Maternal Lifestyle and Prenatal Risk Factors for Childhood Leukemia: A Review of the Existing Evidence.

BACKGROUND: Acute leukemia is the most common pediatric cancer, with an incidence peak at 2-5 years of age. Despite the medical advances improving survival rates, children suffer from significant side effects of treatments as well as its high social and economic impact. The frequent prenatal origin of this developmental disease follows the two-hit carcinogenesis model established in the 70s: a first hit in prenatal life with the creation of genetic fusion lesions or aneuploidy in hematopoietic progenitor/stem cells, and usually a second hit in the pediatric age that converts the preleukemic clone into clinical leukemia. Previous research has mostly focused on postnatal environmental factors triggering the second hit. SUMMARY: There is scarce evidence on prenatal risk factors associated with the first hit. Mainly retrospective case-control studies suggested several environmental and lifestyle determinants as risk factors. If these associations could be confirmed, interventions focused on modifying prenatal factors might influence the subsequent risk of leukemia during childhood and reveal unexplored research avenues for the future. In this review, we aim to comprehensively summarize the currently available evidence on prenatal risk factors for the development of childhood leukemia. According to the findings of this review, parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Other factors such as socioeconomic status, consumption of caffeinated beverages, and smoking consumption have been suggested with inconclusive evidence. Additionally, investigating the association between prenatal factors and genetic lesions associated with childhood leukemia at birth is crucial. Prospective studies evaluating the link between lifestyle factors and genetic alterations could provide indirect evidence supporting new research avenues for leukemia prevention. Maternal diet and lifestyle factors are modifiable determinants associated with adverse perinatal outcomes that could be also related to preleukemic lesions. KEY MESSAGES: Parental age, ethnicity, maternal diet, folate intake, alcohol consumption, X-ray exposure, pesticides, perinatal infections, and fetal growth may have a significant role in the appearance of preleukemic lesions during fetal life. Dedicating efforts to studying maternal lifestyle during pregnancy and its association with genetic lesions leading to childhood leukemia could lead to novel prevention strategies.

Linking infant size and early growth with maternal lifestyle and breastfeeding - the first year of life in the CRIBS cohort.

BACKGROUND: Every third child in Croatia is classed as overweight or obese. Infant growth can represent early warning signs for obesity. AIM: To detect early risk factors for obesity by investigating infant size and early growth trajectories and their association with maternal lifestyle and breastfeeding. SUBJECTS AND METHODS: Ninety-eight mother-child pairs from the Croatian Islands' Birth Cohort Study (CRIBS) cohort were included in the study. Data were collected from questionnaires and medical records. Growth data were converted to Z-scores using World Health Organisation (WHO) standards and used as the primary outcome. RESULTS: Z-score trajectories in the first year of life were in line with WHO standards. A direct link between infant size and maternal socioeconomic status (SES) or breastfeeding was not detected. However, child weight gain in the first 6 months was associated with maternal body mass index (BMI) before pregnancy (p < 0.01). A positive association was also established between breastfeeding and maternal SES and mothers that report an unhealthy diet have heavier children (p < 0.05, respectively). CONCLUSION: Infant size and early growth in Croatia is in line with WHO standards and risk factors for obesity development were detectable in the first year of life, but not highly pronounced. However, more effective BMI monitoring and promotion of a healthy diet and lifestyle of women before and during pregnancy is needed.

Impact of Maternal Mediterranean-Type Diet Adherence on Microbiota Composition and Epigenetic Programming of Offspring.

Understanding how maternal diet affects in utero neonatal gut microbiota and epigenetic regulation may provide insight into disease origins and long-term health. The impact of Mediterranean diet pattern adherence (MDA) on fetal gut microbiome and epigenetic regulation was assessed in 33 pregnant women. Participants completed a validated food frequency questionnaire in each trimester of pregnancy; the alternate Mediterranean diet (aMED) score was applied. Umbilical cord blood, placental tissue, and neonatal meconium were collected from offspring. DNA methylation patterns were probed using the Illumnia EPICarray Methylation Chip in parturients with high versus low MDA. Meconium microbial abundance in the first 24 h after birth was identified using 16s rRNA sequencing and compared among neonates born to mothers with high and low aMED scores. Twenty-one mothers were classified as low MDA and 12 as high MDA. Pasteurellaceae and Bacteroidaceae trended towards greater abundance in the high-MDA group, as well as other short-chain fatty acid-producing species. Several differentially methylated regions varied between groups and overlapped gene regions including NCK2, SNED1, MTERF4, TNXB, HLA-DPB, BAG6, and LMO3. We identified a beneficial effect of adherence to a Mediterranean diet on fetal in utero development. This highlights the importance of dietary counseling for mothers and can be used as a guide for future studies of meconium and immuno-epigenetic modulation.

