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Ectodermal markers of early developmental impairment in very preterm individuals
Psychiatry Research 200 (2012) 715–718
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Ectodermal markers of early developmental impairment in very preterm individuals Nadia Vilahur a, Matthew P.G. Allin b, Muriel Walshe b, Chiara Nosarti b, Larry Rifkin b, Robin M. Murray b, Araceli Rosa a,n a Unitat d0 Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), ´n Biome´dica en Red de Salud Mental (CIBERSAM), Avinguda Diagonal 643, 08028 Barcelona, Spain Centro de Investigacio b Department of Psychosis Studies, Biomedical Research Centre for Mental Health, Institute of Psychiatry and King’s College London, De Crespigny Park, London SE5 8AF, United Kingdom
a r t i c l e i n f o
abstract
Article history: Received 20 January 2012 Received in revised form 1 June 2012 Accepted 19 July 2012
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. & 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Prenatal markers Neurodevelopment Prenatal suffering Very preterm birth Very low birth weight Dermatoglyphics Total a–b ridge count
1. 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
n
Corresponding author. Tel.: þ34 93 402 14 61; fax: þ 34 93 403 57 40. E-mail address: [email protected] (A. Rosa).
0165-1781/$ - see front matter & 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2012.07.032
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
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conditions having postulated neurodevelopmental aetiology, such as mental retardation of idiopathic origin, autism, schizophrenia or ˜ana´s et al., 1996b; bipolar disorder (Hartin and Barry, 1979; Fan 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, 1991). So far, TABRC studies have mainly been conducted in the field of schizophrenia research, that have found decreased TABRC in ˜ana´s et al., schizophrenia patients compared to controls (Fan 1996a, 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.
2. Methods
two groups: (i) low birth weight (LBW) including 42 individuals with weights ranging from 1500 to 2500 g (mean birth weight¼ 1720.23 g, S.D.¼ 193.03, range¼ 1510–2590 g) and (ii) very low birth weight (VLBW), including 102 individuals of birth weight 1500 g or less (mean birth weight¼ 1155 g, S.D.¼ 203.38, range¼ 781–1490 g). The study was approved by the ethical committee of the Institute of Psychiatry. Written, informed consent was obtained from each participant. 2.2. Dermatoglyphic variables Palm prints were taken using an ink-less method (Prints Kit, PrintscanVerification Systems, Ltd., Printscan Distributorships, UK) for a total of 208 individuals, including 144 VPT and 64 controls. The dermatoglyphic analysis was conducted following the norms established by Cummins and Midlo (1943) by one of the authors (NV), with extensive prior experience and entirely blind to the status of the sample or any other relevant sociodemographic information. The a–b ridge count (ABRC) is a measure of the second interdigital area of the hand, consisting in the number of dermal ridges encompassing the hand surface between the bases of the index digit (trirradius a) and the bases of the medium digit (trirradius b) (Fig. 1). The dermatoglyphic variable analyzed was the total a–b ridge count (TABRC), which was determined by the sum of the ABRC in both hands, representing a quantitative variable with normal distribution across populations ˜ana´s et al., 1996a)). Although this dermatoglyphic (for further details, see Fan variable is partially genetically determined, one part of the morphology is determined by intrauterine environmental influences acting during ridge differentiation. TABRC was chosen because of the evidence of its sensitivity to the effect of disruptive environmental factors (Babler, 1978), and its simplification (reduction in the total ridge count) described in several brain related disorders. 2.3. Statistical analysis Analyses were performed using SPSS 17.0 software. Since the continuous variable TABRC was normally distributed, two-tailed ANOVA tests were performed for comparison of TABRC among independent groups of gestational length (Term versus VPT) and birth weight (Term, LBW and VLBW). Sex was included in all comparisons as a covariate to adjust for its effects and sex interactions were tested. The threshold level of significance was set at p value below 0.05 for all reported differences.
