Extremely Low Birth Weight Children Research Articles

Perfused boundary region as biomarker for endothelial integrity in former preterms in adolescence.

Extremely low birth weight (ELBW) survivors have microvascular structural differences already described in kidney and retina, suggesting changes in endothelial integrity. A biomarker of endothelial integrity is perfused boundary region (PBR), which measures glycocalycal thickness. The endothelial glycocalyx is a complex, highly versatile structure with essential roles in vascular integrity and function. We explored PBR patterns together with other microvascular markers in healthy controls and former ELBW children. In the PREMATCH cohort (87 healthy controls, 93 ELBW survivors), we assessed endothelial integrity by calculating PBR (sidestream dark-field imaging), several microvascular markers (blood pressure, estimated glomerular filtration rate (eGFRcysC)), and retinal imaging in early adolescence. We explored differences between both groups, and searched for perinatal determinants of PBR and correlations between different microvascular markers. We provided reference values for PBR (average 1.90 µm, SD 0.30) in children. PBR was not different from ELBW survivors during early adolescence, despite their higher blood pressure, lower eGFRcysC, and different retinal vessel width and tortuosity. We generated reference values for PBR in early adolescence. Despite some correlations between microvascular parameters, there seem to be numerous confounders to propose PBR as a marker for endothelial integrity in ELBW survivors. The endothelial glycocalyx is a complex and versatile structure. Changes in blood pressure and retinal and renal vascularization suggest a disturbance of its integrity in extremely low birth weight (ELBW) survivors. Its thickness can be measured by calculating perfused boundary region (PBR) using sidestream dark-field imaging, with a higher PBR indicating a thinner glycocalyx. We generated reference values for PBR in healthy adolescents. These values were not different in former ELBW children. Despite some correlations of PBR with other microvascular biomarkers, these are not strong enough to describe endothelial integrity and its covariates in former ELBW children.

Вакцинопрофилактика недоношенных новорожденных: реальная клиническая практика

Objective. To analyze the vaccination coverage and adherence to the vaccination schedule among premature newborns with a birthweight of <2,500 g. Patients and methods. This study included 119 children aged 5 to 6 years followed up within the "National prospective multicenter cohort study of newborns" in Tomsk. The experimental group comprised 96 children born prematurely, including 36 low-birthweight (LBW), 25 very low-birthweight (VLBW), and 36 extremely low-birthweight (ELBW) children. The control group included 23 healthy children born full-term. We analyzed their clinical data and information on vaccination. Results. The number of children who had completed their vaccination by the age of 5 years varied across the groups: 34.8% of controls; 16.7% of LBW children; 28% of VLBW children; and 17.1% of ELBW children (p > 0.05). Thirteen percent of controls and 5.6% of LBW children were timely vaccinated, whereas none of the VLBW and ELBW children had their vaccination in time. We observed no differences in the vaccination profiles (types of administered vaccines) between the VLBW children and controls; vaccination profiles of the LBW and ELBW children were similar. ELBW children were less likely to be vaccinated against tuberculosis, pertussis, diphtheria, tetanus, and polio than controls (p < 0.01). None of the ELBW children received vaccines against hepatitis B, pertussis, diphtheria, and tetanus, as well as third vaccine against polio at birth. In the rest of the groups, the proportion of timely vaccinated children did not exceed 20%. Parents in the control group were less likely to refuse vaccination for their children than those in the experimental group. Non-adherence to the vaccination schedule was more common in the LBW children. VLBW and ELBW children had medical exemptions more frequently than LBW children and controls. Conclusion. We observed low vaccination coverage among premature newborns for all vaccines caused both by medical exemption and non-adherence to the vaccination schedule. Key words: vaccination, premature newborns, extremely low birth weight

Risk Factors for the Incidence of Dental Caries in Low, Very Low, and Extremely Low Birth Weight Children: A Cohort Study

Objective: To assess the incidence of caries in a two-year period among low birth weight (LBW), very low birth weight (VLBW), and extremely low birth weight (ELBW) children considering socioeconomic indicators, dietary factors and oral hygiene. Material and Methods: A convenience sample was formed of 42 low birth weight children aged two to five years at baseline. Two examiners diagnosed caries using the World Health Organization criteria. Birth weight, socioeconomic indicators and diet were collected from medical records and questionnaires. Binomial models were used to estimate unadjusted and adjusted rate ratios (RR) and respective 95% confidence intervals for the factors evaluated. Results: Thirty-six children were re-examined after two years. The incidence of dental caries was 36.7%. The dmft index was 0.44 (±1.25) at baseline and increased to 1.36 (±3.85) at follow-up. VLBW children (1,000 to 1,500 g) (RR=0.23; 95%CI: 0.08-0.72) and LBW children (1,500 to 2,500 g) (RR=0.06; 0.01-0.55) had fewer carious lesions compared to ELBW children (<1,000 g). Carious lesions were more frequent among children with a lower income (RR=6.05; 1.05-34.84) and less frequent among those who did not consume sweetened juice, tea or yogurt (RR: 0.21; 0.07-0.62). Conclusion: An inverse dose-response relation was found between birth weight and the incidence of caries. A lower income and the consumption of sweetened beverages were risk factors for the development of caries.

