Strong associations between neural tube defects (NTDs) and monozygotic (MZ) twinning have long been noted, and it has been suggested that NTD cases who do not present as MZ twins may be the survivors of MZ twinning events. We have recently shown that MZ twins carry a strong, distinctive DNA methylation signature and have developed an algorithm based on genomewide DNA methylation array data that distinguishes MZ twins from dizygotic twins and other relatives at well above chance level. We have applied this algorithm to published methylation data from five fetal tissues (placental chorionic villi, kidney, spinal cord, brain and muscle) collected from spina bifida cases (n = 22), anencephalic cases (n = 15) and controls (n = 19). We see no difference in signature between cases and controls, providing no support for a common etiological role of MZ twinning in NTDs. The strong associations therefore continue to await elucidation.

Objectives: Fluency is a major problem for individuals with neurodevelopmental disorders, including fluency deficits for academic skills. The aim of this study was to determine neurocognitive predictors of academic fluency within and across domains of reading, writing, and math, in children and adults, with and without spina bifida. In addition to group differences, we expected some neurocognitive predictors (reaction time, inattention) to have similar effects for each academic fluency outcome, and others (dexterity, vocabulary, nonverbal reasoning) to have differential effects across outcomes. Methods: Neurocognitive predictors were reaction time, inattention, dexterity, vocabulary, and nonverbal reasoning; other factors included group (individuals with spina bifida, n=180; and without, n=81), age, and demographic and untimed academic content skill covariates. Univariate and multivariate regressions evaluated hypotheses. Results: Univariate regressions were significant and robust (R2=.78, .70, .73, for reading, writing, and math fluency, respectively), with consistent effects of covariates, age, reaction time, and vocabulary; group and group moderation showed small effect sizes (<2%). Multivariate contrasts showed differential prediction across academic fluency outcomes for reaction time and vocabulary. Conclusions: The novelty of the present work is determining neurocognitive predictors for an important outcome (academic fluency), within and across fluency domains, across population (spina bifida versus typical), over a large developmental span, in the context of well-known covariates. Results offer insight into similarities and differences regarding prediction of different domains of academic fluency, with implications for addressing academic weakness in spina bifida, and for evaluating similar questions in other neurodevelopmental disorders. (JINS, 2019, 25, 249–265)

The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case–control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0·48 in the first period, and 0·53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan.

We compared neuropsychological profiles in children with shunted hydrocephalus secondary to aqueductal stenosis (AS), a rare form of congenital hydrocephalus, and spina bifida myelomeningocele (SBM), a common form of congenital hydrocephalus. Participants were 180 children with shunted hydrocephalus grouped according to etiology: SBM (n = 151), AS (n = 29), and typically developing (TD; n = 60) individuals. The group with AS performed below the TD group on all tasks except for reading, and their overall performance was higher than the group with SBM, who had the lowest performance in the sample. Both clinical groups significantly differed from the TD group on tasks of spatial function, concept formation, motor function, and memory. Performance of the subgroup of AS children with normal cerebellum status approximated that of the TD group, while those with cerebellar anomalies performed lower than others with AS. Cerebellar abnormalities (present in the whole SBM group and in a subset of the AD group) are associated with more compromise of cognitive as well as motor function. (JINS, 2012, 18, 1–10)

Neurodevelopmental disorders such as spina bifida meningomyelocele (SBM) are often associated with dysrhythmic movement. We studied rhythm discrimination in 21 children with SBM and in 21 age-matched controls, with the research question being whether both groups showed a strong-meter advantage whereby rhythm discrimination is better for rhythms with a strong-meter, in which onsets of longer intervals occurred on the beat, than those with a weak-meter, in which onsets of longer intervals occurred off the beat. Compared to controls, the SBM group was less able to discriminate strong-meter rhythms, although they performed comparably in discriminating weak-meter rhythms. The attenuated strong-meter advantage in children with SBM shows that their rhythm deficits occur at the level of both perception and action, and may represent a central processing disruption of the brain mechanisms for rhythm. (JINS, 2009, 15, 521–528.)

