British Journal of Obstetrics and Gynaecology February 1978. Vol 85. pp 90-95
NON-PREGNANT MATERNAL PLASMA VOLUME AND FETAL GROWTH RETARDATION BY
J. CROALL”
SUSANSHERRIF AND
JENNIFERMATTHEWS Regional Medical Physics Department, Shefield, England Summary The hypothesis that low maternal blood volume is an aetiological factor in fetal growth retardation was considered. It was found that a high proportion of women who had repeatedly given birth to small-for-dates babies had a low non-pregnant plasma volume.
FETAL growth retardation can result from reduced placental blood flow (Wigglesworth, 1966; Fox, 1967); if evidence of local pathology is absent, the possibility of a general maternal circulatory deficiency exists. Gruenwald (1974) thought maternal circulatory factors important in the aetiology of poor fetal growth, citing suggestive (Raiha, 1959; Unnerus, 1959) but disputed (Hytten et al, 1963) evidence that insufficient adaptation of maternal heart size to pregnancy results in small fetal size. The increase in maternal blood volume during pregnancy varies widely between individuals (Lund and Donovan, 1967); it is possible that the lower extremes of the range may, on occasion, prove inadequate to meet the demands of the utero-placental circulation. A correlation has been established between the amount of the maternal blood volume increase and the fetal weight (Hytten and Paintin, 1963; Retief and Brink, 1967) and it is usually assumed that the size of the fetus is a factor in determining the size of the blood volume increase. It is also possible that the size of the blood volume
increase, by influencing uterine blood supply, is a determinant of fetal size. Gibson (1973), in a prospective study of plasma volume in a group of patients with a poor obstetric history (‘poor reproducers’), found that their plasma volume increment in pregnancy was less than in controls, and while this might reasonably have been attributed to the ‘poor reproducers’ having more small babies, she found that even for a given birth weight their plasma volume increment tended to be less than in controls. In animal experiments, Duncan and Lewis (1969) found that extremes of feto-placental size did not adequately account for the associated extremes in uterine blood flow. The blood volume in pregnancy could be inadequate to meet the needs of the uteroplacental circulation either because of an abnormally low non-pregnant blood volume, or because of an abnormally low blood volume increase in pregnancy, or both. When the first of these is present, the second will tend to follow. Lund and Sisson (1958) found that if a mother had a high, or low, blood volume early in pregnancy, it remained relatively high, or low, throughout the pregnancy, and Lund and
* Present address: Box 2157, Whyalla, South Australia. 90
PLASMA VOLUME A N D FETAL GROWTH
Donovan (1967) found that the size of the nonpregnant plasma volume was a factor of influence in determining the size of the pregnancy increase. The hypothesis that a low blood volume increase might be a cause of fetal growth retardation is not easily tested, since an association between the two would not determine which was cause and which effect. However, the hypothesis that a low non-pregnant blood volume could be a factor in fetal growth retardation can be tested by measuring the nonpregnant blood volume of women who have repeatedly given birth to small-for-dates infants and comparing the results with those obtained in controls. This was the aim of our work. PATIENTS AND METHODS The non-pregnant plasma volumes of multiparous women, all of whose babies had been markedly small-for-dates, were compared to the plasma volumes of a control group of mothers. The index patients were selected from a maternity unit’s records of 11 000 consecutive deliveries. Thirty-two women whose babies were all below the fifth birth weight centile after correction for infant sex, infant maturity, maternal height, maternal weight and parity (Thomson et al, 1968) were asked to attend for plasma volume measurements. Nineteen patients responded and had the tests performed satisfactorily after informed consent had been obtained. In addition, 8 patients, mostly of high parity, who had had small-for-dates babies but also at least one baby with a birth weight above the fifth centile, were investigated, making a total of 27 patients. The 19 patients who had given birth to smallfor-dates babies were subdivided into those whose babies had invariably had a birth weight which was 100 g or more below the fifth centile (12 patients) and those who did not meet these criteria (7 patients). However, the mean birth weight in the latter group was only marginally greater. The 41 control patients consisted of 31 women whose babies were of average or above average birth weight, and 10 women who had had one small-for-dates baby (birth weight below the fifth centile) and one or more of average birth weight. Many of the controls were selected from women attending a postnatal clinic. The controls
91
