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Homocysteine is a marker for derangements in one-carbon metabolism. Elevated ho-mocysteine may represent a causal link between poor maternal nutrition and impaired embryonic and fetal development. We sought to investigate associations between reference range maternal homocysteine and embryonic and fetal growth. We enrolled 1060 singleton pregnancies (555 natural and 505 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) pregnancies) from Novem-ber 2010 to December 2020. Embryonic and fetal body and head growth was assessed throughout pregnancy using three-dimensional ultrasound scans and virtual reality techniques. Homocysteine was negatively associated with first trimester embryonic growth in the included population (crown-rump length B −0.023 mm, 95% CI −0.038,−0.007, p = 0.004, embryonic volume B −0.011 cm3, 95% CI −0.018,−0.004, p = 0.003). After stratification for conception mode, this association remained in IVF/ICSI pregnancies with frozen embryo transfer (crown-rump length B −0.051 mm, 95% CI −0.081,−0.023, p < 0.001, embryonic volume B −0.024 cm3, 95% CI −0.039,−0.009, p = 0.001), but not in IVF/ICSI pregnancies with fresh embryo transfer and natural pregnancies. Homocysteine was not associated with longitudinal measurements of head growth in first trimester, nor with second and third trimester fetal growth. Homocysteine in the highest quartile (7.3–14.9 µmol/L) as opposed to the lowest (2.5–5.2 µmol/L) was associated with reduced birth weight in natural pregnancies only (B −51.98 g, 95% CI −88.13,−15.84, p = 0.005). In conclusion, high maternal homocysteine within the reference range is negatively associated with first trimester embryonic growth and birth weight, and the effects of homocysteine are dependent on conception mode.

Post-bariatric weight loss can cause iatrogenic malnutrition and micronutrient depletion. In this study, we evaluated the impact of gastric bypass surgery (GB) and multivitamin supplement use on maternal micronutrient status before and across pregnancy. A retrospective medical chart review of 197 singleton pregnancies after GB with a due date between 2009 and 2019 was performed at a bariatric expertise center in the Netherlands. Hemoglobin, calcium, iron status, folate, vitamin D, vitamin B12 and ferritin levels were determined before and after GB during standard follow-up and at all gestational trimesters and analyzed using linear mixed models. Patients were prescribed standard multivitamin supplements or multivitamins specifically developed for post-bariatric patients (FitForMe WLS Forte (FFM)). Overall, hemoglobin and calcium levels decreased after surgery and during pregnancy, whereas folate, vitamin D, and vitamin B12 levels increased, and iron levels remained stable. FFM use was associated with higher hemoglobin, folate, vitamin D, and ferritin levels. In conclusion, through adequate supplementation and follow-up, GB does not have to result in impaired micronutrient status. Supplements developed specifically for post-bariatric patients generally result in higher micronutrient values than regular multivitamins before and during preg-nancy. These data emphasize the urgent need for nutritional counseling including dietary and multivitamin supplement advise for post-bariatric women contemplating and during pregnancy.

BACKGROUND: Worldwide, the prevalence of obesity in women of reproductive age is increasing. Bariatric surgery is currently viewed as the most effective, long-term solution for this problem. Preconception bariatric surgery can reduce the prevalence of obesity-related subfertility and adverse maternal, pregnancy and birth outcomes. Maternal health during the periconception period is crucial for optimal gametogenesis and for embryonic and fetal development which also affects health in the later lives of both mother and offspring. Although preconception bariatric surgery improves several pregnancy outcomes, it can also increase the prevalence of pregnancy complications due to excessive and rapid weight loss. This can lead to iatrogenic malnutrition with vitamin deficiencies and derangements in metabolic and endocrine homeostasis. Thus, bariatric surgery can greatly influence periconception maternal health with consequences for reproduction, pregnancy and health in later life. However, its influence on periconception maternal health itself has never been reviewed systematically. OBJECTIVE AND RATIONALE: The aim of this review was to investigate associations between bariatric surgery and determinants of periconception maternal health such as endocrine changes, fertility, vitamin status, irregular menstrual cycles, miscarriages and congenital malformations. SEARCH METHODS: Medline, Embase, PubMed, Web of Science, Google Scholar and the Cochrane databases were used for the literature search until 1 November 2020. The search strategy terms included, among others, bariatric surgery, hormones, fertility, malformations, miscarriages and vitamin status. We searched for human studies that were written in English. Abstracts, reviews, meta-analyses and conference papers were excluded. The ErasmusAGE score was used to assess the quality of the included studies. OUTCOMES: A total of 51 articles were analysed. The mean quality score was 5 (range 2-8). After bariatric surgery, horm

Introduction The worldwide obesity epidemic has resulted in a rise of bariatric surgery in women of reproductive age, which can lead to â € iatrogenic undernutrition'. Long-lasting undernutrition can affect maternal health, pregnancy outcomes and offspring. We hypothesise that embryonic and placental growth are impaired in pregnancies after bariatric surgery due to the changed nutritional and microbiome dynamics. Therefore, our aim is to conduct the Bariatrics and EmbrYONic Development (BEYOND) study to investigate parameters of maternal nutritional and health status after bariatric surgery, both periconceptionally and during pregnancy, particularly concentrating on embryonic and fetal growth trajectories as well as placental development. Methods and analysis We designed a single-centre prospective, observational cohort, which investigates the iatrogenic nutritional and health status of women after bariatric surgery, periconceptionally and during pregnancy. The BEYOND study is embedded in the Rotterdam Periconceptional Cohort, a tertiary hospital-based birth cohort study. Eligible participants are women planning pregnancy or <12+0 weeks pregnant, ≥18 and ≤45 years of age, who have undergone bariatric surgery (cases) or without prior bariatric surgery (controls) and their male partners. Medical charts will be reviewed and questionnaires regarding general health, lifestyle and food intake will be collected. Moreover, we will perform serial three-dimensional ultrasounds to assess embryonic growth and placental development and two-dimensional ultrasounds for fetal growth assessment. The microbiome, including the virome, and blood samples will be sampled during the preconception period and in each trimester. Multivariable linear mixed model analyses will be used to assess the associations between bariatric surgery and pregnancy outcomes. Ethics and dissemination This proposal was approved by the Medical Ethics Committee from the Erasmus MC, Rotterdam, The Netherlan