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Background: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS., Methods: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants., Results: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis., Conclusions: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics., (© 2023. The Author(s).)

Objective: Smoking during pregnancy has harmful effects on the fetus and infant. Although some studies suggest that exposure to fetal-maternal smoking adversely affects both fetal growth and cardiovascular development, the mechanisms and biochemical consequences of smoking in pregnancy and newborns are not yet fully understood. We aimed to investigate whether maternal smoking during pregnancy causes fetal cardiovascular effect by measuring serum asymmetric dimethylarginine (ADMA) level and abdominal aortic intima-media thickness (aIMT)., Study Design: This prospective study was conducted in newborns of smoking mothers and never-smoker control mothers during their pregnancies. The babies were evaluated echocardiographically on the first day following birth. In two-dimensional mode, abdominal aIMT measurements were performed. ADMA was measured in umbilical cord blood at birth., Results: There were 25 mothers in the study group and 25 mothers in the control group. Serum ADMA levels were 0.459 ± 0.119 μmol/L in the study group and 0.374 ± 0.1127 μmol/L in the control group ( p  = 0.034). The aIMT value in the study group was 0.84 ± 0.026 mm and the aIMT value in the control group was 0.63 ± 0.011 mm ( p  = 0.005)., Conclusion: We found that both the serum ADMA and the aIMT significantly increased in the group with newborns of smoker mothers compared with the group of the newborns of never-smoker mothers. It may also be suggested that exposure to fetal-maternal smoking adversely affects cardiovascular development., Key Points: · It is a known fact that smoking during pregnancy has harmful effects on the development of the fetus and infant.. · We found that both the serum ADMA and aIMT were significantly higher in the group of infants of smoker mothers.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Data on free thyroxine (FT4) concentrations beyond first 2 weeks of preterm infants are limited. This study was aimed to describe the association between perinatal characteristics and FT4 concentrations and the incidence of hypothyroxinemia at 4 weeks., Study Design: Retrospective analysis of serum thyroid function tests at 4 weeks in preterm infants <30 weeks of gestation. Association between FT4 at 4 weeks of life and perinatal characteristics were determined by bivariate analysis and multivariable regression. Incidence of hypothyroxinemia was determined using a gestational age adjusted definition based on in utero levels at the equivalent postmenstrual age., Results: The study cohort consisted of 280 infants. FT4 concentrations at 4 weeks of life were significantly associated with gestational age, birth weight, gender, and maternal history of thyroid disease. Hypothyroxinemia was found in 32.8% of the study cohort., Conclusion: Perinatal characteristics are associated with FT4 concentrations at 4 weeks of life. Nearly one-third of infants born <30 weeks had hypothyroxinemia at 4 weeks of life when compared with in utero levels at the equivalent postmenstrual age., Competing Interests: None declared., (Thieme. All rights reserved.)

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: This study aimed to establish neonatal serum triglyceride (TG) level reference ranges during lipid infusion and correlate peak TG with neonatal outcomes., Study Design: This is a retrospective review of 356 neonates with 696 TG measures obtained in four neonatal intensive care units between 2015 and 2017. TG was evaluated collectively to establish a reference range and a threshold limit. To analyze the effects of a higher TG threshold, neonates were categorized by their peak TG: <180 (TG <180 ), 180 to 400 (TG 180-400 ), and > 400 mg/dL (TG >400 ). Univariable and multivariable regression models were constructed to compare peak TG to patient characteristic and clinical outcomes., Results: The frequency of TG > 400 mg/dL was 5% and found only in neonates weighing < 1.5 kg. Neonates in the TG 180-400 ( n  = 91) group were significantly lower in birth weight and gestational age, had lower 5-minute APGAR scores, and had increased ventilatory requirement when compared with neonates in the TG <180 ( n  = 240) group (all p  < 0.001). The TG 180-400 group had increased risk of severe intraventricular hemorrhage ( p  = 0.02) and bronchopulmonary dysplasia ( p  = 0.03). Elevated TG was associated with mortality (odds ratio [OR]: 14.4, p  < 0.001) in univariable analysis, but the relationship weakened (OR: 4.4, p  = 0.05) after adjusting for comorbidities in multivariable logistic regression., Conclusion: It is unclear if the adverse outcomes seen in neonates with higher peak TG were due to elevated TG alone, or whether illness severity predicted the increased TG. More prospective studies are needed to further delineate the relationships., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The lead-in-water impact of the Flint water crisis on the youngest and most neurodevelopmentally vulnerable population was largely unknown. The objective of this study was to investigate and compare cord blood lead levels (CBLLs) in newborns in Flint, Michigan, after the Flint water crisis, to a group of Detroit newborns., Study Design: Mothers of 99 Flint newborns were surveyed about potential lead exposures. These neonates were born after the recognition of population-wide lead-in-water contamination. CBLLs were measured and maternal-fetal metrics were reviewed. CBLLs and maternal-fetal metrics were then compared with those of a retrospective cohort of 116 Detroit newborns who previously shared the same water source. Analysis involved descriptive statistics, independent t -test, and χ 2 analysis., Results: CBLLs greater than or equal to 1 μg/dL (0.05 μmol/L) were more prevalent among Flint newborns (14%), as compared with Detroit newborns (2%; p  = 0.001). This was a sevenfold disparity between Flint and Detroit newborns. No statistically significant differences were found in birth weight, head circumference, small for gestational age status, gestational age, or preterm status among the two groups., Conclusion: The Flint water crisis potentially exposed newborns to lead in utero, implicating maternal-fetal outcomes and future health and development. Primary prevention efforts, including identification and mitigation of lead exposure before conception and during pregnancy, are needed. New environmental exposure detection methods and long-term neurodevelopmental follow-up will complement the findings of this study., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The relationship between severe anemia, red blood cell transfusion and Neonatal necrotizing enterocolitis (NEC) remains controversial. The purpose of this study was to determine the association of severe anemia and RBC transfusion with NEC in neonates., Methods: The clinical characteristics of NEC were observed in 467 infants with different birth weights from January 2012 to July 2020. A 1:1 ratio case-control study was performed in very low birth weight (VLBW) infants. Severe anemia, RBC transfusion, and confounding factors, including maternal and perinatal complications, feeding, and antibiotics administration were collected in both groups. Univariate and multivariate analyses were used to investigate effects on the risk of NEC., Results: The day of NEC onset and mortality were inversely associated with birth weight. In VLBW infants, adjusting for other factors, severe anemia within 72 h [OR = 2.404, P = 0.016], RBC transfusion within 24 h [OR = 4.905, P = 0.016], within 48 h [OR = 5.587, P = 0.008], and within 72 h [OR = 2.858, P = 0.011] increased the risk of NEC., Conclusion: Both severe anemia and RBC transfusion appears to increase the risk of NEC in VLBW infants. The early prevention and treatment of anemia, strict evaluation of the indications for transfusion and enhanced monitoring after transfusion is encouraged in the NICU., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Sphingosine-1-phosphate (S1P) is a signalling lipid involved in embryonic development, physiological homeostasis, and pathogenic processes in multiple organ systems. Disturbance of S1P homeostasis has been associated with various human diseases in which the immune response and vascular integrity are severely compromised. Up-to-date, no study has analyzed S1P levels in neonates. The objective of this study was to determine S1P serum concentrations in neonates and establish S1P reference ranges., Methods: S1P levels in the umbilical cord blood of 460 term and preterm neonates were compared to a previously described cohort of healthy adult blood donors. S1P levels were further correlated with demographic characteristics, cellular sources of S1P, and inflammatory markers., Results: The median S1P serum level in neonates was 1.70 μmol/L (IQR 1.41-1.97 μmol/L) and significantly higher than normal values reported in adults. S1P levels correlated positively with the number of red blood cells (p<0.001) and negatively with neutrophil precursors (p=0.028)., Conclusions: Elevated S1P levels in neonates compared to adults possibly result from higher S1P content in its cellular sources due to the essential role of S1P during embryogenesis. Generated S1P ranges may be used as reference ranges for future studies in neonates., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth., Methods: A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected., Results: The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency., Conclusions: Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight., Trial Registration: Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.

