The effect of cigarette or sheesha smoking on first-trimester markers of Down syndrome.

OBJECTIVE: To investigate the influence of cigarette or sheesha smoking on first-trimester markers of Down syndrome. DESIGN: A prospective observational study. SETTING: Primary care centres and antenatal clinics of Maternity and Children Hospital, King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah, Saudi Arabia. POPULATION: Women with a singleton pregnancy who were either nonsmokers (n = 1736) or cigarette smokers (n = 420) or sheesha smokers (n = 181). METHODS: Fetal nuchal translucency thickness (fetal NT), maternal serum free beta-human chorionic gonadotrophin (free beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) were measured at 11 weeks 0 days to 13 weeks 6 days of gestation in all women. Women were grouped according to smoking status, confirmed by maternal serum cotinine measurements, and analyte levels between groups were compared. MAIN OUTCOME MEASURES: Fetal NT, maternal serum free beta-hCG, PAPP-A and cotinine measurements. RESULTS: Compared with nonsmoking women, fetal NT was significantly increased and free beta-hCG and PAPP-A levels were significantly decreased in both cigarette and sheesha smokers. There were significant relationships between all three markers and the number of sheeshas consumed per day. CONCLUSIONS: Cigarette and sheesha smoking significantly affect first-trimester markers of Down syndrome (fetal NT, free beta-hCG and PAPP-A). Correction for this effect in women who smoke might improve the effectiveness of first-trimester screening for Down syndrome in these women. The underlying mechanism(s) relating smoking to the changes in first-trimester markers require further studies.

Autoantibodies to GAD and IA-2 in Saudi Arabian diabetic patients.

AIMS: To determine the prevalence of autoantibodies in sera of Saudi diabetic patients including Type 1 and Type 2 diabetes mellitus (DM) and gestational diabetes mellitus (GDM) living in Jeddah, Saudi Arabia. Apart from data on the prevalence of islet-cell antibodies in patients in Ryhadh (Al-Attas et al. Frequency of islet cell antibodies in adult newly diagnosed diabetic patients. Ann Saudi Med 1990; 10: 369-373) immunological markers of autoimmune diabetes have not been explored in Saudi Arabians. METHODS: Autoantibodies to GAD65 (GADA) and IA-2 (IA-2A) were determined using radio-immunoprecipitation assays. RESULTS: In Type 1 DM patients, 54% were GADA+ and 27% were IA-2A+. A greater negative effect of disease duration was noted for IA-2A than for GADA positivity. Autoantibodies were more prevalent with younger age of onset. GADA were slightly more common in female Type 1 DM patients. In Type 2 DM, 8/99 patients were GADA+, and three of these patients with shorter disease duration were also IA-2A+. GADA, and particularly IA-2A, were associated with a younger age of onset of Type 2 DM and all the autoantibody-positive Type 2 DM patients were insulin-treated. GADA were detected in 2.2% of GDM patients, but none of these patients possessed IA-2A. CONCLUSIONS: The prevalence and associations of autoantibodies in Saudi diabetic patients are very similar to those reported for diabetic patients in other ethnic groups.

Screening for gestational diabetes mellitus in pregnant females.

