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

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

Contains fulltext : 170075.pdf (publisher's version ) (Closed access)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 0.45, 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

Detection of Chromosome Aneuploidies in Chorionic Villus Samples by Multiplex Ligation-Dependent Probe Amplification

The objective of this study was to examine the suitability of multiplex ligation-dependent probe amplification (MLPA) in chorionic villus samples as a replacement for traditional karyotyping for the detection of (an)euploidies of chromosomes 21, 18, 13, X, and Y. Chorionic villus samples were diagnosed by traditional karyotyping using short-term cultures (STC) and long-term cultures (LTC), and by MLPA using kit P095. DNA was extracted after digestion of whole villi with proteinase K and/or trypsin and collagenase. Different cell-dissociation procedures were tested to obtain MLPA results representative of the cytotrophoblast layer and the mesenchymal core. Over 95% of the MLPA results were in concordance with the traditional karyotyping of STC and LTC. Traditional karyotyping revealed seven mosaics. After digestion of whole villi with proteinase K, only abnormal cell lines confined to the STC gave rise to abnormal MLPA results. In one sample, the complete discrepancy between STC and LTC was resolved after enzymatic dissociation of cells from the cytotrophoblast layer and the mesenchymal core. MLPA in chorionic villus samples was found to be a reliable test for the detection of (an)euploidies of chromosomes 21, 18, 13, X, and Y. Whole villi digestion with proteinase K resulted in the over-representation of cytotrophoblasts in the DNA pool. To obtain MLPA results representative for STC and LTC, enzymatic dissociation of cells from the cytotrophoblast layer and mesenchymal core is required

Prognostic model on niche development after a first caesarean section:development and internal validation

Objective: To develop and internally validate a prognostic prediction model for development of a niche in the uterine scar after a first caesarean section (CS). Study design: Secondary analyses on data of a randomized controlled trial, performed in 32 hospitals in the Netherlands among women undergoing a first caesarean section. We used multivariable backward logistic regression. Missing data were handled using multiple imputation. Model performance was assessed by calibration and discrimination. Internal validation using bootstrapping techniques took place. The outcome was ‘development of a niche in the uterus’, defined as an indentation of = 2 mm in the myometrium. Results: We developed two models to predict niche development: in the total population and after elective CS. Patient related risk factors were: gestational age, twin pregnancy and smoking, and surgery related risk factors were double-layer closure and less surgical experience. Multiparity and Vicryl suture material were protective factors. The prediction model in women undergoing elective CS revealed similar results. After internal validation, Nagelkerke R2 ranged from 0.01 to 0.05 and was considered low; median area under the curve (AUC) ranged from 0.56 to 0.62, indicating failed to poor discriminative ability. Conclusions: The model cannot be used to accurately predict the development of a niche after a first CS. However, several factors seem to influence scar healing which indicates possibilities for future prevention such as surgical experience and suture material. The search for additional risk factors that play a role in development of a niche should be continued to improve the discriminative ability