Thrombophilia and fetal growth restriction

OBJECTIVE: Genetic thrombophilia may represent a new risk factor for obstetrical complications. The aim of the study was to determine which subgroups may be associated with genetic thrombophilia for small for gestational age infants (SGA). METHODS: A case-control study was performed in three different maternity wards in Normandy. Cases (n=203) were women who had pregnancies complicated by unexplained SGA infants defined as a birth weight below the 3rd centile and control subjects (n=203) were women who had infants with birth weight > or =10th centile. Patients were tested in the immediate postpartum period and 2 months later for factor V Leiden mutation, and prothrombin 20210A mutation. Frequencies of these mutations were observed in different subgroups of SGA infants depending on pregnancy or neonatal outcomes usually associated with intrauterine growth restriction (IUGR), and were then compared with the overall prevalence for these mutations detected in the control group. RESULTS: Prevalences for factor V Leiden mutation (or=2.58; 95% confidence interval: 0.83-8.04), prothrombin 20210A mutation (or=2.03; 95% confidence interval: 0.51-8.01), were comparable between cases and controls (4.9% versus 1.9% and 2.9% versus 1.4%, respectively). Frequencies for these two polymorphisms significantly increased in subgroups of SGA infants with a normal Pourcelot index (13/133 versus 7/203; P=0.04), a gestational age > or =37 weeks of gestation (15/143 versus 7/203; P=0.01), a vaginal delivery (11/117 versus 7/203; P=0.04), a birth weight > or =2000 g (12/121 versus 7/203; P=0.03), no admission to paediatric ward (11/116 versus 7/203; P=0.01), a low Ponderal index <2.5(e) centile (6/45 versus 7/203; P=0.04), and normal head circumference >10th centile (7/53 versus 7/203; P=0.01) in comparison with the control group. CONCLUSIONS: An association was found between polymorphisms for factor V Leiden and prothrombin, and asymmetrical intrauterine growth restriction with immediate favourable neonatal outcomes.     

Does small for gestational age worsen outcomes in gestational diabetics?*

Objective: Our goal was to determine whether pregnancy outcomes are worse in gestational diabetics with small for gestational age (SGA) than those without.

Methods: This was a retrospective cohort study of 114 199 pregnancies with gestational diabetes mellitus (GDM) in California, 6446 of which were complicated by SGA. SGA was defined as birth weight Results: In the term 37?+?0 to 41?+?6 week GDM cohort the risk of RDS increased from 0.4% to 1.3%, the risk of neonatal demise from 0.02% to 0.09%, the risk of IUFD from 0.1% to 0.4%, the risk of hypoglycemia from 0.4% to 1.0% and the risk of jaundice from 18.0% to 23.3% (p?Conclusions: The presence of SGA in a patient with gestational diabetes is associated with significantly increased risks of adverse outcomes compared to gestational diabetics without SGA including increased risks of RDS, neonatal demise, IUFD, hypoglycemia and jaundice.     

Maternal serum activin A levels in association with intrauterine fetal growth restriction

Objective To assess maternal serum activin A as a potential marker of fetal growth restriction.
Design A cohort study.
Setting A maternal–fetal medicine unit, university teaching hospital.
Population Fifty-seven women with a small fetus (less than 10th centile for gestation) referred for assessment of fetal size by ultrasound biometry.
Methods At the time of presentation for fetal biometry, maternal blood was collected for activin A measurement. The case records of each woman were independently reviewed after delivery and the pregnancy grouped into one of three groups: constitutionally small fetus, intrauterine growth restricted (IUGR) fetus or IUGR fetus and maternal pre-eclampsia (IUGR–pre-eclampsia). Activin A levels in the three groups were compared.
Main outcome measures Maternal serum activin A levels.
Results Sixteen of the 57 pregnancies were classified as constitutionally small, 17 as IUGR and 24 as IUGR–pre-eclampsia. Expressed as multiples of a normal median (MoMs), the median (95% CI) activin A level in the constitutionally small pregnancies was 1.12 (0.72–1.39) MoMs significantly lower than the level in both the IUGR pregnancies, 3.00 (1.84–4.11) MoMs, and the IUGR–pre-eclampsia pregnancies, 7.96 (5.73–10.62) MoMs (   P = 0.002 and 0.0001 for IUGR vs constitutionally small and IUGR–pre-eclampsia vs constitutionally small, respectively  ).
Conclusions Maternal serum activin A may be useful in the assessment of the small for gestational age fetus.     

