Pub Date : 2025-11-01DOI: 10.1016/j.earlhumdev.2025.106435
Oludamilola Adeshina , Tara P. Menon , Ayushi Ambekar , Collin Tanchanco , Jordan Darden
The earlier a baby is born, the greater the risk for developing complications, particularly relating to the development of the brain and neurological development. Common conditions seen with premature infants are periventricular leukomalacia (PVL), also known as white matter injury, intraventricular hemorrhage (IVH), and hydrocephalus. These conditions may result in varying degrees of structural damage to the brain parenchyma. This paper aims to discuss the shared pathophysiological mechanisms, clinical presentation, and current treatment approaches for PVL, IVH and hydrocephalus in premature infants with a focus on future research directions at improving neurodevelopmental outcomes. While the basic science continues to evolve rapidly, it is essential that future work prioritizes clinical translatability. Our review highlights an urgent need for therapies that balance efficacy and safety in these vulnerable patient populations. Collaborative efforts between clinicians and researchers will be vital to bridge this gap and ultimately improve outcomes for preterm infants affected by PVL, IVH, and hydrocephalus.
{"title":"Exploring the neurological impact of prematurity: Shared mechanisms in periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and hydrocephalus","authors":"Oludamilola Adeshina , Tara P. Menon , Ayushi Ambekar , Collin Tanchanco , Jordan Darden","doi":"10.1016/j.earlhumdev.2025.106435","DOIUrl":"10.1016/j.earlhumdev.2025.106435","url":null,"abstract":"<div><div>The earlier a baby is born, the greater the risk for developing complications, particularly relating to the development of the brain and neurological development. Common conditions seen with premature infants are periventricular leukomalacia (PVL), also known as white matter injury, intraventricular hemorrhage (IVH), and hydrocephalus. These conditions may result in varying degrees of structural damage to the brain parenchyma. This paper aims to discuss the shared pathophysiological mechanisms, clinical presentation, and current treatment approaches for PVL, IVH and hydrocephalus in premature infants with a focus on future research directions at improving neurodevelopmental outcomes. While the basic science continues to evolve rapidly, it is essential that future work prioritizes clinical translatability. Our review highlights an urgent need for therapies that balance efficacy and safety in these vulnerable patient populations. Collaborative efforts between clinicians and researchers will be vital to bridge this gap and ultimately improve outcomes for preterm infants affected by PVL, IVH, and hydrocephalus.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106435"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-06DOI: 10.1016/j.earlhumdev.2025.106368
Laith R Sultan, Karen I Ramirez-Suarez, Sara Rae Schenkel, Monica Miranda Schaeubinger, Carmen Cerron-Vela, Samuel W Kgole, Gosego Masasa, Boitshepo Phale, Joseph Makhema, Thuso Mokane, Elizabeth D Lowenthal, Kathleen M Powis, Hansel J Otero
Background: Over 1 million infants born annually with fetal exposure to HIV and maternal antiretroviral treatment (ART) who remain HIV-uninfected (HEU) are at higher risk of neurodevelopmental delays compared to infants HIV-unexposed (HU).
Objective: We explored the use of brain ultrasound radiomics, specifically texture analysis, as an early imaging neurodevelopmental biomarker, comparing findings by newborn in utero HIV exposure status.
Methods: Brain ultrasound was performed on full-term newborns (≥ 37 weeks gestation) enrolled in a prospective observational study in Botswana. Radiomic ultrasound features, including first-order statistics, run-length, and co-occurrence matrix parameters, were extracted from the basal ganglia and periventricular white matter. Statistical comparisons were conducted based on fetal exposure to maternal HIV. The diagnostic performance of individual features was assessed, and logistic regression was used to combine the features for overall performance evaluation.
Results: Thirty-three infants (HEU: 20, HU: 13) were included in the analysis. The basal ganglia of HEU infants exhibited significantly lower heterogeneity (176.6 ± 10.76 vs. 205.97 ± 13.26, p = 0.04) and entropy (0.37 ± 0.01 vs. 0.41 ± 0.01, p = 0.03), and marginally lower gray level non-uniformity (310.04 ± 15.32 vs. 352.37 ± 24.20, p = 0.06) compared to HU infants, suggesting reduced parenchymal complexity. These combined radiomic features yielded an AUC of 0.72 with a specificity of 0.86. Similar trends were observed in the white matter, where HEU infants demonstrated marginally lower heterogeneity (191.66 ± 14.32 vs. 231.76 ± 17.34, p = 0.06). Gray level non-uniformity and run length non-uniformity were significantly lower in the HEU group (1996.87 ± 157.06 vs. 2487.43 ± 223.67, p = 0.04 and 284.66 ± 20.37 vs. 406.61 ± 47.77, p = 0.01, respectively). The combined white matter model demonstrated an AUC of 0.76 and a sensitivity of 0.86, indicating greater discriminatory power compared to the basal ganglia.
Conclusion: Ultrasound radiomics reveals distinct differences in brain texture between HEU and HU newborns, with significant findings in both basal ganglia and white matter features. These results highlight the potential of radiomics in identifying subtle neuroanatomical variations. Further research is needed to explore the neurodevelopmental implications of these findings.
