Small For Gestational Age Pregnancies Research Articles

Early-pregnancy soluble Fas levels in idiopathic small-for-gestational-age pregnancies

We sought to determine first- and second-trimester serum soluble Fas (sFas) and placental growth factor (PlGF) levels in idiopathic small-for-gestational-age (SGA) pregnancies. We measured sFas and PlGF levels in women who delivered SGA infants uncomplicated by preeclampsia and in control subjects. For sFas there were 34 cases and 318 control subjects in the first trimester and 9 cases and 11 control subjects in the second trimester. For PlGF there were 31 cases and 281 control subjects in the first trimester and 8 cases and 11 control subjects in the second trimester. SGA pregnancies had lower sFas levels than control subjects in the second trimester (3703 + or - 209 pg/mL vs 4562 + or - 241 pg/mL; P = .015), but not in the first trimester (4892 + or - 191 pg/mL vs 4971 + or - 177 pg/mL; P = .68). There was no difference in PlGF levels between SGA and normal pregnancies in both trimesters. Serum sFas levels were lower in idiopathic SGA pregnancies in the second trimester, but not in the first. There was no difference in serum PlGF levels in either trimester.

113. VASCULAR ENDOTHELIAL GROWTH FACTOR GENE POLYMORPHISMS IN PLACENTAL IMPAIRMENT AND SMALL FOR GESTATIONAL AGE BIRTH

Impaired placental angiogenesis is implicated in the pathophysiology of small for gestational age (SGA) infants. Placental expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, is reduced in SGA pregnancies. We aimed to evaluate the association of two single nucleotide polymorphisms (SNPs, VEGF-2578C/A and VEGF+936C/T) in VEGF gene which reduce VEGF expression, in SGA pregnancies andexamine their effects on first trimester placental VEGF expression. 3196 nulliparous pregnant women, their partners and babies were recruited in Adelaide and Auckland to a prospective multicentre cohort study (SCOPE Study). Amongst 2123 Caucasian women, 216 (11.9%) delivered a SGA infant defined as <10th customised centile. Uncomplicated Caucasian pregnancies served as controls (n = 1176). Uterine and umbilical artery Doppler velocimetry was performed at 20 weeks gestation. DNA extracted from peripheral blood from couples and cord blood from babies was genotyped using Sequenom MassARRAY. 74 first trimester placentae collected from elective terminations of pregnancy were genotyped for the same SNPs and the VEGF expression determined by RT-PCR. Neonatal VEGF+936 CT+TT genotypes associate with SGA (OR 1.6, 95%CI 1.1–2.3), lower birthweight (P = 0.005), customised birthweight centile (p=0.03), lower placental weight (P = 0.04) and an increased uterine artery resistance index (RI, P = 0.004). Maternal VEGF+936 CT+TT associate with bilateral notching of the uterine artery waveform (OR 1.4, 95%CI 1.0–1.8) and an increased umbilical artery RI (OR 1.5, 95%CI 1.1–2.1). VEGF+936 CT first trimester placentae have lower VEGF expression compared to CC (P = 0.045). Neonatal VEGF-2578 AA associates with bilateral uterine artery notching (OR 1.5, 95%CI 1.1–2.2) and increased umbilical artery RI (OR 1.6, 95%CI 1.0–2.6). Maternal VEGF-2578 CA+AA associate with increased umbilical artery RI (OR 1.5, 95%CI 1.0–2.2). VEGF polymorphisms reduce first trimester VEGF expression and associate with increased resistance in the placental circulation suggesting impaired placental function. VEGF+936 SNP confers increased risk for SGA.

