Do small for gestational age infants have less severe neonatal abstinence syndrome?

BACKGROUND: Small for gestational age (SGA) infants are likely to have decreased placental transfer of opioids and other substances and lower amounts of fat deposition, hence less severe neonatal abstinence syndrome (NAS). The goal of this study is to correlate SGA status and severity of NAS in infants admitted to the neonatal intensive care unit (NICU). METHODS: This is a retrospective analysis of term and late-preterm infants (≥35 weeks gestation) exposed to in-utero substances, born between September 2006 and May 2021, and admitted to an inner-city NICU for medical therapy for NAS. Indicators of the severity of NAS (duration of medical treatment, duration of hospitalization, use of phenobarbital, and use of clonidine) were compared between infants characterized as SGA (birth weight <10th percentile for gestational age) to those not categorized as SGA (non-SGA). RESULTS: A total of 992 infants met the study criteria; 205 (20.7%) in the SGA group and 787 (79.3%) in the non-SGA group. The median duration of medical treatment was significantly lower in infants in the SGA group (22 days vs. 26 days, p = 0.04) and they were less likely to be treated with phenobarbital (19% vs. 26.8%, p = 0.02). CONCLUSION: SGA infants displayed less severe NAS symptoms as indicated by shorter a duration of medical treatment and decreased need for phenobarbital. Our findings may impact decisions around identifying the optimum treatment protocols catered to SGA infants with NAS.

Management of well appearing infants born to afebrile mothers with inadequate GBS prophylaxis: A retrospective comparison of the three approaches recommended by the COFN.

BACKGROUND: There are three different approaches set forth by the Committee on the Fetus and Newborn (COFN) for managing asymptomatic neonates born to mothers with inadequate intrapartum antibiotic prophylaxis (IAP) for early-onset Group B Strep (GBS) infection. The first approach is that of categorical risk factor assessments, and recommends that asymptomatic infants born to afebrile mothers with inadequate IAP for GBS be monitored with clinical observation for 36-48 hours. The second approach recommends serial physical examinations and vital signs for 36-48 hours to closely monitor changes in clinical condition for all patients. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, a multivariate risk assessment, and it takes into consideration several perinatal risk factors. This multivariate risk assessment then provides recommendations for reassessment and management based on presume risk of the infant developing or having Early Onset Sepsis (EOS). The aim of our study was to compare these three recently published recommendations from the COFN for the management of asymptomatic neonates born to afebrile mothers with inadequate IAP for GBS. STUDY DESIGN: This is a retrospective study of asymptomatic neonates with gestational age ≥35 weeks born to afebrile mothers with indicated inadequate IAP for GBS between April 2017 and July 2020. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition. RESULTS: A total of 7,396 infants were born during the study period, 394 (5.3%. to mothers with inadequate IAP. Recommendations for these infants according to both the categorical risk factor guideline and the clinical condition guideline include extended, close observation. However, the SRC recommended routine newborn care for 99.7%.f these infants. None of the infants developed EOS. CONCLUSION: The SRC recommend routine neonatal care without enhanced and prolonged observation for nearly all asymptomatic infants born to afebrile mothers with inadequate IAP. As none of the infants in this cohort had EOS, further studies in a larger cohort are needed to establish the safety of SRC in neonates born to mothers with inadequate IAP.

Management of infants born to mothers with chorioamnionitis: A retrospective comparison of the three approaches recommended by the committee on fetus and newborn.

BACKGROUND: Based on the most recently published recommendations from the Committee on the Fetus and Newborn (COFN), three approaches currently exist for the use of risk factors to identify infants who are at increased risk of early-onset sepsis (EOS). Categorical risk factor assessments recommend laboratory testing and empiric antibiotic therapy for all infants born to mothers with a clinical diagnosis of chorioamnionitis. Risk assessments based on clinical condition recommend frequent examinations and close vital sign monitoring for infants born to mothers with chorioamnionitis. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, multivariate risk assessments. The aim of our study was to compare the three risk stratification approaches recommended by the COFN for management of chorioamnionitis-exposed infants. METHODS: Retrospective study of 1,521 infants born ≥35 weeks to mothers with chorioamnionitis. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition (CCA). RESULTS: Hypothetical application of SRC and CCA resulted in 79.6% and 76.8-85.1% respectively fewer infants allocated empiric antibiotic therapy. While CCA recommended enhanced observation for all chorioamnionitis-exposed infants, SRC recommended routine care without enhanced observation in 44.3% infants. For the six infants (0.39%) with EOS, SRC and CCA recommended empiric antibiotics only for three symptomatic infants. CONCLUSION: The SRC and CCA can reduce antibiotic use but potentially delay antibiotic treatment. The SRC does not recommend enhanced observation with frequent and prolonged vital signs for >44% of chorioamnionitis-exposed infants.

