140 Chapter Five Ultrasound Prediction of At Risk Birth Weight in Chinese and Caucasian Fetuses in Normal Pregnancy and those Complicated by Gestational Diabetes Mellitus 5.1 Introduction Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of any level with onset or first diagnosis during pregnancy. Pregnant women at the Royal North Shore and Hornsby Ku-Ring-Gai Hospitals in Northern Sydney undergo a 50g glucose challenge test (GCT) at 28 weeks gestation and those with a level > 7.8mm/l proceed to a 75g glucose tolerance test (GTT), where a positive diagnosis of GDM is made if 2 of the 3 levels are increased (Fasting >5.2mm/l, 1hr >9.9mm/l, 2hr >8.5mm/l). The aim of management with GDM is to keep glucose levels in normal range with a combination of moderate exercise, diet and/or insulin therapy. If glucose levels are poorly controlled it can result in increased fetal growth and a higher risk incidence of macrosomia (birth weight > 4000 grams) with associated birth complications. Ultrasonic fetal monitoring is appropriate if the pregnancy is complicated by poor glucose control, hypertension, large for gestational age or intra uterine growth restriction. In Australia around 3% of Caucasian pregnancies are affected by GDM compared with up to 15% in Asians (Fulcher et al 1998). In Chapter Four it was demonstrated that in an Australian Chinese population problems associated with birth weight and macrosomia occur when the birth weight is over 3,500 grams compared with 4000 grams in the Caucasian population. In this group of Chinese women it was found that there was a high level of obstetric 140 141 intervention (60%) and a 20% incidence of post partum haemorrhage and concluded that there was a failure to recognise the at risk Chinese fetus due to applying Caucasian standards. Homko et al (1995) assessed the interrelationship between gestational diabetes mellitus, ethnicity and fetal macrosomia, concluding that the ethnic variation seen in fetal growth may be as a result of genetic factors and influences of different in-utero growth promoters in those populations. Sabbagha (1976), Parker (1981), Hadlock et al (1990) and Arenson (1995) have written on the plausibility of racially specific growth charts, with the general consensus being that it is not necessary to differentiate between the groups because, even though there may be a difference in birth weights due to ethnicity, there is a similar rate of growth during the last trimester. Spencer et al (1995) thought it was inappropriate to use standard charts for abdominal circumference and estimated fetal weight charts for Asian women due to their lower body mass index as the stature of the mother can affect birth weight. Gardosi et al (1992) did not concur with this, finding instead that ethnicity affected birth weight but that stature did not. Sabbagha et al (1980) used serial ultrasound in the assessment of evolving macrosomia and suggested that the abdominal circumference was the fetal parameter of choice for predicting macrosomia. Studies by Buchanan et al (1994) determined that ultrasound of the abdominal circumference prior to 33 weeks gestation could identify Caucasian women at risk of a macrosomic baby whilst studies by Hadlock et al (1984), Deter et al (1982) and Benson and Doubilet (1998) all stressed the importance of the abdominal circumference in fetal weight estimations. The fetal fat layer must be included in the measurement (Picker 1982). 141 142 5.2 ASUM vs Queen Mary Abdominal Circumference The ultrasonic fetal measurement charts used in Australia are the Australasian Society for Ultrasound in Medicine (ASUM) charts, which are based on a diverse ethnic population mix. The Queen Mary Chart is commonly used in hospitals in Hong Kong and China, and compared with the charts of both ASUM and Deter and Hadlock et al (Graphs 2/7 – 2/11), all fetal parameters are similar except for the abdominal circumference, which has lower mean values in the last five weeks of gestation (Table 5/1). Lai and Yeo constructed fetal measurement charts based on the Asian population in Singapore which also showed a difference in the abdominal circumference when compared with both the ASUM and Deter charts and in 1981 Meire and Farrant suggested that ‘oriental’ babies had a smaller mean abdominal circumference and a lower birth weight than white European babies. If the abdominal circumference difference seen between ASUM AC and the Queen Mary AC is reflected in our Chinese population then, when the AC is included in a fetal weight formula, this relates to a smaller baby (Table 5/2). Table 5/1 Abdominal Circumference Chart Comparison ASUM vs ‘Queen Mary’ _____________________________________________________________________ Weeks Gestation 33 34 35 36 37 38 39 40 41 ASUM mean Abdominal Circumference (mm) 294 305 315 325 333 342 356 362 367 Queen Mary – mean Abdominal Circumference (mm) 288 296 304 311 318 324 331 337 342 _____________________________________________________________________ 142 143 Applying the abdominal circumference figures from Table 5/1 to the following fetal weight formula by Hadlock et al (1984), which incorporates the BPD, head circumference, abdominal circumference and femur length, the weight differences are demonstrated in Table 5/2. Log10 (EFW in grams) = 1.3596 – (0.00386 AC FL) + (0.0064 HC) + (0.00061 BPD AC) + (0.0424 AC) + (0.174 FL). Standard deviation (EFW) = +/- 7.5% of EFW (predicted mean). Table 5/2 Weeks Gestation 34 Weeks 36 Weeks 38 Weeks 40 Weeks Caucasian/Chinese Weight Difference Parameter Mm BPD 86 HC 305 FL 66 BPD 90 HC 317 FL 69 BPD 93 HC 328 FL 73 BPD 96 HC 340 FL 76 Caucasian Weight 2388 +/- 358g 5lb 4oz AC mm Cauc Chin 305 296 Chinese Weight 2289 +/- 343g 5lb 1oz 2845 +/- 427g 6lb 4oz 325 311 2653 +/- 398g 5lb 14oz 3322 +/- 498g 7lb 5oz 342 324 3056 +/- 458g 6lb 12oz 3843 +/- 576g 8lb 8oz 362 337 3446 +/- 517g 7lb 10oz As can be seen from Table 5/2, using the same BPD, HC and femur length but substituting the AC for either ASUM or Queen Mary, there is a difference of almost 400 grams or 12 ounces at birth. 143 144 5.3 Aims of Objective Four 1. To compare fetal size/growth in the third trimester of pregnancy in both Chinese and Caucasian women with gestational diabetes mellitus and in Chinese pregnancies with normal glucose levels. 2. To determine if any ultrasonically measured fetal parameter predicts an at risk birth weight for Chinese or Caucasian babies and to determine if babies of Chinese women with normal glucose levels have a lower mean birth weight than either Caucasian or Chinese babies of mothers with GDM. 3. To estimate the growth per day of fetuses with gestational diabetes mellitus in both Caucasian and Chinese pregnancies. 5.4 Patient Selection Criteria Criteria needed to be set to help determine which patients were to be included in the study. Recruitment was via the antenatal clinics at both Hornsby Ku-Ring-Gai Hospital and the Royal North Shore Hospital. Caucasian and Chinese women were the main focus of the studies and it was necessary to further define Chinese as being born in China, Taiwan or Hong Kong. At between 26 and 28 weeks gestation all patients coming through these two clinics are screened for diabetes in pregnancy. This glucose challenge test entails drinking 300ml of Glucaid containing a 50gram glucose load, within ten minutes, then waiting for one hour, timed from the first sip, in which period the patient cannot eat, drink or smoke. Blood is collected to measure the blood sugar level. Women 144 145 with a glucose level equal to or greater than 7.8mm/litre are referred for a formal glucose tolerance test (GTT). For three days prior to the GTT the patient has a high carbohydrate diet with at least 150 grams of carbohydrate per day. After fasting overnight blood is taken and if this fasting level is < 6mm/l the patient is given a drink containing a 75 gram glucose load with further blood taken at 1 and 2 hours. Gestational diabetes is diagnosed if any two of the three glucose readings are high. Normal levels are equal to or less than 5.2mm/l at 0 hours, 9.9mm/l at 1 hour and 8.5mm/l at 2 hours. Any Caucasian woman testing positive to the formal GTT was invited to join the study provided the father of the baby was also Caucasian. Chinese women both with and without gestational diabetes were also required, for comparison, and so all Chinese women, with Chinese partners, coming through the clinics were asked to participate. For those women who could not speak or understand English it was necessary to obtain the services of either interpreters or the midwives responsible for running the non-English speaking clinics. Hornsby Hospital had its own Midwife interpreters who ran special clinics for non-English speaking patients. These midwives play an integral role in helping the pregnant Chinese women feel more relaxed with their confinement, and were also responsible for explaining the research study, questionnaire and scanning procedure. At Royal North Shore it was more difficult as antenatal clinic staff had to wait for the arrival of medical interpreters before proceeding with appointments. For this study, seventy-five women were eventually recruited from both clinics. Twenty five Caucasian women with GDM, 25 Chinese women with GDM and 25 Chinese women without GDM, to be used as the control, were invited and accepted 145 146 inclusion in the study after their glucose tolerance / challenge test at around 28 weeks gestation. The following criteria were to be met by each pregnant woman invited to participate: Gestation of between twenty eight weeks and term Known date of last menstrual period or a dating ultrasound in first trimester. Singleton pregnancy with no fetal abnormalities seen on ultrasound examination Glucose challenge /tolerance test at around 28 weeks gestation or earlier. Caucasian woman with Caucasian partner, with gestational diabetes. Chinese woman with Chinese partner, with or without gestational diabetes. 5.5 Subject Information Statement and Patient Consent The patient information and consent form followed the format suggested by the Northern Health Area Services Ethics Committee. The study explanation needed to be simple and concise, remembering that some of the participants used English as a second language. An abbreviated patient information was available in Chinese (Appendix 8A & 8B). 