Rebekah Shallcross

The prevalence of neurodevelopmental disorders in children prenatally exposed to antiepileptic drugs

The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug treatments. A prospective cohort of women with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until 6 years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR 6.05, 95%CI 1.65 to 24.53, p=0.007) and in those exposed to polytherapy with sodium VPA (3/20, 15.0%; aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared with control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found among children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium VPA is a treatment option.

IQ at 6 years after in utero exposure to antiepileptic drugs A controlled cohort study

Objective: To delineate the risk to child IQ associated with frequently prescribed antiepileptic drugs. Methods: Children born to women with epilepsy (n = 243) and women without epilepsy (n = 287) were recruited during pregnancy and followed prospectively. Of these, 408 were blindly assessed at 6 years of age. Maternal and child demographics were collected and entered into statistical models. Results: The adjusted mean IQ was 9.7 points lower (95% confidence interval [CI] −4.9 to −14.6; p < 0.001) for children exposed to high-dose (>800 mg daily) valproate, with a similar significant effect observed for the verbal, nonverbal, and spatial subscales. Children exposed to high-dose valproate had an 8-fold increased need of educational intervention relative to control children (adjusted relative risk, 95% CI 8.0, 2.5–19.7; p < 0.001). Valproate at doses <800 mg daily was not associated with reduced IQ, but was associated with impaired verbal abilities (−5.6, 95% CI −11.1 to −0.1; p = 0.04) and a 6-fold increase in educational intervention (95% CI 1.4–18.0; p = 0.01). In utero exposure to carbamazepine or lamotrigine did not have a significant effect on IQ, but carbamazepine was associated with reduced verbal abilities (−4.2, 95% CI −0.6 to −7.8; p = 0.02) and increased frequency of IQ <85. Conclusions: Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine.

Child development following in utero exposure Levetiracetam vs sodium valproate

Objective: Children born to women with epilepsy (WWE), exposed in utero to levetiracetam (LEV, n = 51), were assessed for early cognitive development and compared to children exposed to sodium valproate in utero (VPA, n = 44) and a group of children representative of the general population (n = 97). Methods: Children were recruited prospectively from 2 cohorts in the United Kingdom and assessed using the Griffiths Mental Development Scale (1996), aged <24 months. Information regarding maternal demographics were collected and controlled for. This is an observational study with researchers not involved in the clinical management of the WWE. Results: On overall developmental ability, children exposed to LEV obtained higher developmental scores when compared to children exposed to VPA (p < 0.001). When compared, children exposed to LEV did not differ from control children (p = 0.62) on overall development. Eight percent of children exposed to LEV in utero fell within the below average range (DQ score of <84), compared with 40% of children exposed to VPA. After controlling for maternal epilepsy and demographic factors using linear regression analysis, exposure to LEV in utero was not associated with outcome (p = 0.67). Conversely, when compared with VPA exposure, LEV exposure was associated with higher scores for the overall developmental quotient (p < 0.001). Conclusion: Children exposed to LEV in utero are not at an increased risk of delayed early cognitive development under the age of 24 months. LEV may therefore be a preferable drug choice, where appropriate, for WWE prior to and of childbearing age.

In utero exposure to levetiracetam vs valproate Development and language at 3 years of age

Objective: To compare the cognitive and language development of children born to women with epilepsy (WWE) exposed in utero to levetiracetam (LEV) or sodium valproate (VPA) and control children born to women without epilepsy not taking medication during pregnancy. Methods: The children, aged between 36 and 54 months, were recruited from the United Kingdom and assessed using the Griffiths Mental Development Scales and the Reynell Language Development Scale. Maternal demographic and epilepsy information was also collected for use in statistical regression. This is an observational study with researchers not involved in the clinical management of the mothers enrolled. Results: After controlling for confounding variables, children exposed to LEV in utero (n = 53) did not differ from unexposed control children (n = 131) on any scale administered. Children exposed to VPA (n = 44) in utero scored, on average, 15.8 points below children exposed to LEV on measures of gross motor skills (95% confidence interval [CI] −24.5 to −7.1, p < 0.001), 6.4 points below on comprehension language abilities (95% CI −11.0 to −1.8, p = 0.005), and 9.5 points below on expressive language abilities (95% CI −14.7 to −4.4, p < 0.001). Conclusion: The current study indicates that children exposed to LEV in utero were superior in their language and motor development in comparison to children exposed to VPA. This information should be used collaboratively between health care professionals and WWE when deciding on womens preferred choice of antiepileptic drug.