Altered first-trimester screening markers after IVF/ICSI: no relationship with small-for-gestational-age and number of embryos transferred

First-trimester serum markers in 110 in-vitro fertilization (IVF) and 331 intracytoplasmatic sperm injection (ICSI) pregnancies were compared with 1431 pregnancies with spontaneous conception. Alterations of serum markers were evaluated with respect to small-for-gestational-age (SGA) growth and number of embryos transferred. For pregnancy-associated plasma protein A (PAPP-A), significantly lower concentrations were observed in IVF and ICSI pregnancies compared with controls (0.86 and 0.9 versus 1.06; P<0.001). Free beta-human chorionic gonadotrophin (betaHCG) values were significantly higher in the IVF/ICSI groups than in controls (1.1 and 1.1 versus 0.94; P<0.005). IVF and ICSI pregnancies showed higher rates of SGA (10.0% and 8.2%) compared with natural conception (4.6%), but differences in PAPP-A concentrations remained significant (P<0.005) after the exclusion of SGA pregnancies. No relationship between serum values and the transfer of one, two or three embryos was observed. Centre-specific corrections may be needed to adjust screening parameters for assisted reproductive technology.

Ultrasound estimation of fetal weight in small for gestational age pregnancies

Objective. Approximately half of small for gestational age (SGA) cases are due to maternal or fetal pathology, and may result in significant neonatal morbidity and mortality. The estimated fetal weight (EFW) measurement is the cornerstone of ultrasonographic findings when diagnosing and managing SGA pregnancies. Our objective was to determine the ultrasound accuracy of EFW in SGA pregnancies.Methods. A retrospective chart review was performed of all pregnancies complicated by SGA from a single institution (Stanford University) over a 2-year-period (2004–2006). SGA was defined as EFW ≤ 10%. 98 neonates whose last ultrasound for EFW occurred within 7 days of delivery were included in the study. The absolute differences between the EFW and birthweight (BW) were analyzed, and the absolute percent errors were calculated as (EFW − BW)/BW × 100. The mean absolute differences and mean absolute percent errors were analyzed across all gestational ages (GA) and EFWs using one-way analysis of variance.Results. The mean absolute percent error for the entire cohort was 8.7% (±6.3%). There was no statistically significant difference in the mean absolute percent error across all GAs (<32 weeks, 32–36 weeks, >36 weeks), and EFWs (<1500 g, 1500–2000 g, >2000 g).Conclusion. Ultrasound measurement of EFW in SGA pregnancies is consistent across all GAs and EFW measurements.

Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population

To determine if there are sex differences in risk and incidence of stillbirth, preterm delivery and small-for-gestational age (SGA) in pregnancies complicated by maternal asthma relative to a non-asthmatic population. Univariant and multiple regression analysis of the incidence of preterm delivery, SGA and stillbirth in singleton pregnancies complicated by asthma in Newcastle, NSW, Australia, from 1995 to 1999. Asthma complicated 12% of all singleton pregnancies. The incidence of preterm delivery was not significantly different between asthmatic (13%) and non-asthmatic (11%) pregnancies. Male fetuses (53%) were more likely to deliver preterm than female fetuses (47%) in both asthmatic and non-asthmatic populations. There were significantly more male neonates of pregnancies complicated by asthma that were SGA at term relative to those of the non-asthmatic population. There were significantly more preterm female neonates that were SGA in pregnancies complicated by asthma relative to those of the non-asthmatic population. Male fetuses were more likely to be associated with a stillbirth in pregnancies complicated by asthma than female fetuses. The presence of maternal asthma during pregnancy increases the risk of stillbirth for the male fetus and is associated with changes in fetal growth, but does not increase the incidence of a preterm delivery.

Is placental size a good predictor of obstetric complications?

Is placental size a good predictor of obstetric complications?

First‐trimester uterine artery Doppler indices in the prediction of small‐for‐gestational age pregnancy and intrauterine growth restriction

