Pregnancy intention in relation to maternal and neonatal outcomes in women with versus without psychiatric diagnoses.

BACKGROUND: Studies have identified adverse maternal and neonatal outcomes for women with psychiatric disorders. Additionally, psychiatric disorders may pose an increased risk for unintended pregnancies (UPs) which in turn may also impact negatively on outcomes. The present study aims to compare the incidence of UPs in women with versus without current/past psychiatric diagnoses and investigates whether psychiatric history modifies the relation between delivery outcomes in women with and without UPs. METHODS: A retrospective cohort was compiled of women who gave birth in a large hospital in Amsterdam, the Netherlands. Women ≥18 years old with singleton pregnancies and birth registrations in the electronic patient file during January 1, 2015 to March 1, 2020 were included. Patient characteristics (including pregnancy intention and psychiatric history), maternal (gestational diabetes, mode of delivery) and neonatal outcomes (e.g., gestational age [GA], birthweight and Apgar scores) were registered by health care providers in hospital charts. Incidence of UPs was compared between women with versus without current/past psychiatric diagnoses. Maternal and neonatal outcomes were compared between women with versus without UPs with linear or logistic regression models adjusted for relevant confounders with an interaction term for UP with current/past psychiatric diagnoses. RESULTS: We included 1219 women with and 1093 women without current/past psychiatric diagnoses. Current/past psychiatric diagnoses were significantly associated with UPs after adjustment for confounders (39.0% vs. 29.6%, OR 1.56, CI 1.23-2.00, p < 0.001). In sub-analyses, women with depressive (OR 1.67, CI 1.24-2.26, p = 0.001), personality (OR 2.64, CI 1.38-5.11, p = 0.004) and substance-related and addictive disorders (OR 4.29, CI 1.90-10.03, p = 0.001) had higher odds of UPs compared to women without current/past psychiatric diagnoses. Amongst women with UPs, current/past psychiatric diagnoses did not modify maternal or neonatal outcomes, except for GA at delivery as women with both UPs and current/past psychiatric diagnosis had a 2.21-day higher mean GA at delivery than women in the reference group (p-value interaction = 0.001). CONCLUSIONS: Current/past psychiatric diagnoses are associated with a higher odd of UPs. In our sample, maternal and neonatal outcomes were comparable for women with and without UPs and these results were similar for women with and without current/past psychiatric diagnoses, except for GA at delivery. Although our study is limited by several factors, we found that women with current/past psychiatric diagnoses, irrespective of pregnancy planning status, do not have more adverse maternal or pregnancy outcomes. Increased efforts are needed to ensure that psychoeducation and conversations about pregnancy planning and UPs are available for women with current/past psychiatric diagnoses.

The conversation about family planning and desire for children in mental healthcare: Patients' perspective versus Professionals' perspective in a mixed methods study.

BACKGROUND: Reproductive health and mental health are intertwined, but studies investigating family planning needs and desire for children in mental healthcare are scarce. METHODS: We studied the experiences of (former) patients, those with close relationships with the (former) patients (close ones) and mental health professionals (MHP) on discussing family planning and desire for children in mental healthcare. We combined quantitative (two nationwide surveys) and qualitative data (four focus groups) in a mixed-methods approach with sequential analytical design. RESULTS: Combined data from focus groups (n = 19 participants) and two surveys (n = 139 MHPs and n = 294 (former) patients and close ones) showed that a considerable group of MHPs (64.0%), patients (40.9%) and close ones (50.0%) found that family planning should be discussed by a psychiatrist. However, several obstacles impeded a conversation, such as fear of judgment, lack of time and knowledge and limited opportunity for in-depth exploration of life themes in therapeutic relationships. CONCLUSIONS: To increase the autonomy of patients in discussing family planning, we suggest MHPs explore the desire to discuss family planning with all patients in the reproductive phase of life, prior to discussing contraceptive care. MHPs should receive education about psychiatric vulnerability in relation to family planning and desire for children, and patients and close ones should be empowered to initiate a conversation themselves.

Continuing the conversation: a cross-sectional study about the effects of work-related adverse events on the mental health of Dutch (resident) obstetrician-gynaecologists (ObGyns).

