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Background: Progesterone is widely used in prenatal care. However, long‐term effects of prenatal progesterone treatment on child development are unclear. Objectives: To evaluate long‐term outcomes in children after prenatal progesterone treatment. Search strategy: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. Selection criteria: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. Data collection and analysis: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. Main results: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta‐analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley‐III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference −0.04, 95% Confidence Interval −0.26 to 0.19), I2 = 22%. Heterogeneity prohibited additional meta‐analyses. Other long‐term outcomes showed no differences. Conclusions: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow‐up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of transabdominal amnioinfusion or no intervention on long-term outcomes in children born after second-trimester prelabour rupture of the membranes (PROM between 16+0/7 -24+0/7  weeks) and oligohydramnios.Population: Follow up of infants of women who participated in the randomised controlled trial: PPROMEXIL-III (NTR3492).Methods: Surviving infants were invited for neurodevelopmental assessment up to 5 years of corrected age using a Bayley Scales of Infant and Toddler Development or a Wechsler Preschool and Primary Scale of Intelligence. Parents were asked to complete several questionnaires.Main Outcome Measures: Neurodevelopmental outcomes were measured. Mild delay was defined as -1 standard deviation (SD), severe delay as -2 SD. Healthy long-term survival was defined as survival without neurodevelopmental delay or respiratory problems.Results: In the amnioinfusion group, 18/28 children (64%) died versus 21/28 (75%) in the no intervention group (relative risk 0.86; 95% confidence interval [CI] 0.60-1.22). Follow-up data were obtained from 14/17 (82%) children (10 amnioinfusion, 4 no intervention). In both groups, 2/28 (7.1%) had a mild neurodevelopmental delay. No severe delay was seen. Healthy long-term survival occurred in 5/28 children (17.9%) after amnioinfusion versus 2/28 (7.1%) after no intervention (odds ratio 2.50; 95% CI 0.53-11.83). When analysing data for all assessed survivors, 10/14 (71.4%) survived without mild neurodevelopmental delay and 7/14 (50%) were classified healthy long-term survivor.Conclusions: In this small sample of women suffering second-trimester PROM and oligohydramnios, amnioinfusion did not improve long-term outcomes. Overall, 71% of survivors had no neurodevelopmental delay.Tweetable Abstract: Healthy long-term survival was comparable for children born after second-trimester PROM and treatment with amnioinfusion or no intervention. [ABSTRACT FROM AUTHOR]

Objective: To explore whether maternal vitamin B12 and folate status during early pregnancy are associated with cardiometabolic risk factors in the offspring at age 5-6.Design: Prospective multi-ethnic birth cohort, the Amsterdam Born Children and their Development study (ABCD).Setting: 12,373 pregnant women living in Amsterdam were approached between 2003 and 2004 for participation in the study.Population: Mother-child pairs for whom information on maternal vitamin B12 or folate status in early gestation and health at age 5-6 years was available (n = 1950).Methods: Vitamin B12 and folate concentrations were determined in maternal serum at intake in early pregnancy (median 13 weeks' gestation). Anthropometric measurements, blood pressure and fasting blood samples were collected during a health check of children aged 5-6 years. Multiple linear regression was performed to investigate the association between maternal serum concentrations and children's outcomes, corrected for confounders.Main Outcome Measures: Gestational age at birth, birthweight, body mass index (BMI), glucose levels, triglyceride levels, blood pressure and heart rate of the offspring at age 5-6.Results: Low maternal folate levels during early pregnancy were associated with slightly higher BMI in the offspring [decrease per 10 units: β 0.07 kg/m(2), 95% confidence interval (CI) 0.01, 0.13]. Low maternal vitamin B12 concentrations were associated with higher heart rates (decrease per 100 units: β 0.49 beats/min, 95% CI 0.11, 0.87).Conclusion: This study provides further evidence that maternal nutrition in early pregnancy may possibly program cardiometabolic health of the offspring.Tweetable Abstract: Low folate and vitamin B12 levels during pregnancy are associated with higher BMI and heart rate in offspring. [ABSTRACT FROM AUTHOR]

