Altered gene expression in umbilical cord mononuclear cells in preterm infants with periventricular leukomalacia

Aim

Periventricular leukomalacia (PVL) is one of the most important causes of adverse outcome of preterm infants. We hypothesized that inflammatory or some other specific pathways will have been activated at birth in preterm infants who later develop PVL. The aim of this study is to examine the difference in mRNA expression in umbilical cord blood according to the presence or absence of PVL.

Methods

A total of 61 umbilical cord blood samples were collected from preterm infants with gestational age less than 33 weeks together with the patients' medical information during perinatal period. RNA expression patterns in the collected cord bloods were analyzed by microarray. On the basis of cranial ultrasonography and brain MRI examination, 3 infants (4.9%) were diagnosed as cystic PVL and selected as the subjects. Five patients who showed similar perinatal factors to those of infants with PVL but did not show PVL were selected as the normal control.

Results

Five of the 15 up-regulated genes are coding ribosomal proteins, and another encodes a translation elongation factor. Three of the 7 down-regulated genes encode proteins that may be related to immune response and/or inflammation.

Conclusions

Up-regulation of the ribosomal proteins may indicate an activation of lymphocytes during the fetal period.     

Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age

Background

To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants > 28 gestational age (GA) submitted to heel lancing.

Objective

To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA).

Methods

In six infants < 28 + 0 GA and 4 infants ≥ 28 + 0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA.

Results

Baseline SC prior to intervention took longer time to stabilise and was higher in < 28 than in ≥ 28 + 0 PNA. The combination of heel lancing and squeezing gave an increased SC in < 28 PNA, whereas heel lancing alone gave the same SC response in ≥ 28 + 0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in < 28 PNA.

Conclusion

Changes in SC could be detected in infants at < 28 + 0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born < 28 GA. SC seems to be able to differentiate between pain and discomfort.     

Maternal sensitivity moderates the impact of prenatal anxiety disorder on infant mental development

Background

Animal studies have shown that postnatal rearing style can modify the association between prenatal stress exposure and offspring neurodevelopmental outcomes. However, little is known about how parenting quality impacts the association between maternal prenatal anxiety and development in human infants.

Aim

This prospective study examined the impact of maternal prenatal anxiety disorder and maternal caregiving sensitivity on cognitive and psychomotor development in healthy, full-term, 7-month-old infants.

Measures

Women completed a clinical interview during the third trimester of pregnancy to assess anxiety symptoms meeting DSM-IV diagnostic criteria. At infant age 7 months, maternal sensitivity to infant distress and non-distress were observed and coded during the still-face procedure. Maternal postnatal (concurrent) anxiety and depression were also assessed at this time. Infant mental and psychomotor development was assessed at infant age 7 months using the Bayley Scales of Infant Development II.

Results

Analyses were based on 77 mother-infant dyads. Maternal sensitivity to infant distress moderated the association between maternal prenatal anxiety disorder and infant mental development, F (1, 77) = 5.70, p = .02. Whereas there was a significant positive association between sensitivity and mental development among infants whose mothers were anxious during pregnancy, sensitivity had little impact on mental development among infants of control (non-anxious) women. Results were independent of prenatal depression and postnatal anxiety and depression. A caregiving moderation effect was not found for infant psychomotor development, p > .10.

Conclusions

These findings are consistent with a cumulative risk model suggesting that maternal prenatal anxiety and quality of maternal care act in concert to shape infant outcomes.     

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.     

Prenatal diagnosis of trisomy 21 through detection of trophoblasts in cervical smears

Background

Fetal cells exfoliate in the uterine cavity during early pregnancy and are a potential source of material for NIPD.

Aims

This study was designed to test the hypothesis that fetal cells obtained from the uterine cervix during the first trimester of pregnancy could be utilized for prenatal diagnosis of chromosomal aneuploidy.

Study design

Fetal cells retrieved from the distal endocervical canal during the first trimester of pregnancy were hybridized with chromosome 21 specific FISH probes and analyzed with an automated fluorescence microscope.

Subjects and outcome measures

Cells with 3 copies of chromosome 21 were detected in 5 out of 5 trisomy 21 pregnancies.

Results

The number of trisomic cells detected ranged from 1 to 27 with a median value of 5.

