Postnatal steroid therapy is associated with autism spectrum disorder in children and adolescents of very low birth weight infants.

BACKGROUND: This study evaluates the association between major neonatal morbidities and autism spectrum disorder (ASD) in children and adolescents born of very low birth weight (VLBW). METHODS: Historical cohort study using the Israel national VLBW infant database linked with the Maccabi Healthcare Services (MHS) medical records. The study cohort comprised 4963 VLBW subjects born from 1999 to 2012, >1 year of age. Multivariable logistic regression analyses were used to assess factors associated with ASD. RESULTS: The diagnosis of ASD was confirmed in 113 children (2.3%). Infants with major neonatal morbidities had higher rates of ASD; however, in the multivariable analyses these were not significantly associated with ASD: severe intraventricular hemorrhage (OR 1.21 [95% CI 0.60-2.45]), post-hemorrhagic hydrocephalus (OR 1.77 [0.73-4.29]), periventricular leukomalacia (OR 1.02 [0.42-2.51]), severe retinopathy of prematurity (OR 1.91 [0.995-3.67]), and bronchopulmonary dysplasia (OR 1.44 [0.84-2.45]). Postnatal steroid therapy when included separately was associated with an OR of 1.97 [1.18-3.29] for ASD. This association remained significant when postnatal steroid therapy was included with each of the neonatal morbidities (ORs ranging from 1.91 to 2.11). CONCLUSIONS: This study suggests a significant association between postnatal steroid therapy and ASD in VLBW infants. This possible association should be considered in future studies evaluating potential risk factors for ASD in preterm infants.

Very Low Birth Weight Preterm Infants have Decreased Celiac Disease Autoimmunity During Childhood and Adolescence.

Little is known about the effect of prematurity on later development of celiac disease (CD). We conducted a retrospective analysis of real-world data examining the association between very low birth weight (VLBW) prematurity and later development of CD autoimmunity (CDA) in 3580 infants born between years 2000 and 2012 and their matched controls. At a median of 12 years, VLBW prematurity was negatively associated with later development of CDA with a cumulative prevalence of 5.9 per 1000 versus 10.3 per 1000 (P = 0.02), though more former VLBW premature infants were ever tested for CDA (48.5% vs 37.4%, P < 0.001). The odds ratio for developing CDA among children born preterm at VLBW was 0.57 (95% confidence interval (CI) 0.35-0.92) as compared with matched controls. There was no difference in clinical characteristics of CDA between both groups. In conclusion, VLBW preterm infants present a decreased risk for the development of CDA during childhood and adolescence.

Intergenerational relations, circumstances, and changes in mothers' marital quality during two years following childbirth.

In this study, the researchers examined, from an attachment theory perspective, changes in mothers' (n = 707) perception of the marital relationship over the course of the two years following childbirth. We found a decline in perceived quality of mothers' marital relationship over time, as well as several significant associations between birth circumstances (assisted reproductive technology, first/non-first baby), insecure attachment, and certain forms of support from the grandmothers on the one hand, and marital quality immediately after childbirth and over time on the other. Some forms of support served as partial mediators between attachment orientation and marital quality. We believe that the current findings can assist in designing interventions aimed at improving the spousal relationship after childbirth and decreasing potential stressors for both parents and newborns.

Maternal mental health over the course of 4 years following childbirth: The contribution of birth circumstances and psycho-social factors.

The aim of this study is to identify mothers at risk for poorer maternal mental health (MMH) 1 month post-partum and to determine changes in MMH over 4 years in relation to birth circumstances (singleton/twins, full-term/pre-term infant/s, first/non-first child), internal resources (adult attachment styles), and external resources (marital quality and maternal grandmother's support) at 1 month post-partum. The mediating effects of external resources were also investigated. Questionnaires were completed between 2001 and 2012 by 561 Israeli mothers. Shortly after birth, mothers at risk for poorer MMH were those who gave birth prematurely or were characterized by insecure attachment styles, lower marital quality, younger age, or a higher level of education. The mothers with a good prognosis for improvement in MMH were those who had given birth prematurely or were younger, more highly educated, or multiparous. Women with insecure attachment or lower marital quality reported lower MMH one month after delivery that did not improve over time, and the MMH of older or less educated mothers deteriorated over time. Marital quality mitigated or exacerbated the effects of birth circumstances and insecure attachment style on MMH shortly after giving birth. Findings suggested that early interventions may be important to help identify women at risk.