5.6 The Patient Questionnaire This was the only study that required a patient questionnaire (Appendix 9). The information required related to the patients ethnicity, obstetric history and social history. Two-thirds of the patients to be included in the study spoke English as a second language 146 147 and so the questionnaire had to be available in both English and Chinese. With this in mind, the questions needed to be clear, short and kept to a minimum. A Chinese medical interpreter translated the questionnaire into Chinese and a Chinese midwife was present to assist the patient in answering the questions in English. Each participant in the study had their own individual folder to store a copy of the consent form, questionnaire, images and measurement data. A separate copy of the consent form was placed into the medical records of each participant. 5.7 Choosing the Ultrasonic Fetal Parameters A longitudinal study was deemed to be most appropriate for the investigation of the effect of gestational diabetes on fetal growth as fetal size was to be tracked from 28 weeks gestation until term. The women recruited for the study were to be scanned at their routine antenatal clinic visits and so no separate appointments were required. A fiveminute time span was estimated as being adequate to image and measure the required fetal parameters. Only one sonographer, the author, was involved with data collection and to avoid bias no reference was made to the previous ultrasound measurements. It was necessary to decide which fetal measurement parameters were most appropriate for determining fetal growth. Hadlock (1991) said that parameters should be chosen based on their ease of measurement and the degree to which they can reflect gestational age and growth. Measurements of the fetal head, abdomen and long bones are needed to estimate gestational age/growth and, when applied to a formula, to give an 147 148 estimation of fetal weight. Head measurements include the biparietal diameter (BPD), head circumference (HC) and the occipito frontal diameter (OFD). The OFD is not as common a measurement and is often ignored in preference to the HC. For this study it was decided to incorporate both the OFD & HC as, particularly in late pregnancy, head shape can distort the BPD measurement. If the BPD is severely affected as in dolichocephaly, it will only be used in a fetal weight formula if the cephalic index is within the normal range. CI = (BPD/OFD) x 100% (Normal range = 73.9 - 82.7%). The head circumference is less likely than the BPD to be affected by head shape due to moulding and is therefore a reliable parameter to use in a weight formula. The femur length has a linear relationship to the crown-heel length and is an important parameter to add to any fetal weight formula as it makes allowances for population differences. As well as the femur length, the humerus length was also chosen. Researchers such as Benacerraf (1992) and Nyberg (1992) have linked shortened long bones, in particular the humerus as one of the first parameters to alert to intra uterine growth retardation. Abdominal circumference (AC) measurements have been demonstrated to have a linear relationship to the gestational age similar to the BPD and is the parameter that may display fetal overgrowth by way of fat layer deposition (Picker 1982). It was necessary to use this parameter, as the Queen Mary Hospital fetal measurement chart for the abdominal circumference used in Hong Kong & Beijing is different to the abdominal circumference 148 149 on the ASUM 2001 fetal measurement charts in the last few weeks of gestation. All other fetal parameters are similar between the two sets of charts. Fetal wellbeing was also to be examined and in the third trimester this involves assessing the integrity of the placenta along with umbilical artery Doppler for analysis of the flow velocity waveform. In the normal pregnancy there should be a progressive increase in diastolic flow velocity with advancing gestation, which is believed to reflect the progressive decreasing placental resistance. The most commonly used indices to measure flow velocity are the systolic/diastolic ratio, resistive index and pulsatility index. All three indices show similar predictive values when correlated against adverse perinatal events and for this study the resistive index was chosen. Normal waveforms are unidirectional and demonstrate frequencies throughout the cardiac cycle. Abnormal waveforms reflect the placental resistance caused by damage to placental tertiary villi and show decreased end-diastolic flow that may be absent or reversed. There are a number of factors that affect the waveform including maternal position, fetal heart rate and fetal compression of the cord. Other factors include technical errors such as the sampling site too close to either the placenta or fetal abdominal insertion, the insonation angle and Doppler gain. 5.8 Safety of Repeated Ultrasound Scans The main purpose of this study was to record