Objective: To investigate the consequences of weight loss in pregnancy on pregnancy outcomes and cardiometabolic profile in childhood.Design: Prospective birth cohort (ABCD study).Setting: Between 2003 and 2004, all pregnant women in Amsterdam were approached for study participation.Population: 7818 pregnant women were included, of which 3165 consented to having their children examined at 5-6 years of age. In 1956 children fasting capillary blood samples were also taken.Methods: At antenatal booking, women answered questions about their pregnancy and whether they suffered from severe weight loss (SWL; >5 kg). Pregnancy details and outcomes were available through the obstetric caregiver.Main Outcome Measures: At birth main outcome measures were prematurity (<37 weeks) and birthweight. At follow-up, body mass index (BMI), blood pressure, glucose and lipids were assessed.Results: SWL occurred in 6.8% of cases. Women with SWL had similar preterm birth rates compared with women without these complaints (adjusted OR 1.1, 95%CI 0.7, 1.7). Birthweight (adjusted difference - 31 g, 95%CI -76, 15) and BMI at 5-6 years of age (adjusted difference 0.2 kg/m(2) , 95%CI 0.0, 0.5) were similar in children born to mothers with SWL and without SWL, but blood pressure was increased. For diastolic blood pressure this association was independent of confounders (adjusted difference 1.4 mmHg, 95%CI 0.4, 2.4). Lipid and glucose levels were not significantly different between these groups.Conclusion: Early pregnancy weight loss, usually occurring as a manifestation of hyperemesis gravidarum, could have long-term consequences for offspring health. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the association between (self-reported) maternal pre-pregnancy body mass index (pBMI), and child's weight, height and BMI at age 14 months. DESIGN: Prospective multi-ethnic community-based cohort study. SETTING: Amsterdam, The Netherlands. PARTICIPANTS: 8266 pregnant women from the Amsterdam Born Children and their Development study, filled out a questionnaire covering socio-demographic data, obstetric history, lifestyle, dietary habits and psychosocial factors, 2 weeks after their first antenatal visit. 7730 gave birth to a viable term singleton infant with information on birth weight, gender and pregnancy duration. Growth data were available for 3171 of these children. MAIN OUTCOME MEASURES: Weight (g), height (cm) and BMI (kg/m(2)) of the child at age 14 months. RESULTS: pBMI was linearly associated with weight and BMI of the child at age 14 months. One unit increase in pBMI resulted in an increment of 29 g (95% CI 19 to 39) in weight and 0.041 kg/m(2) (95% CI 0.030 to 0.053) in BMI. The effect size decreased after adjustment for birth weight (weight: beta coefficient 19 g, 95% CI 10 to 28; BMI: beta coefficient 0.034 kg/m(2), 95% CI 0.023 to 0.046) and hardly changed after adjustment for all other variables (weight: beta coefficient 21 g, 95% CI 11 to 30; BMI: beta coefficient 0.031 kg/m(2), 95% CI 0.019 to 0.043). pBMI was not related to height. CONCLUSIONS: pBMI is an independent determinant of weight and BMI of the child at age 14 months. At least one third of this effect is mediated through birth weight. [ABSTRACT FROM AUTHOR]

Objective: An adverse fetal environment may permanently modify the effects of specific genes on glucose tolerance, insulin secretion, and insulin sensitivity. In the present study, we assessed a possible interaction of the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism with prenatal exposure to famine on glucose and insulin metabolism.Research Design and Methods: We measured plasma glucose and insulin concentrations after an oral glucose tolerance test and determined the PPAR-gamma2 genotype among 675 term singletons born around the time of the 1944-1945 Dutch famine.Results: A significant interaction effect between exposure to famine during midgestation and the PPAR-gamma2 Pro12Ala polymorphism was found on the prevalence of impaired glucose tolerance and type 2 diabetes. The Ala allele of the PPAR-gamma2 gene was associated with a higher prevalence of impaired glucose tolerance and type 2 diabetes but only in participants who had been prenatally exposed to famine during midgestation. Similar interactions were found for area under the curve for insulin and insulin increment ratio, which were lower for Ala carriers exposed to famine during midgestation.Conclusions: The effects of the PPAR-gamma2 Pro12Ala polymorphism on glucose and insulin metabolism may be modified by prenatal exposure to famine during midgestation. This is possibly due to a combined deficit in insulin secretion, as conferred by pancreatic beta-cell maldevelopment and carrier type of the Ala allele in the PPAR-gamma2 gene. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether SIRT1, a nutrient-sensing histone deacetylase, influences fetal programming during malnutrition.Research Design and Methods: In 793 individuals of the Dutch Famine Birth Cohort, we analyzed the interaction between three SIRT1 single nucleotide polymorphisms (SNPs) and prenatal exposure to famine on type 2 diabetes risk.Results: In the total population (exposed and unexposed), SIRT1 variants were not associated with type 2 diabetes. A significant interaction was found between two SIRT1 SNPs and exposure to famine in utero on type 2 diabetes risk (P = 0.03 for rs7895833; P = 0.01 for rs1467568). Minor alleles of these SNPs were associated with a lower prevalence of type 2 diabetes only in individuals who had been exposed to famine prenatally (odds ratio for rs7895833 0.50 [95% CI 0.24-1.03], P = 0.06; for rs1467568 0.48 [0.25-0.91], P = 0.02).Conclusions: SIRT1 may be an important genetic factor involved in fetal programming during malnutrition, influencing type 2 diabetes risk later in life. [ABSTRACT FROM AUTHOR]

The foundations of human wellbeing are laid in early life during the preconception stage and the 1,000-days of life from conception to the child's second birthday. This period is therefore receiving scrutiny as a concept for guiding pregnancy-care innovation and public health policy. The Dutch government took responsibility to invest in this. In September 2018, the Dutch Ministry of Health, Welfare, and Sport launched the Solid Start action programme. Coordinated nationally, the programme is implemented locally through coalitions in all 342 Dutch municipalities involving collaboration between medical and social-care professionals, policymakers, parents and organisations. The programme has generated a nationwide movement in which medical and social-care professionals now develop forms of structural collaboration that support (future) parents by offering evidence-based interventions that simultaneously enhance early healthy human development and prevent unwanted pregnancies. Although monitoring of the programme does not currently make it possible to address the causal effects of the programme itself, lessons can be distilled which have contributed to the successful implementation of this nationwide programme. These lessons include 1) having and maintaining an unambiguous narrative, 2) creating a lasting sense of urgency among stakeholders, and 3) ensuring that the programme is multi-sectoral., Competing Interests: Declaration of competing interest EAPS was the initiator of the local Rotterdam programme ‘Ready for a baby’ and the ‘Healthy Pregnancy for All’ programme in 17 Dutch cities. He is a member of the national coalition of the national Solid Start programme. JS supervised the monitoring of the Solid Start programme. Since 2019, AU has been the national programme manager of Solid Start at the Ministry of Health, Welfare and Sport. TR is chair of the scientific steering committee of the Solid Start programme and a member of the national coalition. The authors of this manuscript received no personal remuneration for writing this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Context: The aim of this scoping review was to provide an overview of recent studies in peer reviewed journals investigating self-reported motivations to have an abortion or to continue an unwanted pregnancy in different countries and settings, including both qualitative and quantitative results., Methods: We searched for English language publications published between 2008 and 2023 indexed in four scientific databases. We included studies if they captured people's own motivations for abortion and/ or for continuing an unwanted pregnancy., Results: Of the included 19 studies, all focused on abortion, and four also included motivations to carry an initially unwanted pregnancy to term. Motivations for abortion often related to family planning (e.g., complete family, no desire for children, not the right time), the relationship with the person involved in the pregnancy, and life or material circumstances (such as financial resources, housing or future plans), and sometimes with stigma, shame, or expected negative reactions. Motivations to continue an unwanted pregnancy were having a supportive partner and personal beliefs about the pregnancy. Despite different settings, different methods, and methodological limitations, studies showed similar multifactorial and interrelated motivations in decision making around unwanted pregnancies., Conclusions: This research showed that in different places throughout the world multiple interrelated motivations play a role in a decision to have an abortion or to continue an unwanted pregnancy. The findings mainly provide insight into retrospective explanatory accounts, which may be biased because respondents may feel the need to justify their choice. Future research should discontinue asking people to rationalize unwanted pregnancy decisions., (© 2025 The Author(s). Perspectives on Sexual and Reproductive Health published by Wiley Periodicals LLC on behalf of University of Ottawa.)

