Nicole M. Talge

Stressor paradigms in developmental studies: what does and does not work to produce mean increases in salivary cortisol.

The stress response system is comprised of an intricate interconnected network that includes the hypothalamic-pituitary-adrenocortical (HPA) axis. The HPA axis maintains the organisms capacity to respond to acute and prolonged stressors and is a focus of research on the sequelae of stress. Human studies of the HPA system have been facilitated enormously by the development of salivary assays which measure cortisol, the steroid end-product of the HPA axis. The use of salivary cortisol is prevalent in child development stress research. However, in order to measure childrens acute cortisol reactivity to circumscribed stressors, researchers must put children in stressful situations which produce elevated levels of cortisol. Unfortunately, many studies on the cortisol stress response in children use paradigms that fail to produce mean elevations in cortisol. This paper reviews stressor paradigms used with infants, children, and adolescents to guide researchers in selecting effective stressor tasks. A number of different types of stressor paradigms were examined, including: public speaking, negative emotion, relationship disruption/threatening, novelty, handling, and mild pain paradigms. With development, marked changes are evident in the effectiveness of the same stressor paradigm to provoke elevations in cortisol. Several factors appear to be critical in determining whether a stressor paradigm is successful, including the availability of coping resources and the extent to which, in older children, the task threatens the social self. A consideration of these issues is needed to promote the implementation of more effective stressor paradigms in human developmental psychoendocrine research.

United States Birth Weight Reference Corrected For Implausible Gestational Age Estimates

OBJECTIVES: To provide an updated US birth weight for gestational age reference corrected for likely errors in last menstrual period (LMP)-based gestational age dating, as well as means and SDs, to enable calculation of continuous and categorical measures of birth weight for gestational age. METHODS: From the 2009–2010 US live birth files, we abstracted singleton births between 22 and 44 weeks of gestation with at least 1 nonmissing estimate of gestational age (ie, LMP or obstetric/clinical) and birth weight. Using an algorithm based on birth weight and the concordance between these gestational age estimates, implausible LMP-based gestational age estimates were either excluded or corrected by using the obstetric/clinical estimate. Gestational age– and sex-specific birth weight means, SDs, and smoothed percentiles (3rd, 5th, 10th, 90th, 95th, 97th) were calculated, and the 10th and 90th percentiles were compared with published population-based references. RESULTS: A total of 7 818 201 (99% of eligible) births were included. The LMP-based estimate of gestational age comprised 85% of the dataset, and the obstetric/clinical estimate comprised the remaining 15%. Cut points derived from the current reference identified ∼10% of births as ≤10th and ≥90th percentiles at all gestational weeks, whereas cut points derived from previous US-based references captured variable proportions of infants at these thresholds within the preterm and postterm gestational age ranges. CONCLUSIONS: This updated US-based birth weight for gestational age reference corrects for likely errors in gestational age dating and allows for the calculation of categorical and continuous measures of birth size.

Inhibited temperament and parent emotional availability differentially predict young children's cortisol responses to novel social and nonsocial events

Preschool-aged children (n = 274) were examined in the laboratory to assess behavioral and cortisol responses to nonsocial and social threat. Parents also responded to scales on the Childrens Behavior Questionnaire reflecting exuberant approach to novel/risky activities (reversed scored) and shyness. Multi-method measures of Nonsocial and Social Inhibition were computed. Parents and children were observed engaging in a series of interactive tasks and the Emotional Availability scales were scored for parental sensitivity, nonintrusiveness, nonhostility, and structuring. These scores were factored to yield one measure of Parenting Quality. Analyses revealed that Nonsocial and Social Inhibition could be distinguished and that associations with cortisol response were stressor specific. Moderation analyses revealed that parenting quality buffered cortisol elevations for extremely socially, but not nonsocially inhibited children. These findings are consistent with evidence that sensitive, supportive parenting is an important buffer of the HPA axis response to threat in infants and toddlers, and extends this finding to the preschool period.

To spear or not to spear: Comparison of saliva collection methods

The eye spear, or an absorbent sponge-like material, has been proposed as a useful method of obtaining repeated saliva samples from infants and young children for cortisol determination. This brief report examines possible interference effects of different types of eye spears under conditions of relatively high and low cortisol levels, with or without the use of oral stimulant, and using two common assays. In Study 1, one type of eye spear was compared to passively collected drool using two different assays (EIA, DELFIA), across high and low concentrations of cortisol. No differences were found between methods for either assay or cortisol level, indicating that the spears are potentially a viable method of collecting saliva. Study 2 compared three other types of absorbent eye spears to passive drooling under the presence or absence of oral stimulant use. This study revealed that the degree of interference varied as a function of the specific type of eye spear that was employed; stimulant use had no effect. Taken together, the results raise important considerations to take into account when selecting collection materials and procedures in the measurement of salivary cortisol.