OBJECTIVES: To evaluate the applicability of the 50-g glucose challenge test as a screening test for gestational diabetes mellitus in relation to pregnancy outcomes. METHODS: A prospective study was conducted on 818 Saudi pregnant females who were randomly recruited from the Antenatal Clinics at King Abdulaziz University Hospital and New Jeddah Clinic Hospital, Jeddah. All females underwent a 50-g glucose challenge test between 24-28 weeks gestation. A result for 50-g glucose challenge test was considered positive at > 7.2 mmol/L and the female was asked to undergo a 100-g oral glucose tolerance test. The diagnosis of gestational diabetes mellitus was carried out according to the National Diabetes Data Group criteria. RESULTS: A total of 289 females exhibited plasma glucose level > 7.2 mmol/L following the 50-g glucose challenge test. Of the 289 females enrolled for the 100-g oral glucose tolerance test, 102 were diagnosed to have gestational diabetes mellitus (positive oral glucose tolerance test) and 187 were considered oral glucose tolerance test negative according to the National Diabetes Data Group diagnostic criteria. This gave a prevalence of gestational diabetes mellitus of 12.5%. Gestational diabetes mellitus females were significantly older in age, heavier in weight, with higher gravidity, greater percentage of operative deliveries and still-births, and heavier fetal birth weight as compared with the non-gestational diabetes mellitus group (P<0.05 in each case). The maximum sensitivity and specificity of the 50-g glucose challenge test were found to be at plasma glucose value of 7.8 mmol/L post the 50g glucose load. The sensitivity and specificity of this value was 88% and 84%, with a positive predictive value of 82%. To determine whether the values of plasma glucose after a 50-g glucose load were detecting abnormalities similar to those detected according to that of oral glucose tolerance test; the values obtained one-hour post the 50-g glucose challenge test were compared with zero-, one-, 2- and 3-hour values and also the area under the curve in the 100-g oral glucose tolerance test. Plasma glucose post the 50-g glucose challenge test showed marked correlation with oral glucose tolerance test results. This was mostly occurring at the one- and 2-hour oral glucose tolerance test values and was stronger in the gestational diabetes mellitus group and in both the gestational diabetes mellitus plus negative oral glucose tolerance test combined, than in the negative oral glucose tolerance test group on its own. CONCLUSION: It is concluded that plasma glucose level measured one-hour post a 50-g glucose challenge test at 24-28 weeks of gestation with a cut-off value of 7.8 mmol/L is a reliable screening test for gestational diabetes mellitus in the local population studied. This test offers the best combination of ease and economy of use and reproducibility in screening for gestational diabetes mellitus.

"Near miss" obstetric morbidity in an inner city hospital in Saudi Arabia.

A defined "near-miss" end-point, e.g. peripartum hysterectomy, is a more useful measure of obstetric care in a modern inner-city hospital than maternal mortality. Thus, indication(s), type of operation, risk factors and surgical morbidity of all cases of peripartum hysterectomy conducted over a period of 85 months at King Abdul Aziz Hospital, Jeddah were reviewed. The incidence of hysterectomy was 1.22 per 1000 deliveries. Atonic postpartum haemorrhage was the most common reason (43.5%), followed by ruptured uterus (30.4%) and placenta accreta (26.1%). Of the atonic group, five patients were primigravidae, three of whom had severe pre-eclampsia. Abnormally prolonged labour was noted in this group. In the uterine rupture group, only two patients had had previous caesarean sections. In the placenta accreta group, three patients had placenta praevia, two of whom had scars from previous caesarean sections. One maternal death was attributed to amniotic fluid embolism.

"Near miss" obstetric morbidity in an inner city hospital in Saudi Arabia

A defined "near-miss" end-point, e.g. peripartum hysterectomy, is a more useful measure of obstetric care in a modern inner-city hospital than maternal mortality. Thus, indication[s], type of operation, risk factors and surgical morbidity of all cases of peripartum hysterectomy conducted over a period of 85 months at King Abdul Aziz Hospital, Jeddah were reviewed. The incidence of hysterectomy was 1.22 per 1000 deliveries. Atonic postpartum haemorrhage was the most common reason [43.5%], followed by ruptured uterus [30.4%] and placenta accreta [26.1%]. Of the atonic group, five patients were primigravidae, three of whom had severe pre-eclampsia. Abnormally prolonged labour was noted in this group. In the uterine rupture group, only two patients had had previous caesarean sections. In the placenta accreta group, three patients had placenta praevia, two of whom had scars from previous caesarean sections. One maternal death was attributed to amniotic fluid embolism

Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study.

