Study protocol for two randomised controlled trials evaluating the effects of Cerclage in the reduction of extreme preterm birth and perinatal mortality in twin pregnancies with a short cervix or dilatation: the TWIN Cerclage studies.

INTRODUCTION: Twin pregnancies have a high risk of extreme preterm birth (PTB) at less than 28 weeks of gestation, which is associated with increased risk of neonatal morbidity and mortality. Currently there is a lack of effective treatments for women with a twin pregnancy and a short cervix or cervical dilatation. A possible effective surgical method to reduce extreme PTB in twin pregnancies with an asymptomatic short cervix or dilatation at midpregnancy is the placement of a vaginal cerclage. METHODS AND ANALYSIS: We designed two multicentre randomised trials involving eight hospitals in the Netherlands (sites in other countries may be added at a later date). Women older than 16 years with a twin pregnancy at <24 weeks of gestation and an asymptomatic short cervix of ≤25 mm or cervical dilatation will be randomly allocated (1:1) to both trials on vaginal cerclage and standard treatment according to the current Dutch Society of Obstetrics and Gynaecology guideline (no cerclage). Permuted blocks sized 2 and 4 will be used to minimise the risk of disbalance. The primary outcome measure is PTB of <28 weeks. Analyses will be by intention to treat. The first trial is to demonstrate a risk reduction from 25% to 10% in the short cervix group, for which 194 patients need to be recruited. The second trial is to demonstrate a risk reduction from 80% to 35% in the dilatation group and will recruit 44 women. A cost-effectiveness analysis will be performed from a societal perspective. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committees in the Netherlands on 3/30/2023. Participants will be required to sign an informed consent form. The results will be presented at conferences and published in a peer-reviewed journal. Participants will be informed about the results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT05968794.

Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks' gestation: open label, multicentre, randomised, controlled trial.

OBJECTIVE: To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks' gestation and who have a short cervix of 35 mm or less. DESIGN: Open label, multicentre, randomised, controlled trial. SETTING: 20 hospitals and five obstetric ultrasound practices in the Netherlands. PARTICIPANTS: Women with a healthy singleton pregnancy and an asymptomatic short cervix of 35 mm or less between 18 and 22 weeks' gestation were eligible. Exclusion criteria were prior spontaneous preterm birth at less than 34 weeks, a cerclage in situ, maternal age of younger than 18 years, major congenital abnormalities, prior participation in this trial, vaginal blood loss, contractions, cervical length of less than 2 mm or cervical dilatation of 3 cm or more. Sample size was set at 628 participants. INTERVENTIONS: 1:1 randomisation to an Arabin cervical pessary or vaginal progesterone 200 mg daily up to 36 weeks' of gestation or earlier in case of ruptured membranes, signs of infection, or preterm labour besides routine obstetric care. MAIN OUTCOME MEASURES: Primary outcome was a composite adverse perinatal outcome. Secondary outcomes were rates of (spontaneous) preterm birth at less than 28, 32, 34, and 37 weeks. A predefined subgroup analysis was planned for cervical length of 25 mm or less. RESULTS: From 1 July 2014 to 31 March 2022, 635 participants were randomly assigned to pessary (n=315) or to progesterone (n=320). 612 were included in the intention to treat analysis. The composite adverse perinatal outcome occurred in 19 (6%) of 303 participants with a pessary versus 17 (6%) of 309 in the progesterone group (crude relative risk 1.1 (95% confidence interval (CI) 0.60 to 2.2)). The rates of spontaneous preterm birth were not significantly different between groups. In the subgroup of cervical length of 25 mm or less, spontaneous preterm birth at less than 28 weeks occurred more often after pessary than after progesterone (10/62 (16%) v 3/69 (4%), relative risk 3.7 (95% CI 1.1 to 12.9)) and adverse perinatal outcomes seemed more frequent in the pessary group (15/62 (24%) v 8/69 (12%), relative risk 2.1 (0.95 to 4.6)). CONCLUSIONS: In women with a singleton pregnancy with no prior spontaneous preterm birth at less than 34 weeks' gestation and with a midtrimester short cervix of 35 mm or less, pessary is not better than vaginal progesterone. In the subgroup of a cervical length of 25 mm or less, a pessary seemed less effective in preventing adverse outcomes. Overall, for women with single baby pregnancies, a short cervix, and no prior spontaneous preterm birth less than 34 weeks' gestation, superiority of a cervical pessary compared with vaginal progesterone to prevent preterm birth and consecutive adverse outcomes could not be proven. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP, EUCTR2013-002884-24-NL).

