Porphyromonas gingivalis within Placental Villous Mesenchyme and Umbilical Cord Stroma Is Associated with Adverse Pregnancy Outcome

Intrauterine presence of Porphyromonas gingivalis (Pg), a common oral pathobiont, is implicated in preterm birth. Our aim was to determine if the location of Pg within placental and/or umbilical cord sections was associated with a specific delivery diagnosis at preterm delivery (histologic chorioamnionitis, chorioamnionitis with funisitis, preeclampsia, and preeclampsia with HELLP-syndrome, small for gestational age). The prevalence and location of Pg within archived placental and umbilical cord specimens from preterm (25 to 32 weeks gestation) and term control cohorts were evaluated by immunofluorescent histology. Detection of Pg was performed blinded to pregnancy characteristics. Multivariate analyses were performed to evaluate independent effects of gestational age, being small for gestational age, specific preterm delivery diagnosis, antenatal steroids, and delivery mode, on the odds of having Pg in the preterm tissue. Within the preterm cohort, 49 of 97 (51%) placentas and 40 of 97 (41%) umbilical cord specimens were positive for Pg. Pg within the placenta was significantly associated with shorter gestation lengths (OR 0.63 (95%CI: 0.48–0.85; p = 0.002) per week) and delivery via caesarean section (OR 4.02 (95%CI: 1.15–14.04; p = 0.03), but not with histological chorioamnionitis or preeclampsia. However, the presence of Pg in the umbilical cord was significantly associated with preeclampsia: OR 6.73 (95%CI: 1.31–36.67; p = 0.02). In the term cohort, 2 of 35 (6%) placentas and no umbilical cord term specimens were positive for Pg. The location of Pg within the placenta was different between preterm and term groups in that Pg within the villous mesenchyme was only detected in the preterm cohort, whereas Pg associated with syncytiotrophoblasts was found in both preterm and term placentas. Taken together, our results suggest that the presence of Pg within the villous stroma or umbilical cord may be an important determinant in Pg-associated adverse pregnancy outcomes.     

microRNA expression in the cervix during pregnancy is associated with length of gestation

Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified 6 miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2–1.5) days shorter on average (P = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.Key words: Cervix, delivery, gestational age, labor, microRNA, Pap smear, preterm     

Pap smear screening in women under 30 in the Norwegian Coordinated Cervical Cancer Screening Program, with a comparison of immediate biopsy vs Pap smear triage of moderate dysplasia

OBJECTIVE: Top provide population based estimates of Pap smear screening results among women under 30 and to compare the outcomes of 2 triage options for women under 30 with a moderate dysplastic Pap smear: immediate biopsy vs. Pap smear follow-up. STUDY DESIGN: All Pap smears, histologically verified cervical intraepithelial lesion (CIN) 2/3 and invasive cervical cancer in 1999-2002 from women in Norway under 30 in 2000-2002 were analyzed. Due to different triage recommendations in different laboratories, 836 women under 30 with a moderately dysplastic Pap smear were recommended for immediate biopsy, while 109 were recommended for a Pap smear within 6 months. Risk estimates for triage outcome were estimated by multinominal logistic regression. RESULTS: The prevalence of squamous intraepithelial lesion was highest around 20 years. The first moderate dysplasia was diagnosed at age 16, as was CIN 2/3. Of the women with Pap smear triage, one third were diagnosed with a CIN 2+ lesion, one third had a normal outcome, while the last third were in uncertain state 12 months later. Among those recommended for immediate biopsy, nearly 70% were diagnosed with a CIN 2+, thus having odds of 4.2 (95% CI 2.5-7.1) higher than did women with Pap smear triage of being diagnosed with CIN2+ 12 months later. CONCLUSION: The choice of triage has a profound impact on the proportion of young women diagnosed with CIN 2+ after a moderately dysplastic Pap smear.     

