Postmenstrual Weeks Research Articles

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions

Introduction: The innate branch of the immune system is important in early life, in particular for infants born preterm. Methods: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively. Results: The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness. Conclusion: Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.

Increased enteral lipid supplementation is not associated with weight gain in extremely preterm infants with sufficient energy intakes.

Practices for fortifying human milk vary among neonatal intensive care units (NICUs). It is unclear whether enteral energy intake above 140 kcal/kg/day with increased fat supplementation leads to greater weight gain in breastmilk-fed extremely preterm (EPT) infants. Anthropometric and nutritional data were collected from clinical records for Swedish EPT infants born between gestational weeks 26 + 0 and 27 + 6. Included infants were treated at NICU A (n = 17) or NICU B (n = 39). The primary outcome was change in standard deviation (SD) scores (ΔSDS) for weight between postmenstrual weeks 29 + 0 and 34 + 0. At birth, the mean gestational age was 26.9 (±0.45 SD) weeks and the mean birthweight was 969 (±107 SD) g. Between postmenstrual weeks 29 + 0 and 33 + 6, the energy intake was significantly higher at NICU B: mean (SD) 149 (±14.9) versus 132 (±11.2) kcal/kg/day, p ≤ 0.001. This was driven by a higher fat intake at NICU B: mean (SD) 7.97 (±1.05) versus 6.20 (±0.92) g/kg/day, p ≤ 0.001, which in turn was explained by more liberal use of lipid supplements at NICU B. No significant differences were found in ΔSDS for weight, length or head circumference between the two NICUs. Despite considerable differences in energy intake due to the use of enteral lipid supplements, our study showed no differences in ΔSDS for weight, length or head circumference. This may be due to limited fat absorption in infants already receiving adequate energy and fat, and poor absorption of fat from human donor milk.

Characterizing normal perinatal development of the human brain structural connectivity.

Early brain development is characterized by the formation of a highly organized structural connectome, which underlies brain's cognitive abilities and influences its response to diseases and environmental factors. Hence, quantitative assessment of structural connectivity in the perinatal stage is useful for studying normal and abnormal neurodevelopment. However, estimation of the connectome from diffusion MRI data involves complex computations. For the perinatal period, these computations are further challenged by the rapid brain development, inherently low signal quality, imaging difficulties, and high inter-subject variability. These factors make it difficult to chart the normal development of the structural connectome. As a result, there is a lack of reliable normative baselines of structural connectivity metrics at this critical stage in brain development. In this study, we developed a computational method based on spatio-temporal averaging in the image space for determining such baselines. We used this method to analyze the structural connectivity between 33 and 44 postmenstrual weeks using data from 166 subjects. Our results unveiled clear and strong trends in the development of structural connectivity in the perinatal stage. We observed increases in measures of network integration and segregation, and widespread strengthening of the connections within and across brain lobes and hemispheres. We also observed asymmetry patterns that were consistent between different connection weighting approaches. Connection weighting based on fractional anisotropy and neurite density produced the most consistent results. Our proposed method also showed considerable agreement with an alternative technique based on connectome averaging. The new computational method and results of this study can be useful for assessing normal and abnormal development of the structural connectome early in life.

Establishing feasibility and reliability of subcutaneous fat measurements by ultrasound in very preterm infants.

Regional fat distribution may be a marker of metabolic health and brain growth in preterm infants. Point of care ultrasound has been used to assess regional fat in term infants but has not been used widely in preterm infants. To longitudinally quantify changes in body composition metrics using bedside ultrasound in very preterm infants. Very preterm infants (N = 69) were enrolled after birth and body composition assessments were done through 36 completed weeks' postmenstrual age (PMA). Linear mixed effects regression was used to model change in body composition assessments over time. There was an average increase across PMA for each body composition outcome. Biceps ultrasound subcutaneous fat (SQF) thickness increased by 0.11 mm (95% CI: 0.09, 0.13) each postmenstrual week. Triceps, subscapular, and abdominal ultrasound SQF remained constant through 28 weeks' PMA, then increased each week through 36 completed weeks' PMA. The inter-rater and intra-rater intraclass correlation coefficients for the ultrasound SQF measures ranged from 85.8 to 99.9. Use of ultrasound as a novel method to assess regional fat distribution in very preterm infants is feasible and reliable. Regional fat distribution may be a marker of metabolic health and brain growth in preterm infants. Gold standard body composition assessments may not be feasible in medically fragile very preterm infants. This study assesses longitudinally changes in regional adiposity development using bedside ultrasound techniques in a multicenter cohort of very preterm infants. Results of this study show that bedside ultrasound as a novel method to assess regional subcutaneous fat distribution and development in very preterm infants is both feasible and reliable.

