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RESEARCH
A Descriptive Study of Transient Neonatal Feeding Intolerance in a Tertiary Care Center in Turkey Mehmet Nevzat Cizmeci, Mehmet Kenan Kanburoglu, Ahmet Zulfikar Akelma, Naile Tufan, and Mustafa Mansur Tatli
Correspondence Mehmet Nevzat Cizmeci, MD Department of Pediatrics Division of Neonatology Fatih University Medical School, 06510 Emek/Ankara, Turkey [email protected] Keywords feeding intolerance newborn refusal to feed vomiting in infancy
ABSTRACT Objective: To investigate the characteristic features of transient neonatal feeding intolerance (TNFI) during the hospitalization for birth in the maternity ward. Design: A prospective follow-up study. Setting: Maternity ward and neonatal intensive care unit (NICU) in an academic medical center. Participants: Term (≥ 37-weeks gestation) infants admitted to the neonatal intensive care unit with recurrent vomiting and refusal to feed between January and December 2011. These infants were prospectively followed-up at 1, 2, 4, 6 months of age in the outpatient clinic. Results: During the study period 1280 infants were evaluated in the maternity ward. Forty-eight (3.75%) neonates with repeated vomiting and refusal to feed were hospitalized from the maternity unit to the NICU Level I on the first postnatal day for further investigation. All infants started vomiting in the first day (median 5.75 hours; interquartile range: 1–24) and recovered by the 48th postnatal hour (median 27.5 hours; interquartile range: 14–48 hours). Laboratory and imaging studies showed no abnormalities. After discharge, 6-month follow-up of these infants showed no vomiting or feeding intolerance during well-child visits. Conclusions: Infants with TNFI can be managed with close observation and supportive measures if they have no other indications of underlying disease. We believe that expectant management and supportive measures under skilled nursing care will prevent unnecessary diagnostic evaluation, mother/infant separation, and prolonged hospital stay.
JOGNN, 43, 200-204; 2014. DOI: 10.1111/1552-6909.12292 Accepted December 2013
Mehmet Nevzat Cizmeci, MD, is a neonatology fellow in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Mehmet Kenan Kanburoglu, MD, is a neonatology fellow in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey.
(Continued)
The authors report no conflict of interest or relevant financial relationships.
200
he ability to feed by mouth is of paramount importance in the newborn infant, and successful achievement of breastfeeding during the birth hospitalization in the maternity ward is a critical task for the infant/mother dyad. A full-term infant should be offered the breast as soon after the birth as possible, preferably within the first hour after delivery (Gartner et al., 2005). Establishing adequate feeding is a vital component of newborn care (Flaherman & Newman, 2011; Gartner et al.,). The development of feeding skills is a complex process, and attainment of oral feeding skills during the hospital stay is a criteria for allowing discharge home (Stevenson & Allaire, 1991). However, feeding intolerance in the early postnatal period is a common condition and when refusal to feed accompanies repeated vomiting, it can be distressing for health care providers and families (Di Lorenzo, 2012).
T
Feeding intolerance in the newborn might be a symptom of a multitude of conditions that can range from mild, self-limited diseases to severe, life-threatening disorders (Di Lorenzo, 2012; Piazza & Stoll, 2007). It is usually a benign condition; however, some infants exhibit refusal to feed with voluminous and frequent vomiting as a forceful expulsion of the feedings in the first few days after birth, despite being in a good clinical condition. These infants may undergo unnecessary diagnostic evaluations, until vomiting abates within several days under close observation without any treatment. To the best of our knowledge, there is no definition or classification in the literature to describe this condition, giving rise to a diagnostic dilemma. We designed a study to define the characteristic features of infants with transient neonatal
C 2014 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses
http://jognn.awhonn.org
RESEARCH
Cizmeci, M. N. et al.
feeding intolerance (TNFI) to prevent this population from unnecessary mother/infant separation for diagnostic purposes.
