Factors associated with mental health of young children during the COVID-19 pandemic in the Netherlands.

BACKGROUND: The COVID-19 pandemic and accompanying societal measures have impacted children and their families all over the world. Little is known about the factors associated with mental health outcomes in young children (i.e., 1 to 6 years old) during the pandemic. The current study aimed to examine associations with potential risk and protective factors, i.e., direct COVID-19 exposure factors as well as within-family characteristics. METHODS: Caregivers of children aged 1-6 years old were recruited in the Netherlands to participate in an ongoing longitudinal research project. In the current study, baseline data-collected during the 1st year of the pandemic-are reported. The final sample consisted of 2762 caregivers who answered questionnaires assessing negative and positive dimensions of their children's mental health (i.e., anxiety, depressive symptoms, anger, sleep problems, positive affect, and self-regulation). Furthermore, caregivers provided information regarding: (1) Direct COVID-19 related factors, i.e., parental infection and death of a family member or close friend due to COVID-19, (2) Family related COVID-19 factors, i.e., parental perceived impact of the pandemic and COVID-19 related parent-child emotion regulation strategies (i.e., active, avoidant and information-focused strategies), (3) General caregiver's distress, i.e., parental mental health, parental feelings of rejection towards their child. Regression analyses were used to examine associations with children's mental health. RESULTS: Direct COVID-19 related factors were not associated with more mental health problems in the children, though parental COVID-19 infections were related with less anger in children. Family related COVID-19 factors and caregiver's distress were related with children's mental health. Higher parental perceived negative impact of the pandemic, lower parental perceived positive impact of the pandemic, more avoidant as well as more active and information-focused parent-child emotion regulation strategies, more caregiver's mental health problems and more parental feelings of rejection towards their child were related with more mental health problems in the child. CONCLUSION: Direct exposure to COVID-19 was not related with more mental health problems in the child. Family related COVID-19 factors and caregiver's distress appear to play a more important role for young children's mental health. Findings may inform prevention and intervention programs for potential future global crises as well as other stressful events.

Is maternal negative affectivity related to psychosocial behavior of preterm and term-born toddlers through mother-child interaction?

Introduction: Children born moderately to late preterm (MLP) are more prone to psychosocial difficulties than their term-born counterparts. Maternal negative affectivity (NA)-a relatively stable personality trait characterized by the tendency to experience negative thoughts, feelings and emotions-has been related to more psychosocial problems in their offspring, and to a lower quality of mother-child interactions. As MLP children seem more sensitive to their early caregiving environment, they might be more affected by maternal NA and interaction style than their term-born peers. The current study investigated whether maternal NA predicted child's psychosocial outcomes through quality of mother-child interaction, and if these associations differed between MLP and term-born children. Methods: The sample consisted of 108 MLP and 92 term-born children and their mothers. At 18 months corrected age, maternal NA was measured using a self-report questionnaire and mother-child interaction was observed during two structured tasks. Five subscales of mother-child interaction were assessed: negative interaction, reciprocal engagement, emotional support, maternal stimulation and mother-led interaction. At 24 months corrected age, social-emotional difficulties, internalizing, and externalizing problems were assessed using mother-report. Results: For MLP children, maternal NA directly, positively, predicted social-emotional difficulties (b = 0.57) and internalizing problems (b = 0.45), but no mediation effect of mother-child interaction was found. For term-born children, no direct effect but a mediation effect of mother-led interaction was found. Higher levels of maternal NA predicted less mother-led interaction which in turn predicted more problems. Birth status did not moderate any of the relationships, showing that the differences in patterns of effects found within the MLP and term-born group did not reach statistical significance. Discussion: Maternal NA was found to be a risk factor for psychosocial outcomes in toddlers, either directly for MLP children or indirectly through mother-led interaction for term-born children. These findings suggest that the process through which maternal NA affects psychosocial outcomes may be different for MLP and term-born children. However, as the examined moderation effects of birth status did not reach statistical significance, more research using larger sample sizes is needed to study mother-child interaction in greater detail.

Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events.

