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Objective: In studies of concomitant arterial-venous umbilical cord blood gases (CAV-UBGs), approximately 10% of technically valid samples have very similar pH and/or pCO 2 values and were probably drawn from the same type of blood vessel. Without a way to objectively determine the source in these cases, it has been argued that most of these same-source CAV-UBGs are venous because the vein is larger and more easily sampled than the artery. This study aimed to calculate the probability of an arterial (ProbAS) or venous source (ProbVS) of same-source CAV-UBGs in the clinically and medicolegally important pH range of 6.70 to 7.25 using a statistical predictive model based on the cord blood gas values., Study Design: Starting with a dataset of 56,703 CAV-UBGs, the ProbAS, ProbVS, and respective 95% confidence intervals (CIs) were calculated for the 241 sample pairs with near-identical pH, pCO 2 , and pO 2 values and a pH of 6.70 to 7.25. Using a previously validated generalized additive model, the source was categorized as: Probable Arterial or Highly Probable Arterial if the ProbAS and CIs were >0.5 or >0.8, respectively; Probable Venous or Highly Probable Venous if the ProbVS and CIs were >0.5 or >0.8, respectively; or Indeterminant if the CIs encompassed ProbAS/VS = 0.5., Results: A total of 39% of the same-source CAV-UBGs were Probable Arterial, 56% were Probable Venous, and 5% were Indeterminant. However, considering samples with a pH ≤7.19, 80% were Probable Arterial and 16% were Probable Venous. Considering the Highly Probable categories, the more acidemic specimens were 9 times more likely to be arterial than venous. Similarly, CAV-UBGs with pCO 2  > 8.2 kPa (62 mm Hg) or pO 2 ≤ 1.9 kPa (14 mm Hg) were more likely to be in the arterial rather than the venous categories., Conclusion: Same-source CAV-UBGs in the more acidemic, hypercarbic, or hypoxemic ranges are more likely to be arterial than venous., Key Points: · Umbilical cord arterial/venous gases (CAV-UBGs) with similar values are thought to be mainly venous.. · A validated statistical model was used to predict the probability an arterial or venous source.. · CAV-UBGs with very similar values and pH >  7.19 are likely venous; however, those with pH ≤ 7.19 and/or pCO2 >  8.2 kPa and/or pO2 ≤1.9 kPa are more likely arterial.., Competing Interests: D.M. has no potential conflicts of interest. R.L.S. is the President of Grand Rounds Software, LLC; the company has no financial interest in this study. Dr. Stavis is also a consultant in a medicolegal case that involves, among other issues, the identification of the source of an umbilical cord blood gas. His compensation as a consultant is entirely independent of this study., (Thieme. All rights reserved.)

