Family functioning, burden and parenting stress 2 years after very preterm birth

Background

Examining rates of difficulties in family functioning following very preterm birth has been a relatively neglected area of research.

Aims

To examine family functioning, burden and parenting stress in families with very preterm compared with term born children, and investigate influences of parental mental health problems and child neurodevelopmental disability on family outcomes in families with preterm children.

Study design

Participants were 184 very preterm and 71 term children and their parents. Parents completed the Family Assessment Device, Parenting Stress Index and Impact on Family questionnaires when their children were 2 years old (corrected for prematurity). Parental mental health and social risk information were also collected. Children were assessed for neurodevelopmental disability.

Results

Families with very preterm children reported poorer family functioning (p = .03) compared with families with term born children, with less evidence for differences between families with very preterm and term born children in parenting stress and family burden. Within very preterm families, parental mental health problems were associated with higher levels of parenting stress (p = .001), and parents of children with a neurodevelopmental disability were more likely to report higher family burden (p = .04).

Conclusions

For families with very preterm children, parental mental health symptoms and child neurodevelopmental disability may identify families at risk of greater stress and burden who may benefit from additional support.     

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.     

Recurrent otitis media with effusion in preterm infants with histologic chorioamnionitis--a 3 years follow-up study

Background

Recurrent otitis media with effusion (OME) is a leading cause of acquired hearing loss in childhood. Histological chorioamnionitis (HCA) is an important cause of preterm delivery and neonatal morbidity and mortality. Here, we tested the hypothesis of an association between recurrent OME during the first 3 years of life and HCA in very low birth weight (VLBW) infants.

Methods

A total of 110 randomly selected VLBW preterm newborns with HCA and 135 gestational age and gender-matched, HCA-negative VLBW infants were evaluated prospectively during the first 3 years of life for the presence of OME, as diagnosed on the basis of otoscopy, type B or C tympanogram, ipsilateral absence of transient evoked otoacoustic emissions responses, and ipsilaterally increased threshold at diagnostic auditory brain responses evaluation. Potential risk factors for OME were also examined in the two groups.

Results

The HCA-positive infants showed a ~ six times higher frequency of recurrent OME (P < 0.0001), increased frequency (> 5/yr) of clinical otitis media episodes (P = 0.000020), ~ five times higher frequency of adenoid hypertrophy (P < 0.00001), a significant seasonal pattern of birth with autumn predominance (P < 0.00001), and the first OME occurred earlier (P < 0.0001), as compared to the HCA-negative counterparts. Recurrent OME was significantly associated with HCA (O.R. = 17.76, 95% CI: 8.98-35.13, P < 0.00001), adenoid hypertrophy (O.R. = 9.96, 95% CI: 5.17-19.18, P < 0.00001), frequency of acute otitis episodes > 5/yr (O.R. = 8.91, 95% CI: 1.96-40.41, P = 0.0005), and birth in autumn (O.R. = 5.58, 95% CI: 2.79-11.12, P < 0.00001).

Conclusions

These findings indicate that HCA is a previously unrecognized risk factor for the development of recurrent bilateral OME in VLBW preterm infants during the first 3 years of life.     

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

Background

Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs).

Objective

To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome.

Design/methods

We included 82 children (born 1998-2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP).

Results

Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98-7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42-32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90-5.36; P < .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99-32.97, P = .051. We found no association between seizure aetiology and outcome.

Conclusions

In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.     

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.     

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.     

Power spectrum analysis of fetal heart rate variability at near term and post term gestation during active sleep and quiet sleep

Background

Spectral analysis of fetal heart rate variability is promising for assessing fetal condition. Before using spectral analysis for fetal monitoring it has to be determined whether there should be a correction for gestational age or behavioural state.

Aims

Compare spectral values of heart rate variability between near term and post term fetuses during active and quiet sleep.

Study design

Case-control. Cases had a gestational age of ≥ 42 weeks; controls were 36 to 37 weeks. Fetuses were matched for birth weight percentile.

Subjects

STAN^® registrations from healthy fetuses. For each fetus one 5-minute segment was selected during active and one during quiet sleep.

Outcome measures

Absolute and normalized low (0.04-0.15 Hz) and high frequency power (0.4-1.5 Hz) of heart rate variability.

Results

Twenty fetuses were included. No significant differences were found between cases and controls in absolute (481 and 429 respectively, P = 0.88) or normalized low (0.78 and 0.80 respectively, P = 0.50) or absolute (41 and 21 respectively, P = 0.23) or normalized high frequency power (0.08 and 0.07 respectively, P = 0.20) during active state. During rest, normalized low frequency power was lower (0.58 and 0.69 respectively, P = 0.03) and absolute (16 and 10 respectively, P = 0.04) and normalized high frequency power were higher (0.21 and 0.14 respectively, P = 0.01) in cases compared to controls. Absolute and normalized low frequency power were higher during active state compared to rest in both groups (all P values < 0.05).

