Long-term effects on growth in preterm and small for gestational age infants: A national birth cohort study.

BACKGROUND: Premature and small-for-gestational-age (SGA) infants tend to have long-term growth morbidities such as short stature, failure to thrive, and obesity. Although most of these infants show catch-up growth at 2-4 years of age, they are still more susceptible to childhood obesity and related metabolic disorders. Those who fail to achieve catch-up will suffer from pathological short stature and neurodevelopmental impairment through adulthood. This study aims to depict the growth pattern of premature or SGA infants and their growth morbidities in Taiwan. METHODS: Data were obtained from a nationally representative cohort of 24,200 pairs of postpartum women and newborns in the Taiwan Birth Cohort Study (TBCS), using structured questionnaire interviews. A total of 16,358 infants were included and three follow-up surveys were completed at 6, 18, and 36 months after the deliveries. We constructed growth curves to conduct an in-depth investigation into anthropometric data, applying a linear mixed model. Logistic regression was used to model the relevant outcomes, with adjustment for various potential confounding factors. RESULTS: Despite being born shorter and lighter, preterm and SGA infants generally showed catch-up growth and had no higher odds ratios (ORs) of developing short stature or failure to thrive compared to appropriate-for-gestational-age (AGA) term infants before 3 years of age. Preterm SGA infants, particularly females, had higher ORs for obesity at the 36-month follow-up. CONCLUSION: This is the first nationwide population-based study depicting the growth of SGA infants in Taiwan. The growth patterns of preterm and term SGA infants are different from those of preterm and term AGA infants. Further research is necessary to understand the growth trajectories of preterm and SGA infants and their associations with later diseases.

Pre-pregnancy shift work's influence on postpartum weight retention: Body mass index's role.

Shift work is a prevalent workplace exposure, which increases the possibility of unhealthy behaviours and circadian rhythm disruptions and elevates the risk of metabolic diseases and adverse reproductive outcomes. But its potential of increasing the risk of postpartum weight retention remains uncertain. This study aimed to investigate the association between maternal shift work prior to conception and postpartum weight retention, and to identify modifiable factors during pregnancy for prevention. We analysed data from the Taiwan Birth Cohort Study, a prospective cohort of Taiwanese women who gave birth in 2005. We examined the pre-conceptional shift work status of 13,575 mothers and their body weight before pregnancy, before delivery, six and eighteen months after delivery. We used multivariable linear models to examine associations and effect modifications. Maternal shift work before pregnancy was significantly associated with increased postpartum weight retention at six and eighteen months (ß-estimate for six months: 0.19-kilogram, 95% CI: 0.03-0.34; eighteen months: 0.23-kilogram, 95% CI: 0.04-0.40). The association between shift work and weight retention at six months postpartum was stronger among mothers who were overweight or obese before pregnancy than mothers with normal weight. This study showed the impact of shift work on postpartum weight retention and suggested a stronger association among mothers with overweight or obesity before pregnancy.

Adrenal hemorrhage in neonates: Incidence, perinatal characteristics and follow-up outcomes.

BACKGROUND AND OBJECTIVES: Neonatal adrenal hemorrhage (NAH) is relatively uncommon in neonates and it is often noted accidently by abdominal ultrasonogram. Few studies discussed risk factors for and impacts of NAH. This study aimed to assess incidence, perinatal characteristics and follow-up outcomes in neonates with adrenal hemorrhage. METHODS: This was a retrospective cohort study in a single institute from April 2008 to August 2018. All neonates who received abdominal ultrasonogram within seven days-of-life were recruited and divided in to 2 groups according to the presence of NAH. The perinatal characteristics and anthropometric measurements, the follow-up course and the clinical impact of NAH were reviewed in detail. RESULTS: 7217 neonates had received abdominal ultrasonogram within seven days-of-life and 29 of them (0.4%) were diagnosed with NAH. Mean gestation age was 38 ± 1.2 weeks and mean birth weight was 3406 ± 403 g. Most infants (96.6%) had unilateral hemorrhage over the right adrenal gland. Compared with the control group, infants with NAH were significantly heavier (3406 vs. 3094 gm, p < 0.001), longer in body length (50.1 vs. 48.8 cm, p < 0.001) and wider in chest girth (33.2 vs. 32.4 cm, p = 0.006). They also tended to be delivered via vaginal delivery with vacuum-extraction rather than cesarean section. The prevalence of nuchal cord, neonatal jaundice and subgaleal hemorrhage was higher in the NAH group. The hemorrhage area of adrenal gland had a positive correlation with the peak bilirubin level (r = 0.422, p < 0.001) and the days to resolution (r = 0.198, p = 0.033). All infants had resolution of AH before 7 months of age. CONCLUSIONS: NAH occurred more frequently in heavier neonates that were delivered via vaginal delivery with vacuum extraction. The hemorrhage involved mostly over the right adrenal gland. Neonatal jaundice was the major comorbidity. All infants had spontaneous resolution of AH before 7 months of age.