Utility of measuring direct bilirubin at first 72 h of age in neonates admitted to the neonatal intensive care unit.

OBJECTIVE: To assess the utility of measuring direct bilirubin (DB) during the first 72 h of life in infants admitted to the neonatal intensive care unit (NICU). STUDY DESIGN: Infants born between May 2006 and June 2013, and admitted to the NICU were included. Abnormal DB was defined as: DB level⩾1 mg dl-1 with a corresponding TB of ⩽5 mg dl-1 or DB level >20% of the corresponding TB>5 mg dl-1. RESULTS: The DB levels were measured in 3715 infants during the first 72 h of life. Sixty-three infants (1.7%) had abnormal DB. In a number of infants with potentially treatable diseases (biliary atresia and choledochal cyst), the only abnormal finding was a mildly elevated DB (1 to 2 mg dl-1) during the first 3 days of life. In 22 infants (35%), the cause for high DB was unknown (16%) or not investigated (19%). CONCLUSIONS: Routine measurement of DB in neonates admitted to NICU may be helpful in identifying potentially treatable causes of cholestasis.

Limb hypoplasia resulting from intrauterine infection with herpes simplex virus: a case report.

Intrauterine infection with herpes simplex virus, although very rare, has devastating effects on multiple organ systems in the fetus and can lead to in utero fetal demise. Neonates born following intrauterine herpes simplex virus infection commonly manifest with cutaneous lesions, ocular damage and/or brain abnormalities. We describe the case of a dichorionic, diamniotic twin gestation complicated by intrauterine herpes simplex virus infection. This infection led to the fetal demise of twin A and a very uncommon presentation of limb hypoplasia in twin B.

H-Y antibody titers are increased in unexplained secondary recurrent miscarriage patients and associated with low male : female ratio in subsequent live births.

BACKGROUND: The birth of a boy is significantly more common than a girl prior to secondary recurrent miscarriage (SRM) and is associated with a poorer chance of a subsequent live birth. Children born after SRM are more likely to be girls. High-titer antisera specific for male antigens (H-Y) have been shown to arrest development of male bovine embryos efficiently. We consequently questioned the role of H-Y antibodies in women with SRM. METHODS: Serum samples from patients with unexplained SRM (n = 84), unexplained primary recurrent miscarriage (PRM) (n = 12) and healthy women (n = 37) were obtained. The samples were taken during pregnancy (gestational weeks 4-5) for 77 (80%) of the patients. Enzyme-linked immunosorbent assay was used to detect immunoglobulin G antibodies that specifically recognized any of the five recombinant H-Y proteins (EIF1AY, RPS4Y1, ZFY, DDX3Y and UTY) and their H-X homologs. RESULTS: H-Y-specific antibodies were more frequent in SRM patients (46%) compared with female controls (19%, P = 0.004) and PRM patients (8%, P = 0.01). The presence of H-Y antibodies in early pregnancy was associated with a low male: female birth ratio among the subsequent live births, as only 12% of children born to H-Y antibody-positive patients were boys compared with 44% boys born to H-Y antibody negative patients (P = 0.03). CONCLUSIONS: The high frequency of H-Y antibody-positive SRM patients and the association between the presence of these antibodies in early pregnancy and the low number of male offspring, suggest that maternal immune responses against H-Y antigens can cause pregnancy losses. Further exploring these mechanisms may increase our understanding of unexplained SRM.

High-mobility group box-1 protein in tracheal aspirates from premature infants: relationship with bronchopulmonary dysplasia and steroid therapy.

OBJECTIVE: High-mobility group box-1 (HMGB1) is a potent inflammatory mediator and contributes to acute lung injury in adults. The role of HMGB1 in neonatal lung injury and the development of bronchopulmonary dysplasia (BPD) is unknown. We studied the association between HMGB1 levels in tracheal aspirates (TAs) and adverse outcomes (BPD/death) in ventilated premature infants (VPIs) and modulation of HMGB1 levels with dexamethasone (Dex) use. STUDY DESIGN: Infants born before 32 weeks gestation and requiring mechanical ventilation were enrolled. Serial TA samples were collected on days 1, 3, 5 and 7 and HMGB1 levels were measured. HMGB1 levels in TA samples were compared between infants with no BPD and infants who developed BPD or died. HMGB1 TA levels were also compared before and after using Dex. RESULT: In all, 24 infants (gestational age 26.4+/-1.9 weeks, birth weight 859+/-200 g) had no BPD, 60 infants (gestational age 25.4+/-1.8 weeks, birth weight 749+/-156 g) developed BPD or died before 36 weeks postmenstrual age. Mean HMGB1 level in first week of life was significantly lower in infants with no BPD (27.3+/-16.5 ng mg(-1)) compared with those who developed BPD or died (45.1+/-30.9 ng mg(-1), P=0.004). In total, 29 VPIs received Dex. There was no significant change in HMGB1 levels with steroid therapy (before 47.0+/-43.9, after 60.1.5+/-58.8, P=0.3). CONCLUSION: Our data suggest that higher HMGB1 levels in TA are associated with the development of BPD or death in VPI. Dex use had no effect on HMGB1 levels.

