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BACKGROUND: Existing research indicates that pregnant women who conceived through fertility treatment might experience more stress and anxiety compared to women who conceived spontaneously. Therefore, these women might have additional antenatal care needs. METHODS: A search for both quantitative and qualitative studies was performed in PubMed, PsycINFO, CINAHL and MEDLINE through May 2021, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. 21 articles met the inclusion criteria. After methodological quality appraisal using the Mixed Methods Appraising Tool, 15 studies were included in the review. RESULTS: Analysis of the studies identified behavioral, relational/social, emotional, and cognitive needs and women's preference about maternity care. Women who conceived through fertility treatment reported lower social and physical functioning scores and elevated levels of anxiety and depression compared to women who conceived spontaneously. They reported difficulties adjusting to pregnancy and experienced a care gap between discharge from the fertility clinic and going to local maternity care services for their first consultation, and a care gap postpartum. CONCLUSIONS: Women who conceived through fertility treatment have additional antenatal care needs. We recommend to offer these women more frequent check-ins, and to pay attention to the impact of their infertility and treatment on their pregnancy.

Context There is increasing evidence that intrauterine lipid metabolism influences the adiposity of the newborn and the first years thereafter. It remains unclear if these effects persist when these children grow older. Objective This study examined the associations between maternal lipid blood levels during the 13th week of pregnancy and an offspring’s adiposity, measured at age 11-12, and if these associations were moderated by the child’s sex. Methods Data were obtained from a community-based birth cohort, the Amsterdam Born Children and their Development (ABCD) study. At a median of 13 weeks’ gestation, nonfasting blood samples of triglycerides (TGs), total cholesterol (TC), free fatty acids (FFAs), and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) were measured. An offspring’s body mass index (BMI), subcutaneous fat (SCF), waist-to-height-ratio (WHtR), and fat percentage (fat%) were measured at age 11-12. Mothers with at-term born children were included (n = 1853). Multivariable linear regression analyses were performed to assess the associations between maternal lipids and each offspring’s adiposity outcome separately. Sex differences were additionally evaluated. Results TGs, TC, ApoB/ApoA1, and FFAs were significantly positively associated with BMI, WHtR, and fat% (adjusted for gestational age at blood sampling, child’s age, sex, and sexual maturation). After additional adjustments for potential confounders and covariates, only TGs remained significantly associated with WHtR (0.45, 95% CI –0.007; 0.91). There were no associations between maternal lipids and SCF and no clear sex-specific results were found. Conclusion Overall, our results do not strongly support that maternal lipid profile during the 13th week of pregnancy has programming effects on adiposity in preadolescence.

Objectives Maternal anxiety during pregnancy is a risk factor for child behavioral/emotional problems. Knowledge about explanatory factors mediating this link is scarce. Maternal anxiety during pregnancy may be an indicator of adverse postnatal environmental conditions, including maternal anxiety and poor parenting, possibly affecting child behavior. This study investigated whether maternal anxiety and mindful parenting in early childhood mediate the association between maternal anxiety during pregnancy and child behavioral/emotional problems. Methods This study was based on a sample of 118 mother-child dyads who participated in a cohort study that followed participants from pregnancy until 4 years after birth. At 21 weeks’ gestation and when the child was 4 years old, mothers completed questionnaires to assess state anxiety (State-Trait Anxiety Inventory) and general anxiety (Symptom Checklist-90 anxiety subscale). At age 4 years, mothers reported mindful parenting (Interpersonal Mindfulness in Parenting Scale) and child behavioral/emotional problems (Child Behavior Checklist). Results Maternal state anxiety during pregnancy was positively associated with child internalizing problems and negatively with mindful parenting. Maternal general anxiety during pregnancy was related with more child internalizing and externalizing problems but not with mindful parenting. The association between maternal state anxiety during pregnancy and child internalizing problems was sequentially mediated via concurrent maternal general anxiety and mindful parenting. Conclusions These findings suggest that maternal anxiety during pregnancy continues into early childhood and, because of this, it subsequently affects child internalizing behavior via poor mindful parenting. Replication studies are needed before developing interventions for tackling maternal anxiety during pregnancy and promoting mindful parenting.

