A Prospective Longitudinal Study of Early Childhood Caries Onset in Initially Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex oral disease that is prevalent in US children. OBJECTIVES: The purpose of this 2-y prospective cohort study was to examine baseline and time-dependent risk factors for ECC onset in initially caries-free preschool children. METHODS: A cohort of 189 initially caries-free children aged 1 to 3 y was recruited. At each 6-mo study visit, children were examined using the ICDAS index; salivary samples were collected to assess mutans streptococci (MS), lactobacilli, Candida species, salivary cortisol (prior and after a stressor), and salivary IgA. Diet and oral health behavior were assessed from parent report. Child and family stress exposure was assessed from measures of psychological symptoms, stressful life event exposure, family organization and violence exposure, and social support. Sociodemographic factors were also considered. A Kaplan-Meier estimator of survival function of time to ECC and a Cox proportional hazards model were used to identify predictors of ECC onset. RESULTS: Onset of ECC was associated with high salivary MS levels at baseline (log-rank test, P < 0.0001). Cox proportional hazards regression showed that the risk of dental caries significantly increased with salivary MS in log scale over the 6-mo period (hazard ratio, 1.08; P = 0.01). Other risk factors in the model did not reach statistical significance. CONCLUSION: Our results provide prospective evidence that an increase in salivary MS predicts ECC onset in young, initially caries-free children, confirming that a high salivary MS count likely plays a causal role in ECC onset, independent of covariates. KNOWLEDGE TRANSFER STATEMENT: These results suggest that we must focus on reducing salivary MS counts in young children and preventing or delaying MS colonization in infants and young children determined to be at risk for ECC.

Social, Psychological, and Behavioral Predictors of Salivary Bacteria, Yeast in Caries-Free Children.

INTRODUCTION: Early childhood caries (ECC) is a complex, multifactorial oral disease that is a major public health concern because it is prevalent, profoundly alters a child's quality of life, is difficult to treat effectively, and has a distressing tendency to recur following treatment. OBJECTIVES: The purpose of the study was to examine social, psychological, and behavioral predictors of salivary bacteria and yeast in young children at risk for ECC. METHODS: A sample of 189 initially caries-free preschool children was assessed for child stress physiology from salivary cortisol, child and family stress exposure, diet, oral health behaviors, and sociodemographic risks. Multiple logistic regression analysis was implemented to examine the associations between these risk factors and cariogenic microorganisms: mutans streptococci (MS), lactobacilli (LB), and Candida species. RESULTS: Higher baseline salivary cortisol (odds ratio [OR] = 6.26; 95% confidence level [CL], 1.69-23.16) and a blunted response to an acute laboratory stressor (OR = .56; 95% CL, .37-.83) were associated with an increased likelihood of elevated salivary MS (≥105 colony-forming units/mL) in caries-free children. Sociodemographic risk for cariogenic microorganisms was also found. Specifically, lower education attainment of the parent/primary caregiver was associated with children being more likely to carry salivary Candida species and elevated salivary MS; in addition, children from households with an unemployed parent/primary caregiver were more likely (OR = 3.13; 95% CL, 1.2-8.05) to carry salivary Candida species and more likely (OR = 3.03; 95% CL, 1.25-7.33) to carry elevated levels of MS and/or salivary Candida and/or LB. CONCLUSIONS: The impact of sociodemographic risk and stress physiology on cariogenic disease processes are evident prior to ECC onset. The findings provide novel data on the early onset of cariogenic processes in children and the importance of considering sociodemographic, psychosocial, and behavioral factors when judging ECC risk. KNOWLEDGE TRANSFER STATEMENT: The findings provide valuable and novel findings that, pre-ECC onset, the caries disease process is explicable from a detailed assessment of behavioral, sociodemographic, and psychosocial stress variables.

Oral Microbiota Composition Predicts Early Childhood Caries Onset.

