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Background Objectives Methods Results Conclusion We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64.Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately.We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944–1945 Dutch famine. We compared overall and cause‐specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression.In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups.This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does preconceptional exposure to oil-based iodinated contrast media during hysterosalpingography (HSG) impact children's neurodevelopment compared with exposure to water-based alternatives? SUMMARY ANSWER Our study found no large-sized effects for neurodevelopment in children with preconceptional exposure to oil-based iodinated contrast media during HSG compared with water-based alternatives. WHAT IS KNOWN ALREADY HSG is widely used as a diagnostic tool in the female fertility work-up. Tubal flushing with oil-based iodinated contrast has been shown to enhance fertility outcomes in couples with unexplained infertility, increasing the chances of pregnancy and live birth compared with water-based alternatives. However, oil-based contrast contains higher doses of iodine and has a longer half-life, and concerns exist that iodinated contrast media can affect women's iodine status and cause temporary (sub)clinical hypothyroidism in mothers and/or foetuses. Considering that thyroid hormones are vital to embryonal and foetal brain development, oil-based contrast media use could increase the risk of impaired neurodevelopment in children conceived shortly after HSG. Here we examine neurodevelopmental outcomes in school-aged children conceived after HSG. STUDY DESIGN, SIZE, DURATION This is a long-term follow-up of the H2Oil trial in which oil-based or water-based contrast was used during HSG (Netherlands; 2012–2014; NTR3270). Of 369 children born <6 months after HSG in the study, we contacted the mothers of 140 children who gave consent to be contacted for follow-up. The follow-up study took place from January to July 2022 (NCT05168228). PARTICIPANTS/MATERIALS, SETTINGS, METHODS The study included 69 children aged 6–9 years who were conceived after HSG with oil-based (n = 42) or water-based contrast (n = 27). The assessments targeted intelligence (Wechsler Intelligence Scale for Children), neurocognitive outcomes (computerized neurocognitive tests), behavioural functioning (parent and teacher questionnaires), and academic performance. Linear regression models, adjusted for age, sex, and parental educational attainment were employed to compare groups. MAIN RESULTS AND THE ROLE OF CHANCE School-aged children born to mothers after oil-based contrast HSG did not significantly differ from children born to mothers after water-based contrast HSG, in regards to intelligence, neurocognitive functioning, behavioural functioning, or academic performance, with the exception of better performance for visuomotor integration functions in children exposed to oil-based contrast preconception. After exploratory correction for multiple comparisons, none of the group differences was statistically significant. LIMITATIONS, REASONS FOR CAUTION The small sample size of this follow-up study limited statistical power. This study provides evidence for the absence of large-sized differences between preconceptional exposure to the two contrast media types but does not rule out more subtle effects on neurodevelopment compared to naturally conceived children without preconceptional exposure to HSG. WIDER IMPLICATIONS OF THE FINDINGS This study contributes to our knowledge about the long-term effects of different types of iodinated contrast media used in fertility work-up, indicating that choosing oil-based over water-based iodinated contrast media is unlikely to have major effect on the long-term neurodevelopmental outcomes of children conceived shortly after HSG. However, further research should focus on the overall safety of iodine exposure during HSG, comparing children conceived after HSG to those conceived naturally as both types of contrast contain high amounts of iodine. STUDY FUNDING/COMPETING INTEREST(S) The original H2Oil randomized controlled trial was an investigator-initiated study that was funded by the two academic hospitals now merged into the Amsterdam University Medical Centre. The current follow-up study (Neuro-H2Oil) is funded through a research grant awarded to the authors by the Amsterdam Reproduction & Development (AR&D) research institute. S.K. is