fetal growth in pregnant Chinese women, both with & without gestational diabetes and Caucasian women with gestational diabetes. The main concern with the Chinese women was the safety of repeated fetal ultrasounds 149 150 on their unborn child and so they needed to be reassured that the scan would be brief. A five-minute time span was estimated as being adequate to image and measure the required fetal parameters. When first discussing this project with the Chinese midwives from the Non-English Speaking Antenatal Clinic at Hornsby Hospital they mentioned the fact that some Chinese women from traditional backgrounds are superstitious about any tests during pregnancy. Most of the women from this group had mothers and grandmothers residing with them in Australia who strongly influenced any decisions made in regard to diet, blood tests, type of labour and delivery. It was not surprising therefore to be asked numerous questions on safety issues, not only by the mother-to-be but also by her partner, mother or friend. The help of the Chinese midwives and medical interpreters was invaluable in reassuring the women that the ultrasounds would take no more than a few minutes and would not harm their baby. Only one non-diabetic Chinese woman pulled out of the study, and was replaced by another candidate. The Caucasian women had a totally different outlook towards the ultrasounds with only one being slightly apprehensive and the others looking forward to seeing their baby each week. 5.9 Methodology Fifty pregnant Chinese women were recruited from the Antenatal Clinics at either the Royal North Shore Hospital or Hornsby & Ku-Ring-Gai Hospital. This represented 19.6% of total annual Chinese births for the two hospitals. Twenty-five Chinese women had GDM (83% of total Chinese GDM pregnancies) and 25 Chinese women with a normal glucose challenge test were included in the study (power 80%, df 2/40, d=0.65). 150 151 Twenty-five Caucasian women with GDM were also recruited (56% of total Caucasian GDM pregnancies). The percentage participation rate was based on the total from each group and did not allow for further differentiation with partner ethnicity, which would have increased the individual group percentages. As mentioned earlier, all Caucasian women recruited had Caucasian partners and Chinese participants Chinese partners. This was to ensure there was no bias due to a mix of ethnicity. Maternal height, pre- pregnancy weight and parity data was collected, with body mass index being within normal range (15-29) for all participants. From 28 weeks gestation the women attended the antenatal clinic at two to four week intervals till 36 weeks when weekly visits commenced. All women with GDM were assessed at specialist antenatal clinics from the time of diagnosis, where glucose levels and diet were closely monitored. 5.9.1 Fetal Parameters At each antenatal visit from 28 weeks gestation a fetal ultrasound examination was performed by the same sonographer, with the biometry measurements including the biparietal diameter (BPD), head (HC) and abdominal circumference (AC), femur (FL) and humerus lengths (HL) taken at the imaging planes recommended by ASUM (Chapter Two). The relevant head image required for the measurement of the BPD, OFD and HC is a transverse axial plane, which includes the falx cerebri anteriorly and posteriorly, cavum septum pellucidum anteriorly in the midline, and the thalami. The BPD is measured at the widest point of the head from the outer edge of the nearest parietal bone to the inner edge of the more distant parietal bone. The OFD is measured perpendicular 151 152 to the BPD from mid to mid occipital bones. The head circumference can be traced either with an ellipse mode or manually around the outer perimeter of the skull. The imaging plane for the abdominal circumference is a true transverse cut at the level of the fetal liver and stomach at the umbilical region. Although the AC can be measured using the ellipse mode, in the third trimester it is usually more accurate to manually trace the perimeter of the abdomen, including the fat layer. Long bones should be imaged in the axial plane to achieve the longest length, with clean blunt ends and a strong acoustic shadow behind the bone. Measuring must be along the diaphyseal shaft, excluding the epiphysis. The spectral Doppler analysis of the umbilical cord arteries is performed with the patient in a semi recumbent position so as to minimise the risk of supine hypotension syndrome due to compression of the inferior vena cava. Fetal movements/ hiccups should be at a minimum before a free loop of cord is identified for sampling. The image field is maximised, colour analysis activated, the pulsed wave Doppler cursor positioned in one of the umbilical arteries and the Doppler gain set to a level where the spectrum can be readily identified. Three consecutive cardiac cycles are measured to reduce the coefficient of variation of measurements to less than 5%. 