Down Syndrome Infants Research Articles

Serial Assessment of Cardiac Function and Pulmonary Hemodynamics in Infants With Down Syndrome

There is a dearth of longitudinal data describing the evolution of cardiopulmonary hemodynamics in infants with Down syndrome (DS) beyond infancy. We hypothesized that babies with DS, independent of the presence of congenital heart disease (CHD), demonstrate biventricular systolic and diastolic impairment and sustained elevation of pulmonary pressures compared with controls over the first 2years of age. This was a prospective observational cohort study of 70 infants with DS (48 with CHD and 22 without CHD) and 60 controls carried out in 3 tertiary neonatal intensive care units in Dublin, Ireland. Infants with DS with and without CHD and non-DS controls underwent serial echocardiograms at birth, 6months, 1year, and 2years of age to assess biventricular systolic and diastolic function using deformation analysis. Pulmonary vascular resistance was assessed using pulmonary artery acceleration time and left ventricular (LV) eccentricity index. Infants with DS exhibited smaller LV (birth: 27±4 vs 31±2mm, P<.01; 2years: 43±5 vs 48±4mm, P<.01) and right ventricular (birth: 28±3 vs 31±2mm, P<.01; 2years: 40±4 vs 44±3mm, P<.01) lengths and lower LV (birth: -19%±3% vs -22%±2%, P<.01; 2years: -24%±2% vs -26%±2%, P<.01) and right ventricular (birth: -19%±4% vs -22%±3%, P<.01; 2years: -29%±6% vs -33%±4%, P<.01) systolic strain over the 2-year period. Pulmonary artery acceleration time was lower in the DS group throughout the study period (birth: 44±10 vs 62±14ms, P<.01; 2years 71±12 vs 83±11ms, P<.01). No differences were observed between DS infants with and without CHD (all P>.05). Infants with DS exhibit impaired maturational changes in myocardial function and pulmonary vascular resistance. Such novel findings provide valuable insights into the pathophysiology affecting cardiorespiratory morbidity in this population.

Early Visual Attention Abilities and Audiovisual Speech Processing in 5-7 Month-Old Down Syndrome and Typically Developing Infants.

Communicative abilities in infants with Down syndrome (DS) are delayed in comparison to typically developing (TD) infants, possibly affecting language development in DS. Little is known about what abilities might underlie poor communication and language skills in DS, such as visual attention and audiovisual speech processing. This study compares DS and TD infants between 5–7 months of age in a visual orientation task, and an audiovisual speech processing task, which assessed infants’ looking pattern to communicative cues (i.e., face, eyes, mouth, and waving arm). Concurrent communicative abilities were also assessed via the CSBS-DP checklist. We observed that DS infants orient their visual attention slower than TD infants. Both groups attended more to the eyes than the mouth, and more to the face than the waving arm. However, DS infants attended less to the eyes than the background, and equally to the face and the background, suggesting their difficulty to assess linguistically relevant cues. Finally, communicative skills were related to attention to the eyes in TD, but not in DS infants. Our study showed that early attentional and audiovisual abilities are impaired in DS infants, and might underlie their communication skills, suggesting that early interventions in this population should emphasize those skills.

Characteristics of the pulmonary circulation in infants with complete atrioventricular septal defect.