Systemic lupus erythematosus is associated with an increased frequency of spontaneous preterm births: systematic review and meta-analysis.

OBJECTIVE: Preterm birth is one of the most frequent complications of pregnancy in women with systemic lupus erythematosus. The high indicated preterm birth proportion due to hypertensive disorders of pregnancy and/or fetal growth restriction is well known, and preventive measures and screening for early detection are performed. The risk of spontaneous preterm birth is less well recognized. This study aimed to determine the proportions of spontaneous and indicated preterm birth in pregnancies of women with systemic lupus erythematosus. DATA SOURCES: A systematic literature search using Pubmed, Embase, Web of Science, and Google Scholar was performed in June 2021. STUDY ELIGIBILITY CRITERIA: Studies in pregnant women with systemic lupus erythematosus reporting spontaneous and indicated preterm birth rates were selected. Original research articles published from 1995 to June 2021 were included. METHODS: Quality and risk of bias of the included studies were assessed using the Newcastle-Ottawa quality assessment scale. To estimate the pooled event rates and 95% confidence intervals, meta-analysis of single proportions with a random-effects model was performed. RESULTS: We included 21 articles, containing data of 8157 pregnancies in women with systemic lupus erythematosus. On average, 31% (95% prediction interval, 0.14-0.50) of the pregnancies resulted in preterm birth, including 14% (95% prediction interval, 0.04-0.27) spontaneous and 16% (95% prediction interval, 0.03-0.35) indicated preterm birth. CONCLUSION: In pregnant women with systemic lupus erythematosus, spontaneous and indicated preterm birth proportions are high. This information should be applied in (prepregnancy) counseling and management in pregnancy. The knowledge obtained by this meta-analysis paves the way for further research of associated risk factors and development of interventions to reduce spontaneous preterm birth in systemic lupus erythematosus pregnancies.

The value of a mobile educative Application additional to Standard counselling on aspirin Adherence in Pregnancy: the ASAP study, a randomised controlled trial.

Objective: To assess the added value of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy versus standard counselling alone. Methods: Participants were randomly assigned for additional use of a mobile educative application or standard counselling alone. Main outcome measures were adherence to aspirin measured by two validated questionnaires: Simplified Medication Adherence Questionnaire (SMAQ), Believes and Behaviour Questionnaire (BBQ), and patients reported tablet intake >90%. Results: A total of 174 women with an indication for aspirin during pregnancy were included. The questionnaires were filled in by 126 out of the 174 participants (72.4%). Similar results were found in the app group and the standard counselling groups for both validated questionnaires. Tablet intake >90% was seen in 88.7% and 87.5% (p = 0.834) of the app group and standard counselling group respectively. Subgroup analyses demonstrated a negative effect of BMI and a positive effect of educational level on adherence. Conclusions: Our study revealed no added effect of a novel, mobile educative application to standard counselling on aspirin adherence during pregnancy. Tablet intake was equally high in both groups probably explained by our high educated population. Innovation: Future studies should focus on tailored counselling on medication to pregnant women's needs including medication reminders, addressing concerns, adequate health literacy and side effects, offering rewards to further stimulate aspirin adherence in pregnancy with optimal outcome for mother and their neonate.

Methods of induction of labor in women with obesity: A secondary analysis of two multicenter randomized controlled trials.

