The Ribavirin Pregnancy Registry: Findings after 5 years of enrollment, 2003–2009

INTRODUCTION : Ribavirin, with interferons or pegylated interferons, is used to treat chronic hepatitis C. Ribavirin is contraindicated in pregnancy (FDA Pregnancy Category X) and in men whose partners may become pregnant. In 2003, the Ribavirin Pregnancy Registry was established to monitor pregnancy exposures to ribavirin and to evaluate the potential human teratogenicity of prenatal exposure. METHODS : This voluntary registry enrolls pregnant women who have been exposed to ribavirin during pregnancy or during the six months prior to conception either directly, by taking ribavirin, or indirectly through sexual contact with a man taking ribavirin. Women are followed until delivery; live born infants are followed for one year. The Registry aims to enroll 131 live births following direct (maternal) exposure to ribavirin and 131 live births following indirect (male) exposures. RESULTS : After more than five years of operation, the Registry has enrolled 49 live births with direct exposure and 69 live births following indirect exposure. Six outcomes with birth defects have been reported. All were among live born infants: torticollis (2), hypospadias (1), polydactyly and a neonatal tooth (1), glucose‐6‐phosphate dehydrogenase deficiency (1), ventricular septal defect and cyst of 4th ventricle of the brain (1). Three received direct exposures ([6.1% (95% CI: 1.2, 16.9)], three were exposed indirectly [4.3% (95% CI: 0.9, 12.2)]. CONCLUSIONS : Although current enrollment is far short of the required sample size, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin. However, findings must be interpreted with caution concerning direct or indirect prenatal ribavirin exposures. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.     

Proffered Papers 10.30–11.15 Monday 15 September 2003 3 5 year outcome of women with borderline and mild dyskaryosis smears 3 5 year outcome of women with borderline and mild dyskaryosis smears

Aims

• 1 To identify the outcome status of women with borderline and mild dyskaryosis smears.
• 2 To determine whether the presence or absence of koilocytosis influences the outcome status.
• 3 To identify the proportion of women with borderline smears showing koilocytosis.

Materials and methods Borderline and mild dyskaryosis cervical smears diagnosed during January to March 1997 were identified from the laboratory database. Each slide was reviewed by two researchers independently, who then agreed a final consensus diagnosis. All slides were classified according to the presence or absence of koilocytosis. Slides were excluded from the study if the review diagnosis was negative, inadequate or high‐grade dyskaryosis. The outcome status was classified according to the worst lesion identified histologically and/or cytologically during the 5‐year follow‐up period. Results 1974 women were identified with borderline or mild dyskaryosis cervical smears of which 1597 were included in the study. Table 1 shows the outcome status of these women.

Table 1. . The outcome status of these women

Applying the light : nutrient hypothesis to stream periphyton

1. The light : nutrient hypothesis (LNH) states that algal nutrient content is determined by the balance of light and dissolved nutrients available to algae during growth. Light and phosphorus gradients in both laboratory and natural streams were used to examine the relevance of the LNH to stream periphyton. Controlled gradients of light (12–426 μmol photons m^?2 s^?1) and dissolved reactive phosphorus (DRP, 3–344 μg L^?1) were applied experimentally to large flow‐through laboratory streams, and natural variability in canopy cover and discharge from a wastewater treatment facility created gradients of light (0.4–35 mol photons m^?2 day^?1) and DRP (10–1766 μg L^?1) in a natural stream. 2. Periphyton phosphorus content was strongly influenced by the light and DRP gradients, ranging from 1.8 to 10.7 μg mg AFDM^?1 in the laboratory streams and from 2.3 to 36.9 μg mg AFDM^?1 in the natural stream. Phosphorus content decreased with increasing light and increased with increasing water column phosphorus. The simultaneous effects of light and phosphorus were consistent with the LNH that the balance between light and nutrients determines algal nutrient content. 3. In experiments in the laboratory streams, periphyton phosphorus increased hyperbolically with increasing DRP. Uptake then began levelling off around 50 μg L^?1. 4. The relationship between periphyton phosphorus and the light : phosphorus ratio was highly nonlinear in both the laboratory and natural streams, with phosphorus content declining sharply with initial increases in the light : phosphorus ratio, then leveling off at higher values of the ratio. 5. Although light and DRP both affected periphyton phosphorus content, the effects of DRP were much stronger than those of light in both the laboratory and natural streams. DRP explained substantially more of the overall variability in periphyton phosphorus than did light, and light effects were evident only at lower phosphorus concentrations (≤25 μg L^?1) in the laboratory streams. These results suggest that light has a significant negative effect on the food quality of grazers in streams only under a limited set of conditions.     

Proffered papers 9.30–10.00 Monday 15 September 2003 2 Clinicopathologic significance of the ‘borderline nuclear change – high grade dyskaryosis not excluded’ report

Both the original Bethesda system and the current UK classifications of cervical cytology have proved robust but each has a major weakness in the area of abnormalities of uncertain significance. Cytologists recognize that sometimes it is simply impossible to differentiate between reactive and dyskaryotic material. For this reason, the Australian version of the Bethesda system introduced a new category of ‘high grade inconclusive’ with a recommendation for referral to colposcopy. Approximately 60% of such cases are found to have high grade lesions at colposcopy (Schoolland M, Sterrett G, Knowles S et al.). The present UK system even with the proposed changes requires of the pathologist, a decision as to whether such cases are probably high grade (=a report of moderate dyskaryosis) or not (= a report of borderline). This continues to ignore the fact that sometimes you just cannot tell, even on review. We have taken a consecutive series of 50 referral smears, reported as moderate dyskaryosis, where the histological outcome (by loop cone) is known. These cases were rescreened and then reviewed blind by a pathologist with extensive experience of the Australian NH & MRC modified Bethesda system. On review, the material was reclassified along NH & MRC lines. The results were compared with the biopsy findings in order to determine whether the category of ‘inconclusive’ might be of value in the context of the NHSCSP.