2.1. Sample
3. Results The sample, recruited as part of a longitudinal study of brain development and the long-term effects of preterm birth at the Institute of Psychiatry (London), consisted of 144 very preterm individuals (VPT), 72 females and 72 males, born before 33 weeks of gestation between 1979 and 1981, and admitted to the neonatal unit of University College Hospital (UCL, London) within five days of birth, as described elsewhere (Stewart et al., 1999). Sixty-four individuals born at term (between 38 and 42 weeks of gestation) represented the Term group and included 27 females and 37 males without a history of low birth weight or neurological illness (mean birth weight¼ 3588 g, S.D.¼164.03, range¼3200–4200 g). They were recruited by advertisement in the local (South London) and national press. Additionally, the detailed information about birth weight to the nearest gram was recorded for all the participants and allowed further division of the VPT group into
Complete data on the TABRC were available for 137 VPT individuals and 62 controls. Six individuals from the VPT group and one control were excluded from the analysis because the handprints were not sufficiently legible. Additionally, one control and one LBW individual were removed as outliers for TABRC, presenting a value 3 standard deviations above the mean for that variable. In the VPT group, mean birth weight did not significantly differ between males (1361 g, S.D.¼328) and females (1280 g, S.D.¼321) (t(1,142) ¼ 1.51, p¼ 0.13).
b a
Fig. 1. A right hand print. The palmar triradii a and b are located at the base of the index and middle finger (area amplified). The a–b ridge count is calculated by counting the number of epidermal ridges which cross a line drawn from the a to the b trirradius. The total a–b ridge count (TABRC) was determined by the sum of the ABRC in both hand.
N. Vilahur et al. / Psychiatry Research 200 (2012) 715–718
Table 1 Descriptive of the Total a–b ridge count (TABRC) by sex and overall among the different birth weight groups.
Males Females Overall
Term (42500 g) Mean (S.D.)
LBW (1500–2500 g) Mean (S.D.)
VLBW (o2500 g) Mean (S.D.)
86.29 (1.60) 90.25 (12.43) 88.40 (9.09)
86.27 (17.11) 84.32 (9.30) 85.90 (13.96)
80.94 (9.93) 78.45 (10.60) 79.68 (10.30)
Term: control group; LBW: low birth weight group; VLBW: very low birth weight group.
No significant sex differences were found for TABRC, in either the Term (p ¼0.35) or VPT groups (p¼0.15), although males had slightly higher TABRC means than females in the VPT group (VPT: males¼ 82.93, S.D. ¼12.84 and females¼80.09, S.D. ¼10.52) while in the Term groups the trend was in the opposite direction (Term: males¼ 86.29, S.D. ¼1.60 and females ¼91.14, S.D. ¼13.14). The VPT group had a significantly lower mean TABRC compared to the Term group after adjusting by sex (81.53, S.D.¼11.8 vs. 88.71, S.D.¼9.30 (F(1,148) ¼4.92, p¼0.02). VPT individuals were further classified into two groups according to birth weight: very low birth weight (VLBW, less than 1500 g) (n¼97) and low birth weight (LBW, between 1500 g and 2000 g) (n¼40), and compared to the Term group (n¼62). Two-way ANOVA including birth weight group and sex as main effects showed a significant birth weight group effect on the association with decreased TABRC (F(2,147) ¼6.58, p¼0.002) (VLBW: mean¼79.68, S.D.¼10.30; LBW: mean¼85.90, S.D.¼13.96; Term: mean¼ 88.40, S.D.¼ 9.09), while the main effect of sex was not statistically significant (F(2,147) ¼0.042, p¼0.838), neither was the interaction between birth weight group and sex (F(2,147) ¼0.58, p¼0.563). Post-hoc analyses with Bonferroni correction revealed a significant lower TABRC in the VLBW subgroup compared both to the LBW (p¼0.013) and the Term group (p¼0.02) respectively (Table 1). No differences in TABRC were found between LBW and Term groups (p40.05).