[COMMUNITY PEDIATRICS IN ISRAEL DURING THE NEXT DECADE - A NEED FOR A CHANGE].

INTRODUCTION: Community pediatrics in Israel is based on service by pediatricians who have been trained in hospitals in Israel or elsewhere. At the same time, the field of community pediatrics is changing its nature from the management of common acute diseases, to a field dealing with a variety of chronic problems, behavioral issues, family and social issues, developmental delays, problems relating to nutrition and growth' sleep problems, learning disabilities, and of late, excessive exposure to a host of digital media. In addition, lifestyle issues such as adequate physical activity, addictions, accidents and various types of abuse are increasingly part of the pediatric role. The hospital-based residency training of pediatricians does not offer the future pediatrician the opportunity to learn these elements of the "New Morbidity". As a result, many community-based pediatricians choose not to confront these problems, and either ignore them or refer them to various consultants outside of the clinic. The entire health system, including the Ministry of Health, the Israel Medical Association, the medical schools, the health service providers (Kupot Holim) and the hospitals must cooperate in changing the format of residency training, both undergraduate and residency. This is required in order to create a new generation of pediatricians who are better equipped to deal with the increasing number of children needing help with the above-mentioned pathology. Advancing the field of primary care pediatrics by attending to these New Morbidity issues, together with pediatric involvement in community agencies, after appropriate training, will improve the health and development of the child population, together with improvement of their physical, emotional and social welfare.

Rehospitalization Through Childhood and Adolescence: Association with Neonatal Morbidities in Infants of Very Low Birth Weight.

OBJECTIVE: To evaluate the impact of major neonatal morbidities on the risks for rehospitalization in children and adolescents born of very low birth weight. STUDY DESIGN: An observational study was performed on data of the Israel Neonatal Network linked together with the Maccabi Healthcare Services medical records. After discharge from the neonatal intensive care unit, 6385 infants of very low birth weight born from 1995 to 2012 were registered with Maccabi Healthcare Services and formed the study cohort. Multivariable negative binomial regression models were calculated to estimate the adjusted relative risk (aRR) and 95% CI for hospitalization. RESULTS: Up to 18 years following discharge, 3956 infants were hospitalized at least once. The median age of follow-up was 10.7 years with total of follow-up of 67 454 patient years and 10 895 hospitalizations. The risks for rehospitalization were increased significantly for each of the neonatal morbidities: surgical necrotizing enterocolitis (NEC), aRR 2.71 (95% CI 2.08-3.53), intraventricular hemorrhage grades 3-4, 2.13 (1.85-2.46), periventricular leukomalacia (PVL), 1.83 (1.58-2.13), bronchopulmonary dysplasia, 1.94 (1.72-2.17), and retinopathy of prematurity stages 3-4, 1.59 (1.36-1.85). During the first 4 years, children with surgically treated NEC, intraventricular hemorrhage, PVL, or bronchopulmonary dysplasia had 1.5- to 2.5-fold greater risks for hospitalization compared with those without the specific morbidity. In the 11th-14th and 15th-18th years, respectively, surgically treated NEC was associated with a 3.05 (1.32-7.04) and 3.26 (0.99-10.7) aRR for hospitalization, and PVL was associated with a 2.67 (1.79-3.97) and 3.47 (2.03-5.92) aRR for hospitalization. CONCLUSIONS: Specific major neonatal morbidities as well as the number of morbidities were associated with excess risks of rehospitalization through childhood and adolescence.

Brainstem as a developmental gateway to social attention.