Objective: Cord gas values and Apgar scores, currently used as markers for newborn wellbeing and postpartum complications, provide rough estimates, and their use remains elusive. Circulating cell-free DNA (cfDNA) may better represent newborn status at birth and the effect of parturition on the fetus. This pilot study investigates the association between cord blood (CB) cfDNA and neonatal outcomes., Study Design: In a prospective cohort study, cfDNA concentration was measured in immediately following delivery collected CB sera of newborns using our rapid fluorescent assay., Results: During the study period, blood samples from umbilical cords of 100 newborns were collected. Vaginal delivery was associated with a higher median CB cfDNA than cesarean delivery (277 [95% confidence interval [CI] 199-377] vs. 100 [95% CI 43-265] ng/mL, p  < 0.01). cfDNA levels were significantly associated with gestational age at delivery (rho = 0.308, p  = 0.002) and CB base deficit (BD, r  = 0.252, p  = 0.017). According to maternal and fetal complications, CB cfDNA was elevated in fetuses with category II of heart rate tracing ( p  < 0.05), with maternal positive vaginal culture ( p  < 0.01), and with premature rupture of membranes (PROM, p  < 0.001). Logistic regression models of CB cfDNA fourth quartiles demostrate a double odds ratio for elevated BD (>3mmol/L) and for worse heart rate tracing category., Conclusion: Serum CB cfDNA concentration reflects the newborn's status and hazards with an excellent association with CB BD, fetal heart rate category, and maternal risk factors for infection (positive vaginal culture and PROM). This preliminary observation suggests that cfDNA can serve as a point of care biomarker for newborn status at the time of delivery., Key Points: · CB cfDNA levels correlated with newborn's BD.. · CB cfDNA levels reflect parturition stress and inflammation.. · cfDNA serve as a diagnostic and prediction tool for the identification of newborns at risk for morbidity.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: We examined the impact of perinatal factors on cord serum club cell protein (CC16) and the association of CC16 with mechanical ventilation and bronchopulmonary dysplasia (BPD) in preterm neonates., Study Design: A retrospective cohort study including 60 neonates born with gestational age (GA) < 34 weeks. The impact of categorical perinatal factors on cord blood levels of CC16 was examined with univariate and multivariate regression analyses., Results: In neonates with GA < 32 weeks, cord blood CC16 concentrations were significantly lower compared to neonates with GA between 32 0/7 and 33 6/7 weeks (5.4 ± 2.5 compared to 7.6 ± 2.9 ng/mL, p  = 0.039). Neonates with prolonged rupture of membranes had significantly lower CC16 compared to those without prolonged rupture of membranes (4.0 ± 1.9 compared to 7.2 ± 2.2, p  < 0.001). Finally, neonates with BPD had significantly lower CC16, compared to neonates without BPD (4.2 ± 2.1 compared to 7.0 ± 2.2 ng/mL, p  = 0.004).Prolonged rupture of membranes was significantly negatively associated with CC16 (b = -2.67, 95% confidence interval [CI] -0.49 to -4.85, p  = 0.017), after adjusting for GA (b = 0.23, 95% CI 0.03-0.42, p  = 0.022), mode of conception, and mode of delivery. Finally, higher CC16 levels were significantly inversely associated with BPD (odds ratio = 0.33, 95% CI 0.12-0.88, p  = 0.028), after adjusting for GA (b = 0.27, 95% CI 0.09-0.78, p  = 0.015), and birth weight., Conclusion: Prolonged rupture of membranes was significantly negatively associated with cord serum CC16, after adjusting for GA, conception, and delivery mode, and CC16 was significantly inversely associated with BPD, after adjusting for GA and birth weight., Key Points: · Neonates with prolonged rupture of membranes had lower CC16 levels.. · CC16 was significantly negatively associated with BPD.. · CC16 could be a biomarker of lung injury and BPD.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The clinical significance of nuchal cord (NC) at the time of delivery is unclear. Studies have found that NC is associated with lower umbilical artery (UA) pH. Since fetal hypercarbia precedes respiratory acidosis, we hypothesize UA pCO 2 is elevated in neonates with NC at the time of delivery., Study Design: This is a secondary analysis of a prospective cohort study of women with full-term singleton pregnancies admitted in labor or for induction of labor at an institution with a universal umbilical cord gas policy. We compared patients with NC at the time of delivery to those without NC. Women were excluded if they did not have validated UA gases, had a major fetal anomaly, or had an intrauterine fetal demise. The primary outcome of the study was UA pCO 2 . Secondary outcomes were other components of UA gas and neonatal morbidity composite. Baseline characteristics were compared utilizing chi-square or Fisher's exact test or the Student's t -test. UA gas parameters were compared using the Kruskal-Wallis test. Multivariable logistic regression was utilized to adjust for confounders., Results: Of the 8,580 study participants, 7,608 had validated umbilical cord gases. The incidence of NC in the population was 24.15% ( n  = 1,837). UA pCO 2 was higher in those with NC than without (58 mm Hg [53-64] vs. 55 mm Hg [50-60], p  < 0.01). There was a greater odds of hypercarbia in the NC group (pCO 2  > 65 mmHg; adjusted odds ratio [aOR]: 1.97, 95% confidence interval [CI]: 1.72-2.25, p  < 0.01). Additionally, the NC group was more likely to be mildly acidemic (pH < 7.2, aOR: 1.74, 95% CI: 1.51-2.01, p  < 0.01). There was no difference in composite neonatal morbidity between the groups., Conclusion: NC is associated with an increased risk of hypercarbia and acidemia. However, this is not associated with increased risk of neonatal morbidity., Key Points: · Nuchal cord is associated with an increased risk of hypercarbia and mild acidemia.. · Nuchal cord is not likely associated with neonatal morbidity.. · Neonatal management should not be altered due to the presence of a nuchal cord at delivery.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: The study aimed to explore the prevalence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among male newborn infants in northeastern Thailand and its relationship with neonatal jaundice (NJ)., Study Design: This prospective cohort study included male newborn infants with gestational age (GA) ≥35 weeks born between July 1, 2019, and March 1, 2021. Cord blood was sent for G-6-PD fluorescent spot test (FST) and results were reported as normal, partial, or complete deficiency. Infants with NJ would have blood tested for total serum bilirubin (TSB) level and other possible causes of NJ. Duration of phototherapy, length of hospital stays, and complications were documented., Results: There were 922 male infants included in this study with 854 (93.1%) term and 63 (6.9%) preterm infants. FST showed 132 infants (14.4%) had G-6-PD deficiency. Incidence of NJ was significantly higher among infants with G-6-PD deficiency compared with infants with normal G-6-PD level (47.7 vs. 25.8%; relative risk [RR]: 2.62, 95% confidence interval [CI]: 1.79-3.82; p  < 0.001). Regardless of G-6-PD level, preterm infants had significantly higher incidence of NJ than term infants (52.4 vs. 27.3%; RR: 2.93, 95% CI: 1.75-4.92; p  < 0.001). Duration of phototherapy was significantly longer in infants with G-6-PD deficiency with NJ but hospital stays were similar. Infants with combined G-6-PD deficiency and other causes of hemolysis did not have higher TSB level than infants with isolated G-6-PD deficiency. Risk factors associated with NJ were G-6-PD deficiency and preterm infants, whereas more advance GA was associated with reduced risk for NJ., Conclusion: G-6-PD deficiency and preterm infants were important risk factors for NJ. Routine G-6-PD screening, close monitoring for signs of NJ in infant with risks, and appropriate parental counseling should be implemented., Key Points: · G-6-PD deficiency increases risk of neonatal jaundice.. · Preterm infants have higher risk for neonatal jaundice.. · G-6-PD deficiency does not link with severe jaundice.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To examine whether a correlation exists between electronic fetal monitoring (EFM) in the final 120 minute prior to delivery and neonatal cord blood pH among parturients with preeclampsia., Study Design: A retrospective cohort study of parturients with term and near-term preeclampsia who delivered at Soroka University Medical Center between 2013 and 2020 was conducted. EFM tracings, demographical data, and obstetrical outcomes were retrieved from the patients' electronic medical records. Using MATLAB program, area under the curve (AUC) measurements were applied. Correlation was calculated using the Spearman's correlation coefficient., Results: EFM of 88 parturients with preeclampsia were assessed. A significant negative correlation was demonstrated between cord blood pH and the decelerations AUC, total decelerations duration, and deceleration depth. No correlation was demonstrated between area over the curve (acceleration) and cord blood pH. In a multivariate linear regression, total deceleration AUC was found independently negatively associated with cord blood pH (beta = -0.264, p  = 0.011) controlling for second stage of labor duration and induction of labor., Conclusion: Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia. Further studies are needed to strengthen and establish the use of electronic EFM in the management of labor and delivery., Key Points: · A negative correlation was demonstrated between cord blood pH and the decelerations AUC.. · Total deceleration AUC was found independently negatively associated.. · Among parturients with preeclampsia, EFM indices may assist in the diagnosis of fetal acidemia.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To test the hypothesis that elevated umbilical artery (UA) partial pressure of carbon dioxide (pCO 2 ) is associated with neonatal morbidity and to compare the risk of neonatal morbidity with different patterns of UA acidosis., Study Design: This was a secondary analysis of a prospective cohort of term, singleton, nonanomalous deliveries with universal cord gas collection. The primary outcome was composite neonatal morbidity. Multivariable logistic regression was used to determine the relative risk (RR) for neonatal morbidity in patients with and without UA hypercarbia. A receiver operating characteristic curve determined the predictive value of pCO 2 for neonatal morbidity. An additional multivariable logistic regression was used to evaluate the risk of neonatal morbidity in different patterns of UA acidosis., Results: UA hypercarbia was associated with an increased risk of neonatal morbidity (RR: 2.56, 95% confidence interval [CI]: [2.07, 3.17]). After adjusting for UA acidemia, this association remained significant (adjusted RR: 1.39, 95% CI: [1.05, 1.83]). UA pCO 2 was less predictive of neonatal morbidity than UA pH (area under the curve [AUC]: 0.65, 95% CI: [0.62, 0.68] vs. AUC: 0.72, 95% CI: [0.69, 0.75], p  < 0.01). The odds ratios for neonatal morbidity for respiratory, mixed, and metabolic acidosis compared with normal cord gases were 1.48 (95% CI: [0.88, 2.49]), 6.41 (95% CI: [3.68, 11.17]), and 7.49 (95% CI: [5.76, 9.72]), respectively, p -trend < 0.01., Conclusion: UA hypercarbia is an independent predictor of neonatal morbidity, even in the setting of concomitant UA acidemia. UA mixed and metabolic acidosis carry significantly greater risk of neonatal morbidity compared with respiratory acidosis., Key Points: · UA pCO2 is associated with neonatal morbidity.. · UA respiratory acidosis is the UA cord gas pattern least associated with neonatal morbidity.. · UA pH is a superior predictor of neonatal morbidity compared with UA pCO2.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood., Study Design: Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid ( n  = 13) and cord blood samples ( n  = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health., Results: Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples., Conclusion: Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health., Key Points: · NNS consumption during pregnancy has increased in recent years.. · Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies.. · In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood.. · It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure.. · This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Umbilical cord blood (UCB) for admission laboratories is an approach to decrease anemia risk in very low birth weight (VLBW) neonates. We hypothesized that UCB use results in higher hemoglobin concentration [HgB] around 24 hours of life., Study Design: A randomized control trial among VLBW infants whose admission laboratories were drawn from UCB ( n  = 39) or the infant ( n  = 41) in three U.S. military NICUs (clinicaltrials.gov#NCT02103296)., Results: No demographic differences were observed between groups. UCB infants had higher [HgB] at 12 to 24 hours of life (15.5 vs. 14.0 g/dL, p  = 0.02). The median time to first transfusion was 17 days longer in the experimental group ( p  = 0.04), and at discharge, their number of donor exposures was lower (1.1 vs. 1.8, p  = 0.04)., Conclusion: In the first 24 hours of life that is a period of higher risk for hemodynamic instability, UCB utilization for admission bloodwork in VLBW infants results in higher [HgB]., Key Points: · Umbilical cord blood laboratory work in preterm infants is feasible.. · Cord blood use for admission laboratories results in increased hemoglobin in the first 24 hours of life.. · Cord blood use for admission laboratories delays time to first transfusion in preterm infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study examined patterns of care after birth in newborns treated with therapeutic hypothermia to identify remediable causes for the poorer outcomes observed in outborn infants., Study Design: This was a secondary analysis of 150 newborns (68 outborn) prospectively enrolled at our center in the Vermont Oxford Neonatal Encephalopathy Registry from January 2008 to October 2016., Results: The 5-minute Apgar's score and cord pH value did not differ, but cord blood gases were obtained far less frequently in outborns ( p  = 0.002). Outborns needed more chest compressions ( p  = 0.01) and epinephrine ( p  = 0.04), and had more brain injury on neuroimaging ( p  = 0.05). Outborns took longer to reach target hypothermia temperature ( p  < 0.0001)., Conclusion: The lack of cord gas values and longer time to reach target temperature observed in the outborns are two observed differences in care that can be potentially remedied by providing education and resources at delivering hospitals in rapid identification of hypothermia candidates, though further research is needed to define the effects of such measures. Possible solutions are also discussed here., Competing Interests: M.J.A.H. reports grants from The Hartwell Foundation during the conduct of the study., (Thieme. All rights reserved.)

