A first-in-human study of PDC31 (prostaglandin F2α receptor inhibitor) in primary dysmenorrhea.

STUDY QUESTION: What is the safe and pharmacodynamically active dose range for PDC31 (prostaglandin F2α receptor inhibitor) in patients with primary dysmenorrhea (PD)? SUMMARY ANSWER: The 1 mg/kg/h dose of PDC31 appears to be safe and potentially effective in reducing intrauterine pressure (IUP) and pain associated with excessive uterine contractility when given as a 3-h infusion in patients with PD. WHAT IS KNOWN ALREADY: PDC31 has previously been shown to reduce the duration and strength of PGF2α-induced contractions in human uterine myometrial strip models and to delay delivery in animal models of preterm labor. STUDY DESIGN, SIZE, DURATION: This was a prospective, multi-center, dose-escalating first-in-human Phase I study conducted from March 2011 to June 2012. A total of 24 women with PD were enrolled and treated with one of five doses (0.01, 0.05, 0.15, 0.3, 0.5 and 1 mg/kg/h) of PDC31 given as a 3-h infusion. Patients were observed for a further 24 h. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted at four hospitals in Europe in non-pregnant, menstruating women with PD. Women with PD (n = 24) received PDC31 infused over 3 h within 8-10 h of the onset of menstruation. IUP and pain monitoring through the visual analog scale (VAS) was assessed prior to, during and following the infusion. Patients were observed for dose-limiting toxicities and other adverse events. Pharmacokinetic samples were also taken to profile the drug. MAIN RESULTS AND THE ROLE OF CHANCE: A 3-h infusion of PDC31 was safe up to and including doses of 1 mg/kg/h. Most adverse events were mild (n = 15; 83.3%) and not considered associated with PDC31 (n = 14; 77.8%). PDC31 infusion decreased uterine activity based on IUP and pain (VAS) scores. IUP was decreased by 23% over all dose levels, reaching a minimum at 135-150 min. There appeared to be a dose-dependent effect on IUP, with the high dose group (1 mg/kg/h) showing the largest decrease in IUP. There was a statistically significant linear dose-effect and concentration-effect relationship for several IUP parameters over the evaluation period of 60-180 min. A dose differentiating effect on pain was seen with the two highest doses. PDC31 demonstrated uncomplicated, linear pharmacokinetics with a terminal half-life of ∼2 h. LIMITATIONS, REASONS FOR CAUTION: This was a first-in-human study and exposure to PDC31 was limited for safety reasons. As such, pharmacodynamic parameters were assessed at a two-sided Type I error of 20%, an appropriate level for the exploratory nature of this study without a placebo control arm. This limited the chance of false positive findings to one in five. WIDER IMPLICATIONS OF THE FINDINGS: Like PD, preterm labor is associated with prostaglandin-mediated uterine contractions; therefore, the findings of this study support further development of PDC31 as a treatment for both PD and preterm labor. STUDY FUNDING/COMPETING INTERESTS: This work was funded by PDC Biotech GmbH, Vienna, Austria. B.B., R.M.L., L.W., R.J.S., K.J.B. and C.F.S. received reimbursement for the conduct of this study from PDC Biotech GmbH. W.H., M.S. and R.P.S. are paid consultants for PDC Biotech GmbH. P.G. is a paid consultant and shareholder of PDC Biotech GmbH. TRIAL REGISTRATION NUMBER: NCT01250587 at www.clinicaltrials.gov.

The use of complementary and alternative medicine by women transitioning through menopause in Germany: results of a survey of women aged 45-60 years.