Conclusions

We found sympathetic predominance during active state in fetuses around term. Post term parasympathetic modulation during rest was increased compared to near term.     

Nutritional and socioeconomic factors in motor development of Santal children of the Purulia district, India

Aims

The aim of this study was to characterize the motor development of 5-12 year-old Santal children of the Purulia district of West Bengal, India. The effect of socioeconomic and nutritional status on motor development was also examined.

Study design

841 (427 boys and 414 girls) Santal children were examined in this cross-sectional study. The nutritional status of each child was assessed by height-for-age z-score based on WHO reference data. Socioeconomic status (SES) was measured by the updated Kuppusswami scale. Motor development was measured using the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition, Short Form (BOT-2).

Results

Sex had a significant (p < 0.05) effect on children's score of running speed and agility, upper-limb coordination and strength with higher scores for boys than girls. Children with a height-for-age z-score of − 2 or less were significantly more likely to have a total BOT-2 z-score of − 2 or less compared with children at a healthier height-for-age range (Χ² = 271.136, p < 0.0001). Well-nourished children scored significantly higher (p < 0.05) than undernourished children in total BOT-2 score and in all individual motor subtests. Regression analysis showed that nutritional status, socioeconomic status and height have a significant impact on total BOT-2 score (p < 0.001). Age and sex were found to be influencing factors in motor development.

Conclusion

Santal children's motor proficiency is around the 1st percentile when compared with normative BOT-2 data. This may be, in part, a result of nutritional and economic disparities between children on who the BOT-2 was normed and Santal children, supporting the role of nutrition in motor development. Additionally, Santal children with lower SES and poorer nutritional status have lower motor proficiency compared with Santal children with comparatively higher SES and nutritional status.     

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.     

Perinatal cerebral insults alter auditory event-related potentials

Background

Auditory event-related potentials (AERPs) can be used as indices of neural information processing. Altered AERPs have been reported in children and young adults with frontal lobe infarction.

Aim

To test the hypothesis that perinatal brain injury affects cortical auditory processing.

Methods

We assessed AERPs at term, 6 and 12 months of age in preterm infants [n = 9, median gestational age (GA) 27.9, range 23.9-30.0 wk], term infants with perinatal intracerebral hemorrhage (ICH) [n = 5, GA 40.3, range 37.4-42.3 wk], and term infants with perinatal asphyxia [n = 4, GA 39.4, range 37.9-40.3 wk]. Healthy preterm (n = 16) and term infants (n = 22) served as controls. A harmonic tone of 500-Hz frequency was used as standard and of 750-Hz as deviant stimulus. Mean AERP amplitudes were calculated over 100 ms periods from 50 to 350 ms. The developmental outcome was followed until 2 years of age.

Results

The term ICH (p = 0.012) and asphyxia (p = 0.0016) group had smaller or more negative responses to the deviant, resulting in smaller or more negative MMR amplitudes than those of the controls. The preterm ICH group did not differ significantly from their preterm born controls. MMR varied in all patient groups and was not associated with adverse outcome.

Conclusion

AERP alterations suggest that perinatal cerebral insults affect cortical auditory processing.     

Cardiovascular and metabolic outcome in 6-8 year old offspring of women with type 1 diabetes with near-optimal glycaemic control during pregnancy

Background

High maternal glucose concentrations during diabetic pregnancy may lead to health problems in the offspring later in life. We showed in a previous nationwide study on pregnancy outcome in type 1 diabetic women that prepregnancy care was good and a near-optimal glycaemic control during pregnancy was achieved (mean HbA1c 6.2%).

Aims

We investigated to what extent current care and treatment of pregnant women with type 1 diabetes were related to cardiovascular and metabolic disturbances in the offspring at school age. Additionally, we studied the influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia (birth weight > p90).

Study design

Observational cohort study.

Subjects

6-8 year old offspring of women with type 1 diabetes (ODM, n = 213) and a control group of children of non-diabetic women (n = 79).

Outcome measures

BMI, blood pressure, parameters of fasting glucose regulation and lipid metabolism, components of the metabolic syndrome (overweight, hypertension, impaired fasting glucose, dyslipidaemia).

Results

Parameters of fasting glucose regulation and lipid metabolism and the frequency of components of the metabolic syndrome did not significantly differ between ODM and controls. Systolic blood pressure was slightly higher in ODM. The influence of level of maternal glycaemic control, preterm birth and neonatal macrosomia on outcome in ODM was limited.

