Temperamental Difficulty Research Articles

Prenatal Hair Cortisol Concentrations during the COVID-19 Outbreak: Associations with Maternal Psychological Stress and Infant Temperament

Maternal psychological stress during pregnancy, including stress resulting from disasters and trauma, has been linked to temperamental difficulties in offspring. While heightened cortisol concentrations are often hypothesized as an underlying mechanism, evidence supporting this mechanism is inconsistent. To address these issues, this preregistered study investigated the following associations between: 1) prenatal psychological stress and hair cortisol, as a biomarker for chronic stress, during the COVID-19 outbreak (i.e., as a worldwide psychological stressor), and 2) maternal hair cortisol during the COVID-19 outbreak and later infant temperamental negative affectivity and orienting/regulation. Additionally, we explored whether associations were different for women with low versus high socioeconomic status (SES) and at different stages of pregnancy. Pregnant women (N =100) filled out online questionnaires during the first COVID-19 lockdown. Maternal hair samples were collected during home visits. When infants were six months old, mothers reported on their infant’s temperament. While analyses revealed no associations between prenatal COVID-19 psychological stress and hair cortisol during the COVID-19 outbreak, SES proved to be a moderator in this association. Only pregnant women with higher levels of SES, showed a positive association between work-related and social-related COVID-19 worries and hair cortisol. Finally, prenatal hair cortisol was not associated with later infant temperamental negative affectivity and orienting/regulation. While the COVID-19 outbreak proved to be a major psychological stressor, the physiological impact of the crisis might be different for pregnant women with higher SES as compared to lower SES.

Prenatal hair cortisol concentrations during the COVID-19 outbreak: Associations with maternal psychological stress and infant temperament

BackgroundMaternal psychological stress during pregnancy, including stress resulting from disasters and trauma, has been linked to temperamental difficulties in offspring. Although heightened cortisol concentrations are often hypothesized as an underlying mechanism, evidence supporting this mechanism is not consistent, potentially because of methodological issues and low stress in the population. AimTo address these issues, this preregistered study investigated the following associations between: 1) prenatal psychological stress and hair cortisol, as a biomarker for chronic stress, during the COVID-19 outbreak (i.e., as a major worldwide psychological stressor), and 2) maternal hair cortisol during the COVID-19 outbreak and later infant temperamental negative affectivity and orienting/regulation. Additionally, we explored whether associations were different for women with low versus high socioeconomic status (SES; maternal education and annual household income) and at different stages of pregnancy. MethodPregnant women (N = 100) filled out online questionnaires during the first COVID-19 lockdown. Six months later, when most mothers were still pregnant or had just given birth, maternal hair samples were collected during home visits. When infants were six months old, mothers reported on their infant’s temperament. ResultsAlthough hierarchical regression analyses revealed no associations between prenatal COVID-19 psychological stress and hair cortisol during the COVID-19 outbreak, SES proved to be a moderator in this association. Only pregnant women with higher levels of SES, not lower levels, showed a positive association between work-related and social support-related COVID-19 worries and hair cortisol. Finally, prenatal hair cortisol was not associated with later infant temperamental negative affectivity and orienting/regulation. ConclusionAlthough the COVID-19 outbreak proved to be a major psychological stressor worldwide, the physiological impact of the crisis might be different for pregnant women with higher SES as compared to lower SES.

Children's early difficulty and agreeableness in adolescence: Testing a developmental model of interplay of parent and child effects.

Although the trait of Agreeableness is broadly considered a key facet of adjustment, mental health, and socioemotional competence, surprisingly little is known about its developmental origins. Laursen and Richmond (2014) proposed that children's early difficulty poses a challenge for their future social relationships, ultimately leading to low Agreeableness. Drawing from that model, we examined a path to Agreeableness in adolescence, originating in children's early temperamental difficulty and involving bidirectional effects of parenting and children's self-regulation. In a community sample of 102 mothers, fathers, and children, we assessed children's difficulty at age 3, and parental power-assertive discipline and children's self-regulation at ages 4.5 and 5.5, using behavioral observations in lengthy interactive contexts and in standard laboratory paradigms. Agreeableness at age 14 was modeled as a latent construct, derived from mothers', fathers', and teachers' ratings. Model-fitting analyses, testing the unfolding developmental path from child difficulty to Agreeableness while controlling for continuity of parental power assertion and child self-regulation, supported a process linking early difficulty with Agreeableness at age 14 through transactions over time between the child's self-regulation and power-assertive parenting. The findings highlight the early dynamics of children's temperament characteristics and parenting in the origins of Agreeableness. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Weight gain, feeding and eating in the first year of life of babies of smoking and non-smoking mothers

