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.     

Digit ratio (2D:4D) is associated with gastric cancer

Background

Sex steroid exposure during early human development may influence disease susceptibility. Digit ratio (2D:4D) is a putative marker for prenatal hormone exposure and sensitivity, as well as the action of genes closely related to carcinogenesis. Digit ratio could act as a possible marker for cancer predisposition.

Aims

The aim of this study is to investigate the possible correlations between right hand, left hand and right minus left (R − L) 2D:4D and gastric cancer (GCA) in men and women and assess the correlations with tumor staging and histological diagnosis.

Methods

Digital images of the right and left hand palms of patients diagnosed with GCA (n = 57, 42 males, 15 females) and age and sex-matched controls (n = 59, 41 males, 18 females) were obtained. Means for 2D:4D were compared. Data were analyzed by repeated-measures one-way ANOVA and Student's t-test for finger measurements and group comparisons and Pearson's and Spearman's tests for correlations with tumor staging (α = 0.05).

Results

GCA group presented significantly higher left 2D:4D, but significantly lower R − L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging. However, low R − L was significantly related to adenocarcinomas.

Conclusions

Early developmental conditions, including prenatal testosterone seem to play a role on the malignant transformation of gastric lesions. The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer. The findings suggest that 2D:4D could add to the list of etiological factors and be a putative marker for the screening of patients’ susceptibility to develop gastric cancer.     

Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome

Aims

Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24 h.

Methods

Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24 h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24 h was recruited.

Results

44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3/100 WBC [range of 0-11] vs 12.3/100 WBC [0-240]) (p < 0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate/severe HIE than mild (16/100 WBC [range of 0-240] vs 8/100 WBC [1-23]) (p = 0.016), and among infants with abnormal outcome compared to normal (21.3/100 WBC [1-239.8] vs 8.3/100 WBC [0-50])(p = 0.03).The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24 h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12 h: r = 0.661 vs r = 0.622), (24 h: r = 0.645 vs r = 0.598), and with outcome at 2 years (12 h: r = 0.756 vs r = 0.652), (24 h: r = 0.802 vs r = 0.746).

Conclusion

Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.     

Infant cardiac surgery and the father–infant relationship: Feelings of strength,strain, and caution

Objective

The purpose of this study was to examine the father–infant relationship in infants with congenital heart disease (CHD).

Method

Sixty-three fathers whose infants had cardiac surgery before 3 months of age reported on their attachment relationship with their infant within two months of hospital discharge using both qualitative and quantitative methods.

Results

Mean scores on the Paternal Postnatal Attachment Scale and scores for patience and tolerance were not different from previously published community norms, ps > .05. Scores for pleasure and interaction (t[50] = − 2.383, p = .021, CI: − 2.93, − .25) and affection and pride subscale (t[56] = − 2.935, p = .005, CI: − 1.20, − .23) were significantly lower than community norms. Additionally, 37% of fathers described feeling a strong relationship with their infant whereas 17% reported initial apprehension or condition-specific worry. Fathers with infants who spent fewer days at home prior to admission reported feelings of relationship strain as well as lower pleasure in interaction, affection and pride, patience and tolerance, and overall attachment quality.

Conclusion

Having an infant with CHD affects some father–infant relationships differently than others with some fathers feeling closer to their infant and other fathers feeling reservation about getting too close. One explanation for these differences may be that spending a great deal of time in hospital restricts the number and quality of interactions infants have with their fathers. Opportunities for intervention include clinical psychosocial services encouraging fathers to interact with and provide physical care of their infant, especially if fathers perceive their infant as medically fragile.     

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.     

Early identification of the risk for free radical-related diseases in preterm newborns

Background

Despite recent advances in preterm newborns healthcare, perinatal pathologies and disabilities are increasing. Oxidative stress (OS) is determinant for the onset of an unbalance between free radicals (FRs) production and antioxidant systems which plays a key role in pathogenesis of pathologies such as retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), grouped as ‘free radical-related diseases’ (FRD).

Aim

This study tests the hypothesis that OS markers levels in cord blood may predict the onset of FRD pathologies.

Patients and methods

168 preterm newborns of GA: 24-32 weeks (28.09 ± 1.99); and BW: 470-2480 gr (1358.11 ± 454.09) were consecutively recruited. Markers of potential OS risk (non-protein bound iron, NPBI; basal superoxide anion, BSA; under stimulation superoxide anion, USSA) and markers of OS-related damage (total hydroperoxides, TH; advanced oxidation protein products, AOPP) were assessed in cord blood. Associations between FRD onset and OS markers were checked through inferential analysis (univariate logistic regression).

