Child Health Development Research Articles

Landscape Analysis of Neurodevelopmental Comorbidities in Newborn Screening Conditions: Challenges and Opportunities.

Newborn screening (NBS) is a large-scale public health program in the US that screens 3.8 million newborns for up to 81 genetic conditions each year. Many of these conditions have comorbidities, including neurodevelopmental disorders (NDDs). These comorbidities can have a significant impact on health outcomes across the lifespan. Most screened conditions are inborn errors of metabolism. PKU, the first condition identified by NBS, is an inherited metabolic disorder that can cause developmental delays and intellectual/developmental disabilities if not treated. The Newborn Screening Translational Research Network (NBSTRN) is a program that has been funded by the National Institute of Child Health and Human Development since 2008. NBSTRN is charged with developing, maintaining, and enhancing tools, resources, and expertise supporting NBS research. One of the tasks led by NBSTRN is to provide direction for developing question/answer sets used in the Longitudinal Pediatric Data Resource (LPDR) to create consensus-based and standardized common data elements (CDEs) for NBS conditions. There is growing interest in the NBS community in assessing neurodevelopmental trajectories through long-term follow-up studies. This could be streamlined by employing uniform CDEs. To address this unmet need, we conducted a landscape analysis to (1) explore the co-occurrence of NDD-related comorbidities and NBS conditions using text mining in MedGen, (2) compile a list of NDD-related CDEs from existing repositories as well as LPDR data dictionaries, and (3) identify challenges and knowledge gaps hindering the early identification of risks for NDDs in NBS conditions. Our findings can inform future efforts toward advancing the research infrastructure for this established public health program. The renewed awareness of the risk of NDDs after a positive NBS and diagnosis could lead to improved treatment guidelines for mental health conditions.

Comparing the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia in preterm infants

Objective: To compare the prognostic value of 3 diagnostic criteria of bronchopulmonary dysplasia (BPD) in preterm infants with gestational age<32 weeks. Methods: The retrospective cohort study was conducted to collect the clinical data of 285 preterm infants with BPD admitted to the Department of Neonatology, Children's Hospital Affiliated to Zhengzhou University from January 2019 to September 2021, who were followed up regularly after discharge. The primary composite adverse outcome was defined as death or severe respiratory morbidity from 36 weeks of corrected gestational age to 18 months of corrected age, and the secondary composite adverse outcome was defined as death or neurodevelopmental impairment. According to the primary or secondary composite adverse outcomes, the preterm infants were divided into the adverse prognosis group and the non-adverse prognosis group. The 2001 National Institute of Child Health and Human Development (NICHD) criteria, 2018 NICHD criteria, and 2019 Neonatal Research Network (NRN) criteria were used to diagnose and grade BPD in preterm infants. Chi-square test, Logistic regression analysis, receiver operating characteristic (ROC) curve and Delong test were used to analyze the prognostic value of the 3 diagnostic criteria. Results: The 285 preterm infants had a gestational age of 29.4 (28.1, 30.6) weeks and birth weight of 1 230 (1 000, 1 465) g, including 167 males (58.6%). Among 285 premature infants who completed follow-up, the primary composite adverse outcome occurred in 124 preterm infants (43.5%), and the secondary composite adverse outcome occurred in 40 preterm infants (14.0%). Multivariate Logistic regression analysis showed that severe BPD according to the 2001 NICHD criteria, gradeⅡand Ⅲ BPD according to the 2018 NICHD criteria and grade 2 and 3 BPD according to the 2019 NRN criteria were all risk factors for primary composite adverse outcomes (all P<0.05). ROC curve showed that the area under the curve (AUC) of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.70 and 0.70 vs. 0.61, Z=4.49 and 3.35, both P<0.001), but there was no significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.38, P=0.702). Multivariate Logistic regression analysis showed that the secondary composite adverse outcomes were all associated with grade Ⅲ BPD according to the 2018 NICHD criteria and grade 3 BPD according to the 2019 NRN criteria (both P<0.05). ROC curve showed that the AUC of the 2018 NICHD criteria and 2019 NRN criteria were both higher than that of the 2001 NICHD criteria (0.71 and 0.71 vs. 0.58, Z=2.93 and 3.67, both P<0.001), but there was no statistically significant difference between the 2018 NICHD and 2019 NRN criteria (Z=0.02, P=0.984). Conclusion: The 2018 NICHD and 2019 NRN criteria demonstrate good and comparable predictive value for the primary and secondary composite adverse outcomes in preterm infants with BPD, surpassing the predictive efficacy of the 2001 NICHD criteria.