4. Discussion We have shown that individuals born VPT have lower total a–b ridge count than individuals born at term. This difference was accounted for by the VLBW individuals within the VPT group. This suggests that early intrauterine factors may be involved in the dermatoglyphic deviations described here but also to the reduced growth in utero of these individuals. Dermatoglyphic simplification (e.g.: lower total a–b ridge count) has been previously found in a number of studies among schizophrenic patients compared to controls and especially on those patients suffering obstetric complications or low birth weight (Bramon et al., 2005; Fatjo-Vilas et al., 2008). However, to the present author’s knowledge this is the first time that dermatoglyphics have been studied on healthy very preterm individuals. The embryology of dermatoglyphics is well established and the study of ‘‘fingerprints’’ of young foetuses has been used to better understand the biologic foundation of variation in dermatoglyphic traits. In a previous study of human foetuses derived from either spontaneous or elective abortions, Babler (1978) reported evidence of prenatal selection and dermatoglyphic patterns. He found that spontaneous abortuses without clinical indication of anatomical, chromosomal or morphological abnormalities had simpler dermatoglyphic patterns that ‘‘normal’’ foetuses derived from elective termination of pregnancy.
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Additionally, our results suggest that reduced TABRC is specific to VPT individuals who were also of very low birth weight. Since VLBW is likely to reflect restriction of growth in utero, this association with TABRC has faced validity. Further research should aim to clarify the causal pathways leading to low birth weight and prematurity. Both VPT birth and VLBW have been associated with the later appearance of developmental neuropsychiatric disorders such as schizophrenia (Cannon et al., 2002), and VPT young adults present different patterns of personality compared to term-born controls (Allin et al., 2006a). However, VPT individuals have not been followed up into adulthood so far, and the true risk of psychiatric or neurodevelopmental disorders among these individuals are not known yet. This would be a useful area for further longitudinal studies. It is commonly recognized, that there are maternal, foetal and genetic factors involved in the determination of birth weight (Goldenberg et al., 2008). These include poor gestational nutrition, low pre-pregnancy maternal weight, several maternal infections and high levels of psychological or social maternal stress (Sweet et al., 1987; Lobel et al., 1992; Copper et al., 1996; Cotch et al., 1997). Maternal smoking during pregnancy also has adverse effects on reproductive outcomes, including low birth weight and preterm delivery (Kramer, 1987; Suzuki et al., 2008). The effect of smoking habits during pregnancy extends until week 12 of gestation (Vardavas et al., 2010), and it has recently been shown that the effect of maternal smoking on birth weight could be influenced by polymorphic variants of two metabolic genes, suggesting a genetic–environmental interplay related to birth weight outcomes (Vogler and Kozlowski, 2002; Wang et al., 2002). Dermatoglyphic abnormalities provide valuable information about timing of brain development in which these anomalies have occurred during the gestational period. Reduced dermatoglyphic total ridge counts are present in other diseases such as cerebral palsy compared to controls (Simsek et al., 1998). Interestingly, a study involving data from 16 different European centres concludes that the risk for cerebral palsy, the most common neurodevelopmental disability of children in western Europe, is higher in infants of very low birth weight (Platt et al., 2007), and that risk is increased in extremely low birth weight infants (ELBW) (1000 g or less) (Laptook et al., 2005). These findings are consistent with the link that we have reported between ectodermic abnormalities and VLBW, and this is relevant considering the increasing rate of VLBW per 1000 live births in the last decade (Bell et al., 2004). The presence of TABRC abnormalities in VPT individuals also suggests that they may have neuroectodermal anomalies, which might in principle be detected by brain MRI. Research at present has focused on perinatal brain lesions as predictors of MRI outcome (Nosarti et al., 2008). It seems likely that VPT individuals who were also subjected to growth restriction in utero may have a ‘‘double hit’’ of a developmental lesion arising in utero plus brain injuries arising in the perinatal period. The long-term follow-up of these individuals will be important as neurodevelopmental consequences of VPT birth are likely to be life-long (Walshe et al., 2008). A potential weakness of this study is the lack of data about maternal exposure during the first semester of pregnancy to potential neurodisruptive agents (i.e., tobacco, alcohol consumption, infections during pregnancy, nutritional status, etc). That information would be interesting in order to elucidate possible causal agents underlying the altered dermatoglyphic patterns that we have observed in the very premature group especially in the cues for low birth weight. Our results highlight the interest of further dermatoglyphic studies in larger samples of very preterm individuals including other variables such as brain MRI and more detailed history of pregnancy.
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Finally, they support that dermatoglyphics represent a suitable marker of ectodermic alterations during early-mid gestation, which may have implications for further neurodevelopment as previously reported in neuropsychiatric disorders such as schizophrenia.