Background: We hypothesized that variability in practice exists for newborn immunohematology testing due to lack of consensus guidelines. We report the results of a survey assessing that variability at hospitals in the United States and Canada., Study Design and Methods: An AABB Pediatric Subsection working party developed and validated a survey of newborn immunohematology testing practice. The survey was sent electronically to transfusion service leadership at teaching institutions., Results: The response rate was 67% (61/91); 56 surveys meeting inclusion criteria were analyzed. Approximately 90% (50/56) were from birth hospitals and 16.1% (9/56) were from pediatric hospitals. Newborn immunohematology testing is ordered as a panel by 66.0% (33/50) of birth hospitals. ABO group and DAT is mandated before discharge in 14/56 (25.0%) and 13/56 (23.2%), respectively. About 76.8% (43/56) selectively perform a DAT according to blood blank or clinical parameters. The most common DAT practices include anti-IgG only testing by 73.2% (41/56) and use of umbilical cord specimen type by 67.9% (38/56). A positive DAT is a critical value for 26.8% (15/56) and followed with eluate testing when a maternal antibody screen is positive for 48.2% (27/56). In the setting of a non-ABO maternal red cell antibody, 55.4% (31/56), phenotype neonatal red cells when the DAT is positive. Group O RBC are transfused irrespective of the DAT result for 82.1%, (46/56)., Conclusion: There is variability in newborn immunohematology testing and transfusion practice and potential overutilization of the DAT. Evidence-based consensus guidelines should be developed to standardize practice and to improve safety., (© 2021 AABB.)

Objective: Although research suggests a close association between maternal thyroid function and birth outcomes, no clear conclusion has been reached. We aimed to explore this potential association in a retrospective cohort study., Methods: This study included 8985 mother-child dyads. The maternal serum free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab) concentrations and birth outcome data were reviewed from medical records. Subjects with TPO Ab concentrations of >34 and ≤34 IU/ml were classified into the TPO Ab positivity (+) and TPO Ab negativity (-) groups, respectively., Results: Compared with subjects in the normal group (0.1 ≤ TSH < 2.5 mIU/L and TPO Ab-), those with TSH concentrations of 2.5-4.0 mIU/L and TPO Ab- had a 0.65-fold lower risk of low birth weight (LBW). In contrast, those with TSH concentrations of >4.0 mIU/L, regardless of the TPO Ab status, had a 2.01-fold increased risk of LBW. Subclinical hypothyroidism, regardless of the TPO Ab status, was associated with a 1.94-fold higher risk of LBW when compared with that in subjects with euthyroidism and TPO Ab-. No other significant associations were observed., Conclusion: A maternal TSH concentration of 2.5-4.0 mIU/L was associated with a lower risk of LBW when combined with TPO Ab-, whereas subjects with a TSH concentration of >4.0 mIU/L had an increased risk of LBW. Subclinical hypothyroidism appears to be associated with a higher risk of LBW., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Pang, Lu, Li, Zhou, Ye, Yang, Shen, Lin, Fan, Lu and Liu.)

Objective: Breast milk (BM) contains antioxidant molecules which may offer protection against oxidative stress (OS). We aim to investigate oxidant-antioxidant balance in preterm BM during the course of lactation and within a nursing session., Study Design: Total antioxidant capacity (TAC) and total oxidant status (TOS) were measured in colostrum, transitional, and mature BM samples of preterm infants born earlier than 34th week of pregnancy and healthy term infants. Oxidative stress index (OSI) was calculated. Foremilk and hindmilk samples were collected separately., Results: In colostrum and transitional milk, TAC ( p  < 0.001 and p  = 0.001, respectively) and TOS ( p  = 0.005 and p  < 0.001, respectively) were lower in preterm BM compared with term BM. OSI was also lower in preterm BM, but it was statistically significant only in transitional milk ( p  < 0.001). TAC was highest in colostrum and decreased through the course of lactation. However, the decrease in TAC was not statistically significant in preterm BM. Lowest values of TOS and OSI were observed in colostrum. In transitional term BM, hindmilk had a better oxidant-antioxidant profile as indicated by lower TOS and OSI., Conclusion: Oxidant-antioxidant balance is preserved in BM in every stage of lactation. Preterm BM has lower OSI which may offer benefits to preterm newborn against OS., Competing Interests: None declared., (Thieme. All rights reserved.)

Context.—: Automated analyzers have advanced the field of clinical hematology, mandating updated complete blood count (CBC) reference intervals (RIs) to be clinically useful. Contemporary newborn CBC RI publications are mostly retrospective, which some authors have cited as one of their cardinal limitations and recommended future prospective studies., Objective.—: To prospectively establish accurate hematologic RIs for normal healthy term newborns at 24 hours of life given the limitations of the current medical literature., Design.—: This prospective study was conducted at an academic tertiary care center, and hematology samples were collected from 120 participants deemed to be normal healthy term newborns. Distributions were assessed for normality and tested for outliers. Reference intervals were values between the 2.5th percentile and 97.5th percentile., Results.—: The novel RIs obtained for this study population are as follows: absolute immature granulocyte count, 80/μL to 1700/μL; immature granulocyte percentage, 0.6% to 6.1%; reticulocyte hemoglobin equivalent, 31.7 to 38.4 pg; immature reticulocyte fraction, 35.9% to 52.8%; immature platelet count, 4.73 × 103/μL to 19.72 × 103/μL; and immature platelet fraction, 1.7% to 9.8%., Conclusions.—: This prospective study has defined hematologic RIs for this newborn population, including new advanced clinical parameters from the Sysmex XN-1000 Automated Hematology Analyzer. These RIs are proposed as the new standard and can serve as a strong foundation for continued research to further explore their value in diagnosing and managing morbidities such as sepsis, anemia, and thrombocytopenia., (© 2021 College of American Pathologists.)