were not matched for parity and included primiparae. Plasma volumes were measured by a 1251labelled albumin dilution technique in midmorning after the patients had been resting supine for 15 minutes. With the first six patients, blood samples were taken from the opposite arm into heparinized bottles 10, 20 and 30 minutes after an intravenous injection of 1251labelled albumin. With subsequent patients, one sample only was withdrawn after 15 to 20 minutes. Except for a few control patients who were investigated in October and November, all blood volume measurements were made in Sheffield between May and September; thus we avoided the winter reductions in blood volume (Maxfield et al, 1941; Retief and Brink, 1967). There are differing opinions (Muldowny, 1957; Nadler et al, 1962; Lund and Donovan, 1967; Retzlaff et al, 1969) about how plasma volume results are best expressed. All are agreed that net volumes are meaningless except to estimate the mean of a large population. Results can only be related to ‘normal’ if they are expressed in relation to the patient’s size and build. Expressing results in ml/kg achieves this aim in all except the overweight patients in whom misleadingly low results may be obtained. A weight correction can be applied to them, but it does not distinguish between those whose overweight is due to excess lean bulk rather than fat. Most authors, for example Davies et a1 (1974), take the lower limit of normal as 40 ml/kg. We made allowance for those with excess weight by disregarding that portion of any individual’s weight which was in excess of the 75th centile (Kemsley et al, 1962): 26 of the 68 women in the study (38 per cent) were above the 75th centile of weight for height. RESULTS Plasma volume estimates based on blood samples collected at 10, 20 and 30 minutes after injection of isotope in the first six patients tested are shown in Table I, confirming the validity of using a single time point in subsequent measurements. The results for the control group are shown in Table 11. The mean plasma volume was 40.6 ml/kg or, if a correction for overweight was employed, 44.5 ml/kg. Among controls,
92
CROALL, SHERRIF AND MATTHEWS
TABLE I Plasma volumes estimated from blood samples withdrawn 10, 20, and 30 minutes after injection of isotope in six patients
Plasma volume (ml) Patient no.
10-minute sample
20-minute sample
30-minute sample
2290 1710 2420 2480 3200 1830
2340 1680 2410 2480 3120 1880
2200 1730 2470 2560 3320 1910
1 2 3 4 5 6
results in women who had had one small-fordates baby did not differ significantly from those of the women whose babies had all been above average weight. The results for the small-for-dates group are shown in Table 111. The mean plasma volume was not significantly less than the control group unless a weight correction in overweight patients was made (41.0 compared to 44.5 ml/kg, P
NON-PREGNANT MATERNAL PLASMA VOLUME AND FETAL GROWTH RETARDATION BY
J. CROALL”
SUSANSHERRIF AND
JENNIFERMATTHEWS Regional Medical Physics Department, Shefield, England Summary The hypothesis that low maternal blood volume is an aetiological factor in fetal growth retardation was considered. It was found that a high proportion of women who had repeatedly given birth to small-for-dates babies had a low non-pregnant plasma volume.
FETAL growth retardation can result from reduced placental blood flow (Wigglesworth, 1966; Fox, 1967); if evidence of local pathology is absent, the possibility of a general maternal circulatory deficiency exists. Gruenwald (1974) thought maternal circulatory factors important in the aetiology of poor fetal growth, citing suggestive (Raiha, 1959; Unnerus, 1959) but disputed (Hytten et al, 1963) evidence that insufficient adaptation of maternal heart size to pregnancy results in small fetal size. The increase in maternal blood volume during pregnancy varies widely between individuals (Lund and Donovan, 1967); it is possible that the lower extremes of the range may, on occasion, prove inadequate to meet the demands of the utero-placental circulation. A correlation has been established between the amount of the maternal blood volume increase and the fetal weight (Hytten and Paintin, 1963; Retief and Brink, 1967) and it is usually assumed that the size of the fetus is a factor in determining the size of the blood volume increase. It is also possible that the size of the blood volume
increase, by influencing uterine blood supply, is a determinant of fetal size. Gibson (1973), in a prospective study of plasma volume in a group of patients with a poor obstetric history (‘poor reproducers’), found that their plasma volume increment in pregnancy was less than in controls, and while this might reasonably have been attributed to the ‘poor reproducers’ having more small babies, she found that even for a given birth weight their plasma volume increment tended to be less than in controls. In animal experiments, Duncan and Lewis (1969) found that extremes of feto-placental size did not adequately account for the associated extremes in uterine blood flow. The blood volume in pregnancy could be inadequate to meet the needs of the uteroplacental circulation either because of an abnormally low non-pregnant blood volume, or because of an abnormally low blood volume increase in pregnancy, or both. When the first of these is present, the second will tend to follow. Lund and Sisson (1958) found that if a mother had a high, or low, blood volume early in pregnancy, it remained relatively high, or low, throughout the pregnancy, and Lund and
