Using a developmental systems perspective, this review focuses on how genetic predispositions interact with aspects of the eating environment to produce phenotypic food preferences. Predispositions include the unlearned, reflexive reactions to basic tastes: the preference for sweet and salty tastes, and the rejection of sour and bitter tastes. Other predispositions are ( a) the neophobic reaction to new foods and (b) the ability to learn food preferences based on associations with the contexts and consequences of eating various foods. Whether genetic predispositions are manifested in food preferences that foster healthy diets depends on the eating environment, including food availability and child-feeding practices of the adults. Unfortunately, in the United States today, the ready availability of energy-dense foods, high in sugar, fat, and salt, provides an eating environment that fosters food preferences inconsistent with dietary guidelines, which can promote excess weight gain and obesity.

Development of food preferences

Background
Administration of oral sucrose with and without non-nutritive sucking is the most frequently studied non-pharmacological intervention for procedural pain relief in neonates.

Objectives
To determine the efficacy, effect of dose, method of administration and safety of sucrose for relieving procedural pain in neonates as assessed by validated composite pain scores, physiological pain indicators (heart rate, respiratory rate, saturation of peripheral oxygen in the blood, transcutaneous oxygen and carbon dioxide (gas exchange measured across the skin - TcpO2, TcpCO2), near infrared spectroscopy (NIRS), electroencephalogram (EEG), or behavioural pain indicators (cry duration, proportion of time crying, proportion of time facial actions (e.g. grimace) are present), or a combination of these and long-term neurodevelopmental outcomes.

Search methods
We used the standard methods of the Cochrane Neonatal. We performed electronic and manual literature searches in February 2016 for published randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 1, 2016), MEDLINE (1950 to 2016), EMBASE (1980 to 2016), and CINAHL (1982 to 2016). We did not impose language restrictions.

Selection criteria
RCTs in which term or preterm neonates (postnatal age maximum of 28 days after reaching 40 weeks' postmenstrual age), or both, received sucrose for procedural pain. Control interventions included no treatment, water, glucose, breast milk, breastfeeding, local anaesthetic, pacifier, positioning/containing or acupuncture.

Data collection and analysis
Our main outcome measures were composite pain scores (including a combination of behavioural, physiological and contextual indicators). Secondary outcomes included separate physiological and behavioural pain indicators. We reported a mean difference (MD) or weighted MD (WMD) with 95% confidence intervals (CI) using the fixed-effect model for continuous outcome measures. For categorical data we used risk ratio (RR) and risk difference. We assessed heterogeneity by the I2 test. We assessed the risk of bias of included trials using the Cochrane 'Risk of bias' tool, and assessed the quality of the evidence using the GRADE system.

Main results
Seventy-four studies enrolling 7049 infants were included. Results from only a few studies could be combined in meta-analyses and for most analyses the GRADE assessments indicated low- or moderate-quality evidence. There was high-quality evidence for the beneficial effect of sucrose (24%) with non-nutritive sucking (pacifier dipped in sucrose) or 0.5 mL of sucrose orally in preterm and term infants: Premature Infant Pain Profile (PIPP) 30 s after heel lance WMD -1.70 (95% CI -2.13 to -1.26; I2 = 0% (no heterogeneity); 3 studies, n = 278); PIPP 60 s after heel lance WMD -2.14 (95% CI -3.34 to -0.94; I2 = 0% (no heterogeneity; 2 studies, n = 164). There was high-quality evidence for the use of 2 mL 24% sucrose prior to venipuncture: PIPP during venipuncture WMD -2.79 (95% CI -3.76 to -1.83; I2 = 0% (no heterogeneity; 2 groups in 1 study, n = 213); and intramuscular injections: PIPP during intramuscular injection WMD -1.05 (95% CI -1.98 to -0.12; I2 = 0% (2 groups in 1 study, n = 232). Evidence from studies that could not be included in RevMan-analyses supported these findings. Reported adverse effects were minor and similar in the sucrose and control groups. Sucrose is not effective in reducing pain from circumcision. The effectiveness of sucrose for reducing pain/stress from other interventions such as arterial puncture, subcutaneous injection, insertion of nasogastric or orogastric tubes, bladder catherization, eye examinations and echocardiography examinations are inconclusive. Most trials indicated some benefit of sucrose use but that the evidence for other painful procedures is of lower quality as it is based on few studies of small sample sizes. The effects of sucrose on long-term neurodevelopmental outcomes are unknown.

Authors' conclusions
Sucrose is effective for reducing procedural pain from single events such as heel lance, venipuncture and intramuscular injection in both preterm and term infants. No serious side effects or harms have been documented with this intervention. We could not identify an optimal dose due to inconsistency in effective sucrose dosage among studies. Further investigation of repeated administration of sucrose in neonates is needed. There is some moderate-quality evidence that sucrose in combination with other non-pharmacological interventions such as non-nutritive sucking is more effective than sucrose alone, but more research of this and sucrose in combination with pharmacological interventions is needed. Sucrose use in extremely preterm, unstable, ventilated (or a combination of these) neonates needs to be addressed. Additional research is needed to determine the minimally effective dose of sucrose during a single painful procedure and the effect of repeated sucrose administration on immediate (pain intensity) and long-term (neurodevelopmental) outcomes.

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Sucrose for analgesia in newborn infants undergoing painful procedures

Objective To develop evidence-based guidelines for preventing or treating neonatal pain and its adverse consequences. Compared with older children and adults, neonates are more sensitive to pain and vulnerable to its long-term effects. Despite the clinical importance of neonatal pain, current medical practices continue to expose infants to repetitive, acute, or prolonged pain. Design Experts representing several different countries, professional disciplines, and practice settings used systematic reviews, data synthesis, and open discussion to develop a consensus on clinical practices that were supported by published evidence or were commonly used, the latter based on extrapolation of evidence from older age groups. A practical format was used to describe the analgesic management for specific invasive procedures and for ongoing pain in neonates. Results Recognition of the sources of pain and routine assessments of neonatal pain should dictate the avoidance of recurrent painful stimuli and the use of specific environmental, behavioral, and pharmacological interventions. Individualized care plans and analgesic protocols for specific clinical situations, patients, and health care settings can be developed from these guidelines. By clearly outlining areas where evidence is not available, these guidelines may also stimulate further research. To use the recommended therapeutic approaches, clinicians must be familiar with their adverse effects and the potential for drug interactions. Conclusion Management of pain must be considered an important component of the health care provided to all neonates, regardless of their gestational age or severity of illness.

https://jamanetwork.com/journals/jamapediatrics/articlepdf/190335/POA00293.pdf

Consensus Statement for the Prevention and Management of Pain in the Newborn

Acute pain is one of the most common adverse stimuli experienced by children, occurring as a result of injury, illness, and necessary medical procedures. It is associated with increased anxiety, avoidance, somatic symptoms, and increased parent distress. Despite the magnitude of effects that acute pain can have on a child, it is often inadequately assessed and treated. Numerous myths, insufficient knowledge among caregivers, and inadequate application of knowledge contribute to the lack of effective management. The pediatric acute pain experience involves the interaction of physiologic, psychologic, behavioral, developmental, and situational factors. Pain is an inherently subjective multifactorial experience and should be assessed and treated as such. Pediatricians are responsible for eliminating or assuaging pain and suffering in children when possible. To accomplish this, pediatricians need to expand their knowledge, use appropriate assessment tools and techniques, anticipate painful experiences and intervene accordingly, use a multimodal approach to pain management, use a multidisciplinary approach when possible, involve families, and advocate for the use of effective pain management in children.

The Assessment and Management of Acute Pain in Infants, Children, and Adolescents

COLANTUONI, CARLO, PEDRO RADA, JOSEPH Mc-CARTHY, CAROLINE PATTEN, NICOLE M. AVENA,ANDREW CHADEAYNE, AND BARTLEY G. HOEBEL.Evidence that intermittent, excessive sugar intake causesendogenous opiod dependence. Obes Res. 2002;10:478–488.Objective: The goal was to determine whether withdrawalfrom sugar can cause signs of opioid dependence. Becausepalatable food stimulates neural systems that are implicatedin drug addiction, it was hypothesized that intermittent,excessive sugar intake might create dependency, as indi-cated by withdrawal signs.Research Methods and Procedures: Male rats were food-deprived for 12 hours daily, including 4 hours in the earlydark, and then offered highly palatable 25% glucose inaddition to chow for the next 12 hours. Withdrawal wasinduced by naloxone or food deprivation. Withdrawal signswere measured by observation, ultrasonic recordings, ele-vated plus maze tests, and in vivo microdialysis.Results: Naloxone (20 mg/kg intraperitoneally) causedsomatic signs, such as teeth chattering, forepaw tremor,and head shakes. Food deprivation for 24 hours causedspontaneous withdrawal signs, such as teeth chattering.Naloxone (3 mg/kg subcutaneously) caused reduced timeon the exposed arm of an elevated plus maze, whereagain significant teeth chattering was recorded. The plusmaze anxiety effect was replicated with four controlgroups for comparison. Accumbens microdialysis re-vealed that naloxone (10 and 20 mg/kg intraperitoneally)decreased extracellular dopamine (DA), while dose-depen-dently increasing acetylcholine (ACh). The naloxone-inducedDA/ACh imbalance was replicated with 10% sucrose and 3mg/kg naloxone subcutaneously.Discussion: Repeated, excessive intake of sugar created astate in which an opioid antagonist caused behavioral andneurochemical signs of opioid withdrawal. The indices ofanxiety and DA/ACh imbalance were qualitatively similarto withdrawal from morphine or nicotine, suggesting thatthe rats had become sugar-dependent.Key words: glucose, addiction, dopamine, plus maze,acetylcholine

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Evidence That Intermittent, Excessive Sugar Intake Causes Endogenous Opioid Dependence

The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures: blood collection via heel lance and circumcision. Infants who drank 2 mL of a 12% sucrose solution prior to blood collection cried 50% less during the blood collection procedure than did control infants who had received 2 mL of sterile water. Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline. Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision. Specifically, control infants who underwent a standard circumcision procedure without intervention cried 67% of the time. A water-moistened pacifier reduced crying to 49% (P less than .01). Crying was reduced further to 31% (P less than .05) by providing infants with a sucrose-flavored pacifier to suck. These findings, which parallel results obtained in studies of pain in infant rats, provide a potent yet simple, benign intervention to help alleviate stress and pain routinely experienced by human infants.

Sucrose as an analgesic for newborn infants.

This research identifies a coordinative structure of action that integrates hand and mouth activities within hours after birth. Infants in the supine position received 7 presentations of 12% sucrose solution. Differences in hand-mouth coordination relative to preceding and succeeding epochs of nonsucrose presentation were striking: 32% of the sucrose period was spent by infants with hands inside the mouth or in contact with it, and 18%, for the same measures during periods of nonsucrose delivery. In addition the hand was brought to the mouth 50% more often during the sucrose period. These data provide evidence for oropharyngeal control over integration of gross motor patterns of hand movement as they relate to the mouth. A possible functional significance of these findings is discussed.

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Oropharyngeal Control of Hand-Mouth Coordination in Newborn Infants

Hand-mouth coordination was studied in l-3-day-old human infants by delivering 0.2 ml of sterile 12% sucrose solution intraorally once every 2 min. Sucrose was extraordinarily calming and caused sustained hand-in-mouth contact. The calm state persisted well beyond sucrose termination. Handin-mouth behavior, however, stopped upon sucrose termination, demonstrating stimulus control over this integrated behavior. In subsequent studies we demonstrated that hand-in-mouth behavior was not attributable to calming per se. Moreover, hand activity could be prevented by placing a pacifier in the mouth. This demonstrates that the behavior was under intraoral somesthetic control and was not necessarily the expression of a motor pattern triggered by the sweet taste. These findings are interpreted within the contexts of sucrose (a) calming through an endogenous opioid system and (b) activating suckling-feeding mechanisms, causing the expression of integrated hand, mouth, and head motor patterns. In human development, hand-mouth contact is among the earliest cases of a sustained behavioral pattern that integrates two separate motor systems. Studies of human fetal activity have placed this phenomenon as early as 18 weeks menstrual age (Humphrey, 1968). The behavior remains prominent, appearing within the first hours after birth (Kravitz, Goldenberg, & Neyhus, 1978). According to Korner and her associates (Korner & Beason, 1972; Korner, Church, & Dontchos, 1968; Korner & Kraemer, 1972), it occurs up to 20% of the time in awake infants lying prone or on their sides. Hand-mouth integration changes developmentally, coming under the control of perceptual systems by 5 months of age when infants start to reach for (Hofsten, 1979, 1982), then to grasp (Yonas & Granrud, 1985), and finally to bring objects to the mouth (Piaget, 1952; Rochat, 1985; Ruff, 1984; see Gibson & Spelke, 1983, for review). The transitional phases between the early behavior that is independent of eye-hand coordination and the later aspects that integrate reaching and grasping have not been identified or analyzed in any systematic fashion. The early expression of hand-mouth contact, its increased frequency during the pregrasping and prereaching months, its expansion during the period when all grasped objects are brought into the mouth, and its eventual contraction to actions supporting ingestive behavior reflect changing elements of control among integrated perceptual, motor, and affective systems. Analyses of these transitions, and particularly of the circumstances underlying the development of restrictions on what is

/pdf/sensorimotor-and-motivational-determinants-of-hand-mouth-1hy3d4v3vj.pdf

Lisa B. Hoffmeyer

Papers

Sucrose as an analgesic for newborn infants.

Oropharyngeal Control of Hand-Mouth Coordination in Newborn Infants

Sensorimotor and Motivational Determinants of Hand-Mouth Coordination in 1-3-Day-Old Human Infants

Sucrose as an Analgesic for Newborn Infants