Early intervention leads to long-term developmental improvements in very preterm infants, especially infants with bronchopulmonary dysplasia.

AIM: Various early intervention programmes have been developed in response to the high rate of neurodevelopmental problems in very preterm infants. We investigated longitudinal effects of the Infant Behavioral Assessment and Intervention Program on cognitive and motor development of very preterm infants at the corrected ages of six months to five and a half years. METHODS: This randomised controlled trial divided 176 infants with a gestational age <32 weeks or birthweight <1500 g into intervention (n = 86) and control (n = 90) groups. Cognitive development and motor development were assessed with the Bayley Scales of Infant Development at the CAs of six, 12 and 24 months and at five and a half years with the Wechsler Preschool and Primary Scale of Intelligence and the Movement Assessment Battery for Children. RESULTS: We found significant longitudinal intervention effects (0.4 SD, p = 0.006) on motor development, but no significant impact on cognitive development (p = 0.063). Infants with bronchopulmonary dysplasia showed significant longitudinal intervention effects for cognitive (0.7 SD; p = 0.019) and motor (0.9 SD; p = 0.026) outcomes. Maternal education had little effect on intervention effects over time. CONCLUSION: The Infant Behavioral Assessment and Intervention Program led to long-term developmental improvements in the intervention group, especially in infants with BPD.

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.

The effect of preimplantation genetic screening on neurological, cognitive and behavioural development in 4-year-old children: follow-up of a RCT.

STUDY QUESTION: Does embryo biopsy inherent to preimplantation genetic screening (PGS) affect neurological, cognitive and behavioural development of 4-year-old children? SUMMARY ANSWER: PGS does not seem to affect neurological, cognitive and behavioural development of 4-year-old singletons; however, our data suggest that it may be associated with altered neurodevelopment in twins. WHAT IS KNOWN ALREADY: Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce. The present study provides information on neurodevelopmental, cognitive and behavioural outcome of 4-year-old PGS offspring. STUDY DESIGN, SIZE, DURATION: A prospective, assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS. PARTICIPANTS/MATERIALS, SETTING, METHODS: At 4 years, 49 children (31 singletons, 9 sets of twins) born following IVF with PGS and 64 children (42 singletons, 11 sets of twins) born following IVF without PGS (controls) were assessed (post-natal attrition 18%). Neurological development was evaluated with the standardized, age-specific and sensitive neurological examination according to Hempel, resulting in a neurological optimality score (NOS), a fluency score and the rate of adverse neurological outcome. Primary outcome was the fluency score, as fluency of movements is easily reduced by subtle dysfunction of the brain. Cognitive development was evaluated with the Kaufman Assessment Battery for Children; behavioural development was evaluated with the Child Behavior Checklist. The effect of PGS was analysed with a mixed effects model. MAIN RESULTS AND THE ROLE OF CHANCE: Based on the intention to treat analysis, neurodevelopmental outcome of PGS children was similar to that of controls. However, additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons. The fluency score of singletons born following PGS was similar to that of control singletons [mean values, 95% confidence intervals (CIs): 12.2 (11.5;12.8) and 12.2 (11.6;12.8)], respectively, P = 0.977) that was also true for the other neurodevelopmental parameters. The fluency score of PGS twins was significantly lower than that of control twins [mean values, 95% CIs: 10.6 (9.8;11.3) and 12.3 (11.5;13.1)], respectively, P = 0.001); the same was true for the NOS. In addition, PGS in twins was associated with a higher sequential intelligence quotient score. On the other hand, other neurodevelopmental parameters were similar for PGS twins and control twins. Post hoc sample size calculation for the primary outcome parameter, the fluency score, indicated that the study groups, including the subgroups of singletons and twins, were adequately powered. LIMITATIONS, REASONS FOR CAUTION: We assessed singletons and twins who contributed to the generalizability of the study. A limitation of our study is the relative small size of our study groups and the selective dropout in both groups (dropouts PGS group: higher gestational age; control group: less well-educated parents). These preclude the conclusion that PGS per se is not associated with neurodevelopmental, cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins. WIDER IMPLICATIONS OF THE FINDINGS: The need for careful long-term monitoring of children born following embryo biopsy remains, as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome.

