Arterial health during early childhood following abnormal fetal growth

Background Abnormal fetal growth is associated with increased cardiovascular risk in adulthood. We investigated the effect of fetal programming on arterial health and morphology during early childhood. Methods We examined 90 children (median age 5.81 years, interquartile range: 5.67; 5.95), born small for gestational age with fetal growth restriction, large or appropriate for gestational age (SGA, N = 23, LGA, N = 19, AGA N = 48). We measured body composition, anthropometrics, blood pressure, pulse wave velocity (PWV), lipids, glucose and inflammatory markers, and assessed carotid, brachial, radial and femoral arterial morphology and stiffness using very-high resolution ultrasound (46–71 MHz). Results LGA showed increased anthropometry, lean body mass and body mass index. SGA displayed decreased anthropometry and lean body mass. Blood pressure, PWV, carotid artery stiffness and blood work did not differ groupwise. Differences in lumen diameters, intima-media thicknesses (IMT) and adventitia thicknesses disappeared when adjusted for lean body mass and sex. In multiple regression models arterial dimensions were mainly predicted by lean body mass, with birth weight remaining associated only with carotid and brachial lumen dimensions, and not with IMTs. Carotid-femoral PWV was predicted by height and blood pressure only. No independent effect of adiposity was observed. Conclusions Arterial dimensions in childhood associate with current anthropometrics, especially lean body mass, and sex, explaining differences in arterial layer thickness. We found no signs of fetal programming of cardiovascular risk or arterial health in early childhood.

Evaluation of the selected parameters of the fetal diastolic functions in normally grown or macrosomic fetuses of gestational diabetic mothers with poor glycaemic control

Objective: This study aimed to investigate whether the third trimester fetal cardiac diastolic function measured by selected conventional Doppler indices is affected in appropriate-for-gestational-age or macrosomic fetuses of gestational diabetic mothers with poor glycaemic control. Methods: This cross-sectional study included 93 pregnant women divided into two groups. Group 1 included 45 appropriate-for-gestational-age or macrosomic fetuses from gestational diabetic mothers with poor glycaemic control (study group). Group 2 included 48 appropriate-for-gestational-age fetuses from gestational age-matched healthy mothers (control group). Functional fetal cardiac parameters and fetoplacental Doppler parameters were measured. Data were compared between the two groups. Results: Maternal characteristics did not differ significantly between the study and the control group. There were no significant differences in the early and late velocity, early/late velocity ratio of both mitral and tricuspid valves, the fetal pulmonary vein pulsatility index, and the ductus venosus pulsatility index between the study and the control group. Moreover, the rate of abnormal Doppler findings in pulmonary vein (pulmonary vein pulsatility index >95th centile), ductus venosus (ductus venosus pulsatility index >95th centile), and peripheral vessels (umbilical artery pulsatility index >95th centile, middle cerebral artery pulsatility index <5th centile, cerebra-placental index >95th centile) were comparable in both groups. Conclusions: The third trimester fetal diastolic functions measured by selected conventional Doppler techniques do not seem to be altered in appropriate-for-gestational-age or macrosomic fetuses of gestational diabetic mothers who have poor glycaemic control.

G-ROP Criteria for Predicting Retinopathy of Prematurity Among Neonates with Different Birth Weight Percentiles

Purpose: To determine whether being small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) affected the sensitivity and specificity of Postnatal Growth and Retinopathy of Prematurity (G-ROP) model. Methods: We applied the G-ROP criteria, except hydrocephalus, for prematures retrospectively. The infants were divided into three subgroups according to birth weight percentiles (SGA, AGA, LGA), and the performance of the G-ROP criteria was tested for each group by calculating sensitivity and specificity for any stage retinopathy of prematurity (ROP) and severe ROP. Severe ROP was defined as ROP needing treatment. Results: Three hundred and ninety neonates screened for ROP were included. The gestational age and birth weight of the neonates were 29.3±2.9 weeks and 1302.9±416 g, respectively. There were 41 (10.5%) SGA, 312 (80%) AGA and 37 (9.5%) LGA neonates. The sensitivity of the model for any ROP was 67.8%, 66.7%, 73.2%, 55.6% for all of the patients in the study, SGA, AGA, and LGA neonates, respectively. The sensitivity of the model for severe ROP in all group and for each subgroup was 100%. The specificity of the model for any ROP was 65.9%, 70.6%, 87.7%, 90% for all of the patients, SGA, AGA, and LGA neonates, respectively. The specificity for severe ROP was 46.4%, 50%, 44%, 63.6% for all of the patients, SGA, AGA, and LGA neonates, respectively.Conclusion: The sensitivity and specificity of the G-ROP model in SGA infants were similar with the whole group, but was different between SGA, AGA and LGA neonates. Although the model did not miss any severe ROP, the specificity of the model for severe ROP was found low.

Extrauterine Growth Restriction in Preterm Infants: How to Achieve Optimal Catch-Up Growth During Hospitalization?