Cognition in school-age children exposed to levetiracetam, topiramate, or sodium valproate

Objective: To investigate the effects of prenatal exposure to monotherapy levetiracetam, topiramate, and valproate on child cognitive functioning. Methods: This was a cross-sectional observational study. Children exposed to monotherapy levetiracetam (n = 42), topiramate (n = 27), or valproate (n = 47) and a group of children born to women who had untreated epilepsy (n = 55) were enrolled retrospectively from the UK Epilepsy and Pregnancy Register. Assessor-blinded neuropsychological assessments were conducted between 5 and 9 years of age. Information was collected on demographic and health variables and adjusted for in multiple regression analyses. Results: In the adjusted analyses, prenatal exposure to levetiracetam and topiramate were not found to be associated with reductions in child cognitive abilities, and adverse outcomes were not associated with increasing dose. Increasing dose of valproate, however, was associated with poorer full-scale IQ (−10.6, 95% confidence interval [CI] −16.3 to −5.0, p < 0.001), verbal abilities (−11.2, 95% CI −16.8 to −5.5, p < 0.001), nonverbal abilities (−11.1, 95% CI −17.3 to −4.9, p < 0.001), and expressive language ability (−2.3, 95% CI −3.4 to −1.6, p < 0.001). Comparisons across medications revealed poorer performance for children exposed to higher doses of valproate in comparison to children exposed to higher doses of levetiracetam or topiramate. Conclusions: Preconception counseling should include discussion of neurodevelopmental outcomes for specific treatments and their doses and women should be made aware of the limited nature of the evidence base for newer antiepileptic drugs.

Women’s Subjective Experiences of Living with Vulvodynia: A Systematic Review and Meta-Ethnography

Vulvodynia, the experience of an idiopathic pain in the form of burning, soreness, or throbbing in the vulval area, affects around 4–16% of the population. The current review used systematic search strategies and meta-ethnography as a means of identifying, analyzing, and synthesizing the existing literature pertaining to women’s subjective experiences of living with vulvodynia. Four key concepts were identified: (1) Social Constructions: Sex, Women, and Femininity: Women experienced negative consequences of social narratives around womanhood, sexuality, and femininity, including the prioritization of penetrative sex, the belief that it is the role of women to provide sex for men, and media portrayals of sex as easy and natural. (2) Seeking Help: Women experienced the healthcare system as dismissive, sometimes being prescribed treatments that exacerbated the experience of pain. (3) Psychological and Relational Impact of Vulvodynia: Women experienced feeling shame and guilt, which in turn led to the experience of psychological distress, low mood, anxiety, and low self-esteem. Moreover, women reported feeling silenced which in turn affected their heterosexual relationships and their peer relationships by feeling social isolated. (4) A Way Forward: Women found changing narratives, as well as group and individual multidisciplinary approaches, helpful in managing vulvodynia. The findings of the review conclude that interventions at the individual level, as well as interventions aimed at equipping women to challenge social narratives, may be helpful for the psychological well-being of women with vulvodynia.

Women’s Experiences of Vulvodynia: An Interpretative Phenomenological Analysis of the Journey Toward Diagnosis

Vulvodynia is the experience of idiopathic pain characterized by burning, soreness, or throbbing in the external female genitalia or vulva and is estimated to be experienced by 4–16% of the female population, yet only half of women seek help regarding their symptoms. Of the women who do seek help, only around 2% obtain a diagnosis. Therefore, the aim of the current study was to explore the experiences of women with vulvodynia on their journey toward diagnosis, by using semi-structured interviews and an interpretative phenomenological analysis (IPA) methodology. Eight women were interviewed, and their experiences were analyzed and interpreted into three master themes, each with constituent sub-themes: (1) The Journey Is a Battle, (2) “What Is Vulvodynia?”: Ambivalence Toward Diagnosis, and (3) Patriarchy, Women, and Sex. Overall, women perceived a healthcare system which was dismissive and shaming, with an inadequate knowledge of vulvodynia. This in turn impacted on women’s psychological well-being. Psychological understanding, one-to-one therapy, and consultation and training for healthcare professionals may help to improve the psychological well-being of women with vulvodynia.