BACKGROUND: Obstetrician-Gynaecologists (ObGyns) frequently face work-related adverse events such as severe obstetric complications and maternal or neonatal deaths. In 2014, the WATER-1 study showed that ObGyns are at risk of developing work-related posttraumatic stress disorder (PTSD), while many hospitals lacked a professional support system. The aim of the present study is to evaluate the current prevalence of work-related traumatic events and mental health problems among Dutch ObGyns, as well as to examine the current and desired support. METHODS: In 2022, an online questionnaire was sent to all members of the Dutch Society of Obstetrics and Gynaecology (NVOG), including resident and attending ObGyns. The survey included questions about experienced work-related events, current and desired coping strategies, and three validated screening questionnaires for anxiety, depression, and PTSD (HADS, TSQ, and PCL-5). RESULTS: The response rate was 18.8% and 343 questionnaires were included in the analysis. Of the respondents, 93.9% had experienced at least one work-related adverse event, 20.1% had faced a complaint from the national disciplinary board, and 49.4% had considered leaving the profession at any moment in their career. The prevalence rates of clinically relevant anxiety, depression, and psychological distress were 14.3, 4.4, and 15.7%, respectively. The prevalence of work-related PTSD was 0.9% according to DSM-IV and 1.2% according to DSM-5. More than half of the respondents (61.3%) reported the presence of a structured support protocol or approach in their department or hospital, and almost all respondents (92.6%) rated it as sufficient. CONCLUSIONS: The percentages of anxiety, depression, psychological distress and PTSD are comparable to the similar study performed in 2014. Most Dutch ObGyns experience adverse events at work, which can be perceived as traumatic and, in certain cases, may lead to the development of PTSD. Structured support after adverse work-related events is now available in almost two-thirds of workplaces, and was mostly experienced as good. Despite substantial improvements in the availability and satisfaction of professional support after work-related adverse events, the prevalence rates of mental problems remain considerable, and it is imperative to sustain conversation about the mental well-being of ObGyns.

Unplanned cesarean sections in advanced maternal age: A predictive model.

INTRODUCTION: As maternal age during pregnancy is rising all over the world, there is a growing need for prognostic factors that determine maternal and perinatal outcomes in older women. MATERIAL AND METHODS: This study is a retrospective cohort study of women aged 40 years or older at the time of delivery in four Santeon hospitals across the Netherlands between January 2016 and December 2019. Outcomes were compared between women of 40-44 years (advanced maternal age) and 45 years and older (very advanced maternal age). Primary outcome was unplanned cesarean section, secondary outcomes included postpartum hemorrhage and neonatal outcomes. Multivariate regression analysis was performed to analyze predictive factors for unplanned cesarean sections in women who attempted vaginal delivery. Subsequently, a predictive model and risk scores were constructed to predict unplanned cesarean section. RESULTS: A cohort of 1660 women was analyzed; mean maternal age was 41.4 years, 4.8% of the women were 45 years and older. In both groups, more than half of the women had not delivered vaginally before. Unplanned cesarean sections were performed in 21.1% of the deliveries in advanced maternal age and in 29.1% in very advanced maternal age. Four predictive factors were significantly correlated with unplanned cesarean sections: higher body mass index (BMI), no previous vaginal delivery, spontaneous start of delivery and number of days needed for cervical priming. A predictive model was constructed from these factors with an area under the curve of 0.75 (95% confidence interval 0.72-0.78). A sensitivity analysis in nulliparous women proved that BMI, days of cervical priming, age, and gestational age were risk factors, whereas spontaneous start of delivery and induction were protective factors. There was one occurrence of neonatal death. CONCLUSIONS: Women of advanced maternal age and those of very advanced maternal age have a higher chance of having an unplanned cesarean section compared to the general obstetric population in the Netherlands. Unplanned cesarean sections can be predicted through use of our predictive model. Risk increases with higher BMI, no previous vaginal delivery, and increasing number of days needed for cervical priming, whereas spontaneous start of labor lowers the risk. In nulliparous women, age and gestational age also increase risk, but induction lowers the risk of having an unplanned cesarean section.

Fear of childbirth in pregnancy was not increased during the COVID-19 pandemic in the Netherlands: a cross-sectional study.

INTRODUCTION: Fear of childbirth is a well-known problem during pregnancy and can have implications for childbirth, including prolonged labor, use of epidural analgesia, obstetric complications, presence of traumatic stress symptoms, or request for an elective cesarean section. The coronavirus disease 2019 (COVID-19) pandemic has affected mental health and therefore could have increased fear of childbirth during the pandemic. The aim of this study was to investigate fear of childbirth during the pandemic in the Netherlands compared with a reference group from before the pandemic. MATERIAL AND METHODS: We conducted a cross-sectional study to evaluate pregnant women during the first and second waves of COVID-19 compared with both each other and with pregnant women from before the pandemic. Participants were recruited through social media platforms, hospitals, and midwifery practices. Pregnant women aged ≥18 years who had mastered the Dutch language were eligible to participate. Fear of childbirth was measured with the Wijma Delivery Expectancy Questionnaire online using a cut-off score of ≥85 to indicate clinically relevant fear of childbirth. The primary outcome was the prevalence of fear of childbirth. We undertook additional analyses to specifically look at possible effect modification. RESULTS: In total, 1102 pregnant women completed the questionnaire during the first wave of the pandemic, 731 during the second wave, and 364 before the pandemic. Fear of childbirth was present in 10.6%, 11.4%, and 18.4%, respectively. We considered possible effect modification, which indicated that age and parity had a significant influence. In participants during the first wave of COVID-19, nulliparous women had significantly lower odds (odds ratio [OR] 0.50; 95% confidence interval [CI] 0.34-0.73; p < 0.01) of having a fear of childbirth than did the reference group. Both younger participants in the first wave (OR 0.59; 95% CI 0.37-0.93; p < 0.05) and older participants in the first wave (OR 0.44; 95% CI 0.28-0.71; p < 0.01) and the second wave (OR 0.36; 95% CI 0.21-0.62; p < 0.01) of COVID-19 had lower odds of fear of childbirth than the reference group. CONCLUSIONS: Pregnant women during the first and second waves of COVID-19 had lower fear of childbirth scores than pregnant women before the pandemic, indicating less fear of childbirth during the pandemic. This could be explained by an increased level of information, more time to consume information, and better work-life balance with more people working at home during the pandemic.