Value of histiocyte detection in Pap smears for predicting endometrial pathology. An institutional experience

OBJECTIVE: To determine the clinical implications of the finding of histiocytes in Pap smears in 1 patient population. STUDY DESIGN: The medical records and Pap smears which the presence of histiocytes was mentioned in the diagnosis between August 1996 and August 2001 were reviewed in conjunction with follow-up surgical findings. The positive predictive value (PPV) for significant endometrial pathology for the isolated finding of histiocytes on Pap smear was determined. RESULTS: Of the 238,225 women screened over a 60-month period, 325 were reported to have histiocytes in their Pap smears. Of them, 238 (73.2%) had subsequent endometrial sampling, hysterectomy or both, and follow-up Pap smears. Two hundred seven smears (87%) failed to disclose endometrial pathology. Thirty-one cases (13%) resulted in significant histopathologic findings, including 12 uterine malignancies, 8 endocervical polyps, 7 endometrial polyps, 2 submucosal leiomyomata, 1 simple hyperplasia without atypia and 1 case of tamoxifen-related changes. Upon review of the clinical records, 58% (18/31) of those patients had other significant clinical and/or cytologic findings. Five of the 18 patients (27.8%) had associated postmenopausal bleeding, 11 had additional abnormal Pap smear findings (atypical glandular cells, 6/18, or 33.3%; endometrial cells, 5/18, or 27.8%), and another 2 had both postmenopausal bleeding and atypical glandular cells (2/18, or 11.1%). The PPV for significant uterine pathology for women with the isolated finding of histiocytes on a Pap smear was 5.5% and 60% with additional clinical and/or Pap smear findings. The PPV for endometrial cancer was 1.3% in women with the isolated finding of histiocytes on a Pap smear but 20% for women with histiocytes and additional clinical/or Pap smear findings. CONCLUSION: Based on the findings of this study and recently published data, we conclude that the isolated finding of increased histiocytes in the absence of postmenopausal bleeding, endometrial cells or atypical glandular cells on a Pap smear is a poor indicator of uterine disease.     

Pap smear adequacy--is the assessing criterion including endocervical cells really valid?

The significance of endocervical cylindrical cells (EC) as a criterion of sample adequacy has been established on 1,000 patients by comparing VCE smears (vaginal, cervical, endocervical) with or without EC in relation to prevalence of abnormal cells, prevalence of histological diagnosed lesions and sensitivity and negative predictive value of Pap smear, as well as by comparison of negative findings without EC with control smears with the aim of discovering overlooked lesions. A considerably greater yield of cytological (107/536 in relation to 49/464) and histological (105/536 in relation to 55/464) (p < 0.05) abnormalities in smears with EC support the hypothesis that the presence of EC is strongly and positively associated with prevalence of disease. In contrast, the presence of EC predicts only a moderate improvement in Pap smear quality with a weaker effect on sensitivity (95% in relation to 80%). During two-years monitoring of patients with negative Pap smear and negative colposcopy (403 with EC and 390 without EC in smears), no positive cytology/histology diagnosis was made. Also, because the prevalence of missed lesions among negative Pap smears is extremely low in absolute terms, no appreciable impact on negative predictive value was observed (98.8% in relation to 97.3%).     

Cytology and clinical spectrum of sexually transmitted infections in Lebanese women as revealed by Pap smear: a cross-sectional study from 2002-2006

To study the cytology profile of cervical smears and the respective prevalence and incidence of certain cervico-vaginal infections detectable by routine Pap smear cytology in Lebanese women from 2002 to 2006. Pap smear cytology results were compiled from the archives of the Institut National de Pathologie for the period extending from 2002 until 2006. This study covered 118,230 cervical specimens obtained from Lebanese women attending clinics and hospitals in all the five districts of Lebanon; prevalence and incidence rates for infections detectable by routine Pap smear examination were determined. A rise in prevalence of these infections by 2.1 percent (2,555) from 2002 to 2006 was revealed. A doubling of Pap smears showing HPV-associated changes was detected (1.4 percent in 2002 to 2.9 percent in 2006), and a simultaneous almost 7-fold increase of Atypical Squamous Cells of Undetermined Significance (ASCUS) cytology was detected during this period; the rise in ASCUS cytology was age-dependent. Moreover, a 60 percent increase in prevalence of bacterial vaginosis (2.3 percent in 2002 to 3.7 percent in 2006) and a more than 3-fold decline in Trichomonas vaginalis infection (1 percent in 2002 to 0.3 percent in 2006) were also noted in this population during this period. An increase in the prevalence and incidence of cervico-vaginal infections detectable by Pap smear cytology in Lebanese women was revealed from 2002 to 2006. Such changes could point to recent modifications of sexual and health behaviours in the Lebanese community.     