Objective To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart. Background Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management. Methods This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included. We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes. Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score Results We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low. Conclusions The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk. Trial Registration Netherlands Trial Register NTR4367. Registration date March 20th, 2014.

Routine third trimester ultrasonography is increasingly used to screen for fetal growth restriction. However, evidence regarding its cost-effectiveness is lacking. We aimed to evaluate the cost-effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes compared to usual care (selective ultrasonography). An economic evaluation alongside a stepped-wedge cluster-randomized trial was conducted. Via 60 midwifery practices 12,974 Dutch women aged ≥16 years with low-risk pregnancies were enrolled at 22.8 (SD = 2.4) weeks’ gestation. All practices provided usual care. At 3, 7, and 10 months a third of the practices were randomized to the intervention strategy providing routine ultrasonography at 28–30 and 34–36 weeks’ gestation and usual care. The primary clinical outcome was a dichotomous composite measure of 12 severe adverse perinatal outcomes (SAPO) up to one week postpartum. Information on perinatal care and societal costs was derived from Netherlands Perinatal Registry, hospital records and a survey. Cost-effectiveness analyses revealed no significant differences in SAPO and healthcare and societal costs between the intervention strategy (n = 7026) and usual care (n = 5948). Cost-effectiveness acceptability curves showed that the probability of cost-effectiveness was never higher than 0.6 for all possible ceiling ratios. Adding routine third trimester ultrasonography to usual care is not cost-effective in reducing SAPO.

OBJECTIVE: To examine the association between intrapartum synthetic oxytocin and child behavioral and emotional problems and to assess if maternal depressive or anxious symptoms or mother-to-infant bonding play a mediating role in this association.DESIGN: Prospective cohort study.SETTING: Population-based Pregnancy Anxiety and Depression Study.PARTICIPANTS: Pregnant women in their first trimester of pregnancy visiting a total of 109 primary and nine secondary obstetric care centers in the Netherlands between 2010 and 2014 were invited to participate. Follow-up measures used for the present study were collected from May 2010 to January 2019. Women with multiple gestations and with a preterm birth were excluded.MEASUREMENTS: Intrapartum synthetic oxytocin exposure status was based on medical birth records and was defined as its administration (Yes/No), either for labour induction or augmentation. Child behavioral and emotional problems were measured with the Child Behavior Checklist at up to 60 months postpartum. Maternal depressive symptoms, anxiety and mother-to infant bonding were measured with the Edinburgh Postnatal Depression Scale, State Trait Anxiety Inventory and the Mother-to-Infant Bonding Scale from 6 months postpartum. We used multivariable linear regression models to estimate standardized beta coefficients and unique variance explained.FINDINGS: 1,528 women responded. In total 607 women received intrapartum synthetic oxytocin. Intrapartum synthetic oxytocin administration was not associated with child behavioral and emotional problems, mother-to-infant bonding nor with postnatal anxiety. Intrapartum synthetic oxytocin was however significantly but weakly associated with more postnatal depressive symptoms (β=0.17, 95%CI of 0.03 to 0.30) explaining 0.6% of unique variance. Maternal postnatal depressive symptoms, postnatal anxiety symptoms and suboptimal mother-to-infant bonding were positively associated with child behavioral and emotional problems.KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: We found no evidence that intrapartum synthetic oxytocin is associated with child behavioral and emotional problems, mother-to-infant bonding, or with postnatal anxiety symptoms. Because there was no association between intrapartum synthetic oxytocin and behavioral and emotional problems in children no mediation analysis was carried out. However, intrapartum synthetic oxytocin was positively but weakly associated with postnatal depressive symptoms. The clinical relevance of this finding is negligible in the general population, but unknown in a population with a high risk of depression.

