Specific growth velocity reference charts for monochorionic twin pregnancies.

OBJECTIVE: We aimed to create specific growth velocity reference charts for monochorionic (MC) twin pregnancies and provide additional information for assessing fetal growth in MC twins. STUDY DESIGN: This retrospective study collected data from uncomplicated MC twins with serial ultrasound parameters. The four ultrasound parameters, including biparietal diameter, femur length, head circumference, and abdominal circumference, were used to calculate the estimated fetal weight (EFW). Multilevel linear regression models were applied to fit growth velocity charts for each biometric parameter and EFW. Analysis of variance was used to examine differences in birthweight by whether EFW velocity and EFW values were <10th or ≥10th percentiles. RESULTS: The final analysis encompassed a total of 5956 ultrasound examinations conducted on 487 MC twins. The growth velocity of four biparietal diameters exhibited a gradual decrease in a nearly linear fashion progressing from 18 to 37 gestational weeks. The EFW velocity increased steadily from 18 to 36 gestational weeks, reaching a peak of 178.2 g/week, and then the velocity gradually decreased until delivery. At 32 weeks for illustration, the lightest birth weight was observed when both EFW and EFW velocity were <10th percentile (1899 g). The study also found that birth weight was higher when EFW velocity was ≥10th percentile compared with <10th percentile, regardless of EFW being below or above the 10th percentile (2263 and 1906 g, respectively; P < 0.001). CONCLUSION: We developed specific growth velocity reference charts for MC twins, which could provide a valuable reference point for a more precise evaluation of fetal growth in MC twins. Preliminary findings indicate that the inclusion of fetal growth velocity in monitoring fetal growth provides additional information beyond EFW alone.

Assessment of fetal growth trajectory identifies infants at high risk of perinatal mortality.

OBJECTIVE: To analyze perinatal risks associated with three distinct scenarios of fetal growth trajectory in the latter half of pregnancy compared with a reference group. METHODS: This cohort study included women with a singleton pregnancy that delivered between 32 + 0 and 41 + 6 weeks' gestation and had two or more ultrasound scans, at least 4 weeks apart, from 18 + 0 weeks. We evaluated three different scenarios of fetal growth against a reference group, which comprised appropriate-for-gestational-age fetuses with appropriate forward-growth trajectory. The comparator growth trajectories were categorized as: Group 1, small-for-gestational-age (SGA) fetuses (estimated fetal weight (EFW) or abdominal circumference (AC) persistently < 10th centile) with appropriate forward growth; Group 2, fetuses with decreased growth trajectory (decrease of ≥ 50 centiles) and EFW or AC ≥ 10th centile (i.e. non-SGA) at their final ultrasound scan; and Group 3, fetuses with decreased growth trajectory and EFW or AC < 10th centile (i.e. SGA) at their final scan. The primary outcome was overall perinatal mortality (stillbirth or neonatal death). Secondary outcomes included stillbirth, delivery of a SGA infant, preterm birth, emergency Cesarean section for non-reassuring fetal status and composite severe neonatal morbidity. Associations were analyzed using logistic regression. RESULTS: The final study cohort comprised 5319 pregnancies. Compared to the reference group, the adjusted odds of perinatal mortality were increased significantly in Group 2 (adjusted odds ratio (aOR), 4.00 (95% CI, 1.36-11.22)) and Group 3 (aOR, 7.71 (95% CI, 2.39-24.91)). Only Group 3 had increased odds of stillbirth (aOR, 5.69 (95% CI, 1.55-20.93)). In contrast, infants in Group 1 did not have significantly increased odds of demise. The odds of a SGA infant at birth were increased in all three groups compared with the reference group, but was highest in Group 1 (aOR, 111.86 (95% CI, 62.58-199.95)) and Group 3 (aOR, 40.63 (95% CI, 29.01-56.92)). In both groups, more than 80% of infants were born SGA and nearly half had a birth weight < 3rd centile. Likewise, the odds of preterm birth were increased in all three groups compared with the reference group, being highest in Group 3, with an aOR of 4.27 (95% CI, 3.23-5.64). Lastly, the odds of composite severe neonatal morbidity were increased in Groups 1 and 3, whereas the odds of emergency Cesarean section for non-reassuring fetal status were increased only in Group 3. CONCLUSION: Assessing the fetal growth trajectory in the latter half of pregnancy can help identify infants at increased risk of perinatal mortality and birth weight < 3rd centile for gestation. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Does decreased fetal growth estimation in the appropriate for gestational age range affect delivery outcomes?

