Selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors in pregnancy: Infant and childhood outcomes

This position statement provides guidance for the monitoring, care, and follow-up of newborns exposed to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in utero. Depression and anxiety are common during pregnancy and postpartum. While there are risks to taking medications during pregnancy, untreated or incompletely managed depression and anxiety also carry risks for the newborn. Poor neonatal adaptation syndrome (PNAS) occurs in one-third of newborns exposed to SSRIs or SNRIs in utero, and is generally mild and self-limiting. The low levels of SSRIs and SNRIs excreted in breast milk are compatible with breastfeeding. Persistent pulmonary hypertension of the newborn and congenital heart defects are rare associations of exposure to SSRIs or SNRIs in utero. There are inconsistencies in the literature regarding neurodevelopmental outcomes, specifically autism spectrum disorder and attention-deficit hyperactivity disorder. The inconsistencies likely relate to other factors (i.e., genetics, maternal depression, lifestyle, and comorbidities), rather than exposure to SSRIs or SNRIs in utero. Health care providers and parents should be reassured that PNAS is generally treatable with nonpharmacological measures, and that the risk of serious adverse effects from exposure to SSRIs or SNRIs in utero is low.     

Neurobehavioral assessment of infants born at term and in utero exposure to serotonin reuptake inhibitors

Background

Some studies report neurobehavioral symptoms in neonates exposed to serotonin reuptake inhibitors (SRIs) in utero. However, maternal psychiatric illness during the last trimester of pregnancy, as a confounding factor, has not always been assessed.

Aims

In this prospective study we compared neurobehavioral complications among neonates who were born to euthymic women who either took or did not take an SRI during the last trimester of pregnancy.

Study design

Exposed and unexposed infants were assessed for: 1) temperament as measured by the Neonatal Behavioral Assessment Scale (NBAS); 2) activity via Actiwatch electronic monitoring; 3) sleep state using trained observer ratings; and 4) perinatal complications through medical record review. T-tests, Fisher's exact tests, and analyses of covariance were used to assess the relationship between clinical and neurobehavioral factors and exposure status.

Subjects

67 infants (61 controls and 6 exposed to SRIs).

Outcome measures

Neonatal Assessment Behavioral Scale, APGAR scores, infant sleep state (% sleep, % wakeful), startles and tremulousness, gestational age, birth weight, and head circumference.

Results

Infants exposed to SRIs in the third trimester had poorer motor development, lower 5-minute APGAR scores, and shorter mean gestational age as compared to unexposed infants.

Conclusion

Results of this study show differences in autonomic and gross motor activity between neonates who were or were not exposed to SRIs in utero after controlling for active maternal psychiatric illness. Future longitudinal work should compare longer term outcomes of exposed and unexposed infants of depressed mothers.     

Selective serotonin reuptake inhibitors in pregnancy and infant outcomes

Adequate treatment of depression during pregnancy is very important for maternal, fetal and neonatal health. Selective serotonin reuptake inhibitors (SSRIs) are commonly used antidepressants. According to one American study, approximately 7% of pregnant women were prescribed an SSRI in 2004–2005. First trimester use of SSRIs, as a group, is unlikely to increase the risk of congenital malformations. Paroxetine may be associated with a small increased risk of cardiac malformations, but evidence remains inconclusive. Fetal exposure to SSRIs closer to time of birth may result in respiratory, motor, central nervous system and gastrointestinal symptoms in about 10% to 30% of newborns (SSRI neonatal behaviour syndrome). These symptoms are usually mild and transient. Persistent pulmonary hypertension of the newborn is an extremely rare consequence of fetal exposure. This information should be used to make individual risk-benefit decisions when considering the treatment of depression during pregnancy. Newborns with late-pregnancy exposure to SSRIs should be observed in hospital for at least 48 h.     

Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero

Aim: To study the neonatal outcome of infants exposed to buprenorphine in utero .
Methods: We prospectively followed 54 buprenorphine-using pregnant women and their 58 infants. Urinary buprenorphine and norbuprenorphine concentrations in the mothers were measured prior to delivery, and in the infants during the first 3 days of life. The Finnegan score was used to evaluate neonatal abstinence syndrome. Other medical problems as well as social outcomes were recorded.
Results: All infants had buprenorphine in their urine. A total of 38 infants required 20 ± 10 days (range 7–48 days) of morphine treatment for neonatal abstinence syndrome. The length of hospital stay for all infants was 25 ± 19 days (range 3–125 days). The infants' highest urinary norbuprenorphine concentrations across their first 3 days of life correlated with the length of hospital stay and duration of morphine treatment (both p < 0.05). The mean birth weight and mean head circumference (n = 58) were below average (mean −0.7 standard deviation [SD] and mean −0.5 SD, respectively). Eleven infants were discharged home, 19 infants were placed in foster care and 28 infants were discharged with their mothers to Mother and Child homes or to other institutions.
Conclusion: Maternal buprenorphine use at the time of birth may cause neonatal abstinence syndrome, requiring long-term hospitalization. Multiple social problems require a multidisciplinary team approach.     

