From population reference to national standard: new and improved birthweight charts.

BACKGROUND: Antenatal detection of intrauterine growth restriction remains a major obstetrical challenge, with the majority of cases not detected before birth. In these infants with undetected intrauterine growth restriction, the diagnosis must be made after birth. Clinicians use birthweight charts to identify infants as small-for-gestational-age if their birthweights are below a predefined threshold for gestational age. The choice of birthweight chart strongly affects the classification of small-for-gestational-age infants and has an impact on both research findings and clinical practice. Despite extensive literature on pathological risk factors associated with small-for-gestational-age, controversy exists regarding the exclusion of affected infants from a reference population. OBJECTIVE: This study aims to identify pathological risk factors for abnormal fetal growth, to quantify their effects, and to use these findings to calculate prescriptive birthweight charts for the Dutch population. MATERIALS AND METHODS: We performed a retrospective cross-sectional study, using routinely collected data of 2,712,301 infants born in The Netherlands between 2000 and 2014. Risk factors for abnormal fetal growth were identified and categorized in 7 groups: multiple gestation, hypertensive disorders, diabetes, other pre-existing maternal medical conditions, maternal substance (ab)use, medical conditions related to the pregnancy, and congenital malformations. The effects of these risk factors on mean birthweight were assessed using linear regression. Prescriptive birthweight charts were derived from live-born singleton infants, born to ostensibly healthy mothers after uncomplicated pregnancies and spontaneous onset of labor. The Box-Cox-t distribution was used to model birthweight and to calculate sex-specific percentiles. The new charts were compared to various existing birthweight and fetal-weight charts. RESULTS: We excluded 111,621 infants because of missing data on birthweight, gestational age or sex, stillbirth, or a gestational age not between 23 and 42 weeks. Of the 2,599,640 potentially eligible infants, 969,552 (37.3%) had 1 or more risk factors for abnormal fetal growth and were subsequently excluded. Large absolute differences were observed between the mean birthweights of infants with and without these risk factors, with different patterns for term and preterm infants. The final low-risk population consisted of 1,629,776 live-born singleton infants (50.9% male), from which sex-specific percentiles were calculated. Median and 10th percentiles closely approximated fetal-weight charts but consistently exceeded existing birthweight charts. CONCLUSION: Excluding risk factors that cause lower birthweights results in prescriptive birthweight charts that are more akin to fetal-weight charts, enabling proper discrimination between normal and abnormal birthweight. This proof of concept can be applied to other populations.

Choosing a hospital for surgery: the importance of information on quality of care.

OBJECTIVE: To assess whether patients use information on quality of care when choosing a hospital for surgery compared with more general hospital information. METHODS: In this cross-sectional study in 3 Dutch hospitals, questionnaires were sent to 2122 patients who underwent 1 of 6 elective surgical procedures in 2005-2006 (aorta reconstruction [for treatment of aneurysm], cholecystectomy, colon resection, inguinal hernia repair, esophageal resection, thyroid surgery). Patients were asked which information they had used to choose this hospital and which information they intended to use if they would need similar surgical treatment in the future. RESULTS: In total, 1329 questionnaires were available for analysis (response rate 62.6%). Most patients indicated having used the hospital's good reputation (69.1%) and friendly hospital atmosphere (63.3%) to choose a hospital. For future choices, most patients intended to use the fact that they were already treated in that hospital (79.3%) and the hospital's good reputation (74.1%). Regarding quality-of-care information, patients preferred a summary measure (% patients with ''textbook outcome'') over separate more detailed measures (52.1% v. 38.0%, χ2 = 291, P < 0.01). For future choices, patients intend to use more information items than in 2005-2006, both in absolute terms (9 v. 4 items, t = 38.3, P < 0.01) as relative to the total number of available items (41.3% [40.1%-42.5%] v. 29.2% [28.1%-30.2%]). CONCLUSION: Patients intended to use more information for future choices than they used for past choices. For future choices, most patients prefer a summary measure on quality of care over more detailed measures but seem to value that they were already treated in that hospital or a hospital's good reputation even more.

The effect of preconception counselling on lifestyle and other behaviour before and during pregnancy.