Objective: To investigate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in parturient women, their partners, and their newborns and the association of such antibodies with obstetric and neonatal outcomes., Methods: From April 4 to July 3, 2020, in a single university hospital in Denmark, all parturient women and their partners were invited to participate in the study, along with their newborns. Participating women and partners had a pharyngeal swab and a blood sample taken at admission; immediately after delivery, a blood sample was drawn from the umbilical cord. The swabs were analyzed for SARS-CoV-2 RNA by polymerase chain reaction, and the blood samples were analyzed for SARS-CoV-2 antibodies. Full medical history and obstetric and neonatal information were available., Results: A total of 1,313 parturient women (72.5.% of all women admitted for delivery at the hospital in the study period), 1,188 partners, and 1,206 newborns participated in the study. The adjusted serologic prevalence was 2.6% in women and 3.5% in partners. Seventeen newborns had SARS-CoV-2 immunoglobulin G (IgG) antibodies, and none had immunoglobulin M antibodies. No associations between SARS-CoV-2 antibodies and obstetric or neonatal complications were found (eg, preterm birth, preeclampsia, cesarean delivery, Apgar score, low birth weight, umbilical arterial pH, need for continuous positive airway pressure, or neonatal admission), but statistical power to detect such differences was low. Full serologic data from 1,051 families showed an absolute risk of maternal infection of 39% if the partner had antibodies., Conclusion: We found no association between SARS-CoV-2 infection and obstetric or neonatal complications. Sixty-seven percent of newborns delivered by mothers with antibodies had SARS-CoV-2 IgG antibodies. A limitation of our study is that we lacked statistical power to detect small but potentially meaningful differences between those with and without evidence of infection., Competing Interests: Financial Disclosure Henriette Svarre Nielsen has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). Nina la Cour Freiesleben has received a grant from Gedeon Richter (outside the submitted work). Astrid Marie Kolte has received speaker's fees from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest., (Copyright © 2020 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Estradiol (E), testosterone (T), and their ratio are crucial axis in life. Especially during intrauterine growth, they orchestrate the complex development of organs and their interaction, which have lifelong impact on health and an organism's capacity to respond to environmental stressors. The aim of this study was to compare for the first time E, T, and their ratio levels with aromatase (CYP19) gene methylation levels between preterm newborns (PN) and full-term newborns (FN) with respect to their mother's environmental exposure and diet. In this study, 56 FN of 37-42 weeks of gestation age (GA) and 46 PN at GA 27-36 weeks were analysed for E and T levels and CYP19A1 gene pI.3/II promoter region methylation. Results showed there was no difference in E levels between PN and FN, but there were significantly lower levels of T in PN than in FN (2.81 nmol vs. 3.76 nmol, respectively) and consequently a significantly higher E/T ratio in PN than in FN (5278.04 vs. 2891.23, respectively). CYP19A1 methylation was significantly lower in PN than in FN (86.04% vs. 90.04%, respectively). CYP19A1 methylation was significantly reduced in newborns whose mothers reported daily milk consumption. Our study is the first to provide referent values for CYP19A1 methylation levels in FN and PN and shows that PN and FN significantly differ in CYP19A1 methylation levels, T levels, and E/T ratio. Future research should further investigate the mechanisms involved in GA-dependent CYP19A1 methylation levels and mechanisms of sex hormone disturbances which may contribute to preterm birth., (© 2021 S. Karger AG, Basel.)

Background: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia., Methods: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity., Results: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively., Conclusions: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: HIV treatment of neonates requires identifying appropriate antiretroviral dosing regimens. Our aims were to characterize raltegravir elimination kinetics in low birth weight (LBW) neonates after maternal dosing and to develop a pharmacokinetic model to predict raltegravir plasma concentrations for term and preterm neonates., Methods: Mothers living with HIV who received raltegravir during pregnancy and their LBW neonates participated in IMPAACT P1097 study. Up to 6 serial plasma samples were collected from each infant over the first 2 postnatal weeks to characterize raltegravir elimination. Safety laboratory evaluations were obtained, and infants were monitored for 6 weeks for signs of raltegravir toxicity. An integrated maternal-neonatal pharmacokinetic model was developed to predict neonatal raltegravir plasma concentrations., Results: Sixteen mothers and their 18 LBW neonates were enrolled. The median (range) raltegravir elimination half-life was 24.4 (10.1-83) hours (N = 17 neonates). No adverse events related to raltegravir in utero exposure were observed. Pharmacokinetic modeling revealed that raltegravir clearance in full-term LBW neonates was well described by allometric scaling but clearance in preterm LBW neonates was better described using slower clearance maturation kinetics. Simulations suggest receipt of the current dosing recommendations in a 34-week gestation neonate would result in plasma concentrations up to 2.5-fold higher than those observed in full-term LBW infants., Conclusions: Modeling suggests that prematurity reduces raltegravir clearance and a modified raltegravir dosing regimen will be necessary to avoid elevated plasma raltegravir concentrations.

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates., Competing Interests: The authors have declared that no competing interests exist.

Background: There are few reports on reticulocyte count during the early postnatal period, and its clinical significance is not well understood. To examine the relationships between neonatal reticulocyte count and other perinatal variables., Methods: We conducted a retrospective cohort study of neonatal infants who were admitted to the neonatal intensive care unit (NICU) of Ohta Nishinouchi Hospital, Japan, between April 1, 2016 and July 31, 2019. All blood samples were collected within 3 h after admission., Results: Four hundred and twenty-eight infants were included, of whom 317 (74.1%) were preterm and 111 (25.9%) were term. Two hundred and ninety-nine infants (69.9%) were born by cesarean section. The median reticulocyte counts (‰) for all gestational ages (GAs) were as follows: 24-25 wks (n = 11), 124.1 (range: 106.3 to 148.6); 26-27 wks (n = 25), 111.1 (range: 55.5 to 144.3); 28-30 wks (n = 52), 81.9 (range: 35.6 to 131.5); 31-33 wks (n = 86), 71.6 (range: 28.3 to 116.6); 34-36 wks (n = 143); 59.6 (range: 30.2 to 110.9); and 37-41 wks (n = 111), 43.2 (range: 21.9 to 69.2). There were significant relationships between the neonatal reticulocyte count and gender [p < 0.01, odds ratio (OR), 0.37; 95% confidence interval (CI), 0.21 to 0.64], GA (p < 0.01, OR, 0.92; 95% CI, 0.90 to 0.93), delivery type (p = 0.03, OR, 0.51; 95% CI, 0.28 to 0.95), maternal haemoglobin before delivery (p < 0.01, OR, 0.74; 95% CI, 0.60 to 0.91), tracheal intubation at resuscitation (p = 0.04, OR, 2.75; 95% CI, 1.04 to 7.32) and mean platelet volume (p < 0.01, OR, 0.51; 95% CI, 0.35 to 0.74)., Conclusion: A higher neonatal reticulocyte count in NICU infants may be one of the physiological responses to a more rapid environmental change during the early postnatal period., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest to declare in relation to this study., (Copyright © 2020. Published by Elsevier B.V.)

