The architecture of first trimester chorionic villous vascularization: a confocal laser scanning microscopical study.

BACKGROUND: The aim of this study was to investigate normal chorionic villous vascularization using CD31 immunofluorescence and confocal laser scanning microscopy (CLSM) to elucidate the spatial arrangement in terms of connections between vessels and cords and their branching patterns compared to deficient chorionic villous vascularization in complicated pregnancies. METHODS: A descriptive morphologic study using CLSM after CD31 immunofluorescence staining of placental biopsies from normal pregnancies (n = 20), complete hydatidiform molar pregnancies (CHMs; n = 3) and empty sacs (n = 3), with a well documented gestational age (GA). RESULTS: In this three-dimensional study, first trimester chorionic villi were occupied by a complex network of mainly cords with redundant connections as early as 5(+5) weeks GA. With increasing GA cords transform into vessels. From about 9 weeks GA onwards, vascular development is characterized by the presence of two large vessels located centrally and surrounded by and connected to a capillary network. In first trimester CHM and empty sacs, we observed a primitive network of mainly cords. CONCLUSIONS: This first visualization of the spatio-temporal patterns of blood vessel formation in placental villi is characterized by the development of the vasculosyncytial membrane from a complex network of cords and can be regarded as the placental development before it becomes functional at the end of organogenesis.

[Late postpartum eclampsia]. / Late eclampsie post partum.

A 36-year-old woman, who had given birth once before, had an eclamptic epileptic seizure eight days after caesarean delivery of healthy premature twins. Severe headache and loss of vision, leading to blindness, had not been recognised as prodromal signs by the healthcare professionals involved. Thereafter, she suffered a generalised epileptic seizure with tongue bite. She recovered fully after treatment with magnesium sulphate and nifedipine. Eclampsia is a severe condition with high rates of maternal complications, such as abruptio placentae, disseminated intravascular coagulation, neurological problems, pulmonary oedema, acute renal insufficiency and even death. Recognition of prodromal symptoms like headache, visual disturbances and upper abdominal pain is of the utmost importance. Magnesium sulphate intravenously is the treatment of choice. About 25% of the cases of postpartum eclampsia develop 2-28 days after delivery. A history of pre-eclampsia before or during the delivery is often absent. There is a relative increase in the incidence of late postpartum eclampsia, possibly because of misinterpretation ofprodromal symptoms, as illustrated by this case report. Every physician should be able to recognise the symptoms of pre-eclampsia and be aware of the possible consequences.

Reduced intima media thickness in adults after prenatal exposure to the Dutch famine.

BACKGROUND: Restricted prenatal growth is associated with an increased risk of coronary heart disease morbidity and mortality. We studied the effects of exposure to famine during gestation on intima media thickness (IMT) in later life. METHODS AND RESULTS: We studied 730 people aged 58 years who were born as term singletons around the time of the 1944-45 Dutch famine. Persons exposed to famine during gestation (n=293) had reduced carotid artery IMT compared to people who had not been exposed to famine in utero (n=437) (mean 0.71 mm, S.D. 0.16 mm compared to 0.75 mm, S.D. 0.15 mm, sex adjusted p=0.001). Femoral artery IMT was also thinner among people exposed to famine during gestation compared to people unexposed in utero (mean 0.64 mm, S.D. 0.20mm, compared to 0.68 mm, S.D. 0.24), although the difference did not achieve statistical significance. CONCLUSION: Exposure to famine in utero may reduce IMT. However, it does not reduce the risk of coronary heart disease among famine exposed people.

A possible link between prenatal exposure to famine and breast cancer: a preliminary study.

In a study of 475 women born around the 1944-1945 Dutch famine, women exposed to prenatal famine more often reported a history of breast cancer than nonexposed women (hazard ratio, 2.6; 95% confidence interval, 0.9-7.7). They also had alterations in reproductive risk factors. Prenatal famine may increase breast cancer incidence.

Ted (G.J.) Kloosterman: on intrauterine growth. The significance of prenatal care. Studies on birth weight, placental weight and placental index.

In the last century, there was a heated debate on whether fetal growth retardation is caused by a small placenta or whether a placenta is small because the baby is small. One of the active participants in this debate was Kloosterman who studied 80,000 birth weights, and 30,000 placental weights, in relation to gestational age at birth, fetal sex, maternal parity, and perinatal mortality. He found that pregnancies related to heavier placentas last longer. He also found that, from about 32 weeks of gestation onwards, children from primiparous women as compared to those from multiparous women, like twin children as compared to singleton children, are relatively growth retarded, most likely related to prior relatively poor placental growth. He concluded that poor fetal growth is not the cause, but the result of poor placental growth. The clinical implication of all these is that future early detection of poor placental growth may prospect poor fetal growth, and may even allow for early interventions to improve fetal outcome.