The impact of assisted reproductive technology on the association between first-trimester pregnancy-associated plasma protein a and human chorionic gonadotropin and adverse pregnancy outcomes

We evaluated the impact of assisted reproductive technology (ART) on the association between first-trimester pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (β-hCG) and adverse pregnancy outcomes. PAPP-A and β-hCG levels were obtained between 11 and 13 (6)/ (7) weeks' gestation and converted to multiples of the median (MoM). MoM < 5th percentile was defined as low PAPP-A or β-hCG and those > 90th percentile as high. Adverse outcomes included small-for-gestational-age (SGA) infants, preeclampsia, pregnancy loss, and preterm delivery (PTD). Univariate and multivariate analyses were used to estimate the association. Of 4000 women meeting the inclusion criteria, 265 (7.6%) pregnancies were conceived by ART. ART pregnancies with low PAPP-A had a higher risk of having an SGA infant (odds ratio [OR] = 4.1, 95% confidence interval [CI] 1.2, 14.0) or PTD < 32 weeks (OR = 5.3, 95% CI 1.5, 18.6) compared with non-ART pregnancies with low PAPP-A (OR = 2.8, 95% CI 1.7, 4.7; OR = 3.9, 95% CI 2.1, 7.0, respectively). High PAPP-A was associated with pregnancy loss (OR = 6.1, 95% CI 1.1, 33.7) in ART pregnancies. Low β-hCG was associated with increased risk for PTD only in ART pregnancies (OR = 8.3, 95% CI 1.9, 35.9) for PTD < 37 weeks (OR 6.1, 95% CI 1.6, 23.0) for PTD < 35 weeks and (OR = 10.8, 95% CI 2.7, 43.7) for PTD < 32 weeks. High β-hCG was associated with increased risk for SGA (OR = 1.6, 95% CI 1.0, 2.5) and PTD < 37 weeks (OR = 1.4, 95% CI 1.0, 1.9) in non-ART pregnancies. The association between PAPP-A and β-hCG with adverse pregnancy outcomes is influenced by the mode of conception.     

Is the fetal cerebroplacental ratio better that the estimated fetal weight in predicting adverse perinatal outcomes in a low risk cohort?

Objective: In high-risk pregnancies combining the cerebro–placental ratio (CPR) with the estimated fetal weight (EFW) improves the identification of vulnerable fetuses. The purpose of this study was to assess the CPR and EFW’s ability to predict adverse obstetric and perinatal outcomes in a low-risk pregnancy, when measured late in gestation.

Methods: This was a retrospective study of women who birthed at Mater Mothers Hospitals, Brisbane, Australia between 2010 and 2015. We included all nonanomalous singleton pregnancies that had an ultrasound scan performed between 36 and 38 weeks gestation. Excluded was any major congenital abnormality, aneuploidy, multiple pregnancy, preterm birth, maternal hypertension, or diabetes. The primary outcome was a severe composite neonatal outcome (SCNO) defined as severe acidosis (umbilical cord artery pH <7.0, cord lactate ≥6?mmol/L, cord base excess ≤-12?mmol/L) Apgar score ≤3 at 5 minutes, admission to the neonatal intensive care unit (NICU), and death. A low CPR was defined as <10th centile for gestation and small for gestational age (SGA) was defined as an EFW <10th centile and appropriate for gestational age (AGA) was defined as EFW ≥10th centile.

