The impact of periconceptional maternal lifestyle on clinical features and biomarkers of placental development and function: a systematic review

BACKGROUND Worldwide, placenta-related complications contribute to adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction and preterm birth, with implications for the future health of mothers and offspring. The placenta develops in the periconception period and forms the interface between mother and embryo/fetus. An unhealthy periconceptional maternal lifestyle, such as smoking, alcohol and under- and over-nutrition, can detrimentally influence placental development and function. OBJECTIVE AND RATIONALE The impact of maternal lifestyle on placental health is largely unknown. Therefore, we aim to summarize the evidence of the impact of periconceptional maternal lifestyle on clinical features and biomarkers of placental development and function throughout pregnancy. SEARCH METHODS A comprehensive search in Medline, Embase, Pubmed, The Cochrane Library Web of Science and Google Scholar was conducted. The search strategy included keywords related to the maternal lifestyle, smoking, alcohol, caffeine, nutrition (including folic acid supplement intake) and body weight. For placental markers throughout pregnancy, keywords related to ultrasound imaging, serum biomarkers and histological characteristics were used. We included randomized controlled trials and observational studies published between January 2000 and March 2017 and restricted the analysis to singleton pregnancies and maternal periconceptional lifestyle. Methodological quality was scored using the ErasmusAGE tool. A protocol of this systematic review has been registered in PROSPERO International prospective register of systematic reviews (PROSPERO 2016:CRD42016045596). OUTCOMES Of 2593 unique citations found, 82 studies were included. The median quality score was 5 (range: 0-10). The findings revealed that maternal smoking was associated with lower first-trimester placental vascularization flow indices, higher second- and third-trimester resistance of the uterine and umbilical arteries and lower resistance of the middle cerebral artery. Although a negative impact of smoking on placental weight was expected, this was less clear. Alcohol use was associated with a lower placental weight. One study described higher second- and third-trimester placental growth factor (PlGF) levels after periconceptional alcohol use. None of the studies looked at caffeine intake. Adequate nutrition in the first trimester, periconceptional folic acid supplement intake and strong adherence to a Mediterranean diet, were all associated with a lower resistance of the uterine and umbilical arteries in the second and third trimester. A low caloric intake resulted in a lower placental weight, length, breadth, thickness, area and volume. Higher maternal body weight was associated with a larger placenta measured by ultrasound in the second and third trimester of pregnancy or weighed at birth. In addition, higher maternal body weight was associated with decreased PlGF-levels. WIDER IMPLICATIONS Evidence of the impact of periconceptional maternal lifestyle on placental health was demonstrated. However, due to poorly defined lifestyle exposures and time windows of investigation, unstandardized measurements of placenta-related outcomes and small sample sizes of the included studies, a cautious interpretation of the effect estimates is indicated. We suggest that future research should focus more on physiological consequences of unhealthy lifestyle during the critical periconception window. Moreover, we foresee that new evidence will support the development of lifestyle interventions to improve the health of mothers and their offspring from the earliest moment in life.