim HM, Lygre GB, Haug K, Schreuder P, Klock K. A biobank of primary teeth within the Norwegian Mother and Child Cohort Study (MoBa): a resource for the future. Paediatric and Perinatal Epidemiology 2012; ••: ••–••.

The Norwegian Mother and Child Cohort Study (MoBa) is a prospective population-based cohort study including >100 000 pregnancies and following the children through childhood, using questionnaires and collecting biological samples. The aim of MoBa is to test specific aetiological hypotheses by estimating the association between exposure and disease, aiming at prevention. A biobank for exfoliated primary teeth collected from the children participating in MoBa has been established (MoBaTooth Biobank). Samples of tooth tissues from the primary dentition can give information about exposure to toxic and essential elements during fetal life and early infancy. Prenatally and postnatally formed tooth tissues permanently document early exposures unlike other biomarkers, as teeth form incrementally at a known rate. Results from tooth analyses will be coupled with corresponding information in the multiple questionnaires and data from analysis of other biological samples collected by MoBa. Invitations to donate one or more teeth are sent to all mothers/children in the period 2008–2016, when the child is 6.75 years old. By August 2011, 7400 participants had been recorded into the MoBaTooth database donating altogether 9798 teeth (1.3 teeth per child). The response rate was 24%, but there is a lag of >1 year in the response. Data from the tooth biobank can supply MoBa with important additional information on the uptake of trace elements during fetal life and early infancy. This information can illuminate possible causal factors of health and disease in the future.

Kharrazi M, Pearl M, Yang J, DeLorenze GN, Bean CJ, Callaghan WM, Grant A, Lackritz E, Romero R, Satten GA, Simhan H, Torres AR, Westover JB, Yolken R, Williamson DM. California Very Preterm Birth Study: design and characteristics of the population- and biospecimen bank-based nested case–control study. Paediatric and Perinatal Epidemiology 2012; ••:••–••.

Very preterm birth (VPTB) is a leading cause of infant mortality, morbidity and racial disparity in the US. The underlying causes of VPTB are multiple and poorly understood. The California Very Preterm Birth Study was conducted to discover maternal and infant genetic and environmental factors associated with VPTB. This paper describes the study design, population, data and specimen collection, laboratory methods and characteristics of the study population. Using a large, population-based cohort created through record linkage of livebirths delivered from 2000 to 2007 in five counties of southern California, and existing data and banked specimens from statewide prenatal and newborn screening, 1100 VPTB cases and 796 control mother–infant pairs were selected for study (385/200 White, 385/253 Hispanic and 330/343 Black cases/controls, respectively). Medical record abstraction of cases was conducted at over 50 hospitals to identify spontaneous VPTB, improve accuracy of gestational age, obtain relevant clinical data and exclude cases that did not meet eligibility criteria. VPTB was defined as birth at <32 weeks in Whites and Hispanics and <34 weeks in Blacks. Approximately 55% of all VPTBs were spontaneous and 45% had medical indications or other exclusions. Of the spontaneous VPTBs, approximately 41% were reported to have chorioamnionitis. While the current focus of the California Very Preterm Birth Study is to assess the role of candidate genetic markers on spontaneous VPTB, its design enables the pursuit of other research opportunities to identify social, clinical and biological determinants of different types of VPTB with the ultimate aim of reducing infant mortality, morbidity and racial disparities in these health outcomes in the US and elsewhere.

Matijasevich A, Howe LD, Tilling K, Santos IS, Barros AJD, Lawlor DA. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study. Paediatric and Perinatal Epidemiology 2012; ••:••–••.

Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors.

We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0–3 months and 12–29/32 months with very little association at 3–12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted.

Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age 4, indicating that height inequality, which was already present at birth, widened through differential growth rates to age 2 years.

Vinikoor-Imler LC, Gray SC, Edwards SE, Miranda ML. The effects of exposure to particulate matter and neighbourhood deprivation on gestational hypertension. Paediatric and Perinatal Epidemiology 2012; 26: 91–100.