Therapist perceptions of treating posttraumatic stress disorder in pregnancy: The VIP Study.

There is no consensus on the treatment of posttraumatic stress disorder (PTSD) during pregnancy, and therapists' views on the matter are largely unknown. This cross-sectional study aimed to explore therapist beliefs and experiences regarding PTSD treatment during pregnancy. Participants were therapists (N = 301) with experience treating PTSD who completed an online survey. The primary outcome measure was the percentage of therapists who were experienced in treating PTSD symptoms during pregnancy; secondary outcome measures assessed preferred treatments for the general and pregnant populations, perceived reluctance to treat PTSD in pregnancy, and perceived effects and adverse events attributed to treatment for pregnant women and fetuses. The majority of participants (n = 246, 81.7%) had experience with treating PTSD during pregnancy. Eye movement desensitization and reprocessing was the preferred treatment for both the general and the pregnant populations. Almost half of the sample (48.8%) reported hearing that PTSD treatment in pregnancy could be harmful; 30.5% of therapists were reluctant to treat pregnant women with PTSD. Most therapists observed a clinically relevant posttreatment reduction of PTSD symptoms in pregnant women. Perceived adverse maternal and fetal events attributed to treatment were reported by 8.4% and 1.4% of therapists, respectively. Despite reluctance, most therapists reported treating PTSD during pregnancy. The results show that although therapists often reported hearing that treating PTSD during pregnancy was harmful, only a small percentage reported perceived adverse events, and treatment was often viewed as effective. These findings implicate a more positive view on the treatment of PTSD in pregnancy.

Adverse maternal and perinatal pregnancy outcomes related to very advanced maternal age in primigravida and multigravida in the Netherlands: A population-based cohort.

INTRODUCTION: The age at which women give birth is rising steadily in the western world. Advanced maternal age has been associated with adverse pregnancy outcomes. We assessed the association between advanced maternal age and the risk of adverse maternal and perinatal outcome in primigravid and multigravid women. MATERIAL AND METHODS: The study was a population-based cohort study and included women giving birth between January 2000 and December 2018 using data from the Dutch perinatal registration of Perined. Women were divided into age groups. We compared outcomes between women of 40-44, 45-49, and over 50 years old (the study groups) with women of 25-29 years old (reference group), stratified for parity. We employed multivariable regression to correct for possible confounders including methods of conception, multiple pregnancies, ethnicity, and socio-economic status. Our primary outcomes were maternal and perinatal mortality. Secondary outcomes included common maternal and perinatal complications, as well as cesarean section rate. RESULTS: A cohort of 3 700 326 women gave birth during the study period. Of these women, 3.2% were above 40 years of age. Maternal mortality was rare in all groups, but significantly higher in multigravid women over 50 years old. Perinatal mortality was significantly higher in all pregnancies of women over 40 years old, but not for primigravida over 50 years old. The most notable results with the steepest increase were in maternal complications. Both primigravida and multigravida over 40 years old were at a two times higher risk of perinatal mortality, cesarean section, gestational diabetes, hypertensive disorders, and a low Apgar score after 5 minutes. The risk for women over 45 was almost tripled for perinatal mortality and gestational diabetes and six times higher for cesarean section. Women over 50 years old had a seven times higher risk of cesarean section, a four times higher risk of gestational diabetes, postpartum hemorrhage, and neonatal intensive care unit admission, and a 10 times higher risk of hypertensive disorders. CONCLUSIONS: The risk of adverse maternal and perinatal outcomes for women over 40 years old surges as age increases. A novel aspect was the consistent increased risks not only for primigravid women but also for multigravida.

Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring in mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial.

