The relationship between maternal serum and amniotic fluid alpha-fetoprotein in women undergoing early amniocentesis.

alpha-Fetoprotein levels were measured on 148 paired samples from the maternal serum and amniotic fluid in women greater than or equal to age 35, who were undergoing early amniocentesis (12 to 14 weeks) for chromosomal analysis. These 148 women were white, weighed less than 200 pounds, had no serious medical problems, and did not have a fetal abnormality detected by ultrasonography or karyotype analysis. There was a significant rise in the maternal serum alpha-fetoprotein concentration from 12 to 14 weeks' gestation. Amniotic fluid alpha-fetoprotein peaked at 13 weeks and then significantly declined by 14 weeks' gestation. Similar to reports from normal pregnancies at 16 and 17 weeks, we found no correlation between the maternal serum and amniotic fluid alpha-fetoprotein levels between 12 and 14 weeks. Amniotic fluid alpha-fetoprotein levels cannot be predicted by levels in the maternal serum in pregnancies between 12 and 14 weeks' gestation.     

Low maternal serum levels of placenta growth factor as an antecedent of clinical preeclampsia

OBJECTIVE: Maternal serum placenta growth factor levels have been shown to be significantly reduced in women with established preeclampsia. However, the temporal change in serum placenta growth factor levels before the clinical onset of preeclampsia is not known. STUDY DESIGN: Serum samples were collected from patients at the first prenatal (5-15 weeks' gestation), second-trimester (16-20 weeks' gestation), and third-trimester (26-30 weeks' gestation) visits. Serum placenta growth factor levels were determined and analyzed according to pregnancy outcome. RESULTS: Maternal placenta growth factor levels during normal gestation increased dramatically from the first to the third trimester. At the same gestational time points, in contrast, significantly lower serum placenta growth factor levels were found in patients in whom mild or severe preeclampsia eventually developed (P <.01). Low maternal serum placenta growth factor levels during early gestation were associated with a significant odds ratio for development of preeclampsia (P <.005). CONCLUSION: Relatively decreased levels of serum placenta growth factor occur before the onset of clinical preeclampsia, which suggests that placenta growth factor measurement could be used to discriminate those pregnancies predisposed to development of preeclampsia.     

HLA-G antigen and parturition: maternal serum, fetal serum and amniotic fluid levels during pregnancy

OBJECTIVE: To determine whether soluble HLA-G1 (sHLA-G1) concentrations in maternal serum and in amniotic fluid are lower at term than in the second trimester. METHODS: In this prospective study amniotic fluid and maternal serum samples were aspirated from 21 pregnant women during genetic amniocentesis at 16-20 weeks' gestation, and from 19 women undergoing a cesarean section at term. In the latter group arterial umbilical cord blood was aspirated as well. sHLA-G1 levels were determined using ELISA assay. This assay included the anti-HLA-G monoclonal antibodies 87G and 16G1, both as capture antibodies and horseradish-peroxidase-labeled rabbit anti-human beta(2)-microglobulin antibodies, as the detection antibody. The relative concentrations of sHLA-G1 were measured from the absorbancy of the blue product at 650 nm. Student's t test was used for statistical analysis. RESULTS: sHLA-G1 levels in amniotic fluid were significantly lower at term than in the second trimester (0.160 +/- 0.05 vs. 0.272 +/- 0.150 OD units; p < 0.05). Levels of sHLA-G1 in maternal serum declined toward term, but the difference from the second trimester was not statistically significant (0.266 +/- 0.157 vs. 0.205 +/- 0.120 OD units; p = 0.193). There was a strong correlation of sHLA-G1 concentrations between cord serum and maternal serum (R(2) = 0.79; p < 0.001), but not between cord serum and amniotic fluid (R(2) = 0.00004) or amniotic fluid and maternal serum (R(2) = 0.02). CONCLUSIONS: sHLA-G1 antigen expression is higher in amniotic fluid than in maternal-fetal compartments and significantly decreases toward term. We speculate that the declining amniotic fluid sHLA-G1 levels may stimulate a maternal immunological response against the fetus and contribute to the initiation of parturition.     

Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether serum concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a major decidual protein, at 16 weeks' gestation differ between women who later develop pregnancy-related hypertension and normotensive women. METHODS: Concentrations of IGFBP-1 were measured using immunoenzymometric assay in serum samples collected for alpha-fetoprotein (AFP) and free beta subunit of hCG (free beta-hCG) determinations in a Down syndrome screening program at 16 weeks' gestation in a population-based cohort of 1049 nulliparous women. After exclusion of subjects with multiple pregnancies, insulin-dependent diabetes, major fetal malformations, and incomplete data, 917 subjects remained eligible. RESULTS: The mean levels (+/- standard deviation) of IGFBP-1 were significantly lower in 34 women who later developed preeclampsia (73 +/- 43 microg/L, P < .01) and in 80 women with White A diabetes (84.7 +/- 53 microg/L, P < .01) compared with controls (103 +/- 58 microg/L). In seven women with White A diabetes and subsequent preeclampsia IGFBP-1 levels were especially low (41 +/- 34 microg/L). The concentrations of AFP and free beta-hCG in the subgroups with hypertensive disorders were not significantly different from those of normotensive women. CONCLUSION: Decreased IGFBP-1 levels at 16 weeks' gestation in women who develop preeclampsia might indicate impaired decidual function. Hyperinsulinemia, a known risk factor for preeclampsia, might contribute to decreased concentrations of serum IGFBP-1. However, due to low sensitivity, assay of serum IGFBP-1 was not clinically valuable for predicting preeclampsia.     

Fetal erythropoietin and endothelin-1: relation to hypoxia and intrauterine growth retardation

BACKGROUND: We have examined whether endothelin-1 (ET-1) and erythropoietin (EPO) in amniotic fluid, and EPO in fetal serum obtained by cordocentesis from fetuses with signs of intrauterine growth retardation (IUGR), were correlated to fetal growth and/or chronic fetal hypoxia. METHODS: Amniotic fluid and fetal serum were obtained by cordocentesis from 28 fetuses suspected to have IUGR and subsequently analyzed for EPO and ET-1 by ELISA. These data were correlated to blood gas results and fetal/maternal parameters at delivery. RESULTS: A novel finding was that ET-1 correlated to PO2 in amniotic fluid. The average level of ET-1 in amniotic fluid was 48.3+/-4.7 pmol/L. The results also showed a correlation between EPO levels in amniotic fluid and EPO in fetal serum. Furthermore, EPO correlated weakly to birth weight at delivery. Children with the lowest birth weights had the highest EPO levels. High EPO values, similarly to ET-1, correlated to low pO2 values. The level of EPO in amniotic fluid was 8.0+/-1.6 mIU/ml and in cord blood 29.5+/-9.6 mIU/ml. CONCLUSIONS: The results indicate that ET-1 levels may be a marker for short-term hypoxia, but not for fetal growth, since ET-1 in amniotic fluid was correlated to PO2 at the time of cordocentesis, but not to birth weight. The results also indicate that EPO levels in amniotic fluid and in fetal cord serum are highly correlated, and thus both can be used as markers for fetal growth and chronic hypoxia before the onset of labor.     

Second-trimester plasma homocysteine levels and pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction

OBJECTIVE: The purpose of this study was to determine whether second-trimester plasma homocysteine levels are elevated among women whose pregnancies are subsequently complicated by pregnancy-induced hypertension, preeclampsia, or intrauterine growth restriction. STUDY DESIGN: Women with normal but relatively low plasma zinc levels were randomly assigned to receive zinc supplementation or placebo from 19 weeks' gestation until delivery. Plasma homocysteine concentration and plasma and erythrocyte folate levels were determined for all available stored samples (zinc group, 231/294; placebo group, 206/286) at 26 and 37 weeks' gestation. Among all women with available samples, pregnancy-induced hypertension (n = 12) or preeclampsia (n = 4) developed in 16 women, and 22 pregnancies were complicated by intrauterine growth restriction. RESULTS: Mean homocysteine levels in women with pregnancy-induced hypertension and preeclampsia were similar to those of control subjects at 26 weeks' gestation but were significantly higher at 37 weeks' gestation. Homocysteine levels were similar between women with pregnancies complicated by intrauterine growth restriction and control subjects at both time points. CONCLUSION: Second-trimester plasma homocysteine concentrations do not predict the subsequent development of pregnancy-induced hypertension, preeclampsia, and intrauterine growth restriction.     

