Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments.

AIMS: The impact of maternal metformin use during pregnancy on fetal, infant, childhood and adolescent growth, development, and health remains unclear. Our objective was to systematically review the available evidence from animal experiments on the effects of intrauterine metformin exposure on offspring's anthropometric, cardiovascular and metabolic outcomes. METHODS: A systematic search was conducted in PUBMED and EMBASE from inception (searched on 12th April 2023). We extracted original, controlled animal studies that investigated the effects of maternal metformin use during pregnancy on offspring anthropometric, cardiovascular and metabolic measurements. Subsequently, risk of bias was assessed and meta-analyses using the standardized mean difference and a random effects model were conducted for all outcomes containing data from 3 or more studies. Subgroup analyses were planned for species, strain, sex and type of model in the case of 10 comparisons or more per subgroup. RESULTS: We included 37 articles (n = 3133 offspring from n = 716 litters, containing n = 51 comparisons) in this review, mostly (95%) on rodent models and 5% pig models. Follow-up of offspring ranged from birth to 2 years of age. Thirty four of the included articles could be included in the meta-analysis. No significant effects in the overall meta-analysis of metformin on any of the anthropometric, cardiovascular and metabolic offspring outcome measures were identified. Between-studies heterogeneity was high, and risk of bias was unclear in most studies as a consequence of poor reporting of essential methodological details. CONCLUSION: This systematic review was unable to establish effects of metformin treatment during pregnancy on anthropometric, cardiovascular and metabolic outcomes in non-human offspring. Heterogeneity between studies was high and reporting of methodological details often limited. This highlights a need for additional high-quality research both in humans and model systems to allow firm conclusions to be established. Future research should include focus on the effects of metformin in older offspring age groups, and on outcomes which have gone uninvestigated to date.

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Predictive value of fetal growth trajectory from 20 weeks of gestation onwards for severe adverse perinatal outcome in low-risk population: secondary analysis of IRIS study.

OBJECTIVES: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over- or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third-trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low-risk population. METHODS: This was a post-hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster-randomized trial assessing the (cost-)effectiveness of routine third-trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small-for-gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. RESULTS: Our sample included the data of 6296 low-risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. CONCLUSIONS: In a low-risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post-diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Virtual Reality Experience during Labour (VIREL); a qualitative study.

BACKGROUND: There is increasing evidence that virtual reality (VR) is effective in the reduction of labour pain. The implementation of alternative methods like VR to reduce labour pain can contribute to reduce patient request for pharmacological pain management methods and associated side effects. The aim of this study is to examine women's experiences, preferences and satisfaction in regard to the use of VR during labour. METHODS: A qualitative interview study was conducted in a non-university teaching hospital in The Netherlands. Two VR applications, respectively a guided meditation and an interactive game were tested in eligible women with a singleton pregnancy, scheduled for induction of labour. For the primary outcome, patients' VR experience and application preference (meditation vs. game) were examined using a post-intervention questionnaire and a semi-structured interview. Three categories (with sub-categories) were used to guide interviews: "The VR experience", "Pain reduction", and "Usability of the VR application". Labour pain before and directly after VR was evaluated using the NRS score. RESULTS: Twenty-four women, of whom 14 were nulliparous and ten multiparous, were included and 12 of these women participated in semi-structured interviews. Using within-subject paired t-test comparisons, compared to pain pre-VR, patients reported a highly significant 26% decrease in mean NRS scores during VR meditation (pain pre-VR = 6.71 + - 1.65 vs. pain after VR = 4.96 + - 2.01) [p < 0.001]. Compared to pain before VR game, patients also reported a highly significant 19% decrease in mean NRS scores during VR game (pain before VR game = 6.89 + - 1.88 vs. pain after VR game = 5.61 + - 2.23) [p = 0.001]. CONCLUSION: All women were highly satisfied with VR use during labour. Patients reported a highly significant reduction in pain during the interactive VR game and during meditation, patients preferred guided meditation. These results can contribute to the development of a potential promising new non-pharmacological tool to reduce labour pain. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04858984, date of registration: 26/04/2021 (retrospectively registered).

Community midwives' perspectives on perinatal care for asylum seekers and refugees in the Netherlands: A survey study.

