Abdominal Circumference Z-score Research Articles

Association between prenatal exposure to PM2.5 and fetal growth: a prospective cohort study

Objective: To investigate the association of exposure to PM2.5 and its constituents during pregnancy and fetal growth and to further identify critical windows of exposure for fetal growth. Methods: We included 4 089 mother-child pairs from the Jiangsu Birth Cohort Study between January 2016 and October 2019. Data of general characteristics, clinical information, daily average PM2.5 exposure, and its constituents during pregnancy were collected. Fetal growth parameters, including head circumference (HC), abdominal circumference (AC), and femur length (FL), were measured by ultrasound after 20 weeks of gestation, and then estimated fetal weight (EFW) was calculated. Generalized linear mixed models were adopted to examine the associations of prenatal exposure to PM2.5 and its constituents with fetal growth. Distributed lag nonlinear models were used to identify critical exposure windows for each outcome. Results: A 10 μg/m3 increase in PM2.5 exposure during pregnancy was associated with a decrease of 0.025 (β=-0.025, 95%CI: -0.048- -0.001) in HC Z-score, 0.026 (β=-0.026, 95%CI: -0.049- -0.003) in AC Z-score, and 0.028 (β=-0.028, 95%CI:-0.052--0.004) in EFW Z-score, along with an increased risk of 8.5% (RR=1.085, 95%CI: 1.010-1.165) and 13.5% (RR=1.135, 95%CI: 1.016-1.268) for undergrowth of HC and EFW, respectively. Regarding PM2.5 constituents, prenatal exposure to black carbon, organic matter, nitrate, sulfate (SO42-) and ammonium consistently correlated with decreased HC Z-score. SO42- exposure was also associated with decreased FL Z-scores. In addition, we found that gestational weeks 2-5 were critical windows for HC, weeks 4-13 and 19-40 for AC, weeks 4-13 and 23-37 for FL, and weeks 4-12 and 20-40 for EFW. Conclusions: Our findings demonstrated that exposure to PM2.5 and its constituents during pregnancy could adversely affect fetal growth and the critical windows for different fetal growth parameters are not completely consistent.

Associations of solar activity and related exposures with fetal growth

BackgroundSolar and geomagnetic activity have been shown to suppress melatonin and to degrade folate levels, important hormones for fetal development. We examined whether solar and geomagnetic activity were associated with fetal growth. MethodsWe included 9573 singleton births with 26,879 routine ultrasounds at an academic medical center in Eastern Massachusetts from 2011 through 2016. Sunspot number and Kp index were obtained from the NASA Goddard Space Flight Center. Three exposure windows were considered, including the first 16 weeks of pregnancy, one month prior to fetal growth measurement, and conception until fetal growth measurement (cumulative). Ultrasound scans from which we extracted biparietal diameter, head circumference, femur length, and abdominal circumference measurements were categorized as anatomic (<24 weeks' gestation) or growth scans (≥24 weeks' gestation) based on clinical practice. Ultrasound parameters and birth weight were standardized, and linear mixed models adjusted for long-term trends were fitted. ResultsPrenatal exposures were positively associated with larger head parameters measured <24 weeks' gestation, negatively associated with smaller fetal parameters measured ≥24 weeks' gestation, and not associated with birth weight. The strongest associations were observed for cumulative exposure in growth scans, where an interquartile range increase in sunspot number (32.87 sunspots) was associated with a −0.17 (95 % CI: −0.26, −0.08), −0.25 (−0.36, −0.15), and −0.13 (95 % CI: −0.23, −0.03) difference in mean biparietal diameter, head circumference, and femur length z-score, respectively. An interquartile range increase in cumulative Kp index (0.49) was associated with a −0.11 (95 % CI: −0.22, −0.01) and −0.11 (95 % CI: −0.20, −0.02) difference in mean head circumference and abdominal circumference z-score, respectively, in growth scans. ConclusionsSolar and geomagnetic activity were associated with fetal growth. Future studies are needed to better understand the impact of these natural phenomena on clinical endpoints.