BACKGROUND: Postpartum depression is prevalent and concerns a serious health problem for women and their families. The current large-scale birth cohort study investigated: (1) the associations of various potential determinants of postpartum depression using a multidimensional approach, and (2) the individual contribution of obstetric and perinatal determinants and pregnancy-specific anxiety to the risk of postpartum depression.METHODS: This study was based on a large-scale birth cohort study in Amsterdam, the Netherlands (ABCD-study). In 5109 women depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (cut-off ≥16 indicating high risk of postpartum depression). Determinants were assessed using self-report or perinatal registries.RESULTS: In the final multivariable model, other-Western and non-Western ethnic background, increased antepartum depressive symptoms, increased antepartum anxiety, increased pregnancy-specific anxiety, being unemployed, poor sleep quality, unwanted pregnancy, abuse, multiparity, and congenital abnormality were all independently related to an increased risk of postpartum depression. The strongest risk factors for postpartum depression were antepartum depressive symptoms (adjusted odds ratio (AOR) = 3.86, 95% confidence interval (CI) 3.02-4.92), having a baby with a congenital abnormality (AOR = 2.33, 95% CI 1.46-3.73), and abuse (AOR = 1.95, 95% CI 1.02-3.73). The final model accounted for 24.5% of the variance.LIMITATIONS: Our dataset did not provide information on social support or maternal and family history of depression. Next to these determinants, future research should include biological factors.CONCLUSIONS: The determinants identified provide opportunities for the development of multidimensional early screening and early intervention strategies for women with an increased risk of postpartum depression.

OBJECTIVE: There have been substantial medical developments in prenatal anomaly and aneuploidy screening. However, the quality of counseling about these tests tends to lag behind. Additional quality requirements were therefore implemented in the Netherlands in 2017 to optimize this counseling. We compared clients' counseling preferences and experiences before and after implementation of these requirements.METHODS: We used the validated 57-item QUOTEprenatal questionnaire, to measure clients' counseling preferences and experiences before and after counseling in 20 obstetric organizations throughout the Netherlands. Clients' preferences and experiences were compared between pregnant women and partners, nulliparous versus multiparous clients and between results of a Dutch survey in 2011 and the current one.RESULTS: Sixty-five counselors and 649 clients (353 pregnant women and 296 partners) participated in this study. Compared to 2011, slightly more clients considered the three QUOTEprenatal components of counseling (client-counselor relationship, health education, and decision-making support) to be either important or very important, especially decision-making support. More clients than in 2011 perceived their needs as being well addressed, with the lowest percentages for decision-making support.CONCLUSION: Quality requirements seem to benefit the quality of counseling, as perceived by clients.PRACTICAL IMPLICATIONS: Counselors should consider tailoring their decision-making support more to clients' needs.

Birth experiences can be traumatic and may give rise to PTSD following childbirth (PTSD-FC). Peripartum neurobiological alterations in the oxytocinergic system are highly relevant for postpartum maternal behavioral and affective adaptions like bonding and lactation but are also implicated in the response to traumatic events. Animal models demonstrated that peripartum stress impairs beneficial maternal postpartum behavior. Early postpartum activation of the oxytocinergic system may, however, reverse these effects and thereby prevent adverse long-term consequences for both mother and infant. In this narrative review, we discuss the impact of trauma and PTSD-FC on normal endogenous oxytocinergic system fluctuations in the peripartum period. We also specifically focus on the potential of exogenous oxytocin (OT) to prevent and treat PTSD-FC. No trials of exogenous OT after traumatic childbirth and PTSD-FC were available. Evidence from non-obstetric PTSD samples and from postpartum healthy or depressed samples implies restorative functional neuroanatomic and psychological effects of exogenous OT such as improved PTSD symptoms and better mother-to-infant bonding, decreased limbic activation, and restored responsiveness in dopaminergic reward regions. Adverse effects of intranasal OT on mood and the increased fear processing and reduced top-down control over amygdala activation in women with acute trauma exposure or postpartum depression, however, warrant cautionary use of intranasal OT. Observational and experimental studies into the role of the endogenous and exogenous oxytocinergic system in PTSD-FC are needed and should explore individual and situational circumstances, including level of acute distress, intrapartum exogenous OT exposure, or history of childhood trauma.