背景：与未接触艾滋病毒（HU）的婴儿相比，每年有超过100万的胎儿暴露于艾滋病毒和母亲抗逆转录病毒治疗（ART）但仍未感染艾滋病毒（HEU）的婴儿神经发育迟缓的风险更高。目的：我们探索使用脑超声放射组学，特别是纹理分析，作为早期成像神经发育的生物标志物，比较新生儿在子宫内HIV暴露状态的结果。方法：在博茨瓦纳的一项前瞻性观察研究中，对足月新生儿（≥37周妊娠）进行脑超声检查。从基底节区和脑室周围白质中提取放射学超声特征，包括一阶统计量、行程长度和共现矩阵参数。根据胎儿暴露于母体艾滋病毒进行统计比较。评估单个特征的诊断性能，并使用逻辑回归将特征组合起来进行整体性能评估。结果：33例婴儿（HEU: 20, HU: 13）纳入分析。HEU组基底节区异质性（176.6±10.76 vs. 205.97±13.26,p = 0.04）和熵值（0.37±0.01 vs. 0.41±0.01,p = 0.03）显著低于HU组，灰度非均匀性（310.04±15.32 vs. 352.37±24.20,p = 0.06）显著低于HU组，表明HEU组基底节区实质复杂性降低。这些综合放射学特征的AUC为0.72，特异性为0.86。在白质中也观察到类似的趋势，HEU婴儿的异质性略低（191.66±14.32 vs 231.76±17.34,p = 0.06）。HEU组灰度不均匀性和跑程不均匀性显著低于对照组（1996.87±157.06 vs. 2487.43±223.67,p = 0.04; 284.66±20.37 vs. 406.61±47.77,p = 0.01）。联合白质模型的AUC为0.76，灵敏度为0.86，与基底节区相比具有更强的分辨能力。结论：超声放射组学显示HEU和HU新生儿的脑质地存在明显差异，基底节区和白质特征均有显著差异。这些结果突出了放射组学在识别细微神经解剖学变异方面的潜力。需要进一步的研究来探索这些发现对神经发育的影响。
{"title":"Brain ultrasound radiomics identify textural differences in basal ganglia and white matter between full term newborns HIV-exposed uninfected and HIV-unexposed in Botswana.","authors":"Laith R Sultan, Karen I Ramirez-Suarez, Sara Rae Schenkel, Monica Miranda Schaeubinger, Carmen Cerron-Vela, Samuel W Kgole, Gosego Masasa, Boitshepo Phale, Joseph Makhema, Thuso Mokane, Elizabeth D Lowenthal, Kathleen M Powis, Hansel J Otero","doi":"10.1016/j.earlhumdev.2025.106368","DOIUrl":"10.1016/j.earlhumdev.2025.106368","url":null,"abstract":"<p><strong>Background: </strong>Over 1 million infants born annually with fetal exposure to HIV and maternal antiretroviral treatment (ART) who remain HIV-uninfected (HEU) are at higher risk of neurodevelopmental delays compared to infants HIV-unexposed (HU).</p><p><strong>Objective: </strong>We explored the use of brain ultrasound radiomics, specifically texture analysis, as an early imaging neurodevelopmental biomarker, comparing findings by newborn in utero HIV exposure status.</p><p><strong>Methods: </strong>Brain ultrasound was performed on full-term newborns (≥ 37 weeks gestation) enrolled in a prospective observational study in Botswana. Radiomic ultrasound features, including first-order statistics, run-length, and co-occurrence matrix parameters, were extracted from the basal ganglia and periventricular white matter. Statistical comparisons were conducted based on fetal exposure to maternal HIV. The diagnostic performance of individual features was assessed, and logistic regression was used to combine the features for overall performance evaluation.</p><p><strong>Results: </strong>Thirty-three infants (HEU: 20, HU: 13) were included in the analysis. The basal ganglia of HEU infants exhibited significantly lower heterogeneity (176.6 ± 10.76 vs. 205.97 ± 13.26, p = 0.04) and entropy (0.37 ± 0.01 vs. 0.41 ± 0.01, p = 0.03), and marginally lower gray level non-uniformity (310.04 ± 15.32 vs. 352.37 ± 24.20, p = 0.06) compared to HU infants, suggesting reduced parenchymal complexity. These combined radiomic features yielded an AUC of 0.72 with a specificity of 0.86. Similar trends were observed in the white matter, where HEU infants demonstrated marginally lower heterogeneity (191.66 ± 14.32 vs. 231.76 ± 17.34, p = 0.06). Gray level non-uniformity and run length non-uniformity were significantly lower in the HEU group (1996.87 ± 157.06 vs. 2487.43 ± 223.67, p = 0.04 and 284.66 ± 20.37 vs. 406.61 ± 47.77, p = 0.01, respectively). The combined white matter model demonstrated an AUC of 0.76 and a sensitivity of 0.86, indicating greater discriminatory power compared to the basal ganglia.</p><p><strong>Conclusion: </strong>Ultrasound radiomics reveals distinct differences in brain texture between HEU and HU newborns, with significant findings in both basal ganglia and white matter features. These results highlight the potential of radiomics in identifying subtle neuroanatomical variations. Further research is needed to explore the neurodevelopmental implications of these findings.</p>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"210 ","pages":"106368"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12638123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-07-31DOI: 10.1016/j.earlhumdev.2025.106347
Lauren E Staiger, Kara Wong Ramsey, James Davis, Catherine Tarleton, Sheree Kuo
Objectives: The objectives of this study were to determine whether infants born to mothers with gestational or pregestational diabetes (IDM) and infants born to mothers with uncomplicated pregnancies have differences in percent body fat at birth, and to examine the relationship between glycemic control in pregnancy and infant body fat.
