Michel H.P. Hof

Which patients benefit most from primary surgery or neoadjuvant chemotherapy in stage IIIC or IV ovarian cancer? An exploratory analysis of the European Organisation for Research and Treatment of Cancer 55971 randomised trial

BACKGROUND To investigate whether biomarkers consisting of baseline characteristics of advanced stage ovarian cancer patients can help in identifying subgroups of patients who would benefit more from primary surgery or neoadjuvant chemotherapy. METHODS We used data of the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial in which 670 patients were randomly assigned to primary surgery or neoadjuvant chemotherapy. The primary outcome was overall survival. Ten baseline clinical and pathological characteristics were selected as potential biomarkers. Using Subpopulation Treatment Effect Pattern Plots (STEPP), biomarkers with a statistically significant qualitative additive interaction with treatment were considered as potentially informative for treatment selection. We also combined selected biomarkers to form a multimarker treatment selection rule. FINDINGS The size of the largest metastatic tumour and clinical stage were significantly associated with the magnitude of the benefit from treatment, in terms of five-year survival (p for interaction: 0.008 and 0.016, respectively). Stage IIIC patients with metastatic tumours ⩽45 mm benefited more from primary surgery while stage IV patients with metastatic tumours >45 mm benefited more from neoadjuvant chemotherapy. In stage IIIC patients with larger metastatic tumours and in stage IV patients with less extensive metastatic tumours both treatments were equally effective. We estimated that by selecting treatments for patients based on largest metastatic tumour and clinical stage, the potential five-year survival rate in the population of treated patients would be 27.3% (95% confidence interval (CI) 21.9-33.0), 7.8% higher than if all were treated with primary surgery, and 5.6% higher if all were treated with neoadjuvant chemotherapy. INTERPRETATION Although survival was comparable after primary surgery and neoadjuvant chemotherapy in the overall group of patients with ovarian cancer in the EORTC 55971 trial, we found in this exploratory analysis that patients with stage IIIC and less extensive metastatic tumours had higher survival with primary surgery, while patients with stage IV disease and large metastatic tumours had higher survival with neoadjuvant chemotherapy. For patients who did not meet these criteria, both treatment options led to comparable survival rates.

Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery

Please cite this paper as: Schaaf J, Hof M, Mol B, Abu‐Hanna A, Ravelli A. Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery.BJOG 2012;119:1624–1629.

Risk of maternal and neonatal complications in subsequent pregnancy after planned caesarean section in a first birth, compared with emergency caesarean section: a nationwide comparative cohort study

To compare the difference in risks of neonatal and maternal complications, including uterine rupture, in a second birth following a planned caesarean section versus emergency caesarean section in the first birth.

Comparison of growth between native and immigrant infants between 0-3 years from the Dutch ABCD cohort

Background: In the Netherlands separate reference charts have been developed for native and immigrant groups to deal with differences in growth patterns in later childhood. The use of these charts, however, is complicated by methodological issues; they do not represent all large Dutch immigrant groups in separate charts despite the differences that have been suggested and the evidence of ethnic disparities in growth dates back to 1997. Aim: Anthropometric measurements from a contemporary multi-ethnic cohort study were created to quantify differences in childhood growth by creating growth charts, separately for boys and girls between the ages of 0–3 years. Subjects and methods: The infants modelled in the charts had a mother born in the Netherlands (n = 3107), Suriname (n = 225), Turkey (n = 203) and Morocco (n = 336). Charts with and without correction for country of origin of the mother were created by using the LMST method. Results: All models including the covariate country of origin of the mother fitted the data better (p < 0.0005), but the observed differences were small. Conclusion: Most remarkable differences were found in the BMI and weight measurements for age charts. Especially girls from mothers born in Turkey and Morocco had an increasingly heavier weight for their age than girls from mothers born in the Netherlands.

