Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant

Improvements in the management of respiratory distress syndrome (RDS) include pre- and postnatal stimulation of pulmonary maturity, and triiodothyronine (T3) is believed to influence directly surfactant production. Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism. While a state of hypotriiodothyroninemia exists at birth, we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks' gestation. Fifty preterm infants with RDS were studied (mean gestational age 30.4 +/- 1.2 weeks and birth weight 1,180 +/- 220 g). They were at random assigned to treatment with 50 micrograms L-T3 (Thyrotardin) or to the control group. Mortality rate, peak oxygen concentrations, duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS. We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg (p less than 0.05). These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation.     

Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment.

Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland.     

Effect of a single breath of 100% oxygen on respiration in neonates during sleep

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

Longitudinal assessment of pituitary-thyroid axis and adrenal function in preterm infants raised by 'kangaroo mother care'

OBJECTIVE: To assess whether complete kangaroo mother care (KMC), a skin-to-skin contact intervention, would affect longitudinal/developmental patterns of hormonal change. METHOD: An open randomized controlled trial was conducted in a large tertiary care hospital, comparing KMC and traditional care for newborn infants weighing less than 2,001 g. Eighty-seven healthy preterm (<37 weeks gestational age) infants from this study provided three blood-spot samples on filter paper: at randomization (postnatal age 1-5 days), 2 weeks later, and at calculated term (41 weeks gestational age). They met a number of additional inclusion criteria including discharge from the hospital within the first postnatal week. The levels of 17alpha-hydroxy-progesterone (17-OHP), thyroxine-stimulating hormone (TSH) and thyroxine (T(4)) were assessed by radioimmunoassay. Birth weight (<1,800 or > or =1,800 g) and prenatal maternal corticosteroid treatment were taken into account in the analysis. INTERVENTIONS: Complete KMC includes early discharge, positioning the infant on the parent's chest in an upright position, 24 h/day in skin-to-skin contact, and breast-feeding. In the traditional care group, infants were discharged according to routine hospital practice. RESULTS: Levels of 17-OHP and TSH decreased significantly from eligibility to calculated term while T(4) levels did not change significantly over time. Most importantly, overall, treatment (KMC) did not interact with the pattern of physiological change. CONCLUSIONS: Maturation of the pituitary-thyroid axis and adrenal function is apparently not compromised by KMC, at least in healthy preterm infants.     

Maturation of feedback control of thyrotropin in premature infants

Serum thyrotropin (TSH), free T4 and free T3 concentrations were measured longitudinally in 26 preterm infants for 14 weeks after birth, using highly sensitive immunoradiometric assays. Serum TSH values on days 4-5 were positively correlated with gestational age and birth weight. In the premature infants of 25 weeks mean gestation, the mean TSH concentrations increased from a very low value of 0.84 microU/ml at 5 days to a peak value of 6.1 microU/ml by 5 weeks of age, then slightly decreased and remained stable. Serum free T4 and free T3 concentrations increased in parallel and free T3 level reached the range of term infants by 6 weeks. Serum free T4/TSH and free T3/TSH ratios began to increase at the 6th week of age. The results suggest that: (i) the thyroid hormone feedback control of pituitary TSH release in the extremely premature infants begins to mature after 6 weeks of postnatal age, (ii) the maturation pattern of the hypothalamic-pituitary-thyroid system in premature infants is similar to that of the intrauterine fetus.     

Genotype Distribution,Viral Load and Clinical Characteristics of Infants with Postnatal or Congenital Cytomegalovirus Infection

Background

Congenital cytomegalovirus infection is a leading cause of long-term sequelae. Cytomegalovirus is also frequently transmitted to preterm infants postnatally, but these infections are mostly asymptomatic. A correlation between cytomegalovirus genotypes and clinical manifestations has been reported previously in infants with congenital infection, but not in preterm infants with postnatal infection.

Objectives

The main objective of this study was to investigate cytomegalovirus genotype distribution in postnatal and congenital cytomegalovirus infection and its association with disease severity.