Objective: This study aimed to evaluate if maternal serum hormones along the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis, when drawn prior to labor induction, differed between women who delivered vaginally and those who underwent cesarean., Study Design: This was a prospective observational study at a single perinatal center performed from August 2017 to May 2018. Nulliparous women with uncomplicated singleton pregnancies ≥39 weeks had maternal serum collected prior to induction. Corticotrophin-releasing hormone (CRH) was measured by ELISA; dehydroepiandrosterone sulfate (DHEA-S), cortisol, estriol (E 3 ) estradiol (E 2 ), and progesterone (P 4 ) were measured by chemiluminescent reaction. Mean analyte concentrations as well as three ratios (E 2 /P 4 , E 3 /P 4, and E 2 /E 3 ) were compared between women who had a vaginal versus cesarean delivery. Logistic regression was used to model the relationship between CRH and the odds of vaginal birth. We estimated that a sample size of 66 would have 90% power to detect a 25% difference in mean CRH levels assuming a vaginal:cesarean ratio of 2:1 with a baseline CRH concentration of 140 (standard deviation = 36) pg/mL., Results: Of the 88 women who had their serum analyzed, 27 (31%) underwent cesarean. Mean maternal serum CRH levels were similar between the vaginal delivery and cesarean groups (122.6 ± 95.2 vs. 112.3 ± 142.4, p  = 0.73). Similarly, there were no significant differences in any other maternal serum analytes or ratios. Logistic regression showed a nonsignificant odds ratio for successful vaginal birth ( p  = 0.69) even when evaluating only the 16 women who had a cesarean for an arrest disorder ( p  = 0.08)., Conclusion: In low-risk nulliparous women undergoing full-term labor induction, there were no differences noted in a broad array of other maternal-fetal HPA-axis hormones between women who had a vaginal or cesarean delivery., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Intrauterine exposure to a disturbed maternal glucose metabolism is associated with adverse offspring outcomes. DNA methylation is a potential mechanism underlying these associations. We examined whether maternal early-pregnancy glucose and insulin concentrations are associated with newborn DNA methylation. In a population-based prospective cohort study among 935 pregnant women, maternal plasma concentrations of non-fasting glucose and insulin were measured at a median of 13.1 weeks of gestation (95% range 9.4-17.4). DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Ilumina). We analyzed associations of maternal early-pregnancy glucose and insulin concentrations with single-CpG DNA methylation using robust linear regression models. Differentially methylated regions were analyzed using the dmrff package in R. We stratified the analyses on normal weight versus overweight or obese women. We also performed a look-up of CpGs and differently methylated regions from previous studies to be associated with maternal gestational diabetes, hyperglycemia or hyperinsulinemia, or with type 2 diabetes in adults., Results: Maternal early-pregnancy glucose and insulin concentrations were not associated with DNA methylation at single CpGs nor with differentially methylated regions in the total group. In analyses stratified on maternal BMI, maternal early-pregnancy glucose concentrations were associated with DNA methylation at one CpG (cg03617420, XKR6) among normal weight women and at another (cg12081946, IL17D) among overweight or obese women. No stratum-specific associations were found for maternal early-pregnancy insulin concentrations. The two CpGs were not associated with birth weight or childhood glycemic measures (p values > 0.1). Maternal early-pregnancy insulin concentrations were associated with one CpG known to be related to adult type 2 diabetes. Enrichment among nominally significant findings in our maternal early-pregnancy glucose concentrations was found for CpGs identified in a previous study on adult type 2 diabetes., Conclusions: Maternal early-pregnancy glucose concentrations, but not insulin concentrations, were associated with DNA methylation at one CpG each in the subgroups of normal weight and of overweight or obese women. No associations were present in the full group. The role of these CpGs in mechanisms underlying offspring health outcomes needs further study. Future studies should replicate our results in larger samples with early-pregnancy information on maternal fasting glucose metabolism.

Background: Esomeprazole is the S -isomer of omeprazole and is used to treat stomach acid-related diseases. Most data regarding the safety of esomeprazole during pregnancy are derived from studies on omeprazole, and the data characterizing esomeprazole transfer across the placenta and excretion into breast milk are limited. In this report, we discuss the safety of esomeprazole with reference to drug concentrations in maternal and neonatal blood and breast milk. Materials and Methods: After the patient provided informed consent, esomeprazole concentrations in maternal serum, breast milk, cord blood, and infant's serum were measured after 10 mg of maternal oral esomeprazole administration. Case Report: A 34-year-old female diagnosed with rheumatoid arthritis received esomeprazole before and during pregnancy and lactation. The esomeprazole concentration in cord blood was 40% of the level in maternal serum. At 12 hours after delivery (23.2 hours after dose), omeprazole was not detected in the infant's serum. In breast milk, esomeprazole concentrations at 0.7, 4.0, and 8.2 hours after the last dose were 10.5, 19.6, and 3.0 ng/mL, respectively, and esomeprazole was not detected at 10 hours after maternal administration. The calculated daily infant dose of esomeprazole through breast milk was 0.003 mg/[kg·day]. The infant demonstrated normal developmental progress and no detectable drug-related adverse effects. Discussion and Conclusions: Exposure to esomeprazole through placenta and breast milk was not clinically relevant in the infant. Further studies are needed to evaluate any harmful effects after exposure to esomeprazole in utero or during breastfeeding after esomeprazole treatment.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.

Rationale: The outbreak of coronavirus disease 2019 (COVID-19) in 2019 has become a global pandemic. It is not known whether the disease is associated with a higher risk of infection in pregnant women or whether intrauterine vertical transmission can occur. We report 2 cases of pregnant women diagnosed with COVID-19., Patient Concerns: In all of Yichang city from January 20, 2020, to April 9, 2020, only 2 pregnant women, who were in the late stage of pregnancy, were diagnosed with COVID-19; one patient was admitted for fever with limb asthenia, and the other patient was admitted for abnormal chest computed tomography results., Diagnoses: Both pregnant women were diagnosed with COVID-19., Interventions: After the medical staff prepared for isolation and protection, the 2 pregnant women quickly underwent cesarean sections. A series of tests, such as laboratory, imaging, and SARS-CoV-2 nucleic acid examinations, were performed on the 2 women with COVID-19 and their newborns., Outcomes: One of the 2 infected pregnant women had severe COVID-19, and the other had mild disease. Both babies were delivered by cesarean section. Both of the women with COVID-19 worsened 3 to 6 days after delivery. Chest computed tomography suggested that the lesions due to SARS-CoV-2 infection increased. These women began to exhibit fever or reduced blood oxygen saturation again. One of the 2 newborns was born prematurely, and the other was born at full term. Neither infant was infected with COVID-19, but both had increased prothrombin time and fibrinogen, lactate dehydrogenase, phosphocreatine kinase, and creatine kinase isoenzyme contents., Lessons: SARS-CoV-2 infection was not found in the newborns born to the 2 pregnant women with COVID-19, but transient coagulation dysfunction and myocardial damage occurred in the 2 newborns. Effective management strategies for pregnant women with COVID-19 will help to control the outbreak of COVID-19 among pregnant women.