Babies of mothers who smoke during pregnancy tend to be born underweight but are at risk for pediatric obesity. Maternal feeding practices, maternal disordered eating, and child temperament were assessed as potential mediators of early weight gain in babies of smoking and non-smoking mothers. The BMIs of babies of 88 smoking and 107 non-smoking mothers were recorded at birth and reported one year later. Mothers self-reported on disordered eating and child feeding practices, and on their infants' temperament. Babies of smoking mothers had lower BMI at birth but not at age one. For babies of non-smoking but not for those of smoking mothers, BMI at birth predicted BMI at age one. Smoking mothers' disordered eating and pressure for children to eat predicted their babies' BMI at age one. In the non-smoking group only, there were significant correlations between babies' temperamental difficulties and babies' BMI at age one. In contrast to non-smoking mothers, smoking mothers tend to pressure their babies to eat, and not to feed them in response to their distress. This interim picture may provide insight into the transition of the children of smoking mothers from underweight newborns to children classified as overweight.

Infant sleep moderates the effect of infant temperament on maternal depressive symptoms, maternal sensitivity, and family functioning

Observed infant temperamental difficulty and infant sleep efficiency and sleep variability were examined as predictors of maternal depressive symptoms, maternal sensitivity, and family functioning. Eight observations at 8-months postpartum were used to assess infant temperament, and actigraphy was used to measure infant sleep for 1-week at the time of the 8-month assessment. Structured clinical interviews were used to assess maternal depressive symptoms between 5 and 12 months postpartum and at 15 months postpartum, and observational assessments were used to assess maternal sensitivity and family functioning at 15 months postpartum. Variability in infant sleep moderated the effect of infant temperament on maternal depressive symptoms, maternal sensitivity, and family functioning. Infant temperament was positively associated with maternal depressive symptoms when variability in infant sleep efficiency was high, but not when variability in infant sleep efficiency was low. Likewise, infant temperament was negatively associated with maternal sensitivity and family functioning when variability in infant sleep efficiency was high, but not when variability in infant sleep efficiency was low. Results underscore the importance of infant sleep for maternal and family health.

Gender differences in trajectories of depressive symptoms across childhood and adolescence: A multi-group growth mixture model

BackgroundThis study sought to identify depression trajectories across childhood and to model a range of child and family predictors of whether a child may be on an increasing trajectory towards depressive disorder in adolescence. MethodsMulti-group growth mixture modelling (MGMM) was used on a sample of 4983 children from the Longitudinal Study of Australia Children (LSAC). Depressive symptoms of these children were assessed over 10-years with six time-points, administered every second year commencing at 4 years via the parent report version of the Strength and Difficulties Questionnaire. Predictors of class membership were also examined. ResultsFour trajectories were found to be the best fitting model characterising low-stable (75%); decreasing (11%); increasing (9%); high and rising (6%) groups. Females were more likely to be in a trajectory of increasing depressive symptoms between 4 and 14 years of age than males. Reactive temperament and maternal depression at four and six years of age were consistent predictors of increasing and high trajectories while persistent temperament acts as a protective factor for females. LimitationsThe findings should be interpreted in the light of limitations due to common-method variance and the absence of diagnostic indicators of depressive disorder. ConclusionsWe conclude that there are gender differences in patterns of depressive symptoms from childhood to adolescence and meaningful predictors of these early developmental trajectories. Preventative interventions in childhood targeting parents with depression and children with temperamental difficulties may be indicated.

