Small For Gestational Age Pregnancies Research Articles

Placental insufficiency among high-risk pregnancies with a normal umbilical artery resistance index after 32 weeks

ObjectiveTo determine the incidence of abnormal multi-vessel Doppler values among advanced pregnancies at risk of suboptimal placentation but with a normal umbilical artery resistance index (RI), and to assess whether clinical and ultrasonography findings can identify them. MethodsIn a prospective cross-sectional study at Tygerberg Hospital, South Africa, women with high-risk pregnancies but normal umbilical artery RI after 32weeks underwent ultrasonography (fetal biometry, liquor, and placenta maturation) and Doppler assessment (uterine, umbilical, and middle cerebral arteries) between February 11 and October 21, 2013. Study data were compared among four groups: fetuses with normal uterofetoplacental Doppler values and those with any abnormal pulsatility index, each subdivided into small for gestational age (SGA) and appropriate for gestational age (AGA) by estimated fetal weight. ResultsOf 210 participants, 72 (36.2%) had abnormal Doppler results, and 60 (28.6%) fetuses were SGA (38 [63.3%] with abnormal Doppler results). Clinical characteristics did not differ between groups with normal or abnormal Doppler values; however, among normal Doppler results, SGA pregnancies demonstrated poorer fundal growth (P=0.006). Significant associations existed between abnormal Doppler results and asymmetric growth, inappropriately advanced placental maturation, and reduced liquor volume (all P≤0.04), but with very low sensitivities (3.9%, 4.8%, and 14.5%, respectively). ConclusionMaternal characteristics and imaging variables did not reliably identify more than one-third of pregnancies with evidence of suboptimal placentation.

75 How useful is placental growth factor in routine practice? A clinical evaluation in women presenting with suspected placental disease

Introduction Placental growth factor (PlGF) is increasingly recognised as a marker of placental dysfunction. PlGF for the diagnosis of pre-eclampsia (PE) has recently been recommended by the NICE diagnostic assessment panel to rule out PE within one week but the significance of a positive test remains uncertain. Objectives The aim of this study was to evaluate the use of PlGF in routine practice in women with suspected placental disease with and without features of maternal disease. Methods Women with chronic disease (hypertension, renal disease ± diabetes, n = 114) with a change in maternal condition or women with suspected fetal growth restriction (FGR) (n = 146) had a PlGF performed >20 weeks. Results were revealed and standardised care pathways followed. Outcomes were checked by two independent reviewers. Results In line with previous reports, we observed a much shorter median test-delivery interval in women with a low PlGF Despite a strong association between low PlGF and poor outcome (62% delivered 14 days. 62% (n = 18) of these women had PE and 28% (n = 8) had FGR without maternal disease. There was no significant difference in the test-delivery interval between these groups (13 [0–37] compared with 11 [1–35] days, p > 0.05). There were 2 false positive cases of low PlGF without a diagnosis of PE, however these women had confounding medical comorbidities which made the diagnosis ambiguous. Similarly, 2/77 women had a false positive intermediate PlGFs associated with concurrent maternal disease. There were no normal pregnancy outcomes associated with low PlGF. Evaluation of the 7 false negative cases (a diagnosis of PE with a normal PlGF) demonstrated that none were obtained within a week of delivery (27 [7–63] days). Three of these cases had long test-delivery intervals and 3 cases were complicated by complex maternal disease. Of the women with a normal PlGF and small for gestational age (SGA) (n = 51), the median test-delivery interval was 48 [4–90] days. However, 48/51 (94%) were >7 days before delivery.9/51 of these normotensive SGA pregnancies with normal PlGF were delivered for suspected FGR (abnormal growth velocity, oligohydramnios and/or abnormal Dopplers) and had a median birthweight (BW) centile of 2.8 (0–8–8.3), 17 for suspected SGA (median BW centile 3.6 [0.1–9.6]) and 25 delivered for other reasons (median BW centile 5.25 [1–9.3]). There were 3 cases of stillbirth, one of which had a normal PlGF (23 days before delivery; BW centile 1.4). Conclusion In our cohort, a low PlGF was universally associated with a poor outcome and short test-delivery interval which was not affected by the indication (maternal or fetal) for the PlGF. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction, however it has highlighted that several evidence gaps remain before this test can be implemented in routine clinical practice and confirms that abnormal PlGF levels in isolation are not an indication for delivery. Further research linking placental pathology and maternal PlGF levels is urgently needed.

Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses

Introduction: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. Material and Methods: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. Results: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. Discussion: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness.

O114. Maternal cardiovascular changes in pregnancies complicated by small for gestational age neonate with or without maternal hypertension

Objective The literature describing the maternal cardiovascular changes in pregnancies complicated by fetal growth restriction and maternal hypertension is limited, conflicting and does not discriminate the two pathologies. The aim of this study was to investigate maternal cardiovascular changes in pregnancies complicated by small for gestational age (SGA) neonates with or without maternal hypertension. Methods This was a prospective case-control study including pregnancies resulted in SGA neonate (n = 159) and a group of uncomplicated pregnancies (n = 473), recruited after 20 weeks’ gestation. The SGA group was further divided according to fetal Doppler to define fetal growth restriction (FGR; n = 51) and maternal hypertension (n = 51). FGR was defined as estimated fetal weight below the 10th centile with abnormal umbilical artery Doppler (pulsatility index [PI] above the 90th centile or absent or reversed end-diastolic flow). Maternal cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) were recorded using the USCOM®, while the augmentation index (AIx) was assessed using the Arteriograph®.Uterine artery (UtA) mean PI was assessed at the same visit. Mann–Whitney test and regression analysis were used for statistical analysis. Results Compared to controls, the SGA pregnancies had significantly lower CO (median 6.08 L/min, IQR 5.31–6.86 vs 6.65 L/min, IQR 5.68–7.79, p = 0.006), but significantly higher SVR (median 1091 dynes-sec/cm5, IQR 998–1359 vs 1040 dynes-sec/cm5, IQR 878–1263, p = 0.008). Both AIx and UtA mean PI were significantly higher in the SGA pregnancies compared to controls (p = 0.002 and p 0.001, respectively). In normotensive SGA, the results were similar (p 0.05). However, after correcting for body surface area, neither cardiac index nor SVR index were significantly different between the two study groups (p = 0.209 and p = 0.139, respectively). In normotensive FGR pregnancies, SVR, AIx and UtA mean PI were significantly higher (p 0.01 for all), while CO was not significantly different (p = 0.429). Conclusion FGR is associated with maternal cardiovascular changes. The conflicting results reported by previous studies could be explained by failure to correct for maternal body surface area, incorrectly labelling SGA pregnancies as FGR, or lack of distinction between FGR with or without maternal hypertension.

Insulin family polymorphisms in pregnancies complicated by small for gestational age infants.

Being born small for gestational age (SGA) increases the risk for adverse perinatal outcomes and later life vascular and metabolic disorders. The insulin family plays a vital role in intrauterine growth. We investigated the association of functional SNPs in insulin (INS), insulin receptor (INSR) and insulin receptor substrate 2 (IRS2) with small for gestational age (SGA) pregnancies, uterine and umbilical artery Doppler and plasma insulin level. We conducted a nested case-control study of 1401 nulliparous Caucasian women, their partners and babies (216 SGA and 1185 uncomplicated). SGA was defined as a birthweight less than the 10th customized birthweight percentile adjusted for maternal height, weight, parity, ethnicity, gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 ± 1 week gestation. The SNPs in the parent infant trios were genotyped using Sequenom MassARRAY. Plasma insulin was measured by double antibody RIA in 188 healthy non-pregnant adults to assess correlations between SNP genotypes and circulating insulin. Paternal [odds ratio (OR) (95% CI) = 2.2 (1.3-3.9), P = 0.005] and infant [OR (95% CI) = 3.3 (1.7-6.2), P = 0.0001] INSR rs2059806 AA genotype was associated with SGA. Infant INSR rs2059806 A allele was associated with abnormal umbilical artery Doppler [OR (95% CI) = 1.3(1.0-1.7), P = 0.04]. INSR rs2059806 AA homozygous individuals had lower plasma insulin compared with heterozygotes (P = 0.03) and GG homozygotes (P = 0.03). The INSR rs2059806 SNP previously associated with adult vascular and metabolic diseases is also associated with SGA pregnancies. This polymorphism may associate with the risk of vascular and metabolic disorders across the life course.