Results: Of 2425 pregnancies, 13.2% (321/2425) had a fetus with a CPR <10th centile and 13.7% (332/2425) with an EFW <10th centile. Both a low CPR and SGA predicted the SCNO. Individually a low CPR and SGA had sensitivity for detection of SCNO of 23.3% and 24.7%, respectively which increased to 36.7% when combined. Both were associated with emergency caesarean for nonreassuring fetal status (NRFS), as well as early-term birth and admission to NICU. Stratifying the population into EFW <10th centile and EFW ≥10th centile, a low CPR maintained its association with the SCNO, early-term birth and emergency caesarean for NRFS in the cohort with an EFW <10th centile but SCNO lost its association with a low CPR in the EFW >10th cohort. Stratifying the population into CPR <10th centile and CPR >10th centile, a low EFW was associated with early-term birth, induction of labor, admission to NICU, and the SCNO.

Conclusions: In a low-risk cohort both the CPR and EFW individually and in combination predicts adverse obstetric and perinatal outcomes when measured late in pregnancy. However, the predictive value was enhanced when both were used in combination.     

Association between first trimester maternal serum pregnancy associated plasma protein-A and adverse pregnancy outcome

AIMS: To investigate whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester of pregnancy are associated with subsequent intrauterine fetal growth restriction, stillbirth and preterm delivery. METHODS: A retrospective review of pregnancy outcomes was undertaken in women who had PAPP-A carried out in the first trimester of pregnancy at the time of nuchal translucency scan. Pregnancy outcomes were assessed by the review of medical records, and postal questionnaires. Delivery details were collected, including livebirth, neonatal birthweight and gestational age at delivery. The chi2 test was used to investigate the association between low first trimester serum PAPP-A levels and adverse fetal outcomes. Unpaired t-test was used for continuous variables. Sensitivities and specificities were then calculated. RESULTS: A total of 894 women who had blood collected for PAPP-A were identified, and data was obtained for 827 deliveries. Each had a normal karyotype. There were six intrauterine deaths, 13 babies with birthweights below the 3rd centile, 55 babies weighing below the 10th centile, and 96 women who delivered prematurely. Four of six intrauterine deaths had low PAPP-A levels (<0.5 multiples of the median), with a relative risk of 13.75. Low PAPP-A levels were associated with fetal weight below the 10th centile (P = 0.01) but not the 3rd centile. There was no statistically significant association between low maternal serum PAPP-A levels and preterm delivery. CONCLUSION: At 11-13 weeks' gestation, low maternal serum PAPP-A levels are associated with fetal death in utero and birthweight below the 10th centile. First trimester PAPP-A may be a useful tool for identifying pregnancies at risk of adverse fetal outcomes.     

Pregnancies complicated by both preeclampsia and growth restriction between 34 and 37 weeks’ gestation are associated with adverse perinatal outcomes

Objective: To determine whether adverse outcomes were more common in late preterm pregnancies complicated by preeclampsia and growth restriction compared to those affected by preeclampsia alone.

Methods: This was a retrospective cohort study of 8927 singleton pregnancies with preeclampsia. Pregnancies with small for gestational age (SGA) neonates (birth weight <10th percentile) were compared to those appropriate for gestational age (AGA) neonates. Maternal outcomes included cesarean delivery (CD) rate, CD for fetal heart rate (FHR) abnormalities, abruption, postpartum hemorrhage (PPH), maternal transfusion, acute renal failure, and peripartum cardiomyopathy. Neonatal outcomes studied included respiratory distress syndrome (RDS), jaundice, hypoglycemia, seizure, asphyxia, neonatal death, and intrauterine fetal demise (IUFD).