BACKGROUND: Management of preterm hypertensive disorders remains a clinical dilemma. The maternal benefits of delivery need to be weighed against the adverse neonatal consequences of preterm birth. Long-term consequences of obstetric management in offspring of women with hypertensive disorders in preterm pregnancy are largely unknown. We report child neurodevelopmental and behavioral outcomes at 2 years after the Hypertension and Preeclampsia Intervention Trial at near Term (HYPITAT-II) trial, which compared immediate delivery versus expectant monitoring in mild late preterm hypertensive disorders of pregnancy. OBJECTIVE: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 2 years of age in offspring of women with mild late preterm hypertensive disorders. MATERIALS AND METHODS: We studied children born in the HYPITAT-II trial, a study in which women (n = 704) with hypertensive disorders of pregnancy who were between 34 and 37 weeks' gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire for developmental outcome and the Child Behavior Checklist for behavioral problems when their toddlers were 2 years old. RESULTS: We approached 545 of 704 randomized women (77%); 330 of 545 (61%) returned the questionnaires. In the immediate delivery group, 45 of 162 infants (28%) had an abnormal Ages and Stages Questionnaire score compared to 27 of 148 (18%) in the expectant monitoring group (risk difference, 9.6%; 95% CI, 0.3-18.0%); P = .045. In the pregnancies (n = 94) that delivered before reaching 36 weeks, 27% (n = 25) had an abnormal Ages and Stages Questionnaire score compared to 22% (n = 47) when delivered after 36 weeks (odds ratio, 0.77; confidence interval, 0.44-1.34). An abnormal Child Behavior Checklist outcome was found in 31 of 175 (18%) in the delivery group vs 24 of 166 (15%) in the expectant monitoring group (risk difference, 3.2%; 95% CI, -4.6% to 11.0%). After correction for maternal education, management strategy remained an independent predictor of abnormal Ages and Stages Questionnaire score (odds ratio, 0.48; confidence interval, 0.24 to -0.96, P = .03). In multivariable analyses, low birth weight, low maternal education, and immediate delivery policy were all significantly associated with an abnormal Ages and Stages Questionnaire score. CONCLUSION: In this study, we found that early delivery in women with late preterm hypertensive disorders is associated with poorer neurodevelopmental outcomes in their children at 2 years of age. These findings indicate an increased risk of developmental delay after early delivery compared to expectant monitoring. This follow-up study underlines the conclusion of the original HYPITAT-II study that, until the clinical situation deteriorates, expectant monitoring remains the most appropriate management strategy in the light of short- and long-term neonatal outcomes in women with preterm hypertensive disorders.

Work-related adverse events leaving their mark: a cross-sectional study among Dutch gynecologists.

BACKGROUND: Health care professionals who are frequently coping with traumatic events have an increased risk of developing a posttraumatic stress disorder. Research among physicians is scarce, and obstetrician-gynecologists may have a higher risk. Work-related traumatic events and posttraumatic stress disorder among obstetricians-gynecologists and the (desired) type of support were studied. METHODS: A questionnaire was emailed to all members of the Dutch Society of Obstetrics and Gynaecology, which included residents, attending, retired and non-practicing obstetricians-gynecologists. The questionnaire included questions about personal experiences and opinions concerning support after work-related events, and a validated questionnaire for posttraumatic stress disorder. RESULTS: The response rate was 42.8% with 683 questionnaires eligible for analysis. 12.6% of the respondents have experienced a work-related traumatic event, of which 11.8% met the criteria for current posttraumatic stress disorder. This revealed an estimated prevalence of 1.5% obstetricians-gynecologists with current posttraumatic stress disorder. 12% reported to have a support protocol or strategy in their hospital after adverse events. The most common strategies to cope with emotional events were: to seek support from colleagues, to seek support from family or friends, to discuss the case in a complication meeting or audit and to find distraction. 82% would prefer peer-support with direct colleagues after an adverse event. CONCLUSIONS: This survey implies that work-related events can be traumatic and subsequently can lead to posttraumatic stress disorder. There is a high prevalence rate of current posttraumatic stress disorder among obstetricians-gynecologists. Often there is no standardized support after adverse events. Most obstetrician-gynecologists prefer peer-support with direct colleagues after an adverse event. More awareness must be created during medical training and organized support must be implemented.

Increased postpartum haemorrhage, the possible relation with serotonergic and other psychopharmacological drugs: a matched cohort study.

