Background Periconception lifestyle behaviors affect maternal, paternal, offspring, and transgenerational health outcomes. Previous research in other target populations has shown that personalized lifestyle interventions, in which face-to-face counseling and eHealth (“blended care”) are combined, may effectively target these lifestyle behaviors. Objective We aimed to assess the effectiveness of a periconceptional lifestyle intervention on the improvement of specific lifestyle components. Methods A blended periconception lifestyle care approach was developed, combining the outpatient lifestyle counseling service “Healthy Pregnancy” with the eHealth platform “Smarter Pregnancy” (www.smarterpregnancy.co.uk) in which lifestyle was coached for 24 weeks. All couples contemplating pregnancy or already pregnant (≤12 weeks of gestation) who visited the outpatient clinics of the Department of Obstetrics and Gynecology at the Erasmus University Medical Center (Erasmus MC), Rotterdam, the Netherlands, between June and December 2018, were invited to participate. We measured changes in lifestyle behaviors at weeks 12 and 24 compared with baseline. Generalized estimating equations were used to analyze the changes in lifestyle behaviors over time. Subgroup analyses were performed for women with obesity (BMI ≥30 kg/m2), women pregnant at the start of the intervention, and those participating as a couple. Results A total of 539 women were screened for eligibility, and 450 women and 61 men received the blended periconception intervention. Among the participating women, 58.4% (263/450) were included in the preconception period. Moreover, 78.9% (403/511) of the included participants completed the online lifestyle coaching. At baseline, at least one poor lifestyle behavior was present in most women (379/450, 84.2%) and men (58/61, 95.1%). In the total group, median fruit intake increased from 1.8 to 2.2 pieces/day (P<.001) and median vegetable intake increased from 151 to 165 grams/day (P<.001) after 24 weeks of online coaching. The probability of taking folic acid supplementation among women increased from 0.97 to 1 (P<.001), and the probability of consuming alcohol and using tobacco in the total group decreased from 0.25 to 0.19 (P=.002) and from 0.20 to 0.15 (P=.63), respectively. Overall, the program showed the strongest effectiveness for participating couples. Particularly for vegetable and fruit intake, their consumption increased from 158 grams/day and 1.8 pieces/day at baseline to 190 grams/day and 2.7 pieces/day at the end of the intervention, respectively. Conclusions We succeeded in including most participating women in the preconception period. A high compliance rate was achieved and users demonstrated improvements in several lifestyle components. The blended periconception lifestyle care approach seems to be an effective method to improve lifestyle behaviors. The next step is to further disseminate this approach and to perform a randomized trial to compare the use of blended care with the provision of only eHealth. Additionally, the clinical relevance of these results will need to be substantiated further.

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, hormonal axes normalized and menstrual cycle regularity was restored, resulting in increased fertility. Overall, there were no short-term risks for reproductive outcomes such as the increased risk of miscarriages or congenital malformations. However, the risk of vitamin deficiencies was generally increased after bariatric surgery. A meta-analysis of 20 studies showed a significant decrease in infertility (risk difference (RD) −0.24, 95% confidence interval (CI) −0.42, −0.05) and menstrual cycle irregularities (RD −0.24, 95% CI −0.34, −0.15) with no difference in rates of miscarriage (RD 0.00, 95% CI −0.09, 0.10) and congenital malformations (RD 0.01, 95% CI −0.02, 0.03). WIDER IMPLICATIONS The current systematic review and meta-analysis show associations between bariatric surgery and periconception maternal health and underlines the need for providing and personalizing preconception care for women after bariatric surgery. We recommend preconception care including the recommendation of postponing pregnancy until weight loss has stabilized, irrespective of the surgery-to-pregnancy interval, and until vitamin status is normalized. Therefore, regular monitoring of vitamin status and vitamin supplementation to restore deficiencies is recommended. Furthermore, this systematic review emphasizes the need for a long-term follow-up research of these women from the periconception period onwards as well as their pregnancies and offspring, to further improve care and outcomes of these mothers and children.

Homocysteine is a marker for derangements in one-carbon metabolism. Elevated homocysteine 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 November 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 pregnancy. These data emphasize the urgent need for nutritional counseling including dietary and multivitamin supplement advise for post-bariatric women contemplating and during pregnancy.

IntroductionThe worldwide obesity epidemic has resulted in a rise of bariatric surgery in women of reproductive age, which can lead to ‘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 analysisWe 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 disseminationThis proposal was approved by the Medical Ethics Committee from the Erasmus MC, Rotterdam, The Netherlands. Study results will be submitted for publication in high-impact journals, presented at scientific conferences, implemented into guidelines and communicated through the Erasmus MC and collaborating partners.Trial registration numberNL8217 (www.trialregister.nl).