Amniotic fluid volumes in the second half of pregnancy

CURRENT INVESTIGATION Amniotic fluid volumes in the second half of pregnancy DAVID

CHARLES,

HANNAH

E.

FLORENCE Pittsburgh,

M.B.,

JACOBY,

M.R.C.O.G. M.B.,

M.R.C.O.G.

BURGESS Pennsylvania

A T P R E S E N T the clinical importance of amniotic fluid volumes has not been elucidated, mainly on account of the paucity of volumetric determinations in the literature. Our interest in this subject developed because of the inconsistencies encountered in reviewing data of various authors in regard to hydramnios,l and it was apparent that conflicting opinions in this area could be ascribed to the absence of concrete measurements. The problem is further accentuated by the relative lack of information concerning volumes in the second and third trimesters in normal pregnancies. It is essential that any critical evaluation of amniotic fluid volumes should be based on prospective studies in conjunction with isolated readings in individual patients, obtained in the last few weeks of pregnancy. Such studies were not entirely feasible until the introduction of amniocentesis for the assessment of rhesus isoimmunization’ and the status of diabetic pregnancies,3 and in such cases an opportunity exists for accumulating information in regard to amFrom

the Department

of Obstetrics

niotic fluid volumes throughout pregnancy. In previous communication,” sodium aminohippurate appeared to incorporate all the criteria required by a substance for accurate volumetric determinations of amniotic fluid without the production of iatrogenie disease in either mother or fetus. This compound was used in the present communication for compiling data on amniotic fluid volumes in the second and third trimesters, in normal and complicated pregnancies. Materials and methods A total of 95 volumetric determinations of amniotic fluid were performed in 64 patients, 20 primigravidas and 44 multiparas. The blood group distribution was as follows: 0, 33; A, 22; B, 6; AB, 3. Suspected rhesus isoimmunization was the indication for abdominal amniocentesis in 22 patients and the procedure was carried out at varying intervals during pregnancy in these cases. Abdominal amniocentesis was performed as an outpatient procedure, the nature and purpose of the technique being first explained to the patient. Details of the method used for determining amniotic fluid volumes

and

Gynecology, University of Pittsburgh, Magee-Women’s Hospital. 1042

Volume Number

93 7

with sodium aminohippurate (P.A.H.) have been previously described4 and are, therefore, only briefly summarized. After removal of a control sample of amniotic fluid, 400 mg. of P.A.H. were injected into the amniotic cavity and three further samples of fluid were obtained, after an interval of 20 minutes, during the subsequent 10 to 15 minutes. In the laboratory, using the method of Smith,” which is based on a diazo reaction, spectrophotometric readings at a wave length of 540 mp were compared with a standard linear regression curve obtained from solutions of P.A.H. containing 0.0001 to 0.003 mg. per milliliter. The volume of amniotic fluid was calculated by dividing the 400 mg. of P.A.H. introduced into the amniotic sac by the quantity found in 1 ml. aliquot portions of undiluted fluid. In 11 cases in which multiple samples were obtained during periods of up to 75 minutes, the spectrophotometric readings gave consistent results 20 to 40 minutes after injection of P.A.H. Such results implied that the tracer substance had undergone complete diffusion and mixing in the amniotic fluid and had not been transferred. Further confirmation of this supposition was obtained in 4 patients where simultaneous amniocentesis was carried out at two sites 6 inches apart, with uniform results. In order to elucidate the possibility of transfer of P.A.H. from the amniotic cavity to the maternal organism, samples of urine and plasma were obtained before and after amniocentesis. In only 3 of the 27 cases in which plasma was examined for P.A.H. were traces found. Urinalysis in 22 patients demonstrated no P.A.H. in 6, up to 1 mg. in 15, and 2.25 mg. in the remaining case. The cord plasma reading in the baby delivered by cesarean section, 55 minutes after insertion of P.A.H. into the amniotic cavity, was 0.0015 mg. per milliliter. Results Normal pregnancies. Twenty-two out of 27 volumetric determinations were performed in normal pregnancies during the midtrimester (Table I). In 18 of these cases