Objective: The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term., Study Design: This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity., Results: Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19., Conclusion: These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention., Key Points: · Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis.., 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.)

Objective: To assess the incidence and severity of acute kidney injury (AKI) and evaluate risk factors that predict AKI in asphyxiated infants receiving therapeutic hypothermia., Study Design: Infants ≥36 weeks' gestation diagnosed with moderate-to-severe perinatal asphyxia and received therapeutic hypothermia were reviewed retrospectively ( n  = 166). Modified Acute Kidney Injury Network criteria were used to diagnose AKI. The results of infants with AKI were compared with the infants who did not develop AKI., Results: AKI developed in 49 (29.5%) infants, of whom 22 had stage I, 13 had stage II, and 14 had stage III AKI. The overall mortality rate was 15.7% and was significantly higher in infants with AKI when compared with infants without AKI (41 vs. 5%; p  < 0.001). Asystole at birth ( p  = 0.044), placental abruption ( p  = 0.041), outborn status ( p  = 0.041), need for vasopressor support ( p  = 0.031), increased bleeding tendency ( p  = 0.031), initial lactate level ( p  = 0.015), and 12-hour lactate level ( p  = 0.029) were independent risk factors for the development of AKI. Receiver operating characteristic curve analysis demonstrated a good predictive value for initial lactate level (>15 mmol/L), with 69% sensitivity (95% CI: 55-82) and 82% specificity (95% CI: 74-89), and for 12-hour lactate level (>6 mmol/L), with 83.7% sensitivity (95% CI: 70-93) and 73.5% specificity (95% CI: 64.5-81), to predict AKI., Conclusion: AKI is still a common complication of perinatal asphyxia despite treatment with therapeutic hypothermia. Identification of risk factors associated with the development of AKI in asphyxiated infants would be potentially beneficial to reduce morbidity and mortality. Besides perinatal risk factors, initial and 12-hour lactate concentrations can be used for the early prediction of AKI., Competing Interests: None declared., (Thieme. All rights reserved.)

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.)