As the most common chronic disease in preschool children in the United States, early childhood caries (ECC) has a profound impact on a child's quality of life, represents a tremendous human and economic burden to society, and disproportionately affects those living in poverty. Caries risk assessment (CRA) is a critical component of ECC management, yet the accuracy, consistency, reproducibility, and longitudinal validation of the available risk assessment techniques are lacking. Molecular and microbial biomarkers represent a potential source for accurate and reliable dental caries risk and onset. Next-generation nucleotide-sequencing technology has made it feasible to profile the composition of the oral microbiota. In the present study, 16S ribosomal RNA (rRNA) gene sequencing was applied to saliva samples that were collected at 6-mo intervals for 24 mo from a subset of 56 initially caries-free children from an ongoing cohort of 189 children, aged 1 to 3 y, over the 2-y study period; 36 children developed ECC and 20 remained caries free. Analyses from machine learning models of microbiota composition, across the study period, distinguished between affected and nonaffected groups at the time of their initial study visits with an area under the receiver operating characteristic curve (AUC) of 0.71 and discriminated ECC-converted from healthy controls at the visit immediately preceding ECC diagnosis with an AUC of 0.89, as assessed by nested cross-validation. Rothia mucilaginosa, Streptococcus sp., and Veillonella parvula were selected as important discriminatory features in all models and represent biomarkers of risk for ECC onset. These findings indicate that oral microbiota as profiled by high-throughput 16S rRNA gene sequencing is predictive of ECC onset.

Design of a Multisite Study Assessing the Impact of Tic Disorders on Individuals, Families, and Communities.

BACKGROUND: Tic disorders, including Tourette syndrome, are complex, multisymptom diseases, yet the impact of these disorders on affected children, families, and communities is not well understood. METHODS: To improve the understanding of the impacts of Tourette syndrome, two research groups conducted independent cross-sectional studies using qualitative and quantitative measures. They focused on similar themes, but distinct scientific objectives, and the sites collaborated to align methods of independent research proposals with the aim of increasing the analyzable sample size. RESULTS: Site 1 (University of Rochester) was a Pediatric Neurology referral center. Site 2 (University of South Florida) was a Child Psychiatry referral center. A total of 205 children with tic disorders were enrolled from both studies. The University of Rochester also enrolled 100 control children in order to clearly isolate impacts of Tourette syndrome distinct from those occurring in the general population. The majority of children with tic disorders (n = 191, 93.1%) had Tourette syndrome, the primary population targeted for these studies. Children with Tourette syndrome were similar across sites in terms of tic severity and the occurrence of comorbid conditions. The occurrence of psychiatric comorbidities in the control group was comparable with that in the general pediatric population of the United States, making this a well-justified comparison group. CONCLUSIONS: Through collaboration, two sites conducting independent research developed convergent research methods to enable pooling of data, and by extension increased power, for future analyses. This method of collaboration is a novel model for future epidemiological research of tic disorders.

Arginine vasopressin 1a receptor gene and maternal behavior: evidence of association and moderation.

This study examined associations among maternal sensitivity, mothers' early adversity and the Arginine Vasopressin 1a Receptor (AVPR1A) gene. Early adversity in mothers' background has been found to be associated with lower maternal sensitivity. Animal literature suggests that variation in the AVPR1A gene is associated with parenting quality. The goal of the study was to examine the role of the AVPR1A gene in maternal sensitivity, especially under conditions of high early adversity. Participants included 151 Caucasian women from a community sample. The women were videotaped in their home while interacting separately with two of their children (target child = 18 months, older sibling <6 years). Evidence was found for an association between the AVPR1A gene and maternal sensitivity. Mothers with two copies of the long RS3 alleles were less sensitive than mothers with one or zero copies of the long alleles. This association was strongest under conditions of high maternal early adversity.

Prenatal stress and the programming of the HPA axis.

There are several independent prospective studies showing that a wide variety of forms of prenatal stress can have long-term effects on the behavioural and cognitive outcome for the child. Animal studies have shown that prenatal stress, as well as affecting behaviour, can also reprogram the function of the HPA axis in the offspring. However, the effects on the HPA axis are very variable depending on the nature of the stress, its timing in gestation, the genetic strain of the animal, the sex and age of the offspring and whether basal or stimulated HPA axis responses are studied. There are also several recent studies showing long-term effects of prenatal stress on basal cortisol levels, or cortisol responses to stress, in humans. The designs of these studies differ considerably, many are small, and the effects on outcome are also varied. There is little evidence, so far, that altered function of the HPA axis in the child mediates the behavioural or cognitive alterations observed to be associated with prenatal stress.