The Need for Special Education Among ELBW and SGA Preterm Children: A Cohort Study.

Background: Preterm infants with pre- or postnatal growth restriction may have an additional risk of adverse neurodevelopmental outcome. Whereas reduced cognitive ability and behavioral problems have consistently been associated with prematurity, a more comprehensive evaluation is necessary to identify those preterm infants who are at increased risk for difficulties in school performance. This study evaluated the association between extremely low birth weight (ELBW) and the need for special education and determined if there is an additional risk for the need for special education among small for gestational age (SGA) children.Methods: This is a single-center cohort study including singleton children born below 30 weeks' gestation between 1990 and 2011 and followed into 2019. ELBW + was defined as a birth weight below 1,000 g, which was compared to ELBW–. Within all ELBW+ children, SGA+ was defined as a birth weight <10th percentile according to Fenton, which was compared to SGA–. The dichotomous outcome measurement was the need for special education at 8 years of age or not, reflecting if the children required a special educational setting designed to accommodate educational, behavioral, and/or medical needs.Results: In total, 609 children were eligible for follow-up, of whom 390 (64%) children were assessed at 8 years. Of these, 56 (14%) children needed special education, most often determined by cognitive deficiency (43%), behavioral problems (29%), or both (16%). Among the 191 ELBW+ children, 35 (18%) attended special education, compared to 21 (11%) among ELBW– children (p-value 0.041). A decreasing risk for the need for special education was found from 25% in ELBW+/SGA+ children to 16% in ELBW+/SGA– children and 11% in ELBW–/SGA– children (p-value 0.025). Multivariable logistic regression showed an odds ratio of 2.88 (95% CI 1.20–6.78) for ELBW+/SGA+ children vs. ELBW–/SGA– children for the need for special education.Conclusions: This study showed that ELBW children are at increased risk for the need for special education compared to non-ELBW children. In addition, children that are both ELBW and SGA do have the highest risk for the need for special education. Classifying children as ELBW and SGA can be useful in follow-up for identifying preterm children with an additional risk for adverse long-term outcome.

Longitudinal assessment of cardiac function in extremely low birth weight children at 7 and 11 years of age: implications for adult medicine.

The long-term impact of extreme prematurity on cardiac structure and function has not been fully evaluated. The aim of the study was to assess cardiac condition at 11 years of age in a local cohort of extremely low birth weight (ELBW) children born between 2002 and 2004 and to compare it to a previous study in the same group at 7 years of age. Sixty-four children with ELBW (median birth weight of 890 g) and 36 children born at full term underwent echocardiography and physical examination. M-mode echocardiography parameters, expressed as z-scores for body surface area (mean [SD]), showed significant differences in left ventricular end-diastolic dimension (-1.01 [0.91] vs 0.35 [0.71]; P < 0.001), left ventricular end-systolic dimension (-0.29 [0.92] vs 0.57 [0.65]; P < 0.001), aorta dimension (0.63 [1.14] vs 1.63 [1.30]; P < 0.001), and left atrial dimension (-1.75 [0.97] vs -0.01 [0.86]; P < 0.001) between the study group and controls at 11 years of age. Fractional shortening (FS) and ejection fraction (EF) were higher in the ELBW children than in their full-term counterparts (33.6 [5.5] vs 30.8 [4.34]; P = 0.009 and 0.63 [0.07] vs 0.58 [0.06]; P = 0.005, respectively) at a mean age of 11 years. The ELBW children had smaller hearts than full-term controls at both 7 and 11 years of age. The FS and EF were elevated in the group of 11-year-old ELBW children. We observed comparable progress in cardiac growth (approximately 20%) in premature and full-term children over a 4-year study period.

Analysis of neurodevelopmental outcomes of preadolescents born with extremely low weight revealed impairments in multiple developmental domains despite absence of cognitive impairment.