Nuchal translucency screening and anxiety levels in pregnancy and puerperium.

OBJECTIVES: To compare levels of anxiety and depression during pregnancy and puerperium between women who are offered nuchal translucency (NT) screening routinely and those who are not, and to compare levels between women accepting and those declining screening. METHODS: In 12 midwife practices in three different health districts an experimental NT screening program was offered to pregnant women between 1 June 1999 and 1 January 2001. As part of this implementation study, questionnaires including the Hospital Anxiety and Depression Scale (HADS) were completed: after the patient was informed but before screening (T1), at 20 weeks of gestation (T2), and 6 weeks after delivery (T3). A control group of women receiving routine prenatal care (i.e. no screening offered) also completed the HADS questionnaire at 12 and 20 weeks and after delivery. RESULTS: Five hundred and twenty-seven questionnaires were analyzed. There was a screening uptake of 87% in the intervention group (i.e. those offered screening). Women in this group differed significantly in the percentage of previous miscarriages and religious background compared with the control group. We adjusted for these differences in the analysis. There were no significant differences in HADS scores between the intervention and the control groups at T1, suggesting that women receiving information on screening were not more anxious compared with women who were not informed. Women who were offered screening (acceptors as well as decliners) had significantly lower HADS levels at 20 weeks and after delivery. There were no demographic differences between women accepting and those declining screening. CONCLUSION: Informing women and offering them NT screening for Down syndrome does not increase anxiety or depression levels in pregnancy. In fact, women undergoing or declining screening seem less anxious compared with those who are not offered screening. It is possible that informing women and offering them the chance to decide autonomously whether to participate in screening reduces anxiety levels.

Membrane sweeping and prevention of post-term pregnancy in low-risk pregnancies: a randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of membrane sweeping at 41 weeks for the prevention of post-term pregnancy. DESIGN: A multicentre randomised controlled trial. SETTING: Fifty-one primary care midwifery practices in the Netherlands. POPULATION: A total of 742 low-risk pregnant women at 41 weeks of gestation. METHODS: Participants were randomly assigned to serial sweeping of the membranes (every 48 hours until labour commenced up to 42 weeks of gestation) or no intervention. MAIN OUTCOME MEASURES: Post-term pregnancy (>or=42 weeks). Subgroup analyses were performed on nulliparous and parous women. Secondary outcomes included adverse effects. RESULTS: Serial sweeping of the membranes at 41 weeks decreased the risk of post-term pregnancy (87/375 [23%] versus 149/367 [41%]; relative risk [RR] 0.57, 95% CI 0.46-0.71; number needed to treat [NNT] 6 [95% CI 4-9]). Benefits were also seen in both subgroups (nulliparous: 57/198 [29%] versus 89/192 [46%]; RR 0.62 [95% CI 0.48-0.81]; NNT 6 [95% CI 4-12] and parous: 30/177 [17%] versus 60/175 [34%]; RR 0.49 [95% CI 0.34-0.73]; NNT 6 [95% CI 4-6]). Adverse effects were similar in both the groups except for uncomplicated bleeding, which was reported more frequently in the sweeping group. Other obstetric outcomes and indicators of neonatal morbidity were similar in both groups. There were two perinatal deaths in each group. CONCLUSIONS: Membrane sweeping at 41 weeks can substantially reduce the proportion of women with post-term pregnancy.

Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine.

AIMS/HYPOTHESIS: People who were small at birth have an increased risk of type 2 diabetes in later life. People who were in utero during the Dutch famine had decreased glucose tolerance and raised insulin concentrations at age 50. We aimed to evaluate whether prenatal famine exposure leads to more rapid progression of impaired glucose/insulin homeostasis with increasing age. METHODS: We performed an OGTT in 702 men and women at age 50 and in 699 men and women at age 58, all born as term singletons immediately before, during or after the 1944-1945 Dutch famine. RESULTS: People who had been exposed to famine in utero had significantly higher 120-min glucose concentrations at age 58 compared with people who had not been exposed to famine (difference=0.4 mmol/l, 95% CI 0.1 to 0.7, adjusted for sex and BMI). Glucose tolerance deteriorated between the age of 50 and 58. The unadjusted 120-min glucose concentrations rose by 0.2 mmol/l (95% CI 0.0 to 0.4), while 120-min insulin concentrations had increased by 64 pmol/l (95% CI 48 to 82). There were no differences in the rates of glucose and insulin level increase between the famine-exposed group and the unexposed group (p=0.28 for the difference in increase in glucose concentrations and p=0.09 for insulin concentrations). CONCLUSIONS/INTERPRETATION: Although we confirmed that undernutrition during gestation is linked to decreased glucose tolerance, the effect does not seem to become more pronounced at age 58 as compared with age 50.