PURPOSE: To study the effect of decreased estimated fetal weight (EFW) percentiles in appropriate for gestational age fetuses. METHODS: This retrospective cohort study included women who had second and third trimester ultrasound examinations. Delivery and neonatal outcomes of pregnancies with decreased EFW of ≥ 30 percentiles in EFW between ultrasound examinations (decreased growth group) and those without such a decrease (control group) were compared. Deliveries with EFW or birthweight below the 10th percentile were excluded. RESULTS: Among 1610 deliveries, 57 were in the decreased growth group and 1553 in the control group. Maternal characteristics did not differ between the groups except for higher rate of nulliparity in the decreased growth group. We found similar rates of Category II/III monitoring, cesarean deliveries due to non-reassuring fetal heart rate and adverse neonatal outcomes. Neonatal birthweight was lower in the decreased growth group as compared to controls. CONCLUSIONS: This study did not find association between the group of appropriate for gestational age fetuses with decreased growth, with adverse outcomes.

The effects of gestational diabetes mellitus on fetal growth: is it different for low-risk and medium-high-risk pregnant women?

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

Outcome-based comparative analysis of five fetal growth velocity models to define slow growth.

OBJECTIVE: Fetal growth surveillance includes assessment of size as well as rate of growth, and various definitions for slow growth have been adopted into clinical use. The aim of this study was to evaluate the effectiveness of different models to identify stillbirth risk, in addition to risk represented by the fetus being small-for-gestational age (SGA). METHODS: This was a retrospective analysis of a routinely collected and anonymized dataset of pregnancies that had two or more third-trimester ultrasound measurements of estimated fetal weight (EFW). SGA was defined as EFW < 10th customized centile, and slow growth was defined according to five published models in clinical use: (1) a fixed velocity limit of 20 g per day (FVL20 ); (2) a fixed > 50 centile drop, regardless of scan-measurement interval (FCD50 ); (3) a fixed > 30 centile drop, regardless of scan interval (FCD30 ); (4) growth trajectory slower than the third customized growth-centile limit (GCL3 ); and (5) EFW at second scan below the projected optimal weight range (POWR), based on partial receiver-operating-characteristics-curve-derived  cut-offs specific to the scan interval. RESULTS: The study cohort consisted of 164 718 pregnancies with 480 592 third-trimester ultrasound scans (mean ± SD, 2.9 ± 0.9). The last two scans in each pregnancy were performed at an average gestational age of 33 + 5 and 37 + 1 weeks. At the last scan, 12 858 (7.8%) EFWs were SGA, and of these, 9359 were also SGA at birth (positive predictive value, 72.8%). The rate at which slow growth was defined varied considerably (FVL20 , 12.7%; FCD50 , 0.7%; FCD30 , 4.6%; GCL3 , 19.8%; POWR, 10.1%), and there was varying overlap between cases identified as having slow growth and those identified as SGA at the last scan. Only the POWR method identified additional non-SGA pregnancies with slow growth (11 237/16 671 (67.4%)) that had significant stillbirth risk (relative risk, 1.58 (95% CI, 1.04-2.39)). These non-SGA cases resulting in stillbirth had a median EFW centile of 52.6 at the last scan and a median weight centile of 27.3 at birth. Subgroup analysis identified methodological problems with the fixed-velocity model because it assumes linear growth throughout gestation, and with the centile-based methods because the non-parametric distribution of centiles at the extremes does not reflect actual difference in weight gain. CONCLUSION: Comparative analysis of five clinically used methods to define slow fetal growth has shown that only the measurement-interval-specific POWR model can identify non-SGA fetuses with slow growth that are at increased risk of stillbirth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The magnitude rather than the rate of decline in fetal growth is a stronger risk factor for perinatal mortality in term infants.