Study design: Percent body fat was measured in 132 IDM in the well-baby nursery using air displacement plethysmography and compared to a previously published cohort of 249 healthy control infants using t-tests. Linear regression models were used to examine the relationship between maternal glycemic control and infant percent body fat at birth.
Results: The difference in body fat between IDM and infants born to mothers with uncomplicated pregnancies was not clinically significant (12.9 ± 5 % vs 13.9 ± 4 %, p < 0.05). Among IDM, increasing maternal fasting blood glucose values and increasing percentages of elevated post-prandial glucose values were associated with increasing infant percent body fat. (β=0.19 and 0.08 respectively, P < 0.05).
Conclusion: Our cohort of healthy IDM that remained admitted to the term nursery did not have a clinically significant difference in percent body fat compared to control infants born to mothers with uncomplicated pregnancies. Among IDM, elevated maternal glucose levels correlated with increased infant percent body fat, suggesting glycemic control in pregnancy can affect body composition within this population.
目的：本研究的目的是确定患有妊娠期或妊娠期糖尿病（IDM）的母亲所生的婴儿与无并发症妊娠的母亲所生的婴儿出生时体脂百分比是否存在差异，并研究妊娠期血糖控制与婴儿体脂之间的关系。研究设计：使用空气置换体积脉搏仪测量132名健康婴儿托儿所的IDM体脂百分比，并与先前发表的249名健康对照婴儿使用t检验进行比较。使用线性回归模型来检验母亲血糖控制与婴儿出生时体脂百分比之间的关系。结果：IDM与妊娠无并发症母亲所生婴儿的体脂率差异无临床意义（12.9±5% vs 13.9±4%,p）。结论：我们的健康IDM队列与妊娠无并发症母亲所生的对照婴儿相比，体脂率无临床意义差异。在IDM中，孕妇血糖水平升高与婴儿体脂百分比增加相关，这表明孕期血糖控制可以影响该人群的身体组成。
{"title":"The effect of maternal blood glucose control on infant body composition at birth.","authors":"Lauren E Staiger, Kara Wong Ramsey, James Davis, Catherine Tarleton, Sheree Kuo","doi":"10.1016/j.earlhumdev.2025.106347","DOIUrl":"10.1016/j.earlhumdev.2025.106347","url":null,"abstract":"<p><strong>Objectives: </strong>The objectives of this study were to determine whether infants born to mothers with gestational or pregestational diabetes (IDM) and infants born to mothers with uncomplicated pregnancies have differences in percent body fat at birth, and to examine the relationship between glycemic control in pregnancy and infant body fat.</p><p><strong>Study design: </strong>Percent body fat was measured in 132 IDM in the well-baby nursery using air displacement plethysmography and compared to a previously published cohort of 249 healthy control infants using t-tests. Linear regression models were used to examine the relationship between maternal glycemic control and infant percent body fat at birth.</p><p><strong>Results: </strong>The difference in body fat between IDM and infants born to mothers with uncomplicated pregnancies was not clinically significant (12.9 ± 5 % vs 13.9 ± 4 %, p < 0.05). Among IDM, increasing maternal fasting blood glucose values and increasing percentages of elevated post-prandial glucose values were associated with increasing infant percent body fat. (β=0.19 and 0.08 respectively, P < 0.05).</p><p><strong>Conclusion: </strong>Our cohort of healthy IDM that remained admitted to the term nursery did not have a clinically significant difference in percent body fat compared to control infants born to mothers with uncomplicated pregnancies. Among IDM, elevated maternal glucose levels correlated with increased infant percent body fat, suggesting glycemic control in pregnancy can affect body composition within this population.</p>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"210 ","pages":"106347"},"PeriodicalIF":2.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12593238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-27DOI: 10.1016/j.earlhumdev.2025.106426
Meng-Wei Ge , Wei Du , Lu-Ting Shen , Ur-Rehman Attiq , Wei Li , Xi-Yuan Peng , Li Shi , Juan Miao , Rui Feng , Kang Zhong , Si-Qi Gao , Hong-Lin Chen
Objectives
To thoroughly explore how exposure to heat or cold influences the preterm birth (PTB) risk in different time windows.
Methods
Embase, Web of Science, PubMed and Scopus were systematically searched for studies about the association of abnormal temperature exposure and PTB risk from inception to March 2025. Corresponding data like the time window of temperature exposure, temperature, and PTB prevalence etc. were extracted. A random effects model was employed to merge effect estimates (risk ratios, RR) in the statistical analysis, stratified by temperature percentile and exposure time window, and a total of six independent meta-analyses were performed. This research was carried out and documented in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.