Gestational hypertension, pre-eclampsia and eclampsia are conditions that affect the health of both mothers and infants during and after pregnancy. Recent research indicates the importance of considering environmental, social and individual contributors to poor pregnancy outcomes. Our research examined particulate matter (PM) concentrations as one measure of environmental exposure and neighbourhood quality as one measure of the social environment. We used these measures, as well as maternal characteristics, to predict the risk of gestational hypertension (including pre-eclampsia and eclampsia). North Carolina Detailed Birth Record data for 2000–2003 were obtained and geocoded for all singleton births. Levels of PM₁₀ and PM_2.5 were determined using air quality data from the US Environmental Protection Agency. Information on a woman's residential neighbourhood was determined from 2000 Census data. Modified Poisson regression models clustered by tract were used to examine the associations between PM levels, neighbourhood deprivation and maternal characteristics with gestational hypertension. Analysis was restricted to women residing within 20 km of a PM monitor. Both PM₁₀ and PM_2.5 were associated with gestational hypertension; the risk ratios for an interquartile range (IQR) increase in exposure were 1.07 [95% confidence interval (CI) 1.04, 1.11] for PM₁₀ (IQR: 3.92 µg/m³) and 1.11 [95% CI 1.08, 1.15] for PM_2.5 (IQR: 2.24 µg/m³). Living in a neighbourhood with increased levels of deprivation was also associated with gestational hypertension. Any smoking during pregnancy, younger age and higher level of education were inversely associated with risk of gestational hypertension. Compared with non-Hispanic White women, non-Hispanic Black women were at higher risk of gestational hypertension, whereas Hispanic women were at lower risk. Increased levels of PM and neighbourhood deprivation, as well as certain individual characteristics, were associated with higher risk of gestational hypertension.

Whitehouse AJO, Robinson M, Newnham JP, Pennell CE. Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring? Paediatric and Perinatal Epidemiology 2012; 26: 101–108.

The current study sought to determine whether hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) are associated with neurocognitive outcomes in middle childhood. Participants were members of the Western Australian Pregnancy Cohort (Raine) Study. Data were available for 1389 children (675 females; mean age = 10.59 years; SD = 0.19). Twenty-five per cent of these participants were offspring of pregnancies complicated by either gestational hypertension (n = 279), or pre-eclampsia (n = 34). Verbal ability at age 10 years was assessed with the Peabody Picture Vocabulary Test – Revised (PPVT-R), and non-verbal ability with Ravens Colored Progressive Matrices (RCPM). Separate multivariable regression analyses, incorporating sociodemographic, antenatal, obstetric and postnatal covariates, investigated the effect of a two- (normotensive pregnancy vs. hypertensive pregnancy) and three-level (normotensive pregnancy vs. gestational hypertension vs. pre-eclampsia) predictor variable on PPVT-R and RCPM scores. Offspring of pregnancies complicated by maternal hypertension (gestational hypertension or pre-eclampsia) had a mean PPVT-R score that was 1.83 ([95% confidence interval (CI) −3.48, −0.17], P = 0.03) points lower than children from normotensive pregnancies. Multivariable regression analysis also identified a significant inverse association between the three-level predictor variable and offspring PPVT-R scores (P = 0.02). Gestational hypertension (without pre-eclampsia) reduced offspring PPVT-R scores by 1.71 points [95% CI −3.39, −0.03] and pre-eclampsia led to a reduction of 3.53 points [95% CI −8.41, 1.35], although this latter association did not achieve statistical significance. There was no effect of the two- (P = 0.99) or three-level (P = 0.92) predictor variable on RCPM scores. Maternal hypertensive diseases of pregnancy are a risk factor for a small reduction in offspring verbal ability.

Hutcheon JA, Bodnar LM, Joseph KS, Abrams B, Simhan HN, Platt RW. The bias in current measures of gestational weight gain. Paediatric and Perinatal Epidemiology 2012; 26: 109–116.

Conventional measures of gestational weight gain (GWG), such as average rate of weight gain, are likely to be correlated with gestational duration. Such a correlation could introduce bias to epidemiological studies of GWG and adverse perinatal outcomes because many perinatal outcomes are also correlated with gestational duration. This study aimed to quantify the extent to which currently used GWG measures may bias the apparent relationship between maternal weight gain and risk of preterm birth. For each woman in a provincial perinatal database registry (British Columbia, Canada, 2000–2009), a total GWG was simulated such that it was uncorrelated with risk of preterm birth. The simulation was based on serial antenatal GWG measurements from a sample of term pregnancies. Simulated GWGs were classified using three approaches: total weight gain (kg), average rate of weight gain (kg/week) or adequacy of GWG in relation to Institute of Medicine recommendations. Their association with preterm birth ≤32 weeks was explored using logistic regression. All measures of GWG induced an apparent association between GWG and preterm birth ≤32 weeks even when, by design, none existed. Odds ratios in the lowest fifths of each GWG measure compared with the middle fifths ranged from 4.4 [95% confidence interval (CI) 3.6, 5.4] (total weight gain) to 1.6 [95% CI 1.3, 2.0] (Institute of Medicine adequacy ratio). Conventional measures of GWG introduce serious bias to the study of maternal weight gain and preterm birth. A new measure of GWG that is uncorrelated with gestational duration is needed.

