Relation of antepartum stillbirth to birthweight and gestational age: Prospective cohort study.

OBJECTIVES: To investigate the incidence of antepartum stillbirth in relation to the distribution of neonatal/fetal weight for different gestational ages. DESIGN: Prospective observational cohort study. SETTING: Obstetric ultrasound departments in two UK maternity hospitals. POPULATION: 168 966 women with singleton pregnancies attending for routine antenatal care. METHODS: We examined the incidence of antepartum stillbirths, within different birthweight and fetal weight percentile subgroups, conditioning for gestational age. MAIN OUTCOME MEASURES: Incidence of antepartum stillbirth. RESULTS: The risk of stillbirth progressively increased for lower birthweight. Considering the 25-75th percentile as the reference category, the relative risks for stillbirth at <37 weeks' gestation were 7.6 (95% confidence interval [CI] 5.7-10.2) <1st percentile, 2.6 (95% CI 1.8-3.7) 1 to 10th percentile, 1.4 (95% CI 0.9-2.1) 10 to 25th percentile, 0.8 (95% CI 0.4-1.5) 75 to 90th percentile, 0.8 (95% CI 0.4-1.7) 90 to 99th percentile, 0.9 (95% CI 0.3-2.5) >99th percentile. The respective values for births at ≥37 weeks' gestation were 5.0 (95% CI 2.9-8.9), 2.1 (95% CI 1.4-3.3), 1.4 (95% CI 0.9-2.1), 1.2 (95% CI 0.7-1.8), 1.0 (95% CI 0.6-1.8) and 4.0 (95% CI 1.8-9.3). The incidence of stillbirth in ongoing low-risk singleton pregnancies gradually increases for smaller fetuses at any gestational point. The higher incidence (5.56%) was evident for fetal weight <1st percentile between 24 and 28 weeks' gestation. CONCLUSION: Fetal weight and the weight of the stillborn have a continuous association with the incidence of antepartum stillbirth which is affected by gestational age.

Personalized stratification of pregnancy care for small for gestational age neonates from biophysical markers at midgestation.

BACKGROUND: Antenatal identification of pregnancies at high risk of delivering small for gestational age neonates may improve the management of the condition and reduce the associated adverse perinatal outcomes. In a series of publications, we have developed a new competing-risks model for small for gestational age prediction, and we demonstrated that the new approach has a superior performance to that of the traditional methods. The next step in shaping the appropriate management of small for gestational age is the timely assessment of these high-risk pregnancies according to an antenatal stratification plan. OBJECTIVE: This study aimed to demonstrate the stratification of pregnancy care based on individual patient risk derived from the application of the competing-risks model for small for gestational age that combines maternal factors with sonographic estimated fetal weight and uterine artery pulsatility index at midgestation. STUDY DESIGN: This was a prospective observational study of 96,678 singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks of gestation, which included recording of estimated fetal weight and measurement of uterine artery pulsatility index. The competing-risks model for small for gestational age was used to create a patient-specific stratification curve capable to define a specific timing for a repeated ultrasound examination after 24 weeks. We examined different stratification plans with the intention of detecting approximately 80%, 85%, 90%, and 95% of small for gestational age neonates with birthweight <3rd and <10th percentiles at any gestational age at delivery until 36 weeks; all pregnancies would be offered a routine ultrasound examination at 36 weeks. RESULTS: The stratification of pregnancy care for small for gestational age can be based on a patient-specific stratification curve. Factors from maternal history, low estimated fetal weight, and increased uterine artery pulsatility index shift the personalized risk curve toward higher risks. The degree of shifting defines the timing for assessment for each pregnancy. If the objective of our antenatal plan was to detect 80%, 85%, 90%, and 95% of small for gestational age neonates at any gestational age at delivery until 36 weeks, the median (range) proportions (percentages) of population examined per week would be 3.15 (1.9-3.7), 3.85 (2.7-4.5), 4.75 (4.0-5.4), and 6.45 (3.7-8.0) for small for gestational age <3rd percentile and 3.8 (2.5-4.6), 4.6 (3.6-5.4), 5.7 (3.8-6.4), and 7.35 (3.3-9.8) for small for gestational age <10th percentile, respectively. CONCLUSION: The competing-risks model provides an effective personalized continuous stratification of pregnancy care for small for gestational age which is based on individual characteristics and biophysical marker levels recorded at the midgestation scan.

Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature.

BACKGROUND: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. METHODS: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. RESULTS: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. CONCLUSION: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.

Pulmonary hypertension in congenital diaphragmatic hernia: Antenatal prediction and impact on neonatal mortality.

OBJECTIVE: To determine the prevalence of pulmonary hypertension (PAH) in left-sided congenital diaphragmatic hernia (CDH); how we could predict it; and how PAH contributed to the model for mortality prediction. STUDY DESIGN: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day (d) 1, 7, and at discharge. Studied predictors of PAH were: observed/expected-lung/head-ratio (o/e LHR), liver-herniation, fetoscopic endoluminal tracheal occlusion (FETO), and gestational age (GA) at delivery. The combined effect of pre- and postnatal variables on mortality was modeled by Cox regression. RESULTS: Of the 197 neonates, 56 (28.4%) died. At d1, 67.5% (133/197) had PAH and 61.9% (101/163) by d7. Overall, 6.4% (9/141) had PAH at discharge. At d1, o/e LHR (odds ratio (OR) 0.96) and FETO (OR 2.99) independently correlated to PAH (areas under the curve [AUC]: 0.74). At d7, PAH significantly correlated only with the use of FETO (OR 3.9; AUC: 0.65). None were significant for PAH at discharge. Combining the occurrence of PAH with antenatal biomarkers improved mortality prediction (p = 0.02), in a model including o/e LHR (HR: 0.94), FETO (HR: 0.35), liver herniation (HR: 16.78), and PAH (HR: 15.95). CONCLUSIONS: Antenatal prediction of PAH was only moderate. The postnatal occurrence of PAH further increases the risk of death. Whereas this may be used to counsel parents in the postnatal period, our study demonstrates there is a need to find more accurate antenatal predictors for PAH.

Predictive performance for placental dysfunction related stillbirth of the competing risks model for small-for-gestational-age fetuses.

OBJECTIVES: To examine the predictive performance for placental dysfunction related stillbirths of the competing risks model for small-for-gestational-age (SGA) fetuses based on a combination of maternal risk factors, estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI); and second, to compare the performance of this model with that of a stillbirth-specific model using the same biomarkers and with the Royal College of Obstetricians and Gynecologists (RCOG) guideline for the investigation and management of the SGA fetus. DESIGN: Prospective observational study. SETTING: Two UK maternity hospitals. POPULATION: A total of 131 514 women with singleton pregnancies attending for routine ultrasound examination at 19-24 weeks of gestation. METHODS: The predictive performance for stillbirth achieved by three models was compared. MAIN OUTCOME MEASURE: Placental dysfunction related stillbirth. RESULTS: At 10% false-positive rate, the competing risks model predicted 59%, 66% and 71% of placental dysfunction related stillbirths, at any gestation, at <37 weeks and at <32 weeks, respectively, which were similar to the respective figures of 62%, 70% and 73% for the stillbirth-specific model. At a screen positive rate of 21.8%, as defined by the RCOG guideline, the competing risks model predicted 71%, 76% and 79% of placental dysfunction related stillbirths at any gestation, at <37 weeks and at <32 weeks, respectively, and the respective figures for the RCOG guideline were 40%, 44% and 42%. CONCLUSION: The predictive performance for placental dysfunction related stillbirths by the competing risks model for SGA was similar to that of the stillbirth-specific model and superior to that of the RCOG guideline. TWEETABLE ABSTRACT: The competing risks approach for SGA is superior to the RCOG guideline in the prediction of placental dysfunction related stillbirths.

Competing Risks Model for Prediction of Small for Gestational Age Neonates and the Role of Second Trimester Soluble Fms-like Tyrosine Kinase-1.

Small for gestational age (SGA) fetuses/neonates are characterized by the increased risk for adverse outcomes that can be reduced if the condition is identified antenatally. We have recently developed a new approach in SGA prediction that considers SGA a spectrum condition that is reflected in two dimensions: gestational age at delivery and Z score in birth weight for gestational age. The new method has a better predictive ability than the traditionally used risk-scoring systems and logistic regression models. In this prospective study in 40241 singleton pregnancies, at 19-24 weeks' gestation, we examined the potential value of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and the ratio of sFlt-1 to the angiogenic placental growth factor (PlGF) in the prediction of SGA. We found that first, sFlt-1 did not improve the performance of screening by maternal risk factors, and second, the ratio of sFlt-1/PlGF had a worse performance than PlGF alone in the prediction of SGA. Consequently, second trimester sFlt-1 and sFlt-1/PlGF are not useful in screening for SGA.