To assess the relationship of first-trimester uterine artery Doppler indices with subsequent delivery of small-for-gestational age (SGA) neonates or intrauterine growth restriction (IUGR). This was a prospective study in which uterine artery Doppler assessment was performed at 11-14 weeks in 3010 women with singleton pregnancies. Resistance indices (RI) and incidence of bilateral notching were compared between women with normal pregnancies (n = 2445) and those who delivered: SGA neonates (birth weight < 10th centile) (n = 377); SGA neonates who had been affected by pre-eclampsia (n = 27); IUGR neonates (birth weight < 10th centile and abnormal Doppler indices) with delivery > or = 37 weeks (n = 62); and IUGR neonates requiring preterm delivery (delivery < 37 weeks) (n = 36). The first-trimester uterine artery mean RI and prevalence of bilateral notching were significantly higher in women destined to deliver SGA neonates than in women with normal pregnancies (median uterine artery RI, 0.74 vs. 0.70, P < 0.001; prevalence of bilateral notches, 56% vs. 43%, P < 0.001). The areas under the receiver-operating characteristics curves for the prediction of SGA without pre-eclampsia, IUGR, preterm IUGR and SGA with pre-eclampsia were 0.602, 0.687, 0.776 and 0.708, respectively. There was a statistically significant inverse relationship between mean uterine artery RI and gestational age at delivery in the SGA pregnancies without pre-eclampsia (R = - 0.329, P = 0.01). There is a significant relationship between first-trimester uterine artery Doppler RI and the subsequent development of SGA. The sensitivity of first-trimester uterine artery Doppler is greater for SGA with pre-eclampsia than it is for IUGR alone. This could be because these two entities may have different underlying placental abnormalities that are detected variably on first-trimester uterine artery Doppler evaluation.

First‐trimester increase in oxidative stress and risk of small‐for‐gestational‐age fetus

Investigation of increased oxidative stress in early pregnancy and association with an increased risk of small-for-gestational-age (SGA) fetus. Longitudinal case-control study. University Hospitals of Leicester NHS Trust, Leicester, UK. Low-risk pregnant women with no current or pre-existing medical illness were recruited at a large teaching hospital from 2004 to 2006. Recruitment performed at the time of the dating ultrasound scan (12+/-2 weeks of gestation). Spot urine samples collected at 12+/-2 and 28+/-2 weeks of gestation were analysed for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography with tandem mass spectrometry). SGA was defined as birthweight <10th centile based on customised centile calculator (www.gestation.net). This identified the cases (n=55), whereas controls (n=55) were mothers whose babies were appropriate for gestational age (AGA, birthweight 10th-90th centile). Statistical analysis was performed using GraphPad Prism v.5. The relationship between maternal urinary 8-oxodG at different gestations and customised SGA was investigated by nonparametric tests. Customised SGA and AGA pregnancies. Urinary 8-oxodG concentrations were significantly increased in pregnancies with subsequent SGA compared with concentrations in normal pregnancies; 12 weeks: 2.8 (interquartile range [IQR] 1.96-3.67) versus 2.2 (IQR 1.26-3.28) pmol 8-oxodG/micromol creatinine (P=0.0007); 28 weeks: 2.21 (IQR 1.67-3.14) versus 1.68 (IQR 1.16-2.82) pmol 8-oxodG/micromol creatinine (P<0.0002). Concentrations decreased significantly between week 12 and 28 (P=0.04 and P=0.02 for controls and cases). In this study, urinary 8-oxodG at 12 and 28 weeks were elevated in SGA compared with AGA pregnancies. This may reflect early placental changes predating clinical features of SGA.

Leptin in first trimester pregnancy serum: no reduction associated with small-for-gestational-age infants

Leptin is an adipocytokine that is also synthesized by the placenta. Leptin and its receptor, which is also expressed by the placenta, are believed to play an auto- and paracrine role in trophoblast invasion and placental development. The leptin concentration in first trimester maternal serum and its relation to fetal growth disturbances were examined in this study. The study is a case-control study with 36 small-for-gestational-age (SGA) (<5th percentile) pregnancies and 108 appropriate-for-gestational-age (AGA) (> or =5th percentile) pregnancies. The groups were matched by maternal age, gestational age and body mass index (BMI). All were non-smokers. Leptin was measured in maternal serum in weeks 8-13 and was normalized for BMI with concentrations expressed as multiples of the median for the actual BMI. It was found that maternal serum leptin increased strongly (r = 0.7, P < 10(-4))with maternal BMI. There was no significant difference in maternal serum leptin concentrations between SGA and AGA pregnancies. In conclusion, SGA pregnancies are not associated with a lower maternal serum leptin concentration in first trimester. The maternal serum leptin concentration is largely determined by maternal BMI. Variation in the leptin concentration in maternal serum in first trimester does not seem to be associated with impaired fetal growth.