No sex difference in maturation of brain morphology during the perinatal period.

Accumulating evidence have documented sex differences in brain anatomy from early childhood to late adulthood. However, whether sex difference of brain structure emerges in the neonatal brain and how sex modulates the development of cortical morphology during the perinatal stage remains unclear. Here, we utilized T2-weighted MRI from the Developing Human Connectome Project (dHCP) database, consisting of 41 male and 40 female neonates born between 35 and 43 postmenstrual weeks (PMW). Neonates of each sex were arranged in a continuous ascending order of age to capture the progressive changes in cortical thickness and curvature throughout the developmental continuum. The maturational covariance network (MCN) was defined as the coupled developmental fluctuations of morphology measures between cortical regions. We constructed MCNs based on the two features, respectively, to illustrate their developmental interdependencies, and then compared the network topology between sexes. Our results showed that cortical structural development exhibited a localized pattern in both males and females, with no significant sex differences in the developmental trajectory of cortical morphology, overall organization, nodal importance, and modular structure of the MCN. Furthermore, by merging male and female neonates into a unified cohort, we identified evident dependencies influences in structural development between different brain modules using the Granger causality analysis (GCA), emanating from high-order regions toward primary cortices. Our findings demonstrate that the maturational pattern of cortical morphology may not differ between sexes during the perinatal period, and provide evidence for the developmental causality among cortical structures in perinatal brains.

Functional connectome through the human life span.

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimer's disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

Profiling cortical morphometric similarity in perinatal brains: Insights from development, sex difference, and inter-individual variation

The topological organization of the macroscopic cortical networks important for the development of complex brain functions. However, how the cortical morphometric organization develops during the third trimester and whether it demonstrates sexual and individual differences at this particular stage remain unclear. Here, we constructed the morphometric similarity network (MSN) based on morphological and microstructural features derived from multimodal MRI of two independent cohorts (cross-sectional and longitudinal) scanned at 30–44 postmenstrual weeks (PMW). Sex difference and inter-individual variations of the MSN were also examined on these cohorts. The cross-sectional analysis revealed that both network integration and segregation changed in a nonlinear biphasic trajectory, which was supported by the results obtained from longitudinal analysis. The community structure showed remarkable consistency between bilateral hemispheres and maintained stability across PMWs. Connectivity within the primary cortex strengthened faster than that within high-order communities. Compared to females, male neonates showed a significant reduction in the participation coefficient within prefrontal and parietal cortices, while their overall network organization and community architecture remained comparable. Furthermore, by using the morphometric similarity as features, we achieved over 65 % accuracy in identifying an individual at term-equivalent age from images acquired after birth, and vice versa. These findings provide comprehensive insights into the development of morphometric similarity throughout the perinatal cortex, enhancing our understanding of the establishment of neuroanatomical organization during early life.

Development of neonatal connectome dynamics and its prediction for cognitive and language outcomes at age 2.

The functional brain connectome is highly dynamic over time. However, how brain connectome dynamics evolves during the third trimester of pregnancy and is associated with later cognitive growth remains unknown. Here, we use resting-state functional Magnetic Resonance Imaging (MRI) data from 39 newborns aged 32 to 42 postmenstrual weeks to investigate the maturation process of connectome dynamics and its role in predicting neurocognitive outcomes at 2years of age. Neonatal brain dynamics is assessed using a multilayer network model. Network dynamics decreases globally but increases in both modularity and diversity with development. Regionally, module switching decreases with development primarily in the lateral precentral gyrus, medial temporal lobe, and subcortical areas, with a higher growth rate in primary regions than in association regions. Support vector regression reveals that neonatal connectome dynamics is predictive of individual cognitive and language abilities at 2 years of age. Our findings highlight network-level neural substrates underlying early cognitive development.