INTRODUCTION: Obesity is an increasing public health concern worldwide and can lead to more complications in pregnancy and childbirth. Women with obesity more often require induction of labor for various indications. The aim of this study is to assess which method of induction of labor is safest and most effective in women with obesity. MATERIAL AND METHODS: This is a secondary analysis of two randomized controlled trials about induction of labor. Women with a term singleton pregnancy in cephalic presentation, an unfavorable cervix, intact membranes and without a previous cesarean section were randomly allocated to cervical priming with a Foley catheter or vaginal prostaglandin-E2-gel (PROBAAT-I) or a Foley catheter or oral misoprostol (PROBAAT-II). The inclusion and exclusion criteria for the studies were identical. Induction methods were compared in women with obesity (body mass index ≥30.0). Main outcomes were cesarean section and postpartum hemorrhage (blood loss >1000 mL). RESULTS: A total of 2664 women, were included in the trials, 517 of whom were obese: 254 women with obesity received a Foley catheter, 176 oral misoprostol and 87 prostaglandin E2 (PGE2). A cesarean section was performed in 29.1% of women allocated to Foley vs 22.2% in the misoprostol and 23.0% in the PGE2 groups. Comparisons between groups revealed no statistically significant differences: the relative risk [RR] was 1.31 (95% confidence interval [CI] 0.94-1.84) in the Foley vs misoprostol group and 1.27 (95% CI 0.83-1.95) in the Foley vs PGE2 group. The rates of postpartum hemorrhage were comparable (10.6%, 11.4% and 6.9%, respectively; P = 0.512). In women with obesity, more often a switch to another method occurred in the Foley group, (20.1% vs 6.3% in misoprostol vs 1.1% in the PGE2 group; P < 0.001). The risk of a failed Foley placement was higher in women with obesity than in women without obesity (8.3% vs 3.2%; adjusted odds ratio 3.12, 95% CI 1.65-5.90). CONCLUSIONS: In women with obesity we found a nonsignificant trend towards an increased rate of cesarean sections in the group induced with a Foley catheter compared to oral misoprostol; however, the study lacked power for this subgroup analysis. The finding of a higher risk of failed placement of a Foley catheter in women with obesity can be used in shared decision making.

Stress-reducing interventions in pregnancy for the prevention of preterm birth: a systematic review and meta-analysis.

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Maternal stress during pregnancy is an established risk factor for PTB. We aimed to review the effects of stress-reducing interventions during pregnancy on PTB. Studies reporting on stress-reducing interventions during pregnancy and PTB rates in general low-risk obstetric populations were included. PTB rates, low birth weight (LBW) rates, mean gestational age and birth weight, maternal anxiety and stress, and adverse perinatal outcomes were investigated. Data were extracted using a standardized extraction form, pooled effect sizes were calculated with the random effects model. Ten studies with a total of 4.816 women were included. The interventions included Pilates, yoga, a multidisciplinary stress reduction program, combination therapy (combining mindfulness, yoga, music, baby bonding, and education), and hypnosis. The incidence of PTB was significantly lower in the intervention group (RR 0.50, 95% CI 0.35 - 0.71). The overall quality of the included studies was low, and the risk of bias was high. In conclusion, this study provides evidence supporting the potential efficacy of stress-reducing interventions in reducing the incidence of PTB in low-risk women. We propose a RCT of high quality to determine the effectiveness of stress-reducing interventions in reducing PTB risk.

Assessment of cervical softening and the prediction of preterm birth (STIPP): protocol for a prospective cohort study.

INTRODUCTION: Preterm birth (PTB) is among the leading causes of perinatal and childhood morbidity and mortality. Therefore, accurate identification of pregnant women at high risk of PTB is key to enable obstetric healthcare professionals to apply interventions that improve perinatal and childhood outcomes. Serial transvaginal cervical length measurement is used to screen asymptomatic pregnant women with a history of PTB and identify those at high risk for a recurrent PTB. Cervical length measurement, fetal fibronectin test or a combination of both can be used to identify women at high risk of PTB presenting with symptoms of threatened PTB. The predictive capacity of these methods can be improved. Cervical softening is a precursor of cervical shortening, effacement and dilatation and could be a new marker to identify women a high risk of PTB. However, the predictive value of cervical softening to predict spontaneous PTB still needs to be determined. METHODS AND ANALYSIS: This is a single-centre, prospective cohort study, conducted at the Amsterdam University Medical Centers in the Netherlands. Cervical softening will be investigated with a non-invasive CE-marked device called the Pregnolia System. This device has been developed to evaluate consistency of the cervix based on tissue elasticity. Two different cohorts will be investigated. The first cohort includes women with a history of spontaneous PTB <34 weeks. These women undergo biweekly measurements between 14 and 24 weeks of gestation. The second cohort includes women with symptoms of threatened PTB. These women will receive the measurement once at presentation between 24 and 34 weeks of gestation. The primary outcome is spontaneous PTB before 34 weeks for women with a history of PTB and delivery within 7 days for women with threatened PTB. The minimum sample size required to analyse the primary outcome is 227 women in the cohort of women with a history of PTB and 163 women in the cohort of women with symptoms of threatened PTB. Once this number is achieved, the study will be continued to investigate secondary objectives. ETHICS AND DISSEMINATION: The study is approved by the Medical Ethics Committee of Amsterdam UMC (METC2022.0226). All patients will give oral and written informed consent prior to study entry. Results will be disseminated via a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05477381.