Conclusions

FISH-based scanning can identify trisomy 21 pregnancies by analysis of routine cervical brushings. The approach offers the potential for non-invasive prenatal diagnosis as early as 5 weeks gestation.     

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.     

Parental body size and early weight and height growth velocities in their offspring

Background

Whereas weight or height at a given age are the results of the cumulative growth experience, growth velocities allows the study of factors affecting growth at given ages.

Aim

To study the relationships between parental height and body mass index (BMI) and offspring's height and weight growth during infancy and childhood.

Study design

From the FLVSII population-based study, 235 parent-child trios belonging to 162 families examined in 1999.

Outcome measures

From medical records and previous FLVS examinations, child's height and weight history were reconstructed. Weight and height growth velocities from birth to seven years were estimated from a modelling of individual growth curve and correlated with parent's body size in 1999.

Results

Ponderal index and length at birth were significantly associated with maternal but not paternal BMI and height. In the first six months, height growth velocity was significantly associated with maternal stature (at three months: 0.12 ± 0.05 and 0.02 ± 0.05 cm/month for a 10 cm difference in maternal and paternal height respectively) and weight growth velocity with paternal BMI (at three months: 5.7 ± 2.8 and 1.9 ± 2.3 g/month for a difference of 1 kg/m² in paternal and maternal BMI respectively). Between two and five years, height growth velocity was more significantly associated with paternal height whereas weight growth velocity was more closely associated with maternal BMI.

Conclusions

Early childhood growth is characterised by alternate periods associated specifically with maternal or paternal BMI and height. This novel finding should trigger the search for specific genetic, epigenetic or environmentally shared factors from the mothers and fathers.     

Leptin determination in colostrum and early human milk from mothers of preterm and term infants

Background

Leptin is involved in the regulation of food intake and energy expenditure and is therefore important for growth and brain development. Analytical methods used for leptin measurement in human milk differ widely in the literature and yield varying results.

Aims

To compare different preparation methods for the analysis of leptin in human milk and to investigate the leptin levels in colostrum and mature human milk from mothers of preterm or term infants.

Methods

Mothers delivering a preterm (n = 37) or a term infant (n = 40) were recruited for a prospective study and were ask to collect breast milk on the 3rd and 28th day of lactation. Leptin, protein and fat concentrations were analysed. Clinical data of mother and child were recorded prospectively.

Results

Skim milk was most appropriate for leptin analysis. Human milk leptin concentrations did not differ between preterm and term human milk. In term milk, leptin concentration on day 28 was lower than on day 3 (p < 0.05). Milk leptin levels on the 3rd and 28th day were positively correlated with mothers' body mass index, but not with fat content in milk.

Conclusion

Skim milk was the most stabile preparation for leptin analysis. Preterm and term human milk contain leptin in equal concentrations. Human milk leptin depends on mothers' body mass index.     

High plasma cytokine levels, white matter injury and neurodevelopment of high risk preterm infants: assessment at two years

Background

Controversy exists regarding association of high levels of proinflammatory cytokines, neonatal morbidities and poor neurodevelopment outcome in very low birth weight infants.

Objective

To determine association between severity of early inflammatory response and neurodevelopment outcome in high risk very low birth weight infants.

Methods

Sixty-two very preterm infants with high risk for early-onset sepsis were followed up to 24 months corrected age. Blood sample was collected for IL-6, IL-8, IL-10, IL-1β, and TNF-α analysis. Neurodevelopment outcome by Bayley Scales of Infant Development II was assessed at 22 to 24 months. Magnetic Resonance Image was performed at least once during the first 12 months.

Results

In 24 (38.7%) MDI was < 85, and 16 (25.8%) had PDI < 85. Low birth weight was significantly associated with low MDI, and birth weight and periventricular leukomalacia were significantly associated with low PDI by multiple regression analysis. After controlling for birth weight and gestational age, none of the studied variables was associated with low MDI, and only periventricular leukomalacia with low PDI. Each additional 100 g in the birth weight reduced the probability of low MDI and PDI scores in 14%.

Conclusions

There was no association of high cytokines plasma levels with poor neurodevelopment outcome at 22 to 24 months' corrected age, suggesting that elevations of plasma proinflammatory cytokines early in life do not play an important role in pathophysiology of brain injury in high risk preterm infants.     

