Sleep disturbances in late pregnancy: associations with induction of labor.

PURPOSE: Sleep disturbances, which are common during pregnancy, may compromise labor. Nevertheless, little is known about associations between sleep disturbances and the likelihood of ending up induction of labor (IOL). Accordingly, we aimed to evaluate the connections between sleep disturbances during pregnancy and IOL. METHODS: Altogether 1778 women from the FinnBrain Birth Cohort Study with gestation weeks over 37 + 6 were enrolled in the study. The women were divided into IOL (n = 331) and spontaneous onset of labor (SOL, n = 1447) groups. Sleep disturbances in late pregnancy were evaluated using the Basic Nordic Sleep Questionnaire. Logistic regression analyses were conducted with adjustments for age, body mass index, parity, smoking, and depressive symptoms. RESULTS: Sleep disturbances were frequent in both IOL and SOL groups. In the IOL group 43.0% and in the SOL group 39.0% had poor general sleep quality (P = 0.186). Nocturnal awakenings occurred most commonly, in 94.0% and 93.9%, respectively (P = 0.653). In the IOL group, more women (22.7%) were habitual snorers than in the SOL group (17.0%, P = 0.017), however, the difference lost the statistical significance in adjusted analysis (P = 0.848). Women in the IOL group were more likely to be short sleepers (< 7 h) compared to those in the SOL group (20.2% and 15.4%, respectively, P = 0.034) with no difference after adjustment (P = 0.133). The two groups showed no differences in sleep loss (P = 0.252). CONCLUSIONS: Deterioration in sleep quality was noticeable in pregnant women, but it was unconnected with IOL. As the frequency of IOL is increasing, more research for related risk factors is needed.

Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Across ages and places: Unpredictability of maternal sensory signals and child internalizing behaviors.

BACKGROUND: Patterns of sensory inputs early in life play an integral role in shaping the maturation of neural circuits, including those implicated in emotion and cognition. In both experimental animal models and observational human research, unpredictable sensory signals have been linked to aberrant developmental outcomes, including poor memory and effortful control. These findings suggest that sensitivity to unpredictable sensory signals is conserved across species and sculpts the developing brain. The current study provides a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. We tested these associations in three independent cohorts to probe the generalizability of associations across continents and cultures. METHOD: The three prospective longitudinal cohorts were based in Orange, USA (n = 163, 47.2 % female, Mage = 1 year); Turku, Finland (n = 239, 44.8 % female, Mage = 5 years); and Irvine, USA (n = 129, 43.4 % female, Mage = 9.6 years). Unpredictability of maternal sensory signals was quantified during free-play interactions. Child internalizing behaviors were measured via parent report (Orange & Turku) and child self-report (Irvine). RESULTS: Early life exposure to unpredictable maternal sensory signals was associated with greater child fearfulness/anxiety in all three cohorts, above and beyond maternal sensitivity and sociodemographic factors. The association between unpredictable maternal sensory signals and child sadness/depression was relatively weaker and did not reach traditional thresholds for statistical significance. LIMITATIONS: The correlational design limits our ability to make causal inferences. CONCLUSIONS: Findings across the three diverse cohorts suggest that unpredictable maternal signals early in life shape the development of internalizing behaviors, particularly fearfulness and anxiety.

Latent profile analysis of diurnal cortisol patterns at the ages of 2, 3.5, and 5 years: Associations with childcare setting, child individual characteristics, and maternal distress.

This study performed latent profile analysis from more than 4000 saliva cortisol samples collected from children at the ages of 2 (T1), 3.5 (T2), and 5 years (T3). Three clearly different cortisol profiles were identified. The largest group at every age point was the Low/Regular latent profile, in which the cortisol slopes followed typical diurnal variation. A smaller proportion of the children belonged to the latent profile with relatively Low/Flat slope, and a minority belonged to the High/Fluctuating latent group, where the overall cortisol values and variations between the slopes were clearly higher than in the other groups. Most of the children who belonged to the High/Fluctuating group were cared for at home, they had higher temperamental surgency and their mothers had more depressive symptoms than in the other latent profile groups. However, only moderate intraindividual stability in diurnal cortisol profiles was observed across the follow-up period. On average, half of the children moved between the groups from T1 to T3. Neither child temperament, social competence, nor sex explained the stability or movement between the groups across age. Variations in cortisol profiles may be caused by the child's age, and diurnal cortisol rhythm becomes more regular along with development. Methodological issues regarding saliva cortisol research in young children are discussed. Also, more longitudinal research is needed to clarify mechanisms between environmental as well as individual factors and possible dysregulation in a child's HPA axis functioning.

Hair cortisol, cortisone and DHEA concentrations and the composition of microbiota in toddlers.

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research.

Long-term Outcome With Prolonged Use of Interferon-alpha Administered Intermittently for Metastatic Renal Cell Carcinoma: A Phase II Study.

BACKGROUND/AIM: Interferon-alpha (IFN-alpha) has shown survival benefits in metastatic renal cell carcinoma (mRCC), but the knowledge about long-term outcome is sparse. Additional knowledge is beneficial because IFN-alpha usage in combination therapy such as immune checkpoint inhibitor for mRCC is an area of interest. This is the longest follow-up concerning IFN-alpha treatment. PATIENTS AND METHODS: A total of 117 metastatic renal cell cancer (mRCC) patients without prior chemotherapy were enrolled between 1994-2002 and followed-up until January 2022. The median follow-up was 18 months. After progression to IFN-alpha, the patients were not treated with tyrosine kinase, mTOR inhibitors or bevacizumab as these were not standard therapies at that time or the patients' performance status was too poor. Mean treatment duration was 11 months. RESULTS: Median overall survival was 19.0 months, 5-year survival rate 16.2%, and 10-year survival rate 9.0%. There were statistically significant differences in survival in response to treatment (log-rank test, p<0.001): median overall survival was 52.0 months for objective responses, 25.0 months for stable disease and 5.0 months for progressive disease. Proportion of 5-year survivors was 29% in low, 20% in intermediate, and 7% in high-risk groups, respectively (p=0.001). CONCLUSION: With prolonged INF-alpha treatment stable and responding patients can obtain late objective responses, long-lasting complete responses, and long-term outcome with acceptable toxicity. IFN-alpha is an alternative therapy when multiple treatment lines are used for mRCC and an interesting option to study for combined therapies such as immune checkpoint inhibitor-based therapies.