Background: Maternal human immunodeficiency virus (HIV) infection is associated with lower placental transfer of antibodies specific to several childhood pathogens. Our objective for this study was to evaluate the effect of maternal HIV infection on the placental transfer of respiratory syncytial virus (RSV)-neutralizing antibodies., Methods: We conducted a cross-sectional study of mothers and their newborn infants at a tertiary hospital in Gaborone, Botswana, between March 2015 and December 2015. We measured serum RSV antibody levels by using a microneutralization assay. We used multivariable linear regression to evaluate the effect of maternal HIV infection on maternal RSV antibody levels, placental transfer of RSV antibodies, and newborn RSV antibody levels., Results: Of 316 mothers, 154 (49%) were infected with HIV. The placental transfer ratios for RSV antibodies to HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected infants were 1.02 and 1.15, respectively. The geometric mean titer (95% confidence interval) of RSV-neutralizing antibodies was 2657 (2251-3136) among HEU newborns and 2911 (2543-3331) among HIV-unexposed, uninfected newborns. In multivariable analyses, maternal HIV infection was associated with lower placental transfer of RSV antibodies (P = .02) and a lower level of RSV antibodies among newborns (P = .002). Among HEU newborns, higher birth weight (P = .004) and an undetectable maternal antenatal viral load (P = .01) were associated with more effective placental transfer of RSV antibodies., Conclusions: Maternal human immunodeficiency virus (HIV) infection is associated with lower mother-to-fetus transfer of serum RSV-neutralizing antibodies. HEU infants should be prioritized for preventive interventions for RSV. Maternal viral suppression through combination antiretroviral therapy has the potential to improve immunity to RSV among HIV-exposed infants., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Haemoglobin (Hb) disorders are among the most common blood genetic disorders worldwide, and they constitute an important cause of morbidity and mortality, especially in Nigeria. Despite the clinical significance of early diagnosis, newborn screening for these conditions is not routinely done in Nigeria., Objective: This study was undertaken to document the pattern of Hb phenotypes of newborn babies at the National Hospital Abuja and highlight the relevance of neonatal screening for early diagnosis of abnormal Hb phenotypes in Nigeria., Subjects and Methods: A prospective study of eligible newborn babies delivered in the hospital at the study site was undertaken following parental informed consent. Venous blood was collected from the babies into an ethylenediaminetetraacetic acid sample bottles. The samples were analysed using high-performance liquid chromatography (HPLC) techniques, and the Hb phenotypes obtained were documented. Data were analysed using the Statistical Package for Social Sciences (SPSS) version 20 (IBM-SPSS, Armonk, NY, USA)., Results: Three hundred and eleven newborns (male = 173, female = 138) aged 0-28 days were recruited. Two hundred and thirty-six (75.9%) babies had Hb AA (FA) phenotype, 63 (20.3%) Hb AS (FAS), 6 (1.9%) Hb SS (FS), 4 (1.3%) Hb AC (FAC) and 2 (0.6%) had abnormal HbA variants. The overall prevalence of abnormal Hb phenotype was 24.1%. The results showed a significant association of sex (P = 0.003) and ethnicity (P = 0.047) with Hb phenotype., Conclusion: There is a wide spectrum of abnormal Hb phenotypes in Nigeria, and these phenotypes can easily be detected at birth using HPLC. We, therefore, recommend routine neonatal screening for sickle cell disease by HPLC in Nigeria., Competing Interests: None

Introduction: Neonatal sepsis is the most important cause of morbidity and mortality among low birth weight and preterm babies in developing countries. The main objective of this study is to find the level of micro-Erythrocyte sedimentation rate in neonatal sepsis., Methods: This is a descriptive cross-sectional study conducted at the neonatal unit over six months period (November 2019 to April 2020). All preterm, term and post-term babies with neonatal sepsisdelivered at Kathmandu Medical College Teaching Hospital were enrolled. Ethical clearance was received from the Institutional Review Committee of Kathmandu Medical College (Ref: 181020191). Convenient sampling method was applied and statistical analysis was done with Statistical package for social sciences 19 version., Results: Out of 75 babies, confirm sepsis is 13 (17.3%), probable sepsis is 40 (53.4%) and suspected sepsis is 22 (29.2%). Micro-Erythrocyte sedimentation level is elevated (≥15mm in 1st hr) in 25 (33.3%) babies with a mean micro-Erythrocyte sedimentation level 9.32±5.4 (2-18) mm in 1st hr. The elevated micro- Erythrocyte sedimentation level was seen in relation to sepsis types and C-reactive protein., Conclusions: The bedside micro-Erythrocyte sedimentation level aids in the diagnosis of neonatal sepsis.

Objective: Electronic fetal monitoring (EFM) is intended to assess fetal well-being during labor. Our objective was to test the hypothesis that findings of a category I tracing at any time in the 60 minutes prior to delivery would rule out neonatal acidemia., Study Design: This was a planned secondary analysis of a single-center prospective cohort study of 8,580 singleton pregnancies undergoing labor with nonanomalous infants at term. Monitoring was reviewed by obstetric research nurses at 10-minute intervals in the 60 minutes prior to delivery. The primary outcome was acidemia, defined as an umbilical cord arterial pH of 7.10 or less., Results: Of the 4,274 patients included, 42 (0.98%) infants had acidemia at birth. Of the 42 infants with acidemia, 13 (31%) had category I tracings in the 30 minutes prior to delivery. Three (7%) infants had neonatal acidemia despite category I tracing for >40 minutes in the 60 minutes prior to delivery., Conclusion: Even in the presence of category I tracing in the 60 minutes prior to delivery, neonatal acidemia can still occur. Periods of category I should be interpreted within the clinical context of a priori risk for acidemia, knowing that it does not completely rule out acidemia., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

DNA methylation (DNAm) in blood (umbilical cord blood and capillary blood collected after birth on Guthrie cards) during the perinatal period is being increasingly studied with the aim of identifying epigenetic markers of in utero environmental exposures or later disease development. However, the comparability in DNAm between these two sources is unknown. To this end, DNAm from the cord blood and capillary blood of 34 subjects in the Isle of Wight 3 rd Generation Birth Cohort (68 samples) were included to assess the comparability. Differences in average DNAm (overall agreement), correlations in DNAm, and intra-class correlation coefficients (ICC) in DNAm between the two sources, at each of the 430,742 CpG sites, were evaluated. The results showed that a high proportion (70.1%) of the CpGs DNAm agreed between cord blood and neonatal blood on Guthrie cards. A small portion of CpGs showed high correlation (correlation ≥0.5) or high ICC (ICC ≥0.5) in DNAm of the whole genome. This proportion increased dramatically in differentially methylated regions (DMRs) that are associated with exposure to maternal smoking, between the two sources.

During pregnancy, there is a progressive increase in the levels of maternal cholesterol, a lipid that is essential for foetal growth and development. This increase can occur in a physiological (MPH) or supraphysiological (MSPH) manner, where MSPH is associated with detrimental effects on the mother and foetus, including endothelial dysfunction, oxidative stress, and atherosclerosis. Cholesterol is transported from the maternal to the foetal circulation through the placenta by a process that encompasses two main events: cholesterol uptake and efflux. The main receptors and transporters that participate in cholesterol transport are expressed in the human placenta, and their regulation in normal and pathological pregnancies has been evaluated. However, whether elevated levels of cholesterol induce these detrimental changes and whether their expression and function changes in the MSPH condition is still under study, along with the cell types involved in placental cholesterol traffic. Moreover, aside from cholesterol levels, the composition and function of lipoproteins have recently become important to study as these factors may also contribute to the atherogenic process. There is information regarding the maternal and neonatal lipoproteins profile and their changes during pregnancy. However, there are no reports that evaluate the changes of these lipoproteins in MSPH pregnancies. The latter could be relevant considering the consequences that MSPH has on the foetal vasculature. In this review, we summarize the available information regarding cholesterol transport through the placenta and the metabolism of maternal and neonatal lipoproteins in MPH and MSPH conditions, suggesting the importance of increasing our knowledge about these conditions and the monitoring of maternal cholesterol levels during pregnancy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the association of birthweight percentile with cord blood glucose, lipids, and insulin levels., Study Design: Data obtained from 1522 newborns were included in the Born in Guangzhou Cohort study. The generalized additive model and multivariable linear regression model were used to explore the nonlinear and linear relationships between birthweight and cord blood metabolic measures, and to evaluate the differences of metabolic measures Z-scores among small for gestational age, appropriate for gestational age, and large for gestational age babies., Results: Birthweight Z-score was linearly associated with increased cord blood insulin Z-score (adjusted β = 0.30; 95% CI, 0.22-0.37). Compared with appropriate for gestational age babies, neonates born small for gestational age had significantly higher cord blood triglycerides Z-score (adjusted mean difference [MD adj ], 0.60; 95% CI, 0.40-0.79) and lower cord blood insulin (MD adj , -0.37; 95% CI, -0.57 to -0.16), high-density lipoprotein cholesterol (MD adj , -0.34; 95% CI, -0.55 to -0.13), total cholesterol (MD adj , -0.26; 95% CI, -0.47 to -0.05), and low-density lipoprotein (MD adj , -0.23; 95% CI, -0.43 to -0.02) Z-scores, and neonates born large for gestational age had higher cord blood insulin Z-score (MD adj , 0.31; 95% CI, 0.09 to 0.52)., Conclusions: Our findings support the hypothesis that babies born small for gestational age and large for gestational age are exposed to different intrauterine environments, which may contribute to altered fat accumulation patterns with implications for the risk of metabolic dysfunction later in life. There is a need to consider the development of tailored intervention strategies to prevent metabolic dysfunction in adult life for these babies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Maternal physiological (MPH) or supraphysiological hypercholesterolaemia (MSPH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (PHT) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or ≥280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MPH and MSPH neonates was similar. The abundance of LDL receptor (LDLR) and HDL receptor (SR-BI) was comparable between MSPH and MPH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. In PHT from MSPH, the uptake of LDL and HDL was lower compared to MPH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MPH and MSPH cells. However, free cholesterol was increased in MSPH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking.

