Fetal growth retardation and second trimester maternal serum human chorionic gonadotrophin levels.

Second trimester maternal serum human chorionic gonadotrophin (hCG) levels in women who remained normotensive but delivered an unexplained growth retarded infant were compared with those from a control group and a group of women who developed pre-eclampsia in a retrospective observational study. Our hypothesis was that the similar placental pathological changes shared by unexplained normotensive IUGR and pre-eclampsia would be reflected by elevated maternal serum hCG levels in the second trimester. Normotensive women delivering unexplained singleton growth retarded infants were identified (n=43) and their second trimester hCG levels, taken as part of antenatal screening for Down's syndrome, were obtained. These were compared with a control group of 625 women, and a group of 48 women who subsequently developed pre-eclampsia. There was no significant difference in the hCG levels expressed as multiples of the median (MOM) between the women who delivered growth retarded fetuses (median MOM 0.96) and the control group (median MOM 0.97). The levels of hCG in the women who subsequently developed pre-eclampsia were significantly higher (median MOM 1.3, P=0.008). There were no significant differences in AFP levels in the three groups; however, the trend was towards a higher level of AFP in the fetal growth retardation group. Maternal serum hCG in the second trimester does not appear to be elevated in normotensive women who later produce a growth retarded fetus, although human chorionic gonadotrophin levels are significantly higher in women who subsequently develop pre-eclampsia.

Histological study of decidual spiral arteries and the presence of maternal erythrocytes in the intervillous space during the first trimester of normal human pregnancy.

During the first trimester in normal human pregnancy, endovascular trophoblast migrate along the decidual spiral arteries and invade their walls to produce physiological change. There is controversy as to whether invading trophoblast plug the arteries and prevent blood flow into the intervillous space. Using light microscopy, placental bed sections from 25 first trimester gravid hysterectomy specimens were examined. From each specimen, one section was divided into equal central and peripheral compartments. Maternal red blood cells were present in the intervillous space in all specimens, in both central and peripheral areas. In total, 232 decidual spiral arteries were found, each of those represented by several cross sections, 136 in the central area and 96 in the periphery. Seventy-nine per cent had undergone physiological change (significantly more in the centre than in the periphery), 63 per cent contained scattered endovascular trophoblast, 20 per cent had plugs of trophoblast partially occluding the vessel and 17 per cent had plugs totally filling the vessel lumen. These data confirm that in the first trimester of normal pregnancy, maternal blood enters the intervillous space, total plugging of the arterial system by trophoblast is not common, and more spiral arteries undergo physiological change in the centre than in the periphery.

Preventing Rhesus D haemolytic disease of the newborn by giving anti-D immunoglobulin: are the guidelines being adequately followed?

OBJECTIVE: To ascertain whether anti-D immunoglobulin is being administered to Rhesus D negative women in accordance with the 1991 recommendations for its use to cover all events which may result in fetomaternal haemorrhage. DESIGN: The notes of women delivered in 1994 were examined for compliance with the 1991 recommendations. SETTING: Seven maternity units using a central antenatal screening service. PARTICIPANTS: Nine hundred and twenty-two Rhesus D negative women delivered in these seven hospitals. MAIN OUTCOME MEASURES: The prescription, dosage and indications for administration of anti-D immunoglobulin to women during pregnancy and in the puerperium. RESULTS: Postnatal anti-D immunoglobulin was given in appropriate doses to more than 95% of women who required it. Omissions mainly arose from confusion among women who recently had received antenatal treatment with anti-D immunoglobulin. The 1991 recommendations for antenatal administration were less closely followed. Abdominal trauma was covered in only 20% of cases. An inadequate dosage of 250 i.u. was given to 25 women for antepartum haemorrhage after 20 weeks of gestation. The purpose of the Kleihauer test was sometimes poorly understood, with a 'negative' result interpreted as a reason not to give anti-D immunoglobulin. CONCLUSION: Closer adherence to the 1991 recommendations might further reduce the incidence of Rhesus D immunisation below the current 1%. It is suggested that more careful application of the recommendations should be evaluated before considering either routine antenatal prophylaxis, or the European recommendation of a larger dose (1000-1500 i.u.), both of which would increase the requirements for this limited resource.