Background and aimsChildren with extremely low‐birth weight (ELBW) have a high risk for cognitive, motor, and attention impairments and learning disabilities. Longitudinal follow‐up studies to a later age are needed in order to increase understanding of the changes in neurodevelopmental trajectories in targeting timely intervention. The aims of this study were to investigate cognitive and motor outcomes, attention‐deficit hyperactivity (ADHD) behaviour, school performance, and overall outcomes in a national cohort of ELBW children at preadolescence, and minor neuromotor impairments in a subpopulation of these children and to compare the results with those of full‐term controls. The additional aim was to report the overall outcome in all ELBW infants born at 22 to 26 gestational weeks.MethodsThis longitudinal prospective national cohort study included all surviving ELBW (birth weight <1000 g) children born in Finland in 1996 to 1997. No children were excluded from the study. Perinatal, neonatal, and follow‐up data up to the age of 5 years of these children were registered in the national birth register. According to birth register, the study population included all infants born at the age under 27 gestational weeks. At 11 years of age general cognitive ability was tested with the Wechsler Intelligence Scale for Children, ADHD behavior evaluated with a report from each child's own teacher (ADHD Rating Scale IV), and school performance with a parental questionnaire. An ELBW subpopulation consisting of a cohort representative children from the two university hospitals from two regions (n = 63) and the age‐matched full‐term born controls born in Helsinki university hospital (n = 30) underwent Movement Assessment Battery for Children and Touwen neurological examination comprising developmental coordination disorder (DCD) and minor neurological dysfunction (MND), respectively.ResultsOf 206 ELBW survivors 122 (73% of eligible) children and 30 (100%) full‐term control children participated in assessments. ELBW children had lower full‐scale intellectual quotient than controls (t‐test, 90 vs 112, P < .001), elevated teacher‐ reported inattention scores (median = 4.0 vs 1.0, P = .021, r = .20) and needed more educational support (47% vs 17%, OR 4.5, 95% CI 1.6‐12.4, P = .02). In the subpopulation, the incidences of DCD were 30% in ELBW and 7% in control children (P = .012, OR 6.0 CI 1.3‐27.9), and complex MND 12.5% and 0%, (P = .052; RR 1.1 95% CI 1.04‐1.25), respectively. Of survivors born in 24 to 26 gestational weeks, 29% had normal outcome.ConclusionAs the majority of the extremely preterm born children had some problems, long‐term follow‐up is warranted to identify those with special needs and to design individual multidisciplinary support programs.

Refractive state and visual acuity of children with extremely low birth weight at 3years old in Japan.

To investigate the refractive status and visual acuity of 3-year-old children with extremely low birth weight (ELBW). Retrospective cohort study. We examined 161 children born between January 2009 and December 2014. The children were divided into five groups for evaluation of visual acuity and refraction: no retinopathy of prematurity (ROP), reverse ROP, photocoagulation (PC) zone II (ZII), PC (ZI), and PC (ZI + lens-sparing vitrectomy [vit]). Median (1st quartile, 3rd quartile) gestational age was 25 (24, 26) weeks. Median birth weight was 738 (588, 846) g. Spherical equivalence (SE) was +0.38 (-0.06, +0.75) diopters (D) in noROP, +0.63 (-0.25, +1.34) D in reverse ROP, +0.38 (-0.75, +1.31) D in PC (ZII), -3.31 (-8.06, +0.16) D in PC (ZI), and -12.00 (-13.50, -4.50) D in PC (ZI+ vit) children. Best corrected visual acuity (BCVA) in log MAR was 0.15 (0.07, 0.26) in no ROP, 0.17 (0.10, 0.30) in reverse ROP, 0.22 (0.10, 0.38) in PC (ZII), 0.45 (0.22, 0.55) in PC (ZI), and 1.10 (0.82, 1.30) in PC (ZI+ vit) children. There was a significant correlation between SE and BCVA (r = -0.43, p < 0.0001). The no ROP, reverse ROP, and PC (ZII) groups showed no significant differences in SE or BCVA, accounting for 79.5% of ELBW children. SE and BCVA in the PC (ZI) and PC (ZI+ vit) groups were worse than in the other groups. The current results reveal a correlation between SE and BCVA.

Long-term effects of bronchopulmonary dysplasia on lung function: a pilot study in preschool children’s cohort