Association between Cesarean section delivery and increased risk of childhood Kawasaki disease.

AIM: Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. METHODS: We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. RESULTS: Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14-4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14-4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. CONCLUSION: In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan.

Reappraisal of therapeutic vancomycin trough concentrations with empirical dosing in neonatal infections.

BACKGROUND: Vancomycin is commonly used for neonatal sepsis. However, consensus on an empirical neonatal vancomycin regimen remains uncertain. We aimed to reappraise the therapeutic optimum concerning vancomycin trough concentrations with empirical dosing and to evaluate the relationship between trough concentrations and predicted 24-h area under the curve (AUC24). METHODS: This was a 3-year retrospective study. Neonates who were admitted to the neonatal intensive care unit with available vancomycin trough concentrations were enrolled. Trough levels were obtained before the fourth dose. Achievement of goal trough after implementing the vancomycin dosing regimen was based on the Practical Neonatology Medical Manual, published by the National Taiwan University College of Medicine. RESULTS: A total of 46 neonates were included for analysis. Coagulase-negative staphylococci were the most commonly identified pathogens of sepsis. Among these patients, 22 achieved goal trough levels of 10-20 mcg/mL. Trough levels of 5-10 or >20 mcg/mL occurred in 13 and 11 patients, respectively. A moderately positive correlation between trough and predicted AUC24 was found in all patients (Spearman's rho = 0.676, p < 0.001). In patients with body weight 1200-2000 g and postnatal age >7 days, the serum creatinine of those with trough levels >20 mcg/mL was significantly higher than those with goal trough levels (0.61 vs. 0.45 mg/dL, p = 0.01). Among those with trough levels >20 mcg/mL, 5 patients received ibuprofen for patent ductus arteriosus closing prior to vancomycin treatment (45%, 5/11), compared to only 3 patients with trough levels <20 mcg/mL (9%, 3/35) (p = 0.013). CONCLUSION: Only half of the neonates receiving empirical vancomycin regimen achieved goal trough levels of 10-20 mcg/mL. Higher serum creatinine or ibuprofen treatment may increase the risk of overly high trough levels. The vancomycin regimen needs further validation and modification to provide adequate dosing for optimal use in neonates.

Association between maternal shift work during pregnancy child overweight and metabolic outcomes in early childhood.

Background: Previous studies found that maternal shift work during pregnancy was associated with many reproductive hazards, including small for gestational age, preterm birth, stillbirth, and neurodevelopmental impairment. Some studies also showed that these children are more likely to become overweight in early childhood. However, the association with metabolic factors, such as insulin resistance and dyslipidemia, was less studied. Hence, we aimed to understand better the relationship between maternal shift work during pregnancy and the risk of childhood overweight and metabolic outcomes. Confounding factors were also discussed, including diet, exercise, and demographical factors. Methods: We enrolled pregnant women before delivery in the Taiwan Birth Panel Study (TBPS) II conducted between 2010 and 2012, and followed the children of these participants in 2018. The objective of this study is to investigate the influence of prenatal and postnatal factors on infant and early childhood health. During the follow-up in 2018, we checked children's demographic data, obtained blood specimens, and checked their blood sugar, blood insulin, and lipid profiles. Structured questionnaires were used to evaluate demographic data. Multiple linear and logistic regressions were used to examine the associations between maternal shift work during pregnancy and child overweight, metabolic disorders, such as HOMA-IR, and lipid profiles. Results: In this study, we included 407 mother-children pairs with different work shifts (350 day workers and 57 shift workers), and a sub-population without underweight children was also created (290 day workers and 47 shift workers). Shift work during pregnancy was associated with a higher Homeostasis Model Assessment-Insulin Resistance index (HOMA-IR) and a higher odds ratio for overweight in children born from mothers doing shift work during pregnancy after adjustment. The findings were attenuated when we investigated the effect of shift work before pregnancy. Conclusion: Our study suggested that maternal shift work during pregnancy was associated with child overweight and insulin resistance in early childhood.