Assessment of glycogen phosphorylase isoenzyme BB as a biomarker for pre-eclampsia and small for gestational age

BackgroundGlycogen phosphorylase is a key enzyme in the regulation of glycogen metabolism and consists of three isoenzymes, including glycogen phosphorylase isoenzyme BB (GPBB). Pre-eclampsia, gestational hypertension, and small-for-gestational-age (SGA) infants are complications in about 15% of all nulliparous pregnancies. Biomarkers for these adverse pregnancy outcomes remain elusive. GPBB has been proposed as a potential biomarker for the detection of these adverse outcomes. We aimed to investigate this hypothesis. MethodsBlood samples from women with pre-eclampsia or SGA were analysed from the time of disease presentation and from samples collected at 15 and 20 weeks' gestation. They were compared with control samples obtained from women recruited to the Screening for Pregnancy Endpoints (SCOPE) study. These control samples were from healthy women with uncomplicated pregnancies matched for age, ethnicity, parity, body-mass index, and gestational age. GPBB concentrations were measured with ELISA (Diacordon, Diagenics, Essen, Germany). FindingsSignificant differences in GPBB were observed between all three gestations (p=0·03). GPBB concentrations were higher in women with pre-eclampsia than in controls at the time of disease presentation (term pre-eclampsia n=14, median 22·2 ng/mL [IQR 15·1–39·8] vs 16·9 [10·4–19·1], p=0·04; preterm pre-eclampsia n=11, 23·1 [11·2–30·9] vs 17·2 [9·8–19·1], p=0·04) and at 20 weeks' gestation (n=39, 23·0 [15·6–31·4] vs 17·0 [13·4–23·6]; p=0·04). GPBB concentrations were also significantly higher in women with SGA than in controls at the time of disease detection (n=23, 22·7 [12·6–25·5] vs 17·0 [9·8–18·0]; p=0·03) but significantly less than in controls at 15 weeks' gestation before disease detection (n=25, 16·0 [12·1–23·2] vs 22·2 [17·0–28·9]; p=0·02). InterpretationWe have shown that significant variation of GPBB concentrations occurs in normal pregnancy, pre-eclampsia, and SGA pregnancies. GPBB in healthy pregnancy lowers as pregnancy progresses from the first to the third trimester. GPBB might, therefore, be useful as a biomarker in early pregnancy and at the time of disease in the prediction of both preterm and term pre-eclampsia and SGA. FundingNational Institute for Health Research, SCOPE Study was funded by the Health Research Board. This work was performed in the Irish Centre for Fetal and Neonatal Translational Research and partly supported by Science Foundation Ireland.

An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome.

To develop an integrated model with the best performing criteria for predicting adverse outcome in small-for-gestational-age (SGA) pregnancies. A cohort of 509 pregnancies with a suspected SGA fetus, eligible for trial of labor, was recruited prospectively and data on perinatal outcome were recorded. A predictive model for emergency Cesarean delivery because of non-reassuring fetal status or neonatal acidosis was constructed using a decision tree analysis algorithm, with predictors: maternal age, body mass index, smoking, nulliparity, gestational age at delivery, onset of labor (induced vs spontaneous), estimated fetal weight (EFW), umbilical artery pulsatility index (PI), mean uterine artery (UtA) PI, fetal middle cerebral artery PI and cerebroplacental ratio (CPR). An adverse outcome occurred in 134 (26.3%) cases. The best performing predictors for defining a high risk for adverse outcome in SGA fetuses was the presence of a CPR < 10th centile, a mean UtA-PI > 95th centile or an EFW < 3rd centile. The algorithm showed a sensitivity, specificity and positive and negative predictive values for adverse outcome of 82.8% (95% CI, 75.1-88.6%), 47.7% (95% CI, 42.6-52.9%), 36.2% (95% CI, 30.8-41.8%) and 88.6% (95% CI, 83.2-92.5%), respectively. Positive and negative likelihood ratios were 1.58 and 0.36. Our model could be used as a diagnostic tool for discriminating SGA pregnancies at risk of adverse perinatal outcome.

