Abstract
Our aim was to study the feeding behavior of healthy term infants in the first week of life and determine whether this was related to cord blood leptin, ghrelin, and insulin. A total of 100 healthy bottle-fed infants were studied by weighing bottles of milk before and after feeds. Leptin, total ghrelin, and insulin concentrations were measured in cord blood. Mean (SD) birth weight was 3.46 (0.43) kg. Mean milk intake increased from 196.7 (83.0) g on d 1 to 585.0 (128.4) g on d 7. Milk intake over the first 6 d was significantly associated with weight gain to d 7. There was no relationship between cord ghrelin or leptin and milk intake or feed frequency. Cord blood insulin was inversely related to the mean daily number of feeds over the first 6 d (r = −0.21, p < 0.05). Birth weight and milk intake are the major determinants of weight gain in the first week of life in healthy bottle-fed infants. Total cord ghrelin and leptin are not directly related to milk intake or feed frequency in the first week of life. Circulating insulin concentrations may have a role in the initiation of feeding behavior.
Similar content being viewed by others
Main
Locally produced, circulating and central nervous system (CNS) hormones and neurotransmitters regulate appetite in adults.
Ghrelin is a 28-amino-acid peptide secreted primarily by the stomach (1) and by other tissues including the pancreas in fetal life. Ghrelin is the first natural ligand for the growth hormone secretagogue receptor (GHS-R). In addition to stimulating growth hormone (GH) release, ghrelin has a potent orexigenic effect (2,3) and is involved in feeding initiation and termination. At least some of these actions appear to be mediated via the vagus nerve (4). Ghrelin secretion is pulsatile, with increased secretion during fasting and lower levels after food intake (5,6).
Leptin is expressed and secreted by adipocytes in white adipose tissue. Leptin circulates in plasma at concentrations that are proportional to fat mass and provides the CNS with feedback regarding overall nutritional status. Leptin deficient patients are hyperphagic and develop morbid obesity, while leptin has anorectic effects in humans (7). The relationship between obesity and insulin resistance is widely recognized (8), and humoral signals from compounds like ghrelin, leptin, and insulin act on a hypothalamic neuronal network involved in the central regulation of appetite. One network of neurons is associated with appetite inhibition (including pro-opiomelanocortin or POMC) and one with appetite stimulation (neuropeptide-Y or NPY) (9,10).
Whether the hormonal regulators of feeding behavior in adults function in a similar manner in infancy is less well known, although there is evidence to suggest that this is the case. The fact that infants will consume more of a low-energy than a high-energy feed (11,12) suggests that a homeostatic mechanism regulates feeding behavior. Growth in infancy is related to nutritional intake and therefore potentially to the circulating levels of compounds like ghrelin, insulin, and leptin. Ghrelin secretion has been found to be relatively refractory to the effects of feeding in the neonatal period, and the authors have suggested that increased levels in the first days of life may act as an “anabolic drive” to promote food intake (13). The fall in insulin and leptin levels may have a similar effect (14). A negative relationship between ghrelin levels in the first hours of life and birth weight has been described in term infants in some (15) but not all studies (16), and a negative relationship between cord blood ghrelin and ponderal index in term infants has also been reported (17). Recently ghrelin levels were found to be related to nutritional status on the second day of life in preterm infants, although they were receiving oral and intravenous feeding and hence were not regulating their energy intake (18). The fact that low cord ghrelin concentrations are associated with slow weight gain in the first 3 mo of life (19) and cord leptin levels to weight gain at 2 y of age in small-for-gestational age (SGA) children (20) may indicate that these hormones regulate feeding behavior in early life. The negative relationship described between total ghrelin levels and weight gain during the first year of life may also indicate that ghrelin reflects rather than promotes changes in weight beyond the neonatal period (21).
Although linear growth in infancy is maintained during the first week of life (22), weight often decreases (23). In breast-fed infants, more frequent feeding is associated with higher milk intake and reduced weight loss (24). Therefore, there is good reason to believe that poor weight gain in the first week postpartum may be related to nutritional intake, as it is later in infancy.
We have therefore studied milk intake and feeding behavior in the first week of life using milk of known composition and have examined its relationship to (a) cord blood leptin, ghrelin, and insulin concentrations and (b) change in weight over the same period.
METHODS
Subjects.