5.9.2 The Data Collection Sheet Designs Having set patient selection criteria and decided which parameters to measure, a data collection sheet was designed with ease of use the main priority. For the gestational 152 153 diabetes study a single sheet per patient was necessary with all information clearly set out. Hospital identification stickers were used to reduce the risk of confusion and errors, particularly with Chinese patients who used a western name as well as their traditional Chinese names. Names were checked at every visit so as to avoid mistakes. SCW PhD Research Project - HKH and RNSH Antenatal Clinics NAME: Gestational diabetes Y N Unit number: LMP: 01/02/2002 G3 P2 DATE Gestation BPD OFD HC AC FL HL AFI EFW RI 1/10 34w 2d 86 108 306 303 66 59 12 2440 6 15/10 36w 2d 90 112 317 325 69 62 15 2800 5.8 22/10 37w 2d 92 113 321 333 72 63 14 3280 5.7 5.9.3 Statistical Analysis Statistical data used in this study was extracted from Northern Suburbs Area Health Service OBSTET database. Statistical analysis was performed with SPSS for Windows and Minitab with a one-way ANOVA and t-tests used to compare birth weights and groups. As there is no statistically significant difference between any of the ASUM 2001 153 154 and Deter/Hadlock fetal measurement charts in the final ten weeks of pregnancy (Chapter 2: Graphs 2/23 –2/27) only the ASUM charts were used for the final analysis. Scatter graphs were created using Microsoft Excel with measurements superimposed onto the ASUM fetal measurement graphs for each measured parameter, showing the mean regression with plus and minus two standard deviations for each fetal parameter. A Fisher Exact Probability was used to assess the individual hypothesis. Growth per day for each fetus was calculated using the estimated fetal weight from 36 weeks of gestation and between group comparisons utilized a two-way ANOVA. 5.10 Results All women with GDM were assessed at specialist antenatal clinics from the time of diagnosis, where glucose levels and diet were closely monitored and as a result none of the study recruits required insulin therapy during the course of their pregnancy. No significant difference was seen in the growth pattern between Chinese pregnancies with normal GCT/GTT and those affected with gestational diabetes mellitus nor in the mean birth weight of babies from the two groups. There were 3,616 ultrasonic fetal measurements performed by the same sonographer on 75 pregnant women during the third trimester. Twenty-five Caucasian women with gestational diabetes mellitus (1144 measurements), 25 Chinese women with GDM (1176 measurements) and 25 normal Chinese pregnancies (1296 measurements). The mean number of ultrasound examinations for each woman was 6 (range 4–9). 154 155 Unfortunately the assessment of the umbilical cord arteries by pulse wave Doppler on all the pregnancies was incomplete due to technical difficulties encountered. The RNSH ultrasound unit had a major system failure, which could not be repaired. The initial system used at HKH was replaced by a unit, which did not have Doppler mode available. Only twelve patients had completed umbilical cord Doppler analysis. All resistive index readings taken were within the normal range. Table 5/3 Birth Statistics Northern Sydney Health Statistics 2002 Total Caucasian Births Mean Birth-weight Gestational Diabetics GDM & Macrosomia Total births Macrosomia 3435g 2.3% 11.1% 15.3% +/- 502g _______________________________________________________________________________ Total Chinese Births 3344g 12% 6.7% 10% +/- 464g __________________________________________________________________ Study Caucasians GDM 3485g 100% 20% 11.1% +/- 449g _______________________________________________________________________________ Study Chinese GDM 3431g 100% 5% 5% +/- 311g _______________________________________________________________________________ Study Chinese normal GTT 3352g 0% 0% 5% +/- 244g __________________________________________________________________ Table 5/3 compares the 2002 Northern Sydney Health Area mean birth weight, rate of macrosomia and gestational diabetes for Caucasians and Chinese with this study. The mean birth weights of the three groups in the study did not differ statistically from each other nor from the Northern Sydney Health 2002 mean birth weights for Caucasian and Chinese. Chinese (3352g) < Chinese GDM (3431g) < Caucasian (3435g) < Caucasian 155 156 GDM (3485g). A two-way ANOVA with follow-up t-tests were done to compare birthweights between Northern Sydney Health statistics, Caucasian GDM, Chinese GDM and Chinese control, which showed no statistically significant difference in birth weights, suggesting that they probably came from populations with the same mean birth-weight. The number of cases was insufficient for a logistic regression. 