Low Serum Levels of ABCA1, an ATP-Binding Cassette Transporter, Are Predictive of Preeclampsia

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and proteinuria, but the exact cause of preeclamptic hypertension remains unknown. ATP-binding cassette subfamily A member 1 (ABCA1) reverses cholesterol transport and eliminates excess cholesterol from tissues, whereas higher levels of cholesterol may lead to hypertension. Thus, ABCA1 affects the blood lipid profile. We have hypothesized that serum ABCA1 levels may influence the onset of hypertension and increase the risk of preeclampsia. To test this hypothesis, we measured serum ABCA1 levels in 50 normal pregnancies, 36 preeclamptic pregnancies, and 24 small-for-gestational-age (SGA) pregnancies during three trimesters. We also measured the concentrations of serum ABCA1 in non-pregnant women (n = 60), showing its normal ranges of 0.16 to 0.52 ng/ml. Importantly, the serum levels of ABCA1 were similar among non-pregnant women, normal pregnancies and SGA pregnancies. In contrast, the serum ABCA1 levels were significantly lower in preeclamptic pregnancies (0.06 ± 0.03 ng/ml) than those in non-pregnant women, and normal and SGA pregnancies (P < 0.05). Low serum ABCA1 levels were associated with the increases in the concentrations of blood lipid (low density lipoprotein cholesterol, total cholesterol and triglycerides) and with the decrease in the concentration of high-density lipoprotein cholesterol (P < 0.01), all of which may contribute to the onset of hypertension and eventually preeclampsia. Moreover, the preeclamptic pregnancy was diagnosed with high sensitivity from the nulliparous pregnancies if the cutoff value for serum ABCA1 was 0.06 ng/ml. Thus, low serum levels of ABCA1 are predictive of preeclampsia.

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Objectives Current literature suggests that early and late onset preeclampsia should be treated as distinct entities and that early onset preeclampsia shares pathophysiology aspects with intrauterine growth restriction. Our objective was to investigate whether 5th percentile small for gestational age (SGA) in a 1st pregnancy increases 2nd pregnancy risk of early and late onset preeclampsia, and vice versa. Methods We studied a cohort of 1st and 2nd singleton pregnancies of 262.934 women from the Dutch Perinatal Registry who gave birth between 2000 and 2007. We analyzed 2nd pregnancy risk of SGA, early and late onset preeclampsia using logistic regression considering in each case the absence of the outcome in the first pregnancy. Gestational age, maternal age, iatrogenic preterm birth, chronic hypertension, max diastolic pressure, diabetes, ethnicity and socioeconomic status were adjusted for. Results In women without 1st pregnancy preeclampsia, prevalences of early and late onset preeclampsia in the 2nd pregnancy were 0.05% and 0.6%, respectively. SGA in the 1st pregnancy increased these prevalences to 0.1% and 1.1%. After adjustment for confounders, 2nd pregnancy late onset preeclampsia risk was increased (aOR 1.3; 95% CI 1.1–1.6) due to SGA in the 1st pregnancy but early onset preeclampsia did not increase (aOR 1.3; 95% 0.7–2.3). In women that did not present SGA in the 1st pregnancy, SGA prevalence in term 2nd pregnancies was 3.3%. Prevalence was higher in women who presented 1st pregnancy late and early preeclampsia: 5.4% (aOR 1.6; 95% CI 1.4–1.9) and 10.2% (aOR 3.2; 95% CI 2.5–4.0), respectively. Conclusions In the absence of preeclampsia in the 1st pregnancy, SGA increased late but not early onset 2nd pregnancy preeclampsia risks. Second pregnancy SGA risk was increased by preeclampsia in the 1st pregnancy, especially in early onset cases. Disclosures T.P. Bernardes: None. B.W. Mol: None. A.C. Ravelli: None. P.P. van den Berg: None. R.P. Stolk: None. H. Groen: None.