OBJECTIVES: To evaluate calcium-regulating hormones and parathyroid hormone-related peptide (PTHrP) in normal human pregnancy and postpartum in women not deficient in vitamin D. DESIGN: A prospective longitudinal study was conducted in pregnant Saudi women during the course of pregnancy (n = 40), at term and 6 weeks postpartum (n = 18). Maternal concentrations of serum calcidiol and calcitriol were determined, together with those of serum intact-parathyroid hormone (PTH), PTHrP, calcitonin, osteocalcin, human placental lactogen (hPL), prolactin, vitamin D binding protein, alkaline phosphatase, calcium, phosphate and magnesium. A group of non-pregnant women (n = 280) were included for comparative purposes. RESULTS: The calcidiol concentrations decreased (mean +/- S.D.) significantly from 54 +/- 10 nmol/l in the first trimester to 33 +/- 8 nmol/l in the third trimester (P < 0.001) and remained decreased at term and postpartum (both P < 0.001). The calcitriol concentration increased through pregnancy, from 69 +/- 17 pmol/l in the first trimester to 333 +/- 83 pmol/l at term (P < 0.001). Intact-PTH concentrations increased from 1.31 +/- 0.25 pmol/l in the first trimester to 2.26 +/- 0.39 pmol/l in the second trimester, but then declined to values of the first trimester and increased significantly postpartum (4.02 +/- 0.36 pmol/l) (P < 0.001). PTHrP concentration increased through pregnancy from 0.81 +/- 0.12 pmol/l in the first trimester to 2.01 +/- 0.22 pmol/l at term and continued its increase postpartum (2.63 +/- 0.15 pmol/l) (P < 0.001). Significant positive correlations were evident between PTHrP and alkaline phosphatase up to term (r = 0.051, P < 0.001) and between PTHrP and calcitriol (r = 0.46, P < 0.001), osteocalcin (r = 0.23, P < 0.05) and prolactin (r = 0.41, P < 0.05) during pregnancy. Osteocalcin started to increase from 0.13 +/- 0.01 nmol/l in the second trimester, through pregnancy and postpartum (P < 0.001). Calcitonin was increased more than twofold by the second trimester compared with the first trimester (P < 0.001) and subsequently decreased (P < 0.001). Prolactin concentrations were significantly greater in the second (6724 +/- 1459 pmol/l) and third (8394 +/- 2086 pmol/l) trimesters compared with values before pregnancy (P < 0.001). hPL, increased throughout the course of pregnancy, reaching a maximum at term (7.61 +/- 2.57 microIU/ml). There was no direct correlation between serum calcitriol concentrations during pregnancy and serum prolactin (r = -0.12, P < 0.19) or serum hPL (r = 0.17, P < 0.21). Significant changes were observed in the serum concentrations of calcium and phosphate, but not in that of magnesium, during the course of pregnancy; calcium concentrations showed a maximal decrease at term. CONCLUSIONS: Changes in serum PTHrP during the course of pregnancy, at term and postpartum have been demonstrated, suggesting that the placenta (during pregnancy) and mammary glands (postpartum) are the main sources of PTHrP. No support for the concept of 'physiological hyperparathyroidism' of pregnancy could be demonstrated in the present work. The pregnancy-induced increase in calcitriol concentration may thus be the primary mediator of the changes in maternal calcium metabolism, but the involvement of other factors cannot be excluded.

Use of ultrasound longitudinal data in the diagnosis of abnormal fetal growth.

Normal ranges for biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were established from longitudinal data of singleton pregnancies of Arabian mothers. The data were used to develop a normogram of fetal "growth rate" for each parameter. It is suggested that a normogram of "fetal growth" is of less variance than absolute measurements and could be more useful in the early identification of growth abnormalities than absolute fetal measurements.

The diagnosis of "pathological hyperglycaemia' in gestational diabetes in a high risk obstetric population.

