Subjective versus objective evaluation of amniotic fluid volume of pregnancies of less than 24 weeks' gestation: how can we be accurate?

This study was undertaken to compare subjective versus objective ultrasonic evaluation of amniotic fluid volume in pregnancies of less than 24 weeks' gestation. Amniotic fluid volume was subjectively (visualization without ultrasonic measurements) and objectively (visual interpretation with ultrasonic measurements) evaluated in 42 singleton pregnancies undergoing termination. The actual amniotic fluid volume was then determined using a dye-dilution technique. The women evaluated were in their mid-20s, primarily African American, and between 15 and 23 weeks' gestation. There was no significant difference in the total number of correct estimates of amniotic fluid volume when the data were stratified by level of operator experience (P = .34), ultrasonic technique (P = .33), or the combined correct subjective versus combined correct objective estimates (P = .68). We have concluded that the accuracy of amniotic fluid volume assessment in pregnancies of less than 24 weeks is not influenced by the level of operator experience or the type of ultrasonic measurement.     

三维超声测量正常中晚期单胎妊娠胎儿产尿率

目的 应用三维超声测量正常中晚期单胎妊娠胎儿的膀胱容量以估算不同孕期胎儿的产尿率,并探讨胎儿产尿率与孕周及羊水指数之间的关系.方法 对138例正常中晚期单胎妊娠胎儿进行三维超声检查,采用三维超声体积自动测量技术,间隔5～15 min,重复2～3次测量胎儿膀胱容量并计算产尿率.结果 胎儿的产尿率随孕周增加而增加,自孕24周的12.84 ml/h升至孕42周的64.70 ml/h,二者之间有明显相关关系(r=0.900,P<0.05).胎儿的产尿率与羊水指数无明显相关关系(r=-0.199,P>0.05).结论 运用三维超声体积自动测量技术测量正常中晚期单胎妊娠胎儿的膀胱容量变化可估算胎儿的产尿率,并可了解胎儿肾功能状态及宫内安危情况.     

Measurement of fetal urine production by three-dimensional ultrasonography in normal pregnancy.

OBJECTIVES: Measurement of fetal urine production may provide a means of evaluating amniotic fluid volume, which is difficult to measure directly, and predicting fetal hypoxia. Although there have been some reports on fetal urine production, most of these have used two-dimensional (2D) ultrasonography to measure bladder volume. Three-dimensional (3D) ultrasonography is, however, known to be superior to 2D ultrasonography in some organ volume measurements. Thus, we undertook this study to measure bladder volumes using 3D ultrasonography and to establish a nomogram of fetal urine production rate (UPR) according to gestational age (GA). METHODS: One hundred and fifty-four women with a normal singleton pregnancy at 24 to 40 weeks' gestation were enrolled in this cross-sectional study. The women had no medical or obstetric complications affecting amniotic fluid volume. Fetal bladder volume was measured using 3D ultrasound imaging and Virtual Organ Computer-aided AnaLysis (VOCAL) with a rotational angle of 30 degrees and manual surface tracing technique. Bladder volume was measured two or three times within a 5-10-min interval and fetal UPR was calculated from serial measurements. When measurements were performed more than twice, we used the mean rate of calculated UPRs. UPR was then plotted against GA to establish the nomogram. RESULTS: Fetal UPR increased with GA from a median value of 7.3 mL/h at 24 weeks' gestation to 71.4 mL/h at term, and could be calculated from GA using the formula: Ln(UPR) = - 6.29582 + (0.43924 x GA) + (0.000432 x GA2), r2 = 0.63, P = 0.0046. Growth percentiles of UPR according to age are presented. CONCLUSIONS: Fetal UPR can be easily measured by 3D ultrasound assessment of bladder volume. This modality may be a promising alternative to conventional methods of amniotic fluid volume measurement such as amniotic fluid index and single deepest pocket, and might be an alternative option for predicting fetal hypoxia.     

High perinatal survival in monoamniotic twins managed by prophylactic sulindac, intensive ultrasound surveillance, and Cesarean delivery at 32 weeks' gestation.

