Impact of histological chorioamnionitis, funisitis and clinical chorioamnionitis on neurodevelopmental outcome of preterm infants

Background

The role of chorioamnionitis in neurodevelopment of preterm infants is not fully understood.

Aim

To examine the association between different indicators of intrauterine inflammation (clinical chorioamnionitis, histological chorioamnionitis and funisitis) and neurodevelopmental impairment in very preterm infants.

Methods

Preterm infants with a birth weight of < 1500 g or a gestational age of < 32 weeks were included. Follow-up evaluation up to 2 years of age consisted of neurological examination, neurodevelopmental assessment and visual and audiologic tests. Outcome data were compared between the chorioamnionitis and the control groups, controlling for gestational age, birth weight and Apgar score at 5 min.

Results

One hundred seventy-seven patients comprised the study population (mean gestational age 29 ± 2 weeks, mean birth weight 1167 ± 344 g). Histological chorioamnionitis was present in 49% of placentas, whereas funisitis was observed in 25%. In 57% cases clinical maternal chorioamnionitis was suspected. Follow-up was available for 130 (82%) patients. Infants with funisitis, compared with controls, had a significantly higher incidence of moderate to severe disability (18% vs 5%, OR 4.07; 95% CI 1.10-15.09).

Conclusion

The results of this study suggest that, unlike a broad definition of histological chorioamnionitis including inflammation of maternal or fetal placental tissues, funisitis may entail a higher risk of moderate to severe disability at 2 years of age in preterm infants.     

Soluble receptor for advanced glycation end products (sRAGE) in tracheobronchial aspirate fluid and cord blood of very low birth weight infants with chorioamnionitis and funisitis

Background

A systemic fetal inflammatory response, reflected by histological funisitis is associated with pulmonary morbidity and increased mortality after premature birth. The receptor for advanced glycation end products (RAGE) is a membrane-bound multiligand receptor with a key role in inflammation. Soluble RAGE (sRAGE) is created by alternative mRNA splicing or shedding of the receptor's extracellular domain and can inhibit RAGE-activation.

Aims

To assess the association of funisitis with airway and systemic concentrations of sRAGE in very premature infants.

Methods

Forty-two ventilated infants (gestational age: 27.4 ± 1.8 weeks, birth weight: 1017 ± 229 g [mean ± SD]) were studied. sRAGE concentrations were measured in tracheobronchial aspirate fluid (TAF) on days of life 1, 3, 5, 7 and 10 and in umbilical cord serum of 28 infants by ELISA. The secretory component for IgA (SC) served as reference protein in TAF. Placental tissue, membranes and umbilical cords were examined microscopically to distinguish three groups: chorioamnionitis (n = 9), funisitis (n = 17) and controls (n = 16).

Results

The funisitis group had lower sRAGE concentrations than both other groups in cord blood serum (median: 0.52 ng/ml [25th-75th centile: 0.32-0.91]; control, 1.72 [1.02-2.69]; chorioamnionitis, 1.44 [0.92-1.63], p < 0.01) and TAF on day 1 (290 ng/ngSC [140-400]; control, 2750 [1470-28920]; chorioamnionitis, 2150 [1220-7140], p < 0.01). sRAGE in TAF remained lower in the funisitis than in the chorioamnionitis group on days 3 and 10, p < 0.01 respectively.

Conclusions

Decreased sRAGE in airways and circulation after funisitis may contribute to an imbalance between pro- and anti-inflammatory factors priming very premature infants for pulmonary injury and increasing the risk of adverse outcome.     

Serum chemokine levels and developmental outcome in preterm infants

Background

Cytokines and chemokines during perinatal period may involve the neurological development of newborns.

Aims

We investigated the association of circulating chemokines during neonatal period with the outcome of premature infants.

Study design

The prospective study enrolled 29 very low birth weight (< 1500 g) and appropriate-for-date infants having no underlying diseases. Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10 and CCL2) and cytokines at birth and 4 weeks postnatal age were measured. Developmental quotients (DQ) at 3 years of age by the Kyoto Scale of Psychological Development were studied for the association with chemokine/cytokine levels and clinical variables including chorioamnionitis, Apgar scores, ventilator treatment and supplemental oxygen.