BACKGROUND: Postpartum haemorrhage is a major obstetric risk worldwide. Therefore risk factors need to be investigated to control for this serious complication. A recent systematic review and meta-analysis revealed that the use of both serotonergic and non-serotonergic antidepressants in pregnancy are associated with a higher risk of postpartum haemorrhage. However, use of antidepressants in pregnancy is often necessary because untreated depression in pregnancy is associated with adverse maternal and neonatal outcome, such as postpartum depression, preterm birth and dysmaturity. Therefore it is of utmost importance to unravel the possible association between postpartum haemorrhage and the use of serotonergic and other psychopharmacological medication during pregnancy. METHODS: We performed a matched cohort observational study consecutively including all pregnant women using serotonergic medication (n = 578) or other psychopharmacological medication (n = 50) visiting two teaching hospitals in Amsterdam between 2010 and 2014. The incidence of postpartum haemorrhage in women using serotonergic medication or other psychopharmacological medication was compared with the incidence of postpartum haemorrhage in 641,364 pregnant women not using psychiatric medication selected from the database of the Netherlands Perinatal Registry foundation (Perined). Matching took place 1:5 for nine factors, i.e., parity, maternal age, ethnicity, socioeconomic status, macrosomia, gestational duration, history of postpartum haemorrhage, labour induction and hypertensive disorder. RESULTS: Postpartum haemorrhage occurred in 9.7% of the women using serotonergic medication. In the matched controls this was 6.6% (p = 0.01). The adjusted odds ratio (aOR) before matching was 1.6 (95% CI 1.2-2.1) and after matching 1.5 (95% CI 1.1-2.1). Among the women using other psychopharmacological medication, the incidence of postpartum haemorrhage before matching was 12.0% versus 6.1% (p = 0.08) with OR 2.1 (95% CI 0.9-4.9), and after matching 12.1% versus 4.4% (p = 0.03) with aOR of 3.3 (95% CI 1.1-9.8). CONCLUSIONS: Pregnant women using serotonergic medication have an increased risk of postpartum haemorrhage, but this high risk is also seen in pregnant women using other psychopharmacological medication. We suggest that this higher risk of postpartum haemorrhage could not only be explained by serotonin, but also by other mechanisms. An additional explanation could be the underlying psychiatric disorder.

Prediction of progression to severe disease in women with late preterm hypertensive disorders of pregnancy.

INTRODUCTION: If hypertensive disorders of pregnancy are diagnosed before term, the benefits of immediate delivery need to be weighed against the neonatal consequences of preterm delivery. If we are able to predict which women are at high risk of progression to severe disease, they could be targeted for delivery and maternal complications might be reduced. In addition, this may prevent unnecessary preterm births in women at low risk. MATERIAL AND METHODS: We developed a prediction model using data from the HYPITAT-II trail, which evaluated immediate delivery vs. expectant monitoring in women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation. Univariate and multivariate logistic regression analysis were used to identify relevant variables from clinical and laboratory parameters. The performance of the resulting prediction model was assessed by receiver operating characteristic analysis, calibration and bootstrapping, using the average predicted probabilities. RESULTS: We included 519 women, 115 (22.2%) of whom developed severe hypertensive disorders of pregnancy. The prediction model included: maternal age (odds ratio 0.92 per year), gestational age (odds ratio 0.87 per week), systolic blood pressure (odds ratio 1.05 per mmHg), the presence of chronic hypertension (odds ratio 2.4), platelet count (odds ratio 0.996), creatinine (odds ratio 1.02) and lactate dehydrogenase (odds ratio 1.003). The model showed good fit (p = 0.64), fair discrimination (area under the curve 0.76, 95% confidence interval 0.73-0.81, p < 0.001) and could stratify women in three risk groups of average, intermediate and high risk (predicted probabilities <0.22, <0.44 and >0.45, respectively). CONCLUSION: In women with non-severe hypertension in pregnancy near term, progression to severe disease can be predicted. This model requires external validation before it can be applied in practice.

Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial.

BACKGROUND: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women. METHODS: We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). FINDINGS: Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred. INTERPRETATION: For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered. FUNDING: ZonMw.

Systematic review and metaanalysis on nonclassic cardiovascular biomarkers after hypertensive pregnancy disorders.

OBJECTIVE: The aim of this study was to investigate which nonclassic cardiovascular biomarkers are associated with persistent endothelial dysfunction after pregnancy in women with a history of hypertensive pregnancy disorders compared with women with uncomplicated pregnancies. STUDY DESIGN: This was a systematic review and metaanalysis of observational studies. A search was performed in PubMed, Embase, Cochrane, and Cinahl including articles from inception to Feb. 27, 2013. Included were cohort studies and case-control studies. Cases were women with a history of hypertension in pregnancy, control subjects were women with a history of uncomplicated pregnancies. Of the 3136 found, 21 studies on 16 nonclassic cardiovascular biomarkers are described in this review; 12 studies on 5 biomarkers were included in the metaanalysis. RESULTS: Women with a history of hypertensive pregnancy disorders had a higher homocysteine level compared with women with a history of uncomplicated pregnancies (5 studies; pooled mean difference, 0.77 ng/mL; 95% confidence interval, 0.27-1.26; P < .01). For the other nonclassic cardiovascular biomarkers including markers in areas of inflammation, thrombosis, and angiogenesis, we found no significant differences. CONCLUSION: This review and metaanalysis showed that women with a history of hypertensive pregnancy disorders have higher homocysteine levels compared with women with a history of uncomplicated pregnancies. These data suggest persistent endothelial alteration after pregnancies complicated by hypertensive disorders.

