Changes in platelet function in pregnancies complicated by fetal growth retardation.

Platelet function was investigated in three patients with severely decreased fetal growth rates detected by ultrasound scanning. Only one patient had hypertension, which was mild and developed after decreased fetal growth and altered platelet responses had been detected. Much higher concentrations of platelet-activating factor (PAF) (20-500 nM) were required to stimulate maximal platelet aggregation in all three patients compared with the concentrations of PAF (5-10 nM) required in control pregnancies of similar gestational age. In a fourth patient, platelet desensitisation was observed 5 weeks before the detection of decreased fetal growth. These results are similar to those observed in women with hypertensive disorders of pregnancy, and indicate that there may be a similar change in platelet function in gestational hypertension and in fetal growth retardation, although the clinical manifestations are different.     

Cord serum glycodelin concentrations in normal pregnancies and pregnancies complicated by diabetes

Objective Glycodelin is a glycoprotein released by secretory/decidualized endometrial glands. Its synthesis increases during pregnancy. Hormonal factors whose levels have been shown to change in diabetes (vascular endothelial growth factor, relaxin) may mediate the actions or regulate the synthesis of glycodelin. Cord serum glycodelin levels have not been studied in pregnancies complicated by diabetes.Methods Cord serum glycodelin concentrations were measured at birth by an immunofluorometric assay in 62 normal pregnancies, in 67 pregnancies complicated by type 1 diabetes, and in 28 pregnancies complicated by insulin-treated gestational diabetes.Results The mean glycodelin concentration in cord serum was 2.7 ng/ml (standard error of the mean 0.6) in normal pregnancies. The concentration was not altered in pregnancies complicated by diabetes. Cord serum glycodelin concentrations were also unaltered in diabetic pregnancies with hypertensive disorders (chronic hypertension, pregnancy-induced hypertension or pre-eclampsia) or fetal macrosomia. There was a negative borderline correlation between cord serum glycodelin concentrations and the birth weight in pregnancies complicated by diabetes (r=–0.21, p=0.049).Conclusions Decidual function, as assessed by cord serum glycodelin levels, is not markedly altered in diabetic pregnancies. The negative correlation between cord serum glycodelin and the birth weight of the newborns in diabetic pregnancies may be due to the decline in glycodelin levels with advancing pregnancy in the third trimester.     

HPL-positive infiltrating trophoblastic cells in normal and abnormal pregnancy.

In a series of 24 pregnant women, placental bed biopsies were performed in the third trimester at cesarean section. All the resulting specimens contained infiltrating trophoblast with both small and giant cells, and eight also contained vascular trophoblast. On immunoperoxidase staining for HPL, some small interstitial trophoblastic cells were positive in 12 cases. Some cells of the vascular intramural trophoblast and practically all cells of the vascular intraluminal trophoblast were positive. Seven cases were normal pregnancies whereas 17 were complicated by arterial hypertension and/or fetal growth retardation. A significant correlation between abnormal pregnancy and absence of HPL-positive interstitial cells in the placental bed biopsy was found. This probably indicates a diminished overall number of HPL-positive interstitial cells in the group of abnormal pregnancies and might reflect some defect of interstitial trophoblast. Such a defect may play a role in the arrest of the physiological changes of pregnancy in spiral arteries, which has been described in pre-eclampsia and in many cases of idiopathic fetal growth retardation.     

Metalloprotease (ADAM12-S) as a Predictor of Preeclampsia: Correlation with Severity,Maternal Complications,Fetal Outcome,and Doppler Parameters