funded by a AMC MD/PhD Scholarship from the Amsterdam UMC. S.K. reports holding voluntary roles in the civil society organizations Universities Allied for Essential Medicines and People's Health Movement. V.M. reports receiving travel and speaker fees as well as research grants from Guerbet, Merck and Ferring. K.D. reports receiving travel and speaker fees as well as research grants from Guerbet. BWM is supported by a NHMRC Investigator grant (GNT1176437) and reports consultancy, travel support and research funding from Merck, consultancy for Organon and Norgine, and holding stock from ObsEva. The other authors report no conflict of interest. TRIAL REGISTRATION NUMBER NCT05168228 [ABSTRACT FROM AUTHOR]

Accumulating studies suggest that prenatal experiences can shape a child's neurodevelopment. Malnutrition and depression occur in pregnancy relatively often and may affect child neurodevelopment independently as well as synergistically. We aimed to provide an overview of recent studies that have examined malnutrition and (or) depression in pregnancy and associations with child behavioural problems and cognitive function. We conducted a literature search in PubMed, using the following main search terms: 'depression', 'nutrition', 'BMI', 'pregnancy', 'offspring', 'cognition', and 'behaviour'. We included studies in human populations published from 2013 onwards. The literature search yielded 1531 articles, of which 55 were included in the current review. We presented the evidence on the associations between prenatal markers of nutritional status and (or) depression and child behaviour and (or) cognitive function. We additionally discussed interventions and mechanisms. Both malnutrition and depression in pregnancy are associated with increased externalizing behavioural problems and attentional deficits, and to some extent with poorer cognitive function in the child, but the evidence is not conclusive. Studies on synergistic effects of both factors on child behaviour and cognitive function are still scarce, and more research is needed. Potential shared mechanisms include the hypothalamic-pituitary-adrenal axis, the immune system, epigenetics, and oxidative stress. Key words: prenatal programming, malnutrition, depression, pregnancy, cognition, behaviour, mechanisms. Un nombre croissant d'etudes laissent entrevoir que les experiences prenatales peuvent faconner le developpement neurologique chez l'enfant. La malnutrition et la depression surviennent relativement frequemment pendant la grossesse, et elles pourraient affecter le developpement neurologique de l'enfant de maniere independante ainsi que synergique. Nous visions a fournir un apercu des etudes recentes qui ont examine la malnutrition ou la depression pendant la grossesse, ainsi que les associations avec les problemes de comportement et les fonctions cognitives chez l'enfant. Nous avons mene une recherche de litterature dans PubMed avec les principaux termes de recherche suivants : << depression >>, << alimentation >>, << IMC >>, << grossesse >>, << progeniture >>, << fonctions cognitives >> et << comportement >>. Nous avons inclus des etudes publiees menees aupres de populations humaines a partir de 2013. La recherche de litterature a fourni 1531 articles, et nous en avons inclus 55 dans le present article de synthese. Nous avons presente les donnees portant sur les associations entre des marqueurs prenataux de l'etat nutritionnel ou de la depression et le comportement ou les fonctions cognitives chez l'enfant. Nous avons aussi discute des interventions et des modes d'action. Pendant la grossesse, la malnutrition et la depression sont toutes deux associees avec une augmentation de l'exteriorisation des problemes comportementaux et de deficit de l'attention, et jusqu'a un certain point avec de moins bonnes fonctions cognitives chez l'enfant, mais les donnees observees ne sont pas concluantes. Les etudes portant sur les effets synergiques des deux facteurs sur le comportement et les fonctions cognitives de l'enfant sont toujours peu nombreuses, et plus de recherches sont necessaires. Parmi les modes d'action pouvant etre communs, on compte l'axe hypothalamohypophyso-surrenalien, le systeme immunitaire et le stress oxydatif. [Traduit par la Redaction] Mots-cles : programmation prenatale, malnutrition, depression, grossesse, fonctions cognitives, comportement, modes d'action., Introduction The fetal brain is plastic--it is able to adapt to its environment. This neurodevelopmental plasticity allows for learning and shaping of the brain, and acts by adjusting physiological processes [...]