Amniotic

fluid

volumes

in pregnancy

1043

(81.8 per cent), the volumes ranged from 482 to 785 ml.; in one it was over 1,000 ml.; and no patient had a volume of less than 300 ml. Estimations in 11 of the 37 (29.7 per cent) normal pregnancies in the last trimester (Table II) ranged from 450 ml. to 750 ml. and in 9 (25 per cent) the volume was over 1,000 ml. In one patient with an uncomplicated pregnancy, volumetric estimations at twentyeighth, thirty-first, thirty-third, thirty-fifth, and thirty-seventh weeks were 673 ml., 715 ml., 820 ml., 900 ml., and 945 ml., respectively. In a further patient, three estimations at 26, 28, and 35 weeks of gestation showed volumes of 570 ml., 638 ml., and 970 ml. In one patient the volume at the twenty-fourth week of gestation was 665 ml. and a second reading at 35 weeks was

Table I. Midtrimester estimations (ml.)

volumetric

Weeks

Com6licated

18 20 21 22 23 24 25

315 570t 315 505 590t 715 665” 485

26

620 628t 690 708 570

27 28

*para

pregnancies

565* (Erythroblastosis felalis)

1,180$

I ,200* (Lupus erythematow)

1,375$ 85 (Intrauterine death)

482 725 1,204t 626 628 673 718t 785 865 ” or InorP.

tPrimigravida. $Patient who later

developed

hydramnios.

fetal

1044

Charles,

Jacoby,

and

Table II. Last

trimesters j ml. ‘#

cstimations

~ Normnl

i Weeks 29 30

250 360 374 1,310 715

860 1.355

35

610 900 970 1,040

36

520 694 820 850 880 962 1,070 530 945

38

470

39

530 800 855 1.120

40 41 42 Key: a.b. were performed.

Complicated

al ,910 (Hydramnios) 408 (Diabetes) 1,055 (Erythroblastosis fetalis) al ,890 (Hydramnios) 1.180 (Erythroblastosis fetalis) bl,%O 104 (Eclampsia) 860 (Diabetes) 965 (Pre-eclampsia) 1,235 (Twins-l sac) a’,240 (Hydramnios) 740 (Diabetes) 910 (Erythroblastosis fetalis) b1,820 (Hydramnios) a2.020 (Hydramnios) a2.310 (Hydramnios) 830 (Pre-eclampsia) 1.025 (Erythroblastosis fetalis) 1.630 (Hydramnios) b 1.882 I Hvdramnios i a2,070 (Hydramnios) 367 (Pre-eclampsia + essential hypertension 1

1,250 487 573 852 1,370 340 =

pregnancies

1,078 (Diabetes) 1,186 (Diabetes) al ,820 (Hydramnios)

b1,320

395

37

\ olurnc~t t.ir

j

pregnancies

1,375 1,380 450 750 820 34

Burgess

Patients

564 (Erythroblastosis fetalis) .592 720 770 350 \\herr

(Pre-eclampsia) (Pre-eclampsia) ( Pre-eclampsia) (Pre-eclampsia) repeated

determinations

1,040 ml. These patients, therefore, demonstrated a gradual increase of amniotic fluid as pregnancy proceeded from the mid to the last trimester. Hydramnios. Amniotic fluid volumes 1,500

illi.

01

(I\(‘1

\cf‘I’C

C:IICOIttItt~t~‘~~

Itt

:i

j~alit*lli~.

‘ttrd M’(: Ilitv(’ accepted this figIre ;I, 1111, \-olunictr~ic: c%terion for ttic diagnosis 01 hydramnios. One patient with a \olurne 01 1,630 ml. during the thirty-se\,enth week ot gestation suhseyuently had a spontaneous delivery of ‘1 normal infant weighing 2,980 grams. The second patient had four volumetric determinations during a 5 week period. Comparable volumes were present at the thirty-second and thirty-fourth week ol pregnancy 8,1,280 ml., 1.320 ml. I( but t+ the thirty-sixth week there was an increase to 1,820 ml. On the latter occasion, 150 trtl. of amniotic fluid was removed because the patient complained of abdominal discomfort. A further volumetric determination after an interval of 6 days was 1,882 ml. At term. the patient was delivered of a normal infant weighing 4,500 grams. A glucose tolerance test performed in the puerperium was within normal limits. A third patient where estimations wtrc~ obtained hetween twenty-third and thirtyseventh weeks showed a gradual accumulation of fluid from 1.180 ml. to a maximum of 2.310 ml. at the thirty-sixth week. It is of interest that two readings obtained in the midtrimester in this patient were among the highest recorded during this period of gestation f. Eclampsia and pre-eclampsia. A l-l-ycarold girl wa.s admitted at 35 weeks cyesis with rclamptic convulsions. After she had been well sedated, an abdominal amniocentesis was performed and the fluid volume was found to be 104 rnl. Both at the time of surgical induction of labor and deliver). almost no liquor was noted, confirming the volumetric determination. Eight patients with pre-eclampsia, bcthe thirty-fifth and forty-second tween weeks, had volumes varying from 350 to 96.5 ml. These were comparable to volumes found in normal pregnancy-. Erythroblastosis fetalis. In 5 cases rhesus isoimmunization was a. factor, the blood group being A rhesus negative in 4 and AH rhesus ncgativc: in the fifth. One patient had