Research progress of Chinese and Western diet therapy for children and adolescent obesity and overweight

Childhood and adolescent overweight and obesity rates have been increasing year by year, becoming extremely common and posing serious health risks, making it a global epidemic. Childhood obesity should not be ignored, and in-depth prevention and treatment should be implemented to reduce the risk of chronic diseases in adulthood and promote long-term health and physical development in children. Dietary therapy is beneficial for children to maintain a healthy weight, achieve nutritional balance, and prevent obesity. Additionally, specific nutritional requirements such as the ketogenic diet can be used in combination with dietary therapy to target the treatment of obese children. The traffic light diet plan can enhance children’s awareness of healthy eating and promote adherence to a balanced diet. However, childhood obesity is influenced by various factors. This article will analyze the causes of childhood obesity and incorporate the dietary concepts of ancient Chinese scholars. It will compare the different dietary treatment methods for childhood obesity in traditional Chinese medicine and Western medicine, such as the Warm Gallbladder Decoction, and explore other complementary interventions such as medication. By comparing the similarities and differences between traditional Chinese medicine and Western medicine, we can avoid their respective shortcomings and develop their advantages, combining them to provide feasible short-term and long-term treatment methods for obese children and adolescents. Furthermore, it can provide future research prospects for the development of dietary treatments specifically tailored to pediatric obesity patients.

Trend and Equity in Maternal and Child Health Resource Allocation in China Since the New Health System Reform: A Nationwide Study from 2008 to 2020.

China has made considerable efforts to promote the development of maternal and child health (MCH) care since the new health system reform in 2009. This study aims to evaluate the trend and equity of MCH resources allocation in China from 2008 to 2020 and provide a reference for rational distribution of MCH resources. Data were collected from the China Health Statistics Yearbook and China Statistics Yearbook. The number of MCH hospitals, licensed (assistant) physicians, registered nurses and beds were selected for the measurement of the equity of MCH resources allocation. The Health Resource Agglomeration Degree and Theil index were used in evaluating MCH resource allocation equity and to compare differences among regions. From 2008 to 2020, the average annual growth rates for MCH hospitals, beds, licensed (assistant) physicians, and registered nurses were 0.72%, 6.95%, 5.04%, and 9.57%, respectively. However, regional disparities in the equity of MCH resource allocation have been identified. Although the western region has shown growth in MCH resource allocation by geography, the agglomeration degree of the four indicators remains less than 1, significantly lower than the average value of greater than 2 in the eastern region. Additionally, the equity of human resource allocation in the western region is lower than the equity in the allocation of institutions. In the densely populated eastern region, the equity of MCH resource allocation by population is decreasing, with the agglomeration degree of all four indicators below 1 in 2020. The disparity in healthcare resource allocation within regions is the main cause of inequitable MCH resource allocation in China. The allocation of MCH resources in China has improved since 2009, however, geographic equity needs further improvement, particularly in densely populated regions. Population and geographic balances should be considered in the development and implementation of MCH resource allocation policies, and improving intraregional equity should be the focus.

Fibroids and unexplained infertility treatment with epigallocatechin gallate: a natural compound in green tea (FRIEND) – protocol for a randomised placebo-controlled US multicentre clinical trial of EGCG to improve fertility in women with uterine fibroids

IntroductionUterine fibroids affect 30%–77% of reproductive-age women and are a significant cause of infertility. Surgical myomectomies can restore fertility, but they often have limited and temporary benefits, with postoperative complications...

Survival Rate and Short-term Outcomes of Extremely Preterm Infants: A Tertiary Care Center Experience from the Private Sector