5.10.1 Chinese with and without GDM No statistically significant difference in gestational age or birth weight was seen between babies born to Chinese women with GDM (39wks 1day / 3431 grams) and those with normal GCT (39wks 3days / 3352 grams). The average birth weight for all Chinese babies in Northern Sydney Health Area was 3344g with the mean birth weight of males being 42 grams heavier than for female babies. The influence of maternal age, body mass index and parity on eventual birth weight was non-specific. Of the 2472 fetal measurements taken from the Chinese population, 1176 were affected by gestational diabetes and the remaining 1296 were normal Chinese pregnancies. One woman with GDM gave birth preterm to a 3765g infant at 36 weeks 3 days and therefore was discarded from the study. Although there was only one GDM birth over 4000g, another two babies could have had macrosomia, with one emergency caesarean section at 38 weeks 3 days gestation weighing 3810g and another, the discard, at 36 weeks 3days being 3765g. There was a 95% chance that the Chinese non-GDM came from a population between 3230.3g and 3474g (actual 3352g) and Chinese GDM 156 157 from a population between 3275.3g and 3585.7g (3431g). Eight GDM’s and nine nonGDM’s were above the mean Chinese weight with a total of nine of these babies weighing over 3600 grams. Of these nine babies, eight (4 from each group) had an abdominal circumference greater than the ASUM mean for at least three weeks from 34 weeks gestation (sensitivity 88.9%, specificity 97.6%). One baby with an AC > ASUM AC mean at 35 and 37 weeks weighed 2958 grams. As 3600 grams is above the estimated population mean for Chinese babies, the abdominal circumference was thought to be a logical predictor for birth weight greater than 3600 grams in the Chinese population. A Fisher exact probability of < 0.0000001 suggests that an AC greater than the ASUM AC mean from 34 weeks predicts an at risk birth weight for our Chinese population. A raised abdominal circumference prior to 34 weeks gestation gave a false positive result as 22% of fetuses, seven GDM’s and two non-GDM’s, had an AC greater than the ASUM AC mean before 34 weeks gestation which normalised after 34 weeks. The head circumference was greater than one standard deviation above the ASUM HC mean by 34 weeks gestation in seven GDM’s (birth weights 3390g, 3810g, 3595g, 3555g, 3380g, 4065g, 3750g) and three non-GDM’s (birth weights 3600g, 4290g, 3660g). From 35 weeks gestation most fetuses of Chinese women, both with and without GDM, had an abdominal circumference, which followed the mean of the Queen Mary abdominal circumference graph (Graph 5/1). The study results may indicate the racial difference of fetal growth of the abdominal circumference with 3600 grams being above the 90th percentile of the normal Chinese population in Australia. No statistically 157 158 significant difference was seen for the BPD, HC, FL or HL (Graphs 5/2-5/6) between the study groups and the general population based on the ASUM fetal measurement graphs. 5.10.2 Caucasians with GDM There were 1144 ultrasonic fetal measurements performed on 25 pregnant Caucasian women with gestational diabetes mellitus. Each woman had between four and ten ultrasound examinations performed, with a mean of seven scans, between 28 weeks gestation and term. The mean birth weight of babies born to Caucasian women with gestational diabetes mellitus was 3485 grams with a mean gestation of 39 weeks 4 days. Birth weights were recorded for all 25 babies. Nine of these babies were above the mean birth weight with four being macrosomic. Of those nine that were above the mean, six had an abdominal circumference at least one standard deviation above the ASUM mean by 35 weeks gestation. Three of the four macrosomic fetuses had an abdominal circumference two standard deviations above the ASUM mean at 30 weeks gestation but by 35 weeks this had reduced to one standard deviation. There was a 95% chance that the Caucasian GDM’s came from a population with a mean birth weight between 3260.2 grams and 3709.4 grams (actual mean weight 3485 grams). In 75% of the cases of macrosomic births to Caucasian women with GDM both the head and abdominal circumference were greater than one standard deviation above the ASUM HC & AC mean by 35 weeks gestation. Prior to 35 weeks there was no correlation between an increased head and abdominal circumference and raised birth weight. 158 159 5.10.3 Graph Comparisons – Caucasian/Chinese The ultrasonic fetal measurements taken included the BPD, OFD, head and abdominal circumference, femur and humerus lengths. No statistically significant difference was seen for any of these parameters between the study groups and the general population based on the ASUM fetal measurement graphs. On the following set of graphs measurements of the same value are superimposed. Graph 5/1 Abdominal Circumference Comparison Scatter Graph Abdominal Circumference (mm) ASUM / Queen Mary / Caucasian & Chinese Gestational Diabetics Chinese Non GD Abdominal Circumference 450 400 Ch NAC C GD AC Ch GD AC 350 Queen Mary 300 250 200 26 28 30 32 34 36 38 40 42 Weeks Gestation Graph 5/1 is a scatter graph comparing the abdominal circumferences of normal Chinese pregnancies (Ch NAC), Caucasians with GDM (C GD AC) and Chinese with GDM (Ch GD AC). The figures have been superimposed onto the ASUM abdominal circumference 159 160 graph showing the mean, plus/minus two standard deviations with the Queen Mary abdominal circumference mean shown in red. The abdominal circumference