Cognitive and motor development in preterm children from 6 to 36 months of age: Trajectories, risk factors and predictability.

BACKGROUND: Although numerous studies have examined the development of preterm children born very low birth weight (VLBW, birth body weight < 1500 g), variations of developmental progress within individuals have rarely been explored. The aim of this research was to examine the cognitive and motor trajectories in preterm children born VLBW at early ages and to assess the risk factors and predictability of these trajectories. METHOD: Five hundred and eighty preterm infants born VLBW from three cohort studies (2003 to 2014) were prospectively assessed their mental and motor development using the Bayley Scales at 6, 12, 24, and 36 months, and cognitive, motor and behavioral outcomes using the Movement Assessment Battery for Children and the Child Behavior Checklist for Ages 1.5-5 at 4 years of age. RESULTS: Preterm children born VLBW manifested three cognitive patterns (stably normal [64.0 %], deteriorating [31.4 %], and persistently delayed [4.6 %]) and four motor patterns (above average [6.3 %], stably normal [60.0 %], deteriorating [28.5 %], and persistently delayed [5.2 %]) during 6-36 months. Low birth body weight, stage III-IV retinopathy of prematurity and low parental socio-economic status were associated with the deteriorating patterns; prolonged hospitalization and major brain damage were additionally associated with the persistently delayed patterns. Furthermore, the cognitive and motor deteriorating pattern was each predictive of cognitive and motor impairment at 4 years of age; whereas, the persistently delayed patterns were predictive of multiple impairments. CONCLUSION AND IMPLICATIONS: Preterm children born VLBW display heterogeneous trajectories in early cognitive and motor development that predict subsequent developmental and behavioral outcomes.

Can NT-proBNP Levels Be an Early Biomarker of Reduced Left Ventricular Ejection Fraction in Preterm Infants?

Background/Objective: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac natriuretic hormone that cardiomyocytes release in response to ventricular stretch. It helps with the diagnosis of heart failure in adults, but this application in preterm infants has rarely been reported. This study aimed to evaluate whether NT-proBNP could be used for the early detection of reduced cardiac ejection fraction in preterm infants and the optimal timing for NT-proBNP assessment. Design/Methods: This prospective, single-center, observational study enrolled all preterm infants with NT-proBNP measurements from October 2014 to February 2022. They underwent echocardiographic examinations within 48 h of the NT-proBNP measurements. Reduced left ventricular ejection fraction was defined as below 60%. Receiver operator characteristic (ROC) curves were generated to assess the optimal NT-proBNP cutoff point for the early prediction of reduced cardiac ejection fraction. Results: A total of 68 preterm infants were enrolled, with a total of 134 NT-proBNP measurements being available for analysis. Reduced left ventricular ejection fraction was present in seven infants (10.3%) due to various underlying diseases. The NT-proBNP cutoff level for detecting reduced left ventricular ejection fraction was 9248 pg/mL, with 71.4% sensitivity and 60.8% specificity; the area under the curve was 0.623 (95% CI: 0.487~0.760). The threshold for the optimal postnatal age for applying NT-proBNP to detect reduced left ventricular ejection fraction was >2 days of life (AUC: 0.682; 95% CI: 0.518~0.845), with 70% sensitivity and 67.1% specificity. Conclusions: Although the NT-proBNP levels declined dramatically after birth, a NT-proBNP serum level of 9248 pg/mL might be helpful for the early detection of reduced ejection fraction in preterm infants, and the optimal age for detection was after 2 days of life.

Associations between prenatal exposure to perfluoroalkyl substances, hypomethylation of MEST imprinted gene and birth outcomes.

