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Simultaneous use of intrapartum fetal pulse oximetry and amnioinfusion in meconium stained amniotic fluid.

OBJECTIVE: Fetal pulse oximetry is a minimally invasive, simple technique which continuously helps to reflect in utero well-being. The presence of meconium in the amniotic fluid may be a clinical sign of fetal hypoxaemia. Amnioinfusion has a beneficial effect on the incidence of meconium aspiration syndrome (MAS), and the presence of meconium below the level of the vocal cords. STUDY DESIGN: We studied the impact of amnioinfusion combined with fetal pulse oximetry on the incidence of meconium aspiration syndrome and operative delivery. RESULTS: The retrospective analysis revealed that the presence of meconium below the level of vocal cords was significantly reduced. The frequency of cesarean section is decreased, however, it did not reach statistical significance. CONCLUSION: Fetal pulse oximetry may be used in combination with amnioinfusion and cardiotocography (CTG) to reduce the risk of meconium aspiration syndrome and the number of instrumental deliveries and improve perinatal outcome.

Adolescent↗

Predictive value of pulse oximetry and fetal scalp blood pH in the case of meconium-stained amniotic fluid.

OBJECTIVE: To compare the predictive value of intrapartum fetal pulse oximetry to that of fetal scalp blood pH for an abnormal neonatal outcome in the case of thick meconium. STUDY DESIGN: A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was monitored using a Nellcor N-400 fetal pulse oximeter in case of abnormal FHR. The last readings of fetal oxygen saturation and fetal scalp blood pH before birth were used to assess the ability of both techniques to predict an abnormal neonatal status. RESULTS: At a 30% cutoff, the negative predictive value of fetal oxygen saturation was not altered in case of meconium when compared to clear amniotic fluid (79 and 83%, respectively). Fetal scalp blood pH at a 7.20 threshold had a poor negative predictive value in case of meconium when compared to clear amniotic fluid (56% versus 88%, respectively). The receiver operator characteristic curve showed similar performance of fetal scalp blood pH and pulse oximetry in cases with clear amniotic fluid. In cases with meconium, the performance of fetal scalp blood pH was poor, whereas that of pulse oximetry remained unchanged. In three cases with meconium below the vocal cords, a drop in fetal oxygen saturation was observed during labor whereas fetal scalp blood pH remained within normal values. CONCLUSION: The predictive value of fetal scalp blood pH is poor in case of meconium, whereas the predictive value of pulse oximetry seems to be unchanged in this situation.

Amniotic Fluid↗

[Inhibition of meconium induced activation of granulocytes from neonates and adults by pentoxyphylline].

BACKGROUND: Neutrophil activation plays a crucial role in the pathogenesis of the meconium aspiration syndrome. Therefore antiinflammatory strategies may offer therapeutic options. The methylxanthinderivative pentoxyphylline (PTX) is known to inhibit the tumor necrosis factor alpha-synthesis and neutrophil degranulation and thus may have beneficial effects on meconium-induced pulmonary inflammation. Effects of PTX on PMN-degranulation in neonatal whole blood have not yet been studied. PATIENTS AND METHODS: Heparin-anticoagulated (3 IE/ml) whole blood of healthy neonates (n = 6) and adult volunteers (n = 6) was incubated for 45 min. Spontaneous PMN-degranulation was compared with meconium-induced (3 mg/ml) and PTX-inhibited (0,025 - 0,4 mg/ml) degranulation by means of elastase (EL) and lactoferrin (LF) release from azurophilic and specific granules. EL- and LF plasma concentration was measured by immunoluminometric methods. RESULTS: Spontaneous degranulation of neonatal PMN was found to be significantly increased after 15 minutes compared with cells from adults (EL and LF concentration: 674 and 660 ng/10 6 PMN vs. 284 and 261 ng/10 6 PMN). At 45 minutes adult PMN showed an acceleration of degranulation in contrast to neonatal cells (EL and LF: 1827 and 1232 ng/10 6 PMN vs. 1400 and 860 ng/10 6 PMN). In presence of PTX (0,4 mg/ml) spontaneous release of EL and LF from neonatal PMN was inhibited by nearly 70 % at 45 min. while degranulation from adult PMN was found to be completely inhibited at 15 min. and reduced by 82 % and 78 % at 45 min. In presence of meconium (3 mg/ml) an increased degranulation of EL from PMN of both neonates and adults (317 % and 170 %) could be observed while LF release was found to be increased from neonatal cells only (267 % and 113 % respectively). PTX inhibited meconium-induced EL release in blood of bath neonates and adults by 63 % and 66 %, while LF release was inhibited by 72 % and 57 % respectively. CONCLUSION: Neonatal PMN exhibit an increased degranulation from azurophilic and specific granules compared with cells from adults. PTX was found to be an effective inhibitor of spontaneous and meconium induced PMN degranulation and may offer new therapeutic options.