Gestational age and fetal biophysical assessment

With improved neonatal care, biophysical assessment to detect fetal asphyxia is used increasingly at an earlier gestational age. We have tested five fetal biophysical variables: nonstress test, fetal breathing movements, fetal movements, fetal tone, and amniotic fluid volume 11,012 times in 5582 singleton fetuses in whom there was a normal perinatal outcome. The nonstress test and fetal breathing movements were more likely to be abnormal at 26 to 33 weeks' gestation compared with 34 to 41 weeks. The nonstress test, fetal breathing movements, fetal tone, and amniotic fluid volume were more likely to be abnormal at 42 to 44 weeks' gestation compared with 37 to 41 weeks. Fetal biophysical tests should be interpreted in relation to gestational age.     

Altered circulating levels of adhesion molecules at 18 weeks' gestation among women with eventual preeclampsia: indicators of disturbed placentation in absence of evidence of endothelial dysfunction?

OBJECTIVE: The purpose of this study was to investigate whether indications of activation of the maternal endothelium were present at 18 weeks' gestation in women in whom preeclampsia eventually developed. STUDY DESIGN: A total of 2190 blood samples were obtained at 18 weeks' gestation. Circulating levels of von Willebrand factor and soluble vascular adhesion molecule 1, soluble intercellular adhesion molecule 1, and E-selectin were assayed in 71 women with eventual preeclampsia and 71 control subjects. RESULTS: E-selectin and von Willebrand factor levels were similar between the 2 groups. Soluble vascular adhesion molecule 1 concentration was significantly lower in the women with eventual preeclampsia (median, 649.0 ng/mL vs 762.4 ng/mL; P <.001), whereas soluble intercellular adhesion molecule 1 concentration was significantly higher (median, 239.8 ng/mL vs 178.3 ng/mL; P <.001). CONCLUSION: We found no indications of endothelial activation at 18 weeks' gestation in women in whom preeclampsia later developed. However, decreased serum concentration of soluble vascular adhesion molecule 1 and increased serum concentration of soluble intercellular adhesion molecule 1 may reflect the disturbed placentation known to be associated with the development of preeclampsia.     

Granulocyte colony-stimulating factor in preterm and term pregnancy, parturition, and intra-amniotic infection

OJBECTIVE: To determine the sources of granulocyte colony-stimulating factor (G-CSF) in amniotic fluid and to examine its relation to labor and clinically diagnosed intra-amniotic infection. METHODS: We assessed G-CSF and G-CSF receptor expression in placentas (n = 50) from 5-40 weeks' gestation, and G-CSF concentrations were measured in amniotic fluid (n = 146), bronchoalveolar lavage fluid (n = 8), and paired maternal serum, cord blood, neonatal serum, and neonatal urine samples (n = 16). RESULTS: Immunohistochemical staining and messenger RNA analysis showed placental expression of G-CSF and G-CSF receptor throughout gestation. The number of decidual stromal cells expressing G-CSF receptor was significantly higher in women with intra-amniotic infection compared with women without infection (27 +/- 2 versus 18 +/- 3 cells per high power field, P =.02). Amniotic fluid concentrations of G-CSF were not significantly different in noninfected preterm compared with term samples (1708 +/- 1673 versus 1612 +/- 2100 pg/mL, P =.9). Labor was not associated with a significant increase in amniotic fluid G-CSF concentrations (1864 +/- 3151 versus 1612 +/- 2100 pg/mL, P =.77, term labor versus no labor; 3335 +/- 5364 versus 1708 +/- 1673 pg/mL, P =.09, preterm). Concentrations of G-CSF in maternal serum, amniotic fluid, bronchoalveolar lavage fluid, and neonatal urine were increased during intra-amniotic infection (all P <.05). CONCLUSION: Amniotic fluid G-CSF concentrations were similar in preterm and term pregnancies and were not significantly influenced by labor. Intra-amniotic infection was associated with an increased number of placental cells expressing the G-CSF receptor and higher concentrations of G-CSF in amniotic fluid, maternal serum, neonatal urine, and neonatal bronchoalveolar lavage samples.     