Methods

Infants admitted to the neonatal intensive care unit of the University Medical Center Utrecht, The Netherlands between 2003–2010 and diagnosed with postnatal or congenital cytomegalovirus infection were included. Classification of cytomegalovirus isolates in genotypes was performed upon amplification and sequencing of the cytomegalovirus UL55 (gB) and UL144 genes. Clinical data, cerebral abnormalities, neurodevelopmental outcome and viral load were studied in relation to genotype distribution.

Results

Genotyping results were obtained from 58 preterm infants with postnatal cytomegalovirus infection and 13 infants with congenital cytomegalovirus infection. Postnatal disease was mild in all preterm infants and all had favourable outcome. Infants with congenital infection were significantly more severely affected than infants with postnatal infection. Seventy-seven percent of these infants were symptomatic at birth, 2/13 died and 3/13 developed long-term sequelae (median follow-up 6 (range 2–8) years). The distribution of cytomegalovirus genotypes was comparable for postnatal and congenital infection. UL55 genotype 1 and UL144 genotype 3 were predominant genotypes in both groups.

Conclusions

Distribution of UL55 and UL144 genotypes was similar in asymptomatic postnatal and severe congenital CMV infection suggesting that other factors rather than cytomegalovirus UL55 and UL144 genotype are responsible for the development of severe disease.     

Antenatal and early postnatal dexamethasone treatment decreases cortisol secretion in preterm infants

Glucocorticoids are used antenatally to accelerate the maturation of fetal respiratory and cardiovascular systems when a threat of preterm delivery exists. Postnatally, they are used to prevent and treat respiratory distress syndrome. This study investigates the effects of antenatal (ACT) and early postnatal corticosteroid treatment (PCT) on serum cortisol and plasma catecholamine and adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in preterm neonates. The infants in the ACT group had a significantly lower cortisol concentration than the infants in the non-ACT group on the first day of life. After birth, the infants were further divided into non-PCT and PCT groups. PCT suppressed cortisol levels significantly after 2 days, and the cortisol levels were still lower 2 days after discontinuation of PCT. No effect of PCT on plasma cAMP or catecholamine concentrations was observed. The results indicate that both ACT and a short PCT can significantly suppress basal cortisol levels in preterm infants.     

Plasma selenium in preterm and term infants during the first 12 months of life

The goal of the present study was to prospectively assess the plasma selenium (Se) concentrations of term and preterm infants during the first year of life in relation to gestational age and nutrition.

Blood specimens were collected from orally formula-fed preterm infants (gestational age < 32 weeks, birth weight < 1500 g): 1.) in hospital and 2.) corrected for gestational age parallel to healthy term breast and formula-fed infants at the ages of 1, 4 and 12 months. All infants were fed according to a standardized nutritional concept, solids and follow-up formula were introduced at the age of 4 months.

Plasma selenium in preterm infants in hospital was 11.7 (6.5–20.8) g/l and 11.6 (8.8–16.7) g/l at 4 weeks corrected for gestational age. At the age of 4 months plasma selenium was still significantly lower than in the other groups: Preterm infants: 17.1 (10.4–30.5) g/l; formula-fed term infants: 31.3 (24.3–47.5) g/l; breast-fed term infants: 45.6 (27.1–65.1) g/l). The levels of breast-fed infants were significantly higher than those of both formula-fed groups up until the introduction of solids.

Preterm infants had significantly low plasma selenium levels up until a postnatal age of at least 6 months. The levels were lower than those of term infants fed an identical unsupplemented infant formula during the first 4 months of life. These data support routine monitoring in hospital and selenium supplementation of preterm infants, preferably in hospital before discharge.     