Placental System A Amino Acid Transport is Reduced in Pregnancies With Small For Gestational Age (SGA) Infants but Not in Preeclampsia with SGA Infants

Preeclampsia and intrauterine growth restriction (IUGR) are both associated with abnormal remodeling of maternal spiral arteries perfusing the placental site. This would be expected to be associated with reduced fetal growth, yet only one third of infants of mothers with preeclampsia are growth restricted. Infants with IUGR have decreased concentrations of amino acids in their blood and system A amino acid transporter activity is reduced in their placentas. Since infants of preeclamptic pregnancies have increased circulating amino acids, we tested system A amino acid transport activity of placental villous fragments from pregnancies with small for gestational age (SGA) infants with and without maternal preeclampsia and from uncomplicated and preeclamptic pregnancies with normal sized infants. We confirm the reduced uptake of amino acids in SGA pregnancies without preeclampsia but report that placental amino acid uptake of SGA infants with maternal preeclampsia is not reduced and is identical to uptake by normal and preeclamptic pregnancies with normal weight infants.

First-Trimester Markers of Aneuploidy and the Prediction of Small-for-Gestational Age Fetuses

First-trimester estimates of 2 biomarkers of placental origin, pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG), are increasingly used along with ultrasound measurement of nuchal translucency thickness to screen for trisomy 21 and other aneuploidies. There are preliminary indications that reduced levels of these markers—especially PAPP-A—may help to identify at-risk pregnancies including those resulting in delivery of a small-for-gestational age (SGA) infant. The study population included singleton pregnancies with chromosomally normal fetuses that were screened at 11 to 14 weeks’ gestation. Biochemical marker levels were converted to multiples of the expected normal median (MoM) for a pregnancy of the same gestational age. Associations between levels of free β-hCG and PAPP-A and the incidence of SGA were assessed by comparing relative incidence rates at MoM cutoffs and birth weight centile cutoffs. A total of 46,262 pregnancies resulted in live births of infants weighing at or above the 10th centile, whereas 3539 others produced SGA infants weighing less than the 10th centile for gestation. The risk of an SGA infant was significantly and inversely associated with maternal serum PAPP-A MoM, but not with free β-hCG MoM. In pregnancies with PAPP-A levels below the 10th, 5th, and 3rd percentile, the incidence of SGA was 12%, 14%, and 16%, respectively, and the odds ratios for SGA were 2.70, 3.21, and 3.66, respectively. Free β-hCG levels did not predict SGA. The investigators believe that, in the presence of a normal fetal karyotype, low maternal serum levels of PAPP-A are associated with an elevated risk of subsequently delivering a SGA infant. Low levels presumably indicate impaired placentation. Present evidence warrants using low PAPP-A to help identify SGA pregnancies.

Whole-genome microarray and targeted analysis of angiogenesis-regulating gene expression (ENG, FLT1, VEGF, PlGF) in placentas from pre-eclamptic and small-for-gestational-age pregnancies

Objective. To compare the placental pathology associated with pre-eclampsia (PE) and/or fetal growth restriction, the transcriptomes of placental tissues from PE and small-for-gestational-age (SGA) pregnancies were explored. In addition, a targeted analysis of angiogenesis-regulating gene expression was performed.Methods. Whole-genome microarray analysis was performed on placental tissue from gestational age-matched PE (n = 10), SGA (n = 8) and PE + SGA (n = 10) pregnancies. The expression of genes regulating angiogenesis (endoglin (ENG), fms-related tyrosine kinase 1 (FLT1), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)) was analyzed by quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR).Results. Microarray analysis did not reveal any significant differences between groups. However, an increased expression of ENG and FLT1 was detected by qRT-PCR in the PE + SGA group.Conclusions. The placental transcriptome did not differ between groups, although an increased anti-angiogenic gene expression in PE + SGA was observed with qRT-PCR analysis. Based on this, we conclude that although microarray technology may represent a powerful tool in generating new hypothesis in complex fields, it may not be sensitive enough to detect subtle changes in gene expression.

