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OBJECTIVES:The COVID-19 pandemic and associated lockdowns disrupted health care worldwide. High-income countries observed a decrease in preterm births during lockdowns, but maternal pregnancy-related outcomes were also likely affected. This study investigates the effect of the first COVID-19 lockdown (March-June 2020) on provision of maternity care and maternal pregnancy-related outcomes in the Netherlands.STUDY DESIGN: National quasi-experimental study.METHODS: Multiple linked national registries were used, and all births from a gestational age of 24+0 weeks in 2010-2020 were included. In births starting in midwife-led primary care, we assessed the effect of lockdown on provision of care. In the general pregnant population, the impact on characteristics of labour and maternal morbidity was assessed. A difference-in-regression-discontinuity design was used to derive causal estimates for the year 2020.RESULTS: A total of 1,039,728 births were included. During the lockdown, births to women who started labour in midwife-led primary care (49%) more often ended at home (27% pre-lockdown, +10% [95% confidence interval: +7%, +13%]). A small decrease was seen in referrals towards obstetrician-led care during labour (46%, -3% [-5%,-0%]). In the overall group, no significant change was seen in induction of labour (27%, +1% [-1%, +3%]). We found no significant changes in the incidence of emergency caesarean section (9%, -1% [-2%, +0%]), obstetric anal sphincter injury (2%, +0% [-0%, +1%]), episiotomy (21%, -0% [-2%, +1%]), or post-partum haemorrhage: >1000 ml (6%, -0% [-1%, +1%]).CONCLUSIONS: During the first COVID-19 lockdown in the Netherlands, a substantial increase in homebirths was seen. There was no evidence for changed available maternal outcomes, suggesting that a maternity care system with a strong midwife-led primary care system may flexibly and safely adapt to ext

Introduction: Despite a noticeable trend of delayed fatherhood, less is known about the impact of paternal age on the paternally programmed placenta. We hypothesize that paternal aging affects seminal quality and as such induces ageing-related epigenetic alterations that influence placental growth. Our main aim is to investigate associations between paternal age and first trimester (vascular) placental growth trajectories. Methods: Pregnant women were enrolled before 10 weeks of gestation in the Rotterdam Periconceptional Cohort (Predict study). Placental volumes (PV) and utero-placental vascular volumes (uPVV) were measured at 7, 9, and 11 weeks gestation. Associations between paternal age and PV and uPVV were investigated using linear mixed models and the maximum likelihood ratio test to test non-linear relationships. We adjusted for gestational age, fetal sex, parental smoking and maternal age, BMI, education and parity, and stratified for conception mode. Results: From 808 pregnancies we obtained 1313 PV and from 183 pregnancies 345 uPVV measurements. We show no associations between paternal age and PV (p = 0.934) and uPVV (p = 0.489) in our total population or in pregnancies conceived naturally (PV p = 0.166; uPVV p = 0.446) and after IVF/ICSI (PV p = 0.909; uPVV p = 0.749). For example, PV was 0.9% smaller (95% CI -5.7%—7.1%) in fathers aged 40 compared to 30 years old at 9 weeks gestation in the total study population. Discussion: We are not demonstrating a significant impact of paternal age on first trimester placental growth in a tertiary care population. Given the trend of increasing paternal age, our study should be repeated in the general population.