Objective: To evaluate reliability and validity of the Dutch version of the Infant Crying and Parent Well-Being (ICPW) tool in identifying parents struggling with infant crying in the first year of life., Study Design: The original ICPW tool was translated into Dutch following established guidelines. The internal consistency and criterion validity of the Dutch ICPW tool were evaluated using a cross-sectional design. The translated ICPW tool and validated questionnaires on parental depression, stress, anxiety, and parenting balance were presented to parents of infants under 12 months during child health care visits and online., Results: The survey was completed by 488 parents, 400 mothers and 88 fathers. Of these, 172 participated after a child health care visit and 316 via online platforms. The Dutch ICPW showed satisfactory internal consistency (α = 0.69) and excellent criterion validity with parental mental health measures (r = 0.53-0.85). ICPW scores demonstrated positive correlations with parental depression, stress, and anxiety levels, and a negative correlation with parenting balance. Both mothers and fathers with a positive ICPW screen (≥3) reported significantly higher levels of parental mental health issues compared with those with a negative screen (P < .001). The ICPW was positive in 32% of the parents (n = 155), with consistent total scores regardless of the infant's increasing age (r = -0.024, P = .59). The ICPW tool exhibited a strong negative predictive value (93%) for diagnosing postpartum depression., Conclusions: The Dutch ICPW tool is a reliable and valid screening instrument for identifying parents struggling with infant crying., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Evidence suggests that high levels of air pollution and less green space increase depressive symptoms in adults. However, results are mixed and cross-cohort comparisons are scarce, largely due to heterogeneity in exposure assessment. Also, the impact of these exposures on the trajectory of depressive symptoms over time has been less studied. We investigated the association of air pollution and green space with depressive symptoms in adulthood and whether these exposures modify the trajectory of depressive symptoms leveraging harmonized data from four population-based cohorts across the Netherlands and United Kingdom (UK)., Methods: We analyzed data from the Dutch Famine Birth Cohort (DFBC) (n = 840, baseline ages: 56-61), and the Rotterdam Study (RS) (RS-I n = 4,049, baseline ages: 61-101 and RS-II n = 2,861, baseline ages: 55-99), in the Netherlands, and the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 17,100, baseline ages: 18-71) in the UK, each using a different validated instrument for depressive symptoms, with 3-11 repeated measures. European-wide environmental data was linked to participants' addresses at baseline. Linear mixed-models were used to estimate associations of air pollution and green space with standardized cohort-specific depressive symptoms, and whether these exposures modify the trajectory of depressive symptoms., Results: Long-term exposure to fine particulate matter (PM 2.5 ) was positively associated with overall higher standardized depressive symptom scores in ALSPAC and RS-I (β per 10 μg/m 3 increase in PM 2.5 : 0.07 SD, 95%CI 0.02, 0.11 and 0.13 SD, 95%CI 0.02, 0.24, respectively). Exposure to higher normalized difference vegetation index (NDVI) at 300 m buffer was associated with lower depressive symptoms in DFBC (β per 0.1 increase in NDVI: 0.08, 95%CI -0.14, -0.01). In RS-II, the positive effect of higher NDVI at 300-m buffer on depressive symptoms decreased over time, but this effect was very small (β per 0.1 increase in NDVI: 0.01 SD per year, 95%CI 0.00, 0.01)., Conclusion: Air pollution in the form of particulate matter as well as green space were associated with depressive symptoms across multiple cohorts. In the majority of cohorts, depressive symptoms increased with age, but we found little evidence that trajectories of depressive symptoms are influenced by exposure to environmental variables., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: 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., Objectives: Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately., Methods: 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., Results: 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., Conclusion: 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., (© 2024 The Author(s). Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Prenatal adversity affects cognitive and brain aging. Both lipid and leptin concentrations may be involved. We investigated if prenatal undernutrition is associated with a specific blood lipid profile and/or leptin concentrations, and if these relate to cognitive function and brain aging. 801 plasma samples of members of the Dutch famine birth cohort were assessed for lipidomics and leptin at age 58. Cognitive performance was measured with a Stroop task at 58, and MRI-based BrainAGE was derived in a subsample at 68. Out of 259 lipid signals, a signature of five identified individuals who were undernourished prenatally. These five lipids were not associated with cognitive performance, but three were predictive of BrainAGE. Leptin was not associated with prenatal famine exposure, Stroop performance, or BrainAGE. In conclusion, prenatal undernutrition was associated with an altered lipid profile predictive of BrainAGE 10 years later, demonstrating the potential of lipid profiles as early biomarkers for accelerated brain aging., (© 2024. The Author(s).)