Methods Study Population The study was conducted with 48 neonates who were admitted to the Fatih University Medical School’s Neonatal Intensive Care Unit (NICU) Level I from the maternity unit of the same hospital, which is a tertiary care academic center. Enrollment to the study took place between January and December 2011. The study was initiated upon approval by the Local Ethics Committee of Fatih University Medical School. Standard rooming-in was encouraged for all mothers immediately after vaginal delivery and within the first hour after cesarean as per hospital protocol. Inclusion criteria were term gestational age (>37weeks) with no obstetric complications, less than 1 week of age, at least one large-volume vomiting with every feeding attempt, and lactation consultant/nurse practitioner’s expression of infant’s refusal to feed. Preterm infants and term infants with a dysmorphic facial appearance, anatomic malformation of the gastrointestinal system, cleft lip and/or palate, respiratory symptoms, or with a mother with intrapartum fever, prolonged rupture of membranes, and/or chorioamnionitis were excluded. Infants with vomiting who had a good clinical conditions and were able to be fed orally were defined as gastroesophageal reflux (GER) and also excluded from the study. Evaluation of the infant’s clinical condition was left to the nurse practitioner’s or physician’s discretion. The nurse practitioners and lactation consultants who were engaged in the study evaluated the mothers for their understanding of the signs of hunger, including rooting, sucking, fussing, putting hand to mouth, and signs of fullness including closing the mouth, turning the head away, relaxing arms and hands. They also questioned the frequency of feedings (if the mothers were breastfeeding 8–12 times a day) and if the infant was having at least three wet diapers and three stools per day. All infants who had at least one large volume vomiting with every feeding attempt and were unable to be fed orally despite a good latch, which was noted in the maternity unit either by a caregiver, nurse practitioner, or lactation consultant were investigated. Refusal to feed was defined as a neonate’s refusing to latch on or lack of sucking/swallowing while the mother was
JOGNN 2014; Vol. 43, Issue 2
Neonatal feeding intolerance in the maternity ward can be distressing for health care providers and families.
spending adequate effort observed by the lactation consultant. A detailed prenatal maternal and fetal history was obtained before admission to the NICU. It is our policy to evaluate each infant’s serum levels of white blood cell count (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6) upon admission to the NICU along with abdominal radiographs to rule out a possible infection or gastrointestinal obstruction. Any infant with a definitive final diagnosis that may cause vomiting such as early-onset neonatal sepsis, an inborn error of metabolism, urinary tract infection, or intestinal obstruction was excluded from the study. After discharge from the hospital, all infants were prospectively followed at 1, 2, 4, and 6 months of age in the outpatient clinic. Data regarding vomiting or feeding intolerance were recorded in the patient charts.
Laboratory Assessment Venous blood samples were collected and centrifuged at 3000g for 15 min at 4◦ C. IL-6 levels were measured by the Enzyme Amplified Sensitivity Immunoassay (EASIA) method. C-reactive protein levels and complete blood counts were measured in serum specimens.
Statistical Analysis Data were statistically analyzed using SPSS (version 16.0.1). Continuous data regarding the time of the first and last vomit, CRP, and IL-6 were tested for normality using the Kolmogorov-Smirnov test. All the continuous values with nongaussian distribution were presented as median (interquartile range). The categorical values were presented as number and percentage.
Results During the study period, 1280 infants were born in our hospital. Forty-eight (3.75%) neonates with repeated vomiting and refusal to feed were hospitalized from the maternity unit to the NICU Level I on the first postnatal day for further investigation. Twenty infants (42%) with a final diagnosis of early-onset neonatal sepsis, two (4%) with intestinal obstruction, one (2%) with organic acidemia, and one (2%) with urinary tract infection
Ahmet Zulfikar Akelma, MD, is a pediatrician in the Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Naile Tufan, MD, is a pediatrician in the Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Mustafa Mansur Tatli, MD, is a professor in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey.
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Some infants exhibit refusal to feed with vomiting in the first few days after birth, and many undergo unnecessary diagnostic evaluations.
were admitted to Level II and excluded from the study, resulting in 24 neonates evaluated as TNFI (Figure 1). Fifteen (62.5%) of the 24 patients were female; nine (37.5%) patients were male. Ten (41.2%) infants were born via spontaneous vaginal delivery, whereas 14 (58.8%) were delivered via cesarean (eight under general anesthesia and six with epidural anesthesia). Breastfeeding was initiated in the first 3 hours (median 1 hour; interquartile range: 0–3) in all infants. Eighteen (75%) of these infants were exclusively breastfed, whereas six (25%) infants received supplemental formula feedings. When the family histories were investigated, none of these infants had siblings with similar histories. All infants started vomiting in the first day (median 6 hours; interquartile range: 1–24 hours) and experienced recovery by the 48th postnatal hour (median 30 hours; interquartile range: 24–48 hours). When these infants were evaluated for an underlying infection, WBC, CRP, and IL-6 levels were within the normal range in all cases (Table 1). Abdominal radiographs obtained to rule out a possible obstruction revealed no abdominal pathology in any case. Recovery occurred within the 48th postnatal hour in all of the cases and discharge from the hospital was achieved at the third postnatal day (median 60 hours; interquartile range: 50–72 hours). All in-
fants (100%) were exclusively breastfed at the time of discharge from the hospital. All 24 infants with TNFI were reevaluated at 1, 2, 4, and 6 months in the outpatient clinic. Mothers were asked about continuity of vomiting and refusal to feed. None of the infants was reported to have vomited or refused to feed, and all of the infants exhibited normal weight gain.
