Obesity in pregnancy-Long-term effects on offspring hypothalamic-pituitary-adrenal axis and associations with placental cortisol metabolism: A systematic review.

Obesity, affecting one in three pregnant women worldwide, is not only a major obstetric risk factor. The resulting low-grade inflammation may have a long-term impact on the offspring's HPA axis through dysregulation of maternal, placental and fetal corticosteroid metabolism, and children born of obese mothers have increased risk of diabetes and cardiovascular disease. The long-term effects of maternal obesity on offspring neurodevelopment are, however, undetermined and could depend on the specific effects on placental and fetal cortisol metabolism. This systematic review evaluates how maternal obesity affects placental cortisol metabolism and the offspring's HPA axis. Pubmed, Embase and Scopus were searched for original studies on maternal BMI, obesity, and cortisol metabolism and transfer. Fifteen studies were included after the screening of 4556 identified records. Studies were small with heterogeneous exposures and outcomes. Two studies found that maternal obesity reduced placental HSD11ß2 activity. In one study, umbilical cord blood cortisol levels were affected by maternal BMI. In three studies, an altered cortisol response was consistently seen among offspring in childhood (n = 2) or adulthood (n = 1). Maternal BMI was not associated with placental HSD11ß1 or HSD11ß2 mRNA expression, or placental HSD11ß2 methylation. In conclusion, high maternal BMI is associated with reduced placental HSD11ß2 activity and a dampened cortisol level among offspring, but the data is sparse. Further investigations are needed to clarify whether the HPA axis is affected by prenatal factors including maternal obesity and investigate if adverse effects can be ameliorated by optimising the intrauterine environment.

Polypharmacy in polymorbid pregnancies and the risk of congenital malformations-A systematic review.

With an increased prevalence of concurrent morbidities during pregnancy, polypharmacy has become increasingly common in pregnant women. The risks associated with polypharmacy may exceed those of individual medication because of drug-drug interactions. This systematic review aims to evaluate the risk of congenital malformations in polymorbid pregnancies exposed to first-trimester polypharmacy. PubMed, Embase and Scopus were searched to identify original human studies with first- trimester polypharmacy due to polymorbidity as the exposure and congenital malformations as the outcome. After screening of 4034 identified records, seven studies fulfilled the inclusion criteria. Four of the seven studies reported an increased risk of congenital malformations compared with unexposed or monotherapy, odds ratios ranging from 1.1 to >10.0. Particularly, short-term anti-infective treatment combined with other drugs and P-glycoprotein substrates were associated with increased malformation risks. In conclusion, knowledge is limited on risks associated with first-trimester polypharmacy due to polymorbidity with the underlying evidence of low quantity and quality. Therefore, an increased focus on pharmacovigilance to enable safe drug use in early pregnancy is needed. Large-scale register-based studies and better knowledge of placental biology are needed to support the clinical management of polymorbid pregnancies that require polypharmacy.

Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

INTRODUCTION: In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10 µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. MATERIAL AND METHODS: We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. RESULTS: Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75 nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43 ± 33nmol/L; n = 3; P = .006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65 ± 19 nmol/L; n = 8; P = .08) in third trimester compared with uncomplicated pregnancies (79 ± 22 nmol/L; n = 187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P = .009; n = 30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P = .67) and CYP27B1 (P = .34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P = .03) and positively correlated with placental mRNA expression of CYP24A1 (P = .003; n = 30). CONCLUSIONS: Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.

Use of stimulants, over-the-counter and prescription drugs among Danish pregnant women.

Using self-reports and blood samples from 225 unselected Danish first trimester pregnant women, the purpose of this study was to assess their use of stimulants, for example caffeine and nicotine as well as over-the-counter (OTC) and prescription drugs. According to self-reported information, 24% had used prescription drugs and 48% had used OTC drugs mainly acetaminophen (42%), 9.3% were habitual smokers, 44% stated a daily use of caffeinated beverages, and 1.3% used illegal drugs. Ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC-HR-TOFMS) analysis was performed on corresponding blood samples applying golden standards for use of UPLC-HR-TOFMS in forensic medicine. Traces of prescription drugs were detected in 5.3% of the samples and 8.9% contained OTC drugs (acetaminophen 7.1%). Traces of smoking were identified in 8.0%, caffeine in 83% and illegal drugs in 0.9%. These results indicate a substantial use of OTC drugs and caffeine among Danish pregnant women. Blood analysis indicated that many women could be unaware of their caffeine intake. As common substances may be associated with adverse pregnancy outcomes, healthcare professionals should inquire about such habits during pregnancy. The results also underline the need for more research into the molecular effects of such drugs on placental function and foetal development.

Use of alternative medicine, ginger and licorice among Danish pregnant women - a prospective cohort study.

BACKGROUND: The use of alternative medicines and dietary supplements is constantly changing, as are dietary habits. One example of this phenomenon is the current popularity of ginger products as an everyday health boost. Ginger and licorice has also been shown to ameliorate nausea a common complaint in early pregnancy. Alternative medicines are often regarded as safe. However, they might affect fetal development, such as through alterations of hormone metabolism and cytochrome P450 function. Health care professionals may be unaware of the supplementation habits of pregnant women, which may allow adverse exposures to go unnoticed, especially if the rates of use in pregnancy are not known. We therefore investigated the use of alternative medicines and licorice among pregnant Danish women. METHODS: A total of 225 pregnant women were included in a prospective cohort when attending the national prenatal screening program at gestational weeks 10-16. Participants were asked to complete a questionnaire regarding their socio-economic status and lifestyle habits, including their intake of alternative medicine and licorice. RESULTS: We found that 22.7% of women reported taking alternative medicines, with 14.7% reporting daily consumption. Ginger supplements were consumed by 11.1%, mainly as health boost and 87.1% reported consumption of licorice. Regular or daily licorice consumption was reported by 38.2 and 7.1%, respectively. Notably, the use of licorice was reflected by an increase in blood pressure of the pregnant women. CONCLUSIONS: The use of licorice and alternative medicines appears to be common in pregnant Danish women, supporting the need for further investigations into the safety of alternative medicine use during pregnancy and the importance of up-to-date personalized counseling regarding popular health trends and lifestyle habits.