INTRODUCTION: Duodenal Mucosal Resurfacing (DMR) is an endoscopic ablation technique aimed at improving glycaemia and metabolic health in patients with type 2 diabetes mellitus (T2DM). DMR has an insulin sensitizing effect in patients with T2DM. Reducing hyperinsulinemia can improve cardiovascular health. In the INSPIRE trial, we combined a single DMR with a glucagon-like-peptide-1 receptor agonist (GLP-1RA) and demonstrated elimination of insulin treatment in 69% of patients at 6 months and 53% of patients at 18 months while improving glycaemic control and metabolic health. We hypothesized that this treatment approach is associated with improved cardiovascular health, by reducing hyperinsulinemia. METHODS: Before and 6 months after starting the combination treatment to replace insulin, the following assessments were performed to evaluate cardiovascular health: magnetic resonance imaging (MRI) to measure abdominal visceral adipose tissue volume, ambulatory 24 h blood pressure (ABPM) analysis, postprandial insulin and triglycerides, fasting lipid panel and urine microalbumin. The Atherosclerotic Cardiovascular Disease (ASCVD) score was calculated to estimate 10-year risk of cardiovascular disease or stroke and the diabetes lifetime-perspective prediction (DIAL) score was calculated to estimate years free of cardiovascular disease. RESULTS: Six months after replacing exogenous insulin by DMR and GLP-1RA, visceral adipose tissue decreased significantly by 24%. Postprandial triglyceride and insulin concentrations decreased significantly (p < 0.001), as did total cholesterol (from median 3.64 (IQR 3.34-4.89) to 3.48 (3.18-3.97) mmol/l, p = 0.008), LDL (from median 1.92 (IQR 1.49-2.30) to 1.79 (1.49-2.08 mmol/l, p = 0.044), and urine microalbumin (from median 7 (IQR 3-27) to 4 (3-8) mg/l, p = 0.018). All daytime blood pressure values decreased significantly. The ASCVD 10-year risk score decreased (from median 13.6 (IQR 5.7-26.0) to 11.5 (4.2-22.5) %, p = 0.030)) and the DIAL score increased (from median 82 (IQR 81-83) to 83 (81-84) years, (p = 0.039)). DISCUSSION: The combination of DMR and GLP-1RA to replace insulin therapy in patients with T2DM is associated with a positive effect on multiple parameters of cardiovascular health. Taken together, they show a pattern of overall improvement in cardiovascular health, as evidenced by decreased risk scores for cardiovascular complications. However, it is not yet clear whether these improvements will translate into a true reduction in cardiovascular events.

Effects of tocolysis with nifedipine or atosiban on child outcome: follow-up of the APOSTEL III trial.

OBJECTIVE: To compare the long-term effects of tocolysis with nifedipine or atosiban on child outcome at age 2.5-5.5 years. DESIGN: The APOSTEL III trial was a multicentre randomised controlled trial that compared tocolysis with nifedipine or atosiban in 503 women with threatened preterm birth. Neonatal outcomes did not differ between both treatment arms, except for a higher incidence of intubation in the atosiban group. METHODS: Parents were asked to complete four questionnaires regarding neurodevelopment, executive function, behaviour problems and general health. MAIN OUTCOME MEASURES: The main long-term outcome measure was a composite of abnormal development at the age of 2.5-5.5 years. RESULTS: Of the 426 women eligible for follow-up, 196 (46%) parents returned the questionnaires for 115 children in the nifedipine group and 110 children in the atosiban group. Abnormal development occurred in 32 children (30%) in the nifedipine group and in 38 children (38%) in the atosiban group (OR 0.74, 95% CI 0.41-1.34). The separate outcomes for neurodevelopment, executive function, behaviour, and general health showed no significant differences between the groups. Sensitivity analysis for all children of the APOSTEL III trial, including a comparison of deceased children, resulted in a higher rate of healthy survival in the nifedipine group (64 versus 54%), but there was no significant difference in the overall mortality rate (5.4 versus 2.7%). There were no significant subgroup effects. CONCLUSION: Outcomes on broad child neurodevelopment, executive function, behaviour and general health were comparable in both groups. Neither nifedipine nor atosiban can be considered as the preferred treatment for women with threatened preterm birth. TWEETABLE ABSTRACT: Nifedipine- and atosiban-exposed children had comparable long-term outcomes, including neurodevelopment, executive function and behaviour.