Competing risks model for prediction of small-for-gestational-age neonates from biophysical markers at 19 to 24 weeks' gestation.

BACKGROUND: Antenatal identification of women at high risk to deliver small-for-gestational-age neonates may improve the management of the condition. The traditional but ineffective methods for small-for-gestational-age screening are the use of risk scoring systems based on maternal demographic characteristics and medical history and the measurement of the symphysial-fundal height. Another approach is to use logistic regression models that have higher performance and provide patient-specific risks for different prespecified cutoffs of birthweight percentile and gestational age at delivery. However, such models have led to an arbitrary dichotomization of the condition; different models for different small-for-gestational-age definitions are required and adding new biomarkers or examining other cutoffs requires refitting of the whole model. An alternative approach for the prediction of small-for-gestational-age neonates is to consider small for gestational age as a spectrum disorder whose severity is continuously reflected in both the gestational age at delivery and z score in birthweight for gestational age. OBJECTIVE: This study aimed to develop a new competing risks model for the prediction of small-for-gestational-age neonates based on a combination of maternal demographic characteristics and medical history with sonographic estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure at 19 to 24 weeks' gestation. STUDY DESIGN: This was a prospective observational study of 96,678 women with singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks' gestation, which included recording of estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure. The competing risks model for small for gestational age is based on a previous joint distribution of gestational age at delivery and birthweight z score, according to maternal demographic characteristics and medical history. The likelihoods of the estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure were fitted conditionally to both gestational age at delivery and birthweight z score and modified the previous distribution, according to the Bayes theorem, to obtain an individualized posterior distribution for gestational age at delivery and birthweight z score and therefore patient-specific risks for any desired cutoffs for birthweight z score and gestational age at delivery. The model was internally validated by randomly dividing the data into a training data set, to obtain the parameters of the model, and a test data set, to evaluate the model. The discrimination and calibration of the model were also examined. RESULTS: The estimated fetal weight was described using a regression model with an interaction term between gestational age at delivery and birthweight z score. Folded plane regression models were fitted for uterine artery pulsatility index and mean arterial pressure. The prediction of small for gestational age by maternal factors was improved by adding biomarkers for increasing degree of prematurity, higher severity of smallness, and coexistence of preeclampsia. Screening by maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure, predicted 41%, 56%, and 70% of small-for-gestational-age neonates with birthweights of <10th percentile delivered at ≥37, <37, and <32 weeks' gestation, at a 10% false-positive rate. The respective rates for a birthweight of <3rd percentile were 47%, 65%, and 77%. The rates in the presence of preeclampsia were 41%, 72%, and 91% for small-for-gestational-age neonates with birthweights of <10th percentile and 50%, 75%, and 92% for small-for-gestational-age neonates with birthweights of <3rd percentile. Overall, the model was well calibrated. The detection rates and calibration indices were similar in the training and test data sets, demonstrating the internal validity of the model. CONCLUSION: The performance of screening for small-for-gestational-age neonates by a competing risks model that combines maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure was superior to that of screening by maternal characteristics and medical history alone.

Fetally-injected drugs for immobilization and analgesia do not modify fetal brain development in a rabbit model.

OBJECTIVE: During fetal surgery, fetuses receive medication (atropine-fentanyl-curare) to prevent fetal pain, movement and bradycardia. Although essential there has been no detailed review of potential side effects. Herein we aimed to assess the effects of this medication cocktail on fetal brain development in a rabbit model. METHODS: Pregnant does underwent laparotomy at 28 days of gestation. Two pups of each horn were randomized to an ultrasound guided injection with medication (atropine-cisatracurium-fentanyl, as clinically used) or saline (sham). The third pup was used as control. At term, does were delivered by cesarean. Outcome measures were neonatal biometry, neuromotoric functioning and neuro-histology (neuron density, synaptic density and proliferation). RESULTS: Maternal vital parameters remained stable during surgery. Fetal heart rates did not differ before and after injection, and were comparable for the three groups. At birth, neonatal body weights and brain-to-body weight ratios were also comparable. Both motor and sensory neurobehavioral scores were comparable. There were no differences in neuron density or proliferation. Sham pups, had a lower synaptic density in the hippocampus as compared to the medication group, however there was no difference in the other brain areas. CONCLUSION: In the rabbit model, fetal medication does not appear to lead to short-term neurocognitive effects.

Incidence and patterns of abnormal corpus callosum in fetuses with isolated spina bifida aperta.

OBJECTIVE: To determine the incidence and characterise corpus callosum (CC) abnormalities in fetuses with spina bifida aperta (SBA) between 18 and 26 weeks of gestation. METHODS: This was a retrospective study on fetuses with isolated SBA and who were assessed for fetal surgery. Digitally stored ultrasound images of the brain were reviewed for the presence/absence of the CC, and the length and diameter of its constituent parts (rostrum, genu, body and splenium). We used regression analysis to determine the relationship between CC abnormalities and gestational age, head circumference, ventricle size, lesion level and lesion type. RESULTS: Nearly three-quarters of fetuses with isolated SBA had an abnormal CC (71.7%, 76/106). Partial agenesis was most common in the splenium (18.9%, 20/106) and the rostrum (13.2%, 14/106). The most common abnormal pattern was of a short CC with normal diameter throughout. Of note, 20.8% (22/106) had a hypoplastic genu and 28.3% (30/106) had a thick body part. Larger lateral ventricle size was associated with partial agenesis of the CC (odds ratio [OR]: 0.14, p < 0.001) and inversely associated with a shorter CC (OR: 2.60, p < 0.01). CONCLUSION: An abnormal CC is common in fetuses with isolated SBA who are referred for fetal surgery.

Quality assessment of the detailed anomaly ultrasound scan.

OBJECTIVES: The objective of this study is to assess the quality of the views in the detailed anomaly ultrasound scan and examine the parameters that influence it. METHODS: Prospective study on singleton pregnancies examined at 20-24 weeks. Detailed views of all fetal organs were classified by the examiner as optimal/suboptimal. The duration of the examination was observed. Maternal characteristics, Fat Index (FI) (distance between the skin and the surface of the uterus), and fetal position were recorded. RESULTS: The study population consisted of 940 singleton pregnancies. Optimal visualization of all fetal structures was achieved in 66% of cases. Significant predictors were BMI, FI, and fetal position. None of the women with BMI ≥ 44 and none of the women with FI ≥ 60 mm had optimal visualization of all fetal structures. Median duration of the examination was 23 min. In 75% of cases, it was completed in the first attempt. Maternal weight, FI, and fetal position were the significant independent predictors of total examination time. CONCLUSIONS: Optimal visualization of the fetal anatomy is restricted by maternal parameters and fetal position. The main limitation is accumulation of abdominal fat, usually but not always related to maternal obesity. The FI may be recorded as a measure of technical difficulty. The anomaly scan should be allocated at least 30 min scanning time.

Placental volume at 11 to 14 gestational weeks in pregnancies complicated with fetal growth restriction and preeclampsia.

OBJECTIVE: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). METHODS: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. RESULTS: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free ß-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P < 0.001). z-PV provided moderate prediction of FGR with normal fetal Dopplers (AUC = 0.8396, P < 0.001), PE (AUC = 0.8312, P < 0.001), and GH (AUC = 0.7640, P < 0.001). The addition of maternal weight, PAPP-A, ß-hCG, and uterine artery Doppler improved our models. CONCLUSION: At 11 to 14 weeks, PV is an independent predictor of pregnancy complications related to placental insufficiency, and the predictive ability is greater for FGR pregnancies with abnormal fetal Dopplers.

Cervical length at 11-40 weeks: unconditional and conditional longitudinal reference ranges.

INTRODUCTION: Our aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy. MATERIAL AND METHODS: Prospective longitudinal study. In singleton pregnancies repeated cervical length measurements were carried out by transvaginal ultrasound throughout gestation. Multilevel modeling was applied to establish cervical length reference ranges from 11 to 40 weeks. RESULTS: In all, 4397 women contributed to 13 765 cervical length measurements. A linear mixed effects random intercept-random slope model was fitted to the data. Mean cervical length had a negative non-linear polynomial association with gestational age. Unconditional ranges were developed. Terms that allow the construction of personalized cervical length charts conditional to a previous measurement were calculated. CONCLUSIONS: We constructed longitudinal reference charts for cervical length in singleton pregnancies. Cervical length should be adjusted according to specific gestational-age-dependent ranges. Individualization of cervical assessment is feasible by the application of charts conditional to previous measurements.