Biological indicators of the in-utero environment and their association with birth weight for gestational age.

Birth weight for gestational age (BW/GA) has been associated with a risk of adverse health outcomes. Biological indices of pregnancy complications, maternal mid-pregnancy serum biomarkers and placental pathology may shed light on these associations, but at present, they are most often examined as single entities and offer little insight about overlap. In addition, these indices are typically assessed in relation to the extremes of the BW/GA distribution, leaving open the question of how they relate to the entire BW/GA distribution. Addressing issues such as these may help elucidate why postnatal health outcomes vary across the BW/GA continuum. In this study, we focused on a subset of women who participated in the Pregnancy Outcomes and Community Health Study (n = 1371). We examined BW/GA (i.e. gestational age and sex-referenced z-scores) in relation to obstetric complications, second trimester maternal serum screening results and histologic evidence of placental pathology along with maternal demographics, anthropometrics and substance use. In adjusted models, mean reductions in BW/GA z-scores were associated with preeclampsia (β = -0.70, 95% CI -1.04, -0.36), high maternal serum alpha fetoprotein (β = -0.28, 95% CI -0.43, -0.13), unconjugated estriol (β = -0.31/0.5 multiples of the median decrease, 95% CI -0.41, -0.21) and high levels of maternal obstructive vascular pathology in the placenta (β = -0.46, 95% CI -0.67, -0.25). The findings were similar when preterm infants, small-for-gestational age or large-for-gestational age infants were excluded. More research is needed to examine how the factors studied here might directly mediate or mark risk when evaluating the associations between BW/GA and postnatal health outcomes.

Assisted reproductive technology and newborn size in singletons resulting from fresh and cryopreserved embryos transfer

Objectives and Study Design The aim of this study was two-fold: to investigate the association of Assisted Reproductive Technology (ART) and small newborn size, using standardized measures; and to examine within strata of fresh and cryopreserved embryos transfer, whether this association is influenced by parental infertility diagnoses. We used a population-based retrospective cohort from Michigan (2000–2009), Florida and Massachusetts (2000–2010). Our sample included 28,946 ART singletons conceived with non-donor oocytes and 4,263,846 non-ART singletons. Methods Regression models were used to examine the association of ART and newborn size, measured as small for gestational age (SGA) and birth-weight-z-score, among four mutually exclusive infertility groups: female infertility only, male infertility only, combined female and male infertility, and unexplained infertility, stratified by fresh and cryopreserved embryos transfer. Results We found increased SGA odds among ART singletons from fresh embryos transfer compared with non-ART singletons, with little difference by infertility source [adjusted odds-ratio for SGA among female infertility only: 1.18 (95% CI 1.10, 1.26), male infertility only: 1.20 (95% CI 1.10, 1.32), male and female infertility: 1.18 (95% CI 1.06, 1.31) and unexplained infertility: 1.24 (95% CI 1.10, 1.38)]. Conversely, ART singletons, born following cryopreserved embryos transfer, had lower SGA odds compared with non-ART singletons, with mild variation by infertility source [adjusted odds-ratio for SGA among female infertility only: 0.56 (95% CI 0.45, 0.71), male infertility only: 0.64 (95% CI 0.47, 0.86), male and female infertility: 0.52 (95% CI 0.36, 0.77) and unexplained infertility: 0.71 (95% CI 0.47, 1.06)]. Birth-weight-z-score was significantly lower for ART singletons born following fresh embryos transfer than non-ART singletons, regardless of infertility diagnoses.

Placental pathology, corticotropin-releasing hormone, timing of parturition, and fetal growth in the pregnancy outcomes and community health study