Serum homocysteine at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether elevated homocysteine levels precede the development of preeclampsia. METHODS: Study subjects were selected from a population-based cohort of 1049 nulliparous women from whom serum was collected for Down syndrome screening at 16 weeks' gestation. For 34 women who developed preeclampsia, 68 control women were chosen who remained normotensive. Homocysteine was analyzed by high-performance liquid chromatography and fluorescence detection. The sample size allowed detection of a 1.25-micromol/L difference at a significance level of 0.05 and the power of 0.81. RESULTS: At 16 weeks' gestation, concentrations (mean, 95% confidence interval) of homocysteine in women who developed preeclampsia, 6.99 (6.42, 7.55) micromol/L, were similar to those who remained normotensive, 6.91 (6.45, 7.34) micromol/L. CONCLUSION: Significant changes in homocysteine metabolism did not predate the appearance of clinical preeclampsia.     

Effect of prenatal betamethasone administration on maternal and fetal corticosteroid-binding globulin concentrations

OBJECTIVE: This study was undertaken to examine the effects of prenatal betamethasone administration on corticosteroid-binding globulin concentrations in maternal and fetal plasma and amniotic fluid. STUDY DESIGN: Two groups of patients with preterm labor at 24 to 35 weeks' gestation who were receiving prenatal betamethasone (2 intramuscular doses of 12 mg) were studied. Maternal plasma was obtained before and at variable intervals until 1 week after betamethasone administration. Umbilical cord blood and amniotic fluid samples were collected at the time of delivery. Samples were also collected from patients at risk for preterm delivery who did not receive glucocorticoids. RESULTS: Betamethasone suppressed maternal cortisol concentration by >70% within 24 hours of injection but did not significantly alter corticosteroid-binding capacity or relative concentrations of corticosteroid-binding globulin isoforms in either maternal or umbilical cord plasma. Betamethasone reduced corticosteroid-binding capacity in amniotic fluid within 24 hours of injection, and values remained suppressed 1 week after treatment. CONCLUSION: Maternal and fetal plasma corticosteroid-binding globulin concentrations were unchanged after maternal betamethasone administration at 24 to 32 weeks' gestation but amniotic fluid corticosteroid-binding globulin concentrations decreased significantly, suggesting different sites of either corticosteroid-binding globulin production or regulation or both.     

Use of amniocentesis in preterm gestation with ruptured membranes

Sixty-one patients with preterm rupture of membranes were studied. Transabdominal amniocentesis was performed successfully in 42 patients (68.8%). Among these 42, 26 (61.9%) had a lecithin:sphingomyelin (L:S) ratio of 1.8 or greater and 16 (38.1%) demonstrated pulmonary immaturity. Amniotic fluid obtained from vaginal pooling was compared to fluid obtained transabdominally in seven patients and did not demonstrate any significant differences in L:S values. Gram stain and subsequent culturing of amniotic fluid obtained transabdominally was accomplished in 41 patients. Seven of the 41 patients (17.0%) had bacteria on Gram stain and/or subsequent amniotic fluid growth. All patients with either bacteria on Gram stain or a positive amniotic fluid culture developed clinical amnionitis or endometritis. Review of the neonatal morbidity and mortality in relation to gestational age of infants with preterm rupture of membranes suggests that: 1) In infants at less than 32 weeks' gestation, amniocentesis need not be done for pulmonary maturity as the morbidity of prematurity in this group is too high even in the presence of pulmonary maturity. 2) In infants at 32 to 34 weeks' gestation, amniocentesis for L:S ratio, Gram stain, and culture is helpful in selecting those in whom delivery should be instituted. 3) In infants at greater than 34 weeks' gestation, the neonatal morbidity is sufficiently reduced so that delivery should be considered except in cases of suspected delayed pulmonary maturation.     

The amniotic fluid index in normal twin pregnancies

OBJECTIVE: We sought to investigate the amniotic fluid index for individual gestational sacs of twin pregnancies. STUDY DESIGN: Four hundred eighty-eight patients with normal diamniotic twins were examined between 14 and 40 weeks' gestation. The dividing membrane between twin fetuses was identified. An amniotic fluid index was then obtained for each gestational sac. RESULTS: The median amniotic fluid index in individual twin gestational sacs rises slowly from 14 to 16 weeks' gestation to 23 to 28 weeks' gestation and then gradually declines. The median amniotic fluid index values by gestational age for twin A and twin B are not statistically different. Although twin pregnancies have a slightly lower median amniotic fluid index value than singleton pregnancies, the difference is also not statistically significant. CONCLUSION: Individual amniotic fluid indices can be obtained in twin pregnancies, and the values are comparable with those of singleton gestations.     