Prenatal stress and neurodevelopment of the child: focus on the HPA axis and role of the placenta.

Recent human studies have shown that a wide variety of prenatal stressors, from anxiety and partner relationship problems, to natural disasters, increase the risk for a diverse range of adverse neurodevelopmental outcomes in the child. These include impaired cognitive development and behavioral problems, autism and schizophrenia. However, many questions remain about the underlying processes. Much of the research, based on animal studies, has focussed on the maternal HPA axis, with mixed results. Maternal stress or anxiety during pregnancy has been found to be weakly associated with raised maternal cortisol, if at all. The placenta may be a more promising programming vector, because it controls fetal exposure to the maternal environment. Animal studies indicate that prenatal stress can affect the activity of the placental barrier enzyme 11-betaHSD2, which metabolises cortisol. We review the evidence for a similar mechanism in humans and how maternal stress may cause other changes in the placenta which affect fetal neurodevelopment.

Impact of land use on the biodiversity integrity of the moist sub-biome of the grassland biome, South Africa.

South Africa's moist grassland harbours globally significant biodiversity, supplies essential ecosystem services, supports crop and livestock agriculture, forestry and settlement, yet is poorly conserved. Ongoing transformation and limited opportunity for expanding the protected area network require instead that biodiversity conservation is 'mainstreamed' within other land uses. This exercise sought to identify the relative compatibility of 10 land uses (conservation, livestock or game ranching, tourism/recreation, rural settlement, dryland cropping, irrigated cropping, dairy farming, plantation forestry, and urban settlement) with maintaining biodiversity integrity. This was assessed using 46 indicators for biodiversity integrity that covered landscape composition, structure, and functioning. Data was integrated into a single measure per land use through application of the analytic hierarchy process, with supporting information gained from interviews with experts. The rank order of importance amongst indicators was landscape structure, functioning and composition. Consistent differences among land uses for all three categories revealed two clear groupings. Conservation, livestock or game ranching had the lowest impact and retained substantial natural asset, while that for tourism/recreation was intermediate. All other land uses had a severe impact. Impact on biodiversity integrity depended mainly on the extent of transformation and fragmentation, which accounted for the greatest impact on habitats and species, and impairment of landscape functioning. It is suggested that a strategic intervention for maintaining biodiversity integrity of moist grassland is to support livestock or game ranching and limit ongoing urban sprawl.

Quality of child-parent attachment moderates the impact of antenatal stress on child fearfulness.

BACKGROUND: Animal studies have shown that prenatal stress has persisting effects on several aspects of offspring development; more recent studies show that this effect may be eliminated by positive postnatal rearing. Human studies of prenatal anxiety/stress are now also beginning to document links between antenatal stress/anxiety and behavioural and cognitive development of the child; however, there is no human evidence as to whether the early caregiving environment moderates the effect of antenatal anxiety/stress on child outcomes. METHODS: Antenatal and postnatal measures of stress were collected on 123 women who were recruited from an antenatal clinic. Laboratory-based assessment of the children's cognitive development and fearfulness were assessed when the children were aged 17 months. In addition, child-parent attachment quality was assessed using the Strange Situation. RESULTS: Attachment classification moderated the link between antenatal stress and observed fearfulness. The effect of antenatal stress on fearfulness was most accentuated in children with an Insecure/Resistant attachment classification; the significant antenatal stress x attachment classification interaction held after controlling for postnatal stress and obstetric, social and demographic factors. Attachment did not moderate the effects of antenatal anxiety on cognitive development. DISCUSSION: These findings provide the first human evidence that postnatal parenting may moderate the adverse effects of antenatal stress. These results raise developmental questions about the timing and effect of interventions to reduce the adverse effects of antenatal stress exposure.

Maternal antenatal anxiety and amniotic fluid cortisol and testosterone: possible implications for foetal programming.