Background: Given the estimated high rate of unintended pregnancies, it is important to investigate long-term effects on psychological distress in women carrying an unintended pregnancy to term. However, research into associations between unintended pregnancies carried to term and psychological distress postpartum is mixed, and especially, evidence on long-term associations is scarce. Objective: To examine whether carrying an unintended pregnancy to term is associated with maternal psychological distress later in life, up to 12 years postpartum. Design: This study is based on the population-based birth cohort study 'Amsterdam Born Children and their Development' study, which included pregnant people in 2003 (n = 7784) and followed them up until 12 years postpartum. Methods: Unintended pregnancy was measured as a multidimensional construct, based on self-reported data around 16 weeks gestation on pregnancy mistiming, unwantedness and unhappiness. Symptoms of maternal psychological distress were assessed around 3 months, 5 years and 12 years postpartum using multiple questionnaires measuring symptoms of depression, anxiety and stress. Multiple structural equation modelling models were analysed, examining the associations between dimensions of unintended pregnancy and maternal psychological distress per time point, while controlling for important co-occurring risks. Results: Pregnancy mistiming and unhappiness were significant predictors of more maternal psychological distress around 3 months postpartum. Around 5 years postpartum, only pregnancy mistiming was positively associated with maternal psychological distress. Dimensions of unintended pregnancy were no longer associated with maternal psychological distress around 12 years postpartum. Strikingly, antenatal psychological distress was a much stronger predictor of maternal psychological distress than pregnancy intention dimensions. Conclusion: Those who carried a more unintended pregnancy to term reported more symptoms of psychological distress at 3 months and 5 years postpartum. People carrying an unintended pregnancy to term may benefit from extra support, not because of the pregnancy intentions per se, but because they may be related to antenatal psychological distress. Plain Language Summary: Carrying an unintended pregnancy to term and maternal psychological distress over time Every unintended pregnancy is different, like every person is different. Nevertheless, carrying an unintended pregnancy to term might be stressful, that might impact mental health (e.g. depression or anxiety) of people carrying an unintended pregnancy to term. Research into long-term effects of carrying an unintended pregnancy to term on maternal mental health is scarce. In this study, we investigated effects of carrying an unintended pregnancy to term on maternal mental health up to 12 years postpartum. We used data from 7784 pregnant people living in Amsterdam, who participated in the Amsterdam Born Children and their Development (ABCD) study in 2003. Participants were followed up to 12 years postpartum. During pregnancy, participants answered questions about pregnancy mistiming (did the pregnancy happen at the right time), unwantedness (did they want to become pregnant) and unhappiness (how did they feel when they found out they were pregnant). We investigated these 'dimensions' of unintended pregnancy separately, to grasp to complexity of unintended pregnancy. Furthermore, participants answered multiple questions about experienced symptoms of depressions and anxiety around 3 months, 5 years and 12 years postpartum. People, who reported that their pregnancy was more mistimed, reported more mental health problems up to 5 years postpartum. Furthermore, people who reported more unhappiness with their pregnancy, reported more mental health problems around 3 months postpartum. People with an unintended pregnancy reported no longer more mental health problems around 12 years after birth, compared to people with more intended pregnancy. Strikingly, the mental health of people during pregnancy was more important for their mental health later in life, compared to their unintended pregnancy. Thus, the (emotional) circumstances around the pregnancy might be more influential for mental health later in life, compared to their pregnancy intentions. People carrying an unintended pregnancy to term may benefit from extra support, tailored to their individual needs and circumstances. Nevertheless, our results also showed that people are also resilient to deal with the many events and challenges faced during the periods after birth, since the effect of unintended pregnancy on maternal mental health disappeared over time. [ABSTRACT FROM AUTHOR]

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STUDY QUESTION Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen–thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population? SUMMARY ANSWER After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI. WHAT IS KNOWN ALREADY There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF. STUDY DESIGN, SIZE, DURATION A nationwide historical cohort study with prospective follow-up was carried out, including all live-born offspring from women treated with ART between 1983 and 2011 and subfertile women not treated with ART in one of the 13 Dutch IVF clinics and two fertility centers. PARTICIPANTS/MATERIALS, SETTING, METHODS Children were identified through the mothers' records in the Personal Records Database. Information on the conception method of each child was collected through the mother's medical record. In total, the cohort comprises 89 249 live-born children of subfertile couples, of whom 51 417 were conceived using ART and 37 832 were not (i.e. conceived naturally, through ovulation induction, or after IUI). Cancer incidence was ascertained through linkage with the Netherlands Cancer Registry for the period 1989–2019. Cancer risk in children conceived using ART was compared with risk in children born to subfertile couples but not conceived by ART (hazard ratio (HR)) and children from the general population (standardized incidence ratios (SIRs)). MAIN RESULTS AND THE