Background During pregnancy, about 10 to 20% of women experience depressive symptoms. Subclinical depression increases the risk of peripartum depression, maternal neuro-endocrine dysregulations, and adverse birth and infant outcomes. Current treatments often comprise face-to-face psychological or pharmacological treatments that may be too intensive for women with subclinical depression leading to drop-out and moderate effectiveness. Therefore, easily accessible, resilience enhancing and less stigmatizing interventions are needed to prevent the development of clinical depression. This paper describes the protocol of a prospective cohort study with an embedded randomized controlled trial (RCT) that aims to improve mental resilience in a sample of pregnant women through a self-help program based on the principles of Acceptance and Commitment Therapy (ACT). Maternal and offspring correlates of the trajectories of peripartum depressive symptoms will also be studied. Methods Pregnant women (≥ 18 years) receiving care in Dutch midwifery practices will participate in a prospective cohort study (n ~ 3500). Between 12 and 18 weeks of pregnancy, all women will be screened for depression with the Edinburgh Postnatal Depression Scale (EPDS). Women with an EPDS score ≥ 11 will be evaluated with a structured clinical interview. Participants with subclinical depression (n = 290) will be randomized to a 9-week guided self-help ACT-training or to care as usual (CAU). Primary outcomes (depressive symptoms and resilience) and secondary outcomes (e.g. anxiety and PTSD, bonding, infant development) will be collected via online questionnaires at four prospective assessments around 20 weeks and 30 weeks gestation and at 6 weeks and 4 months postpartum. Maternal hair cortisol concentrations will be assessed in a subsample of women with a range of depressive symptoms (n = 300). The intervention’s feasibility will be assessed through qualitative interviews in a subsample of participants (n = 20). Discussion This is the first study to assess the effectiveness of an easy to administer intervention strategy to prevent adverse mental health effects through enhancing resilience in pregnant women with antepartum depressive symptomatology. This longitudinal study will provide insights into trajectories of peripartum depressive symptoms in relation to resilience, maternal cortisol, psychological outcomes, and infant developmental milestones. Trial registration Netherlands Trial Register (NTR), NL7499. Registered 5 February 2019.

OBJECTIVES: Increased body mass index (BMI) is associated with several adverse pregnancy outcomes, though the underlying mechanism of this association has not been fully elucidated. A mediating role of low-grade systemic inflammation in these associations is suspected but has been understudied. Our objective was to examine the effect of pre-pregnancy BMI (pBMI) on maternal and neonatal pregnancy outcomes and to explore potential mediation of these effects by C-reactive protein (CRP), a first trimester peripheral marker of inflammation.METHODS: Data from the prospective community-based ABCD-study cohort (n = 3547) was used to assess associations between self-reported continuous and categorized pBMI and outcome measures gestational hypertension (GH) and preeclampsia (PE), preterm birth (PTB) and small for gestational age (SGA) based on national perinatal registration linkage data. High-sensitivity CRP concentrations determined in serum were used to explore potential mediation of these associations by inflammation.RESULTS: Multivariable logistic regression analyses, adjusted for confounders, showed that pBMI was significantly related to gestational hypertensive disorders (odds ratio (OR) per standard deviation (SD) 1.66, 95% confidence interval (CI) 1.51-1.83) and PTB (OR 1.20, 95% CI 1.05-1.37). Dose-response relationships between categorical pBMI and gestational hypertensive disorders (overweight OR 2.37, 95% CI 1.85-3.03 and obese OR 4.45, 95% CI 2.93-6.72) and PTB (obese OR 2.12, 95% CI 1.16-3.87) were found as well. SGA was only significantly more prevalent in the underweight BMI category (OR 2.06, 95% CI 1.33-3.19). Mediation analyses revealed small but significant indirect effects of pBMI on overall PTB (0.037, bootstrapped 95% CI 0.005-0.065) and spontaneous PTB (0.038, bootstrapped 95% CI 0.002-0.069) through higher CRP. CRP was not a significant mediator of associations between BMI and gestational hypertensive disorders although larger mediation was found for GH than for PE.CONCLUSION: Our findings provide additional evidence that high(er) pBMI increases the risk of adverse maternal and neonatal outcomes and that systemic inflammation mediates some of these risks. Further research in large cohorts including (morbidly) obese women is warranted to identify pathways that may be incorporated in future interventions to reduce the risk of adverse pregnancy outcomes due to maternal obesity.