Activin A, hypoxia and the prediction of obstetric outcomes

On the back of sheep experiments showing that uterine hypoxia induces a rapid and sustained elevation of fetal activin A levels, we undertook two prospective studies to explore whether this novel observation could be exploited clinically. The first was a prospective labour ward study investigating whether umbilical arterial activin A levels at delivery correlated with either neonatal hypoxic ischaemic encephalopathy or pH. Unfortunately, we were unable to demonstrate a link with either, but found that levels were significantly depressed among those who had an emergency Caesarean section, suggesting a possible role in active labour. Second, we investigated the link between activin A and intrauterine growth restriction (IUGR), a condition of fetoplacental hypoxia, by measuring levels in women presenting for antenatal ultrasound biometry with clinical suspicion of a small baby. We found that, compared to pregnancies with a baby that was small for gestational age (SGA) but otherwise healthy, levels were 2.4 and 8 times higher, respectively, in pregnancies complicated by IUGR, and those complicated by both IUGR and preeclampsia. However, a single blood sample of activin A was unable to distinguish between IUGR and SGA pregnancies with sufficient sensitivity to be clinically useful. Our studies were unable to demonstrate clinical utility for the experimental observation linking activin A and hypoxia.

Angiotensinogen gene variants and small‐for‐gestational‐age infants

In 2003, the angiotensinogen (AGT) gene was found to be associated with infants small for gestational age (SGA). The present study of 107 pregnancies affected by SGA infants and 101 normal pregnancies was designed to further investigate this association. Maternal or fetal AGT genotype or haplotype frequencies did not differ between SGA and normal pregnancies (P > 0.35). Quantitative trait analysis of mothers with normal pregnancies demonstrated an association between AGT haplotype and blood pressure and body mass index at antenatal booking (P = 0.04), suggesting that AGT may play a role in the complex relationship between body mass and blood pressure in healthy pregnant women.

Symphysis–fundus measurements for detection of small for gestational age pregnancies

In Sweden measurements of the symphysis-fundus (SF) distance are used to detect small for gestational age (SGA) pregnancies. The aim of this study was to evaluate the efficiency of Swedish ultrasound-based SF reference curves in detecting SGA pregnancies. To assess the sensitivity for detection of SGA pregnancies we performed a case-control study. Through the Swedish Medical Birth Register we identified all singleton SGA infants born in Uppsala in 1993-1997 and randomly recruited non-SGA singleton infants as controls. We included 169 term and 73 preterm SGA cases and 296 controls, all born at term. The reference curves constructed by Steingrimsdottir (S curve) and Kieler (K curve) were evaluated. Gestational age at the first alarm in the preterm SGA group was recorded. In term pregnancies the S curve showed a sensitivity of 32% and specificity of 90% at a cut-off of -2 SDs. The corresponding values for the K curve were 51% and 83%, respectively. In preterm SGA pregnancies the sensitivity of the S curve was 49% and of the K curve 58%. The first alarm below 2 SDs was noted before 32 weeks in 37% with the S curve and 43% with the K curve for preterm SGA pregnancies. Both tested Swedish SF reference curves had low sensitivities for term SGA pregnancies. Sensitivity was higher for the preterm group and SF measurements seem to be better for detecting the most severe cases of SGA.