OBJECTIVES: Increased perinatal mortality in monoamniotic twin pregnancies is attributed to cord accidents in utero and at delivery. We evaluated the following parameters in monoamniotic pregnancies: (1) the incidence of cord entanglement; (2) the effect of sulindac on amniotic fluid volume and stability of fetal lie; and (3) the perinatal outcome with our current management paradigm. METHODS: This is a retrospective review of monoamniotic pregnancies of >or=20 weeks' gestation managed with serial ultrasound surveillance, medical amnioreduction and elective Cesarean delivery at 32 weeks' gestation. Mean amniotic fluid index (AFI) and change in AFI in monoamniotic pregnancies managed with oral sulindac was compared with 40 gestation-matched monochorionic-diamniotic controls. RESULTS: Among 44 monoamniotic pregnancies, 20 with two live structurally normal twins at 20 weeks' gestation satisfied the inclusion criteria. All fetuses survived to 28 days postnatally despite early prenatal cord entanglement in all but one case. Whereas AFI remained stable throughout gestation in the controls, the AFI fell in those patients on sulindac from a mean value of 21.0 cm (95% CI, 18.5-23.6 cm) at 20 weeks to a mean of 12.4 cm (95% CI, 10.1-14.6 cm) at 32 weeks (ANOVA P across gestation = 0.001) but mainly remained within normal limits. Fetal lie was stabilized in 11/20 cases in the monoamniotic group compared with 13/40 in the control group (P < 0.0001). CONCLUSIONS: Cord entanglement appears unpreventable, as it typically occurs in early pregnancy. Sulindac therapy reduces AFI, leads to more stable fetal lie, and may prevent intrauterine death by diminishing the risk of constricting cords that are already entangled. Perinatal survival in monoamniotic pregnancies managed by a regime of sulindac from 20 weeks' gestation, close ultrasound surveillance and elective abdominal delivery at 32 weeks' gestation seems empirically higher than that in the literature.     

Maternal anxiety and fetal behavior at 15 weeks' gestation.

OBJECTIVE: To analyze the relationship between maternal anxiety and fetal behavior at 15 weeks' gestation. METHODS: Twenty women in two groups were studied: 10 women underwent amniocentesis and 10 controls did not. Maternal anxiety was evaluated using the State Trait Anxiety Inventory questionnaire. Maternal plasma catecholamines (noradrenaline, adrenaline, dopamine) and maternal serum adrenocorticotropic hormone, cortisol, glucose, insulin, triiodothyronine, thyroxine and thyroid-stimulating hormone were measured. Catecholamines were also measured in the amniotic fluid of women undergoing amniocentesis. Compiled actograms of 40-min observations were done using ultrasonography. RESULTS: Maternal state-anxiety was significantly increased in the amniocentesis group. Except for fetal hiccups (r = 0.49, P = 0.03) there was no significant correlation between maternal anxiety and any of the other studied fetal movements. Maternal glucose was significantly correlated with hiccups (r = -0.59, P = 0.01), isolated leg movements (r = -0.52, P = 0.03), startles (r = -0.47, P = 0.04) and the total of the studied movements (r = -0.47, P = 0.04). Amniotic fluid catecholamines were significantly correlated with hand-face contact (r = 0.71, P = 0.02 for adrenaline), startles (r = 0.75, P = 0.01 for noradrenaline and r = 0.64, P = 0.04 for dopamine) and general movements (r = 0.89, P = 0.001 for noradrenaline). CONCLUSIONS: This study does not support a relationship between maternal anxiety and fetal behavior in early pregnancy. Maternal glucose and plasma catecholamines could be related to fetal movements at 15 weeks' gestation.     

Association of amniotic fluid index with estimated fetal weight.

OBJECTIVE: The relationship between amniotic fluid volume and gestational age has been described previously. The association of body weight and urine output has been observed in human neonates. Our goal was to assess the correlation of the amniotic fluid index (AFI) with estimated fetal weight (EFW) in the third trimester. METHODS: We conducted a retrospective observational study on 426 pregnant women with singleton gestations who were referred to our unit for sonographic evaluation in the third trimester. The AFI, EFW, and EFW percentile corrected for gestational age were evaluated. The sonographic examinations were stratified into 3 gestational age categories: 28 through 33.9 weeks, 34 through 37.9 weeks, and 38 weeks and later. Maternal and fetal outcome variables were collected from medical records. Linear regression, Mann-Whitney U, and Kruskal-Wallis tests were used for statistical analysis. RESULTS: There was no significant relationship between the AFI and EFW in the entire group of patients (R = 0.08; P = .096). There was a significant relationship between the AFI and EFW after 38 weeks' gestation (R = 0.30; P = .003). In addition, in female fetuses the EFW percentile correlated with higher AFI values at all gestational ages (R = 0.31; P < .001); this, however, was not observed in male fetuses. CONCLUSIONS: There is no relationship between the AFI and EFW during the third trimester, although a positive relationship between the AFI and EFW was noted late in gestation. In pregnancies with female fetuses, the AFI was positively associated with EFW percentile before 38 weeks' gestation.     