Objective: This study aimed to determine the relationship between fetal exposure to intra-amniotic infection/inflammation (IAI) and fetal heart ventricular function as assessed by circulatory levels of N-terminal fragment brain natriuretic protein (NT-proBNP) and the Tei index., Study Design: We analyzed 70 samples of paired amniotic fluid (AF) and cord blood retrieved from mothers who delivered preterm at <34 weeks as follows: Yes-IAI ( n  = 36) and No-IAI ( n  = 34). IAI was diagnosed by amniocentesis and AF mass spectrometry. Fetal exposure to inflammation was determined through the evaluation of cord blood haptoglobin (Hp) switch-on status and level, and interleukin (IL)-6 levels by Western blotting and enzyme-linked immunosorbent assay, respectively. Fetal heart function was assessed by cord blood NT-proBNP immunoassay and fetal echocardiogram (Tei index)., Results: IAI was characterized by significantly higher levels of AF ( p  < 0.001) and umbilical cord IL-6 ( p  = 0.004). Cord blood Hp levels and frequency of switch-on status were higher in fetuses exposed to IAI ( p  < 0.001, both). Fetuses exposed to IAI did not have higher levels of NT-proBNP. Following correction for gestational age and race, neither cord blood NT-proBNP nor the Tei index was significantly different in fetuses with Hp switched-on status ( p  > 0.05, both)., Conclusion: Fetal myocardial left ventricular function does not seem to be significantly impaired in fetuses born alive due to IAI if delivery of the fetus occurs immediately following the diagnosis of IAI., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To assess the current practice of delayed cord clamping (DCC) and to determine patient and hospital factors that predict DCC., Study Design: The California Perinatal Quality Care Collaborative (CPQCC) collects data on preterm and acutely ill infants. In 2016, 52 CPQCC neonatal intensive care units (NICUs) collected data on DCC. Hospital and patient characteristics were analyzed using multivariable logistic regression., Results: Of 5,332 deliveries, 1,555 (29%) newborns received DCC. Hospital rates ranged from 0 to 74.5% and increased from 21 to 37% throughout 2016. Infants delivered at <32 weeks or with birth weight <1,500 g were more likely to receive DCC (odds ratio: 2.80; 95% confidence interval: 2.33, 3.36). Cesarean delivery was associated with less likelihood of DCC (odds ratio: 0.68; 95% confidence interval: 0.59, 0.79). After risk adjustment, 17 (33%) hospitals had higher than expected DCC rate. Hospitals with less than 50 NICU beds are more likely to practice DCC, whereas Level 3 American Academy of Pediatrics NICUs, nonprofit owned hospitals, and teaching institutions were less likely to practice DCC ( p  < 0.001)., Conclusion: There are opportunities to implement quality improvement activities to increase DCC rates., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The calculation of HCO 3 and base excess in current blood gas analysis is based on the Siggaard-Andersen equation. One of the constants in this equation is dependent on the known buffering capacity of hemoglobin A. We sought to investigate differences in buffering capacity between adult hemoglobin A and fetal hemoglobin F as a potential explanation for the observed poor correlation between calculated base excess in umbilical cord blood and newborn outcomes. Such differences would influence a key constant in the Van Slyke/Siggaard-Andersen equation used to calculate HCO 3 and base excess and could be an explanation of these observations., Study Design: This was a prospective observational study. We analyzed umbilical cord blood bicarbonate levels both as calculated values from a traditional blood gas analyzer and as measured values in 20 women giving birth at term. Since the calculated value is dependent upon the concentration and known buffering capacity of hemoglobin A, significant differences in these two analyses would imply differences in the buffering capacity of hemoglobins A and F., Results: The mean calculated HCO 3 value was 25 mEq/L (25.3 ± 1.9) compared with a mean measured value of 25 mEq/L (24.6 ± 1.7) over a range of pH levels of 7.16 to 7.42. This difference was not significant ( p  = 0.07)., Conclusion: The buffering capacity of hemoglobin F, for clinical purposes, is not different than that of hemoglobin A and is not an explanation for the recognized poor correlation between base excess and neonatal outcome., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The present study aimed to assess the global oxidant and antioxidant status in infants born to preeclamptic mothers and their correlation with cardiac functions., Study Design: We compared 40 infants born to preeclamptic mothers with 40 premature infants born to normotensive mothers. We assessed the relationship between echocardiographic measurements and total antioxidant capacity (TAC) and total oxidant status (TOS) values., Results: In the study group, TAC, TOS, and oxidative stress index (OSI) levels were significantly higher in the cord blood ( p  = 0.03, 0.04, and 0.039, respectively) than in the control group. We did not observe any correlation between echocardiographic measurements and TAC, TOS, and OSI levels in infants born to preeclamptic mothers., Conclusion: Compared with the control group, despite higher TAC levels in infants born to preeclamptic mothers, concurrent elevated OSI levels reveal that the oxidant-antioxidant balance is disturbed in favor of oxidants. Furthermore, the findings of this study suggest that echocardiographic parameters are unaffected by the oxidant status., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To assess whether uterine tachysystole (UT) in labor causes an increase in cord blood lactate., Study Design: Secondary analysis of a prospective cohort study of all consecutive singleton gestations ≥ 37 weeks admitted for labor to a single tertiary care institution with universal cord gas policy. Patients with UT in the last hour ("always") were compared with those without UT ("never"). Primary outcome of interest was cord blood lactate ≥ 4 mmol/L. Secondary outcomes included pH ≤ 7.10, base deficit ≥ 8 mmol/L, and admission to the neonatal intensive care unit (NICU). Multivariable logistic regression was used to estimate the risk for elevated cord blood lactate after adjusting for maternal age and body mass index., Results: Of the 8,580 patients included in the analysis, 513 experienced UT 1 hour before delivery (5.9%). UT was significantly associated with elevated cord blood lactate in the "always" (33.5%) compared with the "never" group (26%) (adjusted odds ratio 1.47 [1.17, 1.86]; p  < 0.01). However, there were no differences in either umbilical arterial pH, base deficit, or NICU admission rates., Conclusion: UT in the last hour preceding delivery increases arterial cord blood lactate suggesting that UT proximate to delivery should be considered as a variable when interpreting cord blood gas values., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Herein, we measured the concentration of insulinlike growth factor I (IGF-I), IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin in the umbilical cord blood of newborns categorized as "small for gestational age" (SGA), "appropriate for gestational age" (AGA), and "large for gestational age" (LGA). Our aim was to elucidate the link between the levels of these proteins and fetal growth., Study Design: A total of 96 term infants were included and categorized into three weight categories. Their venous cord blood samples were collected to measure the levels of IGF-I, IGF-II, leptin, adiponectin, ghrelin, resistin, and visfatin., Results: IGF-I, visfatin, and leptin levels showed significant differences among the groups. Pairwise comparisons showed that adiponectin ( p  = 0.023), resistin ( p  = 0.025), and ghrelin ( p  = 0.005) levels were significantly lower in the SGA group than in the LGA group. Correlation analyses showed a strong association of IGF-1, IGF-II, and leptin levels with birth weight ( r  = 0.644, p  < 0.001; r  = 0.441, p  < 0.001; and r  = 0.404, p  < 0.001, respectively)., Conclusion: SGA newborns showed a significantly higher visfatin concentration and lower ghrelin, leptin, resistin, and adiponectin levels than the AGA and LGA newborns did., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Obesity during pregnancy impedes fetal iron endowment. In adults, both iron depletion and hypoxia stimulate erythropoietin (Epo) production, while hepcidin, the primary iron regulator, is inhibited by Epo and stimulated by obesity. To understand this relationship in fetuses, we investigated obesity, inflammation, and fetal iron status on fetal Epo and hepcidin levels., Study Design: Epo, hepcidin, C-reactive protein (CRP), and ferritin levels were measured in 201 newborns of 35 to 40 weeks' gestation with historical risk factors for a low fetal iron endowment, including half with maternal obesity., Results: Epo was unrelated to fetal size, but Epo was directly related to maternal body mass index (BMI; kg/m 2 ) ( p  < 0.03) and CRP ( p  < 0.0005) at delivery. Epo levels were twice as likely to be elevated (≥50 IU/L) while comparing the lowest quartile of ferritin with the upper three quartiles ( p  < 0.01). Hepcidin was directly related to ferritin ( p  < 0.001) and indirectly related to maternal BMI ( p  < 0.015), but BMI became nonsignificant when undergoing multivariate analysis. Hepcidin was unrelated to Epo., Conclusion: Although some of the fetal responses involving Epo were similar to adults, we did not find a hepcidin-Epo relationship like that of adults, where fetal liver is the site of both hepcidin and Epo production., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: We aimed to investigate whether cord blood bilirubin (CBB) level could be used to identify the newborns at a high risk of developing hyperbilirubinemia., Study Design: Total and direct serum bilirubin level were evaluated from umbilical cord blood of newborns. We checked blood groups and Rh status of all mothers and determined blood groups and direct Coombs test (DC) of newborns born to mothers whose blood group was O type or Rh negative to determine the maternal-fetal blood group or Rh incompatibility., Results: A total of 418 newborns were included, and phototherapy (PT) was required in 17 newborns. The cutoff value of CBB for predicting the occurrence of significant hyperbilirubinemia requiring PT was 1.67 mg/dL, with a sensitivity of 82% and specificity of 99%. The mean CBB level in babies receiving PT was 2.4 ± 0.9 mg/dL. When blood group, CBB level, DC, gender, and mode of delivery were assigned as possible risk factors, multıvariate analysis showed ABO, Rh incompatibility, and CBB level increased the risk of PT requirement., Conclusion: CBB could be useful to determine newborns at a risk of developing hyperbilirubinemia and prevent developing severe complications due to delay in diagnosis., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To evaluate the implementation of an institutional protocol for universal delayed umbilical cord clamping (DCC) at term on maternal, neonatal, and umbilical cord blood gas outcomes., Study Design: This is a retrospective cohort study of singleton term gestations from April through July 2017. On June 1, 2017, a protocol was implemented for DCC in all deliveries. Outcomes were compared between patients delivered prior to and those delivered after implementation. The primary outcome was postpartum hemorrhage (PPH). Secondary outcomes were additional adverse maternal, neonatal, and umbilical cord blood gas outcomes. Multivariable logistic regression was used to adjust for potential confounders., Results: Of 682 patients, 341 were delivered preprotocol and 341 were delivered postprotocol. After implementation, there was 91.8% adherence to the protocol. Overall, there was no significant difference in PPH between patients delivered preprotocol and those delivered postprotocol (8.2 vs. 13.2%; adjusted relative risk [aRR]: 1.26, 95% confidence interval [CI]: 0.98-1.51). There was a significant decrease in the ability to obtain paired arterial and venous umbilical cord blood gases from preprotocol to postprotocol (83 vs. 63.6%; aRR: 0.62 [95% CI: 0.50-0.76]). There were no significant differences in abnormal umbilical cord blood gases or neonatal outcomes., Conclusion: We did not find an increased risk of adverse outcomes associated with the widespread use of DCC., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS)., Study Design: Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS ( n  = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS ( n  = 51, GA 26 ± 1 weeks). Placental hepcidin and ferroportin expression were evaluated by immunohistochemistry and real-time-polymerase chain reaction (RT-PCR). Liver hepcidin and ferroportin expression patterns were ascertained in autopsy specimens of neonates ( n  = 8) who died secondary to culture-proven sepsis., Results: Cord blood hepcidin was significantly elevated (GA corrected, p  = 0.018) and was positively correlated with IL-6 ( r  = 0.379, p  = 0.001) in EONS. Hepcidin localized at syncytiotrophoblast and fetal vascular endothelium. Placental ferroportin, but not hepcidin mRNA correlated with cord blood hepcidin levels ( r  = 0.46, p  = 0.039) and funisitis severity ( r  = 0.50, p  = 0.018). Newborns who died from sepsis ( n  = 4) had higher hepatic hepcidin and iron sequestration, but lower ferroportin staining than those who died of nonsepsis causes ( n  = 4)., Conclusion: Premature fetuses with EONS have elevated circulating hepcidin, likely related to lower placenta and liver ferroportin expression. Fetal hepcidin-ferroportin interaction appears to play a role in EONS pathophysiology independent of maternal response to intrauterine inflammation., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective:  The objective of this study was to investigate the relationship between umbilical cord partial pressure of oxygen (pO 2 ) at delivery and neonatal morbidity., Study Design:  This is a secondary analysis of a prospective cohort study of term deliveries with universal cord gas collection between 2010 and 2014. The primary composite outcome of neonatal morbidity included neonatal death, meconium aspiration syndrome, intubation, mechanical ventilation, hypoxic-ischemic encephalopathy, and hypothermia treatment. Umbilical artery (UA), vein (UV), UV minus UA (Δ) pO 2 , and hypoxemia (pO 2  ≤ fifth percentile) were compared between patients with and without neonatal morbidity. Areas under the receiver-operating characteristic curves were used to assess the predictive ability of pO 2 ., Results:  Of 7,789 patients with paired umbilical cord pO 2 , 106 (1.4%) had the composite neonatal morbidity. UA pO 2 was significantly lower in patients with neonatal morbidity compared with those without (median [interquartile range]: 16 (12, 21) vs. 19 (15, 24) mm Hg, p  < 0.001). There was no difference in median UV pO 2 or ΔpO 2 between the groups. UA and UV hypoxemia were significantly more common in patients with neonatal morbidity. UA pO 2 had limited predictive ability for neonatal morbidity (area under the curve: 0.61, 95% confidence interval: 0.6-0.7)., Conclusion:  Although UA pO 2 is significantly lower in patients with neonatal morbidity, it is a poor predictor of neonatal morbidity at term., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  Our aims were to evaluate whether there is an inverse association between body mass index (BMI) and umbilical artery pH and to investigate the contribution of intraoperative hypotension on the umbilical artery pH. Study Design  We conducted a retrospective cohort study of all women with a nonanomalous singleton at 37 to 41 weeks who underwent a scheduled cesarean delivery under spinal anesthesia at our facility from January 2006 to March 2012. The primary outcome was the proportion of patients in each BMI category with arterial cord pH < 7.10. Intraoperative blood pressure data were compared across BMI categories. Results  In total, 717 mother-infant pairs met enrollment criteria. Mean arterial pH was significantly lower in women with elevated BMI ( p  = 0.014), notably with BMI ≥ 40 kg/m 2 . Baseline blood pressure increased linearly with increasing BMI ( p  < 0.001), however, so did the maximum drop in all blood pressure parameters ( p  < 0.001). After adjusting for potential confounders, including blood pressure, there was no longer an association between cord pH and BMI ( p  = 0.72). Conclusion  For women undergoing a scheduled cesarean delivery under spinal anesthesia, umbilical artery pH is lower in women with BMI ≥40 kg/m 2 . Relative hypotension after spinal anesthesia is more pronounced with increasing BMI and may explain this effect., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  To determine whether arterial umbilical cord gas (aUCG) pH, in anatomically normal-term infants, could select infants at risk for brain injury identified on magnetic resonance imaging (MRI). Study Design  We performed a nested case-control within a prospective cohort of 8,580 women. Cases, with an aUCG pH < 7.10, were temporally, age, and sex matched to controls with an aUCG pH ≥ 7.20. Bi- and multivariable analyses compared the presence and severity of brain injury. Secondary analyses estimated whether elevated arterial base excess or lactate were associated with brain injury. Results  Fifty-five cases were matched to 165 controls. There was no statistical difference in brain injury between the groups (adjusted odds ratio [aOR]: 1.8, 95% confidence interval [CI]: 0.7-4.4]). Base excess ≥ -8 mEq/L was not significantly associated with brain injury ( p  = 0.12). There was no increase in risk of injury based on elevation of arterial lactate ≥ 4 mmol ⁄L ( p  = 1.00). Cases were significantly more likely to have an abnormal score in several domains of the Dubowitz neurologic examination. Conclusion  The aUCG acid-base parameters alone are not sufficient clinical markers to identify term infants that might benefit from MRI of the brain to identify