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.     

Aerobic exercise during pregnancy influences fetal cardiac autonomic control of heart rate and heart rate variability

Background

Previous studies using ultrasound technology showed that fetal heart rate (HR) may be responsive to maternal aerobic exercise. Although it is recognized that cardiac autonomic control may be influenced by the intrauterine environment, little is known about how maternal exercise affects fetal heart development.

Aims

This study tested the hypothesis that regular maternal exercise throughout gestation influences fetal cardiac autonomic control of HR and heart rate variability (HRV) when compared to fetuses of non-exercising women.

Study design

Magnetocardiograms (MCGs) were recorded using a dedicated fetal biomagnetometer at 28, 32 and 36 weeks gestational age (GA) from 26 regularly exercising (> 30 min of aerobic exercise, 3× per week) and 35 healthy, non-exercising pregnant women. Fetal MCG was isolated and normal R-peaks were marked to derive fetal HR and HRV in the time and frequency domains. We applied a mixed-effects model to investigate the effects of exercise, GA and fetal activity state.

Results

At 36 weeks GA, during the active fetal state, fetal HR was significantly lower in the exercise group (p = < 0.0006). Post-hoc comparisons showed significantly increased HRV in the exercise group during the active fetal state at 36 weeks GA for both time and frequency domain measures.

Conclusion

These results indicate that regular maternal exercise throughout gestation results in significantly lower fetal HR and increased HRV.     

Sensorimotor skills associated with motor dysfunction in children born extremely preterm

Background

Children born prematurely, despite being free of intellectual and sensorineural deficits, are at risk of motor dysfunction.

Aim

To investigate the association of sensorimotor processing skills and Developmental Coordination Disorder (DCD) in “apparently normal” extreme preterm children.

Study design

In a matched case-control study, 50 preterm children born less than 29 weeks or birthweight < 1000 g, with an IQ > 85 and no identified sensorineural disability, were assessed at 8 years of age along with 50 gender and birth date matched classroom controls born at full term. A battery of sensorimotor tests was administered, which examined visual-motor, visual perception, tactile perception, kinaesthesia, and praxis.

Results

For preterm children with DCD (n = 21), significantly lower scores were found for the visual processing and praxis tests, with the exception of verbal command, in comparison to those 29 preterm children without DCD and term controls (median visual perception scores were 92, 96 and 108 respectively; design copying was 0.07, 0.46 and 0.95; constructive praxis was 0.09, 0.27 and 0.63; and sequencing praxis was 0.14, 0.73 and 0.96). There were no difference on the tactile sensitivity and kinaesthetic processing tests.

Conclusions

Preterm children with DCD have difficulty with visual processing tasks. Praxis or motor planning poses a particular challenge for them. Motor dysfunction in extremely preterm children was related to poorer visual processing and motor planning and may relate to a cognitive processing problem.     

Pre-pregnancy iron reserves, iron supplementation during pregnancy, and birth weight

Background

Early iron supplementation in women with sufficient reserves could provoke iron excess resulting in haemoconcentration and low infant birth weight (IBW).

Aim

To clarify the influence of early iron supplementation on maternal iron status and the IBW, taking into account pre-pregnancy iron deposits.

Study design

Longitudinal, prospective study.

Subjects

Healthy women volunteers (n = 82) intending to become pregnant.

Outcome measures

Women were grouped as a function of their pre-pregnancy (low or present) iron stores (serum ferritin (SF) < or ≥ 20 μg/L) and time of commencement of iron supplementation during pregnancy; “early” (< 20 weeks) or “late” (≥ 20 weeks). Obstetric and clinical history, smoking habit, dietary intake and iron biochemical parameters were obtained at pre-pregnancy as well as at 1st, 2nd and 3rd trimesters. Haemoglobin, MCV, SF and transferrin saturation (TS) were measured.

Results

Overall, 36% of the women had low iron stores at pre-pregnancy. The mean early supplementation with iron was 140.7 mg/d and the mean of late supplementation was 99.01 mg/d. Early supplementation improves the biochemical status of the mother and does not provoke a significant increase in haemoconcentration relative to late supplementation independently of the pre-pregnancy iron levels.Supplemental iron had a positive effect on birth weight among women with pre-pregnancy low iron stores (β = 4.37; SE = 1.8; p = 0.038) and did not affect birth weight among women with present iron stores (β = − 0.008; SE = 3.03; p = 0.998).