Intergenerational transmission of dietary habits among Italian children and adolescents.

The aim of this paper is to investigate the relationship between parental dietary habits and child and adolescent diet quality in Italy by adopting a parent-child perspective. We apply quantile regression modelling to an original database developed within the DEDIPAC knowledge hub, integrating multiple sources of information on the aspects of Italian households' daily lives, food consumption frequency, and calorie intake. Given the relevance of maternal care in shaping children's eating patterns, we focus on mothers' lifestyles and time-use. Results show that the intergenerational transmission of diet quality is a gendered process, especially involving mothers and their daughters. Our findings also highlight the pivotal role schools play in the fight against child malnutrition and indicate that, contrary to what is found in the international research literature, maternal employment is not correlated with a deterioration in their children's diet quality.

Maternal environmental enrichment modulates the immune response against an inflammatory challenge during gestation and protects the offspring.

The production of pro-inflammatory cytokines during inflammatory processes has been associated with preterm birth (PTB) and fetal injury in humans and mice. We previously demonstrated that exposition to an enriched environment (EE), defined as a noninvasive and biological significant stimulus of the sensory pathway combined with voluntary physical activity, prevented PTB and perinatal death induced by the systemic administration of bacterial lipopolysaccharide (LPS) in mice. This work aimed to analyze whether EE modulates the immune response to the inflammatory process induced by LPS in peripheral blood and the amniotic fluid (AF). We observed that EE modulated maternal white blood cell count and its response to LPS. Furthermore, we found higher levels of IL-10 and a higher percentage of B cells in AF from EE exposed mothers compared to controls. Albeit LPS significantly increased IL-6 levels in AF from both groups, it was 3.6 times higher in control environment (CE) exposed group when compared to EE. Similarly, levels of IL-22 were significantly increased by LPS in both groups, but it was 6.7 times higher in EE group. Interestingly, levels of PGE2 in AF were only increased in the EE-LPS treated group, and a positive correlation between IL-22 and PGE2 levels was observed. During lactation, EE prevented LPS-induced delay in physical landmarks analyzed to assess offspring development. Our results suggest that EE modulates the immune response to systemic LPS-administration protecting the offspring. We propose that an EE-like protocol could be designed for pregnant women aiming at preventing the sequelae present in premature children.

An investigation of vitamin D deficiency in pregnant women and their infants in Giresun province located in the Black Sea region of Turkey.

The aim of this study is to investigate vitamin D deficiency and the associated risk factors in pregnant women and their infants in the Black Sea region of Turkey. One hundred and twenty healthy pregnant women in the last trimester and their healthy newborn pairs were observed between June and August 2017 in Giresun province. The serum 25(OH)D3 and calcium levels were measured through the samples collected from maternal and neonatal cord blood. The effects of maternal lifestyle on the maternal vitamin D levels were assessed by multiple regression analysis. The mean concentrations of 25(OH)D3 were found to be 9.54 ± 6.35 ng/mL and 11.16 ± 6.52 ng/mL in the maternal and neonatal cord blood sera, respectively. Vitamin D deficiency (≤20 ng/mL) and severe vitamin D deficiency (≤5 ng/mL) were observed in between 94.2% and 24.2% of mothers and 90% and 10% of infants, respectively. The clothing style, the consumption of milk/dairy products and antenatal multivitamin supplement usage were found as significant factors on the serum vitamin D levels. Even during the Summer months, the vitamin D deficiency in mothers and infants was observed at high rates in the Eastern Black Sea region of Turkey. As a result, it has been concluded that routine maternal serum 25(OH)D3 measurements for clinical follow-up, vitamin D supplementation and regular consumption of dairy products should be recommended. Impact Statement What is already known on this subject? Vitamin D deficiency is a very important risk factor to be considered for maternal and infant health. In a large number of studies, it has been observed that the risk of a vitamin D deficiency in women during their pregnancy was found to be higher, depending on the various strong influences such as the demographic and maternal lifestyles. What the results of this study add? A vitamin D deficiency associated with the demographic and lifestyle factors of pregnant women and their infants was investigated in Giresun province, located in the Eastern Black Sea region of Turkey. The results of this study add that a vitamin D deficiency in the maternal and in the infants may be observed at high rates in regions with mostly rainy weather, even during the Summer months. What the implications are of these findings for clinical practice and/or further research? The vitamin D levels in infants can be determined indirectly by looking at the vitamin D levels in third trimester pregnancies. Furthermore, it is suggested as a non-invasive method to determine vitamin D levels by taking advantage of the maternal level, without measuring the vitamin D levels of infants. Thus, this will be effective to reduce health costs and to prevent the possible diseases affecting the future life of infants. Routine maternal serum 25(OH)D3 measurements for clinical follow-up, vitamin D supplementation and the regular consumption of dairy products should be recommended to pregnant women with risk factors, even in the Summer in the Black Sea Region of Turkey. In addition, further studies are needed to investigate the vitamin D deficiency associated with the demographic and lifestyle factors of pregnant women and their infants, especially for the different locations of Turkey.

