[Show abstract][Hide abstract] ABSTRACT: In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol.
The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015.The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment, and other patient characteristics available at baseline such as gestational age and estimated fetal weight. The secondary outcomes for mothers include co-incidence and severity of the maternal syndrome of pre-eclampsia, mortality, and other serious adverse events.
Trials are expected to start in 2013-2014 and end in 2016-2017. Data analyses of individual trials are expected to finish in 2019. Given the pre-planned and agreed IPD protocol, these results should be available in 2020.
[Show abstract][Hide abstract] ABSTRACT: Objective: To validate a previously published prediction model for recurrent early-onset preeclampsia (PE). Methods: We included 229 pregnant women with a history of early-onset PE and computed their risk using the prediction model, compared the predicted risk to their pregnancy outcomes and assessed performance of the model. Results: Early-onset PE recurred in 6.6% of participants. The area under the receiver operating characteristic curve was 59% (95% CI: 45-73). The model created groups that were only moderately different in terms of their risk. Conclusions: The model's discriminate ability was poor and predictive performance insufficient to classify women into relevant risk groups.
Hypertension in Pregnancy 01/2014; · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To explore hospital costs by pregnant women with a history of early-onset preeclampsia or HELLP syndrome, managed according to customary, but non-standardized prenatal care, by relating maternal and child outcome to maternal health care expenditure.
This was a cohort study, in women of 18 years or older who suffered from early-onset preeclampsia or HELLP syndrome in their previous pregnancy (n = 104). We retrieved data retrospectively from hospital information systems and medical records of patients who had received customary, non-standardized prenatal care between 1996 and 2012. Our analyses focused on the costs generated between the first antenatal visit at the outpatient clinic and postpartum hospital discharge. Outcome measures were hospital resource use, costs, maternal and child outcome (recurrence of preeclampsia or HELLP syndrome, incidence of eclampsia, gestational age at delivery, intrauterine fetal demise, small-for-gestational-age birth and low 5 minutes’ Apgar score). We used linear regression analyses to evaluate whether maternal and child outcome and baseline characteristics correlated with hospital costs.
Maternal hospital costs per patient averaged € 8047. Main cost drivers were maternal admissions and outpatient visits, together accounting for 80% of total costs. Primary cost drivers were preterm birth and recurrent preeclampsia or HELLP syndrome.
Hospital costs in the next pregnancy of formerly preeclamptic women varied widely with over 70% being medically unexplainable. The results of this study support the view that care standardization in these women can be expected to improve costs and efficacy of care without compromising outcome.
European Journal of Obstetrics & Gynecology and Reproductive Biology. 01/2014;
[Show abstract][Hide abstract] ABSTRACT: Objective
The internally validated fullPIERS model predicts adverse maternal outcomes in women with pre-eclampsia within 48 h after eligibility. Our objective was to assess generalizability of this prediction model.
External validation study using prospectively collected data from two tertiary care obstetric centers.
The existing PETRA dataset, a cohort of women (n = 216) with severe early-onset pre-eclampsia, eclampsia, HELLP syndrome or hypertension-associated fetal growth restriction was used. The fullPIERS model equation was applied to all women in the dataset using values collected within 48 h after inclusion. The performance (ROC area and R-squared) of the model, risk stratification and calibration were assessed from 48 h up to a week after inclusion.
Of 216 women in the PETRA trial, 73 (34%) experienced an adverse maternal outcome(s) at any time after inclusion. Adverse maternal outcome was observed in 32 (15%) cases within 48 h and 62 (29%) within 7 days after inclusion. The fullPIERS model predicted adverse maternal outcomes within 48 h (AUC ROC 0.97, 95% CI: 0.87–0.99) and up to 7 days after inclusion (AUC ROC 0.80, 95% CI: 0.70–0.87).
The fullPIERS model performed well when applied to the PETRA dataset. These results confirm the usability of the fullPIERS prediction model as a ‘rule-in’ test for women admitted with severe pre-eclampsia, eclampsia, HELLP syndrome or hypertension-associated fetal growth restriction. Future research should focus on intervention studies that assess the clinical impact of strategies using the fullPIERS model.