Infants with complete atrioventricular septal defect occasionally accompany pulmonary hypertension; however, the pulmonary circulation can be altered by pulmonary vascular conditions as well as the left heart lesions. This study aimed to explore whether the left heart lesions were related to the pulmonary circulation among them. We performed echocardiography and cardiac catheterisation in 42 infants with complete atrioventricular septal defect and studied relationships between the pulmonary haemodynamic parameters and the left heart morphology. Age and weight at preoperative evaluation were 65 days (47-114) (the median following interquartile range) and 5.5 kg (4.0-7.1), respectively. There were 27 individuals with Down syndrome. Gestational age was 38 weeks (37-39). Catheterisation showed mean pulmonary arterial pressure: 36 (29-46) mmHg, the ratio of pulmonary to systemic blood flow: 3.45 (2.79-4.98), pulmonary vascular resistance: 2.20 Wood units·m2 (1.53-3.65), and pulmonary arterial compliance: 2.78 (1.86-4.10) ml/Hg/m2. Echocardiography showed the Rastelli classification type A in 28 and type C in 14, moderate or severe left atrioventricular valve regurgitation in 19 patients (45%), atrioventricular valve index of 0.67 (0.56-0.79), left ventricular end-diastolic volume z score of 4.46 (1.96-7.78), and aortic valve diameter z score of -0.70 (-1.91 to 0.20). Multivariable regression analysis revealed that preoperative pulmonary vascular resistance was significantly correlated to gestational age (p = 0.002), and that preoperative pulmonary arterial compliance was significantly correlated to gestational age (p = 0.009) and Down syndrome (p = 0.036). The pulmonary circulation does not depend upon the presence of left heart lesions but gestational age and Down syndrome in infants with complete atrioventricular septal defect.

Complete blood count differences in a cohort of Down syndrome neonates with transient abnormal myelopoiesis screened for GATA1 pathogenic variants.

Transient abnormal myelopoiesis (TAM) raises the risk for acute myeloid leukemia of Down syndrome (DS) (ML-DS), and both are related to GATA1 pathogenic variants. Here, we analyzed which findings on complete blood count (CBC) are associated with TAM in a cohort of neonates with DS screened for GATA1 pathogenic variants. The CBCs were compared among 70 newborns with DS, including 16 patients (22.9%) with TAM (cases), and 54 patients (77.1%) without TAM (controls). TAM was defined as peripheral circulating blasts (PCBs) ≥ 1%. PCR and direct sequencing were used to screen DNA samples from peripheral blood for GATA1 exon 2 mutations. Multivariate logistic regression analyses determined that the mean count of lymphocytes was significantly higher in DS infants with TAM (p = .035) and that lymphocytosis confers a risk for TAM (adjusted odds ratio = 7.23, 95% confidence intervals: 2.02-25.92). Pathogenic variants of GATA1 were identified in 2 of 70 analyzed DS neonates (2.9%), of which one had ML-DS and another had an asymptomatic TAM. Among those DS infants with TAM, the GATA1 pathogenic variant detection was 12.5%. Our results indicated that lymphocytosis is associated with TAM in neonates with DS. However, since not all infants with an abnormal CBC had TAM, and not all infants with TAM had GATA1 pathogenic variants, we emphasize that only the search for GATA1 pathogenic variants allows the proper identification of the subgroup of DS infants with a real increasing in risk for ML-DS.

Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial

PurposeTo determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS). MethodsThe Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6–18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months. Randomization was done by age and sex. The primary endpoint was adjusted change from baseline in Griffiths Mental Development Scale global development quotient (GDQ) after 12 months. ResultsOf 175 patients randomized, 143 completed the study. The modified intention-to-treat (mITT) population included all randomized patients who did not prematurely discontinue due to elevated baseline thyroid stimulating hormone (TSH). Baseline characteristics in the mITT were well balanced between groups, with reliable developmental assessment outcomes. Adjusted mean change in GDQ in the mITT showed similar decreases in all groups (placebo: −5.10 [95% confidence interval (CI) −7.84 to −2.37]; FA: −4.69 [95% CI −7.73 to −1.64]; L-thyroxine: −3.89 [95% CI −6.94 to −0.83]; FA+L-thyroxine: −3.86 [95% CI −6.67 to −1.06]), with no significant difference for any active treatment group versus placebo. ConclusionThis trial does not support the hypotheses that thyroxine and/or folinic acid improve development of young children with DS or are synergistic. This trial is registered with ClinicalTrials.gov number, NCT01576705.

Transient Myeloproliferative Disorder: An Update for Neonatal Nurses.

