Prenatal health behaviours as predictors of human placental lactogen levels.

Placental lactogen (hPL) is a key hormone of pregnancy responsible for inducing maternal adaptations critical for a successful pregnancy. Low levels of placental lactogen have been associated with lower birth weight as well as symptoms of maternal depression and anxiety. Lower placental lactogen has been reported in women with higher body mass index (BMI) but it is unclear whether prenatal health behaviours predict hPL levels or if hPL is associated with infant weight outcomes. This study utilised data from the longitudinal Grown in Wales cohort, based in South Wales. Participants were recruited at the pre-surgical appointment for an elective caesarean section. This study incorporates data from recruitment, post-delivery and a 12 month follow-up. Measures of maternal serum hPL were available for 248 participants. Analysis included unadjusted and adjusted linear and binary regression. Unadjusted, prenatal smoking and a Health Conscious dietary pattern were associated with hPL levels, however this was lost on adjustment for BMI at booking, Welsh Index of Multiple Deprivation (WIMD) score and placental weight. When stratified by maternal BMI at booking, a Health Conscious dietary pattern remained associated with increased hPL levels in women with a healthy BMI (p=.024, B=.59. 95% CI=.08,1.11) following adjustment for WIMD score and placental weight. When adjusted for a wide range of confounders, maternal hPL was also associated with increased custom birthweight centiles (CBWC) (p=.014, B=1.64. 95% CI=.33,2.94) and increased odds of large for gestational age deliveries (p=<.001, Exp(B)=1.42. 95% CI=1.17,1.72). This study identified that consuming a Health Conscious dietary pattern in pregnancy was associated with increased hPL, within women of a healthy BMI. Moreover, higher hPL levels were associated with increased CBWC and increased odds of delivering a large for gestational age infant. This improves the current limited evidence surrounding the nature of hPL in these areas.

Cord serum brain-derived neurotrophic factor levels at birth associate with temperament outcomes at one year.

Altered serum levels of brain-derived neurotrophic factor (BDNF) are consistently linked with neurological disorders. BDNF is also increasingly implicated in the pathogenesis of neurodevelopmental disorders, particularly those found more frequently in males. At birth, male infants naturally have significantly lower serum BDNF levels (∼10-20% lower than females), which may render them more vulnerable to neurodevelopmental disorders. We previously characterized serum BDNF levels in mothers and their newborn infants as part of the Grown in Wales Study. Here, we analyzed whether cord serum BDNF levels at birth correlate with sex-specific outcomes at one year. The Bayley Scale of Infant Development, Third Edition (BSID-III) and Laboratory Temperament Assessment Battery (Lab-TAB) tasks were used to assess infant behavior and neurodevelopment at 12-14 months (mean ± SD: 13.3 ± 1.6 months; 46% male; n = 56). We found no relationship between serum BDNF levels at birth and BSID-III neurodevelopmental outcomes (cognitive or language), nor with infant behaviors in the Lab-TAB unpredictable mechanical toy or maternal separation tasks. In the sustained attention task, there was a significant positive relationship between serum BDNF and infant negative affect (B = 0.06, p = 0.018) and, for boys only, between serum BDNF and intensity of facial interest (B = 0.03, p = 0.005). However, only the latter remained after correction for multiple testing. This sex-specific association between cord serum BDNF and a parameter of attention at 12-14 months provides some support for the hypothesis that reduced serum BDNF levels at birth are linked to an increased risk for neurodevelopmental disorders.

Symptoms of Prenatal Depression Associated with Shorter Telomeres in Female Placenta.

BACKGROUND: Depression is a common mood disorder during pregnancy impacting one in every seven women. Children exposed to prenatal depression are more likely to be born at a low birth weight and develop chronic diseases later in life. A proposed hypothesis for this relationship between early exposure to adversity and poor outcomes is accelerated aging. Telomere length has been used as a biomarker of cellular aging. We used high-resolution telomere length analysis to examine the relationship between placental telomere length distributions and maternal mood symptoms in pregnancy. METHODS: This study utilised samples from the longitudinal Grown in Wales (GiW) study. Women participating in this study were recruited at their presurgical appointment prior to a term elective caesarean section (ELCS). Women completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Telomere length distributions were generated using single telomere length analysis (STELA) in 109 term placenta (37-42 weeks). Multiple linear regression was performed to examine the relationship between maternally reported symptoms of depression and anxiety at term and mean placental telomere length. RESULTS: Prenatal depression symptoms were significantly negatively associated with XpYp telomere length in female placenta (B = -0.098, p = 0.026, 95% CI -0.184, -0.012). There was no association between maternal depression symptoms and telomere length in male placenta (B = 0.022, p = 0.586, 95% CI -0.059, 0.103). There was no association with anxiety symptoms and telomere length for either sex. CONCLUSION: Maternal prenatal depression is associated with sex-specific differences in term placental telomeres. Telomere shortening in female placenta may indicate accelerated placental aging.

The placenta protects the fetal circulation from anxiety-driven elevations in maternal serum levels of brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) plays crucial roles in brain function. Numerous studies report alterations in BDNF levels in human serum in various neurological conditions, including mood disorders such as depression. However, little is known about BDNF levels in the blood during pregnancy. We asked whether maternal depression and/or anxiety during pregnancy were associated with altered serum BDNF levels in mothers (n = 251) and their new-born infants (n = 212). As prenatal exposure to maternal mood disorders significantly increases the risk of neurological conditions in later life, we also examined the possibility of placental BDNF transfer by developing a new mouse model. We found no association between maternal symptoms of depression and either maternal or infant cord blood serum BDNF. However, maternal symptoms of anxiety correlated with significantly raised maternal serum BDNF exclusively in mothers of boys (r = 0.281; P = 0.005; n = 99). Serum BDNF was significantly lower in male infants than female infants but neither correlated with maternal anxiety symptoms. Consistent with this observation, we found no evidence for BDNF transfer across the placenta. We conclude that the placenta protects the developing fetus from maternal changes in serum BDNF that could otherwise have adverse consequences for fetal development.

Low serum placental lactogen at term is associated with postnatal symptoms of depression and anxiety in women delivering female infants.

BACKGROUND: Placental endocrine insufficiency may increase the risk of depression and anxiety during pregnancy and/or after birth. This study investigated the association between serum human placental lactogen (hPL) and measures of perinatal mental health, accounting for selective serotonin-reuptake inhibitor (SSRI) usage. METHOD: Caucasian women with singleton, term pregnancies recruited at their pre-surgical appointment prior to an elective caesarean section (ELCS) were studied. Serum hPL levels were measured by ELISA in maternal blood collected at the pre-surgical appointment. Depression and anxiety scores were derived from Edinburgh Postnatal Depression Scale (EPDS) and the trait subscale of the State-Trait Anxiety Inventory (STAI) questionnaires completed at recruitment and three postnatal time points. Data was analysed by unadjusted and adjusted multiple linear regression. RESULTS: In adjusted linear regressions, term maternal serum hPL levels were negatively associated with postnatal EPDS and STAI score ten weeks postnatal for mothers who had girls (B= -.367, p = .022, 95% CI -.679, -.056; and B= -.776, p = .030, 95% CI -1.475, -.077 respectively). Excluding women prescribed SSRIs strengthened the relationship at 10 weeks and uncovered an earlier association between hPL and mood scores within one week of delivery (EPDS B= -.357, p = .041, 95 % CI -.698, -.015; and STAI B= -.737, p = .027, 95 % CI -1.387, -.086). In mothers who had boys, there were no associations between hPL and mood scores at any time point. CONCLUSION: Low hPL at term associated with postnatal depression and anxiety symptoms exclusively in mothers of girls. Insufficiency in hPL may contribute to maternal mood symptoms.

Seasonal variation in salivary cortisol but not symptoms of depression and trait anxiety in pregnant women undergoing an elective caesarean section.

OBJECTIVES: Seasonal changes in mood and behaviour are commonly reported in the general population but considerably less is known regarding seasonality and pregnancy. This study investigated the relationship between seasons and depression and anxiety symptoms, salivary cortisol concentrations, custom birthweight centiles (CBWC) and placenta weight for pregnant women living in South Wales. METHODS: This study utilised data from the longitudinal Grown in Wales (GiW) cohort. Women were recruited at the presurgical elective caesarean section (ELCS) appointment, when they provided saliva samples and completed the Edinburgh Postnatal Depression Scale (EPDS) and trait subscale of the State-Trait Anxiety Inventory (STAI). Data on birthweight and placental weight was extracted from medical notes. Seasonal data was available for 316 participants. RESULTS: No association was identified between seasons and EPDS (p = .178), STAI scores (p = .544), CBWC (p = .683) or placental weight (p = .857). Significance was identified between seasons and salivary cortisol concentration (p<.001), with highest levels in autumn and winter. Adjusted linear regression identified spring (B=-.05, p=.007, 95% CI -.09, -.01) and summer (B=-.06, p = .001, 95% CI -09, -.02) compared to autumn, and spring (B=-.05, p=.009, 95% CI -.09, -.01) and summer (B=-.06, p=.002, 95% CI -.10, -.02) compared to winter to be associated with decreased cortisol concentrations. CONCLUSION: This study found no association between season and maternally-reported mental health symptoms, birthweight by CBWC or placental weight but did between season and term salivary cortisol. This finding will have implications for studies that do not account for seasonality when using salivary cortisol as a biomarker.

The Grown in Wales Study: Examining dietary patterns, custom birthweight centiles and the risk of delivering a small-for-gestational age (SGA) infant.

OBJECTIVES: Maternal lifestyles, including diet, have been linked to infant birthweight. However, customised birthweight centiles (CBWC), which more accurately identify small babies that have increased fetal growth restriction and are at higher risk of newborn morbidity and later life health complications, are rarely considered when studying maternal diet. This study investigated maternal dietary patterns and their impact on infant CBWC within a cohort of women living in South Wales. METHODS: This study utilised cross-sectional data from the longitudinal Grown in Wales (GiW) cohort. Women 18-45 years old were recruited the morning prior to an elective caesarean section (ELCS). Women completed a food frequency questionnaire (FFQ). Additional data on pregnancy and birth outcomes was extracted from medical notes. Data from 303 participants was analysed. RESULTS: 'Western' and 'Health conscious dietary patterns were identified. The 'Health Conscious' dietary pattern was significantly associated with maternal BMI, age, education, income and exercise. Adjusted regression analyses indicated that greater adherence to a 'Health Conscious' dietary pattern was significantly associated with increased CBWC (AOR = 4.75 [95% CI: 1.17, 8.33] p = .010) and reduced risk of delivering a small-for-gestational age (SGA) infant (AOR = .51 [95% CI: .26, .99] p = .046). CONCLUSION: A healthier diet was significantly associated with higher birthweight using CBWC and a reduced risk of delivering an SGA infant suggesting that birthweight will be improved in areas of Wales by focused support encouraging healthier dietary habits.

Persistence of anxiety symptoms after elective caesarean delivery.

BACKGROUND: In the UK, 11.8% of expectant mothers undergo an elective caesarean section (ELCS) representing 92 000 births per annum. It is not known to what extent this procedure has an impact on mental well-being in the longer term. AIMS: To determine the prevalence and postpartum progression of anxiety and depression symptoms in women undergoing ELCS in Wales. METHOD: Prevalence of depression and anxiety were determined in women at University Hospital Wales (2015-16; n = 308) through completion of the Edinburgh Postnatal Depression Scale (EPDS; ≥13) and State-Trait Anxiety Inventory (STAI; ≥40) questionnaires 1 day prior to ELCS, and three postpartum time points for 1 year. Maternal characteristics were determined from questionnaires and, where possible, confirmed from National Health Service maternity records. RESULTS: Using these criteria the prevalence of reported depression symptoms was 14.3% (95% CI 10.9-18.3) 1 day prior to ELCS, 8.0% (95% CI 4.2-12.5) within 1 week, 8.7% (95% CI 4.2-13.8) at 10 weeks and 12.4% (95% CI 6.4-18.4) 1 year postpartum. Prevalence of reported anxiety symptoms was 27.3% (95% CI 22.5-32.4), 21.7% (95% CI 15.8-28.0), 25.3% (95% CI 18.5-32.7) and 35.1% (95% CI 26.3-44.2) at these same stages. Prenatal anxiety was not resolved after ELCS more than 1 year after delivery. CONCLUSIONS: Women undergoing ELCS experience prolonged anxiety postpartum that merits focused clinical attention. DECLARATION OF INTEREST: None.