Background: Premature birth is one of the leading causes of death in the world. The global incidence of prematurity ranges from 5% to 11% of all births. The aim of this study was to assess the outcome of extremely preterm infants born below 29 weeks in our institution, with regard to survival and major short-term outcomes, and compare our results with national and international centers. This study is the first to be conducted in a private tertiary care hospital in Saudi Arabia. Materials and Methods: This was a retrospective descriptive cohort study that reviewed the medical records of preterm infants admitted to the neonatal intensive care unit at the International Medical Center, Jeddah, Kingdom of Saudi Arabia, between January 2014 and January 2020. We compared our results to the national data from King Faisal Specialist Hospital and Research Center-Riyadh, King Abdulaziz Medical City (KAMC)-Jeddah and KAMC Riyadh, King Abdulaziz Medical City-Alhasa, the National Institute of Child Health and Human Development Neonatal Research Network, and the Canadian Neonatal Network. Results: A total of 92 preterm infants were included: 3, 8, 17, 17, 29, and 18 infants with a gestational age of 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, and 28 weeks, respectively. The mean gestational age was 25 weeks and 5 days. Fifty-four infants (58.7%) survived to hospital discharge. In terms of short-term outcomes, 13% had bronchopulmonary dysplasia, hemodynamically significant ductus arteriosus was present in 27%, and retinopathy of prematurity was found in 13%, necrotizing enterocolitis was diagnosed in 5.4%, while late-onset sepsis was reported in 23.9% of infants. Conclusion: Our study represents outcomes of Extremely Preterm Infants in a single Private tertiary Care Center from Saudi Arabia with a comparison to national and international data. Though it cannot be generalized our data can be used as an add-value cohort toward establishing countrywide neonatal network to better plan regional resource allocation and utilization and facilitate ongoing audit, benchmarking, and overall quality improvement initiatives.

Prevalence of Exclusive Breastfeeding among Nursing Mothers in Afijio Local Government Area, Southwest, Nigeria: A Cross-sectional Study

Background: Exclusive breastfeeding is public health intervention strategy for child health development and growth from birth to weaning period. It is recommended for nursing mothers during Health promotion sessions by Health Educators according to WHO AND UNICEF guidelines at various health facilities. Nigeria recorded 17.5% prevalence rate of exclusive breastfeeding despite regional variations. This is relatively low to WHO recommendations. Hitherto no study has been conducted in Afijio Local Government, South west of Nigeria for prevalence of exclusive breastfeeding. Hence the aim of this study is to evaluate Knowledge, Altitude and Practice of exclusive breastfeeding by distribution of questionnaires to nursing mothers in Afijio Local Government areas. Methodology: a cross sectional study of randomly selected 172 nursing mothers from Ilora, Awe, Jobele/ Akinmoorin and Fiditi of Afijio Local Government Area. Data analysis was employed by frequency, relative frequency and simple percentage. Results: A total number of 172 nursing mothers were interviewed with mean age of 33 ± 4.0 years. The literacy level is 97%. The employment rate is 65%. Formal education received on knowledge of exclusive breast feeding by respondents (Prevalence) is 89.0 %. The altitude of the participants on benefits of exclusive breastfeeding is 78.5%. Finally, practice of breastfeeding especially within first hours of birth is 84%. Conclusion: There is need for more support from local government’s health authority on exclusive breast feeding in Afijio Local Government Areas. Thus training courses should be provided to skilled birth attendants for skilled support to breastfeeding mothers.

“What Defines Us as People Is How We Treat Others”: Ethnotheories, Socialization Goals, and Practices of “Exemplary” Guatemalan Mothers

Parenting beliefs and practices are deeply embedded in cultural values, ideologies, and norms. The cultural ecologies of Guatemala, a Central American country, highlight familism, religiosity, and collectivism. To understand the parenting goals, parental ethnotheories, and parenting practices of a group of highly educated, economically advantaged Guatemalan mothers of school-age children, we conducted a qualitative study about their goals for their children and ways of inculcating desired qualities. The nine mothers had been nominated by school staff as outstanding mothers. After asking open-ended questions about desired goals and parenting strategies, we posed dilemmas adapted from the United States National Institute of Child Health and Human Development Spanish-language booklet, “¿Qué significa ser padres?” (“What does it mean to be parents?”). Interviews took place in an unoccupied school classroom and lasted an average of 37 minutes; they were recorded and transcribed in the original Spanish. Coding according to reflexive thematic analysis was conducted in Spanish by two members of the research team. Interpersonal relatedness, kindness, and prosocial behavior were foremost among the mothers’ socialization goals. Ethnotheories included the importance of providing both love and limits, recognizing individual differences among children, and promoting children’s autonomy. Mothers’ parenting strategies emphasized preserving emotional intimacy, taking children’s perspectives, and rejecting permissiveness. These goals and practices derive from Guatemalan cultural values of collectivism, familism, and religiosity, in which interpersonal relationships are prioritized. Well-educated, economically advantaged Guatemalan mothers endorsed socialization goals and parenting practices that differed from Western prescriptions. The findings imply that cultural values should inform parenting interventions.