Long-Term Maternal Mental Health after Spontaneous Preterm Birth.

OBJECTIVE: The aim of this study is to investigate whether a history of spontaneous preterm birth (SPTB) is associated with maternal depressive and anxiety symptoms, or psychosocial distress in the fifth decade of life. STUDY DESIGN: This is a secondary analysis of the PreCaris-study, a prospective observational study in which we included 350 women with a history of SPTB between 220/7 and 366/7 weeks of gestation and compared them to 115 women who had a term birth. Primary outcomes were the Depression and Anxiety scores measured using the Hospital Anxiety Depression Scale and Psychosocial distress assessed with the Distress Thermometer for Parents. Secondary outcomes were self-reported impact of the birth in daily life and psychosocial support after delivery. RESULTS: After a median of 13 years after delivery, no significant differences were found in primary outcomes. Significantly more women with a history of SPTB reported that the birth still had impact in daily life; adjusted odds ratio: 2.46 (95% confidence interval: 1.35-4.48). A total of 57 (16.3%) women after SPTB reported to have needed professional psychosocial support after delivery but did not receive it. These women more often had a high Anxiety score (p = 0.030), psychosocial distress (p = 0.001), and influence of birth in daily life (p = 0.000). CONCLUSION: There are no long-term effects on depressive and anxiety symptoms and psychosocial distress in women who experienced SPTB compared with women who had a full-term pregnancy. A significant part of the women who delivered preterm needed psychosocial support but did not receive it and were at higher risk of anxiety, psychosocial distress, and impact in daily life. We therefore recommend offering all women after SPTB psychosocial support after delivery. KEY POINTS: · No long-term effects on depressive and anxiety symptoms and psychosocial distress after SPTB.. · A total of 16.3% of the cases needed professional psychosocial support after delivery but did not receive it.. · This subgroup was at higher risk of anxiety symptoms, psychosocial distress, and impact on daily life..

Spontaneous haemoperitoneum in pregnancy: Nationwide surveillance and Delphi audit system.

OBJECTIVE: To evaluate the incidence, diagnostic management strategies and clinical outcomes of women with spontaneous haemoperitoneum in pregnancy (SHiP) and reassess the definition of SHiP. DESIGN: A population-based cohort study using the Netherlands Obstetric Surveillance System (NethOSS). SETTING: Nationwide, the Netherlands. POPULATION: All pregnant women between April 2016 and April 2018. METHODS: This is a case study of SHiP using the monthly registry reports of NethOSS. Complete anonymised case files were obtained. A newly introduced online Delphi audit system (DAS) was used to evaluate each case, to make recommendations on improving the management of SHiP and to propose a new definition of SHiP. MAIN OUTCOME MEASURES: Incidence and outcomes, lessons learned about clinical management and the critical appraisal of the current definition of SHiP. RESULTS: In total, 24 cases were reported. After a Delphi procedure, 14 cases were classified as SHiP. The nationwide incidence was 4.9 per 100 000 births. Endometriosis and conceiving after artificial reproductive techniques were identified as risk factors. No maternal and three perinatal deaths occurred. Based on the DAS, adequate imaging of free intra-abdominal fluid, and identifying and treating women with signs of hypovolemic shock could improve the early detection and management of SHiP. A revised definition of SHiP was proposed, excluding the need for surgical or radiological intervention. CONCLUSIONS: SHiP is a rare and easily misdiagnosed condition that is associated with high perinatal mortality. To improve care, better awareness among healthcare workers is needed. The DAS is a sufficient tool to audit maternal morbidity and mortality.