Down syndrome (DS) is a well-known genetic disorder that affects 700-1,000 infants per year. One particular comorbidity of DS is transient myeloproliferative disorder (TMD), a disease characterized by leukocytosis with elevated blast counts. Approximately 10 percent of DS infants develop TMD, which usually manifests during the first week of life and can lead to an extended hospitalization in a NICU. In addition to hallmark hematologic findings, other manifestations include jaundice, conjugated hyperbilirubinemia, hepatomegaly, and pericardial or pleural effusions. TMD generally resolves spontaneously in the first three months of life with the provision of timely medical management; however, survivors are at increased risk of developing acute myeloid leukemia (AML). Neonatal nurses need to have knowledge of this disorder to facilitate screening of DS infants and optimize family education and coordination of care.

Relationship Between Pulmonary Arterial Resistance and Compliance in Patients with Down Syndrome.

This study aimed to clarify the characteristics of pulmonary arterial resistance (Rp)-compliance (Cp) coupling in individuals with Down syndrome (DS), who have increased risks of pulmonary arterial hypertension (PAH). We performed cardiac catheterization before and after corrective surgery in 85 DS infants and 85 controls with congenital heart disease and PAH. We retrospectively collected hemodynamic data and compared Rp and Cp between the groups. Age at surgery was 3.5 (2.6-4.6)months. The first and second catheterizations were performed 1month before and after corrective surgery in both groups. Preoperative Cp in DS patients was significantly lower than that in controls [2.27 (1.62-3.0) vs. 2.50 (1.86-3.31) mL/mmHg/m2, p = 0.039], although there was no significant difference in mean pulmonary arterial pressure and Rp between the groups. Analysis of covariance revealed that the slopes of the preoperative regression lines for the logarithmic transformations of Rp and Cp were identical in DS patients and controls (p = 0.299). However, the postoperative regression line was shifted downward in DS patients after corrective surgery. Postoperative home oxygen therapy (HOT) was performed in 39 patients (36 DS patients) and multivariate logistic regression analysis revealed that postoperative HOT was significantly related to low preoperative Cp (p = 0.039) and DS (p = 0.0001). Individuals with DS have the unique pulmonary vasculature characterized with low Cp that is related to postoperative HOT.

Prevalence of thyroid dysfunctions in infants and children with Down Syndrome (DS) and the effect of thyroxine treatment on linear growth and weight gain in treated subjects versus DS subjects with normal thyroid function: a controlled study.

Background: Individuals with Down syndrome (DS) are at an increased risk of developing thyroid disease, primarily autoimmune, with a lifetime prevalence ranging from 13% to 63%. Unfortunately, there are few studies systematically examining the frequency of thyroid disease in very young children. Aim of the study: The aim of the present study was to investigate the prevalence of different thyroid dysfunctions (TD) in a cohort of infants and children with DS and the growth parameters in subjects with normal versus abnormal thyroid function, followed for 3 years. Patients and methods: All children (n = 102; 48 males and 54 females, aged 2.3±3 years) with the diagnosis of DS who were seen at the General Pediatric Clinic of Hamad General Hospital in Doha (Qatar) from 2014 to 2018 were enrolled in our study. We recorded thyroid function and linear growth parameters [BMI, length/height SDS (Ht-SDS) and weight gain/day] and divided them into 3 groups according to their thyroid function. Group 1: (n = 36 subjects) with normal free T4 (FT4) and TSH; Group 2 (n = 44 subjects) with high TSH >5 and <12 mIU/L, and normal FT4, and Group 3 (n = 22 subjects) with TSH >12 mIU/L and/or FT4 <9 pmol/L. We also compared linear growth parameters in subjects with DS and thyroid dysfunction versus those with normal thyroid function at diagnosis and after treatment with L- thyroxine, for an average of 3 years. Results: In infants with DS (<1 year of age; n = 47, mean age: 5±3.5 months) we documented a higher prevalence of hypothyroidism (HT) (7/47 = 14.9%), both primary (5/47; 10.6%) and secondary (2/47; 4.3%). Subclinical hypothyroidism and positive thyroid antibodies were found in (13/47; 27.7%) and (9/47;19%, respectively). Before treatment with L-thyroxine, DS infants of Group 3 had significantly lower BMI-SDS but were not significantly shorter compared to other two Groups (p= 0.03 and p =0.14, respectively). After an average of 3 years of treatment the BMI- SDS and Ht-SDS did not differ among the treated and not treated infant groups. In the older group (>1 year; n=55; mean age: 5.5±3.3 years) primary HT was detected in 7/55 (12.7%). Subclinical HT was diagnosed in 20/55 (36.4%) and positive thyroid antibodies were found in 26/55 (47.3%). Before treatment with L-thyroxine, using the CDC growth charts for DS, we found that the groups with high TSH (Groups 2 and 3) were significantly shorter and heavier compared to the group with normal TSH (Group 1). After treatment with L-thyroxine, the Ht-SDS and Wt-SDS did not differ between the two groups. The linear growth of those diagnosed early during the first year of life was compared to growth parameters of children who were diagnosed with thyroid dysfunction later in life. Conclusion: Our data provided more evidence to support the findings that L- thyroxine treatment can improve growth of infants and young DS children with high TSH (>5 mIU/L), especially in those with TSH >12 mIU/L. (www.actabiomedica.it)

Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis

Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into "progression group" (n=7) that required any therapy and "spontaneous resolution group" (n=15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Three patients developed leukemia during the study period (median, 1147 days; range, 33-3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p<0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30×109/L, p=0.01; CXCL8: 173.8 vs. 34.3pg/ml, p<0.01; CCL2: 790.3 vs. 209.8pg/mL, p<0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p<0.01; CXCL8: sc=-0.46, p=0.02). High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants.

Correction: Growth of the hard palate in infants with Down syndrome compared with healthy infants-A retrospective case control study.

[This corrects the article DOI: 10.1371/journal.pone.0182728.].

Adaptive behavior in infants and toddlers with Down syndrome and fragile X syndrome.

Individuals with Down syndrome (DS) experience deficits across all domains of adaptive functioning, however little is known about the emergence and age-related changes of these impairments compared to other neurogenetic disorders with similar intellectual disability impairments, such as fragile X syndrome (FXS). Adaptive behavior is key for optimal functioning in these populations. Participants aged 5-45 months comprised three age-matched groups, DS (n = 64), FXS (n = 69), and typically developing controls (TD; n = 69). Adaptive behavior was measured on the Vineland Adaptive Behavior Scales-II. Regressions were used to examine adaptive behavior in a cross-sectional design across age. DS infants and toddlers evidenced deficits across all areas of adaptive behaviors compared to the age-matched TD group, with clear impairments present in the first year of life. Motor skills were the area of greatest weakness in children with DS with significant impairment evident at 12 months of age that remained low through 3 years. Compared to age-matched children with FXS, children with DS showed initially lower standard scores at 12 months of age, but slower declines in standard scores across age, resulting in less impaired functioning at 36 months. This is the first study to compare adaptive behavior in infants and toddlers with DS to FXS, and demonstrate the phenotypic specificity of adaptive profiles in this diagnostic group. These findings provide evidence that adaptive behavior should be a major target of intervention in children with FXS and DS, and that these differences are potentially driven by unique etiologies attributable to each disorder.