BACKGROUND: Previous studies identified demographic, reproduction-related and psychosocial correlates of suboptimal mother-to-infant bonding. Their joint informative value was still unknown. This study aimed to develop a multivariable model to screen early in pregnancy for suboptimal postnatal mother-to-infant bonding and to transform it into a risk classification model.METHODS: Prospective cohort study conducted at 116 midwifery centers between 2010-2014. 634 women reported on the Mother-to-Infant Bonding questionnaire in 2015-2016. A broad range of determinants before 13 weeks of gestation were considered. Missing data were described, analyzed and imputed by multiple imputation. Multivariable logistic regression with backward elimination was used to develop a screening model. The explained variance, the Area Under the Curve of the final model were calculated and a Hosmer and Lemeshow test performed. Finally, we designed a risk classification model.RESULTS: The prevalence of suboptimal mother-to-infant bonding was 11%. The estimated probability of suboptimal mother-to-infant can be calculated: P(MIBS≥4) = 1/(1+exp(-(-4.391+(parity× 0.519)+(Adult attachment avoidance score× 0.040))). The explained variance was 14% and the Area Under the Curve was 0.750 (95%CI 0.690-0.809). The Hosmer and Lemeshow test had a p-value of 0.21. This resulted in a risk classification model.CONCLUSION: Parity and adult attachment avoidance were the strongest independent determinants. Higher parity and higher levels of adult attachment avoidance are associated with an increased risk of suboptimal mother-to-infant bonding. The model and risk classification model should be externally validated and optimized before use in daily practice. Future research should include an external validation study, a study into the additional value of non-included determinants and finally a study on the impact and feasibility of the screening model.

Background Because of the considerable negative effects of women's childbirth-related anxiety, fear and worries, and the time constraints that midwives perceive to assess women's antenatal emotional wellbeing, it is important that midwives can identify women with a more severe fear of birth with an easy to administer, validated tool. Objective To investigate the ability of the two-item Fear of Childbirth Scale (FOBS) to discriminate between pregnant women with and without birth-related fear, compared with the 16-item Tilburg Pregnancy Distress Scale (TPDS). Methods A diagnostic accuracy comparative cross-sectional study was performed, comparing two screening tests. Sensitivity, specificity, positive and negative predictive values and accuracy and discriminant property of the FOBS were determined and compared with the TPDS and with the negative affect 11-items TPDS (TPDS-NA) subscale. The TPDS and TPDS-NA were treated as reference standard to establish the discriminative potential of the FOBS for the presence or absence of antenatal birth-related fear. Participants A sample of 396 Dutch women with uncomplicated pregnancies. Results When compared with the 16-items TPDS, the FOBS showed a higher specificity (95%) than sensitivity (70%) to detect fear of childbirth. The FOBS items had a good predictive ability for fear and worries about the forthcoming birth (79%) and a conclusive ability for negative case-finding (92%). The FOBS showed good accuracy (89%). The FOBS discriminated women who were or were not classified as being fearful according to the TPDS (AUC .86). When compared with the 11 items TPDS-NA subscale, the FOBS validity and accuracy decreased: sensitivity: 51%; specificity 92%; positive predictive ability 65%; negative predictive ability 88%; accuracy 83%; AUC .82. Conclusion When compared with the 16-items TPDS, the two-item FOBS shows to be an accurate tool for identifying the presence of antenatal birth-related fear in a sample of Dutch women with uncomplicated pregnancies.