Results

CXCL8 levels at birth and days of ventilator treatment were negatively, CCL2 levels at 4 weeks after birth and 5-minute Apgar scores were positively correlated with the DQ of postural-motor [P-M] area at 3 years of age, respectively (CXCL8: correlation coefficient [CC] = − 0.394, p = 0.037, ventilation: CC = − 0.518, p = 0.006, CCL2: CC = 0.528, p = 0.013, and Apgar score: CC = 0.521, p = 0.005). Infants showing both ≥ 50 pg/ml of CXCL8 at birth and < 250 pg/ml of CCL2 4 weeks after birth had lower DQ of P-M than those who did not (p < 0.001). Multivariate analyses indicated that CCL2 levels at 4 weeks of age were higher in infants who attained normal DQ of P-M (≥ 85) (adjusted mean, 338.4 [95% confidence interval, 225.5-507.8]) than in those who did not (< 85) (159.0, [108.2-233.7]) (p = 0.019).

Conclusion

Circulating patterns of CXCL8 (IL-8) and CCL2 (MCP-1) during the neonatal period might affect the neurological development of preterm infants.     

Signs of fetal brain sparing are not related to umbilical cord blood gases at birth

Background

Fetal chronic hypoxia leads to centralization of circulation in order to spare the vital organs brain, adrenals and the heart. This can be documented by Doppler ultrasound. Increased blood velocity in the fetal middle cerebral artery (MCA) is an acknowledged sign of centralization of circulation in chronic hypoxia, and is called brain sparing.

Aim

Our aim was to assess the relationship between signs of brain sparing in the MCA and umbilical cord blood gases at birth.

Study design

A prospective study.

Subjects

Singleton 57 high-risk pregnancies (outcome was compared with 21 normal pregnancies).

Methods

MCA Doppler was performed within 24 h of elective caesarean section in high-risk pregnancies. Umbilical cord blood gases were analysed at birth.

Main outcome measures

Cord blood gases were related to signs of centralization of fetal circulation in the MCA.

Results

No correlation between signs of brain sparing in the MCA and cord blood gases. Apgar score at 5′ < 7 was seen in three newborns, but only one of these had antenatal signs of brain sparing. Newborns with antenatal brain sparing were admitted more often (p < 0.04) and had a longer duration of stay in NICU (p < 0.03) compared to newborns without brain sparing.

Conclusion

Decreased pulsatility index in MCA is an acknowledged sign of fetal centralization of circulation during chronic hypoxia. However, signs of brain sparing are not related to cord blood gases at birth, which might suggest that redistribution of fetal circulation can maintain normal blood gases for a long time during chronic hypoxia.     

Comparison of salivary cortisol, heart rate, and oxygen saturation between early skin-to-skin contact with different initiation and duration times in healthy, full-term infants

Background

There are few studies that compare the physiological and biological efficacies between different early skin-to-skin contacts (SSC) post birth.

Aim

To investigate physiologically and biochemically how early SSC with different initiation and duration time influence the stress post birth for full-term infants.

Study design

Non-experimental study.

Subjects

Study I; Thirty-two infants who began SSC 5 min or less [birth SSC, mean initiation time (standard deviation): 1.6 (1.1) min] after birth and 36 infants who did so more than 5 min [very early SSC, 26.3 (5.0) min] in heart rate (HR) and oxygen saturation (SpO₂) analysis. Study II; Eighteen infants who underwent SSC for 60 min or less [mean initiation time: 7.5 (12.2) min] and 61 infants who did so for more than 60 min [15.3 (12.5) min] in salivary cortisol analysis.

Outcome measures

HR and SpO₂ measured for 30 min post birth. Salivary cortisol concentration measured at 1 min, 60 min, and 120 min post birth.

Results

Birth SSC group reached HR stability of 120-160 bpm significantly faster than very early SSC group by Kaplan-Meier analysis (P = 0.001 by log-rank test). As for SpO₂ stability of 92% and 96%, no significantly between-group difference was found. Salivary cortisol levels were significantly lower between 60 and 120 min after birth in SSC group, continuing for more than 60 min compared with SSC group for 60 min or less after adjustment for salivary cortisol level at 1 min besides the infant stress factors (P = 0.046).

Conclusions

Earlier SSC beginning within 5 min post birth and longer SSC continuing for more than 60 min within 120 min post birth are beneficial for stability of cardiopulmonary dynamics and the reduction of infant stress during the early period post birth.     