BACKGROUND: Prenatal diagnosis of an infant suspected of having fetal growth restriction is important because of its strong association with perinatal mortality and morbidity. The current Delphi consensus criteria include a decline of >50th percentiles in fetal growth when diagnosing late fetal growth restriction; however, the evidence underpinning this criterion is limited. OBJECTIVE: This study aimed to analyze the relationships among the magnitude of decline in fetal growth and stillbirth, perinatal mortality, and adverse neonatal outcomes. STUDY DESIGN: This cohort study of 15,861 pregnancies was conducted at the Mater Mother's Hospital in Brisbane, Australia. The decline in fetal growth was calculated as a drop in either estimated fetal weight or abdominal circumference percentiles between 2 ultrasound scans performed after 18 weeks of gestation. Relationships between declining fetal growth and the outcomes were, firstly, analyzed as a continuous variable and, if significant, further assessed with the rate of decline and different magnitudes of decline, compared to the referent category (change in growth of ±10 percentiles between scans). The 3 categories of growth decline were >10th to <25th percentiles, ≤25th to <50th percentiles, and ≥50th percentiles. Associations were analyzed by logistic regressions. The primary study outcomes were stillbirth and perinatal mortality (composite of stillbirth and neonatal death). The secondary outcomes were birth of a small-for-gestational-age infant (birthweight of <10th percentile for gestation), emergency cesarean delivery for nonreassuring fetal status, and composite severe neonatal morbidity. RESULTS: The risks of stillbirth and perinatal mortality increased significantly by 2.6% (0.4%-4.6%) and 2.8% (1.0%-4.5%), respectively, per 1 percentile decline in fetal growth. In addition, the odds of stillbirth (adjusted odds ratio, 3.68 (1.32-10.24) and perinatal mortality (4.44) (1.82-10.84)) compared to the referent group were significantly increased only when the decline was ≥50th percentiles, regardless of birthweight. Furthermore, none of the primary outcomes were significantly associated with the rate of growth decline. The risk of a small-for-gestational-age infant increased by 2.4% (2.2%-2.7%) for every percentile decline. Conversely, reduced fetal growth was not associated with emergency cesarean delivery for nonreassuring fetal status or severe neonatal morbidity. CONCLUSION: Our results supported the use of a ≥50th percentile decline in fetal growth as a criterion for identifying infants at risk of late fetal growth restriction. This cutoff also identified fetuses at high risk of perinatal mortality, regardless of birthweight and rate of growth decline. Our findings may guide obstetrical practice by alerting clinicians to the importance of incorporating the magnitude of fetal growth decline into antenatal counseling and decisions regarding the timing of birth.

Evaluating the Growth Assessment Protocol for stillbirth prevention: progress and challenges.

Many stillbirths are associated with fetal growth restriction, and are hence potentially avoidable. The Growth Assessment Protocol (GAP) is a multidisciplinary program with an evidence based care pathway, training in risk assessment, fetal growth surveillance with customised charts and rolling audit. Antenatal detection of small for gestational age (SGA) has become an indicator of quality of care. Evaluation is essential to understand the impact of such a prevention program. Randomised trials will not be effective if they cannot ensure proper implementation before assessment. Observational studies have allowed realistic evaluation in practice, with other factors excluded that may have influenced the outcome. An award winning 10 year study of stillbirth data in England has been able to assess the effect of GAP in isolation, and found a strong, causal association with improved antenatal detection of SGA babies, and the sustained decline in national stillbirth rates. The challenge now is to apply this program more widely in low and middle income settings where the main global burden of stillbirth is, and to adapt it to local needs and resources.