Early pregnancy phthalates and replacements in relation to fetal growth: The human placenta and phthalates study

BackgroundPregnant persons are exposed ubiquitously to phthalates and increasingly to chemicals introduced to replace phthalates. In early pregnancy, exposure to these chemicals may disrupt fetal formation and development, manifesting adverse fetal growth. Previous studies examining the consequences of early pregnancy exposure relied on single spot urine measures and did not investigate replacement chemicals. ObjectiveCharacterize associations between urinary phthalate and replacement biomarkers in early pregnancy and fetal growth outcomes. MethodsAnalyses were conducted among 254 pregnancies in the Human Placenta and Phthalates Study, a prospective cohort with recruitment 2017–2020. Exposures were geometric mean concentrations of phthalate and replacement biomarkers quantified in two spot urine samples collected around 12- and 14-weeks of gestation. Outcomes were fetal ultrasound biometry (head and abdominal circumferences, femur length, estimated fetal weight) collected in each trimester and converted to z-scores. Adjusted linear mixed effects (single-pollutant) and quantile g-computation (mixture) models with participant-specific random effects estimated the difference, on average, in longitudinal fetal growth for a one-interquartile range (IQR) increase in individual (single-pollutant) or all (mixture) early pregnancy phthalate and replacement biomarkers. ResultsMono carboxyisononyl phthalate and the sums of metabolites of di-n-butyl, di-iso-butyl, and di-2-ethylhexyl phthalate were inversely associated with fetal head and abdominal circumference z-scores. A one-IQR increase in the phthalate and replacement biomarker mixture was inversely associated with fetal head circumference (β: -0.36 [95% confidence interval: -0.56, −0.15]) and abdominal circumference (−0.31 [-0.49, −0.12]) z-scores. This association was mainly driven by phthalate biomarkers. ConclusionsUrine concentrations of phthalate biomarkers, but not replacement biomarkers, in early pregnancy were associated with reductions in fetal growth. Though the clinical implications of these differences are unclear, reduced fetal growth contributes to excess morbidity and mortality across the lifecourse. Given widespread global exposure to phthalates, findings suggest a substantial population health burden resulting from early pregnancy phthalate exposure.

Ambient temperature during pregnancy and fetal growth in Eastern Massachusetts, USA.

Left unabated, rising temperatures pose an escalating threat to human health. The potential effects of hot temperatures on fetal health have been under-explored. Here, we examined the association between prenatal ambient temperature exposure and fetal growth measures in a Massachusetts-based pregnancy cohort. We used ultrasound measurements of biparietal diameter (BPD), head circumference (HC), femur length and abdominal circumference (AC), in addition to birthweight (BW), from 9446 births at Beth Israel Deaconess Medical Center from 2011 to 2016. Ultrasound scans were classified into three distinct gestational periods: 16-23 weeks, 24-31 weeks, 32+ weeks; and z-scores were created for each fetal growth measure using the INTERGROWTH-21st standards. We fitted distributed lag models to estimate the time-varying association between weekly temperature and fetal growth, adjusting for sociodemographic characteristics, seasonal and long-term trends, humidity and particulate matter (PM2.5). Higher ambient temperature was associated with smaller fetal growth measures. The critical window of exposure appeared to be Weeks 1-20 for ultrasound parameters, and high temperatures throughout pregnancy were important for BW. Associations were strongest for head parameters (BPD and HC) in early to mid-pregnancy, AC late in pregnancy and BW. For example, a 5ºC higher cumulative temperature exposure was associated with a lower mean AC z-score of -0.26 (95% CI: -0.48, -0.04) among 24-31-Week scans, and a lower mean BW z-score of -0.32 (95% CI: -0.51, -0.12). Higher temperatures were associated with impaired fetal growth. This has major health implications given that extreme temperatures are more common and escalating.

The relation of residential greenness with fetal growth and the role of air pollution in Eastern Massachusetts, USA

Background and Aim: There is growing evidence that green spaces may be beneficial for health. However, the effects on pregnant individuals and fetuses, including the underlying mechanisms, have been underexplored. We examined the association between neighborhood greenness and fetal growth, and the role of air pollution in these relationships (interaction and mediation) in a Massachusetts-based cohort. Methods: Our study consisted of 9,446 pregnancies that delivered at Beth Israel Deaconess Medical Center, Massachusetts in 2011-2016. Neighborhood greenness was estimated using normalized difference vegetation index (NDVI) with 270 m resolution. Fetal growth parameters included birth weight (BW), and ultrasound measures of biparietal diameter (BPD), head circumference (HC), femur length, and abdominal circumference (AC). Ultrasound parameters were classified into three distinct gestational periods: 16-23 weeks, 24-31 weeks, and 32+ weeks. We used distributed lag models to estimate the time-varying association between monthly NDVI and fetal growth. All models were adjusted for sociodemographic characteristics, and time trends. For models in which we identified an association, we tested for potential interaction with particulate matter &amp;#x2264;2.5 µm (PM2.5) and nitrogen dioxide (NO2) —predicted from well-validated ensemble models— and assessed for mediation by these pollutants. Results: We found that higher NDVI was positively associated with BPD, HC, AC, and BW. For example, a 0.1 NDVI increase sustained up until week 32 was associated with a higher mean AC z-score of 0.03 (95% CI: 0.01, 0.06), and a higher mean BW z-score of 0.02 (95% CI: 0.01, 0.03). We found no evidence for interaction or mediation by air pollution. Conclusions: Residential greenness was associated with larger fetal growth measures. Our effect decomposition suggests that the association of greenness with fetal growth is independent from associations with local air pollution. Keywords: greenness, air pollution, fetal growth, ultrasound, pregnancy, interaction, mediation