Several studies investigated short-term risks of children born from unintended pregnancies, however evidence about long-term risks is lacking. We aimed to examine whether children born from unintended pregnancies experience psychosocial problems up into adolescence. This study is based on the longitudinal birth cohort study 'Amsterdam Born Children and their Development' (n = 7784). Unintended pregnancy was measured as a multidimensional construct, based on self-reports on the extent of pregnancy mistiming ('This pregnancy happened too soon'), unwantedness ('I did not want to be pregnant (anymore)') and unhappiness ('I am happy to be pregnant'; recoded). Further, children's psychosocial problems were measured with the Strengths and Difficulties Questionnaire, at 5-6, 11-12 and 15-16 years old. Multiple over-time associations between unintended pregnancy and children's psychosocial problems were analysed using Structural Equation Modelling, while controlling for confounders. Results showed that pregnancy mistiming was a significant predictor of internalizing (β = 0.10, p < 0.001) and externalizing problems (β = 0.07, p = 0.006) and unwanted pregnancy of internalizing problems (β = 0.13, p < 0.001) at 5-6 years. These associations were substantially mediated by maternal mental health and poorer maternal bonding. Associations were no longer present at 11-12 and 15-16 years. Thus, we conclude that children born from unintended pregnancies experience more psychosocial problems at 5-6 years, but no longer at 11-12 and 15-16 years. Unintended pregnancies often coincide with maternal mental health problems and socioeconomic factors. Most importantly, the associations between unintended pregnancy and children's psychosocial problems are influenced by maternal mental health and poorer bonding. Therefore it is important to improve maternal mental health and bonding for the benefit of both mother and child, rather than on the isolated effect of unintended pregnancy per se., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Poorer performance on the Stroop task has been reported after prenatal famine exposure at age 58, potentially indicating cognitive decline. We investigated whether brain activation during Stroop task performance at age 74 differed between individuals exposed to famine prenatally, individuals born before and individuals conceived after the famine., Method: In the Dutch famine birth cohort, we performed a Stroop task fMRI study of individuals exposed (n = 22) or unexposed (born before (n = 18) or conceived after (n = 25)) to famine in early gestation. We studied group differences in task-related mean activation of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and posterior parietal cortex (PPC). Additionally, we explored potential disconnectivity of the DLPFC using psychophysiological interaction analysis., Results: We observed similar activation patterns in the DLPFC, ACC and PPC in individuals born before and individuals exposed to famine, while individuals conceived after famine had generally higher activation patterns. However, activation patterns were not significantly different between groups. Task-related decreases in connectivity were observed between left DLPFC-left PPC and right DLPFC-right PPC, but were not significantly different between groups., Conclusions: Although not statistically significant, the observed patterns of activation may reflect a combined effect of general brain aging and prenatal famine exposure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: A poor prenatal environment adversely affects brain development. Studies investigating long-term consequences of prenatal exposure to the 1944-45 Dutch famine have shown that those exposed to famine in early gestation had poorer selective attention, smaller brain volumes, poorer brain perfusion, older appearing brains, and increased reporting of cognitive problems, all indicative of increased dementia risk., Objective: In the current population-based study, we investigated whether dementia incidence up to age 75 was higher among individuals who had been prenatally exposed to famine., Methods: We included men (n=6,714) and women (n=7,051) from the Nivel Primary Care Database who had been born in seven cities affected by the Dutch famine. We used Cox regression to compare dementia incidence among individuals exposed to famine during late (1,231), mid (1,083), or early gestation (601) with those unexposed (born before or conceived after the famine)., Results: We did not observe differences in dementia incidence for those exposed to famine in mid or early gestation compared to those unexposed. Men and women exposed to famine in late gestation had significantly lower dementia rates compared to unexposed individuals (HR 0.52 (95%CI 0.30-0.89)). Sex-specific analyses showed a lower dementia rate in women exposed to famine in late gestation (HR 0.39 (95%CI 0.17-0.86)) but not in men (HR 0.68 (95%CI 0.33-1.41))., Conclusion: Although prenatal exposure to the Dutch famine has previously been associated with measures of accelerated brain aging, the present population-based study did not show increased dementia incidence up to age 75 in those exposed to famine during gestation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Gestational age is positively associated with cognitive development, but socio-demographic factors also influence school performance. Previous studies suggested possible interaction, putting children with low socio-economic status (SES) at increased risk of the negative effects of prematurity., Objectives: To investigate the association between gestational age in weeks, socio-demographic characteristics, and school performance at the age of 12 years among children in regular primary education., Methods: Population-based cohort study among liveborn singletons (N = 860,332) born in