Prenatal perfluoroalkyl substance (PFAS) exposure has been linked to adverse birth outcomes, but the underlying mechanism has yet to be elucidated. DNA methylation changes in mesoderm-specific transcript (MEST) imprinted gene may be a mechanism of the prenatal exposure effects of PFASs on fetal growth. The aim was to investigate the prenatal PFASs exposure effects on DNA methylation changes in MEST imprinted gene involved in fetal growth. Among 486 mother-infant pairs from the Taiwan Birth Panel Study, PFASs and DNA methylation levels at 5 CpG sites of MEST promoter region were measured in cord blood. Univariable and multivariable linear regressions were performed to estimate the associations between prenatal PFAS exposure, MEST DNA methylation levels, and child birth outcomes. Mediation analysis was performed to examine the potential pathway of MEST methylation between PFASs and birth outcomes. We found that higher prenatal perfluorooctyl sulfonate (PFOS) exposure was significantly associated with lower methylation levels at 5 CpG sites of MEST promoter region (an adjusted ß range: -1.56, -2.22). Significant negative associations were also found between MEST methylation levels and child birth weight. Furthermore, the associations between PFOS and perfluorooctanoic acid (PFOA) exposure and MEST methylation levels were more profound in girls than in boys. The mediated effect of average MEST methylation level between PFOS exposure and birth weight was 18.3 (95% CI = 2.1, 40.2; p = 0.014). The direct effect of PFOS exposure to birth weight independent to average MEST methylation level was -93.2 (95% CI = -170.5, -17.8; p = 0.018). In conclusion, our results suggest that prenatal PFAS exposure, especially PFOS, is associated with lower methylation levels at MEST promoter region, which not only leverages the role of imprinted gene in ensuring the integrity of fetal growth but also provides a potential mechanism for evaluating the prenatal exposure effect.

Fresh Frozen Plasma Transfusion: An Independent Risk Factor for Hemodynamically Significant Patent Ductus Arteriosus in Premature Infants.

OBJECTIVE: The incidence of patent ductus arteriosus (PDA), a major complication of prematurity, may be reduced by restricting fluid administration. Prophylactic fresh frozen plasma (FFP) transfusion may reduce the incidence of intraventricular hemorrhage in these infants, but risks transfusion-related volume overload. We conducted a retrospective study to investigate whether FFP transfusion is a risk factor for hemodynamically significant PDA (hsPDA) in very low birth weight (BW) premature infants. STUDY DESIGN: From January 2009 to December 2014, 102 premature infants with gestational age (GA) less than or equal to 30 weeks were admitted to a level III neonatal intensive care unit, and 88 patients were enrolled. Patients were further divided into non-hsPDA (n = 29) and hsPDA groups (n = 59). We retrospectively reviewed demographic characteristics and various perinatal and postnatal variables. Univariate and multivariable analyses were performed to identify risk factors for hsPDA. RESULTS: Compared with non-hsPDA patients, hsPDA patients had lower mean BW and GA, a higher incidence of severe respiratory distress symptoms, perinatal infection, use of surfactant, and need for FFP transfusion. However, multivariable logistic regression analysis showed that only FFP transfusion remained an independent risk factor for hsPDA (adjusted odds ratio = 3.880, 95% confidence interval: 1.214-12.402, p = 0.022) after adjusting for confounding factors. CONCLUSION: FFP transfusion is a significant risk factor for the subsequent development of hsPDA in our study population. FFP transfusion may complicate the fluid management of premature infants and increase the risk of hsPDA. KEY POINTS: · Hemodynamic significant PDA is an important complication of preterm infant.. · FFP transfusion may complicate the fluid management of premature infants.. · FFP transfusion is an independent risk factor for hsPDA in very low birth weight premature infants..

Lenticulostriate Vasculopathy in Very-Low-Birth-Weight Preterm Infants: A Longitudinal Cohort Study.

BACKGROUND: The pathogenesis and clinical significance of lenticulostriate vasculopathy (LSV) are unclear. Our study aimed to determine the prevalence, presentation, and evolution of LSV, and the perinatal risk factors associated with LSV among very-low-birth-weight (VLBW) preterm infants. METHODS: One-hundred-and-thirty VLBW preterm infants were retrospectively enrolled in this study. Serial cranial ultrasound examinations were performed regularly from birth until a corrected age of 1 year. Infants with LSV were assigned to early-onset (≤10 postnatal days) and late-onset (>10 postnatal days) groups. Data describing the infants' perinatal characteristics, placental histopathology, and neonatal morbidities were collected, and the groups were compared. RESULTS: Of the VLBW infants, 39.2% had LSV before they were 1 year old. Linear-type LSV was the most common presentation, and >50% of the infants had bilateral involvement. LSV was first detected at 112 ± 83 postnatal days, and its detection timing correlated negatively with gestational age (GA) (R2 = 0.153, p = 0.005) and persisted for 6 months on average. The infants with and without LSV had similar perinatal characteristics, placental pathologies, cytomegalovirus infection rates, and clinical morbidities. The late-onset LSV group comprised 45 (88.2%) infants who had a significantly higher rate of being small for gestational age (SGA) and used oxygen for longer than the infants without LSV. After adjusting a multivariable regression model for GA and SGA, analysis showed that the duration of oxygen usage was an independent risk factor for late-onset LSV development in VLBW infants (odds ratio: 1.030, p = 0.032). CONCLUSION: LSV may be a nonspecific marker of perinatal insult to the developing brains of preterm infants. Prolonged postnatal oxygen usage may predispose VLBW preterm infants to late-onset LSV development. The long-term clinical impacts of LSV should be clarified.

Histological chorioamnionitis and its impact on respiratory outcome in very-low-birth-weight preterm infants.

BACKGROUND: The role of intrauterine infection in the development of neonatal pulmonary disease is unclear and the impact of histological chorioamnionitis (HCAM) on respiratory outcomes in preterm infants remains controversial. The aim of this study was to explore the association between HCAM and neonatal respiratory outcomes in very-low-birth-weight (VLBW) preterm infants and evaluate the stepwise difference in the stage and severity of HCAM among neonatal respiratory outcomes. METHODS: We retrospectively enrolled 129 VLBW preterm infants with placenta histopathology examinations in this study. HCAM was subdivided into 3 stages (early, intermediate, and advanced) according to the progression of the maternal inflammatory response. The perinatal characteristics, placental histopathology, and neonatal morbidities, including respiratory outcomes (respiratory distress syndrome (RDS), Wilson-Mikity syndrome (WMS) and bronchopulmonary dysplasia (BPD)), were collected for comparison. RESULTS: A total of 52.7% (68/129) of the infants had HCAM, including 23 early (stage 1), 30 intermediate (stage 2), and 15 advanced (stage 3) stage. There was no significant difference in the gestational age, birth body weight or mortality rate between the HCAM and non-HCAM groups. Mothers with HCAM had a significantly lower incidence of pre-eclampsia but a higher rate of premature rupture of membrane. They also had higher WBC counts and C-reactive protein levels before delivery. Neonates with HCAM had a lower incidence of RDS but were at a higher risk for developing WMS and BPD. After multivariate analysis adjustment, HCAM was still negatively associated with RDS (aOR = .069, p < .001) but without correlation with BPD. However, neonates with intermediate to advanced-stage HCAM had a higher risk of developing WMS and increased home oxygen usage rate compared to those with early-stage HCAM. CONCLUSION: HCAM has a protective effect from RDS in preterm neonates. Additionally, VLBW neonates with intermediate to advanced-stage HCAM are at risk for WMS.

Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status.

INTRODUCTION: Secondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population. AIMS AND METHODS: Term singleton mother-infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification. RESULTS: Higher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye. CONCLUSIONS: Secondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status. IMPLICATIONS: The study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.

Prenatal chlorpyrifos exposure in association with PPARγ H3K4me3 and DNA methylation levels and child development.

