Perinatal Respiratory Distress Research Articles

Status of pulmonary artery pressures on echocardiography among high-risk newborns

Background: There is a paucity of data about the outcome of newborns who have one or more risk factors for persistent pulmonary hypertension of newborn (PPHN) and have some degrees of pulmonary hypertension not significant enough to cause hypoxemia and desaturation to be labeled as PPHN. Objective: Status of pulmonary artery pressures in high risk newborns. Materials and Methods: This was a prospective observational study, in which newborns up to 1 month of age having risk factors for PPHN were included and pulmonary hypertension was identified on echocardiography in neonates more than 48 h of life. Second screening was done at 6 weeks of life independent of subjects having PAH or not at the first screening. Results: Out of 400 cases, 26 patients were lost to follow-up, 2 cases left against medical advice, and 18 patients expired after first screening. Finally, a total of 354 cases came for follow-up at 6 weeks and repeat echocardiography was done in all cases. PAH was found in 54 cases on first screening, 12 neonates had reversal of shunt at the level of patent ductus arteriosus or patent foramen ovale, and only 2 cases had persistence PAH on second screening at 6 weeks. Perinatal asphyxia (43.9%), respiratory distress (31%), and meconium-stained amniotic fluid (30%) have shown a significant association with the development of PAH in these neonates. Development of PAH worsens the prognosis in newborns with asphyxia and sepsis. Conclusion: Newborns with risk factors have some degree of PAH, which can have an adverse impact on outcome.

The complementary role of imaging modalities in Binder phenotype. Can prognostic factors of neonatal respiratory distress be found?

To evaluate the complementarity between prenatal ultrasound, computed tomography, and MRI scans for fetuses with Binder phenotype. We carried out a retrospective study from January 1, 2009, to June 30, 2018, of fetuses with Binder phenotype. Prenatal ultrasound (US) data were collected. A systematic survey of the entire skeleton was performed to look for associated abnormalities such as calcifications, brachytelephalangy, and spinal stenosis. Parents were systematically offered fetal skeletal computed tomography (CT). Thirteen cases were included. Two cases of perinatal respiratory distress (18%) were observed. Chondrodysplasia punctata was diagnosed from the presence of calcifications, especially of the proximal femoral epiphyses and tarsal bones, in five cases (38%) by US and in 10 cases (83%) by CT. Calcifications of the hyoid bone were detected by CT in three cases (25%) one of which had respiratory distress. Polyhydramnios was associated with the Binder phenotype in four cases (30%) one of which had respiratory distress. One single fetus had combined polyhydramnios and laryngeal calcifications, and he suffered from perinatal respiratory distress. An antenatal diagnosis of Binder phenotype is often associated with chondrodysplasia punctata. We recommend the use of fetal CT as a complement to US in this condition.

Distal Arthrogryposis with Impaired Proprioception and Touch: Description of an Early Phenotype in a Boy with Compound Heterozygosity of PIEZO2 Mutations and Review of the Literature

The recessive PIEZO2-associated disease, distal arthrogryposis with impaired proprioception and touch (DAIPT), is characterized by hypotonia, perinatal respiratory distress, significantly delayed motor milestones, and progressive symptoms of distal arthrogryposis and scoliosis. Here, we describe the youngest patient with DAIPT to date, who, at the age of 3.5 years, did not show a single clinical sign of distal arthrogryposis or contractures, but had a history of bilateral clubfoot operations. On the contrary, he presented with some features, not described thus far, such as syringohydromyelia, a small cyst of the spinal cord, moderate microcephaly with premature closure of anterior fontanelle, and spontaneous unilateral patella dislocation at the age of 32 months. Using whole exome sequencing, we identified 2 new different loss-of-function mutations in the PIEZO2 gene in our patient. We also review the phenotypes of all 16 previously published patients with DAIPT, summarize the distinctive clinical features of this rare genetic disorder, and recommend that DAIPT be included in the differential diagnosis of floppy infant. PIEZO2 is a unique ion channel that converts mechanical impulses into cellular signals and is involved in various mechanotransduction pathways. In addition to DAIPT, mutations in PIEZO2 have been described to cause 3 more distinct phenotypes of distal arthrogryposis, which are dominant and associated with gain-of-function mutations. On the contrary, recessive DAIPT is associated with loss-of-function PIEZO2 mutations.

