Impact of birth weight to placental weight ratio and other perinatal risk factors on left ventricular dimensions in newborns: a prospective cohort analysis.

OBJECTIVES: To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. METHODS: A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. RESULTS: We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03-0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=-0.07, p=0.039), LV mass (estimate=-0.11, p=0.024), and LV mass/volume (estimate=-0.55, p=0.005). CONCLUSIONS: This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies.

Perinatal factors impacting echocardiographic left ventricular measurement in small for gestational age infants: a prospective cohort study.

INTRODUCTION: Infants born small for gestational age (SGA) have an increased risk of developing various cardiovascular complications. While many influencing factors can be adjusted or adapt over time, congenital factors also have a significant role. This study, therefore, seeks to explore the effect of perinatal factors on the left ventricular (LV) parameters in SGA infants, as assessed immediately after birth. METHODS AND MATERIALS: This single-center prospective cohort study, conducted between 2014 and 2018, involved healthy SGA newborns born > 35 weeks' gestation, delivered at New York-Presbyterian Brooklyn Methodist Hospital, and a gestational age (GA)-matched control group of appropriate for gestational age (AGA) infants. Data analysis was performed using multivariate linear regression in STATA. RESULTS: The study enrolled 528 neonates, 114 SGA and 414 AGA. SGA infants exhibited a mean GA of 38.05 weeks (vs. 38.54), higher male representation (69.3% vs. 51.5%), lower birth weight (BW) (2318g vs 3381g), lower Apgar scores at birth, and a higher rate of neonatal intensive care unit admission compared to AGA infants (41.2% vs.18.9%; p<0.001). Furthermore, SGA infants were more likely to be born to nulliparous women (63.16% vs. 38.16%; p<0.001), with lower body mass index (BMI) (29.8 vs. 31.7; p=0.004), a lower prevalence of gestational maternal diabetes (GDM) (14.9 % vs. 35.5%; p<0.001), and a higher prevalence of preeclampsia (18.4 % vs. 6.52%; p<0.001). BW was identified as the most significant predictor affecting most LV parameters in this study (p<0.001), except shortening fraction, asymmetric interventricular septal hypertrophy and Inter-ventricular septal thickness/LV posterior wall ratio (IVS/LVPW). Lower GA (coefficient = -0.09, p=0.002), insulin use in GDM (coefficient = 0.39, p=0.014), and low APGAR scores at 1 minute (coefficient = -0.07, p<0.001) were significant predictors of IVS during diastole (R-squared [R2]=0.24). High maternal BMI is marginally associated with LVPW during systole (R2=0.27, coefficient = 0.01, p=0.050), while male sex was a significant predictor of LV internal dimension during diastole (R2=0.29, p=0.033). CONCLUSION: This study highlights the significant influence of perinatal factors on LV parameters in SGA infants, with BW being the most influential factor. Although LV morphology alone may not predict future cardiovascular risk in the SGA population, further research is needed to develop effective strategies for long-term cardiovascular health management in this population.

Ethical dilemmas in decision making at limits of neonatal viability.

The survival rate for extremely preterm infants has improved over the last two decades. Although the incidence of such births is about 2%, the impact of preterm birth on these infants, their families, health-care providers, and society is profound. The birth of an extremely low birth weight (ELBW) and early gestational age infant poses complex medical, social, and ethical challenges to the family and health-care professionals. Survivors have an increased risk of chronic medical problems and disability. It is difficult to make decisions while trying to provide optimal medical care to the infant and supporting the family when delivery occurs at the threshold of viability because outcome at that time is highly unpredictable. Such decisions may have lifelong consequences for those involved. An individualized prognostic strategy appears to be the most appropriate approach. While keeping the patient's best interest as the primary objective, the goal is to reach, through a process of effective communication between the parents and physicians, a consensual decision that respects the parents' wishes and promotes physician beneficence.