OBJECTIVES: To describe prevalence rates of complementary and alternative medicine therapies (CAM) for the relief of menopausal complaints among German women. Furthermore, to investigate the perceived effectiveness of these therapies. DESIGN: A self-administered questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years. RESULTS: A total of 1893 (19.3%) questionnaires have been sent back. The mean age of all participants was 52.6±4.3 years. 81% (n=1517) of the responding women stated that they had experienced menopausal complaints at least once. Symptoms ranged from vasomotor symptoms, including hot flushes and night sweats, in 71.2% of cases, to bladder problems in 42.7%. The average symptom score (MRS II total score, range 1-44) among the respondents was 12.76±9.6. More than half (56%; n=1049/1872) of the responding women had used some form of therapy to alleviate their symptoms at least once. The majority of women undertaking a therapy (64.8%; n=679/1049) had used only CAM interventions (either one or more type of CAM), 14.2% (n=149) had used hormone replacement therapy (HRT) only, while 21.1% (n=221/1049) had tried both CAM and HRT. Popular CAM interventions by the respondents were an alteration of lifestyle (28.7%), St. John's wort (18.3%) and homoeopathy (14.9%). An alteration in lifestyle was rated as the most effective CAM treatment with 84.9% (n=457). Other treatments like hormone yoga (79.2%; n=42), homoeopathy (73.7%; n=205) and TCM (59.1%; n=94) were also perceived to be effective. Phytoestrogens were rated as the most ineffective (45.5%; n=50). CONCLUSION: CAM interventions to alleviate menopausal complaints are popular among German women, with 48.2% (n=900/1872) of respondents reporting having used CAM either alone or in combination with HRT. However, the users rated the effects of CAM differently, with some reporting CAM to be highly effective, while others indicate lower effectiveness. Nevertheless, women with a significantly higher symptom scoring tend to use both CAM and a conventional therapy (HRT).

Attitude of German women towards hormone therapy: results of a lay survey.

OBJECTIVE: Hormone therapy (HT) use has experienced a substantial change since publication of Women's Health Initiative (WHI) controlled trial. We aimed to investigate the attitude towards HT in German women aged 45-60 years. STUDY DESIGN: A questionnaire was sent to 9785 randomly selected women in Germany aged between 45 and 60 years. RESULTS: Response rate was 19.3% (n = 1,893). Of those, 81% experienced climacteric symptoms. Vasomotor symptoms were most frequently reported (71.2%; n = 1332). Of the respondents, 19.7% (n = 369) used HT. The most frequently mentioned benefits of HT were the improvement of climacteric complaints (71.2%; n = 1346), followed by the relief of osteoporosis (37.2%; n = 697) and the "anti-aging" effect (16.3%; n = 305). Breast cancer was stated as the main risk (64.9%; n = 1215), closely followed by weight gain (53.4%; n = 1000) and thromboembolism (48%; n = 898). About 44% of the women who has been advised by gynaecologists choose a HT, whereas this rate dropped down to 14.3% and 11.3% for women who have been advised by friends or media. CONCLUSION: German women were generally aware of the main risks and benefits of HT. "More informed" women appear to be more likely to use HT compared to "less informed" women. The media produces negative impression of HT.

Systemic bioavailability of estriol following single and repeated vaginal administration of 0.03 mg estriol containing pessaries.

UNLABELLED: A prospective monocentric open-label and single-arm trial was performed in 19 postmenopausal women with diagnosed vaginal atrophy. The aim was to determine the extent of a systemic exposure to estriol (CAS 50-27-1). Administration of estriol containing pessaries was daily for 21 days. In order to establish a pharmacokinetic profile after single as well as multiple vaginal doses of 0.03 mg estriol blood samples were taken after the first vaginal administration as well as at day 21 after the last administration. Moreover, in order to control for accumulation additional blood samples were taken predose at days 6, 11 and 16. RESULTS: The initial administration increased the population mean estriol plasma concentration to a maximum of 42.1 pg/ml 1 h after dosing. However, already 12 h after administration the estriol concentration had again dropped below 5 pg/ml (lower limit of quantification) in all patients. Repeated administration did not result in an accumulation of estriol, since 2 h after application of the 21st pessary, the population mean estriol concentration reached a maximum of only 11.9 pg/ml. Moreover, no severe or serious adverse events occurred, and no clinically relevant findings were reported. CONCLUSION: Single vaginal application of pessaries containing 0.03 mg estriol resulted in a very low systemic bioavailability, which decreased even more after multiple dosing confirming a favourable safety profile of low dose pessaries administered daily over 21 days.

Relationship between sonographically estimated fetal subcutaneous adipose tissue measurements and neonatal skinfold measurements.

