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Clinical nutrition, enteral and parenteral nutrition

Long-term effects of enteral feeding on growth and mental health in adolescents with anorexia nervosa—results of a retrospective German cohort study

Abstract

Background/objective:

Anorexia nervosa (AN) is a severe eating disorder with a high mortality rate. Treatment regimes show regional and global variation and are sometimes supported by enteral feeding (EF) via nasogastric tube, although risks and benefits are still unclear. We aimed to find out whether EF improves growth and AN recovery and prevents psychiatric comorbidities.

Subjects/methods:

Data were retrospectively collected from medical records and follow-up data were collected via questionnaires. Two hundred and eight female AN patients who were hospitalized below the age of 18 years with a mean follow-up of 6 years were analyzed. We calculated relative risks for the association between EF and suboptimal growth, remission of AN and the occurrence of psychiatric comorbidities, adjusting for potential confounders.

Results:

A third of the analyzed girls received EF at any time. In the adjusted analyses, we found no significant associations between EF and suboptimal growth, the persistence of AN and the occurrence of psychiatric comorbidities, respectively.

Conclusion:

Our data suggest EF to be neither a risk factor nor beneficial for growth, recovery or persistence of AN and the occurrence of psychiatric comorbidities.

Introduction

Anorexia nervosa (AN) is an eating disorder related with severe weight loss and disturbance of body function affecting mostly female children and adolescents.1 Though AN is a rare disease with a prevalence of some 0.3%, it is the mental disorder with the highest mortality.2 A mortality rate of at least 4% per decade of follow-up was reported to be related to AN.3 Early onset of AN can be a risk factor for impaired growth of body length.4, 5 Furthermore, about 20% of the AN patients remain chronically ill and up to 70% develop psychiatric comorbidities.6

There are different approaches for treating AN, such as family therapy, individual psychological therapies, inpatient care and psychopharmacologic interventions.7, 8 Parenteral nutrition and enteral feeding (EF) via nasogastric tube are suggested to be successful opportunities to support AN therapy.9, 10, 11 This kind of compulsory treatment is increasingly challenged in young patients unwilling or unable to consent to the procedure.12 EF seems to be a tightrope walk: preventing starvation in the malnourished patient confronts to leaving out his individuality and freedom.12 EF is not only a psychological but also a physiological challenge for the patient and, thus, it should be planned and managed carefully.13 As a result, EF is claimed to be the last resort in AN therapy.13

The literature does not provide sufficient evidence to identify an optimal AN therapy.8 The current German guidelines state that forced EF ‘should only take place when all other measures have been exhausted’.14 There are only few studies with very small sample sizes on the efficiency of EN,10, 15 which did not provide evidence for recommendations.

We therefore analyzed in a retrospective study the association between EF and the three outcomes: suboptimal growth, persistence of AN and occurrence of other mental disorders at follow-up.

Materials and methods

Participants

Patients were recruited in four hospital units for child and adolescent psychiatry and psychosomatic paediatrics in Northern Germany. Two researchers reviewed medical records of AN patients, as defined by ICD-10, in the respective hospital. The head of the service invited former patients by mail to participate in a follow-up study. To reach as many patients as possible, not responding persons were contacted by telephone.

Patients were included eligible if they met the following inclusion criteria:

  • – at least one inpatient visit in one of the four included hospitals between 1996–2006

  • – AN was the main reason for admission

  • – hospitalization for more than 14 days

  • – last in-patient visit at least one year ago at time point of reviewing medical records

  • – age at first admission was below 18 years

  • – female sex

Treatment regimes across the four units were similar and included at least individual psychological therapy and family therapy during the in-patient stay.

We included only females, as males are not comparable pertaining the characteristics of AN.16 Patients with incomplete data on EF, age and height (n=57) were excluded.

Ethics approval was obtained from the Ethical Review Board at the University of Lübeck and written informed consent was obtained from participants.