ROLE OF CHANCE In total, 358 cancers were observed after a median follow-up of 18 years. Overall cancer risk was not increased in children conceived using ART, when compared with the general population (SIR = 0.96, 95% CI = 0.81–1.12) or with children from subfertile couples not conceived by ART (HR = 1.06, 95% CI = 0.84–1.33). Compared with children from subfertile couples not conceived by ART, the use of IVF or FET was not associated with increased cancer risk, but ICSI was associated with a slight risk increase (HR = 1.58, 95% CI = 1.08–2.31). Risk of cancer after ART did not increase at older ages (≥18 years, HR = 1.26, 95% CI = 0.88–1.81) compared to cancer risk in children not conceived by ART. LIMITATIONS, REASONS FOR CAUTION The observed increased risk among children conceived using ICSI must be interpreted with caution owing to the small number of cases. WIDER IMPLICATIONS OF THE FINDINGS After a median follow-up of 18 years, children conceived using ART do not have an increased overall cancer risk. Many large studies with prolonged follow-up are needed to investigate cancer risk in (young) adults conceived by different types of ART. In addition, international pooling of studies is recommended to provide sufficient power to study risk of specific cancer sites after ART. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by The Dutch Cancer Society (NKI 2006-3631) that funded the OMEGA-women's cohort, Children Cancer Free (KIKA; 147) that funded the OMEGA-I–II offspring cohort. The OMEGA-III offspring cohort was supported by a Postdoc Stipend of Amsterdam Reproduction & Development, and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Number R01HD088393. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks' gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3-10.6, p [less than or equal to] 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0-64.6, p [less than or equal to] 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56-1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58-1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference -1.2 Kg, 95% CI -2.2 to -0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53-0.84, I.sup.2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study's limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes. Trial registration ClinicalTrials.gov NCT02218931., Author(s): Bassel H. Al Wattar 1,2, Julie Dodds 1, Anna Placzek 1, Lee Beresford 3, Eleni Spyreli 1, Amanda Moore 4, Francisco J. Gonzalez Carreras 1, Frances Austin 5, Nilaani [...]

BACKGROUND Since the birth of the first baby using IVF technology in 1978, over 10 million children have been conceived via ART. Although most aspects of ARTs were developed in animal models, the introduction of these technologies into clinical practice was performed without comprehensive assessment of their long-term safety. The monitoring of these technologies over time has revealed differences in the physiology of babies produced using ARTs, yet due to the pathology of those presenting for treatment, it is challenging to separate the cause of infertility from the effect of treatments offered. The use of systematic review and meta-analysis to investigate the impacts of the predominant ART interventions used clinically in human populations on animals produced in healthy fertile populations offers an alternative approach to understanding the long-term safety of reproductive technologies. OBJECTIVE AND RATIONALE This systematic review and meta-analysis aimed to examine the evidence available from animal studies on physiological outcomes in the offspring conceived after IVF, IVM or ICSI, compared to in vivo fertilization, and to provide an overview on the landscape of research in this area. SEARCH METHODS PubMed, Embase and Commonwealth Agricultural Bureaux (CAB) Abstracts were searched for relevant studies published until 27 August 2021. Search terms relating to assisted reproductive technology, postnatal outcomes and mammalian animal models were used. Studies that compared postnatal outcomes between in vitro -conceived (IVF, ICSI or IVM) and in vivo -conceived mammalian animal models were included. In vivo conception included mating, artificial insemination, or either of these followed by embryo transfer to a recipient animal with or without in vitro culture. Outcomes included birth weight, gestation length, cardiovascular, metabolic and behavioural characteristics and lifespan. OUTCOMES A total of 61 studies in five different species (bovine, equine, murine, ovine and non-human primate) met the inclusion criteria. The bovine model was the most frequently used in IVM studies (32/40), while the murine model was mostly used in IVF (17/20) and ICSI (6/8) investigations. Despite considerable heterogeneity, these studies suggest that the use of IVF or maturation results in offspring with higher birthweights and a longer length of gestation, with most of this evidence coming from studies in cattle. These techniques may also impair glucose and lipid metabolism in male mice. The findings on cardiovascular outcomes and behaviour outcomes were inconsistent across studies. WIDER IMPLICATIONS Conception via in vitro or in vivo means appears to have an influence on measurable outcomes of offspring physiology, manifesting differently across the species studied. Importantly, it can be noted that these measurable differences are noticeable in healthy, fertile animal populations. Thus, common ART interventions may have long-term consequences for those conceived through these techniques, regardless of the pathology underpinning diagnosed infertility. However, due to heterogeneous methods, results and measured outcomes, highlighted in this review, it is difficult to draw firm conclusions. Optimizing animal and human studies that investigate the safety of new reproductive technologies will provide insight into safeguarding the introduction of novel interventions into the clinical setting. Cautiously prescribing the use of ARTs clinically may also be considered to reduce the chance of promoting adverse outcomes in children conceived before long-term safety is confidently documented. [ABSTRACT FROM AUTHOR]