Project description:BackgroundOur understanding of the normative concentrations of urine biomarkers in premature neonates is limited.MethodsWe evaluated urine from 750 extremely low gestational age (GA) neonates without severe acute kidney injury (AKI) to determine how GA affects ten different urine biomarkers at birth and over the first 30 postnatal days. Then, we investigated if the urine biomarkers changed over time at 27, 30, and 34 weeks postmenstrual age (PMA). Next, we evaluated the impact of sex on urine biomarker concentrations at birth and over time. Finally, we evaluated if urine biomarkers were impacted by treatment with erythropoietin (Epo).ResultsWe found that all ten biomarker concentrations differ at birth by GA and that some urine biomarker concentrations increase, while others decrease over time. At 27 weeks PMA, 7/10 urine biomarkers differed by GA. By 30 weeks PMA, 5/10 differed, and by 34 weeks PMA, only osteopontin differed by GA. About half of the biomarker concentrations differed by sex, and 4/10 showed different rates of change over time between males vs. females. We found no differences in urine biomarkers by treatment group.ConclusionsThe temporal patterns, GA, and sex differences need to be considered in urine AKI biomarker analyses.ImpactUrine biomarker concentrations differ by GA at birth. Some urine biomarkers increase, while others decrease, over the first 30 postnatal days. Most urine biomarkers differ by GA at 27 weeks PMA, but are similar by 34 weeks PMA. Some urine biomarkers vary by sex in premature neonates. Urine biomarkers did not differ between neonates randomized to placebo vs. Epo.
Project description:Children born small for gestational age have a higher risk of intellectual disability. We investigated associations of birth weight for gestational age percentile and gestational age with risk of intellectual disability in appropriate-for-gestational-age (AGA) children. We included 828,948 non-malformed term or post-term AGA singleton children (including 429,379 full siblings) born between 1998 and 2009 based on data from the Swedish Medical Birth Register. Diagnosis of intellectual disability after 3 years of age was identified through the Patient Register. Using Cox regression models, we calculated hazard ratios (HRs) with 95% confidence intervals (CIs) of intellectual disability among children with different birth weight percentiles and gestational age in the whole population and in a subpopulation of full siblings. A total of 1688 children were diagnosed with intellectual disability during follow-up. HRs (95% CIs) of intellectual disability for the low birth weight percentile groups (10th-24th and 25th-39th percentiles, respectively) versus the reference group (40th-59th percentiles) were 1.43 (1.22-1.67) and 1.28 (1.10-1.50) in population analysis and 1.52 (1.00-2.31) and 1.44 (1.00-2.09) in sibling comparison analysis. The increased risk for low birth weight percentiles in population analysis was stable irrespective of gestational age. A weak U-shaped association between gestational age and intellectual disability was observed in population analysis, although not in sibling comparison analysis. These findings suggest that among AGA children born at term or post-term, lower birth weight percentiles within the normal range are associated with increased risk of intellectual disability, regardless of gestational age.
Project description:Pregnancy is a vital period affecting both maternal and fetal health, with impacts on maternal metabolism, fetal growth, and long-term development. While the maternal metabolome undergoes significant changes during pregnancy, longitudinal shifts in maternal urine have been largely unexplored. In this study, we applied liquid chromatography-mass spectrometry-based untargeted metabolomics to analyze 346 maternal urine samples collected throughout pregnancy from 36 women with diverse backgrounds and clinical profiles. Key metabolite changes included glucocorticoids, lipids, and amino acid derivatives, indicating systematic pathway alterations. We also developed a machine learning model to accurately predict gestational age using urine metabolites, offering a non-invasive pregnancy dating method. Additionally, we demonstrated the ability of the urine metabolome to predict time-to-delivery, providing a complementary tool for prenatal care and delivery planning. This study highlights the clinical potential of urine untargeted metabolomics in obstetric care.
Project description:This study isolated and analysed extracellular vesicles from human amniotic fluid derived from routine second-trimester amniocentesis and elective Caesarean section at term. Label-free proteomics identified 4137 proteins with high confidence.