BACKGROUND: The rise of forced migration worldwide compels birth care systems and professionals to respond to the needs of women giving birth in these vulnerable situations. However, little is known about the perspective of midwifery professionals on providing perinatal care for forcibly displaced women. This study aimed to identify challenges and target areas for improvement of community midwifery care for asylum seekers (AS) and refugees with a residence permit (RRP) in the Netherlands. METHODS: For this cross-sectional study, data were collected through a survey aimed at community care midwives who currently work or who have worked with AS and RRP. We evaluated challenges identified through an inductive thematic analysis of respondents' responses to open-ended questions. Quantitative data from close-ended questions were analyzed descriptively and included aspects related to the quality and organization of perinatal care for these groups. RESULTS: Respondents generally considered care for AS and RRP to be of lower quality, or at best, equal quality compared to care for the Dutch population, while the workload for midwives caring for these groups was considered higher. The challenges identified were categorized into five main themes, including: 1) interdisciplinary collaboration; 2) communication with clients; 3) continuity of care; 4) psychosocial care; and 5) vulnerabilities among AS and RRP. CONCLUSIONS: Findings suggest that there is considerable opportunity for improvement in perinatal care for AS and RRP, while also providing direction for future research and interventions. Several concerns raised, especially the availability of professional interpreters and relocations of AS during pregnancy, require urgent consideration at legislative, policy, and practice levels.

The effect of a locally tailored intervention on the uptake of preconception care in the Netherlands: a stepped-wedge cluster randomized trial (APROPOS-II study).

BACKGROUND: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design. METHODS: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers. RESULTS: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030). CONCLUSION: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations. TRIAL REGISTRATION: Dutch Trial Register: NL7784 (Registered 06/06/2019).

Prognostic models versus single risk factor approach in first-trimester selective screening for gestational diabetes mellitus: a prospective population-based multicentre cohort study.

OBJECTIVES: To evaluate whether (1) first-trimester prognostic models for gestational diabetes mellitus (GDM) outperform the currently used single risk factor approach, and (2) a first-trimester random venous glucose measurement improves model performance. DESIGN: Prospective population-based multicentre cohort. SETTING: Thirty-one independent midwifery practices and six hospitals in the Netherlands. POPULATION: Women recruited before 14 weeks of gestation without pre-existing diabetes. METHODS: The single risk factor approach (presence of at least one risk factor: BMI ≥30 kg/m2 , previous macrosomia, history of GDM, positive first-degree family history of diabetes, non-western ethnicity) was compared with the four best performing models in our previously published external validation study (Gabbay-Benziv 2014, Nanda 2011, Teede 2011, van Leeuwen 2010) with and without the addition of glucose. MAIN OUTCOME MEASURES: Discrimination was assessed by c-statistics, calibration by calibration plots, added value of glucose by the likelihood ratio chi-square test, net benefit by decision curve analysis and reclassification by reclassification plots. RESULTS: Of the 3723 women included, a total of 181 (4.9%) developed GDM. The c-statistics of the prognostic models were higher, ranging from 0.74 to 0.78 without glucose and from 0.78 to 0.80 with glucose, compared with the single risk factor approach (0.72). Models showed adequate calibration, and yielded a higher net benefit than the single risk factor approach for most threshold probabilities. Teede 2011 performed best in the reclassification analysis. CONCLUSIONS: First-trimester prognostic models seem to outperform the currently used single risk factor approach in screening for GDM, particularly when glucose was added as a predictor. TWEETABLE ABSTRACT: Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes.

Home-based telemonitoring versus hospital admission in high risk pregnancies: a qualitative study on women's experiences.