Introduction Although the long term negative effects of bronchopulmonary dysplasia (BPD) are well known, follow-up studies of preterm infants with BPD into childhood are lacking. Methods Forty-two preschool children (age range 3–6 years) who were born before 32 weeks of gestational age and affected by BPD were enrolled. Pre-, peri-, and post-natal data were collected. During the follow up appointment complete physical examination and lung function (impulse oscillometry (IOS)) were recorded. The European Community Respiratory Health Survey (ECRHS) questionnaire was administered to all enrolled subjects. Results Thirty patients were included in the final analysis. The BPD group did not differ in comparison to the non-BPD group in terms of lung function (p > 0.05). By comparing all subjects enrolled, We detected extremely low-birth-weight (ELBW) infants with height-, weight-, and gender-related reference values and a significant trend of increasing resistance values (R5Hz, R5-20 Hz) and respiratory impedance (Z5Hz) (p < 0.05). No significant difference in bronchial reversibility test was observed among BPD non-BPD groups (p < 0.05). The frequency of gastroesophageal reflux disease was significantly higher in patients with BPD when compared to non-BPD group (p < 0.05). Significant differences in gestational age, oxygen supplementation (days), mechanical ventilation therapy (days), and sepsis between BPD and non-BPD groups were also observed (p < 0.05). There were no significant differences in the prevalence of family and personal history of atopy and/or allergic diseases, tobacco exposure, respiratory symptoms, respiratory syncytial virus bronchiolitis, exercise induced dyspnea, treatment with ß-2 bronchodilators and inhaled corticosteroids among the groups (p > 0.05). Conclusions The respiratory function in preschool children born with ELBW is characterized by an increase in impedance and resistance of small airways. No statistically significant differences were found between ELBW children with BPD and without BPD. With regards to the smallest gestational age, the longer duration of O2 therapy during hospitalization, and sepsis significantly resulted in a worse respiratory function.

Cost-effectiveness Analysis of Screening Extremely Low Birth Weight Children for Hepatoblastoma Using Serum Alpha-fetoprotein

To evaluate the cost-effectiveness of screening children born at extremely low birth weight (ELBW) for hepatoblastoma using serial serum alpha-fetoprotein measurements. We created a decision tree to evaluate the cost effectiveness of screening children born at ELBW between 3 and 48months of age compared with current standard of care (no screening). Our model used discounted lifetime costs and monetary benefits in 2018 US dollars, based on estimates in the published literature. The effects of uncertainty in model parameters were also assessed using univariate sensitivity analyses, in which we changed the values for one parameter at a time to assess the effect on the estimated incremental cost-effectiveness ratio. For the estimated 55 699 children born at ELBW in the US each year, this screening is associated with 77.7 additional quality-adjusted life-years (QALYs) at a cost of $8.7 million. This results in an incremental cost-effectiveness ratio of about $112 000/QALY, which is considered cost effective from a US societal perspective. For children diagnosed with hepatoblastoma, our model finds that the screening regimen is associated with a 10.1% increase in survival, a 4.18% increase in expected QALYs, and a $245 184 decrease in expected cost. Screening ELBW children for hepatoblastoma between 3 and 48months of age dominates the alternative and is cost effective from a societal perspective.

Adaptive Behavioral, Social-Emotional, and Neurodevelopmental Outcomes at 2 Years of Age in Hungarian Preterm Infants Based on Bayley III

ABSTRACT Aim This study aimed to assess cognitive, language, and motor development as well as social-emotional and adaptive behavior skills of low birthweight (LBW) children. Methods Our cohort contained 305 two-year-old LBW children. Developmental functioning was assessed by the Bayley Scales of Infant and Toddler Development, 3rd Edition. Results Performance in language, particularly in expressive communication was the poorest. Extremely low birthweight (ELBW) children were found to be at increased risk of developmental delay: 12.73 times in motor (95%CI = 2.8–57.5), 9.81 times in cognitive (95%CI = 3.2–29.6) and 3.91 times in language (95%CI = 1.6–9.4), and social-emotional skills (95%CI = 1.6–9.5). Parents of children with lower birthweight reported poorer social and practical adaptive skills. Self-care domain seemed to be the least developed. Conclusion Additionally, the screening for developmental delays, monitoring the adaptive behavior skills may also be useful – especially among ELBW children – in order to identify the specific areas, situations, and functions that are most in need of interventions. Abbreviations AB: Adaptive Behavior; ABAS-II: Adaptive Behavior Assessment System-II; BPD: Bronchopulmonary Dysplasia; BSID-III: Bayley Scales of Infant Development 3rd Edition; BW: Birthweight; CI: Confidence Interval; CS: Composite Score; ELBW: Extremely Low Birthweight; GA: Gestational Age; IVF: In Vitro Fertilization; IVH: Intraventricular Hemorrhage; LBW: Low Birthweight; NEC: Necrotizing Enterocolitis; OR: Odds Ratio; ROP: Retinopathy of Prematurity; SE: Social-Emotional Development; VLBW: Very Low Birthweight