Project description:To investigate the potential risk factors for small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) late-term infants, 100 cases of single full-term SGA infants delivered in the Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University in 2017 were enrolled as the SGA group. A total of 100 healthy AGA who were born at the same time with the same gestational age were randomly included as the control group. The perinatal and postpartum adverse conditions of the two groups were recorded, and Apgar tests were performed on all newborns at 1 min (T1), 5 min (T2) and 10 min (T3) after birth. A follow-up survey was conducted in all patients at 6 and 12 months of age. At the second follow-up, the development quotient of the children was measured using the Gesell Developmental Schedule, and the perinatal risk factors of SGA were analyzed. The incidence of intrauterine distress, respiratory distress syndrome and infectious disease in the SGA group was significantly higher compared with that in the AGA group (P<0.05). The Apgar scores at T1, T2 and T3 were significantly lower in the SGA group compared with the AGA group (P<0.05). The Apgar score at T1 was lower compared with that at T2 in the SGA group (P<0.05), and the Apgar score at T2 was lower compared with that at T3 (P<0.05). The length of hospital stay in the SGA group was significantly longer compared with that in the AGA group (P<0.05). The development quotient at the 6 and 12th month in the SGA group was significantly lower compared with that in the AGA group (P<0.05). Logistic regression analysis showed that there was no correlation between SGA and maternal age, regardless of firstborn status, neonatal sex, mode of delivery and living environment. SGA was significantly associated with umbilical cord abnormalities, maternal pregnancy-induced hypertension, gestational diabetes, pregnancy infection and intrauterine distress (P<0.05). An abnormal umbilical cord, maternal pregnancy-induced hypertension, gestational diabetes, infection during pregnancy and intrauterine distress are all perinatal risk factors for SGA. Effective interventions are needed in clinical assessment to prevent the occurrence of SGA.
Project description:BackgroundPreterm birth is associated with lower neurocognitive performance. However, whether children's neurodevelopment improves with longer gestations within the full-term range (37-41 weeks) is unclear. Given the high rate of obstetric intervention in the USA, it is critical to determine whether long-term outcomes differ for children delivered at each week of term.MethodsThis secondary analysis included 39 199 live-born singleton children of women who were admitted to the hospital in spontaneous labour from the US Collaborative Perinatal Project (1959-76). At each week of term gestation, we evaluated development at 8 months using the Bayley Scales of Infant Development, 4 years using the Stanford-Binet IQ (SBIQ) domains and 7 years using the Wechsler Intelligence Scales for Children (WISC) and Wide-Range Achievement Tests (WRAT).ResultsChildren's neurocognitive performance improved with each week of gestation from 37 weeks, peaking at 40 or 41 weeks. Relative to those delivered at 40 weeks, children had lower neurocognitive scores at 37 and 38 weeks for all assessments except SBIQ and WISC Performance IQ. Children delivered at 39 weeks had lower Bayley Mental (β = -1.18; confidence interval -1.77, -0.58) and Psychomotor (β = -1.18; confidence interval -1.90, -0.46) scores. Results were similar for within-family analyses comparing siblings, with the addition of lower WRAT scores at 39 weeks.ConclusionsThe improvement in development scores across assessment periods indicates that each week up to 40 or 41 weeks of gestation is important for short- and long-term cognitive development, suggesting 40-41 weeks may be the ideal delivery window for optimal neurodevelopmental outcomes.
Project description:In children who are born small for gestational age (SGA), an adverse intrauterine environment has led to underdevelopment of both the body and the brain. The delay in body growth is (partially) restored during the first two years in a majority of these children. In addition to a negative influence on these physical parameters, decreased levels of intelligence and cognitive impairments have been described in children born SGA. In this study, we used magnetic resonance imaging to examine brain anatomy in 4- to 7-year-old SGA children with and without complete bodily catch-up growth and compared them to healthy children born appropriate for gestational age. Our findings demonstrate that these children strongly differ on brain organisation when compared with healthy controls relating to both global and regional anatomical differences. Children born SGA displayed reduced cerebral and cerebellar grey and white matter volumes, smaller volumes of subcortical structures and reduced cortical surface area. Regional differences in prefrontal cortical thickness suggest a different development of the cerebral cortex. SGA children with bodily catch-up growth constitute an intermediate between those children without catch-up growth and healthy controls. Therefore, bodily catch-up growth in children born SGA does not implicate full catch-up growth of the brain.