Prostate-specific antigen in amniotic fluid of normal and abnormal pregnancies

Objective: To examine if prostate-specific antigen (PSA) is present in amniotic fluid or maternal serum during pregnancy and if its presence is associated with fetal abnormalities.

Methods: Samples tested included amniotic fluids from 853 pregnant women for whom amniocentesis was performed; 312 nonpregnant women who donated blood; 259 pregnant women who donated blood at various gestational ages. Amniotic fluid or serum PSA was measured with an ultrasensitive time-resolved immunofluorometric procedure. 372 pregnancies were studied for the presence of genotypic or phenotypic fetal abnormalities.

Results: PSA was present in most amniotic fluids; the median PSA concentration increased from gestational week 11 to 22 and stabilized thereafter until delivery. The most prominent PSA concentration change occurred during gestational weeks 13–14. Pregnant women had significantly higher serum PSA concentrations than nonpregnant women; the pattern of serum fSA concentration change during pregnancy was similar to that of amniotic fluid; however, serum PSA concentrations were lower by a factor of 20–40. No association existed between amniotic fluid F'SA and maternal age, gender of fetus, or length of abstinence of mother from sexual intercourse. After gestational week 15, fetuses with trisomy 21 or 18, anencephaly, or renal disorders were associated with low amniotic fluid PSA levels.

Conclusion: Our data suggest that PSA may play a role in fetal development, especially at gestational ages between 13–20 weeks. The diagnostic usefulness of PSA in identifying fetal abnormalities remains to be determined.     

Evaluation of biophysical fetal assessment in high-risk pregnancy to assess ultrasound parameters suitable for screening in the low-risk population.

During a 1-year period, 662 pregnant women at 24-43 weeks' gestation were referred to the Department of Obstetrics and Gynaecology, at the Queens University Belfast, for fetal assessment because they were clinically suspected to be at high risk of perinatal complications. The results of our investigations were made available to the referring obstetricians who undertook the further management of the pregnancies. Subsequently six pregnancies resulted in perinatal deaths and 97 (14.7%) in the delivery of small-for-gestational-age infants. We restrospectively analyzed the data from ultrasonographic evaluation of the fetus and subjective and objective assessments of the amniotic fluid volume to determine their value in the prediction of adverse perinatal outcome. A fetal abdominal circumference < 10th centile for gestation or a subjectively reduced amniotic fluid volume identified 87 (90%) of small-for-gestational-age infants and five of the six perinatal deaths. When comparing the abdominal circumference and subjective liquor volume, both were sensitive in predicting delivery of a small-for-gestational-age fetus (sensitivity 86% vs. 53%, respectively) and perinatal death (sensitivity 50% vs. 83%, respectively). We suggest that, since assessments of these two factors are complementary in evaluating a high-risk pregnancy and can be measured in under 5 min, they now warrant consideration for screening in a prospective randomized trial in an unselected low-risk population.     

Maternal serums and amniotic fluid levels of human placental lactogen in gestational diabetes.

Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 microgram/ml) and normal pregnant women (6.4 microgram/ml). In contrast, the diabetic group was found to have significantly (P less than 0.001) higher concentrations of amniotic fluid hPL (1.2 microgram/ml) than normal pregnant women (0.8 microgram/ml).     

Non-invasive assessment of endothelial function in normal pregnancy.