The successful use of human amniotic fluid for mouse embryo culture and human in vitro fertilization, embryo culture, and transfer

The development of mouse and human embryos was assessed in human amniotic fluid to determine its suitability as a culture medium for human in vitro fertilization (IVF). Two-cell mouse embryos developed to blastocysts after 72 hours at rates similar to that in Whittingham's T6 + 10% fetal calf serum. Significantly more mouse embryos hatched in amniotic fluid. No difference was found between individual patient's amniotic fluids obtained at 16 to 21 weeks' gestation. A preliminary trial comparing amniotic fluid with T6 + maternal serum in human IVF showed no significant difference in fertilization rate and embryo development during 42 to 48 hours in vitro. Expanded blastocysts were obtained in amniotic fluid after 5 days in vitro. Four pregnancies were obtained in 9 patients' transferred embryos grown in amniotic fluid and with 2 or 12 patients' transferred embryos grown in T6 + maternal serum.     

The relationship between the level of expression of intercellular adhesion molecule-1 in placenta and onset of preeclampsia

OBJECTIVE: To investigate the differences in the expression of intercellular adhesion molecule-1 (ICAM-1) in the placenta and the concentration of soluble ICAM-1 between early-onset and late-onset preeclampsia. METHODS: Preeclampsia was divided into early-onset type (EO: 20 to 31 weeks gestation) and late-onset type (LO: > or = 32 weeks gestation). Post delivery, placentas were obtained from 19 control pregnant women and from 9 EO and 8 LO preeclamptic women. The expression of ICAM-1 in placenta was determined by immunohistochemical staining. Blood samples were taken from 21 non-pregnant women, 16 control pregnant women, 13 EO and 8 LO preeclamptic women, and umbilical cord blood samples from 38 control pregnancies and from 16 EO and 14 LO preeclampsia. The concentration of ICAM-1 was measured by enzyme-linked immunosorbent assays. RESULTS: The expression of ICAM-1 in placenta was higher in LO than in EO preeclampsia (48.2 +/- 8.2% vs 17.9 +/- 5.0%) (p < 0.05). ICAM-1 concentration in umbilical cord blood was higher in EO than in LO preeclampsia (umbilical artery, 150.6 +/- 34.0 ng/ml vs 90.3 +/- 9.4 ng/ ml) (umbilical vein, 128.3 +/- 31.2 ng/ml vs 91.3 +/- 10.2 ng/ml) (p < 0.05). CONCLUSIONS: Significant differences were noted in the expression of ICAM-1 between patients with EO and LO preeclampsia, which suggest that the possibility that EO and LO preeclampsia may have different onset mechanisms.     

Fibrinolytic activity in amniotic fluid during late pregnancy

Fibrinolytic activity (FA) was assessed by the fibrin plate technique in 47 amniotic fluid samples obtained at 35 to 39 weeks' gestation. In amniotic fluid the FA (63.1 +/- 2.5 mm2) was considerably elevated when compared with previously reported serum levels of pregnant women. After centrifugation of the amniotic fluid samples a highly significant reduction of FA in the supernatant was recorded (42.9 +/- 1.3 mm2), suggesting that the cells of fetal origin are the main source of the high plasminogen activator activity demonstrated in amniotic fluid. A significant rise in amniotic fluid FA was demonstrated beyond the 37th gestational week. Furthermore, significantly greater FA was recorded in amniotic fluid samples from women with spontaneous onset of labor within a week. However, a single FA determination in amniotic fluid obtained by routine amniocentesis was found to be of little value for prediction of the time interval to delivery.     

Amniotic fluid absorbance at 650 nm: its relationship to the lecithin/sphingomyelin ratio and neonatal pulmonary sufficiency

In the present study, we sought to assess the clinical efficacy of the optical density of amniotic fluid at 650 nm (A650) to predict lung maturity in the human fetus. The A650 of 113 samples of amniotic fluid obtained from 16 to 45 weeks' gestation was determined. Mature values (A650 greater than or equal to 0.11) were not observed until 35 weeks' gestation but were always present after 39 weeks' gestation. In those infants delivered within 48 hours of amniocentesis, the absence rates of respiratory distress syndrome were the same with a mature lecithin/sphingomyelin (L/S) ratio (97.9%) and a mature A650 (97.3%). However, immature values in both tests were poor prognosticators of respiratory distress syndrome, with a rate of 37.5% with the immature L/S ratio and 15.8% with the immature A650. A mature A650 may be substituted for the L/S ratio, but an immature A650 is less reliable. In addition, we found that differences in centrifugation altered the A650 value, whereas exposure to light and cold storage did not.     