Outcome of Extremely Low Birth Weight Children in Iceland 1988-2012

Extremely low birth weight (ELBW) children (birth weight ≤1000 g) are at risk of adverse neurodevelopmental outcome. The objectives of this study were to determine the prevalence of developmental disorders and disabilities among ELBW children born in Iceland during a 25 year period and to assess which clinical factors predict disability among these children. A retrospective study of all ELBW children born in Iceland 1988-2012 and discharged alive. The study group was found in the Children´s Hospital of Iceland NICU registry. Information was gathered from the NICU registry, the children´s and their mothers´ medical records and the State Diagnostic and Counselling Centre database. Of 189 children 45 (24%) had developmental disorders, 13 (7%) had mild disorders and 32 (17%) had major disorders (disability) at 3-6 years. Risk factors for disability were multiple birth (RR 2.21; 95% CI: 1.19-4.09), Apgar < 5 after one minute (RR 2.40; 95% CI: 1.14-5.07), the initiation of enteral feeding more than four days after birth (RR 2.14; 95% CI: 1.11-4.11), full enteral feeding achieved after more then 21 days (RR 2.15; 95% CI: 1.11-4.15), neonatal pneumonia (RR 3.61; 95% CI: 1.98-6.57) and PVL (RR 4.84; 95% CI: 2.81-8.34). The majority of ELBW children do not have major developmental disorders. The rate of disability in this study is similar to other studies. The study probably underestimates the rate of mild developmental disorders in the Icelandic population. Risk factors for disability in this study are comparable to previous studies.

Behaviour of 4- to 5-year-old nondisabled ELBW children: Outcomes following group-based physiotherapy intervention.

Extreme prematurity or extremely low birth weight (ELBW) can adversely affect behaviour. Nondisabled ELBW children are at risk of behavioural problems, which may become a particular concern after commencement of formal education. This study explored the frequency of behavioural and emotional problems amongst nondisabled ELBW children at 4 to 5years of age and whether intervention had a positive influence on behaviour. The relationship between behaviour, gender, and other areas of performance at 5years was explored. Fifty 4-year-old children (born <28weeks gestation or birth weight <1,000g) with minimal/mild motor impairment were randomly allocated to intervention (n=24) or standard care (n=26). Intervention was 6 group-based physiotherapy weekly sessions and home programme. Standard care was best practice advice. The Child Behavior Checklist (CBCL) for preschool children was completed at baseline and at 1-year post-baseline. Other measures at follow-up included Movement Assessment Battery for Children Second Edition, Beery Visual-Motor Integration Test 5th Edition, and Peabody Picture Vocabulary Test 4th Edition. The whole cohort improved on CBCL total problems score between baseline (mean 50.0, SD 11.1) and 1-year follow-up (mean 45.2, SD 10.3), p=.004. There were no significant differences between groups over time on CBCL internalizing, externalizing, or total problems scores. The intervention group showed a mean difference in total problems score of -3.8 (CI [1.5, 9.1]) between times, with standard care group values being -4.4 (CI [1.6, 7.1]). Males had higher total problems scores than females (p=.026), although still performed within the "normal" range. CBCL scores did not correlate with other scores. The behaviour of nondisabled ELBW children was within the "normal" range at 4 to 5years, and both intervention and standard care may have contributed to improved behavioural outcomes. Behaviour was not related to performance in other developmental domains.

Seven Years Cognitive Functioning and Early Assessment in Extremely Low Birth Weight Children.

Infants born preterm are at high risk for the onset of cognitive dysfunctions at school age. The aim of this study was to investigate the association between early neurodevelopmental assessment and the risk of adverse cognitive outcome in extremely low birth weight children. We enrolled all newborns (January 2002 – April 2007) consecutively admitted to our Institution, with a birthweight < 1000 g. Exclusion criteria were genetic abnormalities, severe neurofunctional impairment, and/or neurosensory disabilities. Ninety-nine children were assessed at 1 year of corrected age using the Griffiths Mental Development Scales Revised. The same children were re-assessed at school age through the Wechsler Intelligence Scale for Children. Children with impaired Griffiths General Quotient (i.e., <1 SD) at 1 year of corrected age showed a significantly lower Full Scale Intelligence Quotient at 7 years of chronological age when compared to children who scored in the normal range at 1 year (p < 0.01). Considering the Griffiths Sub-quotients separately, a poor score in the Performance or in the Personal-Social Sub-quotients at 1 year was associated with significantly worse cognitive outcomes both in the Verbal and in the Performance Intelligence Quotients at 7 years (p < 0.01 and p < 0.05, respectively). A score <1 SD in the Locomotor or in the Eye and Hand Coordination Sub-quotients were specifically associated with poorer Performance or Verbal Intelligence Quotients, respectively (p < 0.05). Our findings suggest that a poor score on the Griffiths Scales at 1 year is associated with a higher risk of cognitive impairment at school age. Larger confirmation studies are needed.