OBJECTIVE: To assess endothelial function in normal pregnancy by non-invasive methods. METHODS: Flow-mediated dilatation of the brachial artery was measured by ultrasonography in 157 women with normal singleton pregnancies between 10 and 40 weeks' gestation and 19 non-pregnant controls. RESULTS: Flow-mediated dilatation in the non-pregnant controls was 6.42 +/- 2.45%. In pregnant women, between 10 and 30 weeks, the mean flow-mediated dilatation (8.84 +/- 3.18%) was significantly higher than the non-pregnant controls (P = 0.002), but after 30 weeks of gestation there was a decrease to prepregnancy levels. Resting vessel diameter and blood flow were significantly increased in pregnancy, mainly after 30 weeks' gestation (P < 0.001, P < 0.001, respectively). Flow-mediated dilatation was significantly correlated to resting vessel diameter and reactive hyperemia. CONCLUSION: Normal pregnancy is associated with enhanced endothelial function which is apparent from at least 10 weeks' gestation.     

Prenatal findings in epidermolysis bullosa with pyloric atresia in a family not known to be at risk.

Epidermolysis bullosa with pyloric atresia (EB-PA) is a rare autosomal recessive genetic disease with a poor prognosis. We report a case of EB-PA in a non-consanguineous couple with a non-contributory family history. The primigravid woman was referred to us because of polyhydramnios associated with fetal gastric dilatation at 33 weeks of gestation. Maternal serum alpha-fetoprotein (AFP) had been elevated at 15 weeks' gestation (3.08 multiples of the median), and ultrasound examination showed polyhydramnios with echogenic amniotic fluid, gastric dilatation, and no other associated malformation. The fetal karyotype was normal female (46,XX). Acetylcholinesterase (ACHe) and AFP levels in the amniotic fluid were normal. Labor occurred spontaneously at 35 weeks' gestation. Clinical examination of the newborn showed large areas of cutaneous blisters and erosions, as well as pyloric atresia. Immunofluorescence analysis of skin samples confirmed EB-PA. Molecular analysis showed a new mutation of the integrin beta-4 gene: heterozygote missense deletions (3807delC/310delC, respectively, exons 31 and 5). The child died from severe sepsis at the age of 13 days. Our observation emphasizes the difficulty of interpreting prenatal ultrasound findings when there is no suggestive context.     

Maternal serum and amniotic fluid levels of human placental lactogen in gestational diabetes

Abstract. Human placental lactogen (hPL) levels were measured radioimmunologically in maternal serum and in amniotic fluid between the 37th and 39th weeks of gestation in sixteen gestational diabetic and thirty normal pregnant women. There was no significant difference in maternal serum hPL levels between diabetic (6.1 μ g/ml) and normal pregnant women (6.4 μ g/ml). In contrast, the diabetic group was found to have significantly ( P< 0.001) higher concentrations of amniotic fluid hPL (1.2 μ g/ml) than normal pregnant women (0.8 μ g/ml).     

Amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5'-nucleotidase activity from 13 to 40 weeks' gestation, and alkaline phosphatase as an index of fetal lung maturity

Reference ranges for amniotic fluid alkaline phosphatase, gamma-glutamyltransferase, and 5-nucleotidase are described from 13 to 40 weeks' gestation. Gamma-glutamyltransferase and 5-nucleotidase activities peak early in the second trimester and then decrease to low values. Alkaline phosphatase shows a similar pattern of activity from 13 to 29 weeks' gestation, but thereafter activity increases to term; this late increase is mainly related to the heat-labile particulate form of alkaline phosphatase. Total and heat-labile alkaline phosphatase alone or expressed as a ratio with gamma-glutamyltransferase can be used with or as an alternative to lecithin/sphingomyelin ratios in the investigation of fetal lung maturity. A total alkaline phosphatase activity of 0.36 mukat/L and an alkaline phosphatase/gamma-glutamyltransferase ratio greater than 2 indicate pulmonary maturity.     

Maternal heart rate variability and fetal behavior in hypertensive and normotensive pregnancies

The relation between maternal heart rate variability (HRV) and fetal behavior was examined in hypertensive and normotensive pregnant women. A total of 40 mother-fetal pairs (n = 20 normotensive mothers; n = 20 hypertensive mothers) at 33-41 weeks' gestation were observed using a standardized procedure lasting approximately 50 min. It included the following measurements: maternal beat-by-beat arterial blood pressure and HRV; spontaneous fetal heart rate (HR), body and breathing movements; and an estimate of amniotic fluid volume. The women in the hypertensive group had higher average body mass index (BMI) (33.7 vs. 28.8 kg/m2) than the normotensive group. In the normotensive group, there was no association between maternal HRV and fetal gestational age, HR, body or breathing movements. In the hypertensive group, maternal HRV measures of low-frequency, high-frequency, and total power were associated with fetal gestational age; also, there was an association between maternal autonomic modulation of HR and fetal spontaneous HR. These findings suggest that the maternal autonomic system influences fetal cardiac function in pregnancies complicated by hypertension.     