Protein tyrosine phosphatase PTPN14 is a regulator of lymphatic function and choanal development in humans.

The lymphatic vasculature is essential for the recirculation of extracellular fluid, fat absorption, and immune function and as a route of tumor metastasis. The dissection of molecular mechanisms underlying lymphangiogenesis has been accelerated by the identification of tissue-specific lymphatic endothelial markers and the study of congenital lymphedema syndromes. We report the results of genetic analyses of a kindred inheriting a unique autosomal-recessive lymphedema-choanal atresia syndrome. These studies establish linkage of the trait to chromosome 1q32-q41 and identify a loss-of-function mutation in PTPN14, which encodes a nonreceptor tyrosine phosphatase. The causal role of PTPN14 deficiency was confirmed by the generation of a murine Ptpn14 gene trap model that manifested lymphatic hyperplasia with lymphedema. Biochemical studies revealed a potential interaction between PTPN14 and the vascular endothelial growth factor receptor 3 (VEGFR3), a receptor tyrosine kinase essential for lymphangiogenesis. These results suggest a unique and conserved role for PTPN14 in the regulation of lymphatic development in mammals and a nonconserved role in choanal development in humans.

Myopathy caused by HRAS germline mutations: implications for disturbed myogenic differentiation in the presence of constitutive HRas activation.

BACKGROUND: Rare reports on patients with congenital myopathy with excess of muscle spindles (CMEMS), hypertrophic cardiomyopathy and variable features resembling Noonan syndrome have been published, but the genetic basis of this condition is so far unknown. METHODS AND RESULTS: We analysed PTPN11 and RAS genes in five unrelated patients with this phenotype, and found HRAS mutations in four of them. Two disease-associated mutations, G12V and G12S, have previously been observed in patients with Costello syndrome (CS), and two other mutations, E63K and Q22K, are novel. All four mutations are predicted to enhance downstream HRas signalling, suggesting that CMEMS is a developmental consequence of sustained HRas activation in skeletal muscle. CONCLUSION: This type of myopathy may represent a previously unrecognized manifestation of CS. However, some patients carrying HRAS mutations may exhibit prominent congenital muscular dysfunction, although features of CS may be less obvious, suggesting that germline HRAS mutations may underlie some cases of otherwise unclassified neonatal neuromuscular disorders.

Comparison of clinical criteria with echocardiographic findings in diagnosing PDA in preterm infants.

OBJECTIVE: The purpose of our study was to compare clinical criteria with echocardiographic findings in diagnosing hemodynamically significant patent ductus arteriosus (PDA) in preterm infants. METHODS: We evaluated 25 preterm infants born at 24-32 weeks of gestation with birth weight from 500 to 1700 g for tachycardia, heart murmur, hyperdynamic chest, presence of dorsalis pedis pulse, hypotension, and worsening of the respiratory status at 48-72 h of life. A pediatric cardiologist blinded to clinical findings performed the echocardiograms. Infants with congenital anomalies and conditions, sepsis, IVH, and necrotizing enterocolitis were excluded. RESULTS: Out of 25 preterm infants, 12 infants had hemodynamically significant PDA with left-to-right shunt. Two infants had small PDA and in 11 infants the ductus arteriosus was not patent. PDA infants had lower gestational age (P = 0.02) and birth weight (P = 0.03). Their Apgar scores (1 min) were lower (P = 0.03). The heart rate between the two groups differed, but was clinically within normal limits. Systolic (P = 0.05) and mean blood pressures (P = 0.04) were lower in the PDA group. A poor association between heart murmur, hyperdynamic chest and dorsalis pedis pulse, and the presence of PDA was revealed. CONCLUSION: Echocardiogram is required for early diagnosis of PDA in preterm infants, as clinical signs are not reliable in the first few days of life.

A new syndrome of myopathy with muscle spindle excess.

Arthrogryposis may result from various neuromuscular or connective tissue disorders leading to in utero hypokinesia or akinesia and the prenatal development of joint contractures. We report the case of a preterm neonate born with arthrogryposis and flaccid quadriplegia that led to the diagnosis of myopathy with muscle spindle excess. The rare and unusual histopathologic abnormality associated with the myopathy illustrated in this case has been described in only three other cases in the medical literature. The concurrence of hypertrophic cardiomyopathy, arthrogryposis, and myopathy with muscle spindle excess suggests the presence of a newly described syndrome. This case clearly demonstrates that specific prenatal ultrasonographic findings combined with the presenting clinical manifestations should promptly raise the suspicion of a neuromuscular disorder.

Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine.

BACKGROUND: Trefoil factor 3 (TFF3) or intestinal trefoil factor (ITF), a peptide normally expressed and secreted by goblet cells at the mucosal surface of the small intestine and colon, is important for the maintenance and repair of the intestinal mucosal barrier. AIM: To study the ontogeny and developmental expression of TFF3 in human intestine. SUBJECTS: We examined TFF3 expression in formalin-fixed and paraffin-embedded intestinal tissues from 24 fetuses (gestational age [GA] 12-23 weeks) and 5 adults by immunohistochemical staining. To determine whether TFF3 is excreted into the fetal intestinal tract, first-passed meconium samples were collected from 43 newborn infants (gestational age 24-41 weeks). The presence of TFF3 was examined by Western blot analysis and the relative levels of TFF3 in the meconium were quantified with a slot blot assay. RESULTS: TFF3 can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation. TFF3 is present in the meconium of newborn infants; no significant difference exists in TFF3 levels in the meconium of premature infants with birth weight (BW) less than 1500 g compared to those with birth weight equal to or more than 1500 g. CONCLUSION: Premature infant's susceptibility to intestinal mucosal injury is unlikely to be explained by developmental expression of TFF3 in human intestine since secreted TFF3 is not deficient in premature infants.

Changes in upper extremity position cause migration of peripherally inserted central catheters in neonates.

OBJECTIVE: The migration of peripherally inserted central catheters (PICCs) from the superior or inferior vena cava into the right atrium can pose a significant risk of lethal pericardial effusion and tamponade secondary to myocardial perforation. Arm movement has been reported to cause displacement of the catheter tip toward the heart and lead to ventricular tachycardia in adults. The objective of this study was to investigate whether adduction or abduction at the shoulder and flexion or extension at the elbow affect the position of PICCs placed via upper limb veins. We also hypothesized that arm movements can be used to reposition malpositioned catheters. METHODS: A total of 280 radiographs of 60 neonates with PICCs inserted via upper limb veins from July 2000 through June 2001 were reviewed. Differences in catheter tip position as a result of abduction versus adduction at the shoulder, flexion versus extension at the elbow, and combination changes in arm posture were determined by measurements in paired radiographs. Correction of malpositioned catheters was attempted in 10 patients by using arm movements without any alterations at the site of insertion. RESULTS: Arm movements were associated with significant displacement of catheters. Catheters that were placed via the basilic or axillary vein migrated toward the heart with adduction of the arm, whereas those that were placed via the cephalic vein moved away from the heart with adduction. Flexion of the elbow displaced catheters that were placed in the basilic or cephalic vein below the elbow toward the heart but did not have any effect on catheters that were placed via the axillary vein. For catheters that were placed in the basilic vein, simultaneous shoulder adduction and elbow flexion caused the greatest movement toward the heart (15.11 +/- 1.22 mm). We were able to reposition correctly inappropriately placed catheters in 9 of 10 patients by using arm movements. CONCLUSIONS: Arm movements significantly affect the position of the tip of the PICCs. Prevention of catheter migration into the right atrium requires radiographic determination of vein of insertion and monitoring of catheter tip position with upper extremity in position of maximum inward movement of catheter for that vein. Arm movements can be used to correct the malpositioned catheters.