Aleid van Wassenaer

Ten-Year Follow-up of Children Born at <30 Weeks’ Gestational Age Supplemented With Thyroxine in the Neonatal Period in a Randomized, Controlled Trial

Background. Thyroid hormones are essential for brain development. We conducted a randomized, controlled trial with thyroxine (T4) supplementation in infants <30 weeks’ gestation and with the last neurodevelopmental follow-up moment at the age of 5.5 years. T4 supplementation was associated with improved outcome of infants <28 weeks’ gestation and worse outcome of infants of 29 weeks’ gestation. We studied gestational age–dependent effects of T4 supplementation at the mean age of 10.5 years in children participating in our randomized, controlled trial. Methods. Questionnaires regarding school outcome, behavior, quality of life, motor problems, and parental stress were sent to the parents and children and their teachers at the same time point for all surviving children (9–12 years of age). Results. Seventy-two percent of the families responded to our questionnaires. Nonrespondents had more sociodemographic risk factors and worse development until 5.5 years. At the mean age of 10.5 years, T4 supplementation was associated with better school outcome in those who were <27 weeks’ gestation and better motor outcome in those who were <28 weeks’ gestation, whereas the reverse was true for those who were born at 29 weeks’ gestation. No other gestational age–dependent outcomes were found. Conclusions. Gestation-dependent effects of T4 supplementation remain stable over time. These effects do not prove beneficial effects of T4 in infants <28 weeks but should be the background for a new randomized, controlled trial with thyroid hormone in this age group.

Effects on (neuro)developmental and behavioral outcome at 2 years of age of induced labor compared with expectant management in intrauterine growth-restricted infants: long-term outcomes of the DIGITAT trial

OBJECTIVE We sought to study long-term (neuro)developmental and behavioral outcome of pregnancies complicated by intrauterine growth restriction at term in relation to induction of labor or an expectant management. STUDY DESIGN Parents of 2-year-old children included in the Disproportionate Intrauterine Growth Intervention Trial at Term (DIGITAT) answered the Ages and Stages Questionnaire (ASQ) and Child Behavior Checklist (CBCL). RESULTS We approached 582 (89.5%) of 650 parents. The response rate was 50%. Of these children, 27% had an abnormal score on the ASQ and 13% on the CBCL. Results of the ASQ and the CBCL for the 2 policies were comparable. Low birthweight, positive Morbidity Assessment Index score, and admission to intermediate care increased the risk of an abnormal outcome of the ASQ. This effect was not seen for the CBCL. CONCLUSION In women with intrauterine growth restriction at term, neither a policy of induction of labor nor expectant management affect developmental and behavioral outcome when compared to expectant management.

The effect of the Infant Behavioral Assessment and Intervention Program on mother-infant interaction after very preterm birth

BACKGROUND Prematurity and perinatal insults lead to increased developmental vulnerability. The home-based Infant Behavioral Assessment and Intervention Program (IBAIP) was designed to improve development of preterm infants. In a multicenter randomized controlled trial the effect of IBAIP on mother-infant interaction was studied as a secondary outcome. METHOD Mother-infant interaction was assessed during the Still-face procedure at 6 months corrected age. One hundred and twelve mother-infant dyads (57 intervention, 55 control) were studied. RESULTS Findings partially supported our hypothesis that the intervention would increase maternal sensitivity in interaction with their preterm infants. No effects were found on infant self-regulatory behavior or positive interaction behavior. CONCLUSION   The family-centered and strength-based approach of IBAIP appears to be a promising intervention method to promote sensitive mother-infant interaction at home after discharge from hospital. However, no positive effects were found on infant interaction behavior.

The Infant Behavioral Assessment and Intervention Program to support preterm infants after hospital discharge: a pilot study

In this pilot study we investigated the feasibility of The Infant Behavioral Assessment and Intervention Program (IBAIP) in a group of preterm infants. At the age of 6 months, the neurobehavioural organization and self-regulatory competence of an intervention group was compared with a control group who had received the standard follow-up care. The intervention group consisted of 13 males and seven females (mean gestational age [GA] 29.2 weeks, SD 1.3wks; mean birthweight 1232g, SD 320g). The control group consisted of 11 males and nine females (mean GA 29wks, SD 1.6wks; mean birthweight 1198g, SD 397g). Inclusion criteria were: a GA of 32 weeks and family residence in the district of Amsterdam. Exclusion criteria were: severe congenital abnormalities, intraventricular haemorrhage grade III or IV, periventricular leukomalacia grade III or IV, and infants whose mothers had a history of illicit drug use. The intervention infants received 6 to 8 IBAIP interventions at home, from discharge until 6 months of age. The Neonatal Behavioral Assessment Scale was administered at term; the Infant Behavioral Assessment (IBA) at term, 3, and 6 months of age; and the Bayley Scales of Infant Development-II at 3 and 6 months (corrected age). At 6 months, intervention infants showed less stress and more approach behaviours on the IBA compared with control infants. These promising results warrant further evaluation in a randomized controlled trial.

