Neurodevelopmental Outcomes at 42 Months After Thyroxine Supplementation in Infants Below 28 Weeks' Gestation: A Randomized Controlled Trial.

Infants below 28 weeks' gestation have low thyroid hormone plasma levels compared with more mature infants and this may contribute to their risk of developmental disability. We aimed at determining the effect of supplementation with levothyroxine (LT4) for extremely premature infants born below 28 weeks' gestations on neurodevelopmental outcomes at 42 months. An explanatory double-blind, randomized, placebo-controlled trial consecutively recruited 153 infants below 28 weeks' gestation from 5 neonatal units in the United Kingdom.

Do maternal factors influence neonatal thyroid status in the extreme premature infant?

Background: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits.

Aim: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life.

Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study.

Background: In order to assess relationships between thyroid hormone status and findings on brain MRI, a subset of babies was recruited to a multi-centre randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine supplementation In Preterm InfanTs). These infants were imaged at term-equivalence.

Materials And Methods: Forty-five TIPIT participants had brain MRI using diffusion tensor imaging (DTI) to estimate white matter development by apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography metrics of number and length of streamlines.

An explanatory randomised placebo controlled trial of levothyroxine supplementation for babies born <28 weeks' gestation: results of the TIPIT trial.

Background: Babies born before 28 weeks' gestation have lower plasma thyroid hormone concentrations than more mature infants. This may contribute to their risk of poor developmental outcome. Previous studies have suggested that thyroxine supplementation for extremely preterm neonates may be beneficial.

A novel method of collection of saliva for estimation of steroid levels in extremely premature infants.

Aim: The major advantage of salivary cortisol sampling is that it is considerably less invasive than taking a blood sample. However, previous methods of obtaining saliva in premature infants have been poorly tolerated and inaccurate. We describe a simple, non-distressing technique for obtaining saliva samples to assess extremely premature infants' salivary cortisol status.

Peripheral oxygenation and management in the perinatal period.

The mechanisms for the adequate provision of oxygen to the peripheral tissues are complex. They involve control of the microcirculation and peripheral blood flow, the position of the oxygen dissociation curve including the proportion of fetal and adult haemoglobin, blood gases and viscosity. Systemic blood pressure appears to have little effect, at least in the non-shocked state.

The impact of networks on clinical trials in the United Kingdom.

The conduct of clinical trials in the UK has been affected by the recent introduction of managed clinical networks, clinical research networks and rigorous governance regulations. This commentary considers the challenges that these changes have posed for clinical triallists in the UK, based on experiences derived in the conduct of a multicentre neonatal clinical trial under the conditions that now prevail. We conclude that the considerable skills and knowledge that are now required to be an effective Principal Investigator should be recognised and that application processes, including issuing honorary contracts, should be simplified and centralised.

Cause of death in infants of women with pregestational diabetes mellitus and the relationship with glycemic control.

Background: Perinatal mortality remains high among infants of mothers with type 1 and type 2 diabetes mellitus. Although high glucose levels have been implicated, the mechanism is not well understood.

Aims: 1) to identify the causes of stillbirth and neonatal death in infants of women with type 1 and type 2 diabetes; 2) to determine whether the causes of perinatal mortality are the same for women with type 1 and type 2 diabetes; and 3) to ascertain the relationship between perinatal mortality and maternal glycemic control.

How has research in the last 5 years changed my clinical practice?

This paper considers some of the changes in practice that have occurred in the last 5 years. There have been significant improvements in parental involvement in care. Not all changes have been based on evidence from research: practice has also been affected by changing technology and pressure by industry and other groups.

High versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.

Background: Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome.

Peripheral blood flow and oxygen extraction in the sick, newborn very low birth weight infant shortly after birth.

This study examined the relationship between blood pressure, peripheral blood flow (PBF), and peripheral fractional oxygen extraction (FOE). Variables that may influence PBF and peripheral FOE were also measured. Measurements of PBF by near infrared spectroscopy and fractional shortening by echocardiography were made within 12 h of birth in 24 infants less than 32 wk gestation.

TIPIT: a randomised controlled trial of thyroxine in preterm infants under 28 weeks gestation: magnetic resonance imaging and magnetic resonance angiography protocol.

Background: Infants born at extreme prematurity are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone described as hypothyroxinaemia, which is recognised to be a frequent phenomenon in these infants. Derangements of critical thyroid function during the sensitive window in prematurity when early development occurs, may have a range of long term effects for brain development.

TIPIT: A randomised controlled trial of thyroxine in preterm infants under 28 weeks' gestation.