Discussion Hospitalization after birth in the maternity ward is a critical period for the neonate as dramatic adaptive mechanisms occur in many organ systems to accommodate to the extrauterine environment (Olver, Walters, & Wilson, 2004).Gastrointestinal adaptation is especially important, since the neonate must rapidly adapt from accessing all nutrients via the placenta to obtaining them orally (Burton & Fowden, 2012). In the first few hours after birth, infants may vomit mucus, which rarely persists after a few feedings. Such vomiting may be due to irritation of the gastric mucosa by material swallowed during delivery (Piazza & Stoll, 2007). However, some infants exhibit frequent vomiting along with feeding refusal during the early neonatal period. Despite a good clinical condition, recurrent voluminous vomiting with refusal to feed orally is of concern. We hypothesized that this condition might be a form of transient gastrointestinal maladaptation of the early postnatal period and investigated the characteristic features under close observation. When infants with a final diagnosis that is known to cause vomiting in the early neonatal period were excluded, the remaining infants with TNFI had common features, such as good clinical condition, onset of symptoms in the first day of life, and recovery by the 48th postnatal hour. Negative laboratory tests for sepsis work-up and normal abdominal radiographs for anatomical obstruction further supported the benign nature of
Figure 1. Distribution of the patients in the study population.
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http://jognn.awhonn.org
RESEARCH
Cizmeci, M. N. et al.
this condition. All of the infants were followed up prospectively in the outpatient clinic for 6 months to exclude a possible ongoing problem. The infants had no vomiting or feeding intolerance during well-child visits. Vomiting is a protective mechanism, a complex reflex behavioral response to a variety of stimuli, and may be a symptom of a wide range of conditions from common to complex (Di Lorenzo, 2012). In this context GER, excessive feeding volume, sepsis, pyelonephritis, anatomic insults (e.g., congenital atresias and stenosis, tracheoesophageal fistula, webs and duplications), inguinal hernia, endocrine derangements (e.g., congenital adrenal hyperplasia), increased intracranial pressure, and inborn errors of metabolism are all among the differential diagnosis of feeding intolerance with repeated vomiting (Li & Sunku, 2011). However with a detailed history and physical examination, it is possible to focus on a diagnostic pathway to avoid unnecessary evaluation. Among the variety of conditions that might cause recurrent vomiting, GER may especially be of note.
Table 1: Baseline characteristics and laboratory evaluation of the study population. Patients with TNFI (n = 24) n (%) Gender Male
9 (38)
Female
15 (62)
Route of birth NSVD
9 (38)
NSVD (EA)
1 (4)
Cesarean (GA)
8 (33)
Cesarean (EA)
6 (25)
First vomit, hour median (min-max)
5.75 (1–24)
Last vomit, hour median (min-max)
27.5 (14–48)
CRP (mg/L) median (min-max)
2.43 (1–6.23)
IL-6 (pg/mL) median (min-max)
16.35 (1–56.5)
Note. TNFI = transient neonatal feeding intolerance; EA = epidural anesthesia, GA = general anesthesia, NSVD = normal spontaneous vaginal delivery, TNFI = transient neonatal feeding intolerance.
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Infants with transient neonatal feeding intolerance can be managed with close observation and supportive measures under skilled nursing care.
Physiologic GER is a developmental process that occurs commonly in the neonatal period and resolves spontaneously with maturation, whereas GER disease is present when reflux of gastric contents causes symptoms and/or complications (Sherman et al., 2009). GER appears to be more frequent after feeding, and vomiting is the most common manifestation of this condition (Slocum, Arko, Di Fiore, Martin, & Hibbs, 2009). Despite the bouts of vomiting, the infant looks healthy and the absence of refusal to feed is an important aspect that prevents the care provider from further diagnostic investigation to distinguish the clinical picture from TNFI. Most of the other underlying conditions may be ruled out with a detailed history or laboratory evaluation. Overfeeding due to excessive feeding volumes is elicited by history and observation, whereas sepsis and pyelonephritis may present with poor clinical condition and a positive acute phase reactant (i.e., WBC, CRP and Interleukin-6) (Hofer, Zacharias, Muller, & Resch, 2012; Indrio, Riezzo, Raimondi, Cavallo, & Francavilla, 2009). Obstruction in the gastrointestinal system manifests in the abdominal radiograph, whereas endocrine derangements and inborn errors of metabolism show abnormalities in the electrolyte panel, again with a poor clinical condition (Hryhorczuk & Lee, 2012; Nimkarn, Lin-Su, & New, 2011; Piazza & Stoll, 2007). The ability to safely and efficiently feed by mouth, preferably at the breast, is based on oral-motor competence, neurobehavioral organization, and gastrointestinal maturity. Although most infants successfully achieve oral feedings at term gestation, some might exhibit difficulties in the adaptation period that benefit most from the passage of time (Lemons, 2001). We believe that vomiting and refusal to feed as presentations of feeding intolerance during the early neonatal period may be a form of gastrointestinal maladaptation where close observation and supportive measures will prevent unnecessary diagnostic evaluation and hospital stay. To our knowledge, this phenomenon has not been described previously in the literature. The major limitation of this study was the small sample size, although we describe a condition
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rather than define risk factors. Hence, we believe this cohort of infants may be sufficient to describe a particular condition. Secondly, more than one half of these infants were delivered by cesarean, and a remarkable number of the mothers were exposed to general anesthesia, which is a result of high rates of cesarean in our hospital. However, our objective was to contribute evidence that can be used to prevent the healthy neonatal population from unnecessary diagnostic evaluation, improper treatment, and mother/infant separation. Because very little is known on the physiologic evolution of breastfeeding in natural settings and physiologic transition of infants’ feeding patterns, further studies in large birth centers are warranted to clarify this definition.