SMART on FHIR applications are standards-based tools integrated with electronic health record (EHR) systems and intended for dissemination across EHR platforms. A key challenge for disseminating many apps is that EHR vendors provide different levels of support for FHIR. Thus, app developers must balance functionality versus portability. In this case study, a feature-rich app for neonatal bilirubin management was developed prioritizing physician-requested functionality, with custom FHIR interfaces implemented within the EHR as needed. Following wide intra-institutional use, several approaches are being pursued for adapting the app for cross-institutional dissemination: user surveys and interviews to identify least-valued app features which could potentially be omitted; enabling the application to provide differential features depending on available EHR FHIR capabilities; replacing custom FHIR interfaces with native EHR FHIR interfaces as they became available; and using a canonical logical data model known as QUICK that can be mapped to different FHIR versions and profiles., (©2019 AMIA - All rights reserved.)

Background: Iron is an essential micronutrient which plays a significant role, particularly vital for early brain growth and function. Maternal iron condition influences the iron status of neonates since iron transferred from the mother is the only source for fetal iron. A depletion in iron as a result of rapid growth leads to iron deficiency which is common in neonates. Although there are inconsistencies with regard to the normal reference ranges for neonatal iron level, the current review summarized literature to provide compressive information about neonatal iron status and factors that influence its level., Methods: This is a narrative review on the basis of relevant literatures mainly on neonatal iron from peer-reviewed journals. Electronic databases such as PubMed, PMC, Scopus, Science Direct, Google scholar, Google, and Yahoo were used to retrieve relevant literatures using key terms like "newborn iron, neonatal iron, iron overload, maternal factors, complication, iron level and neonates" separately and in combination., Results: Several factors had been postulated as factors associated with neonatal iron status. The current review figured out that maternal obesity, gestational diabetes mellitus, preterm delivery, placental transferrin receptor, inappropriate iron supplementation, use of iron fortified formula, uses of recombinant erythropoietin therapy, smoking, maternal iron deficiency anemia, umbilical cord clamping, and transfusion are the major factors which can influence neonatal iron level. These factors may have either positive or negative effects on neonatal iron level. Both iron deficiency and iron overload at some stage in the fetal development or at early stage of neonatal development cause abnormal functions of multiple organ system of neonates and subsequently contributed to neonatal and childhood morbidity and mortality., Conclusions: By one and other means insufficient, late and extra maternal iron supplementation, early and delayed umbilical cord clamping have negative effects on the iron level of neonates. Therefore, careful prenatal and antenatal follow-up need to be strengthened with due emphasis for maternal iron assessment.

Objective: To compare the effect of delayed cord clamping on cord blood gas values in vaginally delivered, healthy, term singletons., Data Source: We used MEDLINE, CINAHL, CENTRAL, EMBASE, and ClinicalTrials.gov databases., Methods of Study Selection: Eligible studies included randomized controlled trials (RCTs) comparing cord blood gas values obtained from early compared with delayed cord clamping groups and observational studies using serial cord blood gas from the same umbilical cord. We described the difference in means of cord blood gas parameters and comparative descriptive statistics when a difference in means was not available. We used a domain-based risk bias tool to extract methodologic details and assess potential risk of bias., Tabulation, Integration, and Results: This review included two RCTs and three observational studies. These studies included a total of 234 newborns with early cord clamping and 218 newborns with delayed cord clamping. The observational studies showed that 45-90 seconds delayed cord clamping was associated with mean decreases in umbilical arterial pH (0.02-0.03), HCO3 (0.3-0.8 mmol/L) and increases in base deficit (0.3-1.3 mmol/L) compared with early cord clamping. One observational study showed that delayed cord clamping was associated with decreases in umbilical venous pH (0.01) and HCO3 (0.2 mmol/L) and increase in venous base deficit (0.1-0.3 mmol/L) compared with early cord clamping. These changes were not observed in the two RCTs., Conclusion: Delayed cord clamping up to 120 seconds has either no effect or only a small effect on cord blood acid-base balance; overall, the magnitude of these changes is not clinically significant in vaginally delivered, healthy, term singletons., Systematic Review Registration: PROSPERO, CRD42019135779.

Introduction: Thyroid dysfunction is a common problem in pregnant women. It is usually of an autoimmune origin, with Hashimotós thyroiditis and Graveś disease being the most common conditions. Although hormonal changes and transplacental antibody transfer may occur, specific neonatal screening has not been shown to be useful., Patients and Method: A prospective study of newborns of women with autoimmune thyroid disease born at a level III university hospital (November 2013-December 2016). Neonates were selected during their stay at the maternity. Babies with perinatal asphyxia were excluded. Data were collected from the clinical histories of mothers and newborns., Results: A total of 191 neonates were included. Ninety percent of mothers had been diagnosed with autoimmune hypothyroidism. Only 5.8% of newborns had some laboratory disorder, consisting of slightly increased thyroid-stimulating hormone levels, which returned to normal at the age of one month and did not correlate to thyroid peroxidase antibody levels. Transient hyperthyrotropinemia was diagnosed in one newborn and required thyroxin treatment during the first year of life. Among newborns from mothers with Graveś disease, 36.8% had some abnormal laboratory value during the first 7 days of life, but there were no cases of hyperthyroidism and only one of transient hyperthyrotropinemia., Conclusions: Experience at our hospital in screening of newborns from hypothyroid mothers reveals a high number of laboratory controls with a poor diagnostic yield. No relationship was found between thyroid peroxidase antibody levels and thyroid dysfunction. We support the recommendations to continue testing serum thyroid-stimulating hormone and FT4 levels at 48h of life in newborns of mothers with autoimmune hypothyroidism., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Pulse oximetry for detecting critical CHD produces more false positive tests at high altitudes than at sea level, because at altitude the average resting saturation is lower and the variability is higher. This increases diagnostic difficulties, especially in small isolated communities without paediatric echocardio-graphy, and requires expensive transport to a regional medical centre. One way of reducing diagnostic errors is to measure arterial oxygen saturation while the infant is breathing 100% oxygen. In the absence of right-to-left shunting through the heart, the ductus, or the lungs, arterial oxygen tension will exceed 150 mmHg and arterial oxygen saturation will be 100%. With right-to-left shunting, arterial oxygen tension will be <100 mmHg, and thus <96% (usually much lower).

