Intellectual functioning in survivors of extremely low birthweight: Cognitive outcomes in childhood and adolescence.

BACKGROUND: Infants born at extremely low birthweight (ELBW: ≤1000 g) are vulnerable to intellectual disabilities, but the factors that may distinguish between ELBW survivors with and without these impairments are not well understood. In this study, prospective associations between neonatal factors and functional outcomes in childhood and adolescence were compared in ELBW survivors with and without borderline intellectual functioning (BIF). METHODS: Borderline intellectual functioning was defined by IQ < 85, assessed at 8 years. Among 146 ELBW survivors, 48 (33%) had IQ scores under 85, and 98 (67%) had scores equal to or over 85. Group differences in demographic and risk factors were assessed via t-test, chi-squared analysis or non-parametric tests. Neonatal factors that differed between ELBW groups were tested for association with adaptive behaviour assessed at age 5 years, and reading and arithmetic skills assessed at ages 8 and 15 years, using hierarchical regression models. RESULTS: Extremely low birthweight survivors with BIF had significantly lower birthweights than ELBW survivors without BIF (790 vs. 855 g, P < 0.01) and were more likely to be born to mothers with lower socioeconomic status (SES) (78% vs. 48%, P < 0.01). These ELBW survivors also were more likely to be diagnosed with significant neurosensory impairment (NSI; 35% vs. 19%, P < 0.04), experienced more bronchopulmonary dysplasia (56% vs. 38%, P < 0.04), received more days of respiratory support (median 33 vs. 14 days, P < 0.01) and remained in hospital for longer periods (median 81 vs. 63 days, P < 0.03). Birthweight, familial SES, NSI and duration of respiratory support were significant predictors for one or more outcomes. Across groups, lower familial SES was associated with lower academic scores (Ps < 0.05), and NSI predicted lower adaptive functioning (Ps < 0.001). Other associations were moderated by group: among ELBW survivors with BIF, heavier birthweights predicted better arithmetic skills, the presence of NSI was associated with poorer arithmetic skills and more ventilation days predicted poorer reading skills. CONCLUSIONS: At birth, ELBW survivors with BIF faced more physiological and social disadvantages and required more medical intervention than their ELBW peers without BIF. Smaller birth size, NSI burden and prolonged neonatal ventilatory support displayed gradients of risk for childhood and adolescent academic outcomes across groups. Whereas academic performance in ELBW survivors with BIF was sensitive to variation in birth size, NSI or ventilation days, ELBW survivors without BIF attained thresholds of intellectual ability that were sufficient to support higher levels of academic performance at both ages, regardless of their status on these factors. The findings are discussed in relation to Zigler's developmental theory of intellectual disability.

Exposure to overprotective parenting and psychopathology in extremely low birth weight survivors.

BACKGROUND: Extremely low birth weight (ELBW; <1,000 g) infants are the most vulnerable babies and are at higher risk for experiencing overprotective (i.e., controlling and intrusive) parenting, which is hypothesized to contribute to the risk for mental disorders. Despite the increased risk for anxiety disorders and decreased risk for alcohol or substance use disorders seen in ELBW survivors, no research has examined the impact of parenting. This study investigated if overprotective parenting mediates links between ELBW birth status and psychiatric disorders in adulthood. STUDY DESIGN: Participants included ELBW survivors born in 1977-1982 and matched normal birth weight (≥2,500 g) control participants (ELBW n = 81; normal birth weight n = 87) prospectively followed in Ontario, Canada. These individuals retrospectively reported on whether either of their parents was overprotective using the Parental Bonding Instrument. Presence of a current anxiety disorder and of current alcohol or substance use disorders was assessed using the Mini International Neuropsychiatric Interview at age 29-36 years. RESULTS: Path analysis showed that overprotective parenting was a significant mediator of the association between ELBW status and risk for an anxiety disorder in adulthood and the risk for an alcohol or substance use disorder in adulthood in ELBW survivors. Overprotective parenting accounted for 53% of the association between ELBW status and the risk for an anxiety disorder in adulthood and 26% of the association between ELBW status and alcohol or substance use disorders. CONCLUSIONS: Overprotective parenting accounted for a substantial proportion of the increased risk for anxiety and alcohol or substance use disorders in adulthood in ELBW survivors. Despite their perceived vulnerabilities, it is important that the parents of ELBW survivors be supported in their attempts to facilitate their children's pursuit of independence during childhood and beyond.

Adult social outcomes of extremely low birth weight survivors of childhood sexual abuse.