Abstract Background: Identification of vascular pathologies in delivered placentas and their associations with biomarkers measured during pregnancy may elucidate mechanisms of adverse pregnancy outcomes and inform early detection and intervention strategies. Objectives: To examine associations of placental vascular pathology with birth size and timing of parturition, and to evaluate maternal midpregnancy serum corticotropin-releasing hormone (CRH) levels as a marker of the above associations. Study design: The pregnancy outcomes and community health (POUCH) Study enrolled women at 16–27 weeks of pregnancy from five Michigan communities. Histological assessments of delivered placentas and assays of CRH in maternal blood sampled at enrollment were performed in a subcohort of 1152 participants. Five placental vascular pathology constructs were formulated: Maternal–Vascular-Obstructive (MVO), Fetal Vascular–Obstructive (FVO), Maternal Vascular–disturbance of Integrity (MVI), Fetal Vascular–disturbance of Integrity (FVI), and Maternal Vascular–Developmental (MVD). A four-level outcome variable combined small for gestational (SGA) yes/no and delivery timing preterm/term; the non-SGA/term served as the referent group. In multinomial logistic regression models, the five vascular pathology groups were evaluated in relation to the outcome variable and effect sizes were compared before versus after exclusion of participants with high CRH (top quartile). Results: Adjusted odds ratios (aOR) for MVO among SGA/term and SGA/preterm were 4.1 (95% CI: 2.2, 7.9) and 8.8 (95% CI: 3.3, 23.5) respectively. Among SGA/preterm births, the aOR was attenuated by ∼40%, i.e. 5.4 (95% CI: 1.1, 26.2) after removing high CRH pregnancies. MVI and FVO were each associated with SGA/preterm, aOR = 3.7 (95% CI: 1.3, 10.3) and 10.5 (95% CI: 3.6, 30.8) respectively. Removal of high CRH pregnancies reduced the OR estimates by nearly half, i.e. MVI aOR = 1.9 (95% CI: 0.34, 10.9), FVO aOR = 6.0 (95% CI: 1.3, 28.6). MVI, FVI and MVD were each associated with greater odds of non-SGA/preterm, but the aORs showed little change after removing high CRH pregnancies. Conclusions: Obstructive placental vascular pathologies in maternal or fetal vessels are associated with SGA. High CRH levels coincided with a portion of pregnancies that share these complications, particularly among pregnancies that also ended prematurely.

Click-evoked auditory brainstem responses and autism spectrum disorder: A meta-analytic review: ABRs and ASD

Behavior does not differentiate ASD risk prior to 12 months of age, but biomarkers may inform risk before symptoms emerge. Click‐evoked auditory brainstem responses (ABRs) may be worth consideration due to their measurement properties (noninvasiveness; reliability) and conceptual features (well‐characterized neural generators), but participant characteristics and assessment protocols vary considerably across studies. Our goal is to perform a meta‐analysis of the association between ABRs and ASD. Following an electronic database search (PubMed, Medline, PsycInfo, PsycArticles), we included papers that were written in English, included ASD and typically‐developing (TD) groups, and reported the information needed to calculate standardized mean differences (Hedgess g) for at least one ABR latency component (I, III, V, I‐III, III‐V, I‐V). We weighted and averaged effect sizes across conditions and subsets of participants to yield one estimate per component per study. We then performed random‐effects regressions to generate component‐specific estimates. ASD was associated with longer ABR latencies for Waves III (g = 0.5, 95% CI 0.1, 0.9), V (g = 0.7, 95% CI 0.3, 1.1), I‐III (g = 0.7, 95% CI 0.2, 1.2), and I‐V (g = 0.6, 95% CI 0.2, 1.0). All components showed significant heterogeneity. Associations were strongest among participants ≤8 years of age and those without middle ear abnormalities or elevated auditory thresholds. In sum, associations between ABRs and ASD are medium‐to‐large in size, but exhibit heterogeneity. Identifying sources of heterogeneity is challenging, however, due to power limitations and co‐occurrence of sample/design characteristics across studies. Research addressing the above limitations is crucial to determining the etiologic and/or prognostic value of ABRs for ASD. Autism Res 2018, 11: 916–927.

Maternal cytomegalovirus sero-positivity and autism symptoms in children

Autism spectrum disorder (ASD) is one of the most commonly diagnosed neurodevelopmental disorders in the United States. While ASD can be significantly influenced by genetics, prenatal exposure to maternal infections has also been implicated in conferring risk. Despite this, the effects of several important maternal pathogens, such as cytomegalovirus (CMV) and herpes simplex virus 2 (HSV2), remain unknown.

Preterm delivery trends by maternal race/ethnicity in the United States, 2006–2012

PURPOSE To estimate changes in preterm delivery (PTD) in the United States from 2006 to 2012 by clinical circumstance, timing of delivery, and race/ethnicity. METHODS We used vital statistics natality data on all singleton live births from the 18 U.S. states continuously using the 2003 birth certificate from 2006 to 2012. We estimated change in PTD overall and by clinical circumstance (spontaneous vs. medically indicated) and delivery timing among all women and by race/ethnicity, using descriptive and multivariable regression methods. RESULTS Overall, indicated, and spontaneous PTD declined by 10.31%, 8.40%, and 11.52%, respectively. Late-preterm, early-term, and post-term deliveries decreased substantially (12.13%, 18.37%, and 32.20%, respectively), with simultaneous increase (13.57%) in full-term deliveries. Non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander women experienced larger declines in PTD compared with Hispanic and American Indian/Alaska Native women. Non-Hispanic white women experienced larger declines in late and medically indicated PTD, while non-Hispanic black women experienced larger declines in early and moderate and spontaneous PTD. CONCLUSIONS Overall, spontaneous, and indicated PTD declined from 2006 to 2012. Declines were lower than previously reported and differed substantially by race/ethnicity.