The amniotic fluid index, single deepest pocket, and two-diameter pocket in normal human pregnancy

OBJECTIVE: This study was undertaken to determine normative values for amniotic fluid index, single deepest pocket, and 2-diameter pocket across gestation. STUDY DESIGN: Fifty patients with normal pregnancies at each gestational age between 14 and 41 weeks' gestation were recruited prospectively and scanned once. Data were transformed into logarithmic (base 10) values for analysis. Polynomial regression equations were used to predict the normal values for amniotic fluid index, single deepest pocket, and 2-diameter pocket across gestational age and to predict the weekly percentage changes. RESULTS: The mean amniotic fluid index, single deepest pocket, and 2-diameter pocket values were significantly lower among patients at <37 weeks' gestation (n = 1150) than among those at > or =37 weeks' gestation (n = 250; P <.001 for all comparisons). The calculated prevalences of oligohydramnios (amniotic fluid index < or =5 cm, single deepest pocket <2 cm, or 2-diameter pocket <15 cm(2)) were significantly different (P <.0001) for the three techniques (8%, 1%, and 30%, respectively). Hydramnios (amniotic fluid index >24 cm, single deepest pocket >8 cm, or 2-diameter pocket >50 cm(2)) was also diagnosed with significantly different (P <.0001) frequencies (0%, 0.7%, and 3%, respectively). CONCLUSIONS: This is the largest prospective study to date to provide normative data for each of three ultrasonographic techniques used to assess amniotic fluid volume. The single deepest pocket appears to be the preferable method, because its use is least likely to lead to the false-positive diagnosis of either oligohydramnios or hydramnios.     

N-terminal peptide of pro-opiomelanocortin in human amniotic fluid

N-terminal peptide of pro-opiomelanocortin (N-POMC) was measured in the human amniotic fluid. At the gestational age of 16 to 20 weeks, the radioimmunoassay with three different antibodies demonstrated the respective values of 2.39 +/- 0.78, 4.69 +/- 2.27, and 5.92 +/- 2.66 ng/ml. These values are approximately 10 times higher than the measurements in the plasma of women at the corresponding gestational period. The amniotic fluid collected during the delivery had significantly lower concentrations of N-POMC than the amniotic fluid at 16 to 20 weeks' gestation. However, the plasma values of N-POMC had increased approximately three times when measured at delivery and compared with the plasma values at 16 to 20 weeks' gestation. Adrenocorticotropic hormone, measured simultaneously with N-POMC in some of the samples, showed changes similar to those in N-POMC. The N-POMC immunoreactivity from the amniotic fluid has the same retention time on reversed-phase high-performance liquid chromatographic separation as the peptide purified from the human pituitary gland, thus indicating the identity of both peptides.     

Utility of Head/Abdomen Circumference Ratio in the Evaluation of Severe Early-Onset Intrauterine Growth Restriction

ObjectiveTo determine whether the predominant phenotype of intrauterine growth restriction (IUGR) is symmetric or asymmetric in severe, early-onset disease due to placental insufficiency.MethodsWe conducted a retrospective chart review of high-risk pregnant women with severe, early-onset IUGR who were delivering at < 33+0 weeks’ gestation at Mount Sinai Hospital from 2001 to 2010. Ultrasound images were reviewed for fetal biometry, amniotic fluid volume, and uterine and umbilical Doppler flow studies within seven days of delivery, and the frequency of head circumference/abdominal circumference ratio ≥ 95th percentile for gestation was determined.ResultsSixty-two of 107 pregnancies (58%) with early-onset IUGR had an elevated HC/AC ratio (≥ 95th percentile), which was more than 10-fold greater than the expected proportion (P < 0.001). High rates of severe preeclampsia (53%), abnormal amniotic fluid (70%), and abnormal uterine artery Doppler studies (78%) indicated placental insufficiency.ConclusionFetuses with severe placental IUGR in the second trimester are more likely to have an asymmetric phenotype. This is in contrast to the current belief that asymmetric IUGR is confined to third trimester IUGR.