Association of Doppler parameters with placental signs of underperfusion in late-onset small-for-gestational-age pregnancies

To elucidate the association between Doppler parameters and histological signs of placental underperfusion in late-onset small-for-gestational-age (SGA) babies. Umbilical, fetal middle cerebral and uterine artery pulsatility indices and umbilical vein blood flow (UVBF), which had been recorded within 7 days prior to delivery, were analyzed from a cohort of SGA singleton pregnancies delivered after 34 weeks' gestation and confirmed as having a birth weight < 10(th) percentile by local standards. In each case, the placenta was histologically evaluated for signs of placental underperfusion using a hierarchical and standardized classification system. The independent association of the Doppler parameters with placental underperfusion was evaluated using logistic regression and decision tree analysis. In 51 cases (53.7%), there were 61 placental histological findings indicative of placental underperfusion. These cases had a significantly higher incidence of Cesarean section for non-reassuring fetal status (52.1% vs 11.9%; P < 0.001) and neonatal metabolic acidosis at birth (21.6% vs 0%; P = 0.001). Significant and independent contributions to the presence of placental underperfusion lesions were provided by increased mean UtA pulsatility index (PI) (P = 0.018; odds ratio (OR) 2 (95% CI, 1.1-3.7)) and decreased UVBF normalized to estimated fetal weight (P = 0.027; OR 0.97 (95% CI, 0.95-0.99)). The combination of both parameters revealed three groups with differing risks for placental underperfusion: normalized UVBF > 82 mL/min/kg (risk 31.3%), normalized UVBF ≤ 82 mL/min/kg and mean UtA-PI ≤ 95(th) percentile (risk 65.5%), and normalized UVBF ≤ 82 mL/min/kg and UtA-PI > 95(th) percentile (risk 94.4%). In late-onset SGA pregnancies, uterine Doppler and UVBF are surrogates for placental underperfusion. These findings facilitate phenotypic profiling of cases of fetal growth restriction among the general population of late-onset SGA babies.

Fetal growth and risk of stillbirth: a population-based case-control study.

Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth. We conducted a population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings. Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies. Please see later in the article for the Editors' Summary.

Balancing the risks of stillbirth and neonatal death in the early preterm small-for-gestational-age fetus

Timing of delivery for the early preterm small-for-gestational-age (SGA) fetus remains unknown. Our aim was to estimate the risk of stillbirth in the early preterm SGA fetus compared with the risk of neonatal death. We performed a retrospective cohort study of singleton pregnancies that underwent second-trimester anatomy ultrasound (excluding fetal anomalies, aneuploidy, and pregnancies with incomplete neonatal follow-up data). SGA was defined as birthweight <10th percentile by the Alexander standard. Life-table analysis was used to calculate the cumulative risks of stillbirth per 10,000 ongoing SGA pregnancies and of neonatal death per 10,000 SGA live births for 2-week gestational age strata in the early preterm period (24-33 weeks 6 days of gestation). We further examined the composite risk of expectant management and then compared the risk of expectant management with the risk of immediate delivery. Of 76,453 singleton pregnancies, 7036 SGA pregnancies that met inclusion criteria were ongoing at 24 weeks of gestation; there were 64 stillbirths, 226 live births, and 18 neonatal deaths from 24-33 weeks 6 days of gestation. As the risk of stillbirth increases with advancing gestational age, the risk of neonatal death falls, until the 32-33 weeks 6 days of gestation stratum. The relative risk of expectant management compared with immediate delivery remains <1 for each gestational age strata. Our findings suggest that the balance between the competing risks of stillbirth and neonatal death for the early preterm SGA fetus occurs at 32-33 weeks 6 days of gestation. These data can be useful when delivery timing remains uncertain.