OBJECTIVE: Increased subcutaneous adipose tissue is a well known characteristic of diabetic fetopathy. Prenatal estimation of adipose tissue can be performed by ultrasound, while postnatally skinfold measurements are performed using a Holtain caliper. The aim of this study was to compare these methods in the same patients. METHODS: This was a prospective study of 172 pregnant patients (142 controls and 30 with gestational diabetes) at ≥ 37 gestational weeks. In addition to fetal weight estimation, fetal subcutaneous tissue was measured at the anterior abdomen lateral to the umbilicus (SonoSfAbd) and at the middle of the femur (SonoSfFem). Within 72 h after delivery, a Holtain caliper was used to measure neonatal skinfold thickness at the left anterior iliac spine (SfAbd), at the lower angle of the left scapula (SfSca), at the middle of the femur, above the left quadriceps femoris (SfFem) and at the middle of the left triceps (SfHum). Ultrasound and mechanical measurements were correlated. RESULTS: The sonographic and mechanical methods showed good correlation with each other. Linear regression analysis gave the following equations: SfAbd (mm) = SonoSfAbd (mm) × 0.489 + 1.988 (r(2) = 0.34, P < 0.001); SfSca (mm) = SonoSfAbd (mm) 0.457 + 2.043 (r(2) = 0.40, P < 0.001); SfFem (mm) = SonoSfFem (mm) × 0.714 + 1.763 (r(2) = 0.41, P < 0.001); SfHum (mm) = SonoSfFem (mm) 0.564 + 2.09 (r(2) = 0.39, P < 0.001). CONCLUSIONS: Ultrasound examination is a reliable method for non-invasive intrauterine measurement of fetal subcutaneous tissue and can be used to predict mechanical neonatal skinfold thickness measurements.

Attitude of German gynecologists towards prescribing HRT before and after the WHI study.

OBJECTIVE: The publication of the Women's Health Initiative (WHI) randomized, controlled trial in 2002 resulted in a critical discussion on the risks and benefits of hormone replacement therapy (HRT). The present study aims to evaluate the attitude of German gynecologists regarding changes in the prescription of HRT over recent years. Method A questionnaire was sent to all 9589 German gynecologists in private practice in November 2010. RESULTS: The response rate was 2548 (26.6%). Whereas 82.2% of the responders stated that their advice for primary hormone therapy and alternative agents depended on the severity of symptoms, 9.1% of the responders would recommend HRT in the first place (male: 14.3%; female: 6.1%; p < 0.001). An age limit for hormone prescription was stated by 26.2%, with a mean age limit of 63 ± 5.3 years. An increasing number of patients and becoming more critical about HRT after the WHI was mentioned by 79.8%. Of the responding doctors, 43.9% found that their patients were badly informed by the media, 44.5% stated they were moderately or well (10.1%) informed, whereas only 1% considered their patients to be very well informed. HRT was prescribed for the relief of vasomotor symptoms by 97.4% of responders, making this the primary indication. This percentage decreased slightly to 92.6% between 2003 and 2008 (p < 0.001) and increased again to a similar level at the beginning of 2010 (96.7%, p < 0.05). CONCLUSION: German gynecologists generally have a positive attitude towards HRT, but find it important to focus on the evaluation of the risk-benefit ratio. The major barriers to prescription are multiple concerns of the patients resulting from non-objective media.

[Diagnosis and therapy of gestational diabetes--comparison of two surveys of established gynecologists in Berlin and Saxonia-Anhalt ]. / Diagnostik und Therapie des Gestationsdiabetes -- Vergleich zweier Umfragen unter niedergelassenen Gynäkologen/Innen in Berlin und Sachsen-Anhalt.

PURPOSE: The diagnosis and treatment of gestational diabetes mellitus is controversial. We undertook a survey of obstetricians/gynaecologists to identify current screening practices and differences between Saxonia-Anhalt and Berlin. METHODS: A questionnaire was sent to 267 practicing obstetricians/gynaecologists in Saxonia-Anhalt and 441 in Berlin. The questionnaires included items on the diagnosis and treatment of gestational diabetes. RESULTS: A response rate of 37 % in Saxonia-Anhalt and 35 % in Berlin was achieved. 90 % of the respondents would welcome the integration of a general screening for gestational diabetes into the standard German prenatal care plan. In spite of this great support only 37 % of the obstetricians/gynaecologists in Saxonia-Anhalt and 36 % in Berlin screened their patients generally. Important risk factors for the screening were rarely or not mentioned. CONCLUSION AND DISCUSSION: The survey confirms disparate policies regarding the screening for and treatment of gestational diabetes. There are differences between Saxonia-Anhalt and Berlin. This can only be changed by appropriate inclusion in the German prenatal care plan.