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone.

OBJECTIVES: To study the association between angiopoietin 2 (Ang2) concentrations in tracheal aspirates (TAs) and adverse outcome (bronchopulmonary dysplasia (BPD)/death) in ventilated premature infants (VPIs) and modulation of Ang2 concentrations with dexamethasone (Dex) use. STUDY DESIGN: Serial TA samples were collected on days 1, 3, 5 and 7, and Ang2 concentrations were measured. Ang2 TA concentrations were compared prior to and after 48 to 72 h of using Dex. RESULT: A total of 151 TA samples were collected from 60 VPIs. BPD was defined as the oxygen requirement at 36 weeks postmenstrual age (PMA). Twelve infants (mean+/-s.d.) (gestational age (GA) 26.5+/-2.1 weeks, birth weight (BW) 913+/-230 g) had no BPD, 32 infants (GA 25.8+/-1.4 weeks, BW 768+/-157 g) developed BPD and 16 infants (GA 24.5+/-1.1 weeks, BW 710+/-143 g) died before 36 weeks PMA. Ang2 concentrations were significantly lower in infants with no BPD (median, 25th and 75th percentile) (157, 16 and 218 pg mg(-1)) compared with those who developed BPD (234, 138 and 338 pg mg(-1), P=0.03) or BPD and/or death (234, 157 and 347 pg mg(-1), P=0.017), in the first week of life. Twenty-six VPIs (BW 719+/-136 g, GA 25.1+/-1.3 weeks) received 27 courses of Dex. Ang2 concentrations before starting Dex were 202, 137 and 278 pg mg(-1) and significantly decreased to 144, 0 and 224 pg mg(-1) after therapy (P=0.007). CONCLUSIONS: Higher Ang2 concentrations in TAs are associated with the development of BPD or death in VPIs. Dex use suppressed Ang2 concentrations.

Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis.

BACKGROUND: Extremely low birth weight (ELBW) infants are at increased risk for invasive candidiasis and associated morbidity and mortality. The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians. OBJECTIVES: To evaluate the effectiveness and safety of fluconazole prophylaxis in ELBW infants. STUDY DESIGN: ELBW infants (BW

Work of breathing using high-flow nasal cannula in preterm infants.

OBJECTIVE: To compare the work of breathing (WOB) in premature neonates supported with high-flow nasal cannula (HFNC) and nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: Eighteen preterm neonates <2.0 kg on HFNC or NCPAP support were studied in a random order. A ventilator was used to deliver 6 cm H2O of NCPAP with nasal prongs. High-flow nasal cannula delivered with Vapotherm (VAPO) at 3, 4 and 5 l/min was used. Tidal ventilation was obtained using respiratory inductance plethysmography calibrated with face-mask pneumotachography. An esophageal balloon estimated pleural pressure from which changes in end distending pressure were calculated. Inspiratory, elastic and resistive WOB and respiratory parameters were calculated. RESULTS: No differences were found in the WOB for all settings. Changes in end distending pressure did not vary significantly over all device settings except VAPO at 5 l/min. CONCLUSION: In these preterm infants with mild respiratory illness, HFNC provided support comparable to NCPAP.

Respiratory burst activity in bronchopulmonary dysplasia and changes with dexamethasone.