BACKGROUND: Hospital admission during pregnancy complications is considered to be an event of significant impact. Besides conventional in-clinic maternal and fetal monitoring, recent technologies enable home-based telemonitoring with self-measurements in high risk pregnancy. This study is part of a feasibility pilot to explore the usability and acceptability of telemonitoring and aims to gain insight in the experiences and preferences of high risk pregnant women concerning the novel strategy of telemonitoring, opposed to women who were hospitalized in pregnancy. METHODS: Using secured Facebook Groups, we conducted four online focus groups: two focus groups with women who were admitted during pregnancy (n = 11) and two with women who received home telemonitoring in the pilot phase (n = 11). The qualitative data were analyzed thematically. RESULTS: Four major themes emerged from both participant groups: [1] care experience, [2] emotions regarding pregnancy, [3] privacy and [4] impact on daily life. Different views were reported on all four themes, resulting in a direct comparison of experiences during hospitalization and telemonitoring. Most admitted patients reported a growing sense of boredom and anxiety during their clinical admission. Lack of privacy on ward was a great concern, as it affected their contact with hospital staff and family. This issue was not reported amongst telemonitored women. These participants still felt like a patient at times but responded that the comfort of their own home and bed was pleasant. Only a minority of telemonitored participants reported being anxious at times at home, while not having a physician or nurse nearby. Being at home resulted in less travel time for partners or family for hospital visits, which had its positive effects on family life. CONCLUSIONS: Telemonitoring of a high-risk pregnancy provides an innovative manner to monitor fetal and maternal condition from home. Compared to the experiences of hospital admission in high risk pregnancy, it allows women to be in a comforting and private environment during an anxious time in their lives. As future studies should further investigate the safety and cost effectiveness of this novel strategy, women's views on the preference of telemonitoring need to be taken into consideration.

Cost effectiveness of nifedipine compared with atosiban in the treatment of threatened preterm birth (APOSTEL III trial).

OBJECTIVE: To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. DESIGN: An economic analysis alongside a randomised clinical trial (the APOSTEL III study). SETTING: Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. POPULATION: Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. METHODS: We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. MAIN OUTCOME MEASURES: Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. RESULTS: Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: €34,897 versus €43,376, mean difference (MD) -€8479 [95% confidence interval (CI) -€14,327 to -€2016)]; multiple pregnancies: €90,248 versus €102,292, MD -€12,044 (95% CI -€21,607 to € -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. CONCLUSION: Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. TWEETABLE ABSTRACT: In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

Views and preferences of medical professionals and pregnant women about a novel primary prevention intervention for hypertensive disorders of pregnancy: a qualitative study.

BACKGROUND: Calcium and low-dose aspirin are two potential approaches for primary prevention of hypertensive disorders of pregnancy (HDP). This study aimed to explore the acceptability, views and preferences of pregnant women and primary healthcare providers for a fixed-dose combined preparation of aspirin and calcium (a polypill) as primary prevention of HDP in an unselected pregnant population. METHODS: In this qualitative study eight in-depth semi-structured interviews were conducted with Dutch primary care midwives and general practitioners. Seven focus group discussions were organised with women with low-risk pregnancies. Topics discussed were: perceptions of preeclampsia; information provision about preeclampsia and a polypill; views on the polypill concept; preferences and needs regarding implementation of a polypill. Thematic analysis of the data transcripts was carried out to identify emerging themes. RESULTS: Two major themes shaped medical professionals' and women's views on the polypill concept: 'Informed Choice' and 'Medicalisation'. Both could be divided into subthemes related to information provision, personal choice and discussions with regard to the balance between 'unnecessary medicalisation' and 'scientific progress'. CONCLUSIONS: In general, women and healthcare practitioners expressed a positive attitude towards a polypill intervention as primary prevention strategy with aspirin and calcium, providing some conditions are met. The most important conditions for implementation of such a strategy were safety, effectiveness and the possibility to make a well-informed autonomous decision.

Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease: a systematic review and meta-analysis.