Introductory experience with the continuous glucose monitoring system (CGMS; Medtronic Minimed) in detecting hyperglycemia by comparing the self-monitoring of blood glucose (SMBG) in non-pregnant women and in pregnant women with impaired glucose tolerance and gestational diabetes.

OBJECTIVE: To assess the detection rate of hyperglycemia with a continuous glucose monitoring system compared to a self-monitoring blood glucose profile in non-pregnant, non-diabetic pregnant women, and patients with impaired glucose tolerance or gestational diabetes.. METHODS: Eight non-pregnant (NP) and 56 pregnant women (17 dietary-treated gestational diabetics (GDM), 15 women with impaired glucose tolerance (IGT), and 24 non-diabetic pregnant women (NDP)) underwent a 72-hour measurement with the CGMS (Medtronic Minimed, Northridge, CA, USA). Self-monitored blood glucose measurements, performed 30 minutes before and 120 minutes after each meal, were compared to the duration of hyperglycemia monitored by the continuous glucose monitoring system. RESULTS: No clinically observable infection was found at the subcutaneous tissue where the electrode was placed. A statistically significant difference was found between the groups in body mass index, HbA1c, and in gestational age, but not in age or parity. Using the self-monitored blood glucose (SMBG), 88 % (7/8) of the NP and 54 % (13/24) of the NDP had no measurement above 6.7 mmol/l. However, 17 % (4/24) of the NDP and 40 % (6/15) of the IGT showed more than two measurements above 6.7 mmol/l compared to 24 % (4/17) of the dietary-treated GDM. The differences between these groups were not significant (p = 0.21). The mean durations (+/- SD) of hyperglycemia above 6.7 mmol/l/24 h were: NP 111 +/- 120 min, NDP 138 +/- 120 min, IGT 381.8 +/- 295 min, and GDM 190 +/- 155 min, p = 0.017; above 7.8 mmol/l/24 h NP 24 +/- 49 min, NDP 38 +/- 47 min, IGT 170.7 +/- 190 min, and GDM 64 +/- 88 min, p = 0.016; and above 8.9 mmol/l/24 h NP 9.3 +/- 25 min, NDP 7.5 +/- 14 min, IGT 59 +/- 77 min, and GDM 14 +/- 21 min, p = 0.026. There was no significant difference in the fetal outcome or rate of birth percentiles using the sensor data. CONCLUSIONS: The use of the sensor in pregnant women is unproblematic. a) The CGMS detected more frequent and longer durations of hyperglycemia in GDM compared to non-diabetic pregnant women than the SMBG. b) Women with an IGT exhibited higher glucose levels than patients with gestational diabetes. c) The clinical importance of these hyperglycemic intervals, e.g. with respect to the risk for macrosomia, must be assessed in larger trials.

[Association between amniotic fluid insulin in the second trimester, maternal glucose tolerance and fetal malformations]. / Zusammenhang zwischen Fruchtwasserinsulin im zweiten Trimenon, mütterlicher Glukosetoleranz und fetalen Fehlbildungen.