BACKGROUND: Chlorpyrifos, one of the most widely used pesticides, can penetrate the placenta and affect fetal growth and neurodevelopment. Epigenetic regulation of peroxisome proliferator-activated receptor gamma (PPARγ), such as DNA methylation and trimethylation of lysine 4 of H3 (H3K4me3), may provide a potential mechanism for how fetal growth and development are impacted by chlorpyrifos exposure. The aims of the study were to investigate whether prenatal chlorpyrifos exposure was associated with H3K4me3 and DNA methylation levels of the PPARγ gene in the placenta and the related effects on birth outcomes and neurodevelopment. METHODS: Among 425 mother-infant pairs from the Taiwan Birth Panel Study, chlorpyrifos levels were measured in cord blood by using online SPE-LC/HESI/MS/MS; placental PPARγ H3K4me3 and DNA methylation levels were measured by ChIP-qPCR and pyrosequencing, respectively; the neonates' health outcomes were extracted from the medical records; and childhood neurodevelopment was evaluated by using the Comprehensive Developmental Inventory for Infants and Toddlers in 2-year-old children. Multivariable regression models were used to adjust for potential confounders. RESULTS: After controlling for potential confounders, each unit increase in the natural log-transformed prenatal chlorpyrifos exposure level was associated with an increase in the PPARγ DNA methylation level (adjusted ß (aß) = 0.77, p = 0.032) and poorer performance in the cognitive and language domains at 2 years old, especially in boys (aß = -1.66, p = 0.016, and aß = -1.79, p = 0.023, respectively). PPARγ H3K4me3 levels were positively associated with gestational age (aß = 0.16, p = 0.011), birth weight (aß = 30.52, p = 0.013), birth length (aß = 0.18, p = 0.003 and aß = 0.15, p = 0.042), and gross-motor performance (aß = 1.67, p = 0.036). CONCLUSIONS: Our findings suggested that prenatal chlorpyrifos exposure affected PPARγ DNA methylation levels and performance in the cognitive and language domains.

Associations between household incense burning and delayed motor development among preterm infants modified by gestational age and maternal educational status.

BACKGROUND: Household incense burning is a common ritual behavior in the Asia-Pacific region but has been associated with inferior developmental outcomes in term infants. We aimed to examine these associations among preterm infants. METHODS: Information from 1190 mother-infant pairs during 6- and 18-month follow-up to the Taiwan Birth Cohort Study was examined for associations between household incense burning exposure and infant neurodevelopmental milestone achievement using multivariable Cox proportional hazard model with propensity score weighting, along with stratified, sensitivity, and decomposition analysis. RESULTS: Household incense burning exposure was associated with delayed gross motor milestone achievement among all preterm infants according to the Cox model and after propensity score weighting. Meanwhile, associations for delayed development were found in gross motor domain milestones among late preterm infants, while fine motor domain delay was found among other preterm infants. Furthermore, the associations between household incense burning status and gross motor milestone delays were attenuated by the interaction between higher education level and household incense burning exposure status. CONCLUSIONS: Household incense burning exposure was associated with delays, and the motor domains affected differed according to degree of prematurity. These associations were modified by the attenuation upon higher maternal educational status and exposure status interaction.

Intrauterine exposure to per- and polyfluoroalkyl substances may harm children's lung function development.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA), are common persistent environmental organic pollutants. Animal studies have indicated that PFAS influence inflammatory responses and lung development. However, whether prenatal or childhood PFAS exposure affects children's lung function remains unclear. This study aimed to investigate both in utero exposure and childhood exposure to PFAS and the relationships between them and lung function development in childhood. METHODS: In total, 165 children were recruited from the Taiwan Birth Panel Study (TBPS). Cord blood plasma and children's serum were collected when they were eight years old. PFAS levels were analysed by ultra-high-performance liquid chromatography/tandem mass spectrometry. When these children reached eight years of age, we administered detailed questionnaires and lung function examinations. RESULTS: The mean concentrations of PFOA, PFOS, PFNA and PFUA in cord blood among the 165 study children were 2.4, 6.4, 6.0, and 15.4 ng/mL, respectively. The mean concentrations in serum from eight-year-olds were 2.7, 5.9, 0.6, and 0.3 ng/mL, respectively. At eight years of age, the mean FEV1 (forced expiratory volume per sec), FVC (forced vital capacity), PEF (peak expiratory flow) and FEV1/FVC values were 1679 mL, 1835 mL, 3846 mL/s and 92.0%, respectively. PFOA, PFOS, PFNA and PFUA levels in cord blood were inversely associated with FEV1, FVC and PEF values. The PFOS concentration in cord blood was the most consistently correlated with decreasing lung function before and after adjusting for confounding factors. The PFOS concentration was also significantly inversely correlated with lung function in subgroups with lower birth weight and allergic rhinitis. CONCLUSIONS: Our cohort study revealed that the concentrations of PFOA, PFOS, PFNA and PFUA were higher in cord blood than in serum from eight-year-olds. Some trends were also noted between intrauterine PFOS exposure and children's decreasing FEV1, FVC and PEF, especially in subgroups with lower birth weight and allergic rhinitis. Therefore, intrauterine PFAS exposure, especially PFOS, may play a vital role in lung development.

