Neurodevelopmental outcomes at five years after early-onset fetal growth restriction: Analyses in a Dutch subgroup participating in a European management trial.

OBJECTIVE: The objective of this study is to explore developmental outcomes at five years after early-onset fetal growth restriction (FGR). STUDY DESIGN: Retrospective data analysis of prospective follow-up of patients of three Dutch centres, who participated in a twenty centre European randomized controlled trial on timing of delivery in early-onset FGR. Developmental outcome of very preterm infants born after extreme FGR is assessed at (corrected) age of five. RESULTS: Seventy-four very preterm FGR children underwent follow-up at the age of five. Mean gestational age at birth was 30 weeks and birth weight was 910 g, 7% had a Bayley score <85 at two years. Median five years' FSIQ was 97, 16% had a FSIQ < 85, and 35% had one or more IQ scores <85. Motor score ≤ 7 on movement ABC-II (M-ABC-II-NL) was seen in 38%. Absent or reversed end-diastolic flow, gestational age at delivery, birthweight and neonatal morbidity were related to an FSIQ < 85. Any abnormal IQ scale score was related to birthweight, male sex and severity of FGR, and abnormal motor score to male sex and bronchopulmonary dysplasia (BPD). CONCLUSIONS: Overall, median cognitive outcome at five years was within normal range, but 35% of the children had any abnormal IQ score at age five, depending on the IQ measure, and motor impairment was seen in 38% of the children. GA at delivery, birthweight, EDF prior to delivery and neonatal morbidity were the most important risk factors for cognitive outcomes.

Pilot study demonstrates that placental histology can provide an additional tool for diagnosing early-onset neonatal sepsis.

AIM: We explored whether placental histology could help to diagnose early-onset neonatal sepsis (EONS), guide clinical decision-making 48 hours after birth and reduce antibiotic use. METHODS: This study comprised 109 infants born at less than 32 weeks of gestation, who were admitted to the neonatal intensive care unit of Isala, Zwolle, The Netherlands, between January 2013 and December 2013. EONS was defined as clinical symptoms plus raised serial C-reactive protein (CRP) >10 mg/L and a positive (proven EONS) or a negative (suspected EONS) blood culture. Placentas were studied for a histological inflammatory response and scored according to Redline's criteria. RESULTS: A histological inflammatory response was seen in 15/88 (17%) placentas and this occurred significantly more often in infants with a high suspicion of EONS (p < 0.05). No histological inflammatory response was seen if maternal risk factors for EONS were absent, despite a raised CRP level. Based on placental histology, the duration of antibiotic therapy was reduced from more than five days to 48 hours in 20/27 infants (74%). CONCLUSION: Histological examination of the placenta helped to diagnose EONS and guide clinical decision-making 48 hours after birth and led to a clinically relevant reduction in antibiotic use.

Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maintenance tocolysis with nifedipine in threatened preterm labour: 2-year follow up of the offspring in the APOSTEL II trial.

OBJECTIVE: To evaluate long-term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant. DESIGN, SETTING AND POPULATION: Follow up of infants of women who participated in a multicentre randomised controlled trial on maintenance tocolysis with nifedipine versus placebo. METHODS: Two years after the APOSTEL II trial on maintenance tocolysis with nifedipine versus placebo, we asked participants to complete the Ages and Stages Questionnaire. MAIN OUTCOME MEASURES: Infant development was measured in five domains. Developmental delay was defined as a score of ≤1 SD in one or more developmental domains. We performed exploratory subgroup analysis in women with preterm prolonged rupture of the membranes, and in women with a cervical length <10 mm at study entry. RESULTS: Of the 276 women eligible for follow up, 135 (52.5%) returned the questionnaire, encompassing data of 170 infants. At 2 years of age, infants of women with nifedipine maintenance tocolysis compared with placebo had a higher overall incidence of fine motor problems (22.2 versus 7.6%, OR 3.43, 95% CI 1.29-9.14, P = 0.01), and a lower incidence of poor problem-solving (21.1 versus 29.1%, OR 0.27, 95% CI 0.08-0.95, P = 0.04). CONCLUSIONS: This follow-up study revealed no clear benefit of nifedipine maintenance tocolysis at 2 years of age. As short-term adverse perinatal outcome was not reduced in the original APOSTEL II trial, we conclude that maintenance tocolysis does not appear to be beneficial at this time. TWEETABLE ABSTRACT: No clear benefit of nifedipine maintenance tocolysis in preterm labour on 2-year infant outcome.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres.

OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. STUDY DESIGN: We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. RESULTS: During the study period, there were 1 929 470 deliveries; 163 052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171 days (24(3/7))±10 days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases.

Serum AMH levels in women with a history of preeclampsia suggest a role for vascular factors in ovarian aging.

CONTEXT: The association between early menopause and vascular disease as a possible causative factor has recently received attention. Preeclampsia (PE) is associated with future cardiovascular risk factors, and this premature vascular aging potentially modifies the ovarian aging process. OBJECTIVE: The purpose of this study was to assess whether women with a history of PE have lower anti-Müllerian hormone (AMH) levels than women with normotensive pregnancies. DESIGN: This was a retrospective cohort study. SETTING: The study was conducted in a tertiary referral center. PATIENTS: Clinical data and blood samples of participants in the Preeclampsia Risk EValuation in FEMales study were used (336 women with a history of PE and 329 women after a normotensive pregnancy). INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The relative decrease in AMH levels was assessed after a median follow-up of 10.5 years. RESULTS: The mean AMH level was 2.00 ± 1.87 µg/L in the PE group compared with 2.26 ± 2.56 µg/L in the reference group. Linear regression analysis with censoring for undetectable AMH levels, adjusted for age, smoking, and hormonal contraceptive use, showed a relative reduction in AMH levels of 20.9% at any age (fold change 0.79, 95% confidence interval, 0.67-0.94). CONCLUSIONS: We demonstrate that women with a history of PE have significantly lower AMH levels than women with normotensive pregnancies. Calculations based on a reference population indicate advancement of reproductive age of approximately 1.5 years. Because PE is considered a manifestation of impaired vascular health, these results support the hypothesis that compromised vascular health could act as a causative mechanism in early ovarian aging.

Carbetocin in comparison with oxytocin in several dosing regimens for the prevention of uterine atony after elective caesarean section in the Netherlands.

PURPOSE: The aim of the study was to compare the prophylactic effects of carbetocin with those of oxytocin for the prevention of uterine atony in patients undergoing elective caesarean section (CS) in the Netherlands. The primary endpoint was the need for additional uterotonic medication. METHODS: Each of the five participating Dutch hospitals treated 50-100 term patients with 100 µg of intravenous carbetocin on prescription. Each centre retrieved charts of 250 patients treated with oxytocin according to the hospital's policy for the prevention of uterine atony (oxytocin bolus 5 IU, bolus 10 IU or bolus 5 IU followed by 10 IU in 2 h). RESULTS: In the carbetocin group 462 subjects were included and in the oxytocin group 1,122. The proportion of subjects needing additional uterotonic treatment was 3.1 % (95 % CI 1.7-5.1 %) after carbetocin and 7.2 % (5.8-8.9 %) after oxytocin; relative risk 0.41 (0.19-0.85); p = 0.0110. Carbetocin was most effective compared with the oxytocin 5 IU bolus subgroup with less need for additional uterotonic medication (3.1 vs. 9.3 %, p = 0.0067) and blood transfusions (2.2 vs. 3.6 %, p = 0.0357). CONCLUSIONS: Compared with oxytocin, prophylaxis of uterine atony with carbetocin after an elective CS diminished the need for additional uterotonics by more than 50 %.

Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies.

OBJECTIVES: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. METHODS: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. RESULTS: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use.

