Maria P.H. Koster

External validation of prognostic models to predict risk of gestational diabetes mellitus in one Dutch cohort: prospective multicentre cohort study

Objective To perform an external validation and direct comparison of published prognostic models for early prediction of the risk of gestational diabetes mellitus, including predictors applicable in the first trimester of pregnancy. Design External validation of all published prognostic models in large scale, prospective, multicentre cohort study. Setting 31 independent midwifery practices and six hospitals in the Netherlands. Participants Women recruited in their first trimester (<14 weeks) of pregnancy between December 2012 and January 2014, at their initial prenatal visit. Women with pre-existing diabetes mellitus of any type were excluded. Main outcome measures Discrimination of the prognostic models was assessed by the C statistic, and calibration assessed by calibration plots. Results 3723 women were included for analysis, of whom 181 (4.9%) developed gestational diabetes mellitus in pregnancy. 12 prognostic models for the disorder could be validated in the cohort. C statistics ranged from 0.67 to 0.78. Calibration plots showed that eight of the 12 models were well calibrated. The four models with the highest C statistics included almost all of the following predictors: maternal age, maternal body mass index, history of gestational diabetes mellitus, ethnicity, and family history of diabetes. Prognostic models had a similar performance in a subgroup of nulliparous women only. Decision curve analysis showed that the use of these four models always had a positive net benefit. Conclusions In this external validation study, most of the published prognostic models for gestational diabetes mellitus show acceptable discrimination and calibration. The four models with the highest discriminative abilities in this study cohort, which also perform well in a subgroup of nulliparous women, are easy models to apply in clinical practice and therefore deserve further evaluation regarding their clinical impact.

Strong adherence to a healthy dietary pattern is associated with better semen quality, especially in men with poor semen quality

OBJECTIVEnTo study associations between periconceptional dietary patterns and semen quality parameters.nnnDESIGNnProspective periconception cohort study.nnnSETTINGnTertiary hospital.nnnPATIENT(S)nOne hundred and twenty-nine male partners of pregnant women who participated in the Rotterdam Periconception Cohort (Predict study).nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nSemen quality parameters-ejaculate volume, sperm concentration, total sperm count, progressive motility, immotile sperm, and total motile sperm count (TMSC).nnnRESULT(S)nMen included in our study were on average 35 (±6 standard deviation) years old and had a body mass index of 26.4 ± 4xa0kg/m2. Two dietary patterns were identified using principle component analysis, which were labeled as healthy and unhealthy. An increase of one factor score (stated as β) represented an increase of 1 standard deviation. Sperm concentration (β = 0.278; 95% CI, 0.112-0.444), total sperm count (β = 1.369; 95% CI, 0.244-2.495), progressive motility (β = 4.305; 95% CI, 0.675-7.936), and TMSC (β = 0.319; 95% CI, 0.113-0.526) were all positively associated with a strong adherence to the healthy dietary pattern. Subgroup analysis showed that these associations were mainly present in men with a TMSC <10 million spermatozoa. Although there was a trend toward a diminution in semen quality, we found no statistically significant associations with strong adherence to the unhealthy dietary pattern.nnnCONCLUSION(S)nThe positive associations between strong adherence to a healthy dietary pattern and semen parameters in men with poor semen quality support the importance of preconceptional tailored nutritional counseling and coaching of couples who are trying to conceive.

Absolute first trimester cell-free DNA levels and their associations with adverse pregnancy outcomes

To study associations of first trimester cell‐free fetal DNA levels (in this paper referred to as cell‐free placental DNA (cfpDNA) levels) and preeclampsia (PE), pregnancy‐induced hypertension (PIH), gestational diabetes (GDM) and spontaneous preterm birth (sPB).