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time-international normalized ratio correlated with intraventricular hemorrhage ( p  = 0.000; β  = 0.180) and placental abruption (PA; p  = 0.000; β  = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p  = 0.000; β  =  - 0.217), gestational age (GA; p  = 0.000; β  =  - 0.282), and PA ( p  = 0.000; β  = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome ( p  = 0.007; β  =  - 0.114), pregnancy-induced hypertension ( p  = 0.000; β  =  - 0.141), and Apgar score at 1 minute ( p  = 0.043; β  = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes ( p  = 0.049). Finally, antithrombin III levels positively correlated with GA ( p  = 0.000) and BW ( p  = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Preterm birth (PTB) is a significant public health problem. We aimed to explore whether alpha fetal protein (AFP) or β-human gonadotropin (β-HCG) levels during pregnancy were associated with PTB in Chinese population., Study Design: The clinical data collected Nanjing Medical University Affiliated Suzhou Hospital and Wuxi Maternity and Child Health Care Hospital between January 2006 and December 2011 were analyzed retrospectively. A total of 64,999 pregnant women were registered. In addition, 13,828 pregnant women were collected serum from the second trimester. The maternal serum AFP and β-HCG were measured by enzyme immunoassay., Results: In our study, the rate of PTB is 6.23%. With each unit increase of maternal AFP concentration, the adjusted odds of PTB was increased by 69.3% (odds ratio = 1.693, 95% confidence interval: 1.434-1.999, p  = 0.00). We set AFP concentrations as high, medium, and low levels. When comparing with low concentration of AFP, high concentration of AFP (≥1.179 M) was positively associated with PTB with adjustment for potential confounders ( p  < 0.05). Nevertheless, no statistically significant associations were observed between maternal β-HCG and PTB., Conclusion: In this study, maternal AFP concentration was associated with increased risk of PTB., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

In this prospective cohort study of healthy full-term infants, we hypothesized that high-sensitivity cardiac troponin T (hs-cTnT) would be elevated in cord blood, compared with adult reference values, and that it would further increase over the first days of age. Cardiac troponin T has been shown to be significantly increased in healthy full-term newborns compared with adult reference values, but there is no established reference range. Most studies of cTnT in newborns have been performed before the introduction of high-sensitivity cTnT (hs-cTnT) assay. We conducted a study including 158 full-term newborns, at Stockholm South General Hospital. High-sensitivity cTnT was analyzed in umbilical cord blood and at 2-5 days of age. Median hs-cTnT (interquartile range) in cord blood was 34(26-44) ng/L; 99th percentile 88 ng/L. Median hs-cTnT at 2-5 days of age was 92(54-158) ng/L; 99th percentile 664 ng/L. We conclude that hs-cTnT is elevated in cord blood in healthy, full-term newborn infants compared with adult reference values, and that it increases significantly during the first days of life. Our findings further underline the need of caution when using hs-cTnT as a measurement of cardiac impact in newborns.

Importance: The American College of Obstetricians and Gynecologists recommends a delay in umbilical cord clamping in term neonates for at least 30 to 60 seconds after birth. Most literature supporting this practice is from low-risk vaginal deliveries. There are no published data specific to cesarean delivery., Objective: To compare maternal blood loss with immediate cord clamping vs delayed cord clamping in scheduled cesarean deliveries at term (≥37 weeks)., Design, Setting, and Participants: Randomized clinical trial performed at 2 hospitals within a tertiary academic medical center in New York City from October 2017 to February 2018 (follow-up completed March 15, 2018). A total of 113 women undergoing scheduled cesarean delivery of term singleton gestations were included., Interventions: In the immediate cord clamping group (n = 56), cord clamping was within 15 seconds after birth. In the delayed cord clamping group (n = 57), cord clamping was at 60 seconds after birth., Main Outcomes and Measures: The primary outcome was change in maternal hemoglobin level from preoperative to postoperative day 1, which was used as a proxy for maternal blood loss. Secondary outcomes included neonatal hemoglobin level at 24 to 72 hours of life., Results: All of the 113 women who were randomized (mean [SD] age, 32.6 [5.2] years) completed the trial. The mean preoperative hemoglobin level was 12.0 g/dL in the delayed and 11.6 g/dL in the immediate cord clamping group. The mean postoperative day 1 hemoglobin level was 10.1 g/dL in the delayed group and 9.8 g/dL in the immediate group. There was no significant difference in the primary outcome, with a mean hemoglobin change of -1.90 g/dL (95% CI, -2.14 to -1.66) and -1.78 g/dL (95% CI, -2.03 to -1.54) in the delayed and immediate cord clamping groups, respectively (mean difference, 0.12 g/dL [95% CI, -0.22 to 0.46]; P = .49). Of 19 prespecified secondary outcomes analyzed, 15 showed no significant difference. The mean neonatal hemoglobin level, available for 90 neonates (79.6%), was significantly higher with delayed (18.1 g/dL [95% CI, 17.4 to 18.8]) compared with immediate (16.4 g/dL [95% CI, 15.9 to 17.0]) cord clamping (mean difference, 1.67 g/dL [95% CI, 0.75 to 2.59]; P < .001). There was 1 unplanned hysterectomy in each group., Conclusions and Relevance: Among women undergoing scheduled cesarean delivery of term singleton pregnancies, delayed umbilical cord clamping, compared with immediate cord clamping, resulted in no significant difference in the change in maternal hemoglobin level at postoperative day 1., Trial Registration: ClinicalTrials.gov Identifier: NCT03150641.

Objective: This article identifies the prevalence and associated factors of hypophosphatemia (HP) in very low birth weight (VLBW) infants in the first week of life., Study Design: Prospective exploratory cohort study of 106 consecutive VLBW infants admitted to neonatal intensive care at Foothills Hospital, Calgary, Canada. HP was defined as at least one measurement of serum phosphate < 1.5 mmol/L (4.5 mg/dL)., Results: Seventy-seven percent (82/106) of the VLBW infants had HP, with significantly higher prevalence in infants < 1,000 g (94%) compared to infants ≥ 1,000 g (61%) ( p  < 0.001). Hypophosphatemic infants had lower birth weight ( p  < 0.001), gestational age ( p  < 0.001), and their increase in phosphate intake was slower ( p  = 0.003). Respiratory distress syndrome (RDS) ( p  = 0.002), intraventricular hemorrhage (IVH) ≥ grade III ( p  = 0.020), and hyperglycemia ( p  = 0.013) were more frequent among hypophosphatemic infants, especially among those < 1,000 g. Mortality, seizures, arrhythmias, and need for transfusion were not different between groups. Birth weight modified the association between RDS, IVH, hyperglycemia, and HP., Conclusion: HP was ubiquitous among infants < 1,000 g and highly prevalent among those weighing 1,000 to 1,500 g. While the direction of effect was not clear, RDS, IVH, and hyperglycemia were associated with HP. Prevention of HP in these physiologically immature neonates might improve neonatal outcomes., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Prenatal exposure to persistent organic pollutants (POPs) may be associated with obesogenic effects in offspring. Our study is the first to investigate associations between concentrations of POPs from newborn dried blood spots (DBS) and birth characteristics., Methods: Concentrations of 10 polychlorinated biphenyl congeners (PCBs), polybrominated diphenyl ether-47 (PBDE-47), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were measured from DBSs collected at birth from 2,065 singleton infants. DBS samples were pooled in groups of five and assayed together to reach limits of detection. Differences in risk of large for gestational age (LGA, defined as >90th percentile of birth weight for sex and gestational age), small for gestational age (SGA, <10th), and preterm birth (gestational age <37 weeks) were estimated using logistic regression per unit (ng/ml) increase in concentration of each chemical, adjusting for individual-level covariates, including maternal age, race/ethnicity, prepregnancy BMI, education, parity, smoking, and infant sex while assuming a gamma distribution and using multiple imputation to account for pools., Results: There were 215 (11.3%) singletons born LGA, 158 (7.5%) born SGA, and 157 (7.6%) born preterm. Higher concentrations of POPs were positively associated with slightly higher risk of LGA and higher birth weight., Conclusions: Relationships between POPs measured in newborn DBS and birth size were mixed. Pooled analysis methods using DBS could address challenges in limits of detection and costs for population-based research.

