Tom Lind

Unsuspected pregnancy loss in healthy women.

A sensitive and specific radioimmunoassay was used to determine human chorionic gonadotropin (hCG) in serum samples obtained from 91 normal healthy women during 226 ovulatory cycles in which contraception was not being practised. Known conceptions occurred in 85 of these cycles; 74 ended in the births of live normal babies and the remaining 11 aborted spontaneously. Vaginal bleeding occurred at the expected time on the remaining 141 occasions and was accepted as normal menstruation by the patients; but concentrations of hCG consistent with pregnancy were detected in the serum of 7 individuals. Expressed as a proportion of conceptions, about 8% of human pregnancies are lost at such an early stage of development that the patients are unaware that conception has occurred.

A SERIAL STUDY OF CHANGES OCCURRING IN THE ORAL GLUCOSE TOLERANCE TEST DURING PREGNANCY

Nineteen healthy pregnant women with no family history of diabetes took part in a serial study in which they had a standard 50 g. oral glucose tolerance test (OGTT) at 10, 20, 30 and 38 weeks gestation and again 10 to 12 weeks after delivery. While every test result remained within “normal” limits as defined by any of the standard criteria, subtle and progressive changes in the shape of the glucose response curve were shown to occur throughout pregnancy. These changes in shape were evaluated by means of the H index recently described by Billewicz et al. (1973); in 14 patients the values attained were characteristic of a “suspect” or “abnormal” response in non–pregnant subjects. Nevertheless since all of these women remained clinically normal throughout, and it is unlikely that 14 out of 19 will become diabetic later in life, it seems unreasonable that these changes per se should be regarded as evidence of impending pathology.

BIOCHEMICAL AND CYTOLOGICAL CHANGES IN LIQUOR AMNII WITH ADVANCING GESTATION

THE terms liquor amnii and amniotic fluid both imply a relationship between the membrane and the fluid beyond mere anatomical containment, and many believe the membranes to be the origin of liquor and the regulator of its water and solute contents. This was not always so. Hippocrates is accredited with the belief that the main source of liquor is fetal urine (Shaw and Marriott, 1949) and Mauriceau (1683) said that liquor “only generated out of Vaporous Humidities which transude and exhale continually out of the Infant’s Body”. Joseph Needham, a 17thcentury man-midwife described the liquor as a “private pond” for the fetus (Holland, 1959). Most recent authorities seem to have assumed that amniotic fluid has a relatively stable composition and have published average values for the major constituents (Hannon, 1957; Bonsnes, 1966). Huntingford (1966), however, has reported that the osmolality of the liquor near term is lower than that of maternal plasma, while Pitkin and Zwirek (1967) demonstrated a rise in creatinine content to levels above that of maternal plasma as term approaches. This paper describes a series of investigations into the biochemical and cytological properties of liquor amnii from an early stage of gestation. It will be shown that these properties display several interesting trends, and a theory will be advanced to account for them. MATERIAL AND METHODS Liquor from pregnancies between 8 and 20 weeks of gestation was obtained at hysterotomy. To avoid contamination with maternal blood, the sacs were delivered intact and the liquor then aspirated. From 22 to 37 weeks specimens were obtained at amniocentesis undertaken for diagnostic purposes in cases of rhesus iso-immunization. At later stages of gestation specimens were obtained from patients having labour induced by rupture of the membranes with a Drew-Smythe catheter. Any specimen contaminated with blood or meconium was rejected. The range of observations was extended as the investigation proceeded, so not all observations are available on all the specimens of liquor. With the most recent specimens, samples of maternal blood were also obtained for analysis. The biochemical data come from patients who were confident of the date of their last menstrual period. Experience in the cytological appearance of liquor was gained similarly where the stage of gestation was known with certainty. A paediatrician (F.M.P.) examined the infants after delivery and their “clinical age” was assessed without reference to obstetric data by a point scoring system of physical characteristics (Farr et al., 1966). Later, in cases where the gestational stage was uncertain the “cytological age” was compared with the “clinical age” only.