Results
This study incorporated 32 studies. High temperatures within one week before delivery significantly increased PTB risk (RR = 1.05, 95 % CI: 1.02–1.08), particularly in subtropical regions (RR = 1.09, 95 % CI: 1.01–1.18), developing countries (RR = 1.06, 95 %CI: 1.01–1.12), and prospective studies (RR = 1.23, 95 % CI: 1.02, 1.49). For exposure windows of 1–4 weeks before delivery, a positive association was found (RR = 1.07, 95 % CI: 1.02–1.12), with subtropical regions at highest risk (RR = 1.10, 95 % CI: 1.01–1.20). Exposure beyond four weeks before delivery also increased PTB risk (RR = 1.20, 95 % CI: 1.00–1.44). Cold exposure did not significantly increase PTB risk, but did so more than four weeks (RR = 1.21, 95 % CI: 1.05–1.39).
Conclusions
This study indicates that prenatal high-temperature exposure is associated with an elevated risk of preterm birth, particularly during early pregnancy and in subtropical climates. The impact of cold exposure on PTB is unclear, but highlights the need for climate-resilient prenatal care amid global warming, including heat health warnings and cooling aid. This evidence is vital for tackling climate change's health risks to mothers and infants.
{"title":"Extreme temperature and preterm birth: Time windows and geographical disparities","authors":"Meng-Wei Ge , Wei Du , Lu-Ting Shen , Ur-Rehman Attiq , Wei Li , Xi-Yuan Peng , Li Shi , Juan Miao , Rui Feng , Kang Zhong , Si-Qi Gao , Hong-Lin Chen","doi":"10.1016/j.earlhumdev.2025.106426","DOIUrl":"10.1016/j.earlhumdev.2025.106426","url":null,"abstract":"<div><h3>Objectives</h3><div>To thoroughly explore how exposure to heat or cold influences the preterm birth (PTB) risk in different time windows.</div></div><div><h3>Methods</h3><div>Embase, Web of Science, PubMed and Scopus were systematically searched for studies about the association of abnormal temperature exposure and PTB risk from inception to March 2025. Corresponding data like the time window of temperature exposure, temperature, and PTB prevalence etc. were extracted. A random effects model was employed to merge effect estimates (risk ratios, RR) in the statistical analysis, stratified by temperature percentile and exposure time window, and a total of six independent meta-analyses were performed. This research was carried out and documented in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines.</div></div><div><h3>Results</h3><div>This study incorporated 32 studies. High temperatures within one week before delivery significantly increased PTB risk (RR = 1.05, 95 % CI: 1.02–1.08), particularly in subtropical regions (RR = 1.09, 95 % CI: 1.01–1.18), developing countries (RR = 1.06, 95 %CI: 1.01–1.12), and prospective studies (RR = 1.23, 95 % CI: 1.02, 1.49). For exposure windows of 1–4 weeks before delivery, a positive association was found (RR = 1.07, 95 % CI: 1.02–1.12), with subtropical regions at highest risk (RR = 1.10, 95 % CI: 1.01–1.20). Exposure beyond four weeks before delivery also increased PTB risk (RR = 1.20, 95 % CI: 1.00–1.44). Cold exposure did not significantly increase PTB risk, but did so more than four weeks (RR = 1.21, 95 % CI: 1.05–1.39).</div></div><div><h3>Conclusions</h3><div>This study indicates that prenatal high-temperature exposure is associated with an elevated risk of preterm birth, particularly during early pregnancy and in subtropical climates. The impact of cold exposure on PTB is unclear, but highlights the need for climate-resilient prenatal care amid global warming, including heat health warnings and cooling aid. This evidence is vital for tackling climate change's health risks to mothers and infants.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106426"},"PeriodicalIF":2.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-26DOI: 10.1016/j.earlhumdev.2025.106427
Ceyda Acun , Rakesh Lavu , Wei Liu , Nicholas Nicoletti , Jennifer Ramsey , Hany Aly
Objective
To evaluate short-term and neurodevelopmental outcomes at 18–24 months in infants with mild hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), a population with limited long-term outcome data.
Study design
We conducted a retrospective cohort study of neonates ≥36 weeks gestational age (GA) diagnosed with mild HIE and treated with TH at a single center from March 2017 to February 2022. Neonates with severe congenital malformations or chromosomal anomalies were excluded. Data were extracted from medical charts of eligible neonates and their mothers. Outcomes assessed included short-term measures (neuroimaging findings, seizure incidence, length of hospital stay (LOS), and background electroencephalogram (EEG) abnormalities) and long-term neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development) at 18–24 months or pediatrician-documented developmental delays.
Results
Of the 64 infants meeting inclusion criteria, 17 (27 %) had MRI findings consistent with HIE, and 8 (13 %) experienced seizures. Long-term outcome data were available for 57 (89 %); of whom 9 (16 %) had abnormal outcomes. Among the 39 infants who underwent Bayley assessment at 22 ± 2 months, 6 (15 %) scored <85 in language, cognitive, or motor domains. Of the 17 infants without Bayley assessment but with pediatrician follow-up, 3 (18 %) had documented developmental delays.
