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Objective: To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens., Study Design: Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size., Results: The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range, Conclusion: In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.

Background: Although some paternal components to the predisposition to pre-eclampsia have been demonstrated recently, it is not known whether such paternal factors play a role to thrombophilia-related perinatal mortality., Objective: To compare the paternal and maternal contribution to perinatal mortality., Study Design: Data from a prospective registry of perinatal mortality in a Dutch healthcare region were used. Between December 1999 and May 2000, the prevalence of thrombophilia was studied in 74 women with a history of perinatal mortality (female cases) and 54 of their male partners (male cases). Seventy-one healthy unrelated women after uneventful pregnancies only and 66 of their male partners were used as controls., Setting: Obstetric outpatient clinic in a regional hospital (Remierde Graaf Group, Deflt)., Methods: Presence of various coagulation abnormalities, hyperhomocysteinaemia and anticardiolipins was investigated., Results: The frequency of antithrombin deficiency (12% vs 0%), increased activated protein C (APC) resistance (32% vs 6%), total protein S deficiency (11% vs 1%) and elevated factor VIII:C activity (43% vs 17%) was significantly higher in female cases compared with controls. In male cases, the frequency of increased APC resistance was significantly higher compared with controls (22% vs 0%). In 30 of the 54 couples with a history of perinatal mortality, more than one thrombophilic abnormality was found (55%) compared with 10 of the 62 control couples (17%)., Conclusion: The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies.

Objective: To test the hypothesis that abnormal placentation resulting in intrauterine fetal death (IUFD) is associated with coagulation abnormalities in the fetus., Study Design: We analyzed fetal DNA from umbilical cords from 139 pregnancies complicated by intrauterine fetal death during 1994-1998 (cases). Fetal DNA was tested for the presence of factor V Leiden and prothrombin G20210A mutations. The prevalence of these thrombophilic mutations among cases were compared with the prevalence in a historic control group., Results: Overall, a higher prevalence of fetal genetic risk factors was found in cases (9.8%) as compared to fetuses born from an uncomplicated pregnancy (2%, odds ratio 4.8, 95% CI 1.1-22). Second trimester intrauterine fetal death occurred more frequently in cases with the factor V Leiden mutation as compared with the control group (8/64 versus 0/92). For intrauterine fetal death and factor V Leiden a high risk was found concerning abruption placentae (odds ratio 7.6, 95% CI 1.5-37)., Conclusion: The prevalence of fetal genetic risk factors associated with an increased risk for thrombosis was higher in pregnancies complicated by intrauterine fetal death suggesting an important role of abnormal coagulation in placentation.

Objective: To classify 239 cases of perinatal death in a newly introduced classification system for underlying causes of perinatal death., Design: Prospective, descriptive., Setting: Dutch healthcare region Delft-Westland-Oostland (DWO)., Materials and Methods: In 10 years (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. We used a classification model based upon the underlying cause of death using simple principles of obstetrical and neonatal pathology. A team consisting of a gynaecologist, neonatologist and pathologist classified all cases of perinatal death into seven groups to determine the "most-probable" cause of death., Results: Birth trauma was seen in two cases (0.8%). Infections were seen in 16 cases (6.8%). Acute/subacute placental pathology in 77 cases (32.2%) and chronic placental pathology in 50 cases (21%). Bloodtype antagonism was seen in two cases (0.8%). Lethal congenital malformations in 55 cases (23%). Complications of pre-viable delivery in 20 cases (8.4%). Unclassifiable were 17 cases (7%): two cases could not be classified despite thorough investigation (1%) and 15 cases were lost for follow-up (6%)., Conclusions: Classification of perinatal death causes by using our fundamental classification system gives insight in the possible underlying causes of death. The results of such a classification can be used as guidelines for preventive measures in the future.