Pain assessment in Down Syndrome patients: a narrative review of the literature

The paper provides a description of available measurement tools which are able to adequately assess acute chronic pain in Down Syndrome (DS) patients, regardless of their age and cognitive impairment. Papers referring to DS patients were sought using different databases, such as PubMed, CINAHL, Scopus, Web of Science (ISI) and Cochrane, with no limit of time and published up to October 2017. All validated tools applicable to DS patients were included in the search, which consisted of papers published both in English and Italian. Irrelevant studies not pertaining to this specific query, grey literature publications, Commentaries, Letters and Editorials were excluded. Six pain assessment tools were obtained, based on the observations of caregivers and healthcare's practitioners and on the interpretation of behavioral cues of patients unable to self-report. The identified tools were: the Non-communicating Children's Pain Checklist-Revised (NCCPC-R), the Pediatric Pain Profile (PPP), the Revised Face, Legs, Activity, Cry and Consolability Scale (r- FLACC), the Individualized Numeric Rating Scale (INRS) and the COMFORT-Behavior Scale (COMFORT-B), all applicable to patients affected by chromosomic diseases. The COMFORT- Behavior Scale (COMFORT-B) could be used only in DS infants (0-3 years) undergoing mechanic ventilation. Four of the six tools have also been validated in Italian. To date national and international research studies have not been able to adequately respond to the needs of DS patients who are not be able to clearly express the level of pain they may be experiencing. Only one assessment tool turned out to be suitable for measuring pain intensity in the pediatric population undergoing mechanic ventilation. (COMORT-B), although this latter could not be used for assessing pain intensity in other DS populations. This means that there is the urgent need to carry out further validation studies so that a wider range of pain assessment tools may be used for people with Down's syndrome.

DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down syndrome offspring.

Down syndrome (DS) is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)-methyltransferase 3B (DNMT3B – EC 2.1.1.37) de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (χ2 = 4.53; DF = 1; P = 0.03) and allelic (χ2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50–0.96; P = 0.03), and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31–0.96; P = 0.04). Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Acoustic parameters of infant-directed singing in mothers of infants with down syndrome

This study compared the acoustic parameters and degree of perceived warmth in two types of infant-directed (ID) songs − the lullaby and the playsong − between mothers of infants with Down syndrome (DS) and mothers of typically-developing (TD) infants. Participants included mothers of 15 DS infants and 15 TD infants between 3 and 9 months of age. Each mother’s singing voice was digitally recorded while singing to her infant and subjected to feature extraction and data mining. Mothers of DS infants and TD infants sang both lullabies and playsongs with similar frequency. In comparison with mothers of TD infants, mothers of DS infants used a higher maximum pitch and more key changes during playsong. Mothers of DS infants also took more time to establish a rhythmic structure in their singing. These differences suggest mothers are sensitive to the attentional and arousal needs of their DS infants. Mothers of TD infants sang with a higher degree of perceived warmth which does not agree with previous observations of “forceful warmth” in mothers of DS infants. In comparison with lullaby, all mothers sang playsong with higher overall pitch and slower tempo. Playsongs were also distinguished by higher levels of spectral centroid properties related to emotional expressivity, as well as higher degrees of perceived warmth. These similarities help to define specific song types, and suggest that all mothers sing in an expressive manner that can modulate infant arousal, including mothers of DS infants.

Comorbidities in Down syndrome livebirths and health care intervention: an initial experience from the birth defects registry in Southern Thailand.

Down syndrome (DS) is the most common chromosomal disorder causing mental retardation with a worldwide average prevalence of 1-2 cases per 1000 births. This study aimed to determine the comorbidities associated with DS and the coverage of health care services and developmental interventions for DS livebirths in Southern Thailand. A total of 149 livebirth DS infants, recruited through the prospective birth defects registry system during 2009-2013 in 3 provinces in Southern Thailand, were regularly followed-up every 3-6 months. The data collection form included the infants' demographic data, associated congenital anomalies, and developmental interventions. The DS infants were born at an average gestational age of 38.5±2.3 weeks with average birth weight of 2760±478 g, length 48.5±2.2 cm, and head circumference 32.7±1.2 cm. Congenital heart diseases, gastrointestinal defects and congenital hypothyroidism were found in 43.0%, 6.7%, and 12.1% of the cases, respectively. The percentage of DS infants who received developmental interventions in this current study were significantly greater than in a previous study covering the years 1992-2002: early stimulation program 90.0% vs. 65.6% (P<0.01), and speech training program 74.8% vs. 38.9% (P<0.01), respectively, and the infants in our study began intervention programs significantly earlier, 0.58±0.39 years vs. 1.69±0.66 years, respectively. Congenital heart disease was the most common comorbidity associated with DS. The coverage of health care services and developmental interventions for DS children has generally improved in Southern Thailand. One hundred percent coverage of health services and interventions for children with special needs is expected in the near future.

