Neonatal Adaptation Research Articles

A Needed Information Source

Most sources of information regarding drugs in pregnancy include information on whether a drug causes congenital anomalies and whether a drug causes changes in fetal function or neonatal adaptation. Therapeutic issues related to the treatment of maternal disease are not readily available. Despite known physiologic changes of pregnancy, drug dosages are widely assumed to be the same as the healthy adult. An informational source is needed which addresses the therapeutic issues of pregnant women.

Pulmonary Neuroendocrine Cell System in Pediatric Lung Disease—Recent Advances

The airway epithelium of human and animal lungs contains highly specialized pulmonary neuroendocrine cells (PNEC), distributed as solitary cells and as innervated clusters, neuroepithelial bodies (NEB). The designation "PNEC system" stems from the expression of both neural and endocrine cell phenotypes, including the synthesis and release of amine (serotonin, 5-HT) and a variety of neuropeptides (that is, bombesin). The role and function of PNEC in the lung have remained a subject of speculation for many years. During the last decade, studies using modern techniques of cellular and molecular biology revealed a complex functional role for PNEC, beginning during the early stages of lung development as modulators of fetal lung growth and differentiation and at the time of birth as airway O2 sensors involved in neonatal adaptation. Postnatally and beyond, PNEC/NEB are providers of a lung stem cell niche that is important in airway epithelial regeneration and lung carcinogenesis. The focus of this review is to present and discuss recent findings pertaining to the responses of PNEC to intrauterine environmental stimuli, ontogeny and molecular regulation of PNEC differentiation, innervation of NEB, and their role as airway chemoreceptors, including mechanisms of O2 sensing and chemotransmission of hypoxia stimulus. Abnormalities of PNEC/NEB have been reported in a variety of pediatric pulmonary disorders but the clinical significance or the mechanisms involved are unknown. The discussion on the possible role of PNEC/NEB in the pathogenesis and pathobiology of pediatric lung diseases includes congenital lung disorders, bronchopulmonary dysplasia, disorders of respiratory control, neuroendocrine hyperplasia of infancy, cystic fibrosis, bronchial asthma, and pulmonary hypertension.

Thérapeutique des troubles anxieux et dépressifs de la grossesse et du post-partum. Revue et synthèse

The aim of this article is to review the main methods of treatment of anxious and depressive disorders during pregnancy and the postpartum. To this end, we analyse recent publications about the use and efficacy of psychotherapy and psychosocial interventions (cognitive behavioural therapy, interpersonal psychotherapy, psychoanalytical therapy) in the perinatal period. We also review recent papers about the use of psychotropic medication during pregnancy and breast-feeding, with special emphasis on clinical trials. We particularly focus on the risk/benefit assessment of antidepressants, mood stabilisers, antipsychotics and benzodiazepines, in terms of teratogenicity, and impact on neonatal adaptation and neuropsychological development. Various treatment modalities are presented and discussed. It appears that psychotherapies have proved their efficiency on most pre- and postpartum anxious and depressive disorders and represent a first line treatment in most cases. Psychopharmacological treatment is indicated for severe anxious and depressive disorders. The risks of such medication, especially antidepressants, may have been overestimated in the past. Provided reasonable precautions are taken and mothers and future mothers receive clear information on the potential risks and benefits, psychotropic medication could be more broadly prescribed during pregnancy and the breast-feeding period.

Neonatal Facial Movements in the First Minutes of Life-Eye Opening and Tongue Thrust: An Observational Study

Infants born by caesarean section (CS) near or at term were observed to display spontaneous facial movements in their first minutes. We hypothesized that those are reproducible. Up to now, nothing was known about the significance, frequency, and determinants of such facial activity. Repetitive eye opening (EO) and tongue thrust (TT) actions were documented during 1 to 5 minutes, 5 to 10 minutes, and 1 to 15 minutes in 102 infants. In addition, 32 infants were recorded on video from minute 2 to minute 10. Infant- and maternal- influencing factors were noted and videos analyzed using Interact (Version 7.1, Mangold International, Arnstorf, Germany). According to our results, 99 of 102 newborns (gestational age, 33 to 42 weeks) performed EO or TT during the first 15 minutes. Preterm and infants with lower Apgar scores and infants born under general anesthesia showed less EO. Infants of smoking mothers, newborns admitted to special care, and infants with lower umbilical artery pH had significantly fewer TT episodes. Within a "normal" population of newborns of > 37 weeks at delivery (n = 57), 97% showed EO and 95% showed TT. In the filmed 32 newborns, infants began EO at 2:40 and TT at 2:34 minutes of life on average. Crying had no influence, but suctioning/intervention reduced EO frequency. In conclusion, EO and TT are occurring regularly during neonatal adaptation. TT seems to be an inborn automatic behavior; numerous occurrences of EO argue for neurological well-being. Both facial actions may initiate maternal-infant attachment.