A prenatal standard for fetal weight improves the prenatal diagnosis of small for gestational age fetuses in pregnancies at increased risk

ObjectiveOur aim was to assess diagnostic accuracy in the prediction of small for gestational age (SGA <10th centile) and fetal growth restricted (FGR) (SGA <3rd centile) fetuses using three different sonographic methods in pregnancies at increased risk of fetal growth restriction: 1) fetal abdominal circumference (AC) z-scores, 2) estimated fetal weight (EFW) z-scores according to postnatal reference standard; 3) EFW z-scores according to a prenatal reference standard.MethodsSingleton pregnancies at increased risk of fetal growth restriction seen in two university hospitals between 2014 and 2015 were studied retrospectively. EFW was calculated using formulas proposed by the INTERGROWTH-21st project and Hadlock; data derived from publications by the INTEGROWTH-twenty-first century project and Hadlock were used to calculate z-scores (AC and EFW). The accuracy of different methods was calculated and compared.ResultsThe study group included 406 patients. Prenatal standard EFW z-scores derived from INTERGROWTH-21st project and Hadlock and co-workers performed similarly and were more accurate in identifying SGA infants than using AC z-scores or a postnatal reference standard. The subgroups analysis demonstrated that EFW prenatal standard was more or similarly accurate compared to other methods across all subgroups, defined by gestational age and birth weight.ConclusionsPrenatal standard EFW z-scores derived from either INTERGROWTH-21 st project or Hadlock and co-workers publications demonstrated a statistically significant advantage over other biometric methods in the diagnosis of SGA fetuses.

Exposure to during Pregnancy and Fetal Growth in Eastern Massachusetts, USA.

Background:Prior studies have examined the association between fine particulate matter [PM in aerodynamic diameter ()] and fetal growth with either limited spatial or temporal resolution.Objectives:In this study, we examined the association between exposure during pregnancy and fetal growth measures (ultrasound parameters and birth weight) in a pregnancy cohort using spatiotemporally resolved in Eastern Massachusetts, USA.Methods:We used ultrasound measures of biparietal diameter (BPD), head circumference, femur length, and abdominal circumference (AC), in addition to birth weight, from 9,446 pregnancies that were delivered at the Beth Israel Deaconess Medical Center from 2011–2016. We used linear mixed-effects models to examine the associations of in two exposure windows (the first 16 wk of pregnancy and the cumulative exposure up until the assessment of fetal growth) with anatomic scans (ultrasound ), growth scans (ultrasound ), and birth weight. All models were adjusted for sociodemographic characteristics, long-term trends, and temperature.Results:Higher exposure in the first 16 wk was associated with smaller fetal growth measures, where associations were particularly strong for BPD, AC, and birth weight. For example, a increase in was associated with a lower mean BPD -score of (95% CI: , ) before 24 wk, a lower mean AC -score of (95% CI: , ) after 24 wk, and a lower mean birth weight -score of (95% CI: , ). Analyses examining the associations with cumulative exposure up until the assessment of fetal growth produced attenuated associations.Conclusions:Higher gestational exposure to was associated with smaller fetal growth measures at levels below the current national standards. https://doi.org/10.1289/EHP9824

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort.

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters (p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

Combined Effect of Maternal Vitamin D Deficiency and Gestational Diabetes Mellitus on Trajectories of Ultrasound-Measured Fetal Growth: A Birth Cohort Study in Beijing, China.

