Macronutrient and fibre intake of young Spanish children with reference to their in utero growth status: Are they eating a healthy diet?

AIM: To compare macronutrient and fibre intake by pre-school children born with intra-uterine growth restriction (IUGR) or as appropriate for gestational age (AGA) and to compare their intake with paediatric nutritional recommendations for identification of potential areas of modification during early life. METHODS: A parental 3-day dietary record was obtained for children of age 1-6 years, born at Hospital Clinic, Barcelona, Spain (2002-2007) with IUGR (n = 37) or AGA (n = 53). Mean nutrient intake (adjusted for body mass index), nutrient adequacy ratios (NAR) and percentage of energy intake (EI%) were compared. RESULTS: Macronutrient and fibre intake of the two groups did not differ significantly. However, IUGR children showed significantly higher than the recommended levels of protein EI% (18 (95% confidence interval (CI) 16-19)), NAR for saturated fatty acids (SFAs) (1.2 (95% CI 1.1-1.5)) and NAR for carbohydrate (1.4 (95% CI 1.2-1.6)) and significantly lower than the recommended levels of NAR for unsaturated fatty acids (UFAs) (0.6 (95% CI 0.5-0.8)) and for fibre (0.6 (95% CI 0.5-0.8)). Likewise, children born with AGA showed similar pattern compared to the recommended levels for protein EI% (17 (95% CI 16-18)), NAR for SFAs (1.3 (95% CI 1.2-1.4)), NAR for UFAs (0.6 (95% CI 0.5-0.7)) and NAR for fibre (0.8 (95% CI 0.7-0.9)). CONCLUSION: Spanish pre-school children consume proteins and SFAs in abundance and UFAs and fibre in moderation. Reinforcement of healthy eating is recommended for long-term health benefits, especially for at-risk children born with IUGR, whose consumption of carbohydrate is additionally greater than that recommended.

Influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction.

BACKGROUND: Our aim was to determine the influence of breastfeeding and postnatal nutrition on cardiovascular remodeling induced by fetal growth restriction (FGR). METHODS: A cohort study including 81 children with birthweight <10th centile (FGR) and 121 with adequate fetal growth for gestational age (AGA) was conducted. Cardiovascular endpoints were left ventricular sphericity index (LVSI), carotid intima-media thickness (cIMT), and blood pressure (BP) at 4-5 y of age. The combined effect of FGR and postnatal variables-including breastfeeding, fat dietary intake, and BMI-on cardiovascular endpoints was assessed by linear and robust regressions. RESULTS: FGR was the strongest predictor of cardiovascular remodeling in childhood, leading to lower LVSI and increased cIMT and BP as compared with AGA. Breastfeeding >6 mo (coefficient: 0.0982) and healthy-fat dietary intake (coefficient: -0.0128) showed an independent beneficial effect on LVSI and cIMT, respectively. Overweight/obesity induced an additional increment of 1 SD on cIMT in FGR children (interaction coefficient: 0.0307) when compared with its effect in AGA. BMI increased systolic BP (coefficient: 0.7830) while weight catch-up increased diastolic BP (coefficient: 4.8929). CONCLUSIONS: Postnatal nutrition ameliorates cardiovascular remodeling induced by FGR. Breastfeeding and healthy-fat dietary intake improved while increased BMI worsened cardiovascular endpoints, which opens opportunities for targeted postnatal interventions from early life.

Altered small-world topology of structural brain networks in infants with intrauterine growth restriction and its association with later neurodevelopmental outcome.

Intrauterine growth restriction (IUGR) due to placental insufficiency affects 5-10% of all pregnancies and it is associated with a wide range of short- and long-term neurodevelopmental disorders. Prediction of neurodevelopmental outcomes in IUGR is among the clinical challenges of modern fetal medicine and pediatrics. In recent years several studies have used magnetic resonance imaging (MRI) to demonstrate differences in brain structure in IUGR subjects, but the ability to use MRI for individual predictive purposes in IUGR is limited. Recent research suggests that MRI in vivo access to brain connectivity might have the potential to help understanding cognitive and neurodevelopment processes. Specifically, MRI based connectomics is an emerging approach to extract information from MRI data that exhaustively maps inter-regional connectivity within the brain to build a graph model of its neural circuitry known as brain network. In the present study we used diffusion MRI based connectomics to obtain structural brain networks of a prospective cohort of one year old infants (32 controls and 24 IUGR) and analyze the existence of quantifiable brain reorganization of white matter circuitry in IUGR group by means of global and regional graph theory features of brain networks. Based on global and regional analyses of the brain network topology we demonstrated brain reorganization in IUGR infants at one year of age. Specifically, IUGR infants presented decreased global and local weighted efficiency, and a pattern of altered regional graph theory features. By means of binomial logistic regression, we also demonstrated that connectivity measures were associated with abnormal performance in later neurodevelopmental outcome as measured by Bayley Scale for Infant and Toddler Development, Third edition (BSID-III) at two years of age. These findings show the potential of diffusion MRI based connectomics and graph theory based network characteristics for estimating differences in the architecture of neural circuitry and developing imaging biomarkers of poor neurodevelopment outcome in infants with prenatal diseases.

Risk of perinatal death in early-onset intrauterine growth restriction according to gestational age and cardiovascular Doppler indices: a multicenter study.

OBJECTIVE: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses. METHODS: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates. RESULTS: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality. CONCLUSIONS: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation.

Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction.