Very echogenic amniotic fluid: ultrasonography-amniocentesis correlation.

Very echogenic amniotic fluid has been variably attributed to meconium, blood, or vernix caseosa. However, most previous reports have been case reports, and most cases have not had proof by amniocentesis. In a larger series of patients with proof by amniocentesis, we sought to determine the relative frequency of these substances as causes of very echogenic amniotic fluid. We retrospectively identified obstetric sonograms in which the amniotic fluid was homogeneously filled with innumerable echogenic particles. The cause of the increased echogenicity was determined by fluid appearance at amniocentesis. Of 86 cases identified, immediate proof by amniocentesis was available in 19 patients for whom the gestational age ranged from 32.8 to 39.4 weeks. Vernix was present in 18 (95%) patients and meconium in one (5%) patient. Very echogenic amniotic fluid in the third trimester is most often due to vernix and infrequently due to meconium. This sonographic finding is not a reliable indicator of meconium or blood in amniotic fluid and should not typically alter antenatal management.     

Seropositivity toChlamydia trachomatis during pregnancy and perinatal complications

We studied the relationship between seropositivity toChlamydia trachomatis during pregnancy and perinatal complications. Of 178 pregnant women, 10 (5.62%) had IgG and IgM antibodies toC. trachomatis by enzyme linked immunosorbent assay at 10 and 20 weeks of gestation. Twenty-one of 178 (11.8%) women had IgG and IgA antibodies toC. trachomatis. None of these seropositive women received therapy during pregnancy. Five babies born to women with IgG and IgA antibodies had fetal or neonatal distress; 1 mother had meconium-stained amniotic fluid. Of 307 pregnant women at 30 weeks of gestation, 5 (1.63%) had IgG and IgM antibodies, and 24 (7.82%) had IgG and IgA antibodies toC trachomatis. Seropositive women in this group received therapy with clarithromycin, 400 mg/day, for 2 weeks during pregnancy. No babies born to women with IgG and IgA positive antibodies had fetal or neonatal distress; 9 mothers had premature rupture of the membrane, and 5 had meconium-stained amniotic fluid. Chlamydial antigen (identified as E strain) was detected in 2 of the 5 neonates born to women with IgG and IgM antibodies. The incidence of perinatal complications was significantly higher in pregnant women withC. trachomatis-positive IgG and IgA antibodies than in seronegative pregnant women at 30 weeks of gestation (P<0.05).C. trachomatis infection present near the time of labor was considered to be associated with perinatal complications.     

An improved determination of total glycosaminoglycans in body fluids by formation of complexes with quinacrine: changes in amniotic fluid total glycosaminoglycans during normal pregnancies and in pregnancies at risk for mucopolysaccharidoses.

Acidic glycosaminoglycans form insoluble complexes with quinacrine and this has been exploited for their analysis in blood, urine and amniotic fluid. The method is specific for glycosaminoglycans including keratan sulphate and the samples do not have to be deproteinized. Values for normal urine, serum and amniotic fluid are presented. Urinary total glycosaminoglycans excreted by patients with mucopolysaccharidoses were also determined. The normal changes in amniotic fluid total glycosaminoglycans have been measured between 14 weeks' gestation and term, and values are given for amniotic fluid total glycosaminoglycans in several pregnancies at risk for mucopolysaccharidoses. It is suggested that this method is a potentially valuable analytical tool in the pre-natal diagnosis of mucopolysaccharidoses.     

Accuracy of ultrasonography in evaluating amniotic fluid volume at less than 24 weeks' gestation.