Preterm birth and exposure to childhood sexual abuse (CSA) are early physiological and psychological adversities that have been linked to reduced social functioning across the lifespan. However, the joint effects of being born preterm and being exposed to CSA on adult social outcomes remains unclear. We sought to determine the impact of exposure to both preterm birth and CSA on adult social functioning in a group of 179 extremely low birth weight (ELBW; 2500 g) participants in the fourth decade of life. Social outcome data from a prospective, longitudinal, population-based Canadian birth cohort initiated between the years of 1977 and 1982 were examined. At age 29-36 years, ELBW survivors who experienced CSA reported poorer relationships with their partner, worse family functioning, greater loneliness, lower self-esteem and had higher rates of avoidant personality problems than those who had not experienced CSA. Birth weight status was also found to moderate associations between CSA and self-esteem (P=0.032), loneliness (P=0.021) and family functioning (P=0.060), such that the adverse effects of CSA were amplified in ELBW survivors. Exposure to CSA appears to augment the adult social risks associated with perinatal adversity. Individuals born preterm and exposed to CSA appear to be a group at particularly high risk for adverse social outcomes in adulthood.

Childhood cognition and lifetime risk of major depressive disorder in extremely low birth weight and normal birth weight adults.

In general population samples, better childhood cognitive functioning is associated with decreased risk of depression in adulthood. However, this link has not been examined in extremely low birth weight survivors (ELBW, <1000 g), a group known to have poorer cognition and greater depression risk. This study assessed associations between cognition at age 8 and lifetime risk of major depressive disorder in 84 ELBW survivors and 90 normal birth weight (NBW, ⩾2500 g) individuals up to 29-36 years of age. The Wechsler Intelligence Scale for Children, Revised (WISC-R), Raven's Coloured Progressive Matrices and the Token Test assessed general, fluid, and verbal intelligence, respectively, at 8 years of age. Lifetime major depressive disorder was assessed using the Mini International Neuropsychiatric Interview at age 29-36 years. Associations were examined using logistic regression adjusted for childhood socioeconomic status, educational attainment, age, sex, and marital status. Neither overall intelligence quotient (IQ) [WISC-R Full-Scale IQ, odds ratios (OR)=0.87, 95% confidence interval (CI)=0.43-1.77], fluid intelligence (WISC-R Performance IQ, OR=0.98, 95% CI=0.48-2.00), nor verbal intelligence (WISC-R Verbal IQ, OR=0.81, 95% CI=0.40-1.63) predicted lifetime major depression in ELBW survivors. However, every standard deviation increase in WISC-R Full-Scale IQ (OR=0.43, 95% CI=0.20-0.92) and Performance IQ (OR=0.46, 95% CI=0.21-0.97), and each one point increase on the Token Test (OR=0.80, 95% CI=0.67-0.94) at age 8 was associated with a reduced risk of lifetime depression in NBW participants. Higher childhood IQ, better fluid intelligence, and greater verbal comprehension in childhood predicted reduced depression risk in NBW adults. Our findings suggest that ELBW survivors may be less protected by superior cognition than NBW individuals.

Non-invasive quantification of hepatic steatosis in living, related liver donors using dual-echo Dixon imaging and single-voxel proton spectroscopy.

AIM: To evaluate the diagnostic implications of hepatic fat fraction calculated using dual-echo Dixon imaging and (1)H magnetic resonance spectroscopy (MRS) to detect hepatic steatosis in potential liver donors using histopathology as the reference standard. MATERIALS AND METHODS: One hundred and forty-five potential liver donors were included in the study. Magnetic resonance imaging (MRI) was performed using a 1.5 T system using a three-dimensional dual-echo MRI sequence with automated reconstruction of in-phase (IP), out-of-phase (OP), fat-signal-only, and water-signal-only images. Hepatic fat fraction was calculated by drawing 15 regions of interest on the IP, OP, fat-only, and water-only images. Single-voxel MRS was performed at echo times (TEs) of 30 ms in the right and left lobes of liver. Liver fat fraction was calculated from water and fat peaks. One hundred and forty-five biopsies were prospectively evaluated for steatosis by a pathologist using traditional determination of the cell-count fraction. MRI and pathology values of steatosis were correlated using Pearson's correlation coefficient. The sensitivity and specificity of each of these methods was calculated using histopathology as the reference standard. Reproducibility was assessed in 40 patients who had repeat scanning within 4-40 days. Measurement error was calculated from the coefficient of variation (CoV) with histopathologically proven <5% fat (n=112). RESULTS: The Bland-Altman limits of agreement with 95% confidence intervals (CI) was -2.9 to 5.3%. The intraclass correlation coefficient (ICC) for interobserver variability and reproducibility was 0.94 (95% CI: 0.91-0.97), 0.92 (95% CI: 0.91-0.97). The CoV was 7.6% (95% CI: 3.4-11.85). The area under the receiver operating characteristic (ROC) curve (AUC) for Dixon imaging 0.89 (95% CI: 0.87-0.91), for MRS 0.88 (95% CI: 0.86-0.90). The sensitivity for detecting <5% fat was 84% and specificity was 90%. CONCLUSION: Combination of dual-echo Dixon imaging and proton MRS is a useful tool for the preoperative diagnosis of hepatic steatosis in potential living liver donors. This can help avoid unnecessary biopsies in these patients.