Influence of postconceptual age on the electromyographic characteristics in newborns

The purpose of the study was to investigate the neuromuscular state in the preterm infants using surface electromyography (EMG). Ten preterm (gestational age, 31–32 weeks) and ten term infants (gestational age, 38–39 weeks) participated in the study in the second, fourth and sixth postnatal weeks. Linear and novel nonlinear parameters were used for the treatment of the interference EMG (iEMG) in four muscles (mm. bic. br. dext., trie. br. dext, tib. ant. sin., and gastr. sin.). In the preterm infants aged 33–37 weeks, both linear and nonlinear iEMG parameters were significantly lower in comparison to the term infants. Thus, the iEMG of the preterm infants was characterized by a more primitive time-domain structure and lower amplitude and spectrum frequency. In addition, unlike in term newborns, the lifetime dynamics of the iEMG parameters in the preterm infants was retarded. Thus, the motor system of a preterm infant is likely to be less prepared for postnatal life due to the shorter stay in utero. Nonetheless, the iEMG of the preterm infants may be characterized as more complex in comparison to the term newborns of the same postconceptual age. This may be attributed to the new postnatal sensory stimuli.     

Modification of cord blood IL-6 production with IgM enriched human immunoglobulin in term and preterm infants

Pro-inflammatory cytokines contribute significantly to the morbidity of premature infants. IL-6 and IL-8 are involved in the pathogenesis of pulmonary and cerebral tissue injury. The effect of human immunoglobulin preparations on cytokine production in preterm infants has not been studied. We investigated the influence of immunoglobulin on LPS stimulated IL-6 and IL-8 production in cord blood of healthy preterm neonates. Ten non-infected preterm infants delivered by cesarean section and 5 healthy term neonates were included. In the preterm infants, significant IL-6 production was observed in the absence of immunoglobulin after 4 h [median 113 (39-725) pg/ml], 8 h [375 (234-1795) pg/ml] and 12 h [360 (248-2765) pg/ml] of LPS incubation. IL-6 concentrations were significantly lower after incubation with LPS+immunoglobulin after 4 h [median 38 (5-568) pg/ml; p=0.005], 8 h [178 (10-1830) pg/ml; p=0.001] and 12 h [182 (29-2530) pg/ml; p=0.002]. Cultures from term infants produced IL-6 levels approx. 4 times of those from premature infants unaffected by immunoglobulin. IL-8 production also correlated to gestational age and was not affected by immunoglobulin in both groups. Human immunoglobulin preparation may modify IL-6 production in cord blood cultures from premature infants.     

Cerebral oxygenation is highly sensitive to blood pressure variability in sick preterm infants

Objectives

The significance of blood pressure variability (BPV) for cerebral oxygenation in extremely preterm infants has not been explored, though BPV may well be associated with end organ injury. We hypothesized that increased BPV in sick preterm infants, by exceeding the cerebral autoregulatory capacity, is associated with cerebral oxygenation changes which closely follow the blood pressure fluctuations. We assessed the autoregulatory capacity in the early postnatal period, by determining the correlation between BPV (mmHg²) and coherence of mean arterial blood pressure (MABP mmHg) and cerebral oxygenation (tissue oxygenation index, TOI %).

Study Design

Thirty-two preterm infants of mean gestational age of 26.3 (±1.5) weeks were studied on the first 3 postnatal days. Spectral analysis (Coherence and transfer-function gain analysis) was used to calculate coherence of MABP and TOI; BPV was quantified using power spectral density of MABP.

Results

Overall, maximum Coherence showed a trend for positive correlation with BPV (n = 32, p = 0.06). Infants identified as clinically unstable with documented brain injury (n = 7) had high Coherence values at low BPV. Separate analysis of stable infants (excluding the 7 critically ill infants) revealed a significant association between maximum Coherence and BPV (n = 25, p = 0.006).

Conclusions

Fluctuation in cerebral oxygenation is closely associated with increased BPV in preterm infants undergoing intensive care. Moreover, in the critically sick preterm infant, blood pressure-dependent variations in cerebral oxygenation occur even with relatively lower BPV, suggesting they have severely impaired autoregulation, and placing them at greater vulnerability to cerebral injury arising from blood pressure fluctuations.     