Comparing population-based fetal growth standards in a US cohort

BackgroundNo fetal growth standard is currently endorsed for universal use in the US. Newer standards improve upon the methodologic limitations of older studies but before adopting into practice, it is important to know how recent standards perform at identifying fetal under- or over- growth and predicting subsequent neonatal morbidity or mortality in US populations. ObjectiveTo compare classification of estimated fetal weight (EFW) that is <5th or 10th percentile or >90th percentile by six population-based fetal growth standards and the ability of these standards to predict a composite of neonatal morbidity and mortality. Study DesignWe used data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to be (nuMoM2b) cohort, which recruited nulliparous women in the first trimester at eight U.S. clinical centers (2010-2014). EFW was obtained from ultrasounds at 16-21 and 22-29 weeks (n=9530 women). We calculated rates of fetal growth restriction (EFW <5th and 10th percentiles; FGR<5 and FGR<10) and EFW >90th percentile (EFW>90) from three large prospective fetal growth cohorts with similar rigorous methodologies: INTERGROWTH-21, World Health Organization (WHO) sex-specific and combined, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) race/ethnic-specific and unified, and the historical Hadlock (1991) reference. To determine whether differential classification of FGR or EFW>90 among standards was clinically meaningful, we then compared area under the curve (AUC) and sensitivity of each standard to predict SGA or LGA at birth, composite perinatal morbidity and mortality alone, and SGA or LGA with composite perinatal morbidity and mortality. ResultsThe standards classified different proportions of FGR and EFW>90 for ultrasounds at 16-21 (visit 2) and 22-29 (visit 3) weeks. At visit 2, the NICHD race/ethnic-specific, WHO sex-specific and WHO-combined identified similar rates of FGR<10 (8.4-8.5%) with the other two having lower rates, while NICHD race/ethnic-specific identified the highest rate of FGR<5 (5.0%) compared to the other references. At visit 3, WHO-sex-specific classified 9.2% of fetuses as FGR<10, while the other five classified a lower proportion: WHO-Combined 8.4%, NICHD-race/ethnic-specific 7.7%, INTERGROWTH 6.2%, Hadlock 6.1%, and NICHD unified 5.1%. INTERGROWTH classified the highest (21.3%) as EFW>90 while Hadlock classified the lowest (8.3%). When predicting composite perinatal morbidity and mortality in the setting of early-onset FGR, WHO had the highest AUC of 0.53 (0.51, 0.53) for FGR<10 at 22-29 weeks, but the AUCs were similar among standards (0.52). Sensitivity was generally low across standards (22.7-29.1%). When predicting SGA-BW with composite neonatal morbidity or mortality, for FGR<10 at 22-29 weeks, WHO-sex-specific had the highest AUC (0.64; 95% CI 0.60, 0.67) and INTERGROWTH had the lowest (AUC=0.58; 95% CI 0.55, 0.62), though all standards had low sensitivity (7.0-9.6%). ConclusionsDespite classifying different proportions of fetuses as FGR or EFW>90, all standards performed similarly in predicting perinatal morbidity and mortality. Classification of different percentages of fetuses as FGR or EFW>90 among references may have clinical implications in the management of pregnancies, such as increased antenatal monitoring for FGR or cesarean for suspected LGA. Our findings highlight the importance of knowing how standards perform in local populations, but more research is needed to determine if any standard performs better at identifying risk of morbidity or mortality.

