"Hypertension in Pregnancy Intervention Trial At Term" and "Disproportionate Intrauterine Growth Intervention Trial At Term" Studies.

In 2003, in the context of a national research funding program in which obstetric research was prioritized, several perinatal centers took the initiative to jointly submit a number of applications to the subsidy programs of Effectiveness Research and Prevention of ZonMw. This has led to the funding of the Obstetric Consortium with several projects, including the "Hypertension in Pregnancy Intervention Trial At Term" and the "Disproportionate Intrauterine Growth Intervention Trial At Term" studies. The studies showed that induction of labor for hypertension and growth restriction at term was the appropriate management. Subsequent implementation improved maternal and perinatal outcomes.

Continuous care during labor by maternity care assistants in the Netherlands vs care-as-usual: a randomized controlled trial.

BACKGROUND: Continuous support during labor has many benefits including lower use of obstetrical interventions. However, implementation remains limited. Insights into birth outcomes and peripartum costs are essential to assess whether continuous care by a maternity care assistant is a potentially (cost) effective program to provide for all women. OBJECTIVE: Continuous care during labor, provided by maternity care assistants, will reduce the use of epidural analgesia and peripartum costs owing to a reduction in interventions. STUDY DESIGN: This was a randomized controlled trial comparing continuous support during labor (intervention group) with care-as-usual (control group) with prespecified intention-to-treat and per-protocol analyses. The primary outcome was epidural analgesia use. The secondary outcomes were use of other analgesia, referrals from midwife- to obstetrician-led care, modes of birth, hospital stay, sense of control (evaluated with the Labor Agentry Scale), maternal and neonatal adverse outcomes and peripartum costs. Data were collected using questionnaires. Anticipating incomplete adherence to providing continuous care, both intention-to-treat and per-protocol analyses were planned. Peripartum costs were estimated using a healthcare perspective. Mean costs per woman and cost differences between the intervention and control group were calculated. RESULTS: The population consisted of 1076 women with 54 exclusions and 30 discontinuations, leaving 992 women to be analyzed (515 continuous care and 477 care-as-usual). Intention-to-treat analyses showed statistically nonsignificant differences between the intervention and control group for epidural use (relative risk, 0.88; 95% confidence interval, 0.74-1.04; P=.14) and peripartum costs (mean difference, € 185.83; 95% confidence interval, -€ 204.22 to € 624.54). Per-protocol analyses showed statistically significant decreases in epidural analgesia (relative risk, 0.64; 95% confidence interval, 0.48-0.84; P=.001), other analgesia (relative risk, 0.59; 95% confidence interval, 0.37-0.94; P=.02), cesarean deliveries (relative risk, 0.53; 95% confidence interval, 0.29-0.95; P=.03) and increase in spontaneous vaginal births (relative risk, 1.09; 95% confidence interval, 1.01-1.18; P=.001) in the intervention group, but difference in total peripartum costs remained statistically nonsignificant (mean difference, € 246.55; 95% confidence interval, -€ 539.14 to € 13.50). CONCLUSION: If the provision of continuous care given by maternity care assistants during labor can be secured, continuous care leads to more vaginal births and less epidural use, pain medication, and cesarean deliveries while not leading to a difference in peripartum costs compared with care-as-usual.

Publication trends and usefulness of research in hysteroscopic myomectomy for heavy menstrual bleeding: A review of the published literature.

Despite the amount of research into hysteroscopic myomectomy, questions about the optimal treatment of heavy menstrual bleeding remain. This study reviewed publication trends on this topic from 2002 to 2019 and assessed the usefulness of studies. A total of 580 articles were published on PubMed in this time frame, in 15 different languages. There were meta-analyses (1.6%), systematic reviews (12%), and randomized controlled trials (4.2%). Twelve percent were published in high impact factor journals. After applying our selection criteria, the usefulness of 37 articles was assessed: one article scored high, 31 scored moderate, and five scored low. The costs of these studies were estimated at US$ 971 700.

Depression, anxiety, and post-traumatic stress disorder symptoms after hyperemesis gravidarum: a prospective cohort study.