Spiral artery blood flow in the central and peripheral areas of the placental bed in the second trimester.

OBJECTIVE: To assess impedance to blood flow through spiral arteries in the central and peripheral areas of the placental bed, to determine if in vivo findings are in concordance with histologic observations of cytotrophoblast invasion. METHODS: This study was cross-sectional, using transabdominal color flow and pulsed Doppler imaging in 64 women with normal, singleton pregnancies at 17-20 weeks' gestation. Spiral arteries were visualized by color Doppler in the central and peripheral parts of the placental bed, and blood flow was analyzed using pulsed Doppler to calculate the resistance index (RI) and the pulsatility index (PI). RESULTS: Visualization of flow in the spiral arteries was achieved in 100% of cases in the central area and in 95% in the periphery. Both the RI and PI were significantly lower in the center compared with the periphery (P < .001). There was no significant difference in the peak systolic velocities between the two areas. Regression analysis showed no significant difference in RI or PI at the different weeks of gestation in the central and peripheral areas of the placental bed. CONCLUSION: Impedance to blood flow through spiral arteries in the second trimester is lower in the central area of the placental bed, and is in agreement with previous histologic data. Physiologic change of the spiral arteries is functionally complete around 17 weeks' gestation.

The role of a single progesterone measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability.

OBJECTIVE: To assess the role of a single maternal serum progesterone measurement in the immediate diagnosis of early pregnancy failure and in the long term prognosis of fetal viability. DESIGN: A prospective comparative study of women presenting with vaginal bleeding and abdominal pain in early pregnancy. The comparison group was defined retrospectively as women who presented with abdominal pain without history of, or the subsequent occurrence of, vaginal bleeding and whose pregnancies continued to viability. The study groups were defined retrospectively as threatened-continuing, non-continuing (including blighted ovum, missed abortion, incomplete and complete abortion) and tubal pregnancy groups, according to the outcome of the pregnancies. SETTING: The emergency room at the gynaecology department of a teaching hospital. SUBJECTS: Four hundred and eighty-nine women presenting with singleton pregnancy, vaginal bleeding and/or abdominal pain in the first 18 weeks of pregnancy. The comparison group comprised 131 women without vaginal bleeding whose pregnancies continued to viability. The study group comprised 358 women with 148 threatened-continuing pregnancies, 175 non-continuing and 35 tubal pregnancies. INTERVENTIONS: A 10 ml blood sample was taken and pelvic ultrasonography was performed at presentation. Otherwise, conventional management was used. MAIN OUTCOME MEASURES: Progesterone levels were interpreted in accordance with the outcome of the pregnancy: comparison, threatened-continuing, non-continuing or tubal. Viability was defined as 28 weeks or more weeks of gestation. RESULTS: Progesterone levels were significantly lower in the non-continuing and tubal pregnancy groups than in the comparison and threatened-continuing groups (P < 0.001 in all cases). A cut-off level at 45 nmol/1 was found to differentiate between the viable (comparison and threatened-continuing) pregnancies and the abnormal (non-continuing and tubal) pregnancies with 87.6% sensitivity and 87.5% specificity. CONCLUSIONS: A single serum progesterone measurement taken in early pregnancy is valuable in the immediate diagnosis of early pregnancy failure and the long term prognosis of viability.

Endothelial cell activation by tumour necrosis factor-alpha (TNF-alpha) and the development of pre-eclampsia.