Results: Women with preeclampsia and SGA infants were more likely to experience abruption (5.3% versus 3.0%, p?p?p?p?p?p?p?=?0.015), and IUFD (1.5% versus 0.3%, p?Conclusions: Preeclamptic women and their neonates were more likely to experience adverse perinatal outcomes when SGA pregnancies were compared to those with AGA neonates.     

Maternal serum ferritin as a clinical tool at 34–36 weeks’ gestation for distinguishing subgroups of fetal growth restriction

Objective: To compare maternal ferritin levels across pregnancies with fetal growth restriction including SGA and IUGR compared to appropriate for gestational age (AGA). Methods: Three groups were enrolled: AGA, SGA (birth weight below 10th percentile for gestational age with no placental insufficiency findings), and IUGR (birth weight below 5th percentile for gestational age accompanied by abnormal umbilical artery Doppler waveforms and/or oligohydramnios). Maternal serum ferritin samples were obtained at gestational weeks 34 through 36, and delivery occurred at or beyond 36 weeks. Results: A total of 126 pregnancies with AGA (36%), SGA (40%), and IUGR (24%) were enrolled. The mean maternal serum ferritin level was higher in the IUGR group than in the AGA group (59?μg/l versus 32.5?μg/l, p?Conclusion: Maternal serum ferritin levels differ in pregnancies with IUGR. The role of maternal serum ferritin measurements as a clinical tool for distinguishing different forms of fetal growth restriction warrants further investigation.     

PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction

Placental growth factor (PlGF) is an angiogenic molecule produced by the placenta and implicated in the pathogenesis of preeclampsia (PE) and intrauterine growth restriction (IUGR). We have evaluated utility and applicability of the PlGF test in a clinical setting of pregnancies at risk of PE or complicated by IUGR in order to assess its relationship with pregnancy outcomes. Seventy-three pregnancies were enrolled between 19 and 35 weeks: 57 pregnancies at risk of PE and 16 at diagnosis of IUGR. Maternal circulating PlGF levels were measured by the Triage PlGF test (Alere, San Diego, CA). Pregnancy outcomes were evaluated in relation to three categories of plasma PlGF levels: very low (<12?pg/ml), low (12–100?pg/ml) and normal (≥100?pg/ml). Uterine artery Doppler velocimetry (UADV) pulsatility index (PI) was measured in the same patients on the day of maternal sampling. Pregnancies at risk with very low plasma PlGF levels had significantly lower gestational age at delivery than patients with low or normal PlGF. The rate of emergency C-section was significantly higher in the group with PlGF?<12?pg/ml. IUGR pregnancies with very low and low PlGF delivered earlier than patients with normal PlGF. All IUGR with very low and low PlGF had UADV PI?>?95th percentile. Our data indicate that PlGF may provide useful information to identify fetuses requiring increased surveillance and possibly urgent delivery in pregnancies at risk of adverse outcomes. Furthermore, in IUGR, PlGF can predict adverse pregnancy outcomes that may be secondary to placental insufficiency.     

Outcomes of pregnancies complicated by liver cirrhosis,portal hypertension,or esophageal varices

Objective: To evaluate pregnancy outcomes in women with liver cirrhosis, portal hypertension, or esophageal varices.

Study design: We analyzed a retrospective cohort of 2?284?218 pregnancies in 2005–2009 recorded in the California Birth Registry database. Utilizing ICD-9 codes we analyzed the following outcomes for liver cirrhosis, portal hypertension, or esophageal varices in pregnancy: preeclampsia (PET), preterm delivery (PTD; <37 weeks), cesarean section, low birth weight (LBW; <2500?g), small for gestational age (SGA; <10th percentile), neonatal death (NND), and postpartum hemorrhage (PPH).

Results: Cirrhosis in pregnancy conferred an increased risk of PET, PTD, CS in multiparous women, LBW, and NND. Portal hypertension in pregnancy was associated with PTD, LBW, NND, and PPH. Non-bleeding esophageal varices in pregnancy were not associated with the outcomes assessed in a statistically significant manner. One case of bleeding esophageal varices was observed, resulting in PTD with a LBW infant. There were three cases of concomitant portal hypertension or concomitant esophageal varices with cirrhosis in pregnancy.