Angiogenic factors at diagnosis of late-onset small-for-gestational age and histological placental underperfusion

ObjectiveThis study was designed to explore the association between angiogenic factors levels at diagnosis of small-for-gestational age (SGA) and placental underperfusion (PUP). MethodsIn a cohort of SGA singleton pregnancies, each delivered at >34 weeks, uterine (UtA), umbilical (UA), and middle cerebral (MCA) arteries were evaluated by Doppler upon diagnosis of SGA status. In addition, maternal circulating concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were assayed by ELISA, and each placenta was evaluated for histologic signs of PUP using a hierarchical and standardized classification system. Logistic regression was applied to analyze independent relationships (at diagnosis) between angiogenic factors and Doppler parameters. ResultsA total of 122 suspected SGA pregnancies were studied, 70 (57.4%) of which ultimately met PUP criteria. In this group, 85 placental findings qualified as PUP. Both mean UtA pulsatility index z-values (1.26 vs. 0.84; p = 0.038) and PlGF multiples of normal median (0.21 vs. 0.55; p = 0.002) differed significantly in pregnancies with and without PUP, respectively. By logistic regression, PlGF alone was independently predictive of PUP (OR = 0.11 [95% CI 0.025–0.57]; p = 0.008). DiscussionHistologic placental abnormalities in term SGA neonates reflect latent insufficiency in uteroplacental blood supply. The heightened risk of adverse perinatal outcomes in this context underscores a need for new Doppler or biochemical prenatal markers of placental disease. Angiogenic factors may be pivotal identifying SGA neonates. ConclusionsDiminished circulating levels of placental growth factor, determined upon discovery of SGA status, are associated with histologic evidence of PUP.

First trimester pregnancy volumes and subsequent small for gestational age fetuses

To examine whether in the first trimester, placental, gestational sac and fetal volumes are different in pregnancies that result in small for gestational age (SGA) compared to average for gestational age (AGA) neonates. Case-control study comparing first trimester 3D volumes of the placenta, the fetus and the gestational sac between SGA and AGA pregnancies. 3D volumes were acquired for quality assurance and documentation. Pregnancy volumes were calculated by the virtual organ computer-aided analysis technique. Linear regression analysis was used to compute a normal range for the placental, gestational sac and fetal volume based on the crown rump length (CRL) in AGA pregnancies. Multiple regression analysis was used to examine significant influencing covariates. A Student's t test was used to compare the difference between the SGA and AGA group. The study population consisted of 19 first trimester pregnancies with subsequent SGA neonates and 105 control pregnancies. In the AGA group, all pregnancy volumes were significantly dependent on the CRL. After controlling the CRL effect, the placental, gestational sac and fetal volumes were not significantly different between the SGA and AGA group. First trimester 3D pregnancy volume measurements are not different in SGA or AGA pregnancies.

Risk of stillbirth after 37 weeks in pregnancies complicated by small-for-gestational-age fetuses