Objectives. To compare the first trimesteric serum level of ADAM12-S in women who developed mild and severe preeclampsia and in healthy gravidas and to correlate these changes with the severity of the disease, maternal complications, fetal outcome, and Doppler cerebroplacental ratio (CPR). Design. Comparative prospective observational study. Setting: University hospital. Methods: Serum samples were obtained from 414 women in their first trimester, of which 259 women completed their pregnancy without complications and 155 women developed preeclampsia later in their pregnancies. All were subjected to history taking, examination, laboratory investigations, obstetric ultrasound, and Doppler CPR. Results. ADAM12-S was significantly decreased in patients with severe and in mild preeclampsia compared with the controls. Moreover, there was strong negative correlation with disseminated intravascular coagulopathy (DIC) and HELLP syndrome, cesarean delivery, postpartum hemorrhage, and neonatal intensive care unit admission. ADAM12-S had medium negative correlation with systolic blood pressure and diastolic blood pressure, accidental hemorrhage, cesarean hysterectomy, prematurity, and low birth weight. In addition, it had a weak negative correlation with intracranial hemorrhage, residual hypertension, and intrauterine fetal death. ADAM12-S had strong positive correlation with CPR. There were no correlation with eclampsia, intrauterine growth retardation, acute pulmonary edema, and acute renal failure. Conclusion. ADAM12-S is significantly decreased in severe and mild preeclampsia and is correlated with CPR, severity of preeclampsia, maternal complications, and fetal outcome. It is recommended to measure ADAM12-S in the first trimester to predict maternal complications and fetal outcome in pregnancies complicated by preeclampsia.     

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD-II) activity in human placenta: its relationship to placental weight and birth weight and its possible role in hypertension

It has been assumed that low birth weight and high placenta weight were key factors for predicting hypertension in human adulthood. A deficiency in placental 11 beta-HSD-II enzyme activity was supposed to be the underlying cause. To possibly establish 11 beta-HSD-II as a leading factor, we determined 11 beta-HSD-II activities in 133 healthy pregnancies, 21 proteinuric pregnancies complicated by pregnancy-induced hypertension (PIH), 26 non proteinuric PIH pregnancies and 15 pregnancies complicated by fetal growth restriction (32nd-41st gestational week). We could not identify differences in 11 beta-HSD-II activity between pregnancies with the rare combination of small babies with big placentas and others (p = 0.59; Kruskal-Wallis test). And although there was no correlation between 11 beta-HSD-II activity and birth weight, in the control gestational age correlated with 11 beta-HSD-II activity (r = 0.22; p < 0.05; Spearman). 11 beta-HSD-II activity in the proteinuric PIH group was significantly higher than in the controls (11.7 pmol/min/mg prot.; range 10-13.2 vs. 7.9; range 7.0-9.1; p < 0.05). The lowest, but not significant, enzyme activities were in the IUGR group (5.8 pmol/min/mg prot.; range 4.0-9.2). In this group, analysis of variance detected a correlation between enzyme activity and placental weight. In conclusion, we could not confirm that placental 11 beta-HSD-II deficiencies act as an indicator for the risk of adult hypertension in small fetuses with large placentas. However, in growth restriction 11 beta-HSD-II activity might play a role. To clarify the influence in this group, further research is needed. Increased 11 beta-HSD-II activities with gestational age in the control may serve to sustain fetal adrenal steroid genesis and to prepare the fetus for autonomic life.     

Is fetal growth impaired after in vitro fertilization?

BACKGROUND: The objective was to study fetal growth parameters in in vitro fertilization (IVF) pregnancies and to investigate the relationship between fetal growth and maternal blood pressure. METHODS: We examined 64 women, pregnant after in vitro fertilization, with repeated ultrasound examinations measuring biparietal diameter, femur length, abdominal diameter and fetal weight at 24, 30, and 36 weeks of gestation. We calculated deviations in percent from expected values in regards to biparietal diameter, femur length, abdominal diameter, and fetal weight. Blood pressure was measured every second week. RESULTS: Biparietal diameter in the study group was significantly smaller at 24 (-3.3%, 95%CI -4.4 to -2.2) and 30 (-1.4%; 95%CI -2.5% to -0.3) weeks. Femur length differed significantly on all three occasions, at 24 (-6.3%; 95%CI -7.7 to -5.1), 30 (-6.6%; 95%CI -8.0 to -5.3), and 36 (-3.9%; 95%CI; -5.0 to -2.8) weeks. Abdominal diameter demonstrated a significant deviation at 24 weeks (-1.6%; 95%CI -2.8 to -0.4). Fetal weight did not reach significant deviations at any gestational age. There was no correlation between deviation of the individual growth parameters or estimated fetal weight and elevated blood pressure. CONCLUSION: The growth pattern of in vitro fertilization pregnancies does not seem to differ from spontaneously conceived pregnancies to any appreciable extent. In the present material, no relationship between fetal growth and maternal blood pressure could be observed. We could not show that an impaired fetal growth predates the development of hypertension.     