The first objective of this study was to evaluate longitudinal changes in respiratory burst activity in circulating neutrophils and monocytes in infants of less than 30 weeks of gestation with respiratory distress syndrome (RDS), and to examine differences in neonates who subsequently developed bronchopulmonary dysplasia (BPD) compared with those neonates who did not. The second objective was to investigate the effects of dexamethasone on respiratory burst activity in neutrophils and monocytes. We measured burst activity on neutrophils and monocytes in fresh heparinized blood in response to E. coli, N-formyl-met-leu-phe (fMLP), and phorbol 12-myristate 13-acetate stimulation on days 3, 7, 14, and 21 of life, before and 2-3 days after initiating a 6-day course of dexamethasone treatment. Infants with RDS participating in the study were followed until discharge, and were classified as non-BPD and either 1) BPD d28, reflecting their oxygen requirement at day of life 28, or 2) BPD 36 weeks, reflecting oxygen dependence at 36 weeks' corrected gestational age. The diagnosis of BPD was supported by radiological changes of BPD. The percentage of activated neutrophils producing a respiratory burst increased in all premature infants with increasing postnatal days during the first 28 days of life, when the physiological stimulus E. coli was used as an activator (P < 0.02). There was no significant difference in respiratory burst activity measured either as percent activation or as mean fluorescence intensity between non-BPD and BPD infants after adjusting for the difference in weight and gestational age between the two groups. The treatment of premature infants with dexamethasone was associated with decreased activation of neutrophils (P < 0.005) when E. coli was used as a stimulus. In conclusion, a significant increase in neutrophil respiratory burst activity occurs during the first month of life in very low birth weight infants. Greater pulmonary damage in BPD cannot be attributed to reduced burst activity in either neutrophils or monocytes. Dexamethasone treatment was associated with decreased neutrophil respiratory burst activity.

Stimulation of immune-competent cells in vitro by human cardiac valve-derived endothelial cells.

Both fresh and cryopreserved human cardiac valve allografts are transplanted without matching donor and recipient for blood group or human leukocyte antigens (HLA) and without the usual immunosuppressive therapy that follows organ transplantation. Calcification occurs in almost all transplanted valves, and in children acute valve failure is frequently seen. We hypothesized that failure of the human valve allografts could have an immunologic basis. This hypothesis was tested in a functional way by performing lymphocyte stimulation assays using fresh and cryopreserved valve pieces and endothelial cells derived from valve leaflets as stimulator. Human peripheral blood lymphocytes, both matched and mismatched for HLA antigens, were used as responder cells. The results were expressed as the stimulation index. Fresh valve pieces induced a significantly higher stimulation index (median, 9; range, 4 to 117) compared with the cryopreserved pieces (median, 2; range, 0 to 9; p = 0.002 by Wilcoxon test). The stimulation index was significantly reduced when lymphocytes matched for HLA-DR with the valve pieces were used (median, 1; range, 0 to 5) as compared with the HLA-DR-mismatched combination (median, 4; range, 2 to 117; p = 0.006, Wilcoxon test). Valve leaflet-derived endothelial cells were able to induce a median stimulation index of 8 (range, 3 to 15) when incubated with lymphocytes mismatched for HLA-A, -B, and -DR. In conclusion, stimulation of immune-competent cells in vitro is induced by both fresh and cryopreserved human valve pieces and by endothelial cells derived from fresh valve leaflets. The immune response can be reduced by using cryopreserved valves or by matching valve donor and responder lymphocytes for HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)

Cracks in cryopreserved aortic allografts and rapid thawing.

Cryopreserved aortic allografts are shipped in a frozen state. Cracks in the graft, appearing after thawing, can pose serious problems in the planned operative procedures. Cracks were encountered in approximately 3% of all our shipped cryopreserved human material and were strongly associated with transportation in a "dry shipper." We practice two other modes of transport: on dry ice and directly to our operating room. We studied the temperature behavior during thawing of 17 porcine aortic valves in three groups. The valves were frozen and stored like our human valves. Before thawing, they were subjected to stimulated transport in either a dry shipper, on dry ice, or to the operating room. Differences between the groups were noted in the maximal rate of thawing of the inner as well as the outer wall. The highest maximal thawing rates were observed in the dry shipper group, in which 66% of the valves cracked. We therefore suspended transportation of cryopreserved human valves by means of a dry shipper.

Different endothelin receptors involved in endothelin-1- and sarafotoxin S6B-induced contractions of the human isolated coronary artery.