Adult↗

Surfactant inhibition in experimental meconium aspiration.

Human meconium components were separated into a water-methanol soluble phase containing mainly proteins and bilirubin and a chloroform soluble phase containing free fatty acids, triglycerides and cholesterol. Various amounts of original meconium, the water-methanol soluble fraction or the chloroform soluble fraction were added to standard suspensions of porcine surfactant (Curosurf). In a pulsating-bubble or Wilhelmy-balance system, meconium and its subfractions inhibited surfactant activity, but the chloroform soluble fraction had the highest specific inhibitory activity. Original meconium in saline (130 or 65 mg/ml) was instilled into the airways of ventilated near-term newborn rabbits (dose 6 ml/kg). Lung-thorax compliance was reduced by 38% in animals aspirating the higher dose and by 27% in the low-dose group. Histological sections showed intra-alveolar accumulation of fine meconium particles in experimental animals, but no plugging of larger airways. We conclude that respiratory failure from meconium aspiration may be mediated, in part, by inactivation of surfactant.

Adsorption↗

Pulmonary inflammation associated with aspirated meconium and epithelial cells in calves.

"Meconium aspiration syndrome" is a condition resulting in respiratory distress and the occasional death of newborn human beings. A retrospective study was conducted on 52 calves that were submitted for postmortem examination to the Atlantic Veterinary College, Charlottetown, Prince Edward Island, Canada. These calves died of infectious and noninfectious diseases within the first 2 weeks of life due to a variety of causes. The most common cause of death was infectious enteric disease. Histologic examination of lungs revealed that 42.5% of calves had evidence of meconium, squamous cells, or keratin in the lung. There was considerable variation in the magnitude of histologic changes in lungs containing aspirated material. Typically, affected lungs had only a few inconspicuous pieces of meconium, keratin, and squamous cells within bronchoalveolar spaces. Sporadically, the entire lumen of airways was obliterated by aspirated material. Lungs with aspirated material had a mild but diffuse alveolitis characterized by exudation of a few neutrophils, macrophages, and occasional multinucleated giant cells. Obstruction of small airways and focal atelectasis were also observed. Similar lesions have been reported in human meconium aspiration syndrome. It is concluded that histologic changes similar to those of human meconium aspiration syndrome occur commonly in calves that die within 2 weeks of birth. Further studies involving healthy age-matched calves are required to evaluate the clinicopathologic significance of meconium aspiration in this species.

Animals↗

Promoting meconium clearance from the lungs of the neonatal piglet with asymmetric high frequency oscillation.

To investigate the role of high frequency oscillation (HFO) in promoting meconium clearance from the airway, we used a commercially available ventilator configured with maximal expiratory flow exceeding inspiratory flow (asymmetric HFO or AHFO). We hypothesized that AHFO would move meconium in an expiratory direction (toward the ventilator). We first tested our hypothesis in vitro and, later, in vivo using the neonatal piglet. In vitro experiments using a Plexiglas airway confirmed meconium movement in an expiratory direction when bias ratio was > or = 2. For in vivo experiments, each piglet received a 3 mL/kg intratracheal bolus of a 44 g/100 mL meconium mixture followed by 45 min of mechanical ventilation. Then, in part 1, the piglet was placed in a 15 degree head down tilt position and randomized to either AHFO [ratio of inspiratory time/expiratory time (I:E) of 70:30] or HFO (I:E ratio of 30:70). After 30 min of either AHFO or HFO, the piglet was crossed over to the alternate strategy for an additional 30 min. For part 2, we maintained the piglet on either AHFO or HFO continuously for 4 h. Results demonstrate that, although there was a tendency for larger volumes of meconium to be aspirated from the airway during AHFO in part 1 experiments, there was no difference found in part 2. We also found no significant differences in blood gases or hemodynamic measurements between AHFO and HFO during the prolonged observation period in part 2 of our study. We conclude that AHFO is of no benefit in the treatment of meconium aspiration syndrome.