CPAP combined with inhaled nitric oxide for treatment of lung hypoplasia and persistent foetal circulation due to prolonged PPROM

Background

Second trimester preterm premature rupture of the membranes (PPROM) before 24 weeks of gestation is associated with a high morbidity and mortality rate.

Aim

To demonstrate the efficacy of early continuous positive airway pressure (CPAP) combined with inhaled nitric oxide (iNO) for treatment of preterm infants with lung hypoplasia and persistent foetal circulation (PFC) due to very early PPROM and prolonged severe oligohydramnios.

Methods

Seven infants with prolonged PPROM, lung hypoplasia, respiratory distress and persistent foetal circulation were intubated in the delivery room for subsequent surfactant and iNO application. As our new treatment strategy was to keep the period of mechanical ventilation as short as possible, all infants were switched on nasal CPAP combined with iNO within the first 24 hours.

Results

Mean gestational age at PPROM was 19 + 6 weeks (range 14 + 2 to 23 + 6 weeks) and the average latency period between rupture of membranes and delivery was 10 + 3 weeks (7 + 3 to 16 + 4 weeks). Infants were born at 30 + 3 weeks of gestation (28 + 3 to 33 + 1 weeks) with an average birth weight of 1468 g (884 to 2200 g). In all neonates CPAP combined with iNO reversed PFC and 6 patients stabilised without the need for reintubation and mechanical ventilation. One infant had to be reintubated following 12 hours of CPAP combined with iNO due to respiratory insufficiency. All seven infants survived to discharge.

Conclusion

CPAP combined with iNO might be a promising approach for therapy of preterm infants with lung hypoplasia and persistent foetal circulation due to very early PPROM.     

Patterns in sleep-wakefulness in three-month old infants exposed to methadone or buprenorphine

Background

Infants exposed to opioides in-utero frequently demonstrate withdrawal symptoms in the neonatal period and have difficulties with state regulation.

Aim

This study examines sleep-wakefulness-distress patterns as indicators of regulatory mechanisms at 3 months of age.

Participants

A national infant cohort (N = 35) born to women in high-dose maintenance treatment during pregnancy and a comparison group (N = 36) of low-risk infants born in the same period.

Outcome measures

Distributions and frequencies of sleep, wakefulness and distress measured in hours and episodes on sleep charts recorded by the mothers in the two groups.

Results

Women in maintenance treatment were monitored closely during pregnancy to avoid illicit drug use and to be prepared for motherhood. They were also offered residential treatment before pregnancy and after the child was born. There were no statistical differences between the two groups in any of the 10 measures reflecting diurnal and nocturnal rhythmicity at 3 months despite of neonatal abstinence syndrome in 47% of the exposed infants and significant differences in infant characteristics with respect to birth weight, gestational age and maternal characteristics.

Conclusions

Follow-up procedures combining drug monitoring and counseling during pregnancy and in the first months after birth enhance the development of state regulation in terms of sleep-wakefulness patterns.     

Low Apgar score without acidosis may indicate neuromuscular disorder

Objective

We hypothesized that in term infants low Apgar score with normal umbilical artery pH (UApH) indicates prenatal damage to the neuromuscular system.

Study design

Retrospective database search of 42,117 liveborn infants born 1993—-2005. Medical record analysis of 3104 term infants with cardiorespiratory maladaptation referred for special neonatal care. Focus on infants with UApH > 7.00 and 5-min Apgar < 6 (group A, n = 74), UApH < 7.00 and 5-min Apgar > 5 (group B, n = 49), and UApH < 7.00 and 5-min Apgar < 6 (group C, n = 14).

Results

Incidence of 5-min Apgar score < 6 was 0.50% in term infants. Mean (SD) UApH was 7.262 (0.075, P = 0.075); incidence of UApH < 7.00 was 0.30% in term infants. Nucleated red blood cells were elevated without differences in all three groups. Parental consanguinity was present in 39 of the 137 maladapted infants. In groups A/B/C, 10/18/2 infants were small for gestational age (P = 0.002 for A vs B) and in 16/1/0 neuromuscular anomalies were identified (P = 0.004 for A vs B). Eight of the 17 anomalies had been suspected prenatally. Logistic regression proved neuromuscular disorder the only independent variable discriminating between groups A and B.

Conclusions

Neuromuscular problems are the cause rather than the result of maladaptation. For unexplained low Apgar score, especially without acidosis, meticulous examination of the infant including brain imaging and EEG is justified.     