Epigenetic modifications, including DNA methylation, are proposed mechanisms explaining the impact of parental exposures to foetal development and lifelong health. Micronutrients including folate, choline, and vitamin B12 provide methyl groups for the one-carbon metabolism and subsequent DNA methylation processes. Placental DNA methylation changes in response to one-carbon moieties hold potential targets to improve obstetrical care. We conducted a systematic review on the associations between one-carbon metabolism and human placental DNA methylation. We included 22 studies. Findings from clinical studies with minimal ErasmusAGE quality score 5/10 (n = 15) and in vitro studies (n = 3) are summarized for different one-carbon moieties. Next, results are discussed per study approach: (1) global DNA methylation (n = 9), (2) genome-wide analyses (n = 4), and (3) gene specific (n = 14). Generally, one-carbon moieties were not associated with global methylation, although conflicting outcomes were reported specifically for choline. Using genome-wide approaches, few differentially methylated sites associated with S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), or dietary patterns. Most studies taking a gene-specific approach indicated site-specific relationships depending on studied moiety and genomic region, specifically in genes involved in growth and development including LEP, NR3C1, CRH, and PlGF; however, overlap between studies was low. Therefore, we recommend to further investigate the impact of an optimized one-carbon metabolism on DNA methylation and lifelong health.

Item does not contain fulltext, The COVID-19 pandemic had a major psychological impact on society, particularly affecting its vulnerable members including pregnant women and their (un)born children. Moreover, accumulating evidence indicates that maternal stress can have lifelong effects on the unborn child. Accordingly, pregnant women's vulnerability for mental health problems has become a concern during the COVID-19 pandemic. This chapter highlights the psychological impact of the COVID-19 pandemic on pregnant women and the potential short- and long-term consequences for their offspring. An overview is provided of the effects of prenatal maternal stress caused by previous disasters. Moreover, potential mechanisms are discussed of fetal programming and transgenerational effects of maternal prenatal stress. We conclude that the lessons learned from experiences with previous disasters should quickly be applied to the current COVID-19 pandemic. Close monitoring of offspring after prenatal stress due to the COVID-19 pandemic is necessary to detect and effectively target vulnerable developmental windows and divert adverse outcomes later during the life course.

Purpose: To assess experienced stress on different aspects of life and evaluate patient preferences for the consultation of periconception blended lifestyle care, combining face-to-face counseling with eHealth, during the COVID-19 pandemic among (pre)pregnant women. Using this two-fold aim, we were able to analyze the levels of stress among (pre)pregnant women during the COVID-19 pandemic, and to study whether their preferences for the consultation modality of periconception blended lifestyle care was influenced by the levels of stress. Methods: A quantitative survey among (pre)pregnant women who received blended periconception lifestyle care between March 2020 and December 2021, from the first until the fourth COVID-19 wave in the Netherlands. The questionnaire used a 5-point Likert scale and measured experienced stress and preferred periconception blended lifestyle care modality. Results: 984 women (response rate: 55.2%) filled out the questionnaire. Experienced stress during the COVID-19 pandemic was relatively low and stable over time. The highest percentage of respondents (31.2%) reported to have experienced stress on fertility and pregnancy. 40.4% (309/764) of the respondents indicated that face-to-face consultations could be replaced by digital consultation. Additionally, the mean experienced stress did not differ between the patients who preferred a video consultation (2.60 ± 1.1), or a telephone consultation (2.57 ± 1.2), either a video or telephone consultation (2.54 ± 1.3), still preferred a face-to-face consultation (2.41 ± 1.4) (p =.83). Conclusions: Our findings indicate willingness for wide implementation of telemedicine within health care delivery, and reorganizing of periconception blended lifestyle care toward personalized and value-based health care.

Contains fulltext : 249260.pdf (Publisher’s version ) (Open Access), The COVID-19 pandemic has a major impact on society, particularly affecting its vulnerable members, including pregnant women and their unborn children. Pregnant mothers reported fear of infection, fear of vertical transmission, fear of poor birth and child outcomes, social isolation, uncertainty about their partner’s presence during medical appointments and delivery, increased domestic abuse, and other collateral damage, including vaccine hesitancy. Accordingly, pregnant women's known vulnerability for mental health problems has become a concern during the COVID-19 pandemic, also because of the known effects of prenatal stress for the unborn child. The current narrative review provides a historical overview of transgenerational effects of exposure to disasters during pregnancy, and the role of maternal prenatal stress. We place these effects into the perspective of the COVID-19 pandemic. Hereby, we aim to draw attention to the psychological impact of the COVID-19 pandemic on women of reproductive age (15-49 year) and its potential associated short-term and long-term consequences for the health of children who are conceived, carried, and born during this pandemic. Timely detection and intervention during the first 1000 days is essential to reduce the burden of transgenerational effects of the COVID-19 pandemic.