Customized Birthweight Centiles Predict SGA Pregnancies With Perinatal Morbidity

Birth weight traditionally is classified using population-based, sex-adjusted centiles. An infant weighing less than the 10th percentile at birth is considered to be small for gestational age (SGA). Some of these infants, however, are constitutionally small but not growth-restricted. This study was an attempt to reclassify infants using and percentiles, and to compare perinatal morbidity rates in those classified as and those appropriate for gestational age. The cohort study included 374 pregnancies from a general obstetric of 12,879. Pregnancy outcomes were compared for SGA infants who were below the 10th percentile by both and percentiles; SGA only; and SGA only. All pregnancies were evaluated by an ultrasound at less than 20 weeks gestation and by umbilical Doppler study within 2 weeks of delivery. The National Women's Hospital database of births in the years 1993-2000 was used to study the use of percentiles in a general obstetric population. Customized was the birth weight below 10th percentile using the New Zealand percentile calculator. Population was sex-adjusted birth weight less than 10th percentile and was birth weight of 10th percentile or more by both and parameters. At delivery, 80% of infants were by percentiles and 81% were by percentiles. The proportion of infants who were by both these percentiles was 72%. In addition, 7% of infants were customized only, 9% were population only, and 12% were non-SGA both. Mothers of infants who were reclassified as population only had lower body mass indices than those who were SGA both, and they also were likelier to be nulliparous. Women in the customized only group tended to have higher body mass indices. Rates of preeclampsia, abnormal Doppler findings, and cesarean section for fetal distress all were greater in the SGA and customized only groups than in the non-SGA group. These forms of morbidity were similarly frequent in the SGA and customized only groups. Indices of newborn morbidity, including a long hospital stay and composite morbidity, were increased to similar degrees in the SGA and customized only groups. Morbidity was comparatively low in the population only and non-SGA groups. All seven perinatal deaths were in the SGA group. Morbidity risk in babies who were customized only-and who would not have been detected using percentiles-had high morbidity rates comparable to those of infants in the SGA group. Compared with the non-SGA group, relative risk figures for perinatal death were high in the SGA and customized only groups. It appears that the use of birth weight percentiles is able to identify small infants who are at increased risk of perinatal morbidity and mortality.

Customised birthweight centiles predict SGA pregnancies with perinatal morbidity

To determine the following: (1) the proportion of babies reclassified as small or appropriately grown using customized and population centiles; and (2) the relative risks of perinatal morbidity, including abnormal umbilical Doppler studies, in babies classified as small for gestational age (SGA) and appropriate for gestational age (non-SGA) using the two centile calculations. Cohort study in SGA and general hospital populations. National Women's Hospital, Auckland, NZ. A cohort of SGA pregnancies (n= 374) and a general obstetric population (n= 12,879). Pregnancy outcomes were compared between 'non-SGA both' (> or =10th% by population and customized centiles) and those who were 'SGA both' (<10th% by population and customized centiles), 'SGA customized only' (SGA by customized but non-SGA by population centiles) and 'SGA population only' (SGA by population but non-SGA by customized centiles). Maternal and newborn morbidity and perinatal death. In the SGA cohort 271 (72%) babies were 'SGA both', 27 (7%) were 'SGA customized only', 32 (9%) were 'population SGA only' and 44 (12%) were 'non-SGA both'. In the general obstetric population 863 (6.7%) babies were 'SGA both', 445 (3.5%) were 'customized SGA only', 285 (2.2%) were 'population SGA only' and 11,286 (88%) were 'non-SGA both'. Perinatal death and newborn morbidity including nursery admission and long hospital stay were increased and comparable between 'SGA both' and 'customized SGA only' in both study populations. Newborn morbidity was low and comparable between 'population SGA only' and 'non-SGA both'. No perinatal deaths occurred in 'population SGA only' babies. Abnormal Doppler studies were more common in 'SGA both' or 'customized SGA only' but not in 'population SGA only' groups compared with 'non-SGA both'. Customized birthweight centiles identified small babies at risk of morbidity and mortality. Use of customized centiles is likely to detect more babies at risk of perinatal morbidity and mortality than would be detected by population centiles.