In order to define a level of "pathological hyperglycaemia', i.e. glucose intolerance that predicts perinatal morbidity among the obstetric population, 100 g glucose tolerance tests (GTTs) were performed in 660 patients attending for antenatal care at the University Hospital in Jeddah. The results were analysed in two ways: (1) patients were stratified according to the number of abnormal glucose values on the GTTs and (2) patients were placed into one of three groups according to the 100 g GTT diagnostic criteria, i.e. normal (non-GDM), abnormal with fasting blood glucose (FBG) > or = 5.8 mmol l-1 (GDM), and abnormal with FBG < 5.8 mmol l-1 (gestational induced hyperglycaemia, GIH). Although there was a stepwise association between fetal/maternal morbidity with increasing number of abnormal glucose values, no level of glucose intolerance could be defined as a threshold level for normal response. However, when stratified by FBG, GDM patients were significantly heavier (78.5 kg +/- SD 14.9), had a higher incidence of both macrosomia (27.5%) and operative delivery (25.3%) than the other two groups (14.7%, 14.3%, and 15.4%, 12.8% in the non-GDM and GIH, respectively). It is suggested that among patients with abnormal GTT results a FBG > or = 5.8 mmol l-1 identifies a threshold for true "pathological hyperglycaemia'.

Lactation amenorrhea in Saudi women.

STUDY OBJECTIVE: The study aimed to investigate some aspects of breast feeding, namely-lactation amenorrhea, the average interval between pregnancies, and the extent of knowledge that an average Saudi woman has about breast feeding. DESIGN: This was a cross sectional study in which a pretested questionnaire was used to collect the information. SETTING: The study was conducted in the Taif area between January and April of 1990. Seventy nine primary health care centres participated. PARTICIPANTS: Altogether 1019 of 2400 women contacted who agreed to participate and met the criteria were studied. Eligible subjects were defined as Saudi women, between 16 and 40 years old, who came with their infants for vaccination, and had delivered between one week and 12 months previously. Each mother had at least one other child. MEASUREMENT AND MAIN RESULT: At birth, the percentage of infants who were initially breast fed was 98% but within three days of delivery over two thirds (68.9%) of the mothers gave other supplementary liquids to their infants. At the time of interview more than half (55.1%) of mothers had lactation amenorrhea. The mean (SD) lactation amenorrhea period and birth interval were 5.95 (5) and 26.8 (14.1) months, respectively. Mothers obtained information on breast feeding mainly from their doctors and television. Within families, husbands had the primary role in encouraging their wives to breast feed, followed by the mother and then by the mother in law. It was found that a high percentage (94.2%) of women had breast fed their previous child. CONCLUSION: The lack of adequate information on breast feeding and the short interval between births are local problems which should be considered by the health authorities.

Serum immunoglobulin concentrations in diabetic patients.

The relationship between glycated haemoglobin (an index of long-term diabetic control), fructosamine (an index of intermediate-term diabetic control), and serum IgA, IgG, and IgM was studied in 110 diabetic patients (41 Type 1 and 69 Type 2) and compared with 111 healthy non-diabetic subjects. Significant increases in serum IgA (by 82.7%, p < 0.001) and IgG (by 35.2%, p < 0.001) concentrations were observed whereas the concentration of IgM was significantly decreased (by 46.7%, p < 0.001) in diabetic patients compared with non-diabetic subjects. Using Spearman's rank correlations, IgA correlated with fructosamine (r = 0.77, p < 0.001), HbA1 (r = 0.76, p < 0.001), and albumin (r = -0.58, p < 0.001) for the entire population sample but only fructosamine (r = 0.19, p < 0.05) and HbA1 (r = 0.28, p < 0.001) correlated with IgA in diabetic patients, respectively. It is concluded that abnormal levels of IgA, IgG, and IgM are very common in diabetic patients in whom serum IgA concentrations are influenced by the degree of glycaemic control. Whether changes in IgA and other immunoglobulins are implicated in the pathogenesis of diabetic complications (such as susceptibility to infection) deserve further study.