Cervical cytology screening in Vietnamese asylum seekers in a Hong Kong detention center. Population demographics and historical perspectives

OBJECTIVE: To provide a brief review of the history and demographics of the Vietnamese asylum-seeking population in Hong Kong and their possible effects on the initiation of a cervical cytology screening program at a Hong Kong detention center. STUDY DESIGN: Analysis of case histories, questionnaires and interviews with women in a detention center identified demographic features related to Pap smear history, knowledge of the Pap test, age at first intercourse and cigarette smoking status among women aged 17 years and over. Analysis of Pap smear uptake following initiation of a screening program was undertaken. RESULTS: Of the 1,171 women in the detention center who were eligible for a Pap smear, 536 (45.8%) actually obtained one, although enrollment, which was strong at the initial offering, slowed considerably as the program progressed. None of the women had had a Pap smear prior to leaving Vietnam. Knowledge of the utility and risk status criteria for Pap testing was very limited. The majority (77.9%) of the subjects started sexual activity after age 20 years, and three (0.6%) smoked. There were four (0.2%) abnormal smears identified among those tested. CONCLUSION: Convincing evidence was obtained that the Pap test was not widely used in Vietnam among the asylum-seeking population, and its role in preventing cervical cancer was not well known to the women studied. The initial strong uptake of the Pap smear was not maintained. That may be attributable to psychosocial factors associated with detention under harsh conditions and trauma associated with fleeing Vietnam.     

Is a liquid‐based cytology more sensitive than a conventional Pap smear?

K. Sigurdsson
Is a liquid‐based cytology more sensitive than a conventional Pap smear? Background: The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial. Material and methods: This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC. Results: The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests. Conclusions: The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.     

Clinical value of repeat Pap smear at the time of colposcopy

OBJECTIVE: To determine the clinical value of a repeat (second) Pap smear at the time of colposcopy in the management of patients with recent cytologic abnormalities. STUDY DESIGN: A study of paired Pap smears and their corresponding cervical biopsies during a two-year period, commencing in June 1996, was undertaken. Pap smears and cervical biopsies from 614 patients were evaluated in the Department of Pathology, Royal Darwin Hospital, Northern Territory, Australia. To maintain uniformity, the cytologic and histologic findings were assessed according to the Bethesda System. RESULTS: The original (first) Pap smears included 288 high grade and 326 low grade lesions. The second smears showed 200 high grade, 221 low grade, 167 normal and 26 unsatisfactory cases. Punch biopsies revealed 242 high grade, 300 low grade and 72 inflammatory/reactive lesions. The changes noted in the second Pap smears and in the punch biopsies in the group originally diagnosed as having high grade disease were generally less advanced. The second Pap smears and corresponding cervical punch biopsies showed more advanced changes in the group originally diagnosed as having low grade disease. Removal of part of the abnormal epithelium during the first Pap smear and the desire of the colposcopist not to damage the surface epithelium prior to performing a cervical biopsy may account for some of these findings. Sampling errors and morphological misinterpretation may explain some of the findings. CONCLUSION: In the second smears, new cases of high grade abnormality were discovered mainly in patients with low grade changes on the first smears. Therefore, a second Pap smear at the time of colposcopy is justifiable in the group with low grade changes on the first smear.     

Cervical cytology screening history of women diagnosed with adenocarcinoma in situ of the cervix: a case-control study

OBJECTIVE: To determine whether women diagnosed with adenocarcinoma in situ (AIS) of the cervix are as well screened as healthy control women. STUDY DESIGN: A case-control study was performed (307 cases, 1,228 controls) within a statewide registry. Cases consisted of women diagnosed with AIS on histology between 1995 and 2001. Screening histories were compiled from registry records. Variables of interest included number of previous negative Pap smears, time interval since last negative Pap smear, median time between previous negative Pap smears, proportion of negative Pap smears with an endocervical component and history of cervical abnormality. RESULTS: Conditional logistic regression showed that cases and controls did not differ significantly in the number of previous negative smears or in the median time between previous negative smears. Decreasing time since last negative smear was protective against AIS, with controls more likely to have had a recent negative smear. There was no difference in the proportion of previous negative smears with an endocervical component between cases and controls; however, some complex temporal relationships were observed in the regression analysis. CONCLUSION: Women who are diagnosed with AIS have a screening history similar to that of healthy, control women. The findings are consistent with the concept that AIS is predominantly a screening-detected disease.     