First trimester cervical length is associated with mid-trimester loss.

OBJECTIVE: To study the value of the cervical length (CL) measurement at 11-14 weeks in predicting second trimester miscarriage occurring at 16-24 weeks. METHODS: Prospective study in routine obstetric population using transvaginal ultrasound examination to measure the length of the endocervical canal at 11-14 weeks. RESULTS: The study group consisted of 2836 singleton pregnancies. Eleven (0.0038%) women miscarried between 16 and 24 weeks whereas 2825 delivered after 34 weeks. CL was significantly shorter (Mann-Whitney U test, p = 0.001), in women that had a second trimester miscarriage in comparison to those who delivered after 34 weeks (median CL 28 mm versus 32 mm, respectively). First trimester CL was predictive of a late miscarriage (OR = 0.7093304, R(2 )= 0.1211, AUC = 0.7838, p < 0.001). The detection rate was 63.64% for 20% screen positive rate. CONCLUSIONS: First trimester endocervix is significantly shorter in women destined to miscarry between 16 and 24 weeks. In low risk singleton pregnancies, first trimester CL can be useful in predicting second trimester miscarriage.

Prediction of Preterm Delivery by Late Cervical Length Measurement after 24 Weeks.

OBJECTIVE: To examine the value of the cervical length (CL) measurement at 24-30 gestational weeks in the prediction of spontaneous preterm delivery (SPD) between 30 and 34 weeks (SPD34) and between 34 and 37 weeks (SPD37). METHODS: We performed a prospective cross-sectional study. CL was measured once by transvaginal ultrasound examination between 24 and 30 weeks. RESULTS: The study sample consisted of 1,180 low-risk singleton pregnancies. 10 women (0.85%) had a SPD34 and 60 (5.08%) had a SPD37. CL was shorter (p < 0.001) in the women who had a SPD34 (median 11 mm) compared to the women who delivered after 34 weeks (median 31 mm). CL was shorter (p < 0.001) in the women who had a SPD37 (median 22 mm) compared to the women who delivered after 37 weeks (median 31 mm). CL predicted SPD34 (OR = 0.837, R² = 0.2768, AUC = 0.9406, p < 0.001) and SPD37 (OR = 0.907, R² = 0.1085, AUC = 0.7584, p < 0.001). The model achieved a sensitivity of 70.0 and 38.3% for 10% false-positive rate for SPD34 and SPD37, respectively. CONCLUSIONS: CL after 24 weeks is significantly shorter in women destined to have a SPD. In low-risk singleton pregnancies CL performs very well in predicting SPD34 and adequately in predicting SPD37.

Maternal serum osteocalcin at 11-14 weeks of gestation in gestational diabetes mellitus.

BACKGROUND: Recent studies support that osteocalcin (OC), apart from its skeletal role, is implicated in glucose homoeostasis. Aims of this study were to examine the first-trimester maternal serum concentrations of OC in pregnancies that developed gestational diabetes mellitus (GDM) and to create a first-trimester prediction model for GDM. DESIGN: Case-control study in a prospective cohort of pregnant women. Maternal serum levels of OC were measured in 40 cases that developed GDM and 94 unaffected controls. First-trimester biophysical parameters, biochemical indices, maternal-pregnancy characteristics, and OC concentrations were assessed in relation to GDM occurrence. RESULTS: In the GDM group, first-trimester OC serum levels were increased compared to the control group (mean = 8·81 ng/mL, SD = 2·59 vs. mean = 7·34 ng/ml, SD = 3·04, P = 0·0058). Osteocalcin was independent of first-trimester biophysical and biochemical indices. Osteocalcin alone (OR = 1·21, CI: 1·02-1·43, P = 0·023) was a significant predictor of GDM [Model R(2) = 0·04, area under the curve (AUC) = 0·61, CI: 0·55-0·72, P < 0·001]. The combination of maternal and pregnancy characteristics with OC resulted in an improved prediction model for GDM (Model R(2) = 0·21, AUC = 0·80, CI: 0·71-0·88, P < 0·001). The combined model yields a sensitivity of 72·2% for 25% false-positive rate. CONCLUSIONS: First-trimester maternal serum levels of OC are increased in GDM pregnancies. Osteocalcin combined with maternal and pregnancy characteristics provides an effective screening for GDM at 11-14 weeks.

Towards detecting open spina bifida in the first trimester: the examination of the posterior brain.

INTRODUCTION: Our aim was to examine the value of indirect signs of open spina bifida in the mid-sagittal view of the posterior brain at the 11-13 weeks' ultrasound examination and to summarize the current evidence for the first-trimester diagnosis of spina bifida. METHODS: This was a prospective study in routine obstetric population. The presence of four almost parallel lines (four-line view) in the posterior brain was recorded. Biparietal diameter (BPD), intracranial translucency (IT) and cisterna magna (CM) were measured. The ratio of IT to CM (R ratio) was calculated. RESULTS: 2,491 pregnancies were examined prospectively. Updated reference ranges for IT and CM were constructed. There were 3 cases with open spina bifida, and the four-line view was abnormal in 2 of them. The abnormal fetuses had smaller BPD as well as pronounced reduction in the CM and increase in the R ratio. DISCUSSION: Examination of the posterior brain was feasible in all fetuses in the setting of the routine 11-13 weeks' ultrasound examination. Indirect signs of spina bifida are visible in the mid-sagittal view of the posterior brain, and the assessment of these structures can be a reliable tool in the early identification of this abnormality.

Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan.

AIM: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). METHOD: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. RESULTS: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. CONCLUSIONS: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions.

Elevated placental growth factor concentrations at 11-14 weeks of gestation to predict gestational diabetes mellitus.

OBJECTIVE: To examine maternal serum concentrations of placental growth factor (PlGF) at 11-14 gestational weeks in pregnancies that developed gestational diabetes mellitus (GDM) and to create first trimester prediction models for GDM. METHODS: Case control study including 40 GDM cases and 94 controls. PlGF, biophysical and biochemical markers and maternal-pregnancy characteristics were analyzed. RESULTS: Log10 transformed PlGF (log10 PlGF) was not related to maternal factors. Log10 PlGF was increased (p=0.008) in the GDM group compared to the control group. Log10 PlGF was associated with fasting glucose levels (p=0.04) in the oral glucose tolerance test. Log10 PlGF had a strong relation with birth weight adjusted for gestational age in the control but not in the GDM group. Maternal weight and maternal age were the only predictors of GDM among the maternal factors [area under the curve (AUC)=0.73, p<0.001]. Log10 PlGF alone was a significant predictor of GDM (AUC=0.63, p<0.001). Combination of maternal weight, maternal age and log10 PlGF resulted in an improved prediction (DR=71.4%, for 25% FPR, AUC=0.78, Model R(2)=0.17, p<0.001). CONCLUSION: At 11-14weeks in pregnancies that develop GDM, the maternal serum levels of PlGF are increased. Measurement of serum PlGF at 11-14weeks improves the performance of early screening for GDM provided by maternal factors alone.

Screening for birth weight deviations by second and third trimester ultrasound scan.

OBJECTIVE: The aim of this article was to predict small for gestational age (SGA, at or less than the fifth birth weight percentile) and large for gestational age (LGA, at or greater than the 95th birth weight percentile) fetuses by using maternal and fetal parameters from the second and third trimester ultrasound examinations. METHOD: This article is a retrospective cohort study on 1979 singleton pregnancies that had a routine 20 to 24 weeks anomaly and a 30 to 34 weeks growth ultrasound scans. SGA delivered before 30 gestational weeks were excluded. RESULTS: Second trimester estimated fetal weight (EFW2 ), uterine arteries pulsatility index (PI), and maternal pregnancy characteristics were predictive for SGA (SGA second trimester model: R(2) = 0.225, area under the curve [AUC] = 0.815) and LGA (LGA second trimester model: R(2) = 0.203, AUC = 0.793). Third trimester EFW (EFW3 ), EFW2 , uterine arteries PI2 , umbilical PI, and maternal pregnancy characteristics improved the prediction of SGA (SGA combined model: R(2) = 0.423, AUC = 0.896) and LGA (LGA combined model: R(2) = 0.383, AUC = 0.882). Contingent screening with risk stratification by the second trimester model performed equally well for SGA (AUC = 0.882) and LGA (AUC = 0.861) as the combined models. CONCLUSION: Second trimester model performs well in the prediction of SGA and LGA. The addition of third trimester scan offers substantial improvement. Contingency screening is feasible with similar effectiveness.