Maternal Lifestyle Impairs Embryonic Growth : The Rotterdam Periconception Cohort

Previously, embryonic growth has been assumed to be uniform, but in recent years, it has become more clear that genetic and environmental factors may influence the intrauterine environment and therefore embryonic growth trajectories as well as pregnancy course and outcome. The objective of this study was to investigate associations between modifiable maternal nutrition and lifestyle factors during the periconception period and embryonic growth. We established a prospective cohort including 342 women less than 13 weeks pregnant. At enrollment, women filled out a questionnaire regarding demographic and medical data and a validated food frequency questionnaire. Participants received multiple 3-dimensional ultrasound examinations up until the 12th week of pregnancy, and crown–rump length (CRL) and embryonic volume (EV) were measured offline using V-Scope Virtual Reality software (version 1.0.0) in a Barco I-Space. Associations between maternal periconception vegetable and fruit intake, folic acid supplement use, smoking, and alcohol consumption and embryonic growth measurements were assessed by linear mixed models adjusted for potential confounders. No or postconception initiation of folic acid supplement use was significantly associated with a 0.76 mm (−7.8%) and 1.63 mm (−3.7%) smaller CRL and a 0.01 cm3 (−19.5%) and 0.86 cm3 (−12.2%) smaller EV at 7+0 and 11+0 weeks of gestation, respectively. Smoking, alcohol consumption, and inadequate fruit and vegetable intake showed weaker associations with embryonic growth parameters. These results emphasize the influence of periconceptional maternal folic acid supplement use on embryonic growth. Results regarding maternal nutrition and lifestyle factors also suggest an association with embryonic growth, but this has to be confirmed in a larger study.

Healthy preconception nutrition and lifestyle using personalized mobile health coaching is associated with enhanced pregnancy chance

Periconceptional nutrition and lifestyle are essential in pathogenesis and prevention of most reproductive failures, pregnancy outcome and future health. We aimed to investigate whether personalized mobile health (mHealth) coaching empowers couples contemplating pregnancy to increase healthy behaviour and chances of pregnancy. A survey was conducted among 1053 women and 332 male partners who received individual coaching using the mHealth programme Smarter Pregnancy to change poor nutrition and lifestyle for 26 weeks, depending on pregnancy state and gender. Poor behaviours were translated into a total risk score (TRS) and Poisson regression analysis was performed to estimate associations with the chance of pregnancy adjusted for fertility status, age and baseline body mass index expressed as adjusted hazard ratio (aHR) and 95% confidence interval (95% CI). A lower (a)HR suggests a higher chance of achieving pregnancy. A higher TRS was significantly associated with a lower chance of pregnancy in all women (aHR 0.79, 95% CI 0.72-0.85) and (a)HR was lowest in women whose male partner participated (aHR 0.75, 95% CI 0.61-0.91). This survey shows that empowerment of couples in changing poor nutrition and lifestyle using personalized mHealth coaching is associated with an enhanced pregnancy chance in both infertile and fertile couples.

Placental development and function in women with a history of placenta‐related complications: a systematic review

Women with a history of placenta‐related pregnancy complications, such as preeclampsia, intrauterine growth restriction or preterm delivery, have an increased risk for recurrence of such complications. This recurrence is likely the result of underlying endothelial dysfunction that leads to abnormal placentation, especially in complications with an early onset. This study provides an overview of biomarkers of placental development and function in pregnancies from women with a history of placenta‐related complications.

Prediction models for the risk of gestational diabetes: a systematic review

BackgroundNumerous prediction models for gestational diabetes mellitus (GDM) have been developed, but their methodological quality is unknown. The objective is to systematically review all studies describing first-trimester prediction models for GDM and to assess their methodological quality.MethodsMEDLINE and EMBASE were searched until December 2014. Key words for GDM, first trimester of pregnancy, and prediction modeling studies were combined. Prediction models for GDM performed up to 14xa0weeks of gestation that only include routinely measured predictors were eligible.Data was extracted by the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS). Data on risk predictors and performance measures were also extracted. Each study was scored for risk of bias.ResultsOur search yielded 7761 articles, of which 17 were eligible for review (14 development studies and 3 external validation studies). The definition and prevalence of GDM varied widely across studies. Maternal age and body mass index were the most common predictors. Discrimination was acceptable for all studies. Calibration was reported for four studies. Risk of bias for participant selection, predictor assessment, and outcome assessment was low in general. Moderate to high risk of bias was seen for the number of events, attrition, and analysis.ConclusionsMost studies showed moderate to low methodological quality, and few prediction models for GDM have been externally validated. External validation is recommended to enhance generalizability and assess their true value in clinical practice.

The use of the mHealth program Smarter Pregnancy in preconception care: Rationale, study design and data collection of a randomized controlled trial

BackgroundUnhealthy nutrition and lifestyle contribute to the worldwide rising prevalence of non-communicable diseases. This also accounts for the reproductive population, in which unhealthy behavior affects fertility and pregnancy outcome. Maternal smoking, alcohol consumption and inadequate folic acid supplement use are strongly associated with fetal complications as small for gestational age, premature birth and congenital malformations. In the Netherlands 83% of the perinatal mortality rate is due to these complications and is relatively high compared to other European countries. In order to reduce this prevalence rate, preconception care should be focused on the promotion of health of prospective parents by identification and intervention on modifiable nutrition and lifestyle risk factors. We developed the personal mHealth program ‘Smarter Pregnancy’ (Dutch version available on: https://www.slimmerzwanger.nl) to provide individual coaching and information to improve nutrition and lifestyle during the preconception period in order to improve health of the reproductive population and subsequent generations.MethodsWomen between 18 and 45xa0years of age, and trying to conceive are eligible for inclusion in a randomized controlled trial. Participants are allocated either to a general population cohort or a subfertile (IVF/ICSI) population cohort. The intervention group receives personal online coaching based on the identified nutrition and lifestyle risk factors at baseline. Coaching comprises recipes, incentives, additional questions including feedback and text and e-mail messages, with a maximum of three per week. The control group only receives one recipe per week to maintain adherence to the program and prevent drop out. Screening questionnaires are send in both groups at 6, 12, 18, and 24xa0weeks of the program to monitor the change in the identified risk factors.DiscussionWe expect to demonstrate that the mHealth program ‘Smarter Pregnancy’ can effectively improve nutrition and lifestyle in couples contemplating pregnancy. By the identification and improvement of modifiable nutrition and lifestyle risk factors on a large scale, both reproductive and pregnancy outcomes can be improved and subsequent perinatal morbidity and mortality rates are expected to be reduced. The current use and rapid development of mHealth applications offers new opportunities to reach and educate large populations, which can facilitate the implementation of preconception care.Trial registrationDutch trial register: NTR4150. (Registered 19th August 2013)

The impact of maternal lifestyle factors on periconception outcomes: a systematic review of observational studies

The main risk factors for important reproductive health issues such as subfertility and perinatal mortality largely originate in the periconception period. To evaluate associations between modifiable maternal lifestyle factors and periconception outcomes, a systematic search was conducted for relevant studies published from 1990 to February 2017 on Embase, Medline, Web of Science, Cochrane database, PubMed and Google Scholar. The initial search identified 6166 articles, of which 49 studies were eligible for inclusion. Fecundity (the capacity to have a live birth) showed significant inverse associations with smoking, alcohol use and poor diet. Studies regarding time to pregnancy showed a decline in fecundity ratios (the monthly conception rate among exposed relative to unexposed couples) with increasing body mass index (BMI). Furthermore, risk of first-trimester miscarriage was found to be increased in smokers, alcohol and caffeine consumers, and with increasing BMI. Vitamin supplement use showed a decrease in this risk. This review demonstrates that maternal modifiable lifestyle factors affect periconception outcomes. If couples planning a pregnancy are more aware and supported to adopt healthy lifestyles during the periconceptional window of opportunity, short-term reproductive health as well as health in later life and even of future generations can be further improved.

Virtual reality imaging techniques in the study of embryonic and early placental health

Embryonic and placental growth and development in the first trimester of pregnancy have impact on the health of the fetus, newborn, child and even the adult. This emphasizes the importance of this often neglected period in life. The development of three-dimensional transvaginal ultrasonography in combination with virtual reality (VR) opens the possibility of accurate and reliable visualization of embryonic and placental structures with real depth perception. These techniques enable new biometry and volumetry measurements that contribute to the knowledge of the (patho)physiology of embryonic and early placental health. Examples of such measurements are the length of complex structures like the umbilical cord, vitelline duct, limbs and cerebellum or the volume of the whole embryo and brain cavities. Moreover, for the first time, embryos can now be staged inxa0vivo (Carnegie stages) and vasculature volumes of both the embryo and the early placenta can be measured when VR is combined with power Doppler signals. These innovative developments have already been used to study associations between periconceptional maternal factors, such as age, smoking, alcohol use, diet and vitamin status, and embryonic and early placental growth and development. Future studies will also focus on the identification of abnormal embryonic and early placental development already in the earliest weeks of pregnancy, which provides opportunities for early prevention of pregnancy complications.