Fructosamine in obese normal subjects and type 2 diabetes.

The effect of various grades of obesity on serum fructosamine concentrations was studied in Type 2 diabetic (n = 105) and non-diabetic (n = 128) subjects. In obese diabetic and non-diabetic subjects (body mass index > or = 30 kg m-2), the concentration of fructosamine was markedly lower than that obtained for lean diabetic and non-diabetic subjects with similar glycaemic control. Stepwise multiple-regression analysis showed that fructosamine was associated with glycaemic control (as indicated by fasting plasma glucose and glycated haemoglobin), fasting triglycerides, and body mass index in both diabetic and non-diabetic subjects. In vitro studies showed marked decreases in both the extent of [14C]-glucose incorporation into plasma proteins and fructosamine production by incubated sera of obese patients whether diabetic or non-diabetic, with obese subjects with body mass index > 40 kg m-2 exhibiting the greatest decrease. In conclusion, serum fructosamine concentrations are shown to decrease in obese diabetic and non-diabetic subjects with body mass index > or = 30 kg m-2 giving rise to the underestimation of glycaemic control as indicated by fructosamine measurement. A change in the glycation reaction itself may be partly responsible for such decrease.

Outcome of pregnancy in diabetic mothers.

OBJECTIVE: To study complications seen among newborns of gestational diabetic mothers versus nondiabetics, and to compare the pattern of distribution of those complications to similar reports form Western populations. METHOD: Prospective case controlled study of 384 newborns, (191 of diabetic and 193 of nondiabetic mothers) delivered at the King Abdulaziz University Hospital, Jeddah. RESULTS: The overall rate of infant morbidity was greater among newborns of diabetic mothers, especially those who required insulin for metabolic control. The major complications were those associated with increased incidence of large birth weight infants. Complications such as congenital malformations, intrauterine growth retardation and other severe forms of morbidity often associated with insulin-dependent diabetes were rarely seen. CONCLUSION: Fetal and neonatal risks associated with diabetes in pregnancy depend not only on the severity, but also on the type of diabetes. In modern societies fetal complications associated with diabetes are mainly those due to hyperglycemia in the second half of gestation. The results also emphasize the fact that perinatal morbidity rather than mortality should be the yardstick for the efficacy of management of diabetes in pregnancy.

Prenatal diagnosis of recurrent Meckel syndrome.

We report a rare case of Meckel-Gruber syndrome in a woman who had three affected offsprings in the past with similar condition. Ante-natal ultrasonographic diagnosis and management are presented.

The effect of intrauterine intravascular blood transfusion on iron metabolism in fetuses with Rh alloimmunization.

Fetal plasma ferritin concentrations were measured in 43 normal fetuses at 18-36 weeks and in 78 blood samples collected before transfusion from 23 fetuses with Rh alloimmunization. Among controls, there was a significant correlation between fetal serum ferritin and gestational age (r = 0.39, P = .009), consistent with an increase in fetal storage of iron during normal pregnancy. In Rh-alloimmunized fetuses, the ferritin concentration was above the reference range in 63% of the samples. Before the first transfusion, the fetal ferritin concentration was increased compared with controls (mean multiples of the mean = 2.6, range 1-26) and showed a negative correlation with fetal hematocrit (r = -0.43, P less than .05), suggesting that the worse the fetal anemia, the higher the iron store. Serial transfusions were associated with further increase in serum ferritin, which correlated primarily with the total volume of blood transfused. Three fetuses had plasma serum ferritin concentrations above 1 mg/L, a level compatible with a diagnosis of iron overload in children. These observations suggest that there is a potential risk of iron overload in Rh-alloimmunized fetuses undergoing intrauterine blood transfusion.

Fructosamine as a screening-test for gestational diabetes mellitus: a reappraisal.