BACKGROUND: Women with a history of hypertensive disorders, including pre-eclampsia, during pregnancy have a two- to-five-fold increased risk of cardiovascular disease (CVD). In 15% of women, pre-eclampsia recurs in the following pregnancy. OBJECTIVES: To evaluate all evidence on the future risk of developing hypertension and CVD after multiple pregnancies complicated by pre-eclampsia compared with pre-eclampsia in a single pregnancy followed by normal subsequent pregnancy. SEARCH STRATEGY: Embase and Medline were searched until June 2017. SELECTION CRITERIA: All relevant studies on the risk of developing hypertension, atherosclerosis, ischaemic heart disease, cerebrovascular accident (CVA), thromboembolism, heart failure or overall hospitalisation and mortality due to CVD after having had recurrent pre-eclampsia. DATA COLLECTION AND ANALYSIS: Twenty-two studies were included in the review. When possible, we calculated pooled risk ratios (RR) with 95% CI through random-effect analysis. MAIN RESULTS: Recurrent pre-eclampsia was consistently associated with an increased pooled risk ratio of hypertension (RR 2.3; 95% CI 1.9-2.9), ischaemic heart disease (RR 2.4; 95% CI 2.2-2.7), heart failure (RR 2.9; 95% CI 2.3-3.7), CVA (RR 1.7; 95% CI 1.2-2.6) and hospitalisation due to CVD (RR 1.6; 95% CI 1.3-1.9) when compared with women with subsequent uncomplicated pregnancies. Other studies on thromboembolism, atherosclerosis and cardiovascular mortality found a positive effect, but data could not be pooled. CONCLUSIONS: This systematic review and meta-analysis support consistent higher risk for future development of hypertension and CVD in women with recurring pre-eclampsia as opposed to women with a single episode of pre-eclampsia. TWEETABLE ABSTRACT: The risk of future cardiovascular disease increases when women have recurrence of pre-eclampsia compared with a single episode.

Effect of nifedipine and atosiban on perinatal brain injury: secondary analysis of the APOSTEL-III trial.

OBJECTIVE: Brain injury in neonates born prematurely is associated strongly with poor neurodevelopmental outcome. The aim of this study was to evaluate whether tocolysis with nifedipine or atosiban in women with threatened preterm birth can reduce the incidence of overall brain injury in neonates born prematurely. METHODS: This was a secondary analysis of the APOSTEL-III trial (Dutch Clinical Trial Registry, no. NTR2947), a randomized clinical trial in which women with threatened preterm labor between 25 and 34 weeks of gestation were allocated to treatment with nifedipine or atosiban. In this secondary analysis, women delivered at ≤ 32 weeks of gestational age in the two main contributing centers were included. Primary outcome was the presence of neonatal brain injury, which was defined as presence of abnormalities on ultrasound investigation and classified into mild and severe. To evaluate type and severity of brain injury, all neonatal ultrasounds performed during neonatal intensive and medium care admission were analyzed. To test the robustness of our results, a sensitivity analysis was performed assessing differences in baseline or known risk factors for brain injury. RESULTS: A total of 117 neonates (from 102 women) were studied, of which 51 had been exposed to nifedipine and 66 to atosiban. Brain injury was observed in 22 (43.1%) neonates in the nifedipine group compared with 37 (56.1%) in the atosiban group (OR, 0.60; 95% CI, 0.29-1.24). Presence of mild brain injury was comparable between the nifedipine (33.3%) and atosiban (48.5%) groups (OR, 0.53; 95% CI, 0.25-1.13). Severe brain injury was also comparable between the groups, observed in 9.8% of neonates in the nifedipine vs 7.6% of those in the atosiban group (OR, 1.33; 95% CI, 0.36-4.85). Intraventricular hemorrhage (≥ Grade I) was the most frequently seen ultrasound abnormality, observed in 18 (35.3%) neonates in the nifedipine group vs 25 (37.9%) in the atosiban group (OR, 0.90; 95% CI, 0.42-1.91). The sensitivity analysis, with adjustment for maternal age and gestational age at randomization, showed no statistical difference between the groups for presence of brain injury (OR, 0.58; 95% CI, 0.27-1.27). CONCLUSION: In children born before 32 weeks of gestation after the use of tocolytics, the prevalence of brain injury was high. No significant differences were found with respect to overall brain injury between neonates exposed to nifedipine and those exposed to atosiban. However, as this study was a secondary analysis of the APOSTEL III trial, it was underpowered for brain injury. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Parental perspectives on the awareness and delivery of preconception care.