Associations of Maternal Prenatal Stress and Depressive Symptoms With Childhood Neurobehavioral Outcomes in the ECHO Cohort of the NICHD Fetal Growth Studies: Fetal Growth Velocity as a Potential Mediator.

OBJECTIVE: Maternal prenatal stress and mood symptoms are associated with risk for child psychopathology. Within the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies (ECHO-FGS), a racially and ethnically diverse cohort, we studied associations between prenatal stress and depressive symptoms with child neurobehavior, and potential mediation by fetal growth velocity (FGV) in low-risk pregnancies. METHOD: For 730 mother-child pairs, we had serial ultrasound measurements, self-reports of prenatal stress and depression, observations of child executive functions and motor skills from 4 to 8 years, and maternal reports of child psychiatric problems. We tested associations between prenatal stress and depressive symptoms with child neurobehavior in regression analyses, and associations with FGV in mixed effect models. Post hoc we tested severity of prenatal symptoms; FGV at 25th, 50th, and 75th percentiles; and moderation by biological sex and by race and ethnicity. RESULTS: Prenatal stress and depressive symptoms were associated with child psychiatric problems, and prenatal depressive symptoms with decrements in executive functions and motor skills, especially in biological male children. Neither prenatal stress nor depressive symptoms were associated with FGV. CONCLUSION: In one of the largest cohorts with observed child outcomes, and the first with broad representation of race and ethnicity in the United States, we found that prenatal stress and depressive symptoms were associated with greater reports of child psychiatric symptoms. Only prenatal depressive symptoms were associated with observed decrements in cognitive abilities, most significantly in biological male children. Stress during low-risk pregnancies may be less detrimental than theorized. There was no mediation by FGV. These findings support the need to attend to even small changes in prenatal distress, as these may have long-lasting implications.

Fetal weight projection model to define growth velocity and validation against pregnancy outcome in a cohort of serially scanned pregnancies.

OBJECTIVE: Fetal growth assessment is central to good antenatal care, yet there is a lack of definition of normal and abnormal fetal growth rate which can identify pregnancies at risk of adverse outcome. The aim of this study was to develop and test a model for defining normal limits of growth velocity which are specific to the fetal weight measurement interval. METHODS: The cohort consisted of 102 138 singleton pregnancies which underwent at least two third-trimester measurements of ultrasound estimated fetal weight (EFW), usually carried out because routine early-pregnancy risk assessment had indicated an increased risk of fetal growth restriction. We projected the EFW from the first of each consecutive measurement pair along its own centile rank to the gestational age of the second scan. Normal growth was defined as the second EFW being within a weight range based on limits derived by partial receiver-operating-characteristics-curve (pROC) analyses for small-for-gestational-age (SGA; < 10th centile) and large-for-gestational-age (LGA; > 90th centile) birth weight. The limits were measurement-interval specific and calculated for a fixed false-positive rate (FPR) of 10%. The resultant normal, slow and accelerated growth rates calculated from consecutive EFW pairs were evaluated against the following predefined perinatal outcome measures: stillbirth, neonatal death, SGA and LGA at birth, 5-min Apgar score < 7 and admission to the neonatal intensive care unit. Slow growth based on the last two scans was compared with SGA fetal weight (EFW < 10th centile) at the last scan and association with stillbirth risk was assessed, expressed as relative risk (RR) with 95% CI. RESULTS: The optimal cut-off limits for normal growth rate between consecutive scans varied according to the length of the measurement interval, with an average of -8.0% for slow growth and + 9.3% for accelerated growth at a fixed FPR of 10%. Slow growth between random consecutive scan pairs was associated significantly with all predefined outcome measures including stillbirth (RR, 2.19; 95% CI, 1.84-2.53) and neonatal death (RR, 2.28; 95% CI, 1.60-3.13). Accelerated growth was associated with LGA at birth (RR, 2.15; 95% CI, 2.10-2.20), while normal growth was protective of all adverse outcome measures. Slow growth between the last two scans (which were performed at a median gestational age of 33 + 1 to 36 + 4 weeks) and SGA at the last scan were each predictors of stillbirth, and stillbirth risk was highest when both were present (RR, 2.65; 95% CI, 1.67-4.20). However, 66.2% of pregnancies with slow growth were not SGA at the last scan and these cases also had an increased risk of stillbirth (RR, 2.07; 95% CI, 1.40-3.05). CONCLUSION: Fetal growth velocity defined by projected, measurement-interval specific fetal weight limits is associated independently with perinatal outcome and should be used for antenatal surveillance in addition to assessment by fetal size. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Reduced Growth in Non-Small for Gestational Age Fetuses from 35 Weeks of Gestation to Birth and Perinatal Outcomes.