Catch–up growth in the first two years of life in Extremely Low Birth Weight (ELBW) infants is associated with lower body fat in young adolescence

AimTo investigate growth patterns and anthropometrics in former extremely low birth weight (ELBW, <1000 g) children and link these outcomes to neurocognition and body composition in childhood.MethodsELBW children were examined at birth (n = 140), at 9 and 24 months (n≥96) and at approximately 11 years within the framework of the PREMATCH (PREMATurity as predictor children’s of Cardiovascular and renal Health) case–control (n = 93–87) study. Regional growth charts were used to convert anthropometrics into Z–scores. Catch–up growth in the first two years of life was qualified as present if ΔZ–score >0.67 SDS. At 11 years, anthropometrics, neurocognitive performance, body composition, grip strength and puberty scores were assessed.ResultsELBW neonates displayed extra–uterine growth restriction with mean Z–scores for height, weight and head circumference of –0.77, –0.93 and –0.46 at birth, –1.61, –1.67 and –0.72 at 9 months, –1.22, –1.61 and –0.84 at 24 months, and –0.42, –0.49 and –1.09 at 11 years. ELBW children performed consistently worse on neurocognitive testing with an average intelligence quotient equivalent at 11 years of 92.5 (SD 13.1). Catch–up growth was not associated with neurocognitive performance. Compared to controls, ELBW cases had lower grip strength (13.6 vs. 15.9 kg) and percentage lean body weight (75.1 vs. 80.5%), but higher body fat (24.6 vs. 19.2%) and advanced puberty scores at 11 years (all P≤0.025). Catch–up growth for weight and height in the first two years of life in cases was associated with a lower percentage body fat compared to cases without catch–up growth (16.8% catch-up growth for weight vs. 25.7%, P<0.001; 20.9% catch-up for height vs. 25.8%, P = 0.049).ConclusionsIn young adolescence, former ELBW children still have difficulties to reach their target height. Compared to normal birth weight controls, ELBW adolescents show lower neurocognitive performance and grip strength and a higher percentage body fat, a potential risk factor for adverse health outcomes in adulthood. Our key finding is that catch–up growth in ELBW children in the first two years of life is associated with a lower percentage body fat and is therefore likely to be beneficial.

Clinical Implications

HomeHypertensionVol. 69, No. 3Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Mar 2017https://doi.org/10.1161/HYPERTENSIONAHA.117.09012Hypertension. 2017;69:383IntroductionHypertension in Former Extremely Low Birth Weight Children (p 443)Low birth weight and prematurity are forerunners of hypertension in adulthood. Few studies reported on plasma renin activity in preterm or full-term born children. In prematurely born children with birth weight <1000 g (extremely low birth weight) and healthy controls, we tested the hypothesis whether renin might modulate the pathogenesis of hypertension associated with preterm birth. In cases compared with controls, systolic blood pressure was found to be 7.5 mm Hg higher, but plasma renin activity was found to be 0.54 ng/mL per hour lower. Plasma renin activity decreased with systolic blood pressure but was unrelated to sodium excretion. Extremely low birth weight predisposes young children to a low-renin volume-expanded sodium-sensitive type of hypertension. Extremely low birth weight children might therefore benefit from a life course reduction in salt intake and, if hypertensive, are probably more responsive to diuretics than to inhibitors of the renin–angiotensin system, the currently recommended first-line treatment in children with high blood pressure. Above all, our study highlights the importance of screening for hypertension in all prematurely born infants to avoid the complications associated with high blood pressure later in life. Finally, information on birth weight and on the perinatal history of patients might provide clinically relevant cues to physicians managing hypertension in adults.Download figureDownload PowerPointInterferon Regulatory Factor 3 Modulates Atherosclerosis (p 510)Download figureDownload PowerPointAtherosclerosis is a chronic inflammatory disease in which endothelial dysfunction plays an important role. A major feature of endothelial dysfunction is enhanced adhesion molecule expression, leading to adherence and transmigration of inflammatory cells, including monocytes and macrophages. In this study, we demonstrate that IRF3 (interferon regulatory factor 3) plays an important role in this inflammatory response. IRF3 was found to promote endothelial secretion of vascular cell adhesion molecule-1 and expression of intercellular adhesion molecule-1 by directly binding to its gene promoter. IRF3 was found to be upregulated in endothelial cells in both human and mouse atherosclerotic plaques. Ablation of IRF3 decreased vascular infiltration of macrophages and ameliorated the development of atherosclerosis in apolipoprotein E–deficient mice. IRF3 ablation also improved the stability of atherosclerotic plaques. Because plaque stability is more significant than plaque size in predicting acute clinical events, IRF3 represents a promising target for the treatment of atherogenesis and for prevention of its untoward clinical outcomes.Proton Pump Inhibitors to Treat Preeclampsia (p 457)Preeclampsia is a major complication of pregnancy, responsible for 70 000 maternal deaths annually and far greater fetal losses. A treatment that can quench the disease process could be a major advance, saving the lives of many mothers and babies. Sadly, no treatment exists, except delivery. The preeclamptic placenta releases elevated levels of the antiangiogenic factors sFlt-1 (soluble fms-like tyrosine kinase-1) and soluble endoglin. They disseminate throughout the maternal circulation and cause widespread endothelial dysfunction and hypertension, which then leads to injury to multiple maternal organs. In this issue of Hypertension, Onda et al report preclinical studies showing proton pump inhibitors may have diverse biological effects that make them an unlikely candidate treatment for preeclampsia. Using many functional assays performed on primary human tissues, they show that proton pump inhibitors decrease placental (Figure) and endothelial secretion of sFlt-1 and soluble endoglin, and they decrease endothelial dysfunction. Furthermore, they found that the proton pump inhibitor esomeprazole vasodilates blood vessels isolated from pregnant women and potently decreases blood pressure in a transgenic animal model of preeclampsia where sFlt-1 is overexpressed in the placenta. Proton pump inhibitors are widely prescribed to pregnant women to relieve gastric acid reflux. Large epidemiological studies suggest that proton pump inhibitors are safe to give to pregnant women. Therefore, the exciting clinical implication is that proton pump inhibitors may have the potential to treat or prevent preeclampsia. The team has translated these findings into a phase II placebo-controlled clinical trial to see whether esomeprazole can be used to treat preterm preeclampsia.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails March 2017Vol 69, Issue 3 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.117.09012 Originally publishedMarch 1, 2017 PDF download Advertisement