Hypertensive disorders of pregnancy after multifetal pregnancy reduction: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on hypertensive disorders of pregnancy (HDP) after multifetal pregnancy reduction (MFPR). METHODS: A comprehensive search in PubMed, Embase, Web of Science, and Scopus was performed. Prospective or retrospective studies reporting on MFPR from triplet or higher-order to twin compared to ongoing (i.e., non-reduced) triplets and/or twins were included. A meta-analysis of the primary outcome HDP was carried out using a random-effects model. Subgroup analyses of gestational hypertension (GH) and preeclampsia (PE) were performed. Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Thirty studies with a total of 9,811 women were included. MFPR from triplet to twin was associated with a lower risk for HDP compared to ongoing triplets (OR 0.55, 95% CI, 0.37-0.83; p = 0.004). In a subgroup analysis, the decreased risk of HDP was driven by GH, and PE was no longer significant (OR 0.34, 95% CI, 0.17-0.70; p = 0.004 and OR 0.64, 95% CI, 0.38-1.09; p = 0.10, respectively). HDP was also significantly lower after MFPR from all higher-order (including triplets) to twin compared to ongoing triplets (OR 0.55, 95% CI, 0.38-0.79; p = 0.001). In a subgroup analysis, the decreased risk of HDP was driven by PE, and GH was no longer significant (OR 0.55, 95% CI 0.32-0.92; p = 0.02 and OR 0.55, 95% CI 0.28-1.06; p = 0.08, respectively). No significant differences in HDP were found in MFPR from triplet or higher-order to twin versus ongoing twins. CONCLUSIONS: MFPR in women with triplet and higher-order multifetal pregnancies decreases the risk of HDP. Twelve women should undergo MFPR to prevent one event of HDP. These data can be used in the decision-making process of MFPR, in which the individual risk factors of HDP can be taken into account.

Left ventricular diastolic function in the fifth decade of life in women with a history of spontaneous preterm birth.

OBJECTIVE: Cardiovascular disease (CVD) is the number one cause of death in women and defining its risk factors is necessary to reduce its prevalence. A history of preeclampsia is shown to be associated with hypertension and alterations in left ventricular (LV) diastolic function parameters. Because of overlapping mechanisms between preeclampsia and spontaneous preterm birth (SPTB), our most recent study investigated the association between SPTB and hypertension, and found an almost 2 times higher prevalence of hypertension after SPTB. No previous studies have focused on the association between SPTB and LV diastolic function. The aim of this study is to investigate LV diastolic function as potential early parameter of CVD in women with a history of SPTB. STUDY DESIGN: We included cases with a history of SPTB between 22 and 37 weeks and controls who had a term birth. Women with hypertensive disorders or gestational diabetes in any of their pregnancies, were excluded. Both groups underwent cardiovascular risk assessment and transthoracic echocardiography 9 to 16 years after pregnancy. Echocardiographic measures were adjusted using a linear regression analysis accounting for hypertension and other risk factors known to be associated with CVD. A subgroup analysis was performed based on hypertension at follow-up. RESULTS: A total of 94 cases and 94 controls were included, on average 13 years after pregnancy. There were no significant differences in LV diastolic function parameters. Women with a history of SPTB and diagnosed hypertension at follow-up, showed significant higher late diastolic mitral flow velocity, lower e'septal velocity and higher E/e'ratio, compared to women with a history of SPTB without hypertension, although within normal ranges. CONCLUSIONS: When a history of SPTB is accompanied by hypertension at follow-up, significant changes in LV diastolic function were seen. Therefore, hypertension is the central factor in preventive screening methods, and transthoracic echocardiography has no additional value at this follow-up duration.