OBJECTIVE: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. MATERIAL AND METHODS: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. RESULTS: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively. CONCLUSION: Depression, anxiety, and PTSD symptoms are common years after HG occurred.

The effects of COVID-19 restrictions and other perinatal factors on women's sense of control during childbirth: a prospective cohort study.

BACKGROUND: Restrictions around childbirth, introduced during the COVID-19 pandemic in 2020, could decrease maternal feelings of control during birth. The aim of this study was to compare the sense of control of women who gave birth during the COVID-19 pandemic with women who gave birth before COVID-19. The secondary objective was to identify other factors independently associated with women's sense of control during birth. METHODS: A prospective cohort study, in a sub-cohort of 504 women from a larger cohort (Continuous Care Trial (CCT), n = 992), was conducted. Sense of control was measured by the Labor Agentry Scale (LAS). Perinatal factors independently associated with women's sense of control during birth were identified using multiple linear regression. RESULTS: Giving birth during the COVID-19 pandemic did not influence women's sense of control during birth. Factors statistically significantly related to women's sense of control were Dutch ethnic background (ß 4.787, 95%-CI 1.319 to 8.254), antenatal worry (ß - 4.049, 95%-CI -7.516 to -.581), antenatal anxiety (ß - 4.677, 95%-CI -7.751 to 1.603) and analgesics during birth (ß - 3.672, 95%-CI -6.269 to -1.075). CONCLUSIONS: Despite the introduction of restrictions, birth during the COVID-19 pandemic was not associated with a decrease of women's sense of control.

Hyperemesis gravidarum severity, enteral tube feeding and cardiometabolic markers in offspring cord blood.

This study aimed to investigate the association between hyperemesis gravidarum (HG) severity and early enteral tube feeding on cardiometabolic markers in offspring cord blood. We included women admitted for HG, who participated in the MOTHER randomised controlled trial (RCT) and observational cohort. The MOTHER RCT showed that early enteral tube feeding in addition to standard care did not affect symptoms/birth outcomes. Among RCT and cohort participants, we assessed how HG severity affected lipid, c-peptide, glucose and free thyroxine cord blood levels. HG severity measures were severity of vomiting at inclusion and 3 weeks after inclusion, pregnancy weight gain and 24-h energy intake at inclusion, readmissions and duration of hospital admissions. Cord blood measures were also compared between RCT participants allocated to enteral tube feeding and those receiving standard care. Between 2013-2016, 215 women were included: 115 RCT and 100 cohort participants. Eighty-one cord blood samples were available. Univariable not multivariable regression analysis showed that lower maternal weight gain was associated with higher cord blood glucose levels (ß: -0·08, 95% CI -0·16, -0·00). Lower maternal weight gain was associated with higher Apo-B cord blood levels in multivariable regression analysis (ß: -0·01, 95% CI -0·02, -0·01). No associations were found between other HG severity measures or allocation to enteral tube feeding and cord blood cardiometabolic markers. In conclusion, while lower maternal weight gain was associated with higher Apo-B cord blood levels, no other HG severity measures were linked with cord blood cardiometabolic markers, nor were these markers affected by enteral tube feeding.

Restrictive versus liberal fluid resuscitation strategy, influence on blood loss and hemostatic parameters in mild obstetric hemorrhage: An open-label randomized controlled trial. (REFILL study).

BACKGROUND: Evidence for optimal hemostatic resuscitation in postpartum hemorrhage (PPH) is lacking. Liberal fluid administration may result in acidosis, hypothermia and coagulopathy. OBJECTIVE: We hypothesize that in early PPH a restrictive fluid administration results in less progression to moderate PPH. STUDY DESIGN: In four Dutch hospitals we recruited women of 18 years and over, and more than 24 weeks pregnant. Exclusion criteria were: anticoagulant therapy, known coagulation disorders, pre-eclampsia, antenatal diagnosis of abnormally adhesive placenta, and a contraindication for liberal fluid therapy. We blindly randomized participants at 500 mL and ongoing blood loss in the third stage of labor between restrictive fluid administration (clear fluids 0.75-1.0 times the volume of blood lost) and liberal fluid administration (clear fluids 1.5-2.0 times the volume of blood lost). The primary outcome was progression to more than 1000 mL blood loss. Analyses were according to the intention-to-treat principle. RESULTS: From August 2014 till September 2019, 5190 women were informed of whom 1622 agreed to participate. A total of 252 women were randomized of which 130 were assigned to the restrictive group and 122 to the liberal group. In the restrictive management group 51 of the 130 patients (39.2%) progressed to more than 1000 mL blood loss versus 61 of the 119 patients (51.3%) in the liberal management group (difference, -12.0% [95%-CI -24.3% to 0.3%], p = 0.057). There was no difference in the need for blood transfusion, coagulation parameters, or in adverse events between the groups. CONCLUSIONS: Although a restrictive fluid resuscitation in women with mild PPH could not been proven to be superior, it does not increase the need for blood transfusion, alter coagulation parameters, or cause a rise in adverse events. It can be considered as an alternative treatment option to liberal fluid resuscitation. TRIAL REGISTRATION: NTR3789.

Recurrence, postponing pregnancy, and termination rates after hyperemesis gravidarum: Follow up of the MOTHER study.

INTRODUCTION: Hyperemesis gravidarum (HG) complicates 1% of pregnancies and has a major impact on maternal quality of life and well-being. We know very little about HG's long-term impact after an affected pregnancy, including recurrence rates in future pregnancies, which is essential information for women considering subsequent pregnancies. In this study, we aimed to prospectively measure the recurrence rate of HG and the number of postponed and terminated subsequent pregnancies due to HG. We also aimed to evaluate if there were predictive factors that could identify women at increased risk for HG recurrence, and postponing and terminating subsequent pregnancies. MATERIAL AND METHODS: We conducted a prospective cohort study. A total of 215 women admitted for HG to public hospitals in the Netherlands were enrolled in the original MOTHER randomized controlled trial and associated observational cohort. Seventy-three women were included in this follow-up study. Data were collected through an online questionnaire. Recurrent HG was defined as vomiting symptoms accompanied by any of the following: multiple medication use, weight loss, admission, tube feeding or if nausea and vomiting symptoms were severe enough to affect life and/or work. Outcome measures were recurrence, postponing, and termination rates due to HG. Univariable logistic regression analysis was used to identify predictive factors associated with HG recurrence, and postponing and terminating subsequent pregnancies. RESULTS: Thirty-five women (48%) became pregnant again of whom 40% had postponed their pregnancy due to HG. HG recurred in 89% of pregnancies. One woman terminated and eight women (23%) considered terminating their pregnancy because of recurrent HG. Twenty-four out of 38 women did not get pregnant again because of HG in the past. Univariable logistic regression analysis identifying possible predictive factors found that having a western background was associated with having weight loss due to recurrent HG in subsequent pregnancies (odds ratio 12.9, 95% CI 1.3-130.5, p = 0.03). CONCLUSIONS: High rates of HG recurrence and a high number of postponed pregnancies due to HG were observed. Women can be informed of a high chance of recurrence to enable informed family planning.

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum: A prospective cohort study.

INTRODUCTION: Little is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG. MATERIAL AND METHODS: We conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4. RESULTS: Between 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; ß = 2.00, 95% CI 0.47-3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (ß = 1.74, 95% CI 0.36-3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty-one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03). CONCLUSIONS: Our findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.

External validation of a prediction model on vaginal birth after caesarean in a The Netherlands: a prospective cohort study.

OBJECTIVES: Discussing the individual probability of a successful vaginal birth after caesarean (VBAC) can support decision making. The aim of this study is to externally validate a prediction model for the probability of a VBAC in a Dutch population. METHODS: In this prospective cohort study in 12 Dutch hospitals, 586 women intending VBAC were included. Inclusion criteria were singleton pregnancies with a cephalic foetal presentation, delivery after 37 weeks and one previous caesarean section (CS) and preference for intending VBAC. The studied prediction model included six predictors: pre-pregnancy body mass index, previous vaginal delivery, previous CS because of non-progressive labour, Caucasian ethnicity, induction of current labour, and estimated foetal weight ≥90th percentile. The discriminative and predictive performance of the model was assessed using receiver operating characteristic curve analysis and calibration plots. RESULTS: The area under the curve was 0.73 (CI 0.69-0.78). The average predicted probability of a VBAC according to the prediction model was 70.3% (range 33-92%). The actual VBAC rate was 71.7%. The calibration plot shows some overestimation for low probabilities of VBAC and an underestimation of high probabilities. CONCLUSIONS: The prediction model showed good performance and was externally validated in a Dutch population. Hence it can be implemented as part of counselling for mode of delivery in women choosing between intended VBAC or planned CS after previous CS.

CCT: continuous care trial - a randomized controlled trial of the provision of continuous care during labor by maternity care assistants in the Netherlands.

BACKGROUND: In 2009, the Steering Committee for Pregnancy and Childbirth in the Netherlands recommended the implementation of continuous care during labor in order to improve perinatal outcomes. However, in current care, routine maternity caregivers are unable to provide this type of care, resulting in an implementation rate of less than 30%. Maternity care assistants (MCAs), who already play a nursing role in low risk births in the second stage of labor and in homecare during the postnatal period, might be able to fill this gap. In this study, we aim to explore the (cost) effectiveness of adding MCAs to routine first- and second-line maternity care, with the idea that these MCAs would offer continuous care to women during labor. METHODS: A randomized controlled trial (RCT) will be performed comparing continuous care (CC) with care-as-usual (CAU). All women intending to have a vaginal birth, who have an understanding of the Dutch language and are > 18 years of age, will be eligible for inclusion. The intervention consists of the provision of continuous care by a trained MCA from the moment the supervising maternity caregiver establishes that labor has started. The primary outcome will be use of epidural analgesia (EA). Our secondary outcomes will be referrals from primary care to secondary care, caesarean delivery, instrumental delivery, adverse outcomes associated with epidural (fever, augmentation of labor, prolonged labor, postpartum hemorrhage, duration of postpartum stay in hospital for mother and/or newborn), women's satisfaction with the birth experience, cost-effectiveness, and a budget impact analysis. Cost effectiveness will be calculated by QALY per prevented EA based on the utility index from the EQ-5D and the usage of healthcare services. A standardized sensitivity analysis will be carried out to quantify the outcome in addition to a budget impact analysis. In order to show a reduction from 25 to 17% in the primary outcome (alpha 0.05 and bèta 0.20), taking into account an extra 10% sample size for multi-level analysis and an attrition rate of 10%, 2 × 496 women will be needed (n = 992). DISCUSSION: We expect that adding MCAs to the routine maternity care team will result in a decrease in the use of epidural analgesia and subsequent costs without a reduction in patient satisfaction. It will therefore be a cost-effective intervention. TRIAL REGISTRATION: Trial Registration: Netherlands Trial Register, NL8065 . Registered 3 October 2019 - Retrospectively registered.

Determinants of disease course and severity in hyperemesis gravidarum.

OBJECTIVE: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity. STUDY DESIGN: For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures. RESULTS: We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (ß) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures. CONCLUSION: Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity.

External validation and clinical utility of prognostic prediction models for gestational diabetes mellitus: A prospective cohort study.

INTRODUCTION: We performed an independent validation study of all published first trimester prediction models, containing non-invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated. MATERIAL AND METHODS: Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies. RESULTS: The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models. CONCLUSIONS: The best performing prediction models showed acceptable performance measures and may enable more personalized medicine-based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies.

Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring in mild hypertensive disorders of pregnancy: 5-year outcomes of the HYPITAT II trial.