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Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Ectodermal markers of early developmental impairment in very preterm individuals Nadia Vilahur a, Matthew P.G. Allin b, Muriel Walshe b, Chiara Nosarti b, Larry Rifkin b, Robin M. Murray b, Araceli Rosa a,n a Unitat d0 Antropologia, Departament de Biologia Animal, Facultat de Biologia, Universitat de Barcelona, Institut de Biomedicina de la Universitat de Barcelona (IBUB), ´n Biome´dica en Red de Salud Mental (CIBERSAM), Avinguda Diagonal 643, 08028 Barcelona, Spain Centro de Investigacio b Department of Psychosis Studies, Biomedical Research Centre for Mental Health, Institute of Psychiatry and King’s College London, De Crespigny Park, London SE5 8AF, United Kingdom
a r t i c l e i n f o
abstract
Article history: Received 20 January 2012 Received in revised form 1 June 2012 Accepted 19 July 2012
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. & 2012 Elsevier Ireland Ltd. All rights reserved.
Keywords: Prenatal markers Neurodevelopment Prenatal suffering Very preterm birth Very low birth weight Dermatoglyphics Total a–b ridge count
1. 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
n
Corresponding author. Tel.: þ34 93 402 14 61; fax: þ 34 93 403 57 40. E-mail address: [email protected] (A. Rosa).
0165-1781/$ - see front matter & 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2012.07.032
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
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conditions having postulated neurodevelopmental aetiology, such as mental retardation of idiopathic origin, autism, schizophrenia or ˜ana´s et al., 1996b; bipolar disorder (Hartin and Barry, 1979; Fan 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, 1991). So far, TABRC studies have mainly been conducted in the field of schizophrenia research, that have found decreased TABRC in ˜ana´s et al., schizophrenia patients compared to controls (Fan 1996a, 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.
2. Methods
two groups: (i) low birth weight (LBW) including 42 individuals with weights ranging from 1500 to 2500 g (mean birth weight¼ 1720.23 g, S.D.¼ 193.03, range¼ 1510–2590 g) and (ii) very low birth weight (VLBW), including 102 individuals of birth weight 1500 g or less (mean birth weight¼ 1155 g, S.D.¼ 203.38, range¼ 781–1490 g). The study was approved by the ethical committee of the Institute of Psychiatry. Written, informed consent was obtained from each participant. 2.2. Dermatoglyphic variables Palm prints were taken using an ink-less method (Prints Kit, PrintscanVerification Systems, Ltd., Printscan Distributorships, UK) for a total of 208 individuals, including 144 VPT and 64 controls. The dermatoglyphic analysis was conducted following the norms established by Cummins and Midlo (1943) by one of the authors (NV), with extensive prior experience and entirely blind to the status of the sample or any other relevant sociodemographic information. The a–b ridge count (ABRC) is a measure of the second interdigital area of the hand, consisting in the number of dermal ridges encompassing the hand surface between the bases of the index digit (trirradius a) and the bases of the medium digit (trirradius b) (Fig. 1). The dermatoglyphic variable analyzed was the total a–b ridge count (TABRC), which was determined by the sum of the ABRC in both hands, representing a quantitative variable with normal distribution across populations ˜ana´s et al., 1996a)). Although this dermatoglyphic (for further details, see Fan variable is partially genetically determined, one part of the morphology is determined by intrauterine environmental influences acting during ridge differentiation. TABRC was chosen because of the evidence of its sensitivity to the effect of disruptive environmental factors (Babler, 1978), and its simplification (reduction in the total ridge count) described in several brain related disorders. 2.3. Statistical analysis Analyses were performed using SPSS 17.0 software. Since the continuous variable TABRC was normally distributed, two-tailed ANOVA tests were performed for comparison of TABRC among independent groups of gestational length (Term versus VPT) and birth weight (Term, LBW and VLBW). Sex was included in all comparisons as a covariate to adjust for its effects and sex interactions were tested. The threshold level of significance was set at p value below 0.05 for all reported differences.