Association between Infancy BMI Peak and Body Composition and Blood Pressure at Age 5–6 Years

Introduction The development of overweight is often measured with the body mass index (BMI). During childhood the BMI curve has two characteristic points: the adiposity rebound at 6 years and the BMI peak at 9 months of age. In this study, the associations between the BMI peak and body composition measures and blood pressure at age 5–6 years were investigated. Methods Measurements from the Amsterdam Born Children and their Development (ABCD) study were available for this study. Blood pressure (systolic and diastolic) and body composition measures (BMI, waist-to-height ratio, fat percentage) were gathered during a health check at about 6 years of age (n = 2822). All children had multiple BMI measurements between the 0–4 years of age. For boys and girls separately, child-specific BMI peaks were extracted from mixed effect models. Associations between the estimated BMI peak and the health check measurements were analysed with linear models. In addition, we investigated the potential use of the BMI at 9 months as a surrogate measure for the magnitude of the BMI peak. Results After correction for the confounding effect of fetal growth, both timing and magnitude of the BMI peak were significantly and positively associated (p<0.001) with all body composition measures at the age of 5–6 years. The BMI peak showed no direct association with blood pressure at the age 5–6 year, but was mediated by the current BMI. The correlation between the magnitude of the BMI peak and BMI at 9 months was approximately 0.93 and similar associations with the measures at 5–6 years were found. Conclusion The magnitude of the BMI peak was associated with body composition measures at 5–6 years of age. Moreover, the BMI at 9 months could be used as surrogate measure for the magnitude of the BMI peak.

The Effect of Interpregnancy Interval on the Recurrence Rate of Spontaneous Preterm Birth: A Retrospective Cohort Study

Objective We assessed, in women with a previous spontaneous preterm birth, the effect of interpregnancy interval on the subsequent preterm birth rate. Design Retrospective cohort study. Setting A nationwide longitudinal dataset of the the Netherlands Perinatal Registry. Population Women with three sequential singleton pregnancies between 1999 and 2009 and a spontaneous preterm birth <37 weeks in the first pregnancy. Methods We evaluated the impact of interpregnancy interval on the course of the next pregnancies. Antenatal death and/or congenital abnormalities were excluded. Conventional and conditional logistic regression analysis were applied. We adjusted for maternal age, ethnicity, socioeconomic status, artificial reproductive techniques, and year of birth. Main Outcome Measures Outcomes studied were preterm birth <37 weeks, <32 weeks, low birth weight <2500 g, and small for gestational age <10th percentile. Results Among 2,361 women with preterm birth in the first pregnancy, logistic regression analysis indicated a significant effect of a short interpregnancy interval (0‐5 mo) on recurrent preterm birth <37 weeks (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.62‐3.05), <32 weeks (OR, 2.90; 95% CI, 1.43‐5.87), and low birth weight (OR, 2.69; 95% CI, 1.79‐4.03). In addition, a long interval (≥60 mo) had a significant effect on preterm birth <37 weeks (OR, 2.19; 95% CI, 1.29‐3.74). Conditional logistic regression analysis confirmed the effect of a short interval on the recurrence of preterm birth rate <37 weeks and low birth weight. Conclusion In women with a previous spontaneous preterm birth, a short interpregnancy interval has a strong impact on the risk of preterm birth before 37 weeks and low birth weight in the next pregnancy, irrespective of the type of analysis performed.

Using vaginal Group B Streptococcus colonisation in women with preterm premature rupture of membranes to guide the decision for immediate delivery: a secondary analysis of the PPROMEXIL trials

To investigate whether vaginal Group B Streptococcus (GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes (PPROM) can help in identifying subgroups of women who would benefit from immediate delivery.

Methods for analyzing data from probabilistic linkage strategies based on partially identifying variables

In record linkage studies, unique identifiers are often not available, and therefore, the linkage procedure depends on combinations of partially identifying variables with low discriminating power. As a consequence, wrongly linked covariate and outcome pairs will be created and bias further analysis of the linked data. In this article, we investigated two estimators that correct for linkage error in regression analysis. We extended the estimators developed by Lahiri and Larsen and also suggested a weighted least squares approach to deal with linkage error. We considered both linear and logistic regression problems and evaluated the performance of both methods with simulations. Our results show that all wrong covariate and outcome pairs need to be removed from the analysis in order to calculate unbiased regression coefficients in both approaches. This removal requires strong assumptions on the structure of the data. In addition, the bias significantly increases when the assumptions do not hold and wrongly linked records influence the coefficient estimation. Our simulations showed that both methods had similar performance in linear regression problems. With logistic regression problems, the weighted least squares method showed less bias. Because the specific structure of the data in record linkage problems often leads to different assumptions, it is necessary that the analyst has prior knowledge on the nature of the data. These assumptions are more easily introduced in the weighted least squares approach than in the Lahiri and Larsen estimator.

Fetal Gender of the First Born and the Recurrent Risk of Spontaneous Preterm Birth.

OBJECTIVE To study, in women with a spontaneous preterm birth (sPTB) in the first pregnancy, the effect of fetal sex in that first pregnancy on the recurrent sPTB risk. STUDY DESIGN A nationwide retrospective cohort study (data from National Perinatal Registry) on all women with two sequential singleton pregnancies (1999-2009) with the first delivery ending in sPTB <37 weeks. We used logistic regression analysis to study the association between fetal gender in the first pregnancy and the risk of recurrent sPTB. We repeated the analysis for sPTB < 32 weeks. RESULTS The overall incidence of sPTB <37 weeks in the first pregnancy was 4.5% (15,351/343,853). Among those 15,351 women, the risk of recurrent sPTB <37 weeks was increased when the first fetus was female compared when that fetus was male (15.8 vs. 15.2%; adjusted odds ratio [aOR] 1.2; 95% confidence interval [CI] 1.05-1.3). A similar effect was seen for sPTB <32weeks (8.2 vs. 5.9%; aOR 4.5; 95% CI 1.5-13). CONCLUSION Women who suffer sPTB of a female fetus have an increased risk of recurrent sPTB compared with women who suffer sPTB of a male fetus. This information provides proof for the hypothesis that sPTB is due to an independent maternal and fetal factor.

Does maternal pre-pregnancy overweight or obesity influence offspring's growth patterns from birth up to 7 years? The ABCD-study

BACKGROUND Maternal pre-pregnancy overweight is known to program offspring for adverse health outcomes later in life. AIMS To investigate how growth patterns of weight, height and BMI from birth to 7years differ according to maternal pre-pregnancy weight (normal weight, overweight and obesity), with specific attention for sex differences. STUDY DESIGN Prospective multi-ethnic ABCD-study. SUBJECTS 3805 mother-child pairs were included. Self-reported maternal pre-pregnancy body mass index was categorized into: normal weight (18.5-25kg/m2; n=3354), overweight (25-30kg/m2; n=711) and obesity (≥30kg/m2; n=241). OUTCOME MEASURES Population-specific growth patterns were used to compute SD-scores for weight, height and BMI (on average 12.7 (SD=2.6) measurements for each child) for term born boys and girls separately. Mixed effect models were fitted to these SD-scores to determine the effect of pre-pregnancy BMI category on postnatal growth, corrected for maternal characteristics. RESULTS Compared to children of mothers with normal weight before pregnancy, children of overweight mothers grew faster in weight and BMI (boys and girls) and children of obese mothers grew faster in height (only girls), weight and BMI (boys and girls) during the first years of life. The differences seemed to increase with age and were in general larger in girls. CONCLUSION Maternal overweight and obesity impact on offsprings weight, height and BMI growth pattern with increasing differences when children age. Effects were in general stronger for girls. These results suggest that a healthy weight before pregnancy may be beneficial for optimal weight, height and BMI growth in the offspring.