Background: Oxidative stress is associated with poor perinatal outcomes. Little is known regarding the longitudinal levels of oxidative stress in the perinatal period or the correlation between maternal and neonatal oxidative stress levels., Objective: Describe and compare oxidative stress, specifically superoxide, superoxide dismutase, catalase, and glutathione levels, over the perinatal period., Study Design: Longitudinal descriptive design using a convenience sample of medically high- and low-risk pregnant women ( n = 140) from a maternal-fetal medicine and general obstetrics practice, respectively. Blood was obtained from women at 12-20 and 24-28 weeks' gestation and during labor, from the umbilical cord at birth, and from neonates at 24-72 hr after birth. Levels of superoxide were measured using electron paramagnetic resonance (EPR) spectroscopy; antioxidants (superoxide dismutase, catalase, and glutathione) were measured using commercial assay kits. Relationships between oxidative stress levels at different time points were examined using nonparametric methods. Pregnancy outcome was collected., Results: Demographic variables, outcome variables, and oxidative stress levels in maternal blood, cord blood, and infants differed between medically high- and low-risk women. Descriptive patterns for oxidative stress measures varied over time and between risk groups. Significant correlations between time points were noted, suggesting intraindividual consistency may exist throughout the perinatal period. However, these correlations were not consistent across each medical risk group., Conclusion: EPR spectroscopy is a feasible method for the perinatal population. Results provide new information on perinatal circulating superoxide levels and warrant further investigation into potential relationships between prenatal and neonatal physiologic dysregulation of oxidative stress.

Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Völlger, L., Willers, M., Richter, M., Böhne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Förster, R., von Köckritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Introduction: Early diagnosis of perinatal asphyxia, the major cause of neonatal mortality and morbidity, might be improved by the detection of neonatal stress biomarkers such as cardiac troponin (CTn)T, CTnI, NT-Terminal-pro-Brain Natriuretic Peptide (NT-pro-BNP), copeptin, and high sensitivity C-reactive protein (hs-CRP). However, reference values in neonates are lacking. The objective of our study was therefore to establish a reference range of these biomarkers in healthy full term newborns and to analyze the influence of delivery mode on their cord blood concentrations., Patients and Methods: CTnT, CTnI, NT-pro-BNP, Copeptin and hs-CRP levels were determined in 201 neonates enrolled in this prospective study and correlated to the delivery mode and post-natal outcome., Results: Using the 99th percentile, the upper reference limit in healthy newborns was established for all biomarkers. Neonates born after complicated delivery had significantly higher values of CTnT, CTnI and Copeptin than those born after uncomplicated delivery. In the multiple regression models with CTnT as dependent variable, the delivery mode was the statistically significant independent variable., Conclusion: In this study, we established reference values of cord blood concentrations of cardiac stress biomarkers in healthy newborns. We showed that cardiac-related birth stress is dependent on delivery mode., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Residual dried blood spots from millions of newborns are being stored and used for research. The state of Michigan proactively developed a broad consent process for research use of newborns' blood spots. However, the extent to which mothers make informed choices about this research is unclear. A descriptive, qualitative study was conducted examining this issue. Twenty-nine observations of the consent process and 20 semistructured interviews were conducted with mothers on the postpartum unit of a large, academic hospital in Michigan. Content analysis of the transcripts was conducted. While most mothers agreed to donate the blood spots (n = 14/20; 70%), findings indicated that most decisions were uninformed (n = 16/20; 80%), as mothers lacked knowledge of biobanking research. Misunderstandings about anonymity, the consenter's credentials, and entity conducting the research seemed to influence decision making. Suggestions for improving the consent process include (1) changing the venue of blood spot education and consent from the postpartum period to the perinatal period, (2) strengthening the depth of information and delivery of information provided about the topic, including ethical and values clarification, and (3) increasing consenter education and training. Implementation may help increase the proportion of informed decisions.

Objective: To increase preoperative identification of at-risk infants for severe Retinopathy of prematurity (ROP) to >95% by August 2016, with a secondary aim of reducing the number of infants with 100% intraoperative peripheral oxygen saturation (SpO 2 ) during the same time., Study Design: Prospective quality improvement project centered on preterm surgical infants admitted to Primary Children's Hospital (n = 41). Preoperative ROP risk identification rates were analyzed using an annotated run chart, intraoperative SpO 2 and laser intervention were compared using un-paired t test., Results: Preoperative identification of ROP risk increased from 60 to 100% and no infant was exposed to 100% SpO 2 intraoperatively during the study period. The incidence of laser intervention in this population decreased by 45% from 22 to 12% (p = 0.21)., Conclusion: Simplifying our preoperative handoff increased our rates of correct identification and communication ROP risk in preterm infants while decreasing exposure to 100% SpO 2 .

Background: Persistent pulmonary hypertension of the newborn (PPHN) occurs in 10% of neonatal respiratory insufficiency. To selectively reduce pulmonary vascular resistance, several treatments have been tried. Inhaled epoprostenol (iPGI 2 ) has been used for 12 years in our institution for the management of refractory PPHN despite the gaps in the literature to support this use., Objectives: The primary objective was to evaluate the efficacy of iPGI 2 for PPHN. The secondary objectives were to describe its use in neonates and assess side effects., Study Design: This retrospective cohort study included infants < 28 days with PPHN treated with iPGI 2 in the neonatal or pediatric intensive care units of our institution between 2004 and 2016., Results: We reviewed 43 patient' care episodes (mean gestational age of 36 weeks). This was an extremely ill population with 54% mortality rate. Oxygenation index improved significantly after 12-hour treatment ( p  = 0.047), with a rebound effect when discontinuing nebulization. By the end of the therapy, the fraction of inspired oxygen had significantly dropped ( p  = 0.0018). Echocardiographic markers tended to normalize during treatment. No potential side effects were reported., Conclusion: In these sick newborns, we observed an improvement in PPHN under iPGI 2 without significant adverse effects. To our knowledge, this is the largest neonatal cohort reported to have received iPGI 2 for PPHN., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)