Pengaruh Bermain Congklak Terhadap Memori Jangka Pendek Lansia Di Panti Pelayanan Sosial Lanjut Usia Dewanata Cilacap

Background. Elderly often have problems related to cognitive function, especially short-term memory. Short-term memory disorders can make the elderly become temperamental and face difficulties in social interaction. There are various ways to increase cognitive function. This study aimed to determine effect of playing congklak on short-term memory of elderly living in Dewanata Long Term Care Facility.Methods. This is a quasi experiment research with non-equivalen group design. Total sample was 28 people which divided into 2 group, control and intervention group. Short-term memory is measured by the digit span forward and backward, and the data were analyzed with the Wilcoxon test and Mann-Whitney test.Results. Majority of respondents were female and age 70 years old on average. There was a significant difference in pre and post test score in intervention group (p = 0.002), but it wasn’t found in control group (p = 0.739). Score difference in intervention group was significantly higher compared to those in control group (p = 0.001).Conclusion. Playing congklak can improve short-term memory of the elderly.

Disentangling the Direction of Associations between Sleep and Temperament in Toddlers

ABSTRACT Objectives/Background Although much research has investigated the associations between children’s sleep and their temperament, the direction of these associations remains unclear, largely due to a lack of longitudinal studies with repeated assessments of both sleep and temperament. Aiming to clarify the temporal precedence of these two constructs, the current study investigated reciprocal associations between toddlers’ sleep and temperament with a longitudinal design. Participants The sample consisted of 82 toddlers (39 girls) assessed twice. Methods At both 2 (M = 25.23 months; SD = 1.11) and 3 years of age (M = 36.81 months; SD = 0.91), toddlers’ sleep duration and quality were assessed using actigraphy and their temperament was reported by their mothers with the Toddler Behavior Assessment Questionnaire. Results Shorter nighttime sleep duration (ß = − .28, p = .03) and lower sleep efficiency (ß = − .33, p = .01) at 2 years predicted more temperamental proneness to anger at 3 years, while greater temperamental social fear at 2 years was predictive of shorter 24-hour (ß = − .44, p = .02) and nighttime (ß = − .36, p = .04) sleep duration at 3 years. Associations between temperamental activity level and sleep variables were non-significant. Conclusion The direction of the associations between toddlers’ sleep and their temperament may vary according to which dimension of temperament is considered. These findings should encourage practitioners to identify the beginning of the causal chain leading to sleep or temperamental difficulties so as to develop well-tailored intervention plans.

Behavioral problems and temperamental characteristics among children in alcoholic families

Background: Children of alcoholics (COAs) are at high risk for behavioral problems and temperamental difficulties. Aim: The aim of this study was to compare the behavioral problems and temperamental characteristics in children of persons with and without alcoholism. Materials and Methods: Using a case–control design, 60 children (30 in the study group and 30 controls) were evaluated for their behavioral problems, aggression, and temperamental characteristics. Tools used were: Child Behavior Checklist, Aggression Questionnaire, and the Malhotra's Temperament Schedule. Results: The COAs were found to be more aggressive, manifesting more behavioral problems and temperamental difficulties than the controls. Conclusion: Children in families with an alcohol-dependent father are at increased risk for problem behaviors with a difficult temperament.

The interplay between early language and temperamental difficulties in the prediction of severe antisocial behavior among males

PurposeThe purpose of this paper is to examine whether early language deficits increase the risk of severe antisocial behavior among male children, and whether this association varies as a function of negative temperament during infancy.Design/methodology/approachData are derived from the Early Childhood Longitudinal Study, Birth Cohort. Both survey methods and direct observations were employed to obtain the data. Logistic regression was used to examine the research questions at hand.FindingsMale children with oral vocabulary and grammatical/syntactic deficits during the toddler years exhibited more frequent antisocial behavior across home and school settings during kindergarten, relative to boys without language deficits. However, this relationship was limited to males who manifested negative temperament/affect during their infancy, as reported on by both parents and independent raters.Originality/valuePrior research on language, temperament, and antisocial behavior has generally overlooked the potential for these early-life risk factors for subsequent offending to interact with each other. The findings of the present study suggest that early intervention and prevention efforts should account for ways in which individual temperamental differences can structure behavioral responses to cognitive challenges.