Conclusion: Pregnancy in women with concomitant liver cirrhosis, portal hypertension, or esophageal varices can be successful. However, pregnancy outcomes are worse and may warrant closer antenatal monitoring and patient counseling. Cirrhosis in pregnancy with concomitant portal hypertension or esophageal varices is rare.     

Association between small for gestational age and intrauterine fetal death: comparing a customized South Korean growth standard versus a population-based fetal growth chart

Objective: To determine if a customized growth standard developed for an ethnically homogeneous South Korean population is better at identifying (SGA) fetuses at risk for intra-uterine fetal death (IUFD), compared with a current population based-growth standard.

Study design: A retrospective cohort study comparing the identification of SGA fetuses at risk for IUFD using a customized versus a population based-chart. The association between a SGA infant defined as a birth weight <10th percentile using the South Korean population chart versus the customized chart and IUFD were compared. Intrauterine fetal death was defined as fetal demise occurring after 20 weeks gestation. Statistical analyses including OR, 95% confidence interval (CI), and screening accuracy using each chart were performed.

Results: The customized singleton chart identified 11 (8.2%) of the SGA pregnancies detected by the population chart and classified 15 additional fetuses as SGA. Those identified as SGA using the customized chart had an OR for IUFD that was approximately 15 times as high as those identified using the population chart. The customized chart also showed a higher sensitivity and specificity for identifying SGA pregnancies at risk for IUFD.

Conclusion: In this ethnically homogenous population, the customized growth chart showed improved discrimination in identifying SGA pregnancies at risk for fetal death than the population-based growth chart.     

Placental Protein-13 and Pregnancy-Associated Plasma Protein-A as First Trimester Screening Markers for Hypertensive Disorders and Small for Gestational Age Outcomes

Objective. To investigate the role of placenta protein 13 (PP13) and pregnancy-associated plasma protein-A (PAPP-A) in hypertensive disorders and small for gestational age (SGA) during first trimester of pregnancy. Methods. In this case–control study, first trimester serum samples (11⁺⁰ to 13⁺⁶ weeks) were retrieved from frozen storage of which 452 were from normal pregnancies and 47 samples were identified to have pregnancies with at least one of the following adverse outcomes: SGA, preeclampsia (PE), hemolysis, elevated liver enzymes, and low platelets (HELLP), or gestational hypertension (GH). PP13 concentrations were measured by a new AutoDELFIA method. Levels of PAPP-A were measured for a first trimester screening program using Kryptor analyzer. Results. First trimester levels of PAPP-A are significantly lower in cases of SGA, PE, and most subgroups including HELLP. Levels of PP13 were not found to differ between control and affected pregnancies. Conclusion. PP13 needs to be studied further as our results contrast the majority of previous studies.     