Objective Few studies have examined whether maternal 25(OH)D deficiency and gestational diabetes mellitus (GDM) jointly affect fetal growth. We aimed to examine the separate and combined effects of maternal 25(OH)D deficiency and GDM on trajectories of fetal growth. Methods We established a birth cohort (2016-2017) with 10,913 singleton pregnancies in Tongzhou Maternal and Child Health Hospital of Beijing, China. Maternal 25(OH)D deficiency (serum 25(OH)D concentration < 20.0 ng/mL) was detected, and GDM was diagnosed at 24~28 gestational weeks. Fetal growth was assessed by longitudinal ultrasound measurements of estimated fetal weight (EFW) and abdominal circumference (AC) from 28 gestational weeks to delivery, both of which were standardized as gestational-age-adjusted Z-score. A k-means algorithm was used to cluster the longitudinal measurements (trajectories) of fetal growth. Logistic regression models were used for estimating exposure-outcome associations and additive interactions. Results We identified two distinct trajectories of fetal growth, and the faster one resembling the 90th centile curve in the reference population was classified as excessive fetal growth. Maternal 25(OH)D deficiency and GDM were independently associated with an increased risk of excessive fetal growth. The combination of maternal 25(OH)D deficiency and GDM was associated with an increased risk of excessive fetal growth assessed by EFW Z-score (odds ratio (OR): 1.36; 95% confidence interval (CI): 1.15~1.62) and AC Z-score (OR (95% CI): 1.32 (1.11~1.56)), but the relative excess risks attributable to interaction were nonsignificant (P > 0.05). Conclusion Maternal 25(OH)D deficiency and GDM may jointly increase the risk of excessive fetal growth. Interventions for pregnancies with GDM may be more beneficial for those with 25(OH)D deficiency than those without regarding risk of excessive fetal growth, if confirmed in a large sample.

Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound.

ABSTRACTObjectivesFirst, to evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation in the prediction of a large‐for‐gestational‐age (LGA) neonate born at ≥ 37 weeks' gestation. Second, to assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for prediction of a LGA neonate. Third, to define the predictive performance for a LGA neonate of different EFW cut‐offs on routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Fourth, to propose a two‐stage strategy for identifying pregnancies with a LGA fetus that may benefit from iatrogenic delivery during the 38th gestational week.MethodsThis was a retrospective study. First, data from 21 989 singleton pregnancies that had undergone routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 45 847 that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks were used to compare the predictive performance of EFW and AC for a LGA neonate with birth weight &gt; 90th and &gt; 97th percentiles born at ≥ 37 weeks' gestation. Second, data from 14 497 singleton pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation and had a previous scan at 30 + 0 to 34 + 6 weeks were used to determine, through multivariable logistic regression analysis, whether addition of growth velocity, defined as the difference in EFW Z‐score or AC Z‐score between the early and late third‐trimester scans divided by the time interval between the scans, improved the performance of EFW at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a LGA neonate at ≥ 37 weeks' gestation. Third, in the database of the 45 847 pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, the screen‐positive and detection rates for a LGA neonate born at ≥ 37 weeks' gestation and ≤ 10 days after the initial scan were calculated for different EFW percentile cut‐offs between the 50th and 90th percentiles.ResultsFirst, the areas under the receiver–operating characteristics curves (AUC) of screening for a LGA neonate were significantly higher using EFW Z‐score than AC Z‐score and at 35 + 0 to 36 + 6 than at 31 + 0 to 33 + 6 weeks' gestation (P &lt; 0.001 for all). Second, the performance of screening for a LGA neonate achieved by EFW Z‐score at 35 + 0 to 36 + 6 weeks was not significantly improved by addition of EFW growth velocity or AC growth velocity. Third, in screening by EFW &gt; 90th percentile at 35 + 0 to 36 + 6 weeks' gestation, the predictive performance for a LGA neonate born at ≥ 37 weeks' gestation was modest (65% and 46% for neonates with birth weight &gt; 97th and &gt; 90th percentiles, respectively, at a screen‐positive rate of 10%), but the performance was better for prediction of a LGA neonate born ≤ 10 days after the scan (84% and 71% for neonates with birth weight &gt; 97th and &gt; 90th percentiles, respectively, at a screen‐positive rate of 11%). Fourth, screening by EFW &gt; 70th percentile at 35 + 0 to 36 + 6 weeks' gestation predicted 91% and 82% of LGA neonates with birth weight &gt; 97th and &gt; 90th percentiles, respectively, born at ≥ 37 weeks' gestation, at a screen‐positive rate of 32%, and the respective values of screening by EFW &gt; 85th percentile for prediction of a LGA neonate born ≤ 10 days after the scan were 88%, 81% and 15%. On the basis of these results, it was proposed that routine fetal biometry at 36 weeks' gestation is a screening rather than diagnostic test for fetal macrosomia and that EFW &gt; 70th percentile should be used to identify pregnancies in need of another scan at 38 weeks, at which those with EFW &gt; 85th percentile should be considered for iatrogenic delivery during the 38th week.ConclusionsFirst, the predictive performance for a LGA neonate by routine ultrasonographic examination during the third trimester is higher if the scan is carried out at 36 than at 32 weeks, the method of screening is EFW than fetal AC, the outcome measure is birth weight &gt; 97th than &gt; 90th percentile and if delivery occurs within 10 days than at any stage after assessment. Second, prediction of a LGA neonate by EFW &gt; 90th percentile is modest and this study presents a two‐stage strategy for maximizing the prenatal prediction of a LGA neonate. Copyright © 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.