Both animal and human studies have shown that maternal stress or anxiety during pregnancy is associated with increased risk of disturbance in offspring neurodevelopment and behaviour. In animal models, increased foetal exposure to glucocorticoids has been found to be one mechanism for such foetal programming. Little is understood of the mediating mechanisms in humans, and one aim of our research programme is to investigate this further. This review presents a synopsis of some of our recent results. We aimed to test the hypothesis that maternal anxiety was associated with raised maternal cortisol, and that this in turn was related to increased foetal exposure to cortisol. We studied this by recruiting women at amniocentesis, obtained their Spielberger State Anxiety scores, and assessed maternal plasma cortisol and amniotic fluid cortisol. We also examined maternal plasma and amniotic fluid testosterone levels. Awaiting amniocentesis was in general anxiogenic, but with a wide range of anxiety scores. Maternal anxiety was significantly associated with plasma cortisol before 17 weeks, albeit of modest magnitude (r = 0.0.23), and not after 17 weeks of gestation. This is probably due to the known attenuation of the maternal hypothalamic-pituitary-adrenal axis with increasing gestation. We found a strong correlation between maternal plasma and amniotic fluid cortisol levels, which increased with gestation and became robust after 18 weeks. This correlation increased with maternal anxiety, suggesting a possible effect of maternal mood on placental function. There was a positive correlation between cortisol and testosterone in amniotic fluid, in both male and female foetuses independent of maternal anxiety, plasma testosterone, gestational age, and time of collection. Foetal stress may be associated with increased foetal exposure to testosterone. However, maternal anxiety did not predict amniotic fluid cortisol or testosterone level. Thus, the role of these hormones in mediating the effect of maternal mood on foetal development in humans remains to be demonstrated.

Amniotic fluid testosterone: relationship with cortisol and gestational age.

INTRODUCTION: Foetal exposure to testosterone is increasingly implicated in the programming of future reproductive and non-reproductive behaviour. Some outcomes associated with prenatal exposure to testosterone may be predicted from exposure to prenatal stress, suggesting a link between them. The peak serum levels of testosterone in the foetus are thought to be around 14-18 weeks' gestation, and we explored testosterone levels at different gestations. Although best investigated in foetal plasma, this is now difficult because of the decline in frequency of foetal blood sampling; in this study, we used amniotic fluid as a biomarker to investigate foetal exposure. AIMS: To investigate the relationship between amniotic fluid testosterone, amniotic fluid cortisol, foetal gender, and gestational age. METHODS: Paired amniotic fluid and maternal plasma samples were collected from 264 pregnant women undergoing amniocentesis between 15 and 37 weeks' gestation (median 17 weeks [119 days]). Total testosterone and cortisol in amniotic fluid, and total plasma testosterone (maternal) were measured by radioimmunoassay. RESULTS: Amniotic fluid testosterone levels were higher in male than in female foetuses, with a median (interquartile range) of 0.85 nmol/l (0.60-1.17 nmol/l) and 0.28 nmol/l (0.175-0.45 nmol/l), respectively. No relationship between amniotic fluid testosterone and gestational age was detected in either sex. Amniotic fluid testosterone correlated positively with amniotic fluid cortisol in both sexes (r = 0.30 male foetuses, r = 0.33 female foetuses, P < 0.001 for both), and remained significant in multivariate analysis. CONCLUSION: Testosterone in amniotic fluid did not change with gestation in the second and third trimester, raising questions about the timing of the reported early peak in the male foetus. The positive correlation between cortisol and testosterone in amniotic fluid suggests that increased foetal exposure to cortisol may also be associated with increased exposure to testosterone.

Ontogeny of foetal exposure to maternal cortisol using midtrimester amniotic fluid as a biomarker.

OBJECTIVE: There is increasing evidence that antenatal stress has long-lasting effects on child development, but there is less accord on the mechanisms and the gestational window of susceptibility. One possible mechanism is by foetal exposure to maternal cortisol. To explore this, we investigated the relationship between cortisol in maternal plasma and amniotic fluid, and any moderating influence of gestational age. PATIENTS AND MEASUREMENTS: Two hundred and sixty-seven women awaiting amniocentesis for karyotyping were studied. Samples were collected between 0900 and 1730 h. Gestational age was determined to the nearest day by ultrasound biometry and time of collection noted to the nearest 15 min. Total cortisol was measured by radioimmunoassay in paired amniotic fluid and maternal blood samples (n = 267) [gestation range 15-37 weeks, median 17 weeks (119 days)]. RESULTS: Both maternal and amniotic fluid cortisol levels increased with gestation (r = 0.25, P < 0.001; r = 0.33 P < 0.001, respectively). Amniotic fluid cortisol was positively correlated with time of collection (r = 0.22, P < 0.001) and negatively with maternal age (r =-0.24, P < 0.001). There was a positive correlation between amniotic fluid cortisol with maternal plasma levels (r = 0.32, P < 0.001), which persisted after multivariate analysis controlling for gestation, time of collection and maternal age. The association appeared to be dependent on gestational age, being nonsignificant at 15-16 weeks' gestation and increasing in strength thereafter. CONCLUSION: This study shows a positive correlation between maternal and amniotic fluid cortisol levels, which becomes robust from 17 to 18 weeks onwards. The results provide support for the hypothesis that alterations in maternal cortisol may be reflected in amniotic fluid levels from this gestation.