Background: Infants born at extreme prematurity (below 28 weeks' gestation) are at high risk of developmental disability. A major risk factor for disability is having a low level of thyroid hormone which is recognised to be a frequent phenomenon in these infants. At present it is unclear whether low levels of thyroid hormone are a cause of disability, or a consequence of concurrent adversity.

Additional therapy for young children with spastic cerebral palsy: a randomised controlled trial.

Objectives: To investigate whether, in the short and medium term, additional support by (a) a physiotherapy assistant improved physical function in young children with spastic cerebral palsy and (b) a family support worker improved family functioning.

Design: This was a multi-centre randomised controlled trial (RCT) with blinded assessments and a cost-effectiveness analysis. The children studied had spastic cerebral palsy that was the consequence of perinatal adversity.

The relationship between cardiac output, cerebral electrical activity, cerebral fractional oxygen extraction and peripheral blood flow in premature newborn infants.

Cardiac output is a determinant of systemic blood flow and its measurement may therefore be a useful indicator of abnormal hemodynamics and tissue oxygen delivery. The purpose of this study was to investigate in very premature newborn infants the relationships between cardiac output (left and right ventricular outputs), systemic blood pressure, peripheral blood flow (PBF) and two indicators of cerebral oxygen delivery (cerebral electrical activity and cerebral fractional oxygen extraction (CFOE)). This was a prospective observational study performed on 40 infants of less than 30 wk gestation.

Relationship between blood pressure, cerebral electrical activity, cerebral fractional oxygen extraction, and peripheral blood flow in very low birth weight newborn infants.

There is uncertainty about the level of systemic blood pressure required to maintain adequate cerebral oxygen delivery and organ integrity. This prospective, observational study on 35 very low birth weight infants aimed to determine the mean blood pressure (MBP) below which cerebral electrical activity, peripheral blood flow (PBF), and cerebral fractional oxygen extraction (CFOE) are abnormal. Digital EEG, recorded every day on the first 4 d after birth, were analyzed a) by automatic spectral analysis, b) by manual measurement of interburst interval, and c) qualitatively.

Effect of carbon dioxide on background cerebral electrical activity and fractional oxygen extraction in very low birth weight infants just after birth.

Decreased arterial carbon dioxide tension (PaCO2) results in decreased cerebral blood flow, which is associated with diminished cerebral electrical activity. In such a situation, cerebral fractional oxygen extraction (CFOE) would be expected to increase to preserve cerebral oxygen delivery. This study aimed to determine whether changes in blood gases in infants less than 30 wk' gestation were associated with changes in background electroencephalograms (EEG) and CFOE.

Blood pressure in the neonate.

The paper by Dannevig et al. in this issue of Acta Paediatrica carefully compares the agreement between blood pressure measurements made by three non-invasive blood pressure monitors with those made from an indwelling intra-arterial catheter. Non-invasive blood pressure monitoring is not particularly accurate for making measurements in neonates and generally overestimates the blood pressure as observed by others.

Cerebral fractional oxygen extraction is inversely correlated with oxygen delivery in the sick, newborn, preterm infant.

Cerebral blood flow (CBF) is known to be low in newborn infants, but this has not been shown to be damaging. The purpose of this study was to investigate the relationships between cerebral haemoglobin flow, blood flow, oxygen delivery, oxygen consumption, venous saturation, and fractional oxygen extraction (OEF) in newborn, preterm infants. Measurements were made by near-infrared spectroscopy in 13 very preterm, extremely low birth weight infants (median gestation 25 weeks) during the first 3 days after birth.

Spectral analysis of electroencephalography in premature newborn infants: normal ranges.

Continuous EEG monitoring has not been used widely in neonatal intensive care, especially in the care of extremely premature infants, probably in part because of a lack of a reliable quantitative method. The purpose of this study was to quantify the EEG of the very premature infants just after birth by using spectral analysis and to describe the characteristics of the spectral signal when infants were clinically stable. Digital EEG recordings were performed on 53 infants who were < or =30 wk gestation for 75 min each day during the first 4 d after birth.

Postnatal changes in cerebral oxygen extraction in the preterm infant are associated with intraventricular hemorrhage and hemorrhagic parenchymal infarction but not periventricular leukomalacia.

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI).

Cerebral fractional oxygen extraction in very low birth weight infants is high when there is low left ventricular output and hypocarbia but is unaffected by hypotension.

This study examined the relationships between cerebral fractional oxygen extraction (FOE), mean arterial blood pressure (MABP), left ventricular output (LVO), blood gases, and other physiologic variables in 36 very-low-birth-weight preterm infants during the first 3 d after birth. There was a decrease in cerebral FOE (p = 0.008), and rises in LVO (p < 0.