Soluble fms-Like Tyrosine Kinase 1 Is Increased in Preeclampsia But Not in Normotensive Pregnancies with Small-for-Gestational-Age Neonates: Relationship to Circulating Placental Growth Factor

An excess of the soluble receptor, fms-like tyrosine kinase 1 (sFlt-1) may contribute to maternal vascular dysfunction in women with preeclampsia by binding and thereby reducing concentrations of free vascular endothelial growth factor and placental growth factor (PlGF) in the circulation. The putative stimulus for increased sFlt-1 during preeclampsia, placental hypoxia due to poor perfusion, is common to both preeclampsia and idiopathic intrauterine growth restriction. However, the latter condition occurs without maternal vascular disease. We asked whether, as with preeclampsia, sFlt-1 is increased and free PlGF is decreased in villous placenta and maternal serum of normotensive women with small-for-gestational-age (SGA) neonates. This was a case-control study using banked samples. Groups of women with SGA neonates (birth weight centile < 10th) and women with preeclampsia were matched to separate sets of normal pregnancy controls based on gestational age at blood sampling (serum) or gestational age at delivery (placenta). sFlt-1 levels were higher in preeclamptics than controls (serum, P < 0.0001; placental protein, P = 0.03; placental mRNA, P = 0.007) but not increased in SGA pregnancies. PlGF was lower in both preeclampsia (serum, P < 0.0001; placental protein, P = 0.05) and SGA (serum, P = 0.0008; placental protein, P = 0.03) compared with their controls. PlGF in preeclampsia and SGA groups did not differ. These data are consistent with a role for sFlt-1 in the maternal manifestations of preeclampsia. In contrast to preeclampsia, sFlt-1 does not appear to contribute substantially to decreased circulating free PlGF in SGA pregnancies in the absence of a maternal syndrome.

Does antenatal identification of small‐for‐gestational age fetuses significantly improve their outcome?

Most obstetric clinics have a program for the identification of small-for-gestational age (SGA) fetuses because of the increased risk of fetal complications that they present. We have a structured model for the identification and follow-up of SGA pregnancies. We aimed to determine whether the recognition of SGA antepartum improves fetal outcome. All pregnancies at Malmö University Hospital from 1990 to 1998 (n = 26 968) were reviewed. SGA fetuses identified prior to delivery (n = 681) were compared with those not identified (n = 573). Also, all pregnancies with SGA fetuses were compared with those appropriate-for-gestational age (AGA) (n = 24 585). The risk of serious fetal complications (hypoxic encephalopathy grade 2 or 3, intracranial hemorrhage, Apgar score <4 at 5 min, neonatal convulsions, umbilical pH <7.0, cerebral palsy, mental retardation, stillbirth, intrapartum or infant death) was assessed with cross-tabulation and logistic regression analysis, adjusted for gestational age and degree of SGA. When compared with SGA fetuses identified before delivery (54%), SGA fetuses not identified before delivery were characterized by a four-fold increased risk of adverse fetal outcome (odds ratio, 4.1; 95% CI, 2.5-6.8). Similarly, compared with AGA fetuses, SGA fetuses were associated with a four-fold increased risk of serious fetal complications. A structured antenatal surveillance program for fetuses identified as SGA results in a lower risk of adverse fetal outcome, compared with cases of SGA fetuses not identified antepartum.

Placental System A Transporter mRNA is Not Different in Preeclampsia, Normal Pregnancy, or Pregnancies with Small-for-Gestational-Age Infants

Objective: System A amino acid transporter activity is reduced in placentas from small-for-gestational-age (SGA) compared to normal pregnancies. We compared the expression of the system A transporters between preeclamptic and control and between small-for-gestational-age and controls pregnancies. Methods: We used placental samples from 18 preeclamptic pregnancies matched with 17 normal pregnancies and from 16 SGA pregnancies matched with 15 different normal pregnancies. Using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) we quantified the mRNA for two system A subtype target genes ATA1 and ATA2 as well as beta-actin for normalization. Results: There was no significant difference of mRNA for ATA1 or ATA2 transporters between preeclamptic and their controls or SGA pregnancies and their controls. Conclusions: Despite previous studies reporting reduced activity for system A transporters in small-for-gestational-age pregnancies, we found no difference in steady-state concentrations of the mRNA, of the system A transporters among preeclamptic, SGA, and normal control pregnancies. These resultsdo not exclude differences in actual protein levels or activity of the amino acid transporters, which warrant further study.