BACKGROUND: Evolution preserves social attention due to its key role in supporting survival. Humans are attracted to social cues from infancy, but the neurobiological mechanisms for the development of social attention are unknown. An evolutionary-based, vertical-hierarchical theoretical model of self-regulation suggests that neonatal brainstem inputs are key for the development of well-regulated social attention. METHODS: Neonates born preterm (N = 44, GA 34 w.) were recruited and diagnosed at birth as a function of their auditory brainstem evoked responses (ABR). Participants enrolled in a prospective 8-year-long, double-blind, follow-up study comparing participants with brainstem dysfunctions and well-matched controls. Groups had comparable fetal, neonatal, and familial characteristics. Methods incorporated EEG power analysis and gaze tracking during the Attention Network Test (ANT, four cue types, and two targets) and a Triadic Gaze Engagement task (TGE, three social cue levels). RESULTS: Results showed that neonatal brainstem compromise is related to long-term changes in Alpha- and Theta-band power asymmetries (p < .034, p < .016, respectively), suggesting suppressed bottom-up input needed to alert social attention. Gaze tracking indicated dysregulated arousal-modulated attention (p < .004) and difficulty in gaze engagement to socially neutral compared to nonsocial cues (p < .012). CONCLUSIONS: Integrating models of Autism and cross-species data with current long-term follow-up of infants with discrete neonatal brainstem dysfunction suggests neonatal brainstem input as a gateway for bottom-up regulation of social attention.

Utilization of ultrasonography to detect developmental dysplasia of the hip: when reality turns selective screening into universal use.

BACKGROUND: Developmental dysplasia of the hip (DDH) occurs in 3-5 of 1000 live births and is associated with known risk factors. In most countries, formal practice for early detection of DDH entails the combination of risk factor identification and physical examination of the hip, while the golden standard diagnostic instrument is hip ultrasonography (US). This practice is commonly referred to as selective screening. Infants with positive US findings are treated with a Pavlik harness, a dynamic abduction splint. The objective of our study was to evaluate hip US utilization patterns in Maccabi Healthcare Services (MHS), a large health plan. METHODS: Study population: All MHS members, born between June 2011 and October 2014, who underwent at least one US before the age of 15 months. STUDY VARIABLES: Practice specialty and number of enrolled infants. Positive US result was defined as referral to an abduction splint. Cost was based on Ministry of Health price list. Chi square and correlation coefficients were employed in the statistical analysis. RESULTS: Of the 115,918 infants born during the study period, 67,491 underwent at least one hip US. Of these, 60.6% were female, mean age at performance: 2.2 months. Of those who underwent US, 625 (0.93%) were treated with a Pavlik harness: 0.24% of the male infants and 1.60% of the female infants (p < 0.001). Analysis of physician practice characteristics revealed that referral to US was significantly higher among pediatricians as compared with general practitioners (60% and 35%, respectively). Practice volume had no influence on referral rate. Direct medical costs of the 107 hip US examinations performed that led to detection of one positive case (treated by Pavlik): US$10,000. CONCLUSIONS: Current pattern of hip US utilization for early detection of DDH resembles universal screening more closely than selective screening. This can inform policy decisions as to whether a stricter selective screening or a formal move to universal screening is appropriate in Israel.

Delay in auditory behaviour and preverbal vocalization in infants with unilateral hearing loss.

AIM: To evaluate the impact of unilateral hearing loss (UHL) on early aural/oral communication skills of infants by comparing performance to infants with bilateral normal hearing (BNH). METHOD: Thirty-four infants with UHL (median age 9.4mo, 25th-75th centile 7.34-12.15) and 331 control infants with BNH (median age 9mo, 6.0-13.38) were divided into two subgroups based on risk factors known to cause developmental delay: low risk and high risk. Early auditory skills and preverbal vocalizations were assessed using two parent questionnaires: the Infant-Toddler Meaningful Auditory Integration Scale and the Production of Infants Scale Evaluation. RESULTS: Of the infants with UHL, 21% showed delays in auditory behaviour and 41% delays in preverbal vocalizations, compared to their peers with BNH (p<0.01). After adjusting for risk level, delayed auditory behaviour and preverbal vocalizations were approximately four and nine times more common in infants with UHL compared to BNH respectively (p<0.01). INTERPRETATION: This is the first study to show that infants with UHL are at higher risk of delay in early aural/oral communication abilities compared to infants with BNH even in the absence of other known risk factors for developmental delay. This has important implications for early intervention and habilitation of infants with UHL, in order to reduce some of the negative long-term consequences of what was once considered 'minor' hearing loss.