BACKGROUND: The attention for Preconception Care (PCC) has grown substantially in recent years, yet the implementation of PCC appears challenging as uptake rates remain low. The objective of this study was to assess parental perspectives on how PCC should be provided. METHODS: Recruitment of participants took place among couples who received antenatal care at a Dutch community midwifery practice. Between June and September 2014, five focus group sessions were held with 29 women and one focus group session with 5 men. Thematic analysis was conducted using NVivo 10 software. RESULTS: Participants were generally unfamiliar with the concept of PCC. It was proposed to raise awareness by means of a promotional campaign, stipulating that PCC is suited for every couple with a (future) child wish. Suggestions were made to display marketing materials in both formal and informal (local community) settings. Addressing existing social networks and raising social dialogue was expected to be most efficient. It was recommended to make PCC more accessible by offering multiple forms and to involve male partners. Opportunistic offering PCC by healthcare providers was considered more acceptable when the subject was deliberately raised, for example while discussing contraceptives, lifestyle risks or drug prescriptions. GP's or midwifes were regarded the most suitable PCC providers, however provider characteristics such as experience, empathy and communication skills were considered more important. CONCLUSIONS: This study showed that from the parental perspective it is recommended to address every couple with a (future) child wish by means of enlarging the awareness and accessibility of PCC. In order to enlarge the awareness, it is recommended to address social networks, to raise the social dialogue and to conduct promotional campaigns regarding PCC. In order to improve the accessibility of PCC, it was suggested to simultaneously offer multiple forms: group sessions, individual consultations, walk-in-hours and online sessions, and to involve male partners.

Defining and describing birth centres in the Netherlands - a component study of the Dutch Birth Centre Study.

BACKGROUND: During the last decade, a rapid increase of birth locations for low-risk births, other than conventional obstetric units, has been seen in the Netherlands. Internationally some of such locations are called birth centres. The varying international definitions for birth centres are not directly applicable for use within the Dutch obstetric system. A standard definition for a birth centre in the Netherlands is lacking. This study aimed to develop a definition of birth centres for use in the Netherlands, to identify these centres and to describe their characteristics. METHODS: International definitions of birth centres were analysed to find common descriptions. In July 2013 the Dutch Birth Centre Questionnaire was sent to 46 selected Dutch birth locations that might qualify as birth centre. Questions included: location, reason for establishment, women served, philosophies, facilities that support physiological birth, hotel-facilities, management, environment and transfer procedures in case of referral. Birth centres were visited to confirm the findings from the Dutch Birth Centre Questionnaire and to measure distance and time in case of referral to obstetric care. RESULTS: From all 46 birth locations the questionnaires were received. Based on this information a Dutch definition of a birth centre was constructed. This definition reads: "Birth centres are midwifery-managed locations that offer care to low risk women during labour and birth. They have a homelike environment and provide facilities to support physiological birth. Community midwives take primary professional responsibility for care. In case of referral the obstetric caregiver takes over the professional responsibility of care." Of the 46 selected birth locations 23 fulfilled this definition. Three types of birth centres were distinguished based on their location in relation to the nearest obstetric unit: freestanding (n = 3), alongside (n = 14) and on-site (n = 6). Transfer in case of referral was necessary for all freestanding and alongside birth centres. Birth centres varied in their reason for establishment and their characteristics. CONCLUSIONS: Twenty-three Dutch birth centres were identified and divided into three different types based on location according to the situation in September 2013. Birth centres differed in their reason for establishment, facilities, philosophies, staffing and service delivery.

Healthcare providers' views on the delivery of preconception care in a local community setting in the Netherlands.

BACKGROUND: The attention for preconception care (PCC) has grown substantially in recent years, yet PCC is far from routine in daily practice. One of the major challenges for the implementation of PCC is to identify how it can best be organized and provided within the primary care setting. The aim of this study was to identify bottlenecks and solutions for the delivery of PCC from a healthcare providers' perspective in a local community setting in the Netherlands. METHODS: Health professionals within the region of Zeist, the Netherlands, were invited for a meeting on the local implementation of PCC. Five parallel group sessions were held with 30 participants from different disciplines. The sessions were moderated based on the Nominal Group Technique, in which bottlenecks (step 1) and solutions (step 2) for the delivery of PCC were gathered, categorized and prioritized by the participants. RESULTS: Participants expressed that the provision of PCC is challenging due to lack of awareness, the absence of a costing structure and unclear allocation of responsibilities. The most pragmatic approach considered was to make interdisciplinary arrangements within the local primary care setting. Participants recommended to 1) settle a costing structure by means of third party reimbursement, 2) improve collaboration by means of a local cooperation network and an adequate referral system, 3) invest in education, tools and logistics and 4) increase uptake rates by the routine opportunistic offer of PCC and promotional campaigns. CONCLUSIONS: From a provider's perspective a tailored approach is advocated in which interdisciplinary arrangements for collaboration and referral are set up within the local primary care setting.