Down syndrome as risk factor for respiratory syncytial virus hospitalization: A prospective multicenter epidemiological study.

BackgroundRespiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality.ObjectivesTo compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection.Patients/MethodsIn a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season.ResultsThe hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non‐DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non‐DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively.ConclusionsInfants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non‐DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered.

Ventriculomegaly in very-low-birthweight infants with Down syndrome.

The prevalence of Down syndrome in infants with fetal ventriculomegaly is 5% to 10%; however, the converse, the prevalence of cerebral ventriculomegaly in live-born infants with Down syndrome, is not well established. Because cranial ultrasounds are performed on most very-low-birthweight (VLBW) infants (birthweight <1500g), our aim was to examine ultrasound abnormalities of VLBW infants to determine prevalence of ventriculomegaly and intraventricular hemorrhage (IVH) in VLBW infants with Down syndrome, and whether VLBW infants with Down syndrome are at higher risk for cranial ultrasound abnormalities, compared with the already elevated risk in other VLBW infants. This study comprised retrospective analysis of data from Pediatrix BabySteps Clinical Data Warehouse. The study population consisted of 121 736 VLBW infants (61 869 males, 59 867 females), born between 1996 and 2013, of whom 441 had Down syndrome (233 males, 208 females; mean gestational age 30wks, standard deviation [SD] 2.8wks). Logistic regression was used to calculate odds of ventriculomegaly and IVH for Down syndrome. Prevalence of ventriculomegaly in Down syndrome was 5.2% compared with 0.8% in other VLBW infants. Multivariate analysis indicated 5.8× odds (95% confidence interval [CI] 3.4-9.7) of ventriculomegaly in Down syndrome and 0.9× odds (95% CI 0.7-1.1) of IVH for Down syndrome. Very preterm infants with Down syndrome are at increased risk for ventriculomegaly (but not for IVH) compared with other infants born very preterm.

Repair of complete atrioventricular septal defect in infants with down syndrome: outcomes and long-term results.

In clinical practice, the combination of congenital heart disease (CHD) with malformations of other organs occurs in about 10 % of cases, including chromosomal disease with heart defects, which are observed mainly with certain syndromes. In the Bakoulev SCCS (Moscow, Russian Federation), from 01.2005 to 01.2011, complete atrioventricular septal defect (CAVSD) repair was performed on 163 patients (5.6 ± 3.0 months) with Down Syndrome (DS) using the single-patch (n = 40) and the two-patch (n = 123) methods. The control group consisted of 214 infants aged 6.49 ± 3.03 months with CAVSD and normal karyotype. A retrospective cohort study was made, as well as a comparative analysis of the immediate (up to 30 days) and long-term (12-75 months, at the average of 56 ± 15) results of the repair of CAVSD in infants with DSand normal karyotype/chromosome set (NK). During the hospital treatment period, we registered the following complications: pulmonary hypertensive crises in 6 % (n = 9) of patients with DS and in 10 % (n = 21) of infants with NK, infectious complications in 21% (n = 34) of patients with DS and in 8% (n = 17) of infants with NK. Squeal structures in groups were differentiated. The doses and duration of cardiotonic support in the NK patients were significantly higher in comparison with the DS patients (7.5 ± 2.1 days vs 3.4 ± 1.15 days, p < 0.05). Respiratory infections on the background of immunodeficiency were found more often in the DS group (21% in DS vs 8% in NK, p < 0.05), demanding higher postoperative pulmonary ventilation time in DS patients in comparison with normal infants was required (DS 5.1 ± 2.8 days vs NK 1.7 ± 0.8 days, p < 0.05). In DS infants, abnormalities of the left AV valve (doubling of the mitral valve, single papillary muscle, closely spaced groups of papillary muscles, leaflet or chordal dysplasia, hypoplastic valve ring) occur as statistically significant (8% DS vs 12% NK; p < 0.05) which is rarer than in children having the same defect, but without Down syndrome. Concerning the long-term results, there was no significant difference (Gehan-Wilcoxon test) in actuarial freedom from reoperation after repair of CAVSD between DS and NK groups (p < 0.13). However, the presence of Down Syndrome in patients significantly increases the risk of severe co-morbidities that have a significant impact on the recovery period, as well as on life expectancy even after successful CHD correction.