OBJECTIVE: To compare effects of immediate delivery vs expectant monitoring on neurodevelopmental and behavioral outcomes at 5 years of age in offspring of women with mild late preterm hypertensive disorders. STUDY DESIGN: We studied children born during the HYPITAT-II trial, in which 704 women with a hypertensive disorder between 34 and 37 weeks of gestation were randomized to immediate delivery or expectant monitoring. Participating women were asked to complete the Ages and Stages Questionnaire (ASQ) for developmental outcome and the Child Behavior Checklist (CBCL) for behavioral problems when their child was 5 years old. Outcomes were dichotomized and analyzed by logistic regression analysis. We also assessed factors influencing development and behavior at both 2 and 5 years after a hypertensive pregnancy. RESULTS: Five years after the original study 322(46%) women were contacted for follow-up, of whom 148 (46%) responded. In the delivery group 22%(n = 14/65) of the children had an abnormal ASQ score compared to 21% (n = 13/62) in the expectant monitoring group (p = 0.9). Abnormal CBCL-scores were found in 19% (n = 14/72) of the children in the delivery group versus in 27% (n = 20/75) in the expectant monitoring group (p = 0.3). The main predictor of development and behavior at 2 and 5 years was fetal growth restriction (for abnormal development OR 2.1, CI 1.0-4.4; for behavior problems OR 2.2, CI 1.1-5.5). Higher maternal education decreased abnormal behavior outcomes (OR 0.5, CI 0.2-0.9) and a similar tendency was observed for developmental problems (OR 0.6, CI 0.3 - 1.1). CONCLUSION: We did not find different developmental and behavior outcomes at 5 years of age between a management policy of immediate delivery and expectant management in preterm hypertensive disorders. The increased risk of developmental delay at 2 years of age after immediate delivery, we found in the 2 year follow up study, did not persist at 5 years of age.

Recurrence and prediction of abnormal uterine bleeding and re-intervention after initial hysteroscopic treatment: a retrospective cohort study.

PURPOSE: To estimate the incidence of recurrence of complaints and repeated interventions after hysteroscopic treatment for abnormal uterine bleeding in premenopausal women and to determine potential predictors for re-intervention. METHODS: This is a retrospective cohort study in two secondary care centers in the Netherlands. We included 313 premenopausal women who underwent hysteroscopy for complaints of abnormal uterine bleeding and who had intrauterine pathology visualized at ultrasound. The intrauterine structure was hysteroscopically removed. These women were compared with women who had a hysteroscopy for abnormal uterine bleeding, but in whom hysteroscopy showed no abnormalities. We used Chi-squared test for categorical variables and independent-samples T test for continuous variables. p Values less than 0.05 were considered to indicate statistical significance. RESULTS: In total, 262 women had intrauterine pathology removed at hysteroscopy; 136 (52%) women had recurrence of complaints, while 101 women (39%) underwent re-intervention. Heavy menstrual bleeding at baseline and multiparity were predictive factors for recurrence of abnormal uterine bleeding and re-intervention. In the 51 women with abnormal uterine bleeding in whom hysteroscopy showed no intrauterine abnormality, 29 women (60%) had recurrence of complaints and 12 (24%) a re-intervention. CONCLUSION: In premenopausal women with abnormal uterine bleeding, treatment of intrauterine pathology often does not reduce the complaints, thus questioning the effectiveness of hysteroscopic removal of these structures.

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.

Balloon catheter for induction of labor in women with one previous cesarean and an unfavorable cervix.

INTRODUCTION: When women with a previous cesarean section and an unfavorable cervix have an indication for delivery, the choice is to induce labor or to perform a cesarean section. This study aims to assess the effectiveness and safety of a balloon catheter as a method of induction of labor in women with one previous cesarean section and an unfavorable cervix compared with an elective repeat cesarean section. MATERIAL AND METHODS: We performed a prospective cohort study in 51 hospitals in the Netherlands on term women with one previous cesarean section, a live singleton fetus in cephalic position, an unfavorable cervix and an indication for delivery. We recorded obstetric, maternal and neonatal characteristics. We compared the outcome of women who were induced with a balloon catheter with the outcome of women who delivered by elective repeat cesarean section. Main outcomes were maternal and neonatal morbidity. Mode of delivery was a secondary outcome for women who were induced. Adjusted odds ratios (aOR) were calculated using logistic regression, adjusted for potential confounders. RESULTS: Analysis was performed on 993 women who were induced and 321 women who had a repeat cesarean section (August 2011 until September 2012). Among the women who were induced, 560 (56.4%) delivered vaginally and 11 (1.1%) sustained a uterine rupture. Composite adverse maternal outcome (uterine rupture, severe postpartum hemorrhage or postpartum infection) occurred in 73 (7.4%) in the balloon and 14 (4.5%) women in the repeat cesarean section group (aOR 1.58, 95% confidence interval [CI] 0.85-2.96). Composite adverse neonatal outcome (Apgar score <7 at 5 minutes or umbilical pH <7.10) occurred in 57 (5.7%) and 10 (3.2%) neonates, respectively (aOR 1.40, 95% CI 0.87-3.48). Women who were induced had a shorter postpartum admission time (2.0 vs 3.0 days (P < 0.0001)). CONCLUSIONS: In women with a previous cesarean section and a need for delivery, induction of labor with a balloon catheter does not result in a significant increase in adverse maternal and neonatal outcomes as compared with planned cesarean section.

