Predicting pregnancy chances leading to term live birth in oligo/anovulatory women diagnosed with PCOS.

RESEARCH QUESTION: Which patient features predict the time to pregnancy (TTP) leading to term live birth in infertile women diagnosed with polycystic ovary syndrome (PCOS)? DESIGN: Prospective cohort follow-up study was completed, in which initial standardized phenotyping was conducted at two Dutch university medical centres from January 2004 to January 2014. Data were linked to the Netherlands Perinatal Registry to obtain pregnancy outcomes for each participant. All women underwent treatment according to a standardized protocol, starting with ovulation induction as first-line treatment. Predictors of pregnancies (leading to term live births) during the first year after PCOS diagnosis were evaluated. RESULTS: A total of 1779 consecutive women diagnosed with PCOS between January 2004 and January 2014 were included. In the first year following screening, 659 (37%) women with PCOS attained a pregnancy leading to term birth (≥37 weeks of gestational age). A higher chance of pregnancy was associated with race, smoking, body mass index (BMI), insulin, total testosterone and sex hormone-binding globulin (SHBG) concentrations (c-statistic = 0.59). CONCLUSIONS: Predictors of an increased chance of a live birth include White race, no current smoking, lower BMI, insulin and total testosterone concentrations, and higher SHBG concentrations. This study presents a nomogram to predict the chances of achieving a pregnancy (leading to a term live birth) within 1 year of treatment.

Planning is not equivalent to preparing, how Dutch women perceive their pregnancy planning in relation to preconceptional lifestyle behaviour change - a cross-sectional study.

BACKGROUND: Unhealthy prenatal lifestyle behaviours are associated with adverse pregnancy outcomes, but little is known about what motivates women to comply with preconceptional lifestyle recommendations or consciously plan their pregnancy. Therefore, the objective of this study is to explore the associations between preconceptional lifestyle behaviours, health beliefs and pregnancy planning among Dutch pregnant women. METHODS: In this cross-sectional study based on the data of the APROPOS-II study, 1,077 low-risk pregnant women were eligible for inclusion. Preconception lifestyle behaviours and actively preparing for pregnancy were assessed in relation to planned pregnancies (based on the London Measure of Unplanned Pregnancies) and health beliefs (14 statements). The following preconceptional lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester of pregnancy: fruit intake, vegetable intake, caffeine intake, (second-hand)smoking, alcohol intake, folic acid supplement use and exercise. Data were analysed using multivariate logistic regression analyses. RESULTS: A total of 921 (85.5%) women in our cohort had a planned pregnancy. However, of these women, 640 (69.5%) adequately used folic acid supplements and 465 (50.5%) women consumed alcohol at any point during pregnancy. Of the women considering themselves 'healthy enough and not needing preconception care', 48 (9.1%) women had an adequate vegetable intake, 294 (55.6%) women consumed alcohol at any point during pregnancy and 161 (30.4%) women were either over-or underweight. CONCLUSION: Despite consciously planning their pregnancy, most women did not adhere to preconceptional lifestyle behaviour recommendations. Women's health beliefs and overestimation of their health status seem to interfere with actively planning and preparing for pregnancy. Findings from our study may encourage the development of prospective health-promoting interventions that focus on health beliefs and actively preparing for pregnancy, to improve preconceptional lifestyle behaviours, thereby optimizing the health of future generations.

Cardiometabolic Profiles in Women with a History of Hypertensive and Normotensive Fetal Growth Restriction.