Conclusion
Although TH is increasingly applied to mild HIE, evidence on long-term benefit remains scarce. In our cohort, infants with mild HIE treated with TH exhibited seizures, MRI abnormalities, and developmental impairments, underscoring the persistent risk of morbidity. These findings highlight the limited outcome data available and the urgent need for well designed prospective studies to clarify the role of TH in mild HIE.
{"title":"Therapeutic hypothermia in mild hypoxic ischemic encephalopathy: A clinical dilemma with uncertain long-term outcomes","authors":"Ceyda Acun , Rakesh Lavu , Wei Liu , Nicholas Nicoletti , Jennifer Ramsey , Hany Aly","doi":"10.1016/j.earlhumdev.2025.106427","DOIUrl":"10.1016/j.earlhumdev.2025.106427","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate short-term and neurodevelopmental outcomes at 18–24 months in infants with mild hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), a population with limited long-term outcome data.</div></div><div><h3>Study design</h3><div>We conducted a retrospective cohort study of neonates ≥36 weeks gestational age (GA) diagnosed with mild HIE and treated with TH at a single center from March 2017 to February 2022. Neonates with severe congenital malformations or chromosomal anomalies were excluded. Data were extracted from medical charts of eligible neonates and their mothers. Outcomes assessed included short-term measures (neuroimaging findings, seizure incidence, length of hospital stay (LOS), and background electroencephalogram (EEG) abnormalities) and long-term neurodevelopmental outcomes (Bayley Scales of Infant and Toddler Development) at 18–24 months or pediatrician-documented developmental delays.</div></div><div><h3>Results</h3><div>Of the 64 infants meeting inclusion criteria, 17 (27 %) had MRI findings consistent with HIE, and 8 (13 %) experienced seizures. Long-term outcome data were available for 57 (89 %); of whom 9 (16 %) had abnormal outcomes. Among the 39 infants who underwent Bayley assessment at 22 ± 2 months, 6 (15 %) scored <85 in language, cognitive, or motor domains. Of the 17 infants without Bayley assessment but with pediatrician follow-up, 3 (18 %) had documented developmental delays.</div></div><div><h3>Conclusion</h3><div>Although TH is increasingly applied to mild HIE, evidence on long-term benefit remains scarce. In our cohort, infants with mild HIE treated with TH exhibited seizures, MRI abnormalities, and developmental impairments, underscoring the persistent risk of morbidity. These findings highlight the limited outcome data available and the urgent need for well designed prospective studies to clarify the role of TH in mild HIE.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106427"},"PeriodicalIF":2.0,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-26DOI: 10.1016/j.earlhumdev.2025.106425
Radhika S. Amin , Mark S. Orlando , Sanjiv B. Amin
Background
In studies of term infants, in-utero low level lead exposure was associated with developmental neurotoxicity, including abnormal auditory neural myelination (ANM). However, this association has not been well-studied in premature infants who may be more susceptible to lead associated developmental neurotoxicity.
Aim
To evaluate if low level in-utero lead exposure is associated with developmental neurotoxicity as evaluated by ANM in premature infants.
Methods
A prospective observational study was performed in singleton infants 24–33 weeks gestational age (GA). Cord blood lead level was measured using Inductively Coupled Plasma Mass Spectrometry. Auditory brainstem evoked response (ABR) was performed in each ear at 35 weeks post-menstrual age (PMA) to evaluate inter-peak latencies (IPL), a measure of ANM.
Results
A total of 103 infants were studied. The mean (standard deviation) GA was 29.3 (1.8) weeks. The mean (range) cord blood lead level was 0.54 (0.065–5.30) ug/dL. On multiple linear regression analyses, controlling for confounders, cord lead levels were not associated (p > 0.05) with right ear IPLs (beta coefficients, 95 % confidence intervals): I-III (−0.001, −0.014–0.012), III-V (0.005, −0.007–0.018), or I-V (0.002, −0.015–0.020). There was also no association (p > 0.05) with left ear IPLs: I-III (−0.002, −0.017–0.012), III-V (−0.003, −0.015–0.008), or I-V (−0.006, −0.026–0.013).
Conclusion
Our findings suggest that in-utero low level lead exposure of ≤5.30 μg/dL is not associated with adverse effects on ANM when evaluated at 35 weeks PMA in infants ≤33 weeks GA.