Endothelin 1 and leptin in the pathophysiology of intrauterine growth restriction.

OBJECTIVES: To evaluate the relationship of endothelin 1 (ET-1) and leptin concentrations in women and newborns following a pregnancy complicated with intrauterine growth restriction (IUGR). METHODS: Twenty-five women with a pregnancy complicated with IUGR at 19 different gestational ages were matched with women with uncomplicated pregnancies. Blood samples from the umbilical artery and maternal peripheral venous circulation were collected at delivery, and ET-1 and leptin levels were determined from the blood samples. Data relating to obstetric complications (e.g., pregnancy-induced hypertension), delivery (e.g. mode, birth weight, signs of intrapartum fetal distress, and Apgar scores) were also recorded. RESULTS: Mean maternal ET-1 (13.4+/-6.2-9.9+/-2.9 pmol/l) and mean fetal ET-1 (14.5+/-4.2-11.7+/-3.1 pmol/l) concentrations were significantly higher when women had experienced pregnancies complicated with IUGR than when they had had normal pregnancies. Mean fetal leptin concentration was significantly lower in the study group (6.8+/-2.2 ng/ml) than in the control group (10.6+/-3.6 ng/ml (P<0.05). However, fetal leptin per kilogram of fetal weight was not significantly different in the study group (3.16+/-1.18 ng/ml) than in the control group (3.23+/-0.96 ng/ml) (P>0.05, paired t-test). However, a statistically significant correlation was observed between fetal leptin concentrations per kilogram of fetal weight and fetal endothelin concentrations in pregnancies complicated with IUGR (r=0.546; P<0.05). CONCLUSIONS: These results suggest the intertwined roles of ET-1 and leptin in the pathophysiology of IUGR. Further studies concerning interaction between these peptides in different pregnancy conditions may provide important information about the actions of ET-1 and leptin on fetal growth.     

Maternal left ventricular dimension in pregnancies complicated by fetal growth retardation

Previous studies using two-dimensional chest radiographs have found a significant correlation between prematurity, fetal growth retardation, and the size of the maternal heart. Accordingly, we evaluated maternal left ventricular size and function by M-mode echocardiography near the end of gestation in 42 women with suspected fetal growth retardation and in 79 women whose pregnancies were normal. No significant differences were found between the two groups, implying that maternal left ventricular size and function is adequate in pregnancies complicated by "idiopathic" fetal growth retardation.     

Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia

Objective To investigate the correlation between soluble forms of the intercellular adhesion molecule (SICAM-1) and vascular cell adhesion molecule (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for fetal growth.
Design Prospective observational study.
Setting Institute of Medical Genetics, University of Oslo, Department of Medical Genetics and Haematological Research Laboratory, Ullevål University Hospital; and the Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway.
Participants Seventy-six women with normotensive pregnancies and 157 women with pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with fetal growth retardation.
Methods ELISA-measurements of plasma SICAM-1 and sVCAM-1 were performed in a group of healthy pregnant normotensive women and three groups of women with varying degrees of pre-eclampsia.
Results SICAM-1 concentrations were higher in the pre-eclampsia group compared with the control group, but this difference was not statistically significant. Plasma concentrations of sVCAM-1 were significantly greater ( P < 0.0001) in all pre-eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth retardation ( P = 0.03) compared with mild pre-eclampsia.
Conclusion The observed increases in plasma concentrations of sVCAM-1 suggest that measurements of this adhesion molecule may be useful in monitoring pregnancies with respect to the development of pre-eclampsia or fetal growth retardation.     

First trimester sex hormone-binding globulin and subsequent development of preeclampsia or other adverse pregnancy outcomes.