The intravascular mass of albumin during human pregnancy: a serial study in normal and diabetic women

Objective To quantify the changes in serum albumin during human pregnancy.

Inductively coupled plasma mass spectrometric determination of the absorption of iron in normal women

The determination of iron isotope ratios in blood, without prior sample preparation, using inductively coupled plasma mass spectrometry (ICP-MS) with sample introduction by electrothermal vaporisation (ETV) is described. Following oral administration of 5 mg of enriched 54FeSO4 and intravenous administration of 200 micrograms of 57FeSO4 to non-pregnant women, the 54Fe: 56Fe and 57Fe: 56Fe isotope ratios in serum were measured reliably within 20 min per sample in quintuplicate. Changes in the fractional absorption of iron during human pregnancy could therefore be assessed.

Iron absorption during normal human pregnancy : a study using stable isotopes

The absorption of iron has been determined in nine healthy women studied serially during pregnancy and once post delivery. Following the oral administration of 5 mg aqueous 54FeSO4 plus ascorbic acid and the intravenous injection of 200 micrograms 57FeSO4, the isotope ratios of 54Fe: 56Fe and 57Fe: 56Fe in serum were measured by the use of inductively-coupled-plasma mass spectrometry whereby metal ions are vaporized into an argon plasma without previous blood sample preparation. Mean oral Fe absorption was 7.6 (range 1-22)% at 12 weeks gestation, 21.1 (range 9-58)% at 24 weeks, 37.4 (range 18-56)% at 36 weeks and 26.3 (range 8-54)% at 12 weeks post delivery. All the other biochemical and haematological indices were within normal limits for pregnancy. The significant increase (P less than 0.01) in Fe absorption during normal pregnancy suggests that most women would have the potential to meet the Fe demands of pregnancy without the need for supplementation if dietary Fe has similar availability to the aqueous preparation.

THE EXCRETION OF GLUCOSE DURING NORMAL PREGNANCY

Thirty healthy pregnant women took part in a serial study in which they collected 24‐hour samples of urine for the estimation of glucose excretion at least 8 times during pregnancy and again post partum; for one week before the collection they tested their urine with “Clinistix” each time they passed it. Ten of the women showed no obviously increased glucose excretion during pregnancy. The other twenty excreted glucose in above normal amounts but with great variation both from subject to subject and in the same subject. The pattern of excretion shown by “Clinistix” was one of intermittent glycosuria. Days and groups of days in which glycosuria was the rule were separated by similar periods without it. The value of routine urine testing for glucose in pregnancy is questioned.

Observations on Blood Glucose and Insulin Determinations

The relation of capillary to venous blood glucose concentration, whole blood to plasma values, and, where possible, the effect of pregnancy on the variables have been studied. We have not been able to show constant relations between capillary and venous blood glucose concentrations as have been implied by a W.H.O. expert committee on diabetes mellitus and the British Diabetic Association. The choice of anticoagulant was shown to have a negligible effect on the results of a single antibody-charcoal separation insulin assay method.

Some endocrinological events associated with early pregnancy failure

Serial measurements of serum progesterone, oestradiol, human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) have been determined in 33 women experiencing early pregnancy failure and compared with the values of the same hormones in 72 healthy women having uncomplicated pregnancies. Steroid production by the corpus luteum seemed similar in both groups up to 6 weeks gestation but thereafter placental steroidogenesis was not evident in those women in whom spontaneous pregnancy losses occurred. Placental production of the two protein hormones, hCG and hPL, did take place, and whereas the circulating levels were not as high as in normal pregnancies, levels did usually increase before clinical evidence of miscarriage occurred. hCG was not a sensitive discriminator of subsequent failure. In these women there were no significant hormone differences between those with evidence of a fetus and those without.

COMPOSITION OF AMNIOTIC FLUID AND MATERNAL BLOOD THROUGH PREGNANCY

Samples of amniotic fluid and of maternal blood were obtained at abdominal hysterotomy, by amniocentesis from patients with rhesus iso‐immunization and at surgical induction of labour. In 135 women whose pregnancies were beyond mid‐term, the menstrual dates were accurately known.