J.H. Kok

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

BACKGROUNDnPremature 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.nnnMETHODSnWe 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).nnnRESULTSnMortality 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.nnnCONCLUSIONSnIn infants born before 30 weeks gestation, thyroxine supplementation does not improve the developmental outcome at 24 months.

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age.

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Thyroid function in very preterm infants: influences of gestational age and disease

It is not known how immaturity and disease influence postnatal thyroid function in infants <30 wk of gestational age. We performed serial measurements of plasma thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), TSH, and T4-binding globulin (TBG) in 100 infants of <30 wk of gestation, during the first 8 postnatal weeks, to investigate the influences of disease and gestational age on the time course of thyroid hormones. One hundred infants were divided twice into two groups: 1) in a group of 25-28 and of 28-30 wk of gestation; and 2) in a sick and a healthy group, with similar gestational ages. The time course of T4, FT4, T3, TSH, and TBG, but not rT3 differed significantly (p < 0.005) between the gestational age groups. T4 and FT4 decreased to levels below the cord blood value with a deeper FT4 nadir on d 7 in the youngest group. Disease decreased T4, FT4, T3, TSH, and TBG concentrations especially during the 1st wk after birth (p < 0.005). However, the FT4 nadir on d 7 was similar in sick and healthy infants. After 3 wk, T4, FT4, T3, and TBG were higher in the sick group compared with the healthy group. rT3 levels were not increased in sick infants. We conclude that the extent of the FT4 decrease after birth in infants of <30 wk gestation is mainly influenced by gestational age and probably reflects a transient depletion of thyroidal hormone reserves. rT3 cannot be used as a marker of nonthyroidal illness in very preterm infants.

Thyroxine administration to infants of less than 30 weeks gestational age decreases plasma tri-iodothyronine concentrations

OBJECTIVEnTo investigate the effect on thyroid hormone metabolism of the administration of thyroxine to very preterm infants.nnnDESIGN AND METHODSnTwo hundred infants of less than 30 weeks gestation were enrolled into a randomized, double-blind, placebo-controlled trial. Thyroxine (T4) (at a fixed daily dose of 8 microg/kg birthweight) or placebo was started 12-24h after birth and discontinued 6 weeks later. Plasma concentrations of T4, tri-iodothyronine (T3), reverse T3 (rT3), TSH, and thyroxine-binding globulin were measured weekly during trial medication and 2 weeks thereafter.nnnRESULTSnThe T4 and the placebo group each comprised 100 infants. Antenatal, perinatal, and postnatal clinical characteristics were comparable in both groups. T4 and rT3 were significantly increased in the T4 group. TSH concentrations were depressed in the T4 group and T3 was significantly decreased, probably as a result of TSH depression. The T4/T3 and T4/rT3 ratios differed significantly between the two study groups.nnnCONCLUSIONSnDaily T4 administration during the first 6 weeks after birth to infants of less than 30 weeks gestation prevents hypothyroxinemia, but decreases plasma T3 concentrations. Our finding possibly implies that very preterm infants should receive supplements of both T4 and T3.

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

OBJECTIVEnPurpose of this study was to examine maternal parenting stress as a secondary outcome of the Infant Behavioural Assessment and Intervention Program (IBAIP).nnnMETHODSnIn 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.nnnRESULTSnMothers 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.nnnCONCLUSIONSnThe 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.

Effect of fetal brainsparing on the early neonatal cerebral circulation.

The effect of antenatal brainsparing on subsequent neonatal cerebral blood flow velocity (CBFV) was studied in very preterm infants. CBFV was determined, using a pulsed Doppler technique, both in the fetal and neonatal period. Neonatally, blood pressure and transcutaneous carbon dioxide tension (TcPCO2) was monitored simultaneously; daily cranial ultrasound examinations were performed. In infants with evidence of brainsparing a higher mean value of CBFV and a different pattern of changes of CBFV during the first week of life was demonstrated compared with infants with normal fetal cerebral haemodynamics. No differences were found in blood pressure and TcPCO2. The incidence of intracranial haemorrhages and of ischaemic echo-dense lesions was also the same for both groups. In a multivariate statistical model gestational age, antepartum brainsparing, and TcPCO2 all contributed significantly in explanation of variation in CBFV. It is speculated that a different setting of cerebral autoregulation related to differences in gestational age or to brainsparing might explain the difference in changes found in neonatal CBFV.

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

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.

Normal ranges of T4 screening values in low birthweight infants.

Thyroxine (T4) screening values in infants of low birthweight in relation to birthweight and gestational age are reported. There were 86 healthy infants of low birthweight (group 1), and 29 preterm infants with respiratory distress syndrome (group 2). All the group 2 infants and 36% of those in group 1 had a T4 screening value below the cut-off point (-2.1 SD). In group 1 there was a significant increase in T4 with birthweight at a given gestational age, as well as with gestational age at a given birthweight. In group 2 there was also a significant increase in T4 values in relation to birthweight and gestational age, but it could not be ascertained whether this increase existed at a given gestational age or birthweight. A statistical model giving normal ranges of T4 for both groups of infants is presented, which, if applied to low birthweight infants, makes it possible to estimate the effect of low birthweight on T4 screening values, provided the birthweight and gestational age are known. In this manner the sensitivity of screening for congenital hypothyroidism is enhanced and the recall rate reduced.

Serum thyroglobulin levels in preterm infants with and without respiratory distress syndrome. II. A longitudinal study during the first 3 weeks of life

Abstract: Serum thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) levels were measured in 182 preterm and term infants. Samples were taken from cord blood, and at 1, 3, 7, 14, and 21 days after birth. The infants were divided into groups according to their perinatal characteristics: infants who were appropriate for gestational age, infants who were small for gestational age, and preterm infants who developed respiratory distress syndrome. These groups were subdivided according to gestation age. Tg serum levels showed a significant increase in the 1st day in all groups, and decreased significantly after about 1 wk. The highest Tg levels were found in the 1st wk of life in respiratory distress syndrome infants, and in infants with the lowest gestation ages. TSH levels increased at day 1 but only in appropriate and small for gestational age infants of more than 30 wk of gestation. TSH levels at day 1 in the groups with gestation ages of less than 30 wk and in respiratory distress syndrome infants of more than 30 wk were low, reflecting a low TSH surge. We conclude that the neonatal increase of Tg is not merely caused by the TSH surge. We suggest that the Tg increase is due to an impaired degradation of Tg, and/or to hemoconcentration, which are more pronounced in respiratory distress syndrome infants compared with appropriate for gestational age infants.

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

To evaluate long‐term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant.