Small for gestational age: concept, diagnosis and neonatal characterization, follow-up and recommendations.

Newborns who do not reach a weight appropriate for their gestational age and sex can be classified in different ways. This article defines the concepts of small for gestational age (SGA) and intrauterine growth restriction, as well as the underlying causes of these conditions, with the goal of establishing consensus definitions for these patients, in whom treatment with growth hormone throughout childhood may be indicated and who may be at risk of developing endocrine or metabolic disorders in puberty and adulthood. Most SGA children experience spontaneous catch-up growth that is usually completed by age 2 years. In SGA children who remain short, treatment with recombinant human growth hormone is effective, increasing adult height. Small for gestational age infants with rapid catch-up growth and marked weight gain are at increased risk of premature adrenarche, early puberty, polycystic ovary syndrome (girls), insulin resistance and obesity, all of which are risk factors for type 2 diabetes and metabolic syndrome in adulthood. The SGA status can affect different areas of neurodevelopment and manifest at different stages in life; neurodevelopmental outcomes are better in SGA infants with spontaneous catch-up growth. Due to the potential risks associated with SGA, adequate characterization of these patients at birth is imperative, as it allows initiation of appropriate follow-up and early detection of abnormalities.

Plasma metabolites are altered before and after diagnosis of preeclampsia or fetal growth restriction.

Metabolomics is the study of small molecules (metabolites), within cells, tissues and biofluids. Maternal metabolites can provide important insight into the health and development of both mother and fetus throughout pregnancy. This study assessed metabolic profiles in the maternal circulation prior to and at the time of diagnosis of preeclampsia and fetal growth restriction. Maternal plasma samples were collected from two independent cohorts: (1) Established disease cohort: 50 participants diagnosed with early-onset preeclampsia (< 34 weeks' gestation), 14 with early-onset fetal growth restriction, and 25 gestation-matched controls. (2) Prospective cohort, collected at 36 weeks' gestation before diagnosis: 17 participants later developed preeclampsia, 49 delivered infants with fetal growth restriction (birthweight < 5th centile), and 72 randomly selected controls. Metabolic evaluation was performed by Metabolomics Australia on the Agilent 6545 QTOF Mass Spectrometer. In the established disease cohort, 77 metabolites were altered in circulation from participants with preeclampsia - increased L-cysteine (3.73-fold), L-cystine (3.28-fold), L-acetylcarnitine (2.57-fold), and carnitine (1.53-fold) (p < 0.05). There were 53 metabolites dysregulated in participants who delivered a fetal growth restriction infant-including increased levulinic acid, citric acid (1.93-fold), and creatine (1.14-fold) (p < 0.05). In the prospective cohort, 30 metabolites were altered in participants who later developed preeclampsia at term - reduced glutaric acid (0.85-fold), porphobilinogen (0.77-fold) and amininohippuric acid (0.82-fold) (p < 0.05) was observed. There were 5 metabolites altered in participants who later delivered a fetal growth restriction infant - including reduced 3-methoxybenzenepropanoic acid (p < 0.05). Downstream pathway analysis revealed aminoacyl-tRNA biosynthesis to be most significantly altered in the established cohort in preeclampsia (13/48 hits, p < 0.001) and fetal growth restriction (7/48 hits, p < 0.001). The predictive cohort showed no significant pathway alterations. This study observed altered metabolites in maternal plasma collected before and after diagnosis of a preeclampsia or fetal growth restriction. While a significant number of metabolites were altered with established disease, few changes were observed in the predictive cohort. Thus, metabolites measured in this study may not be useful as predictors of preeclampsia or fetal growth restriction.

Does the use of angiogenic biomarkers for the management of preeclampsia and fetal growth restriction improve outcomes?: Challenging the current status quo.

Monitoring and timing of delivery in preterm preeclampsia and fetal growth restriction is one of the biggest challenges in Obstetrics. Finding the optimal time of delivery of these fetuses usually involves a trade-off between the severity of the disease and prematurity. So far, most clinical guidelines recommend the use of a combination between clinical, laboratory and ultrasound markers to guide the time of delivery. Angiogenic biomarkers, especially placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1), have gained significant attention in recent years for their potential role in the prediction and diagnosis of placenta-related disorders including preeclampsia and fetal growth restriction. Another potential clinical application of the angiogenic biomarkers is for the differential diagnosis of patients with chronic kidney disease, as this condition shares similar clinical features with preeclampsia. Consequently, angiogenic biomarkers have been advocated as tools for monitoring and deciding the optimal time of the delivery of fetuses affected by placental dysfunction. In this clinical opinion, we critically review the available literature on PlGF and sFlt-1 for the surveillance and time of the delivery in fetuses affected by preterm preeclampsia and fetal growth restriction. Moreover, we explore the use of angiogenic biomarkers for the differentiation between chronic kidney disease and superimposed preeclampsia.

The value of angiogenetic biomarkers in the detection of early onset fetal growth restriction.

OBJECTIVE: The identification of fetal growth restriction (FGR) due to uteroplacental insufficiency is important to improve perinatal outcomes. To distinguish FGR from small for gestational age (SGA), FGR consensus definition is currently based on biometry and/or additional biophysical parameters. This study aims to verify if this definition might be modified by including circulating angiogenic factors. STUDY DESIGN: This historical cohort study included singleton pregnancies with SGA fetuses after 20 weeks. All patients underwent detailed ultrasound and measurements of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) at first assessment. ISUOG criteria for FGR were applied. Total PlGF was calculated using free PlGF, sFlt-1 and a receptor pharmacology model, and multiple of the median (MoM) values for sFlt-1, free PlGF, total PlGF and sFlt-1/PlGF ratio were calculated to adjust for gestational age. RESULTS: 72 pregnancies with SGA were first evaluated at median (IQR) of 28+5 (26+2 -31+3) weeks' gestation, and 51 fetuses (70.8 %) satisfied the FGR consensus definition. Pregnancies with FGR showed significantly lower levels of free and total PlGF MoM (0.12, 95 % IQR: 0.07-0.36 vs 0.32, 95 % IQR: 0.20-0.53, p = 0.008) and 0.26, 95 % CI: 0.16-0.55 vs 0.43, 95 % IQR: 0.23-0.53, p = 0.028) respectively; and higher sFlt-1 MoM (4.62, 95 % IQR: 1.80-7.30 vs 1.74, 95 % IQR:1.11-3.61, p = 0.014) than pregnancies not classified as FGR. Free and total PlGF MoM correlated significantly with gestational age at delivery (r = 0.776, p < 0.001 and r = 0.707, p < 0.001, respectively). sFlt-1 MoM and sFlt-1/PlGF ratio MoM also correlated with gestational age at delivery (r = -0.681, p < 0.001 and r = -0.823, p < 0.001). Six cases identified as FGR at first ultrasound were not confirmed at birth showing significantly higher levels of free PlGF MoM (0.77, 95 % IQR: 0.27-3.07 vs 0.17, 95 % IQR: 0.08-0.43, p = 0.022). CONCLUSION: These findings show that total as well as free PlGF levels are lower in pregnancies affected with placental growth restriction. Angiogenic biomarkers might improve the differentiation between placental growth restriction and constitutional smallness. Further studies are needed to determine how to integrate them into the current definitions of FGR.

Does a sFlt-1/PlGF ratio result > 655 before 34 weeks' gestation necessitate preterm delivery within 2 days? A retrospective observational study.