Animals↗

Meconium is a potent activator of complement in human serum and in piglets.

Meconium aspiration syndrome (MAS) is a clinical condition in the newborn infant with a significant morbidity and mortality. The complex pathophysiology of MAS, leading to both pulmonary and systemic complications, is characterized by an incompletely understood inflammatory reaction. Treatment is symptomatic, mainly limited to airway cleaning and ventilatory support. In this study, we show for the first time that meconium is a potent activator of complement, a key mediator of inflammation. In vitro, meconium activated the alternative complement pathway in human umbilical cord serum as judged by a substantial increase in the alternative pathway convertase C3bBbP. The activation proceeded through C3 (C3bc) and the terminal C5-9 pathway (terminal SC5b-9 complement complex), whereas the classical and lectin pathways were not activated (C1rs-C1-inhibitor complexes and C4bc). The lipid fraction, containing, e.g. free fatty acids, and the water fraction, containing, e.g. bile acids, contributed equally to the complement activation. A blocking antibody to factor D (alternative pathway) completely inhibited the meconium-induced complement activation, whereas blocking antibodies to mannose-binding lectin (lectin pathway) and C2 (classical and lectin pathway) had no effect. In vivo, meconium induced systemic complement activation in a piglet model of MAS, paralleling the increase in lung dysfunction. In conclusion, meconium is a potent activator of the complement system both in vitro and in vivo. Complement may be important in the pathogenesis of MAS, and specific complement inhibition might be a possible treatment approach in MAS.

Age Factors↗

Hyaluronan reduces surfactant inhibition and improves rat lung function after meconium injury.

Hyaluronan (HA), an ionic polymer, is normally present in the alveolar subphase and is known to decrease lung surfactant inactivation caused by serum in vitro. In this study, we examined whether HA can ameliorate the inactivating effects of meconium in vitro and in vivo. Surface activities of various mixtures of Survanta, HA, and meconium were measured using a modified pulsating bubble surfactometer. With meconium, almost all surface activity measures were improved by the addition of HA of several molecular weights at a concentration of 0.25%. Anesthetized, paralyzed rats were maintained on positive-pressure ventilation. After lung injury by instillation of meconium, they were treated with Survanta, Survanta with HA, or control mixtures. Serial measures of blood gases and peak inspiratory pressure were recorded for the duration of the experiment. When the Survanta plus HA group was compared with the Survanta alone group, arterial oxygen tension averaged 117% higher, peak inspiratory pressure was 27% lower at the end of the experiment, and lung compliance also showed significant improvement. These results indicate that HA added to Survanta decreases inactivation caused by meconium in vitro and improves gas exchange and pulmonary mechanics of animals with meconium-induced acute lung injury.

Animals↗

Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial.

OBJECTIVE: Disagreement exists concerning the appropriate delivery room management of the airway of vigorous meconium-stained infants. Some suggest a universal approach to intubation and suctioning of the airway in all such neonates, whereas others advocate a selective approach. We performed this investigation: 1) to assess whether intubation and suctioning of apparently vigorous, meconium-stained neonates would reduce the incidence of meconium aspiration syndrome (MAS); and 2) to determine the frequency of complications from delivery room intubation and suctioning of such infants. METHODS: Inclusion criteria included: 1) gestational age >/=37 weeks; 2) birth through meconium-stained amniotic fluid of any consistency; and 3) apparent vigor immediately after birth. Subjects were randomized to be intubated and suctioned (INT) or to expectant management (EXP). Primary outcome measures included: 1) the incidence of respiratory distress, including MAS, and 2) the incidence of complications from intubation. RESULTS: A total of 2094 neonates were enrolled from 12 participating centers (1051 INT and 1043 EXP). Meconium-stained amniotic fluid consistency was similar in both groups. Of the 149 (7.1%) infants that subsequently demonstrated respiratory distress, 62 (3.0%) had MAS and 87 (4.2%) had findings attributed to other disorders. There were no significant differences between groups in the occurrence of MAS (INT = 3.2%; EXP = 2.7%) or in the development of other respiratory disorders (INT = 3.8%; EXP = 4.5%). Of 1098 successfully intubated infants, 42 (3.8%) had a total of 51 complications of the procedure. In all cases, the complications were mild and transient in nature. CONCLUSIONS: Compared with expectant management, intubation and suctioning of the apparently vigorous meconium-stained infant does not result in a decreased incidence of MAS or other respiratory disorders. Complications of intubation are infrequent and short-lived.