The purpose of this investigation was to evaluate the accuracy of common sonographic techniques in assessing the amniotic fluid volume in pregnancies of less than 24 weeks' gestation. Patients at less than 24 weeks' gestation undergoing an amniocentesis for the placement of prostaglandin F2 alpha for termination (because of genetic or fetal anomalies, or both) were assessed for amniotic fluid volume. All fetuses were alive at the time of prostaglandin instillation. The amniotic fluid index and two-diameter pocket were used to determine the amniotic fluid volume. Prior to the prostaglandin instillation, the amniotic fluid volume was determined with para-aminohippurate using a diazo dye reaction with spectrophotometric analysis. The amniotic fluid volume was determined in 21 pregnancies between 15 and 24 weeks' gestation, yielding volumes ranging from 189 to 1840 ml. Using published standards for amniotic fluid volume in singleton pregnancies, oligohydramnios was present in three gestations, the volume was found to be normal in 15, and hydramnios complicated three pregnancies. The two-diameter pocket identified the amniotic fluid volumes correctly more often (18 of 21 [85.7%]) than the amniotic fluid index (10 of 21 [47.6%]) (P = 0.02). Normal amniotic fluid volume was identified in nine of 15 (60%) pregnancies by the amniotic fluid index and in 14 of 15 (93.3%) by the two-diameter pocket (P = not significant). Abnormal amniotic fluid volumes, oligohydramnios, and hydramnios were recognized more often by the two-diameter pocket (66.7%) than by the amniotic fluid index (1 of 6 [16.7%], P = not significant).     

Relationship of maternal protein turnover and lean body mass during pregnancy and birth length.

Epidemiological evidence shows that small size at birth is associated with an increased risk of developing cardiovascular and metabolic disease in adult life. We have examined the relationships between size at birth and maternal body composition and protein turnover in normal pregnant women. A group of 27 multiparous Caucasian women with singleton pregnancies were studied at around 18 and 28 weeks' gestation. Body composition was determined by anthropometry, and whole-body protein turnover was estimated by using a single oral dose of [(15)N]glycine and the end-product method. The baby's weight and length were measured within 48 h of birth. Mothers with a greater lean body mass had higher rates of protein turnover at 18 weeks' gestation. This association was largely accounted for by differences in the mother's visceral, rather than muscle, mass. Mothers who had higher protein turnover at 18 weeks' gestation had babies that were longer at birth. After adjustment for the duration of gestation and the baby's sex, 26% of the variation in length at birth was accounted for by maternal protein synthesis at 18 weeks' gestation. Maternal protein intake was not associated with the baby's birth length. Thus the mother's ability to nourish her fetus is influenced by her body composition and her rate of protein turnover. Dietary intake does not adequately characterize this ability.     

Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies.

OBJECTIVE: To determine reference values of fetal subcutaneous tissue thickness (SCTT) throughout gestation in a healthy population and to compare them with those from a population of pregnant women with gestational diabetes under standard therapy. METHODS: Three hundred and three women recruited from a high-risk pregnancy clinic were classified as being healthy (n = 218) or as having gestational diabetes (n = 85) on the basis of a negative or positive oral glucose tolerance test, respectively. They were enrolled into the cross-sectional study at 20 weeks' gestation. Ultrasound examinations were performed approximately every 3 weeks until delivery at term. The mid-arm fat mass and lean mass (MAFM, MALM), the mid-thigh fat mass and lean mass (MTFM, MTLM), the abdominal fat mass (AFM) and the subscapular fat mass (SSFM) were evaluated. Time-specific reference ranges were constructed from the 218 healthy women and a conventional Student's t-test was performed to compare SCTT values between the two study groups throughout gestation. RESULTS: Normal ranges, including 5th, 50th and 95th centiles of the distribution, were generated for each SCTT parameter obtained in each of the two groups of women. Significant differences were found between the two study groups at 37-40 weeks' gestation for MTFM, at 20-22 and 26-28 weeks for MTLM, at 31-34 and 35-37 weeks for MAFM, at 26-28 and 38-40 weeks for SSFM, and at 39-40 weeks for AFM, the mean residual values always being greater in gestational diabetic women than they were in the group of healthy pregnant women. CONCLUSIONS: We provide gestational age-specific reference values for fetal SCTT. Fetal fat mass values, particularly in late gestation, are greater in women with gestational diabetes compared with healthy women. The reference values may have a role in assessing the influence of maternal metabolic control on fetal state.