Episodes of hypocarbia and early-onset sepsis are risk factors for cystic periventricular leukomalacia in the preterm infant

Background

Septic episodes in preterm infants recently have been reported to be associated with periventricular leukomalacia (PVL). The role of hypocarbia as an independent risk factor for PVL in clinical studies raises many questions without conclusive answers.

Aims

To evaluate risk factors for cystic PVL focussing on the influence of hypocarbia.

Study design

Retrospective single centre case-control study.

Subjects

Preterm infants 24 to 35 weeks of gestational age and matched (1:2 for gender, birth year, gestational age and birth weight) controls.

Outcome measures

Multivariate analysis of perinatal factors being associated with cystic PVL diagnosed by serial ultrasound examinations.

Results

Univariate analysis of risk factors revealed lower 5 and 10 min Apgar scores, and higher rates of neonatal seizures, early-onset sepsis, neonatal steroids, respiratory distress syndrome with surfactant replacement therapy, and episodes of hypocarbia significantly being associated with PVL. Multivariate analysis using a logistic regression model revealed early-onset sepsis and hypocarbia being significantly associated with PVL (p = .022 and .024, respectively). Lowest PaCO₂ values did not differ as did not the duration of hypocarbia, but the onset of hypocarbia was significantly later in PVL cases compared to controls (mean 26 vs. 15 h, p = .033). Neurodevelopmental follow-up at a median time of 46 months was poor showing 88% of the cases having an adverse neurological outcome.

Conclusion

We found early-onset sepsis and episodes of hypocarbia within the first days of life being independently associated with PVL.     

Effect of ibuprofen on bilirubin-albumin binding in vitro at concentrations observed during treatment of patent ductus arteriosus

Background

In vitro studies have shown that ibuprofen (IBU) may interfere with bilirubin-albumin binding at concentrations of 100 µg/mL and above.

Objectives

The present study evaluates the in vitro bilirubin displacement over the range of IBU plasma concentrations observed in vivo during curative treatment of patent ductus arteriosus in preterm infants.

Methods

Considering that individual plasma concentrations obtained during the clinical development of IBU in preterm infants were ranging between 10 and 70 µg/mL and exceptionally above 100 µg/mL, we used the modified peroxidase method to determine total and unbound bilirubin concentrations without IBU and with IBU over this specific concentration range.

Results

Total bilirubin and albumin concentrations were respectively 6.6 mg/dL and 2.87 g/dL in pooled newborn plasma. No displacement of bilirubin from its albumin binding sites by IBU was observed over a range of concentrations from 10 to 100 µg/mL. Only a concentration of 200 µg/mL significantly increased the unbound bilirubin by 1.5-fold (p = 0.0008).

Conclusions

This in vitro study confirms displacement of bilirubin by a high IBU concentration of 200 µg/mL, however it retrieves no significant displacement over a range of concentrations up to and including 100 µg/mL, i.e. within the range of in vivo concentrations at the recommended dose regimen.     

Cystic periventricular leukomalacia in preterm infants: an analysis of obstetric risk factors

Objective

To identify obstetric risk factors and to elucidate the effect of prolonged rupture of the membranes on the development of cystic periventricular leukomalacia (PVL) in preterm infants.

Methods

A retrospective case-control study of 95 preterm infants with the diagnosis of PVL and 245 healthy controls matched for gestational age. A total of 52 antenatal, intrapartum and neonatal characteristics were studied by univariate methods and logistic regression.

Results

Preterm premature rupture of membranes (PPROM) (odds ratio 2.1 [95% CI 1.3-3.4], P = .003), gestational age at PPROM (P = .025), prolonged rupture of membranes (P < .0001), administration of tocolytic agents (1.8 [1.1-3.0], P = .019) and antibiotics (1.9 [1.2-3.1], P = .008) were associated with PVL. The use of tocolytic agents > 24 h (P = .008), prolonged latency between the increase in maternal leukocyte count and birth (P = .034), spontaneous onset of labor (1.8 [1.0-2.9], P = .026), vaginal delivery (1.7 [1.1-2.8], P = .029) and male gender (1.5 [1.0-2.0], P = .04) were found more frequently in PVL cases. Preeclampsia (0.4 [0.1-0.9], P = .034), hypertension at booking (P = .009), sonographic IUGR (P = .020), abnormal blood flow of the umbilical artery (P = .032) and cesarean section without labor (0.5 [0.3-0.8], P = .006) were found less frequently. In logistic regression analysis, prolonged rupture of the membranes (P = .748), preeclampsia (P = .973), the use of antibiotics (P = .617) and beta-sympathomimetic tocolytic agents (P = .563) lost statistical significance, whereas birth weight (P = .036) became significant.