European Journal of Obstetrics & Gynecology and Reproductive Biology. 01/2014; 179:58–62.
[Show abstract][Hide abstract] ABSTRACT: Objectives
To assess the recurrence risk of term hypertensive disease of pregnancy and to determine which potential risk factors are predictive of recurrence.
We performed a retrospective cohort study in two secondary and one tertiary care hospitals in the Netherlands. We identified women with a hypertensive disorder in the index pregnancy and delivery after 37 weeks of gestation between January 2000 and December 2002. Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. Adverse outcome was defined as recurrence of a hypertensive disorder in the next subsequent pregnancy.
Main outcome measures
The absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive of recurrence.
We identified 638 women for potential inclusion, of whom 503 could be contacted. Of these women, 312 (62%) had a subsequent pregnancy. Hypertensive disorders recurred in 120 (38%, 95% CI 33–44) women, of whom 15 (5%, 95% CI 3–7) delivered preterm. Women undergoing recurrence were more at risk to develop chronic hypertension after pregnancy (35% versus 16%, OR 2.8, 95% CI 1.5–5.3). Body mass index, non-White European origin, chronic hypertension, maximum diastolic blood pressure, no use of anticonvulsive medication and interpregnancy interval were predictors for recurrence.
Women with hypertensive disorders and term delivery have a substantial chance of recurrence, but a small risk of preterm delivery. A number of predictors for recurrence could be identified and women with a recurrence more often developed chronic hypertension.
Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health. 01/2014;
[Show abstract][Hide abstract] ABSTRACT: Objectives. Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery.
Methods. We report cohort outcomes for a prospective multicenter randomized management study of fetal
growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20
European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26–32 weeks of
gestation, with abdominal circumference < 10th percentile and umbilical artery Doppler pulsatility index >95th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis.
Results Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall,
81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were signiﬁcantly related to estational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome.
Conclusions Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions.
Ultrasound in Obstetrics and Gynecology. 01/2013; 42:400-408.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: In preterm hypertensive disorders of pregnancy, fetal growth restriction (FGR) occurs frequently. The timing and severity of FGR impacts childhood growth and is associated with metabolic changes later in life. AIM: To examine growth and the impact of FGR in early childhood. DESIGN: Prospective cohort study. PARTICIPANTS: Children (n=135) born to mothers who were admitted before 34 weeks' gestational age with a severe hypertensive disorder of pregnancy. OUTCOME MEASURES: Height, weight, body mass index (BMI), head circumference (HC), SD scores (SDS) at 3 months, and 1 and 4.5 years of age, and complete catch-up growth (height SDS-target height SDS >-1.6). RESULTS: Growth scores were lower compared to Dutch growth curves, except for BMI at 3 months and girls' HC at all ages. Mean height SDS increased over time from -1.4 to -0.5 at 4.5 years, with 94% having complete catch-up growth. Mean BMI SDS decreased from -0.2 at 3 months to -1.0 at 1 year, and was -0.8 at age 4.5. Mean HC SDS was stable over time and -0.3 at 4.5 years. The customised birth weight ratio, as a measure of the degree of FGR, was related to all growth SDS at 4.5 years, while gestational age at birth was not. CONCLUSIONS: Although the majority of children born growth restricted had catch-up growth of height within the normal range at 4.5 years of age, they were smaller, but especially lighter compared to Dutch growth charts. The degree of FGR was associated with all growth outcomes.
Archives of Disease in Childhood 11/2012; · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the recurrence risk of late-preterm hypertensive disease of pregnancy, and to determine whether potential risk factors are predictive.
Retrospective cohort study.
Three secondary and three tertiary care hospitals in the Netherlands.
We identified women with a hypertensive disorder in the index pregnancy and delivery at 34-37 weeks of gestation, between January 2000 and December 2002.
Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. An adverse outcome was defined as the recurrence of a hypertensive disorder in the next subsequent pregnancy.
Absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive for adverse outcome.