The effectiveness of multifetal pregnancy reduction in trichorionic triplet gestation.

OBJECTIVE: The objective of the study was to assess in trichorionic triplet pregnancies the effectiveness of elective reduction to twins. STUDY DESIGN: This was a nationwide retrospective cohort study. We compared the time to delivery and perinatal mortality in trichorionic triplet pregnancies electively reduced to twins with ongoing trichorionic triplets and primary dichorionic twins. RESULTS: We identified 86 women with reduced trichorionic triplet pregnancies, 44 with ongoing trichorionic triplets, and 824 with primary twins. Reduced triplets had a median gestational age at delivery of 36.1 weeks (interquartile range [IQR], 33.3-37.5 weeks) vs 33.3 (IQR, 28.1-35.2) weeks for ongoing triplets and 37.1 (IQR, 35.3-38.1) weeks for primary twins (P < .001). The total number of surviving children in the reduced group was 155 (90%) vs 114 (86%) in the ongoing triplet group. After reduction, 75 of women (87%) had all their fetuses surviving, compared with 36 (82%) (relative risk [RR], 1.3; 95% confidence interval [CI], 0.72-2.3) for ongoing triplets and 770 (93%) (RR, 0.91; 95% CI, 0.82-1) for primary twins. There were 6 women without any surviving children (7%) after reduction vs 5 (11.4%) (RR, 0.81; 95% CI, 0.47-1.4) among women with ongoing triplets and 32 (3.9%) (RR, 1.7; 95% CI, 0.8-3.7) in women with primary twins. CONCLUSION: In women with a triplet pregnancy, fetal reduction increases gestational age at birth with 3 weeks as compared with ongoing triplets. However, there the impact on neonatal survival is limited.

Follow up of intima-media thickness after severe early-onset preeclampsia.

OBJECTIVE: Early-onset preeclampsia is associated with premature cardiovascular disease. We previously demonstrated that femoral intima-media thickness (IMT) and markers of cardiovascular disease were increased in women 1 year after early-onset preeclampsia. The current study measured (progression of) IMT, cardiovascular disease risk factors and markers of endothelial cell dysfunction 4-5 years postpartum in the same women. STUDY DESIGN: Case-control study. POPULATION: Formerly preeclamptic women. METHODS: IMT of carotid and femoral arteries was measured by ultrasound, as a marker of subclinical atherosclerosis. Various conventional cardiovascular risk factors were determined, as well as serum markers of endothelial cell activation and inflammation. Values were compared with those 1 year after the first (preeclamptic) pregnancy. MAIN OUTCOME MEASURES IMT RESULTS: We included 17 formerly preeclamptic women (cases) and 16 controls. Mean interval between index delivery and day of investigation was 4.7 years for the cases and 4.3 years for the controls. Neither differences nor progression of IMT was observed between the cases and the controls. Increased blood pressure, body mass index, serum triglycerides and inflammatory markers were found in the cases compared with the controls. CONCLUSION: IMT was not increased in women with an almost 5-year history of severe preeclampsia as an indicator of increased cardiovascular risk. This study suggests a transient adaptive response of the arteries in formerly preeclamptic women. The persistence of cardiovascular risk factors in this group emphasizes the need for long-term follow-up.

Prediction of postpartum hemorrhage in women with gestational hypertension or mild preeclampsia at term.

OBJECTIVE: To assess whether postpartum hemorrhage can be predicted in women with gestational hypertension or mild preeclampsia at term. DESIGN: A cohort study in which we used data from our multicentre randomized controlled trial (HYPITAT trial). SETTING: The study was conducted in 38 hospitals in the Netherlands between 2005 and 2008. POPULATION: Women with gestational hypertension or mild preeclampsia at term (n = 1132). METHODS: An antepartum model (model A) and an antepartum/intrapartum model (model B) were created using logistic regression. The predictive capacity of the models was assessed with receiver operating characteristic analysis and calibration. MAIN OUTCOME MEASURE: Postpartum hemorrhage, defined as blood loss >1000 mL within 24 h after delivery. RESULTS: Postpartum hemorrhage occurred in 118 (10.4%) women. Maternal age (odds ratio 1.03), prepregnancy body mass index (odds ratio 0.96), and women with preeclampsia (odds ratio 1.5) were independent antepartum prognostic variables of postpartum hemorrhage. Intrapartum variables incorporated in the model were gestational age at delivery (odds ratio 1.2), duration of dilatation stage (odds ratio 1.1), and episiotomy (odds ratio 1.5). Model A and model B showed moderate discrimination, with areas under the receiver operating characteristic curve of 0.59 (95% confidence interval 0.53-0.64) and 0.64 (95% confidence interval 0.59-0.70), respectively. Calibration was moderate for model A (Hosmer-Lemeshow p = 0.26) but better for model B (Hosmer-Lemeshow p = 0.36). The rates of postpartum hemorrhage ranged from 4% (lowest 10%) to 22% (highest 10%). CONCLUSION: In the assessment of performance of a prediction model, calibration is more important than discriminative capacity. Our prediction model shows that for women with gestational hypertension or mild preeclampsia at term, distinction between low and high risk of developing postpartum hemorrhage is possible when antepartum and intrapartum variables are combined.