Extrauterine growth restriction (EUGR), a serious risk that potentially impairs the growth of preterm infants after birth and during childhood, triggers a thought of how to achieve optimal catch-up growth during hospitalization.We aimed to access the incidence of optimal catch-up growth in small-for-gestational-age (SGA), appropriate-for-gestational age (AGA) and large-for-gestational-age (LGA) infants, and identify the factors for optimal catch-up growth in preterm infants during hospitalization. Premature infants admitted to Shanghai Children’s Medical Center within 24 hours after birth from January 1,2016 to December 31, 2018 were enrolled. Prenatal, neonatal etiological, and nutrition data were collected and analyzed to identify factors associated with optimal catch-up growth during hospitalization. 105 (9.9%) of 1065 preterm newborns achieved predischarge optimal catch-up growth, including 27 (17.2%) of 157 SGA, 74 (8.5%) of 868 AGA, and 4 (10.0%) of 40 LGA infants. Logistic regression analysis indicated SGA, avoiding BPD and less days to regain birth weight as the contributing factors of optimal catch-up growth during hospitalization.Conclusion: SGA infants showed greater potential in predischarge optimal catch-up growth. Early abundant nutrition and avoiding BPD are essential for achieving optimal catch-up growth during hospitalization.

Adjusting growth standards for fetal sex improves correlation of small babies with stillbirth and adverse perinatal outcomes: A state-wide population study

Objective: Identify the proportion of infants reclassified if sex-specific birthweight charts were used, and if this reclassification has an impact on the correlation between birthweight centile and adverse perinatal outcome. Design: Retrospective cohort study Setting: Victoria, Australia. Population: All infants born from 2005-2015 (529,261) Methods: We applied GROW centiles, either adjusted or unadjusted for fetal sex. We compared proportions of small for gestational age (SGA, <10th centile) infants, then the populations of males considered small only by sex-specific charts and females considered small only by unadjusted charts. Main Outcome Measures: Stillbirth, combined perinatal mortality, NICU admissions, Apgars <7 at 5 minutes, emergency caesarean sections. Results: Of those <10th centile by unadjusted charts, 39.6% were male, and 60.5% female. Using sex-specific charts, 50.3% <10th centile were male and 49.7% female. 9,449 (19.2%) females that were SGA according to unadjusted charts were appropriate for gestational age (AGA,>10th-<90th centile) using sex-specific charts. These reclassified newborn females were not at increased risk of adverse outcomes compared with an AGA infant, but were at increased risk of being iatrogenically delivered for suspected growth restriction (RR 4.90, 95%CI 4.39–5.48). 8,048 male infants were reclassified as SGA by sex-specific charts (25% SGA increase). Compared with AGA infants, these reclassified male newborns were at greater risk of stillbirth (RR 1.94, 95%CI 1.30-2.90) and all other adverse perinatal outcomes. Conclusions: Sex-specific growth standards classify a new high-risk cohort of male infants as SGA, and exclude a cohort of females, whose risk is no greater than appropriately grown infants.

Comprehensive Morphological Assessment of Cord Blood: Normal Values and the Prevalence of Morphologically Aberrant Leukocytes

Introduction: Cord blood (CB) is becoming a valuable source for stem cells utilized in a variety of cell therapy applications, as well as for newborn diagnostics. Some parameters of the CB cellular components can be provided by automated analyzers, while others, such as immature or aberrant cells, require blood film morphological assessment. The objectives of the study were to establish normal CB morphology, and to determine the prevalence of morphologically aberrant leukocytes in CB. Methods: We performed a comprehensive morphological analysis of 100 CB samples taken from healthy term and appropriate-for-gestational-age neonates born to healthy mothers, preterm neonates, neonates of diabetic mothers, and small-for-gestational-age neonates. Blood counts were assessed, and manual morphological analyses were performed by laboratory specialists. Results: The manual differential count of normal CB samples established the following values: 47.8±10.7% neutrophils, 31.2±9.8% lymphocytes, 10.0±4.0% monocytes, and 3.0±2.5% eosinophils, with no significant sex-related differences. Blasts were observed in 44/100 samples with an average of 0.5±0.7% per sample, and only a minor left shift was observed. There were significant populations of large granular lymphocytes (19.1±10.6% of the total lymphocytes) and morphologically aberrant lymphocytes (12.4±5.4% of the total lymphocytes) in the samples, irrespective of neonatal status. The differentials of preterm CB samples differ significantly from normal term CB samples, including the reverse of neutrophils/lymphocytes ratio, and the lack of basophils. Conclusions: Normal values and unique morphological features in the CB of neonates are described. The abundant morphologically aberrant lymphocytes in CB may represent an immature state of the immune system at birth.