Low-dose short-term hepatitis B immunoglobulin with high genetic barrier antivirals: the ideal post-transplant hepatitis B virus prophylaxis?

BACKGROUND: Low-dose hepatitis B immunoglobulin (HBIG) and nucleos(t)ides analogs (lamivudine/adefovir) used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT) are associated with some risk of HBV recurrence and antiviral resistance. METHODS: The study cohort included 176 patients (at least >12 months follow-up) with HBV cirrhosis/hepatocellular carcinoma who received secondary prophylaxis with indefinite entecavir/tenofovir after living-donor LT (LDLT). All patients received 10,000 IU intravenous HBIG in anhepatic phase followed by 600-1000 IU intramuscularly daily for 7 days, weekly for 3 weeks, and then monthly, to keep antiHBs levels >100 mIU/mL for 1 year. Hepatitis B surface antigen (HBsAg) and HBV DNA were tested every 6 months. RESULTS: The study cohort is composed of 157 men and 19 women, mean age 47.9 ± 10.1 years, all HBsAg positive, 35 (19.8%) had HBV DNA >2000 IU/mL before LT. After LT, patients received entecavir (n = 126, 71.5%), tenofovir (n = 20, 11.3%), or a combination of entecavir and tenofovir (n = 30, 17% for 3 months), followed by entecavir alone. During follow-up of 43 (12-117) months, 2 patients (including 1 with non-compliance) had HBV recurrence. CONCLUSION: In a large cohort of LDLT recipients for HBV-related liver disease, use of low-dose short-term HBIG with high genetic barrier drugs results in a substantially lower incidence of HBV recurrence, even in high-risk patients.

Comparison between Three Rare Cases of Co-Infection with Dengue, Leptospira and Hepatitis E: Is Early Endothelial Involvement the Culprit in Mortality?

Co-infection in immunocompetent patients is rare. Though co-infection with dengue and leptospira cases is increasingly reported, a co-infection of this combination along with hepatitis E is rarely thought of. Until date only two case of triple co-infection have been reported world-wide. Here, we are reporting a patient with co-infection of dengue, leptospirosis and hepatitis E admitted to our intensive care unit. Early septic shock and increasing procalcitonin in dengue patient raised suspicion of co-infection. Our aim is to educate intensivists about this rare co-infection and hence that timely initiation of appropriate diagnostic, therapeutic and supportive measures can alter outcome favorably.

India's first successful intestinal transplant: the road traveled and the lessons learnt.

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.

Use of ABO-incompatible grafts in living donor liver transplantation--first report from India.

ABO incompatibility is the commonest reason for rejection of donors in living donor liver transplantation (LDLT). The donor pool could be expanded by 25 % to 35 % if the ABO barrier is overcome. In the absence of pre-conditioning, transplantation across the blood groups is fraught with the almost universal risk of antibody-mediated rejection (AMR) that rapidly leads to graft loss. However, AMR can be prevented by removal of preformed antibodies and reducing their production by B cells. We describe our initial experience of three cases of ABO-incompatible (ABO-i) LDLT: a 42-year-old male, an 8-month-old male and a 28-month-old female, all of blood group O+ who received blood group B + right lobe, B + left lateral segment, and A + left lateral segment liver grafts, respectively. Pre-LDLT conditioning included administration of anti-CD20 antibody (Rituximab(®)) to the adult 4 weeks prior, and four to seven sessions of double-filtration plasmapheresis to all, to remove preformed antibodies and achieve anti-donor blood group antibody (ADA) titers of ≤ 1:16 IgG and ≤ 1:8 IgM, respectively. In addition, cases 1 and 3 received mycophenolate mofetil for 7 days prior to LDLT. After LDLT, all three patients achieved normal graft function over 8-17 days with no evidence of AMR and without the need for further plasmapheresis. Postoperative complications included portal vein thrombosis (one successfully re-explored), CMV (one), Pseudomonas and Klebsiella sepsis (one each), and abdominal collection (one treated with percutaneous drainage). All are currently well with normal graft function and low ADA titers at 8, 16, and 19 months after ABO-i LDLT.