Association between vascular health and ovarian ageing in type 1 diabetes mellitus.

STUDY QUESTION: Is vascular health associated with ovarian reserve status using type 1 diabetes mellitus (DM-1) as a model for vascular compromise? SUMMARY ANSWER: No conclusive evidence for an association between vascular health and ovarian ageing was found in women with DM-1. WHAT IS KNOWN ALREADY: The mechanism behind advanced ovarian ageing has not yet been elucidated. We hypothesize that vascular impairment precedes ovarian ageing. DM-1 is hallmarked by premature vascular complications that may consequently play a role in the rate of primordial follicle decline. STUDY DESIGN, SIZE, DURATION: A cross-sectional, patient-control study was performed in 150 premenopausal, regular cycling women with DM-1, as well as a reference population of 177 healthy, fertile women. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a single-study visit, an inventory of both ovarian reserve and vascular status was carried out in the DM-1 group. A transvaginal ultrasound to calculate the antral follicle count (AFC) and blood sampling for anti-Müllerian hormone (AMH), lipids, C-reactive protein and HbA1c measurements were performed. Furthermore, vascular screening including measurements of blood pressure, flow-mediated dilation, peripheral arterial tonometry, pulse wave velocity, pulse wave analysis and intima-media thickness was carried out. The relative decrease in serum AMH levels in women with DM-1 compared with healthy references was investigated. MAIN RESULTS AND THE ROLE OF CHANCE: Systolic blood pressure was negatively correlated with both serum AMH (P= 0.006) and AFC (P= 0.004) in the DM-1 group. A non-linear relationship between HDL-cholesterol and serum AMH was found (P= 0.0001). No associations were detected between other vascular risk factors or vascular function tests and serum AMH or AFC in women with DM-1. With regard to the comparison of AMH levels between women with and without DM-1, mean AMH levels were 2.5 ± 1.9 ng/ml and 3.0 ± 2.8 ng/ml, respectively. After adjustment for confounders the difference in AMH levels between both groups appeared non-significant (fold change: 0.92, 95% confidence interval: 0.68-1.23). LIMITATIONS, REASON FOR CAUTION: The use of different AMH assays and the cross-sectional design may limit the interpretation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The lack of evident association between vascular health and ovarian ageing may be the result of an insufficient vascular compromise in the relatively young, DM-1 group. STUDY FUNDING/COMPETING INTERESTS: No external funding was received for conducting or publishing this study. F.Y., W.S., A.F., F.L.J.V., M.J.C.E. and H.W.d.V. have nothing to disclose. F.J.M.B. has received fees and grant support from the following companies: Ferring, Gedeon Richter, Merck Serono, Medical Specialties Distributors and Roche. TRIAL REGISTRATION NUMBER: Not applicable.

Maintenance tocolysis with nifedipine in threatened preterm labour: 2-year follow up of the offspring in the APOSTEL II trial.

OBJECTIVE: To evaluate long-term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant. DESIGN, SETTING AND POPULATION: Follow up of infants of women who participated in a multicentre randomised controlled trial on maintenance tocolysis with nifedipine versus placebo. METHODS: Two years after the APOSTEL II trial on maintenance tocolysis with nifedipine versus placebo, we asked participants to complete the Ages and Stages Questionnaire. MAIN OUTCOME MEASURES: Infant development was measured in five domains. Developmental delay was defined as a score of ≤1 SD in one or more developmental domains. We performed exploratory subgroup analysis in women with preterm prolonged rupture of the membranes, and in women with a cervical length <10 mm at study entry. RESULTS: Of the 276 women eligible for follow up, 135 (52.5%) returned the questionnaire, encompassing data of 170 infants. At 2 years of age, infants of women with nifedipine maintenance tocolysis compared with placebo had a higher overall incidence of fine motor problems (22.2 versus 7.6%, OR 3.43, 95% CI 1.29-9.14, P = 0.01), and a lower incidence of poor problem-solving (21.1 versus 29.1%, OR 0.27, 95% CI 0.08-0.95, P = 0.04). CONCLUSIONS: This follow-up study revealed no clear benefit of nifedipine maintenance tocolysis at 2 years of age. As short-term adverse perinatal outcome was not reduced in the original APOSTEL II trial, we conclude that maintenance tocolysis does not appear to be beneficial at this time. TWEETABLE ABSTRACT: No clear benefit of nifedipine maintenance tocolysis in preterm labour on 2-year infant outcome.