Results

The development of FRD was significantly associated to high cord blood levels of TH, AOPP and NPBI (respectively p = 0.000, OR = 1.025, 95%CI = 1.013-1.038; p = 0.014, OR = 1.092, 95%CI = 1.018-1.172; p = 0.007, OR = 1.26995%CI = 1.066-1.511).

Conclusions

Elevated levels of TH, AOPP and, above all, NPBI, in cord blood are associated with increased risk for FRD. OS markers allow the early identification of infants at risk for FRD because of perinatal oxidant exposure. This can be useful in devising strategies to prevent or ameliorate perinatal outcome.     

Prenatal stress and infant affective reactivity at five months of age

Background

Prospective studies concerning prenatal stress and its outcome on children's emotional development postulated a potential influence of prenatal hormonal levels or emotional stressors on child development [1-3]. In a retrospective study, an influence of maternal emotional stress on infant affective reactivity was found [4].

Aims

This study was conducted in order to confirm these findings in a prospective study design.

Study design

A prospective longitudinal study design was conducted with three study waves during pregnancy and one time point five months postnatally.

Subjects

The final sample consisted of n = 104 mother-infant dyads.

Outcome measures

Maternal baseline cortisol levels and emotional stress were assessed in each trimester of pregnancy. Children were examined with the infant reactivity battery according to Kagan & Snidman [5] at the age of five months.

Results

Mothers of children with high affective reactivity (cry score ≥ 7) were significantly less depressed (p < .10) and perceived less stress (p < .05) in mid-pregnancy and were confronted with less external stress factors (p < .10) at the end of pregnancy. Cortisol levels did not differ in both groups in any pregnancy trimenon (p > .05).

Conclusions

These data add a new specific aspect to the ‘fetal programming hypothesis’ and are the first to confirm the speculative data from retrospective studies. Baseline cortisol does not seem to be the ‘hormonal mediator’ of this association. Therefore, cortisol stress reactivity or other neuroendocrine mechanisms should be assessed in future studies.     

Is meconium stained amniotic fluid related to occult myocardial injury in term low risk pregnancies?

Aim

The present study aimed to compare Troponin T (Tp T) levels of infants born with meconium stained amniotic fluid (MSAF) to those with clear amniotic fluid.

Study design

Case–control study

Subjects

Thirty-five women who had delivery complicated by MSAF between 37 and 41 weeks of gestation were defined as the study group and women with healthy uncomplicated pregnancies with clear amniotic fluid who were matched for age, parity, and gestational age were defined as the control group.

Outcome measures

Cord blood Tp T level, gas analysis and neonatal outcomes were compared between groups.

Results

Tp T levels of the study and control groups were 0.026 ± 0.013 ng/ml and 0.031 ± 0.016 ng/ml, respectively. The difference was not statistically significant (p = 0.132). On the other hand, the study group had a statistically lower HCO₃ level (21.80 vs 23.60 mmol/l ) and higher rate of base deficit (4.85 vs 3.25 mmol/l) than the control group.

Conclusion

The presence of meconium during labor is not related to occult myocardial injury in low-risk term pregnancies.     

Infant developmental outcomes following prenatal exposure to antidepressants,and maternal depressed mood and positive affect

Background

Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants has been associated with delays in early developmental milestones, but there remains uncertainty. Even among a subset of studies examining the Bayley Scales of Infant Development (BSID), some have reported normal mental and psychomotor development while others have suggested a delay in motor development. Given an increasing number of infants exposed to SRIs, furthering our understanding of the possible developmental implications of SRI exposure in utero is critical.

Aims

To examine the effects of prenatal serotonin reuptake inhibitor exposure and maternal mood on infant developmental outcomes at 10 months of age.

Study design

Prospective study of mothers and their 10-month-old infants.

Subjects

We examined 31 mother–child pairs exposed prenatally to SRIs and 52 mother–child pairs who were nonexposed.

Outcome measure

The Bayley Scales of Infant Development (third edition) scores.

Results

Infants exposed prenatally to SRIs scored significantly lower than nonexposed infants on gross motor (P = 0.03), social–emotional (P = 0.04) and adaptive behavior (P = 0.05) subscales of the BSID-III, controlling for pre- and postnatal maternal depressed mood, smoking and alcohol use during pregnancy. No significant differences in any of the BSID-III subscales were observed between infants exposed and infants nonexposed to pre and postnatal maternal depressed mood (P > 0.05). Increased levels of maternal positive affect at 10 months predicted increased social–emotional scores (P = 0.03).