Parental psychological distress and anxiety after a successful IVF/ICSI procedure with and without preimplantation genetic screening: follow-up of a randomised controlled trial.

BACKGROUND: Infertility treatment has an acknowledged psychological impact on women and their partners; however, information about the development of parental well-being after child birth is inconclusive. Preimplantation genetic screening (PGS) has been suggested to increase the efficacy of infertility treatments, but the effect it may have on parental well-being is unknown. AIM: To evaluate parental distress and anxiety at one and two years after successful infertility treatment and to explore variables that might affect parental outcome, including PGS and child behaviour. STUDY DESIGN: Follow-up of a randomised controlled trial (RCT) on the efficacy of PGS. SUBJECTS: Parents (n=101) that successfully underwent IVF/ICSI with or without PGS. OUTCOME MEASURES: At one and two years, parental distress and anxiety were assessed with the General Health Questionnaire 30 and State Trait Anxiety Inventory, respectively. At two years, child development and behaviour were assessed with the Dutch Bayley Scales of Infant Development-II and the Child Behaviour Checklist 1½-5, respectively. RESULTS: PGS had no effect on parental distress or anxiety. Child behaviour problems were associated with parental distress and anxiety. There was a main effect of time on parental distress, with distress levels decreasing over time. CONCLUSIONS: We found no objection to PGS related to parental psychological distress and anxiety. When parental psychological problems are present after infertility treatment, the results of this study could be useful to support counselling.

Visual perception and visual-motor integration in very preterm and/or very low birth weight children: a meta-analysis.

A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual perceptive and visual-motor integration abilities. Very preterm born children showed deficits in visual-spatial abilities (medium to large effect sizes) but not in visual closure perception. Tests reporting broad visual perceptive indices showed inconclusive results. In addition, impaired visual-motor integration was found (medium effect size), particularly in boys compared to girls. The observed visual-spatial and visual-motor integration deficits may arise from affected occipital-parietal-frontal neural circuitries.

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.

Development and growth in very preterm infants in relation to NIDCAP in a Dutch NICU: two years of follow-up.

AIM: To study development and growth in relation to newborn individualized developmental and assessment program (NIDCAP) for infants born with a gestational age of less than 30 weeks. METHODS: Developmental outcome of surviving infants, 25 in the NIDCAP group and 24 in the conventional care group, in a prospective phase-lag cohort study performed in a Dutch level III neonatal intensive care unit (NICU) was compared. Main outcome measure was the Bayley scales of infant development-II (BSID-II) at 24 months corrected age. Secondary outcomes were neurobehavioral and developmental outcome and growth at term, 6, 12 and 24 months. RESULTS: Accounting for group differences and known outcome predictors no significant differences were seen between both care groups in BSID-II at 24 months. At term age NIDCAP infants scored statistically significant lower on neurobehavioral competence; motor system (median [IQR] 4.8 [2.9-5.0] vs. 5.2 [4.3-5.7], p = 0.021) and autonomic stability (median [IQR] 5.7 [4.8-6.7] vs. 7.0 [6.0-7.7], p = 0.001). No differences were seen in other developmental outcomes. After adjustment for background differences, growth parameters were comparable between groups during the first 24 months of life. CONCLUSION: At present, the strength of conclusions to be drawn about the effect of NIDCAP on developmental outcome or growth at 24 months of age is restricted. Further studies employing standardized assessment approaches including choice of measurement instruments and time points are needed.

A case of neonatal dural sinus malformation: clinical symptoms, imaging and neuropathological investigations.

We report a case of neonatal dural sinus malformation already visible on antenatal ultrasound. This is a rare disease entity in infants and children. Clinical diagnosis was made by demonstrating a cranial murmur on auscultation; macrocrania and signs of progressive cardiac failure. Imaging studies as cerebral ultrasound, postnatal MRI scan and MR angiography demonstrated a large dural sinus malformation originating from the sagittal sinus with extensive arteriovenous fistulae. Due to the extent of the lesion, the existing ischemic brain damage and involvement of the torcular, no therapeutic options were available and the child died of irreversible cardiac failure. The diagnosis was confirmed with autopsy. We discuss the clinical presentation, imaging and neuropathological results and relate our findings to embryological data and the existing literature.