Antenatal Depression: Navigating the Treatment Dilemmas

“Ms. A” was a 35-year-old married Caucasian health care professional with a history of recurrent major depressive disorder that responded well to treatment with a selective serotonin reuptake inhibitor (SSRI). She discontinued her antidepressant prior to conception for a planned pregnancy because she did not want to expose her baby to medication. She soon relapsed, and by the first trimester of her pregnancy, she was in a major depressive episode. Her symptoms included anhedonia, tearfulness, irritability, insomnia, and diminished appetite. She presented for participation in an open-label pilot trial of omega-3 fatty acids for antenatal major depressive disorder (1). At intake, after hearing the risks and benefits of available treatment options, Ms. A declined antidepressant medication and a referral for psychotherapy and consented to participate in the study of omega-3 fatty acids, which she started at 16 weeks’ gestation. She was assessed every 2 weeks throughout pregnancy. At 8 weeks she had not responded to omega-3 fatty acids and was again presented with other treatment options, including medication and psychotherapy. She again declined these treatments and continued to do so throughout the remainder of her pregnancy. She was concerned about the safety of medications in pregnancy and believed that taking medication would make her a bad mother. She also declined referral for psychotherapy, stating that she was “too busy.”

The postnatal changes in red blood cell NO levels

To determine the levels of RBC HbSNO and HbFe(II)NO using chemiluminescence in very low birth weight infants breathing room air, during the first 2 days of life. RBC NO values were compared to the levels obtained in cord blood at birth from infants of similar gestational age. Five infants ranging from 25 to 27 weeks of gestation were sampled between 12 and 24 h after birth. These infants were considered as the postnatal group and had normal blood gases at room air. The HbSNO levels were increased in the postnatal group from 49.0 +/- 17.4 nm to 152.3 +/- 54.3 nm (p = 0.0006). There was no difference in HbFe(II)NO levels between the two groups (mean of 267.6 +/- 186.5 nm in cord blood and 180.3 +/- 89.2 nm in the postnatal sample. The increase in HbSNO postnatally could be an important mechanism for the neonatal pulmonary adaptation to extra-uterine life.

The medicolegal implications of hypoglycaemia in the newborn

Neonatal hypoglycaemia is commonly physiological, but failure of normal neonatal metabolic adaptation may occur, causing persistent and severe hypoglycaemia with concomitant brain injury. Little is known about the level and duration of neonatal hypoglycaemia which cause brain injury, and studies of the long-term effects of hypoglycaemia are flawed by confounding factors. This paper reviews the etiology, clinical significance and preventive management of neonatal hypoglycaemia, and makes recommendations for safe practice. Criteria for establishing an association between neonatal hypoglycaemia and brain injury are outlined.

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P<0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.

Perinatal Physiology in Cloned And Normal Calves: Hematologic And Biochemical Profiles

Although a majority of clones are born normal and apparently healthy, mortality rates of nearly 30% are described in many reports. Such losses are a major limitation of cloning technology and represent substantial economic investment as well as justifiable animal health and welfare concerns. Prospective, controlled studies are needed to understand fully the causes of neonatal mortality in clones and to develop preventive and therapeutic strategies to minimize losses. We report here the findings of studies on the hematologic and biochemical profiles of cloned and control calves in the immediate 48-h postpartum period. Cloned calves were similar to control calves for a majority of parameters studied including blood gases, concentrations of plasma proteins, minerals and electrolytes, and white blood cell, neutrophil, lymphocyte, and platelet counts. The most notable differences between clones and controls in this study were reduced red- and white-blood cell counts in clones at birth and 1 h of age. As a group, plasma electrolyte concentrations were more variable in clones, and the variability tended to be shifted either higher (sodium, chloride) or lower (potassium, bicarbonate) than in controls. Previously, we noted differences in carbohydrate parameters, the length of time required for clones to make the neonatal adaptation to life ex utero, and morphology of the cloned placenta. Taken together, our findings suggest that cloned calves experience greater difficulty adjusting to life ex utero and that further research is warranted to determine the nature of the relationship between the physiological differences noted here in clones at birth and concomitant abnormal placental morphology.

