Gus Dekker

The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP

There has never been a definite consensus on the classification and diagnostic criteria for the hypertensive disorders of pregnancy. This uncertainty is likely to have led to between-centre differences in rates of adverse maternal and foetal outcomes for the various hypertensive disorders in pregnancy, particularly pre-eclampsia. In 2000, the International Society for the Study of Hypertension in Pregnancy (ISSHP) recognised that this lack of consensus was one reason for controversies concerning counselling, management and documentation of immediate and remote pregnancy outcomes. Accordingly, the Society appointed a committee that reviewed available classifications and endorsed and published an international recommendation for how these disorders should be classified and diagnosed in pregnancy [1]. The major stumbling block remained whether or not proteinuria should be retained as a sine qua non for the diagnosis of pre-eclampsia; the Society recommended that a broad definition, at times not including proteinuria, could be applied for the clinical definition of pre-eclampsia whilst the inclusion of proteinuria would ensure more specificity around the diagnosis when reporting clinical criteria for patients enrolled in scientific research. The purpose of this document is to update ISSHP thinking on this subject.

Primary, secondary, and tertiary prevention of pre-eclampsia

Pre-eclampsia remains one of the major obstetrical problems in less-developed countries. The causes of this condition are still unknown, thus effective primary prevention is not possible at this stage. Research in the past decade has identified some major risk factors for pre-eclampsia, and manipulation of these factors might result in a decrease in its frequency. In the early 1990s aspirin was thought to be the wonder drug in secondary prevention of pre-eclampsia. Results of large trials have shown that this is not the case: if there is an indication for using aspirin it is in the patient at a very high risk of developing severe early-onset disease. The calcium story followed a more or less similar pattern, with the difference that existing evidence shows that women with a low dietary calcium intake are likely to benefit from calcium supplementation. Proper antenatal care and timed delivery are of utmost importance in tertiary prevention of pre-eclampsia. There is evidence to suggest that the intrinsic direct effect of moderate degrees of maternal hypertension is beneficial to the fetus. Severe hypertension needs treatment. If antihypertensive is indicated, there is no clear choice of a drug. Hydralazine should no longer be thought of as the primary drug, most studies show a preference for calcium channel blockers.

Tocolysis with nifedipine or beta-adrenergic agonists: a meta-analysis

Abstract Objective: To clarify the relative efficacy of nifedipine and beta-agonists for tocolysis. Data Sources: The literature was searched in the following databases: MEDLINE 1965–1998, Embase 1988–1998, Current Contents 1997–1998, and the Cochrane Database for 1998. We also sought unpublished trials and abstracts submitted to major international congresses. Search terms were: “tocolysis,” “nifedipine,” “calcium channel blocker,” “ritodrine,” “terbutaline,” and “salbutamol.” Methods of Study Selection: Randomized controlled trials comparing tocolysis with nifedipine and beta-adrenergic agonists during preterm labor were reviewed. In cases with postrandomization exclusions, authors were contacted to obtain intent-to-treat results and to avoid analytical bias. We identified 11 published and two unpublished randomized trials. Tabulation, Integration, and Results: Data were extracted by two reviewers and analyzed by a blinded biostatistician with RevMan 3.1 software from the Cochrane Collaboration. We analyzed nine relevant randomized controlled trials that included 679 patients. Meta-analysis showed that nifedipine was more effective than the beta-agonists in delaying delivery at least 48 hours [odds ratio (OR) 1.52, 95% confidence interval (CI) 1.03, 2.24], or over 34 weeks (OR 1.87, 95% CI 1.11, 3.15). The agents did not differ as to the incidence of deliveries after 37 weeks (OR 1.29, 95% CI 0.85, 1.96) or the neonatal mortality rate (OR 1.51, 95% CI 0.63, 3.65). Treatment with nifedipine was interrupted significantly less often because of side effects (OR 0.12, 95% CI 0.05, 0.29) and led to better neonatal outcomes (fewer infants with respiratory distress syndrome: OR 0.57, 95% CI 0.37, 0.89) or transferred to neonatal intensive care units (OR 0.65, 95% CI 0.43, 0.97). Conclusion: With respect to neonatal outcome, nifedipine appears to be more effective than beta-agonists for tocolysis and should be considered for use as a first-line tocolytic agent.