Individualized developmental care in a Dutch NICU: short-term clinical outcome.

AIM: To compare the short-term clinical outcomes of Newborn Individualized Developmental Care and Assessment Program (NIDCAP) and conventional care. METHODS: A prospective phase-lag cohort study was performed in a Dutch tertiary level neonatal intensive care unit (NICU). Infants born before 30 weeks of gestational age (GA) were included, 26 in the conventional and 25 in the NIDCAP group. Outcomes were respiratory status, cerebral ultrasound findings, growth and length of NICU stay. RESULTS: At study entry, NIDCAP infants had a lower birth weight (mean [SD]: 1043 [191] vs. 1154 [174] g, p = 0.044), were more often small for GA (8 vs. 2, p = 0.038), had smaller head circumferences (mean [SD]: 25.1 [1.3] vs. 26.1 [1.8] cm, p = 0.041) and were less often multiples (6 vs. 14, p = 0.029) than conventional care infants. During NICU stay, more infants in the NIDCAP group developed pneumonia (9 vs. 3, p = 0.040) due to nosocomial infections. After adjustment for these differences, a decreased risk for more severe cerebral damage in favour of NIDCAP was seen (Odds ratio: 0.12, 95% CI: 0.03-0.46, p = 0.002). No differences were observed for the other outcomes. CONCLUSIONS: We conclude with precaution that in this phase-lag cohort study NIDCAP may have resulted in less severe cerebral damage, but was not associated with other clinical outcomes. In light of these findings, NIDCAP deserves further exploration.

[The practice guideline 'Volume suppletion in critically-ill neonates and children up to the age of 18 years' of the Dutch Paediatric Association]. / Richtlijn 'Volumesuppletie bij kritisch zieke pasgeborenen en kinderen tot 18 jaar' van de Nederlandse Vereniging voor Kindergeneeskunde.

Hypovolaemia is the most common cause of circulatory failure in children. Treatment consists of volume suppletion with a crystalloid or colloid solution; which agent is the best in children is not clear. This evidence-based practice guideline formulates recommendations as to which fluid should be used for volume suppletion in critically-ill neonates and children up to the age of 18 years with hypovolaemia. Before the guideline development first-choice fluid for volume resuscitation was in 50% a colloid and in 50% a crystalloid solution for both neonatologists and paediatric intensivists. The neonatologists used human albumin as a priority, and the paeditric intensivists predominantly used a synthetic colloid. The guideline was developed on the basis of a comprehensive search and analysis of the literature according to the principles of evidence-based guideline development. The recommendations were formulated by a committee based on evidence from the literature and, when evidence from the literature was insufficient, on consensus after discussion in the committee. Since colloids are much more expensive than crystalloids and can give an anaphylactic reaction, their added value over crystalloids must be proven. In sick neonates and children, insufficient clinical trials have been done to reach the conclusion that colloids are more effective than crystalloids in hypovolaemia. A number of meta-analyses in adults revealed excess mortality in the group treated with albumin, but one recent, large, randomised study showed no difference in mortality. No added value could be demonstrated for the administration of synthetic colloids. On the basis of data from the literature and considerations regarding the applicability of evidence in adults to children and neonates, the side effects of resuscitation fluids, pathophysiology and costs, the first-choice fluid for neonates and children with hypovolaemia is isotonic saline. Albumin should not be used for the treatment of hypovolaemia. The volume to be administered and the infusion rate depend on the severity of the hypovolaemia and should be determined on an individual basis.

Effect of ventilation strategy and surfactant on inflammation in experimental pneumonia.