Safety of Newer Antidepressants in Pregnancy

Pharmacotherapy for depression is often necessary during pregnancy. The information available about use of the newer antidepressants in pregnant women is limited by trial design and lack of long-term follow-up of exposed infants. Selective serotonin reuptake inhibitors (SSRIs) are not generally thought to be major teratogens. Some recent studies, however, have suggested that paroxetine may be associated with a small increase in risk of congenital abnormalities, particularly cardiac defects. Data on the effect of SSRIs on the incidence of preterm birth, spontaneous abortion, and fetal death are conflicting. Third-trimester exposure to newer antidepressants, including SSRIs and serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine), has been associated with a poor neonatal adaptation syndrome. In addition, SSRI use may be associated with an increased risk of persistent pulmonary hypertension of the newborn. Preliminary evidence suggests that SSRI exposure in utero does not have significant long-term effects on cognition or behavior. Based on limited information, mirtazapine, bupropion, and venlafaxine do not appear to be major teratogens. Little or no information is available on duloxetine.

Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks’ gestation: a randomised controlled trial

Objective:To investigate the effects of umbilical cord milking on the need for red blood cell (RBC) transfusion and morbidity in very preterm infants.Patients and Methods:40 singleton infants born between 24...

Externalizing and Attentional Behaviors in Children of Depressed Mothers Treated With a Selective Serotonin Reuptake Inhibitor Antidepressant During Pregnancy

To evaluate attentional and activity behaviors in 4-year-olds following prenatal selective serotonin reuptake inhibitor (SSRI) exposure. Prospective cohort design. Tertiary care center. Twenty-two 4-year-olds with prolonged prenatal SSRI medication exposure and 14 children without prenatal exposure. Prenatal SSRI exposure. Group differences in externalizing behaviors (according to the Child Behavior Checklist) and direct observations of child attention, activity, and impulsiveness in a laboratory setting using the procedure by Crowell and colleagues were compared, including measures of the duration of prenatal SSRI exposure, umbilical cord drug levels, a history of poor neonatal adaptation, and maternal mood. Externalizing behaviors did not differ between groups. Maternal depression and anxiety at the 4-year follow-up were associated with increased reports of externalizing behaviors. Increased externalizing behaviors were associated with increased umbilical cord drug levels (F(1,34) = 6.3; P = .02), but when controlling for maternal depressed mood at the 4-year follow-up, such levels only accounted for 11.2% of the behavioral outcomes (P>.05). On direct observation, the persistence score for child behavior was significantly lower in the exposed group. Increased aggressiveness scores were associated with a history of poor neonatal adaptation, even when parental report of stress was added to the model (F(1,34) = 4.0; P = .03); however, neither parental report of stress nor poor neonatal adaptation were significant (both P = .09), suggesting that both are important, if not unique, predictors of child behavior. These findings suggest that the best predictors of externalizing behaviors at age 4 years are current maternal mood and parental stress, regardless of prenatal depressed mood and SSRI treatment during pregnancy. It remains uncertain whether poor neonatal adaptation can be excluded as a possible predictor of externalizing behaviors.

Clinic-morphological aspects of the state of the fetoplacental complex at pregnant women with hyperandrogenism

The study of the fetoplacental complex and the morphological research of placenta of 50 pregnant women with hyperandrogenism were conducted by the ultrasonic method, dopplerometry and cardiotocography. It was shown that hyperandrogenism causes destructive and neonatal adaptation changes of placenta leading to its dysfunction. The high frequently of occurrence of complications in the gestational process at late diagnostics of hyperandrogenism (during pregnancy) was observed.