Spontaneous preterm birth with placental maternal vascular malperfusion is associated with cardiovascular risk in the fifth decade of life.

Women with a history of spontaneous preterm birth (SPTB) have a mildly elevated cardiovascular risk (CVR) later in life and women with a history of preeclampsia have a highly elevated CVR. In placentas of women with preeclampsia pathological signs of maternal vascular malperfusion (MVM) are often seen. These signs of MVM are also seen in a substantial part of the placentas of women with SPTB. We therefore hypothesize that in women with a history of SPTB, the subgroup with placental MVM has an elevated CVR. This study is a secondary analysis of a cohort study including women 9-16 years after a SPTB. Women with pregnancy complications known to be associated with CVR were excluded. The primary outcome was hypertension defined as blood pressure ≥ 130/80 mmHg and/or treatment with antihypertensive medication. Secondary outcomes were mean blood pressure, anthropometrics, blood measurements including cholesterol and HbA1c, and creatinine in urine. Placental histology was available in 210 (60.0%) women. MVM was found in 91 (43.3%) of the placentas, most often diagnosed by the presence of accelerated villous maturation. Hypertension was diagnosed in 44 (48.4%) women with MVM and in 42 (35.3%) women without MVM (aOR 1.76, 95% CI 0.98 - 3.16). Women with a SPTB and placental MVM showed significantly higher mean diastolic blood pressure, mean arterial pressure and HbA1c approximately 13 years after delivery, compared to women with a SPTB without placental MVM. We therefore conclude that placental malperfusion in women with a SPTB might differentiate in CVR later in life.

Sexual intercourse during pregnancy and its association with spontaneous preterm birth.

This study investigated whether sexual intercourse during pregnancy is associated with spontaneous preterm birth (SPTB). We included 77 women with SPTB and 145 women with a term birth. A total of 195 (87.8%) women had sexual intercourse during pregnancy, which was comparable between the groups. Primiparas with SPTB tended to report more often having sexual intercourse 3 - 4 times a week compared to primiparas with a term birth (8.8% vs. 0%, p =.082). We advise not to completely discourage sexual intercourse among pregnant women. Yet, high sexual intercourse frequency could be associated with SPTB.

The influence of various induction methods on adverse outcomes in small for gestational age neonates: A secondary analysis of the PROBAAT 1 and 2 trials.

OBJECTIVE: To evaluate the safety aspects of different induction methods in pregnancies with small-for-gestational-age neonates. STUDY DESIGN: This was a secondary analysis of two previously reported multicenter, randomized controlled trials conducted in the Netherlands. In the original trials, women were randomized to either a 30 cc Foley catheter, vaginal prostaglandin E2 (PROBAAT-1) or oral misoprostol (PROBAAT-2). A total of 425 patients with a term, singleton pregnancy in cephalic presentation with an indication for labor induction and a small-for-gestational-age neonate were included in this secondary analysis. Our primary outcome was a composed adverse neonatal outcome of Apgar score < 7 after 5 min and/or a pH in the umbilical artery < 7.05 and/or NICU admission. Secondary outcomes were mode of birth, operative birth for fetal distress and pH < 7.10 in the umbilical artery. For these outcome measures, multivariate as well as bivariate analyses were performed. RESULTS: An adverse neonatal outcome occurred in 4.7 % (10/214) induction with a Foley catheter, versus 12.8 % (19/149) after misoprostol (RR 0.36; 95 % CI 0.17-0.76) and 4.7 % (3/64) after Prostaglandin E2 (RR 0.98; 95 %CI 0.28-3.51). For individual components of the composed outcome of adverse events, a difference was found between a Foley catheter and misoprostol for Apgar score < 7 at 5 min (0.5 % versus 3.4; RR 0.14; 95 %CI 0.02-1.16) and NICU admission (1.9 % versus 6.1 %; RR 0.31; 0.10-0.97). No differences were found for mode of birth. CONCLUSIONS: For women who gave birth to a small-for-gestational-age neonate, a Foley catheter is probably a safer induction method compared to oral misoprostol.

The association between spontaneous preterm birth and maternal hypertension in the fifth decade of life: a retrospective case-control study.