Predictive and Diagnostic Values of Systemic Inflammatory Indices in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants, and there is a lag in the diagnosis of BPD. Inflammation is a vital pathogenic factor for BPD; we aim to evaluate the predictive and diagnostic values of systemic inflammatory indices in BPD. Between 1 January 2019 and 31 May 2023, the clinical data of 122 premature infants with a gestational age of <32 weeks in the Department of Neonatology, the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, were retrospectively collected and classified into non-BPD (n = 72) and BPD (n = 50) groups based on the National Institute of Child Health and Human Development 2018 criteria. To compare the general characteristics of each group, we identified the independent risk variables for BPD using multivariate logistic regression analysis, compared the systemic inflammatory indices at birth, 72 h, 1 week, 2 weeks, and 36 weeks postmenstrual age (PMA), and constructed the receiver operating characteristic curves of neutrophil-to-lymphocyte ratio (NLR) diagnosis of BPD at different time points. ① The independent risk factors for BPD in preterm infants were birth weight, small for gestational age, and days of oxygen therapy (all p < 0.05). ② At 72 h and 1 week after birth, the serum NLR of the BPD group was higher than for the non-BPD group (p < 0.05). Furthermore, the neutrophil count (N), NLR, monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value of infants with BPD were higher than the non-BPD group at 3 weeks after birth (p < 0.05). Moreover, at 36 weeks of PMA, the serum N, NLR, MLR, and SIRI of BPD infants were higher than those of non-BPD infants (p < 0.05). ③ The NLR of infants with and without BPD gradually increased after birth, reaching a peak at 72 h and 1 week, respectively. At 3 weeks postnatal, the NLR had the highest predictive power for BPD, with an area under the curve (AUC) of 0.717 (p < 0.001); the sensitivity was 56% and specificity was 86.1%. In addition, the NLR at 36 weeks of PMA exhibited some diagnostic value for BPD. The AUC was 0.693 (p < 0.001), the sensitivity was 54%, and specificity was 83.3%. At 3 weeks after birth and 36 weeks of PMA, some systemic inflammation indices (like N, NLR, SIRI) of preterm infants with BPD have specific predictive and diagnostic values; these indices may help the management of high-risk preterm infants with BPD.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28weeks but not among infants born at 22-25weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Early childhood SARS experience leads to long-lasting impacts on adulthood mental health in China

The association between pandemic experience and immediate mental health risks, such as depression, is well-documented, yet the long-term effects remain unclear. This study examines the impact of early childhood exposure to the 2003 SARS pandemic on adulthood mental health after 17 years in China, using data from the 2020 China Family Panel Studies (CFPS). The analysis included 6289 participants, aged 3 to 30 years during the SARS outbreak, with an average age of 35.3 years at the time of survey. Adulthood mental health was assessed using Center for Epidemiologic Studies Depression Scale (CESD) and an indicator of clinical depression. The severity of local SARS outbreaks was assessed by cumulative cases per 10,000 population. Results show that each additional case per 10,000 population was linked to a 1.617-fold (95% confidence interval (CI): 1.425–1.836) increase in odds of depression after 17 years for younger children (aged 3–12 years in 2003) relative to older cohorts (aged 13-30). This risk was higher in children from rural areas (adjusted odds ratio (aOR) 3.64; 95% CI 2.92–4.55), with poor physical health (1.98; 1.59–2.48), and from low-income families (2.87; 2.03–4.05). The childhood pandemic experience elevated the probability of developing depression-prone personality traits, which contributes to the enduring impact of childhood pandemic experiences on adulthood mental health. These findings highlight the long-lasting psychological impact of early-childhood pandemic exposure, underscoring the need for targeted interventions to mitigate its effects on the younger generation and emphasizing the importance of monitoring long-term mental health and personality development in children post-pandemics, particularly in light of COVID-19.

International progress on stillbirth reduction: Changes in Stillbirth Rates in Selected Low and Middle-Income Countries from 2000 to 2021

In this paper, we attempted to determine if there were reductions in low and middle – income country stillbirth rates since 2000 - focusing on sub-Saharan Africa, Asia and Latin America and the Caribbean. We used data made available by the United Nations Inter-agency Group for Child Mortality Estimation and the World Health Organization as well as the National Institute of Child Health and Human Development Global Network for Women's and Children's Health Research.. Overall, nearly every country evaluated had at least a small reduction in stillbirth rate from the year 2000 to 2021, but the reductions varied substantially between regions. Asia and Latin America/Caribbean had similar levels of reductions with a number of countries in each of those regions having rates in 2021 that were 40 % or more lower than those documented in 2000. No country in Africa documented a reduction in stillbirths of 40 % and many had stillbirth reductions of less than 15 %.