Paroxetine Use During Pregnancy: Is it Safe?

To evaluate the literature assessing the neonatal risks of antepartum paroxetine use. MEDLINE (1966-August 2006) and International Pharmaceutical Abstracts (1970-August 2006) searches were performed. Key search terms included paroxetine, SSRI, pregnancy, malformations, neonate, and fetus. Selective serotonin-reuptake inhibitors (SSRIs) are associated with neonatal withdrawal symptoms such as respiratory distress, irritability, lethargy, and tremors. In a cohort study, 30% of infants exposed to SSRIs had poor neonatal adaptation, compared with 9% of controls (p = 0.018). Some reports indicate that paroxetine is more commonly associated with neonatal withdrawal than other SSRIs. Recently, paroxetine was associated with a 1.82-fold (95% CI 1.17 to 2.82) increased risk of congenital malformations compared with other antidepressants. Other SSRIs were also associated with an increased risk of congenital malformations; however, the results were not statistically significant. Literature supporting these findings includes case reports and case-control or cohort studies. The Food and Drug Administration recommendations regarding paroxetine use during pregnancy have been added to the labeling information. Paroxetine may cause adverse outcomes in the neonate when used during pregnancy and should be discontinued in women who are pregnant or trying to become pregnant. The risks and benefits of other antidepressant use should be analyzed on an individual basis.

P02.91: Perinatal outcome after first‐ and second‐trimester screening

Aim of this study was to assess the perinatal outcome after first- and second-trimester screening depending on chromosomal and structural abnormalities. We performed a first-trimester nuchal translucency screening at 11 to 14 weeks of gestation in 603 singleton pregnancies including a detailed morphological scan, additionally the investigation of the four chamber view and the left- and right ventricular outflow tracts. From this group, in 585 singleton pregnancies second-trimester-screening at 18–22 weeks was performed. The perinatal outcome (mode of delivery, birth weight, Apgar score, umbilical cord pH and perinatal mortality) of 570 cases was recorded. The median maternal age of the 603 cases was 31 (range, 16–44), the median gestation at first-trimester-screening was 12 + 6 (11 + 1 to 13 + 6) weeks and the median gestation at second-trimester-screening was 19 + 2 (18 + 0 to 21 + 6). Nineteen (3%) of the 603 fetuses had a chromosomal abnormality. Of the 603 fetuses had twenty a termination of pregnancy, 6 a spontaneous abortion and 7 an intrauterine fetal death. 44 of the 603 fetuses had 88 structural abnormalities considered as being detectable by sonography. 6 fetuses of the 570 with perinatal outcome had a chromosomal abnormality (2x 47XXY and 4x other) and 21 fetuses had 31 structural abnormalities detected at first- and second-trimester-screening. However, parameters of initial neonatal adaptation did not differ significantly. First-trimester screening leads to an early identification and selection of pregnancies with adverse outcome. Fetuses with structural abnormities are regarding the early neonatal period and postnatal adaptation comparable to healthy newborns.

Elective cesarean section and fetal immune-endocrine response

There is today much evidence that labor and vaginal delivery have beneficial shortand longterm effects on neonatal respiratory adaptation to extrauterine life [1]. Indeed, the increased rates of elective cesarean section (ECS), a procedure long believed to be less distressing for the fetus, have been associated with a higher risk of iatrogenic respiratory distress syndrome (RDS) for the neonate [2,3]. In animal and human studies, pulmonary edema, decreased secretion and deposition of surfactant in the alveolar space, and decreased levels of catecholamines and stress hormones have been found to occur in individuals with RDS. More recently, it has also become clear that cytokines

Morbimortalidad perinatal de la rotura prematura de membrana en el embarazo pretérmino

Objective A retrospective and descriptive study was undertaken to determine the association between perinatal morbidity and mortality and premature rupture of membranes over a period of 1 year at the Ana Betancourt de Mora Gynecology and Obstetrics Provincial Hospital in Camagüey. Material and method The study included 52 women who presented with premature rupture of membranes and delivered during this period. The parameters analyzed included the patient's age, pregnancyrelated diseases, place of occurrence, duration of the rupture, and perinatal morbidity and mortality. Results The main associated abnormalities were anemia and vaginal infection. The principal causes of morbidity in neonates were neonatal pneumonia and adaptation distress, which were closely associated with the latency period of membrane rupture and birth weight. A total of 90.9% of the neonates survived. Conclusions There is a high incidence of perinatal morbidity and mortality associated with premature rupture of membranes en preterm pregnancies. This occurs mainly as a results of infections, which are more likely the longer the latent period is.