A twin study of attachment in preschool children.

The degree to which individual differences in child-parent attachment were mediated by genetic, shared environmental, and nonshared environmental influences was investigated. One hundred and ten preschool-aged twin pairs (N = 220) were assessed in the Strange Situation and coded using conventional four-way classifications and a continuous measure of attachment security. The degree of sibling similarity in attachment was substantial, with an overall concordance rate of 67% at the secure/insecure level. The degree of concordance was equally high in monozygotic and dizygotic twin pairs, 70% and 64%, respectively, suggesting little genetic influence but a moderate degree of discordance. Twin similarity on the continuous measure of attachment security was r(57) = .48 and r(53) = .38 for monozygotic and dizygotic twin pairs, respectively, also consistent with a modest role for genetic influence but a significant effect for shared and nonshared environment. The implications for genetic influences on the environment and for understanding nonshared and shared environmental influences are discussed.

Specificity and heterogeneity in children's responses to profound institutional privation.

BACKGROUND: The sequelae of profound early privation are varied. AIMS: To delineate the behavioural patterns that are specifically associated with institutional privation. METHOD: A group of 165 children adopted from Romania before the age of 42 months were compared at 4 years and 6 years with 52 non-deprived UK children adopted in infancy. Dysfunction was assessed for seven domains of functioning. The groups were compared on which, and how many, domains were impaired. RESULTS: Attachment problems, inattention/overactivity, quasi-autistic features and cognitive impairment were associated with institutional privation, but emotional difficulties, poor peer relationships and conduct problems were not. Nevertheless, one-fifth of children who spent the longest time in institutions showed normal functioning. CONCLUSIONS: Attachment disorder behaviours, inattention/overactivity and quasi-autistic behaviour constitute institutional privation patterns.

Family settings and children's adjustment: differential adjustment within and across families.

BACKGROUND: Children in stepfamilies and single-parent families exhibit elevated levels of behavioural and emotional problems compared with children in intact (biological) families, but there is variation within and across these family types. AIMS: To examine the sources of variation in children's behavioural and emotional problems across diverse family settings. METHOD: Levels of behavioural and emotional problems in children from diverse stepfamilies and single-parent families were compared with children living with both biological parents. Psychosocial risks were measured at the individual child and family levels. RESULTS: Behavioural and emotional problems were elevated in children in stepmother/complex stepfamilies and single-parent families, but not in simple stepfather families, relative to 'biological' families. Psychopathology associated with family type was explained by compromised quality of the parent-child relationship, parental depression and socio-economic adversity. Sibling similarity in behavioural and emotional problems was most pronounced in high-risk family settings. CONCLUSIONS: Family type is a proxy for exposure to psychosocial risks; the extent of family-wide influence on children's development may be strongest in high-stress settings.

Family lives and friendships: the perspectives of children in step-, single-parent, and nonstep families.

Children's reports on their experiences in different family settings (stepfamilies, single-parent families, and intact families), their contact with friends, and the quality of their friendships were studied with data from 238 children drawn from a community sample. A particular focus was on children's confiding and communication: children's recall of communication about family transitions and their current communication about stepfamily issues with family and friends. Friends were found to be key confidants. The relations between children's family lives (confiding, parent-child relationships, family activities, involvement in parental conflict, and communication about stepfamily issues) and their friendships were investigated and found to be linked to biological relatedness and family setting.

Longitudinal change in parenting associated with developmental delay and catch-up.