Both prenatal and postnatal parental bonding (i.e., the affective tie from parent to child) have important effects on parental and child functioning. However, research on the continuity and correlates of parental bonding is lacking. Therefore, the goal of the present study was to examine the stability of bonding levels and to explore distinct bonding patterns with a latent class analysis. Moreover, the correlates of these bonding patterns in the parental-, child-, and contextual domain were studied. Levels of maternal (N = 370) and paternal (N = 292) bonding and potential correlates were assessed at 26 weeks of pregnancy, 6 months, and 24 months postpartum. Results showed moderate stability of bonding from pregnancy to toddlerhood. For both mothers and fathers, 4 distinct bonding patterns were found. Parents with low bonding patterns were characterized by increased anxiety and parenting stress, less partner support, less adaptive personality profiles, and children with difficult temperament. These findings indicate the importance of monitoring young children's parents with poor levels of bonding as their bonding patterns remain stable from pregnancy until toddlerhood and because those parents experience problems in multiple domains.

Early executive functioning is an important predictor for future development of children’s cognitive skills and behavioral outcomes. Parenting behavior has proven to be a key environmental determinant of child executive functioning. However, the association of parental affect and cognitions directed to the child with child executive functioning has been understudied. Therefore, in the present study we examine the associations between parental bonding (i.e., the affective tie from parent to child), parenting stress, and child executive functioning. At 26 weeks of pregnancy, and at 6 months and 24 months postpartum the quality of the maternal (N = 335) and paternal (N = 261) bond with the infant was assessed. At 24 months, postnatal parenting stress and child executive functioning were measured by means of parent-report questionnaires. Results indicated that for both mothers and fathers feelings of bonding negatively predicted experienced parenting stress over time. In addition, for both parents a negative indirect effect of bonding on child executive functioning problems was found via experienced parenting stress. These findings indicate the importance of monitoring parents who experience a low level and quality of early parent-child bonding, as this makes them vulnerable to parenting stress, consequently putting their children at risk for developing executive functioning problems.Keywords: Maternal bonding, Paternal bonding, Prenatal bonding, Parenting stress

Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal thyroid-stimulating hormone (TSH) levels, can negatively affect the foetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing foetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring intelligence quotient (IQ). More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long-term observational studies should identify molecular, neuroanatomical and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences.

Although relations of various parental psychological problems and family functioning with child development are well documented, it remains unclear whether specific prenatal or specific postnatal risk factors are independently associated with child emotional and behavioural problems, or whether observed associations can be explained by general parental psychopathology. Using a stepwise approach, we examined the effects of prenatal and postnatal parental depressive symptoms, prenatal and postnatal hostility of the parents, as well as prenatal family functioning on the risk of child emotional and behavioural problems. This study was embedded in Generation R: a population-based cohort from foetal life onwards. Mothers and fathers of 2,698 children provided information about depressive symptoms, symptoms of hostility and family functioning during pregnancy and 3 years after birth. Mother and father each reported on child behaviour when the child was 3 years old. Parental depressive symptoms increased the risk of child emotional and behavioural problems, but this increase was explained by postnatal parental hostile behaviour. Postnatal symptoms of hostility of mothers (OR = 1.34, p value

Maternal thyroid function during pregnancy is implicated in the neurodevelopment of the offspring, yet little is known about the effect of maternal thyroid parameters on the behavior of children. We investigated the association of maternal thyroid function during the first half of pregnancy with parent-reported problem behavior of the offspring up to age of 3 y. In the Generation R study, a population-based cohort of 3736 children and their mothers, data on maternal thyroid function and child's behavior were examined. The degree of internalizing and externalizing problems in the children were assessed with the Child Behavior Checklist at ages 1 1/2 and 3 y. Higher levels of maternal TSH during pregnancy predicted a higher externalizing scores in children at 1 1/2 and 3 y (B = 0.22 per SD of TSH; 95% CI: 0.04, 0.40; B = 0.10 per SD for internalizing scores; 95% CI: -0.01, 0.21). Maternal free thyroxine (T4) and total T4 were not associated with internalizing or externalizing scores of children. The linear relationship with more externalizing scores was across the range of TSH; this implies that subtle impairments of maternal thyroid function may affect the child. The results suggest that thyroid function is crucial for fetal brain development, which determines problem behavior later in life. (Pediatr Res 69: 454-459, 2011)

BackgroundPrevious research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth.MethodPregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length.ResultsIn mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) −69.22 to −6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI −4.48 to −1.23, pConclusionsThe study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy.