Mother-child interactions in young children with excessive physical aggression and in typically developing young children.

Among the multiple risk factors, the emergence of conduct problems in young children may be linked to harsh parenting and child's temperamental difficulties, leading to a reciprocal early discordant relationship. Little is known about the characteristics of early parent-child interactions in young children with physical aggression. The purpose of the current study was to evaluate the characteristics of mother-child interactions in dyads referred for excessive physical aggression in young children under 5 years of age compared to mother-child interactions in typically developing young children. Mother-child interactions were assessed during a free-play session in both a clinical sample ( N = 70, child mean age = 3.5 years) and a nonclinical sample ( N = 80, child mean age = 3.5 years) by using the Rating Scale of Interaction Style (Clark and Seifer, adapted by Molitor and Mayes). Significant differences were found between several interactive features in clinical and nonclinical dyads. In clinical dyads, mothers' behaviors were often characterized by intrusiveness and criticism toward children, and poor facilitative positioning. Children with excessive aggressive behavior often displayed poor communication, initiation of bids, and poor responsiveness toward the mother. They displayed fewer sustained bouts of play than typically developing children did. In clinical dyads, strong positive correlations were found between child responsiveness and maternal interest in engagement ( r = .41, p < .001), while the child displaying sustained bouts of play was negatively correlated with the mother's attempts to intrude on the child's activity ( r = .64, p < .05). These data show that children with excessive aggressive behavior develop disrupted mother-infant interactions from a very young age. Several negative interactive features and correlations between child behavior and maternal behavior were found in clinical samples. The effects of these features add up and probably strengthen each other, thus leading to interactive difficulties from a very young age. More attention should be paid to early parent-child interactions in case of child behavioral problems. The recognition of these interactive dysfunctions is discussed in terms of clinical implications for therapeutic interventions.

The link between infant regulatory problems, temperament traits, maternal depressive symptoms and children\u2019s psychopathological symptoms at age three: a longitudinal study in a German at-risk sample

BackgroundDifficult conditions during childhood can limit an individual’s development in many ways. Factors such as being raised in an at-risk family, child temperamental traits or maternal traits can potentially influence a child’s later behaviour. The present study investigated the extent of regulatory problems in 6-month-old infants and their link to temperamental traits and impact on externalizing and internalizing problems at 36 months. Moderating effects of maternal distress and maternal depressive symptoms were tested as well.MethodsIn a quasi-experimental, longitudinal study, a sample of 185 mother-infant dyads at psychosocial risk was investigated at 6 months with SFS (infants’ regulatory problems) and at 3 years with CBCL (children’s behavioural problems), EAS (children’s temperament), ADS (maternal depressive symptoms) and PSI-SF (maternal stress).ResultsA hierarchical regression analysis yielded a significant association between infants’ regulatory problems and both externalizing and internalizing behaviour problems at age 3 (accounting for 16% and 14% variance), with both externalizing and internalizing problems being linked to current maternal depressive symptoms (12 and 9% of the variance). Externalizing and internalizing problems were found to be related also to children’s temperamental difficulty (18 and 13% of variance) and their negative emotionality. With temperamental traits having been taken into account, only feeding problems at 6 months contributed near-significant to internalizing problems at 3 years.ConclusionsOur results underscore the crucial role of temperament in the path between early regulatory problems and subsequent behavioural difficulties. Children’s unfavourable temperamental predispositions such as negative emotionality and generally “difficult temperament” contributed substantially to both externalizing and internalizing behavioural problems in the high-risk sample. The decreased predictive power of regulatory problems following the inclusion of temperamental variables indicates a mediation effect of temperamental traits in the path between early regulatory problems and subsequent behavioural problems. Our results support the main effects of a child’s temperament, and to some degree maternal depressive symptoms, rather than the diathesis stress model of interaction between risky environment and temperamental traits.Trial registration D10025651 (NZFH)

Self-regulated compliance in preschoolers with autism spectrum disorder: The role of temperament and parental disciplinary style