injury., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  The objective of this study was to determine the maternal and fetal pharmacokinetic (PK) profiles of acetaminophen after administration of a therapeutic oral dose. Study Design  After obtaining Institutional Review Board approval and their written informed consent, pregnant women were given a single oral dose (1,000 mg) of acetaminophen upon admission for scheduled cesarean delivery. Maternal venous blood and fetal cord blood were obtained at the time of delivery and acetaminophen levels were measured using gas chromatography-mass spectroscopy. PK parameters were calculated by noncompartmental analysis. Nonparametric correlation of maternal/fetal acetaminophen levels and PK curves were calculated. Results  In this study, 34 subjects were enrolled (median, 32 years; range, 25-39 years). The median maternal weight was 82 kg (range, 62-100 kg). All but two subjects were delivered beyond 39 weeks' gestation. The median newborn birth weight was 3,590 g (interquartile range, 3,403-3,848 g). Noncompartmental analysis described similar PK parameters in the maternal ( T 1/2 , 84 minutes; apparent clearance [Cl/F], 28.8 L/h; apparent volume of distribution [V d /F], 57.5 L) and fetal compartments ( T 1/2 , 82 minutes; Cl/F, 31.2 L/h; V d /F, 61.2 L). Paired maternal/fetal acetaminophen levels were highly correlated ( p  < 0.0001). Conclusion  Fetal acetaminophen PKs in the fetus parallels that in the mother suggesting that placental transfer is flow limited. Maternal acetaminophen levels can be used as a surrogate for fetal exposure., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  The objective of this study was to determine the correlation between umbilical artery lactate with brain lactate in nonanomalous term infants. Study Design  We performed a nested case-control study within an on-going prospective cohort of more than 8,000 consecutive singleton term (≥ 37 weeks) nonanomalous infants. Neonates underwent cerebral magnetic resonance imaging (MRI) within the first 72 hours of life. Cases (umbilical artery pH ≤ 7.10) were gender and race matched 1:3 to controls (umbilical artery pH > 7.20). Single voxel magnetic resonance spectroscopy (MRS), lactate, and N-acetyl aspartate (NAA) for normalization were calculated using Siemens software (Plano, TX). Linear regression estimated the association between incremental change in umbilical artery lactate and brain lactate, both directly and as a ratio with NAA. Results  Of 175 infants who underwent MRI with spectral sequencing, 52 infants had detectable brain lactate. The 52 infants with brain lactate peaks had umbilical artery lactate values of 1.6 to 11.4 mmol/L. For every 1.0 mmol/L increase in umbilical artery lactate, there was an increase in brain lactate of 0.02, which remained significant even when corrected for NAA. Conclusion  MRS measured brain lactate is significantly correlated with umbilical artery lactate in nonanomalous term infants, which may help explain the observed association between umbilical artery lactate and neurologic morbidity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  The objective of this study was to determine ability to detect neonatal acidemia and interobserver agreement with the FIGO 3-tier and 5-tier fetal heart rate (FHR) classification systems. Design  This was a case-control study. Setting  This study was set at the University Medical Center. Population  A total of 202 FHR tracings of 102 women who delivered an acidemic fetus (umbilical arterial cord gas pH ≤ 7.10 and BE < - 8) and 100 who delivered a nonacidemic fetus (umbilical arterial cord gas pH > 7.10) were assessed. A subanalysis was performed for those fetuses who suffered severe metabolic acidemia (pH ≤ 7.0 and BE < - 12). Methods  Two reviewers blind to clinical and outcome data classified tracings according to the new 3-tier system proposed by the FIGO and the 5-tier system proposed by Parer and Ikeda. Main Outcome Measures  Sensitivity and specificity for detecting neonatal acidemia and interobserver agreement in classifying FHR tracings into categories of both systems were studied. Results  The 3-tier system showed a greater sensitivity and lower specificity to detect neonatal acidemia (43.6% sensitivity, 82.5% specificity) and severe metabolic acidemia (71.4% sensitivity, 74.0% specificity) compared with the 5-tier system (36.3% sensitivity, 88% specificity and 61.9% sensitivity, 80.1% specificity, respectively). Both systems were compared by area under the receiver-operating characteristic curve, with comparable predictive ability for detecting neonatal acidemia (FIGO-area under the curve [AUC]: 0.63 [95% confidence interval [CI]: 0.57-0.68] and Parer-AUC: 0.62 [95% CI: 0.56-0.67]). Interobserver agreement was moderate for both systems, but performance at each specific category showed a better agreement for the 5-tier system identifying a pathological tracing (orange or red, κ: 0.625 vs. pathological category, κ: 0.538). Conclusion  Both systems presented a comparable ability to predict neonatal acidemia, although the 5-tier system showed a better interobserver agreement identifying pathological tracings., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective  Previous data examining the association between the interval between the delivery of the first and second twin (intertwin interval) and adverse neonatal outcomes are conflicting. We sought to evaluate whether intertwin interval is associated with adverse neonatal outcomes for the second twin in a contemporary U. S. cohort. Methods  This is a cohort study of women who delivered twins at or after 32 weeks gestation between 2006 and 2014 and whose first twin was delivered vaginally vertex. The intertwin interval was dichotomized as < 10 minutes or ≥ 10 minutes. Adverse outcomes included arterial cord pH ≤ 7.1, admission to the neonatal intensive care unit, respiratory distress, intraventricular hemorrhage, and death. Results  Of the 171 subjects, 61 (35.7%) had an intertwin interval of ≥ 10 minutes. There were no differences in maternal characteristics. Intertwin interval of ≥ 10 minutes was associated with an increased frequency of arterial pH ≤ 7.1 (22.0 vs. 8.2%, p  = 0.03), which persisted after adjusting for confounders (adjusted odds ratio, 2.94; 95% confidence interval, 1.04-8.33). Other adverse outcomes did not differ. Conclusion  Intertwin interval of ≥ 10 minutes was associated with increased frequency of arterial pH ≤ 7.1 in the second twin, but no other adverse neonatal outcomes., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background  Establishing lung inflation prior to umbilical cord clamping may improve the cardiovascular transition and reduce the risk of intraventricular hemorrhage in preterm infants. We developed a pilot feasibility and safety study in which infants < 33 weeks' gestation received assisted ventilation during delayed cord clamping (DCC). Methods  Infants born between 24 0/7 and 32 6/7 weeks' gestation whose mothers consented were enrolled. All infants received continuous positive airway pressure or positive pressure ventilation during 90 seconds of DCC. Outcomes included feasibility (ability to complete protocol and maintain a sterile field during cesarean deliveries) and safety variables (Apgar scores, umbilical cord pH and base deficit, admission temperature, and postcesarean infection). Results  A total of 29 infants were enrolled, including one set of twins (median gestation: 30 weeks; 72% cesarean births). In all cases, the protocol was completed. Heart rate at 60 seconds was more than 100 beats per minute in all infants. Apgar scores, cord blood gas values, and admission temperature were comparable to other preterm deliveries at our institution. Conclusion  Assisting ventilation of very preterm infants during 90 seconds of DCC is challenging but feasible and appears to be safe in this small pilot study. A randomized clinical trial is warranted to determine clinical benefit., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective Maternal obesity presents several challenges at cesarean section. In an effort to routinely employ a transverse suprapubic skin incision, we often retract the pannus in a rostral direction using adhesive tape placed after induction of anesthesia and before surgical preparation of the skin. We sought to understand the association between taping and neonatal cord blood gases, Apgar scores, and time from skin incision to delivery of the neonate. Study Design This is a retrospective study, performed using prospectively collected anesthesiology records with data supplemented from the patients' medical records. Singleton pregnancies with morbid obesity (body mass index [BMI] > 40 kg/m(2)) between 37 and 42 weeks of gestation who delivered via nonurgent, scheduled cesarean delivery under regional (spinal, combined spinal-epidural, or epidural) anesthesia between March 2007 and March 2013 were identified. Maternal demographics including BMI, comorbidities, type of anesthesia, time intervals during the surgery, cord gas results, and Apgar scores were collected. The relationship between taping and blood acid-base status, Apgar scores, and interval from skin incision to delivery was investigated using appropriate statistical tests. Results There were 2,525 (27.5%) cesarean deliveries out of 9,189 total deliveries. Applying the described inclusion/exclusion criteria, 141 patients were identified (33 taped and 108 nontaped). There was no significant difference in BMI between the taped (51.9 kg/m(2)) and nontaped groups (47.4 kg/m(2)), p > 0.05. There was no difference in type of anesthesia (p > 0.05). The only significant difference between the taped and not-taped groups was the presence of chronic hypertension in the taped group (p = 0.03). There were no significant differences in cord blood gas values, Apgar scores, or skin incision to delivery interval (p > 0.05 for all outcomes). Conclusions Taping of the pannus at cesarean section is a safe intervention that is not associated with adverse neonatal outcomes. Furthermore, over a set of parturients with BMI > 40 kg/m(2), it does not hasten skin incision to delivery time., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The aim of this study is to examine the hypothesis that prolonged rupture of membranes (PROM) is associated with increased cord blood erythropoietin (EPO) concentrations, proportional to the duration of ruptured membranes., Study Design: This study is a prospective, cross-sectional, observational (noninterventional) cohort study of mother-infant pairs. Criteria for inclusion were as follows: active labor with or without ruptured membranes and vaginally delivered neonates. Excluded were infants with major factors known to be associated with a potential increase in fetal erythropoiesis., Results: A total of 40 mother-infant pairs were recruited. EPO was not influenced by duration of ruptured membranes and significantly correlated only with maternal body mass index., Conclusion: Cord blood concentrations of EPO do not appear to be significantly affected by the duration of ruptured membranes. We speculate that erythropoiesis is upregulated in PROM by mechanisms that involve the production of cytokines and are not EPO driven., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The objective of this study was to investigate the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) levels and respiratory distress syndrome (RDS) development in preterm infants., Study Design: Between January 2012 and January 2013, 81 preterm infants, gestational age below 32 weeks, were prospectively enrolled into the study. Cord bloods of these newborns were tested for 25(OH)D levels. Low level was defined as ≤ 15 ng/mL (Group 1) and normal level as > 15 ng/mL (Group 2). Patients in Group 1 were also divided further into two subgroups as severe deficiency (Group 1a, ≤ 5 ng/mL) and mild deficiency (Group 1b, 5-15 ng/mL)., Results: In this study, 57 infants had low 25(OH)D levels (Group 1, median 8.0 ng/mL [interquartile range, IQR, 5-10]; Group 2, median 21 ng/mL [IQR, 19-24.7]). RDS rate was significantly higher in Group 1a (n = 18, 32.7%) and Group 1b (n = 34, 61.8%) compared with Group 2 (n = 3, 5.4%) (p = 0.001). There were no difference of having RDS between Group 1a (94.7%) and Group1b (89.5) (p = 0.512). Multivariate analysis showed that higher 25(OH)D level can be preventive for the development of RDS (odds ratio, 0.6; 95% confidence interval (0.5-0.8); p = 0.001)., Conclusion: Lower cord blood 25(OH)D levels might be associated with increased risk of RDS in preterm infants with very low birth weight., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM)., Study Design: Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment., Results: A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women., Conclusion: There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: The aim of the article was to investigate the effect of ondansetron preloading with crystalloid infusion after spinal anesthesia during cesarean delivery., Study Design: A total of 66 parturient women scheduled for elective caesarean sections were randomly assigned to two groups. Five minutes before spinal anesthesia, Group O patients were injected with 4 mg of ondansetron, while Group S patients were injected with 5 mL physiological saline. Maternal blood pressure and heart rate were measured at 2 minute intervals for 30 minutes. After delivery, umbilical cord blood samples were analyzed., Results: Maternal hypotension and nausea were significantly lower in ondansetron-treated patients versus placebo (p = 0.011 vs. 0.004). Umbilical venous pH was significantly higher in ondansetron-treated patients (p = 0.006), while partial pressure of carbon dioxide (Pco 2) was significantly lower (p = 0.002). Decreases in maternal systolic and mean arterial blood pressures were significantly lower in ondansetron-treated patients (p = 0.008 vs. 0.025), with less requirement for phenylephrine administration compared with controls (p = 0.029)., Conclusion: Ondansetron preloading combined with crystalloid infusion significantly reduced hypotension and nausea, while improving acid-base status, as well as reducing vasoconstrictor use., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To study the influence of policy changes in the evaluation of neonatal hyperbilirubinemia on discharge process from the nursery. Changes included early assessment of risk factors by universal umbilical blood sampling for blood type, Coombs test, and glucose-6-phosphate dehydrogenase (G6PD) and universal noninvasive transcutaneous bilirubinometry at discharge., Study Design: The 1,569 newborns (≥ 36 weeks' gestation) admitted after the implementation of changes were compared with the 1,822 born before., Results: Policy changes improved the diagnosis of G6PD deficiency and ABO incompatibility and decreased the number of referrals from the community for jaundice follow-up. The average number of needlesticks per baby as well as the time required for the analysis of serum bilirubin levels on discharge day decreased. Changes did not significantly increase costs., Conclusion: Changes seem to have improved the quality of medical care, including early identification of risk factors and better follow-up of neonatal hyperbilirubinemia with reduction of pain and increased efficiency., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To compare the safety and tolerability of metformin to insulin for glycemic control among women with preexisting type 2 and early A2 gestational diabetes., Study Design: Women with preexisting type 2 diabetes and those diagnosed with gestational diabetes who required medical management prior to 20 weeks were randomly assigned to metformin or insulin. Glycemic control, defined as >50% capillary blood glucose within target range, was compared between groups. Other outcomes included patient tolerance, neonatal and obstetric complications, maternal weight gain, neonatal cord blood C-peptide, and patient satisfaction with therapy., Results: Twenty-eight women completed the study, with 14 in each group. Of the 15 women assigned to metformin, 100% continued to receive metformin until delivery, although 43% required supplemental insulin to achieve glycemic control. Glucose measures did not differ between the groups, and the proportion who met fasting and postprandial glycemic target values did not differ between the groups. Women treated with metformin had significantly fewer subjective episodes of hypoglycemia compared with those using insulin (0% versus 36%; p = 0.04) as well as reported glucose values < 60 mg/dL (7.1% versus 50%; p = 0.03)., Conclusion: Metformin should be considered for treatment of overt diabetes and early A2 gestational diabetes in pregnancy., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objectives: Determine the prevalence of prenatal opioid and other drug positivity among women delivering infants in Utah and compare the findings with national data., Study Design: Umbilical cord tissue samples and nonidentifiable demographic data were collected anonymously in 13 labor and delivery units throughout Utah. Samples were analyzed for opioids, amphetamines, cannabinoids, cocaine, phencyclidine, barbiturates, benzodiazepines, propoxyphene, and alcohol biomarkers., Results: Fifty-eight (6.8%) of 850 umbilical cord samples were positive for one or more substances. Opioids were the most frequently detected drugs (4.7%). Fewer samples were positive for alcohol (0.4%), methamphetamine (0.1%), cocaine (0.1%), and marijuana (0.4%)., Conclusion: Opioids were the most frequently detected drugs at delivery. Although some of the samples positive for opioids might have been a result of intrapartum exposure, a significant number were positive for opioids that are not given during labor. This parallels the increasing nonmedical use of prescription pain medications in the general population and has important implications for neonates because of the potential for significant morbidity secondary to neonatal abstinence syndrome., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

