Corpus Callosum Length and Cerebellar Vermian Height in Fetal Growth Restriction.

INTRODUCTION: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses. METHODS: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC). RESULTS: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [-0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = -0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI. CONCLUSIONS: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations.

Umbilical Venous Volume Flow in Late-Onset Fetal Growth Restriction.

OBJECTIVES: Umbilical vein flow (UVF) is reduced in fetal growth restriction (FGR). We compared absolute and size-adjusted UVF (estimated fetal weight [EFW] and abdominal circumference [AC]) and rates of abnormal UVF parameters (<10th percentile) among FGR fetuses meeting Delphi criteria (FGR-D) against small for gestational age (SGA) fetuses and appropriate for gestational age (AGA) controls. METHODS: Absolute UVF, UVF/EFW, and UVF/AC were compared between 73 FGR pregnancies (35 FGR-D, 38 SGA) and 108 AGA controls. Rates of abnormal UVF were compared to abnormal umbilical artery pulsatility index (UAPI). Independent samples t-tests, Mann-Whitney U, odds ratio (OR), chi-squared, and Fisher's exact tests were used as appropriate. RESULTS: Mean absolute UVF was significantly decreased in FGR-D compared to AGA (P = .0147), but not between SGA and AGA fetuses. The incidence of both abnormal absolute UVF and UVF/AC values (<10th centile) was higher among late-onset FGR fetuses versus AGA fetuses (UVF: OR 2.7, confidence interval [CI] 1.37-5.4; UVF/AC: OR 2.73, CI 1.37-5.4). UVF was more frequently abnormal than UAPI and in only two fetuses were both Doppler values abnormal. CONCLUSION: Absolute UVF is altered in late-onset FGR, and most pronounced among FGR-D. UVF may provide additional insight into fetal compromise in those affected by growth restriction.

Altered Cord Blood Lipid Concentrations Correlate with Birth Weight and Doppler Velocimetry of Fetal Vessels in Human Fetal Growth Restriction Pregnancies.

Fetal growth restriction (FGR) is associated with short- and long-term morbidity, often with fetal compromise in utero, evidenced by abnormal Doppler velocimetry of fetal vessels. Lipids are vital for growth and development, but metabolism in FGR pregnancy, where fetuses do not grow to full genetic potential, is poorly understood. We hypothesize that triglyceride concentrations are increased in placentas and that important complex lipids are reduced in cord plasma from pregnancies producing the smallest babies (birth weight < 5%) and correlate with ultrasound Dopplers. Dopplers (umbilical artery, UA; middle cerebral artery, MCA) were assessed longitudinally in pregnancies diagnosed with estimated fetal weight (EFW) < 10% at ≥29 weeks gestation. For a subset of enrolled women, placentas and cord blood were collected at delivery, fatty acids were extracted and targeted lipid class analysis (triglyceride, TG; phosphatidylcholine, PC; lysophosphatidylcholine, LPC; eicosanoid) performed by LCMS. For this sub-analysis, participants were categorized as FGR (Fenton birth weight, BW ≤ 5%) or SGA "controls" (Fenton BW > 5%). FGRs (n = 8) delivered 1 week earlier (p = 0.04), were 29% smaller (p = 0.002), and had 133% higher UA pulsatility index (PI, p = 0.02) than SGAs (n = 12). FGR plasma TG, free arachidonic acid (AA), and several eicosanoids were increased (p < 0.05); docosahexaenoic acid (DHA)-LPC was decreased (p < 0.01). Plasma TG correlated inversely with BW (p < 0.05). Plasma EET, non-esterified AA, and DHA correlated inversely with BW and directly with UA PI (p < 0.05). Placental DHA-PC and AA-PC correlated directly with MCA PI (p < 0.05). In fetuses initially referred for inadequate fetal growth (EFW < 10%), those with BW ≤ 5% demonstrated distinctly different cord plasma lipid profiles than those with BW > 5%, which correlated with Doppler PIs. This provides new insights into fetal lipidomic response to the FGR in utero environment. The impact of these changes on specific processes of growth and development (particularly fetal brain) have not been elucidated, but the relationship with Doppler PI may provide additional context for FGR surveillance, and a more targeted approach to nutritional management of these infants.

Patterns of Brain Sparing in a Fetal Growth Restriction Cohort.