Prevention of Hypertensive Disorders of Pregnancy: a Novel Application of the Polypill Concept.

Nearly all of the annual 287,000 global maternal deaths are preventable. Hypertensive disorders of pregnancy (HDP) are among the major causes. A novel fixed-dose combination pill or polypill to prevent cardiovascular disease is a promising strategy for prevention of HDP. The aim of this study was to identify eligible candidates for a polypill for the prevention of HDP. A comprehensive review of systematic reviews on drug and dietary interventions to prevent HDP was conducted. Interventions were evaluated based on efficacy, dose, route of administration, and side effects. Fourteen interventions were assessed. Low-dose aspirin and calcium were identified as candidates for a polypill, with risk reduction estimations for pregnancy-induced hypertension and preeclampsia ranging between 10 and 62 %, depending on patient population characteristics including a priori risk, and gestation age at start of intervention. Their effect may be augmented through the addition of vitamin D, vitamin B12, and folic acid. The effect and optimal composition needs to be evaluated in future trials. Given the persistent burden of maternal and perinatal mortality associated with HDP, prevention of these disorders is key-especially in low-resource settings. The polypill approach with a combination of aspirin, calcium, vitamin D, vitamin B12, and folic acid is a promising strategy to improve maternal and perinatal health outcomes.

Age at menopause in women with type 1 diabetes mellitus: the OVADIA study.

STUDY QUESTION: Is type 1 diabetes a determinant of advanced ovarian ageing, resulting in an early age at natural menopause? SUMMARY ANSWER: No clear evidence was provided that type 1 diabetes is a determinant of accelerated ovarian ageing resulting in an early menopause. WHAT IS KNOWN ALREADY: The association between type 1 diabetes and early menopause has been examined previously with inconsistent results. STUDY DESIGN, SIZE, DURATION: A cross-sectional study was performed in 140 post-menopausal women with, and 5426 post-menopausal women without, diabetes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Both women with and without diabetes had experienced natural menopause. Study participants filled out a standardized questionnaire including report of their age at last menstrual period. Differences in menopausal age were analysed using linear regression analyses, with adjustment for possible confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at natural menopause was 49.8 ± 4.7 years in women with type 1 diabetes and 49.8 ± 4.1 in women without diabetes. Linear regression analyses showed that type 1 diabetes was not associated with an earlier menopause compared with the reference group without diabetes, after adjustment for age, smoking history and parity (difference in age at menopause between women with type 1 diabetes and reference group 0.34 years, 95% confidence interval -0.34, 1.01). LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. We had no information regarding microvascular complications therefore a possible association between vascular health and menopausal age could not be investigated. WIDER IMPLICATIONS OF THE FINDINGS: It has been hypothesized that the possible mechanism behind an accelerated ovarian ageing process in type 1 diabetes is prolonged poor glycaemic control and subsequent effects on vascular health. The improved glycaemic control during the last decades may have prevented vascular damage from occurring to an extent that would affect organ function. Nevertheless, the present findings are reassuring for reproductive health prospects in women with type 1 diabetes.

Human fetal growth is constrained below optimal for perinatal survival.

OBJECTIVE: The use of fetal growth charts assumes that the optimal size at birth is at the 50(th) birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery. METHODS: Data from over 1 million births occurring at 28-43 weeks' gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied. RESULTS: In the 1 170 534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3(rd) centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80(th) and 84(th) centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90(th) and 95(th) centiles. Data were almost identical when the analysis was restricted to infants born at ≥ 37 weeks' gestation. CONCLUSION: From an immediate survival perspective, optimal fetal growth requires a birth weight between the 80(th) and 84(th) centiles for the population. Median birth weight in the population is, by definition, substantially lower than these centiles, implying that the majority of fetuses exhibit some form of maternal constraint on growth. This finding is consistent with adaptations that have evolved in humans in conjunction with a large head and bipedalism, to reduce the risk of obstructed delivery. These data also fit remarkably well with those on long-term adult cardiovascular and metabolic health risks, which are lowest in cases with a birth weight around the 90(th) centile.