Development of segregation and integration of functional connectomes during the first 1,000 days

The first 1,000days of human life lay the foundation for brain development and later cognitive growth. However, the developmental rules of the functional connectome during this critical period remain unclear. Using high-resolution, longitudinal, task-free functional magnetic resonance imaging data from 930 scans of 665 infants aged 28 postmenstrual weeks to 3 years, we report the early maturational process of connectome segregation and integration. We show the dominant development of local connections alongside a few global connections, the shift of brain hubs from primary regions to high-order association cortices, the developmental divergence of network segregation and integration along the anterior-posterior axis, the prediction of neurocognitive outcomes, and their associations with gene expression signatures of microstructural development and neuronal metabolic pathways. These findings advance our understanding of the principles of connectome remodeling during early life and its neurobiological underpinnings and have implications for studying typical and atypical development.

Seasonality of Infections Caused by Respiratory Viruses in Newborns and Their Relation to Meteorological Factors

Objectives − Most viral respiratory tract infections (VRTI) are seasonal diseases and frequently severely affect public health by causing seasonal epidemics and pandemics, also in newborns. The objective of this study was to analyse the relation of meteorological factors to the occurrence of neonatal VRTI and to estimate their predictive role for VRTI seasonality.Patients and methods − The retrospective observational cohort study enrolled 228 newborns (56% male and 29% preterm) aged up to 44 postmenstrual weeks, hospitalized due to acute VRTI between January 2015 and December 2020 in the central Slovenian region. The meteorological data for the same geographical region and time period were assessed, and correlation, multiple regression and cut-off values were analysed. Results − A typical seasonal distribution of VRTI from December to March was observed and the large majority of cases were due to respiratory syncytial virus (RSV) infection. Low air temperature, high relative humidity, shorter daily solar radiation and increased cloud cover were associated with an increased risk of neonatal, either RSV or non-RSV VRTI.Conclusions − Meteorological factors, particularly air temperature and relative humidity, were associated with neonatal VRTI occurrence in the temperate climate of central Slovenia. The average daily air temperature below 4.9 and 3.8 °C could predict the onset of the VRTI and RSV VRTI season, respectively. These factors could be used as real-time predictive warning, especially for RSV season onset and the need to begin RSV immunoprophylaxis in vulnerable newborns.

Association between patent ductus arteriosus flow and home oxygen therapy in extremely preterm infants

BackgroundCentral blood flow measurements include the estimation of right and left ventricular output (RVO, LVO), superior vena cava (SVC) flow, and calculated patent ductus arteriosus (PDA) flow. We aimed to provide an overview of the maturation patterns of these values and the relationship between PDA flow and the need for home oxygen therapy.MethodsThis prospective single-center study was conducted in infants born at <26 weeks of gestation. We performed echocardiographic measurements five times during their life (from the 4th post-natal day to the 36th postmenstrual week).ResultsSixty patients with a mean birth weight of 680 (590, 760) g were included. Postnatal development of LVO and PDA flow peaked at the end of the second postnatal week (427 and 66 mL/kg/min, respectively). The RVO increased between days 4 and 7–8. The SVCF was most stable. The development curves of PDA flow differed between the groups with (n = 28; 47%) and without home oxygen therapy.ConclusionWe present the central blood flow values and their postnatal development in infants <26 weeks of gestation. This study demonstrates the association between PDA flow and the future need for home oxygen therapy.ImpactThis study enriches our knowledge of the long-term development of central blood flow parameters and derived patent ductus arteriosus (PDA) flow in extremely preterm infants (<26 weeks).While pulmonary resistance decreased, PDA flow continued to increase from day 4 to the end of the second week of life. Similarly, left ventricular output increased as a marker of preload. The superior vena cava flow remained stable.The observed association between PDA flow and an unfavorable respiratory outcome is important for future studies focusing on the prevention of chronic lung disease.

Scaling patterns of cortical folding and thickness in early human brain development in comparison with primates.

Across mammalia, brain morphology follows specific scaling patterns. Bigger bodies have bigger brains, with surface area outpacing volume growth, resulting in increased foldedness. We have recently studied scaling rules of cortical thickness, both local and global, finding that the cortical thickness difference between thick gyri and thin sulci also increases with brain size and foldedness. Here, we investigate early brain development in humans, using subjects from the Developing Human Connectome Project, scanned shortly after pre-term or full-term birth, yielding magnetic resonance images of the brain from 29 to 43 postmenstrual weeks. While the global cortical thickness does not change significantly during this development period, its distribution does, with sulci thinning, while gyri thickening. By comparing our results with our recent work on humans and 11 non-human primate species, we also compare the trajectories of primate evolution with human development, noticing that the 2 trends are distinct for volume, surface area, cortical thickness, and gyrification index. Finally, we introduce the global shape index as a proxy for gyrification index; while correlating very strongly with gyrification index, it offers the advantage of being calculated only from local quantities without generating a convex hull or alpha surface.