Paediatric Cushing syndrome: a prospective, multisite, observational cohort study

Paediatric endogenous Cushing syndrome is a rare condition with variable signs and symptoms of presentation. We studied a large cohort of paediatric patients with endogenous Cushing syndrome with the aim of describing anthropometric, clinical, and biochemical characteristics as well as associated complications and outcomes to aid diagnosis, treatment, and management. In this prospective, multisite cohort study, we studied children and adolescents (≤18 years at time of presentation) with a diagnosis of Cushing syndrome. Patients had either received their initial diagnosis and evaluation at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Bethesda, MD, USA) or been referred from other centres in the USA or outside the USA. We collected participants' clinical, biochemical, and imaging findings and recorded their post-operative course until their latest appointment. Of 342 paediatric patients with a diagnosis of Cushing syndrome, 193 (56%) were female and 149 (44%) male. 261 (76%) patients had corticotroph pituitary neuroendocrine tumours (Cushing disease), 74 (22%) had adrenal-associated Cushing syndrome, and seven (2%) had ectopic Cushing syndrome. Patients were diagnosed at a median of 2 years (IQR 1·0-3·0) after the first concerning sign or symptom, and patients with adrenal-associated Cushing syndrome were the youngest at diagnosis (median 10·4 years [IQR 7·4-13·6] vs 13·0 years [10·5-15·3] for Cushing disease vs 13·4 years [11·0-13·7] for ectopic Cushing syndrome; p<0·0001). Body-mass index z-scores did not differ between the diagnostic groups (1·90 [1·19-2·34] for adrenal-associated Cushing syndrome vs 2·18 [1·60-2·56] for Cushing disease vs 2·22 [1·42-2·35] for ectopic Cushing syndrome; p=0·26). Baseline biochemical screening for cortisol and adrenocorticotropin at diagnosis showed overlapping results between subtypes, and especially between Cushing disease and ectopic Cushing syndrome. However, patients with ectopic Cushing syndrome had higher urinary free cortisol (fold change in median cortisol concentration from upper limit of normal: 15·5 [IQR 12·7-18·0]) than patients with adrenal-associated Cushing syndrome (1·5 [0·6-5·7]) or Cushing disease (3·9 [2·3-6·9]; p<0·0001). Common complications of endogenous Cushing syndrome were hypertension (147 [52%] of 281 patients), hyperglycaemia (78 [30%] of 260 patients), elevated alanine transaminase (145 [64%] of 227 patients), and dyslipidaemia (105 [48%] of 219 patients). Long-term recurrence was noted in at least 16 (8%) of 195 patients with Cushing disease. This extensive description of a unique cohort of paediatric patients with Cushing syndrome has the potential to inform diagnostic workup, preventative actions, and follow-up of children with this rare endocrine condition. Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health.

Preconception sleep duration, non-daytime work schedules, and incidence of spontaneous abortion: a prospective cohort study.

To what extent do self-reported sleep duration and non-daytime work schedules in either partner affect the rate of spontaneous abortion (SAB)? Incidence of SAB had little association with female sleep duration and a modest positive association with male short sleep duration, female work at night, and discrepant work schedules among partners. Several studies have reported an association between short sleep duration in either partner and reproductive health outcomes, including fecundability. Moreover, certain types of female occupational exposures during pregnancy have been associated with an increased risk of SAB. No studies have evaluated SAB risk in relation to male sleep and work schedules, or joint exposures within a couple. This prospective cohort study included 9357 female participants and 2602 of their male partners residing in North America (June 2013 to April 2023). Participants enrolled when they were attempting pregnancy and completed self-administered baseline questionnaires about their average sleep duration and work schedules. Among those who conceived, we ascertained SAB and gestational age at loss via follow-up questionnaires. We used multivariable Cox proportional hazards models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% CIs relating SAB with sleep duration and non-daytime work schedules for female and male participants, and the couple. We used inverse probability weighting to account for potential selection bias due to the possibility of differential participation of male partners with respect to the exposures. Compared to female participants with recommended sleep (7-8.9 h), those reporting short sleep duration (<6 h) did not have a higher rate of SAB (HR 0.88, 95% CI 0.69, 1.13). Short self-reported sleep duration among male participants was modestly associated with a higher rate of SAB (adjusted and weighted HR 1.30, 95% CI 0.96, 1.75). Female night work at night (adjusted HR 1.19, 95% CI 1.02, 1.38) and male non-daytime work (adjusted and weighted HR 1.26, 95% CI 1.00, 1.59) were associated with modestly higher rates of SAB, whereas female rotating shift work was not (adjusted HR 0.91, 0.78, 1.05) compared with daytime workers. Couples in which work schedules were discrepant had an elevated rate of SAB if the male partner worked a non-daytime shift (adjusted and weighted HR 1.46, 95% CI 1.13, 1.88) compared with couples in which both members worked during the day. The corresponding HR if only the female partner worked a non-daytime shift was 1.21 (95% CI 0.92, 1.58). Data on sleep duration and work schedules were based on self-report, which is vulnerable to misclassification, particularly since participants were asked to report their average sleep duration during the past month. Work exposures were heterogeneous, as many different types of employment may require night and shift work and may have different associations with SAB. Our findings are consistent with previous research indicating that some types of female employment schedules may be associated with SAB incidence. This is the first study to indicate a relationship between SAB and male employment schedules, indicating that discrepant work schedules within a couple might be relevant. This work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01HD105863 (PIs: L.A.W. and M.L.E.), R01HD086742 (PIs: L.A.W. and E.E.H.), and R21HD072326 (PI: L.A.W.). PRESTO has received in-kind donations from Swiss Precision Diagnostics and Kindara.com for primary data collection. L.A.W. is a consultant for AbbVie, Inc. and the Gates Foundation. M.L.E. is an advisor for and holds stock in Ro, Hannah, Dadi, Underdog, Vseat, & Doveras. The other authors have no competing interests to declare. N/A.