Aim The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth. Method Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10–17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records. Results After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71–0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73–0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49–0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy. Interpretation Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

BackgroundAccumulating evidence shows that maternal anxiety during pregnancy adversely affects child outcomes. The positive effects of maternal psychosocial factors during pregnancy on child outcomes are not yet studied. This prospective study addresses the association between maternal mindfulness during pregnancy and socio-emotional development and temperament in 10 months-old infants. We also investigated whether this association was mediated by maternal anxiety.MethodMothers (N = 90) provided information about mindfulness and anxiety at the beginning of the second trimester of pregnancy. Infant socio-emotional development (Ages and Stages Questionnaire: Social Emotional; ASQ:SE) and temperament (Infant Behaviour Questionnaire—Revised; IBQ-R) were assessed at age 10 months.ResultsHigher maternal mindfulness during pregnancy was associated with less infant self-regulation problems and less infant negative affectivity. Mediation analysis showed that maternal anxiety mediated the association between infant self-regulation problems and maternal mindfulness.ConclusionThese results suggest that maternal mindfulness during pregnancy may have positive effects on infant development. This association may be mediated by reduced anxiety symptoms in pregnant women who score high on mindfulness. Additional replication studies are needed using objective measures of infant behavioural/emotional outcomes and mindfulness of the mother during child development.Keywords: Foetal programming, Maternal mindfulness, Maternal anxiety, Self-regulation, Temperament

Animal models and epidemiological studies suggest that mild maternal thyroid hormone deficiency in early gestation has adverse consequences on the cognitive abilities of the children. However, methodological problems, lack of a consistent definition for mild thyroid hormone deficiency, and short follow-up of the children reduce the confidence in the conclusion of existing studies. In this review, we summarize the main findings of a series of studies performed in Generation R, a population-based birth cohort in Rotterdam, the Netherlands. In this iodine sufficient region, we aimed to investigate the relation between mild maternal thyroid hormone deficiency in early gestation and children's verbal and nonverbal cognitive function and executive function. We discuss the main findings of these studies, present recommendations for clinicians and formulate suggestions for future research.Keywords: thyroid, pregnancy, cognition, behaviour, children, hypothyroxinaemia, executive function, iodine

We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n = 3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative Development Inventory, measuring children's verbal cognitive functioning, when children were 18 months and they completed the Parent Report of Children's Abilities, measuring nonverbal cognitive functioning, when children were 2 years old. Maternal prenatal family stress was related to children's low word comprehension and poorer nonverbal cognitive development independent of paternal reports. In a subset of 639 children, maternal prenatal family stress was also associated with observational assessments of poor effortful control at age 37 months. Paternal prenatal family stress was only related to poorer nonverbal cognitive development, independent of the mother. When both parents had high levels of prenatal family stress, children displayed particularly poor nonverbal cognitive development. These findings emphasize the significance of parental prenatal family stress for child developmental outcomes. (C) 2011 Elsevier Inc. All rights reserved.