Pap smears in women with endometrial carcinoma

OBJECTIVE: To correlate Pap smear findings with the histology of endometrial carcinoma and stage of the disease. STUDY DESIGN: Between 1995 and 1998, 76 women with endometrial carcinoma, having had Pap smears done within two to three months of hysterectomy at Memorial Sloan-Kettering Cancer Center, formed the basis for this study. All Pap smears and histologic sections were reviewed. RESULTS: Thirty-four patients had normal Pap smears (45%), and 42 had abnormal ones (55%). The mean age of the two groups was 65.1 and 65.2 years, respectively. Histologic subtypes included 44 International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid adenocarcinoma (low grade) and 32 high grade carcinomas, including 19 FIGO grade 2 or 3 endometrioid adenocarcinomas, 5 papillary serous carcinomas (PSC), 2 clear cell carcinomas (CC), 1 adenosquamous carcinoma, 3 endometrioid adenocarcinomas mixed with PSC and 2 endometrioid adenocarcinomas mixed with CC. The proportions of patients with low and high grade tumors with abnormal Pap smears were 43% (19/44) and 72% (23/32), respectively (P=.01). The proportions of patients with abnormal Pap smears and no myometrial invasion, invasion of <50% and >50% myometrial thickness were 40% (8/20), 62% (26/42) and 57% (8/14), respectively (P =.27). Vascular invasion was identified in 56% (9/16) of patients with abnormal Pap smears and in 55% (33/60) of patients with normal ones (P = .93). The proportions of patients having abnormal Pap smears with stage I and stages II, III or IV disease were 48% (30/62) and 86% (12/14), respectively (P =.01). CONCLUSION: Although the Pap smear is not a sensitive screening test for endometrial cancer and a negative Pap smear does not rule it out, this study revealed that abnormal Pap smears are significantly associated with high grade of tumor and stage II-IV endometrial carcinoma. However, they are not associated with patient age, depth of myometrial invasion or vascular invasion.     

Collagen balls in cervical smears. A previously undescribed finding

OBJECTIVE: To evaluate several conventional cervical smears obtained from women undergoing routine screening for cervical dysplasia or carcinoma and whose smears contained structures resembling collagen balls. STUDY DESIGN: Between 1995 and 1998, cervical smears containing collagen balls were analyzed. The clinical histories of the patients whose smears contained collagen balls, including the gestational history, were reviewed. Histopathologic material from any related surgical specimens was reviewed, with special attention to mesothelial surfaces. RESULTS: Collagen balls were found in 5 of 77,891 Pap smears examined (0.006%). None of the patients had evidence of neoplasms of the genital tract. One of the patients was in the first trimester of pregnancy. CONCLUSION: We suggest that collagen balls in cervical smear originate in mesothelium-covered organs, from where they are transported via the fallopian tubes into the uterine cavity. Their significance lies in their being mistaken for mucin-distended cells exfoliated from a neoplasm or from detached fragments of a papillary ovarian neoplasm.     

Opportunistic testing of medically underserved women for cervical cancer in South Africa

OBJECTIVE: To determine the yield of opportunistic Pap smears taken in an unscreened and medically underserved population in the Transkei Region of South Africa. STUDY DESIGN: Cross-sectional study of 22,160 cervical cytology specimens from an unscreened population attending gynecologic outpatient clinics between January 1990 and December 1996. RESULTS: The overall prevalence of atypical squamous cells of uncertain significance (ASCUS), low grade squamous intraepithelial lesions (LSIL) and high grade squamous intraepithelial lesions (HSIL) was, respectively, 34.7%, 8.3% and 2.4%. The ASCUS: SIL ratio was 3:1. The prevalence of invasive squamous cell carcinoma was 1.6%. The yield of opportunistic Pap smears was 10.7% including only LSIL and HSIL. CONCLUSION: The pathologic process of precursor lesions of cervical cancer appears to start at an early age since > 20% of cases are diagnosed before the age of 30 years. In the absence of a national screening program, opportunistic testing of medically underserved women needs to be maintained and encouraged.     