Volume

93

Number

i

Amniotic

lost 3 previous infants from hydrops fetalis, and an amniocentesis was therefore performed at the eighteenth week. The volume of fluid was 565 ml. In view of the poor obstetric history, and the finding of a very high peak (at 450 mp) on spectrophotometry, an intrauterine transfusion was performed. Fetal death occurred and 3 weeks later following insertion of 20 per cent salt solution she expelled a fetus weighing 270 grams. The patient previously described with hydramnios of over 2,000 ml. was delivered of an infant with erythroblastosis fetalis requiring one exchange transfusion. Amniotic fluid volumes in the remaining 3 patients ranged from 560 to 1,180 ml. Lupus erythematosus. A midtrimester volumetric estimation in a 46-year-old patient with lupus erythematosus complicated by severe renal involvement was 1,200 ml. Examination of the cellular content revealed no L.E. cells and an indirect L.E. preparation using donor cells, on the fluid, was negative. One week later she went into premature labor and thus, no further investigations could be performed. Intrauterine fetal death. This death occurred at approximately 24 weeks cyesis in a 34-year-old woman, blood group 0, rhesus Table III. Comparison of amniotic volumes and infant weights at birth in 17 normal pregnancies* Weeks cvesis

Volume (ml.)

25 36

628 520 694 962 530 367 470 530 800 855 1.120 (250 487 573 852 1,370 340

37 38

39 40 41 42 *Infants born amniotic fluid.

within

2 weeks

fluid

Birth weight /prams)

1,020 2,710 2,500 3,060 3,080 3.500 2:290 3,190 4,175 3,395 3.485 3j150 4,600 3,350 2,630

3,720 2,600 of volumetric

estimation

of

fluid

volumes

in pregnancy

1045

positive. At 26 weeks, labor was induced by inserting 185 ml. of 20 per cent salt solution into the amniotic cavity. Simultaneously, 400 mg. of P.A.H. was also introduced and after correcting for the salt solution, the volume was found to be 85 ml. Correlation of amniotic fluid volume with fetal weight. In 17 normal pregnancies where the infant was delivered within 2 weeks of volumetric determination, there was no correlation between fluid volume and infant weight (Table III). Placental weights are not routinely recorded in this hospital, and it was thus impossible to compare placental weight and amniotic fluid volume. Comment Most obstetricians would agree that the clinical assessment of the quantity of amniotic fluid present in the second half of pregnancy is fallacious. Direct measurement is difficult as this necessitates the collection of all liquor at the time of hysterotomy or cesarean section.” It is thus apparent that dilution methods7-l3 are the only feasible means at present of determining amniotic fluid volumes at various stages of normal and abnormal pregnancies. The principles of volumetric determinations in any body fluid compartment are essentially similar. In respect to the amniotic sac, the properties of the agent employed must be such as to insure uniform distribution throughout the fluid medium, and furthermore, its retention must be for a sufficient period of time to allow comparable results in each patient. One of the objects of the present investigation was to further assess the value of P.A.H. as a dilution substance for the determination of amniotic fluid volumes. Its ability to diffuse and mix in the fluid compartment was illustrated by the consistent results obtained in 5 patients where amniocentesis was simultaneously performed at two sites separated by a distance of 6 inches. The slow rate of transfer to the maternal organism is exemplified by the negligible quantity of the compound in the maternal plasma and urine at the completion of the procedure. Similarly the minute