INTRODUCTION: Preeclampsia is associated with adverse perinatal outcomes, including fetal growth restriction (FGR) and preterm delivery. The maternal serum ratio of soluble fms-like tyrosine kinase receptor-1 (sFlt-1) to placental growth factor (PlGF) can be used to evaluate placental dysfunction in cases of preeclampsia and FGR. A need for delivery within 2 days has been recommended for sFlt-1/PlGF ratios > 655 (normal ratio < 38) measured before 34 weeks' gestation. However, few studies have assessed this recommendation in a real-world setting and there remains a need for further evidence-based guidance on the use of the ratio in delivery timing planning in this situation. AIM: To assess the need for delivery within 2 days associated with sFlt-1/PlGF ratios > 655 before 34 weeks' gestation. METHODS: A retrospective audit of all sFlt-1/PlGF ratio test results obtained at a single maternity hospital between September 2016 and November 2022. The primary outcome was time to delivery after recording a ratio > 655 in patients with a pregnancy between 20 + 0 and 33 + 6 weeks' gestation. Statistical analysis was performed using IBM SPSS Statistics v29.0.0.0. RESULTS: During the study period a total of 33 patients with suspected or confirmed preeclampsia and/or FGR recorded sFlt-1/PlGF ratios > 655 before 34 + 0 weeks' gestation. Amongst cases with ratios > 655, median time to delivery was 4 days (IQR 1.0-9.0), with 14 (42.4%) delivering in ≤ 2 days, 8 (24.2%) delivering between 2 and 7 days and 11 (33.3%) delivering after 7 days. A significant inverse correlation was observed between time to delivery and gestational age at the time of ratio testing (rs = -0.484, p = 0.004). DISCUSSION: This study provides updated recommendations on the use of the sFlt-1/PlGF ratio in predicting the risk of imminent delivery amongst those with high ratios > 655 measured before 34 weeks' gestation. Our results suggest that the risk of imminent delivery can be stratified based on ratio level and gestational age, which in combination with the results of other clinical assessments, can be used to plan delivery timing and allow for considerations of fetal lung maturing corticosteroid and neuroprotective magnesium sulfate therapies prior to delivery.

Real-time predictive model of extrauterine growth retardation in preterm infants with gestational age less than 32 weeks.

The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0-95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Growth charts for use at birth and in the neonatal period: Recommendations of the French Neonatal Society.

INTRODUCTION: The use of different growth charts can lead to confusion in discussions between professionals. There are obstetric charts (of fetal growth) and neonatal charts (of measurements at birth and of postnatal growth). These charts can be descriptive (derived from an unselected population) or prescriptive (derived from of a population at low risk and with optimal conditions for growth). OBJECTIVES: (1) To describe available charts for infants at birth and in the neonatal period and compare them, and (2) to recommend one or more charts for use in neonatology in France. METHODS: Bibliographic research was conducted on MEDLINE and completed by the guidelines of professional societies. RESULTS: Antenatal information about fetal growth restriction or fetuses identified as small-for-gestational-age using Intrauterine charts must be integrated into the identification of newborns at risk, but the use of Intrauterine charts to evaluate birthweight is not recommended to allow consistency with postnatal charts used in neonatal practice. Z-score variations using the updated Fenton postnatal charts are the most appropriate for the assessment of birthweight and postnatal growth for infants born preterm. These charts are sex-specific, include the three measurements (length, weight, and head circumference) and enable longitudinal follow-up of growth up to 50 weeks of corrected age and are linked to the World Health Organization charts at term. The French Audipog charts, although are individualized, accessible online and can be used in maternity units to evaluate birthweight for term infants, but do not allow the follow-up of postnatal growth, while Fenton charts may be used to evaluate birthweight and postnatal growth in the first month for hospitalized term infants. CONCLUSION: The updated Fenton charts are the neonatal charts that best suit the objectives of pediatricians in France for monitoring the growth of preterm newborns. The use of the Audipog charts at term remains an alternative in maternity wards, while Fenton charts can be used for hospitalized term newborns.

Hepatic arterial buffer response in monochorionic twins with selective fetal growth restriction.

OBJECTIVES: Monochorionic twins (MC) have higher risk of perinatal morbi-mortality compared to singletons and dichorionic twins (DC). Selective fetal growth restriction (sFGR) increases the chances of adverse outcome. Hepatic arterial buffer response (HABR) is an important mechanism for maintaining liver perfusion. We hypothesised that HABR is active in monochorionic diamniotic twins (MCDA) with sFGR where restricted fetus may have liver hypoperfusion. The objective of this study is to test whether the HAV-ratio is diminished in pregnancies affected by selective fetal growth restriction pointing to activation of HABR in the growth-restricted fetus. METHODS: sFGR was defined according to a consensus definition. Hepatic artery (HA) peak systolic velocity (PSV) was measured and its correlation with fetal Dopplers and pregnancy characteristics were determined. A ratio using HA-PSV (HAV-ratio) was calculated and its association with sFGR was established. Further analysis of HA-PSV was performed comparing z-scores between normal and growth restricted fetuses. RESULTS: We included 202 MCDA pregnancies, 160 (79 %) normal and 42 (21 %) with sFGR. HAV-ratio was significant different between groups. The mean HAV-ratio was 1.01 (±0.20) for normal twins and 0.77 (±0.25) for sFGR. Furthermore, HA-PSV z-scores was significant increased in in growth-restricted fetus (0.94±1.45), while in normal fetuses was -0.16 (±0.97). CONCLUSIONS: Our findings demonstrate that, in pregnancies with sFGR, HAV-ratio is significantly lower than in normal MCDA pregnancies. The lower HAV-ratio is due to an increase in HA PSV in the growth restricted fetus. This observation indicates an activation of HABR in the small fetus.

Indicated vs universal third-trimester ultrasound examination in low-risk pregnancies: a pre-post-intervention study.

BACKGROUND: In low-risk pregnancies, a third-trimester ultrasound examination is indicated if fundal height measurement and gestational age discrepancy are observed. Despite potential improvement in the detection of ultrasound abnormality, prior trials to date on universal third-trimester ultrasound examination in low-risk pregnancies, compared with indicated ultrasound examination, have not demonstrated improvement in neonatal or maternal adverse outcomes. OBJECTIVE: The primary objective was to determine if universal third-trimester ultrasound examination in low-risk pregnancies could attenuate composite neonatal adverse outcomes. The secondary objectives were to compare changes in composite maternal adverse outcomes and detection of abnormalities of fetal growth (fetal growth restriction or large for gestational age) or amniotic fluid (oligohydramnios or polyhydramnios). STUDY DESIGN: Our pre-post intervention study at 9 locations included low-risk pregnancies, those without indication for ultrasound examination in the third trimester. Compared with indicated ultrasound in the preimplementation period, in the postimplementation period, all patients were scheduled for ultrasound examination at 36.0-37.6 weeks. In both periods, clinicians intervened on the basis of abnormalities identified. Composite neonatal adverse outcomes included any of: Apgar score ≤5 at 5 minutes, cord pH <7.00, birth trauma (bone fracture or brachial plexus palsy), intubation for >24 hours, hypoxic-ischemic encephalopathy, seizure, sepsis (bacteremia proven with blood culture), meconium aspiration syndrome, intraventricular hemorrhage grade III or IV, periventricular leukomalacia, necrotizing enterocolitis, stillbirth after 36 weeks, or neonatal death within 28 days of birth. Composite maternal adverse outcomes included any of the following: chorioamnionitis, wound infection, estimated blood loss >1000 mL, blood transfusion, deep venous thrombus or pulmonary embolism, admission to intensive care unit, or death. Using Bayesian statistics, we calculated a sample size of 600 individuals in each arm to detect >75% probability of any reduction in primary outcome (80% power; 50% hypothesized risk reduction). RESULTS: During the preintervention phase, 747 individuals were identified during the initial ultrasound examination, and among them, 568 (76.0%) met the inclusion criteria at 36.0-37.6 weeks; during the postintervention period, the corresponding numbers were 770 and 661 (85.8%). The rate of identified abnormalities of fetal growth or amniotic fluid increased from between the pre-post intervention period (7.1% vs 22.2%; P<.0001; number needed to diagnose, 7; 95% confidence interval, 5-9). The primary outcome occurred in 15 of 568 (2.6%) individuals in the preintervention and 12 of 661 (1.8%) in the postintervention group (83% probability of risk reduction; posterior relative risk, 0.69 [95% credible interval, 0.34-1.42]). The composite maternal adverse outcomes occurred in 8.6% in the preintervention and 6.5% in the postintervention group (90% probability of risk; posterior relative risk, 0.74 [95% credible interval, 0.49-1.15]). The number needed to treat to reduce composite neonatal adverse outcomes was 121 (95% confidence interval, 40-200). In addition, the number to reduce composite maternal adverse outcomes was 46 (95% confidence interval, 19-74), whereas the number to prevent cesarean delivery was 18 (95% confidence interval, 9-31). CONCLUSION: Among low-risk pregnancies, compared with routine care with indicated ultrasound examination, implementation of a universal third-trimester ultrasound examination at 36.0-37.6 weeks attenuated composite neonatal and maternal adverse outcomes.

Bias in the prenatal lung measurements in fetal congenital diaphragmatic hernia with intrauterine growth restriction.

OBJECTIVES: The failure of a fetus to develop to its full potential due to maternal or placental factors is known as intrauterine growth restriction (IUGR). Fetal head growth is usually preserved in that situation producing a potential discordance between head and body size. Our goal is to discover if IUGR has an impact on the prenatal ultrasound measurements taken to assess pulmonary development in congenital diaphragmatic hernia (CDH). METHODS: A retrospective chart review (IRB#2017-6361) was performed on all prenatally diagnosed CDH patients from 2007 to 2016. Patient demographics, fetal and neonatal anthropometric measurements, and fetal lung parameters were the main subjects of the data that were gathered. Fetal growth was assessed by the curves based on US data by Olsen et al. and by Peleg et al. Of 147 CDH patients, 19 (12.9 %) patients were diagnosed with IUGR before the 30th gestational week while there were 20 (13.6 %) patients after the 30th gestational week. RESULTS: Patients with IUGR and the observed-to-expected lung-to-head ratio (O/E LHR) less than 25 % had better survival rates both to discharge and date compared to non IUGR group (p=0.226, OR 2.25 95 % CI 0.60-1.08 and p=0.175, OR 2.40 95 % CI 0.66-1.17, respectively). Moreover, the ECMO need of the patients who had IUGR and O/E LHR less than 25 % was significantly less than the patients without IUGR (38.5 vs. 80.0 %, p=0.005). CONCLUSIONS: This study confirms that the intrauterine measurements to predict pulmonary hypoplasia in CDH patients are misleading in the presence of IUGR and cause an overestimation.

Etiologic evaluation and pregnancy outcomes of fetal growth restriction (FGR) associated with structural malformations.

This study aimed to evaluate the etiology and pregnancy outcomes of fetuses underwent invasive prenatal diagnosis for fetal growth restriction (FGR) accompanied by structural malformations. Data from 130 pregnancies referred for prenatal diagnosis for FGR accompanied by structural malformations were obtained between July 2011 and July 2023. Traditional karyotyping was conducted for all the subjects. A total of 37 (28.5%) cases of chromosomal abnormalities were detected by karyotyping, including 30 cases of numerical anomalies and seven cases of unbalanced structural anomalies. Trisomy 18 was the most common abnormalities, accounting for 51.4%, significantly higher than any other chromosomal abnormality. The cohort was predominantly comprised of early-onset FGR (88.5%) compared to late-onset FGR (11.5%). The incidences of chromosomal abnormalities in this two groups were 29.6% (34/115) and 20.0% (3/15), respectively (p > 0.05). The majority (74.6%, 97/130) of the cohort were affected by a single system malformation, with chromosomal abnormalities found in 19.6% (19/97) of cases. In pregnancies of structural malformations involving two and multiple systems, the frequencies were 56.5% (13/23), and 50.0% (5/10), respectively. Single nucleotide polymorphism array (SNP array) was performed in parallel for 65 cases, revealing additional 7.7% cases of copy number variants (CNVs) compared to karyotyping. Polymerase chain reaction (PCR) was used for detection of cytomegalovirus (CMV) DNA in 92 cases. All fetuses with FGR associated with two or more system malformations were either terminated or stillborn, irrespective of chromosomal aberrations. Conversely, 71.8% of pregnancies with a single-system malformation and normal genetic testing results resulted in live births. Furthermore, two (2.2%) cases tested positive for CMV DNA, leading to one termination and one case of serious developmental disorder after birth. Our study suggests that structural malformations associated with FGR are more likely to affect a single organ system. When multiple systems are involved, the incidence of chromosomal abnormalities and termination rates are notably high. We advocate for the use of CMA and CMV DNA examinations in FGR cases undergo invasive prenatal diagnosis, as these tests can provide valuable insights for etiological exploration and pregnancy management guidance.

Evaluation of systemic immune-inflammation index for predicting late-onset fetal growth restriction.

INTRODUCTION: To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). MATERIALS AND METHODS: This case-control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. RESULTS: We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs - 65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. DISCUSSION: Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings.

Prediction of preterm birth in women with fetal growth restriction - Is the weekly change in sFlt-1/PlGF ratio or PlGF levels useful?

INTRODUCTION: To assess the rate of change in soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio and PlGF levels per week compared to a single sFlt-1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction. MATERIAL AND METHODS: A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt-1/PlGF ratio were measured at 4-weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt-1/PlGF ratio, change in PlGF levels per week or sFlt-1/PlGF ratio per week. Cox-proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth. RESULTS: The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt-1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85-0.76). The rate of increase per week of the sFlt-1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39-10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25-1.67, p = 0.37, Harrell's C: 0.68). CONCLUSIONS: Both a high sFlt-1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt-1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt-1/PlGF ratio or low PlGF level.

The role of confined placental mosaicism in fetal growth restriction: A retrospective cohort study.

OBJECTIVE: To evaluate which cytogenetic characteristics of confined placental mosaicism (CPM) detected in the first trimester chorionic villi and/or placentas in terms of chromosome aberration, cell lineage involved and trisomy origin will lead to fetal growth restriction and low birthweight. METHODS: Cohort study using routinely collected perinatal data and cytogenetic data of non-invasive prenatal testing, the first trimester chorionic villi sampling and postnatal placentas. RESULTS: 215 CPM cases were found. Fetal growth restriction (FGR) and low birthweight below the 10th percentile (BW < p10) were seen in 34.0% and 23.1%, respectively. Excluding cases of trisomy 16, 29.1% showed FGR and 17.9% had a BW < p10. The highest rate of FGR and BW < p10 was found in CPM type 3, but differences with type 1 and 2 were not significant. FGR and BW < p10 were significantly more often observed in cases with meiotic trisomies. CONCLUSION: There is an association between CPM and FGR and BW < p10. This association is not restricted to trisomy 16, neither to CPM type 3, nor to CPM involving a meiotic trisomy. Pregnancies with all CPM types and origins should be considered to be at increased risk of FGR and low BW < p10. A close prenatal fetal monitoring is indicated in all cases of CPM.

Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth.

OBJECTIVES: Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). METHODS: We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. RESULTS: No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. CONCLUSIONS: The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

Fetal Growth Restriction Leads to an Enlarged Cup-to-Disc Ratio in Adults Born at Full Term.

PURPOSE: This study explores associations between fetal growth restriction or excessive fetal growth, along with perinatal factors on the optic nerve head morphology in adulthood. DESIGN: Retrospective cohort study. METHODS: This retrospective cohort study involved a prospective ophthalmological examination of individuals born at full term (with a gestational age of ≥37 weeks) from 1969 to 2002. Each participant underwent nonmydriatic fundus camera photography to capture images of the optic discs, followed by manual measurements. The vertical cup-to-disc ratio (VCDR) and optic disc area were examined and analyzed in relation to the baby's birth weight relative to the gestational age. These categories included those with former moderate (birth weight percentile between the 3rd and <10th), severe SGA (below the third percentile), normal (AGA, 10th-90th percentile), and moderately (birth weight >90th-97th percentile) and severely (birth weight >97th percentile) large for gestational age (LGA) adults within the age range of 18 to 52 years. RESULTS: Overall, 535 eyes of 280 individuals (age 29.7 ± 9.2 years, 144 females) born at full term were included. Multivariable analysis showed a significant association between a larger VCDR and the severe SGA group (B = 0.05, 95% CI 0.01-0.10; P = .02). In the univariable model, placental insufficiency was associated with VCDR (B = 0.10, 95% CI 0.01-0.19; P = .03). Other perinatal factors did not demonstrate an association with VCDR. Furthermore, there was an indication of an association suggesting a smaller optic disc area in individuals born moderately SGA at full term (B = -0.17, 95% CI -0.33 to -0.001; P = .05). CONCLUSIONS: This study provides evidence that individuals born at-term with severe SGA have an increased VCDR, suggesting that fetal growth restriction has a lasting impact on optic disc morphology independent of prematurity throughout adulthood.