Conclusions

Infants prenatally exposed to SRIs score significantly lower on the gross motor, social–emotional and adaptive behavior subscales of the BSID-III, and this was not explained by underlying maternal depression.     

Sunflower oil versus no oil moderate pressure massage leads to greater increases in weight in preterm neonates who are low birth weight

Background

Growth velocity is one of the most important problems in low birth weight (LBW) neonates.

Aims

The purpose of this study was to compare the effects of body massage with and without sunflower oil on the growth of LBW preterm neonates in Iran.

Study design

A single-blinded randomized clinical trial

Subjects

This study examined neonates admitted to NICU with gestational age of 33–37 weeks and birth weight of 1500–1999 g, without birth asphyxia and medically stable

Outcome measures

Neonates were randomly assigned to two groups to receive moderate pressure massage alone or the same massage with sunflower oil by their mothers, three times a day for 14 consecutive days. The primary variables were increases in mean of growth parameters (weight, height and head circumference) that were evaluated 14 days after intervention, at ages 1 and 2 months. Secondary variables were clinical side effects.

Results

Fifty-four neonates including 25 girls and 29 boys with mean gestational age of 35.3 ± 1.26 weeks were evaluated. Means of gestational age, birth weight and length of NICU stay were not different in both groups. In the oil massage group, mean weight at ages 1 month (mean ± SD: 2339 ± 135 vs. 2201 ± 93 g, P = 0.04) and 2 months (mean ± SD: 3301 ± 237 vs. 3005 ± 305 g, P = 0.005) was significantly greater than that of the body massage group. No adverse events were seen in the two groups.

Conclusion

Sunflower oil massage might be used as an effective and safe intervention for weight gain in LBW preterm neonates.     

Prenatal depression restricts fetal growth

Objective

To identify whether prenatal depression is a risk factor for fetal growth restriction.

Methods

Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birthweight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates.

Results

Depressed women had a 13% greater incidence of premature delivery (Odds ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth.

Conclusion

Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes.     

Reduced cerebellar diameter in very preterm infants with abnormal general movements

Background

Abnormal General Movements (GMs) early in life are predictive of later neuromotor deficits and are related to white matter abnormalities on magnetic resonance imaging (MRI). However, other structural correlates of abnormal GMs have not been defined.

Aims

The objective of this study was to explore brain-metrics (linear brain measurements on MRI representative of 3-D brain volumes) at term as a predictor of abnormal GMs at 1 and 3 months' corrected age in preterm infants. It was hypothesized that abnormal GMs would be related to reduced brain-metrics in primary motor areas, namely the cerebellum and parietal lobes.

Study design

Eighty three preterm infants (< 30 weeks' gestational age) were scanned at term-equivalent age. MRI was assessed for white matter abnormality and brain-metrics in six predefined brain regions (i.e. bifrontal, biparietal, lateral ventricles and transverse cerebellar diameters, and inter-hemispheric distance).

Outcome measures

At 1 and 3 months' corrected age infants' GMs were assessed from video-taped footage and rated as normal or abnormal using standardized methodology.

Results

At 1 month, 63% (n = 52) of infants had abnormal GMs with no association between any of the brain-metrics and abnormal GMs. At 3 months, 23% (n = 18) of infants had abnormal GMs (absent fidgety movements n = 18; abnormal fidgety movements n = 0). Reduced bifrontal, biparietal, and cerebellar transverse diameters, along with an increase in lateral ventricle sizes were associated with an increased risk of abnormal GMs at 3 months' corrected age. After controlling for white matter abnormality and grade III/IV intraventricular haemorrhage, only the cerebellar transverse diameter was predictive of abnormal GMs at 3 months.

Conclusions

Reduced cerebellar diameter at term equivalent age is related to abnormal GMs at 3 months' corrected age, independent of white matter abnormality and intraventricular haemorrhage.     

Changes in spectral power of fetal heart rate variability in small-for-gestational-age fetuses are associated with fetal sex

Background

Little is known about the influences of fetal weight and sex on spectral analysis of fetal heart rate (FHR) variability.

Aim

The study aims to assess whether there are differences in spectral power of FHR variability according to fetal weight and sex during labor.

Study design

Case–control study. A total of 414 singleton term deliveries without fetal acidemia were divided into small-for-gestational-age (SGA) (n = 29) and non-SGA (n = 385) groups. Analyses were performed separately according to fetal sex.

Subjects

FHR recordings obtained with cardiotocography during the last 2 h of labor preceding delivery.