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system

BACKGROUND: PAPP-A is a marker used as part of the most effective method of screening for chromosomal anomalies in the first trimester. ADAM12 is a recently discovered pregnancy associated member of the ADAM (a multidomain glycoprotein metalloprotease) family. Recently, ADAM12 has been shown as a potential marker for early screening for chromosomal anomalies. Both PAPP-A and ADAM12 have been identified as proteases to insulin-like growth factor binding proteins. In this role, they may have a regulatory function in controlling the amount of free bioactive insulin-like growth factor (IGF). We therefore wish to examine if the levels of either of these proteases are related to various growth related adverse pregnancy outcomes. MATERIALS AND METHODS: PAPP-A and ADAM12 were measured in a subset of samples collected at 11 to 14 weeks as part of an OSCAR clinic screening for chromosomal anomalies. Follow-up of pregnancies screened between September 1999 and August 2003 identified 1705 pregnancies with an outcome of intrauterine fetal demise on or after 24 weeks, preterm delivery at 24-34 weeks or 35-36 weeks, very low birthweight (<1.5 kg), low birthweight (<2.5 kg), large birthweight (>4.5 kg), and birth weight below the 3rd or 5th or 10th centile for gestation. A series of 414 normal outcome pregnancies constituted the control group.Marker levels were adjusted for gestation and maternal weight and the log MoM of the markers were compared using t-test of unequal variance between the control group and the various adverse outcome groups. RESULTS: ADAM12 and PAPP-A concentrations were reduced in low for gestational age birth weights and in all births with weights below 2.5 kg. There was a linear relationship between the severity of the IUGR and the decrease in PAPP-A and ADAM12. In the larger babies, only ADAM12 was found to be significantly increased in babies above the 90th centile of weight for gestation. CONCLUSIONS: The results of our study are compatible with the proposed role of ADAM12 and PAPP-A in promoting growth and development by breaking down IGF binding proteins and causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses.     

Reference curves of symphysis-fundus height in twin pregnancies

OBJECTIVE: To generate reliable new reference ranges for symphysis-fundus height (SFH) in twin pregnancies using modern statistical methods and to evaluate whether small-for-gestational age (SGA) babies of women who had a SFH measurement after the 25th gestational week could be predicted by the SFH measurement in the reference curves and other maternal data. STUDY DESIGN: In a retrospective cross-sectional study at the obstetric outpatient clinic, Zurich University Hospital, SFH was determined in 257 twin-pregnant women with accurately dateable twin pregnancies (Caucasians: N=217, Asians: N=15, Blacks: N=10, and 15 others). Exclusion criteria were intrauterine fetal death, and known fetal and maternal diseases, which influence SFH. Pregnant women with twins were divided in three groups according to the birth weight of the babies. Group I: both babies were appropriate for gestational age (AGA), group II: one baby was AGA and one SGA, and group III: both babies were SGA. RESULTS: SFH measurements increased linearly with gestational age (GA). The following rule of thumb is suggested for the 50th centile of SFH (cm)=gestational week+10% of gestational week. Age, height, weight and body mass index (BMI) before pregnancy, parity and ethnic group were insignificant determinants in SFH measurement. A prognostic score for identification of group III was created for a GA> or =25 weeks and BMI<30 kg/m2. CONCLUSIONS: Measuring SFH is simple, inexpensive and non-invasive and may be of some use for identifying twin mothers with SGA twin pairs.     

Pregnancy and perinatal outcomes of first-trimester crown−rump length discordant IVF dichorionic twin pregnancies – a retrospective cohort study

Research QuestionThis study aimed to evaluate the association between discordance in crown–rump length (CRL) and adverse pregnancy and perinatal outcomes in dichorionic twin pregnancies.DesignThis was a retrospective cohort study of dichorionic twin pregnancies after IVF that showed two live fetuses at the first ultrasound scan between 6 ⁺⁵ and 8 weeks gestational age from 1 January 2015 to 31 December 2016. Study groups were defined by the presence or absence of 20% or more discordance in CRL. The primary outcomes were early fetal loss of one or both fetuses before 12 weeks and birthweight discordance. Secondary outcomes included fetal anomalies, fetal loss between 12 and 28 weeks, stillbirth, small for gestational age (SGA) at birth, low birthweight (LBW), very low birthweight (VLBW), admission to the neonatal intensive care unit (NICU) and preterm delivery (PTD).ResultsCRL-discordant twin pregnancies were more likely to end in the loss of one fetus before 12 weeks’ gestation (odds ratio [OR] 15.877, 95% confidence interval [CI] 10.495–24.019). Discordant twin pregnancies with twin deliveries had a significantly higher risk of birthweight discordance (OR 1.943, 95% CI 1.032–3.989). There was no significant difference in perinatal outcomes including fetal anomalies, PTD, LBW, VLBW, SGA, neonatal death and admission to NICU between singleton or twin deliveries.ConclusionsDiscordant twin pregnancies were at increased risk of one fetal loss prior to 12 weeks’ gestation. Except for birthweight discordance, there was no significant difference between CRL discordance and other adverse perinatal outcomes.     

Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications.

OBJECTIVE: Uterine artery Doppler is becoming a routine part of pregnancy surveillance in high-risk pregnancies. Which blood flow velocity waveform index to measure is debated and the 'notch' in early diastole is not widely accepted, as it is a subjective measure. The aim of the present study was to evaluate the different indices in the prediction of adverse outcome of pregnancies suspected for intrauterine fetal growth restriction (IUGR). METHODS: Uterine artery blood flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance due to suspected IUGR. The median gestational age at examination was 38 weeks (range 25-42 weeks). Only cases having bilateral uterine artery notching were included in the evaluation. The uterine artery Doppler spectrum was analyzed for different indices, including evaluation of notch and end-diastolic velocities. Umbilical artery Doppler velocimetry was also performed. The outcome variables chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and abdominal delivery. ROC-curve calculations were used to compare the different indices. RESULTS: The uterine artery blood velocity pulsatility index (PI) and resistance indices (RI) were the best predictors of adverse outcome of pregnancy. Apart from premature birth, the systolic/end-diastolic ratio was less predictive of adverse outcome. The indices including only diastolic blood velocities were the least predictive of adverse outcome. The group with notch velocity above end-diastolic velocity was compared with those having notch velocity below the end-diastolic velocity. No difference in outcome was seen between the two groups. CONCLUSIONS: RI and PI as measures of third trimester utero-placental vascular impedance are the best predictors of adverse outcome of IUGR-suspected pregnancies.     

Perinatal correlates and neonatal outcomes of small for gestational age infants born at term gestation

OBJECTIVE: We sought to examine the current perinatal correlates and neonatal morbidity associated with intrauterine growth failure among neonates born at term gestation. STUDY DESIGN: We compared 372 small for gestational age (SGA, birth weight <10th percentile) infants born at term gestation to 372 appropriate for gestational age controls (AGA, birth weight 10th to 90th percentile) matched by sex, race, and gestational age within 2 weeks. RESULTS: Compared with AGA controls, significant (P < .05) maternal risk factors for SGA status included single marital status (59% versus 53%), lower prepregnancy weight (144 +/- 41 lbs versus 153 +/- 40 lbs), lower weight gain during pregnancy (29 +/- 15 lbs versus 33 +/- 15 lbs), smoking (25% versus 17%), hypertension (14% versus 7%), and multiple gestation (9% versus 2%). Mothers of SGA infants were more likely to undergo multiple (>or=3) antenatal ultrasound evaluations (19% versus 7%), biophysical profile monitoring (11% versus 4%), and oxytocin delivery induction (28% versus 16%) (P < .05). Pediatrician attendance was more common among SGA deliveries (50% versus 37%, P < .05). SGA infants had significantly higher rates of hypothermia (18% versus 6%) and symptomatic hypoglycemia (5% versus 1%). These neonatal problems remained significant even when medical or pathologic causes of intrauterine growth failure, including pregnancy hypertension, multiple gestation, and congenital malformations, were excluded. CONCLUSION: Despite higher rates of pregnancy complications among mothers of SGA infants, the rates of neonatal adverse outcomes are low. However, SGA infants remain at risk for hypothermia and hypoglycemia and require careful neonatal surveillance.     