the Netherlands in 1999-2006 at 25-42 weeks' gestation, with school performance from 2011 to 2019. Regression analyses were conducted investigating the association of gestational age and sociodemographic factors with school performance and possible interaction., Results: School performance increased with gestational age up to 40 weeks. This pattern was evident across socio-demographic strata. Children born at 25 weeks had -0.57 SD (95% confidence interval -0.79, -0.35) lower school performance z-scores and lower secondary school level compared to 40 weeks. Low maternal education, low maternal age, and non-European origin were strongly associated with lower school performance. Being born third or later and low socioeconomic status (SES) were also associated with lower school performance, but differences were smaller than among other factors. When born preterm, children from mothers with low education level, low or high age, low SES or children born third or later were at higher risk for lower school performance compared to children of mothers with intermediate education level, aged 25-29 years, with intermediate SES or first borns (evidence of interaction)., Conclusions: Higher gestational age is associated with better school performance at the age of 12 years along the entire spectrum of gestational age, beyond the cut-off of preterm birth and across socio-demographic differences. Children in socially or economically disadvantaged situations might be more vulnerable to the negative impact of preterm birth. Other important factors in school performance are maternal education, maternal age, ethnicity, birth order and SES. Results should be interpreted with caution due to differential loss to follow-up., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

People commonly face adverse circumstances throughout life, which increases risk for psychiatric disorders, such as anxiety, depression, psychosis, and posttraumatic stress disorder (PTSD). Adversities may occur during different periods in life. Especially adversity during early periods has been suggested to put individuals at risk for adverse mental health outcomes. Here, we investigated whether timing of adversity during the prenatal period, childhood, or mid-to-late adulthood differentially impacted classification into late adulthood symptom profiles. We performed sex-stratified Latent Profile Analysis to identify latent profiles regarding anxious, depressive, psychotic, and PTSD symptoms in n = 568 Dutch famine birth cohort members ( n = 294 women, n = 274 men, mean age(SD) = 72.9(0.8)). Cross-sectional late adulthood symptomatology, childhood traumatic maltreatment, and adulthood trauma were based on self-report questionnaires. Prenatal adversity was considered present when individuals were prenatally exposed to the 1944-45 Dutch famine. In both men and women we identified one anxious/depressive profile and three profiles with approximately equal severity of all symptom types within each profile, yet differentiating in overall severity (low, mild, high) between profiles. We additionally found a PTSD symptom profile in women. In men, logistic regression models showed significant associations between prenatal, childhood and adulthood adversity, and profile classification, with differential effects depending on timing and most profound effects of child maltreatment. In women, childhood and adulthood adversity significantly increased classification probability into almost all profiles, with no significant effect of prenatal adversity. These findings support a time-dependent and sex-specific impact of adversity during different periods across the lifespan on psychological health, with consequences into late adulthood.

Background: Maternal obesity during pregnancy is associated with poorer cardiovascular health (CVH) in children. A strategy to improve CVH in children could be to address preconception maternal obesity by means of a lifestyle intervention. We determined if a preconception lifestyle intervention in women with obesity improved offspring's CVH, assessed by magnetic resonance imaging (MRI)., Methods: We invited children born to women who participated in a randomised controlled trial assessing the effect of a preconception lifestyle intervention in women with obesity. We assessed cardiac structure, function and geometric shape, pulse wave velocity and abdominal fat tissue by MRI., Results: We included 49 of 243 (20.2%) eligible children, 24 girls (49%) girls, mean age 7.1 (0.8) years. Left ventricular ejection fraction was higher in children in the intervention group as compared to children in the control group (63.0% SD 6.18 vs. 58.8% SD 5.77, p = 0.02). Shape analysis showed that intervention was associated with less regional thickening of the interventricular septum and less sphericity. There were no differences in the other outcomes of interest., Conclusion: A preconception lifestyle intervention in women with obesity led to a higher ejection fraction and an altered cardiac shape in their offspring, which might suggest a better CVH., Impact: A preconception lifestyle intervention in women with obesity results in a higher ejection fraction and an altered cardiac shape that may signify better cardiovascular health (CVH) in their children. This is the first experimental human evidence suggesting an effect of a preconception lifestyle intervention in women with obesity on MRI-derived indicators of CVH in their children. Improving maternal preconception health might prevent some of the detrimental consequences of maternal obesity on CVH in their children., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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 Interests: 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., Competing Interests: The authors declare no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)