Prediction of preterm birth in multiple pregnancies: development of a multivariable model including cervical length measurement at 16 to 21 weeks' gestation.

OBJECTIVE: To develop a multivariable prognostic model for the risk of preterm delivery in women with multiple pregnancy that includes cervical length measurement at 16 to 21 weeks' gestation and other variables. METHODS: We used data from a previous randomized trial. We assessed the association between maternal and pregnancy characteristics including cervical length measurement at 16 to 21 weeks' gestation and time to delivery using multivariable Cox regression modelling. Performance of the final model was assessed for the outcomes of preterm and very preterm delivery using calibration and discrimination measures. RESULTS: We studied 507 women, of whom 270 (53%) delivered < 37 weeks (preterm) and 66 (13%) < 32 weeks (very preterm). Women with cervical length < 30 mm delivered more often preterm (hazard ratio 1.9; 95% CI 0.7 to 4.8). Other independently contributing predictors were previous preterm delivery, monochorionicity, smoking, educational level, and triplet pregnancy. Prediction models for preterm and very preterm delivery had a c-index of 0.68 (95% CI 0.63 to 0.72) and 0.68 (95% CI 0.62 to 0.75), respectively, and showed good calibration. CONCLUSION: In women with a multiple pregnancy, the risk of preterm delivery can be assessed with a multivariable model incorporating cervical length and other predictors.

Objectif : Élaborer un modèle pronostique multivarié (comportant la mesure de la longueur cervicale à 16 - 21 semaines de gestation et d'autres variables) pour ce qui est du risque d'accouchement préterme chez les femmes connaissant une grossesse multiple. Méthodes : Nous avons utilisé les données issues d'un essai randomisé précédent. Nous avons évalué l'association entre les caractéristiques maternelles et de grossesse (dont la mesure de la longueur cervicale à 16 - 21 semaines de gestation et le délai avant l'accouchement) au moyen du modèle de régression multivariée de Cox. Le rendement du modèle final a été évalué en fonction de critères d'évaluation traitant du moment de l'accouchement (préterme et très préterme) au moyen de mesures d'étalonnage et de discrimination. Résultats : Nous avons étudié 507 femmes, dont 270 (53 %) ont accouché < 37 semaines (préterme) et 66 (13 %) < 32 semaines (très préterme). Les femmes qui présentaient une longueur cervicale < 30 mm ont plus souvent connu un accouchement préterme (densité de l'incidence, 1,9; IC à 95 %, 0,7 - 4,8). Parmi les autres facteurs prédictifs indépendants, on trouvait les antécédents d'accouchement préterme, la monochorionicité, le tabagisme, le niveau de scolarité et la présence d'une grossesse triple. Les modèles prédictifs pour ce qui est des accouchements préterme et très préterme comptaient un indice C de 0,68 (IC à 95 %, 0,63 - 0,72) et de 0,68 (IC à 95 %, 0,62 - 0,75), respectivement, et présentaient un bon étalonnage. Conclusion : Chez les femmes qui connaissent une grossesse multiple, le risque d'accouchement préterme peut être évalué au moyen d'un modèle multivarié comportant la mesure de la longueur cervicale et d'autres facteurs prédictifs. 

Cardiovascular risk factors in women who had hypertensive disorders late in pregnancy: a cohort study.

OBJECTIVE: The purpose of this study was to determine cardiovascular risk factors in women with a history of hypertensive pregnancy disorders at term (HTP) 2.5 years after pregnancy. STUDY DESIGN: In a multicenter cohort study in The Netherlands from June 2008 through November 2010, cardiovascular risk factors were compared between women with a history of HTP (HTP cohort, n = 306) and women with a history of normotensive pregnancies at term (NTP cohort, n = 99). HTP women had participated in a randomized, longitudinal trial assessing the effectiveness of induction of labor in women with hypertensive pregnancy disorders at term. All women were assessed 2.5 years after pregnancy for blood pressure, anthropometrics, glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, high-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and microalbumin and metabolic syndrome. RESULTS: After a mean follow-up period of 2.5 years, hypertension (HTP, 34%; NTP, 1%; P < .001) and metabolic syndrome (HTP, 25%; NTP, 5%; P < .001) were more prevalent in HTP women compared with NTP women. HTP women had significantly higher systolic and diastolic blood pressure, higher body mass index, and higher waist circumference. Glucose, glycosylated hemoglobin, insulin, homeostatic model assessment score, total cholesterol, triglycerides, and high-sensitivity C-reactive protein levels were significantly higher and high-density lipoprotein cholesterol was significantly lower in HTP women. CONCLUSION: In women with a history of HTP, hypertension and metabolic syndrome are more common, and they have higher levels of biochemical cardiovascular risk factors 2.5 years after pregnancy.