Induction of the apoptotic pathway by oxidative stress in spontaneous preterm birth: Single nucleotide polymorphisms, maternal lifestyle factors and health status.

The purpose of the present study was to search for associations between spontaneous preterm birth (sPTB), single nucleotide polymorphisms (SNPs) associated with the apoptotic pathway as triggered by oxidative stress, maternal lifestyle and health status. SNP genotyping [rs7560 for c-Jun N-terminal kinase (JNK), rs9517320 for mammalian STE20-like protein kinase 3 (MST3), rs1049216 for caspase 3 (CASP3)] in the placenta and maternal blood of 300 controls with at-term birth and 43 cases of sPTB was performed. No association was identified in genotype frequencies or combinations of foetal/maternal genotypes between single SNPs and sPTB. The risk of sPTB was significantly reduced by physical activity and significantly increased by current hypertensive diseases, premature rupture of membranes (PROM) or preterm PROM (P-PROM) and previous sPTB. The TT/GA genotype of JNK/CASP3 in maternal blood and maternal health status (current hypertensive diseases, current PROM/P-PROM, previous sPTB) were independently associated with sPTB. The present findings suggested that, independently of other maternal factors, pregnant women carrying the TT/GA genotype of JNK/CASP3 were more susceptible to sPTB than women bearing the GT/GA (our reference) genotype; that the apoptotic pathway triggered by oxidative stress was involved; and that genetic and non-genetic factors contributed to sPTB. Knowledge of these aspects may aid to improve the management of pregnancies by indicating the lifestyle to be adopted on the basis of sPTB susceptibility.

Cohort profile: maternal lifestyle and diet in relation to pregnancy, postpartum and infant health outcomes in Vietnam: A multicentre prospective cohort study.

PURPOSE: To determine modifiable maternal risk factors for adverse pregnancy, postpartum maternal and child health outcomes in Vietnam. PARTICIPANTS: This prospective cohort study included pregnant women seeking prenatal care at six hospitals in three large cities in Vietnam. After enrolment, eligible participants who gave their consent to participate in the study were interviewed at 24-28 weeks' gestation. Glucose testing was conducted and blood pressure was measured during this period. Each participant will be assessed prospectively during their postnatal visits at delivery, 1, 3, 6, 12, 18 and 24 months, and will be followed up for 5 years. FINDINGS TO DATE: Of 2248 eligible pregnant women, 2030 were recruited (participation rate 90.3%) between August 2015 and July 2016. All participants completed the baseline assessment. Their mean (SD) age was 27.6 (5.3) years. The mean pre-pregnancy body mass index (BMI) was 20.2 (SD 2.6) kg/m2, with nearly two-thirds of participants having a normal pre-pregnancy BMI (18.5 to <23.0 kg/m2) and one-quarter being underweight (pre-pregnancy BMI <18.5 kg/m2). Overweight or obese mothers (pre-pregnancy BMI ≥23.0 kg/m2) accounted for 12.8%. No pregnant women reported smoking during their pregnancy while 13.4% of them had continued drinking. 22.8% of participants had hyperglycaemia. Their mean systolic blood pressure was 105.6 (SD 8.2) mm Hg, and diastolic blood pressure was 67.4 (SD 7.5) mm Hg. FUTURE PLANS: The relationships of maternal lifestyle and nutritional status with the health outcomes of pregnancy, postpartum maternity and infants will be analysed. Meanwhile, participants will be closely tracked to minimise loss to follow-up.

Maternal lifestyle and nutritional status in relation to pregnancy and infant health outcomes in Western China: protocol for a prospective cohort study.