Retrospective analysis of prenatal ultrasound of children with Hirschsprung disease.

OBJECTIVE: Hirschsprung disease (HD) is a rare gastrointestinal disorder. Our aim was to study the prenatal ultrasound findings of children who were diagnosed with HD after birth. METHODS: The study population included children who suffered from HD between 1990 and 2008. Data of anomaly scan findings in prenatal ultrasound, demographic and post-natal physical abnormalities and treatment were retrieved from medical files and interviews with the parents. RESULTS: Twenty-two patients confirmed histopathological diagnosis of HD at age of 1 day to 15 months. Nineteen fetuses had anomaly scan during pregnancy, which revealed minor sonographic abnormalities in three fetuses; two of them had hyperechogenic bowel. One fetus with hyperechogenic bowel had polyhydramnion, and another had a family history of three brothers with HD. A third fetus had dilated pelvic kidney. None of them had sonographic evidence of bowel dilatation. After birth, six patients (31%) were found to have other structural anomalies: ventriculoseptal defect, atriseptal defect, atrio-ventricular septal defect, and pyloric stenosis. CONCLUSIONS: Abnormal sonographic findings of fetal bowel are absent in the vast majority of fetuses who are diagnosed with HD after birth. In women with a family history of HD, a third trimester anomaly scan may be warranted.

Well-being and distress in mothers of two-year-old singletons and twins.

The present study investigated well-being and distress in 274 Israeli mothers of two-year-olds. Of these, 127 were mothers of singletons and 147 mothers of twins. The study examined the contribution to the explanation of well-being and distress of a range of variables relating to the mother, including sociodemographic characteristics, internal resources (attachment style, self-differentiation, and maternal self-efficacy), and external resources (marital quality and grandmothers' support). The findings showed that being a mother of a singleton or twins did not contribute to the explanation of variance in well-being or distress. Marital quality provided the strongest explained variance for both well-being and distress. Mother's health, attachment anxiety and self-differentiation also explained significant amounts of the variance. Several differences were found in the contribution of certain other variables, such as maternal grandmother's support, which contributed only to well-being. The results indicated the lesser role of sociodemographic variables, as opposed to the centrality of personality traits and marital quality, in the relationships with well-being and distress. Practical implications are discussed.

Delivery room breastfeeding for prevention of hypoglycaemia in infants of diabetic mothers.

OBJECTIVE: To evaluate the effect of duration of early breastfeeding in the delivery room on blood glucose levels among term neonates of diabetic mothers. METHODS: Mothers with gestational diabetes were encouraged to breastfeed their infants immediately after birth in the delivery room. The breastfeeding duration was recorded by the midwife. RESULTS: The longer duration of breastfeeding subgroup (n = 39) demonstrated a lower rate of hypoglycaemia in the first 8 hours of life (< 40 mg/dl) compared to the shorter duration subgroup (n = 40), but this difference did not reach statistical significance (2.6% vs. 17.5% respectively, p = 0.057). Hypoglycaemia was mainly predicted by lower cord glucose for each decrease of 10 mg/dl (OR 2.11 [CI 1.1-4.03] p = 0.024. CONCLUSION: Longer duration of delivery room breastfeeding did not reduce the rate of hypoglycaemia, which was mainly influenced by lower cord blood glucose level.

Waterhouse Friderichsen syndrome complicating fulminant Enterobacter cloacae sepsis in a preterm infant: the unresolved issue of corticosteroids.

Bilateral adrenal hemorrhage can complicate severe sepsis in the neonate and is most commonly attributed to meningococcal disease; however, it can be caused by other etiologic agents as well. We report herein a fatal case of Enterobacter cloacae sepsis in a preterm infant, resulting in massive adrenal hemorrhages. This is the first documented case of adrenal hemorrhage following infection with this pathogen.

The impact of genetic and environmental factors on homocysteine levels in preterm neonates.