Project description:ImportanceDifferences in academic achievement by gestational age of children born at term, especially at 39 to 41 weeks, are not well understood.ObjectiveTo examine differences in academic achievement among children born between 37 and 41 weeks' gestational age.Design, setting, and participantsThis retrospective cohort study linked birth certificates of children born in Iowa from 1989 to 2009 with school test scores for grades 2 to 11 from 2017 to 2018. Statistical analysis was performed from January to March 2023.ExposuresGestational age at 37, 38, 39, and 41 weeks vs 40 weeks from clinical or obstetric and calendar measures.Main outcomes and measuresOutcomes were scores in national percentile rankings (NPRs) on standardized school tests in math and reading. Covariates included demographic and prenatal risk factors.ResultsThe sample included 536 996 children (50.7% male children and 49.3% female children) with math scores (3 576 045 child-grade observations; 6.6%, 15.7%, 28.6%, 35.5%, and 13.7% born at 37, 38, 39, 40, and 41 weeks, respectively) and 537 078 children with reading scores (3 590 408 child-grade observations). Score differences for those born at 39 vs 40 weeks were -0.028 NPRs (95% CI, -0.18 to 0.12 NPRs) for math and 0.085 NPRs (95% CI, -0.067 to 0.24 NPRs) for reading using the clinical or obstetric measure and 0.03 NPRs (95% CI, -0.14 to 0.20 NPRs) for math and 0.13 NPRs (95% CI, -0.042 to 0.31 NPRs) for reading using the calendar measure. With the clinical or obstetric measure, score differences between those born at 41 and 40 weeks were 0.19 NPRs (95% CI, -0.0052 to 0.38 NPRs) for math and 0.098 NPRs (95% CI, -0.096 to 0.29 NPRs) for reading. With the calendar measure, score differences for those born at 41 weeks were -0.22 NPRs (95% CI, -0.43 to -0.013 NPRs) for math and -0.28 NPRs (95% CI, -0.49 to -0.074 NPRs) for reading. With the clinical or obstetric measure, score differences between those born at 37 and 38 weeks vs 40 weeks were -0.59 NPRs (95% CI, -0.84 to -0.33 NPRs) and -0.44 NPRs (95% CI, -0.62 to -0.26 NPRs), respectively, for math, and -0.066 NPRs (95% CI, -0.32 to 0.19 NPRs) and -0.19 NPRs (95% CI, -0.37 to 0.0038 NPRs), respectively, for reading.Conclusions and relevanceThis study suggests that there is no evidence of a difference in math and reading scores over grades 2 to 11 among children born between 39 and 40 weeks' gestation, and overall no evidence of better scores among those born at 41 weeks' gestation compared with 40 weeks' gestation. The results can further inform decisions on delivery timing at term birth by offering insights into long-term associations of delivery timing with cognitive development and school achievement.
Project description:BackgroundLittle is known on long-term survival and causes of death among individuals born small or large for gestational age. This study investigates birth weight in relation to survival and causes of death over time.MethodsA national cohort of 1.7 million live-born singletons in Denmark was followed during 1979-2011, using the Danish Civil Registration System, the Medical Birth Registry and the Cause of Death Registry. Cox proportional hazards were estimated for the impact of small (SGA) and large (LGA) gestation weight and mortality overall, by age group and birth cohort.ResultsCompared to normal weight children, SGA children were associated with increased risk of dying over time. Though most of the deaths occurred during the first year of life, the cumulative mortality risk was increased until 30 years of age. The hazard ratios [HR] for dying among SGA children ages <2 years were: 3.47 (95% CI, 3.30-3.64) and 1.06 (95% CI, 0.60-1.87) in 30 years and older. HR for dying among SGA adults (20-29 years) were: 1.20 (95% CI, 0.99-1.46) in years 1979-1982 and 1.61 (95% CI, 1.04-2.51) in years 1989-1994. The SGA born had increased risk of dying from infection, heart disease, respiratory disease, digestive disease, congenital malformation, perinatal conditions, and accidents, suicide, and homicide. Individuals born LGA were associated with decreased mortality risk, but with increased risk of dying from malignant neoplasm.ConclusionsSurvival has improved independently of birth weight the past 30 years. However, children born SGA remain at significantly increased risk of dying up till they turn 30 years of age. Individuals born LGA have lower mortality risk but only in the first two years of life.
Project description:BackgroundVaginal microbiota and its potential contribution to preterm birth is under intense research. However, only few studies have investigated the vaginal microbiota in later stages of pregnancy or at the onset of labour.MethodsWe used 16S rRNA gene amplicon sequencing to analyse cross-sectional vaginal swab samples from 324 Finnish women between 37-42 weeks of gestation, sampled before elective caesarean section, at the onset of spontaneous labour, and in pregnancies lasting ≥41 weeks of gestation. Microbiota data were combined with comprehensive clinical data to identify factors associated with microbiota variation.FindingsVaginal microbiota composition associated strongly with advancing gestational age and parity, i.e. presence of previous deliveries. Absence of previous deliveries was a strong predictor of Lactobacillus crispatus dominated vaginal microbiota, and the relative abundance of L. crispatus was higher in late term pregnancies, especially among nulliparous women.InterpretationThis study identified late term pregnancy and reproductive history as factors underlying high abundance of gynaecological health-associated L. crispatus in pregnant women. Our results suggest that the vaginal microbiota affects or reflects the regulation of the duration of gestation and labour onset, with potentially vast clinical utilities. Further studies are needed to address the causality and the mechanisms on how previous labour, but not pregnancy, affects the vaginal microbiota. Parity and gestational age should be accounted for in future studies on vaginal microbiota and reproductive outcomes.FundingThis research was supported by EU H2020 programme Sweet Crosstalk ITN (814102), Academy of Finland, State Research Funding, and University of Helsinki.