[Tertiary obstetric care: the aims of the planning decree on perinatal care of 2001 have not yet been achieved]. / Derdelijns verloskundige zorg: doelstellingen van het 'planningsbesluit bijzondere perinatologische zorg' uit 2001 nog niet gehaald.

OBJECTIVE: To compare the actual situation in tertiary perinatal care in the Netherlands with the objectives laid down in the 2001 decree on perinatal care by the Dutch Ministry of Health, Welfare and Sport. DESIGN: Descriptive, retrospective. METHOD: Data on tertiary perinatal care, the transfer or refusal of women with very endangered pregnancies and the personnel of obstetric high care (OHC) units in 2006 were compared with the targets laid down in the planning decree on perinatal care and in a report by the Dutch Health Council from 2000. Parameters of tertiary perinatal care output were the number of admissions, and the number of beds in OHC units and neonatal intensive care units (NICU). RESULTS: In 2006, 128 of the 250 beds intended for OHC had been obtained. The degree of capacity utilisation was 94%, while the norm is 80%. 312 women were transferred due to lack of capacity of OHC units and NICU. The number of staff, specialised physicians as well as nurses, was considerably lower than the planned capacity. But training for obstetric perinatologists and OHC nurses was given. CONCLUSION: The targets for the number of beds for tertiary obstetric care and associated medical personnel have not been achieved as yet. As a consequence, the number of transfers is still too high. The funding of OHC units is not attuned to the complexity of tertiary perinatal care. Closer supervision of the execution of the planning decree and an adequate financing system are needed to achieve the objectives of the planning decree in the next 3 years.

Comparison of transvaginal sonography in recumbent and standing maternal positions to predict spontaneous preterm birth in singleton and twin pregnancies.

OBJECTIVE: To evaluate whether serial transvaginal sonographic examination of the cervix with the woman in a standing position improves the prediction of spontaneous preterm birth (SPB) compared with the conventional posture. METHODS: For both a recumbent and upright maternal position, the inter- and intraobserver agreement of cervical length (CL) measurement was calculated. In 363 pregnancies at risk for SPB, we determined prospectively CL and funnel width (FW) including differences between the positions and between longitudinal measurements from 15 weeks onwards. Multivariate logistic regression analysis, contingency tables and receiver-operating characteristics (ROC) curves were used. Data were stratified according to singleton or twin pregnancy, maternal position, gestational age at examination and different cut-off values to predict SPB < 36 weeks. RESULTS: The interobserver variability in each position was similar, with an interclass correlation coefficient (95% CI) of 0.952 (0.811-0.984) in the recumbent and 0.942 (0.837-0.978) in the upright maternal position. After exclusion of pregnancies with iatrogenic preterm birth, 15/138 (11%) singletons and 29/153 (19%) twin pairs were born at <36 weeks. The incidence of funneling was greater in an upright compared with a recumbent maternal position by 12.3% in singleton and 13.1% in twin pregnancies before 25 weeks, and by 13.0% and 21.6% between 25 and 30 weeks, respectively. This resulted in an earlier and more accurate prediction of SPB by transvaginal ultrasound in an upright compared with a recumbent maternal position, which could be shown by all applied statistical methods. The influence of posture on the prognostic value of the CL varied depending on the cut-off value. Differences in CL or FW between 15-20 and 25-30 weeks predicted SPB better than did differences between shorter intervals. CONCLUSIONS: Evaluation of the cervix with the woman in the upright position permits earlier detection of funneling. This may enable earlier and more appropriate intervention to avoid SPB.

Recurrence rate of pre-eclampsia in women with thrombophilia influenced by low-molecular-weight heparin treatment?