Risk and protective factors for pre- and postnatal bonding.

Since disturbances in the mother-child bond increase the risk of negative consequences for child development, it is important to identify risk and protective factors for bonding as well as longitudinal associations. Previous research has used different bonding instruments during pregnancy and the postnatal phase, leading to inconsistent results. In the current study, the same instrument was used during the various phases. In a large, community-based sample (N = 793), general information, feelings of pre- and postnatal bonding (Pre- and Postnatal Bonding Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and partner support (subscale Tilburg Pregnancy/Postnatal Distress Scale) were measured at both 32 weeks of pregnancy and 8 months postnatally. Partner support was found to be a protective factor for suboptimal pre- and postnatal bonding, as was the engagement with fetal movements for prenatal bonding. High maternal educational level was a risk factor for suboptimal prenatal bonding, as were depressive symptoms for suboptimal postnatal bonding. The associations between most prenatal determinants and postnatal bonding were mediated by prenatal bonding, which underlines the importance of promoting prenatal bonding. Professionals in clinical practice should be aware of partner support, engagement with fetal movements, and postnatal depressive symptoms: All these factors offer opportunities for improving the bonding processes.

Dado que las perturbaciones en la unión afectiva entre madre y niño aumentan el riesgo de consecuencias negativas para el desarrollo del niño, es importante identificar los factores de riesgo y de protección de la unión afectiva, así como también las asociaciones longitudinales. La investigación anterior ha utilizado diferentes instrumentos para la unión afectiva durante el embarazo y la fase postnatal, lo que ha llevado a resultados inconsistentes. En el presente estudio, el mismo instrumento se usó durante las diferentes fases. En un grupo muestra grande con base comunitaria (N = 793), se midieron, tanto a las 32 semanas del embarazo como a los ocho meses después del nacimiento, la información general, los sentimientos sobre la unión afectiva pre- y postnatal (Escala de Unión Afectiva Pre- y Postnatal), los síntomas depresivos (Escala de Edimburgo de la Depresión Postnatal), y el apoyo de la pareja (Sub-escala Tilburg sobre el Embarazo / Escala de la Angustia Postnatal). Se detectó el apoyo de la pareja como un factor de protección para la unión afectiva pre- y postnatal por debajo del punto óptimo, lo cual también se dio con respecto a la interacción con los movimientos fetales en la unión afectiva prenatal. El alto nivel de educación materna fue un factor de riesgo para la unión afectiva prenatal sub-óptima, así como los síntomas depresivos lo fueron para la unión afectiva postnatal sub-óptima. Las asociaciones entre la mayoría de los determinantes prenatales y la unión afectiva postnatal fueron mediadas por la unión afectiva prenatal, lo cual subraya la importancia de promover la unión afectiva prenatal. Los profesionales de la práctica clínica deben estar conscientes del apoyo de la pareja, la interacción con los movimientos fetales, y los síntomas depresivos postnatales: todos estos factores ofrecen oportunidades de mejorar los procesos de afectividad.

Etant donné que les perturbations du lien mère-enfant augmentent le risque de conséquences négatives pour le développement de l'enfant il est important d'identifier les facteurs de risque et les facteurs de protection du lien, ainsi que les associations longitudinales. Jusqu'à présent les recherches ont utilisé divers instruments de lien durant la grossesse et la phase postnatale, menant à des résultats n'étant pas uniformes. Dans cette étude, le même instrument a été utilisé durant les phases multiples. Chez un grand échantillon représentatif de la communauté (N = 793), les renseignements généraux, les sentiments de lien pré- et postnatal (Echelle Pré- et Postnatale) les symptômes dépressifs (Echelle de Dépression Postnatale d'Edinbourg) et le soutien du conjoint (sous-échelle de grossesse Tilburg/Echelle de Détresse Postnatale) ont été mesurés à la fois à 32 semaines de grossesse et à huit mois postnatalement. Le soutien du conjoint s'est avéré être une facteur de protection pour le lien sous-optimal pré- et postnatal, tout comme l'était le fait de s'engager avec les mouvements du foetus pour le lien prénatal. Un niveau élevé d'éducation chez la mère était un facteur de risque de lien prénatal sous-optimal, tout comme l'étaient des symptômes dépressifs pour le lien sous-optimal postnatal. Les associations entre la plupart des déterminants prénataux et le lien postnatal étaient toutes influencées par le lien prénatal, ce qui souligne l'important de la promotion du lien prénatal. Les professionnels en pratique clinique devraient être vigilants quant au soutien du partenaire, au fait de s'engager avec les mouvements du foetus et aux symptômes dépressifs postnataux: tous ces facteurs offrent des possibilités d'amélioration des processus de lien.

Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3-year follow-up study.

OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. RESULTS: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. CONCLUSION: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Maintenance tocolysis with nifedipine in threatened preterm labour: 2-year follow up of the offspring in the APOSTEL II trial.

OBJECTIVE: To evaluate long-term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant. DESIGN, SETTING AND POPULATION: Follow up of infants of women who participated in a multicentre randomised controlled trial on maintenance tocolysis with nifedipine versus placebo. METHODS: Two years after the APOSTEL II trial on maintenance tocolysis with nifedipine versus placebo, we asked participants to complete the Ages and Stages Questionnaire. MAIN OUTCOME MEASURES: Infant development was measured in five domains. Developmental delay was defined as a score of ≤1 SD in one or more developmental domains. We performed exploratory subgroup analysis in women with preterm prolonged rupture of the membranes, and in women with a cervical length <10 mm at study entry. RESULTS: Of the 276 women eligible for follow up, 135 (52.5%) returned the questionnaire, encompassing data of 170 infants. At 2 years of age, infants of women with nifedipine maintenance tocolysis compared with placebo had a higher overall incidence of fine motor problems (22.2 versus 7.6%, OR 3.43, 95% CI 1.29-9.14, P = 0.01), and a lower incidence of poor problem-solving (21.1 versus 29.1%, OR 0.27, 95% CI 0.08-0.95, P = 0.04). CONCLUSIONS: This follow-up study revealed no clear benefit of nifedipine maintenance tocolysis at 2 years of age. As short-term adverse perinatal outcome was not reduced in the original APOSTEL II trial, we conclude that maintenance tocolysis does not appear to be beneficial at this time. TWEETABLE ABSTRACT: No clear benefit of nifedipine maintenance tocolysis in preterm labour on 2-year infant outcome.

Parenting stress in mothers after very preterm birth and the effect of the Infant Behavioural Assessment and Intervention Program.

OBJECTIVE: Purpose of this study was to examine maternal parenting stress as a secondary outcome of the Infant Behavioural Assessment and Intervention Program (IBAIP). METHODS: In a randomized controlled trial 86 very preterm infants and their parents were assigned to the intervention group and 90 to the control group. Maternal parenting stress was assessed with the Dutch version of the Parenting Stress Index at 12 and 24 months post term. RESULTS: Mothers in the intervention group mothers assessed their infants as happier and less hyperactive/distractible compared with the control group mothers. However, mothers in the intervention group reported more feelings of social isolation. CONCLUSIONS: The IBAIP appears to have made mothers more satisfied about their infants' mood and distractibility, but also may have evoked more feelings of social isolation. Next to long-term evaluation of the development in very preterm born children, follow-up on functioning of their parents is important.

Developmental monitoring using caregiver reports in a resource-limited setting: the case of Kilifi, Kenya.

AIM: The main aim of the current study was to evaluate the reliability, validity and acceptability of developmental monitoring using caregiver reports among mothers in a rural African setting. METHODS: A structured interview for parents of children aged 24 months and less was developed through both participant consultation and a review of literature. The reliability and validity of the schedule was evaluated through a 10-month monitoring programme of 95 children, aged 2-10 months. The acceptability of the process was evaluated by studying retention rates and by organizing focus group discussions with participating mothers. RESULTS: The structured interview 'Developmental Milestones Checklist' consisted of 66 items covering three broad domains of child functioning: motor, language and personal-social development. The interview yielded scores of developmental achievements that showed high internal consistency and excellent test-retest reliability. The results were sensitive to maturational changes and nutritional deficiencies. In addition, acceptable retention rates of approximately 80% were found. Participating mothers reported that they found the procedures both acceptable and beneficial. CONCLUSION: Developmental monitoring using caregiver report is a viable method to identify and monitor at-risk children in Sub-Saharan Africa.