INTRODUCTION: Maternal hyperglycemia during gestational diabetes leads to fetal hyperinsulinemia, which is associated with increased perinatal morbidity and mortality. Amniotic fluid insulin levels are therefore considered by some researchers to be ideal parameters to use in diagnosing gestational diabetes and making decisions about correct therapy. There are various recommendations about determining gestational diabetes early in pregnancy (< 24 weeks) by measuring amniotic fluid insulin. This study tests this association -- taking additional risk factors into account -- in a group of pregnant women who had genetic indications requesting for amniocentesis (AC). MATERIALS AND METHODS: All pregnant women who came to our clinic for genetically-determined amniocentesis from April 10, 1995 - Jan. 31, 2000 and who were between 12 and 24 weeks were included in our study. After a sample of amniotic fluid was taken, the laboratory performed a competitive radio-immuno-assay to determine the insulin concentration. O'Sullivan's cut-off values were used in diagnosing gestational diabetes. Since not all pregnant woman in our clinic were screened for gestational diabetes, we gathered our data retrospectively by checking all birth records; these were available in our clinic's data archive. RESULTS: A total of 483 pregnant women were included in our study. 22 (4.6 %) of them were classified as gestational diabetics. The average value for amniotic fluid insulin was 1.21 mU/L +/- 0.89. The insulin values for the entire study population exhibited a weekly increase of 0.1 mU/L from the 12th through the 24th week. The insulin concentrations for the 22 gestational diabetics were not significantly higher than those of the non-diabetics (1.05 mU/L vs. 1.0 mU/L; p = 0.34). In the 90 (th) percentile and above of the amniotic fluid insulin levels (2.2 mU/L) for the entire study population, the rate of gestational diabetics was at 11.8 % three times that of the non-diabetics, at 3.7 % (p = 0.021). Among the risk factors for gestational diabetes, an increased body mass index (BMI) value correlated significantly with increased insulin concentration (p < 0.001). The patients at and above the 90th percentile also had significantly higher BMI values (p = 0.002). In the multivariate analysis, the following influences were determined to be significant: maternal body mass index (p < 0.001) and the gestational age (p < 0,001), not the mere diagnosis of "gestational diabetes". A significant association was not found between elevated insulin values in amniotic fluid and the child's birth weight, APGAR values, pH-levels and blood glucose values. However, a significant association was found regarding fetal malformations and chromosome abnormalities. CONCLUSION: Even very low concentrations of insulin can be identified in amniotic fluid early in the pregnancy. The values increase during the course of the pregnancy. There is a positive correlation between maternal weight (BMI) and insulin levels in the amniotic fluid. Pregnant women with gestational diabetes have higher insulin levels in their amniotic fluid. The multivariant analysis shows, however, that this association can be traced to the maternal BMI and the time point during the pregnancy when the AC was performed. Malformations, especially those with a neural tube defect, are an additional cause for elevated insulin values in amniotic fluid.

[Recognition of gestational diabetes]. / Erkennung des Gestationsdiabetes.

In Germany, the diagnosis of gestational diabetes is recognized in only 10% of the patients with gestational diabetes. Therefore 36,000 pregnant patients per year are undiagnosed. The reason is an insufficient screening system which plans only the determination of the glucosuria at each prenatal visit. Several studies have shown the low sensitivity of glucosuria in the detection of gestational diabetes. The majority of the gynecologists are under the assumption of having a healthy pregnant woman in front of them. Therefore a screening with the 50 g-glucose screening test or the 75 g-oral glucose tolerance test is necessary. Our observations have shown an influence of the previous meal on the 50 g-glucose screening test. Therefore we would prefer the one-step screening with the 75 g-oral glucose test. The costs of the one-step or two-step regimen are similar. Also a screening only of high risk pregnancies appears insufficient. Using an average age below 25 years and body-mass index below 25 kg/mg2, only 13.7% of our patients would not be screened. Of those, 3.1% have gestational diabetes. The decision to offer the screening as an individual health achievement, which has to be paid by the patients, does not take into consideration the importance of the illness. A general screening, preferably one-step screening should be offered to each pregnant woman.

Amniotic fluid insulin levels and fetal abdominal circumference at time of amniocentesis in pregnancies with diabetes.

AIMS: Fetal hyperinsulinism is a strong predictor for excessive growth and fetopathy in pregnancies complicated by diabetes. We examined (i). the relationship between measurements of amniotic fluid insulin (AF insulin) and fetal abdominal circumference (AC) at the time of amniocentesis, and (ii). whether there is a threshold for fetal AC percentiles which can identify low vs. high-risk levels of AF insulin without performing an amniocentesis. METHODS: In a retrospective study, AF insulin from 121 pregnant diabetic women (32 pregestational; 89 gestational) was measured during the 3rd trimester as part of a diabetes management protocol. AC measurements were transformed into a continuous variable of percentile growth for gestational age (Hadlock). Division of the cohort according to deciles or quartiles of AC percentiles was performed to identify a threshold AC with a significant increase in elevated AF insulin, previously defined as AF insulin >or= 7 microU/ml. A receiver operator characteristic (ROC) curve was created and the negative predictive value (NPV) of the determined threshold was calculated. RESULTS: AF insulin levels were significantly correlated with the AC percentiles (r = 0.3, P = 0.0005) by linear regression. No AC threshold could reliably identify a moderate elevated AF insulin >or= 7 microU/ml (NPV 77.2%), but an AC threshold >or= 75th percentile could identify with fetal hyperinsulinism with an AF insulin >or= 16 microU/ml. All 10 cases of AF insulin >or= 16 microU/ml were identified with a NPV of 100% (74/74). CONCLUSIONS: Our data indicate that an AC >or= 75th percentile determined by a 3rd trimester ultrasound examination may discriminate between pregnancies at low vs. high risk for AF insulin >or= 16 microU/ml. This AF insulin concentration corresponds to a level of hyperinsulinism reported to be associated with considerable neonatal and long term morbidity.

