Ectodermal markers of early developmental impairment in very preterm individuals

Abstract

Individuals born very preterm (before 33 weeks' gestation; VPT) are at risk of life-long, neurological impairments, behavioural and other health problems. It is not clear whether these neurodevelomental abnormalities originate prenatally, postnatally or a combination of both. Dermatoglyphics are stable ectodermal markers of neurodevelopmental disruption in the early prenatal period, as it has previously been reported in neuropsychiatric disorders such as schizophrenia or bipolar disorder. We have analyzed the dermatoglyphic variable total a–b ridge count (TABRC), which is a sensitive marker of ectodermal disruption during the first 24 weeks of foetal development, in 142 very preterm (VPT) individuals and 64 term born young adults. The VPT group showed significantly lower TABRC than the term group, especially those individuals presenting very low birth weight (VLBW), considered a proxy for more extreme prenatal stress, as shown by a two-way Anova analysis. These individuals, at risk of brain abnormalities and behavioural impairments, may have undergone disturbances before preterm birth occurs and prior to the 24th week of gestation. Our results support that dermatoglyphics represent a suitable marker to detect ectodermal alterations which have occurred very early in the course of development, and point out the vulnerability of the immature brain during the first half of gestation which may have adverse health consequences later in life.

Introduction

Disruptions of neurodevelopment have been implicated in cognitive, neurological and behavioural impairments and neuropsychiatric illnesses. Individuals who are born before term are at risk of disruption of brain development, particularly of processes that are active at the time that premature birth occurs (Volpe, 2009). For example, neurogenesis, neural migration and gyrification, are ongoing between 24 and 32 gestational weeks (Huppi et al., 1995). Thus individuals born at or before 32 weeks (very preterm; VPT) are more likely to suffer cognitive and sensorimotor impairments than their term-born peers (Foulder-Hughes and Cooke, 2003, Powls et al., 1995) and do not tend to perform as well at school as term-born children (Saigal and Doyle, 2008). The survivors of very preterm birth show an excess of neurological and cognitive impairment (Bhutta and Anand, 2002, Allin et al., 2006b), as well as a variety of structural brain abnormalities in later life (Stewart et al., 1999). However, it is unclear whether the abnormalities found in very preterm individuals reflect neurodevelopmental events that take place in utero, post-natally or a combination of both.

Dermatoglyphics are ectodermally-derived skin structures present only in primates which are formed on the surface of palms and soles. Their complete formation, including the formation of both primary and secondary epidermal ridges, spans the 10th–24th week of foetal development (Okajima, 1975), which broadly corresponds to the second trimester of gestation.

The brain and the epidermis (with its dermatoglyphics) share a common ectodermal origin, and their formation results from a complex pathway which includes the interplay of genetically governed biological processes and a number of experiential/environmental factors (Capone, 1996). However, while the development of the central nervous system (CNS) may be protracted — at least into the 3rd decade in humans — dermatoglyphics are frozen after their formation by week 24, and subsequently remain unchanged for life representing stable markers for a specific period of prenatal life. Dermatoglyphic abnormalities have been reported in conditions having postulated neurodevelopmental aetiology, such as mental retardation of idiopathic origin, autism, schizophrenia or bipolar disorder (Hartin and Barry, 1979, Fañanás et al., 1996b, Gutierrez et al., 1998, Rosa et al., 2001). They are also found in foetal alcohol syndrome and congenital rubella syndrome, where they are directly related to in utero exposure to a disruptive environmental factor, resulting in global developmental delay and a wide range of later cognitive and behavioural problems (Purvis-Smith and Menser, 1972, Purvis-Smith et al., 1969, Wilber et al., 1993).

Total a–b ridge count (TABRC) is a palmar dermatoglyphic measure representing a metric count of ridges on the second interdigital area of the hand. It has lower heritability than other dermatoglyphic measures such as digital counts (Holt, 1968) and it can be influenced by environmental factors acting during its formation in the second trimester (Babler, 1978, Babler, 1991).

So far, TABRC studies have mainly been conducted in the field of schizophrenia research, that have found decreased TABRC in schizophrenia patients compared to controls (Fañanás et al., 1996a, Fañanás et al., 1996b, Rosa et al., 2000, Fearon et al., 2001), and especially in patients who had experienced obstetric complications or were of very low birth weight (less than 2500 g) (Bramon et al., 2005). A recent study found reduced TABRC only among schizophrenia patients of low birth weight (Fatjo-Vilas et al., 2008).

In the present work we aimed to evaluate the timing of neurodevelopmental insult in a cohort of individuals born before 33 weeks' gestation compared to a group of individuals born at term. We used TABRC, as a marker for prenatal neurodevelopmental disturbance during early-mid foetal development. We hypothesized that the VPT group would have a lower TABRC than the control group.