Background: The majority of evidence on associations between pregnancy complications and future maternal disease focuses on hypertensive (Ht) complications. We hypothesize that impaired cardiometabolic health after pregnancies complicated by severe fetal growth restriction (FGR) is independent of the co-occurrence of hypertension. Materials and Methods: In a prospective cohort of women with a pregnancy complicated by early FGR (delivery <34 weeks gestation), with or without concomitant hypertension, cardiometabolic risk factors were assessed after delivery. A population-based reference cohort was used for comparison, and analyses were adjusted for age, current body mass index (BMI), smoking habits, and hormonal contraceptive use. Results: Median time from delivery to assessment was 4 months in both the Ht (N = 115) and normotensive (Nt) (N = 42) FGR groups. Compared with the reference group (N = 380), in both FGR groups lipid profile and glucose homeostasis at assessment were unfavorable. Women with Ht-FGR had the least favorable cardiometabolic profile, with higher prevalence ratios (PRs) for diastolic blood pressure >85 mmHg (PR 4.0, 95% confidence interval [CI] 2.1-6.7), fasting glucose levels >5.6 mmol/L (PR 2.9, 95% CI 1.4-5.6), and total cholesterol levels >6.21 mmol/L (PR 4.5, 95% CI 1.9-8.8), compared with the reference group. Women with Nt-FGR more often had a BMI >30 kg/m2 (PR 2.5, 95% CI 1.2-4.7) and high-density lipoprotein-cholesterol levels <1.29 mmol/L (PR 2.4, 95% CI 1.4-3.5), compared with the reference group. Conclusions: Women with a history of FGR showed unfavorable short-term cardiometabolic profiles in comparison with a reference group, independent of the co-occurrence of hypertension. Therefore, women with a history of FGR may benefit from cardiovascular risk factor assessment and subsequent risk reduction strategies.

Associations between periconceptional lifestyle behaviours and adverse pregnancy outcomes.

BACKGROUND: While the potential adverse outcomes of prenatal exposure to unhealthy lifestyle are widely evidenced, little is known about these exposures in the periconception period. We investigated the associations between lifestyle behaviours and adverse pregnancy outcomes with a unique distinction between preconceptional- and prenatal lifestyle behaviours. METHODS: A secondary analysis took place within a prospective multicentre cohort study in the Netherlands, including 3,684 pregnant women. Baseline characteristics and preconceptional and first trimester lifestyle behaviours were assessed through a self-administered questionnaire in the first trimester. Adverse pregnancy outcomes (hypertensive disorders in pregnancy (HDP), small for gestational age (SGA), gestational diabetes (GDM) and spontaneous preterm birth (sPTB)) were reported by healthcare professionals. Data were collected between 2012 and 2014 and analysed using multivariate logistic regression. RESULTS: Women who are overweight, and especially obese, have the highest odds of developing any adverse pregnancy outcome (adjusted odds ratio (aOR) 1.61 (95 % Confidence Interval (CI) 1.31-1.99) and aOR 2.85 (95 %CI 2.20-3.68), respectively), particularly HDP and GDM. Women who prenatally continued smoking attained higher odds for SGA (aOR 1.91 (95 %CI 1.05-1.15)) compared to the reference group, but these odds decreased when women prenatally quit smoking (aOR 1.14 (95 %CI 0.59-2.21)). Women who did not use folic acid supplements tended to have a higher odds of developing adverse pregnancy outcomes (aOR 1.28 (95 %CI 0.97-1.69)), while women who prenatally started folic acid supplements did not (aOR 1.01 (95 %CI 0.82-1.25)). CONCLUSIONS: Our results indicate that smoking cessation, having a normal body mass index (BMI) and initiating folic acid supplements preconceptionally may decrease the risk of adverse pregnancy outcomes. Therefore, intervening as early as the preconception period could benefit the health of future generations.

Implementation of a first-trimester prognostic model to improve screening for gestational diabetes mellitus.