Outcome measures

Our outcome measures include spectral power of FHR variability.

Results

For the male group, SGA fetuses had significantly lower values for low, movement, high, and total frequencies of spectral power compared with non-SGA fetuses (all P < 0.005). Normalized low frequency (LFn) was significantly higher, and normalized high frequency (HFn) was significantly lower in SGA fetuses compared with non-SGA fetuses (all P < 0.005). In contrast, for the female group, there were no significant differences in any of the indices of spectral power between the SGA and non-SGA fetuses. In addition, SGA males had significantly higher LFn spectral power and lower HFn spectral power compared to SGA females (P = 0.016, and 0.041, respectively).

Conclusions

SGA males have decreased spectral power of FHR variability compared with non-SGA males during labor. However, there are no differences between SGA and non-SGA female fetuses. It is important in the clinical setting to take fetal weight and sex into account during FHR monitoring using spectral analysis.     

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.     

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.     

Different functional cardiac characteristics observed in term/preterm neonates by echocardiography and tissue doppler imaging

Background and aim

To establish, using echocardiography, color-flow Doppler and tissue doppler imaging (TDI), physiological values of systolic/diastolic indexes in healthy term/pre-term newborns, and to identify how different degrees of maturity influence morpho-functional cardiac alterations during the transitional period.

Study design and subjects

33 term newborns (M = 19, F = 14; gestational ages: 37th-41st week), and 20 pre-term infants (M = 11, F = 9; gestational ages: 31st-36th week) admitted to our department were studied. All infants underwent to clinical and Doppler ultrasound evaluations, carried out by the third to fourth day. Investigations included: M-mode echocardiography, color-flow Doppler and TDI.

Outcome measures and results

Term and preterm neonates differed for: interventricular septum and left systolic/diastolic ventricle diameters (p < 0.01 and < 0.05 respectively); left ventricle posterior wall in systole (p < 0.01); shortening and ejection fraction (p < 0.05). Color-flow Doppler parameters on the tricuspid (peak E, peak A, ratio E/A; p < 0.05) and on the mitral (peak E and E/A ratio; p < 0.01) significantly differed between the two groups. Significant differences were also present for basal left ventricular lateral wall and right ventricular lateral wall in the Ew (p < 0.01 and < 0.05 respectively), Sw peak (p < 0.01 and < 0.05 respectively), and Ew/Aw (p < 0.05). The isovolumetric relax time and the E/Ew measured on the medial mitral annulus also demonstrated significant differences (p < 0.01) between the two groups.

Conclusions

TDI is feasible in preterm neonates and enables assessment of myocardial velocities. With increasing gestational age, higher myocardial velocities and lower E/E′ Œ ratios were found. TDI addition to standard neonatal echocardiography may provide further important information about cardiac function.     

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.     

Preschool regulatory problems and attention-deficit/hyperactivity and cognitive deficits at school age in children born at risk: Different phenotypes of dysregulation?

Background

Early regulatory problems (RP), i.e., excessive crying, feeding, and sleeping difficulties, have been reported to be predictors of cognitive and attention-deficit/hyperactivity problems. However, previous studies had limitations such as small sample size or retrospective design.

Aim

To investigate whether persistent RP from infancy until preschool age are precursors of ADHD problems and cognitive deficits at school age.

Study design

A prospective study from birth to 8.5 years of age.

Subjects

1120 infants born at risk.

Measures

RP were assessed at 5 months (i.e., excessive crying, feeding, and sleeping problems), 20, and 56 months (i.e., eating and sleeping problems) via parent interviews and neurological examination. At 8.5 years of age, IQ was assessed by a standard test (K-ABC), and ADHD problems by direct observations in the test situation and by the Mannheimer Parent Interview (MPI, DSM-IV diagnosis of ADHD).

Results

23.8% of the sample born at risk had RP at least at two measurement points until preschool age. Persistent RP predicted lower IQ (β = − .17; 95% CI (− .21; − .10)), behaviour problems (β = − .10; 95% CI (− .15; − .03)), attention (OR 2.43; 95% CI (1.16; 5.09)) and hyperactivity problems (OR 3.10; 95% CI (1.29; 7.48)), and an ADHD diagnosis (OR 3.32; 95% CI (1.23; 8.98)) at school age, even when controlled for psychosocial and neurological confounders.

Conclusions

Early persistent RP increased the odds of ADHD and associated problems at school age, indicating a cascade model of development, i.e., infant behaviour problems provide the starting point of a trajectory of dysregulation through time.