We performed multifractal analysis of fetal heart rate (FHR) variability in fetuses with and without acidosis during labor. Multifractal analysis was performed on fetal electrocardiograms in 10-minute sliding windows within the last 2 hours before delivery in 45 term fetuses divided in three groups according to umbilical arterial pH and FHR pattern: group A had pH ≥7.30 and normal FHR, group B had pH ≥7.30 and intermediate or abnormal FHR, and group C had acidosis (pH ≤7.05) and intermediate or abnormal FHR. Six multifractal parameters were compared using Wilcoxon rank sum test. Multifractal parameters were significantly different between the three groups in the last 10 minutes before delivery (P <0.05). Two parameters (H(min), zeta(2)) exhibited a significant difference 70 minutes before delivery, and one parameter (C(2)) was different 10 minutes before birth (P <0.05). Multifractal parameters were significantly different in acidotic and nonacidotic fetuses, independently from FHR pattern., (© Thieme Medical Publishers.)

We undertook this in vitro study to quantify the effect that addition of magnesium (Mg) sulfate to neonatal serum, as compared with adult serum, might have on ionized Mg (Mg (2+)) concentration. We used one cord blood sample and one adult blood sample that we made hypermagnesemic by adding various amounts of magnesium sulfate to study five levels of serum Mg. Each sample was then studied at one of three levels of pH, from extreme alkalosis to extreme acidosis. We measured the changes in serum Mg (2+) and serum ionized calcium (Ca (2+)) in reaction to these changes in pH and Mg. At each pH level, there was an exponential increase in the serum Mg (2+) (and no significant change in serum Ca (2+)) with increasing serum Mg. Multiple regression analysis using Mg (2+) as the dependent variable and baseline Ca (2+), phosphorous, albumin, and blood type (adult versus cord blood) as well as blood pH and serum Mg as independent variables indicated that serum Mg and pH were the only variables significantly influencing serum Mg (2+). Within the range of serum Mg considered, the addition of magnesium sulfate in vitro causes an exponential increase in Mg (2+) and no significant change in serum Ca (2+)., (Copyright Thieme Medical Publishers.)