{"title":"In utero lead exposure and auditory neural myelination in premature infants","authors":"Radhika S. Amin , Mark S. Orlando , Sanjiv B. Amin","doi":"10.1016/j.earlhumdev.2025.106425","DOIUrl":"10.1016/j.earlhumdev.2025.106425","url":null,"abstract":"<div><h3>Background</h3><div>In studies of term infants, in-utero low level lead exposure was associated with developmental neurotoxicity, including abnormal auditory neural myelination (ANM). However, this association has not been well-studied in premature infants who may be more susceptible to lead associated developmental neurotoxicity.</div></div><div><h3>Aim</h3><div>To evaluate if low level in-utero lead exposure is associated with developmental neurotoxicity as evaluated by ANM in premature infants.</div></div><div><h3>Methods</h3><div>A prospective observational study was performed in singleton infants 24–33 weeks gestational age (GA). Cord blood lead level was measured using Inductively Coupled Plasma Mass Spectrometry. Auditory brainstem evoked response (ABR) was performed in each ear at 35 weeks post-menstrual age (PMA) to evaluate inter-peak latencies (IPL), a measure of ANM.</div></div><div><h3>Results</h3><div>A total of 103 infants were studied. The mean (standard deviation) GA was 29.3 (1.8) weeks. The mean (range) cord blood lead level was 0.54 (0.065–5.30) ug/dL. On multiple linear regression analyses, controlling for confounders, cord lead levels were not associated (p > 0.05) with right ear IPLs (beta coefficients, 95 % confidence intervals): I-III (−0.001, −0.014–0.012), III-V (0.005, −0.007–0.018), or I-V (0.002, −0.015–0.020). There was also no association (p > 0.05) with left ear IPLs: I-III (−0.002, −0.017–0.012), III-V (−0.003, −0.015–0.008), or I-V (−0.006, −0.026–0.013).</div></div><div><h3>Conclusion</h3><div>Our findings suggest that in-utero low level lead exposure of ≤5.30 μg/dL is not associated with adverse effects on ANM when evaluated at 35 weeks PMA in infants ≤33 weeks GA.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106425"},"PeriodicalIF":2.0,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Responsive caregiving is a key component of nurturing care and crucial for early child development. While responsive caregiving has been examined in multiple studies, a comprehensive review summarizing findings from these studies across diverse caregiver, child, cultural, and socio-economic contexts is currently lacking.
Methods
We conducted a scoping review to synthesize evidence on (1) caregiver, child, and contextual factors influencing responsive caregiving and (2) association between responsive caregiving and children's neurodevelopment and mental health. We included peer-reviewed English articles describing responsive caregiving for children aged 0–8 years. Articles were systematically searched in PubMed, Web of Science, APA PsychInfo, APA PsycArticles, SocINDEX, Google Scholar, and the reference lists of included articles. Relevant data were extracted, collated, and synthesized into descriptive summaries and associations with children's development.
Results
We retrieved 7412 unique studies for title/abstract screening and 541 full-texts were screened and 138 studies met the inclusion criteria. Caregiver characteristics, including caregiver type, maternal health, and demographics, influenced responsive caregiving, with notable differences between mothers and fathers. Child-level factors, such as developmental disabilities, age, term or preterm birth status, and gender, also shaped responsive caregiving. Cultural context and socio-economic status also influenced responsive caregiving across populations. Language development was the most frequently reported with responsive caregiving.
Conclusion
This scoping review maps how caregiver, child, and contextual factors influence responsive caregiving. Significant gaps remain in understanding caregiving in the under-researched Global South settings. Policymakers and practitioners should consider socio-cultural contexts, along with the pathways and mechanisms, when designing inclusive interventions that strengthen caregiving and support child development.
响应性照料是养育照料的关键组成部分，对儿童早期发展至关重要。虽然已有多项研究对响应式护理进行了研究，但目前还缺乏一项综合综述，总结了不同护理者、儿童、文化和社会经济背景下这些研究的结果。方法本研究对影响反应性照料的照料者、儿童和环境因素以及反应性照料与儿童神经发育和心理健康之间的关系进行综述。我们纳入了同行评议的英文文章，这些文章描述了0-8岁儿童的响应式护理。系统检索PubMed、Web of Science、APA PsychInfo、APA PsycArticles、SocINDEX、谷歌Scholar以及收录文章的参考文献列表。对相关数据进行提取、整理，并将其综合成描述性的总结和与儿童发展的关联。结果我们检索了7412项独立研究进行标题/摘要筛选，筛选了541篇全文，其中138项研究符合纳入标准。照顾者特征，包括照顾者类型、产妇健康和人口统计，影响响应性照顾，母亲和父亲之间存在显著差异。儿童层面的因素，如发育障碍、年龄、足月或早产状况以及性别，也影响了响应性护理。文化背景和社会经济地位也影响了所有人群的响应性护理。语言发展是最常见的反应性护理。结论：本综述描绘了照料者、儿童和环境因素如何影响响应性照料。在研究不足的全球南方环境中，对护理的理解仍存在重大差距。政策制定者和从业人员在设计加强照顾和支持儿童发展的包容性干预措施时，应考虑社会文化背景以及途径和机制。
{"title":"A scoping review of responsive caregiving in diverse populations and its association with child development","authors":"Eunice Lobo , Sandeep Mahapatra , Joshua Jeong , Giridhara Rathnaiah Babu , Prashanth Nuggehalli Srinivas , Debarati Mukherjee , Onno C.P. van Schayck","doi":"10.1016/j.earlhumdev.2025.106424","DOIUrl":"10.1016/j.earlhumdev.2025.106424","url":null,"abstract":"<div><h3>Background</h3><div>Responsive caregiving is a key component of nurturing care and crucial for early child development. While responsive caregiving has been examined in multiple studies, a comprehensive review summarizing findings from these studies across diverse caregiver, child, cultural, and socio-economic contexts is currently lacking.</div></div><div><h3>Methods</h3><div>We conducted a scoping review to synthesize evidence on (1) caregiver, child, and contextual factors influencing responsive caregiving and (2) association between responsive caregiving and children's neurodevelopment and mental health. We included peer-reviewed English articles describing responsive caregiving for children aged 0–8 years. Articles were systematically searched in PubMed, Web of Science, APA PsychInfo, APA PsycArticles, SocINDEX, Google Scholar, and the reference lists of included articles. Relevant data were extracted, collated, and synthesized into descriptive summaries and associations with children's development.