Pre-eclampsia may develop as a result of an endothelial activation. Tumour necrosis factor-alpha (TNF-alpha) activates endothelial cells which release soluble E-selectin, a putative circulating marker specific for endothelial damage. A retrospective longitudinal study of maternal blood samples, collected at different gestational ages in pregnancy, was undertaken to determine whether the development of pre-eclampsia is associated with TNF-alpha-mediated endothelial activation. This study included 19 women who developed pre-eclampsia and 22 women whose pregnancy outcome was normal. Ten women had blood samples taken before pre-eclampsia was clinically detected and, in all these, TNF-alpha was below the immunoassay limit of detection (< 80 pg/ml). Five had further samples taken after pre-eclampsia was clinically diagnosed and, initially, TNF-alpha was still below the lower limit of detection in all five pregnancies, but rose later in three (80, 156 and 250 pg/ml). In nine other patients with diagnosed pre-eclampsia, TNF-alpha was detected in only two (80 and 650 pg/ml). TNF-alpha was identified in only one of the 22 normal pregnancies (80 pg/ml), this being at term. There was no statistical difference in soluble E-selectin levels between normal and pre-eclamptic pregnancies, neither before nor after pre-eclampsia was diagnosed. Hence, blood TNF-alpha levels measured by immunoassay can be elevated in approximately 36% of cases of established pre-eclampsia, but this rise occurs only after the syndrome is detected clinically. Blood concentrations of TNF-alpha and soluble E-selectin are not related to severity of the disorder. These findings suggest that circulating TNF-alpha does not contribute to the initiation of endothelial cell activation that may be associated with the development of pre-eclampsia, but may rise as a consequence of the pathological processes of this disorder.

A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies.

OBJECTIVE: To investigate trophoblast invasion and vascular changes in placental bed spiral arteries in normal and severe pre-eclamptic pregnancies. DESIGN: A histological and immunohistochemical study of placental bed biopsies containing spiral arteries. SETTING: The University Hospital, Leuven, Belgium. SUBJECTS: Twenty-one placental bed biopsies from 21 normal pregnancies and 24 placental bed biopsies from 24 severe pre-eclamptic pregnancies, taken at caesarean section. OBSERVATIONS: Histological and immunohistochemical appearance of spiral arteries (stained with haematoxylin and eosin), periodic acid schiff, and a monoclonal antibody to low molecular weight cytokeratin. RESULTS: One hundred and twenty-seven spiral arteries were studied. In the 21 biopsies from clinically normal pregnancies at term, 100% of the decidual spiral arteries and 76% of the myometrial arteries showed trophoblast invasion. In the 24 biopsies from women with severe pre-eclampsia, trophoblast invasion was seen in 44% and 18% of the decidual and myometrial segments, respectively. Endovascular trophoblast invasion was complete, partial or isolated. A variety of morphological features was present not only in different spiral arteries from the same biopsy but also in different segments of the same artery. The vascular change most commonly associated with normal pregnancies was physiological change and subintimal thickening of both segments of the spiral arteries. In pre-eclampsia medial disorganisation and hyperplasia in the myometrial arteries and acute atherosis in decidual arteries were common. CONCLUSION: Endovascular trophoblast did not show an all or none invasive phenomenon in normal and pre-eclamptic pregnancies. More decidual than myometrial arteries were invaded in both groups of patients, and there was a gradient in the percentage of decidual and myometrial arteries invaded from normal pregnancy to pre-eclampsia. Morphological features in one spiral artery may not necessarily be representative of all of those in a placental bed.

Immunohistochemical detection of lipoprotein(a) in the wall of placental bed spiral arteries in normal and severe preeclamptic pregnancies.

In normal pregnancy trophoblast invades the spiral arteries and produces the physiological fibrinoid degeneration of the vessel wall. In pre-eclampsia, physiological change is restricted and pathological change develops in the non-invaded arteries, including acute atherosis. This study was undertaken to determine if lipoprotein(a) [Lp(a)], which is associated with atherogenesis is present in the wall of spiral arteries that have undergone physiological and pathological change. One hundred and sixteen spiral arteries were examined from 18 normal and 24 severe pre-eclamptic pregnancies. Lp(a) was detected in all atherotic and necrotic lesions, in 57% of spiral arteries with medical disorganization or hyperplasia, and in 45% of those with physiological change. When Lp(a) was detected differences were found in the amount seen: it was most in atherosis, less in necrosis, less still in medical change, and least in physiological change. For the same vascular change generally more Lp(a) was detected in the pre-eclamptic group than in the normal group. The detection of Lp(a) helps to distinguish physiological fibrinoid from atherotic and necrotic fibrinoid. Many atherotic and necrotic areas initially overlooked using standard histology were highlighted using immunohistochemistry. Atherosis can develop in spiral arteries that have been invaded by trophoblast. In those with pre-eclampsia, atherosis was found in 56% of decidual but only in 8% of myometrial spiral arteries. Small areas of necrosis were common in physiologically changed arteries from normal pregnancies.