Long-term follow up of children exposed in utero to nifedipine or ritodrine for the management of preterm labour.

OBJECTIVE: To compare the long-term psychosocial and motor effects on children exposed in utero to nifedipine or ritodrine for the management of preterm labour. DESIGN: Randomised controlled trial. SETTING: Multicentre study in two university and one primary hospital in the Netherlands. POPULATION: In the original trial, 185 women were randomised to either nifedipine (n = 95) or ritodrine (n = 90). Of the 185 liveborn children, 171 survived (92%), and of these 102 (61%) were followed up at age 9-12 years. METHODS: Age-specific questionnaires were administered to the parent and teacher. Additional data were obtained from medical records. MAIN OUTCOME MEASURES: Questionnaires were used to assess the child's behavioural-emotional problems, quality of life (QoL), motor functioning, parenting distress and the child's education. RESULTS: Of the 171 eligible families, 102 (61%) agreed to participate and completed the questionnaires. Response was equal in the ritodrine group (n = 54 of 83 surviving children, 65%) compared with the nifedipine group (n= 48 of 88 surviving children, 55%). After controlling for differing perinatal characteristics at birth, no significant differences between the groups were detected with respect to long-term behaviour-emotional outcome, QoL, education, motor functioning or parenting distress. Psychosocial outcome was slightly better in the nifedipine group. CONCLUSIONS: The results do not support any differential postnatal effect of the tocolytic agents ritodrine or nifedipine on the child's long-term psychosocial and motor functioning. The slightly better outcome of children randomised in the nifedipine group is most likely due to more favourable perinatal outcomes in this group. These results merit further investigation in a larger group of survivors.

Histological classification of chorionic villous vascularization in early pregnancy.

BACKGROUND: The objective of the study was to assess the reproducibility of a new classification for early pregnancy chorionic villous vascularization (Grade: I, normal; IIA, mild hypoplasia; IIB, severe hypoplasia and III, avascular) for routine microscopic examination in daily clinical practice. METHODS: In this observational study, four observers scored first trimester chorionic villous vascularization. Scoring was performed in microscopic slides of chorionic tissue obtained by D&C in 30 patients with early pregnancy loss due to empty sac (n = 10), fetal death (n = 10) and termination of pregnancy (n = 10) using the new classification. Ultrasonographic measurement of trophoblastic thickness (TT) at the implantation site was available in all patients and in a reference group of 100 ongoing singleton pregnancies. The vascularization score could therefore be related to the TT. RESULTS: The new classification resulted in a good-to-excellent agreement in histological scoring (0.73-0.90) between investigators (kappa 0.64-0.86). TT was not related to either vascularization or pregnancy outcome and only partly to hydropic degeneration. CONCLUSION: The vascularization scoring system is a simple, valid and effective method for assessment of chorionic villous vascularization. It is helpful in understanding the underlying cause of pregnancy loss, as the classification can distinguish between normal and abnormal embryonic development. We did not find either a relation between TT and pregnancy outcome or between TT and vascularization.

Adult mortality at age 57 after prenatal exposure to the Dutch famine.

Prenatal famine exposure has previously been shown to be associated with cardiovascular disease and type II diabetes in adulthood. In the current study, we could not demonstrate an effect of prenatal exposure to famine in 2254 term singletons born during the 1944-1945 Dutch famine on adult mortality up to the age of 57 years. Follow-up of this cohort will resolve whether famine exposure is linked to increased adult mortality.

Vasculogenesis in complete and partial hydatidiform mole pregnancies studied with CD34 immunohistochemistry.

BACKGROUND: Defective chorionic villous vascularization is present in pregnancies complicated by absent or abnormal embryonic development. The aim of this study was to investigate the embryonic and/or maternal genomic influence on vasculogenesis in diploid complete hydatidiform mole (CHM) and in triploid partial hydatidiform mole (PHM) in comparison with normal development. METHODS: Mean villous stromal area and functional vascular area, vessels with a lumen and haemangiogenetic cords, peripherally or centrally located were measured and counted in chorionic villi of 12 CHM, 12 normal pregnancies (termination of pregnancy, TOP) and 15 PHM of which nine were without an embryo (PHM-E) and six were with an embryo (PHM + E), using quantitative CD34 immunohistochemistry. RESULTS: TOP showed significantly more vessels per chorionic villus, centrally and peripherally located (median, range), than CHM, PHM-E and PHM + E (4.0, 0-9 versus 0.0, 0-11, 0.0, 0-18 and 1.0, 0-21). CHM showed significantly more centrally located cords than PHM-E, PHM + E and TOP (1.5, 0-22 versus 1.0, 0-15, 0.5, 0-8 and 1.0, 0-2). CONCLUSIONS: Initiation of chorionic villous vasculogenesis is independent of the maternal genome (CHM). The development of an embryo, however, is obligatory for the modulation of normal vascularization resulting in a well developed vasculosyncytial membrane.