BACKGROUND: Hyperhomocysteinemia may be associated with vascular complications in adults. Whereas pediatric thrombosis risk peaks in neonates, data on homocysteine (Hcy) levels assessed in term and preterm infants during the perinatal period are scarce. In the present study, we aimed to establish Hcy reference values for preterm infants and study their potential associations with the early post-natal health status. Plasma Hcy and hematocrit levels and MTHFR polymorphisms (C677T and A1298C substitution) were studied in a large cohort of preterm infants in a tertiary referral medical center during an 18-month period. Data were collected on maternal history and delivery as well as on post-natal complications. RESULTS: The study cohort included 167 infants whose mean gestational age was 30.98 ± 2.34 weeks (range: 26-36 weeks), mean birth weight 1327.6 ± 327 g, and mean Hcy level 7.99 ± 3.27 (range: 2.2-21.2) µmol/L. Maternal intake of folic acid was inversely associated with the babies' Hcy levels (P = 0.0001). Increased Hcy levels positively correlated with birth weight, gestational age (P < 0.005), total number of pregnancies (P = 0.012), and presence of MTHFR polymorphism. Higher Hcy levels were associated with feeding (P = 0.008), especially total parenteral nutrition (P = 0.0001). There was no correlation between Hcy levels and any vascular post-natal complications. CONCLUSIONS: During their post-natal hospitalization, preterm infants may have relatively high, that is, within the adult normal range, Hcy levels which are influenced by genetic and environmental factors. Despite the fact that no correlation was found between Hcy levels and post-natal complications, these associations should be further studied.

Meconium-stained amniotic fluid and the need for paediatrician attendance.

AIM: To determine perinatal parameters among term newborn infants born by vaginal delivery with meconium-stained amniotic fluid (MSAF) that needed paediatrician assistance. METHODS: Paediatricians who were in attendance in the delivery room due to MSAF among term infants completed 775 reports regarding the infants' delivery conditions, and the assistance provided. We defined 'paediatrician attendance needed' for a subgroup of infants for whom we retrospectively determined that paediatrician attendance in the delivery room was required. RESULTS: 'Paediatrician attendance needed' was determined in 31 (4%) cases. Among cases with documented normal foetal monitor, only 10 (1.8%) were defined as 'paediatrician attendance needed', a percentage significantly lower than among infants born following non-reassuring foetal monitor: 21 (9.7%) (p < 0.001). 'Paediatrician attendance needed' was predicted by non-reassuring foetal monitor [OR 6.02 (CI 2.72-13.31), p < 0.001], maternal fever [OR 6.34 (1.92-20.92), p = 0.002] and younger maternal age (for every year) [OR 0.889 (CI 0.82-0.96), p = 0.003]. CONCLUSIONS: Term newborn infants born by vaginal delivery with MSAF with documented normal tracing foetal monitor are at low risk of the need for paediatrician assistance. Paediatrician attendance in the delivery room in labour involving MSAF should be recommended when non-reassuring foetal monitor tracing is observed and should also be considered when maternal fever is recorded, and/or thick meconium is observed.

Cerebellar hemorrhage in very low birth weight premature infants: the advantage of the posterolateral fontanelle view.

OBJECTIVE: The purpose of this study was to determine the prevalence of cerebellar hemorrhage in very low birth weight infants using the posterolateral fontanelle for ultrasound (US) examination. METHODS: The study included 125 very low birth weight premature infants (defined as equal or less than 1500 grams at birth) hospitalized in the premature or neonatal intensive care departments that had at least one head US examination including both anterior and posterolateral fontanelle scans. RESULTS: On US performed through the posterolateral fontanelle, four (3.2%) infants had echogenic posterior fossa lesions interpreted as hemorrhages. None of these lesions were initially or retrospectively observed through the standard anterior fontanelle scan. Two infants died at age 4 and 39 days, respectively. All survivors are being followed up in the hospital's neurodevelopment outpatient clinic. CONCLUSIONS: Cerebellar hemorrhage may be overlooked on standard anterior fontanelle views. The posterolateral approach may assist in diagnosing these lesions.

Newborn screening for congenital cytomegalovirus using real-time polymerase chain reaction in umbilical cord blood.