</div></div><div><h3>Results</h3><div>We retrieved 7412 unique studies for title/abstract screening and 541 full-texts were screened and 138 studies met the inclusion criteria. Caregiver characteristics, including caregiver type, maternal health, and demographics, influenced responsive caregiving, with notable differences between mothers and fathers. Child-level factors, such as developmental disabilities, age, term or preterm birth status, and gender, also shaped responsive caregiving. Cultural context and socio-economic status also influenced responsive caregiving across populations. Language development was the most frequently reported with responsive caregiving.</div></div><div><h3>Conclusion</h3><div>This scoping review maps how caregiver, child, and contextual factors influence responsive caregiving. Significant gaps remain in understanding caregiving in the under-researched Global South settings. Policymakers and practitioners should consider socio-cultural contexts, along with the pathways and mechanisms, when designing inclusive interventions that strengthen caregiving and support child development.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106424"},"PeriodicalIF":2.0,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145369778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advances in perinatal care have improved survival rates of preterm infants; however, concerns regarding their neurodevelopmental outcomes persist. This study investigates the relationship between intraindividual variability (IIV) in sleep duration and crystallized intelligence in very low birth weight (VLBW) children at the preschool stage. This study had 38 participants, including 18 VLBW children and 20 full-term children aged 5 to 6 years. Sleep duration was assessed using actigraphy and sleep diaries, while crystallized intelligence was evaluated using the Achievement Scale (ACH) of the Kaufman Assessment Battery for Children (K-ABC). Statistical analyses, including correlation and multiple regression analyses, were conducted to examine the effect of preterm birth on the relationship between sleep variability and learning outcomes. The results revealed that sleep duration IIV adversely affected ACH scores of preterm children but had no impact on those of full-term children. In multiple regression analysis, the interaction term between sleep variability and preterm birth significantly predicted ACH scores (p = 0.032), suggesting that early childhood learning in preterm children is more vulnerable to the effects of sleep instability. Additionally, among VLBW children, older age was associated with lower ACH scores, implying that learning difficulties may become more pronounced with age. These results show the potential role of sleep regulatory mechanisms in cognitive development. The findings show the importance of monitoring and supporting healthy sleep habits in preterm children to mitigate potential learning difficulties. Early interventions targeting sleep stability may play a critical role in improving academic performance in this high-risk population.
{"title":"Sleep variability and learning outcomes in preterm and full-term children: An observational study","authors":"Yusuke Mitani , Yuko Yoshimura , Shinichiro Mizutomi , Tetsujiro Shirahashi , Hidenori Iwasaki , Ikuko Hama , Takashi Ikeda , Sanae Tanaka , Chiaki Hasegawa , Hidenobu Ohta , Akiko Ando , Kazutoshi Cho , Mitsuru Kikuchi , Taizo Wada","doi":"10.1016/j.earlhumdev.2025.106413","DOIUrl":"10.1016/j.earlhumdev.2025.106413","url":null,"abstract":"<div><div>Advances in perinatal care have improved survival rates of preterm infants; however, concerns regarding their neurodevelopmental outcomes persist. This study investigates the relationship between intraindividual variability (IIV) in sleep duration and crystallized intelligence in very low birth weight (VLBW) children at the preschool stage. This study had 38 participants, including 18 VLBW children and 20 full-term children aged 5 to 6 years. Sleep duration was assessed using actigraphy and sleep diaries, while crystallized intelligence was evaluated using the Achievement Scale (ACH) of the Kaufman Assessment Battery for Children (K-ABC). Statistical analyses, including correlation and multiple regression analyses, were conducted to examine the effect of preterm birth on the relationship between sleep variability and learning outcomes. The results revealed that sleep duration IIV adversely affected ACH scores of preterm children but had no impact on those of full-term children. In multiple regression analysis, the interaction term between sleep variability and preterm birth significantly predicted ACH scores (<em>p</em> = 0.032), suggesting that early childhood learning in preterm children is more vulnerable to the effects of sleep instability. Additionally, among VLBW children, older age was associated with lower ACH scores, implying that learning difficulties may become more pronounced with age. These results show the potential role of sleep regulatory mechanisms in cognitive development. The findings show the importance of monitoring and supporting healthy sleep habits in preterm children to mitigate potential learning difficulties. Early interventions targeting sleep stability may play a critical role in improving academic performance in this high-risk population.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"212 ","pages":"Article 106413"},"PeriodicalIF":2.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Compared with formula-fed infants, those who are breast-fed consistently demonstrate superior immune maturation, neurodevelopment, and cognitive performance, an advantage attributable, in part, to the complex bioactive lipidome of human milk. This review highlights the mechanistic roles of milk-derived phospholipids and sphingolipids in orchestrating these benefits. It critically evaluates their emerging clinical applications in preventing infection, allergy, and neurodevelopmental disorders, thereby establishing a framework for future strategies to optimize infant nutrition and developmental trajectories.