High resolution and contrast 7 tesla MR brain imaging of the neonate.

Ultra-high field MR imaging offers marked gains in signal-to-noise ratio, spatial resolution, and contrast which translate to improved pathological and anatomical sensitivity. These benefits are particularly relevant for the neonatal brain which is rapidly developing and sensitive to injury. However, experience of imaging neonates at 7T has been limited due to regulatory, safety, and practical considerations. We aimed to establish a program for safely acquiring high resolution and contrast brain images from neonates on a 7T system. Images were acquired from 35 neonates on 44 occasions (median age 39 + 6 postmenstrual weeks, range 33 + 4 to 52 + 6; median body weight 2.93 kg, range 1.57 to 5.3 kg) over a median time of 49 mins 30 s. Peripheral body temperature and physiological measures were recorded throughout scanning. Acquired sequences included T2 weighted (TSE), Actual Flip angle Imaging (AFI), functional MRI (BOLD EPI), susceptibility weighted imaging (SWI), and MR spectroscopy (STEAM). There was no significant difference between temperature before and after scanning (p = 0.76) and image quality assessment compared favorably to state-of-the-art 3T acquisitions. Anatomical imaging demonstrated excellent sensitivity to structures which are typically hard to visualize at lower field strengths including the hippocampus, cerebellum, and vasculature. Images were also acquired with contrast mechanisms which are enhanced at ultra-high field including susceptibility weighted imaging, functional MRI, and MR spectroscopy. We demonstrate safety and feasibility of imaging vulnerable neonates at ultra-high field and highlight the untapped potential for providing important new insights into brain development and pathological processes during this critical phase of early life.

Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial

Mortality and severe morbidity remain high in extremely preterm infants. Human milk-based nutrient fortifiers may prevent serious complications and death. We aimed to investigate whether supplementation with human milk-based fortifier (HMBF), as compared to bovine milk-based fortifier (BMBF), reduced the incidence of the composite outcome of necrotising enterocolitis (NEC), sepsis, and mortality in extremely preterm infants exclusively fed human milk. In this multicentre, randomised controlled trial at 24 neonatal units in Sweden, extremely preterm infants born between gestational week 22+0 and 27+6 fed exclusively human breast milk (mother's own and/or donor milk), were randomly assigned (1:1) to receive targeted fortification with either HMBF or BMBF. Randomisation was conducted before the enteral feeds reached 100mL/kg/day, and was stratified by enrolment site, gestational age, singleton/twin, and sex. The allocation was concealed before inclusion, but after randomisation the study was not blinded for the clinical staff. For the NEC diagnosis, the study group was masked to an independent radiologist, and the final assessment of NEC and culture-proven sepsis was done by a blinded consensus panel review. The primary outcome was the composite of NEC stage II-III, culture-proven sepsis, and mortality from inclusion to discharge, no longer than postmenstrual week 44+0, in the intention-to-treat population (ClinicalTrials.gov, NCT03797157). Between February 21st, 2019, and May 21st, 2021, 229 neonates were randomly assigned (115 HMBF, 114 BMBF). After exclusion of one infant due to parents' withdrawal of consent, 228 infants were included in the intention-to-treat analysis. Of the 115 infants assigned to HMBF, 41 (35.7%) fulfilled the criteria of either NEC, sepsis, or death, compared with 39 (34.5%) of 113 infants assigned to BMBF (OR 1.05, 95% CI 0.61-1.81, p=0.86). Adverse events did not differ significantly between groups. Supplementation with HMBF, as compared with BMBF, did not reduce the incidence of the composite outcome of NEC, sepsis, or death. Our results do not support routine supplementation with HMBF as a nutritional strategy to prevent NEC, sepsis, or death in extremely preterm infants exclusively fed human milk. ALF grant, Prolacta Bioscience, Swedish Research Council, and Research Council for Southeast Sweden.