Preconception folic acid supplement use is a well-known method of primary prevention of neural tube defects (NTDs). Obese women are at a higher risk for having a child with a NTD. As different international recommendations on folic acid supplement use for obese women before and during pregnancy exist, this narrative review provides an overview of epidemiology of folate deficiency in obese (pre)pregnant women, elaborates on potential mechanisms underlying folate deficiency, and discusses considerations for the usage of higher doses of folic acid supplements. Women with obesity more often suffer from an absolute folate deficiency, as they are less compliant to periconceptional folic acid supplement use recommendations. In addition, their dietary folate intake is limited due to an unbalanced diet (relative malnutrition). The association of obesity and NTDs also seems to be independent of folate intake, with studies suggesting an increased need of folate (relative deficiency) due to derangements involved in other pathways. The relative folate deficiency, as a result of an increased metabolic need for folate in obese women, can be due to: (1) low-grade chronic inflammation (2) insulin resistance, (3) inositol, and (4) dysbiotic gut microbiome, which plays a role in folate production and uptake. In all these pathways, the folate-dependent one-carbon metabolism is involved. In conclusion, scientific evidence of the involvement of several folate-related pathways implies to increase the recommended folic acid supplementation in obese women. However, the physiological uptake of synthetic folic acid is limited and side-effects of unmetabolized folic acid in mothers and offspring, in particular variations in epigenetic (re)programming with long-term health effects, cannot be excluded. Therefore, we emphasize on the urgent need for further research and preconception personalized counseling on folate status

Background: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Poor lifestyle behaviors impact (pre)pregnant women by affecting pregnancy outcomes and offspring health. This systematic review provides an overview of psychological therapies to support lifestyle behavior changes among (pre)pregnant women. Scientific databases were searched from their inception to 20 December 2020 for studies investigating the effects of psychological therapies on improvements in lifestyle behaviors. Studies were eligible if they included (pre)pregnant women, examined the effects of a psychological therapy on at least one lifestyle behavior and used a control group receiving usual pregnancy care or a non-psychological intervention. Lifestyle behaviors of interest were dietary intake, physical activity, smoking, alcohol consumption, drug use, body weight loss and body weight gain during pregnancy. Pregnancy complications were included as outcome measures. Motivational interviewing (MI) (n = 21), cognitive behavioral therapy (CBT) (n = 8), incentive-based contingency management (IBCM) (n = 9), mindfulness (n = 1) and hypnosis (n = 1) were investigated as lifestyle behavior interventions. The findings revealed that MI was effective in reducing (self-reported) smoking and alcohol consumption and restricting gestational weight gain (GWG). CBT was only studied as an intervention to restrict GWG and the results predominantly confirmed its effectiveness. IBCM showed the strongest effect on reducing smoking and substance use. The studies using hypnosis or mindfulness to reduce smoking or restrict GWG, respectively, showed no associations. The use of psychological therapies to improve lifestyle behaviors among (pre)pregnant women is new and the scientific proof is promising. Before wide implementation is legitimated, more evidence is needed on the consequences of lifestyle change for pregnancy outcomes.

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.

Background Preterm birth is the leading cause of child mortality globally, with many survivors experiencing long-term adverse consequences. Preliminary evidence suggests that numbers of preterm births greatly reduced following implementation of policy measures aimed at mitigating the effects of the COVID-19 pandemic. We aimed to study the impact of the COVID-19 mitigation measures implemented in the Netherlands in a stepwise fashion on March 9, March 15, and March 23, 2020, on the incidence of preterm birth. Methods We used a national quasi-experimental difference-in-regression-discontinuity approach. We used data from the

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis.