This study explored, the inflammatory response during experimental pneumonia in surfactant-depleted animals as a function of ventilation strategies and surfactant treatment. Following intratracheal instillation of Group B streptococci (GBS), surfactant-depleted piglets were treated with conventional (positive-end expiratory pressure (PEEP) of 5 cmH2O, tidal volume 7 mL x kg(-1)) or open lung ventilation. During the latter, collapsed alveoli were recruited by applying high peak inspiratory pressures for a short period of time, combined with high levels of PEEP and the smallest possible pressure amplitude. Subgroups in both ventilation arms also received exogenous surfactant. Conventionally ventilated healthy animals receiving GBS and surfactant-depleted animals receiving saline served as controls. In contrast with both control groups, surfactant-depleted animals challenged with GBS and conventional ventilation showed high levels of interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and myeloperoxidase in bronchoalveolar lavage fluid after 5 h of ventilation. Open lung ventilation attenuated this inflammatory response, but exogenous surfactant did not. Systemic dissemination of the inflammatory response was minimal, as indicated by low serum levels of IL-8 and TNF-alpha. In conclusion, the current study indicates that the ventilation strategy, but not exogenous surfactant, is an important modulator of the inflammation during Group B streptococci pneumonia in mechanically ventilated surfactant-depleted animals.

Assessment of the rectoanal inhibitory reflex in preterm infants with delayed meconium passage.

BACKGROUND: There is an inverse relationship between gestational age, birth weight and the time of first neonatal bowel movement. The authors hypothesized that delayed passage of meconium might result from a delayed maturation of the recto-anal inhibitory reflex (RAIR) in premature infants. OBJECTIVE: To evaluate whether the RAIR is absent in very preterm infants 28-32 weeks postmenstrual age with delayed meconium production. STUDY DESIGN: Anorectal manometry was performed in 10 preterm infants (seven male) with delayed meconium production (no meconium in the first 48 hours). Median postmenstrual age was 30 weeks (28-31 weeks). Birth weight ranged from 780 to 1930 g (median, 1395 g). A micromanometric assembly (outer diameter, 2.0 mm) was used which incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressure and relaxation. Four side-holes recorded anal and rectal pressures. Rectal distension was performed with direct air insufflation to elicit the RAIR. RESULTS: The time from birth to passage of meconium ranged from 48 to 105 hours (median, 82 hours). The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 22.0 +/- 5.0 mm Hg, 6.9 +/- 2.0 mm Hg, and 9.8 +/- 1.9/min, respectively. A normal RAIR was elicited in all infants. CONCLUSION: Anorectal manometry recordings in premature infants with delayed passage of meconium showed normal anorectal pressures and a normal RAIR, suggesting that delayed meconium passage is not related to the absence of a RAIR.

Maturation of the rectoanal inhibitory reflex in very premature infants.

OBJECTIVE: To characterize anal sphincter function in very premature infants < or =30 weeks' postmenstrual age (PMA) and to evaluate the time of maturation of the rectoanal inhibitory reflex (RAIR) by using a sleeve catheter. STUDY DESIGN: Anorectal manometry was performed in 16 healthy neonates (nine girls) with a mean PMA of 29 weeks (range, 27-30 weeks) and a birth weight of 640 to 1590 g (median, 1220 g) with a micromanometric assembly (outer diameter, 2.0 mm). The assembly incorporated a 1.5-cm-long sleeve sensor for measurement of resting anal sphincter pressures and relaxation, and four side holes recorded anal and rectal pressures. Rectal distention was performed with direct air insufflation to elicit the RAIR. RESULTS: The mean anal sphincter pressure, rectal pressure, and anal sphincter oscillation frequency were 24.5+/-11.4 mm Hg, 6.5+/-4.8 mm Hg, and 11.1+/-2.3/min, respectively. A normal RAIR could be elicited in 13 (81%) infants studied. In two infants, the RAIR could not be elicited because of a low anal sphincter pressure of only 5 mm Hg. In the other child, no RAIR was seen despite the repeated insufflation of at least 5 mL of air. CONCLUSION: The majority (81%) of premature infants older than 26 weeks' PMA have normal anorectal pressures and a normal RAIR.

Implementation of a nation-wide automated auditory brainstem response hearing screening programme in neonatal intensive care units.