The local ethical committee approved this study, and parents of each infant provided written informed consent. Women with singleton term pregnancies (between 37 and 42 wk of gestation) were recruited on the delivery suite at the Royal Victoria Infirmary, Newcastle-upon-Tyne. They were approached if they had no known medical conditions and if they intended to feed their infant with formula milk. We used formula feeding as the availability of formula milk to the infant does not depend on the mother's lactogenesis, and its nutritional composition does not vary. Women were not recruited if they had diabetes mellitus (gestational or insulin dependent), hypertension (familial, essential or pregnancy induced), or any other serious medical condition requiring drug treatment before or during pregnancy.
One hundred infants (50 males and 50 females) with no known physical, metabolic, or congenital abnormalities and with an Apgar score of 8 or above at 5 min and a birth weight of 2500 g or more were recruited. Infants with a birth weight less than 2500 g were excluded as their spontaneous feeding behavior was overruled by a strict feeding regimen that included regular waking and nasogastric feeding if they did not consume a set amount of milk. The mothers were between 17 and 43 y of age; 55% smoked during the pregnancy. Their mean height (±1 SD) was 161.9 (6.3) cm (range, 149.5–179.4 cm). Forty-four percent were primiparous and 56% were multiparous.
Auxology.
The infants were weighed on electronic weighing scales (Seca, Model 727). The scales used on the delivery suite in the hospital were set to 5-g resolution and were accurate to 0.05% from 0 to 10 kg. They were calibrated at 1-kg intervals from 1 to 5 kg using M3 calibration weights on four separate occasions during the study. The length of the infant was measured in centimeters (accurate to 0.1 cm) using a Kiddimetre (Raven Equipment Limited, Essex, UK). The head circumference of the infant was measured in cm (accurate to 0.1 cm) using a pediatric tape measure (Perspectives Enterprises). Placental weight was measured by the midwife to the nearest 10 g on the Salter balance on the delivery suite.
Cord blood sampling.
The sample of cord blood was taken following delivery of the baby and before delivery of the placenta. The cord was double clamped with forceps and cut. Ten milliliters of cord blood was taken by either the attending midwife or the researcher from the clamped portion of the cord at the placental end and placed in the prepared blood bottles.
Feed preparation and milk intake.
The infants were fed using numbered 100-mL bottles of ready-made formula milk for the first 7 d of life. The bottles of milk were weighed on a portable Ohaus strain gauge electronic balance (Model CT1200-S, accurate to 0.1 g). Mothers had a choice of two milk preparations (SMA Gold and Cow & Gate Premium) provided in ready-to-feed weighed and labeled bottles. The two types of feed had an identical energy content and a similar carbohydrate, fat, and protein content. SMA gold contains 280 kJ (67 kcal), 1.5 g protein, 7.2 g carbohydrate, 3.6 g fat, and 16 mg sodium per 100-mL bottle, while Cow & Gate Premium contains 280 kJ (67 kcal), 1.4 g protein, 7.5 g carbohydrate, 3.5 g fat, and 19 mg sodium per 100-mL bottle. The weights were recorded on a data collection sheet. In the delivery suite, the researcher explained the procedure that the mother needed to follow for the subsequent 7 d. Although no specific instructions were given to the mothers about how much to feed their infants, the midwives suggested that they give the infants as much as they demanded. The mothers were asked to feed the infants with the milk, starting with the bottle labeled number 1 for the first feed and following the numbers in order until d 7. On completion of the feed, the mother was asked to record on the feed chart provided the number and time of the feed, the amount taken, and whether the baby was sick or if any of the milk was accidentally spilled. She was then asked to replace the lid on the bottle with the remainder of the milk that was left in it and place it in the container provided. A feed was defined as milk consumed at one sitting. If mothers undertook tasks other than nursing the infant between episodes of milk consumption, then this was defined as two feeds rather than one. A date and time was arranged for the 7-d visit and documented on the instruction sheet for the mother. The time of the 7-d visit was scheduled as near to the time of birth as possible (usually within 2 h). The contact telephone number of the researcher was provided in case further advice was required in the interim. On d 7, all the bottles that had been used were reweighed and the difference between the prefeed and postfeed weight of the bottles was used to calculate the milk consumed.
Biochemical assays.