High arachidonic acid levels in the cord blood of infants of mothers on vegetarian diets.

1. Maternal and umbilical cord plasma samples were collected from forty-seven Asian women, twenty-eight life-long vegetarians and seventeen non-vegetarians, during delivery of their babies. The concentrations and fatty acid profiles of the plasma free fatty acid and triacylglycerol fractions were determined. 2. There were no significant differences between the levels of free fatty acid and triacylglycerol in either maternal or cord plasma from vegetarian compared with non-vegetarian Asian women. The fatty acid profiles of the lipid fractions in the two groups were similar. Total plasma free fatty acid levels in the maternal circulation correlated with umbilical cord levels. 3. The levels of linoleic acid in the maternal plasma free fatty acid fraction of the Asian women were much higher than previous reports on mixed populations of European women. In the Asian women arachidonic acid concentrations in both maternal and umbilical circulations were over four times higher than those reported for women unselected for race and diet.

Prenatal diagnosis of 3-hydroxy-3-methylglutaric aciduria by GC-MS and enzymology on cultured amniocytes and chorionic villi.

This paper reports the prenatal diagnosis of HMG CoA lyase deficiency at 16 weeks' gestation by direct chemical analysis of cell-free amniotic fluid and by measurement of HMG CoA lyase activity in cultured amniocytes. Termination of an affected fetus allowed study of chorionic villus tissue, the results providing the basis for future first trimester prenatal diagnoses of this condition. An abstract report of this work has appeared elsewhere.

Assessment of trace metal intake and status in a Gujerati pregnant Asian population and their influence on the outcome of pregnancy.

Dietary assessments and biochemical indices including plasma zinc and copper were determined in pregnant vegetarian and non-vegetarian Gujerati women in India at 28 weeks gestation, and the results were contrasted with those of a comparable group of Gujerati pregnant women living in Harrow. Even though the dietary intake of energy, protein and zinc was significantly lower in the Indian vegetarian Gujerati group when compared to the equivalent group in Harrow, the birthweights of the babies delivered at term were similar. The intake of zinc in the diet of the Gujerati Indian vegetarian and non-vegetarian groups was only one quarter of the US recommended intake during pregnancy and was approximately one half in the Harrow Indian groups. Even so, the plasma concentrations of zinc were similar in all dietary groups in either India or Harrow. The albumin content in the plasma of both the Gujerati Indian vegetarian and non-vegetarian was significantly reduced when compared to the equivalent Harrow dietary groups. The plasma concentrations of both calcium and sodium were significantly correlated with the albumin concentration but not with the plasma content of zinc. Copper levels were elevated to the normal range in both dietary groups of the Gujerati and were similar to the concentrations found in the Harrow groups.

Acute bacterial endocarditis on a normal aortic valve following vaginal delivery.

We present a case of post-partum bacterial endocarditis on a normal aortic valve. Infection occurred following vaginal delivery. This complication, due to group D Streptococcus faecalis, has not been previously described in this context.

Diets of Asian pregnant women in Harrow: iron and vitamins.

In a study of the Asian pregnancy, the dietary intakes of 813 Asians and 54 Europeans living in Harrow were compared. Results of calculation of intakes of iron and vitamins are presented in this paper. The key findings were that vitamins D and B12 intakes were markedly lower amongst the Asians, particularly the Hindu vegetarians. Asians had lower intakes of other vitamins but these levels are unlikely to lead to deficiency and therefore not relevant in clinical terms. The Hindu vegetarians can be regarded as a fairly homogenous group with differences occurring within the group only in vitamin B12 intake. From the nutritional data it appears unnecessary to advocate any change in the Gujarati diet other than supplementation with vitamin D.