Monitoring psychomotor development in a resource-limited setting: an evaluation of the Kilifi Developmental Inventory.

BACKGROUND: Modifications made to the Kilifi Developmental Checklist and the psychometric characteristics of the new measure (The Kilifi Developmental Inventory) which assess the psychomotor functioning of children aged 6-35 months are described. METHODS: Two groups of community children (319 rural and 104 urban dwellers) and nine children with neurodevelopmental disorders were recruited for a cross-sectional study. RESULTS: In both a rural and urban reference population, the inventory showed excellent internal consistency, interobserver agreement, test-retest reliability and sensitivity to maturational changes. Children with neurodevelopmental impairment and those who were underweight had significantly lower scores than the community sample, attesting to the sensitivity of the measure. Mothers found the assessment procedures acceptable and informative. CONCLUSIONS: The Kilifi Developmental Inventory is a culturally appropriate measure that can be used to monitor and describe the development of at-risk children in resource-limited settings in Kenya.

Delayed cord clamping in preterm infants delivered at 34 36 weeks' gestation: a randomised controlled trial.

BACKGROUND: Even mild iron deficiency and anaemia in infancy may be associated with cognitive deficits. A delay in clamping the cord improves haematocrit levels and results in greater vascular stability and less need for packed cell transfusions for anaemia in the first period after birth. Follow-up data on haemoglobin levels after the neonatal period were not available. OBJECTIVE: To provide neonatal and follow-up data for the effects of early or delayed clamping of the cord. METHODS: 37 premature infants (gestational age 34 weeks, 0 days-36 weeks, 6 days) were randomly assigned to one of two groups in the first hour after birth, and at 10 weeks of age. In one group the umbilical cord was clamped within 30 seconds (mean (SD) 13.4 (5.6)) and in the other, it was clamped at 3 minutes after delivery. In the neonatal period blood glucose and haemoglobin levels were determined. At 10 weeks of age haemoglobin and ferritin levels were determined. RESULTS: The late cord-clamped group showed consistently higher haemoglobin levels than the early cord-clamped group, both at the age of 1 hour (mean (SD) 13.4 (1.9) mmol/l vs 11.1 (1.7) mmol/l), and at 10 weeks (6.7 (0.75) mmol/l vs 6.0 (0.65) mmol/l). No relationship between delayed clamping of the umbilical cord and pathological jaundice or polycythaemia was found. CONCLUSION: Immediate clamping of the umbilical cord should be discouraged.

Behavioural and emotional problems in very preterm and very low birthweight infants at age 5 years.

BACKGROUND: Children born very preterm (VP; <32 weeks' gestation) or with very low birth weight (VLBW, <1500 g; hereafter called VP/VLBW) are at risk for behavioural and emotional problems during school age and adolescence. At school entrance these problems may hamper academic functioning, but evidence on their occurrence at this age in VP/VLBW children is lacking. AIM: To provide information on academic functioning of VP/VLBW children and to examine the association of behavioural and emotional problems with other developmental problems assessed by paediatricians. DESIGN, SETTING AND PARTICIPANTS: A cohort of 431 VP/VLBW children aged 5 years (response rate 76.1%) was compared with two large national samples of children of the same age (n = 6007, response rate 86.9%). OUTCOME MEASURES: Behavioural and emotional problems measured by the Child Behavior Checklist (CBCL), and paediatrician assessment of other developmental domains among VP/VLBW children. RESULTS: The prevalence rate of a CBCL total problems score in the clinical range was higher among VP/VLBW children than among children of the same age from the general population (13.2% v 8.7%, odds ratio 1.60 (95% confidence interval 1.18 to 2.17)). Mean differences were largest for social and attention problems. Moreover, they were larger in children with paediatrician-diagnosed developmental problems at 5 years, and somewhat larger in children with severe perinatal problems. CONCLUSION: At school entrance, VP/VLBW children are more likely to have behavioural and emotional problems that are detrimental for academic functioning. Targeted and timely help is needed to support them and their parents in overcoming these problems and in enabling them to be socially successful.