Flaherman, V. J., & Newman, T. B. (2011). Regulatory monitoring of feeding during the birth hospitalization. Pediatrics, 127(6), 1177– 1179. doi:10.1542/peds.2011–0056 Gartner, L. M., Morton, J., Lawrence, R. A., Naylor, A. J., O’Hare, D., Schanler, R. J., & Eidelman, A. I. (2005). American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics, 115(2), 496–506. doi:10.1542/peds.2004-2491 Hofer, N., Zacharias, E., Muller, W., & Resch, B. (2012). An update ¨ on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology, 102(1), 25–36. doi:10.1159/000336629 Hryhorczuk, A. L., & Lee, E. Y. (2012). Imaging evaluation of bowel obstruction in children: updates in imaging techniques and review of imaging findings. Seminars in Roentgenology, 47(2), 159– 170. doi:10.1053/j.ro.2011.11.007 Indrio, F., Riezzo, G., Raimondi, F., Cavallo, L., & Francavilla, R. (2009). Regurgitation in healthy and non healthy infants. Italian Journal Pediatrics, 35(1), 35–39. doi:10.1186/1824-7288-35-39 Lemons, P. K. (2001). From gavage to oral feedings: just a matter of time. Neonatal Network, 20(3), 7–14. doi:10.1891/0730-
Conclusion Refusal to feed with recurrent vomiting is a common presentation of feeding intolerance during hospitalization after birth in the maternity ward. We have observed that infants with this condition can be managed with close observation and supportive measures under skilled nursing care. Further clarification of this terminology will help health care providers protect newborn infants from harmful effects of unnecessary medical interventions, prolonged hospital stay, and mother/infant separation by recognizing the benign nature of this transient condition.
0832.20.3.7 Li, B. U. K., & Sunku, B. K. (2011). Vomiting and nausea. In R. Wyllie, J. S. Hyams, & M. Kay (Eds.), Pediatric gastrointestinal and liver disease (pp. 151–242). Philadelphia, PA: Saunders. Nimkarn, S., Lin-Su, K., & New, M. I. (2011). Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. Pediatric Clinics of North America, 58(59), 1281–1300. doi:10.1016/ j.pcl.2011.07.012 Olver, R. E., Walters, D. V., & M Wilson, S. (2004). Developmental regulation of lung liquid transport. Annual Review of Physiology, 66, 77–101. doi:10.1146/annurev.physiol. 66.071702.145229 Piazza, A. J., & Stoll, B. S. (2007). Digestive system disorders. In R. M. Kliegman, R. E. Behrman, H. B. Jenson, & B. F. Stanton (Eds.), Nelson textbook of pediatrics (pp. 1521–1719). Philadelphia, PA: Saunders. Sherman, P. M., Hassall, E., Fagundes-Neto, U., Gold, B. D., Kato, S., Koletzko, S., Orenstein, S., Rudolph, C., Vakil, N., & Vandenplas, Y. (2009). A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric popula-
REFERENCES Burton, G. J., & Fowden, A. L. (2012). Review: The placenta and developmental programming: balancing fetal nutrient demands with maternal resource allocation. Placenta, 33(2), 3–10. doi:10.1016/j.placenta.2011.11.013 Di Lorenzo, C. (2012). Approach to the infant and child with nausea and vomiting. Retrieved from http://www.uptodate.com/contents/ approach-to-the-infant-or-child-with-nausea-and-vomiting
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tion. American Journal of Gastroenterology, 104(5), 1278–1295. doi:10.1038/ajg.2009.129 Slocum, C., Arko, M., Di Fiore, J., Martin, R. J., & Hibbs, A. M. (2009). Apnea, bradycardia and desaturation in preterm infants before and after feeding. Journal of Perinatology, 29(3), 209–212. doi:10.1038/jp.2008.226 Stevenson, R. D., & Allaire, J. H. (1991). The development of normal feeding and swallowing. Pediatric Clinics of North America, 38(6), 1439–1453.
http://jognn.awhonn.org
RESEARCH
A Descriptive Study of Transient Neonatal Feeding Intolerance in a Tertiary Care Center in Turkey Mehmet Nevzat Cizmeci, Mehmet Kenan Kanburoglu, Ahmet Zulfikar Akelma, Naile Tufan, and Mustafa Mansur Tatli
Correspondence Mehmet Nevzat Cizmeci, MD Department of Pediatrics Division of Neonatology Fatih University Medical School, 06510 Emek/Ankara, Turkey [email protected] Keywords feeding intolerance newborn refusal to feed vomiting in infancy
ABSTRACT Objective: To investigate the characteristic features of transient neonatal feeding intolerance (TNFI) during the hospitalization for birth in the maternity ward. Design: A prospective follow-up study. Setting: Maternity ward and neonatal intensive care unit (NICU) in an academic medical center. Participants: Term (≥ 37-weeks gestation) infants admitted to the neonatal intensive care unit with recurrent vomiting and refusal to feed between January and December 2011. These infants were prospectively followed-up at 1, 2, 4, 6 months of age in the outpatient clinic. Results: During the study period 1280 infants were evaluated in the maternity ward. Forty-eight (3.75%) neonates with repeated vomiting and refusal to feed were hospitalized from the maternity unit to the NICU Level I on the first postnatal day for further investigation. All infants started vomiting in the first day (median 5.75 hours; interquartile range: 1–24) and recovered by the 48th postnatal hour (median 27.5 hours; interquartile range: 14–48 hours). Laboratory and imaging studies showed no abnormalities. After discharge, 6-month follow-up of these infants showed no vomiting or feeding intolerance during well-child visits. Conclusions: Infants with TNFI can be managed with close observation and supportive measures if they have no other indications of underlying disease. We believe that expectant management and supportive measures under skilled nursing care will prevent unnecessary diagnostic evaluation, mother/infant separation, and prolonged hospital stay.
JOGNN, 43, 200-204; 2014. DOI: 10.1111/1552-6909.12292 Accepted December 2013
Mehmet Nevzat Cizmeci, MD, is a neonatology fellow in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Mehmet Kenan Kanburoglu, MD, is a neonatology fellow in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey.
(Continued)
The authors report no conflict of interest or relevant financial relationships.
200
he ability to feed by mouth is of paramount importance in the newborn infant, and successful achievement of breastfeeding during the birth hospitalization in the maternity ward is a critical task for the infant/mother dyad. A full-term infant should be offered the breast as soon after the birth as possible, preferably within the first hour after delivery (Gartner et al., 2005). Establishing adequate feeding is a vital component of newborn care (Flaherman & Newman, 2011; Gartner et al.,). The development of feeding skills is a complex process, and attainment of oral feeding skills during the hospital stay is a criteria for allowing discharge home (Stevenson & Allaire, 1991). However, feeding intolerance in the early postnatal period is a common condition and when refusal to feed accompanies repeated vomiting, it can be distressing for health care providers and families (Di Lorenzo, 2012).
T
Feeding intolerance in the newborn might be a symptom of a multitude of conditions that can range from mild, self-limited diseases to severe, life-threatening disorders (Di Lorenzo, 2012; Piazza & Stoll, 2007). It is usually a benign condition; however, some infants exhibit refusal to feed with voluminous and frequent vomiting as a forceful expulsion of the feedings in the first few days after birth, despite being in a good clinical condition. These infants may undergo unnecessary diagnostic evaluations, until vomiting abates within several days under close observation without any treatment. To the best of our knowledge, there is no definition or classification in the literature to describe this condition, giving rise to a diagnostic dilemma. We designed a study to define the characteristic features of infants with transient neonatal
C 2014 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses
http://jognn.awhonn.org
RESEARCH
Cizmeci, M. N. et al.
feeding intolerance (TNFI) to prevent this population from unnecessary mother/infant separation for diagnostic purposes.
Methods Study Population The study was conducted with 48 neonates who were admitted to the Fatih University Medical School’s Neonatal Intensive Care Unit (NICU) Level I from the maternity unit of the same hospital, which is a tertiary care academic center. Enrollment to the study took place between January and December 2011. The study was initiated upon approval by the Local Ethics Committee of Fatih University Medical School. Standard rooming-in was encouraged for all mothers immediately after vaginal delivery and within the first hour after cesarean as per hospital protocol. Inclusion criteria were term gestational age (>37weeks) with no obstetric complications, less than 1 week of age, at least one large-volume vomiting with every feeding attempt, and lactation consultant/nurse practitioner’s expression of infant’s refusal to feed. Preterm infants and term infants with a dysmorphic facial appearance, anatomic malformation of the gastrointestinal system, cleft lip and/or palate, respiratory symptoms, or with a mother with intrapartum fever, prolonged rupture of membranes, and/or chorioamnionitis were excluded. Infants with vomiting who had a good clinical conditions and were able to be fed orally were defined as gastroesophageal reflux (GER) and also excluded from the study. Evaluation of the infant’s clinical condition was left to the nurse practitioner’s or physician’s discretion. The nurse practitioners and lactation consultants who were engaged in the study evaluated the mothers for their understanding of the signs of hunger, including rooting, sucking, fussing, putting hand to mouth, and signs of fullness including closing the mouth, turning the head away, relaxing arms and hands. They also questioned the frequency of feedings (if the mothers were breastfeeding 8–12 times a day) and if the infant was having at least three wet diapers and three stools per day. All infants who had at least one large volume vomiting with every feeding attempt and were unable to be fed orally despite a good latch, which was noted in the maternity unit either by a caregiver, nurse practitioner, or lactation consultant were investigated. Refusal to feed was defined as a neonate’s refusing to latch on or lack of sucking/swallowing while the mother was
JOGNN 2014; Vol. 43, Issue 2
Neonatal feeding intolerance in the maternity ward can be distressing for health care providers and families.
spending adequate effort observed by the lactation consultant. A detailed prenatal maternal and fetal history was obtained before admission to the NICU. It is our policy to evaluate each infant’s serum levels of white blood cell count (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6) upon admission to the NICU along with abdominal radiographs to rule out a possible infection or gastrointestinal obstruction. Any infant with a definitive final diagnosis that may cause vomiting such as early-onset neonatal sepsis, an inborn error of metabolism, urinary tract infection, or intestinal obstruction was excluded from the study. After discharge from the hospital, all infants were prospectively followed at 1, 2, 4, and 6 months of age in the outpatient clinic. Data regarding vomiting or feeding intolerance were recorded in the patient charts.
Laboratory Assessment Venous blood samples were collected and centrifuged at 3000g for 15 min at 4◦ C. IL-6 levels were measured by the Enzyme Amplified Sensitivity Immunoassay (EASIA) method. C-reactive protein levels and complete blood counts were measured in serum specimens.
Statistical Analysis Data were statistically analyzed using SPSS (version 16.0.1). Continuous data regarding the time of the first and last vomit, CRP, and IL-6 were tested for normality using the Kolmogorov-Smirnov test. All the continuous values with nongaussian distribution were presented as median (interquartile range). The categorical values were presented as number and percentage.
Results During the study period, 1280 infants were born in our hospital. Forty-eight (3.75%) neonates with repeated vomiting and refusal to feed were hospitalized from the maternity unit to the NICU Level I on the first postnatal day for further investigation. Twenty infants (42%) with a final diagnosis of early-onset neonatal sepsis, two (4%) with intestinal obstruction, one (2%) with organic acidemia, and one (2%) with urinary tract infection
Ahmet Zulfikar Akelma, MD, is a pediatrician in the Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Naile Tufan, MD, is a pediatrician in the Department of Pediatrics, Fatih University Medical School, Ankara, Turkey. Mustafa Mansur Tatli, MD, is a professor in the Division of Neonatology, Department of Pediatrics, Fatih University Medical School, Ankara, Turkey.
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Some infants exhibit refusal to feed with vomiting in the first few days after birth, and many undergo unnecessary diagnostic evaluations.
were admitted to Level II and excluded from the study, resulting in 24 neonates evaluated as TNFI (Figure 1). Fifteen (62.5%) of the 24 patients were female; nine (37.5%) patients were male. Ten (41.2%) infants were born via spontaneous vaginal delivery, whereas 14 (58.8%) were delivered via cesarean (eight under general anesthesia and six with epidural anesthesia). Breastfeeding was initiated in the first 3 hours (median 1 hour; interquartile range: 0–3) in all infants. Eighteen (75%) of these infants were exclusively breastfed, whereas six (25%) infants received supplemental formula feedings. When the family histories were investigated, none of these infants had siblings with similar histories. All infants started vomiting in the first day (median 6 hours; interquartile range: 1–24 hours) and experienced recovery by the 48th postnatal hour (median 30 hours; interquartile range: 24–48 hours). When these infants were evaluated for an underlying infection, WBC, CRP, and IL-6 levels were within the normal range in all cases (Table 1). Abdominal radiographs obtained to rule out a possible obstruction revealed no abdominal pathology in any case. Recovery occurred within the 48th postnatal hour in all of the cases and discharge from the hospital was achieved at the third postnatal day (median 60 hours; interquartile range: 50–72 hours). All in-
fants (100%) were exclusively breastfed at the time of discharge from the hospital. All 24 infants with TNFI were reevaluated at 1, 2, 4, and 6 months in the outpatient clinic. Mothers were asked about continuity of vomiting and refusal to feed. None of the infants was reported to have vomited or refused to feed, and all of the infants exhibited normal weight gain.
Discussion Hospitalization after birth in the maternity ward is a critical period for the neonate as dramatic adaptive mechanisms occur in many organ systems to accommodate to the extrauterine environment (Olver, Walters, & Wilson, 2004).Gastrointestinal adaptation is especially important, since the neonate must rapidly adapt from accessing all nutrients via the placenta to obtaining them orally (Burton & Fowden, 2012). In the first few hours after birth, infants may vomit mucus, which rarely persists after a few feedings. Such vomiting may be due to irritation of the gastric mucosa by material swallowed during delivery (Piazza & Stoll, 2007). However, some infants exhibit frequent vomiting along with feeding refusal during the early neonatal period. Despite a good clinical condition, recurrent voluminous vomiting with refusal to feed orally is of concern. We hypothesized that this condition might be a form of transient gastrointestinal maladaptation of the early postnatal period and investigated the characteristic features under close observation. When infants with a final diagnosis that is known to cause vomiting in the early neonatal period were excluded, the remaining infants with TNFI had common features, such as good clinical condition, onset of symptoms in the first day of life, and recovery by the 48th postnatal hour. Negative laboratory tests for sepsis work-up and normal abdominal radiographs for anatomical obstruction further supported the benign nature of
Figure 1. Distribution of the patients in the study population.
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Cizmeci, M. N. et al.
this condition. All of the infants were followed up prospectively in the outpatient clinic for 6 months to exclude a possible ongoing problem. The infants had no vomiting or feeding intolerance during well-child visits. Vomiting is a protective mechanism, a complex reflex behavioral response to a variety of stimuli, and may be a symptom of a wide range of conditions from common to complex (Di Lorenzo, 2012). In this context GER, excessive feeding volume, sepsis, pyelonephritis, anatomic insults (e.g., congenital atresias and stenosis, tracheoesophageal fistula, webs and duplications), inguinal hernia, endocrine derangements (e.g., congenital adrenal hyperplasia), increased intracranial pressure, and inborn errors of metabolism are all among the differential diagnosis of feeding intolerance with repeated vomiting (Li & Sunku, 2011). However with a detailed history and physical examination, it is possible to focus on a diagnostic pathway to avoid unnecessary evaluation. Among the variety of conditions that might cause recurrent vomiting, GER may especially be of note.
Table 1: Baseline characteristics and laboratory evaluation of the study population. Patients with TNFI (n = 24) n (%) Gender Male
9 (38)
Female
15 (62)
Route of birth NSVD
9 (38)
NSVD (EA)
1 (4)
Cesarean (GA)
8 (33)
Cesarean (EA)
6 (25)
First vomit, hour median (min-max)
5.75 (1–24)
Last vomit, hour median (min-max)
27.5 (14–48)
CRP (mg/L) median (min-max)
2.43 (1–6.23)
IL-6 (pg/mL) median (min-max)
16.35 (1–56.5)
Note. TNFI = transient neonatal feeding intolerance; EA = epidural anesthesia, GA = general anesthesia, NSVD = normal spontaneous vaginal delivery, TNFI = transient neonatal feeding intolerance.
JOGNN 2014; Vol. 43, Issue 2
Infants with transient neonatal feeding intolerance can be managed with close observation and supportive measures under skilled nursing care.
Physiologic GER is a developmental process that occurs commonly in the neonatal period and resolves spontaneously with maturation, whereas GER disease is present when reflux of gastric contents causes symptoms and/or complications (Sherman et al., 2009). GER appears to be more frequent after feeding, and vomiting is the most common manifestation of this condition (Slocum, Arko, Di Fiore, Martin, & Hibbs, 2009). Despite the bouts of vomiting, the infant looks healthy and the absence of refusal to feed is an important aspect that prevents the care provider from further diagnostic investigation to distinguish the clinical picture from TNFI. Most of the other underlying conditions may be ruled out with a detailed history or laboratory evaluation. Overfeeding due to excessive feeding volumes is elicited by history and observation, whereas sepsis and pyelonephritis may present with poor clinical condition and a positive acute phase reactant (i.e., WBC, CRP and Interleukin-6) (Hofer, Zacharias, Muller, & Resch, 2012; Indrio, Riezzo, Raimondi, Cavallo, & Francavilla, 2009). Obstruction in the gastrointestinal system manifests in the abdominal radiograph, whereas endocrine derangements and inborn errors of metabolism show abnormalities in the electrolyte panel, again with a poor clinical condition (Hryhorczuk & Lee, 2012; Nimkarn, Lin-Su, & New, 2011; Piazza & Stoll, 2007). The ability to safely and efficiently feed by mouth, preferably at the breast, is based on oral-motor competence, neurobehavioral organization, and gastrointestinal maturity. Although most infants successfully achieve oral feedings at term gestation, some might exhibit difficulties in the adaptation period that benefit most from the passage of time (Lemons, 2001). We believe that vomiting and refusal to feed as presentations of feeding intolerance during the early neonatal period may be a form of gastrointestinal maladaptation where close observation and supportive measures will prevent unnecessary diagnostic evaluation and hospital stay. To our knowledge, this phenomenon has not been described previously in the literature. The major limitation of this study was the small sample size, although we describe a condition
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Transient Neonatal Feeding Intolerance in Turkey
rather than define risk factors. Hence, we believe this cohort of infants may be sufficient to describe a particular condition. Secondly, more than one half of these infants were delivered by cesarean, and a remarkable number of the mothers were exposed to general anesthesia, which is a result of high rates of cesarean in our hospital. However, our objective was to contribute evidence that can be used to prevent the healthy neonatal population from unnecessary diagnostic evaluation, improper treatment, and mother/infant separation. Because very little is known on the physiologic evolution of breastfeeding in natural settings and physiologic transition of infants’ feeding patterns, further studies in large birth centers are warranted to clarify this definition.
Flaherman, V. J., & Newman, T. B. (2011). Regulatory monitoring of feeding during the birth hospitalization. Pediatrics, 127(6), 1177– 1179. doi:10.1542/peds.2011–0056 Gartner, L. M., Morton, J., Lawrence, R. A., Naylor, A. J., O’Hare, D., Schanler, R. J., & Eidelman, A. I. (2005). American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics, 115(2), 496–506. doi:10.1542/peds.2004-2491 Hofer, N., Zacharias, E., Muller, W., & Resch, B. (2012). An update ¨ on the use of C-reactive protein in early-onset neonatal sepsis: current insights and new tasks. Neonatology, 102(1), 25–36. doi:10.1159/000336629 Hryhorczuk, A. L., & Lee, E. Y. (2012). Imaging evaluation of bowel obstruction in children: updates in imaging techniques and review of imaging findings. Seminars in Roentgenology, 47(2), 159– 170. doi:10.1053/j.ro.2011.11.007 Indrio, F., Riezzo, G., Raimondi, F., Cavallo, L., & Francavilla, R. (2009). Regurgitation in healthy and non healthy infants. Italian Journal Pediatrics, 35(1), 35–39. doi:10.1186/1824-7288-35-39 Lemons, P. K. (2001). From gavage to oral feedings: just a matter of time. Neonatal Network, 20(3), 7–14. doi:10.1891/0730-
Conclusion Refusal to feed with recurrent vomiting is a common presentation of feeding intolerance during hospitalization after birth in the maternity ward. We have observed that infants with this condition can be managed with close observation and supportive measures under skilled nursing care. Further clarification of this terminology will help health care providers protect newborn infants from harmful effects of unnecessary medical interventions, prolonged hospital stay, and mother/infant separation by recognizing the benign nature of this transient condition.
0832.20.3.7 Li, B. U. K., & Sunku, B. K. (2011). Vomiting and nausea. In R. Wyllie, J. S. Hyams, & M. Kay (Eds.), Pediatric gastrointestinal and liver disease (pp. 151–242). Philadelphia, PA: Saunders. Nimkarn, S., Lin-Su, K., & New, M. I. (2011). Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. Pediatric Clinics of North America, 58(59), 1281–1300. doi:10.1016/ j.pcl.2011.07.012 Olver, R. E., Walters, D. V., & M Wilson, S. (2004). Developmental regulation of lung liquid transport. Annual Review of Physiology, 66, 77–101. doi:10.1146/annurev.physiol. 66.071702.145229 Piazza, A. J., & Stoll, B. S. (2007). Digestive system disorders. In R. M. Kliegman, R. E. Behrman, H. B. Jenson, & B. F. Stanton (Eds.), Nelson textbook of pediatrics (pp. 1521–1719). Philadelphia, PA: Saunders. Sherman, P. M., Hassall, E., Fagundes-Neto, U., Gold, B. D., Kato, S., Koletzko, S., Orenstein, S., Rudolph, C., Vakil, N., & Vandenplas, Y. (2009). A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric popula-
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