INTRODUCTION: Improving the health and nutrition of women and children is a priority for Western China, where the economy is less developed. Due to the dynamic nature of lifestyle, modern food habits and nutrition, there is a need to update our limited knowledge and understanding of maternal lifestyle and nutritional status and their impact on pregnancy and infant health outcomes. While breast milk is the preferred feeding option, infant formula use is widespread in China. It is thus necessary to examine the effects of formula consumption on growth and morbidity. METHODS AND ANALYSIS: This is an ongoing prospective cohort study started in 2015 in Chengdu, Sichuan Province. A sample of 1901 pregnant women at 15-20 weeks of gestation were recruited from four maternal and child health hospitals and are followed prospectively to 12 months post partum. Detailed information on maternal lifestyle and nutritional status, obstetric complications, pregnancy outcomes, infant feeding practices, illnesses of the mother and infant and growth trajectory is collected through personal interviews, anthropometric measures and medical records and local health management system records retrieval. Multilevel mixed regression models, adjusted for clustering, will be applied to investigate the association between various exposure variables of interest and the longitudinal outcomes, taking into account the correlated data structure and the nesting of observations. Kaplan-Meier test and Cox regression analysis will be used to analyse the time-to-event data. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethics committee of West China School of Public Health, Sichuan University and the Human Research Ethics Committee of Curtin University. Results will be presented at national and international conferences and published in peer-reviewed journals.

Eat Well Keep Active: Qualitative findings from a feasibility and acceptability study of a brief midwife led intervention to facilitate healthful dietary and physical activity behaviours in pregnant women.

BACKGROUND: overweight and obesity in the pregnant population is increasing and this is a public health concern. Many women have difficulty in following the recommendation to maintain a healthy diet and to keep active, indeed some identify pregnancy as the start of their concern with being overweight. OBJECTIVE: to assess the feasibility and acceptability of the 'Eat Well Keep Active' intervention programme designed to promote healthy eating and physical activity in pregnant women. This brief midwife led intervention was based upon the Self Determination Theory (SDT) framework and utilised Motivational Interviewing and individualised goal setting. DESIGN: this was a prospective qualitative study to explore women's views on the acceptability and perceived efficacy of the 'Eat Well Keep Active' programme obtained through one-to-one interviews 6 weeks after the delivery of the intervention. Data were also analysed to assess fidelity of the intervention to the psychological constructs of SDT; autonomy, competence and relatedness. SETTING: Wales, UK. PARTICIPANTS: pregnant women suitable for Midwife Led Care and therefore deemed to be 'low risk' were recruited from a large maternity unit in South Wales (n=20). FINDINGS: the results indicated that the 'Eat Well Keep Active' intervention programme was well received by participants who reported that it positively influenced their health behaviours. There was clear evidence of the intervention supporting the three SDT psychological needs. KEY CONCLUSIONS: The Eat Well Keep Active intervention was designed to be incorporated into existing antenatal provision and findings from this study have demonstrated its acceptability. The brief midwife led intervention based on SDT was found to be acceptable by the participants who embraced the opportunity to discuss and explore their lifestyle behaviours with a midwife. IMPLICATIONS FOR PRACTICE: theoretically designed interventions that can facilitate women to pursue a healthy lifestyle during pregnancy are lacking and the 'Eat Well Keep Active' programme has the potential to address this. Further research is needed in order to assess the acceptability of the intervention to midwives and other groups of pregnant women prior to assessing its efficacy in changing and maintaining healthful behaviours.

Adipokine-myokine-hepatokine compartment-system in mothers and children: An explorative study.

OBJECTIVE: Maternal lifestyle during pregnancy has an effect of gestational development and neonatal outcome. Overweight gravidas and gravidas with excessive weight gain have an increased risk of gestational complications and neonatal metabolic disorder. The underlying mechanisms are still under discussion, but the hormonally active fat mass and its biomarkers, adipocytokines, may play a key role by potentially having a direct impact on the metabolic homeostasis of the system in concert with other biomarkers like hepatokines and myokines. Up to now little is known in terms of lifestyle habits and their effect on this complex model on maternal and fetal outcome. Therefore, we aim to investigate the influence of maternal lifestyle clusters during pregnancy on the maternal and fetal biomarkers of compartments, specifically those implying maternal fat and muscle mass, maternal liver and the placenta and who are associated with maternal body composition and birth weight. METHODS: In this exploratory pilot study at least 100 singleton pregnancies and their newborns will be included. The women will undergo assessments of anthropometric measurements, venous blood samples will be drawn and physical activity and nutritional status will be collected through questionnaires. Newborns will undergo assessments of anthropometric measurements, umbilical cord samples will be drawn and birth outcomes will be evaluated. We will measure adipokines, myokines and hepatokines and relate them to maternal lifestyle clusters and fetal outcome. CONCLUSION: Our study will be the first to examine the relationship between maternal body composition, birth weight and potential biomarkers based on an innovative compartment model.