We applied the concept of umbilical arterial and venous (A-V) blood gas difference in evaluating placental respiratory function to establish normative values for these relationships. Umbilical A-V cord blood gas samples were obtained in standardized fashion in uncomplicated singleton pregnancies. A-V pO (2) and A-V pCO (2) differences were related to obstetric factors, placental weight, and gestational age. Mean absolute differences in uncomplicated vaginal deliveries between umbilical artery and umbilical vein were: pO (2) 11.4 +/- 7.0 mm Hg and pCO (2) 11.9 +/- 6.8 mm Hg. Values in nonlabor cesarean section cases did not differ significantly from those of cases delivered vaginally. A-V pO (2) differences did not vary significantly across gestation (Pearson's R = 0.05, P = 0.43) and did not correlate with birth weight ( R = 0.06, P = 0.30). A-V pCO (2) differences showed increases with gestational age ( R = 0.15, P = 0.008) and with birth weight ( R = 0.18, P = 0.002). Results similar to those of women delivered vaginally were seen in nonlabor cesarean deliveries. Duration of labor did not impact the A-V blood gas relationship. Umbilical A-V oxygen differences reflect placental respiratory function independent of gestational age, birth weight, duration of labor, and mode of delivery. They are easy to collect and represent a potentially valuable resource for assessment of placental function.

Insulinlike growth factors (IGFs) exert profound effects on somatic growth and cellular proliferation of many tissues and play an essential role in bone metabolism. The aim of this study was to investigate how fetal growth and bone mineralization correlate with IGF-I and IGF-binding protein-3 (IGFBP-3) levels of newborn infants and their mothers. In addition, we aimed to determine the predictive value of anthropometric measurements on variability in bone mineral status. Umbilical cord venous blood samples were obtained at delivery from 100 term newborn infants. Forty of the newborn infants had birthweights appropriate for gestational age (AGA), 30 were small for gestational age (SGA), and 30 were large for gestational age (LGA). Data were acquired using whole-body dual-energy X-ray absorptiometry scanner with a pediatric platform. Umbilical cord serum IGF-I concentrations were higher in LGA newborns ( P < 0.01), but lower in SGA newborns ( P < 0.01) than in AGA newborns. Umbilical cord serum IGFBP-3 concentrations in LGA newborns were significantly greater than in SGA and AGA newborns ( P < 0.01 and P < 0.01, respectively). Whole-body bone mineral density (WB BMD) was higher in LGA babies (0.442 +/- 0.025 g/cm2 [SD]; P < 0.01) but lower in SGA (0.381 +/- 0.027 g/cm 2; P < 0.0001) than in AGA babies (0.426 +/- 0.022 g/cm2). WB BMD and content (WB BMC) were correlated significantly with birthweight, birth height, head circumference, body mass index (BMI) of the infants; ponderal index and triceps skinfold thickness (reflecting fat stores) of the infants; cord serum IGF-I concentration, serum IGF-I concentration of the mothers; and fat mass, proportionate fat mass, weight, and BMI of the mothers. In contrast, WB BMC was also correlated positively with cord serum IGFBP-3 concentration and gestational age, and WB BMD was positively correlated with serum IGFBP-3 levels of the mothers. Umbilical cord serum IGF-I concentration of the infants was correlated significantly with the concentration of the mothers ( R = 0.232; P = 0.020). Umbilical cord serum IGF-I and IGFBP-3 concentrations were correlated significantly with the fat mass, gestational age, birthweight, birth height, head circumference, and BMI of the infants. Umbilical cord IGF-I concentration was also correlated with ponderal index and triceps skinfold thickness of the infants, maternal weight, BMI, and proportionate fat mass of the infants. Stepwise multiple regression analyses showed no significant relation between bone indices (WB BMD, WB BMC) and the infant's or mother's variations including serum IGF-I and IGFBP-3 concentrations. Birthweight and gestational age are related to bone indices. However, the present study does not provide support for the hypothesis that serum IGF-I and IGFBP-3 levels of infants and their mothers may play a major role in the regulation of bone metabolism in the developing skeleton.