We identified 425 women who matched the criteria, of whom 351 could be contacted. Of these women, 189 (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%, 95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37 weeks of gestation. Chronic hypertension and maternal age were the strongest predictors for recurrence. Women undergoing recurrence had a nine-fold chance of developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI 3.3-23).
Women with hypertensive disorders and late-preterm delivery have a 50% chance of recurrence, but only a 9% chance of recurrence resulting in delivery before 37 weeks of gestation. Women with chronic hypertension are prone to develop recurrence, and women with a recurrence more often developed chronic hypertension.
BJOG An International Journal of Obstetrics & Gynaecology 04/2012; 119(7):840-7. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the recurrence risk of late preterm hypertensive disease of pregnancy and to determine whether potential risk factors are predictive.
Retrospective cohort study.
Our study cohort included 425 women with a pregnancy-related hypertensive disorder who had delivered between 34 and 37 weeks of gestation at three different academic and three tertiary care hospitals in the Netherlands during the 2000-2002 period. Data were collected from medical files and by telephone interviews with the women. An adverse outcome was defined as the recurrence of a hypertensive disorder during the subsequent pregnancy. We also designed a prediction model containing demographic and clinical factors predictive for an adverse outcome.
Of the 425 women who met the inclusion criteria, 351 could be contacted, of whom 189 (54%) had had a subsequent pregnancy. Pregnancy-related hypertensive disorders had recurred in 96 (51%; 95% CI: 43-58) women. Seventeen women (9%; 95% CI: 5-14) had delivered again before the 37th week. Pre-existing hypertension and maternal age were the strongest predictors for recurrence. Women who had experienced a recurrence had a 9-fold chance of developing chronic hypertension (37 vs. 6%; OR 8.7; 95% CI: 3.3-23).
Women with hypertensive disorders and late preterm deliveries have a 50% chance of recurrence of the disorder and a 9% chance of recurrent premature delivery. Women with pre-existing hypertension or who are older are prone to recurrence. Women with a recurrent hypertensive disorder during a subsequent pregnancy often later develop chronic hypertension.
Nederlands tijdschrift voor geneeskunde 01/2012; 156(39):A5314.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The objective of the study was to determine the neonatal morbidity in late preterm infants born from mothers with a hypertensive disorder. STUDY DESIGN: Data were obtained from the national Perinatal Registry in The Netherlands on women who delivered between 34(+0) and 36(+6) weeks with gestational hypertension (n = 4316), preeclampsia (n = 1864), and normotensive controls (n = 20,749). RESULTS: Children from mothers with preeclampsia had an increased risk for admission to the neonatal intensive care unit compared with children from normotensive mothers (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2). A cesarean delivery and decreasing gestational age were independent risk factors for neonatal respiratory morbidity. Gestational hypertension or preeclampsia reduced the risk of respiratory distress syndrome compared with the control group (OR, 0.81; 95% CI, 0.64-1.0 and OR, 0.69; 95% CI, 0.49-0.96, respectively). CONCLUSION: Neonatal morbidity in the late preterm period is considerable. Hypertensive disorders appear to protect for neonatal respiratory morbidity, but higher rates of cesarean section diminish this protective effect
American journal of obstetrics and gynecology 07/2011; 205(6). · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to describe neurodevelopmental outcome at the age of 4.5 years in 216 children, born after expectant management of severe early-onset hypertensive complications of pregnancy.
This was a prospective follow-up study until age 4.5 years from maternal admission onward. Developmental outcome measurements included child intelligence quotient and behavioral, motor, and neurological outcome. Abnormal composite outcome (perinatal mortality or abnormal developmental outcome) was studied in relation to gestational age (GA), birthweight (BW), and perinatal variables.
Fetal and neonatal mortality was 9% and 8%, respectively. Of the 178 survivors, 149 (84%) were seen for follow-up. Mean GA was 31.4 weeks and 90% were born growth restricted. Abnormal developmental outcome occurred in 20% and abnormal composite outcome in 37%.
Perinatal mortality or abnormal child development occurs in one third of pregnancies with early-onset and severe hypertensive complications and is highest in the lowest GA and BW ranges.