Conclusion

PPROM and prolonged rupture of the membranes may provoke adverse effects on the neurodevelopmental outcome of the preterm fetus. These findings may have implications on the obstetric management of PPROM beyond 30 weeks of gestation. Cesarean section without labor was less likely associated with the diagnosis of PVL.     

Placental pathology is associated with illness severity in preterm infants in the first twenty-four hours after birth

Background

Placental pathology is associated with long-term neurological morbidity. Little is known about the association of placental pathology and illness severity directly after birth in preterm infants.

Objective

To determine the association between placental pathology and illness severity in preterm infants during the first 24 h after birth.

Study design

Placentas of 40 preterm infants, born after singleton pregnancies (gestational age 25.4-31.7 weeks, birth weight 560-2250 g) were assessed for histopathology. Illness severity was measured using the Score of Neonatal Acute Physiology Perinatal Extension (SNAPPE). A high SNAPPE reflects high illness severity.

Results

Examination of the 40 placentas revealed: pathology consistent with maternal vascular underperfusion (MVU) (n = 24), ascending intrauterine infection (AIUI) (n = 17), villitis of unknown aetiology (VUE) (n = 6), foetal thrombotic vasculopathy (FTV) (n = 6), elevated nucleated red blood cells (NRBCs) (n = 6), and chronic deciduitis (n = 10). SNAPPE ranged from 1 to 53 (median 10). Infants with elevated NRBCs had a higher SNAPPE than infants without elevated NRBCs (median 30 vs. 10, p = 0.014). The same was found for the presence of FTV (median 30 vs. 10, p = 0.019). No relation existed between SNAPPE and the other placental pathologies.

Conclusions

Elevated NRBCs and FTV were associated with higher illness severity during the first 24 h after birth in preterm infants. Ascending intrauterine infection was not associated with high illness severity.     

Standardization of the Alberta infant motor scale in full-term Greek infants: Preliminary results

Background

The Alberta Infant Motor Scale (AIMS) is a norm-referenced test that assesses the spontaneous motor performance of infants from birth through independent walking (0-18 months). This scale has been utilized for clinical and research purposes in various countries, however, whether the initial standardization in Canadian infants is also representative of other countries' populations has been questioned.

Aim

To assess whether the AIMS needs new reference values for Greek infants.

Methods

A cohort of 424 healthy full-term infants (250 boys and 174 girls), aged between 7 days and 18 months, derived from various areas of the Prefecture of Attica and from all socio-economic classes to ensure a true representation, was studied. The AIMS-scores of Greek infants were compared with the norm-referenced values of the original Canadian population reported by Piper and Darrah.

Results

The mean AIMS-scores did not differ significantly between Greek and Canadian infants at any age level from birth to 18 months, except for the 2-<3 month of age when higher scores were observed in Greek infants (p = 0.02). There was no significant difference in AIMS-values corresponding to the 5th and 90th percentile between Greek and Canadian infants. Inter-rater reliability was excellent in our study population [ICC: 0.99 (95% CI: 0.99-0.99)].

Conclusion

In healthy full-term Greek infants, gross motor maturity assessed by the AIMS during the first 18 months of age, seems to follow a similar course to that of Canadian infants.     

Intrauterine growth restriction in a low-income country: Risk factors, adverse perinatal outcomes and correlation with current WHO Multicenter Growth Reference

Objective

To determine risk factors and adverse perinatal outcomes including nutritional status in the first week of life for newborns with intrauterine growth restriction-low birth weight (IUGR-LBW) in settings lacking facilities for routine intrauterine growth monitoring.

Methods

A cross-sectional study of all infants in an inner-city hospital in Lagos, Nigeria. IUGR-LBW was defined as full-term (gestational age ≥ 37 weeks) infant with low birth weight (< 2500 g). Nutritional/growth status at enrolment was determined by z-scores for length-for-age (HAZ), head circumference-for-age (HCZ), weight-for-age (WAZ) and weight-for-length (WHZ) based on current World Health Organization's Multicentre Growth Reference (WHO-MGR). Factors and adverse outcomes associated with IUGR-LBW were explored with multivariable logistic regression analyses.