Perinatal Adverse Effects in Newborns with Estimated Loss of Weight Percentile between the Third Trimester Ultrasound and Delivery. The GROWIN Study

Fetal growth restriction has been associated with an increased risk of adverse perinatal outcomes (APOs). We determined the importance of fetal growth detention (FGD) in late gestation for the occurrence of APOs in small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) newborns. For this purpose, we analyzed a retrospective cohort study of 1067 singleton pregnancies. The newborns with higher APOs were SGA non-FGD and SGA FGD in 40.9% and 31.5% of cases, respectively, and we found an association between SGA non-FGD and any APO (OR 2.61; 95% CI: 1.35–4.99; p = 0.004). We did not find an increased APO risk in AGA FGD newborns (OR: 1.13, 95% CI: 0.80, 1.59; p = 0.483), except for cesarean delivery for non-reassuring fetal status (NRFS) with a decrease in percentile cutoff greater than 40 (RR: 2.41, 95% CI: 1.11–5.21) and 50 (RR: 2.93, 95% CI: 1.14–7.54). Conclusions: Newborns with the highest probability of APOs are SGA non-FGDs. AGA FGD newborns do not have a higher incidence of APOs than AGA non-FGDs, although with falls in percentile cutoff over 40, they have an increased risk of cesarean section due to NRFS. Further studies are warranted to detect these newborns who would benefit from close surveillance in late gestation and at delivery.

The correlation between the cerebroplacental ratio and fetal arterial blood gas in appropriate-for-gestational-age fetuses: A cross-sectional study

Background: The cerebroplacental ratio (CPR) is an important index for predicting adverse pregnancy outcomes in small-for-gestational-age and appropriate-forgestational-age fetuses. Objective: To find out whether there is an association between the CPR level and the blood cord gases analysis in appropriate for gestational age fetuses. Materials and Methods: This cross-sectional study included 347 pregnant women at the gestational age of 37-40 wk. Patients had an appropriate-for-gestational-age fetus confirmed from their first ultrasonography results. Participants were divided into two groups based on their CPR, measured before delivery. Finally, after delivery, arterial blood gas level and the incidence of emergency cesarean section, intrapartum fetal distress and neonatal intensive care unit admissions were compared between the two groups. Results: Fifty-four (15.6%) cases had a CPR below the detection limit of the assay. The incidence of fetal distress, emergency cesarean section, neonatal hospitalization in the neonatal intensive care unit, and pH < 7.2 were significantly lower in women with CPR ≥ 0.67 multiples than in women with a CPR < 0.67 multiples of the median. Conclusion: The third-trimester CPR is an independent predictor of stillbirth and perinatal mortality and morbidity. The role of UA/MCA Doppler and the CPR in assessing the risk of adverse pregnancy outcomes should be evaluated prospectively. Key words: Umbilical cord blood, Color Doppler ultrasonography, Gestational age.

Fetal growth velocity references from a Chinese population–based fetal growth study

Background Fetal growth velocity standards have yet to be established for the Chinese population. This study aimed to establish such standards suitable for the Chinese population. Methods We performed a multicenter, population–based longitudinal cohort study including 9075 low–risk singleton pregnant women. Data were collected from the clinical records of 24 hospitals in 18 provinces of China. Demographic characteristics, reproductive history, fetal ultrasound measurements, and perinatal outcome data were collected. The fetal ultrasound measurements included biparietal diameter (BPD), abdominal circumference (AC), head circumference (HC), and femur diaphysis length (FDL). We used linear mixed models with cubic splines to model the trajectory of four ultrasound parameters and estimate fetal weight. Fetal growth velocity was determined by calculating the first derivative of fetal size curves. We also used logistic regression to estimate the association between fetal growth velocities in the bottom 10th percentile and adverse perinatal outcomes. Results Fetal growth velocity was not consistent over time or among individuals. The estimated fetal weight (EFW) steadily increased beginning at 12 gestational weeks and peaked at 35 gestational weeks. The maximum velocity was 211.71 g/week, and there was a steady decrease in velocity from 35 to 40 gestational weeks. The four ultrasound measurements increased in the early second trimester; BPD and HC peaked at 13 gestational weeks, AC at 14 gestational weeks, and FDL at 15 gestational weeks. BPD and HC also increased from 19 to 24 and 19 to 21 gestational weeks, respectively. EFW velocity in the bottom 10th percentile indicated higher risks of neonatal complications (odds ratio [OR] = 2.23, 95% confidence interval [CI]: 1.79–2.78) and preterm birth < 37 weeks (OR = 3.68, 95% CI: 2.64–5.14). Sensitivity analyses showed that EFW velocity in the bottom 10th percentile was significantly associated with more adverse pregnancy outcomes for appropriate–for–gestational age neonates. Conclusions We established fetal growth velocity curves for the Chinese population based on real–world clinical data. Our findings demonstrated that Chinese fetal growth patterns are somewhat different from those of other populations. Fetal growth velocity could provide more information to understand the risk of adverse perinatal outcomes, especially for appropriate–for–gestational age neonates.