Treatment With Selective Serotonin Reuptake Inhibitors During Pregnancy: Deceleration of Weight Gain Because of Depression or Drug?

In 1996, Chambers and colleagues (1) reported that exposure to fluoxetine in the third trimester of pregnancy was associated with an increased risk of preterm birth, smallfor-gestational-age infants, admission to special care nurseries, and poor neonatal adaptation, including respiratory difficulty, cyanosis on feeding, and jitteriness. This landmark article generated substantial concern among clinicians that third-trimester exposure to fluoxetine (and potentially other selective serotonin reuptake inhibitors [SSRIs]) was contributing to adverse outcomes in pregnancy. Of interest, no

Prenatal diagnostic indicators of paternal uniparental disomy 14

To present clinical findings of a child with paternal uniparental isodisomy 14 (pat UPD14) focusing on relevant prenatal characteristics. Ultrasonography at 23 weeks of gestation of a 37-year-old multigravid woman revealed a fetus with polyhydramnios, small thorax, and short, distinctively angled ribs. Fetal karyotype was 46,XY. The child was born spontaneously at 35 weeks with poor neonatal adaptation. From birth, he presented with severe respiratory insufficiency due to severe thoracic malformation. Clinical examination revealed a small, bell-shaped thorax, redundant lax skin, mild contractures of the fingers and dysmorphic facial features. Chest X rays showed short, abnormally curved ribs that suggested the possibility of pat UPD14, which was confirmed by molecular analysis. Pat UPD14 is associated with a distinct clinical phenotype. Prognosis is poor because of severe respiratory insufficiency and neurodevelopmental retardation. Our report confirms salient postnatal signs of previous descriptions, especially the characteristic radiological abnormalities with ribs showing a 'coat-hanger' configuration. Retrospective fetal ultrasound of our case allowed the identification of this pathognomonic feature prenatally, which makes it possible to consider pat UPD14 at routine prenatal sonography, in particular in combination with a small bell-shaped thorax and polyhydramnios.

Is there a correlation of Venlafaxin (Efexor®) therapy during pregnancy and a higher incidence of necrotizing enterocolitis?

Background: Neonates exposed to Venlafaxine (Efexor®), a serotonin and norepinephrine reuptake inhibitor, are at risk for severe withdrawal symptoms, poor neonatal adaptation including respiratory difficulties and as previously reported necrotizing enterocolitis (NEC). We present twins who both developed necrotizing enterocolitis on the 6th day of life. Objective: The twins were delivered by cesarian section at a gestational age of 33+2 weeks due to persistent vaginal bleeding and contractions secondary to placenta praevia marginalis. Until 4 days before delivery the mother was treated with Venlafaxine (Efexor®) for depression. The pregnancy was otherwise uneventful. Twin A: birthweight 1700g (P15), Apgar 6/ 7/ 8, pHa 7.22. Twin B: brithweight 1980g (P30), Apgar 4/ 5/ 8, pHa 7.24. Both twins were intubated in the first hour of life because of respiratory insufficiency and exceeding need for oxygen. They could be extubated on the second day of life and further treatment was without complications. Enteral feeding was started on the first day of life with maltodextrin® and breast milk. On the 6th day of life twin B developed abdominal distension, sings of peritonitis, bloody stool and gastric residuals. Conservative management was started with intravenous antibiotics and oral feeds were stopped. A few hours later also twin A showed sings of NEC. Apart from clostridium difficile toxin in the stool of twin A stool cultures were negative. Because the conservative therapy in twin B failed surgical intervention was necessary and it showed multiple perforations of the hemorrhagic ischemic colon. Conclusion: Despite of prematurity as a risk factor for NEC we should keep in mind that medication with Venlafaxine (Efexor®) could also have the potential to increase the risk for NEC.