OBJECTIVES: (1) To assess the recurrence rate of pre-eclampsia in women with this history before 34 weeks of pregnancy and thrombophilia. (2) To evaluate the effects of low-molecular-weight heparin (LMWH) on pregnancy outcome. METHODS: In a multicentre retrospective study subsequent pregnancies of women with a history of pre-eclampsia necessitating birth before 34 weeks and thrombophilia were analysed. Of 58 women, 26 received LMWH and aspirin (ASA) and 32 ASA (22) or no (10) medication in their subsequent pregnancies. RESULTS: In eight women treated with LMWH and ASA and in 16 women receiving ASA or no medication pre-eclampsia recurred in the subsequent pregnancy. (OR 0.55, 95% CI 0.15-1.31) There were no significant differences in birth weight or gestational age between both groups. CONCLUSIONS: The recurrence rate of pre-eclampsia in women with thrombophilic disorders is high in this small retrospective study. No positive effect was found for LMWH treatment. A multicentred randomised study has been started to reach an adequate number of patients to evaluate the influence of LMWH treatment.

Minimal enteral feeding, fetal blood flow pulsatility, and postnatal intestinal permeability in preterm infants with intrauterine growth retardation.

OBJECTIVE: To study the effect of minimal enteral feeding (MEF) on intestinal permeability and feeding tolerance in preterm infants with intrauterine growth retardation (gestational age < 37 weeks, birth weight for gestational age p < 10). Furthermore, to determine whether fetal blood flow pulsatility or intestinal permeability predict feeding tolerance in these infants. DESIGN: Randomised controlled trial. METHODS: Within 48 hours of birth, infants were randomised to MEF or no enteral feeding (NEF) for five days in addition to parenteral feeding. Intestinal permeability was measured by the sugar absorption test before (SAT1) and after (SAT2) the study. The sugar absorption test measured the urinary lactulose/mannitol (LM) ratio after oral ingestion of a solution (375 mosm) containing mannitol and lactulose. Charts of all infants were assessed for measures of feeding tolerance. Fetal blood flow pulsatility index (U/C ratio) was measured within the seven days before birth. RESULTS: Of the 56 infants enrolled, 42 completed the study: 20 received MEF and 22 NEF. The decrease in LM ratio (LM ratio 1 - LM ratio 2) was not significantly different between the two groups (0.25 v 0.11; p = 0.14). Feeding tolerance, growth, and incidence of necrotising enterocolitis were not significantly different between the two groups. Neither the U/C nor the LM ratio 1 predicted feeding tolerance. CONCLUSIONS: The results suggest that MEF of preterm infants with intrauterine growth retardation has no effect on the decrease in intestinal permeability after birth. Neither fetal blood flow pulsatility nor intestinal permeability predicts feeding tolerance.

Two cases with dichorionic diamniotic triplet pregnancy and early cord entanglement.

Within a period of 6 years (1994-99) we registered 29 triplet deliveries out of a total of 13,969 hospital deliveries (0.02%). Since there is limited information about specific problems of chorionicity in triplet pregnancies, we analysed the 29 cases according to origin of pregnancy and chorionicity. We here report on two cases with a high risk according to chorionicity with dichorionic (DC) diamniotic (DA) triplet pregnancies. Out of the two cases, one pregnancy was spontaneous and one originated after in-vitro fertilization. In both pregnancies, cord entanglement was detected early in pregnancy (at 10 and 15 weeks) by color Doppler velocimetry demonstrating different heart rates within the segment of the entangled umbilical branches. The pregnancies were followed by documenting fetal behavior and color Doppler velocimetry of umbilical and fetal arteries at weekly intervals. In both cases, a primary Cesarean section was performed after detection of lung maturity. In the first case, one of the MA triplets had a transposition of the great arteries and abnormal lung vein drainage, which was the reason for neonatal death three weeks postnatally. Although early cord entanglement has been described in MA twins, this series demonstrates that it can as well be demonstrated in MA triplets. The early detection allows for extensive surveillance of the a priori high risk triplet pregnancy.

The role of ultrasound in multiple pregnancy.