Conclusion

Early iron supplementation with doses ~ 100 mg/d improves the biochemical status of the mother independently of her pre-pregnancy iron status. Supplementation with iron improves newborn birth weight in those women who start pregnancy with iron deficiency, and makes no significant difference to those women who are not iron deficient.     

Assessment of risk factors for survival of neonates born after second-trimester PPROM

Objective

Assess fetal risk factors which impact survival of infants delivered after second-trimester PPROM.

Study design

Clinical records of 87 patients, who all had second-trimester rupture of membranes between 14 + 0 and 24 + 6 weeks of gestation treated January 1998 to July 2005 were reviewed regarding perinatal outcome. This study is based on 25 surviving infants.

Results

13 of these 25 infants died in the hospital. Survivors had a higher birth weight (p = 0.008) and higher Apgar scores after 5 min (p = 0.005) than those infants dying. No differences in UA pH, the need of catecholamines and no association between histological verified chorioamnionitis and early onset sepsis were seen between survivors and nonsurvivors.

Conclusion

Higher gestational age at birth, higher birth weight, the absence of histologically verified chorioamnionitis and 5 min Apgar scores of ≥ than 6 have positive prognostic value for survival of neonates delivered preterm after second-trimester PPROM.     

No short-term benefits of antenatal corticosteroid treatment in severely preterm growth restricted fetuses: A case-control study

Background

Antenatal corticosteroid administration to premature, growth restricted fetuses may not be beneficial and even have adverse effects on neonatal outcome.

Aims

To determine if preterm growth restricted fetuses benefit from antenatal corticosteroids.

Study design

Retrospective cohort study.

Methods

All singleton pregnancies with growth restricted fetuses delivered at our department before 34 weeks' gestation or weighing less than 1500 g, between January 2001 and December 2005, were retrospectively reviewed. Neonatal outcome was compared between growth restricted fetuses (defined as abnormal flow patterns in umbilical and middle cerebral arteries) that received antenatal CST (CST group) and those who did not receive antenatal CST (no CST group). The administration of CST appeared to be quasi randomized.

Results

A total of 88 pregnancies fulfilled the inclusion criteria (CST group, n = 54; no CST group, n = 34). The incidence of neonatal respiratory distress syndrome in the CST and no CST group was 42% (22/54) and 50% (17/34), respectively (p = 0.44). Neonatal mortality in the CST and no CST group was 9% (5/54) and 12% (4/34), respectively (p = 0.73). The prevalence of adverse neonatal outcome (neonatal mortality, major neonatal morbidity or severe cerebral lesions) in the CST and no CST group was 28% (15/54) versus 24% (8/34), (p = 0.62).

Conclusions

Administration of CST to growth restricted preterm fetuses does not appear to be beneficial with respect to short term neonatal outcome.     

Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: a randomized controlled trial

Objective

To determine the better approach for weaning preterm infants from nasal continuous positive airway pressure (NCPAP) with or without transitioning to nasal cannula (NC).

Design/methods

This is a randomized, open label, controlled trial. Preterm infants born at ≥ 28 weeks gestation who were clinically stable on NCPAP of 5 cm H₂O with FiO₂ < 0.30 for at least 24 h were randomly assigned to one of 2 groups. The no-NC group were kept on NCPAP until they were on FiO₂ = 0.21 for 24 h, and then were weaned off NCPAP completely without any exposure to NC. If they met failing criteria, NCPAP was re-instituted. The NC-group was weaned off NCPAP when FiO₂ was ≤ 0.30 to NC (2 L/min) followed by gradual weaning from oxygen. Infants who failed NC were supported back with NCPAP for 24 h before making a second attempt of NC.

Results

Sixty neonates were enrolled; 30 in each group. The two groups were similar in birthweight, gestational age, sex, antenatal steroids, mode of delivery, use of surfactant and xanthines, and duration of mechanical ventilation. After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p < 0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p = 0.03]. There were no differences between groups regarding success of weaning from NCPAP.

Conclusions

Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support.     

Preconception risk factors and SGA babies: Papilloma virus, omega 3 and fat soluble vitamin deficiencies

Background

Small for gestational date (SGA) babies have a poor ‘whole of life’ prognosis and major factors affecting SGA may be present prior to conception.