Surgically obtained sperm, and risk of gestational hypertension and pre-eclampsia

The cause of pre-eclampsia is unknown, although a partner-specific immune maladaptation might be involved. We compared rates of pre-eclampsia and gestational hypertension in women whose genital tracts had and had not been exposed to their partners sperm cells. Our aim was to ascertain whether or not protective partner-specific immune-tolerance is conveyed by sperm cells, rather than seminal fluid. Our findings indicate that, compared with women exposed to their partners sperm cells and seminal fluid--ie, those treated with in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) with ejaculated sperm--the risk of hypertension was doubled and the risk of pre-eclampsia tripled in those never exposed to their partners sperm--ie, those treated with ICSI done with surgically obtained sperm.

Low-dose aspirin in the prevention of preeclampsia and fetal growth retardation: Rationale, mechanisms, and clinical trials

Preeclampsia is characterized by a functional imbalance between vascular prostacyclin and thromboxane A 2 production. On the basis of the hypothesis that preeclampsia is at least partially caused by an increase in thromboxane A 2 , some studies attempted to correct this pathologic condition by pharmacologic manipulation with low-dose aspirin. The current literature suggests that the use of low-dose aspirin during pregnancy is safe with regard to congenital anomalies and fetal, neonatal, and maternal cardiovascular physiologic state and hemostasis. Aspirin at least partially corrects the pathologic increase in angiotensin II sensitivity that precedes the clinical development of preeclampsia. In addition, some clinical trials have demonstrated that low-dose aspirin is effective in reducing the incidence of preeclampsia and/or fetal growth retardation in selected high-risk women. Currently, large clinical trials are in progress to evaluate the effectiveness and side effects of the use of low-dose aspirin in preventing preeclampsia and/or fetal growth retardation. Until these studies have been completed, it will remain unclear whether antiplatelet therapy, such as low-dose aspirin, should be adopted for the prevention of either preeclampsia or fetal growth retardation.

Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia. # Novelty and Significance {#article-title-41}More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Maternal and perinatal outcome in obese pregnant patients

Introduction. Obesity represents a rapidly emerging epidemic amongst pregnant patients in South Australia, in particular in Adelaides Northern suburbs, one of the poorest urban areas in Australia. The aim of the current study was to prepare a comprehensive overview of maternal and perinatal outcome in overweight, obese and morbidly obese pregnant patients. Material and methods. Retrospective review of women with singleton pregnancies delivering in the first 6 months of 2006; 100 with normal BMI (group I: BMI 19.1–25 kg/m2), 100 overweight (group II: BMI 25.1–30 kg/m2), 110 obese (group III: BMI 30.1–40 kg/m2) and 60 morbidly obese women (group IV: BMI >40 kg/m2) were identified with access to complete medical records. Outcome measures included booking demographics, booking blood pressures, glucose challenge and glucose tolerance results, hypertensive complications, pre-existing and gestational diabetes, instrumental deliveries, caesarean deliveries, blood loss, birth weights, Apgar scores, post-partum complications and psychological problems. Results. Women in group II, III and IV were characterised by higher systolic booking blood pressure (mean differences: 3.92, 9.94 and 9.84 respectively for group II, III and IV) and higher diastolic booking blood pressures (mean differences 3.02, 6.92 and 9.22 respectively). As a combined group II–IV, women were at increased risk for pre-existing morbidity (OR 2.33) and requiring medication (OR 2.13). Pregnancy hypertension occurred significantly more in group III and IV with OR 2.38 and 3.75. Women without pre-existing hypertension were also found to be at increased risk to develop gestational hypertension only if they belonged to group IV (OR 3.69). Women in group III and IV are at increased risk at gestational diabetes with OR 8.82 and 27.38. Women in group III and IV are less likely to have a spontaneous onset of labour with ORs of 2.18 and 3.51 for not having spontaneous onset of labour. Induction of labour occurred more often in group IV (OR 3.17). Requirement of instrumental deliveries or lower segment caesarean section occurred more often in group II, III and IV with OR 2.20, 3.28 and 5.47 respectively. Significant more blood loss was found in group III and IV with mean differences of 135.42 and 207.94 ml compared with group I. The birthweight in group III and IV are significantly higher with mean differences of 104.86 and 324.94 g. Macrosomia occurred more often in group IV (OR 4.04). Women in group III and IV had a longer overall hospital stay with mean differences of 0.58 and 1.09 days. Mental health issues were more common in group II, III and IV with OR 3.16, 3.53 and 4.17 respectively. Conclusion. These South Australian data from a socio-economically deprived area in Adelaides Northern suburbs confirm that obesity during pregnancy represents a major risk for adverse outcome for patients with a whole spectrum of adverse pregnancy outcomes; obesity represents a major challenge for health care providers.