Development of the human medullary arcuate nucleus from mid-gestation to the perinatal period: A morphometric study

IntroductionDevelopment of the human medullary arcuate nucleus (AN) has not been sufficiently investigated. The present study provides morphometric data by examining the brains from preterm and perinatal infants. Materials and methodsNine brains were obtained from infants aged 21–43 postmenstrual weeks (PW). Serial celloidin sections were cut and stained using the Klüver–Barrera method. After microscopic observations, morphometric parameters [AN volume, numerical density (Nv) and total number (Nt) of neurons, and neuronal profile area (PA)] were analyzed. ResultsThe AN was found as a pair of neuronal masses on the ventral medullary surface at 21 PW. Caudally, it was ventrolateral to the pyramidal tract (PT), and rostrally, medial to the PT. In the middle, it was diminished in size or interrupted. The AN neurons were gradually enlarged with age, showing multiplicity in size and shape. The following findings had a marked asymmetry and individual variability: (1) complete or partial inclusion of the AN in the PT; (2) connection between the rostral AN and the pontine nuclei; (3) coexistence of pyknotic neurons. The AN volume increased exponentially with age, while the Nv decreased exponentially. The Nt changed along two phases (decrease–increase) after mid-gestation. The mean PA increased linearly with age. Asymmetry and/or individual variability were demonstrated in the AN volume, Nt, and mean PA. ConclusionsAsymmetry and individual variability in the AN morphology are present in fetal period. The AN may undergo neuron death and neuroblasts production in tandem after mid-gestation.

The Derivation of Epigastric Motion to Assess Neonatal Breathing and Sleep: An Exploratory Study.

New non-medical monitors are offered for respiration monitoring of neonates. Epigastric motion during sleep was investigated by means of a wearable tracker in parallel to clinical monitoring. 23 hospitalised neonates ready for discharge. A 3-axes-accelerometer and -gyroscope was placed in a standard epigastric position. Between two routine care rounds signals were recorded in parallel to monitoring of impedance pneumography (IP), ECG and pulse oximetry. Motion signals vs. time charts were evaluated using 10-min episodes and semiquantitatively assigned to breathing signal quality, regular breathing, periodic breathing and confounding artefacts. The results were compared with the impedance pneumographic data. 26 recordings (mean duration: 210 min/infant) were conducted without bradycardia or apnea alarm. The gestational age at birth ranged 28.9 to 41.1 and at recording from 35.6 to 42.3 postmenstrual weeks. Motion patterns of quiet sleep with regular breathing, periodic breathing and active sleep with confounding body movements were found. The longitudinal and transversal gyroscope axes resulted in best signal quality. Periodic breathing was found in up to 80% of episodes and decreased inversely with gestational age showing significantly more periodic breathing in preterm infants. Respiration signals of the gyroscope vs. IP showed a low bias and highly variating frequencies. Standardized motion trackers may detect typical neonatal breathing and body-motion-patterns, that could help to classify neonatal sleep. Respiratory rates can only be determined during quiet sleep.

Early development of the functional brain network in newborns.

During the prenatal period and the first postnatal years, the human brain undergoes rapid growth, which establishes a preliminary infrastructure for the subsequent development of cognition and behavior. To understand the underlying processes of brain functioning and identify potential sources of developmental disorders, it is essential to uncover the developmental rules that govern this critical period. In this study, graph theory modeling and network science analysis were employed to investigate the impact of age, gender, weight, and typical and atypical development on brain development. Local and global topologies of functional connectomes obtained from rs-fMRI data were collected from 421 neonates aged between 31 and 45 postmenstrual weeks who were in natural sleep without any sedation. The results showed that global efficiency, local efficiency, clustering coefficient, and small-worldness increased with age, while modularity and characteristic path length decreased with age. The normalized rich-club coefficient displayed a U-shaped pattern during development. The study also examined the global and local impacts of gender, weight, and group differences between typical and atypical cases. The findings presented some new insights into the maturation of functional brain networks and their relationship with cognitive development and neurodevelopmental disorders.

Dexmedetomidine versus fentanyl for sedation in extremely preterm infants.

Few studies have compared the efficacy and complications of dexmedetomidine (DEX) and fentanyl (FEN) in extremely preterm infants. We conducted a single-institution, retrospective controlled before and after study of preterm infants before 28 weeks of gestation admitted between April 2010 and December 2018 to compare the complications and efficacy of DEX and FEN for preterm infants. Patients were administered FEN prior to 2015 and DEX after 2015 as the first-line sedative. A composite outcome of death during hospitalization and developmental quotient (DQ) < 70 at a corrected age of 3 years was compared as the primary outcome. Secondary outcomes including postmenstrual weeks at extubation, days of age when full enteral feeding was achieved and additional sedation by phenobarbital (PB) were compared. Sixty-six infants were enrolled into the study. The only perinatal factor that differed between the FEN (n = 33) and DEX (n = 33) groups was weeks of gestation. The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different. Postmenstrual weeks at extubation did not significantly differ between groups after adjustment for weeks of gestation and being small for gestational age. On the other hand, full feeding was significantly prolonged by DEX (p = 0.031). Additional sedation was less common in the DEX group (p = 0.044). The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different by DEX or FEN for primary sedation. Prospective randomized controlled trials should examine the long-term effects on development.