Predictive Value of Fetal Abdominal Circumference in Diagnosing Large for Gestational Age Infants [9D

INTRODUCTION: Macrosomia is associated with adverse perinatal outcomes and has implications for mode of delivery. Research increasingly supports the use of fetal abdominal circumference (AC) as an additional measure to capture large for gestational age (LGA) infants. We evaluated the predictive value of sonographic fetal abdominal circumference (AC) measurement from 25-36 weeks' gestation for detection of LGA infants. METHODS: Retrospective chart review following IRB approval. LGA was defined as a newborn birth weight >90th percentile on the Fenton Growth Curve. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) at various gestational age ranges (25-28, 29-32 and 33-36 weeks' gestation) for a Z-score >+1.88, corresponding to the 97th percentile, were calculated. Area under receiver operating characteristic curve (AUROCC) of AC Z-scores ranging from -3.00 to +3.00 was calculated. RESULTS: Ultrasounds of 4801 women with 5799 pregnancies were reviewed. Our study population had an LGA infant prevalence of 5.8%. An AC Z-score of +1.88 had a maximal sensitivity of 34.3%, specificity of 98.2%, and NPV of 96.2% for detecting LGA births at 29-32 weeks' gestation. The AUROCC at this time point was 0.88. CONCLUSION: Fetal AC <97th percentile in the third trimester has a very high specificity and negative predictive value in ruling out LGA newborns. These measures indicate that this modality can identify pregnancies that are not at high risk for fetal macrosomia and would not benefit from unnecessary cesarean delivery. High AUROCC demonstrates independent predictive potential of AC and supports its adjunct use with more traditional measurements.

STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early-onset fetal growth restriction.

To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early-onset fetal growth restriction. A randomised placebo-controlled trial. Thirteen maternal-fetal medicine units across New Zealand and Australia. Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks. Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first). The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre-eclampsia. Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil-treated, 39/57 (68.4%) placebo-treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23-1.05] and had no effect on abdominal circumference Z-scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil-treated and 47/59 (79.7%) for placebo-treated (adjusted OR 2.50, 95% CI 0.80-7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil-treated and 33/59 (55.9%) for placebo-treated (adjusted OR 1.93, 95% CI 0.84-4.45); and new-onset pre-eclampsia was 9/51 (17.7%) for sildenafil-treated and 14/55 (25.5%) for placebo-treated (OR 0.67, 95% CI 0.26-1.75). Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta-analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing. Maternal sildenafil use has no beneficial effect on growth in early-onset FGR, but also no evidence of harm.

Femur-sparing pattern of abnormal fetal growth in pregnant women from New York City after maternal Zika virus infection