Plasma and erythrocyte selenium and glutathione peroxidase activity in preterm infants at risk for bronchopulmonary dysplasia

The purpose of this study was to examine the relationships between selenium status, as measured by plasma and erythrocyte selenium and glutathione peroxidase (GPx) activity, and other postnatal factors, including selenium intake, gestational age, and oxygen dependence in preterm infants at risk for bronchopulmonary dysplsia. Eighteen preterm infants of 30 wk gestational age or less were included. At postnatal wk 1 and 4, selenium concentrations and GPx activity were measured and oxygen dependence and daily selenium intakes were determined from the medical chart. Plasma and erythrocyte selenium concentrations decreased from wk 1 to wk 4, whereas erythrocyte GPx activity increased. Increased selenium intakes during wk 1 were associated with increased erythrocyte GPx activity at both time-points, as well as a decreased need for supplemental oxygen on d 28. Preterm infants display increasing erythrocyte GPx activity despite declines in plasma and erythrocyte selenium. GPx activity might be enhanced by very early selenium supplementation.     

Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care

In 51 sick newborns the influence of two different nonionic, iodine-containing contrast agents, Amipaque (group 1) and Omnipaque (group 2) and of long-term treatment with polyvinylpyrrolidone-iodine (PVP-I) (group 3) on thyroid function was studied. In the dose given, freshly dissolved Amipaque releases roughly 100 micrograms 'free' iodide/kg body weight; this release may be even higher in the solubilized agent Omnipaque because of increased breakdown. Urinary iodine excretion was elevated in all groups on day 5 after iodine exposure. In group 1, which included 17 term newborns, the median TSH level was normal after 5 days and 2 weeks, only 1 case of transient hypothyrotropinemia was observed; T4 and T3 median levels were in the lower range of normal. In groups 2 and 3, which included 8 preterm infants of 15 newborns and 9 preterm infants of 19 newborns, respectively, the median TSH values were elevated and T4 and T3 levels were very low. Hypothyroidism was diagnosed in 6 of the 8 preterm and in 1 of the 7 term newborns of group 2. In group 3, 7 of the 9 preterm and 3 of the 10 term newborns reacted with hypothyroidism. Eight preterm and 3 term newborns had to be substituted with thyroxine. The thyroid function of term newborns was less affected by Amipaque or Omnipaque than by PVP-I. The data show that preterm infants are very sensitive to an iodine load.     

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.     

Postnatal Temporal,Spatial and Modality Tuning of Nociceptive Cutaneous Flexion Reflexes in Human Infants

Cutaneous flexion reflexes are amongst the first behavioural responses to develop and are essential for the protection and survival of the newborn organism. Despite this, there has been no detailed, quantitative study of their maturation in human neonates. Here we use surface electromyographic (EMG) recording of biceps femoris activity in preterm (<37 weeks gestation, GA) and term (≥37 weeks GA) human infants, less than 14 days old, in response to tactile, punctate and clinically required skin-breaking lance stimulation of the heel. We show that all infants display a robust and long duration flexion reflex (>4 seconds) to a single noxious skin lance which decreases significantly with gestational age. This reflex is not restricted to the stimulated limb: heel lance evokes equal ipsilateral and contralateral reflexes in preterm and term infants. We further show that infant flexion withdrawal reflexes are not always nociceptive specific: in 29% of preterm infants, tactile stimulation evokes EMG activity that is indistinguishable from noxious stimulation. In 40% of term infants, tactile responses are also present but significantly smaller than nociceptive reflexes. Infant flexion reflexes are also evoked by application of calibrated punctate von Frey hairs (vFh), 0.8–17.2 g, to the heel. Von Frey hair thresholds increase significantly with gestational age and the magnitude of vFh evoked reflexes are significantly greater in preterm than term infants. Furthermore flexion reflexes in both groups are sensitized by repeated vFh stimulation. Thus human infant flexion reflexes differ in temporal, modality and spatial characteristics from those in adults. Reflex magnitude and tactile sensitivity decreases and nociceptive specificity and spatial organisation increases with gestational age. Strong, relatively non-specific, reflex sensitivity in early life may be important for driving postnatal activity dependent maturation of targeted spinal cord sensory circuits.     