American journal of obstetrics and gynecology 04/2011; 204(6):510.e1-9. · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pre-eclampsia has a strong association with adverse outcomes: high incidences at term, and low incidences of morbidity; low incidences remote from term, high incidences of morbidity. The ultimate cure for pre-eclampsia is delivery of the placenta, but gestational age at delivery has an effect on perinatal outcome. We review aspects of two contrasting management approaches, and their indication areas are described (i.e. a more interventionist approach of stabilization (with antihypertensive drugs if needed and corticosteroids for acceleration of fetal lung maturation) and delivery, compared with a more temporizing approach, that treats the symptoms until delivery is necessary. In general, the temporizing approach has been shown to be safe, but beyond 37 weeks gestational age, there is evidence for better outcomes after early delivery. Below that gestational age, trials are awaited that help determine the balance in individual cases, depending on severity of maternal disease and fetal condition.
Best practice & research. Clinical obstetrics & gynaecology 03/2011; 25(4):463-76. · 1.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to report outcomes of the subsequent pregnancy after early-onset pre-eclampsia in a first pregnancy (index), and to evaluate the potential risk factors for recurrence of pre-eclampsia and preterm delivery.
We performed a retrospective cohort study of all women who developed early-onset pre-eclampsia (delivery before 34 weeks of gestation) in their first pregnancy between January 1996 and December 2004 in two perinatal centres with regional function. All patients were included consecutively. Information was retrieved on the course of subsequent pregnancies.
Two tertiary centres with regional function.
Women with a delivery under 34 weeks due to a hypertensive disorder (N=380).
We determined the absolute risk of recurrence of an adverse outcome, defined as a hypertensive complication resulting in delivery before 34 weeks of gestation. The available clinical parameters were evaluated as predictors for recurrence using logistic regression analysis.
We identified 380 patients, of whom 46 were lost to follow-up. In total, 123 patients refrained from subsequent pregnancy (79 [64%] from fear of recurrence). Of the 211 patients with a subsequent pregnancy, 36 (17%, 95% CI 12-22%) had a recurrent delivery before 34 weeks of gestation, 30 (14%, 95% CI 9.5-19%) delivered between 34 and 37 weeks of gestation, and 145 (69%, 95% CI 62-75%) delivered later than 37 weeks of gestation. Of this last group, only 67 (32%, 95% CI 25-38%) pregnancies were completely uneventful. Chronic hypertension, maximum diastolic blood pressure, caesarean delivery and level of 24-h proteinuria were independent predictors for an adverse pregnancy outcome.
Women that had early severe pre-eclampsia in their first pregnancy have a 17% risk of recurrence, with a delivery before 34 weeks of gestation. Only 32% had a completely uneventful pregnancy.
BJOG An International Journal of Obstetrics & Gynaecology 02/2011; 118(5):589-95. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early onset hypertensive disorders of pregnancy are associated with adverse maternal and neonatal outcome. The risk of recurrence influences parents' choices on subsequent pregnancies and the counseling obstetrician, but evidence so far has been limited. We performed the first systematic review on the risk of recurrence of hypertensive disorders that had caused delivery <34 weeks. We searched Medline, Embase, and the Cochrane Library for articles published until September 2009 that report on pregnancy outcome after an earlier pregnancy complicated by early hypertension, preeclampsia, or hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, which resulted in a delivery before 34 weeks. Recurrence rates of premature deliveries due to hypertensive disorders were calculated for each study separately. Pooled data were calculated. The search retrieved 36 relevant articles, of which 11 fulfilled the inclusion criteria. These 11 studies reported on 2377 patients (range 18 to 1754 patients per study), who had 2461 deliveries. Seven studies were included for further calculation. The pooled risk of a delivery before 34 weeks due to recurrence of hypertension, preeclampsia, or HELLP was 7.8% (95% confidence interval 6.7 to 9.0%). Opposed to some previous studies, the overall recurrence rate is generally low. The pooled recurrence risk of an early onset hypertensive disorder is approximately 8%.