Objective: Our objective was to compare differences in Doppler blood flow in four fetal intracranial blood vessels in fetuses with late-onset fetal growth restriction (FGR) vs. those with small for gestational age (SGA). Methods: Fetuses with estimated fetal weight (EFW) <10th percentile were divided into SGA (n = 30) and FGR (n = 51) via Delphi criteria and had Doppler waveforms obtained from the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and vertebral artery (VA). A pulsatility index (PI) <5th centile was considered "abnormal". Outcomes included birth metrics and neonatal intensive care unit (NICU) admission. Results: There were more abnormal cerebral vessel PIs in the FGR group versus the SGA group (36 vs. 4; p = 0.055). In FGR, ACA + MCA vessel abnormalities outnumbered PCA + VA abnormalities. All 8 fetuses with abnormal VA PIs had at least one other abnormal vessel. Fetuses with abnormal VA PIs had lower BW (1712 vs. 2500 g; p < 0.0001), delivered earlier (35.22 vs. 37.89 wks; p = 0.0052), and had more admissions to the NICU (71.43% vs. 24.44%; p = 0.023). Conclusions: There were more anterior vessels showing vasodilation than posterior vessels, but when the VA was abnormal, the fetuses were more severely affected clinically than those showing normal VA PIs.

Doppler velocimetry discordance between paired umbilical artery vessels and clinical implications in fetal growth restriction.

BACKGROUND: Studies revealing a discrepancy in umbilical artery Dopplers between the two umbilical arteries in normally-grown fetuses necessitates further evaluation of the paired umbilical arteries in the setting of fetal growth restriction as this is a critical component in the surveillance of this population. OBJECTIVE: Umbilical artery Doppler sampling in fetal growth restriction is typically assessed in 1 umbilical artery in a free loop of cord. Although discrepancies of >20% between the 2 umbilical arteries occur in 1 of 3 normal pregnancies, this has not been assessed in fetal growth restriction. Our objectives were to determine the frequency of discordant Doppler pulsatility indices between paired umbilical arteries in a fetal growth restriction cohort and to determine if sampling of 1 or both arteries alters surveillance or timing of delivery. STUDY DESIGN: A cohort of 425 growth-restricted fetuses between 25 and 39 weeks of gestation had umbilical artery Doppler pulsatility indices determined from both umbilical arteries in a midsegment of the cord to determine: (1) the discrepancy percentage between paired umbilical artery pulsatility indices and (2) the frequency of both arteries being normal, abnormal, or discordant (pulsatility index < and >95th percentile). To determine what sampling method increased the detection of an abnormal Doppler index, 3 sampling methods were compared: (1) average pulsatility index from both umbilical arteries, (2) pulsatility index from 1 umbilical artery chosen randomly, and (3) highest pulsatility index of the 2 umbilical arteries. RESULTS: The mean percentage difference between umbilical artery pulsatility indices was 11.7%, and in 15.8% of cases, it exceeded 20%. Both umbilical artery pulsatility indices were normal in 71.1% (302/425), abnormal in 12.2% (52/425), and discordant in 16.7% (71/425) of cases (P<.0001). Of the 3 sampling methods, the pulsatility index was abnormal in: (1) 19.2% (82/425) of cases when averaged from both umbilical arteries, (2) 22.1% (94/425) of cases when choosing 1 umbilical artery at random, and (3) 28.9% (123/425) of cases when the highest umbilical artery pulsatility index was used (P=.003). CONCLUSION: In this large fetal growth restriction cohort, the overall discrepancy between the 2 umbilical artery pulsatility indices was 11.7%. Among fetuses with at least 1 abnormal umbilical artery pulsatility index, 71 of 123 (57.7%) had 1 normal pulsatility index and 1 abnormal. Thus, the number of arteries sampled and the sampling method used may alter clinical decision-making, including frequency of surveillance and timing of delivery.

3D Fractional Limb Volume Identifies Reduced Subcutaneous and Lean Mass in Fetal Growth Restriction.

OBJECTIVES: Fetal 2D and 3D fractional limb volume (FLV) measurements by ultrasound can detect fetal lean and subcutaneous mass and possibly percent body fat. Our objectives were to 1) compare FLV measurements in fetuses with fetal growth restriction (FGR) versus small for gestational age (SGA) defined by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)-supported international Delphi consensus and 2) correlate FLV findings with birth metrics. We hypothesize that FLV measurements will be significantly smaller in FGR versus SGA fetuses and will correlate closer with Ponderal index (PIx) in the neonate than abdominal circumference (AC). METHODS: Patients were categorized as FGR or SGA as defined by ISUOG. Total thigh volume (TTV), volumes of lean mass (LMV), and fat mass volume (FMV) were calculated from 3D acquisitions. Measurements were compared between groups and correlated with birthweight (BW) and PIx (BW/crown-heal length). RESULTS: The FGR group (n = 37) delivered earlier (37/2 versus 38/0; P = .0847), were lighter (2.2 kg versus 2.6 kg; P = .0003) and had lower PIx (0.023 versus 0.025; P = .0013) than SGAs (n = 22). FGRs had reduced TTV (40.6 versus 48.4 cm3 ; P = .0164), FMV (20.8 versus 25.3 cm3 ; P = .0413), and LMV (19.8 versus 23.1 cm3 ; P = .0387). AC had the highest area under the curve (0.69) for FGR. FMV was more strongly associated with PIx than the AC (P = .0032). CONCLUSIONS: The AC and FLV measurements were significantly reduced in FGR fetuses compared to SGAs. While the AC outperformed FLV in predicting FGR, the FLV correlated best with PIx, which holds investigative promise.

