Early changes in serum interleukin-6 levels in extremely premature newborns for detecting fetal inflammation.

BACKGROUND: Fetal inflammatory response syndrome (FIRS) is defined by elevated levels of inflammatory cytokines circulating in fetal blood, which may result in preterm morbidities. Serum interleukin-6 (IL-6) level has been reported to be a good indicator of FIRS; however, changes in IL-6 levels after birth remain to be elucidated. Herein, we characterized early changes in serum IL-6 levels in extremely premature newborns (EPNs, < 28 wks gestation), and then determined the cut-off values for detecting fetal inflammation at each postnatal epoch. METHODS: In this single-center study, 49 EPNs were retrospectively studied. Serum IL-6 measurements are routinely performed at delivery, 1-3, 6-12, and 24-36 h of life. Receiver operating characteristic (ROC) curve analyses were performed for detecting the presence of funisitis, the histologic counterpart of FIRS. RESULTS: Overall, serum IL-6 levels were significantly elevated at 1-3 (298 [31-4719] pg/mL) and 6-12 (29 [2-12,635] pg/mL) hours of life, then returned to at-delivery levels at 24-36 h of life. When comparing serum IL-6 levels at each postnatal epoch, the levels at delivery, 1-3, and 6-12 h of life were significantly higher in the EPNs with funisitis. Serum IL-6 cut-off values at delivery, 1-3, 6-12, and 24-36 h of life for the presence of funisitis were 20, 572, 290, and 13 pg/mL with area under ROCs of 0.75, 0.71, 0.68, and 0.53, respectively. CONCLUSIONS: Serum IL-6 levels in EPNs significantly increase early after birth, then decrease to at-delivery levels by 24-36 h of life. Therefore, postnatal age-dependent cut-off values of serum IL-6 might be considered for detecting fetal inflammation with confirmed funisitis.

Determination and verification of reference intervals of serum immunoglobulin G at birth.

BACKGROUND: To accurately assess hypogammaglobulinemia at birth, it is essential to determine the reference intervals of serum immunoglobulin (IgG) levels in newborns. In the present study, we determined the gestational age (GA)-/birth weight (BW)-dependent percentile-based reference intervals of serum IgG levels and converted them into simple formulas for practical use. METHODS: Serum IgG levels were measured in cord blood from 2902 newborns delivered at 22 to 41 weeks of GA or 264 to 4642 g of BW after exclusion of those with congenital disorders. Linear regression analysis was used to correlate GA and UC-IgG levels and BW and UC-IgG levels. After calculation of the percentile values of UC-IgG levels for each GA or BW, the distributions were approximated by the least-squares method. Fitness was evaluated by the coefficient of determination (R2). RESULTS: Significant positive correlations were found both between GA and UC-IgG levels (rs = 0.790, P < 0.001) and BW and UC-IgG levels (rs = 0.626, P < 0.001). The distribution of the 5%ile of UC-IgG levels (Y) by GA or BW (X) was approximated as a straight line (Y = 37.5 *X - 775.8; Y = 0.161 *X + 95.34, respectively). The fitness was stronger in the GA-derived formula than the BW-derived formula (R2 = 0.973 vs 0.913). CONCLUSIONS: We established GA-/BW-dependent reference percentile-based intervals for serum IgG levels using cord blood from 2902 newborns without congenital disorders. Using GA-dependent reference intervals may be useful for assessing hypogammaglobulinemia at birth.

Corrigendum: Influences of Orogastric and Nasogastric Tubes on Sucking Pressure during Bottle Feeding in Immature Infants.

This corrects the article in Kobe J Med Sci. 2023 May 31; 69(1): E25-E32.

Impact of tracheostomies on the long-term survival of patients with trisomy 13 syndrome.

In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266-1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.

The Association between the First Cry and Clinical Outcomes in CDH Neonates: A Retrospective Study.

Congenital diaphragmatic hernia (CDH) is a life-threatening condition characterized by the herniation of abdominal organs into the thorax, resulting in hypoplastic lungs and pulmonary hypertension. The impact of the first cry, a crucial event for lung transition during birth, on CDH patients remains unclear. This study investigated the impact of the first cry during birth on CDH patient survival, along with other prognosis factors. A multi-institutional retrospective study assessed CDH patient characteristics and survival rates by analyzing factors including the first cry, disease severity, birth weight, Apgar scores, oxygenation index (OI) and surgical closure. Among the CDH patients in the study, a positive first cry was linked to 100% survival, regardless of disease severity (p < 0.001). Notably, the presence of a positive first cry did not significantly affect survival rates in patients with worse prognostic factors, such as low birth weight (<2500 g), high CDH severity, low Apgar scores (1 min ≤ 4), high best OI within 24 h after birth (≥8), or those who underwent patch closure. Furthermore, no significant association was found between the first cry and the use of inhaled nitric oxide (iNO) or extracorporeal membrane oxygenation (ECMO). In conclusion, this study suggests that the first cry may not have a negative impact on the prognosis of CDH patients and could potentially have a positive effect.

Influences of Orogastric and Nasogastric Tubes on Sucking Pressure during Bottle Feeding in Immature Infants.