Zika virus is a mosquito-transmitted flavivirus, which can induce fetal brain injury and growth restriction following maternal infection during pregnancy. Prenatal diagnosis of Zika virus-associated fetal injury in the absence of microcephaly is challenging due to an incomplete understanding of how maternal Zika virus infection affects fetal growth and the use of different sonographic reference standards around the world. We hypothesized that skeletal growth is unaffected by Zika virus infection and that the femur length can represent an internal standard to detect growth deceleration of the fetal head and/or abdomen by ultrasound. We sought to determine if maternal Zika virus infection is associated with a femur-sparing pattern of intrauterine growth restriction through analysis of fetal biometric measures and/or body ratios using the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic references. Pregnant women diagnosed with a possible recent Zika virus infection at Columbia University Medical Center after traveling to an endemic area were retrospectively identified and included if a fetal ultrasound was performed. Data were collected regarding Zika virus testing, fetal biometry, pregnancy, and neonatal outcomes. The 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart sonographic standards were applied to obtain Z-scores and/or percentiles for fetal head circumference, abdominal circumference, and femur length specific for each gestational week. A novel 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project standard was also developed to generate Z-scores for fetal body ratios with respect to femur length (head circumference:femur length, abdominal circumference:femur length). Data were then grouped within clinically relevant gestational age strata (<24, 24-27 6/7, 28-33 6/7, >34 weeks) to analyze time-dependent effects of Zika virus infection on fetal size. Statistical analysis was performed using Wilcoxon signed-rank test on paired data, comparing either abdominal circumference or head circumference to femur length. A total of 56 pregnant women were included in the study with laboratory evidence of a confirmed or possible recent Zika virus infection. Based on the Centers for Disease Control and Prevention definition for microcephaly after congenital Zika virus exposure, microcephaly was diagnosed in 5% (3/56) by both the 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project and World Health Organization Fetal Growth Chart standards (head circumference Z-score ≤-2 or ≤2.3%). Using 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, intrauterine fetal growth restriction was diagnosed in 18% of pregnancies (10/56; abdominal circumference Z-score ≤-1.3, <10%). Analysis of fetal size using the last ultrasound scan for all subjects revealed a significantly abnormal skewing of fetal biometrics with a smaller abdominal circumference vs femur length by either 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project or World Health Organization Fetal Growth Chart (P<.001 for both). A difference in distribution of fetal abdominal circumference compared to femur length was first apparent in the 24-27 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P= .002; World Health Organization Fetal Growth Chart, P= .001). A significantly smaller head circumference compared to femur length was also observed by 2014 International Fetal and Newborn Growth Consortium for the 21st Century Project as early as the 28-33 6/7 week strata (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project, P= .007). Overall, a femur-sparing pattern of growth restriction was detected in 52% of pregnancies with either head circumference:femur length or abdominal circumference:femur length fetal body ratio <10th percentile (2014 International Fetal and Newborn Growth Consortium for the 21st Century Project Z-score ≤-1.3). An unusual femur-sparing pattern of fetal growth restriction was detected in the majority of fetuses with congenital Zika virus exposure. Fetal body ratios may represent a more sensitive ultrasound biomarker to detect viral injury in nonmicrocephalic fetuses that could impart long-term risk for complications of congenital Zika virus infection.

Second‐ to third‐trimester longitudinal growth assessment for prediction of small‐for‐gestational age and late fetal growth restriction

Detection of fetal growth restriction (FGR) remains poor and most screening strategies rely on cross-sectional evaluation of fetal size during the third trimester. A longitudinal and individualized approach has been proposed as an alternative method of evaluation. The aim of this study was to compare second- to third-trimester longitudinal growth assessment to cross-sectional evaluation in the third trimester for the prediction of small-for-gestational age (SGA) and late FGR in low-risk singleton pregnancy. This was a prospective cohort study of 2696 unselected consecutive low-risk singleton pregnancies scanned at 21 ± 2 and 32 ± 2 weeks. For cross-sectional growth assessment, abdominal circumference (AC) measurements were transformed to z-values according the 21st-INTERGROWTH standards. Longitudinal growth assessment was performed by calculating the AC z-velocity and the second- to third-trimester AC conditional growth centile. Longitudinal assessment was compared with cross-sectional assessment at 32 weeks. Association of cross-sectional and longitudinal evaluations with SGA and late FGR was assessed by logistic regression analysis. Predictive performance was determined by receiver-operating characteristics curve analysis. In total, 210 (7.8%) newborns were classified as SGA and 103 (3.8%) as late FGR. Neither longitudinal measurement improved the association with SGA or late FGR provided by cross-sectional evaluation of AC z-score at 32 weeks. Areas under the curves of AC z-velocity and conditional AC growth were significantly smaller than those of cross-sectional AC z-scores (P< 0.001), although AC z-velocity performed significantly better than did conditional AC growth (P< 0.001). Longitudinal assessment of fetal growth from the second to third trimester has a low predictive capacity for SGA and late FGR in low-risk singleton pregnancy compared with cross-sectional growth evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Human umbilical and fetal cerebral blood flow velocity waveforms following maternal glucose loading: a cross-sectional observational study.