1. Endothelin receptors, that mediate contraction of the human isolated coronary artery, were characterized by use of a number of agonists and antagonists. Contraction induced by the non-selective agonists, endothelin (ET)-1 and sarafotoxin S6b, was compared in endothelium-intact and endothelium-denuded ring segments. The effects of ET-1 and BQ-123 (an ETA receptor antagonist) were investigated both in ring segments and in spirally cut strips. Lastly, the effect of phosphoramidon was studied on contraction induced by big-ET-1. 2. The order of agonist potency (pD2) in endothelium-intact coronary artery ring segments was: ET-1 (8.27) approximately sarafotoxin S6b (8.16) > big-ET-1 (< 7.1) approximately ET-3 (< 6.9). [Ala1,3,11,15]ET-1 (ETB receptor agonist) caused significant contraction only at 1 microM, whereas 0.3 microM big-ET-3 had no effect. Removal of the endothelium in ring segments did not affect the contractile response to ET-1 or to sarafotoxin S6b. 3. After a full concentration-response curve had been obtained to ET-1 or sarafotoxin S6b, further contractions of the endothelium-intact coronary artery segments could only be achieved by applying ET-1 in segments exposed to sarafotoxin S6b, and not the reverse. 4. BQ-123 (0.1 microM) antagonized contractions of endothelium-intact ring segments induced by sarafotoxin S6b (pKB 7.86). Only 10 microM BQ-123 antagonized contractions induced by ET-1 (pKB 5.75). FR139317 was also more potent against sarafotoxin S6b (pKB 8.24-8.47) than against ET-1 (pKB 6.11). [Ala1,3,11,15]ET-1 (1 microM) had no effect on the contractile response to ET-1 or to sarafotoxin S6b. 5. In strip preparations with intact endothelium, the pD2 of ET-l increased to 9.04 =/- 0.16 (vs.8.50 +/- 0.07 in rings), and BQ-123 (1 microM) caused a rightward shift of the ET-l induced concentration response curve (pKB 6.62 vs. 5.75 in rings).6. Contractile responses to big-ET-1 of endothelium-intact coronary artery segments were attenuated in the presence of phosphoramidon (100 microM), indicating conversion of big-ET-1 to ET-1 within the coronary artery segment.7. The present study indicates that ET-1 and sarafotoxin S6b contract the human isolated coronary artery via different receptors, which can probably be best characterized as subtypes of the ETA receptor.Furthermore, it is demonstrated that the type of preparation (ring or strip) may affect the potency of ET-1 as an agonist and of BQ-123 as an antagonist.

Kidney transplantation in rhesus monkeys. Matching for D/DR antigens, pretransplant blood transfusions, and immunological monitoring before transplantation.

The effect of matching for D/DR antigens and of three pretransplant blood transfusions on kidney allograft survival was investigated in unrelated rhesus monkeys treated with standard immunosuppression. A control group consisting of host-donor combinations mismatched for one or two DR antigens (mixed lymphocyte culture (MLC) positive) and not receiving transfusions showed a MST of 13 +/- 1.2 days with a range from 9 to 22 days. The administration of pretransplant blood transfusions led to a MST of 28 +/- 5.4 days with 5 of 12 animals showing survival times of more than 22 days (i.e., a bimodal distribution of survival times). Recipients matched with their donors for two DR antigens and given transfusions showed an even better MST of 39 +/- 4.0 days. Under these conditions, MLC-negative combinations fared slightly better than MLC-positive ones: only 1 of 10 animals showed a survival time of less than 22 days and kidney function in the first weeks after transplantation was significantly better. When mixed lymphocyte reactions (MLC reactivity) between host and donor before and after the transfusions were compared, it was possible to predict to some extent the eventual fate of an allograft: increased mixed lymphocyte reaction predicted relatively short survival times, decreased mixed lymphocyte reaction relatively long ones (P less than 0.01).

Influence of prophylactic treatment with gamma-immunoglobulins on renal function after kidney transplantation in rhesus monkeys.

The effect of prophylactic i.v. administration of high doses of human gamma-immunoglobulin (IgG) on kidney graft survival was investigated in rhesus monkeys treated with azathioprine and prednisolone. In nontransfused recipients not treated with IgG (controls), graft survival ranged from 9 to 22 days; if nontreated animals had been given three pretransplant blood transfusions, graft survival ranged from 9 to 61 days with 42% of the animals showing a prolonged survival time (greater than 22 days). However, in both transfused and nontransfused recipients, the additional pretransplant administration of IgG appeared to have an adverse effect: about 25% of the animals showed accelerated rejection. In addition, serum creatinine levels in IgG-treated recipients were significantly higher on the 3rd day after transplantation than in non-treated monkeys. We concluded that renal transplant patients should be treated with IgG for protection against life-threatening infections only if they have good kidney function.

Histocompatibility antigens (HLA) in multiple sclerosis in Iran.

Thirty-five patients (19 male and 16 female) with clinically definite multiple sclerosis and 100 healthy control subjects were studied for the A and B locus of the HLA system. A significant increase of HLA A3 and A11 of the A locus and B7 of the B locus was observed in patients with multiple sclerosis compared with controls. An increase of antigen A3 was also observed in eight cases of probable multiple sclerosis. A significant increase of both A3 and B7 was observed in patients with multiple sclerosis.