Genetic Diseases of PIEZO1 and PIEZO2 Dysfunction.

Mutations in the genes encoding the mechanosensitive cation channels PIEZO1 andPIEZO2 are responsible for multiple hereditary human diseases. Loss-of-function mutations in the human PIEZO1 gene cause autosomal recessive congenital lymphatic dysplasia. Gain-of-function mutations in the human PIEZO1 gene cause the autosomal dominant hemolytic anemia, hereditary xerocytosis (also known as dehydrated stomatocytosis). Loss-of-function mutations in the human PIEZO2 gene cause an autosomal recessive syndrome of muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis. Gain-of-function mutations in the human PIEZO2 gene cause three clinical types of autosomal dominant distal arthrogryposis. This chapter will review the hereditary diseases caused by mutations in the PIEZO genesand will discuss additional physiological systems in which PIEZO channel dysfunction may contribute to human disease pathophysiology.

Biallelic Loss of Proprioception-Related PIEZO2 Causes Muscular Atrophy with Perinatal Respiratory Distress, Arthrogryposis, and Scoliosis

We report ten individuals of four independent consanguineous families from Turkey, India, Libya, and Pakistan with a variable clinical phenotype that comprises arthrogryposis, spontaneously resolving respiratory insufficiency at birth, muscular atrophy predominantly of the distal lower limbs, scoliosis, and mild distal sensory involvement. Using whole-exome sequencing, SNPchip-based linkage analysis, DNA microarray, and Sanger sequencing, we identified three independent homozygous frameshift mutations and a homozygous deletion of two exons in PIEZO2 that segregated in all affected individuals of the respective family. The mutations are localized in the N-terminal and central region of the gene, leading to nonsense-mediated transcript decay and consequently to lack of PIEZO2 protein. In contrast, heterozygous gain-of-function missense mutations, mainly localized at the C terminus, cause dominant distal arthrogryposis 3 (DA3), distal arthrogryposis 5 (DA5), or Marden-Walker syndrome (MWKS), which encompass contractures of hands and feet, scoliosis, ophthalmoplegia, and ptosis. PIEZO2 encodes a mechanosensitive ion channel that plays a major role in light-touch mechanosensation and has recently been identified as the principal mechanotransduction channel for proprioception. Mice ubiquitously depleted of PIEZO2 are postnatally lethal. However, individuals lacking PIEZO2 develop a not life-threatening, slowly progressive disorder, which is likely due to loss of PIEZO2 protein in afferent neurons leading to disturbed proprioception causing aberrant muscle development and function. Here we report a recessively inherited PIEZO2-related disease and demonstrate that depending on the type of mutation and the mode of inheritance, PIEZO2 causes clinically distinguishable phenotypes.

Perinatal features of congenital cystic lung diseases: results of a nationwide multicentric study in Japan.

The current study aimed to assess the perinatal risk and clinical features of congenital cystic lung diseases (CCLD). Of the 874 CCLD patients identified in a nationwide survey, 428 patients born between 1992 and 2012 and treated at 10 high-volume centers, were retrospectively reviewed. Fetal hydrops was visualized using MRI in 9.2% of the patients. Prenatal interventions were described for 221 of the 428 patients, including the maternal administration of steroid and pleuro-amniotic shunting. Postnatally, a right-to-left shunt flow through a persistent ductus arteriosus was observed in 7.8% of the patients. The fetal lung lesion volume ratio (LVR) was significantly higher among these symptomatic patients (2.04±1.71 vs. 0.98±0.50, P<0.00071), and decreased to a greater degree in non-CCAM patients compared with CCAM patients during the late gestational period (from 1.37±1.28 to 1.14±0.84 in CCAM and from 1.08±0.47 to 0.46±0.64 in non-CCAM). An estimated 8-9% of prenatally diagnosed patients carry the highest risk of perinatal respiratory distress. Fetal LVR remaining at a high level during the late gestational period seems to predict a high risk.