The evidence for delivering small-for-gestational-age (SGA) fetuses at 37 weeks remains conflicting. We examined the risk of stillbirth per week of gestation beyond 37 weeks for pregnancies complicated by SGA. Singleton pregnancies undergoing routine second trimester ultrasound from 1990-2009 were examined retrospectively. The risk of stillbirth per 10,000 ongoing SGA pregnancies with 95% confidence intervals (CIs) was calculated for each week of gestation ≥37 weeks. Using a life-table analysis with correction for censoring, conditional risks of stillbirth, cumulative risks of stillbirth per 10,000 ongoing SGA pregnancies and relative risks (RRs) were calculated with 95% CIs for each week of gestation. Among 57,195 pregnancies meeting inclusion criteria the background risk of stillbirth was 56/10,000 (95% CI, 42.3-72.7) with stillbirth risk for SGA pregnancies of 251/10,000 (95% CI, 221.2-284.5). The risk of stillbirth after the 37th week was greater compared with pregnancies delivered in the 37th week (47/10,000, 95% CI, 34.6-62.5 vs 21/10,000, 95% CI, 13.0-32.1; RR, 2.2; 95% CI, 1.3-3.7). The cumulative risk of stillbirth rose from 28/10,000 ongoing SGA pregnancies at 37 weeks to 77/10,000 at 39 weeks (RR, 2.75; 95% CI, 1.79-4.2). Among pregnancies complicated by SGA <5% the cumulative risk of stillbirth at 38 weeks was significantly greater than the risk at 37 weeks (RR, 2.3; 95% CI, 1.4-3.8). There is a significantly increased risk of stillbirth in pregnancies complicated by SGA delivered after the 37th week. Given these findings, we advocate a policy of delivery of SGA pregnancies 37-38 weeks.

Changes in Maternal Serum Transforming Growth Factor Beta-1 during Pregnancy: A Cross-Sectional Study

Changes in circulating levels of maternal serum transforming growth factor beta-1 (TGF-β1), collected from 98 women (AGA) at different gestational ages (10–38 weeks) were measured and comparisons were made between levels in pregnant and nonpregnant controls and also between 10 women with small-for-gestational age (SGA) and 7 with appropriate-for-gestational age (AGA) fetuses. Maternal serum TGF-β1 levels at all stages of pregnancy were higher than those in normal healthy nonpregnant adults. The mean TGF-β1 levels in SGA pregnancies at 34-week gestation (32.5 + 3.2 ng/mL) were significantly less than those in AGA pregnancies (39.2 + 9.8 ng/mL) while at 38-week gestation, the levels were similar in the two groups (36.04 + 4.3 versus 36.7 + 7.0 ng/mL). This differential change in TGF-β1 levels is probably an important modulating factor in the aetiopathogenesis of abnormal intrauterine fetal growth.

Intrauterine growth restriction and congenital malformations: a retrospective epidemiological study

BackgroundIntrauterine growth restriction (IUGR) and small for gestational age (SGA) birth have been considered possible indicators of the presence of malformations. The aim of this study is to evaluate such relationships in a population of newborns, along with other epidemiological and auxological parameters, in particular the ponderal index (PI).MethodsWe analyzed the birth data of 1093 infants, classified according to weight for gestational age as SGA, appropriate for gestational age (AGA) or large for gestational age (LGA). The prevalence of malformations was analyzed in relation to weight percentile at birth and SGA birth, maternal smoking, pregnancy diseases and PI.ResultsOur analysis showed no significant relationship between the prevalence of malformations and SGA birth. Maternal smoking and pregnancy diseases were strongly related to SGA birth, but not to a higher prevalence of malformations. PI, however, had a significant relationship with a higher prevalence of malformations, if analyzed as either a continuous variable or a categorical variable (cutoff: < 2.4).ConclusionsThe association between congenital malformations and birth weight for gestational age seems to be weak. As part of diagnostic screening for malformations in the neonatal period, PI could be considered a better predictor of risk than weight percentile.

Two‐dimensional sonographic placental measurements in the prediction of small‐for‐gestational‐age infants

To determine the utility of two-dimensional (2D) sonographic placental measurements in the prediction of small-for-gestational-age (SGA) infants. The maximal diameter along the fetal surface of the placenta and the maximal placental thickness were measured at 18-24 weeks' gestation, and the measurements repeated in the orthogonal plane. 'Biometric lags' were calculated as the difference between sonographic gestational age, estimated using each of a number of fetal biometric measurements, and actual gestational age. These variables were analyzed individually and in combination as predictors of birth weight<10(th) percentile (SGA<10) and <5(th) percentile (SGA<5). 1909 singleton pregnancies were included. Mean placental diameter (SGA<10, P<0.001; SGA<5, P=0.002) and thickness (SGA<10, P<0.006; SGA<5, P=0.065) were significantly smaller in SGA pregnancies. The biometric lags were greater in SGA pregnancies, the lag in abdominal circumference (AC) being the most predictive of SGA (P<0.0001). Multivariable models were significantly predictive of both SGA<10(th) percentile (area under the receiver-operating characteristics curve (AUC) =0.7404) and <5(th) percentile (AUC=0.7204), the best fitting models including AC lag and mean placental diameter and thickness. 2D placental measurements taken in mid-gestation are significantly associated with the incidence of SGA. Biometric lags can improve the predictive ability further. These easily obtained variables should be considered in future efforts to develop a clinically useful predictive model for adverse outcome of pregnancy.