Objective: To validate a newly introduced classification system for the registration of perinatal mortality., Design: Descriptive., Setting: Dutch Healthcare region Delft-Westland-Oostland (DWO)., Material and Methods: In a 10-years period (1983-1992), all cases of perinatal death with a birthweight above 500 g (n=239) were included into the study. Six assessors: four gynaecologists and two paediatricians were asked to classify all cases using a classification model proposed by the authors. This model is based on the underlying cause of death using simple principles of obstetrical and neonatal pathology: birth trauma, infection, placenta or cord pathology, pathology of immune tolerance of mother and fetus, congenital malformation of the fetus and complications of a pre-viable delivery. Therefore, we used the term fundamental classification. The six assessors worked independently of each other in classifying all cases of perinatal death, were not involved in the original development of the system and were unaware of the results of the classification of their colleagues. Agreement beyond chance between assessors was calculated using kappa's coefficient for multiple observers and multiple test results., Results: Overall kappa was 0.70 (95% confidence interval (C.I.) 0.68-0.72). Reproducibility was poor for the categories trauma and unclassifiable, fair for the categories infections and placental/cord pathology, and very good to excellent for the categories maternal immune system pathology, congenital malformations and complications of prematurity., Conclusions: The proposed system showed a good level of agreement and appeared to be simply applicable. It offers a good insight in the underlying cause of death with the possibility for recognising preventive factors in future pregnancies and will enable (inter)national comparisons in causes of perinatal death. A reliable uniform registration of perinatal death based on the underlying causes should be the basis for improvement of the quality of perinatal care.

Background: The correlation between human papillomavirus (HPV) infection and tumor prognosis in 159 Russian women with cervical carcinoma was investigated. The presence of various HPV types was correlated with the histologic parameters of the carcinomas and with their immunoreactivity with antibodies to p53, Ki-67-Ag, and bcl-2., Methods: Formalin fixed, paraffin embedded tissue specimens representing 159 cases of International Federation of Gynecology and Obstetrics Stage I and II were used. HPV DNA was detected by polymerase chain reaction (PCR) using a general primer set that targets the L1 region and synthesizes a product of only 65 base pairs. The HPV types were determined by direct sequencing and compared with known HPV types., Results: All 159 carcinomas were positive for HPV. HPV 16 (64.8%) was most frequently found, followed by HPV 18 (10.7%) and HPV 45 (8.2%). In 6 patients (3.8%), HPV types could not been further classified, and these cases were therefore categorized as HPV X. Although a trend was noted toward poorer prognosis for women with carcinomas harboring HPV types 16, 18, and 45 than for patients with carcinomas harboring HPV types 31, 33, 35, 52, 56, 58, and 68, the differences were not statistically significant. The prevalence of adenocarcinoma and adenosquamous carcinoma was higher among HPV 18 positive patients than among patients with the other known HPV types (P=0.0002)., Conclusions: The rate of HPV positivity in these 159 cervical carcinomas was 100%. These findings challenge the assumption that HPV negative cervical carcinomas exist. This high rate might be attributed to the use of a new broad-spectrum HPV PCR test. HPV typing in cervical carcinoma was not significantly related to clinical outcome. HPV 18 was significantly more frequently found in adenocarcinoma and adenosquamous carcinoma. The possibility of classifying HPV 45 as an oncogenic high risk type should be considered.

Objective: : To determine the precise contribution of congenital malformations to perinatal mortality in a region., Design: Prospective, descriptive., Setting: Region, Delft-Westland-Oostland (DWO) in the Netherlands., Material and Methods: The registration was based on data concerning all deliveries of women domiciled in the health region DWO of the Netherlands. The incidence and contribution of congenital malformations to perinatal death was evaluated by a team consisting of a gynaecologist. a paediatrician and a paediatric pathologist. Malformations were classified as lethal or nonlethal and recorded separately for stillbirth (from 28 weeks gestation) and liveborn infants with 7-day follow-up., Results: In 10 years (1993-1992) 28983 children were born in the region DWO. The perinatal mortality was calculated as 247 cases (0.85%). The overall incidence of congenital malformations in the perinatal death-group was 33%. Lethal congenital malformations were found in 51% of the cases in the stillbirth-group and 70% of the cases in the neonatal death-group. Congenital malformations of the central nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular- and pulmonary-defects were more prominent in the neonatal period (27% and 33% respectively of the neonatal deaths). Uro-genital and minor malformations (miscellaneous) are more often seen in perinatal deaths without being a contributor to the cause of death., Conclusions: As most congenital malformations are multifactorial in origin, it is in the understanding and control of such conditions that efforts and resources should now be turned. Through a detailed postmortem fetal and placental examination and clinical-pathological correlations lethal congenital malformations were found in 51% in stillbirths (mainly central nervous system) and 70% in neonates (mainly cardiovascular and pulmonary defects).