Regulatory difficulties are common in children with autism spectrum disorder. This study focused on an important aspect of self-regulation-the ability to willingly comply with frustrating demands of socialization agents, termed "self-regulated compliance." We studied compliance to parental demands in 40 preschoolers with autism spectrum disorder and 40 matched typically developing preschoolers, during separate interactions with mother and father, while engaging in two paradigms: toy pick-up and delayed gratification, which tap the "do" and "don't" aspects of self-regulated socialization at this age. Parents' disciplinary style was micro-coded from the two paradigms and child temperament was parent reported. Compared to their typically developing peers, children with autism spectrum disorder showed more noncompliance and less self-regulated compliance to parental demands and prohibitions and greater temperamental difficulties across several domains. No group differences were found in parental disciplinary style. Child self-regulated compliance was associated with parental supportive disciplinary style and with child attention focusing. Findings highlight the importance of parental supportive presence in structuring the development of socialization in children with autism spectrum disorder. Implications for parent-child emotion regulation interventions are discussed.

Cognition, temperament, and cerebral blood flow velocity in toddlers and preschool children with sleep-disordered breathing or behavioral insomnia of childhood

BackgroundCognitive decrements, problematic behaviors, and increased cerebral blood flow velocities (CBFVs) have been reported in children aged 3–7 years with sleep-disordered breathing (SDB). Whether similar impairments exist in younger children or those with behavioral insomnia of childhood (BIC) remains unclear. This study aimed to compare cognition and temperament in children aged 1–5 years with SDB or BIC to healthy control children, and to investigate whether cognitive or behavioral deficits associated with sleep problems are related to changes in CBFV. MethodToddlers and preschool-aged children (12–67 months) who had been referred for the clinical evaluation of SDB (n = 20) or BIC (n = 13) and a comparative sample of non-snoring healthy sleepers (controls; n = 77) were recruited from the community. Children underwent cognitive assessment (Mullen's Scale of Early Learning) and measurement of resting bilateral CBFV in the middle cerebral artery (MCA) using Transcranial Doppler. Parents completed temperament scales (Early Childhood or Childhood Behavior Questionnaire), a sleep problem questionnaire (Pediatric Sleep Problem Survey Instrument) and performed home-based pediatric sleep monitoring (Actigraphy and Sleep Diary). ResultsSDB children demonstrated impaired receptive skills, more hyperactive and energetic temperaments, and higher bilateral CBFV than controls and children with BIC. Logistic regression analyses indicated that impaired cognition, temperamental difficulties, and increased CBFV are independently associated with SDB. ConclusionsDuring early childhood, problematic temperaments, cognitive deficits, and altered cerebrovascular functioning are associated with SDB but not BIC. CBFV does not appear to mediate these daytime deficits and instead may be an independent outcome of SDB. The findings support the need for an early intervention in pediatric SDB.

Weakened Resilience in Parenting Self-Efficacy in Pregnant Women Who Were Abused in Childhood: An Experimental Test.

This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243) participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25%) experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success) and a difficult-to-soothe infant (20% soothing success). Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline), but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood.

Serotonin Transporter Gene (SLC6A4) Methylation Associates With Neonatal Intensive Care Unit Stay and 3-Month-Old Temperament in Preterm Infants.

Preterm birth and Neonatal Intensive Care Unit (NICU) stay are early adverse stressful experiences, which may result in an altered temperamental profile. The serotonin transporter gene (SLC6A4), which has been linked to infant temperament, is susceptible to epigenetic regulation associated with early stressful experience. This study examined a moderation model in which the exposure to NICU-related stress and SLC6A4 methylation moderated infant temperament at 3 months of age. SLC6A4 methylation at 20 CpG sites was quantified in preterm infants (N = 48) and full-term infants (N = 30) from Italian middle-class families. Results suggested that in preterm infants NICU-related stress might be associated with alterations of serotonergic tone as a consequence of SLC6A4 methylation, which in turn, might associate with temperamental difficulties assessed at 3 months of age.

RELATIVE CONTRIBUTIONS OF PARENT-PERCEIVED CHILD CHARACTERISTICS TO VARIATION IN CHILD FEEDING BEHAVIOR.