The leptin assays were carried out using a commercial leptin RIA (Linco, St. Charles, MO). Intra- and interassay coefficients were 8.3% and 6.2% at 4.9 ng/mL and 3.9% and 4.7% at 10.4 ng/mL, respectively. Insulin assays were performed using the DAKO insulin assay (DAKO, Glostrup, Denmark). This assay is an enzyme-linked immunosorbent assay based on two monoclonal antibodies that measures biologically active insulin with a high degree of specificity. The limit of sensitivity was 0.5 μIU/mL; the intra-assay coefficient was <5% and the interassay coefficient was <5.3%. Total plasma immunoreactive ghrelin levels were measured with a commercial radioimmunoassay kit (Phoenix Pharmaceuticals, Belmont, CA) at the Diagnostic Systems Laboratories, UK Ltd. The limit of sensitivity was 0.14 ng/mL, intra-assay coefficient was 3.4% at 1.14 ng/mL, and the interassay coefficient was <14%. The assays were all carried out at the end of the study, and so all other measurements were recorded blind to hormone data.
Data analysis.
Missing data due to a bottle being discarded by accident on two occasions were dealt with by interpolating from adjacent days in the same infant. A small number of mothers did not complete the study. Complete data were available for 100 infants to d 3, 99 to d 5, 97 to d 6, and 89 to d 7. The data were initially summarized by calculating a total milk intake for each day for each infant with each 24-h period commencing at the time that the infant was born and compared using analysis of variance (ANOVA). Means of these totals over the first 6 d were also used. Pearson correlations were used to relate continuous variables to one another, with multiple regression used to analyze more complex relationships. Comparisons between the sexes used independent-sample t tests or U tests as appropriate. Birth weight data were compared with UK National Growth Standards (25).
RESULTS
Birth data.
The infants in the study had a gestational age from 37 wk 4 d to 42 wk 1 d. They were born following a first stage of labor that lasted a median of 455 min (interquartile range, 295 min) and a second stage that lasted a median of 48 min (interquartile range, 97 min). The mean birth weight was 3.458 kg with an SD of 0.43 and ranged from 2.51 to 4.61 kg. The mean birth weight SD score was 0.05, which is not significantly different from the median of the UK National Growth Standards. The mean birth length was 49.8 cm (SD = 1.8) and ranged from 45.0 cm to 54.0 cm.
Milk intake and infant feeding behavior.
Infant milk intake is illustrated in Figure 1. In an analysis using repeated-measures ANOVA, restricted to infants with data on all 7 d (n = 89), milk intake rose significantly from d 1 to d 7 (F6,83 = 168.8, p < 0.001). Both the linear and quadratic trends, but no higher order trend, were statistically significant. The number of feeds varied from three to 12 per day (Table 1). Again, there was a highly significant trend over time (F6,83 = 6.153, p < 0.001) with significant linear and quadratic components. The number of feeds rose over the first 3 d, remaining the same thereafter. There was a significant relationship between the number of feeds recorded and total milk intake for each separate 24-h period from birth to 7 d of age. There was no difference in milk intake between the male and female infants from d 1 to d 7 (F1,98 = 1.97; p = 0.164, not significant). There was no relationship between length of labor, analgesia, anesthesia, or Apgar score and milk intake in the first 24 h or the first 7 d. By 7 d of age, 38% of infants had lost weight (when compared with birth weight), 5% had a weight that was the same as birth weight, and 57% had gained weight.
The milk data for d 7 were excluded from subsequent analyses because of the missing data for this day in 11 infants (Table 1). Mean total daily intakes were based on data from the first 6 d.
Birth weight was significantly associated with mean daily milk consumption over the first 6 d (r = 0.35. p < 0.0001). In a multiple regression, weight on d 7 was significantly associated with birth weight (t = 38.35, p < 0.001) and with mean milk intake over the first 6 d (t = 5.99, p < 0.001). Figure 2 shows the relationship between mean milk intake and the change in weight.
Birth variables, milk intake, feeding frequency, and cord hormone levels.
Mean (SD) cord blood leptin concentrations were 10.1 ng/mL (6.7) (range, 1.6–36.7 ng/mL); mean total ghrelin concentrations were 760.9 pg/mL (282.8) (range, 210.0–1670.0 pg/mL); mean cord blood insulin concentrations were 4.5 mU/L (3.0) (range, 0.9–15.8 pmol/L).
Table 2 shows that cord blood leptin was significantly related to birth weight and birth length and to placental weight. Female infants had higher leptin levels than male infants (the means were 12.2 with SD = 7.2 and 8.0 with SD =5.4, respectively). By the Mann-Whitney U test, Z = 3.4 (p < 0.01). Cord blood total ghrelin levels were not significantly related to any of the growth measurements made at birth. There was no relationship between cord blood leptin, ghrelin, and maternal smoking status.