Disappearance of enlarged nuchal translucency before 14 weeks' gestation: relationship with chromosomal abnormalities and pregnancy outcome.

OBJECTIVE: The aim of this study was to investigate the natural course of enlarged nuchal translucency (NT) and to determine if its disappearance before 14 weeks' gestation is a favorable prognostic sign in relation to fetal karyotype and pregnancy outcome. METHODS: A total of 147 women with increased NT (> 95th centile) at first measurement were included in this study. A second measurement was performed in all cases, at an interval of at least 2 days. Both measurements were taken between 10 + 3 and 14 + 0 weeks. All women underwent chorionic villus sampling or amniocentesis for subsequent karyotyping. In those women with a normal karyotype, a fetal anomaly scan was performed at 20 weeks' gestation. Pregnancy outcome was recorded in all cases. The finding of persistent or disappearing NT enlargement was analyzed in relation to fetal karyotype and pregnancy outcome. RESULTS: Of the 147 paired measurements, NT remained enlarged at the second measurement in 121 (82%) cases. An abnormal karyotype was found in 35% of these cases. In 26 (18%) fetuses the NT measurement was found to be below the 95th percentile at the second measurement and in only two of them an abnormal karyotype was found (8%). In the 103 chromosomally normal fetuses an adverse outcome (i.e. fetal loss or structural defects) was recorded in 22 fetuses with persistent enlargement (28%) and in four fetuses with disappearing enlargement (17%). CONCLUSIONS: Disappearance of an enlarged NT before 14 weeks' gestation is not a rare phenomenon and seems to be a favorable prognostic sign with respect to fetal karyotype. Overall, no significant difference in pregnancy outcome was found between chromosomally normal fetuses with persisting or disappearing NT enlargement.

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis.

OBJECTIVES: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. METHODS: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). RESULTS: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65+/-12 vs. 70+/-8, P=0.001) and 48 h (65+/-12 vs. 71+/-8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105+/-17 vs. 86+/-13, P<0.0001) and 48 h (100+/-21 vs. 85+/-12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68+/-2.53 vs. 4.93+/-1.23, P=0.0016), while mean potassium levels were lower (3.52+/-0.84 vs. 3.81+/-0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. CONCLUSIONS: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

[Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes']. / CBO-richtlijn 'seksueel overdraagbare aandoeningen en herpes neonatorum' (herziening).

The Dutch Institute for Health Care Improvement revised guideline, 'Sexually transmitted diseases and neonatal herpes' summarises the current scientific position on the diagnosis and treatment of a great number of sexually transmitted diseases (STD) and neonatal herpes. Symptomatic treatment of suspected Chlamydia trachomatis infection and gonorrhoea without previous diagnosis is not recommended. Treatment can be started immediately, once samples have been taken. Risk groups eligible for screening or proactive testing on C. trachomatis infection include: partners of C. trachomatis-positive persons, visitors of STD clinics, women who will undergo an abortion, mothers of newborns with conjunctivitis or pneumonitis, young persons of Surinam or Antillean descent, young women with new relationships and individuals whose history indicates risky sexual behaviour. A period of 3 months can be adopted between a risky contact and the HIV test (this used to be 6 months), unless post-exposure prophylaxis was used. For the treatment of early syphilis no distinction is drawn between HIV-infected and non-HIV-infected persons. It is no longer recommended that women in labour with a history of genital herpes are tested for the herpes simplex virus. Virological testing of the neonate is only advised if the mother shows signs of genital herpes during delivery.

Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.

Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

Adult survival after prenatal exposure to the Dutch famine 1944--45.

Early life events may affect adult survival. We studied the effect of prenatal exposure to the Dutch famine 1944--45 on survival among 2254 people born in Amsterdam. Mortality up to age 50 was highest among those born before the famine (15.2%) and among those exposed to famine in late gestation (14.6%). It was lower among those exposed in mid- (11.2%) or early gestation (11.5%), and was lowest among those conceived after the famine (7.2%). These differences were caused by effects on mortality in the first year after birth and were mainly related to nutrition and infections. There was no effect of exposure to famine on mortality after the age of 18. The hazard ratio was 1.4 [0.8, 2.3] for those born before the famine, 1.1 [0.5, 2.3] for those exposed in late gestation, 0.8 [0.3, 1.8] for those exposed in mid-gestation and 1.1 [0.5, 2.5] in those exposed in early gestation compared with those conceived after the famine. We could not demonstrate effects of prenatal exposure to famine on cause-specific mortality after the age of 18. Because prenatal exposure to famine is linked to cardiovascular risk factors and disease, increased cardiovascular mortality in the future may be expected.