2.1. Sample
3. Results The sample, recruited as part of a longitudinal study of brain development and the long-term effects of preterm birth at the Institute of Psychiatry (London), consisted of 144 very preterm individuals (VPT), 72 females and 72 males, born before 33 weeks of gestation between 1979 and 1981, and admitted to the neonatal unit of University College Hospital (UCL, London) within five days of birth, as described elsewhere (Stewart et al., 1999). Sixty-four individuals born at term (between 38 and 42 weeks of gestation) represented the Term group and included 27 females and 37 males without a history of low birth weight or neurological illness (mean birth weight¼ 3588 g, S.D.¼164.03, range¼3200–4200 g). They were recruited by advertisement in the local (South London) and national press. Additionally, the detailed information about birth weight to the nearest gram was recorded for all the participants and allowed further division of the VPT group into
Complete data on the TABRC were available for 137 VPT individuals and 62 controls. Six individuals from the VPT group and one control were excluded from the analysis because the handprints were not sufficiently legible. Additionally, one control and one LBW individual were removed as outliers for TABRC, presenting a value 3 standard deviations above the mean for that variable. In the VPT group, mean birth weight did not significantly differ between males (1361 g, S.D.¼328) and females (1280 g, S.D.¼321) (t(1,142) ¼ 1.51, p¼ 0.13).
b a
Fig. 1. A right hand print. The palmar triradii a and b are located at the base of the index and middle finger (area amplified). The a–b ridge count is calculated by counting the number of epidermal ridges which cross a line drawn from the a to the b trirradius. The total a–b ridge count (TABRC) was determined by the sum of the ABRC in both hand.
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Table 1 Descriptive of the Total a–b ridge count (TABRC) by sex and overall among the different birth weight groups.
Males Females Overall
Term (42500 g) Mean (S.D.)
LBW (1500–2500 g) Mean (S.D.)
VLBW (o2500 g) Mean (S.D.)
86.29 (1.60) 90.25 (12.43) 88.40 (9.09)
86.27 (17.11) 84.32 (9.30) 85.90 (13.96)
80.94 (9.93) 78.45 (10.60) 79.68 (10.30)
Term: control group; LBW: low birth weight group; VLBW: very low birth weight group.
No significant sex differences were found for TABRC, in either the Term (p ¼0.35) or VPT groups (p¼0.15), although males had slightly higher TABRC means than females in the VPT group (VPT: males¼ 82.93, S.D. ¼12.84 and females¼80.09, S.D. ¼10.52) while in the Term groups the trend was in the opposite direction (Term: males¼ 86.29, S.D. ¼1.60 and females ¼91.14, S.D. ¼13.14). The VPT group had a significantly lower mean TABRC compared to the Term group after adjusting by sex (81.53, S.D.¼11.8 vs. 88.71, S.D.¼9.30 (F(1,148) ¼4.92, p¼0.02). VPT individuals were further classified into two groups according to birth weight: very low birth weight (VLBW, less than 1500 g) (n¼97) and low birth weight (LBW, between 1500 g and 2000 g) (n¼40), and compared to the Term group (n¼62). Two-way ANOVA including birth weight group and sex as main effects showed a significant birth weight group effect on the association with decreased TABRC (F(2,147) ¼6.58, p¼0.002) (VLBW: mean¼79.68, S.D.¼10.30; LBW: mean¼85.90, S.D.¼13.96; Term: mean¼ 88.40, S.D.¼ 9.09), while the main effect of sex was not statistically significant (F(2,147) ¼0.042, p¼0.838), neither was the interaction between birth weight group and sex (F(2,147) ¼0.58, p¼0.563). Post-hoc analyses with Bonferroni correction revealed a significant lower TABRC in the VLBW subgroup compared both to the LBW (p¼0.013) and the Term group (p¼0.02) respectively (Table 1). No differences in TABRC were found between LBW and Term groups (p40.05).