Serum levels of the protein S-100beta are dependent on three factors: rate of production, permeability of the blood-brain barrier, and rate of clearance. In the developing fetus and neonate all of these factors change at different rates. This study was performed to determine how serum S-100 levels varied during fetal and early postnatal life. Blood samples were obtained from 41 fetal and neonatal lambs. The blood was separated in a centrifuge and the serum drawn off and assayed for S-100beta using a commercially available radioimunoassay kit. S-100beta did not appear in the blood until halfway through pregnancy. Thereafter, levels steadily increased until 1 month after birth. Following this, S-100beta levels decreased progressively until by 1 year of age, they had reached a plateau. S-100beta levels change significantly with normal fetal and neonatal maturation. Valid interpretation of other data from subjects of similar developmental stage must take into consideration this physiological variation.

Increased levels of unbound Free Fatty acid (FFAu) have been found in adults undergoing coronary angioplasty as a result of acute hypoxia-ischemia. We hypohesized that infants suffering from a 1-minute Apgar score of less than 5 will demonstrate elevated FFAu levels in the cord blood. One hundred ninety-nine infants between 25 and 41 weeks gestational age were enrolled in the study. Infants with an Apgar score of less than 5 at 1 minute served as the study group. Blood samples were collected from the umbilical cord and serum FFAu levels were measured with the fluorescent probe acrylodan-derivatized intestinal fatty acid binding protein. The low Apgar score group (n=32, birthweight 3153+/-780 g, gestational age 37.9+/-3.1 weeks) and normal Apgar score group (n=167, birthweight 3067+/-847 g, gestational age 37.5+/-3.5 weeks) were significantly different with respect to Apgar score at 1 minute (3.0+/-1.2 versus 8.4+/-1.1), Apgar score at 5 minutes (6.9+/-versus 8.9+/-0.5), cord pH (7.16+/-0.12 versus 7.28+/-0.07), and in the frequency of meconium passage (40.6% versus 14.9%). Cord FFAu levels were 4.4+/-1.7 versus 3.2+/-1.2 nM (p<0.001), respectively. Cord FFAu correlated inversely with Apgar score at 1 minute (r=-0.31, p<0.05) and with cord pH (r=-0.12, p<0.05), but not with birthweight or gestational age. In infants with low 1-minute Apgar scores, cord free fatty acid levels were significantly elevated compared with those from controls.

We evaluated an association of nonreassuring fetal heart rate (FHR) patterns and subsequent cerebral palsy (CP) in pregnancies with intrauterine bacterial infection. Among 10,030 infants born during 1995 to 2000, 139 were complicated with acute intrauterine bacterial infection in labor. The FHR patterns 2 hours immediately before delivery were interpreted according to the guidelines of the National Institute of Child Health and Human Development. The correlations between the FHR patterns and umbilical blood gases, as well as FHR patterns and CP were studied. Statistics included unpaired t test, contingency table with chi (2) and Fisher test, and one-way analysis of variance with Bonferroni/Dunn test. Fifteen infants (11%) developed CP at 2 years or older. Nonreassuring FHR patterns including recurrent late deceleration, severe variable deceleration, and prolonged deceleration occurred in 24% of pregnancies with intrauterine infection. Incidence of CP was not different according to the FHR deceleration patterns or umbilical pH values. Multiple logistic regression analysis revealed that fetal tachycardia (OR, 11; 95% CI, 1.8 to 67) and lower gestational age (< 34 weeks; OR, 9.4; 95% CI, 0.96 to 93) was associated with CP in intrauterine infection. Nonreassuring FHR patterns were increased in intrauterine infection. CP occurred more frequently and was associated with tachycardia and lower gestational age, but not with FHR deceleration patterns or acidemia, suggesting different pathophysiology from acute hypoxia-ischemia.

Umbilical plasma levels of lipoproteins-cholesterol were measured in 480 normal newborns delivered by spontaneous vaginal delivery at 39 to 40 weeks of gestation. Plasma concentrations of lipids were related to fetal weight, abdominal and head circumference, and ponderal index at birth. Plasma concentration of low-density lipoprotein cholesterol (LDL-C) correlated negatively with abdominal circumference (AC), birth weight, and head circumference of newborns (p < 0.021, p < 0.023, p < 0.044, respectively). The baby with the smallest AC had the highest plasma concentration of LDL-C (p < 0.015). In the 165 neonates with ponderal index < 10th percentile, LDL-C was substantially elevated (p < 0.018). These findings suggest that disproportionate size at birth is associated with altered lipid metabolism. These abnormalities, if they persist, might lead to metabolic diseases in adulthood.

Several methods for detection of fetal components in maternal blood have been reported. However, few have proven clinically useful for determining the treatment in cases of placental injuries. Here, we report a case of extensive intervillous hematoma diagnosed at 25 weeks of gestation with severe intrauterine growth restriction and oligohydramnios. Marked elevation of fetal DNA levels was observed in maternal blood. Fetal DNA levels decreased after 27 weeks of gestation, concurrent with recovery of fetal growth. We conservatively managed this case until 30 weeks of gestation, when a male infant was delivered. He weighed 508 g and displayed Apgar scores of 7 at 1 minute and 9 at 5 minutes. Histological examination of the placenta revealed intervillous thrombosis without infarction or inflammatory changes. In this case, decreasing fetal DNA levels in maternal plasma correlated with recovery of fetal growth and provided useful information for fetal management as well as insight into the pathogenesis of placental injuries.

The use of maternal epidural analgesia in labor may be associated with nonreassuring fetal heart rate (FHR) patterns. Fetal oxygen saturation (FSpO2) monitoring may improve assessment of fetal well-being during this time. Mean FSpO2 values were compared over seven 5-minute epochs: 5 minutes prior to an epidural event (combined insertion of epidural/top-up epidural analgesia and infusion pump bolus), to 30 minutes following the event, including possible effects of maternal position and FHR pattern on FSpO2 values. Mean FSpO2 values were significantly different between the 5 minutes prior (49.5%) versus 16-20 minutes (44.3%, p <0.05), 21-25 minutes (43%, p <0.01), and 26-30 minutes (43.8%, p <0.05) epochs; and 6-10 minutes (48.3%) versus 21-25 minutes (43%, p <0.05) epochs, but were not influenced by FHR pattern or maternal position. There were no differences in mean FSpO2 values following administration of an epidural infusion bolus. We conclude that fetal oxygenation was affected following initial or top-up epidural analgesia and that fetal intrapartum pulse oximetry may be useful in assessing fetal status following these events.