This case illustrates the importance of multidisciplinary counselling and management of pregnancies in women with complex medical conditions, especially concerning women with cognitive impairment. We present a woman with hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This syndrome is characterised by recurrent episodes of hypoglycaemia and elevated ammonia levels, which are potentially harmful to both the patient and a developing fetus. We describe a successful multidisciplinary approach during the pregnancy of a mentally challenged patient with HI/HA syndrome. This case illustrates the importance of personalised counselling during the preconception period and emphasises to include all disciplines involved in the medical and daily care of such a patient. In our case, the extensive multidisciplinary care during the preconception period, pregnancy, delivery and postpartum period resulted in a good maternal and neonatal outcome.

We present a case of a 38+1 weeks pregnant patient (G1P0) with a proven COVID-19 infection, who was planned for induction of labour because of pre-existent hypertension, systemic lupus erythematosus, respiratory problem of coughing and mild dyspnoea without fever during the COVID-19 pandemic in March 2020. To estimate the risk of vertical transmission of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) during labour and delivery, we collected oropharyngeal, vaginal, urinary, placental and neonatal PCRs for SARSCoV-2 during the period of admission. All PCRs, except for the oropharyngeal, were negative and vertical transmission was not observed. Labour and delivery were uncomplicated and the patient and neonate were discharged the next day. We give a short overview of the known literature about SARS-CoV-2-related infection during pregnancy, delivery and outcome of the neonate.

Scope: The effectiveness of maternal folate in reducing the risk of congenital malformations during pregnancy is well established. However, the role of the paternal folate status is scarcely investigated. The aim of this study is to investigate the evidence of associations between the paternal folate status and sperm quality, sperm epigenome, and pregnancy outcomes. Methods and results: Databases are searched up to December 2017 resulting in 3682 articles, of which 23 are retrieved for full-text assessment. Four out of thirteen human and two out of four animal studies show positive associations between folate concentrations and sperm parameters. An additional meta-analysis of four randomized controlled trials in subfertile men shows that the sperm concentration increases (3.54 95% confidence interval (CI) [−1.40 to 8.48]) after 3–6 months of 5 mg folic acid use per day compared to controls. Moreover, two out of two animal and one out of three human studies show significant alterations in the overall methylation of the sperm epigenome. One animal and one human study show associations between low folate intake and an increased risk of congenital malformations. Conclusions: This systematic review and meta-analysis shows evidence of associations between paternal folate status and sperm quality, fertility, congenital malformations, and placental weight.

Radboud University, 31 januari 2019, Promotores : Heskes, T.M., Desain, P.W.M., Gerven, M.A.J. van, Contains fulltext : 200811.pdf (publisher's version ) (Open Access)

Background: The phosphodiesterase-5 inhibitor (PDE5) sildenafil has emerged as a promising treatment for preeclampsia (PE). However, a sildenafil trial was recently halted due to lack of effect and increased neonatal morbidity. Methods: Ex vivo dual-sided perfusion of an isolated cotyledon and wire-myography on chorionic plate arteries were performed to study the effects of sildenafil and the non-selective PDE inhibitor vinpocetine on the response to the NO donor sodium nitroprusside (SNP) under healthy and PE conditions. Ex vivo perfusion was also used to study placental transfer of sildenafil in 6 healthy and 2 PE placentas. Furthermore, placental mRNA and protein levels of eNOS, iNOS, PDE5 and PDE1 were quantified. Findings: Sildenafil and vinpocetine significantly enhanced SNP responses in chorionic plate arteries of healthy, but not PE placentas. Only sildenafil acutely decreased baseline tension in arteries of both healthy and PE placentas. At steady state, the foetal-to-maternal transfer ratio of sildenafil was 0·37 ± 0·03 in healthy placentas versus 0·66 and 0·47 in the 2 PE placentas. mRNA and protein levels of PDE5, eNOS and iNOS were