Cockerill R, Whitworth MK, Heazell AEP. Do medical certificates of stillbirth provide accurate and useful information regarding the cause of death? Paediatric and Perinatal Epidemiology 2012; 26: 117–123.

Stillbirth affects one in 200 pregnancies in the UK. Understanding the causes of stillbirth is essential to reducing perinatal mortality. Stillbirth certificates represent a potential source of data on perinatal mortality. We aimed to assess whether the information on stillbirth certificates used in the UK is accurate.

A retrospective cross-sectional audit of stillbirth certificates issued in a geographical region of the UK in 2009 was undertaken. Data were recorded from the stillbirth certificate and health records. The cause of death was classified using the ReCoDe system. Two hundred and thirteen stillbirth certificates were issued for stillbirths (feticides for fetal anomaly were excluded). Agreement for the primary factor associated with the stillbirth was fair (Kappa = 0.286). This contrasts with the gestation of stillbirth, which was almost complete agreement (Kappa = 0.883). The majority of stillbirths (58.7%) were classified on the certificate as ‘unknown cause’. A proportion of 9.4% of stillbirths were classified as congenital anomaly and 8.0% as placental abruption. Only 0.5% of stillbirth certificates cited fetal growth restriction as a relevant condition contributing to death. A total of 49.6% of ‘unexplained’ stillbirths were associated with fetal growth restriction on review. Errors were present in 77.9% of certificates, including missing co-morbidities (55.9%) and the wrong cause of death (40.4%).

The cause(s) of death is (are) not recorded accurately on the UK medical certificate of stillbirth, and the majority of certificates contain one or more errors. Training is required to improve understanding of the causes of stillbirth and completion of medical certificates. Data recorded directly from medical certificate of stillbirths are not sufficiently reliable for descriptive studies of causation and epidemiology.

Gordon DE, Ghazaryan LR, Maslak J, Anderson BJ, Brousseau KS, Carrascal AF, Smith LC. Projections of diagnosed HIV infection in children and adolescents in New York State. Paediatric and Perinatal Epidemiology 2012; 26: 131–139.

Decreasing mother-to-child transmission is changing the population of children and adolescents with HIV. This project used recent epidemiological data to develop short-term projections of children and adolescents living with diagnosed HIV infection in New York State. A population simulation model was created to project prevalence of diagnosed HIV cases aged 0–19 years by age, sex, race/ethnicity and risk for years 2007–2014. Using 2006 data as the baseline population and 2001–2006 diagnosis and death data, annual diagnoses and deaths were calculated for each age/sex/race/risk category and known cases were ‘aged’ into the next year. The model produced annual estimates until 2014. The model predicts a decline in the number of persons aged 0–19 years living with diagnosed HIV in New York from 2810 in 2006 to 1431 in 2014, a net decrease of 49%. Living cases with paediatric risk continue to decrease. Cases aged 13–19 with non-paediatric risk increase slowly, leading to a shift in the risk composition of the population. The dominant effect seen in the model is the ageing out of perinatally infected children born before measures to prevent mother-to-child transmission were broadly implemented in the mid- to late 1990s. Changing trends in the young HIV-infected population should be considered in developing public health programmes for HIV prevention and care in New York State for the coming years.

Jäderberg I, Thomsen SF, Kyvik KO, Skytthe A, Backer V. Atopic diseases in twins born after assisted reproduction. Paediatric and Perinatal Epidemiology 2012; 26: 140–145.