OBJECTIVE: To investigate whether first trimester maternal serum sex hormone-binding globulin (SHBG) concentrations are altered in women who subsequently develop preeclampsia or other pregnancy complications. POPULATION: Women undergoing first trimester combined ultrasound and biochemical screening for chromosomal anomalies. We searched the database and identified 32 pregnancies resulting in miscarriage, 64 pregnancies with preexisting or gestational diabetes mellitus, 107 with fetal growth restriction, 103 with preeclampsia, 64 with pregnancy-induced hypertension, and 26 with spontaneous preterm delivery. We also selected 400 controls from among the population of pregnancies that had a delivery of a normal baby with no pregnancy complications. METHODS: Maternal serum SHBG concentrations were measured retrospectively using a competitive chemiluminescent immunoassay. The levels between those with normal outcome and those resulting in adverse outcome were compared. RESULTS: The median maternal serum SHBG concentration was not significantly different from controls, in those that subsequently developed preeclampsia (median MoM 1.05), non-proteinuric hypertension (median MoM 0.94) or preterm delivery (median MoM 1.15). The levels were significantly lower in those with diabetes (median MoM, 0.81 p=0.0005) and those pregnancies resulting in miscarriage (median MoM 0.80, p=0.008). CONCLUSION: First trimester maternal serum SHBG concentrations are no different from controls in women who subsequently develop preeclampsia, pregnancy-induced hypertension, fetal growth restriction, or preterm delivery. Levels are reduced in those who subsequently miscarry or in those presenting with diabetes.     

Altered prolactin bioactivity in amniotic fluid of hypertensive pregnancy

The high concentrations of prolactin (hPRL) in human amniotic fluid appear to be derived principally from maternal decidua. The present study evaluated both the biologic and immunologic activity of amniotic fluid hPRL obtained from normal and selected complicated pregnancies. Biologic and immunologic activities of amniotic fluid hPRL were also compared with lecithin:sphingomyelin ratios and phosphatidylglycerol content. No significant correlation existed between amniotic fluid hPRL activities and fetal lung maturation. However, a significant increase in amniotic fluid hPRL concentration as well as specific biologic activity of the hormone was found in pregnancies complicated by hypertension. These findings suggest alterations in the synthesis of decidual hPRL and/or its transport to the amniotic fluid that may influence pregnancy-induced hypertension.     

Corticotropin-releasing hormone in maternal and cord plasma in pre-eclampsia.

The concentration of corticotropin-releasing hormone (CRH) in maternal plasma increases greatly during the last trimester of normal pregnancy. This CRH has been proposed to originate from the placenta. We studied plasma immunoreactive CRH in 46 uncomplicated pregnancies, in 10 pregnant women with chronic hypertension, in 17 women with pregnancy-induced hypertension (PIH) and in 24 women with pre-eclampsia, and correlated it to the levels of corticotropin (ACTH) and cortisol. CRH levels were greatly increased in women with pre-eclampsia, less significantly in women with PIH, while no change was found in pregnant women with chronic hypertension. ACTH levels also were increased in pregnancies with pre-eclampsia or PIH and there was a positive correlation between CRH and ACTH levels. CRH levels in cord venous plasma were significantly increased in pregnancies with pre-eclampsia but cortisol did not show any significant increase. These findings suggest that placental release of CRH into the maternal and fetal circulation is increased in pre-eclampsia.     

Transforming growth factor-beta1 in fetal serum correlates with insulin-like growth factor-I and fetal growth

OBJECTIVE: To estimate whether transforming growth factor-beta1 in fetal serum obtained by umbilical cord sampling at delivery is correlated with fetal growth. We also estimated whether transforming growth factor-beta1 is correlated with insulin-like growth factor-I and insulin-like growth factor binding protein-1, which have been shown to correlate with fetal growth. METHODS: The active form of transforming growth factor-beta1 was analyzed in serum from cord blood from 68 fetuses by the enzyme-linked immunosorbent assay technique. Of the 68 pregnant women, 12 had preeclampsia, 14 had preeclampsia and intrauterine growth restriction, 15 had intrauterine growth restriction alone, and seven had fetuses that were large for gestational age (LGA). Twenty pregnancies with fetuses appropriate for gestational age (AGA) served as controls. RESULTS: Transforming growth factor-beta1 concentrations were significantly correlated with birth weight. The average transforming growth factor-beta1 concentration in the following groups were: intrauterine growth restriction, 22.4 +/- 2.7 microg/L; intrauterine growth restriction plus preeclampsia, 22.9 +/- 2.0 microg/L; preeclampsia without intrauterine growth restriction, 28.8 +/- 2.1 microg/L; LGA, 30.3 +/- 4.3 microg/L; and AGA, 36.8 +/- 2.0 microg/L. Transforming growth factor-beta1 levels were significantly lower in pregnancies complicated by intrauterine growth restriction and showed a positive correlation with birth weight (r = 0.48, P <.001). Furthermore, there was a positive correlation between insulin-like growth factor-I levels and birth weight (r = 0.36, P <.01) and a negative correlation between insulin-like growth factor binding protein-1 and birth weight (r = -0.32, P <.01). There was also a correlation between transforming growth factor-beta1 and insulin-like growth factor-I (r = 0.29, P <.05) and between transforming growth factor-beta1 and insulin-like growth factor binding protein-1 (r = -0.25, P <.05). CONCLUSION: Transforming growth factor-beta1 might be related to fetal growth in pregnancy. The results also support previous data showing that insulin-like growth factor-I and insulin-like growth factor binding protein-1 are related to fetal growth.     