OBJECTIVE: This study aimed to assess reduced fetal growth between 35 weeks of gestation and birth in non-small for gestational age fetuses associated with adverse perinatal outcomes (APOs). MATERIAL AND METHOD: It is a retrospective cohort study of 9,164 non-small for gestational age fetuses estimated by ultrasound at 35 weeks. The difference between the birth weight percentile and the estimated percentile weight (EPW) at 35 weeks of gestation was calculated, and we studied the relationship of this difference with the appearance of APO. APOs were defined as cesarean or instrumental delivery rates for nonreassuring fetal status, 5-min Apgar score <7, arterial cord blood pH <7.10, and stillbirth. Fetuses that exhibited a percentile decrease between both moments were classified into 6 categories according to the amount of percentile decrease (0.01-10.0, 10.01-20.0, 20.01-30.0, 30.01-40.0, 40.01-50.0, and >50.0 percentiles). It was evaluated whether the appearance of APO was related to the amount of this percentile decrease. Relative risk (RR) was calculated in these subgroups to predict APOs in general and for each APO in particular. Receiver operating characteristic and area under curves (AUC) for the difference in the percentile was calculated, used as a continuous parameter in the entire study population. RESULTS: The median gestational age at delivery in uncomplicated pregnancies was 40.0 (39.1-40.7) and in pregnancies with APOs 40.3 (49.4-41.0), p < 0.001. The prevalence of APOs was greater in the group of fetuses with a decrease in percentile (7.6%) compared to those with increased percentile (4.8%) (p < 0.001). The RR was 1.63 (95% CI: 1.365-1.944, p < 0.001). Although the differences were significant in all decreased percentile groups, RRs were significantly higher when decreased growth values were >40 points (RR: 2.036, 95% CI: 1.581-2.623, p < 0.001). The estimated value of the AUC for percentile decrease was 0.58 (0.56-0.61, p < 0.001). CONCLUSION: Fetuses with a decrease in the EPW between the ultrasound at 35 weeks of gestation and birth have a higher risk of APOs, being double in fetuses with a decrease of >40 percentile points.

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.

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.

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

BACKGROUND: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth. OBJECTIVE: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21st Fetal Growth Standards. STUDY DESIGN: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression. RESULTS: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work. CONCLUSION: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21st tools at https://intergrowth21.tghn.org/standards-tools/.

Prenatal exposure to fine particulate matter and fetal growth: a cohort study from a velocity perspective.

BACKGROUND: Reduced growth velocity before birth increases the risk of adverse health outcomes in adult life. However, until recently, there has been a lack of studies demonstrating the impact of prenatal PM2.5 exposure on fetal growth velocity. METHODS: The current study was embedded in a previous cohort built between January 1, 2014, and April 30, 2015, in Shanghai First Maternity and Infant Hospital, China, in 6129 eligible singleton pregnancies. The PM2.5 concentration was estimated by an inverse distance weighted method according to the residential addresses of the participants. Repeated fetal biometry measurements, including head circumference (HC), abdominal circumference (AC), femur length (FL), and biparietal diameter (BPD), were measured through ultrasound between 14 and 41 gestational weeks. A principal component analysis through conditional expectation for sparse longitudinal data was used to estimate the corresponding velocities. RESULTS: A total of 22782 ultrasound measurements were conducted among 6129 participants with a median of 2 and a maximum of 9 measurements. With each 10 µg/m3 increase in cumulative PM2.5 exposure, the velocity of HC, AC FL and BPD decreased by 0.12 mm/week, 0.17 mm/week, 0.02 mm/week and 0.02 mm/week, respectively, on average. The results of the Generalized Functional Concurrent Model showed that the velocity decreased significantly with PM2.5 exposure between 22 and 32 gestational weeks, which might be the potential sensitive exposure window. CONCLUSIONS: There are negative associations between prenatal exposure to PM2.5 and fetal growth velocity, and the late second trimester and early third trimester might be the potential sensitive window.

'Postnatal growth during the first five years of life in SGA and AGA neonates with reduced fetal growth'.

BACKGROUND: Even though a lot of research has been done on postnatal growth and the occurrence of catch-up growth in small-for-gestational age (SGA) neonates, this phenomenon has not been studied well in appropriate-for-gestational age (AGA) neonates. Postnatal catch-up growth may also occur in AGA neonates indicating a compensatory mechanism for undiagnosed intrauterine growth restriction, especially in AGA neonates with reduced fetal growth velocity. AIMS: To describe postnatal growth during the first 5 years of life in SGA and AGA neonates and evaluating the role of fetal growth velocity in catch-up growth. STUDY DESIGN: Retrospective study in a Dutch tertiary hospital. SUBJECTS: 740 singleton neonates, without congenital anomalies, with ultrasound fetal growth data from 20 weeks and 32 weeks of pregnancy. OUTCOME MEASURES: Postnatal growth measurements of height (cm) and weight (kg) from birth until five years of age. Postnatal catch-up growth defined as difference (delta) in both height and weight between 4 weeks and 3 years of age. RESULTS AND CONCLUSIONS: SGA neonates had a significantly lower height and weight compared to the AGA group for all available measurement moments till 3 years. The catch-up growth between the SGA and AGA groups from 4 weeks up to 3 years after birth was not different between the two groups. However, neonates with reduced fetal growth velocity had a significantly higher risk for catch-up growth in height during the first 3 years after birth. This suggests a role for fetal growth velocity measurement in predicting fetal and subsequent postnatal growth potential.

Neonatal hair profiling reveals a metabolic phenotype of monochorionic twins with selective intrauterine growth restriction and abnormal umbilical artery flow.

BACKGROUND: Selective intrauterine fetal growth restriction (sIUGR) in monochorionic diamniotic twins, especially types 2&3 with abnormal umbilical artery Doppler, results in increased risk of fetal/perinatal mortality and postnatal disability. We investigate whether the hair metabolome profiles of neonates were associated with the pathophysiological differences across the different clinical forms of sIUGR in twins. METHODS: Hair samples were collected at delivery from 10 pairs of type 1 sIUGR twins, 8 pairs of types 2&3 sIUGR twins, and 11 pairs of twins without sIUGR. The hair metabolome was characterized using gas chromatography-mass spectrometry. RESULTS: Our results demonstrated that the hair metabolite profiles of the different sIUGR subclinical forms were associated with the averaged fetal growth rate after 28 weeks of gestation but not with birthweight. The hair profiles were capable of discriminating type2&3 sIUGR twins from twins without sIUGR. In particular, the metabolites 2-aminobutyric acid, cysteine, alanine, and tyrosine all displayed areas under the receiver operating characteristic curve were above 0.9. The metabolic pathway analysis highlighted the associations of sIUGR twins with abnormal umbilical artery flow with increased metabolites from a nutrient depletion pathway, glutathione metabolism, and nerve development. CONCLUSION: This study offers novel insight into the severity of intrauterine ischemia and hypoxia for T2&3 sIUGR twins, through evaluation of the neonatal hair metabolome.

Fetal growth velocity: the NICHD fetal growth studies.

BACKGROUND: Accurately identifying pregnancies with accelerated or diminished fetal growth is challenging and generally based on cross-sectional percentile estimates of fetal weight. Longitudinal growth velocity might improve identification of abnormally grown fetuses. OBJECTIVE: We sought to complement fetal size standards with fetal growth velocity, develop a model to compute fetal growth velocity percentiles for any given set of gestational week intervals, and determine association between fetal growth velocity and birthweight. STUDY DESIGN: This was a prospective cohort study with data collected at 12 US sites (2009 through 2013) from 1733 nonobese, low-risk pregnancies included in the singleton standard. Following a standardized sonogram at 10w0d-13w6d, each woman was randomized to 1 of 4 follow-up visit schedules with 5 additional study sonograms (targeted ranges: 16-22, 24-29, 30-33, 34-37, and 38-41 weeks). Study visits could occur ± 1 week from the targeted GA. Ultrasound biometric measurements included biparietal diameter, head circumference, abdominal circumference, and femur length, and estimated fetal weight was calculated. We used linear mixed models with cubic splines for the fixed effects and random effects to flexibly model ultrasound trajectories. We computed velocity percentiles in 2 ways: (1) difference between 2 consecutive weekly measurements (ie, weekly velocity), and (2) difference between any 2 ultrasounds at a clinically reasonable difference between 2 gestational ages (ie, velocity calculator). We compared correlation between fetal growth velocity percentiles and estimated fetal weight percentiles at 4-week intervals, with 32 (±1) weeks' gestation for illustration. Growth velocity was computed as estimated fetal growth rate (g/wk) between ultrasound at that gestational age and from prior visit [ie, for 28-32 weeks' gestational age: velocity = (estimated fetal weight 32-28)/(gestational age 32-28)]. We examined differences in birthweight by whether or not estimated fetal weight and estimated fetal weight velocity were <5th or ≥5th percentiles using χ2. RESULTS: Fetal growth velocity was nonmonotonic, with acceleration early in pregnancy, peaking at 13, 14, 15, and 16 weeks for biparietal diameter, head circumference, femur length, and abdominal circumference, respectively. Biparietal diameter, head circumference, and abdominal circumference had a second acceleration at 19-22, 19-21, and 27-31 weeks, respectively. Estimated fetal weight velocity peaked around 35 weeks. Fetal growth velocity varied slightly by race/ethnicity although comparisons reflected differences for parameters at various gestational ages. Estimated fetal weight velocity percentiles were not highly correlated with fetal size percentiles (Pearson r = 0.40-0.41, P < .001), suggesting that these measurements reflect different aspects of fetal growth and velocity may add additional information to a single measure of estimated fetal weight. At 32 (SD ± 1) weeks, if both estimated fetal weight velocity and size were <5th percentile, mean birthweight was 2550 g; however, even when size remained <5th percentile but velocity was ≥5th percentile, birthweight increased to 2867 g, reflecting the important contribution of higher growth velocities. For estimated fetal weight ≥5th percentile, but growth velocity <5th, birthweight was smaller (3208 vs 3357 g, respectively, P < .001). CONCLUSION: We provide fetal growth velocity data to complement our previous work on fetal growth size standards, and have developed a calculator to compute fetal growth velocity. Preliminary findings suggest that growth velocity adds additional information over knowing fetal size alone.

Retrospective study of tadalafil for fetal growth restriction: Impact on maternal and perinatal outcomes.

AIM: The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes. METHODS: We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group). The conventional management for FGR was performed according to guidelines for obstetric practice in Japan. RESULTS: Both birthweight and fetal growth velocity from enrollment to birth were significantly higher in the tadalafil group than in the conventional management group. The cesarean delivery rate was approximately twofold higher in the conventional management group than in the tadalafil group. Importantly, cesarean section due to non-reassuring fetal status was performed in seven pregnant women in the conventional management group (58.3%) but in none in the tadalafil group (P < 0.05, chi-squared test). CONCLUSIONS: Tadalafil may improve perinatal outcome in FGR by modulating fetal growth through maintenance or improvement of fetal well-being.