Acute Histologic Chorioamnionitis Is a Risk Factor for Adverse Neonatal Outcome in Late Preterm Birth after Preterm Premature Rupture of Membranes

Background

The objective of this study was to determine whether acute histologic chorioamnionitis is associated with adverse neonatal outcomes in late preterm infants who were born after preterm PROM.

Methodology/Principal Findings

The relationship between the presence of acute histologic chorioamnionitis and adverse neonatal outcome was examined in patients with preterm PROM who delivered singleton preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Nonparametric statistics were used for data analysis. The frequency of acute histologic chorioamnionitis was 24% in patients with preterm PROM who delivered preterm newborns between 34 weeks and 36 6/7 weeks of gestation. Newborns born to mothers with histologic chorioamnionitis had significantly higher rates of adverse neonatal outcome (74% vs 51%; p<0.005) than those without histologic chorioamnionitis. This relationship remained significant after adjustment for gestational age at preterm PROM, gestational age at delivery, and exposure to antenatal corticosteroids.

Conclusions/Significance

The presence of acute histologic chorioamnionitis is associated with adverse neonatal outcome in late preterm infants born to mothers with preterm PROM.     

Knowledge and acceptability of pap smears, self-sampling and HPV vaccination among adult women in Kenya

Objectives

Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies.

Methods

Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit.

Results

Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost.

Conclusions

These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.     

Maternal diabetes and congenital anomalies in South Australia 1986-2000: a population-based cohort study

BACKGROUND: This study examined the risk of congenital anomalies in infants born in South Australia to women with maternal diabetes in a population-based cohort study of births over a 15-year period, 1986-2000. Differences in the reporting, recording, and diagnosis of pre-existing diabetes mellitus, gestational diabetes mellitus, and impaired glucose tolerance make comparisons between studies difficult. In order to compare published research, details of research methods and analytic approaches are required to understand the potential confounding, bias, and effect modification that may occur. METHODS: Data on congenital anomalies from the South Australian Birth Defects Register were linked to birth data from the Pregnancy Outcome Statistics Unit of the South Australian Department of Health. This enabled information on congenital anomalies to be linked to pregnancy details, including diabetes status. RESULTS: Between 1986 and 2000, the prevalence of congenital anomalies in the infants of mothers with pre-existing diabetes mellitus, gestational diabetes mellitus, or impaired glucose tolerance was significantly higher than in the total population; relative risk = 2.01 (1.66-2.43) and 1.19 (1.08-1.31), respectively. This increased prevalence was not modified by adjustments for maternal age, ethnicity, or other demographic factors, nor did the rate change over the 15 years of the study period. CONCLUSIONS: The prevalence of congenital anomalies was found to be significantly higher in the infants of mothers with maternal diabetes. Larger population-based studies are needed to determine which anomalies are involved and how their occurrence can be reduced.     

Medical records vs. interview responses: a comparative analysis of selected variables for linked birth defect cases

BACKGROUND: Data pertaining to birth defects are subject to certain limitations depending on the collection method. This study compares the agreement of data from medical records and maternal interviews. METHODS: The medical records and maternal interviews were linked for 1017 deliveries. Prevalence, concordance and kappa coefficients were calculated for maternal gestational and non-gestational diabetes, insulin use, seizures/epilepsy, Hispanic ethnicity, and infant/fetus sex. RESULTS: The prevalence of non-gestational diabetes was 4.3% in the medical records and 3.4% in the maternal interviews, with 98.1% agreement. The prevalence of gestational diabetes was 7.9% in medical records and 9.2% in maternal interviews, with 94.3% agreement. Similar prevalences and high levels of agreement were observed between the two systems for infant/fetus sex and mother's Hispanic ethnicity. Although high concordance was observed for seizures/epilepsy, kappa value was moderate. CONCLUSIONS: The availability of two distinct sources of data provides an exceptional opportunity to compare and validate both data sources. We found that the data for certain variables from maternal interviews strongly agreed with information from medical records. However, the extent of that agreement depended on the type of variable measured. Our results suggest that for some variables such as demographic variables, researchers can use either of the two data sources.     