* Present address: Box 2157, Whyalla, South Australia. 90
PLASMA VOLUME A N D FETAL GROWTH
Donovan (1967) found that the size of the nonpregnant plasma volume was a factor of influence in determining the size of the pregnancy increase. The hypothesis that a low blood volume increase might be a cause of fetal growth retardation is not easily tested, since an association between the two would not determine which was cause and which effect. However, the hypothesis that a low non-pregnant blood volume could be a factor in fetal growth retardation can be tested by measuring the nonpregnant blood volume of women who have repeatedly given birth to small-for-dates infants and comparing the results with those obtained in controls. This was the aim of our work. PATIENTS AND METHODS The non-pregnant plasma volumes of multiparous women, all of whose babies had been markedly small-for-dates, were compared to the plasma volumes of a control group of mothers. The index patients were selected from a maternity unit’s records of 11 000 consecutive deliveries. Thirty-two women whose babies were all below the fifth birth weight centile after correction for infant sex, infant maturity, maternal height, maternal weight and parity (Thomson et al, 1968) were asked to attend for plasma volume measurements. Nineteen patients responded and had the tests performed satisfactorily after informed consent had been obtained. In addition, 8 patients, mostly of high parity, who had had small-for-dates babies but also at least one baby with a birth weight above the fifth centile, were investigated, making a total of 27 patients. The 19 patients who had given birth to smallfor-dates babies were subdivided into those whose babies had invariably had a birth weight which was 100 g or more below the fifth centile (12 patients) and those who did not meet these criteria (7 patients). However, the mean birth weight in the latter group was only marginally greater. The 41 control patients consisted of 31 women whose babies were of average or above average birth weight, and 10 women who had had one small-for-dates baby (birth weight below the fifth centile) and one or more of average birth weight. Many of the controls were selected from women attending a postnatal clinic. The controls
91
were not matched for parity and included primiparae. Plasma volumes were measured by a 1251labelled albumin dilution technique in midmorning after the patients had been resting supine for 15 minutes. With the first six patients, blood samples were taken from the opposite arm into heparinized bottles 10, 20 and 30 minutes after an intravenous injection of 1251labelled albumin. With subsequent patients, one sample only was withdrawn after 15 to 20 minutes. Except for a few control patients who were investigated in October and November, all blood volume measurements were made in Sheffield between May and September; thus we avoided the winter reductions in blood volume (Maxfield et al, 1941; Retief and Brink, 1967). There are differing opinions (Muldowny, 1957; Nadler et al, 1962; Lund and Donovan, 1967; Retzlaff et al, 1969) about how plasma volume results are best expressed. All are agreed that net volumes are meaningless except to estimate the mean of a large population. Results can only be related to ‘normal’ if they are expressed in relation to the patient’s size and build. Expressing results in ml/kg achieves this aim in all except the overweight patients in whom misleadingly low results may be obtained. A weight correction can be applied to them, but it does not distinguish between those whose overweight is due to excess lean bulk rather than fat. Most authors, for example Davies et a1 (1974), take the lower limit of normal as 40 ml/kg. We made allowance for those with excess weight by disregarding that portion of any individual’s weight which was in excess of the 75th centile (Kemsley et al, 1962): 26 of the 68 women in the study (38 per cent) were above the 75th centile of weight for height. RESULTS Plasma volume estimates based on blood samples collected at 10, 20 and 30 minutes after injection of isotope in the first six patients tested are shown in Table I, confirming the validity of using a single time point in subsequent measurements. The results for the control group are shown in Table 11. The mean plasma volume was 40.6 ml/kg or, if a correction for overweight was employed, 44.5 ml/kg. Among controls,
92
CROALL, SHERRIF AND MATTHEWS
TABLE I Plasma volumes estimated from blood samples withdrawn 10, 20, and 30 minutes after injection of isotope in six patients
Plasma volume (ml) Patient no.
10-minute sample
20-minute sample
30-minute sample
2290 1710 2420 2480 3200 1830
2340 1680 2410 2480 3120 1880
2200 1730 2470 2560 3320 1910
1 2 3 4 5 6
results in women who had had one small-fordates baby did not differ significantly from those of the women whose babies had all been above average weight. The results for the small-for-dates group are shown in Table 111. The mean plasma volume was not significantly less than the control group unless a weight correction in overweight patients was made (41.0 compared to 44.5 ml/kg, P