4. Discussion We have shown that individuals born VPT have lower total a–b ridge count than individuals born at term. This difference was accounted for by the VLBW individuals within the VPT group. This suggests that early intrauterine factors may be involved in the dermatoglyphic deviations described here but also to the reduced growth in utero of these individuals. Dermatoglyphic simplification (e.g.: lower total a–b ridge count) has been previously found in a number of studies among schizophrenic patients compared to controls and especially on those patients suffering obstetric complications or low birth weight (Bramon et al., 2005; Fatjo-Vilas et al., 2008). However, to the present author’s knowledge this is the first time that dermatoglyphics have been studied on healthy very preterm individuals. The embryology of dermatoglyphics is well established and the study of ‘‘fingerprints’’ of young foetuses has been used to better understand the biologic foundation of variation in dermatoglyphic traits. In a previous study of human foetuses derived from either spontaneous or elective abortions, Babler (1978) reported evidence of prenatal selection and dermatoglyphic patterns. He found that spontaneous abortuses without clinical indication of anatomical, chromosomal or morphological abnormalities had simpler dermatoglyphic patterns that ‘‘normal’’ foetuses derived from elective termination of pregnancy.
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Additionally, our results suggest that reduced TABRC is specific to VPT individuals who were also of very low birth weight. Since VLBW is likely to reflect restriction of growth in utero, this association with TABRC has faced validity. Further research should aim to clarify the causal pathways leading to low birth weight and prematurity. Both VPT birth and VLBW have been associated with the later appearance of developmental neuropsychiatric disorders such as schizophrenia (Cannon et al., 2002), and VPT young adults present different patterns of personality compared to term-born controls (Allin et al., 2006a). However, VPT individuals have not been followed up into adulthood so far, and the true risk of psychiatric or neurodevelopmental disorders among these individuals are not known yet. This would be a useful area for further longitudinal studies. It is commonly recognized, that there are maternal, foetal and genetic factors involved in the determination of birth weight (Goldenberg et al., 2008). These include poor gestational nutrition, low pre-pregnancy maternal weight, several maternal infections and high levels of psychological or social maternal stress (Sweet et al., 1987; Lobel et al., 1992; Copper et al., 1996; Cotch et al., 1997). Maternal smoking during pregnancy also has adverse effects on reproductive outcomes, including low birth weight and preterm delivery (Kramer, 1987; Suzuki et al., 2008). The effect of smoking habits during pregnancy extends until week 12 of gestation (Vardavas et al., 2010), and it has recently been shown that the effect of maternal smoking on birth weight could be influenced by polymorphic variants of two metabolic genes, suggesting a genetic–environmental interplay related to birth weight outcomes (Vogler and Kozlowski, 2002; Wang et al., 2002). Dermatoglyphic abnormalities provide valuable information about timing of brain development in which these anomalies have occurred during the gestational period. Reduced dermatoglyphic total ridge counts are present in other diseases such as cerebral palsy compared to controls (Simsek et al., 1998). Interestingly, a study involving data from 16 different European centres concludes that the risk for cerebral palsy, the most common neurodevelopmental disability of children in western Europe, is higher in infants of very low birth weight (Platt et al., 2007), and that risk is increased in extremely low birth weight infants (ELBW) (1000 g or less) (Laptook et al., 2005). These findings are consistent with the link that we have reported between ectodermic abnormalities and VLBW, and this is relevant considering the increasing rate of VLBW per 1000 live births in the last decade (Bell et al., 2004). The presence of TABRC abnormalities in VPT individuals also suggests that they may have neuroectodermal anomalies, which might in principle be detected by brain MRI. Research at present has focused on perinatal brain lesions as predictors of MRI outcome (Nosarti et al., 2008). It seems likely that VPT individuals who were also subjected to growth restriction in utero may have a ‘‘double hit’’ of a developmental lesion arising in utero plus brain injuries arising in the perinatal period. The long-term follow-up of these individuals will be important as neurodevelopmental consequences of VPT birth are likely to be life-long (Walshe et al., 2008). A potential weakness of this study is the lack of data about maternal exposure during the first semester of pregnancy to potential neurodisruptive agents (i.e., tobacco, alcohol consumption, infections during pregnancy, nutritional status, etc). That information would be interesting in order to elucidate possible causal agents underlying the altered dermatoglyphic patterns that we have observed in the very premature group especially in the cues for low birth weight. Our results highlight the interest of further dermatoglyphic studies in larger samples of very preterm individuals including other variables such as brain MRI and more detailed history of pregnancy.
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Finally, they support that dermatoglyphics represent a suitable marker of ectodermic alterations during early-mid gestation, which may have implications for further neurodevelopment as previously reported in neuropsychiatric disorders such as schizophrenia.
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