Results

Some 145 (4.3%) infants were IUGR-LBW out of 2619 eligible singletons enlisted for this study. IUGR-LBW was significantly associated with teenage mothers (OR:2.90, 95% CI:1.22-6.89), lack of antenatal care (OR:1.88, 95% CI:1.33-2.65) and female gender (OR:1.38, 95% CI: 0.98-1.93; p = 0.062). The incidence of adverse outcomes across gestational age showed significant linear trend only for low five-minute Apgar scores (p = 0.024) and WAZ (p = 0.065). IUGR-LBW was associated with poor nutritional status across all four indices (p < 0.001) as well as low 5-minute Apgar scores (p = 0.095), sepsis (p = 0.053), hyperbilirubinemia (p < 0.001) and admission into special care baby unit (p = 0.009) after multivariable logistic regression analyses.

Conclusions

IUGR-LBW correlates with poor nutritional status in the first week of life based on WHO-MGR and affected infants can be detected early for effective surveillance in resource-poor settings. Improved prenatal care among teenage mothers is necessary for reducing IUGR-LBW burden.     

Circulating adipocyte fatty acid binding protein levels in healthy preterm infants: Positive correlation with weight gain and total-cholesterol levels

Background

Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.

Aim

To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.

Study design

Prospective cohort study.

Subjects

55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).

Outcome measures

Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.

Results

Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (β = 0.33; p = 0.01 and β = 0.33; p = 0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (β = 0.36, p = 0.01).

Conclusions

An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.     

Functional impairments at school age of preterm born children with late-onset sepsis

Background

Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants.

Aim

We aimed to determine the motor, cognitive, and behavioural outcome at school age of preterm children with late-onset sepsis compared to matched controls.

Study design and subjects

A prospective case-control study that included preterm infants (gestational age < 32 weeks and/or birth weight < 1500 g) admitted to our Neonatal Intensive Care Unit in 2000-2001 with a culture-proven late-onset sepsis, and controls matched for gestational age.

Outcome measures

At school age we assessed motor skills, intelligence, visual perception, visuomotor integration, verbal memory, attention, executive functioning, and behaviour.

Results

At 6-9 years, 21 of 32 children with late-onset sepsis (68%) had borderline or abnormal motor outcome with most problems in fine motor skills. Their total IQ was 89 compared to 98 in controls. In addition, verbal memory and attention were affected compared to controls (0.61 standard deviations (SD), 95% confidence interval (CI) 0.04-1.17, p = 0.033 and 0.94 SD, 95% CI 0.32-1.62, p = 0.011, respectively). Multiple episodes of sepsis and gram-negative sepsis were risk factors for worse cognitive outcome.

Conclusions

At school age, a majority of preterm children with late-onset sepsis had motor problems. Their IQ was considerably lower than matched controls, and memory and attention were specifically impaired. Outcome at school age of preterm children with late-onset sepsis was worse than previously thought.     

General movements in the perinatal period and its relation to echogenicity changes in the brain

Background

In preterm born infants abnormal general movements (GMs) generally normalize before three months post term, but may persist when perinatal brain injury is present.

Aims

To assess the continuity of GM quality from fetal to early neonatal period and its relation to brain echogenicity changes.

Study design

Prospective study examining GMs and three vulnerable brain areas before and 7 days after birth. The quality of GMs was classified as normal or abnormal by Gestalt-perception. The brain was examined for moderate echogenicity changes (periventricular: brighter than choroid plexus, intraventricular: filling equal or more than 50% of the ventricle, and locally increased basal ganglia/thalami).

Subjects

94 fetuses from pregnancies complicated by preterm hypertensive disorders or labour at a gestational age between 26 and 34 weeks.

Outcomes measures

Correlations of fetal GMs, echogenicity changes, and clinical parameters (e.g. gestational age, parity, hypertensive disorders or preterm labour, oligohydramnios and fetal growth restriction) with neonatal GMs.

Results

Fetal GMs were abnormal in 64%, normalizing in 68% within 7 days after birth. Fetal GMs were significantly related to postnatal GMs (p = 0.045). Moderate fetal brain echogenicity changes and clinical parameters were not significantly related to neonatal GM.

Conclusions

In this population of pregnancies compromised by hypertensive disorders or preterm labour fetal GMs correlated with neonatal GMs. Presence of moderate echogenicity changes in the fetal brain was not related to neonatal GMs.     