Cardiovascular risk estimation in women with a history of hypertensive pregnancy disorders at term: a longitudinal follow-up study.

BACKGROUND: Cardiovascular disease is associated with major morbidity and mortality in women in the Western world. Prediction of an individual cardiovascular disease risk in young women is difficult. It is known that women with hypertensive pregnancy complications have an increased risk for developing cardiovascular disease in later life and pregnancy might be used as a cardiovascular stress test to identify women who are at high risk for cardiovascular disease. In this study we assess the possibility of long term cardiovascular risk prediction in women with a history of hypertensive pregnancy disorders at term. METHODS: In a longitudinal follow-up study, between June 2008 and November 2010, 300 women with a history of hypertensive pregnancy disorders at term (HTP cohort) and 94 women with a history of normotensive pregnancies at term (NTP cohort) were included. From the cardiovascular risk status that was known two years after index pregnancy we calculated individual (extrapolated) 10-and 30-year cardiovascular event risks using four different risk prediction models including the Framingham risk score, the SCORE score and the Reynolds risk score. Continuous data were analyzed using the Student's T test and Mann-Whitney U test and categorical data by the Chi-squared test. A poisson regression analysis was performed to calculate the incidence risk ratios and corresponding 95% confidence intervals for the different cardiovascular risk estimation categories. RESULTS: After a mean follow-up of 2.5 years, HTP women had significantly higher mean (SD) extrapolated 10-year cardiovascular event risks (HTP 7.2% (3.7); NTP 4.4% (1.9) (p<.001, IRR 5.8, 95% CI 1.9 to 19)) and 30-year cardiovascular event risks (HTP 11% (7.6); NTP 7.3% (3.5) (p<.001, IRR 2.7, 95% CI 1.6 to 4.5)) as compared to NTP women calculated by the Framingham risk scores. The SCORE score and the Reynolds risk score showed similar significant results. CONCLUSIONS: Women with a history of gestational hypertension or preeclampsia at term have higher predicted (extrapolated) 10-year and 30-year cardiovascular event risks as compared to women with a history of uncomplicated pregnancies. Further large prospective studies have to evaluate whether hypertensive pregnancy disorders have to be included as an independent variable in cardiovascular risk prediction models for women.

Induction of labour with a Foley catheter or oral misoprostol at term: the PROBAAT-II study, a multicentre randomised controlled trial.

BACKGROUND: Induction of labour is a common obstetric procedure. At present, different methods are used for induction of labour in women with an unfavourable cervix. Recently, we showed that in term women with an unfavorable cervix the use of a Foley catheter in comparison with vaginal Prostaglandin E2 gel, results in a comparable vaginal delivery rate. A meta-analysis on the subject indicated lower rates of hyperstimulation, and probably as a sequel fewer cases of postpartum haemorrhage. Misoprostol (PgE1) is another type of prostaglandin frequently used for labour induction, recommended by the international federation of gynaecology and obstetrics (FIGO). Misoprostol can be administered by vaginal, rectal and oral route. There is evidence that oral administration results in less asphyxia and hyperstimulation than vaginal administration. At present, valid comparisons between oral misoprostol and Foley catheter are lacking. Therefore, we propose a randomised controlled trial comparing Foley catheter to oral misoprostol in order to assess safety and cost-effectiveness. METHODS/DESIGN: We plan a multicentre, randomised, controlled, open-label clinical trial among term pregnant women with a vital singleton in cephalic presentation, unfavorable cervix, intact membranes and an indication for induction of labour. After informed consent, women will be randomly allocated by a webbased randomisation system to transcervical Foley catheter or oral misoprostol (50 mcg every 4 hours). The primary outcome will be a composite of complications of uterine hyperstimulation, i.e. post partum haemorrhage and asphyxia. Secondary outcomes are mode of delivery, maternal and neonatal morbidity, costs and women's preference. Serious adverse events such as severe maternal or neonatal morbitity or mortality will be monitored and reported to an independent data safety monitory board. With a sample size of 1860 women we will be able to demonstrate a 5% non-inferiority of the Foley catheter as compared to misoprostol for the composite outcome. DISCUSSION: Worldwide, various methods are being used for labour induction. Results of the proposed trial will contribute to the answer which method of induction of labour is most safe, cost-effective, and patient friendly and will help to construct evidence based guidelines. TRIAL REGISTRATION: The Netherlands Trial Register NTR3466.