We compared the effects of continuous epidural infusion of ropivacaine 0.25% with bupivacaine 0.25% on pain relief and motor block during labor, and on the neonate. Seventy-six full-term parturients in active labor requiring epidural analgesia were randomly allocated to receive either bupivacaine 0.25% or ropivacaine 0.25%. Fifteen minutes after a loading dose of 10 mL of the study drug, an epidural infusion with the same drug was started at 6-12 mL/h to maintain an adequate block. Top-up doses of 6-10 mL were given as required. At full cervical dilation, the epidural infusion was discontinued. The onset of pain relief (verbal scale), contraction pain (visual analog scale), intensity of motor block (modified Bromage scale), and duration of motor block were not statistically different between the groups. Apgar scores at 1 and 5 min after delivery were comparable. There was a higher proportion of the neonates in the ropivacaine group (26/31 = 84%) who had a neurologic and adaptive capacity score (NACS) > or = 35 2 h after delivery than in the bupivacaine group (18/29 = 62%). We conclude that ropivacaine 0.25% and bupivacaine 0.25% are equally effective for epidural pain relief during labor. Ropivacaine may have an advantage over bupivacaine regarding neonatal neurobehavioral performance during the first few hours after delivery, although further studies will be required to substantiate this.

In this paper we discuss the results of a study, conducted in the Netherlands, involving 143 women who experienced a miscarriage or stillbirth (response of 69%). The main questions were: how women with a fetal loss before the 20th week (miscarriage) versus women with a loss later in pregnancy (stillbirth) coped with the death of their baby; how the lapse of time since the loss related to grief intensity; and how satisfied women were with the professional care and support. The relationship between some other variables and grief intensity was also examined. It was found that grief intensity was greater and there was more satisfaction with professional care when gestational age was longer. With regard to the care, we concluded that some aspects needed improvement, especially the professional support for women who miscarry and the coordination of care for all women after discharge from hospital.

In 17 preterm neonates and 7 small-for-date neonates, all formula-fed, vitamin K-dependent coagulation factors II and X remained near 45% of adult values from the moment of birth until 28 days postnatally. Vitamin K1 levels, however, showed a remarkable rise from below the detection limit of 0.022 ng/ml in umbilical cord blood, to serum levels with a range of 0.99-7.29 ng/ml vitamin K1 on day 3, with a further rise on days 7 and 28 postnatally. Vitamin K1 (Konakion) parenterally given to a third group of four preterm neonates as a 1 mg dose resulted in very high serum levels of vitamin K1 (64.08-157.10 ng/ml), but without any significant increase in plasma levels of vitamin K-dependent coagulation factors II and X, compared to the group without any extra vitamin K1. It is concluded that in healthy preterm and small-for-date neonates no correlation is seen between serum levels of vitamin K1 and plasma levels of coagulation factors II and X. After administration of 1 mg Konakion no accelerated increase is seen in coagulation factor activities.

Vitamin K1 serum levels were assessed by means of an off-line multidimensional liquid chromatography in 18 mothers, shortly after delivery, and in their healthy term infants. Umbilical cord and venous blood samples were assayed up to 4 weeks of life. Concurrently, levels of coagulation factors II and X, antithrombin III and platelets were established. Although the detection limit of the assay was as low as 22 pg/ml, vitamin K1 concentration appeared to be still beyond that level in cord blood or in newborn serum within 30 min after birth, whereas vitamin-K-dependent coagulation factors are already at a level of 40%, without evidence for the presence of descarboxy prothrombin, in any of the investigated neonates. After 3 days, breast-fed neonates had lower vitamin K1 levels than formula-fed infants (0.76 and 1.44 ng/ml, respectively). The levels of the vitamin-K-dependent coagulation factors II and X, however, were comparable, regardless of the kind of feeding. After 28 days, breast-fed neonates had even lower vitamin K1 levels (0.49 ng/ml, while the formula-fed infants showed higher vitamin K1 levels (4.45 ng/ml). But even then, the levels of vitamin-K-dependent coagulation factors II and X were comparable, regardless of the kind of feeding. From this we conclude that the serum levels of vitamin K1 in formula-fed neonates exceed those of breast-fed infants from the moment of feeding (24 h and later) without a concomitant rise in vitamin-K-dependent coagulation factors. A relationship between vitamin K1 levels and vitamin-K-dependent coagulation factors could not be established in healthy term breast-fed or formula-fed infants.