AIM: As part of a future national neonatal hearing screening programme in The Netherlands, automated auditory brainstem response (AABR) hearing screening was implemented in seven neonatal intensive care units (NICUs). The objective was to evaluate key outcomes of this programme: participation rate, first stage success rate, pass/referral rates, rescreening compliance, diagnostic referral rates, age of first diagnostic evaluation and prevalence of congenital hearing loss (CHL). METHODS: This prospective cohort study collected data on 2513 survivors. NICU graduates with one or more risk factors according to the Joint Committee on Infant Hearing were included in a two-stage AABR hearing screening programme. Conventional ABR was used to establish a diagnosis of CHL. RESULTS: A total of 2513 newborns enrolled in the programme with a median gestational age of 31.6 (range 24-43) wk and a median birthweight of 1450 (range 510-4820) g. In 25 (1%) cases parents refused screening. Four out of 2513 newborns were initially lost; 2484 newborns have been tested initially. A final 98% participation rate (2465/2513) was obtained for the whole programme. After a median postmenstrual age at the first test of 33.7 (range 27-54) wk, a pass rate of 2284/2484 (92%) resulted at the first stage. The rescreening compliance after the first test was 92% (184/200). A referral rate for diagnostic ABR of 3.1% (77/2484) resulted. Of the 77 referrals 14 (18.2%) had normal screening thresholds, 15 (19.5%) had unilateral CHL and 48 (62.3%) had bilateral CHL. The prevalence of unilateral CHL was 0.6% (15/2484) and of bilateral CHL 1.9% (48/2484). CONCLUSION: A financially supported two-stage AABR hearing screening programme can be successfully incorporated in NICU centres and detects a high prevalence of CHL in NICU graduates. Neonatal hearing screening should be part of standard clinical practice in all NICU infants.

A practical approach to and long-term results of fitting silicone contact lenses in aphakic children after congenital cataract.

PURPOSE: This prospective study investigated characteristics of fit and performance of silicone contact lenses under conditions of permanent wear in cases of aphakia after congenital cataract. METHODS: Seventeen aphakic children (8 eyes unilateral, 18 eyes bilateral) were fitted with silicone contact lenses on an empirical basis without the use of keratometry. The lenses were worn on a permanent basis, with a routine replacement every 3 months. The follow up was 6 years, with evaluation lens parameters, fitting characteristics, lens condition, replacement rate, wearing time, complications, and visual acuity. RESULTS: The back optical zone radius (BOZR) remained stable at 7.50 mm, up to the age of 1.5 years old. At the age of 4 years, almost all eyes needed a BOZR of 7.90 mm. Mean +/- SD contact lens power was +25.47 diopter (D) +/- 4.0 (range +32.00 D - +20.00 D) at 3 months of age, and +17.94 D +/- 3.8 (range +29.00 D - +15.00 D) at 3 years of age. This represents an average decrease of 0.23 D per month. The power decrease in unilateral cases was significantly lower (P < 0.01) than in bilateral aphakia. Snellen visual acuity at 4 years of age was 0.1 to 0.3 (20/200-20/60) in 15 eyes, 0.3 to 0.5 (20/60-20/40) in 10 eyes and greater than 0.5 (>20/40) in 1 eye. Lens usage over a total period of 90 wearing years was 5.6 lenses/eye/year, including the regular exchange every 3 months. No serious complications occurred. A positive correlation (r = 0.89) was found between age and deposit buildup. With the need for permanent wear reduced, therefore, 73% of the eyes were refitted with high-water content soft lenses or high gas-permeable (HGP) lenses, when the patients ranged in age from 4 to 6 years old. CONCLUSIONS: The procedure for fitting silicone lenses in aphakic children is feasible in an easy and logical way without keratometry. Permanent wear with a low complication rate is possible up to the age of 3. with a lens usage (including a 3-month regular exchange) of 5.6 lenses/eye/year. From the age of 3, deposit formation is the determining factor for refitting with high-water content soft or HGP lenses.

Efficacy of automated auditory brainstem response hearing screening in very preterm newborns.