Progeria: pathogenesis and oral manifestation--a review.

Our life span is genetically programmed and it is possible that a defect in produced proteins encoded by the longevity gene is a cause of aging. Progeria which is a rare, fatal genetic condition which affects between one in four million and one in eight million children of both sexes equally and characterized by premature and accelerated aging. The appearance and physiology of these children resembles to elderly people but they typically have life span to their mid teens. It is also known as the Hutchinson-Gilford syndrome, which was initially reported by Johnathan Hutchinson in 1886 and further described by Hastings Gilford in 1904. It is an autosomal recessive disorder, which means an individual has inherited a mutated gene from both parents. It is added to the expanding catalogue of laminopathies, diseases caused by mutations affecting nuclear lamina proteins known as lamin A (LMNA). In oral manifestation primary finding is micrognathia with delayed tooth eruption and incomplete formation of root of permanent tooth. Presently there are no known cures for this abnormality.

Psychopathology in young adults born at extremely low birth weight.

BACKGROUND: Little is known about the long-term mental health of extremely low birth weight (ELBW) (<1000 g) survivors. We test whether young adults aged 22 to 26 years born at ELBW differ from normal birth weight (NBW) controls in self-reported levels of psychopathology. METHOD: Participants included 142 ELBW survivors (86% response) born between 1977 and 1982 to residents of central-west Ontario, Canada and 133 NBW control subjects (92% response). The Young Adult Self-Report measure was used to create five DSM-IV oriented scales aggregated to form internalizing (depressive problems, anxiety problems, avoidant personality problems) and externalizing (attention deficit-hyperactivity disorder problems and antisocial personality problems) scales. RESULTS: After adjusting for family background characteristics, mean scores for ELBW survivors were 3.02 [95% confidence interval (CI) 0.78-5.26] points higher for internalizing problems and no different, i.e. 0.00 (95% CI -1.17 to 1.17), for externalizing problems. There was a sex × group statistical interaction such that being male muted the risk for externalizing problems among those born at ELBW: -2.11 (95% CI -4.21 to -0.01). Stratifying ELBW adults as born small for gestational age (SGA) versus appropriate weight for gestational age (AGA) revealed a significant gradient of risk for levels of internalizing problems that was largest for SGA, i.e. 4.75 (95% CI 1.24-8.26), and next largest for AGA, 2.49 (95% CI 0.11-4.87), compared with NBW controls. CONCLUSIONS: Depression, anxiety and avoidant personality problems (internalizing problems) are elevated in young adulthood among ELBW survivors. This effect is relatively small overall but noticeably larger among ELBW survivors born SGA.

Comparison of PCR, culture & serological tests for the diagnosis of Mycoplasma pneumoniae in community-acquired lower respiratory tract infections in children.

BACKGROUND & OBJECTIVE: Mycoplasma pneumoniae is known to be a major cause of lower respiratory tract infections in children. A specific diagnosis is important to institute the appropriate treatment. Information on diagnostic methods used for M. pneumoniae in Indian paediatric population is scarce. The study was thus conducted to compare polymerase chain reaction (PCR), culture and serology for the diagnosis of M. pneumoniae in community-acquired lower respiratory tract infections in children. METHODS: Seventy five children aged 6 months to 12 yr with signs of community-acquired lower respiratory tract infections were selected for the study. Culture of nasopharyngeal aspirates was done. The serum samples were analyzed for the detection of IgM and IgG antibodies to M. pneumoniae. A 543 base pairs (bp) region of P1 gene of M. pneumoniae was selected for amplification in PCR assay applied to nasopharyngeal aspirates. RESULTS: M. pneumoniae was isolated in culture from 4 (5.33%) children. Serological evidence of M. pneumoniae infection was observed in 16(21.3%) children. All culture positive patients were also positive by serology. Overall, PCR for M. pneumoniae was positive in 13 (17.3%) patients. All four culture positive patients were also positive by PCR. In 11 out of 13 (84.62%) PCR positive patients, serological evidence was there. Culture and/or serology and/or PCR positive results diagnosed M. pneumoniae infection in 18 (24%) of 75 patients. INTERPRETATION & CONCLUSION: A combination of culture, serology and PCR may provide diagnostic information on the aetiology of M. pneumoniae community-acquired lower respiratory tract infections in paediatric population.