This review proposes a new taxonomy of automatic and controlled attention. The taxonomy distinguishes among the role of the attendee (puppet and robot, critic and actor), the attention process (stimulus orienting vs. response control), and the attention operation (activation vs. inhibition vs. adjustment), and identifies cognitive phenotypes by which attention is overtly expressed. We apply the taxonomy to four childhood attention disorders: attention deficit hyperactivity disorder, spina bifida meningomyelocele, traumatic brain injury, and acute lymphoblastic leukemia. Variations in attention are related to specific brain regions that support normal attention processes when intact, and produce disordered attention when impaired. The taxonomy explains group differences in behavioral inattention, hyperactivity, and impulsiveness, as well as medication response. We also discuss issues relevant to theories of the cognitive and neural architecture of attention: functional dissociations within and between automatic and controlled attention; the relative importance of type of brain damage and developmental timing to attention profile; cognitive-energetic models of attention and white matter damage; temporal processing deficits, attention deficits and cerebellar damage; and the issue of cognitive phenotypes as candidate endophenotypes. (JINS, 2008, 14, 673–690.)

Reading and writing were studied in 31 young adults with spina bifida and hydrocephalus (SBH). Like children with this condition, young adults with SBH had better word decoding than reading comprehension, and, compared to population means, had lower scores on a test of writing fluency. Reading comprehension was predicted by word decoding and listening comprehension. Writing was predicted by fine motor finger function, verbal intelligence, and short-term and working memory. These findings are consistent with cognitive models of reading and writing. Writing, but not reading, was related to highest level of education achieved and writing fluency predicted several aspects of functional independence. Reading comprehension and writing remain deficient in adults with SBH and have consequences for educational attainments and functional independence. (JINS, 2004, 10, 655–663.)

In a large population-based study in Northern Ireland during the period 1974-1979, the rate of anencephalus in twins (9.1/10,000) was found to be less than that in singletons (24.3/10,000). This finding is in contrast with most other studies and the possibility of underascertainment of twin cases is considered, but it is concluded that chance is the likeliest explanation. The rate of spina bifida in twins (36.4/10,000) was similar to that in singletons (31.9/10,000). All of the twins with anencephalus were female and from pairs of like sex. Rates of spina bifida in twins from pairs of the two sex types were similar but, unusually, there was a male preponderance. As in previous studies, the great majority of twins with NTDs had unaffected cotwins.

Selective feticide by fetoscopic air embolism was carried out in six twin pregnancies complicated by discordance for a severe abnormality. In three, a previous diagnostic fetoscopy had been performed. The procedure was effective and uncomplicated in all cases. One patient is undelivered and five have delivered healthy babies, three at term and two preterm. One of the latter, delivered at 28 weeks, died of complications in the neonatal period.

Accurate, unbiased malformation rates in twins must be obtained unselectively from population-based studies that include livebirths and stillbirths after a thorough ascertainment of cases. This type of study was conducted in Los Angeles County, California, where 28 twins with a neural tube defect (NTD) were identified. The prevalence in twins (1.6/1,000) was significantly higher than in singletons (1.1/1,000). The study then was expanded to include population-based data from the Medical Birth Registry of Norway which has a comparable overall NTD prevalence (1.0/1,000) and twinning rate (2%). The combined material shows a higher prevalence of anencephaly and encephalocele but not of spina bifida in twins compared to singletons. The male/female ratios in total twin and singleton cases were comparable (0.8), but varied by specific defect. Like-sex twin females appeared at highest risk for NTD as well as for fetal death.

This study supports theories which associate NTDs with monozygotic twins, either through developmental disruptions that cause susceptibility to environmental agents or through a common etiology. Furthermore, it suggests that twins and singletons differ in their response to etiologic factors for the development of NTDs and that the development of each type of NTD may be related to different factors.