OBJECTIVE: To investigate whether a history of spontaneous preterm birth (SPTB) predisposes to maternal hypertension. DESIGN: Retrospective case-control study. SETTING: Two affiliated university medical hospitals in Amsterdam, the Netherlands. POPULATION: We included 350 women with a history of SPTB between 22 and 36+6  weeks and 166 women with a history of a term birth. Women with pregnancy complications that are known to be associated with cardiovascular disease were excluded. METHODS: Both groups underwent cardiovascular risk assessment 9-16 years after pregnancy. We performed a subgroup analysis based upon the severity of SPTB. MAIN OUTCOME MEASURES: Hypertension. Secondary outcomes - metabolic syndrome, mean blood pressure, anthropometrics, blood and urine sampling, Framingham Risk Score and Systematic Coronary Risk Evaluation. RESULTS: A history of SPTB was significantly associated with hypertension; adjusted odds ratio 1.60 (95% confidence interval 1.04-2.46, p = 0.033). Abdominal obesity was more often diagnosed after SPTB (n = 163, 46.6% versus n = 54, 32.5%, p = 0.003) and was more pronounced with more severe preterm birth (p = 0.002). CONCLUSIONS: The presence of hypertension 9-16 years after pregnancy was statistically significantly higher among women with a history of SPTB than among women with a history of uncomplicated term birth. Women with a history of SPTB were more often diagnosed with abdominal obesity, especially those with a history of extreme preterm birth.

Added prognostic value of Doppler ultrasound for adverse perinatal outcomes: A pooled analysis of three cohort studies.

BACKGROUND: Fetal growth restriction (FGR) is an obstetric complication associated with adverse perinatal outcomes. Doppler ultrasound can improve perinatal outcomes through monitoring at-risk fetuses and helping time delivery. AIM: To investigate the prognostic value of different Doppler ultrasound measurements for adverse perinatal outcomes. MATERIALS: Individual participant data. METHODS: We performed a pooled analysis on individual participant data. We compared six prognostic models using multilevel logistic regression, where each subsequent model added a new variable to a base model that included maternal characteristics. Estimated fetal weight (EFW) and four Doppler ultrasound measurements were added in turn: umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), cerebroplacental ratio (CPR), and mean uterine artery pulsatility index (mUtA PI). The primary outcome was a composite adverse perinatal outcome, defined as perinatal mortality, emergency caesarean delivery for fetal distress, or neonatal admission. Discriminative ability was quantified with area under the curve (AUC). RESULTS: Three data sets (N = 3284) were included. Overall, the model that included EFW and UA PI improved AUC from 0.650 (95% CI 0.624-0.676) to 0.673 (95% CI 0.646-0.700). Adding more ultrasound measurements did not improve further the discriminative ability. In subgroup analysis, the addition of EFW and UA PI improved AUC in both preterm (AUC from 0.711 to 0.795) and small for gestational age pregnancies (AUC from 0.729 to 0.770), but they did not improve the models in term delivery or normal growth subgroups. CONCLUSIONS: Umbilical artery pulsatility index added prognostic value for adverse perinatal outcomes to the already available information, but the combination of other Doppler ultrasound measurements (MCA PI, CPR or UtA PI) did not improve further prognostic performance.

Exposure to Thioguanine During 117 Pregnancies in Women With Inflammatory Bowel Disease.

BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease [IBD] is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and birth. METHODS: In this multicentre case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications, and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most [78%] had Crohn's disease and the mean age at delivery was 31 years. In 18 pregnancies [15%], IBD flared. Obstetric and infectious complications were seen in 15% [n = 17] and 7% [n = 8] of pregnancies, respectively. Ten pregnancies [8.5%] resulted in a first trimester miscarriage, one in a stillbirth at 22 weeks of gestational age and one in an induced abortion due to trisomy 21. In total, 109 neonates were born from 101 singleton pregnancies and four twin pregnancies. One child was born with a congenital abnormality [cleft palate]. In the singleton pregnancies, 10 children were born prematurely and 10 were born small for gestational age. Screening for myelosuppresion was performed in 16 neonates [14.7%]; two had anaemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from three Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series, the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes.