Associations between interpregnancy interval and preterm birth by previous preterm birth status in four high-income countries: a cohort study.

OBJECTIVE: To investigate the effect of interpregnancy interval (IPI) on preterm birth (PTB) according to whether the previous birth was preterm or term. DESIGN: Cohort study. SETTING: USA (California), Australia, Finland, Norway (1980-2017). POPULATION: Women who gave birth to first and second (n = 3 213 855) singleton livebirths. METHODS: Odds ratios (ORs) for PTB according to IPIs were modelled using logistic regression with prognostic score stratification for potential confounders. Within-site ORs were pooled by random effects meta-analysis. OUTCOME MEASURE: PTB (gestational age <37 weeks). RESULTS: Absolute risk of PTB for each IPI was 3-6% after a previous term birth and 17-22% after previous PTB. ORs for PTB differed between previous term and preterm births in all countries (P-for-interaction ≤ 0.001). For women with a previous term birth, pooled ORs were increased for IPI <6 months (OR 1.50, 95% CI 1.43-1.58); 6-11 months (OR 1.10, 95% CI 1.04-1.16); 24-59 months (OR 1.16, 95% CI 1.13-1.18); and ≥ 60 months (OR 1.72, 95%CI 1.60-1.86), compared with 18-23 months. For previous PTB, ORs were increased for <6 months (OR 1.30, 95% CI 1.18-1.42) and ≥60 months (OR 1.29, 95% CI 1.17-1.42), but were less than ORs among women with a previous term birth (P < 0.05). CONCLUSIONS: Associations between IPI and PTB are modified by whether or not the previous pregnancy was preterm. ORs for short and long IPIs were higher among women with a previous term birth than a previous PTB, which for short IPI is consistent with the maternal depletion hypothesis. Given the high risk of recurrence and assuming a causal association between IPI and PTB, IPI remains a potentially modifiable risk factor for women with previous PTB. TWEETABLE ABSTRACT: Short versus long interpregnancy intervals associated with higher ORs for preterm birth (PTB) after a previous PTB

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Beyond the Global Brain Differences: Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure. Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference. Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness. Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment

Genetic variants for head size share genes and pathways with cancer

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

A particular effect of sleep, but not pain or depression, on the blood-oxygen-level dependent response during working memory tasks in patients with chronic pain

Nicolas A Elvemo,1 Nils I Landr&oslash;,2,3 Petter C Borchgrevink,3,4 Asta K H&aring;berg1,5 1Department of Neuroscience, Medical Faculty, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 2Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway; 3Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 4National Norwegian Advisory Unit for Complex Disorders, St Olav University Hospital, Trondheim, Norway; 5Department of Medical Imaging, St Olav University Hospital, Trondheim, Norway Background: Patients with chronic pain (CP) are often reported to have deficits in working memory. Pain impairs working memory, but so do depression and sleep problems, which are also common in CP. Depression has been linked to changes in brain activity in CP during working memory tasks, but the effect of sleep problems on working memory performance and brain activity remains to be investigated. Methods: Fifteen CP patients and 17 age-, sex-, and education-matched controls underwent blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging at 3T while performing block design 0-back, 2-back, and paced visual serial addition test paradigms. Subjects also reported their level of pain (Brief Pain Inventory), depression (Beck Depression Inventory II), and sleep problems (Pittsburgh Sleep Quality Index) and were tested outside the scanner with neuropsychological tests of working memory. Results: The CP group reported significantly higher levels of pain, depression, and sleep problems. No significant performance difference was found on the neuropsychological tests in or outside the scanner between the two groups. There were no correlations between level of pain, depression, and sleep problems or between these and the neuropsychological test scores. CP patients exhibited significantly less brain activation and deactivation than controls in parietal and frontal lobes, which are the brain areas that normally show activation and deactivation during working memory tasks. Sleep problems independently and significantly modulated the BOLD response to the complex working memory tasks and were associated with decreased brain activation in task-positive regions and decreased deactivation in the default mode network in the CP group compared to the control group. The pain and depression scores covaried with working memory activation. Discussion: Sleep problems in CP patients had a significant impact on the BOLD response during working memory tasks, independent of pain level and depression, even when performance was shown not to be significantly affected. Keywords: magnetic resonance imaging, 2-back, serial addition test, deactivation, activatio

Patients with chronic pain lack somatic markers during decision-making

Nicolas-Andreas Elvemo,1 Kristian Bernhard Nilsen,1,2 Nils Inge Landr&oslash;,3,4 Petter Christian Borchgrevink,4,5 Asta Kristine H&aring;berg1,6 1Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; 2Department of Neurology, Section for Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway; 3Clinical Neuroscience Research Group, Department of Psychology, University of Oslo, Oslo, Norway; 4Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 5Department of Anesthesiology, St Olav University Hospital, Trondheim, Norway; 6Department of Medical Imaging, St Olav University Hospital, Trondheim, Norway Abstract: Patients with chronic pain have impaired cognitive functions, including decision making, as shown with the Iowa gambling task (IGT). The main aim of this study was to elucidate whether patients&#39; decision making is associated with a lack of the anticipatory skin conductance response (SCR). An increase in anticipatory SCR before making unfavorable choices is known to guide decisions in healthy controls during the IGT. Since several brain regions involved in decision making are reported to have altered morphology in patients with chronic pain, the second aim was to explore the associations between IGT performance and brain structure volumes. Eighteen patients with chronic pain of mixed etiology and 19 healthy controls matched in terms of age, sex, and education were investigated with a computerized IGT during the recording of SCR, heart rate, and blood pressure. The participants also underwent neuropsychological testing, and three-dimensional T1-weighted cerebral magnetic resonance images were obtained. Contrary to controls, patients did not generate anticipatory SCRs before making unfavorable choices, and they switched between decks of cards during the late phase of the IGT significantly more often, and this was still observed after adjusting for depression scores. None of the other autonomic measures differed during IGT performance in either group or between groups. In patients, IGT scores correlated positively with total cortical grey matter volume. In controls, there was no such association, but their IGT scores correlated with the anticipatory SCR. It may be speculated that the reduction in anticipatory SCRs makes the chronic pain patients rely more on cortical resources during decision making. Keywords: Iowa gambling task, skin conductance response, autonomic measures, magnetic resonance imaging, corte