Clinical Features of Congenital Cystic Lung Diseases: A Report on a Nationwide Multicenter Study in Japan.

The current study aimed to assess the perinatal risk of congenital cystic lung diseases (CCLD) and to establish a suitable surgical strategy in consideration of postoperative lung growth and problems during adulthood. Among 874 CCLD patients identified in a nationwide survey, 428 patients were born between 1992 and 2012 and treated at 10 high-volume centers were retrospectively reviewed with statistical analysis. In the 194 patients who were prenatally diagnosed to have CCLD, 16.7% presented with fetal hydrops as observed using ultrasonography. The Apgar score (5 minutes) was lower than 5 in 5.4%. As of postnatal day 30, 14.0% of the neonatal patients required respiratory support, and 3.3% (8/243) had died because of pulmonary hypoplasia. Among those who were asymptomatic immediately after birth, 33.6% of the patients developed the respiratory infectious symptoms during their first year of life, and 22.1% did so between the age of 1 and 2 years. The postoperative percent vital capacity among the prenatally diagnosed patients was significantly higher than that among the postnatally diagnosed patients (98.3 ± 11.9 vs. 81.7 ± 9.7, p < 0.0222). Late complications included thoracic deformity in 30 patients and persistent lung cyst in 4 patients, whereas malignancy was not observed in the present series. Approximately 10 to 15% of prenatally diagnosed CCLD patients may carry a high risk of perinatal respiratory distress. Early operation before developing episodes of lung infection, seem to be associated with a better development of the reserved lung during later life. The incidence of carcinogenesis among patients with CCLD may be extremely low.

Lung liquid transport components in human perinatal respiratory distress

Lung liquid transport components in human perinatal respiratory distress

Haemorrhagic gastritis in a neurologically impaired boy

A 7-year-old boy, affected by spastic quadriplegia secondary to perinatal respiratory distress, presented with a 15-day history of severe abdominal pain. Paracetamol and omeprazole brought no relief. On physical examination,...

Secuencia de Moebius: hallazgos clinicorradiológicos

Moebius syndrome is an infrequent congenital, non-progressive disorder that is defined by facial palsy (usually bilateral) and oculomotor compromise. Its clinical spectrum is variable but it affects other cranial nerves and is associated with multiple malformations. We report the clinical, neurological and neuroimaging features and the progress of 20 patients (16 males and 4 females) who satisfied diagnostic criteria for Moebius sequence. Ages at the first visit ranged from 9 days to 23 months. Births had been normal in 50% of the patients. Facial nerve compromise was observed in all cases, 70% being bilateral. Cranial nerves VI (85%), XII (40%), VIII (25%) and IX (60%) were also involved. Perinatal respiratory distress was seen in 35% of the patients, apnoeas in 25% and retarded development in 60% of cases. They also presented other associated malformations such as microretrognathia, ogival palate, club foot, hand and foot malformations, and four cases presented unilateral agenesis of the pectoralis major. An electromyogram study showed absence of spontaneous and voluntary activity and muscle evoked potentials on stimulating the facial nerve; magnetic resonance imaging of the brain showed hypoplasia of the trunk, agenesis of the cranial nerves and abnormalities in the posterior fossa in three of the ten cases in which the scan was performed. The association of multiple malformations and dysfunction of the cranial nerves suggests a disruption in the process of morphogenesis during the embryonic period, and therefore Moebius syndrome is considered to be a malformative sequence.

Low-normal gestational age as a predictor of asthma at 6 years of age.

Perinatal factors, including gestational age and birth weight, influence the development of atopy in early life. However, the role of these factors in the development of asthma in later life among children who do not develop perinatal respiratory disease remains unclear. Four hundred fifty-four infants who had a history of allergy or asthma in at least 1 parent, were born in the 36th week of gestation or later, and did not develop perinatal respiratory distress were monitored for at least 6 years. Associations between predictor variables and asthma and wheeze were assessed with multivariate logistic regression and repeated-event analyses. Although we previously observed a relationship between low birth weight and persistent wheeze in the first 1 year of life, we did not observe similar associations between low birth weight and asthma at 6 years of age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 0.40-2.73). However, a strong relationship was found between low-normal gestational age and asthma at 6 years of age (OR: 4.7; 95% CI: 2.1-10.5). The effects of low-normal gestational age were significantly greater among boys than among girls (boys: OR: 8.15; 95% CI: 2.98-22.3; girls: OR: 1.90; 95% CI: 0.38-13.83). Longitudinal analysis of the relationship between gestational age and wheeze during the 6 years of observation confirmed these gender differences. Among children at high risk of developing atopic disease, late prematurity might be an important additional determinant of asthma later in life, and these effects are gender specific.

Esteroides prenatales: ¿hora de redefinirlos?

La administración de Esteroides Prenatales (EP) con el fin de inducir la maduración pulmonar fetal ha sido una práctica aceptada durante los últimos 20 años, constituyéndose en una de las medidas prenatales más exitosas en términos de reducción de morbilidad y mortalidad perinatal secundaria a Síndrome de Dificultad Respiratoria Neonatal (SDRN). Reciente evidencia, asocia la administración de tales compuestos a diferentes efectos tanto fetales como maternos que suponen riesgos hasta el momento ignorados. Se revisa la literatura publicada en los últimos 6 años en lo referente a aspectos de dosificación, condiciones clínicas específicas (Ruptura prematura de membranas, recién nacido de muy bajo peso), así como las relaciones existentes entre los EP y ciertos desenlaces perinatales (hemorragia subaracnoidea, leucomalacia periventricular). Se concluye que es necesario redefinir sus indicaciones e individualizar su manejo en entornos clínicos específicos, mientras ensayos clínicos controlados que se llevan a cabo en este momento, permiten juicios sólidos.

Alveolar fluid clearance in late-gestational guinea pigs after labor induction: mechanisms and regulation.

We tested the hypothesis that labor-induced epinephrine release would stimulate alveolar fluid clearance in preterm fetuses. Preterm fetuses were obtained by cesarean section from timed-pregnant guinea pigs at 61-69 days postconception. Fetal guinea pigs were euthanized and placed on continuous positive airway pressure oxygenation, and an isosmolar 5% albumin solution was instilled. Alveolar fluid clearance was measured over 1 h. The fetal lung began to absorb fluid at 64-66 days postconception, and at birth, alveolar fluid clearance quadrupled. Baseline alveolar fluid clearance when present was sensitive to propranolol inhibition and depended on beta-adrenergic stimulation. Measurements of plasma epinephrine in fetal animals confirmed high epinephrine levels in 66- to 69-day postconception fetuses. Prenatal alveolar fluid clearance when present was highly amiloride sensitive, suggesting that amiloride-sensitive Na+ channels were critical. Oxytocin-induced labor initiated an amiloride- and propranolol-sensitive net alveolar fluid clearance in 61-day-gestation animals. Moreover, oxytocin induced significant epinephrine release in all fetuses. These results have clinical implications for infants delivered by cesarean section before the onset of labor. Use of pharmacological agents to induce labor may reduce the occurrence and severity of perinatal respiratory distress.

Factors Affecting the Mortality of Sick Newborns Admitted to Intensive Care Units

In order to provide better understanding of the factors affecting the mortality of sick newborns in the Taipei metropolitan area, data of newborns admitted to the intensive care units (ICU) were analyzed retrospectively according to the hospital type f care. Fourteen of the 19 hospitals with an ICU admitting sick newborns joined the data collection. 3 were local hospitals, 7 were regional hospitals and 4 were medical centers. Perinatal and neonatal data of 1083 sick newborns were analyzed: 60% were premature newborns and 58% were male newborns. The maternal referral rate was 7.8% and the neonatal transport rate was 36.2%. Fifty-nine percent of very low birth-weight newborns and 66% of extremely low birth-weight (ELBW) newborns were admitted to the medical centers. The two most common illnesses were perinatal asphyxia and respiratory distress syndrome. About 40% needed assisted ventilation. There were higher incidence of maternal referral, fetal distress, resuscitation in the delivery room, perinatal asphyxia, and necrotizing enterocolitis; lower incidence of meconium aspiration syndrome, sepsis and pneumothorax in newborns admitted to the medical center than those newborns admitted to other hospitals. A total of 153 newborns (14%) died. The most common cause of death was sepsis (22.9%). Multivariate logistic regression analysis revealed that factors significantly related to the mortality were gestational age＜28 weeks, congenital anomaly, sepsis, resuscitation in the delivery room, neonatal transport, congenital heart disease, hospital type of care, ELBW, pneutnothorax and high-risk pregnancy. The results of the study stress the importance of regionalization of perinatal and neonatal care, organization of neonatal transport system, newborn resuscitation training, infection control, and delicate ventilatory care in the further improvement of the outcome of sick newborns in the Taipei metropolitan area.

Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice.

Genetic ablation of the murine SP-B gene in transgenic mice caused lethal perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild-type littermates, consistent with the inactivation of a single SP-B allele. Expression of SP-A, SP-C, and SP-D proteins was not affected in SP-B(+/-) mice. Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian inheritance of a recessive gene. Lung morphology and both intracellular and extracellular phospholipid pool size and composition were unaltered in the SP-B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP-B(+/-) mice. Abnormalities of inflation/deflation curves demonstrated airway collapse at low deflation pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP-B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in abnormalities of lung compliance and air trapping, suggesting a potential susceptibility to pulmonary dysfunction associated with SP-B deficiency.

Quality of Survivals on Conservative Neonatal Care

Quantity as well as quality of survivals determine the performance of a neonatal centre. Our centre has succeeded in improving survival with low cost technology without compromising the quality. Neurodevelopmental handicap was low on a 1-year follow-up. No baby had retinopathy of prematurity or hearing deficit. Dropout rate has been high although comprising of mainly full-term or near-term babies with mild perinatal asphyxia or mild respiratory distress or requiring instrumentation during delivery. Longer follow-up is desirable.

Follow-up of visual evoked potential in full-term and pre-term control newborns and in subjects who suffered from perinatal respiratory distress

Thirty-five healthy newborns (18 pre-term) and 13 subjects who had suffered from slight (5), middle (3) or severe (5) respiratory syndromes were examined with VEP recording and clinically. Twelve subjects (9 pre-term) affected by perinatal troubles of different kinds (dismetabolic, infectious, etc.) were used for further comparison. A total of 102 records were taken between the 5th and 15th days of life, while for 6 controls, 6 of the second group and 2 of the third one, VEP records and clinical examinations were performed at the 2nd, 6th and 9th months of life. The evoked response was analysed as follows: P 2 wave latency, number of waves, maximal driving frequency with intermittent stimulation and prevalent polarity of the evoked waves. VEPs in normals were well correlated with gestational age, chronological age and body weight for P 2 latency decrement (from about 200 msec at birth down to 110 msec at the 9th month), increase in number of evoked waves, progressively higher maximal frequency of flicker response and clear-cut prevalence of negative polarities in the final response. Neonatal respiratory distress (middle and severe types) induced a severely altered VEP (mainly with delayed peaks and positive polarity) even at the 9th month of extrauterine life.

Transient myocardial ischemia of the newborn infant demonstrated by thallium myocardial imaging

Five term and two premature newborn infants were referred for respiratory distress and congestive heart failure, and were found to have electrocardiographic Q or ST-T abnormalities suggesting ischemia. Echocardiographic and/or hemodynamic assessment excluded anatomic heart disease in six infants. In three infants, moderate or severe hemodynamic impairment within 36 hours of age was suggested by these studies. Myocardial perfusion images in all patients showed very poor myocardial uptake of thallium 201, compatible with global myocardial ischemia. Infants of similar age with myocarditis, or with congenital heart disease and congestive failure, had normal myocardial uptake. Rapid clinical improvement occurred within three to seven days. Two to five months later, all infants were well. Two had persistent electrocardiographic abnormalities but repeat thallium 201 imaging in six demonstrated almost normal myocardial uptake. These data provide further evidence that perinatal respiratory distress may be associated with myocardial dysfunction and congestive heart failure in some infants without anatomic heart disease, and suggest that myocardial dysfunction in these infants is associated with global myocardial ischemia, most of which is transient. The timing and nature of the insult causing the ischemia are unclear.