Infant behavioral assessment and intervention program in very low birth weight infants improves independency in mobility at preschool age

OBJECTIVE To evaluate the effects of the Infant Behavioral Assessment and Intervention Program(©) (IBAIP) in very low birth weight infants on sensory processing and daily activities at preschool age. STUDY DESIGN Follow-up of children included in a randomized controlled trial. Eighty-six infants were enrolled in post-discharge IBAIP until 6 months corrected age, and 90 infants received standard care. At 3.5 years of age, the Sensory Profile-Dutch version (SP-NL) and Pediatric Evaluation of Disability Inventory-Dutch version (PEDI-NL) were administered. For comparison, parents of 41 term-born children also completed the SP-NL. RESULTS Seventy-six children (88%) in the IBAIP group and 75 children (83%) children in the control group were examined at 44 months corrected age. After adjustment for pre-randomization differences in perinatal characteristics, the IBAIP group outperformed the control group significantly on SP-NL domains of oral sensory processing and sensory processing related to endurance/tone and PEDI-NL domains of mobility. The control group only scored significantly lower than the term group on the SP-NL domain endurance/tone. The very low birth weight groups performed significantly below the PEDI-NLs norm. CONCLUSION In line with the positive developmental effects of the IBAIP until 24 months corrected age, independency in mobility in daily activities was improved at 3.5 years.

The infant behavioral assessment and intervention program in very low birth weight infants; outcome on executive functioning, behaviour and cognition at preschool age.

BACKGROUND The Infant Behavioral Assessment and Intervention Program (IBAIP©) improved motor function at 24 months, and mental and behavioural development in high risk subgroups of very low birth weight (VLBW) infants. AIM To determine IBAIPs effects on executive functioning, behaviour and cognition at preschool age. STUDY DESIGN Follow-up of a randomised controlled trial (RCT). SUBJECTS At 44 months corrected age, all 176 VLBW infants were invited for follow-up. Forty-one term born children were assessed for comparison. OUTCOME MEASURES Visual Attention Task (VAT), Gift delay, Peabody Picture Vocabulary Test III-NL (PPVT), Visual motor integration tests and Miller assessment for preschoolers. Parents completed Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and Child Behavior Checklist (CBCL). RESULTS At preschool age, 76 (88%) children of the intervention group and 75 (83%) children of the control group participated. There were no significant differences between the intervention and the control group. However, positive interaction effects between intervention and infants with bronchopulmonary dysplasia, infants born at gestational age<28 weeks, and infants of low educated mothers were found on CBCL, CBCL and BRIEF-P, and PPVT respectively. Most interaction effects exceeded 1 standard deviation in favour of the intervention children. The 151 VLBW children performed significantly worse than the term born children on the VAT, BRIEF-P and CBCL. CONCLUSION IBAIP effects in VLBW children did not sustain until preschool age on executive functioning, behaviour and cognition. However, the most vulnerable children had a clinical relevant profit from IBAIP. VLBW children performed worse than the term born children. This study is a follow-up at preschool age of the multi-centre RCT of IBAIP versus usual care in VLBW infants. The RCT was performed in Amsterdam, The Netherlands (IBAIP).

The quantity of thyroid hormone in human milk is too low to influence plasma thyroid hormone levels in the very preterm infant.

background Thyroid hormone is crucial for brain development during foetal and neonatal life. In very preterm infants, transient low levels of plasma T4 and T3 are commonly found, a phenomenon referred to as transient hypothyroxinaemia of prematurity. We investigated whether breast milk is a substantial resource of thyroid hormone for very preterm neonates and can alleviate transient hypothyroxinaemia. Both the influence of breast feeding on plasma thyroid hormone levels and the thyroid hormone concentration in preterm human milk were studied.

A Randomized, Masked Study of Triiodothyronine Plus Thyroxine Administration in Preterm Infants Less Than 28 Weeks of Gestational Age: Hormonal and Clinical Effects

A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T3) 24 h after birth, followed by a daily dose of thyroxine (T4) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups:1) group A: T3 24 h after birth plus daily T4 during 6 wk; 2) group B: placebo T3 and T4 during 6 wk; and 3) group C: placebo T3 and placebo T4. T4, free T4, T3, free T3, reverse T3, thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T3 (0.5 μg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T3 levels were comparable between the groups. T4, free T4, and reverse T3 were increased in groups A and B during the period of T4 administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T3 and T4 administration did not have any effect on cortisol levels. We did not find any effects of T3 or of T4 administration on the cardiovascular system. A single injection of T3 (0.5 μg/kg) given 22–26 h after birth only leads to a 2-d increase of T3 levels and does not have effects on the cardiovascular system. This study does not support the use of T3 according to our regimen in preterm infants.

Transient hypothyroxinemia in severe hypertensive disorders of pregnancy

OBJECTIVE: Assess whether and to what extent thyroid function is affected in pregnant women with early and severe hypertensive disorders and in their newborns. METHODS: Patients were 80 women with preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome or gestational hypertension combined with fetal growth restriction in the 24th to 34th week of singleton pregnancies. Maternal thyroid hormone levels and thyroid peroxidase antibodies were determined at admission and 3 months postpartum. Neonatal levels were determined from cord blood at delivery. Maternal hypothyroxinemia was defined as free T4 (fT4) value below 9 pM. RESULTS: At admission 26 (33%) women in the study group had fT4 levels below 9 pM, with spontaneous normalization during pregnancy. There were no statistically significant differences between thyroid hormone values in women in the study group and 10 normotensive pregnant women in their third trimester. Three months postpartum, 97.5% of patients had normal thyroid hormone levels. Thyroid peroxidase antibodies were elevated in 10% of women postpartum. Their infants, born at a median gestational age of 30 6/7 weeks, had lower cord blood fT4 and thyroid-stimulating hormone values compared with preterm infants of the comparison group, appropriate for gestational age. Cord blood fT4 had no correlation with gestational age or maternal fT4, but there was a significant correlation of cord blood fT4 with umbilical artery pH. CONCLUSION: Women with severe hypertensive disorders of pregnancy may have transiently lower fT4 levels, without evidence of a thyroid disorder. Their neonates have lower fT4 levels at birth unrelated to maternal fT4, but related to prenatal acidosis. LEVEL OF EVIDENCE: II-2

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 γ/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.