Intra-uterine growth restriction and increased risk of hypertension in adult life: A follow-up study of 50-year-olds

OBJECTIVE:

To compare blood pressure between 50-year-old adults who were born at term (37-42 weeks of gestation) with intra-uterine growth restriction (IUGR; birth weight <10th centile) and a control group of similar age born at term without IUGR (birth weight =10th centile).

STUDY DESIGN:

Controlled comparative study.

METHODS:

Participants included 232 men and women who were born at the Royal Maternity Hospital, Belfast, a large regional maternity hospital in Northern Ireland, between 1954 and 1956. One hundred and eight subjects who were born with IUGR were compared with 124 controls with normal birth weight for gestation. The main outcome measures were systolic and diastolic blood pressure at approximately 50 years of age, measured according to European recommendations.

RESULTS:

The IUGR group had higher systolic and diastolic blood pressure than the control group: 131.5 [95% confidence interval (CI) 127.9-135.1] vs 127.1 (95% CI 124.3-129.2) mmHg and 82.3 (95% CI 79.6-85.0) vs 79.0 (95% CI 77.0-81.0) mmHg, respectively. After adjustment for gender, the differences between the groups were statistically significant: systolic blood pressure 4.5 (95% CI 0.3-8.7) mmHg and diastolic blood pressure 3.4 (95% CI 0.2-6.5) mmHg (both P < 0.05). More participants in the IUGR group were receiving treatment for high blood pressure compared with the control group [16 (15%) vs 11 (9%)], although this was not statistically significant. The proportion of subjects with blood pressure >140/90 mmHg or currently receiving antihypertensive treatment was 45% (n = 49) for the IUGR group, and 31% (n = 38) for the control group (odds ratio 1.9, 95% CI 1.1-3.3). Adjustment for potential confounders made little difference.

CONCLUSIONS:

IUGR is associated with higher blood pressure at 50 years of age. Individuals born with IUGR should have regular blood pressure screening and early treatment as required. Hypertension remains underdiagnosed and undertreated in adult life.

BRCA1 Immunohistochemical Staining as a Prognostic Indicator in Uterine Serous Carcinoma

OBJECTIVES: The objective of this study was to investigate the relationship between BRCA1 protein expression, as determined by immunohistochemistry, and clinical outcome in uterine serous carcinoma (USC). METHODS: A tissue microarray containing duplicate cores of 73 cases of USC was immunohistochemically stained with mouse anti-BRCA1 (Ab-1) mouse monoclonal (MS110) antibody. The cores were scored in a semiquantitative manner evaluating both the distribution and intensity of nuclear staining. BRCA1 protein expression was correlated with progression-free survival. RESULTS: Seventy-two of 73 cases were assessable, and there was a statistically significant decreased progression-free survival for those cases exhibiting tumor cell nuclei staining of 76% or greater (P = 0.0023). CONCLUSIONS: Our study illustrates that a low level of BRCA1 protein expression is a favorable prognostic indicator in USC, similar to what is observed in high-grade serous ovarian carcinoma. Further studies should focus on the BRCA1 status of USCs at a molecular level and also investigate whether BRCA1 protein expression is associated with response to chemotherapy in USC.

Comparison of Wavelet Transform and Time-Domain Analysis of Second Trimester Uterine Artery Doppler Waveforms in Screening for Pre-Eclampsia

The aim of this study was to compare time-domain waveform analysis of second-trimester uterine artery Doppler using the resistance index (RI) with waveform analysis using a mathematical tool known as wavelet transform for the prediction of pre-eclampsia (PE). This was a retrospective, nested case-cohort study of 336 women, 37 of whom subsequently developed PE. Uterine artery Doppler waveforms were analysed using both RI and waveform analysis. The utility of these indices in screening for PE was then evaluated using receiver operating characteristic curves. There were significant differences in uterine artery RI between the PE women and those with normal pregnancy outcome. After wavelet analysis, significant difference in the mean amplitude in wavelet frequency band 4 was noted between the 2 groups. The sensitivity for both Doppler RI and frequency band 4 for the detection of PE at a 10% false-positive rate was 45%. This small study demonstrates the application of wavelet transform analysis of uterine artery Doppler waveforms in screening for PE. Further prospective studies are needed in order to clearly define if this analytical approach to waveform analysis may have the potential to improve the detection of PE by uterine artery Doppler screening.

Commissioned Research on HPV Frequency in Cervical Cancers and Premalignant lesions of the Cervix

This report documents an investigation of the frequency of human papillomavirus (HPV) genotypes across cervical disease states in Northern Ireland ranging from koilocytosis to cervical cancer. It builds upon earlier work by the Northern Ireland HPV Working Group which reported a HPV prevalence of 17.1% overall in women aged 20-65 years irrespective of pathology and 13.2% among women in the screening age group (20-60 years) with normal cytology (Anderson et al. 2012, Anderson et al. 2013).

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre-malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16-93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche^® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high-risk (HR) HPV infection; 37.4% were positive for HPV-16 (n=684) and 5.1% for HPV-18 (n=93). HPV type-specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I-III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n=283), 34.1% CIN II (n=145), 18.7% of CIN III (n=146), 7.8% of SCC (n=5), and 35.7% of AC (n=5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR-HPV genotypes apart from 16 and 18, including HPV-45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines.

Regulación del promotor del gen de IL-10 por papilomavirus humano en células epiteliales transformadas derivadas de cervix

Tesis (Maestría en Ciencias con Especialidad en Inmunobiología) UANL

Prediction of hypertensive disorders in pregnancy by combined uterine artery Doppler, serum biomarkers and maternal characteristics

Objectif: Évaluer l'efficacité du dépistage de l’hypertension gestationnelle par les caractéristiques démographiques maternelles, les biomarqueurs sériques et le Doppler de l'artère utérine au premier et au deuxième trimestre de grossesse. Élaborer des modèles prédictifs de l’hypertension gestationnelle fondées sur ces paramètres. Methods: Il s'agit d'une étude prospective de cohorte incluant 598 femmes nullipares. Le Doppler utérin a été étudié par échographie transabdominale entre 11 +0 à 13 +6 semaines (1er trimestre) et entre 17 +0 à 21 +6 semaines (2e trimestre). Tous les échantillons de sérum pour la mesure de plusieurs biomarqueurs placentaires ont été recueillis au 1er trimestre. Les caractéristiques démographiques maternelles ont été enregistrées en même temps. Des courbes ROC et les valeurs prédictives ont été utilisés pour analyser la puissance prédictive des paramètres ci-dessus. Différentes combinaisons et leurs modèles de régression logistique ont été également analysés. Résultats: Parmi 598 femmes, on a observé 20 pré-éclampsies (3,3%), 7 pré-éclampsies précoces (1,2%), 52 cas d’hypertension gestationnelle (8,7%) , 10 cas d’hypertension gestationnelle avant 37 semaines (1,7%). L’index de pulsatilité des artères utérines au 2e trimestre est le meilleur prédicteur. En analyse de régression logistique multivariée, la meilleure valeur prédictive au 1er et au 2e trimestre a été obtenue pour la prévision de la pré-éclampsie précoce. Le dépistage combiné a montré des résultats nettement meilleurs comparés avec les paramètres maternels ou Doppler seuls. Conclusion: Comme seul marqueur, le Doppler utérin du deuxième trimestre a la meilleure prédictive pour l'hypertension, la naissance prématurée et la restriction de croissance. La combinaison des caractéristiques démographiques maternelles, des biomarqueurs sériques maternels et du Doppler utérin améliore l'efficacité du dépistage, en particulier pour la pré-éclampsie nécessitant un accouchement prématuré.