Interaction Between Prematurity and the MAOA Gene on Mental Development in Children: A Longitudinal View.

This study aimed to examine the association of dopamine-related genes with mental and motor development and the gene-environment interaction in preterm and term children. A total of 201 preterm and 111 term children were examined for their development at 6, 12, 18, 24, and 36 months and were genotyped for 15 single-nucleotide polymorphisms (SNPs) in dopamine-related genes (DRD2, DRD3, DAT1, COMT, and MAOA). An independent sample of 256 preterm children was used for replication. Since the developmental age trends of preterm children differed from those of term children, the analyses were stratified by prematurity. Among the 8 SNPs on the MAOA gene examined in the whole learning sample, the results of linkage disequilibrium analysis indicated that they were located in one block (all D' > 0.9), and rs2239448 was chosen as the tag (r2 > 0.85). In the analysis of individual SNPs in each dopamine-related gene, the tag SNP (rs2239448) in MAOA remained significantly associated with the mental scores of preterm children for the interaction with age trend (p < 0.0001; largest effect size of 0.65 at 24 months) after Bonferroni correction for multiple testing. Similar findings for rs2239448 were replicated in the independent sample (p = 0.026). However, none of the SNPs were associated with the motor scores of preterm children, and none were related to the mental or motor scores of term children. The genetic variants of the MAOA gene exert influence on mental development throughout early childhood for preterm, but not term, children.

The gestational effect of antenatal corticosteroids on respiratory distress syndrome in very low birth weight infants: A population-based study.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the efficacy of antenatal corticosteroids for preventing very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) from surfactant use at different gestational ages (GA). METHODS: We retrospectively analyzed the VLBW preterm infants registered in the Premature Baby Foundation of Taiwan from 1997 through 2014. Infants at 20-37 weeks' gestation were included, and infants with lethal congenital anomaly, chromosomal anomaly, and congenital infection were excluded. Antenatal corticosteroid courses were classified into two groups (<2 doses or ≧2 doses). The beneficial effect of antenatal corticosteroids on preventing VLBW infants with RDS from surfactant use was evaluated according to gestational ages. RESULTS: Total 12,685 VLBW infants were included. For VLBW infants with gestational age 26-33 weeks, antenatal corticosteroid therapy has significantly protective effect (odds ratio 0.43 [95% CI 0.26 to 0.72] - 0.60 [95% CI 0.48 to 0.75], P < 0.05). The effect was not obvious for VLBW infants with gestational age 34 weeks and more (odds ratio 0.32 [95% CI 0.08 to 1.38], P = 0.127). CONCLUSION: For VLBW infants with RDS at 34 weeks' gestation and more, the beneficial effect of antenatal corticosteroids on preventing surfactant use was not evident. In conclusion, completion of two doses or more of antenatal corticosteroids is of great importance for VLBW infants with RDS at gestational age between 26 and 33 weeks on preventing surfactant use.

Involution of retinopathy of prematurity and neurodevelopmental outcomes after intravitreal bevacizumab treatment.

This single-centered, retrospective cohort study investigated the timing of involution of retinopathy of prematurity (ROP) and retinal vascularization to zone III after intravitreal bevacizumab (IVB) treatment and its possible impacts on postnatal growth and neurodevelopment. Premature infants with birth weight ≤1500 g, born between 2008 to 2014 and diagnosed with ROP were enrolled. All patients with type 1 ROP underwent IVB as 1st line treatment and were recruited as the study group; those with any stage of ROP except type 1 ROP without treatment served as controls. Neurodevelopmental outcomes were assessed using the Bayley Score of Infant Development (BSID) editions II or III. The study group included 35 eyes from 18 patients; the control group included 86 patients. Twenty-three eyes (65.7%) exhibited ROP regression after a single dose of IVB. The majority of plus sign and extraretinal neovascularization regressed within two weeks. The length of time for retinal vascularization to reach zone III was significantly longer in the treatment group compared with the control (mean post-menstruation age 54.5 vs. 47.0 weeks, p<0.001). Long-term follow-up showed no significant differences in body weight and neurodevelopment between the study and control groups up to the 2-year corrected age.