The current study examined the predictors of parent-child relationship quality and developmental change in a sample of children adopted into the U.K. following severe early privation, and in a comparison sample of nondeprived, within-country adoptees. One hundred and fifty-eight children adopted from Romania and 52 U.K. adoptees were assessed at age 6 years; longitudinal data (age 4 and 6 years) were available on the 110 Romanian adoptees placed into U.K. homes before 24 months of age and all U.K. adoptees. Ratings of parent-child positivity and negativity during a semistructured interaction task were obtained from coders who were blind to the child's background. Results indicated that adoptive parent-child relationship quality was related to duration of deprivation and that cognitive/developmental delay mediated this association. The magnitude of this effect was modest and diminished over time. Longitudinal analyses revealed that positive change in parent-child relationship quality was most marked among children who exhibited cognitive catch-up between assessments. The direction of effects appeared to be primarily child to parent. The findings underscore the need for further research on the long-term impact of early experiences on psychosocial development.

Can inattention/overactivity be an institutional deprivation syndrome?

Elevated rates of attention deficit and overactivity have been noted previously in samples of institution-reared children. This study examined the hypothesis that inattention/overactivity(I/O) might constitute a specific deprivation syndrome. One hundred and sixty five children adopted at varying ages (e.g., 0-42 months of age) into the UK following severe early deprivation were compared with 52 within-UK adoptees who did not suffer deprivation. The children were rated by teachers and parents on levels of I/O, conduct difficulties, and emotional difficulties using the Revised Rutter Scales. Data were collected at age 6 for the entire sample and at age 4 for the UK adoptees and for the subsample of Romanian children who entered the UK before the age of 2 years. Mean level analyses suggested a significant effect of duration of deprivation on I/O, but not on conduct or emotional difficulties. The effects of duration of deprivation were specific to I/O and were not accounted for by low birth weight, malnutrition, or cognitive impairment. Levels of I/O correlated with attachment disturbances. Furthermore, the effects of duration of deprivation on I/O did not attenuate over time. We conclude that I/O may well constitute an institutional deprivation syndrome, but that the type of attention deficit and overactivity exhibited by these children may present a different clinical picture from that of "ordinary" varieties of attention deficit disorder or hyperkinetic syndrome.

Parents' and partners' life course and family experiences: links with parent-child relationships in different family settings.

Life course and current family factors associated with individual differences in parent-child relationships were investigated in a sample of 467 children from 192 families, including stepfather, single-parent, stepmother, and complex stepfamilies; informants were fathers, mothers, and children. Both positive and negative dimensions of father-child and mother-child relationships were linked to earlier life course experiences of parent and of partner, to current family factors, and to the quality of partner's relationship with the child. The pattern of associations between the adults' life course experiences meant that children were at risk for a "double dose" of less affectionate relationships in families in which parents had experienced early adversities. The significance of biological relatedness, family setting, and child partner relationships was highlighted.

Distribution of accidents, injuries, and illnesses by family type. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

OBJECTIVE: To investigate whether family type and psychosocial risks indexed by family type were systematically associated with differences in health outcomes in children. DESIGN AND SUBJECTS: The study is based on a longitudinal, prospective study of a large (n = approximately 10 000) community sample of families, the Avon Longitudinal Study of Pregnancy and Childhood. MAIN OUTCOME MEASURES: Frequency of accidents, illnesses, and medical interventions. RESULTS: At 2 years of age, children in single-parent and stepfamilies were disproportionately likely to experience accidents and receive medical treatment for physical illnesses. In addition, children in single-parent families and stepfamilies were more likely to be hospitalized or receive attention from a hospital doctor for an injury or illness. Exposure to psychosocial risks also were elevated in single-parent families and stepfamilies, compared with intact or nonstepfamilies, and these factors primarily accounted for the connection between family type and children's physical health. CONCLUSIONS: The consequences of family transitions on children's health extend beyond traditional mental health and behavioral outcomes and include accident proneness, illness, and receipt of medical attention. The mediating processes are not entirely attributable to social class differences connected to family type and may instead be associated with a range of psychosocial risks that are more frequently found in single-parent families and stepfamilies, compared with intact or nonstepfamilies. Prevention and intervention efforts directed toward children at risk for poor behavioral and mental health adjustment secondary to family disruption should consider children's physical health and health-related behaviors.