Effect of night and day on preterm infants in a newborn nursery: randomised trial.

The effect of alternating night and day on sleep, feeding, and weight gain in 41 healthy preterm infants was examined in a randomised controlled trial. Twenty infants from a night and day nursery, where the intensity of light and noise was reduced between 7 pm and 7 am, spent longer sleeping and less time feeding and gained more weight than 21 infants from a control nursery, where the intensity of light and noise was not reduced. Differences were significant and became apparent only after discharge home; they were still present three months after the expected date of delivery, when infants from the night and day nursery were an average of 0.5 kg heavier (p less than 0.02). These findings suggest that physical environment has an effect (either direct or indirect) on the subsequent behaviour of preterm infants and that exposure to night and day is beneficial.     

Parameters of Surface Electromyograms in Full-Term and Preterm Infants in the Neonatal Period: The Possible Contribution of Gravity

The purpose of this study was to compare the postnatal evolution of spectral–amplitude and nonlinear parameters of surface electromyogram (sEMG) in the full-term and preterm infants with regard to their biological and calendar age. In full-term infants, all sEMG parameters (dimension, entropy, mean frequency, and amplitude) are increased by 10–30% two weeks after birth. On the contrary, sEMG parameters in preterm infants were constant for six weeks after birth. This finding indicates that both postnatal and antenatal periods are important for the development of the motor system of infants. Therefore, the adaptation of the motor system to extrauterine conditions consists of two stages. The authors suppose that gravity can be a driving factor of these sEMG metamorphoses.     

The association between proinflammatory cytokine polymorphisms and cerebral palsy in very preterm infants

Cerebral palsy (CP) is a nonprogressive motor disorder caused by white matter damage in the developing brain and is often accompanied with cognitive and sensory disabilities. The risk of CP is higher among infants born preterm than in more mature infants. Intrauterine infection/inflammation, activation of the cytokine network and elevated levels of proinflammatory cytokines in neonatal blood or in amniotic fluid to which the preterm infant is exposed, has been identified as the most common cause of preterm delivery, periventricular leukomalacia (PVL) and CP. The aim of our study was to evaluate the possible association of four TNFα promoter single nucleotide polymorphisms (SNPs) (-1031 T/C, -857 C/T, -308 G/A and -238 G/A), two IL1β SNPs (-511 C/T and +3954 C/T) and one IL6 (-174 C/G) polymorphism with susceptibility to CP in very preterm infants. Statistically significant association between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.339; p=0.016) as well as between TNFα -1031 C high expression allele (OR, 2.065; p=0.013) and risk of CP was observed. In addition, statistically significant association was found between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 3.286; p=0.034) and risk of CP. Statistically significant association between IL1β TT, CC -511/+3954 genotypes combination and risk of CP (OR, 4.000; p=0.027) was also found. In CP patients with cystic PVL (cPVL) statistically significant association was found between TNFα -1031 T/C high expression genotypes (TC and CC) (OR, 2.361; p=0.038), IL1β -511 C/T high expression genotype TT (OR, 3.215; p=0.030) as well as IL1β -511 T high expression allele (OR, 1.956; p=0.019) and risk of CP. Statistically significant association was also found in patients with cPVL between TNFα TC, CC, GG, GG -1031/-857/-308/-238 genotypes combination (OR, 4.107; p=0.024), as well as IL1β TT, CC -511/+3954 genotypes combination (OR, 7.333; p=0.005) and risk of CP. Our results suggest the role of TNFα and IL1β polymorphisms which have previously been associated with higher circulating levels of these cytokines in genetic susceptibility to white matter damage and consequently CP in very preterm infants.