Abnormal multiple marker screens are associated with adverse perinatal outcomes in cases of intrauterine growth restriction

OBJECTIVE: The purpose of this study was to determine if abnormal multiple marker screens (MMS) are associated with adverse perinatal outcomes in intrauterine growth restriction (IUGR) pregnancies. STUDY DESIGN: This was a case control study of IUGR pregnancies (birth weight <10th percentile for gestational age [GA]) delivered in our unit over 6 years. Cases were compared with controls for the association between abnormal MMS and adverse perinatal outcomes (APO). RESULTS: Of the 261 IUGR pregnancies, 39 (16%) had at least 1 APO. An elevated HCG was significantly associated with an APO (OR 2.6, 95% CI 1.1-6.4). A low uE3 was also associated with an APO (OR 5.5, 95% CI 2.2-14). The association between an elevated AFP and APO was not statistically significant (OR 1.6, 95% CI, 0.6-4.6). CONCLUSION: An elevated HCG and low uE3 were associated with APO in cases of IUGR. This information could be useful in identifying a subset of IUGR cases deserving closer surveillance.     

Combining 2nd-trimester maternal serum homocysteine levels and uterine artery Doppler for prediction of preeclampsia and isolated intrauterine growth restriction

AIM: To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening at 20 weeks of gestation for complications of pregnancy: preeclampsia, isolated intrauterine growth restriction (IUGR), placental abruption, and stillbirths. METHODS: Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed. Sensitivity, specificity, positive and negative predictive values, odds ratio, and positive and negative likelihood ratios for the subsequent development of preeclampsia, isolated IUGR, placental abruption, stillbirth, and preterm delivery were calculated for the following methods (1) homocysteine cut-off level 6.3 micromol/l (95th centile); (2) on Doppler ultrasound bilateral notches with a mean resistance index (RI) >0.55 (50th centile), all unilateral notches with a mean RI >0.65 (80th centile), and absence of notches with a mean RI >0.7 (95th centile), and (3) Doppler ultrasound notch evaluation (bilateral, unilateral, absence as in method 2) combined with the homocysteine cut-off level of 6.3 micromol/l. RESULTS: By using a logistic regression model, methods 1 and 2 predicted preeclampsia (p < 0.001), isolated IUGR (p < 0.01), and "any complication" (p < 0.01). The sensitivity for prediction of preeclampsia using the combined method (3) was 61.3% for a false-positive rate of 2%, better than that for isolated IUGR (54%) below the 5th centile and "any complication" (56%). CONCLUSION: This prospective study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia, isolated IUGR, and any obstetric complication.     

Evaluation of third trimester uterine artery flow velocity indices in relationship to perinatal complications

Objective.?Uterine artery Doppler is becoming a routine part of pregnancy surveillance in high-risk pregnancies. Which blood flow velocity waveform index to measure is debated and the ‘notch’ in early diastole is not widely accepted, as it is a subjective measure. The aim of the present study was to evaluate the different indices in the prediction of adverse outcome of pregnancies suspected for intrauterine fetal growth restriction (IUGR).

Methods.?Uterine artery blood flow was recorded in 217 pregnancies admitted for Doppler ultrasound surveillance due to suspected IUGR. The median gestational age at examination was 38 weeks (range 25–42 weeks). Only cases having bilateral uterine artery notching were included in the evaluation. The uterine artery Doppler spectrum was analyzed for different indices, including evaluation of notch and end-diastolic velocities. Umbilical artery Doppler velocimetry was also performed. The outcome variables chosen were: a small-for-gestational-age (SGA) newborn, preterm birth, and abdominal delivery. ROC-curve calculations were used to compare the different indices.

Results.?The uterine artery blood velocity pulsatility index (PI) and resistance indices (RI) were the best predictors of adverse outcome of pregnancy. Apart from premature birth, the systolic/end-diastolic ratio was less predictive of adverse outcome. The indices including only diastolic blood velocities were the least predictive of adverse outcome. The group with notch velocity above end-diastolic velocity was compared with those having notch velocity below the end-diastolic velocity. No difference in outcome was seen between the two groups.

Conclusions.?RI and PI as measures of third trimester utero-placental vascular impedance are the best predictors of adverse outcome of IUGR-suspected pregnancies.