Spatiotemporal Developmental Gradient of Thalamic Morphology, Microstructure, and Connectivity fromthe Third Trimester to Early Infancy.

Thalamus is a critical component of the limbic system that is extensively involved in both basic and high-order brain functions. However, how the thalamic structure and function develops at macroscopic and microscopic scales during the perinatal period development is not yet well characterized. Here, we used multishell high-angular resolution diffusion MRI of 144 preterm-born and full-term infants in both sexes scanned at 32-44 postmenstrual weeks (PMWs) from the Developing Human Connectome Project database to investigate the thalamic development in morphology, microstructure, associated connectivity, and subnucleus division. We found evident anatomic expansion and linear increases of fiber integrity in the lateral side of thalamus compared with the medial part. The tractography results indicated that thalamic connection to the frontal cortex developed later than the other thalamocortical connections (parieto-occipital, motor, somatosensory, and temporal). Using a connectivity-based segmentation strategy, we revealed that functional partitions of thalamic subdivisions were formed at 32 PMWs or earlier, and the partition developed toward the adult pattern in a lateral-to-medial pattern. Collectively, these findings revealed faster development of the lateral thalamus than the central part as well as a posterior-to-anterior developmental gradient of thalamocortical connectivity from the third trimester to early infancy.SIGNIFICANCE STATEMENT This is the first study that characterizes the spatiotemporal developmental pattern of thalamus during the third trimester to early infancy. We found that thalamus develops in a lateral-to-medial pattern for both thalamic microstructures and subdivisions; and thalamocortical connectivity develops in a posterior-to-anterior gradient that thalamofrontal connectivity appears later than the other thalamocortical connections. These findings may enrich our understanding of the developmental principles of thalamus and provide references for the atypical brain growth in neurodevelopmental disorders.

Relation between perinatal outcome and gestational duration in term primiparous pregnancies stratified by body mass index.

There is growing evidence that induction of labor at 41 completed weeks improves neonatal outcome, at least among primiparous women. This study was performed to investigate whether maternal body mass index (BMI) should be considered when deciding on timing of intervention in term pregnancies. The study design was a historical cohort study using data from the Swedish Medical Birth Register, singletons in cephalic presentation with births 39+0 to 41+6 weeks, with available information on maternal BMI 2005-2017 (n= 352 567). Modified Poisson regression analyses were used to investigate the association between gestational duration and stillbirth or death before 45 postmenstrual weeks (primary outcome) and Apgar score <7 at 5 minutes (secondary outcome) by BMI, respectively. Adjustments were made for maternal age, smoking, country of birth and educational level. The adjusted relative risk (ARR) of stillbirth or death before 45 weeks among infants born at 41+0 to 41+6 vs 40+0 to 40+6 weeks, was 1.26 with a 95% confidence interval (CI) of 1.07-1.48. Among women with BMI≥30, the offspring mortality risk in pregnancies lasting 39+0 to 39+2 weeks was significantly above the corresponding risk among women of normal BMI who delivered at 41+0 to 41+2 weeks (ARR=1.95; 95% CI 1.07-3.56) but no statistically significant heterogeneity was found regarding the magnitude of the association between gestational duration and offspring mortality. The ARR, for Apgar <7 at 5minutes (41+0 to 41+6 vs 40+0 to 40+6 weeks, regardless of BMI), was 1.36 (95% CI 1.27-1.45). The risk for low Apgar score at 41+0 weeks was 1.5% among all children regardless of maternal BMI. Among children to women with BMI≥30, this magnitude of risk was found already at 39+3 weeks. In primiparous women with obesity the risk of stillbirth or death before 45 postmenstrual weeks were increased throughout all full-term gestational age categories, compared with women with overweight or normal BMI. Children to obese women had the same risk for Apgar scores <7 at 5minutes compared with women overall at earlier gestational age. The results suggest that maternal BMI needs to be considered when discussing timing of elective induction in term healthy pregnancies of primiparous women.