Fructosamine, glycosylated hemoglobin (HbA1c) and serum total proteins were measured in normal nondiabetic pregnant women (n = 170) at three stages of pregnancy (14-18, 24-28, and 32-40 weeks of gestation). No significant correlation was found between fructosamine and either HbA1c or total plasma proteins. Only early in pregnancy (less than 20 weeks of gestation) was a correlation found between fructosamine and fasting blood glucose (r = 0.40, P less than 0.05). There was also no correlation between either tests (i.e. fructosamine and HbA1c) and fetal birthweight. The value of fructosamine measurement in the detection of diabetes in pregnancy was further tested in a group of high-risk patients (n = 98) for developing carbohydrate intolerance. It is concluded that fructosamine has limited value as a screening test for gestational diabetes mellitus, particularly for the mild form of the glucose intolerance.

Loss of growth hormone responsiveness to normal physiological stimuli during pregnancy.

The response of pituitary GH to acute hyperglycaemia induced by 75 g oral glucose load in 73 pregnant women at various stages of gestation was examined. According to the age of gestation, patients were grouped into three groups: less than 20 weeks, between 20-30 and more than 30 weeks. Plasma glucose, GH and C-peptide were measured at fasting and then at 30, 60, 120 and 180 min following the glucose load. There was a significant increase in plasma GH concentration with weeks of gestation. The results also showed a loss of the normal physiological suppressive effects of hyperglycaemia on GH secretion in tests performed after 20 weeks of gestation. Only in tests performed before 20 weeks, there was a significant negative correlation between plasma glucose and GH values. These findings are consistent with recent reports suggesting an almost complete suppression of pituitary GH secretion by a placental variant of GH. These changes in the dynamics of GH secretion suggest that, in pregnancy, GH plays a more significant role than was previously thought.

New criteria for interpretation of the 75 g oral glucose tolerance test in pregnancy.

A 75 g oral glucose tolerance test (OGTT) was performed on 135 high-risk pregnant patients. When the current World Health Organization (WHO) criteria for the diagnosis of gestational-glucose tolerance were applied, 88 patients were considered normal, 11 had gestational diabetes, and 36 patients had impaired-glucose tolerance, respectively. The plasma glucose, insulin, and C-peptide levels during the OGTT were further studied in the 88 patients (who had normal results). Two metabolically distinct groups were identified; a group (n = 53) with a 2-hour plasma glucose less than or equal to 6.6 mmol/L (118.8 mg/dL), had a normal insulin and C-peptide pattern, and a second group (n = 35) who had 2-hour plasma glucose greater than 6.6 mmol/L displayed a glycemic, insulin, and C-peptide pattern similar to that of patients with gestational diabetes mellitus. The risks of macrosomic babies and operative delivery were significantly greater in the latter group. These results suggest that in our pregnant population, a group of patients with impaired glucose tolerance will be under-diagnosed using the current WHO criteria. Based on our results new criteria for gestational glucose intolerance are suggested for our population.

Perinatal effects of nicotine.

Nicotine alkaloid as a base was administered to 3 groups of pregnant Swiss albino mice during each trimester of their pregnancy. Three doses of the drug (900, 1,800 and 2,700 micrograms/kg/day) which respectively correspond to 3 levels of cigarette smoking (10, 20 and 30 cigarettes per day) were used. In order to find out which stage of pregnancy is most vulnerable to the effects of nicotine, each dose of the drug was administered subcutaneously to a group of animals during each trimester of their pregnancy. The perinatal effects, i.e., gestation period, percent of delivering mothers, the male to female ratio of the offspring, and the perinatal mortality, i.e. still-birth and neonatal death, were observed. In general, nicotine has increased the perinatal mortality. When large doses of the drug were given especially in the second and third trimesters of gestation, there was a significant shortening of the gestation period (p less than 0.05; p less than 0.01). Hence, during pregnancy, mothers who smoke should be warned against the harmful effects of smoking especially in the late period of their pregnancy.