We examined the risk of atopic diseases in twins born after assisted reproduction. Data on atopic diseases and assisted reproduction in 9694 twin pairs, 3–20 years of age, from the Danish Twin Registry were collected via multidisciplinary questionnaires. The risk of atopic diseases in twins born after assisted reproduction was compared with the risk in twins born after spontaneous conception using logistic regression and variance components analysis. Children born after assisted reproduction did not have a different risk of atopic outcomes (adjusted odds ratios [95% confidence intervals] for asthma: 0.95 [0.85, 1.07], P = 0.403; hay fever: 1.01 [0.86, 1.18], P = 0.918; and atopic dermatitis: 1.02 [0.81, 1.11], P = 0.773 respectively) compared with children born after spontaneous conception. Assisted reproduction did not modify the heritability of atopic diseases. This study does not support an association between assisted reproduction and development of atopic diseases. This result must be confirmed in subsequent studies, preferably of singleton populations.

Chen B-Y, Chan C-C, Han Y-Y, Wu H-P, Guo YL. The risk factors and quality of life in children with allergic rhinitis in relation to seasonal attack patterns. Paediatric and Perinatal Epidemiology 2012; 26: 146–155.

A questionnaire survey was conducted to examine whether risk factors and allergic rhinitis (AR)-related quality of life (QOL) were different among children with different seasonal patterns of AR. Participants were students enrolled in elementary and middle schools in Taipei County, Taiwan. Using moving average and principal component analysis, children with current AR were grouped by attack seasons. The effects of personal and environmental factors on AR seasonality were assessed by logistic regression models. AR severity and AR-related QOL were compared within AR seasonal subtypes.

Among 4221 children who completed the questionnaire, 1144 and 1605 children were current AR cases and healthy controls, respectively. Four AR subtypes were categorised as follows: perennial, spring, summer/fall, and winter. Age, gender, parental education, maternal passive smoking during pregnancy, breast feeding, and mouldy walls were found to contribute differentially to different AR subtypes. Children suffering from perennial and winter AR were found to have more severe symptoms and significantly lower QOL score compared with other subtypes. Specific personal and environmental risk factors could contribute to different AR seasonal subtypes. Active allergen avoidance and symptomatic treatment should be the focus of management aiming to improve the QOL among children with perennial and winter subtype.

Hoornweg MJ, Smeulders MJC, Ubbink DT, van der Horst CMAM. The prevalence and risk factors of infantile haemangiomas: a case–control study in the Dutch population. Paediatric and Perinatal Epidemiology 2012; 26: 156–162.

Haemangiomas are considered to be the most common tumours of infancy. However, despite their frequent occurrence the aetiological determinants of their development remain unknown. Identifying these factors may provide insight on their pathogenesis. We performed cross-sectional screening for haemangiomas in newborns (0–16 months of age) in the general Dutch population. Haemangioma-specific and pregnancy-related data were collected in children with a haemangioma. These data were compared in a case–control design using multivariable logistic regression analysis. Among 2204 newborns, 219 (9.9%) had a haemangioma. The male-to-female ratio was 1:2. The majority of haemangiomas were located on the trunk (37%). The general practitioners or medical specialists were consulted in only a minority of cases (<7%). Amniocentesis [odds ratio (OR) 3.6, 95% confidence interval (CI) 1.11, 11.42], breech presentation [OR 2.3, 95% CI 1.14, 4.44], being first-born [OR 1.55, 95% CI 1.03, 2.33] and a birthweight ≤2500 g [OR 4.95, 95% CI 1.63, 15.05] were independent factors associated with the development of a haemangioma. Duration of pregnancy did not differ between study groups. Our study showed that the prevalence of a haemangioma is 9.9% in the general (Dutch) population. Four factors appear relevant in the development of haemangiomas. These factors may provide clues to its pathogenesis.

Adgent MA, Daniels JL, Rogan WJ, Adair L, Edwards LJ, Westreich D, Maisonet M, Marcus M. Early-life soy exposure and age at menarche. Paediatric and Perinatal Epidemiology 2012; 26: 163–175.

This study examines the timing of menarche in relation to infant-feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early-life feeding regimes, categorised as primarily breast, early formula, early soy and late soy, were defined using infant-feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed using questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, White females. We used Kaplan–Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period.

The present analysis included 2920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144–163], approximately 12.8 years. The median age at menarche among early soy-fed girls was 149 months (12.4 years) [IQR, 140–159]. Compared with girls fed non-soy-based infant formula or milk (early formula), early soy-fed girls were at 25% higher risk of menarche throughout the course of follow-up (hazard ratio 1.25 [95% confidence interval 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine-disrupting effects of soy isoflavone exposure. However, our study is limited by few soy-exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more in-depth evaluation in future studies.