Size and shape of the four-chamber view of the fetal heart in fetuses with an estimated fetal weight less than the tenth centile.

BACKGROUND: Fetuses with an estimated fetal weight below the 10th centile have an increased risk of adverse perinatal and long-term outcomes as well as increased rates of cardiac dysfunction, which often alters cardiac size and shape of the 4-chamber view and the individual ventricles. As a result, a simple method has emerged to screen for potential cardiac dysfunction in fetuses with estimated fetal weights <10th centile by measuring the size and shape of the 4-chamber view and the size of the ventricles. OBJECTIVE: To determine the number of fetuses with an abnormal size and shape of the 4-chamber view and size of the ventricles in fetuses with an estimated fetal weight <10th centile. MATERIALS AND METHODS: This was a retrospective study of 50 fetuses between 25 and 37 weeks of gestation with an estimated fetal weight <10th centile. Data from their last examination were analyzed. From an end-diastolic image of the 4-chamber view, the largest basal-apical length and transverse width were measured from their corresponding epicardial borders. This allowed the 4-chamber view area and global sphericity index (4-chamber view length/4-chamber view width) to be computed. In addition, tracing along the endocardial borders with speckle tracking software enabled measurements of the right and left ventricular chamber areas and the right ventricle/left ventricle area ratios to be computed. Doppler waveform pulsatility indices from the umbilical (umbilical artery pulsatility index) and middle cerebral arteries (middle cerebral artery pulsatility index) were analyzed, and the cerebroplacental ratio (middle cerebral artery pulsatility index/umbilical artery pulsatility index) computed. Umbilical artery pulsatility indices >90th and cerebroplacental ratios <10th centile were considered abnormal. Using data from the control fetuses, the centile for each of the cardiac measurements was categorized by whether it was <10th or >90th centile, depending upon the measurement. RESULTS: Of the 50 fetuses with estimated fetal weight <10th centile, 50% (n = 25) had a normal umbilical artery pulsatility index and cerebroplacental ratio. These fetuses had significantly more (P < 0.02 to <0.0001) abnormalities of the size and shape of the 4-chamber view than controls. In all, 44% had a 4-chamber view area >90th centile, 32% had a 4-chamber view global sphericity index <10th centile, 56% had a 4-chamber view width >90th centile, and 80% had 1 or more abnormalities of size and/or shape. The remaining 50% of fetuses (n = 25) had abnormalities of 1 or both for the umbilical artery pulsatility index and/or cerebroplacental ratio. These fetuses had significantly higher rates of abnormalities (P <0.05 to <0.0001) than controls for the following 4-chamber view measurements: 36% had a 4-chamber view area >90th centile; 28% had a 4-chamber view global sphericity index <10th centile; and 68% had a 4-chamber view width >90th centile. Only those fetuses with an abnormal umbilical artery pulsatility index had significant changes in ventricular size; 56% had a left ventricular area <10th centile; 28% had a right ventricular area <10th centile; 36% had right ventricular/left ventricular area ratio >90th centile. One or more of the above abnormal measurements were present in 92% of the fetuses. CONCLUSION: Higher rates of abnormalities of cardiac size and shape of the 4-chamber view were found in fetuses with an estimated fetal weight <10th centile, regardless of their umbilical artery pulsatility index and cerebroplacental ratio measurements. Those with a normal umbilical artery pulsatility index and an abnormal cerebroplacental ratio had larger and wider measurements of the 4-chamber view. In addition, the shape of the 4-chamber view was more globular or round than in controls. These fetuses may have an increased risk of perinatal complications and childhood and/or adult cardiovascular disease. Screening tools derived from the 4-chamber view, acting as surrogates for ventricular dysfunction, may identify fetuses who could benefit from further comprehensive testing and future preventive interventions.

Does Prenatal Maternal Distress Contribute to Sex Differences in Child Psychopathology?

PURPOSE OF REVIEW: Prenatal maternal psychological distress is an established risk factor for the development of psychopathology in offspring. The purpose of this review is to evaluate whether sex differences in fetal responses to maternal distress contribute to sex differences in subsequent psychopathology. RECENT FINDINGS: Male and female fetuses respond differently to stress signals. We review recent evidence that demonstrates a sex-specific pattern of association between prenatal maternal distress and pathways associated with risk for psychopathology including offspring hypothalamic pituitary adrenocortical (HPA) axis regulation, brain development, and negative emotionality. Prenatal maternal distress exerts sex-specific consequences on the fetus. These differences may contribute to the well-established sex differences in psychopathology and in particular to greater female vulnerability to develop internalizing problems.