CIN 2/3 and cervical cancer after an ASCUS pap smear. A 7-year, prospective study of the Norwegian population-based, coordinated screening program

OBJECTIVE: To estimate the risk of being diagnosed with cervical intraepithelial neoplasia (CIN) 2/3 or invasive cervical cancer (ICC) based on diagnostic and screening procedures performed after a diagnosis of atypical squamous cells of undetermined significance (ASCUS) and to compare this risk to that in women with a normal Pap smears. STUDY DESIGN: A 7-year, prospective, cohort study was performed in the Norwegian population-based, coordinated screening program. After excluding women in the midst of follow-up of an abnormal Pap smear or with a history of CIN 2/3 or ICC, the study population consisted of women 25-69 years of age with a normal (n = 526,661) or ASCUS Pap smear (n = 10,037) in 1995-1996. Risk estimates were calculated by logistic and parametric survival regression. RESULTS: Within 7 years of an ASCUS smear, 1,017 women (10.1%) were diagnosed with CIN 2/3 and 62 (0.62%) with ICC. Women with an ASCUS index Pap smear had a relative risk of 15-30 of being diagnosed with histologically verified CIN 2/3 or ICC within the first 2 years of follow-up as compared to women with a normal index smear. In long-term follow-up, women with an ASCUS index smear followed by a normal smear, which cancelled further clinical follow-up, were at > 3.5 times higher risk of both CIN 2/3 and invasive cancer as compared to women with a normal index smear. CONCLUSION: Pap smear follow-up of women with an ASCUS smear does not identify all women at higher risk of CIN 2/3 and ICC. Other diagnostic procedures should be implemented to improve the screening program.     

Risk factors and outcomes of maternal obesity and excessive weight gain during pregnancy

Objective:

The prevalence of overweight and obesity among women of reproductive age is increasing. We aimed to determine risk factors and maternal, fetal and childhood consequences of maternal obesity and excessive gestational weight gain.

Design and Methods:

The study was embedded in a population‐based prospective cohort study among 6959 mothers and their children. The study was based in Rotterdam, The Netherlands (2001–2005).

Results:

Maternal lower educational level, lower household income, multiparity, and FTO risk allel were associated with an increased risk of maternal obesity, whereas maternal European ethnicity, nulliparity, higher total energy intake, and smoking during pregnancy were associated with an increased risk of excessive gestational weight gain (all p‐values <0.05). As compared to normal weight, maternal obesity was associated with increased risks of gestational hypertension (OR 6.31 (95% CI 4.30, 9.26)), preeclampsia (OR (3.61, (95% CI 2.04, 6.39)), gestational diabetes (OR 6.28 (95%CI 3.01, 13.06)), caesarean delivery (OR 1.91 (95% CI 1.46, 2.50)), delivering large size for gestational age infants (OR 2.97 (95% CI 2.16, 4.08)), and childhood obesity (OR 5.02 (95% CI:2.97, 8.45)). Weaker associations of excessive gestational weight gain with maternal, fetal and childhood outcomes were observed, with the strongest effects for first trimester weight gain.

Conclusions:

Our study shows that maternal obesity and excessive weight gain during pregnancy are associated with socio‐demographic, lifestyle, and genetic factors and with increased risks of adverse maternal, fetal and childhood outcomes. As compared to prepregnancy overweight and obesity, excessive gestational weight gain has a limited influence on adverse pregnancy outcomes.     

Atypical glandular cells of undetermined significance favor endometrial origin. Criteria for separating low grade endometrial adenocarcinoma from benign endometrial lesions

OBJECTIVE: To evaluate cytologic criteria for separating atypical glandular cells of undetermined significance favor endometrial origin (AGUS-EM), on Papanicolaou-stained (Pap) smears into favor benign and favor malignant categories. STUDY DESIGN: All patients who had a Pap smear diagnosis of AGUS-EM, not further qualified, followed by tissue follow-up were identified from the surgical pathology and cytopathology files from January 1992 through December 1996. The Pap smears were scored blindly for the presence or absence of 40 cytologic criteria, and univariate analysis was performed to determine which criteria were most indicative of malignancy by tissue follow-up. RESULTS: The presence of an atrophic smear, nuclear size greater than twice that of an intermediate cell nucleus and absence of clusters with irregular borders were highly indicative of adenocarcinoma, although other criteria were also helpful in identifying malignancy. CONCLUSION: There are no combinations of cytologic criteria that definitely separate AGUS-EM cases into those with benign or malignant findings on follow-up. However, some isolated criteria were useful in the differential diagnosis in a [table: see text] significant number of cases.