1046

Charles,

Jaboby,

and

Burgess

tract found in the cord plasma 55 min1ltt.s after instillation of P.A.H. into the amniotic‘ sac substantiates the previous observation<. It can thus be concluded that calorimetric determinations 20 to 40 minutes after injection of the compound furnish valid data. All too frequently in the few reports concerning dilution techniques for the determination of amniotic fluid volumes: thr methods were confined to the later weeks of pregnancy and were incidental to other investigations.!‘, I” Elliot and Inmanb l’eported volumes determined by the dilution of the dye, Coomassie blue, in 59 normal and 70 abnormal pregnancies near term. In their series only onr determination pc’r patient was obtained and therefore, dubiety exists concerning their conclusions. Partially to circumvent such criticism, repeated determinations on 18 individual patients were performed in the present study. Previous investigators have hesitated to perform mort than one determination because of the fear of inducing premature labor. We have not encountered this complication, and no case of intrauterine or maternal infection occurred in this series. The study illustrates that volumetric determinations from the twentieth to twentyeighth weeks inclusive, range between 480 ml. and 785 ml. in more than 80 per cent of patients. In the later weeks of pregnancy. the variation was much greater (Table II I. Similar readings were obtained in different individuals at varying times during the second half of pregnancy. This statement is exemplified by a volume of 715 ml. at 23 weeks’ gestation in one patient, and similar volumes at 31, 33, and 36 weeks in others. In 5 patients in the midtrimester and 5 in the last trimester, determinations were obtained on two occasions. 2 weeks apart. The change in volume for each patient was negligible, but definite increments were discerned as the pregnancy proceeded from the middle to the later weeks. The above find-

Although WY’ haves oncb \.olunlr:tric: cstimation of 340 ml. at 42 weeks’ gestation. MY do not suggest that this illustrates oligohydramnios associated with prolongation of the pregnancy.4-‘9 as sequential studies wtlr(* not performed. Similarly, until prospectivts studies arr conducted in paticmts who ary clinically norrnal between the twentieth and thirtieth werks of pregnancy, but later dt<\.elop pre-eclampsia can the claims of various authors”, ” concerning reduced volumes associated with this condition. he substantiated. The isolated reading- of 10 1 ml. in an eclamptic patient i:, not necessarily significant. but indicatrs the necessity for further work in this area. One of the 3 patients with hydramnios, in whom a volume of over 1,500 ml. was obtained in the last trimester, had detrrminations prior to the twenty-eighth week and these \vere in excess of 1,000 ml. A \,olume of over 1,000 ml. in the midtrimester was only encountered in one patient with no subsequent complications. Such results indicate the necessity for prospective studies in the c\.aluation oi amniotic fluids cncountered in normal and complicated pregnancies. Summary The volume of amniotic fluid in 64 patients during the second half of pregnancy, using P.A.H. has been previewed. A total of 95 determinations were performed. The importance of prospective studies and repeated determinations in individual patients is emphasized as being essential for the acquisition of valid data, not only in respect to normal pregnancy, but also in the presence of such complications as pre-eclampsia and hvdramnios.

Volume Number

93 7

Amniotic

fluid

volumes

in

pregnancy

1047

REFERENCES

Jacoby, H. E., and Charles, D.: AM. J. OBST. & GYNEC. In press, 1965. 2. Liley, ,4. W.: AM. J. OBST. & GYNEC. 82: 1359, 1961. 3. Peel, J.: Proc. R. Sot. Med. 56: 1009, 1963. 4. Charles, D., and Jacoby, H. E.: AM. J. OBST. & GYNEC. In press, 1965. 5. Smith, H. W., Finkelstein, N., .4liminos, A. L., Crawford, B.. and Graber, M. J.: J. Clin. Invest. 24: 338, 1945. 6. Wagner, G., and Fuchs, F.: J. Obst. & Gynaec. Brit. Comm. 69: 131, 1962. 7. Dieckmann, B. S., and Davis, M. E.: AM. 1. OBST. & GYNEC. 25: 623. 1933. P. M., and Inman, W.‘H. W.: Lancet 8. Elliott, 2: 835, 1961. I.

9.

10.

11. 12. 13.

14.

Hutchinson, D. L., Hunter, C. B., Neslen, E. D., and Plentl, A. A.: Surg. Gynec. & Obst. 100: 391, 1955. Hutchinson, D. L., Gray, M. J., Plentl, A. A., Alvarez, H., Caldeyro-Barcia, R., Kaplan, B., and Lind, J.: J. Clin. Invest. 38: 971, 1959. Lambiotte, C.. and Rosa, P.: Gym%. et obst. 48: 161, 1949. Marsden, D., and Huntingford, P. J.: J. Obst. & Gynaec. Brit. Comm. 72: 65, 1965. Neslen, E. D., Hutchinson, D. L., Hallett, R. L., and Plentl, A. A.: Obst. & Gynec. 3: 598, 1954. Elliot, P. M.: Australia New Zealand J. Obst. & Gynaec. 4: 113, 1964.