AIM: To evaluate the neurodevelopmental outcome at 12 months' corrected age in preterm infants with and without severe intrauterine growth restriction. METHODS: This prospective follow-up study included 37 infants with severe intrauterine growth restriction and 36 appropriate-for-gestational-age infants born between 26 and 34 weeks. Neonatal and infant data were prospectively recorded. Infants were assessed at 12 ± 2 months' corrected age with the Hammersmith Infant Neurological Examination and the Bayley Scale for Infant Development version-II. RESULTS: Both groups were similar in demographic characteristics and perinatal status. No significant differences in neurodevelopmental performance were found. The mental development index was 98.8 (SD 9.0) vs 98.4 (SD 13.1) (p = 0.9) and the psychomotor development index was 91.7 (SD 9.9) vs 95.5 (SD 13.4) (p = 0.2) for the study and reference groups respectively. Neurological assessment showed no significant differences between the two groups. CONCLUSION: Although the study group showed a non-significant trend towards a lower score in the psychomotor development index than the reference group, significant differences at 12 months could not be demonstrated. IUGR infants continued to have significantly lower weight, length and head circumference at 1 year.

Risk factors for neurodevelopment impairment in twin-twin transfusion syndrome treated with fetoscopic laser surgery.

OBJECTIVE: To estimate the risk factors for adverse long-term neurodevelopment outcome in twin-twin transfusion syndrome treated with laser surgery. METHODS: Twin-twin transfusion syndrome cases treated with laser surgery at three European centers from August 2000 to December 2005 were included in this case-control study. Neurological, mental, and psychomotor development (using the Bayley Scales of Infant Development, 2nd edition) was evaluated at 2 years of age. RESULTS: A total of 212 twin-twin transfusion syndrome pregnancies were treated with laser surgery during the study period. Overall mortality rate was 30% (129 of 424). Seventeen children (6%) were lost to follow-up. Long-term outcome was assessed in 278 infants. The incidence of neurodevelopment impairment was 18% (50 of 278). Four risk factors were found to be significantly associated with increased risk for neurodevelopment impairment: greater gestational age at laser surgery (odds ratio [OR] 1.30, 95% confidence interval [CI] 1.00-1.69; P=.05), higher Quintero stage (OR 3.55 for each increment in stage, 95% CI 1.07-11.82, P=.04), lower gestational age at birth (OR 1.39 for each week, 95% CI 1.06-1.81; P=.01), and lower birth weight (OR 1.18 for each 100-g decrease, 95% CI 1.05-1.32; P<.01). In a multivariable analysis, lower gestational age at birth was the only factor independently associated with neurodevelopmental impairment (OR 1.33 for each week, 95% CI 1.05-1.67, P=.02). CONCLUSION: Neurodevelopment impairment in twin- twin transfusion syndrome survivors treated with laser surgery is associated with advanced gestational age at laser surgery, low gestational age at birth, low birth weight, and high Quintero stage. LEVEL OF EVIDENCE: II.

Cerebral venous blood flow in growth restricted fetuses with an abnormal blood flow in the umbilical artery before 32 weeks of gestation.

OBJECTIVE: To evaluate the brain venous circulation in fetuses with severe intrauterine growth restriction (IUGR) before 32 weeks of gestation. STUDY DESIGN: Fifty fetuses with severe IUGR diagnosed between 27 and 32 weeks of gestation and 50 appropriate-for-gestational age (AGA) fetuses matched by gestational age were evaluated. IUGR fetuses were classified according to their hemodynamic deterioration pattern in relation to the Doppler examination of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). The fetal venous brain blood flow was evaluated in the vein of Galen (VG), superior sagittal (SS), straight and transverse venous sinuses. RESULTS: Only the transverse sinus (TS) showed a significant reduction in the pulsatility index (PI) values in IUGR fetuses. All other veins showed similar PI values between IUGR and AGA fetuses. All cerebral veins of IUGR fetuses showed significantly increased maximum and mean velocities. All these findings did not change in relation to the hemodynamic IUGR deterioration. In nearly all normal and all IUGR fetuses, a pulsatile blood flow pattern was observed in the straight and transverse sinuses, whereas an increased pulsatile pattern in the VG and in the SS was noted in IUGR fetuses. CONCLUSION: Brain venous blood flow in IUGR fetuses shows an increment in the maximum and mean velocities of all veins and a reduction in the PI in the transverse sinus.

Prevalence of neonatal ultrasound brain lesions in premature infants with and without intrauterine growth restriction.

AIM: To compare the prevalence of transient periventricular echodensities (TPE), periventricular leukomalacia (PVL) and haemorrhagic brain lesions (HBL) in singleton intrauterine growth-restricted (IUGR) infants and in those appropriate for gestational age (AGA). METHODS: Thirty-five IUGR and 35 AGA singleton infants born between 24- and 34-week gestational age were studied. The presence of TPE, PVL and HBL was assessed with ultrasound (US) at day 3 (US-I), 2 weeks (US-II) after delivery and at term-equivalent age (US-III). RESULTS: IUGR neonates had an increased prevalence of TPE at US-I (18/35 vs. 8/35, p= 0.02) and an increased prevalence of PVL at US-II (8/32 vs. 1/31, p = 0.03) and US-III (8/29 vs. 1/29, p = 0.02). No significant differences in the prevalence of HBL were found between the two groups. CONCLUSIONS: IUGR is associated with an increased prevalence of white matter damage on US brain scans in preterm neonates.