The advances in reproductive technologies have changed the demographics of multifetal pregnancies. In the first trimester, ultrasound allows to diagnose the number of multiples, chorionicity and amnionicity, the presence or absence of nuchal translucency, early growth discordance, severe malformations and the origin of activities and contacts between multiples. In the second and third trimester, the opportunity to examine the cervix by transvaginal ultrasound should not be missed to detect the risk of premature delivery. Ultrasound is essential for the early grading and treatment of twin-to-twin transfusion syndrome (TTTS), the diagnosis of malformations and growth disturbances. Doppler velocimetry has proven to be able to reduce perinatal mortality in twin pregnancies. Finally, ultrasound is used for the detection of the position of multiples and the decision of the optimal route of delivery. This is of main importance in delayed interval delivery and expectant management of multifetal pregnancies and early cervical dilatation.

Preeclampsia and maladaptation to pregnancy: a role for atrial natriuretic peptide?

BACKGROUND: The majority of women with a history of preeclampsia have either an underlying thrombophilic disorder or a vascular disorder. In this study, we tested the hypothesis that only the latter condition predisposes for abnormal hemodynamic adaptation to pregnancy. METHODS: Thirty-seven formerly preeclamptic subjects were subdivided into a hypertensive (HYPERT, N = 10), a normotensive thrombophilic (THROMB, N = 13) and a normotensive nonthrombophilic subgroup (NONTHROMB, N = 14). In these women and in 10 normal parous controls, the following variables were measured at least five-months postpartum at day 5 (+/-2) of the menstrual cycle and again at five- and seven-weeks amenorrhea in the next pregnancy: mean arterial pressure, heart rate, cardiac output, central cardiovascular dimensions, plasma volume, glomerular filtration rate, effective renal plasma flow, 17-beta estradiol, progesterone, the hormones of the renin-angiotensin-aldosterone (RAAS) axis, catecholamines and alpha-atrial natriuretic peptide. RESULTS: The early pregnancy rise in cardiac output, renal variables, RAAS activity, and plasma volume was comparable in all groups. However, the HYPERT and NONTHROMB subgroups differed from controls by a lower plasma volume in the prepregnant state. In addition, only the women in these two subgroups responded to pregnancy by a rise in circulating alpha-atrial natriuretic peptide. In addition, at seven weeks, in the subjects belonging to the HYPERT and NONTHROMB subgroups, plasma volume was the lowest and correlated inversely with the concomitant circulating level of alpha-atrial natriuretic peptide. CONCLUSION: The hemodynamic adaptation to pregnancy in the HYPERT and NONTHROMB subgroups differs from that in THROMB and controls by an early pregnancy rise in alpha-atrial natriuretic peptide. As a consequence, the early pregnancy plasma volume expansion in the NONTHROMB and HYPERT subgroups is less than in normal parous controls.

Non-pregnant circulatory volume status predicts subsequent pregnancy outcome in normotensive thrombophilic formerly preeclamptic women.