Quantitative electroencephalographic patterns in normal preterm infants over the first week after birth

Background

Currently available tools to assist clinicians with prediction of neurodevelopmental outcome of preterm infants are inadequate. Modified cotside electroencephalography (EEG) has the ability to produce quantitative electrophysiologic measures. These measures may be useful in future prediction of outcome.

Aim

To determine patterns of change in quantitative EEG measures in preterm infants during their first week after birth.

Design

Observational.

Subjects

Preterm infants born at less than 32 weeks completed gestation surviving to discharge with unremarkable serial ultrasound scans.

Outcome measures

Changes in continuity, amplitude and spectral edge frequency measures of EEGs obtained over the first week after birth.

Results

Results of EEGs performed using a novel EEG device on 63 infants are reported here. Their median (range) gestation was 29 (24-31) weeks and birthweight was 1235 (540-1980) g. Quantitative measures of EEG continuity increased over the first week after birth from 72 (25-99)% to 92 (54-100)% at the 25 μV threshold, and from 39 (10-87)% to 64 (34-75)% at the 50 μV threshold, both p < 0.0001. There was a related 32% increase in median amplitude from 5.8 (2.6-10.6) μV on day 1 to 7.6 (4.3-9.4) μV on day 4, p = 0.005. There was a trend for average spectral edge frequency to fall from 10.7 (9.3-12.9) Hz on day 1 to 9.9 (8.1-12.3) Hz on day 3, p = 0.06. Each gestational tertile showed similar patterns.

Conclusions

There are consistent changes in quantitative neurophysiologic measures over the first week after birth, and particularly measures of continuity over the first 4 days, in normal preterm infants.     

Maternal anxiety is related to infant neurological condition, paternal anxiety is not

Background

Parental anxiety and stress may have consequences for infant neurological development.

Aims

To study relationships between parental anxiety or well-being and infant neurological development approximately one year after birth.

Study design

Longitudinal study of a birth cohort of infants born to subfertile couples. Subjects: 206 parent-child dyads.

Outcome measures

Infant neurology was assessed with the Touwen Infant Neurological Examination (TINE) at 10 months and a developmental questionnaire at 12 months. Parental measures included trait anxiety measured by the State-Trait Anxiety Inventory (STAI) and well-being measured by the General Health Questionnaire (GHQ).

Results

Maternal trait anxiety was associated with a less optimal neurological condition (r_s = − 0.19, p < 0.01) of the infant. This association persisted after adjusting for confounders and results were confirmed by the outcome of the developmental questionnaire. Paternal trait anxiety and parental well-being were not related to the infant's neurodevelopmental outcome.

Conclusions

Infants of mothers with high trait anxiety have an increased vulnerability to develop a non-optimal nervous system. The association may be mediated in part by early programming of monoaminergic systems. Future research should include an exploration of specific windows of vulnerability to maternal anxiety.     

A patient care system for early 3.0 Tesla magnetic resonance imaging of very low birth weight infants

Background

Very low birth weight (VLBW) infants (weight < 1500 g) are increasingly cared for without prolonged periods of positive pressure ventilation (PPV).

Aims

To develop a system for 3.0 T magnetic resonance (MR) image acquisition from VLBW infants who are not receiving PPV, and to test the clinical stability of a consecutive cohort of such infants.

Design

Seventy VLBW infants whose median weight at image acquisition was 940 g (590-1490) underwent brain MR imaging with the developed care system as participants in research. Twenty infants (29%) received nasal continuous positive airway pressure (nCPAP), 28 (40%) received supplemental oxygen by nasal cannulae, and 22 (31%) breathed spontaneously in air during the MR examination.

Results

There were no significant adverse events. Seventy-six percent had none or transient self-correcting oxygen desaturations. Desaturations that required interruption of the scan for assessment were less common among infants receiving nCPAP (2/20) or breathing spontaneously in air (2/22), compared with those receiving nasal cannulae oxygen (13/28), p = 0.003. Sixty-four (91%) infants had an axillary temperature ≥ 36 °C at completion of the scan (lowest 35.7 °C), There was no relationship between weight (p = 0.167) or use of nCPAP (p = 0.453) and axillary temperature < 36 °C. No infant became hyperthermic.

Conclusion

VLBW infants who do not require ventilation by endotracheal tube can be imaged successfully and safely at 3.0 T, including those receiving nCPAP from a customised system.