{"title":"Hidden heroes in breast milk: The dual roles of phospholipids and sphingolipids in infant immunity and brain development","authors":"Yequan Xu , Xinkai Zhao , Zhenyu Ding , Shanyu Jiang , Renqiang Yu","doi":"10.1016/j.earlhumdev.2025.106409","DOIUrl":"10.1016/j.earlhumdev.2025.106409","url":null,"abstract":"<div><div>Compared with formula-fed infants, those who are breast-fed consistently demonstrate superior immune maturation, neurodevelopment, and cognitive performance, an advantage attributable, in part, to the complex bioactive lipidome of human milk. This review highlights the mechanistic roles of milk-derived phospholipids and sphingolipids in orchestrating these benefits. It critically evaluates their emerging clinical applications in preventing infection, allergy, and neurodevelopmental disorders, thereby establishing a framework for future strategies to optimize infant nutrition and developmental trajectories.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"211 ","pages":"Article 106409"},"PeriodicalIF":2.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-16DOI: 10.1016/j.earlhumdev.2025.106414
Hadi Nobari , Elena Mainer-Pardos , Demetrio Lozano , John T. Manning , Koulla Parpa , Laura Mason , Marcos Michaelides , Alberto Roso-Moliner
Background
Lactate, an important respiratory substrate, is generated during exercise. Digit ratio (2D:4D) is strongly associated with lactate in men over a range of exercise intensities, but in women the association has been reported as weaker and restricted to high running speeds. Here we report a replication of this finding in women employing the 30–15 Intermittent Fitness Test (30–15 IFT).
Method
The participants were amateur female football players. Digit lengths, height, body composition and VO2max were measured. The 30–15 IFT involves 30-s shuttle runs between lines positioned 40 m apart. Audio signals determine the pace, starting at 10 km/h and increasing by 0.5 km/h to a maximum of 18 km/h.
Results
Mean lactate levels (mmol/L) rose with running speed, ranging from 2.13 (±0.78) to 13.63 (±2.83). At running speeds 12 km/h to 16 km/h (n = 28 and 26 respectively) there were positive correlations between lactate and weight and BMI and negative associations with VO2max. At 18 km/h (n = 16) right 2D:4D was positively related and height negatively related to lactate. The former remained significant after the effect of height was removed.
Conclusion
Our findings from the 30–15 IFT in the field are similar to those reported from a laboratory treadmill test. The digit ratio, especially right 2D:4D, is positively associated with lactate levels during running in women, independent of height. In contrast previous findings in men the association applies to high running speeds only.
{"title":"Digit Ratio (2D:4D) and lactate response during a football-specific intermittent field fitness test in women","authors":"Hadi Nobari , Elena Mainer-Pardos , Demetrio Lozano , John T. Manning , Koulla Parpa , Laura Mason , Marcos Michaelides , Alberto Roso-Moliner","doi":"10.1016/j.earlhumdev.2025.106414","DOIUrl":"10.1016/j.earlhumdev.2025.106414","url":null,"abstract":"<div><h3>Background</h3><div>Lactate, an important respiratory substrate, is generated during exercise. Digit ratio (2D:4D) is strongly associated with lactate in men over a range of exercise intensities, but in women the association has been reported as weaker and restricted to high running speeds. Here we report a replication of this finding in women employing the 30–15 Intermittent Fitness Test (30–15 IFT).</div></div><div><h3>Method</h3><div>The participants were amateur female football players. Digit lengths, height, body composition and VO<sub>2max</sub> were measured. The 30–15 IFT involves 30-s shuttle runs between lines positioned 40 m apart. Audio signals determine the pace, starting at 10 km/h and increasing by 0.5 km/h to a maximum of 18 km/h.</div></div><div><h3>Results</h3><div>Mean lactate levels (mmol/L) rose with running speed, ranging from 2.13 (±0.78) to 13.63 (±2.83). At running speeds 12 km/h to 16 km/h (<em>n</em> = 28 and 26 respectively) there were positive correlations between lactate and weight and BMI and negative associations with VO<sub>2max</sub>. At 18 km/h (<em>n</em> = 16) right 2D:4D was positively related and height negatively related to lactate. The former remained significant after the effect of height was removed.</div></div><div><h3>Conclusion</h3><div>Our findings from the 30–15 IFT in the field are similar to those reported from a laboratory treadmill test. The digit ratio, especially right 2D:4D, is positively associated with lactate levels during running in women, independent of height. In contrast previous findings in men the association applies to high running speeds only.</div></div>","PeriodicalId":11435,"journal":{"name":"Early human development","volume":"211 ","pages":"Article 106414"},"PeriodicalIF":2.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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