Few studies have examined the relative impact of co-occurring child characteristics on problematic feeding behavior. The aim of the current study was to assess the relative contributions of parent-perceived child characteristics in multivariable models of child feeding behavior. One hundred sixty-one mothers reported on their child's feeding behavior and a number of key child characteristics. These characteristics were entered into controlled multivariable models of child feeding behavior, using child and parent frequency domains of the Behavioral Pediatrics Feeding Assessment Scale (BPFAS; W. Crist et al., 1994) as outcome measures. Child feeding problems were positively associated with food neophobia and external behavioral and social issues, but not with most domains of temperamental difficulty or sensory sensitivity. Feeding problem frequency was associated with externalizing symptoms whereas parental perceptions of problems and coping were associated with social-interaction problems in the child. Population feeding problems appear to be external and interactive problems rather than driven by innate or internalizing factors. The association with externalizing symptoms suggests that feeding problems at this level may fall within a wider profile of challenging behavior; however, the existence of problematic feeding behaviors may constitute a challenge for parents only when the child's social interactions also are seen to be deficient.

Trajectories of Early Television Contact in Japan: Relationship with Preschoolers’ Externalizing Problems

We examined the link between trajectories of television contact time at ages 1–5 and externalizing problems at age 5, using data from a Japanese longitudinal study of media use and child development (N = 1,189). Despite the American Academy of Pediatrics recommendation for no television contact before age 2, growth mixture modeling identified 3 trajectory classes, comprising heavy-start contact (8%, mean contact time at age 0 = 331.44 min/day), characterized by remarkably long television contact time in infancy and maintenance of longer contact, while mild contact (51%, 147.57 min/day) and moderate contact (41%, 236.64 min/day) had relatively shorter contact in infancy and moderate declines in later years. The findings suggest that both infant temperamental difficulties and family characteristics predicted trajectory classification of television contact time. Scores for attention problems and conduct problems at age 5 did not significantly differ among trajectory groups, nor did regression coefficients.

The story of a girl with weeping blood: Childhood depression with a rare presentation.

Ms. V, a 10-year-old girl was referred to Child Psychiatry Department with complaints of bleeding from eyes for last 3 months. Bleeding was spontaneous, recurrent, painless, and self-limited. History revealed significant Psychological stressors, Temperamental Difficulties and Conflicts with Mother. Mental status examination revealed Depression in Ms. V. During hospital stay, Ms. V developed repeated bleeding episodes. The presence of hemoglobin is confirmed in the bleeding sample. Hematologic investigations and computed tomography brain were normal. Ms. V was started on Sertraline, Propranolol, and Clonazepam. Both Ms. V and her Mother were psycho-educated about the nature of the illness. Ms. V was discharged and under follow-up. This case is reported for the rarity of presentation (bleeding from Eyes) of a childhood Depression.

Maternal psychological state and infant’s temperament at three months

Objective: The study aimed to investigate the possible relationship between maternal psychological state in the perinatal period and the child’s temperament at 3 months postpartum. Background: The perinatal period is a phase of intense psychological complexity which may increase the risk of the development, or a recurrence of psychological disturbances in parents. The current literature highlights the potential negative effects of a perturbed maternal psychological state on fetal and newborn development. Among the consequences of fetal exposure to maternal states of depression or anxiety are increased inconsolable crying and sleep disturbance in the newborn, difficult temperament, motor and cognitive development delays in children and a higher risk of depression in adolescence. Methods: A longitudinal design using self-report measures of maternal mood, and maternal report of the infant’s temperament, was used. The sample comprised 107 Italian, low-risk nulliparous women. Maternal and infant variables were assessed in the third trimester of pregnancy and at 3 months postpartum. The variables measured included: maternal depression, anxiety, prenatal attachment, alexithymia, social support, maternal bonding with parents, stressful events, and the infant’s temperament. Results: Higher scores of antenatal depression and postnatal state anxiety were independent predictors of increased temperamental difficulties of the baby. Conclusion: The results support the hypothesis that maternal perinatal states of depression or anxiety are associated with increased difficulty in the temperament of the baby as perceived by mothers. This therefore supports the need for prevention-treatment programmes from the early stages of pregnancy.