Relationships with feeding variables are shown in Table 3. There was no relationship between cord blood leptin and ghrelin and any of the feeding variables, but cord blood insulin was inversely related to the mean number of feeds during the first 6 d of life, i.e. the infants with lower insulin levels at birth took more feeds over that time period.
DISCUSSION
Milk intake is the sole provider of both water and food to the infant. Healthy infants gain weight at different rates, suggesting that there are inherent differences in hunger. Milk intake will be affected by the complex interaction between mother and child, but the discovery of gastrointestinal and CNS hormones involved in the regulation of feeding behavior and energy homeostasis in adults has provided a mechanism to explain differences in feeding behavior and hence growth earlier in life. A relationship between leptin and ghrelin in cord blood and subsequent growth parameters has been described, and we wanted to establish whether feeding behavior in the first week of life was related to levels of these hormones in cord blood.
Our data on infant feeding in the first week of life were collected from term infants of normal birth weight. Cord hormone levels were correlated with milk intake and feed frequency. We elected to study bottle-fed infants because of the practical difficulties associated with determining milk intake and milk energy content in breast-fed babies (26,27), and this is one of the most detailed studies of infant feeding in bottle-fed infants in the first week of life conducted to date.
We found that birth weight and milk intake during the first 6 d of life were each significantly associated with weight at 7 d of age. We did not, however, find a relationship between milk intake and feeding behavior in the first week of life and cord blood total ghrelin and leptin concentrations. The extent to which the placenta contributes to cord venous blood ghrelin levels is unclear, with similar values documented in the umbilical vein and artery in some studies (28) but not others (29). However, it is of note that cord values are closely related to levels in the first week of life (13). In contrast to some earlier studies, we did not identify a relationship between ghrelin and birth weight, although we were careful to exclude potential confounders that appear to affect ghrelin such as being born SGA or preterm (16,30).
There are a number of potential explanations for the fact that total cord ghrelin was not directly related to feeding behavior. Serum osmolality and thirst may have a more significant role in determining feeding behavior at this stage of life. However, the immature kidney generates relatively dilute urine, and there is no direct evidence that osmotic thirst affects milk intake in the early days of life, and some direct evidence that it does not (31). Studies in rodents have suggested that there may be relative immaturity of the CNS connections in early life (32) with development of a fasting-associated increase in ghrelin at the end of the first postnatal week (33). Circulating ghrelin and leptin may therefore become more important regulators of infant feeding beyond 7 d of age. Feeding does not appear to have the same inhibitory effect on ghrelin levels in the first days of life in humans either, although this does not necessarily preclude a role in the regulation of feeding behavior (13). Recent studies in rodents have also indicated that the impact of ghrelin on body composition may be more complex than the impact on food intake alone; food intake is not different in ghrelin knockout animals and wild-type controls, but the ghrelin knockout animal is resistant to diet-induced obesity and consumes less food and preferentially uses fat as an energy substrate (34,35).
A potential criticism of our study is that the ghrelin assay measured total (acylated and deacylated) ghrelin rather than the bioactive nonacylated portion alone that amounts to less than 20% of total values. Although the concentrations of total ghrelin reflect those of the acylated fraction in cord blood (36), further studies may also need to take into account the extent to which the different forms of ghrelin are bound to larger molecules (37,38).
Unlike ghrelin and leptin, insulin concentrations fluctuate according to whether an infant is fed or fasted, and we identified an inverse relationship between feed frequency and cord insulin levels. Insulin receptors reside in neural tissues involved in energy regulation and intracerebroventricular administration of insulin to rodents reduces food intake, while the administration of insulin antibodies into the CNS has the opposite effect (39,40). Insulin levels will be reduced in the fasting state and, as in cord blood, will tend to be lower in lighter infants. Low or falling insulin levels or intrinsic insulin “tone” may therefore be an important stimulus to feed in infancy.
In summary, milk intake is a major determinant of weight gain in the first week of life in healthy bottle-fed infants. Cord ghrelin and leptin levels are not directly related to feed volume or feed frequency, but a relationship between insulin in cord blood and feed frequency suggests that insulin concentrations may be involved in the regulation of neonatal feeding behavior.
Abbreviations
- CNS:
-
central nervous system
- GH:
-
growth hormone
- GHS-R:
-
growth hormone secretagogue receptor
- POMC:
-
pro-opiomelanocortin
- SGA:
-
small for gestational age
References
Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda H, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A, Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K 2001 Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 86: 4753–4758
Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR 2000 The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141: 4325–4328
Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR 2001 Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86: 5992–5995
Le Roux CW, Neary NM, Halsey TJ, Small CJ, Martinez-Isla AM, Ghatei MA, Theodorou NA, Bloom SR 2005 Ghrelin does not stimulate food intake in patients with surgical procedures involving vagotomy. J Clin Endocrinol Metab 90: 4521–4524
Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS 2001 A preprandial rise in plasma ghrelin levels suggest a role in meal initiation in humans. Diabetes 50: 1714–1719
Cummings DE, Wiegle DS, Scott Frayo R, Breen PA, Ma MK, Dellinger EP, Purnell JQ 2002 Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346: 1623–1630
Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S 2002 Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110: 1093–1103
Kahn BB, Flier JS 2000 Obesity and insulin resistance. J Clin Invest 106: 473–481
Farooqi IS, Yeo GS, Keogh JM, Aminian S, Jebb SA, Butler G, Cheetham T, O'Rahilly S 2000 Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest 106: 271–279
Gehlert DR 1999 Role of hypothalamic neuropeptide Y in feeding and obesity. Neuropeptides 33: 329–338
Fomon SJ, Filer LJ, Thomas LN, Anderson TA, Nelson SE 1975 Influence of formula concentration on caloric intake and growth of normal infants. Acta Paediatr Scand 64: 172–181
Cooke RJ, Griffin IJ, McCormick K, Wells JC, Smith JS, Robinson SJ, Leighton M 1998 Feeding preterm infants after hospital discharge: effect of dietary manipulation on nutrient intake and growth. Pediatr Res 43: 355–360
Bellone S, Baldelli R, Radetti G, Rapa A, Vivenza D, Petri A, Savastio S, Zaffaroni M, Broglio F, Ghigo E, Bona G 2006 Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake. J Clin Endocrinol Metab 91: 1929–1933
Mami C, Manganaro R, Saitta G, Marseglia L, Martino F, Gemelli M 2005 Plasma leptin, insulin, and neuropeptide Y concentrations in infants. Arch Dis Child Fetal Neonatal Ed 90: F86–F87
Ng PC, Lee CH, Lam CW, Chan IH, Wong E, Fok TF 2005 Ghrelin in preterm and term newborns: relation to anthropometry, leptin and insulin. Clin Endocrinol (Oxf) 63: 217–222
Bellone S, Rapa A, Vivenza D, Vercellotti A, Petri A, Radetti G, Bellone J, Broglio F, Ghigo E, Bona G 2004 Circulating ghrelin levels in the newborn are positively associated with gestational age. Clin Endocrinol (Oxf) 60: 613–617
Soriano-Guillen L, Barrios V, Chowen JA, Sanchez I, Vila S, Quero J, Argente J 2004 Ghrelin levels from fetal life through early adulthood: relationship with endocrine and metabolic and anthropometric measures. J Pediatr 144: 30–35
Hubler A, Rippel C, Kauf E, Hoyer H, Mainz J, Schlenvoigt D, Schramm D 2006 Associations between ghrelin levels in serum of preterm infants and enteral nutritional state during the first 6 months after birth. Clin Endocrinol (Oxf) 65: 611–616
James RJ, Drewett RF, Cheetham TD 2004 Low cord ghrelin levels are associated with slow weight gain over the first 3 months of life. J Clin Endocrinol Metab 89: 3847–3850
Ong KK, Ahmed ML, Sherriff A, Woods KA, Watts A, Golding J, Dunger DB 1999 Cord blood leptin is associated with size at birth and predicts infancy weight gain in humans. J Clin Endocrinol Metab 84: 1145–1148
Savino F, Liguori SA, Fissore MF, Oggero R, Silvestro L, Miniero R 2005 Serum ghrelin concentration and weight gain in healthy term infants in the first year of life. J Pediatr Gastroenterol Nutr 41: 653–659
Bishop NJ, King FJ, Lucas A 1990 Linear growth in the early neonatal period. Arch Dis Child 65: 707–708
Macdonald PD, Ross SR, Grant L, Young D 2003 Neonatal weight loss in breast and formula fed infants. Arch Dis Child Fetal Neonatal Ed 88: F472–F476
Yamauchi Y, Yamanouchi I 1990 Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Pediatrics 86: 171–175
Preece MA, Freeman JV, Cole TJ 1996 Sex differences in weight in infancy: Published centile charts for weight have been updated. BMJ 313: 1486
Dewey KG, Heinig MJ, Nommsen LA, Lonnerdal B 1991 Adequacy of energy intake among breast-fed infants in the Darling study: Relationships to growth velocity, morbidity and activity levels. J Pediatr 119: 538–547
Michaelsen KF, Larsen PS, Thomsen BL, Samuelsom G 1994 The Copenhagen cohort study on infant nutrition and growth: breast-milk intake, human macronutrient content and influencing factors. Am J Clin Nutr 59: 600–611
Cortelazzi D, Cappiello V, Morpurgo PS, Ronzoni S, Nobile De Santis MS, Cetin I, Beck-Peccoz P, Spada A 2003 Circulating levels of ghrelin in human fetuses. Eur J Endocrinol 149: 111–116
Onal EE, Cinaz P, Atalay Y, Turkyilmaz C, Bideci A, Akturk A, Okumus N, Unal S, Koc E, Ergenekon E 2004 Umbilical cord ghrelin concentrations in small- and appropriate-for- gestational age newborn infants: relationship to anthropometric markers. J Endocrinol 180: 267–271
Kitamura S, Yokota I, Hosoda H, Kotani Y, Matsuda J, Naito E, Ito M, Kangawa K, Kuroda Y 2003 Ghrelin concentration in cord and neonatal blood: relation to fetal growth and energy balance. J Clin Endocrinol Metab 88: 5473–5477
Drewett RF 2007 The Nutritional Psychology of Childhood. Cambridge University Press, Cambridge, pp 1–298
Grove KL, Smith MS 2003 Ontogeny of the hypothalamic neuropeptide Y system. Physiol Behav 79: 47–63
Hayashida T, Nakahara K, Mondal MS, Date Y, Nakazato M, Kojima M, Kangawa K, Murakami N 2002 Ghrelin in neonatal rats: distribution in stomach and its possible role. J Endocrinol 173: 239–245
Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, Jones JE, Deysher AE, Waxman AR, White RD, Williams TD, Lachey JL, Seeley RJ, Lowell BB, Elmquist JK 2005 Mice lacking ghrelin receptors resist the development of diet-induced obesity 2005. J Clin Invest 115: 3564–3572
Wortley KE, Anderson KD, Garcia K, Murray JD, Malinova L, Liu R, Moncrieffe M, Thabet K, Cox HJ, Yancopoulos GD, Wiegand SJ, Sleeman MW 2004 Genetic deletion of ghrelin does decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci U S A 101: 8227–8232
Kitamura S, Yokota I, Hosoda H, Kotani Y, Matsuda J, Naito E, Ito M, Kangawa K, Kuroda Y 2004 N-octanoylated ghrelin levels in cord and neonatal blood. J Clin Endocrinol Metab 89: 4768[ letter]
Murphy KG, Dhillo WS, Bloom SR 2006 Gut peptides in the regulation of food intake and energy homeostasis 2006. Endocr Rev 27: 719–727
Mackelvie KJ, Meneilly GS, Elahi D, Wong AC, Barr SI, Chanoine JP 2007 Regulation of appetite in lean and obese adolescents after exercise: role of acylated and desacyl ghrelin. J Clin Endocrinol Metab 92: 648–654
Air EL, Benoit SC, Blake Smith KA, Clegg DJ, Woods SC 2002 Acute third ventricular administration of insulin decreases food intake in two paradigms. Pharmacol Biochem Behav 72: 423–429
McGowan MK, Andrews KM, Fenner D, Grossman SP 1993 Chronic intrahypothalamic insulin infusion in the rat: behavioral specificity. Physiol Behav 54: 1031–1034
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
James, R., James, A., Drewett, R. et al. Milk Intake and Feeding Behavior in the First Week of Life and Its Relationship to Cord Blood Ghrelin, Leptin, and Insulin Concentrations. Pediatr Res 62, 695–699 (2007). https://doi.org/10.1203/PDR.0b013e318159a28c
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/PDR.0b013e318159a28c
This article is cited by
-
Population pharmacokinetic modeling of tramadol and its O-desmethyl metabolite in plasma and breast milk
European Journal of Clinical Pharmacology (2011)