Orogastric (OG) and nasogastric (NG) tubes have been reported to delay breastfeeding initiation and affect respiratory function. However, the effects of feeding tubes on sucking pressure have not been well studied. Fourteen preterm infants were enrolled in this study, and their sucking pressures during bottle feeding with an OG tube, NG tube, and without any tube were measured. Sucking pressure significantly increased after changing the OG tube to an NG tube (p = 0.044). However, sucking pressure showed no significant differences after changing the feeding method from an NG tube to oral intake. Thus, NG tubes are superior to OG tubes in terms of sucking pressure.

Sustained lower bilirubin-binding affinity of albumin in extremely preterm infants.

BACKGROUND: Elevated albumin-free or unbound bilirubin (UB) levels beyond the first week of life have been associated with the development of bilirubin encephalopathy in preterm infants. However, the mechanism(s) that induces this prolonged unbound bilirubinemia has remained unknown. We hypothesized that it may due to a sustained lower bilirubin-binding affinity of albumin in extremely premature infants. METHODS: Twenty-two very preterm infants born at 28-31 weeks' gestational age (GA) (VPT Group) and 21 extremely preterm infants born at 22-27 weeks' GA (EPT Group) were retrospectively studied. On days 14, 21, and 28, bilirubin-binding affinity of albumin was assessed by calculating of the UB/total bilirubin ratio, bilirubin-albumin molar ratio (BAMR), and binding affinity (Ka). RESULTS: On days 14, 21, and 28, significantly higher UB/total bilirubin ratios were found in the EPT than in the VPT Group. Although BAMRs were comparable, significantly lower Ka values on days 14, 21, and 28 were observed in the EPT than those in the VPT Group (56.1 vs. 70.9 L/µmol, p < 0.001; 55.2 vs. 74.7 L/µmol, p < 0.001; 53.0 vs. 86.5 L/µmol, p < 0.001, respectively). CONCLUSIONS: EPT infants have a sustained lower bilirubin-binding affinity of albumin beyond the first week of life. IMPACT: Bilirubin encephalopathy is still reported in extremely preterm (EPT) infants. EPT infants often have prolonged unbound bilirubinemia beyond the first week of life. Sustained lower bilirubin-binding affinity of albumin, regardless of the bilirubin-albumin molar ratio (BAMR), is observed in EPT infants. BAMRs should not be used as a surrogate marker of unbound bilirubinemia, especially in EPT infants at a later postnatal period.

Decreased moderate admission hypothermia in extremely preterm newborns.

BACKGROUND: Admission temperature is inversely correlated with mortality and morbidity risk in extremely preterm newborns (EPNs). As almost all EPNs require advanced resuscitation at birth, we improved a simple and comprehensive management protocol to reduce admission hypothermia. This study reports the changes over the past 15 years in the rate of admission hypothermia in all EPNs. It clarified the distribution of admission temperature and the risk factors for developing admission hypothermia in recent EPNs. METHODS: This single-center study retrospectively analyzed the EPNs delivered at our institution between January 2006 and December 2020. The comprehensive management protocol, including warming equipment, plastic wrapping, aluminum-polyethylene sheet, and room temperature, was applied to avoid heat loss during resuscitation. On admission, the rectal temperature was measured and defined as moderate (32.0-35.9 °C) or mild (36.0-36.4 °C) hypothermia. RESULTS: Overall (n = 432), the rate of admission with moderate hypothermia decreased from 48% in 2006 to 8% in 2020. In the recent evaluation of 80 EPNs delivered in 2017-2020, 10 (13%) and 26 (33%) had moderate and mild hypothermia on admission, respectively. Extremely preterm newborns with moderate-to-mild hypothermia had a significantly smaller gestational age and lower birthweight than those without hypothermia. No significant differences in the other perinatal and environmental risk factors were observed between EPNs with and without hypothermia. CONCLUSIONS: Our comprehensive management protocol reduced the rate of moderate hypothermia on admission in EPNs to only 13%. However, eliminating mild hypothermia remains a challenge and requires continuous improvement, especially in smaller EPNs.

Gestational Age-Dependent Reference Ranges for Albumin Levels in Cord Serum.

BACKGROUND: To diagnose hypoalbuminemia in newborns, it is essential to establish a definition applicable to those with a different gestational age (GA) and clinical conditions. A positive correlation between serum albumin levels and GA has been reported, but the study was limited to small numbers of newborns. We therefore investigated the GA-dependent reference ranges for serum albumin levels using cord venous blood (UC-Alb levels) from a large number of newborns delivered at a tertiary perinatal center. METHODS: Albumin levels were assessed in 2,917 newborns at 22-41 weeks of GA after exclusion of those with congenital disorders. Linear regression analysis was used to correlate GA and UC-Alb levels. After calculation of the percentile values of UC-Alb levels for each week of GA, the distributions were approximated by the least-squares method. To validate the determined linear approximation of the 5%ile value, the UC-Alb levels in newborns with hydrops fetalis and gastroschisis were used. RESULTS: A significant positive correlation between GA and UC-Alb levels was found (rs = 0.701, p < 0.001, respectively). The distribution of the 5%ile of UC-Alb levels (Y) by GA (X) was approximated as a straight line (Y = 0.062 × X + 0.326, R2 = 0.951). Among the 59 and 18 newborns with hydrops fetalis and gastroschisis, 51 (86.4%) and 15 (83.3%), respectively, were below the line. CONCLUSIONS: We established GA-dependent reference ranges for serum albumin levels, which may be useful to accurately diagnose hypoalbuminemia in newborns.