Development and evaluation of a follow up assessment of preterm infants at 5 years of age.

BACKGROUND: Long term follow up shows a high frequency of developmental disturbances in preterm survivors of neonatal intensive care formerly considered non-disabled. AIMS: To develop and validate an assessment tool that can help paediatricians to identify before 6 years of age which survivors have developmental disturbances that may interfere with normal education and normal life. METHODS: A total of 431 very premature infants, mean gestational age 30.2 weeks, mean birth weight 1276 g, were studied at age 5 years. Children with severe handicaps were excluded. The percentage of children with a correctly identified developmental disturbance in the domains cognition, speech and language development, neuromotor development, and behaviour were determined. RESULTS: The follow up instrument classified 67% as optimal and 33% as at risk or abnormal. Of the children classified as at risk or abnormal, 60% had not been identified at earlier follow up assessments. The combined set of standardised tests identified a further 30% with mild motor, cognitive, or behavioural disturbances. The paediatrician's assessment had a specificity of 88% (95% CI 83-93%), a sensitivity of 48% (95% CI 42-58%), a positive predictive value of 85% (95% CI 78-91%), and a negative predictive value of 55% (95% CI 49-61%). CONCLUSIONS: Even after standardised and thorough assessment, paediatricians may overlook impairments for cognitive, motor, and behavioural development. Long term follow up studies that do not include detailed standardised tests for multiple domains, especially fine motor domain, may underestimate developmental problems.

Does the Edinburgh Postnatal Depression Scale measure anxiety?

OBJECTIVE: The existence of a separate anxiety and depression dimension within the Edinburgh Postnatal Depression Scale (EPDS) has been reported previously. However, the concurrent validity of this anxiety subscale was never evaluated. We investigated whether (1) this existence of an anxiety subscale could be confirmed and (2) it more highly correlated with other measures of anxiety than the total EPDS. METHODS: The SCL-90-R, the EPDS, and the State-Trait Anxiety Inventory (STAI) were filled out by 197 pregnant women. A principal component analysis (PCA) was used for confirmation of the subscales and correlations were computed between the (subscales of the) EPDS and the other measures of anxiety. RESULTS: The existence of an anxiety scale within the EPDS was confirmed. However, this subscale did not yield higher correlations with other measures of anxiety than did the total EPDS. CONCLUSION: Investigators using the EPDS to screen for depression should realise that the instrument does not exclusively measure depression. It seems that both anxiety symptoms and depressive symptoms are more accurately measured when using the total 10-item EPDS than when using the subscales.

Neonatal thyroxine supplementation in very preterm children: developmental outcome evaluated at early school age.

OBJECTIVE: Transient hypothyroxinemia in very premature infants is associated with developmental problems. A randomized, placebo-controlled trial of thyroxine (T(4)) supplementation was conducted in a group of 200 infants <30 weeks' gestation. T(4) supplementation improved mental outcome at 2 years old in children of 25/26 weeks' gestation only. The effect of T(4) supplementation beyond 2 years of age is unknown. We present the effects of neonatal T(4) supplementation on outcome at early school age. METHODS: Standardized measurements were used to assess cognitive, behavioral, and motor outcome, as well as a qualitative assessment of neurologic functioning. Survivors of the T(4) trial were assessed at the age of 5.7 years. RESULTS: Ninety-nine percent of the 157 survivors participated. Outcome on all domains was comparable between the T(4) group and placebo group. In children <27 weeks' gestation, a 10 IQ point difference was found in favor of the T(4) group, whereas in children of 29 weeks' gestation, a difference of 15 IQ points was found in favor of the placebo group. Teachers' reports showed less behavioral problems in the T(4)-treated children of 25/26 weeks' gestation, but more behavioral problems in the T(4)-treated children of 27 weeks' gestation. Differences in motor outcome and neurologic outcome were in favor of the T(4)-treated children <29 weeks' gestation, but not of the T(4)-treated children of 29 weeks' gestation. CONCLUSIONS: We found benefits of T(4) supplementation for children <29 weeks' gestation, and especially in children of 25/26 weeks' gestation. However, in children of 29 weeks' gestation T(4) supplementation is associated with more developmental problems.

Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy.