Aims

To discover whether lifestyle risk factors can be identified in women planning a pregnancy.

Study design

Prospective study of women who were planning a pregnancy, who agreed to answer a detailed 250 question questionnaire prior to commencing to try to conceive, to being monitored, and within 7 days of a positive pregnancy test having a vaginal ultrasound scan and answering further questions about the events since the last menstrual period. Details of all outcomes were recorded.

Subjects

585 couples completed the study.

Outcome measures

The relationships between birth weights and questionnaire data was analysed using SPSS and parametric statistical analysis.

Results and conclusions

401 women (67.9% of all participants) had live births. Eleven babies (2.7%) were less than the 3rd percentile in weight and a further 22 babies (5.4%) were between the 3rd and 10th weight percentiles. Mothers of SGA babies had a lower than average education, diets that were low in meat, fish, dairy foods and nuts or seeds and were more likely to conceive in the winter. Mothers of SGA babies were significantly more likely to have had a recent abnormal Pap smear test. Air travel in the month of conception was a risk factor in having a baby less than 10th percentile.

Conclusion

The quality of lifestyle prior to conception is critical: prenatal counselling needs to be undertaken prior to conception.     

Standard fortification of preterm human milk fails to meet recommended protein intake: Bedside evaluation by Near-Infrared-Reflectance-Analysis

Background

Protein content of preterm human milk (HM) is relatively low and extremely variable among mothers: thus, recommended protein intake is rarely met.

Objectives

To evaluate in a NICU setting if HM protein content after standard fortification meets the recommended intake, and also to check the effect of fortification on the osmolality of HM, as an index of feeding intolerance.

Methods

Protein content of 34 preterm HM samples was evaluated by a bedside technique (Near-Infrared-Reflectance-Analysis — NIRA); osmolality was also checked. Seventeen samples were fortified with Aptamil BMF, Milupa (Group A) and 17 with FM85, Nestlé (Group B). Fortification was performed as recommended by the manufacturer (“full fortification [FF]”) and also with a lower amount of fortifier (“low-dose fortification [LF]”). After fortification, actual protein content was calculated and compared to that needed to meet recommended intake (2.33-3 g/dl), and osmolality was measured.

Results

After FF, protein content was above 3 g/dl in none of the samples, and below 2.33 g/dl in 16/34 samples (11 in Group A, 5 in Group B). After LF, protein content was above 3 g/dl in none of the samples and below 2.33 g/dl in 32/34 samples (15 in Group A, 17 in Group B). Osmolality exceeded 400 mOsm/kg in 19 samples after FF (10 in Group A, 9 in Group B) and in 2/34 samples after LF (1 in each group).

Conclusion

HM protein content after standard fortification fails to meet the recommended intake for preterm infants in approximately half of the cases.     

The link between sleep problems in infancy and early childhood and attention problems at 5 and 14 years: Evidence from a birth cohort study

Background

Little research has examined the associations between early sleep problems and attention problems over several developmental periods.

Aims

To examine whether sleep problems in infancy and early childhood are independently related to attention difficulty at 5 and 14 years, and to the continuity of attention difficulties from 5 to 14 years.

Study design

The study was a prospective, population-based birth cohort study.

Subjects

7223 women who delivered a live, singleton child between 1981 and 1983 were recruited at the first antenatal visit. Of these, 4204 had complete information on all key measures.

Outcome measures

Attention problems were assessed with items from the Child Behaviour Checklist (CBCL) and were classified as adolescent onset (i.e. problems at 14 but not at 5); early remitter (problems at 5, no problem at 14); and persistent (i.e. at both 5 and 14).

Results

At 6 months, sleep problems ‘sometimes’ were associated with the early remitter group in boys. For sleep problems between 2 and 4 years of age, findings were generally similar for boys and girls with strong associations with adolescent attention. Sleep problems ‘often’ were independently associated with early remitter and persistent attention problems, and ‘sometimes’ with early remitter and adolescent onset attention problems.

Conclusions

Sleep problems in early childhood are an indicator of subsequent attention problems that may persist into adolescence. Whether these associations are causal requires further research, however their presence provides an opportunity for early intervention and monitoring.