Conclusions

Current care and treatment of pregnant women with type 1 diabetes result in cardiovascular and metabolic outcome in the offspring at 6-8 years of age that is comparable to that in children of non-diabetic women. Further follow-up should substantiate these results at later age.     

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.     

Quantitative analysis of maturational changes in EEG background activity in very preterm infants with a normal neurodevelopment at 1 year of age

Background

The electroencephalographic (EEG) background pattern of preterm infants changes with postmenstrual age (PMA) from discontinuous activity to continuous activity. However, changes in discontinuity have been investigated by visual analysis only.

Aim

To investigate the maturational changes in EEG discontinuity in healthy preterm infants using an automated EEG detection algorithm.

Study design

Weekly 4 h EEG recordings were performed in preterm infants with a gestational age (GA) < 32 weeks and normal neurological follow-up at 1 year. The channel C3-C4 was analyzed using an algorithm which automatically detects periods of EEG inactivity (interburst intervals). The interburst-burst ratio (IBR, percentage of EEG inactivity during a moving time window of 600 s) and mean length of the interburst intervals were calculated. Using the IBR, discontinuous background activity (periods with high IBR) and continuous background activity (periods with low IBR) were automatically detected and their mean length during each recording was calculated. Data were analyzed with regression and multivariate analysis.

Results

79 recordings were performed in 18 infants. All recordings showed a cyclical pattern in EEG discontinuity. With advancing PMA, IBR (R² = 0.64; p < 0.001), interburst interval length (R² = 0.43; p < 0.001) and length of discontinuous activity (R² = 0.38; p < 0.001) decreased, while continuous activity increased (R² = 0.50; p < 0.001). Multivariate analysis showed that all EEG discontinuity parameters were equally influenced by GA and postnatal age.

Conclusion

Analyzing EEG background activity in preterm infants is feasible with an automated algorithm and shows maturational changes of several EEG derived parameters. The cyclical pattern in IBR suggests brain organisation in preterm infant.     

Myocardial function in offspring 5-8years after pregnancy complicated by preeclampsia

Introduction

Preeclampsia and diabetic pregnancies share pathophysiological features suggested to influence epigenetic changes during foetal life with importance for later development and metabolic and cardiovascular diseases.

Aim

Our objective was to study the myocardium in offspring after pregnancy complications.

Methods

Forty-five children (age 5-8 years) delivered from pregnancies complicated by preeclampsia (n = 25), diabetes mellitus type 1 (n = 8) or gestational diabetes mellitus (n = 12) were included. Fifteen children from uneventful pregnancies served as controls. Myocardial functions of right and left ventricle were examined by conventional Doppler and tissue Doppler imaging (TDI).

Results

No major differences were found in the myocardial function between offspring of pregnancy complications and control group. However, the preeclampsia group had smaller hearts, increased heart rate and increased late diastolic velocity (A′-wave) at mitral valve attachments shown by both pulsed wave and colour TDI compared to the control and diabetic groups together (p ≤ 0.01).

Conclusion

Children born after preeclampsia may show effects of a negative impact on the heart already at the age of 5 to 8 years. The numbers of examined children were, however, limited.     

Neurophysiological evaluation in children with Friedreich's ataxia

Introduction

In children with Friedreich's ataxia (FRDA children), clinical ataxia outcomes are hardly substantiated by underlying neurophysiological parameters. In young FRDA children, some reports (based upon International Cooperative Ataxia Rating Scale scores (ICARS)) mention transient neurological improvement upon idebenone treatment. However, these outcomes are obtained with adult instead of pediatric reference values. It is unknown whether age-related neurophysiological parameters can really substantiate neurologic improvement.

Aim

In young FRDA children, we aimed to determine longitudinal neurophysiological parameters during idebenone treatment.

Methods

During a two-year study period, 6 genetically proven FRDA children with cardiomyopathy (6-18 years) were longitudinally assessed for neurophysiological parameters [sensory evoked potentials (SEPs), F response, peripheral nerve conduction and dynamometry] in association with age-matched ICARS-scores.

Results

In all FRDA children, SEPs remained absent during the two-year study period. Peroneal nerve conduction velocity declined (from − 1SD to − 2SD; p < .05), whereas F responses remained essentially unaltered. Total muscle force and leg muscle force decreased (from − 2 to − 3SD and − 2.5 to − 3.5SD; both p < .05) and age-related ICARS-scores deteriorated (median increase + 41%; p < .05).

Conclusion

In FRDA children, age-related neurophysiological and ataxia parameters deteriorate during idebenone treatment. Although we cannot exclude some (subjective) disease stabilization, age-related neurophysiological parameters do not substantiate neurologic improvement.     