BACKGROUND: Maternal thyroid function during early pregnancy is an important determinant of early fetal brain development because the fetal thyroid is unable to produce any T4 before 12-14 weeks' gestation. Overt maternal hypothyroidism as seen in severe iodine-deficient areas is associated with severely impaired neurological development of the offspring. At present, it is not known whether low free T4 (fT4) levels during pregnancy in healthy women from iodine sufficient areas may affect fetal neurodevelopment. METHODS: Neurodevelopment was assessed at 10 months of age in a cohort of 220 healthy children, born after uncomplicated pregnancies and deliveries, using the Bayley Scales of Infant Development. Maternal TSH, fT4 and TPO antibody status were assessed at 12 and 32 weeks' gestation. Maternal gestational fT4 concentration was defined as an independent parameter for child development. RESULTS: Children of women with fT4 levels below the 5th (< 9.8 pmol/l, n = 11) and 10th (< 10.4 pmol/l, n = 22) percentiles at 12 weeks' gestation had significantly lower scores on the Bayley Psychomotor Developmental Index (PDI) scale at 10 months of age, compared to children of mothers with higher fT4 values (t test, mean difference: 14.1, 95% confidence interval (CI): 5.9-22 and 7.4, 95% CI: 1.1-13.9, respectively). At 32 weeks' gestation, no significant differences were found. In the group of women with the lowest 10th percentile fT4 concentrations at 12 weeks' gestation, a positive correlation was found between the mothers' fT4 concentration and children's PDI scores (linear regression, R: 0.46, P = 0.03). After correction for confounding variables, a fT4 concentration below the 10th percentile at 12 weeks' gestation was a significant risk factor for impaired psychomotor development (RR): 5.8, 95% CI: 1.3-12.6). CONCLUSIONS: Low maternal plasma fT4 concentrations during early pregnancy may be an important risk factor for impaired infant development.

Evaluation of the effect of thyroxine supplementation on behavioural outcome in very preterm infants.

Two-hundred infants of <30 weeks gestational age were included in a randomized double-blind controlled trial to study the effect of thyroxine administration on neurodevelopmental outcome in very preterm children. The infants were given either a fixed dose of thyroxine (8 microg/kg birthweight/day) or placebo for the first 6 weeks of life. This paper evaluates the effect of thyroxine administration on behavioural outcome at the age of 2 years. More externalizing, especially destructive, behaviours were found in the group given thyroxine than in the placebo group. This difference was more pronounced in boys and in children born after 27 weeks' gestation. The thyroxine-treated children with behavioural problems had lower plasma-free thyroxine levels than the thyroxine-treated children without behavioural problems. This finding suggests that the presence of more behavioural problems in the group given thyroxine was not an immediate consequence of the treatment.

Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation.

BACKGROUND: Premature infants who have transient hypothyroxinemia in the first weeks of life may have developmental delay and neurologic dysfunction. Whether thyroxine treatment during this period results in improved developmental outcomes is not known. METHODS: We carried out a randomized, placebo-controlled, double-blind trial of thyroxine supplementation in 200 infants born at less than 30 weeks' gestation. Thyroxine (8 microg per kilogram of birth weight) or placebo was administered daily, starting 12 to 24 hours after birth, for six weeks. Plasma free thyroxine concentrations were measured weekly for the first eight weeks after birth. Scores on the Bayley Mental and Psychomotor Development Indexes and neurologic function were assessed at 6, 12, and 24 months of age (corrected for prematurity). RESULTS: Mortality and morbidity up to the time of discharge from the hospital were similar in the study groups. At 24 months of age, 157 infants were evaluated. Overall, neither mental nor psychomotor scores differed significantly between the study groups at any time, nor was the frequency of abnormal neurologic outcome significantly different. In thyroxine-treated infants born at gestational ages of less than 27 weeks, the score on the Bayley Mental Development Index at 24 months of age was 18 points higher than the score for the infants with similar gestational ages at birth in the placebo group (P=0.01); for thyroxine-treated infants born at 27 weeks or later, the mental-development score was 10 points lower than that of their counterparts in the placebo group (P=0.03). There was no relation between the initial plasma free thyroxine concentration and the effect of treatment. CONCLUSIONS: In infants born before 30 weeks' gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.