Data collection

Data collection was conducted in two stages: first, data were abstracted from medical records. These included: information on sex, date of birth, dates of hospital admission and discharge, repeated hospitalizations, outpatient therapies, psychiatric comorbidities, anthropometric data, type of AN, comorbidities, occurrence of menarche and EF.

Second, a follow-up was conducted by contacting the patients via mail and asking them to answer questionnaires to assess the persistence or relapse of eating disorders and occurrence of any other mental disorders. Furthermore, a self-created questionnaire was used to obtain data about the current life situation, physical health, age and anthropometric data.

The Structured Inventory for Anorexic and Bulimic Eating Disorders (SIAB-S)17 was used to determine the presence of AN at follow-up. This standardized validated questionnaire on eating disorders collects self-reported information on AN, bulimia nervosa (BN), binge eating disorders and eating disorders not otherwise specified (EDNOS) as defined by DSM-IV18 (EDNOS) and ICD-101 (AN, BN). Presence of AN was defined as meeting at least three ICD-10 criteria for AN. In the following text we use the word ‘recovery’ for no longer diagnosis of AN.

The occurrence of other mental disorders (except eating disorders) was identified with the Hopkins Symptom Checklist (SCL-90-R),19 which enables a quantification of the general psychopathology based on self-reported physiological and psychological symptoms. A mental disorder was suspected by a General Symptomatic Index of 60 or more.19

Definitions of variables

The explanatory variable EF was dichotomized and defined as any EF at any hospitalization versus no EF. Height percentiles were calculated using the current German age- and sex-specific height references.20 Body mass index (BMI) was defined as body weight divided by squared body length (kg/m2). BMI s.d. scores are based on German age- and sex-specific reference percentiles for BMI.21 As the patients had different follow-up periods due to varying starting points we report the time since last discharge as a proxy for follow-up time. The three outcomes optimal growth, persistence of AN and occurrence of other psychiatric comorbitities were dichotomized (yes/no). We used body length percentiles in increments of 10 to define optimal and suboptimal growth of height; girls who maintained their initial height decile until follow-up or reached a higher decile had optimal growth. Girls who fell on a lower decile had suboptimal growth. As in girls with a body height below the third percentile both initially and at follow-up, suboptimal growth could not be defined, these girls were included in the category ‘optimal growth’, although the girls might not realize their full growth potential.

Statistical analyses

For descriptive analyses, we compared characteristics of responders with non-responders and tube-fed with non-tube-fed girls. We further compared patients with and without optimal growth of height, patients with and without persistent AN at follow-up and patients with and without occurrence of any other mental disorders at follow-up. Data are shown as mean and s.d. or frequency (%) as appropriate. To test for statistical significant differences between the two respective groups we used t-test or Pearson’s χ2-test, respectively (α=0.05).

We calculated Poisson Regression models to quantify the association of EF with growth, remission of AN and the occurrence of other mental disorders. Relative risks (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated for crude and adjusted models. All variables that were significantly associated with the exposure and the respective outcome, as suggested in the descriptive analyses, were considered as potential confounders. These variables were added stepwise to the models. We additionally performed some stratified analyses to detect potential effect modification (data not shown).

We calculated the detectable RR assuming a study power of 80% and a 5% level of significance by using the software Power and Sample Size Calculations version 2.1.31.

Descriptive and regression analyses were performed using SAS 9.2 for Windows.

In addition, we calculated a propensity score22 considering age at beginning of disease, BMI at first hospitalization and time between diagnosis and hospitalization as covariates. On the basis of the calculated propensity score subclasses (quintiles) were formed and RRs between tube feeding and the specific outcome were calculated for each quintile. The RRs were pooled using Mantel–Haenzel method.

Results

Five hundred and twenty-eight patients met the inclusion criteria and data were abstracted from the records, 265 of whom agreed to participate in our study. Two hundred and sixty-three patients did not participate because they could not be contacted, refused because they did not wish to talk about the disease again, had no time, had unsuccessful therapy or did not want to give confident information. After excluding subjects with incomplete data (n=57) 208 remained for our analyses (Figure 1). The contribution of the four sites ranged from 16–32% of the entire sample. The median follow-up period was 5.5 years (mean: 6.3 years) and ranged between 1.3 and 12.7 years. Sixty-eight cases (32.7 %) had more than one hospitalization.

Figure 1
figure1

Flow of participants through study.

There were no statistically significant differences between participants and non-responders pertaining age at beginning of the disease, sex, EF, beginning of disease before first menarche, BMI at first hospitalization and BMI at discharge (data not shown).

We found a recovery rate of 69.7% (95% CI: 63.0–75.9), which was similar in patients with (65%) and without EF (72%) (P=0.27).

Thirty-four percent of the analyzed girls received EF at any hospitalization. Table 1 shows the characteristics of girls with and without EF. Patients with EF were significantly younger, shorter and had lower BMI at the time of hospitalization. Time between onset of disease and hospital admission was shorter and the duration of hospitalization was significantly longer in girls with EF. Girls who experienced EF had more hospitalizations. At follow-up, 16.9% (n=12) of the EF girls and 14.6% (n=20) of the non-EF girls reported to have BN.

Table 1 Characteristics of study subjects stratified by EF

Descriptive data on the outcomes optimal growth, persistence of AN and psychiatric comorbidity are shown in Tables 2, 3, 4. One hundred and fifty-five (75%) girls showed normal growth in height by our definition; three girls had initially and at follow-up heights below the third percentile. Girls with optimal growth were older and had higher BMI s.d. scores at their first hospitalization.

Table 2 Characteristics of subject stratified by growth
Table 3 Characteristics of subjects stratified by persistence of AN at follow-up
Table 4 Characteristics of subjects stratified by the occurrence of psychiatric comorbidities, other than eating disorders, at follow-up

Patients with AN persistence had more frequent outpatient treatments and hospitalizations than patients with recovery at follow-up (Table 3). Age at beginning of disease did not differ between patients with and without persistent AN.

Patients with persistent AN have an increased risk to report symptoms of psychiatric comorbidities at follow-up (RR=1.39, 95% CI: 1.04–1.84). Forty-five percent (n=94) of the girls have had psychiatric comorbidities at time of hospitalization. Of these, 45% (n=42) had high scores in the Symptom Checklist indicating persisting psychiatric comorbidity, although the others recovered from their comorbid conditions. Forty girls without comorbidity at the time of hospitalization reported symptoms indicating psychiatric comorbidities at follow-up resulting in 39.6% (n=82) of the study population with suspected psychiatric comorbidities at follow-up (Table 4). These participants were also smaller and had higher BMI s.d. scores at onset. The follow-up period was significantly shorter in patients with persistent AN and in patients with other mental disorders compared with their more healthy counterparts.

The regression for the association between EF and suboptimal growth yielded a crude RR of 1.64 (95% CI: 0.94–2.87) (Table 5). Stepwise adjustment for potential confounders reduced the RR towards 1.0. Likewise, we did not find significant associations in the crude and adjusted analyses between EF and the remission of AN or occurrence of psychiatric comorbidity, respectively.

Table 5 RRs (95% CI) for the association between tube feeding and suboptimal growth (I), remission of AN (II) and occurrence of other mental disorders at follow-up (III)

Discussion

In a catamnestic retrospective cohort study on 208 adolescent girls, who were hospitalized for AN with a follow-up of at least one year, we found no evidence for an association between EF via nasogastric tube (EF) and growth, persistence or remission of AN or the occurrence of psychiatric comorbidities at follow-up, respectively.

A number of outcomes need to be addressed to balance the potential benefits and drawbacks of EF. Previous studies focused on safety of EF,9 weight restoration,23 psychological outcomes such as anxiety, compulsive disorders and depression,9, 10, 15 medical complications15 and recovery rate9, 10 after AN therapy supported by EF. In adolescent girls persistence or remission of AN, the occurrence of psychiatric comorbidities at follow-up and the growth of body length appear to be of particular relevance with respect to potential harms and benefits of EF.

In his comprehensive review, Steinhausen reported an on-average recovery rate of only 46.9% (range: 0–92) for AN patients, whereas 20% (range: 0–79) of the patients had persistent chronic AN and a third improved only partly (range: 0–75).6 In our study we found a higher recovery rate of 69.7%, which was similar in patients with (65%) and without EF (72%). There are surprisingly few studies comparing artificial feeding, either by tube or parenterally, to oral feeding. A previous cohort study with a mean follow-up of 3 years showed that patients who received oral and parenteral refeeding had nearly the same recovery rate (61%) as patients who received oral refeeding alone (64%).9 A recent randomised controlled trial (RCT) on adult AN and BN patients by Rigaud and colleagues,10 however, concluded that tube fed patients had significantly less binge eating and purging episodes one year after hospitalization than non-tube-fed patients. This trial, however, had patients with an unusual high compliance, and the authors may have had a conflict of interest as it was supported by Nestlé Home Care. Our fully adjusted regression model yielded no evidence for an association between EF and AN remission, which is in accordance with two previous smaller observational studies.9, 15 Because of comparatively high sample size our study substantially supports the concept of no clinically relevant association between EF and persistence or recovery of AN: the study was sufficient to detect a RR below 0.56 (risk related to EF) or above 1.66 (beneficial effect of EF) with a power of 80%.

Psychiatric comorbidities, such as depression and compulsive behaviors, are frequent phenomena during and after recovery of eating disorders.24, 25 More than half of the AN patients suffered from psychiatric comorbidities in a 12-year follow-up study by Fichter et al.26 We found nearly 40% of the patients reported symptoms indicating another mental disorder at follow-up. Half of these (n=42) have already had any psychiatric comorbidity at hospitalization, as reported in medical records.

There are only few studies examining the effect of EF on psychiatric outcomes.10, 15 The above mentioned RCT by Rigaud10 suggested that EF combined with cognitive behavioral therapy significantly improved anxiety and depression levels compared with cognitive behavioral therapy only in patients with AN and BN. Our regression model indicated neither an increased nor a reduced risk for the occurrence of other mental disorders at follow-up after EF. The sample size was sufficient to detect a RR below 0.60 (beneficial effect of EF on the occurrence of mental disorders) or above 1.62 (increased risk for mental disorders by EF) with a power of 80%.

We additionally performed an analysis stratified by absence of documented mental disorders at hospitalization to compare incidence of and remission from mental disorders; we could not observe any significant differences of the effect of EF between the strata (data not shown).

This study was designed as a part of health services research and used a catamnestic approach, which allows for retrospective cohort analyses. Owing to the catamestic approach diagnostic criteria for psychiatric disorders were different at hospitalization (as documented in medical records) and follow-up (based on validated questionnaires). We therefore based our analyses on suspected diagnosis of mental disorders at follow-up indicated.

An additional analysis corroborated that patients with persistent AN had an increased risk for later psychiatric comorbidities. Stratification by persistence of AN did not suggest effect modification of EF by AN.

We are not aware of a study examining the effect of EF on young patients’ growth. It is known that AN patients have diminished growth hormone activity, which might account for growth retardation.4 Nutritional rehabilitation may increase growth hormone status allowing for ‘normal’ growth.4 We therefore examined whether EF—as a sort of nutritional rehabilitation—prevents growth retardation. A quarter of the analyzed patients did not grow normally by our definition. Our data, however, did not suggest EF to prevent suboptimal growth in the adjusted analyses. Treated patients might feel worse with their AN and be more prone to surreptitious compensatory behaviors. Thus, a significant difference in growth might not have been detected. The sample size, however, was sufficient to detect a RR below 0.52 (beneficial effect of EF on growth) or above 1.72 (risk for suboptimal growth after EF). As the study was a retrospective cohort study, we are unable to provide evidence that the outcome for participants with EF would have been similar had they not received EF. We cannot exclude that they would have shown less optimal growth below a RR of 1.72. An RCT comparing adolescent patients with severe nutritional deprivation randomly allocated to EF could provide data on the efficacy of such treatment, however is unlikely to be feasible.

We therefore additionally applied a supplemental analysis based on a propensity score, which has been suggested to mimic an RCT with observational data, as it reduces the bias in covariates simultaneously.22 The analyses yielded similar results for all outcomes (see Supplementary Information).

Strength and limitations

This retrospective cohort study examined a selected sample of AN patients of considerable size with a mean follow-up time of 6.3 years. Therefore, clinically relevant effects of EF on AN remission, mental disorders and growth could have been detected.

We used validated self-reporting questionnaires to assess the outcomes of AN persistence and mental disorder occurrence. The definition of suboptimal growth was not based on height at last measurement but considered growth velocity between admission to hospital and follow-up in adherence to up-to-date German percentiles.20 Anthropometric follow-up data were self-reported and thus might have been biased.27

As anorectic women tend to slightly overestimate their true weight,28 reporting bias cannot be excluded. Information on exposure to EF and data pertaining hospitalization were retrospectively abstracted from medical records by researchers who were not aware of the outcome. Therefore, information bias is unlikely.

Unfortunately, we do not have sufficient information on frequency and duration of EF, which might have had an impact on patients’ growth.

As this was no RCT, other risk factors for the outcomes considered might not be balanced between the observation groups. We therefore compared potentially relevant variables of the patients with and without EF and the patient groups with and without the respective outcome and considered significant factors as potential confounders. Nevertheless, residual confounding cannot be excluded.

Furthermore, there might be some risk of attrition bias because the response rate was only about 50%. The non-responder analysis, however, did not show any significant differences between participants and non-responders. Particularly the frequency of EF was almost identical in the two groups suggesting a low risk of attrition bias.

The supplemental analyses are based on subclassification on the propensity score. This approach allows for a better comparability in treatment and control groups without randomization.22 These analyses yielded similar results as detected by Poisson regression. This further strengthens the results of our study.

Conclusion

EF does not appear to account for a clinically relevant improvement of growth in young AN patients. Regarding potential harms, there was no indication of a clinically relevant risk for persistence of AN or occurrence of mental disorders related to EF. Decisions for EF in adolescent girls can neither be justified by potential improved length growth nor by reduced AN persistence or occurrence of mental comorbidities. However, it may remain a treatment option as a last resort in very young nutritionally deprived patients if other treatments fail, as EF is often experienced as extremely stressful and should, therefore, be avoided as much as possible through intensive motivational support and treatment. Should it still be necessary, a stepwise performance (arrangement of guardianship, compulsory admission, EF)14 is recommended.

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Acknowledgements

We are grateful to the support of Dr med. Günther Hinrichs (ZIP Kiel), Dr med. Joachim Walter (Katholisches Kinderkrankenhaus Wilhelmstift, Hamburg), Dr med. Jan Gerrit Behrens (MediClin Seepark, Bad Bodenteich) and Dr phil. Dipl. Psych. Dorothé Verbeek (UKSH Lübeck) who gave clinical advice and made the data available. We thank all patients who took part in this study. We thank Kristiane Krüger for her help in recruiting the sample and collecting the data and to Sabine Brehm, the medical documentalist. We furthermore thank Lucia Albers and Dr Otmar Bayer for statistical support. Parts of the manuscript arose from the PhD Thesis of KK (at the University of Lübeck) and from the Master Thesis of IN (at the University of Munich).

Author Contributions

The author’s responsibilities were as follows: IN: analyses and principle authorship of the manuscript; KK: recruitment and data collection, descriptive analyses; RvK: interpretation of the data and contribution to final draft; UT: conception of research question, project management, contribution to final draft of the manuscript.

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Correspondence to I Nehring.

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Nehring, I., Kewitz, K., von Kries, R. et al. Long-term effects of enteral feeding on growth and mental health in adolescents with anorexia nervosa—results of a retrospective German cohort study. Eur J Clin Nutr 68, 171–177 (2014). https://doi.org/10.1038/ejcn.2013.244

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Keywords

  • anorexia nervosa
  • enteral feeding
  • treatment
  • adolescence

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