External Validation and Clinical Usefulness of First Trimester Prediction Models for the Risk of Preeclampsia: A Prospective Cohort Study.

INTRODUCTION: This study assessed the external validity of all published first trimester prediction models for the risk of preeclampsia (PE) based on routinely collected maternal predictors. Moreover, the potential utility of the best-performing models in clinical practice was evaluated. MATERIAL AND METHODS: Ten prediction models were systematically selected from the literature. We performed a multicenter prospective cohort study in the Netherlands between July 1, 2013, and December 31, 2015. Eligible pregnant women completed a web-based questionnaire before 16 weeks' gestation. The outcome PE was established using postpartum questionnaires and medical records. Predictive performance of each model was assessed by means of discrimination (c-statistic) and a calibration plot. Clinical usefulness was evaluated by means of decision curve analysis and by calculating the potential impact at different risk thresholds. RESULTS: The validation cohort contained 2,614 women of whom 76 developed PE (2.9%). Five models showed moderate discriminative performance with c-statistics ranging from 0.73 to 0.77. Adequate calibration was obtained after refitting. The best models were clinically useful over a small range of predicted probabilities. DISCUSSION: Five of the ten included first trimester prediction models for PE showed moderate predictive performance. The best models may provide more benefit compared to risk selection as used in current guidelines.

Prediction models for the risk of spontaneous preterm birth based on maternal characteristics: a systematic review and independent external validation.

INTRODUCTION: Prediction models may contribute to personalized risk-based management of women at high risk of spontaneous preterm delivery. Although prediction models are published frequently, often with promising results, external validation generally is lacking. We performed a systematic review of prediction models for the risk of spontaneous preterm birth based on routine clinical parameters. Additionally, we externally validated and evaluated the clinical potential of the models. MATERIAL AND METHODS: Prediction models based on routinely collected maternal parameters obtainable during first 16 weeks of gestation were eligible for selection. Risk of bias was assessed according to the CHARMS guidelines. We validated the selected models in a Dutch multicenter prospective cohort study comprising 2614 unselected pregnant women. Information on predictors was obtained by a web-based questionnaire. Predictive performance of the models was quantified by the area under the receiver operating characteristic curve (AUC) and calibration plots for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation. Clinical value was evaluated by means of decision curve analysis and calculating classification accuracy for different risk thresholds. RESULTS: Four studies describing five prediction models fulfilled the eligibility criteria. Risk of bias assessment revealed a moderate to high risk of bias in three studies. The AUC of the models ranged from 0.54 to 0.67 and from 0.56 to 0.70 for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation, respectively. A subanalysis showed that the models discriminated poorly (AUC 0.51-0.56) for nulliparous women. Although we recalibrated the models, two models retained evidence of overfitting. The decision curve analysis showed low clinical benefit for the best performing models. CONCLUSIONS: This review revealed several reporting and methodological shortcomings of published prediction models for spontaneous preterm birth. Our external validation study indicated that none of the models had the ability to predict spontaneous preterm birth adequately in our population. Further improvement of prediction models, using recent knowledge about both model development and potential risk factors, is necessary to provide an added value in personalized risk assessment of spontaneous preterm birth.

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial.

AIM: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. MATERIAL AND METHODS: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. RESULTS: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. CONCLUSIONS: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome.