Failure to thrive

Feeding problems, vomiting and short stature in prematurely born child
Short Summary

The patient is a 21 month old female who was born prematurely (at almost 29 weeks) weighing only 650g. She was released after 3 months from NICU, when she was 41 weeks old, weight 2kg. Her parents did not have any problems till she was 5 months old. Her major problems since have been: poor feeding, failure to gain weight and linear growth retardation. The poor feeding has been handled by an NG tube and later, food administration through a direct gastric tube via a gastrostomy. She gradually gained weight to the extent of being overweight for her height and subsequently she was weaned from gastrostomy. She failed to improve her height in spite of increased weight and vomiting continued as before. All along, her development has been normal for her corrected age (both motor and cognitive). She underwent allergies, endocrynology and genetic workup regarding her short stature (as described below) that was normal.

Patient's Questions

1. What’s causing the vomiting and how can it be handled?
2. Are the feeding problems caused by the vomiting?
3. If not, what is the cause of the feeding problems and how can it be handled?
4. Is the short stature caused by the feeding problems?
5. If not, what is the cause of the short stature and how can it be handled?

Medical Background

The patient was born prematurely (gestational week 28+6), weight 650g, 31cm long (IUGR). According to her parents,she had no major problems in the NICU or premature ward. She was released after 3 months, when she was 41 weeks old, weight 2kg. Her parents did not have any problems till she was 5 months old. She gained a kilo in a little more than a month. She was not a great eater (never really asked for food like a regular child) but she succeeded in eating approximately 130cc/kg/day. She was eating breast milk, then partially breast milk, partially formula. Around the same time she started to vomit. The more she vomited, the less she ate. Her parents tried different formulas without success.

By the age of 6 months she was hospitalized under the heading of failure to thrive and anorexia. The following work up was done during this hospitalization:

  1. Ultra-sound for pyloric stenosis – normal.
  2. Renal function – normal.
  3. Metabolic disorders – normal.
  4. Brain MRI – normal.
  5. Barium contrast study – showed mild reflux.

For several months around the same time she was treated with Zantac and Losec (anti reflux medication) which had no visible effect. At the end of 2 weeks of hospitalization, she gained a bit of weight and she was released while nothing was actually solved.

As the anorexia and vomiting continued and she was now 4 months of corrected age and still 3 kg, she was put on NG tube feeding for 3 weeks. She gained weight but she vomited a lot (about 3 to 5 times per day). Her parents therefore arrived at considering the gastrostomy. They did a last trial of feeding her as much as she wanted when she would want (cry). She ate about half of what she should have and lost close to 300 gr in less than a week. She was now about 5 months of corrected age, and weighed 2.8 kg. They did the gastrostomy.

The patient gained weight nicely in the following months with the gastrostomy but never ceased to vomit between 1 to 5 times per day. Her parents were advised against the fundoplication on the basis that it has its own side effects and she was gaining weight.

She was now 1 year of corrected age and 15 month of chronological age. She weighed 7.2 kg and was only 61cm long. She was fat for her lengh and looked fat. There was no change in terms of the vomiting and she was no longer eating by mouth at all. All her food was being given to her straight through the gastrostomy tube. No other food, spoon or anything else would be accepted by her either.

Her parents, therefore followed a protocol for weaning a child off of a gastrostomy (48 hours wean). She hardly ate the first 2 days but then restarted with oral feeding by bottle and within a few days her parents stopped feeding her by tube completely.She was not eating enough but as her parents were told that she needed to lose weight  they continued hoping that things would adjust themselves. After 4 months she had gone down to 6.5kg very slowly but had not gained or regained any weight. She would eat 500cc of Nutren Junior in a day whereas she needs about 650 to 700 to gain weight. Vomiting continued as before. Very recently her parents started to complete her meals by using the tube and she is slowly regaining weight. However she still vomits daily and weight gain is not easy.

An important thing to note is that it is visible on her growth chart that she only grows in height/length when she receives sufficient amount of calories. Otherwise there is no growth whatsoever. It is to be noted also, that all along her development has been normal for her corrected age (both motor and cognitive).

She eats only the Nutren Junior of Nestle. She does not eat with a spoon and eats no solid food. Nothing enters her mouth except her own fingers or cloth that she sucks on ,or the nipple of the Nutren bottle. She lightly licks some food. Her vomiting is unchanged. It can happen right after the food or 3 hours after a meal. It also happens while she sleeps. It can and does also happen on a completely empty stomach and only mucus or water comes out. Eating causes the appearing of mucus instantly. Her parents report that when she drinks about 50cc they can hear wet mucus in her throat/way and this is usually when she will stop eating.

Since the age of 5 months, there were two periods of times (two weeks each) where she didn’t vomit at all. Both occurred after a two days fasting (once after she had the gastrostomy insertion operation and was fed by IV and once after the 48 hours wean of gastrostomy feeding). She also had been tested for allergies and she was not found to be allergic.

She was seen by 2 endocrynologist with regards to her very short stature.
Endocrynology workup:
1. Glucaton test indicated growth hormones normal.
2. X rays were done to determine her bone age and diseases-the parents were told that the result were unconclusive.

Genetics workup

  1. Familial dysautonomia- negative.
  2. Sweat test for CF- negative
  3. Bloom syndrome- negative.
  4. Russel Silver syndrome- negative.
  5. Cockayne Syndrome- negative.
  6. Check of many genetic disorders done in the US (see attached) found nothing as well.

Expert's Opinion

The patient is a 21 month old female who was born by C section to a 38y old mother (1st delivery, second pregnancy) at almost 29 weeks weighing only 650g and with birth height of 31 cm (her parents average height was 157cm). She was born at Apgar 6 at one minute and seven at five minutes. She received CPAP and 26% oxygen. Her physical examination appeared normal.
Head ultrasound was essentially normal. She suffered episodes of apnea and bradycardia for more than 2 months for which she received Theophylline. She had 2 possible infection episodes one was a sepsis workup at day 1 of life and the other at day 11.
Mother received 2 courses of steroids beginning at 22-23 weeks gestation for IUGR. No mention of head circumference at birth. Neurological assessment was apparently normal, in and after NICU.

Her major problems since have been: poor feeding, failure to gain weight and linear growth retardation. The poor feeding has been handled by an NG tube and subsequently, food administration through a direct gastric tube via a gastrostomy. I understand that weight gain improved dramatically following this mode of nutrition. She gradually gained weight to the extent of being overweight for her height. This would suggest that she may not have a problem in absorbing nutrients but rather a possible aversion to food as well as failure to progress normally with linear growth. Laboratory evaluation at 6 and 8 months revealed low absolute numbers of neutrophils in the first evaluation and low lymphocyte count at both assessments. No other evaluations were provided. Various genetic testing for Familial dysautonomia, Cockayne syndrome, Bloom syndrome and Russel Silver syndrome were normal as well as whole genome scanning using CGH array and evaluation of copy number variants did not reveal an obvious anomally. Sweat chloride test for CF was negative as was the metabolic screen. Further, transcription coupled DNA repair was tested and found normal.

Answers to parents questions:
1. Vomiting small amounts of food is not uncommon in infancy and more so in children who receive feeding through an NG or a gastrostomy. What is important is the frequency and amount of nutrition lost. I understand that inspite of the gastric feeding, she gained weight very well, suggesting that the amount of vomiting was not critical. I therefore do not think that the feeding problems are caused by the vomiting. To reduce vomiting, in such patients, it is recommended to use smaller volumes more frequently.
2. Feeding in infants and children is a complex process. It requires timely introduction of various foods, like solids, in order for a normal eating pattern to take place. Sometimes by missing a window of opportunity, food aversions and feeding disorders may develop. Physicians have to rule out first mechanical or other known causes of feeding disorders which was largely already done in this case.
3. Short stature may be in general terms either primary or secondary. Secondary growth retardation may be seen in very sick babies or the ones who do not get sufficient calories. Without the consumption of solid foods it is hard to introduce sufficient amounts of protein and other nutrients in the diet. Gradual dietary modifications to change feeding habits may prove beneficial.
4. There are many causes for primary growth retardation. Short stature may be a feature associated with several syndromes. Most were excluded in this case by doing CGH and other more specific tests. The lack of neurological involvement also excludes many possible syndromes.
In conclusion, the patient suffers possible anorexia and failure to progress normally with linear growth. The fact that she was born small for gestational age and she failed to improve her height in spite of increased weight, raises the possibility that she might have an underlying disorder. I would therefore recommend the following.

Recommendations:
1. A more consistent assessment of lymphocyte and neutrophil counts should be carried out. On 2 occasions the absolute lymph count was low.
2. Evaluation of the immune system including lymphocyte markers and mitogen responses should be performed.
3. A skeletal survey should be done to exclude skeletal dysplasia such as cartilage hair hypoplasia or others (bone age is insufficient).
4. If lymphocyte and neutrophil counts are consistently low, a bone marrow should be considered.
5. Endocrine abnormalities should be checked thoroughly (parathyroid, thyroid, adrenal etc.)
6. Molecular analysis for RMRP and AIRE genes should be considered.

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