BACKGROUND: Improvement in the accuracy of identifying women who are at risk to develop gestational diabetes mellitus (GDM) is warranted, since timely diagnosis and treatment improves the outcomes of this common pregnancy disorder. Although prognostic models for GDM are externally validated and outperform current risk factor based selective approaches, there is little known about the impact of such models in day-to-day obstetric care. METHODS: A prognostic model was implemented as a directive clinical prediction rule, classifying women as low- or high-risk for GDM, with subsequent distinctive care pathways including selective midpregnancy testing for GDM in high-risk women in a prospective multicenter birth cohort comprising 1073 pregnant women without pre-existing diabetes and 60 obstetric healthcare professionals included in nine independent midwifery practices and three hospitals in the Netherlands (effectiveness-implementation hybrid type 2 study). Model performance (c-statistic) and implementation outcomes (acceptability, adoption, appropriateness, feasibility, fidelity, penetration, sustainability) were evaluated after 6 months by indicators and implementation instruments (NoMAD; MIDI). RESULTS: The adherence to the prognostic model (c-statistic 0.85 (95%CI 0.81-0.90)) was 95% (n = 1021). Healthcare professionals scored 3.7 (IQR 3.3-4.0) on implementation instruments on a 5-point Likert scale. Important facilitators were knowledge, willingness and confidence to use the model, client cooperation and opportunities for reconfiguration. Identified barriers mostly related to operational and organizational issues. Regardless of risk-status, pregnant women appreciated first-trimester information on GDM risk-status and lifestyle advice to achieve risk reduction, respectively 89% (n = 556) and 90% (n = 564)). CONCLUSIONS: The prognostic model was successfully implemented and well received by healthcare professionals and pregnant women. Prognostic models should be recommended for adoption in guidelines.

First trimester secreted Frizzled-Related Protein 4 and other adipokine serum concentrations in women developing gestational diabetes mellitus.

BACKGROUND: The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM). METHODS: In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC). RESULTS: First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793). CONCLUSION: In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.

First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial.

OBJECTIVE: To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing in vitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI). DESIGN: Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March 2017. SETTING: IVF clinics. PATIENT(S): A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners. INTERVENTIONS(S): Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period. MAIN OUTCOME MEASURE(S): Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program. RESULT(S): Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors. CONCLUSION(S): The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome. NETHERLANDS TRIAL REGISTER NUMBER: NTR4150.

Preconceptional Maternal Vegetable Intake and Paternal Smoking Are Associated with Pre-implantation Embryo Quality.

Inadequate nutrition and lifestyle behaviors, particularly during the periconception period, are associated with a negative impact on embryonic and subsequent fetal development. We investigated the associations between parental nutritional and lifestyle factors and pre-implantation embryo development. A total of 113 women and 41 partners, with a corresponding 490 embryos, who underwent intracytoplasmic sperm injection (ICSI) treatment subscribed to the mHealth coaching platform "Smarter Pregnancy." At baseline, nutrition and lifestyle behaviors (intake of fruits, vegetables, folic acid, and smoking and alcohol use) were identified and risk scores were calculated. A lower risk score represents healthier behavior. As outcome measure, a time-lapse morphokinetic selection algorithm (KIDScore) was used to rank pre-implantation embryo quality on a scale from 1 (poor) to 5 (good) after being cultured in the Embryoscope™ time-lapse incubator until embryonic day 3. To study the association between the nutritional and lifestyle risk scores and the KIDScore in men and women, we used a proportional odds model. In women, the dietary risk score (DRS), a combination of the risk score of fruits, vegetables, and folic acid, was negatively associated with the KIDScore (OR 0.86 (95% CI 0.76 to 0.98), p = 0.02). This could mainly be attributed to an inadequate vegetable intake (OR 0.76 (95% CI 0.59 to 0.96), p = 0.02). In men, smoking was negatively associated with the KIDscore (OR 0.53 (95% CI 0.33 to 0.85), p < 0.01). We conclude that inadequate periconceptional maternal vegetable intake and paternal smoking significantly reduce the implantation potential of embryos after ICSI treatment. Identifying modifiable lifestyle risk factors can contribute to directed, personalized, and individual recommendations that can potentially increase the chance of a healthy pregnancy.

Study design of a stepped wedge cluster randomized controlled trial to evaluate the effect of a locally tailored approach for preconception care - the APROPOS-II study.

BACKGROUND: In a previous feasibility study (APROPOS) in a single municipality of the Netherlands, we showed that a locally tailored preconception care (PCC) approach has the potential to positively affect preconceptional lifestyle behaviours. Therefore, we designed a second study (APROPOS-II) to obtain a more robust body of evidence: a larger group of respondents, more municipalities, randomization, and a more comprehensive set of (clinical) outcomes. The aim of this study is to assess the effectiveness and the implementation process of a local PCC-approach on preconceptional lifestyle behaviours, health outcomes and the reach of PCC among prospective parents and healthcare providers. METHODS: This study is an effectiveness-implementation hybrid type 2 trial. This involves a stepped-wedge cluster randomized controlled trial design aiming to include over 2000 future parents from six municipalities in the Netherlands. The intervention has a dual-track approach, focusing on both the uptake of PCC among future parents and the provision of PCC by healthcare providers. The PCC-approach consists of 1) a social marketing strategy directed towards prospective parent(s) and 2) a local care pathway to improve interdisciplinary collaboration. Data will be collected before and after the introduction of the intervention through questionnaires and medical records in each of the participating municipalities. The primary outcome of this study is change in lifestyle behaviours (e.g. folic acid use, smoking and alcohol use). Secondary outcomes are pregnancy outcomes (e.g. miscarriage, preterm birth, gestational diabetes) and the uptake of PCC. Moreover, a process evaluation will be performed, providing information on the efficacy, feasibility, barriers and facilitators regarding the implementation of the intervention. DISCUSSION: The APROPOS-II study introduces a locally tailored PCC-approach in six municipalities in the Netherlands that will contribute to the body of evidence regarding the effectiveness of PCC and its implementation. If this intervention has a positive effect on lifestyle behaviour changes, leading to improved pregnancy outcomes and the future health of prospective parents and their offspring, it could subsequently be upscaled to (inter)national implementation. TRIAL REGISTRATION: Dutch Trial register: NL7784 (Registered June 6th, 2019).

The Impact of Neighbourhood Deprivation on Embryonic Growth Trajectories: Rotterdam Periconception Cohort.

BACKGROUND: Neighbourhood deprivation is a risk factor for impaired health and adverse pregnancy outcomes. We investigated whether living in a deprived neighbourhood is associated with embryonic growth. METHODS: From the Predict cohort, we studied 566 women who underwent repeated first trimester ultrasound examinations. Crown rump length (CRL; n = 1707) and embryonic volume (EV; n = 1462) were measured using three-dimensional techniques. Neighbourhood deprivation was assessed using the neighbourhood status scores (NSS) of the Dutch Social Cultural Planning office. A high NSS represents a non-deprived neighbourhood. Associations between the NSS and embryonic growth were investigated using linear mixed models. Adjustment was performed for individual-level factors: maternal age, geographic origin, educational level, BMI, folic acid supplement use, fruit and vegetable intake, alcohol use and smoking habits. RESULTS: The NSS was negatively associated with embryonic growth: a higher score (a less deprived neighbourhood) was associated with a smaller CRL and EV; adjusted ß: -0.025 (95% CI -0.046, -0.003) and adjusted ß: -0.015 (95% CI -0.026, -0.003). At 11 weeks of pregnancy, we observed a 0.55 cm3 smaller EV (7.65 cm3 vs. 7.10 cm3) and 1.08 mm smaller CRL (43.14 mm vs. 42.06 mm) in the highest compared to the lowest category. CONCLUSION: In deprived neighbourhoods, embryos are larger than in non-deprived neighbourhoods.

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 in vivo (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.

Cardiovascular and Metabolic Health of 74 Children From Women Previously Diagnosed With Polycystic Ovary Syndrome in Comparison With a Population-Based Reference Cohort.

Women with polycystic ovary syndrome (PCOS) have compromised cardiovascular health profiles and an increased risk of pregnancy complications. In order to evaluate potential consequences, we aim to compare the cardiovascular and metabolic health of the children from women with PCOS with a population-based reference cohort. We included children from women with PCOS between the age of 2.5 to 4 years (n = 42) and 6 to 8 years (n = 32). The reference groups consisted of 168 (3-4 years old) and 130 children (7-8 years old). In an extensive cardiovascular screening program, we measured anthropometrics and blood pressure (all children), heart function and vascular rigidity (young children), metabolic laboratory assessment and carotid intima thickness (old age-group). Results showed that young PCOS offspring have a significantly lower diastolic blood pressure (ß = 2.3 [95% confidence interval, CI: 0.5-4.0]) and higher aortic pulse pressure (ß = -1.4 [95% CI: -2.5 to -0.2]), compared to the reference population. Furthermore, a higher left ventricle internal diameter but a lower tissue Doppler imaging of the right wall in systole compared to the reference group was found. Older offspring of women with PCOS presented with a significantly lower breast and abdominal circumference, but higher triglycerides (ß = -0.1 [95% CI: -0.2 to -0.1]), LDL-cholesterol (ß = -0.4 [95% CI: -0.6 to -0.1]), and higher carotid intima-media thickness (ß = -31.7 [95% CI: -46.6 to -16.9]) compared to the reference group. In conclusion, we observe subtle but distinct cardiovascular and metabolic abnormalities already at an early age in PCOS offspring compared to a population-based reference group, despite a lower diastolic blood pressure, breast, and abdominal circumference. These preliminary findings require confirmation in independent data sets.

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.

Increased rates of complications in singleton pregnancies of women previously diagnosed with polycystic ovary syndrome predominantly in the hyperandrogenic phenotype.

OBJECTIVE: To study the presence of several maternal and neonatal complications in a cohort of women with hyperandrogenic as well as normoandrogenic polycystic ovary syndrome (PCOS) and women with PCOS who received different fertility treatments. DESIGN: Prospective multicenter cohort study. SETTING: Hospitals and midwifery practices. PATIENT(S): One hundred and eighty-eight women with PCOS and singleton pregnancies (study group) and 2,889 women with a naturally conceived singleton pregnancy (reference group). INTERVENTION(S): Observational study. MAIN OUTCOME MEASURE(S): Maternal and neonatal pregnancy complications. RESULT(S): Women with PCOS had a statistically significantly increased risk of developing gestational diabetes (adjusted odds ratio [AOR] 4.15; 95% confidence interval [CI], 2.07-8.33) compared with the reference group, and their infants were more often born small for gestational age (AOR 3.76; 95% CI, 1.69-8.35). In a subgroup analysis, maternal complications were statistically significantly more often present in women with hyperandrogenic (defined as a free androgen index >4.5) PCOS (n = 76; 40% of all PCOS women) compared with those with normoandrogenic PCOS (n = 97; 52% of all PCOS women) (45% vs. 24%; P=.003); no statistically significant differences were observed between these groups regarding neonatal complications. CONCLUSION(S): Women with PCOS have an increased risk of maternal and neonatal pregnancy complications, especially women with the hyperandrogenic phenotype. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

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.

Actively preparing for pregnancy is associated with healthier lifestyle of women during the preconception period.

OBJECTIVE: To assess whether actively preparing for pregnancy by women is associated with lifestyle changes during the preconception period. DESIGN: retrospective cross-sectional study. SETTING: primary care community midwifery practice in the Netherlands. PARTICIPANTS: convenience sample of 283 women who received antenatal care. MEASUREMENTS AND FINDINGS: the association between pregnancy preparation (defined as searching for information and/or consulting a healthcare provider) and preconception lifestyle changes (healthier diet, folic acid, alcohol and tobacco cessation) was measured and adjusted for age, body mass index and educational level. Almost 60% (n=160) of women acquired preconception information themselves and 25% (n=68) consulted a healthcare provider regarding their pregnancy wish. The former group was significantly more likely to quit drinking (adjusted OR 5.46 (95% CI 1.76-16.96)), improve their diet (adjusted OR 7.84 (95% CI 3.03-20.30)) and use folic acid (adjusted OR 3.90 (95% CI 2.00-7.62)) compared with women who did not prepare for pregnancy. Effect sizes were even larger for women who (also) consulted a healthcare provider with regard to folic acid use, healthier diet and smoking cessation. KEY CONCLUSIONS: gathering preconception information, either by women themselves or by means of a PCC consult, is associated with women positively changing lifestyles during the preconception period. IMPLICATIONS FOR PRACTICE: we recommend to not solely focus interventions on increasing the uptake of PCC consults, yet providing a suitable offer of preconception health information, which enables women to properly inform themselves.

Endocrine and cardiometabolic cord blood characteristics of offspring born to mothers with and without polycystic ovary syndrome.

OBJECTIVE: To compare the endocrine and cardiometabolic cord blood characteristics of offspring of mothers with polycystic ovary syndrome (PCOS) with those of healthy controls. DESIGN: Cross-sectional case control study. SETTING: University medical centers. PATIENT(S): Offspring from mothers with PCOS (n = 61) and healthy controls (n = 82). INTERVENTION(S): Cord blood withdrawal from neonates. MAIN OUTCOME MEASURE(S): Cord blood estradiol, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone-binding globulin, free androgen index (FAI), insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, c-reactive protein, adiponectin, and leptin. RESULT(S): Androstenedione and leptin concentrations were increased in the offspring of women with PCOS compared with the controls: androstenedione median 2.9 (interquartile range [IQR] 2.3-3.9) nmol/L vs. 2.2 [IQR 1.6-2.7] nmol/L; and leptin median 13.6 [IQR 8.3-22.9] µg/L vs. 9.8 [IQR 6.0-16.5] µg/L. After adjusting for maternal and pregnancy-related confounders (such as maternal age, gestational age, birth weight), androstenedione appeared associated with PCOS in both male (relative change 1.36 [1.04; 1.78]) and female offspring (relative change 1.40 [1.08; 1.82]). Similarly, in male offspring the leptin concentrations appeared associated with PCOS after correction for confounders (relative change 1.55 [1.12; 2.14]). After correction for multiple testing, these associations attenuated. CONCLUSION(S): Observed results suggest that androstenedione concentrations are increased in the cord blood of male and female offspring of women with PCOS, although this requires confirmation. This finding would support the hypothesis that a maternal hyperandrogenic environment during pregnancy in women with PCOS may predispose their offspring to fetal hyperandrogenism. The potential associations between fetal hyperandrogenism and long-term health effects remain to be elucidated. CLINICAL TRIAL REGISTRATION NUMBER: NCT00821379.

Perspectives, preferences and needs regarding early prediction of preeclampsia in Dutch pregnant women: a qualitative study.

BACKGROUND: To improve early risk-identification in pregnancy, research on prediction models for common pregnancy complications is ongoing. Therefore, it was the aim of this study to explore pregnant women's perceptions, preferences and needs regarding prediction models for first trimester screening for common pregnancy complications, such as preeclampsia, to support future implementation. METHOD: Ten focus groups (of which five with primiparous and five with multiparous women) were conducted (n = 45). Six focus groups were conducted in urban regions and four in rural regions. All focus group discussions were audio taped and NVIVO was used in order to facilitate the thematic analysis conducted by the researchers. RESULTS: Women in this study had a positive attitude towards first trimester screening for preeclampsia using prediction models. Reassurance when determined as low-risk was a major need for using the test. Self-monitoring, early recognition and intensive monitoring were considered benefits of using prediction models in case of a high-risk. Women acknowledged that high-risk determination could cause (unnecessary) anxiety, but it was expected that personal and professional interventions would level out this anxiety. CONCLUSION: Women in this study had positive attitudes towards preeclampsia screening. Self-monitoring, together with increased alertness of healthcare professionals, would enable them to take active actions to improve pregnancy outcomes. This attitude enhances the opportunities for prevention, early recognition and treatment of preeclampsia and probably other adverse pregnancy outcomes.

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

BACKGROUND: Unhealthy 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. METHODS: Women between 18 and 45 years 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 24 weeks of the program to monitor the change in the identified risk factors. DISCUSSION: We 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 REGISTRATION: Dutch trial register: NTR4150 . (Registered 19th August 2013).