Adult↗

[Meconium-stained amniotic fluid and intra-amniotic infection].

OBJECTIVE: To explore the relationship between meconium-stained amniotic fluid and Fifty-six women of cesarean section with intact membrane and intra-amniotic infection. METHODS: without parturient were divided into 3 groups according to the property of amniotic fluid (no meconium, I to approximately II degree meconium stainedness, and III degree mecomium stainedness). The content of interleukin-6 in amniotic fluid was measured with ELISA. The infiltration of inflammatory cells in the placenta and its membrane was determined by the pathological diagnosis. The neonatal Apgar score and puerperial infection after the surgery were analyzed. RESULTS: There were no significant differences in the content of IL-6 in amniotic fluid and in the infiltration of inflammatory cells among the 3 groups. But the rate of neonatal asphyxia in the meconium-stained cases was significantly higher than that without meconium. CONCLUSION: Meconium-stained amniotic fluid is a marker of fetal distress, but it is not related to intra-amniotic infection.

Adult↗

Liquid assisted ventilation: an alternative ventilatory strategy for acute meconium aspiration injury.

Evidence of surfactant inactivation by meconium has led to the use of exogenous surfactant therapy in the management of meconium aspiration syndrome (MAS). Liquid assisted ventilation has been shown to improve the cardiopulmonary function in lungs with high surface tension. We compared exogenous surfactant therapy with liquid assisted ventilation in the management of experimental acute meconium aspiration injury. Thirty-two newborn lambs were ventilated at peak inspiratory pressures of 13-16 cm H2O, positive end expiratory pressure of 3-4 cm H2O, fractional inspired oxygen concentration (FiO2) of 1.0, and a respiratory frequency range between 30 and 35 breaths/min. Baseline arterial blood gases, pulmonary function, and arterial blood pressure measurements were taken. All lambs were given 2-3 ml/kg of an unfiltered 25% meconium solution. Lambs were then randomized into either gas-ventilated meconium control, or one of three treatment groups: 1) surfactant; 2) partial liquid ventilation (PLV); or 3) total liquid ventilation (TLV) for 4 hours after meconium injury. All treated groups demonstrated a significant increase in arterial oxygenation (P < 0.05); surfactant and PLV-treated lambs demonstrated significantly decreased arterial PCO2 (P < 0.05). Compliance in all groups increased compared with injury values; compliance of the TLV group increased more than in all other treatment groups (P < 0.05). In addition, lung histology of the TLV group demonstrated clear, intact alveolar epithelium and homogeneously expanded alveoli, while no such improvement was evident in the other groups. These data suggest roles for both exogenous surfactant therapy and liquid assisted ventilation techniques in the management of MAS.

Animals↗

Treatment of meconium aspiration syndrome with surfactant lavage in an experimental rabbit model.

Meconium aspiration syndrome (MAS) is a frequent cause of respiratory distress in term infants. Recent reports suggested that surfactant dysfunction contributes to the pathophysiology of MAS. In the present study, we assessed the effect of three different concentrations of surfactant suspensions in the lavage fluid of a rabbit model of MAS. Young animals were given 5 mL/kg of a 20% slurry of human meconium into the endotracheal tube and were then mechanically ventilated. The animals were divided into four groups receiving lavage fluids with either saline or surfactant suspensions (2.5 mg/mL, 5 mg/mL, and 10 mg/mL). Lavage was performed an hour after meconium instillation with one of the four solutions at 10 mL/kg in three divided doses. After lavage, the total amount of meconium recovered was measured. The 10 mg/mL surfactant lavage group had the best improvement in gas exchange, whereas the saline group had no improvement. The amount of meconium recovered was the best in the 10 mg/mL surfactant group among the four groups studied. On histologic examination, alveolar inflammation was less evident in the surfactant lavage groups than in the saline lavage group. It was concluded that lavage with surfactant solution at a concentration of 10 mg/mL washed out meconium most effectively, and improved gas exchange and lung histology in the rabbit model of MAS more than saline lavage.

Analysis of Variance↗

Enhanced release of thromboxane A(2) after exposure of human airway epithelial cells to meconium.

Meconium aspiration syndrome (MAS) is a cause of significant morbidity and mortality in the perinatal period. Despite the clinical relevance of MAS, its pathogenesis is poorly understood. Epithelial cell-derived prostanoids are involved in the regulation of several cellular functions within the lung, including the control of tone and reactivity of airway and vascular smooth muscle. In this study, we evaluated whether exposure to meconium affects the metabolic function of human airway epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell line, were incubated with various concentrations of meconium. Control cells were incubated with serum-free medium in a similar manner. The supernatant fluid was removed at various time points and assayed for thromboxane A(2) (TXA(2)) production. The latter was accomplished by measuring its immediate and stable metabolite thromboxane B(2), using an enzyme-linked immunosorbent assay (ELISA). In selected experiments, the modulatory effects of indomethacin (10(-6) M), dexamethasone (10(-6) M), and L-nitroarginine methyl ester (L-NAME, 10(-6) M) on TXA(2) production were evaluated. Results were expressed in terms of pg/mg protein (mean +/- SE). We found that exposure to meconium produced a significant release of TXA(2) from A549 cells. Indomethacin, dexamethasone, and in part, L-NAME inhibited meconium-induced release of TXA(2). Our findings demonstrate that meconium enhances the production of thromboxanes from A549 cells, suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.

Dexamethasone↗

Treatment of experimental meconium aspiration syndrome with surfactant lung lavage and conventional vs. asymmetric high-frequency jet ventilation.

Respiratory failure caused by meconium aspiration requires combined strategies. We hypothesized that surfactant lung lavage with asymmetric high-frequency jet ventilation (AHFJV) can increase the removal of meconium and improve lung function. During conventional ventilation (CV), a suspension of human meconium (25 mg/ml, 4 ml/kg) was instilled into the tracheal tube of anesthetized rabbits to cause respiratory failure. Animals were then divided into four groups: saline lavage + CV (Sal-CV), surfactant lavage + CV (Surf-CV), saline lavage + HFJV (Sal-HFJV), and surfactant lavage + HFJV (Surf-HFJV). Lung lavage (10 ml/kg in 3 portions) was performed with diluted surfactant (Curosurf, 100 mg of phospholipids/kg) or saline during CV (frequency (f), 30/min; inspiration time (Ti), 50%) or AHFJV (f, 300/min; Ti, 70%). Animals were ventilated for an additional hour with either CV or HFJV (Ti, 50%). Surfactant lavage with both CV and AHFJV removed more meconium than saline lavage. However, the highest removal was found in the Surf-HFJV group vs. all other groups (P < 0.05). The oxygenation index decreased after surfactant lavage in both groups compared to controls (P < 0.001), and more prominently in the Surf-CV group. Elimination of CO(2) was significantly higher in the Surf-HFJV group vs. all other groups (P < 0.05). The ventilation efficiency index increased after lavage in both surfactant groups vs. saline controls (P < 0.05). Dynamic lung-thorax compliance gradually increased, and right-to-left pulmonary shunts decreased in both surfactant groups vs. saline controls after lavage (P < 0.05). Combination of surfactant lavage with both CV and AHFJV was beneficial in rabbits with meconium aspiration syndrome. While AHFJV was more effective in the removal of meconium, CV had a more favorable effect on lung function in the postlavage period.

Animals↗

An unusual case of meconium peritonitis associated with perforated hydrocolpos.

Meconium peritonitis results from intestinal wall perforation with meconium spillage into the peritoneum during intrauterine life. Anal atresia is associated with meconium peritonitis and is also associated with cloacal malformation. A female neonate presented with a distended abdomen, anal atresia, and meconium peritonitis as diagnosed by calcification in the peritoneal cavity on abdominal radiograph. Sonography and cystography demonstrated a cloacal malformation with perforation of the hydrocolpos and resultant spillage of meconium into the peritoneum. There was no evidence of further perforation of bowel at surgery. This unusual case of meconium peritonitis is reported.

Anus, Imperforate↗

The effect of hyperbaric oxygen treatment on the inflammatory changes caused by intraperitoneal meconium.

Exposure of the peritoneal cavity to meconium causes a marked inflammatory response. The effect of intraperitoneal meconium on intestinal morphology and plasma nitrite and nitrate (NO2(-) + NO3(-)) levels and how this inflammatory process is influenced by hyperbaric oxygen (HBO) treatment were investigated in this study. The purpose was to determine whether HBO treatment could be considered a useful adjunct in the resuscitative treatment of severely ill patients admitted with meconium peritonitis (MP). Rats were divided into three groups. Human meconium (MP group, n=10) and sterile saline (control group, n=10) were injected intraperitoneally for 3 days. The procedure for meconium injection was combined with HBO treatment for the HBO group (n=10). HBO was administered for 7 days. In all groups, peritoneal swap cultures, plasma NO2(-) + NO3(-) levels, intestinal diameters, and macroscopic and microscopic changes in the intestine were determined on the 8th day. Bacterial growth was not detected in the peritoneal swap cultures. There was a significant difference in NO2(-) + NO3(-) levels between the MP and HBO groups ( P<0.05), between the MP and control groups ( P<0.01), and between the HBO and control groups ( P<0.05). Thin fibrinous adhesions in both the MP and HBO groups, and thickened and dilated intestinal loops in the MP group were observed macroscopically. The intestinal diameter in the MP group was significantly greater than in the HBO and control groups. The only microscopic difference was seen in the serosal layer. Compared with the animals in the control and HBO groups, the intestine of the rats in the MP group showed prominent serosal thickening, edema, capillary proliferation and cellular infiltration. The ameliorated inflammatory changes and decreased dilatation of the intestine accompanied by a significant decrease in NO2(-) + NO3(-) levels suggest that as an adjunctive treatment, HBO may have a beneficial effect in the resuscitative treatment of meconium peritonitis.

Animals↗

Meconium plug obstruction.

We reviewed the final diagnosis and incidence of bowel pathology in neonates presenting with large bowel obstruction that was relieved by the passage of meconium plugs. A retrospective case-note review was undertaken of all patients with a discharge diagnosis of meconium plug syndrome (MPS), meconium ileus (MI), Hirschsprung's disease (HD), or small left colon syndrome (SLCS) from January 1996 to April 2002. Of 21 patients with meconium plug obstruction, eight (38%) had HD, nine had MPS, four had SLCS, and none had MI. However, there was considerable clinical and radiological overlap between MPS and SLCS, suggesting that these terms are imprecise. We found a much higher incidence of HD in babies presenting with meconium plug obstruction than has previously been reported. Overlap between MPS and SLCS suggests that these are not specific diagnoses and that current terminology needs to be changed. All babies with meconium plug obstruction should have HD and cystic fibrosis (CF) excluded.

Colonic Diseases↗

Prophylactic amnioinfusion during labor complicated by meconium: a preliminary report.

The purpose of this prospective and randomized study is to evaluate the safety and efficacy of prophylactic transcervical amnioinfusion in the management of labor complicated by meconium. A preexisting intrauterine pressure catheter was used for amnioinfusion. The incidence of thick meconium was significantly lower after amnioinfusion, compared with standard management (5% versus 62% p less than 0.0005). This was also demonstrated with spectrophotometry. Significant differences between the amnioinfusion group and the control group were found for the following: arterial cord pH less than 7.20 (16% versus 38%, p less than 0.05); meconium more than trace below the vocal cords at delivery (0% versus 29%, p less than 0.05) and need for positive pressure ventilation at birth (16% versus 48%, p less than 0.05). No complications related to amnioinfusion were observed. We conclude that (1) transcervical amnioinfusion during labor complicated by meconium is a simple and apparently safe procedure, and that (2) amnioinfusion effectively decreases the frequency of thick meconium, the frequency of neonatal acidemia, the frequency of more than trace meconium below the vocal cords, and the need for positive pressure ventilation.

Adult↗