Measurement of spiral artery jets: general principles and differences observed in small‐for‐gestational‐age pregnancies

To investigate whether the jets of blood from the mouths of the spiral arteries could be measured reliably, as well as their relationship with the uterine artery (UtA) and any differences in small-for-gestational-age (SGA) pregnancies. Participants underwent serial ultrasound scans, from 11 weeks' gestation. Pulsatility index (PI) and resistance index (RI) of jets into the intervillous space (IVS) and UtA were recorded at every visit. Intra- and interobserver variability studies were performed. Customized birth weight centiles were calculated and SGA was defined as < 10(th) centile. Linear mixed model analysis was used to allow for the longitudinal nature of the data. Sixty-six women were recruited; 58 remained normotensive and delivered at term. Of these, six women delivered SGA newborns and 52 delivered appropriate-for-gestational-age newborns. All had pulsatile jets until 20 weeks' gestation. The PI and RI of the jets decreased with advancing gestation, following a trend similar to that of the UtAs. There was no correlation between the jets and UtA waveforms when gestational age was controlled for. For intraobserver variability the intraclass correlation coefficient was 0.9. The interobserver study showed no significant difference between the observers. Mixed model analysis demonstrated that PI and RI of jets were different in SGA pregnancies (P < 0.06). This difference was not seen for the UtAs (P = 0.8). This technique enables examination of characteristics of the jets of blood flowing from spiral arteries into the IVS. It is both precise and reproducible, with biologically plausible results. Further work is required to assess differences in pregnancies with adverse outcomes.

A functional variant in the thrombospondin-1 gene and the risk of small for gestational age infants.

Thrombospondin-1 (TSP-1) is a prothrombotic and anti-angiogenic glycoprotein expressed in the placenta. A functional single nucleotide polymorphism in the TSP-1 gene (TSP-1 A2210G) is a risk factor for familial premature myocardial infarction. Small for gestational age (SGA) infants are at increased risk of coronary artery disease in adult life and common genetic factors may underlie both conditions. We investigated the association of TSP-1 A2210G in SGA infants and their parents. The 3234 nulliparous pregnant women, their partners and babies were recruited in Adelaide and Auckland to a prospective multicenter cohort study. Amongst 2123 Caucasian women, 216 (10.2%) delivered an SGA infant, defined as birth weight < 10th customized centile adjusted for maternal height, weight, parity and ethnicity, as well as gestational age at delivery and infant sex. Uncomplicated pregnancies served as controls (n = 1185). DNA extracted from peripheral/cord blood or buccal swabs was genotyped using Sequenom MassARRAY. Multivariable logistic regression was used to compare the odds of SGA between the genotype groups adjusting for potential confounders. Paternal (adjOR, 1.4; 95% CI 1.0-2.0) and neonatal (adjOR, 1.8; 95% CI, 1.1-2.7) TSP-1 A2210G associates with SGA. The maternal polymorphism approaches significance for an association with SGA (adjOR, 1.3; 95% CI, 0.9-1.9). Maternal TSP-1 A2210G associates with a reduced maternal birth weight adjusted for gestational age at delivery (P = 0.03). The TSP-1 A2210G polymorphism, which is a risk factor for myocardial infarction, is associated with SGA pregnancies, suggesting that this polymorphism may associate with the risk of vascular disorders across the life course.