Our aim was to study umbilical and fetal cerebral arterial blood flow velocity waveforms related to fetal biometric measures and maternal body mass index, glucose levels and parity following maternal oral glucose loading. The study had an experimental design in a cross-sectional observational study including 105 low-risk pregnancies (30-32weeks of gestation). Ultrasound Doppler measurements of umbilical and middle cerebral arterial (UA and MCA) velocity waveforms were performed before and at 2h after completed 75-g oral glucose tolerance tests (OGTT). We assessed changes in UA and MCA pulsatility indices (PI). MCA PI was significantly reduced following OGTT (p<0.001); these changes were not related to changes in fetal heart rate (r=-0.11, p=0.278). UA PI was also significantly reduced following OGTT (p=0.033); these changes were related to fetal heart rate (r=-0.47, p<0.001). This reduction was not significant (p=0.230) when the PI values were adjusted for fetal heart rate. The ratio MCA PI to UA PI was reduced (p=0.001). The effect of OGTT on MCA PI was not related to fetal abdominal circumference whereas the effect on the adjusted UA PI values was correlated to abdominal circumference (r=-0.20, p=0.045) but not to abdominal circumference Z-score (r=-0.16, p=0.115). The influence of OGTT on the Doppler parameters as well as heart rates was not related to prepregnant body mass index, glucose levels before or after OGTT, parity, fetal sex or gestational age. Maternal glucose loading seems to decrease fetal cerebral blood flow impedance independent of fetal size.

Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses.

To investigate the association of fetal growth and cerebrovascular resistance at different periods in gestation with neurodevelopment (ND) at 14 months in the univentricular subject. We reviewed serial prenatal ultrasound (US) examinations from 133 infants enrolled in the Pediatric Heart Network's Single Ventricle Reconstruction or Infants with Single Ventricle trials, including a subset of 82 infants in whom ND was assessed at 14 months using mental (MDI) and psychomotor (PDI) developmental indices. US examinations were assigned to one of four gestational time periods: (1) 20-23 weeks, (2) 24-29 weeks, (3) 30-33 weeks and (4) ≥ 34 weeks. Middle cerebral artery (MCA) flow velocity was measured and pulsatility index (PI), a measure of downstream resistance, was calculated. Data on fetal head circumference (HC), femur length, abdominal circumference (AC) and estimated fetal weight (EFW) were collected and their Z-scores were calculated. We evaluated the rate of change of these parameters over time within individuals, tested correlations between fetal growth and ND and assessed predictors of ND using linear regression. The mean prenatal HC Z-score was < 0 at each gestational-age period and became more negative later in pregnancy. There was less growth in HC from time period 3 to period 4 compared with from period 2 to 3 (Δ HC Z-score, -0.07 ± 0.1 vs 0.11 ± 0.22, P = 0.03). Though ND did not correlate with HC, HC Z-score or MCA-PI Z-score, HC growth from period 2 to period 3 correlated with MDI (r = 0.45, P = 0.047). AC Z-score in period 4 predicted MDI (β = 4.02, P = 0.04). EFW Z-score and AC Z-score in period 2 predicted PDI (β = 10.6, P = 0.04 and β = 3.29, P = 0.047, respectively). Lower MCA-PI at initial US predicted higher PDI (β = -14.7, P = 0.03). In univentricular fetuses, lower cerebrovascular resistance may be protective for ND. Decreased fetal somatic growth may predict developmental abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Placental MFSD2a transporter is related to decreased DHA in cord blood of women with treated gestational diabetes

Maternal-fetal transfer of docosahexaenoic acid (DHA) is impaired by gestational diabetes mellitus (GDM), but the underlying mechanisms are still unknown. MFSD2a was recently recognized as a lyso-phospholipid (lyso-PL) transporter that facilitates DHA accretion in brain. The role of this transporter in placenta is uncertain. We evaluated effects of GDM and its treatment (diet or insulin) on phospholipid species, fatty acid profile in women, cord blood and placental fatty acid carriers. Prospective observational study of pregnant women recruited in the third trimester (25 controls, 23 GDM-diet, 20 GDM-insulin). Fetal ultrasound was performed at gestational week 38. At delivery, maternal and neonatal anthropometry was performed, and fatty acids in total lipids and phospholipid species were analyzed in placenta, maternal and venous cord blood. Western-blot analyses were performed for placental fatty acid carriers. Fetal abdominal circumference z-score at 38 weeks tended to higher values in GDM (P=0.071), pointing toward higher fetal fat accretion in these babies. DHA percentage in cord serum total lipids (P=0.029) and lyso-PL (P=0.169) were reduced in GDM. Placental MFSD2a was reduced in both GDM groups and was positively correlated to DHA values in cord serum total lipids (r=0.388, P=0.003). Among established placental lipid carriers, only FATP4 was correlated to DHA concentration in placental lyso-PL. In all compartments, DHA percentage was inversely correlated to fetal abdominal circumference. In offspring of women with GDM treated either with diet or insulin, higher fetal fat accretion and lower placental MFSD2a contribute to reduce DHA availability. Lyso-PL appear to contribute to materno-fetal DHA transport.

Second-trimester prediction of delivery of a small-for-gestational-age neonate: integrating sequential Doppler information, fetal biometry, and maternal characteristics.

The aim of this study was to investigate the predictive accuracy of second-trimester ultrasound parameters, maternal characteristics, and sequential Doppler changes between first and second trimesters for the prediction of small-for-gestational-age (SGA) infants (birth weight < 10th percentile). We conducted a prospective study of singleton pregnancies enrolled in the first trimester with subsequent second-trimester follow-up. Maternal characteristics, uterine artery (UtA) pulsatility index (PI), fetal biometry, and umbilical artery (UA)-PI were ascertained. UtA and UA-PI change from first to second trimester was calculated (ΔUtA-PI and ΔUA-PI). These parameters were tested for their ability to predict delivery of an SGA infant. Among 1982 women, 172 delivered an SGA neonate. African-American ethnicity, nulliparity, tobacco use, and low abdominal circumference (AC) z-score were independent predictors of SGA. No difference was found in the magnitude of ΔUtA-PI and ΔUA-PI between SGA and no-SGA. Receiver-operating characteristics curve analysis yielded an area under the curve of 0.700 for AC z-score. The combination of low AC and bilateral notching had high specificity (99%) but low sensitivity (7%) for SGA prediction. A small second-trimester fetal AC is a specific marker for SGA when found with bilateral UtA notching. Only a small proportion is predicted by the factors studied, suggesting a small contributory role or later evolution of SGA.

Human fetoplacental and fetal liver blood flow after maternal glucose loading: a cross-sectional observational study.

To study umbilical vein and fetal liver blood flow related to fetal anthropometric measures following maternal oral glucose loading. Experimental design in a cross-sectional observational study. University hospital. A total of 113 low-risk pregnancies (30-32weeks of gestation). Ultrasound Doppler measurements of umbilical vein and ductus venosus blood flow (ml/min) before and 2h after completed 75-g oral glucose tolerance test (OGTT). Liver blood flow was defined as the umbilical vein blood flow minus ductus venosus blood flow. Changes in umbilical vein and fetal liver blood flow following OGTT related to fetal biometric measurements. In the fasting state, fetal abdominal circumference z-scores did not correlate with any of the flow parameters; 120min after glucose loading, the z-scores correlated positively with the changes in umbilical vein (r=0.25, p=0.010) and fetal liver blood flow (r=0.25, p=0.009), but not with those in ductus venosus (p=0.84). In simultaneous multiple linear regression analyses, the effects of the changes in umbilical vein or fetal liver blood flow after OGTT on the fetal abdominal circumference z-scores were almost equal to or greater than other parameters related to fetal size (body mass index, fasting plasma glucose, parity, and sex). Fetal heart rate increased after OGTT, but did not influence the association between the blood flow parameters and fetal abdominal circumference z-scores. Changes in umbilical vein and fetal liver blood flow after glucose loading were positively related to fetal abdominal size.

Influence of gestational diabetes on circadian rhythms of children and their association with fetal adiposity

To analyse the circadian rhythm maturation of temperature, activity and sleep during the first year of life in offspring of diabetic mothers (ODM) and its relationship with obesity markers. A prospective analysis of the children of 63 pregnant women (23 controls, 21 gestational diabetes mellitus (GDM) controlled with diet and 19 GDM with insulin). Fetal abdominal circumference was evaluated ecographically during gestation. Skin temperature and rest-activity rhythms were monitored for 3 consecutive days in children at 15 days and 1, 3 and 6 months. Anthropometrical parameters of the children were evaluated during the first year of life. Children from the GDM groups tended to higher fetal abdominal circumference z-score than controls at the beginning of the last trimester (p = 0.077) and at delivery (p = 0.078). Mean skin temperature or activity was not different among the groups. The I < O sleep index pointed to increasing concordance with parental sleeping at 3 and 6 months but no significant GDM-dependent differences. However, some of the parameters that define temperature maturation and also the circadian function index from the temperature-activity variable were significantly lower at 6 months in the GDM + insulin group. Fetal abdominal circumference z-score, as a predictor of fetal adiposity, correlated negatively with parameters related to circadian rhythm maturation as the circadian/ultradian rhythm (P1 /Pult ratio). Fetal adiposity correlated with a worse circadian rhythm regulation in ODM. In addition, ODM insulin-treated showed a disturbed pattern of the circadian function index of temperature activity at 6 months of age.