Does social need fulfillment moderate the association between socioeconomic status and health risk behaviours during pregnancy?

Socioeconomic differences in health risk behaviours during pregnancy may be influenced by social relations. In this study, we aimed to investigate if social need fulfillment moderates the association between socioeconomic status (SES) and health risk behaviours (smoking and/or alcohol consumption) during pregnancy. We used baseline data from the Lifelines Cohort Study merged with data from the Lifelines Reproductive Origin of Adult Health and Disease (ROAHD) cohort. Education level was used to determine SES, categorized into low, middle, and high, with middle SES as the reference category. Social need fulfillment was taken as indicator for social relations and was measured with the validated Social Production Function Instrument for the Level of Well-being scale. The dependent variable was smoking and/or alcohol consumption during pregnancy. Univariable and multivariable logistic regression analysis was conducted to assess the association of SES and social need fulfillment with health risk behaviours and to test for effect modification. We included 1107 pregnant women. The results showed that women with a high SES had statistically significantly lower odds of health risk behaviours during pregnancy. The interaction effect between SES and social need fulfillment on health risk behaviours was not statistically significant, indicating that no moderation effect is present. The results indicate that social need fulfillment does not modify the effect of SES on health risk behaviours during pregnancy. However, in literature, social relations are identified as an important influence on health risk behaviours. More research is needed to identify which measure of social relations is the most relevant regarding the association with health risk behaviours.

Adverse Maternal and Infant Outcomes of Women Who Differ in Smoking Status: E-Cigarette and Tobacco Cigarette Users.

The electronic cigarette (e-cigarette) became commercially available around 2004, yet the characteristics of pregnant women who use these devices and their effects on maternal and infant health remain largely unknown. This study aimed to investigate maternal characteristics and pregnancy outcomes according to maternal smoking status. We conducted a cross-sectional study of Dutch women with reported pregnancies between February 2019 and May 2022, using an online questionnaire to collect data on smoking status and demographic, lifestyle, pregnancy, and infant characteristics. Smoking status is compared among non-smokers, tobacco cigarette users, e-cigarette users, and dual users (tobacco and e-cigarette). We report descriptive statistics and calculate differences in smoking status between women with the chi-square or Fisher (Freeman-Halton) test. Of the 1937 included women, 88.1% were non-smokers, 10.8% were tobacco cigarette users, 0.5% were e-cigarette users, and 0.6% were dual users. Compared with tobacco users, e-cigarette users more often reported higher education, having a partner, primiparity, and miscarriages. Notably, women who used e-cigarettes more often had small infants for gestational age. Despite including few women in the e-cigarette subgroup, these exploratory results indicate the need for more research to examine the impact of e-cigarettes on pregnancy outcomes.

Offspring Birth Weight Is Associated with Specific Preconception Maternal Food Group Intake: Data from a Linked Population-Based Birth Cohort.

The preconception period has been recognized as one of the earliest sensitive windows for human development. Maternal dietary intake during this period may influence the oocyte quality, as well as placenta and early embryonic development during the first trimester of pregnancy. Previous studies have found associations between macronutrient intake during preconception and pregnancy outcomes. However, as food products consist of multiple macro- and micronutrients, it is difficult to relate this to dietary intake behavior. Therefore, the aim of this study was to investigate the association between intake of specific food groups during the preconception period with birth weight, using data from the Perined-Lifelines linked birth cohort. The Perined-Lifelines birth cohort consists of women who delivered a live-born infant at term after being enrolled in a large population-based cohort study (The Lifelines Cohort). Information on birth outcome was obtained by linkage to the Dutch perinatal registry (Perined). In total, we included 1698 women with data available on birth weight of the offspring and reliable detailed information on dietary intake using a semi-quantitative food frequency questionnaire obtained before pregnancy. Based on the 2015 Dutch Dietary Guidelines and recent literature 22 food groups were formulated. Birth weight was converted into gestational age-adjusted z-scores. Multivariable linear regression was performed, adjusted for intake of other food groups and covariates (maternal BMI, maternal age, smoking, alcohol, education level, urbanization level, parity, sex of newborn, ethnicity). Linear regression analysis, adjusted for covariates and intake of energy (in kcal) (adjusted z score [95% CI], P) showed that intake of food groups "artificially sweetened products" and "vegetables" was associated with increased birth weight (resp. (ß = 0.001 [95% CI 0.000 to 0.001, p = 0.002]), (ß = 0.002 [95% CI 0.000 to 0.003, p = 0.03])). Intake of food group "eggs" was associated with decreased birth weight (ß = -0.093 [95% CI -0.174 to -0.013, p = 0.02]). Intake in food groups was expressed in 10 g per 1000 kcal to be able to draw conclusions on clinical relevance given the bigger portion size of the food groups. In particular, preconception intake of "artificially sweetened products" was shown to be associated with increased birth weight. Artificial sweeteners were introduced into our diets with the intention to reduce caloric intake and normalize blood glucose levels, without compromising on the preference for sweet food products. Our findings highlight the need to better understand how artificial sweeteners may affect the metabolism of the mother and her offspring already from preconception onwards.

Altered Levels of Decidual Immune Cell Subsets in Fetal Growth Restriction, Stillbirth, and Placental Pathology.

Immune cells are critically involved in placental development and functioning, and inadequate regulation of the maternal immune system is associated with placental pathology and pregnancy complications. This study aimed to explore numbers of decidual immune cells in pregnancies complicated with fetal growth restriction (FGR) and stillbirth (SB), and in placentas with histopathological lesions: maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), delayed villous maturation (DVM), chorioamnionitis (CA), and villitis of unknown etiology (VUE). Placental tissue from FGR (n = 250), SB (n = 64), and healthy pregnancies (n = 42) was included. Histopathological lesions were classified according to criteria developed by the Amsterdam Placental Workshop Group. Tissue slides were stained for CD68 (macrophages), CD206 (M2-like macrophages), CD3 (T cells), FOXP3 [regulatory T (Treg) cells], and CD56 [natural killer (NK) cells]. Cell numbers were analyzed in the decidua basalis using computerized morphometry. The Mann-Whitney U-test and Kruskal Wallis test with the Dunn's as post-hoc test were used for statistical analysis. Numbers of CD68+ macrophages were higher in FGR compared to healthy pregnancies (p < 0.001), accompanied by lower CD206+/CD68+ ratios (p < 0.01). In addition, in FGR higher numbers of FOXP3+ Treg cells were seen (p < 0.01) with elevated FOXP3+/CD3+ ratios (p < 0.01). Similarly, in SB elevated FOXP3+ Treg cells were found (p < 0.05) with a higher FOXP3+/CD3+ ratio (p < 0.01). Furthermore, a trend toward higher numbers of CD68+ macrophages was found (p < 0.1) in SB. Numbers of CD3+ and FOXP3+ cells were higher in placentas with VUE compared to placentas without lesions (p < 0.01 and p < 0.001), accompanied by higher FOXP3+/CD3+ ratios (p < 0.01). Elevated numbers of macrophages with a lower M2/total macrophage ratio in FGR suggest a role for a macrophage surplus in its pathogenesis and could specifically indicate involvement of inflammatory macrophages. Higher numbers of FOXP3+ Treg cells with higher Treg/total T cell ratios in VUE may be associated with impaired maternal-fetal tolerance and a compensatory response of Treg cells. The abundant presence of placental lesions in the FGR and SB cohorts might explain the increase of Treg/total T cell ratios in these groups. More functionality studies of the observed altered immune cell subsets are needed.

Lower FOXP3 mRNA Expression in First-Trimester Decidual Tissue from Uncomplicated Term Pregnancies with a Male Fetus.

Pregnancies with a male fetus are associated with higher risks of pregnancy complications through maladaptation of the maternal immune system. The pathophysiology of this phenomenon is unknown. A possible pathway could be a fetal sex-dependent maternal immune response, since males have a Y chromosome encoding specific allogenic proteins, possibly contributing to a different response and higher complication risks. To analyze whether fetal sex affects mRNA expression of maternal immune genes in early pregnancy, real-time PCR quantification was performed in the decidual tissue from primigravid pregnancies (n = 20) between 10 and 12 weeks with uncomplicated term outcomes. Early-pregnancy decidual mRNA expression of the regulatory T-cell marker, FOXP3, was sixfold lower (p < 0.01) in pregnancies with a male fetus compared to pregnancies with a female fetus. Additionally, mRNA expression of IFNγ was sixfold (p < 0.05) lower in pregnancies with a male fetus. The present data imply maternal immunologic differences between pregnancies with male and female fetuses which could be involved in different pregnancy pathophysiologic outcomes. Moreover, this study indicates that researchers in reproductive immunology should always consider fetal sex bias.

Seasonality of hypertensive disorders of pregnancy - A South Australian population study.

OBJECTIVES: To investigate the seasonal variation of hypertensive disorders of pregnancy (HDP) in South Australia. STUDY DESIGN: Retrospective population study including all 107,846 liveborn singletons during 2007-2014 in South Australia. Seasonality in incidence of HDP in relation to estimated date of conception (eDoC) and date of birth (DoB) were examined using Fourier series analysis. MAIN OUTCOME MEASURES: Seasonality of HDP in relation to eDoC and DoB. RESULTS: During 2007-2014, the incidence of HDP was 7.1% (n = 7,612). Seasonal modeling showed a strong relationship between HDP and eDoC (p < .001) and DoB (p < .001). Unadjusted and adjusted models (adjusted for maternal age, body mass index, ethnicity, parity, type of health care, smoking and gestational diabetes mellitus) demonstrated the presence of a peak incidence (7.8%, 7.9% respectively) occurring among pregnancies with eDoC in late Spring (November) and a trough (6.4% and 6.3% respectively) among pregnancies with eDoC in late Autumn (May). Both unadjusted and adjusted seasonal modelling showed a peak incidence of HDP for pregnancies with DoB in August (8.0%, 8.1% respectively) and a nadir among pregnancies with eDoB in February (6.2%). CONCLUSION: The highest incidence of HDP was associated with pregnancies with eDoC during late spring and summer and birth in winter, while the lowest incidence of HDP was associated with pregnancies with eDoC during late autumn and early winter and birth in summer. Nutrient intake, in particular vitamin D, sunlight exposure and physical activity may affect maternal, fetal and placental adaptation to pregnancy and are potential contributors to the seasonal variation of HDP.

Long-term Trends in Singleton Preterm Birth in South Australia From 1986 to 2014.

OBJECTIVE: To describe long-term trends in the prevalence of preterm birth and rates of preterm birth in singleton pregnancies complicated by hypertensive disorders of pregnancy, small for gestational age (SGA), and preterm prelabor rupture of membranes (PROM) in South Australia. METHODS: We conducted a retrospective population study including all singleton live births in the state of South Australia from 1986 to 2014. Long-term trends for preterm birth, hypertensive disorders of pregnancy, SGA, preterm PROM as well as stillbirth were assessed using joinpoint regression analyses. Trends in maternal age, body mass index (BMI), ethnic diversity, parity, and smoking over time were also assessed. RESULTS: From 1986 to 2014, with a total of 539,234 singleton births, the overall preterm birth rates increased from 5.1% to 7.1% (P<.001) and for iatrogenic preterm birth increased from 1.6% to 3.2% (P<.001). The incidence of hypertensive disorders of pregnancy decreased from 8.7% to 7.2%. Among pregnancies complicated by hypertensive disorders of pregnancy, the proportion of preterm birth increased (10.4-17.5%, P<.001). The incidence of SGA decreased from 11.1% to 8.0%. Among pregnancies complicated by SGA, the proportion of preterm birth increased (2.9-5.4%, P<.001). The incidence of preterm PROM increased from 1.4% to 2.2%. Among pregnancies complicated by preterm PROM, the proportion of preterm birth remained stable. Preterm stillbirth rates declined (4.23-2.32%, P<.001). Maternal age, BMI, and ethnic diversity have all increased since 1986, whereas maternal smoking has decreased. CONCLUSION: In South Australia, the preterm birth rate among singletons increased from 1986 to 2014 by 40%, with iatrogenic preterm birth being responsible for 80% of this increase. Incidence of hypertensive disorders of pregnancy and SGA declined. Among pregnancies complicated by hypertensive disorders of pregnancy and SGA, the proportions of preterm birth increased, indicating earlier interventions in these women. The diagnosis of preterm PROM increased from 1% to 2%, and greater than 80% of preterm PROM was associated with preterm birth after 1990. Increasing iatrogenic delivery may be attributable, in part, to changing maternal phenotype and to altered clinicians' behavior. However, improvements in fetal surveillance, particularly ultrasonography, and advanced neonatal care may underpin perinatal clinical decision-making and the likelihood of iatrogenic birth.

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells.

OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor α (PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin (ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. CONCLUSIONS: This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

DNA Methylation and Expression Patterns of Selected Genes in First-Trimester Placental Tissue from Pregnancies with Small-for-Gestational-Age Infants at Birth.

Variations in DNA methylation levels in the placenta are thought to influence gene expression and are associated with complications of pregnancy, like fetal growth restriction (FGR). The most important cause for FGR is placental dysfunction. Here, we examined whether changes in DNA methylation, followed by gene expression changes, are mechanistically involved in the etiology of FGR. In this retrospective case-control study, we examined the association between small-for-gestational-age (SGA) children and both DNA methylation and gene expression levels of the genes WNT2, IGF2/H19, SERPINA3, HERVWE1, and PPARG in first-trimester placental tissue. We also examined the repetitive element LINE-1. These candidate genes have been reported in the literature to be associated with SGA. We used first-trimester placental tissue from chorionic villus biopsies. A total of 35 SGA children (with a birth weight below the 10th percentile) were matched to 70 controls based on their gestational age. DNA methylation levels were analyzed by pyrosequencing and mRNA levels were analyzed by real-time PCR. None of the average DNA methylation levels, measured for each gene, showed a significant difference between SGA placental tissue compared to control tissue. However, hypermethylation of WNT2 was detected on two CpG positions in SGA. This was not associated with changes in gene expression. Apart from two CpG positions of the WNT2 gene, in early placenta samples, no evident changes in DNA methylation or expression were found. This indicates that the already reported changes in term placenta are not present in the early placenta, and therefore must arise after the first trimester.

Smoking during pregnancy influences the maternal immune response in mice and humans.

OBJECTIVE: During pregnancy the maternal immune system has to adapt its response to accommodate the fetus. The objective of this study was to analyze the effects of smoking on the maternal immune system. STUDY DESIGN: First-trimester decidual tissue and peripheral blood of smoking and nonsmoking women were analyzed by real time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry. A mouse model was used to further analyze the effects of smoking. Murine tissue was analyzed by flow cytometry, real-time RT-PCR, and immunohistochemistry. RESULTS: Smoking caused lower percentages of viable pups in mice and lower birthweights in humans. Smoking mothers, both mice and human, had more natural killer cells and inflammatory macrophages locally, whereas systemically they had lower percentages of regulatory T cells than nonsmoking controls. CONCLUSION: Maternal smoke exposure during pregnancy influences local and systemic immune responses in both women and mice. Such changes may be involved in adverse pregnancy outcomes in smoking individuals.

Stillbirths: the way forward in high-income countries.

Stillbirth rates in high-income countries declined dramatically from about 1940, but this decline has slowed or stalled over recent times. The present variation in stillbirth rates across and within high-income countries indicates that further reduction in stillbirth is possible. Large disparities (linked to disadvantage such as poverty) in stillbirth rates need to be addressed by providing more educational opportunities and improving living conditions for women. Placental pathologies and infection associated with preterm birth are linked to a substantial proportion of stillbirths. The proportion of unexplained stillbirths associated with under investigation continues to impede efforts in stillbirth prevention. Overweight, obesity, and smoking are important modifiable risk factors for stillbirth, and advanced maternal age is also an increasingly prevalent risk factor. Intensified efforts are needed to ameliorate the effects of these factors on stillbirth rates. Culturally appropriate preconception care and quality antenatal care that is accessible to all women has the potential to reduce stillbirth rates in high-income countries. Implementation of national perinatal mortality audit programmes aimed at improving the quality of care could substantially reduce stillbirths. Better data on numbers and causes of stillbirth are needed, and international consensus on definition and classification related to stillbirth is a priority. All parents should be offered a thorough investigation including a high-quality autopsy and placental histopathology. Parent organisations are powerful change agents and could have an important role in raising awareness to prevent stillbirth. Future research must focus on screening and interventions to reduce antepartum stillbirth as a result of placental dysfunction. Identification of ways to reduce maternal overweight and obesity is a high priority for high-income countries.

Parental factors affecting the weights of the placenta and the offspring.

AIM: To determine parental, especially paternal factors associated with the weight of the placenta and offspring. METHODS: This population-based birth-cohort study includes 2947 singleton children born from April 2006 to 2007 and living in Drenthe, The Netherlands. Placental weight and birth weight were measured and questionnaires were filled out for this cohort. Associations between parental factors, and the weight of the placenta and the offspring were evaluated using univariate and multivariate linear regression models. RESULTS: Univariate regression revealed that the paternal birth weight and body mass index (BMI) of the father were predictors for placental and birth weight of the offspring. However, they were not independent predictors. Independent predictors for placental weight were the maternal factors of pre-pregnancy BMI, birth weight, and diabetes. The maternal factors of weight gain during pregnancy, birth weight, smoking during pregnancy, and diabetes were independent predictors for birth weight of the offspring. CONCLUSION: Paternal as well as maternal factors influence the weight of the placenta and the offspring.

Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants.

DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movements at 3 months have been associated with a non-optimal current brain condition. We investigated whether supplementation of DHA during pregnancy and lactation influences the infant's brain development and whether additional AA modulates this effect. Healthy women were randomly assigned to DHA (220 mg/d, n 42), DHA+AA (220 mg each/d, n 41) or control (n 36), from about week 17 (range 14-20 weeks) of pregnancy until 12 weeks postpartum. The control and the DHA+AA groups had approximately comparable dietary DHA/AA ratios. The standardised neonatal neurological examination was carried out at 2 weeks. General movement quality was assessed at 2 and 12 weeks. Neither DHA alone nor DHA+AA influenced outcomes in the traditional examination. General movement quality of infants in the DHA group was lower than that of infants in the other two groups, especially at 12 weeks: 61 % of the infants in the DHA group showed mildly abnormal general movements compared with 31 % in the control group (P = 0.008) and 34 % in the DHA+AA group (P = 0.015). We conclude that general movement quality at 12 weeks is sensitive to the maternal dietary DHA/AA balance.