Are behaviour problems in extremely low-birthweight children related to their motor ability?

To investigate whether behaviour problems are independently related to mild motor impairment in 11-13-year-old children born preterm with extremely low birthweight (ELBW). The cross-sectional study included 48 (27 males) non-disabled, otherwise healthy ELBW children (<1000 g) and 55 (28 males) term-born peers. Parents reported behaviour using the Child Behaviour Checklist (CBCL). Children completed the Movement Assessment Battery for Children (Movement ABC). Extremely low birthweight children had poorer behaviour scores (CBCL Total Problem T score: mean difference = 5.89, 95% confidence interval = 10.29, 1.49, p = 0.009) and Movement ABC Total Motor Impairment Scores (ELBW group median = 17.5, IQR = 12.3; term-born group median = 7.5, IQR = 9, p < 0.01) than term-born peers. Behaviour was related to motor score (regression coefficient 2.16; 95% confidence interval 0.34, 3.97, p = 0.02) independent of gender, socio-economic factors or birthweight. Motor score had the strongest association with attention (ρ = 0.51; p < 0.01) and social behaviours (ρ = 0.50; p < 0.01). Behaviour problems of otherwise healthy 11- to 13-year-old ELBW children are not related to prematurity independent of their motor difficulties. Supporting improved motor competence in ELBW preteen children may support improved behaviour, particularly attention and social behaviours.

Mother-Toddler Play Interaction in Extremely, Very Low Birth Weight, and Full-Term Children: A Longitudinal Study.

Introduction: Although preterm birth represents a risk factor for early mother-infant interactions, few studies have focused on toddlerhood, an important time for the development of symbolic play, autonomous skills, and child's socialization competences. Moreover, no study has looked at the effect of birth weight on mother-child interactions during this period. Expanding on the available literature on prematurity, the main objective of this study was to explore the quality of mother-toddler interactions during play, using a longitudinal research design, as well as taking into account the effect of birth weight.Method: 16 Extremely Low Birth Weight (ELBW), 24 Very Low Birth Weight (VLBW), 25 full-term children, and their mothers were recruited for the present study. Mother-child dyads were evaluated at 18, 24, and 30 months of child age. Ten minutes of mother-child play interaction were recorded and later coded according to the Emotional Availability Scales (EAS). Furthermore, the child's level of development was assessed through the Griffiths Scale, and its contribution controlled for.Results: ELBW dyads showed an overall lower level of emotional availability, compared to VLBW and full-term dyads, but no main effect of birth weight was found on specific EA dimensions. Moreover, a significant effect of child age emerged. Overall scores, and Child Responsiveness and Involvement scores improved over time, independently of birth weight. Lastly, a significant effect of the interaction between birth weight and child age was found. Between 18 and 30 months, the overall quality of the interaction significantly increased in ELBW and VLBW dyads. Additionally, between 18 and 30 months, VLBW children significantly improved their responsiveness, while their mothers' sensitivity, structuring, and non-intrusive behaviors improved. In contrast, no change emerged in full-term dyads, although scores were consistently higher than those of the other groups.Discussion: Birth weight affects the quality of mother-toddler interactions. Monitoring the relational patterns of preterm dyads during toddlerhood is important, especially in the case of ELBW children.