of fetuses of the 25 Caucasian women with gestational diabetes mellitus showed no significant difference to the ASUM AC mean when the birth weight was appropriate for gestational age. Fetuses of Chinese women, both with and without GDM with eventual mean Chinese birth weight, had abdominal circumferences below the ASUM AC mean and followed the mean of the Queen Mary abdominal circumference graph. Graph 5/2 shows the individual group AC means - Queen Mary (red), Caucasian GDM (green), Chinese GDM (blue) and normal Chinese (yellow). Note how the Caucasian mean is similar to the ASUM mean whilst both the Chinese groups follow the mean of the Queen Mary abdominal circumference. Graph 5/2 Abdominal Circumference Comparison Line Graph Abdominal Circumference (mm) Abdominal Circumference Comparison ASUM (+/- 2SD), Queen Mary, Caucasian GDM, Chinese GDM Chinese Non GM 420 400 380 360 340 320 300 280 260 240 220 200 180 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Weeks Gestation 160 161 Graph 5/3 Head Circumference Comparison Scatter Graph Head Circumference (mm) ASUM / Caucasian & Chinese Gestational Diabetics Chinese Non GD Head Circumference 380 Ch NHC Ch GD HC C GD HC 360 340 320 300 280 260 240 220 200 26 28 30 32 34 36 38 40 42 Weeks Gestation Graph 5/3 is a scatter graph of the group head circumferences superimposed onto the ASUM head circumference curve with the mean and plus/minus two standard deviations. There is no statistically significant difference seen between the normal Chinese pregnancies (CH NHC), Chinese with GDM (CH GD HC) and the Caucasian pregnancies with GDM (C GD HC). The outlier dots represent the macrosomic fetuses. 161 162 Graph 5/4 BPD Comparison Scatter Graph ASUM / Caucasian & Chinese Gestational Diabetics / Chinese Non GD BPD 120 110 BPD (mm) Ch NBPD 100 Ch GDBPD CGD BPD 90 80 70 60 26 28 30 32 34 36 38 40 42 Weeks Gestation Graph 5/4 is the biparietal diameter scatter graph for the groups. There is no statistically significant difference seen between the normal Chinese pregnancies (CH NBPD), Chinese with GDM (CH GDBPD) and Caucasian GDM (CGD BPD). 162 163 Graph 5/5 Femur Length Comparison Scatter Graph Caucasian & Chinese Gestational Diabetics Chinese Non GD / ASUM Femur Length Femur Length (mm) 90 Ch NGD F CGD FL Ch GDFL 80 70 60 50 40 26 28 30 32 34 36 38 40 42 Weeks Gestation Graph 5/5 is a scatter graph of the group femur lengths superimposed onto the ASUM femur length curve with the mean and plus/minus two standard deviations. There is no statistically significant difference seen between the normal Chinese pregnancies (Ch NGD F), Chinese with GDM (Ch GDFL) and the Caucasian pregnancies with GDM (CGD FL). 163 164 Graph 5/6 Humerus Length Comparison Scatter Graph Humerus Length (mm) Caucasian & Chinese Gestational Diabetics, Chinese non GDM / ASUM Humerus Length 80 75 70 65 Ch non GD 60 ChGD HL 55 CGD 50 45 40 26 28 30 32 34 36 38 40 42 Weeks Gestation Graph 5/6 is a scatter graph of the group humerus lengths. There is no statistically significant difference seen between the normal Chinese pregnancies (Ch non GD), Chinese with GDM (ChGD HL) and the Caucasian pregnancies with GDM (CGD). 164 165 5.10.4 Mean Measurements of Fetal Parameters Mean fetal parameter measurements for each of the three groups from 32 weeks gestation to term are shown in Tables 5/4 to 5/7. The ASUM and Queen Mary mean measurements are also shown. Table 5/4 Weeks Mean Abdominal Circumference Measurements. 28 29 30 31 32 33 34 35 36 37 38 39 40 242 259 262 272 283 294 305 315 325 333 342 356 362 241 264 278 282 283 288 302 322 324 333 340 343 361 247 258 261 269 278 297 304 313 314 316 324 327 332 245 248 260 266 272 287 295 306 308 315 324 332 333 244 253 262 271 280 288 296 304 311 318 324 331 337 Gestation ASUM AC mm Caucasian GDM AC Chinese GDM AC Chinese Non-GDM Queen Mary AC mm Note how the abdominal circumference of the Chinese are similar to the Queen Mary AC compared with the Caucasians and the ASUM figures. This was the only table to display a variance between the Chinese and Caucasian groups. 165 166 Table 5/5 Weeks Mean Head Circumference Measurements 28 29 30 31 32 33 34 35 36 37 38 39 40 263 269 274 284 288 300 305 310 317 321 328 336 340 261 270 280 291 292 296 308 317 320 325 332 336 348 265 268 283 286 292 299 309 312 318 324 330 335 337 255 264 275 280 290 297 307 311 314 322 325 333 335 Gestation ASUM HC mm Caucasian GDM HC Chinese GDM HC Chinese HC Non-GDM Table 5/6 Weeks Mean Biparietal Diameter Measurements 28 29 30 31 32 33 34 35 36 37 38 39 40 72 75 76 80 81 84 86 88 90 92 93 95 96 70 75 78 79 79 81 83 88 89 90 91 93 95 72 74 76 78 82 84 85 86 88 90 91 93 95 72 73 78 79 81 83 84 86 88 90 91 93 94 73 75 78 80 83 85 87 89 91 92 94 95 96 Gestation ASUM BPD mm Caucasian GDM BPD Chinese GDM BPD Chinese BPD Non-GDM Queen Mary BPD mm 166 167 Table 5/7 Weeks Mean Femur Length Measurements 28 29 30 31 32 33 34 35 36 37 38 39 40 54 55 58 59 62 65 66 67 69 72 73 75 76 52 53 59 61 62 65 66 68 69 70 73 74 76 50 53 56 60 63 64 65 66 68 69 70 71 73 52 55 57 61 62 64 65 67 68 70 72 73 75 55 57 60 62 64 66 68 70 71 73 75 76 78 Gestation