HIV-1 reservoir size after neonatal antiretroviral therapy and the potential to evaluate antiretroviral-therapy-free remission (IMPAACT P1115): a phase 1/2 proof-of-concept study

Infants born with HIV-1 require lifelong antiretroviral therapy (ART). We aimed to assess whether very early ART in neonates might restrict HIV-1 reservoirs, an important step towards ART-free remission. IMPAACT P1115 is an ongoing, phase 1/2, proof-of-concept study in which infants were enrolled at 30 research clinics in 11 countries (Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the USA, Zambia, and Zimbabwe) into two cohorts. Infants at least 34 weeks' gestational age at high risk for in-utero HIV-1 with either untreated maternal HIV-1 (cohort 1) or who were receiving pre-emptive triple antiretroviral prophylaxis outside of the study (maternal ART permissible; cohort 2) were included. All infants initiated treatment within 48 h of life. Cohort 1 initiated three-drug nevirapine-based ART, and cohort 2 initiated three-drug nevirapine-based prophylaxis then three-drug nevirapine-based ART following HIV diagnosis by age 10 days. We added twice-daily coformulated oral ritonavir 75 mg/m2 and lopinavir 300 mg/m2 from 14 days of life and 42 weeks postmenstrual age. We discontinued nevirapine 12 weeks after two consecutive plasma HIV-1 RNA levels below limit of detection. We tracked virological suppression, safety outcomes, and meeting a predetermined biomarker profile at age 2 years (undetectable RNA since week 48, HIV-1 antibody-negative, HIV-1 DNA not detected, and normal CD4 count and CD4 percentage) to assess qualification for analytical treatment interruption. This study is registered with ClinicalTrials.gov, NCT02140255. Between Jan 23, 2015, and Dec 14, 2017, 440 infants were included in cohort 1 and 20 were included in cohort 2. 54 of these infants (34 from cohort 1 and 20 from cohort 2) had confirmed in-utero HIV-1 and were enrolled to receive study ART. 33 (61%) of 54 infants were female and 21 (39%) were male. The estimated probability of maintaining undetectable plasma RNA through to 2 years was 33% (95% CI 17-49) in cohort 1 and 57% (28-78) in cohort 2. Among infants maintaining protocol-defined virological control criteria through to study week 108, seven of 11 (64%, 95% CI 31-89) in cohort 1 and five of seven (71%, 29-96) in cohort 2 had no detected HIV-1 DNA. Ten of 12 (83%, 52-100) in cohort 1 and all seven (100%, 59-100) in cohort 2 tested HIV-1 antibody-negative at week 108. Among 54 infants initiated on very early ART, ten (19%; six in cohort 1 and four in cohort 2) met all criteria for possible analytical treatment interruption. Reversible grade 3 or 4 adverse events occurred in 15 (44%) of 34 infants in cohort 1 and seven (35%) of 20 infants in cohort 2. Very early ART for in-utero HIV-1 can achieve sustained virological suppression in association with biomarkers indicating restricted HIV-1 reservoirs by age 2 years, which might enable potential ART-free remission. National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

Placental accelerated aging in antenatal depression

Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging. This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery. The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment. There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses. Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.

Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort

Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort. We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using weighted correlation network analysis and common networks using consensus network analysis across four visits using linear mixed-effects models with the adjustment of false discover rate. Multiple triglycerides (TG) were positively associated with birth weight (BW), BW Z-score, length and head circumference, while some cholesteryl ester (CE), phosphatidylcholine (PC), sphingomyelines (SM), phosphatidylethanolamines (PE), and lysophosphatidylcholines (LPC 20:3) families were inversely associated with BW, length, abdominal and head circumference at different GWs. Longitudinal trajectories of TG, PC, and glucosylcermides (GlcCer) were associated with BW, and CE (18:2) with BW z-score, length, and sum of skinfolds (SS), while some PC and PE were significantly associated with abdominal and head circumference. Modules of TG at GW 10-14 and 15-26 mainly were associated with BW. At GW 33-39, two networks of LPC (20:3) and of PC, TG, and CE, showed inverse associations with abdominal circumference. Distinct trajectories within two consensus modules with changes in TG, CE, PC, and LPC showed significant differences in BW and length. The results demonstrated that longitudinal changes of TGs during early- and mid-pregnancy and changes of PC, LPC, and CE during late-pregnancy were significantly associated with neonatal anthropometry. National Institute of Child Health and Human Development intramural funding.

Comprehensive Analysis of Risk Factors for Bronchopulmonary Dysplasia in Preterm Infants in Taiwan: A Four-Year Study.

Bronchopulmonary dysplasia (BPD) is a major respiratory condition mainly affecting premature infants. Although its occurrence is global, risk factors may differ regionally. This study, involving 3111 infants with birth weight ≤ 1500 gm or gestational age (GA) < 30 weeks, aimed to identify risk factors for BPD and BPD/mortality in Taiwan using data from the Taiwan Neonatal Network. The BPD criteria were based on the National Institute of Child Health and Human Development standards. Average GA was 27.5 weeks, with 23.7% classified as small for GA (SGA). Multivariate analysis highlighted low GA, low birth weight, and other perinatal factors as significant risk indicators for BPD. For moderate-to-severe BPD, additional risk factors included male gender and SGA, endotracheal intubation (ETT) or cardiopulmonary cerebral resuscitation (CPCR) in initial resuscitation. In the moderate-to-severe BPD/death group, SGA and ETT or CPCR in initial resuscitation remained the only additional risk factors. The study pinpoints male gender, SGA and ETT or CPCR as key risk factors for moderate-to-severe BPD/death in low-birth-weight infants in Taiwan, offering a basis for focused interventions and further research.

Selection of Standards for Sonographic Fetal Femur Length by Use of z-scores.

This study aimed to evaluate which of four established norms should be used for sonographic assessment of fetal femur length (FL). Cross-sectional study using pooled data from four maternal-fetal medicine practices. Inclusion criteria were singleton fetus, gestational age (GA) 220/7 to 396/7 weeks, biometry measured, and fetal cardiac activity present. Four norms of FL were studied: Hadlock et al, the INTERGROWTH-21st Project (IG-21st), the World Health Organization Fetal Growth Curves (WHO), and the National Institutes of Child Health and Human Development Fetal Growth Studies, unified standard (NICHD-U). The fit of our FL measurements to each norm was assessed by these criteria: mean z-score close to 0, standard deviation (SD) of z close to 1, Kolmogorov-Smirnov D-statistic close to zero, Youden J-statistic close to 1, approximately 5% of exams <5th percentile, and approximately 5% of exams >95th percentile. In 26,177 ultrasound exams, our FL measurements had the best fit to the WHO standard (mean z-score 0.15, SD of z 1.02, D-statistic <0.01, J-statistic 0.95, 3.4% of exams <5th percentile, 7.0% of exams >95th percentile). The mean of the IG-21st standard was smaller than the other norms and smaller than our measurements, resulting in underdiagnosis of short FL. The mean of the Hadlock reference was larger than the other norms and larger than our measurements, resulting in overdiagnosis of short FL. The SD of the NICHD-U standard was larger than the other norms and larger than our observations, resulting in underdiagnosis of both short and long FL. Restricting the analysis to a subgroup of 7,144 low-risk patients without risk factors for large- or small-for- GA produced similar results. Of the norms studied, the WHO standard is likely best for diagnosis of abnormal FL. · There are >30 norms for fetal FL.. · It is unknown which norm should be used.. · Our data fit the World Health Organization standard better than the other norms..