[Supply of iodine during pregnancy--an inventory in Berlin, Germany]. / Jodversorgung in der Schwangerschaft--eine aktuelle Bestandsaufnahme in Berlin.

BACKGROUND: Iodised salt was introduced in Germany in the early 1980s. A nation-wide study in 1996 showed that iodine levels among the population had improved since the introduction of the supplementation. The study did not separately investigate the iodine status of pregnant women. In our prospective study, we used three parameters to assess the iodine levels among pregnant women. PATIENTS AND METHODS: Between October 1999 and February 2000, we asked 109 German-speaking patients seeking prenatal care in our clinic to participate. Following informed consent, we measured goiter volume by ultrasound and collected venous blood (serum) and urine samples. We asked patients about any history of thyroid gland illnesses and about iodine supplementation which is generally given to pregnant patients in Germany. The blood and urine samples were stored at -18 degrees C until measurement. We used the iodine-creatinine-ratio to measure ioduria. Iodine was measured using the Cer-Arsenite-method (Dade-Behring). The thyroglobulin concentration in serum was measured using RIA. RESULTS: The mean iodine-creatinine ratio was 181 +/- 109 microg/g, 20.4 % of the patients had a ratio between 50 and 100 microg/g which is defined as iodine deficiency I degrees (WHO). 8.7 % of the patients had thyreoglobulin levels above the cut-off value of 50 ng/ml. 12.6 % of the patients had a goiter (volume > 18 ml). 58 % of the patients were taking iodine supplements. These patients had significantly higher iodine-creatinine ratio levels (204 microg/g vs. 148 microg/g, P = 0.007) and lower serum thyroglobulin levels (38.4 vs. 34.1 pmol/l, P = 0.06) than non-supplemented patients. CONCLUSIONS: The prevalence of goiter reflects an extended period of iodine deficiency. Using laboratory methods, up to 20.4 % of pregnant women were identified as having an iodine deficiency which indicates the need for a general iodine supplementation during pregnancy.

Prenatal sonographic findings of thalamic cavernous angioma.

A cavernous angioma of the thalamus is a rare congenital brain tumor. We report the perinatal management and follow-up to 2 years in a case diagnosed in utero at 37 weeks of gestation, and review the literature.

[Association of low 50 g glucose screening test in pregnancy and fetal retardation]. / Assoziation von niedrigem 50-g-Glukose-Screeningtest in der Schwangerschaft und fetaler Retardierung.

BACKGROUND: The connection between elevated blood sugar and macrosomia is sufficiently well known and studied. The following study, however, examines whether patients with lower blood sugar values--based on the result of the 50 g-glucose screening test--delivered smaller children than patients with normal blood sugar based on the current criteria of blood sugar levels. PATIENTS RESPECTIVELY AND METHODS: In this study, all patients were included who visited our Prenatal Counseling Center between September 21, 1994 and July 31, 1996. Not included were patients with one-hour values greater or equal to 140 mg/dl. For assessing the 50 g-screening tests, percentiles were used. Based on the tables of Voigt, children below the 10th percentile were considered to be growth retarded. The student's t-test and chi-square test were employed as statistical tests. RESULTS: Of the 1416 participating patients in the study, 868 fulfilled the aforementioned criteria. A significant statistical correlation was shown between the development of fetal retardation and nicotine consumption, weight gain, and maternal height. It was also shown that patients with a lower (< 93 mg/dl) 50 g-screening test more often delivered a retarded child than patients with a normal value (23% vs. 12%, p = 0.034). No significant connection was found between the screening test groups and the described influencing factors. The clinical outcome, measured by the Apgar-scores and the transferal rate, was statistically significantly worse with the retarded children. CONCLUSIONS: The maternal glucose metabolism influences the fetal growth not only with respect to macrosomia but also growth retardation. The growth curves that have been used until now wrongly do not take into consideration the maternal anthropometric data. In light of this, the former ought to be re-evaluated. The data of this study emphasize the necessity of need-adapted nutrition. Maybe also pregnant women with a growth retarded child need a dietary consultation.