Distinct Ocular Expression in Infants and Children With Down Syndrome in Cairo, Egypt

The study establishes the importance of genetic background for the expression of Down syndrome phenotype. To define the ocular manifestations of Down syndrome in infants and children in Cairo, Egypt, a historically isolated region, and compare them with systemic features and with findings in other geographic groups. We prospectively studied the ocular status and systemic features of 90 infants and children with Down syndrome and monitored all patients for 3 years. The complete ophthalmic examinations were performed along with ultrasonography, if media opacities were evident. Thyroid and cardiac status were assessed. An extensive literature search for comparison was performed. Outpatient clinical genetics department at the National Research Centre in Cairo, Egypt. Ocular and systemic manifestations of Down syndrome in infants and children in Cairo, and comparison of these features with patients with this anomaly from other geographic regions and ethnic populations. Fifty-two infants or children (58%) had at least 1 abnormal ocular finding identified at the first visit. Significant refractive errors (in 37 [41%] patients) were the most common. Nasolacrimal duct obstruction, blepharoconjuctivitis, or conjunctivitis was found in 18 (20%), strabismus in 13 (14%), cataract in 5 (6%), nystagmus in 3 (3%), and optic nerve dysplasia in 2 (2%). Brushfield spots were not found. Additional ocular features developed over time. Thirty-six patients (40%) had congenital heart defects, and many (31 [86%]) had associated ocular disorders; a statistically significant correlation with myopia was established. Chromosomal translocations were high. The phenotype in Cairo was distinct. More than half of infants and children with Down syndrome in Cairo had ophthalmic abnormalities; myopia was correlated with congenital heart defects. Comparison of the specific ocular features in our population with those in previous worldwide studies shows differences that may be related to overexpression or polymorphisms of key, modifying genes or other mutations in this historically isolated region along the Nile River. Down syndrome is more common in the highly consanguineous and multiparous Middle Eastern populations, and our Cairo findings underscore regional differences.

Betaine–homocysteine methyltransferase 742G&gt;A polymorphism and risk of down syndrome offspring in a Brazilian population

Down syndrome (DS) is the most common form of mental retardation of genetic etiology. Several polymorphisms in genes involved with the folic acid cycle have been associated to the risk of bearing a DS child; however, the results are controversial. Betaine-homocysteine methyltransferase (BHMT) is a key enzyme of folate pathway, and catalyzes the remethylation of homocysteine into methionine. Recent studies suggest that the polymorphism BHMT 742G>A may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 94 mothers of DS infants (DSM) and 134 control mothers (CM) for this polymorphism through PCR-RFLP, and found significant differences for both BHMT 742G>A genotype (P=0.04) and allele (P=0.03) frequencies between DSM and CM. The observed genotypic frequencies were GG=0.45; GA=0.45 and AA=0.10 in CM, and GG=0.54; GA=0.38 and AA=0.02 in DSM. Allelic frequencies were G=0.68 and A=0.32 in CM and G=0.78 and A=0.22 in DSM. The presence of the mutant BHMT 742 A allele decreases 40% the risk of bearing a DS child (OR=0.61; 95% CI: 0.40-0.93; P=0.03), and the risk is diminished up to >80% in association with the homozygous genotype (OR=0.17; 95% CI: 0.04-0.80; P=0.01). Our results indicate that women harboring the single nucleotide polymorphism BHMT 742G>A have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.