BACKGROUND: Congenital cytomegalovirus (C-CMV) infection affects 0.4-2% of newborn infants in Israel, most of whom are asymptomatic. Of these, 10-20% will subsequently develop hearing impairment and may have benetitted from early detection by neonatal screeing. OBJECTIVES: To retrospectively anaIyze the results of a screening program for C-CMV performed at the Sheba Medical Center, Tel, Hashomer, during a 1 year period, using real-time polymerase chain reaction (rt-PCR) from umbilical cord blood. METHODS: CMV DNA was detected by rt-PCR performed on infants' cord blood. C-CMV was confirmed by urine culture (Shell-vial). All confirmed cases were further investigated for C-CMV manifestations by head ultrasound, complete blood count, liver enzyme measurement, ophthalmology examination and hearing investigation. RESULTS: During the period 1 June 2009 to 31 May 2010, 11,022 infants were born at the Sheba Medical Center, of whom 8105 (74%) were screened. Twenty-three (0.28%) were positive for CMV and 22 of them (96%) were confirmed by urine culture. Two additional infants, who had not been screened, were detected after clinical suspicion. All 24 infants were further Investigated, and 3 (12.5%) had central nervous system involvement (including hearing impairment) and were offered intravenous ganciclovir for 6 weeks. Eighteen infants (82%) would not otherwise have been diagnosed. CONCLUSION: The relatively low incidence of C-CMV detected in our screening program probably reflects the low sensitivity of cord blood screening. Nevertheless, this screening program reliably detected a non-negligible number of infants who could benefit from early detection. Other screening methods using saliva should be investigated further.

Short-term outcome among term singleton infants with intrapartum oligohydramnios.

AIM: To evaluate rates of early short-term neonatal complications among term singleton newborn infants with oligohydramnios. METHODS: Retrospective data were collected on 456 term infants with prenatal diagnosis of oligohydramnios and on matched controls, including information on maternal condition and on infant perinatal complications. RESULTS: Infants in the study group were born with lower birthweight and were SGA compared with those in the control group. Rates of renal malformations were significantly higher in the study group compared with the controls (15-3.3% and 3-0.7%, respectively; p = 0.007). Among the severe oligohydramnios subgroup (Amniotic Fluid Index <2), renal anomalies were even more prevalent compared to other infants with oligohydramnios and to the controls (6-9.8%, 9-2.3% and 3-0.7%, respectively; p < 0.001). The incidence of skeletal deformities (developmental dislocation of hip and torticollis) was higher among the study group. CONCLUSION: Term infants with oligohydramnios that was detected near birth are associated with a greater prevalence of renal malformations (mostly mild hydronephrosis) as well as congenital torticollis and developmental dislocated hips compared with controls. Postnatal renal evaluation should be considered in infants with severe oligohydramnios.

Macrocephaly-capillary malformation presenting with fetal arrhythmia.

Macrocephaly-capillary malformation (OMIM 602501) is a rare overgrowth and asymmetry syndrome. Cardiac arrhythmias were reported to occur in few patients. We present a case in which fetal arrhythmia was the presenting symptom of the syndrome.

Human milk versus formula feeding among preterm infants: short-term outcomes.

We evaluated short-term neonatal outcomes among preterm infants according to type of feeding administered (human milk or formula). Retrospective data were collected on 400 preterm infants at gestational age ≤32 weeks. Groups were chosen and compared according to feeding type. The premature infants who were fed human milk had lower gestational age and birth weight than those who were formula fed. Lower rates of necrotizing enterocolitis (NEC) were detected in the group of infants fed human milk (p = 0.044). Lower rates of retinopathy of prematurity (ROP) were detected in a subgroup of breast-fed infants born at 24 to 28 weeks' gestational age, but the results did not reach statistical significance using univariate analysis (p = 0.06). Using multivariate analysis, however, ROP stage III among this subgroup was significantly lower (p = 0.022). No differences were recorded for other neonatal complications such as infections or for growth parameters. The advantage of human milk feeding, found mainly among preterm infants with respect to rates of NEC and ROP, supports efforts to encourage mothers to feed their infants human milk.