ASUM BPD mm Caucasian GDM BPD Chinese GDM BPD Chinese BPD Non-GDM Queen Mary BPD mm 5.10.5 Fetal Weight Gain in Pregnancies Affected by GDM Fetal weight gain per day was calculated from 36 weeks of gestation (Table 5/8). A twoway ANOVA to compare group to average weight gain per day across the last four weeks of gestation showed no statistically significant difference between the three groups (F2,40=2.39, p=0.1) and no interaction between group and week (F6,120=0.38, p=0.89). There was a significant linear trend across weeks with the weight gain in all groups declining in the final four weeks of gestation (F1,40=13.78, p=0.001). Levene's test for equality of variances was significant at 36 weeks. However, the results may be accepted because the violation of equality of variances was not serious, it would tend to produce a falsely significant group difference and interaction yet neither were noted here, and the linear trend was supported by a Friedman rank order test at 36-37-38-39 weeks (2=8.45, p=0.038). 167 168 Table 5/8 Fetal Daily Weight Gain (grams/day) Weeks 36 37 38 39 Caucasian GDM 29.6 28.6 27.5 27.2 Chinese GDM 27.3 26.9 26.8 25.6 Normal Chinese 25.2 24.7 23 21.8 5.11 Discussion The careful monitoring of all women with GDM in our antenatal clinics resulted in none of the studies 25 recruits requiring insulin therapy. It was initially hypothesised that the GDM fetuses would have larger abdominal circumference and be heavier than the nonGDM fetuses, but with glucose levels so well controlled by diet and exercise this hypothesis was rejected. This study found that ultrasonic measurements of the fetal BPD, head circumference and long bones were inconclusive for predicting large babies. This was in agreement with Murata and Martin (1973) who measured the BPD of diabetic and nondiabetic pregnancies and found no significant difference. Whilst Buchanan et al (1994) concluded that if ultrasound of the abdominal circumference was above the 75th percentile as early as 29 weeks gestation it could be an identifier for macrosomia and Benson and Doubilet (1995) indicated that an AC above the 90th percentile between 30 and 33 weeks of gestation has a predictive accuracy of 56% for macrosomia, this study 168 169 concluded that in our Chinese population, ultrasound of the abdominal circumference prior to 34 weeks gave a high level of false positives but that after 34 weeks an increased abdominal circumference helped identify those fetuses that were larger than average and therefore potentially at risk of birth complications. The abdominal circumference difference seen between the ASUM and the Queen Mary fetal measurement charts is reflected in our Chinese population and when these differences are applied to a fetal weight formula (Hadlock et al 1984) incorporating the BPD, HC, AC and FL the birth weight differences can be understood. Benson and Doubilet (1998) found that in diabetic pregnancies the weight formula incorporating the head, abdominal and femur measurements have a 95% confidence interval of 24% compared with 15% in non-diabetic pregnancies due to the abdominal fat layer. The smaller abdominal circumference and lower birth weight compared with the Caucasian population seen in this study is also in agreement with the 1981 work of Meire and Farrant and Woo and Wan (1984). For Chinese fetuses an abdominal circumference greater than the ASUM abdominal circumference mean from 34 weeks gestation may identify a birth weight above 3,600 grams, a size considered to be similar to macrosomia, or birth weight over 4000 grams, in the Caucasian population, and so at risk for intervention and post partum haemorrhage. In Chapter Four it was suggested that with the high level of obstetric intervention (60%) and 20% incidence of post partum haemorrhage amongst Chinese women with babies greater than 3500 grams, there may be failure to detect pregnancies with fetal overgrowth. 169 170 Chinese pregnancies thought to be small for gestational age were within the normal range for Chinese and those pregnancies assessed as ‘normal’ were Chinese women carrying bigger babies due to gestational diabetes mellitus or other genetic and environmental factors. This is in agreement with the work of Homko et al (1995) who thought that the interrelationship between gestational diabetes mellitus, ethnic variation seen in fetal growth and fetal macrosomia was as a result of not only genetic factors but influences of varying in-utero growth promoters in those populations. With the differences displayed in this study for the abdominal circumference and problems associated with increased birth weight in the Chinese population the study agrees with Spencer et al (1995) who thought it was inappropriate to use standard charts for abdominal circumference and estimated fetal weight charts for Asian women due to their lower body mass index. Although it is agreed with Sabbagha (1976), Parker (1981), Hadlock et al (1990) and Arenson (1995) that racially specific growth charts are not necessary, it is important to recognise, like Gardosi et al (1992), that ethnicity affects birth weight. 170