A prospective study on intrauterine cannabis exposure and fetal blood flow

Background

Cannabis is commonly used among pregnant women. It is unclear whether cannabis exposure causes hemodynamic modifications in the fetus, like tobacco does.

Aims

This study aims to ascertain fetal blood redistribution due to intrauterine cannabis exposure.

Methods

This study was embedded in the Generation R Focus Study, a population-based cohort of parents and children followed from pregnancy onwards. In late pregnancy, fetal hemodynamics was assessed with ultrasound measurements in cannabis-exposed and non-exposed fetuses. Pregnant women reported about substance use during pregnancy. A distinction was made between continued cannabis use (n = 9), cannabis use only in early pregnancy (n = 14), continued tobacco use (n = 85), tobacco use only in early pregnancy (n = 92), and no tobacco or cannabis use during pregnancy (n = 85).

Results

Continued cannabis use was associated with an increased pulsatility and resistance index of the uterine artery, while discontinued cannabis use was associated with a decreased pulsatility, and resistance index, as compared to controls. Additionally, continued cannabis exposure resulted in a significantly higher uterine pulsatility index and uterine resistance index compared to tobacco exposure. Continued cannabis use was found to be associated with a smaller aortic diameter, as well. No association between intrauterine cannabis exposure and the fetal cerebral vascular system was found.

Conclusions

Our findings suggest that intrauterine cannabis exposure was associated with changes in hemodynamic programming of the vascular system of the fetus in late pregnancy mainly due to tobacco exposure, but intrauterine cannabis exposure did demonstrate a specific effect on the uterine blood flow.     

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.     

Achievement of feeding milestones after primary repair of long-gap esophageal atresia

Objectives

To determine the pattern of feeding milestones following primary repair of long-gap esophageal atresia (EA).

Method

A questionnaire based upon well established feeding milestones was used. Children after long-gap EA repair, n = 40, were compared from after primary repair to healthy children from birth, n = 102.

Results

The age when surveyed of the EA group and controls was different: 6.2 ± 4.7 (mean ± standard deviation) years, range 1.1-20.9, versus 2.5 ± 2.4 years, range 0.0-12.1, p = 0.00. The esophageal gap length in the EA group was 5.1 ± 1.2 cm and age at repair was 5.5 ± 5.0 months. There was no statistically significant difference between the atresia group and controls for feeding milestones; Self feeding finger foods approached significance. There was, however, greater variability in the timing of milestones in the atresia group compared to controls. Feeding milestones were negatively correlated with age at primary repair: drinking with a covered sippy cup, ρ = − 0.51, p = 0.01 and self feeding finger foods, ρ = − 0.36, p = 0.04 were statistically significant. Drinking from a cup correlated with gestational age, ρ = 0.38, p = 0.04, and negatively correlated to esophageal gap length, ρ = − 0.45, p = 0.01.

Conclusions

Despite delayed onset of feeding, major milestones after EA repair occurred in similar pattern to normal infants. An early referral for primary repair is beneficial for earlier acquisition of milestones for infants with long-gap EA.     

Gender-related effects of prenatal administration of estrogen and progesterone receptor antagonists on VEGF and surfactant-proteins and on alveolarisation in the developing piglet lung

Background

Vascular endothelial growth factor (VEGF) is essential for embryonic lung development and has been shown to be regulated by estradiol (E2) and progesterone (P).

Aim

To investigate the effects of prenatal E2 and P withdrawal by specific receptor antagonists on the mRNA expression of VEGF, surfactant proteins (SP-B and SP-C) and on alveolarisation in lung tissue of male and female pig fetuses.

Methods

Fetuses from 10 sows were randomized to receive either both an intramuscular injection of the E2 receptor blocker ICI 182.780 and the P receptor blocker RTI 3021-022 (ICI + RTI, n = 5) or a placebo injection (n = 5) at 90 days of gestation (DOG, 115 = term). After delivery by cesarean section on 114 DOG, tissue of the left lingula of the piglet's lung (28 placebo, 26 ICI + RTI) was obtained to determine the mRNA expression of VEGF, SP-B and SP-C. Lungs from 15 placebo and 14 ICI + RTI group piglets were removed and alveolar counts performed.

Results

The ICI + RTI group showed significantly lower SP-C mRNA expression and alveolar counts compared to the placebo group (p = 0.04 and 0.03, respectively). Diminished alveolarisation in the ICI + RTI group was mainly due to the reduction of alveolar counts in male piglets (p = 0.02). Within the placebo group VEGF and SP-B mRNA expression in male piglets were significantly lower compared to female piglets (p = 0.01 and 0.004, respectively). ICI + RTI treatment abolished this gender-related difference.

Conclusion

Estradiol and P antagonism affected gender-related differences of key proteins for pulmonary function and development and especially in males was associated with diminished alveolarisation.