American Journal of Perinatology 02/2010; 27(7):565-71. · 1.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the accuracy of a non-invasive beat-to-beat continuous blood pressure monitoring device (Nexfin) in pregnancy according to the International Protocol of the European Society of Hypertension.
The validation was performed according to the International Protocol of the European Society of Hypertension. The test device (Nexfin, BMEYE, Amsterdam, the Netherlands) calculates beat to beat blood pressure from finger pulse wave analysis. Measurements of systolic and diastolic BP in 33 volunteers were obtained using the mercury sphygmomanometer and the Nexfin alternatingly.
The device passed phase 1 as 30 systolic and 32 diastolic readings fell within 5 mmHg (25 required). In addition, the device also passed phase 2.1 as 68 systolic and 67 diastolic readings fell within 5 mmHg (65 required). Finally, it failed to pass phase 2.2 as 24 subjects for systolic and 23 for diastolic had at least 2/3 of their comparisons falling within 5 mmHg (22 required) but 6 subjects for systolic and 8 for diastolic had all three comparisons more than 5 mmHg different from the mercury readings (three allowed). The mean differences were 2.3 mmHg (SD 6.8) for SBP and 0.8 mmHg (SD 6.3) for DBP.
The Nexfin device passed phase 1 and phase 2.1 but failed to pass phase 2.2. However, adaptation of the data to the more permissive AAMI (mean difference <5 +/- 8 mmHg) and BHS (systolic grade B, diastolic grade A) protocols indicated adequate accuracy for application in research settings or for longitudinal within-patient tracking of blood pressure, given the possibility for continuous monitoring.
Hypertension in Pregnancy 05/2009; 28(2):230-42. · 0.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this work was to study the effect of maternal psychological symptoms on infant development 1 year after early-onset hypertensive disorders of pregnancy.
All mothers were enrolled in the Pre-eclampsia, Eclampsia TRial Amsterdam. Mothers were asked to complete the 90-item Symptom Check List (SCL-90) at the corrected ages of their infants of 0, 3 and 12 months. The total sum score of these three checklists was calculated. Infants were examined at the corrected age of 12 months using the Bayley Scales of Infant Development (Mental Developmental Index [MDI] and Psychomotor Developmental Index [PDI] subscales). The Bayley scores were compared between infants of mothers with SCL-90 sum scores in the highest 25% and lowest 75%.
For 141 mother-infant pairs (80%) all three SCL-90 checklists and Bayley scores were available. Mean gestational age was 32 weeks and 90% of the infants were growth restricted. The mean MDI was 87 in the highest 25% and 89 in the lowest 75% group. This was 79 versus 80 for the PDI.
In this population of high-risk growth-restricted infants born after a pregnancy complicated by early-onset hypertensive disorders, there is no additional impact of negative maternal psychological symptoms on infant development after 1 year.
[Show abstract][Hide abstract] ABSTRACT: Assessment of general movements (GMs) at three months is considered useful for prediction of adverse neurological outcome in high risk infants.
To study the prevalence of abnormal GMs in infants born from women with early-onset hypertensive disorders of pregnancy and the association of GMs with neurodevelopmental outcome at one year.
Prospective study, part of a randomised controlled trial of pre-birth management strategies.
Infants born from women with early-onset hypertensive disorders of pregnancy.
GMs observation and neurological examination at term and three months corrected age; at one year neurological examination and Bayley Scales of Infant Development.
From 216 women included, 175 of 178 surviving infants (mean gestational age 31.6 weeks [SD 2.3], mean birth weight 1346 grams [SD 458]), were examined at three months. At term age normal, mildly abnormal and definitely abnormal GMs were observed in 54%, 36% and 10% respectively; and at three months in 47%, 40% and 13%. Mildly or definitely abnormal GMs at three months were not associated with abnormal neurological examination at one year, however, they were associated with delayed psychomotor development at one year (p = 0.01).
In this prospective study, including small for gestational age, preterm infants about half of them did not have normal GMs at term and three months. There was no association of GMs at term nor three months with neurological outcome at one year, but there was a significant association of GMs at three months with one year psychomotor development.
Early Human Development 05/2008; 84(9):605-11. · 2.02 Impact Factor