The partner's role in the etiology of preeclampsia

The etiology of preeclampsia is often considered to be purely maternal, i.e. maternal constitutional factors that impair maternal cardiovascular/endothelial mechanisms normally required to cope with the specific pregnancy demands, being primarily a generalised inflammatory response and a hyperdynamic circulation. Recent data strongly indicate an important role for the male partner in the causation of this common pregnancy disorder. The aim of this review is to discuss the relevant literature and to explain how paternal, relational and sexual factors play an important role in the etiology of preeclampsia.

Epidemiologic associations with cerebral palsy

OBJECTIVE: To estimate epidemiologic risk factors for cerebral palsy. METHODS: Data were collected by linkage to state-based perinatal repositories and cerebral palsy registers and using a maternal questionnaire. The cohort included 587 individuals with cerebral palsy and 1,154 non–cerebral palsy controls. RESULTS: The following factors were associated with cerebral palsy: recorded maternal infection during pregnancy (41.4% patients compared with 31.3% controls; odds ratio [OR] 1.55, 95% confidence interval 1.26–1.91), small for gestational age ([birth weight less than third customized centile] 43.9% patients compared with 6.3% controls; OR 11.75, 6.25–22.08), gestational age less than 32 weeks (29.3% patients compared with 0.7% controls; OR 59.20, 28.87–121.38), multiple birth (OR 6.62, 4.00–10.95), a relative with cerebral palsy (OR 1.61, 1.12–2.32), breech position (13.7% patients compared with 6.0% controls; OR 2.48, 1.76–3.49), bleeding at any time in pregnancy (29.3% patients compared with 16.9% controls; OR 2.04, 1.61–2.58), male sex (58.8% patients compared with 45.8% controls; OR 1.68, 1.38–2.06), multiple miscarriage (7.7% patients compared with 3.5% controls; OR 2.30, 1.38–3.82), smoking (14.0% patients compared with 10.6% controls; OR 1.37, 1.02–1.85), and illicit drug use (3.3% patients compared with 1.5% controls; OR 2.22, 1.14–4.30). Factors not associated with cerebral palsy were “disappearing twin,” diabetes, maternal body mass index, hypertension, alcohol consumption, anemia, maternal hypothyroidism, forceps or vacuum delivery, and maternal age. CONCLUSION: Preterm birth, intrauterine growth restriction, perinatal infection, and multiple birth present the largest risks for a cerebral palsy outcome. Reassuringly, upper respiratory tract and gastrointestinal infections during pregnancy were not associated with cerebral palsy. LEVEL OF EVIDENCE: II

Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies

Objectives To compare the prevalence and predictors of alcohol use in multiple cohorts. Design Cross-cohort comparison of retrospective and prospective studies. Setting Population-based studies in Ireland, the UK, Australia and New Zealand. Participants 17 244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study. Primary and secondary outcome measures Prevalence of alcohol use pre-pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort. Results Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1–2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70). Conclusions Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates.