Obesity and pregnancy

Obesity and pregnancy Weight

control

RICHARD New

York,

with

X. New

a resinate

SANDS,

M.D.,

F.R.C.O.G.

York

I N A recent report’ we described a simple method for evaluating the effectiveness of obesity control during pregnancy. This was based on the known average weekly increment (0.86 pound) during the third trimester.’ Multiplying this by the number of weeks of therapy and adding the result to the weight at the beginning of treatment gave a figure termed the expected weight. The weight at the end of pregnancy, the actual weight, was subtracted from the expected weight and called the weight benefit. If this was negative, the result was successful; if positive, it was a failure. The positive and negative numbers were then statistically evaluated. In dealing with obesity one realizes that the mechanism of normal appetite control, derangements of which may lead to excessive food intake and consequent obesity, is highly complex and may be further complicated by psychogenic and environmental factors. The stress of pregnancy plus the tensions, anxieties, and frustrations of present-day life also contribute. The women eat to overcome boredom, despondency, and frustration, and their distorted eating pattPrns destroy the relationship between choice of food and metabolic needs and energy requirements. This state is aggravated by the easy availability of high-calorie foods as well as by a sedentary existence and by physical inactivity.

From the Obstetrics Hospital.

Woman’s Hospital, and Gynecology

of

Data regarding the mechanism of normal appetite regulation are based, mainly, on animal experiment, the center for its control supposedly being located in the ventromedial nucleus of the hypothalamus. It has been referred to as the “appestaP and acts by influencing the level of satiety. However, in the human being neither the central site nor the precise mechanism has yet been definitely established.4 Obesity may be looked upon as a form of malnutrition which requires urgent treatment, particularly during the third trimester, which is the period of greatest wei‘ght increment, especially in the obese patient. Since the available time is too short for the successful establishment of new eating patterns-and since pregnancy is not a suitabl~~ time for such efforts-the clinician is compelled to use more rapid methods. Fortunately, certain compounds are available which, in varying degrees, can control appetite by lowering the level of satiety 01 desire for food and thus affect weight increment. Butylamine resin,* an appetite-inhibiting drug, has therefore been used therapeutically in an attempt to control obesity in a group of markedly overweight pregnant women. Method

to

and

Some form of control is essential obtain greatest objectivity in

*Phenyl-tert-butylamine supplied through the Rochester, New York.

Division of St. Luke’s

1617

material

in order assessing

resin for these experiments courtesy of R. J. Strasenburgh

was Co.,

1618

Sands

the effectiveness of any therapeutic agent. Since obesity is considered sufficiently serious to warrant active treatment and since thr therapeutic interval is too short for placebo experiments, another form of control was devised. The first 16 patients had no dietary or salt restriction. The next 14 women were similarly instructed except that all food was forbidden after the evening meal, a time when the obese love to munch on highcalorie foods. In this way, the value of food restriction in this type of patient was assessed. Both groups knew that an anoretic used. Thenceforth, no agent was being dietary restriction of any sort was imposed, neither food nor salt, and the patients were unaware of the nature of the medication used. Since pregnant women are probably the most medicated of patients and in hospital practice appear to take one more pill or capsule without question, this presented no problem. Phenyl-tert-butylaminc, in the form of a resin complex, was the anoretic agent used. This drug is a relatively weak sympathomimetic compound with significant appetitedepressing activity.’ It is released from its resinate by the gastrointestinal cations, and, the concentration of these being fairly constant, the release of the active compound is gradual, continuous, and controlled.6s 7 Doses larger than those recommended

AIII.

June 15, 1962 .I. Ohst. 8s Gynec.

were used because rapid control was desirrd and because previous experience had shown pregnant women are able to tolerate relati\-ely large amounts of this type of agent. Patients weighing less than 200 pounds were gil.rrr 30 mg. daily in thr mornin?. Thosr~ o\‘t’t. 200 pounds were given 60 nlg. daily. in equal doses both in the morninS and in tl~c. late afternoon. The drug was given orall!,. in thr form of a caps&l. and dosagt, ‘~V:IS individualized as necessary. The entire group studied numbered I 18 patients. many being non-whit-c and all weighing between 180 and 3 15 pounds. ‘I‘htb average age and height were 29.1 years and 5 feet. 6 inches, respectively. The women ranged up to gravida xii, 21 being primigravidas and 13 multiparas 1.Fig. 1). l‘rcaarment was carried out for intervals varyine from 3 to 16 weeks. The normal nonpregnancy weight for women with the abo\,cs physique is 133 pounds.’ In view> of this the avrra,ge patient would bc expected to weigh 145.8 pounds at the end of the second trimcster ( 12.8 pounds, normal average incr(*merit during the first two thirds of prrynancy I. The base weight of 180 pounds. 23 per cent above the mean weight for thiy group, was therefore considered true ohcsity. Trcattnent was begun at different tin1c.s during the third trimcstcr and continucc! until the onsrt of labor. The detailed tntthocl of evaluation has been described in a pn*vious paper.’ However. in this instant-r. to obtain greater objective accuracy, a COVCCtiol~ factor was introduc.rd. This can h< looked upon as a form of control and consisted of adding one to the rwiglzt h~rlc,/~i figure in each case so that a c.c,rrc~cf~,rl r~G,~ll( ht~ncfit was obtained. This numhcr was INYI in the final statistical analysis. As a rcbsult of this correction some castIs which bvcrc onl) slightly sllccessful became. failllrc~s. Results

A group of 102 patients, out of the entire series, wrre left for final analysis. Of these. 89 patients had some degrrcb of weight bcnc~iit from the treatment employed, and a comparison of the expected weight and the

v”lume

83

Number

12

Obesity

actual weight shows a distinct trend in a downward direction (Fig. 2). Statistical analysis, with the method of paired replicates and ranking, showed the results to be highly significant. There were 13 failures. That is to say, these women obtained no weight benefit from the treatment used during the period of therapy. Because of insufficient length of treatment, 16 cases, in the entire series, were omitted from final evaluation. It is interesting to note that 10 of these paticnts were responding to therapy when labor set in. In the initial group of 16 patients, those without any dietary restriction at all, every patient obtained some weight benefit and many to a considerable degree. In the contrasting group of 14 patients, those who were forbidden food after the evening meal, there were 4 failures. These 4 women actually gained weight during the period of therapy. The following cases, which can also be considered as controls, are of interest. One patient who had lost 10 pounds (from 240 to 230) during 7 weeks of therapy was experimentally placed on placebo medication. Her weight loss continued for a short time, but at full term, 4 weeks later, she had regained 8 pounds. Another patient who had also benefited from the treatment

and

pregnancy

regained 9 pounds when left without medication for 7 weeks. Under similar circumstances still another woman regained 9f/2 pounds in 3 weeks. There were many such instances in which weight gain began to increase rapidly when treatment was discontinued for short intervals. In the entire series there were 3 patients who developed side effects which were sufficiently severe to stop treatment in spite of the fact that they were deriving benefit from it. The symptoms cleared up immediately thereafter. One patient found it impossible to continue therapy after four attempts to do so because of severe vomiting. Another found that her mouth became so “stiff and dry” that continued medication was impossible. A third patient, when treated with 90 mg. of the drug (three times the recommended dose) developed edema of the face and lips as well as a rash which spread from the neck up to her face. Both rash and swelling began to improve at once when the drug was stopped. Other side effects complained of insomnia, were nausea, nervousness, and dizziness. Generally, patients did not find these too disturbing, particularly since the symptoms, in most cases, cleared up with continued medication. In some the speed of

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adaptation was increased by the use of s grain of phenobarbital twice daily. These disturbances, which have also been reported by others,” are not surprising in view of the fact that rather heavy doses of a sympathomimetic amine were being used. Blood cholesterol levels were distinctly on the high side of normal in the cases investigated. Response to weight control therapy did not appear to affect these levels in any significant manner. Incidental observations. Fourteen patients in the entire series developed pre-eclampsia, an incidence which is double that found in all pregnancies. ‘I’ This is one of the complications of obesity. There were 29 babies who weighed over 8 pounds. One of these actually weighed 1-l pounds, 6 ounces (6,520 grams). In a professional lifetime WilliamP encountered only one newborn infant approximately this weight; it wei,ghed 14 pounds, 4 ounces (6,470 grams). The incidence of oversized babies in the present series was 24.5 per cent, which is similar to the incidence rcported in a previous investigation.’ In the entire group there were 5 stillborn babies, 4 weighing between 9 and 10 pounds and the fifth (abruptio placentae) just over 4 pounds. Eastman’” states that the stillbirth rate is higher in male infants. In this series there were 3 females and 2 males. Mild pre-eclampsia was diagnosed in one case. Comment

We have now studied obesity control during the third trimester in almost 400 women, all weighing between 180 and 330 pounds. Some of these patients have been treated during more than one pregnancy and the only difference found was in the degree of obesity. It would seem that obesity is an almost incurable disease unless the personality pattern of the individual or her environment and lifetime habits can be altered. Animals offered a free choice of diet will select a variety and quantity of food which ensures optimum growth. Experimentally induced diabetic rats spontaneously decreased carbohydrate and increased fat and

protein consumption in contrast to insulintreated animals whose selection was similar to that of the intact animals which obtained the major part of their caloric requirements from food rich in starch.“’ Furthermore. if yellow-haired mice are mated with those of another color, a litter containing a certain number of yellow-haired mice results. If the entire litter is given the same food, the yellow-haired siblings, at the time of sexual maturity, be,gin to gain wei,ght more rapidly than the others. This is most marked among the female mice, many of which reach a weight twice that of their non-yellow-haired sisters. It is interestina that the fat of both varieties of female mice responds to starvation in a similar manner and that when fcrding is controlled the gain in wei,ght is similar in both instances.” Unfortunately it is easier to control feeding habits of a mouse than of a woman, particularly a pregnant one. The above animal experiments suggest that the level of satiety for an individual may be a hereditary factor. Obesity in the human being also appears to have a strong genetic background. One investigator’” reported that 82 per cent of his patients had parents one or both of whom were obese. In the present series the incidence of parental obesity was 75 per cent, with maternal obesity largely predominatin,g. In view of this apparent diathesis. can anything really constructive be done to avert obesity and to protect these persons from the complications to which their excess weight exposes them? Attempts at voluntary control of food intake do not seem to be too successful. Before reaching the third trimester many of the patients in the present study had been instructed to follow 1,200-calorie diets and to restrict salt intake. When closely questioned, some of the patients insisted that they had faithfully adhered to the regimen but the majority confessed to nothing more than “I did my best.” Very few lost any significant weight. The mediocre results of dietary therapy alone, followed in the way it was, made one wonder whether these patients subconsciously overate as a protest against restriction. The release from all

Obesity

dietary restraint, when these same women were admitted to the study, resulted in an obvious sense of relief which was considered psychologically important. The difficulties of combating the obese state during pregnancy should not lead to undue pessimism. The problem is difficult and the patients’ background would appear to make a cure impossible. However, the method of treatment described offers an effective means of dealing with the problem when we judge from the encouraging results. Summary

Phenyl-tert-butylamine, in the form of a resin

an anoretic agent complex, has been

REFERENCES

1. Sands, R. X.: Obst. & Gynec. 16: 605, 1960. 2. Chesley, L. C.: AM. J. OBST. & GYNEC. 48: 565, 1944. 3. Jolliffe, N.: Reduce and Stay Reduced, rd. 2. New York, 1957, Simon & Schuster. 4. Model], W.: J. A. M. A. 173: 1131, 1960. 5. Becker, B. A.: Fed. Proc. 18: 1448, 1959. 6. Freed, S. C., Keating, J. W., and Hays, E. E.: Ann. Int. Med. 44: 1136, 1956. 7. Cass, L. J., and Frederick. W. S.: Ann. Int. Med. 49: 151, 1958. 8. Society of .4ctuaries Publication: Build and Blood Pressure Study, Chicago, 1959.

and

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used to control obesity during pregnancy without dietary restriction. The effectiveness of this compound was evaluated in a series of 118 patients whose weights ranged from 180 pounds to 315 pounds. The patients were treated only during the third trimester, and a novel method of evaluation was used to determine the results of therapy. All side effects encountered during this study have been described. Some aspects of the genetic background of obesity have been discussed. Statistical analysis of the results obtained has shown that these were highly significant.

9. 10.

11. 12. 13. 14.

Freed, S. C., and Hays, E. E.: Am. J. M. SC. 238: 55, 1959. Eastman, N. J.: Williams Obstetrics, ed. 11. New York, 1956. Appleton-Century-Crofts. Inc. Williams, J. W.: Obstetrics, ed. 6, New York. 1930, D. Appleton & Company. Eastman, N. J.: Obst. & Gynec. Surv. 15: 638, 1960. Donhoffer. S.: Triangle 4: 233, 1960. Kalb, S. W.: J. M. Sot. New Jersey 55: 471, 1958. 1212 New

Fifth York

Ave. 29, New

York