Learning Disabilities in Extremely Low Birth Weight Children and Neurodevelopmental Profiles at Preschool Age

At school age extremely low birth weight (ELBW) and extremely low gestational age (ELGAN) children are more likely to show Learning Disabilities (LDs) and difficulties in emotional regulation. The aim of this study was to investigate the incidence of LDs at school age and to detect neurodevelopmental indicators of risk for LDs at preschool ages in a cohort of ELBW/ELGAN children with broadly average intelligence. All consecutively newborns 2001–2006 admitted to the same Institution entered the study. Inclusion criteria were BW < 1000 g and/or GA < 28 weeks. Exclusion criteria were severe cerebral injuries, neurosensory disabilities, genetic abnormalities, and/or a Developmental Quotient below normal limits (< 1 SD) at 6 years. The presence of learning disabilities at school age was investigated through a parent-report questionnaire at children's age range 9–10 years. Neurodevelopmental profiles were assessed through the Griffiths Mental Development Scales at 1 and 2 years of corrected age and at 3, 4, 5, and 6 years of chronological age and were analyzed comparing two groups of children: those with LDs and those without. At school age 24 on 102 (23.5%) of our ELBW/ELGAN children met criteria for LDs in one or more areas, with 70.8% comorbidity with emotional/attention difficulties. Children with LDs scored significantly lower in the Griffiths Locomotor and Language subscales at 2 years of corrected age and in the Personal-social, Performance and Practical Reasoning subscales at 5 years of chronological age. Our findings suggest that, among the early developmental indicators of adverse school outcome, there is a poor motor experimentation, language delay, and personal-social immaturity. Cognitive rigidity and poor ability to manage practical situations also affect academic attainment. Timely detection of these early indicators of risk is crucial to assist the transition to school.

Increased Steroid Excretion in Children with Extremely Low Birth Weight at a Median Age of 9.8 years

Background: Events during foetal or early extrauterine life may affect bodily structure and/or functions and even pave the way for adult diseases. Aims: To find whether extremely low birth weight (ELBW) infants differ from healthy controls regarding the excretion of steroid metabolites. Methods: The study compared 17 female and 10 male ELBW infants, all prepubertal, aged 8-11 years, birth weight <1,000 g, with 27 age- and sex-matched controls. All were healthy at the time of the study. Height, weight and BMI did not differ between the groups. Results were adjusted according to body surface area. 36 urinary steroid metabolites were quantified by gas chromatography-mass spectrometry. Results: In the ELBW girls 33/36 steroid metabolites were higher (19 significantly) than in the controls. All 36 steroid metabolites were higher in the ELBW boys (9 significantly) than in the controls. Sums of mineralocorticoid precursors, metabolites descriptive for cortisol and parameters of adrenal androgen production were significantly higher in ELBW infants (both sexes). Only the sum of the metabolites known to be illustrative for adrenal 11β-hydroxysteroid dehydrogenase activity was not different. Conclusion: Prepubertal ELBW children have an augmented urinary excretion of adrenal androgens, cortisol and mineralocorticoid precursors. These findings corroborate and help to explain the link between early-life adversity and subsequent adrenocortical function.

Parents tend to underestimate cognitive deficits in 10- to 13-year-olds born with an extremely low birth weight.

This study determined the cognitive outcomes of Finnish children born with an extremely low birth weight (ELBW) and assessed the agreement between their neuropsychological assessment and how their parents evaluated their cognitive difficulties. The study focused on 121 children from an ELBW cohort with a mean age of 11.6 years (range 10.3-13.8) and assessed them using a standardised test of intelligence, a neuropsychological test battery and a parental developmental questionnaire. The results were compared with the test norms. ELBW children exhibited global cognitive impairment compared to the test norms, with no differences between children who were small or appropriate for gestational age. Children with average intelligence displayed specific impairment in executive, sensorimotor and visuospatial functions. Corresponding functions in the parental evaluation and neuropsychological assessment were associated, but 16-26% of children scoring under the clinical cut-off value in the neuropsychological test domains were not detected by the parental evaluations. Children born with an ELBW faced a high risk of global cognitive impairment at a mean age of 11.6 years, and those with average intelligence were at risk of specific cognitive sequelae. Compared to the neuropsychological tests, up to one-fourth of the parents underestimated their child's cognitive problems.