OBJECTIVE: To investigate the efficacy of an automated auditory brainstem response (AABR) hearing screening method in very preterm newborns in the neonatal intensive care setting. STUDY DESIGN: In this prospective cohort study, 90 consecutive preterm newborns (<32 weeks' gestational age) had AABR hearing screening weekly from birth until a bilateral pass result was obtained. If the newborn had a unilateral pass result, AABR screening was repeated in the same week. Data were analyzed by using the Kaplan-Meier survival function technique, resulting in a cumulative pass rate curve for postmenstrual age. Cox's regression method was used to analyze the effect of co-variables, such as sex and growth restriction, on pass rates. RESULTS: Median gestational age was 29.5 weeks (range, 25.3-31.9 weeks), and median birth weight was 1115 g (range, 600-1960 g). Mean age was 6.2 days (SD 4.3) at first test, 15.7 (SD 8.1) at second test, and 21.4 (SD 8.6) at third test. Eighty percent (CI: 70.2%-89.8%) of the newborns passed at 30.3 weeks' postmenstrual age, 90% (CI: 83.6%-96.4%) passed at 31.2 weeks, and 100% passed at 34 weeks' postmenstrual age. The attainment of these pass rates correlated to postmenstrual age was not significantly influenced by sex, growth restriction, or gestational age at birth. Postnatal pass rates (in days) were strongly influenced by gestational age. CONCLUSION: AABR pass rates of >80% can be obtained from 30 weeks' postmenstrual age. Therefore AABR neonatal hearing screening can be used before discharge from a neonatal intensive care unit.

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.

Postnatal thyroid hormone replacement in very preterm infants.

Transient hypothyroxinemia occurs frequently in very preterm infants and is caused by a combination of factors as immaturity of the hypothalamo-pituitary-thyroid system, loss of the maternal thyroxine (T4) contribution, immaturity of thyroid hormone metabolism, and neonatal illness. Thyroid hormone is important in maturation of the brain, but also of heart and lungs. Low neonatal T4 concentrations in plasma are related to worse clinical and neurodevelopmental outcome. Despite these relationships, only few randomized clinical trials have been performed to find out whether T4 supplementation can improve clinical and/or neurodevelomental outcome of preterm infants. The currently available evidence does not support use of supplemental T4 in all preterm infants. There are, however, indications that T4 might improve neurodevelopmental outcome in infants born before 27 to 29 weeks of gestation. Therefore, it is necessary that new trials are set up to further study the benefits of thyroid hormones given in the neonatal period of very preterm infants.

Changes in plasma thyroid hormone levels after a single dose of triiodothyronine in premature infants of less than 30 weeks gestational age.

OBJECTIVE: Evaluation of thyroid hormone response to a single administration of triiodothyronine (T3) early postnatally to premature infants of <30 weeks gestational age. DESIGN: A prospective clinical trial with historical control. METHODS: Ten infants born <28 weeks gestational age and ten infants born between 28 and 30 weeks gestational age were given 0.5 microg/kg T3 intravenously at 12 h after birth. The infants <28 weeks gestational age were also treated with thyroxine (T4; 8 microg/kg, once daily) during the first 6 weeks of life. Premature infants from a previous trial served as a matched historical control group. Analysis of variance for repeated measurements was performed. RESULTS: For the infants <28-30 weeks gestational age mean plasma T3 concentrations were significantly higher in the T3-treated group (P=0.027) for at least 2 weeks, whereas mean plasma levels of T4, free T4 and TSH were comparable. For the infants <28 weeks gestational age plasma T3 levels were also significantly different after correction for gestational age (P=0.0002), with either comparable or higher values in the T3-treated infants up to 56 days after injection of T3. Mean plasma free T4 levels were lower during the first 3 days and higher or comparable thereafter (P=0.0014), and TSH suppression was more evident in the T3-treated infants (P=0.003). CONCLUSION: A single administration of T3 to premature infants <30 weeks gestational age early postnatally results in a sustained increase of plasma T3 levels during the first weeks of life. In infants of 28-30 weeks gestational age this occurs without change in plasma free T4 levels, whereas in infants <28 weeks gestational age a transient decrease of plasma free T4 was present. The increase in plasma T3 is possibly caused by a T3-induced increase of type I deiodinase activity.