Context: Thyroid hormones are essential for neurodevelopment from early pregnancy onward. Yet population-based data on the association between maternal thyroid function in early pregnancy and children's cognitive development are sparse. Objective: Our objective was to study associations of maternal hypothyroxinemia and of early pregnancy maternal TSH and free T-4 (FT4) levels across the entire range with cognitive functioning in early childhood. Design and Setting: We conducted a population-based cohort in The Netherlands. Participants: Participants included 3659 children and their mothers. Main Measures: In pregnant women with normal TSH levels at 13 wk gestation (SD = 1.7), mild and severe maternal hypothyroxinemia were defined as FT4 concentrations below the 10th and 5th percentile, respectively. Children's expressive vocabulary at 18 months was reported by mothers using the MacArthur Communicative Development Inventory. At 30 months, mothers completed the Language Development Survey and the Parent Report of Children's Abilities measuring verbal and nonverbal cognitive functioning. Results: Maternal TSH was not related to the cognitive outcomes. An increase in maternal FT4 predicted a lower risk of expressive language delay at 30 months only. However, both mild and severe maternal hypothyroxinemia was associated with a higher risk of expressive language delay across all ages [odds ratio (OR) = 1.44; 95% confidence interval (CI) = 1.09-1.91; P = 0.010 and OR = 1.80; 95% CI = 1.24-2.61; P = 0.002, respectively]. Severe maternal hypothyroxinemia also predicted a higher risk of nonverbal cognitive delay (OR = 2.03; 95% CI = 1.22-3.39; P = 0.007). Conclusions: Maternal hypothyroxinemia is a risk factor for cognitive delay in early childhood. (J Clin Endocrinol Metab 95: 4227-4234, 2010)

The aim of this study was to investigate within a population-based cohort of 4384 infants (2182 males, 2202 females) whether fetal growth from early pregnancy onwards is related to infant development and whether this potential relationship is independent of postnatal growth.Ultrasound measurements were performed in early, mid-, and late pregnancy. Estimated fetal weight was calculated using head and abdominal circumference and femur length. Infant development was measured with the Minnesota Infant Development Inventory at 12 months (SD 1.1mo, range 10-17mo). Information on postnatal head size and body weight at 7 months was obtained from medical records.After adjusting for potential confounders and for postnatal growth, faster fetal weight gain from mid- to late pregnancy predicted a reduced risk of delayed social development (odds ratio [OR] 0.82; 95% confidence interval [CI] 0.71-0.95, p=0.008), self-help abilities (OR 0.84; 95% CI 0.73-0.98, p=0.023), and overall infant development (OR 0.65; 95% CI 0.49-0.87, p=0.003). Similar findings were observed for fetal head growth from mid- to late pregnancy.Faster fetal growth predicts a lower risk of delayed infant development independent of postnatal growth. These results suggest that reduced fetal growth between mid- and late pregnancy may determine subsequent developmental outcomes.

The aim of this study was to investigate whether maternal anxiety that is temporary or chronic during the pre- and postnatal period predicts infant temperament. Mothers of 2997 infants in a population-based birth cohort reported levels of pregnancy-specific anxiety (Pregnancy Outcome Questionnaire) and general anxiety symptoms (Brief Symptom Inventory) prenatal and at 6 months postnatal. Temperament characteristics were assessed by maternal report using the Infant Behavior Questionnaire—Revised when the infants were 6 months of age. Maternal pregnancy-specific and general anxiety during the pre- and postnatal period were all independently associated with perceived infant temperamental difficulties. Chronically high maternal anxiety predicted the highest perceived infant activity level and negative affectivity. These findings show that different forms of maternal anxiety during both the pre- and postnatal period are independently related to perceived temperamental problems in infancy. They also emphasize the significance of chronic maternal anxiety for infant mental health. Copyright © 2009 John Wiley & Sons, Ltd.

The vulnerability for behavioral problems is partly shaped in fetal life. Numerous studies have related indicators of intrauterine growth, for example, birth weight and body size, to behavioral development. We investigated whether fetal size in mid- and late pregnancy is related to infant irritability and alertness. In a population-based birth cohort of 4,255 singleton full-term infants ultrasound measurements of fetal head and abdominal circumference in mid- and late pregnancy were performed. Infant irritability and alertness scores were obtained by the Mother and Baby, Scales at 3 months and z-standardized. Multiple linear regression analyses revealed curvilinear associations (inverted J-shape) of measures of fetal size in both mid- and late pregnancy with infant alertness. Fetal. size characteristics were not associated with infant irritability These results suggest that alterations 4 intrauterine growth affecting infant alertness are already detectable front mid-pregnancy onwards. (C) 2008 Wiley Periodicals, Inc. Dev Psychobiol 51: 119-130, 2009.