Is screening for bacteriuria in pregnancy worth while?

A total of 4470 pregnant women were screened for bacteriuria by the dipslide method and significant growth found in 226 (5.1%). In 198 cases the urine was re-examined, in 119 by using suprapubic aspiration or catheterisation (62 (52%) samples contained bacteria) and in 79 by using midstream urine samples (26 (33%) samples contained greater than 10(8) colony forming units/1), showing the maximum prevalence of confirmed bacteriuria to be 2.6%. Overt urinary tract infection developed later in four of 80 patients with proved bacteriuria who had been given antibiotics, in one of eight untreated patients with bacteriuria, in one of 110 patients with unconfirmed bacteriuria, and in one of 226 non-bacteriuric controls. A history of urinary tract infection was given by 18% of controls and 42% of women with confirmed bacteriuria. Screening for bacteriuria and treatment with antibiotics to prevent later overt infection is expensive. Whether it is worth while and cost effective depends largely on the prevalence of bacteriuria in the local population and the proportion who develop overt infection. The screening and treatment programme reported here appeared to prevent only six cases of overt infection.

Single-dose treatment of bacteriuria in pregnancy.

Comparison of the results of single-dose treatment of urinary tract infection in women is confused by differences between published series in the duration of follow-up and in the diagnosis of infection. Pregnancy allows prolonged follow-up in a motivated population, but increases the possibility of false positive diagnosis of infection from midstream urines due to increased vulvovaginal contamination. Suprapubic aspiration (SPA) is safe in pregnancy and accurately confirms the presence or absence of bacteria in the bladder urine. Bacteriuria was diagnosed by SPA in 86 pregnant women. Thirty-seven of these were treated with a single dose of 3 g cephalexin and 49 with 3 days of cephalexin 1 g or of a combined preparation of pivmecillinam-pivampicillin. Both single-dose and 3-day treatments prevented further bacteriuria in 65% of the patients for the remainder of their pregnancies. This is similar to the results achieved with 10-day treatment. If extended trials confirm that single-dose treatment is as effective as conventional treatment with the same drug, then single-dose treatment has the advantages in pregnancy of minimal medication, good patient compliance and lack of side-effects.

The relation of birthweight to histological appearances in vessels of the placental bed.

Biopsy of the placental bed was attempted at caesarean section in 109 patients: 77 consecutive and 32 selected because of the maternal or fetal condition. Forty-seven (44%) of these biopsies were from the placental bed and contained spiral arteries suitable for comment. Histological examination separated the patients into four groups: comprising 11 whose vessels showed normal physiological changes, 20 who showed inadequate physiological change, 12 with acute atherosis, and four with a mixed pattern. There was no relation between these changes and maternal age, parity, race or smoking habit, but no physiological change and atherosis were more common in association with maternal hypertension. Mean adjusted birthweight was greatest in those with physiological changes, less in those without physiological changes or the mixed pattern, and least in those with atherosis. The four patients in the mixed group did not have any unifying clinical characteristics.

The relation between plasma urate and placental bed vascular adaptation to pregnancy.

Placental bed biopsies were obtained at caesarean section from 34 women. Their plasma urate was directly related to maximum mean arterial pressure and inversely to adjusted birthweight; but it was related most closely to the histological appearances of the spiral arteries in the placental bed. Nine women had physiological changes in the spiral arteries: their mean urate (233, SD 28.9 mumol/l) was significantly (P less than 0.001) lower than the mean urate in those who did not have adequate physiological changes (339, SD 90.3 mumol/l) or that in the nine women who had atherosis (397, SD 153.2 mumol/l). Raised plasma urate appears to be better related to maternal vascular pathology than to the clinical condition or infant birthweight.