SYNOPSIS There is a significant fall in the serum folic acid level during pregnancy, reaching its lowest level at term. This is most pronounced in twin pregnancies. A similar but less spectacular fall occurs in the vitamin B12 concentration.In megaloblastic anaemia both folic acid and vitamin B12 levels are lower than in other pregnant women. The degree of megaloblastic change in the bone marrow, as measured by the type and number of megaloblasts, is reflected in the vitamin levels, cases with florid megaloblastosis showing the most marked depression of vitamin B12 and folic acid activity.Although there is a significant difference in the mean folic acid levels between megaloblastic and normoblastic pregnant women, a considerable overlap exists between individual values in the two groups. When the labile folic-acid factor is determined separately the test becomes much more specific. In the present series, all cases of megaloblastic anaemia yielded labile-factor levels below 1 0 m,ug. per ml., while a similar value was encountered in only one of 35 normal pregnancies.In five women with megaloblastic anaemia the vitamin B12 concentration was less than 100 ,u,ug. per ml. but rose to normal levels on folic acid therapy alone.

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SIR,-On 26 December 1964 a memorandum signed by Dr. J. J. Brown and his colleagues, dealing with plasma renin in a case of primary aldosterorrism, appeared in the British Medical 7ournal.1 Several erroneous statements and implications regarding our work require comment.We are pleased, indeed, to have confirmation in a preliminary report from this group of excellent investigators that the reninangiotensin system has been found to be suppressed pre-operatively in two more cases of primary aldosteronism from whom adrenal cortical tumours have recently been removed. Our earlier reports2' have emphasized repeatedly that in the face of restriction of dietary sodium suppression of plasma-renin activity, as we measure it, in combination with oversecretion of aldosterone, is unique and, to date, characteristic only of an aldosterone-secreting tumour. We have now documented these findings before operation in five consecutive patients with primary aldosteronism from whom aldosteronesecreting adrenal tumours have been removed.Dr. Brown and his colleagues indicate that our method of evaluating the activity of the renin-angiotensin system will tte "misleading " because we don't know what we are measuring. They state that we have used the technique developed by Boucher et al.4 This is incorrect. Our paper' indicates that the method has been modified. It points out that, while the extraction procedure is that of Boucher et al.,' the sensitivity of the bioassay itself has been improved by the incorporation of a " potentiometric chart recorder." Thus, while it is true that " the originators of the method failed to detect renin activity in 3 out of 16 normal subjects (Veyrat et al., 1964), " we, with our modification, have not failed to detect renin activity in any normal subject ingesting 180 mEq of sodium per day. But this objection of Dr. Brown and his colleagues is not even pertinent. Our major point has been " that, in primary aldosteronism, plasma-renin activity is extremely low and does not increase when those stimuli are applied which result in greatly elevated levels of plasma-renin activity in normal subjects."' ' We reported5 that, upon sodium privation for three days, and with the blood sample drawn after the subject has not been allowed to sit down or lie down for four hours, an eightfold increase in plasma-renin activity is observed in normal people by the method which we employ. In primary aldosteronism, under the same conditions, plasma-renin activity is either undetectable or, when detectable, is very severely suppressed.By these manceuvres, low sodium diet, and the upright posture the sensitivity of the whole testing procedure is multiplied many times.In one of our recent cases this method of evaluating the degree of suppression of the renin-angiotensin system was given a severe test.The patient, with a typical clinical and biochemical picture of primary aldosteronism, had had an exploration of her adrenals in another hospital. Careful inspection and palpation of both adrenal glands had revealed no tumour. 'B...