BACKGROUND: Preeclampsia seems to be superimposed upon a preexisting hemodynamic, hemostatic, autoimmune or metabolic disorder. We tested the hypothesis that in normotensive thrombophilic formerly preeclamptic subjects, the non-pregnant circulatory volume status predicts the development of subsequent hypertensive pregnancy and/or fetal growth restriction. METHODS: In 250 non-diabetic formerly preeclamptic women and 15 normal parous controls, we measured and calculated the following variables at least 5 months postpartum at day 5 (+/-2) of the menstrual cycle: mean arterial pressure, body mass index, plasma volume and the clotting function. In the subsequent pregnancy we determined, birth weight, birth-weight centile and the incidence of preterm birth, fetal growth restriction, pregnancy-induced hypertension, preeclampsia and HELLP-syndrome. We only included in the final analysis normotensive subjects with a thrombophilic phenotype at the time of the pre-pregnant screening, who had a subsequent singleton pregnancy, ongoing beyond 16 weeks gestation within 1 year after pre-pregnant evaluation. As a consequence, 23 formerly preeclamptic women and 12 controls were eligible for final analysis. The thrombophilic formerly preeclamptic participants received aspirin in combination with low-molecular-weight heparin throughout pregnancy. If thrombophilia was diagnosed on the basis of hyperhomocysteinemia, the treatment consisted of aspirin, pyridoxine and folic acid, instead. RESULTS: Among 250 formerly preeclamptic 131/250 (52%) had a normotensive thrombophilic phenotype. Only 23 (18%) of these 131 participants had an ongoing pregnancy within 1 year. They were allocated to subgroup THROMB. None of the controls had hypertension or thrombophilia. In contrast, 12/15 (80%) controls had an ongoing pregnancy within a year. The observations in the THROMB subgroup were compared with those in the control group. None of the baseline demographic and blood pressure variables differed between THROMB and controls. With respect to pregnancy outcome, the incidence of the following pregnancy complications were observed in THROMB subjects: preterm birth: 9%, pregnancy-induced hypertension: 44%, preeclampsia: 13%, HELLP-syndrome: 13%, and fetal growth restriction: 30%. A low non-pregnant plasma volume was found to predispose for hypertensive complications in a subsequent pregnancy. CONCLUSION: Pre-pregnant plasma volume in normotensive thrombophilic formerly preeclamptic women have predictive value with respect to hypertensive complications in the subsequent pregnancy.

Ketanserin for the treatment of preeclampsia.

OBJECTIVE: To compare maternal and perinatal outcome with the use of either intravenous ketanserin or dihydralazine in treatment of women with preeclampsia. METHODS: The records from January 1989 to January 1997 of all patients receiving intravenous ketanserin or dihydralazine as first line antihypertensive therapy were reviewed and standardized data forms were completed. 315 charts of patients were identified and evaluated for effects on blood pressure, laboratory parameters, maternal and perinatal outcome. RESULTS: During the study interval 169 patients received ketanserin and 146 dihydralazine. Significantly fewer antepartum (27% versus 38%, p = 0.04) and postpartum (25% versus 39%, p = 0.01) maternal complications were noted in patients receiving ketanserin. Occurrence of HELLP syndrome was significantly lower among patients who received ketanserin (20%) than among those who received dihydralazine (40%, p = 0.0001). Side-effects were reported with significantly higher frequency in patients receiving dihydralazine (60%) as compared to those receiving ketanserin (17%, p < 0.0001). Perinatal outcome was comparable, however, umbilical cord arterial pH values (mean +/- SD) were higher with ketanserin compared to dihydralazine (7.25 +/- 0.07 vs 7.23 +/- 0.09, p = 0.038). The incidence of placental abruption was higher in patients receiving dihydralazine (5.5%) versus those receiving ketanserin (0.6%, p = 0.014). CONCLUSION: Ketanserin appears to be a better option than dihydralazine for treatment of severe preeclampsia since fewer maternal complications and side-effects were observed in patients receiving ketanserin.

Effects of rectally administered paracetamol on infants delivered by vacuum extraction.

OBJECTIVE: To evaluate whether paracetamol (20 mg/kg rectally) relieves pain in infants delivered by vacuum extraction, and improves clinical condition. METHODS: Prospective, randomised, double-blind, placebo-controlled study. Infants delivered by vacuum extraction were randomised either to the study group (n=61) and given paracetamol or to the control group (n=61) receiving placebo. Pain assessment was performed by a validated pain score and by scoring the clinical condition. Both scores and clinical symptoms in these groups were compared with symptoms in a reference group (n=66) with uncomplicated pregnancy and delivery in vertex position without vacuum extraction. RESULTS: Pain score did not differ between groups; clinical condition in the study group improved only after the first dose. There was a significant difference (P<0.05) in objective clinical symptoms in the vacuum extraction groups, compared to the reference group. CONCLUSION: One dose of paracetamol given to neonates delivered by vacuum extraction significantly improved their clinical condition, but did not result in a significant change in objective pain scores. Subsequent doses of paracetamol did not show any effect on the clinical symptoms or appearance of the neonates studied.