BACKGROUND: Recent studies suggest that the basis for adverse pregnancy outcomes is often established early in pregnancy, during organogenesis. It is therefore important to take preventive action as early as possible, preferably before pregnancy. Because most adverse pregnancy outcomes occur in women who are unaware of being at risk, we conducted a randomized controlled trial, "Parents to Be." With this study, we sought to assess the extent to which women who have participated in preconception counseling (PCC) increase their knowledge on pregnancy-related risk factors and preventive measures and change their behavior before and during pregnancy and to provide an overview of adverse pregnancy outcomes among such women. METHODS: Knowledge: Women aged 18-40 who attended PCC and women who received standard care were matched on previous pregnancy, time since last pregnancy, age, country of birth, and educational achievement. They were sent a questionnaire on knowledge about pregnancy-related risk factors and preventive measures. Behavior: Data on pregnancies and outcomes were collected. Two months after pregnancy, a questionnaire was sent regarding behavior before and during pregnancy. RESULTS: Knowledge of women who received PCC (81.5%; n=211) exceeded that of women who did not (76.9%; n=422). Levels of knowledge in women who were not yet pregnant after PCC were comparable to those in women who became pregnant after PCC, indicating that, even before pregnancy, PCC increased knowledge in women contemplating pregnancy. After PCC, significantly more women started using folic acid before pregnancy (adjusted odds ratio [OR], 4.93; 95% confidence interval [CI], 2.81-8.66) and reduced alcohol use during the first 3 months of pregnancy (adjusted OR, 1.79; 95% CI, 1.08-2.97). Among the group receiving standard care, about 20% of all pregnancies ended in an adverse outcome; in the group with PCC this was 16% (OR, 0.77; 95% CI, 0.48-1.22). CONCLUSION: After PCC, women have more knowledge about essential items. Importantly, they gained this greater knowledge before pregnancy and more women changed their behavior to reduce adverse pregnancy outcomes.

Pre-conception counselling in primary care: prevalence of risk factors among couples contemplating pregnancy.

The outcome of pregnancy can be influenced by several risk factors. Women who are informed about these risks during pre-conception counselling (PCC) have an opportunity to take preventive measures in time. Several studies have shown that high-risk populations have a high prevalence of such risk factors. However, prevalence in the general population, which is assumed to be low risk, is largely unknown. We therefore provided a systematic programme of PCC for the general population and studied the prevalence of risk factors using the risk-assessment questionnaire which was part of the PCC. None of the couples reported no risk factors at all and only 2% of the couples reported risk factors for which written information was considered to be sufficient. Therefore, 98% of all couples reported one or more risk factors for which at least personal counselling by a general practitioner (GP) was indicated. Many of these factors were related to an unhealthy lifestyle. Women with a low level of education reported more risk factors than women with a high level of education. There is a great need for PCC as shown by the fact that almost all couples reported risk factors for which personal counselling was indicated. Pre-conception counselling may reduce the risk of adverse pregnancy outcome by enabling couples to avoid these risks. PCC can be provided by GPs, who have the necessary medical knowledge and background information to counsel couples who wish to have a baby.

Serrated adenomas and mixed polyposis caused by a splice acceptor deletion in the mouse Smad4 gene.

Serrated adenomas, hyperplastic polyps, and admixed hyperplastic/adenomatous polyps form a distinct group of colorectal tumors, the molecular genetic basis of which is still poorly understood. We describe a novel mouse model for serrated adenomas and mixed polyposis, here referred to as Sad (serrated adenomas), caused by a spontaneously risen splice site mutation in the murine Smad4 gene. The Sad chromosomal region was identified by genetic linkage and loss of heterozygosity (LOH) analysis. Subsequently, several candidate genes were investigated by expression and mutation analysis. By use of genetic linkage and LOH analysis, we mapped the Sad candidate to mouse chromosome 18, 44-48 cM, syntenic to human chromosome band 18q21. Within this chromosomal interval, the Smad2, Smad4, and Smad7 genes were analyzed for the presence of a disease-causing mutation in affected animals. A single nucleotide (nt) deletion was identified in the intron 5/exon 6 splice acceptor site of the Smad4 gene. The single base deletion results in a frameshift and an early termination codon through activation of a cryptic splice site 4 nt downstream in exon 6. The resulting mRNA is unstable, and the Sad mutation is thus likely to represent a null allele. Identification of a Smad4 mutation in the Sad mouse model provides further support for the involvement of the Smad genes, and thus the TGFB pathway, in the serrated/hyperplastic route to colorectal cancer.