Fetal superior mesenteric artery blood flow velocimetry in normal and high-risk pregnancy

THE AIM: To record blood flow velocimetry in the fetal superior mesenteric artery in normal pregnancy and to evaluate if blood flow recordings in the vessel might predict adverse outcome in high-risk pregnancy. METHODS: The fetal superior mesenteric artery blood velocimetry was recorded in a cross sectional manner in 75 normal pregnancies between 27 and 41 weeks of gestation. Reference curves were performed for pulsatility and resistance indices. The superior mesenteric artery was also located in 48 singleton pregnancies complicated by pregnancy-induced hypertension and/or intra-uterine growth retardation. Middle cerebral artery, umbilical artery and vein and uterine artery velocimetry were also recorded. RESULTS: Superior mesenteric artery PI and RI values expressed an increase in resistance to blood flow with gestational age after 32 weeks of gestation. In all except eight high-risk pregnancies the fetal mesenteric artery PI values were within normal range. Among the pregnancies with absent or reversed blood flow in the umbilical artery, all had abnormal mesenteric artery pulsatility index (PI) (> 97.5th percentiles), one fetus died intrauterine and two others died after delivery due to prematurity, growth retardation and necrotizing enterocolitis. In the remaining fetuses with increased mesenteric artery PI, necrotizing enterocolitis was diagnosed in three cases. CONCLUSIONS: Increased vascular resistance in the mesenteric artery might be a late sign of fetal circulation redistribution and frequently related to necrotizing enterocolitis in the newborn.     

Obstetrical and neonatal outcome in pregnancies after liver transplantation

The obstetrical and neonatal courses in pregnancies following orthotopic liver transplantation were studied. Maternal and neonatal records were reviewed from six patients (eight pregnancies), cared for by a single practitioner, who had undergone orthotopic liver transplantation prior to pregnancy between 1984 and 1999. Demographic data, reason for transplantation, interval from transplantation to pregnancy, immunosuppressive agents, antepartum complications, and maternal and neonatal outcomes were reviewed. Many reasons for transplantation were noted, and no acute graft rejection occurred. Maternal complications noted were mild renal insufficiency, chronic hypertension, pregestational diabetes, and erythema nodosum. Antepartum complications included oligohydramnios, preterm labor, premature rupture of membranes, severe preeclampsia, fetal growth restriction, multiple congenital anomalies, and intra-amniotic infection. There was one miscarriage at 8 weeks, one previable and one periviable delivery, and the remainder delivered after 34 weeks. In our cohort of patients, once fetal viability was achieved, patients with a prior liver transplant had reasonable maternal and neonatal outcomes.     

Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation.

Saline extracts were made from portions of 17 normal placentae and from 8 placentae from pregnancies complicated by fetal growth retardation, but not hypertension. The ability of these extracts to inhibit urokinase-induced fibrinolysis was measured using a fibrin plate technique. Placental extracts from pregnancies complicated by fetal growth retardation exhibited greater inhibition of urokinase-induced fibrinolysis. There was no evidence of disseminated intravascular coagulation in these patients, but certain coagulation factors in the peripheral blood were raised.     

Systemic Lupus Erythematosus in Pregnancy

systemic lupus erythematosus (SLE) in pregnancy is associated with increased maternal and fetal morbidity including fetal loss, growth restriction, and maternal hypertension. Pregnancy complications are more frequent and more severe when conception occurs in patients with lupus nephritis or antiphospholipid antibodies, or during a period of active disease. Lupus flares occur in the majority of pregnancies and often involve the renal and haematologis systems. They tend to be mild to moderate and are treatable with medical therapy, primarily glucocorticoids. Neonatal lupus syndrome is a rare complication of maternal SLE. It is associated with transplacental passage of anti-Ro and/or anti-La antibodies, resulting in cutaneous, haematologic, and cardiac manifestations. Cardiac involvement is common in this syndrome, manifesting as complete congenital heart block due to destruction of the fetal conduction system by antibodies. Antepartum steroid use may be useful in treatment or prevention of congenital heart block. With optimal prenatal care and fetal antepartum surveillance, patients with SLE may have successful, although high risk, pregnancies.     

Beta-endorphin in amniotic fluid in normal and hypertensive gestations: relationship with maternal blood pressure parameters.

beta-Endorphin (beta-E) immunoreactivity was measured in the amniotic compartment of 52 normotensive and 45 hypertensive gestations. All the fetuses of the normal group were healthy and showed appropriate intrauterine growth, whereas only suffering and growth-retarded fetuses were included in the pathological group. As expected, amniotic beta-E concentration was found to be significantly higher in hypertensive than in normotensive pregnancies (mean +/- SEM: 129.1 +/- 8.15 vs. 59.1 +/- 2.68 pg/ml; p < or = 0.005). A positive correlation between the hormone levels and the diastolic as well as the mean maternal blood pressure (r: 0.554; p < or = 0.05 and r: 0.525; p < or = 0.05, respectively) was present only in pregnancies complicated by hypertension. Furthermore, a negative correlation (r: -0.555; p < or = 0.05) linked amniotic beta-E and the pulse pressure in normal but not in complicated pregnancies. Unless beta-E in the amniotic compartment is also of amniochorial origin, our results suggest that the fetal endorphinergic tone is either activated by elevated diastolic and mean maternal pressure levels or lowered by increased pulse pressure values in normally elapsing pregnancies.     

Fetal Growth and Placental Pathology in Maternal Hypertensive Diseases

Among 252 pregnancies complicated by hypertension, the following associations were found: (1) At term, isolated chronic hypertension was associated with higher birthweight compared to normotensive controls and to preeclamptic pregnancies; only preeclampsia was independently related to low birthweight at term. (2) Preeclampsia was independently related to preterm intrauterine growth retardation as compared to normotensive preterm deliveries. (3) Decreased placental weight and the presence of placental infarction were both independently related to decreased birthweight and length (p<0.01). Decreased placental weight was inconsistently related to blood pressure elevation, and not independently related to other maternal characteristics. Placental infarction was associated with increasing levels of proteinuria. (4) Only proteinuria was associated with decreased fetal growth independent of placental pathology. We suggest that there is a “fetal syndrome” of chronic decreased fetal oxygenation and growth failure linked tightly to placental pathology, which may be poorly correlated with the degree of maternal hypertension. Hypertension in pregnancy is more likely to be accompanied by placental pathology and decreased fetal growth when severe proteinuria is present.     

Quantitative structural studies on human placentas associated with pre-eclampsia, essential hypertension and intrauterine growth retardation

Placentas from pregnancies complicated by pre-eclampsia, essential hypertension, hypertension complicated by pre-eclampsia and from normotensive pregnancies resulting in the birth of a singleton small-for-dates (SFD) infant have been studied by quantitative morphometry. The findings have been compared with those from placentas of uncomplicated pregnancies. The placentas from pregnancies complicated by pre-eclampsia and those resulting in a SFD baby had a significantly lower total volume, volume of parenchyma and villous surface area when compared with normal pregnancies of comparable gestation. They also had an increase in areas of multiple infarction and in the volume proportions occupied by fetal capillaries. The placentas from women with essential hypertension uncomplicated by pre-eclampsia were as large as those from normal pregnancies and the villous surface areas were as high. Villous surface area measurements in the different groups were related to gestation and to fetal weight.