Effects of bathing immediately after birth on early neonatal adaptation and morbidity: A prospective randomized comparative study

OBJECTIVE: Because the risks and benefits of early bathing of newborn infants are not well established, we investigated the effects of bathing immediately after birth on rectal temperature, respiratory rate, heart rate, blood pressure, percutaneous arterial blood oxygen saturation (SpO2) and early neonatal morbidity. METHODS: The study was designed as a randomized prospective comparative study in the neonatal care unit of a university hospital. A total of 187 healthy term and near-term newborn infants, who were delivered vaginally without asphyxia, between January and December 1997 were the study subjects. We compared findings in newborns who were bathed 2-5 min after birth (n = 95) with those of a control group (n = 92) who received dry care instead. Groups were comparable with respect to gestational age, birthweight, male: female ratio, Apgar score and umbilical blood pH. Rectal temperature was measured with an electronic thermometer immediately before the intervention bathing or dry care and at 30 min and 1, 2, 3, 8 and 12 h after birth. Heart rate, respiratory rate, systolic and diastolic blood pressure and SpO2 were measured at 1, 2, 8 and 12 h after birth. The incidence of early neonatal morbidity, including hyperbilirubinemia and gastrointestinal and respiratory problems, was also compared. RESULTS: Rectal temperature changed over time postnatally in both groups (P < 0.0001, ANOVA) and there was a significant difference in rectal temperature between groups (P< 0.0001, ANOVA). Mean (+/- SEM) rectal temperature at 30 min after birth (i.e. approximately within 20 min after intervention) was significantly higher in the bathed group than in the control (dry care) group (37.30 +/- 0.06 is 37.00 +/- 0.05 degrees C, respectively; P = 0.000022). Respiratory rate, heart rate, blood pressure and the ratio of the number of infants with SpO2 90-94% and 95-100% did not differ significantly between the two groups. The incidence of early neonatal morbidity, including vomiting, acute gastric mucosal lesion, polycythemia, need for tube feeding, phototherapy and oxygen therapy, also did not differ between the two groups. CONCLUSIONS: Early bathing, minutes after birth, did not appear to adversely affect the adaptation of healthy full-term and near-term newborn infants.     

254例双胎新生儿不良结局危险因素分析

目的：探讨双胎新生儿不良结局的危险因素,为提高双胎新生儿的存活及改善预后提供参考。方法：收集2005年1月至2009年12月入住我科的254例双胎新生儿临床资料进行回顾性分析,分析不良结局的危险因素。结果：254例双胎儿中,84例有不良结局（33.1％）,其中死亡10例（3.9％）。多因素分析结果显示通过辅助生殖技术受孕是不良结局的保护因素（OR＝0.389,P＜0.05）;胎龄（≤34周）、脐带异常、羊水粪染和5 min Apgar评分≤7是不良结局的独立危险因素（OR分别为4.434、4.731、3.424、18.958,P＜0.05）。结论：胎龄≤34周、脐带异常、羊水粪染或5 min Apgar评分≤7的双胎儿易出现新生儿期不良结局。［中国当代儿科杂志,2010,12（10）：777-780］     

新生儿细菌性脑膜炎预后不良的危险因素分析

目的 探讨新生儿细菌性脑膜炎预后不良的危险因素。方法 回顾性分析152例细菌性脑膜炎新生儿的临床资料,根据转归分为预后良好组（n=122）与预后不良组（n=30）,比较两组患儿的一般情况、首发症状及实验室检查结果,分析预后不良的危险因素。结果 预后不良组极低出生体重、外周血WBC < 5×10⁹/L或 > 20×10⁹/L、C-反应蛋白 > 50 mg/L、脑脊液WBC > 500×10⁶/L、脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L比例高于预后良好组（P < 0.05）,血培养和/或脑脊液培养阳性率、革兰阳性菌及无乳链球菌培养阳性率高于预后良好组（P < 0.05）。多因素logistic回归分析显示,脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L是新生儿细菌性脑膜炎预后不良的独立危险因素。结论 脑脊液糖 < 1 mmol/L、脑脊液蛋白 > 2 g/L是新生儿细菌性脑膜炎预后不良的危险因素。     

双胎配对早产儿坏死性小肠结肠炎发生危险因素分析

目的探讨早产儿坏死性小肠结肠炎(NEC)发病的危险因素。方法以双胎配对为基础,回顾分析2012年1月1日至2018年12月31日出生、仅1胎患NEC早产双胞胎的临床资料,比较NEC组与对照组之间的基本资料(出生体质量、产时窒息、出生顺序、性别)、危险因素(喂养情况、治疗措施、疾病状态)。结果 NEC组发生喂养不耐受的比例高于对照组,发病前48小时内浓缩红细胞输注比例高于对照组,生后1周内血红蛋白最低值、起病前最后一次输浓缩红细胞当日血红蛋白水平低于对照组,差异均有统计学意义(P0.05)。条件logistic回归分析显示,喂养不耐受(P=0.018,OR=7.26,95%CI:1.40～37.77)、早期贫血(P=0.022,OR=10.21,95%CI:1.41～74.01)、NEC发病前48小时内浓缩红细胞输注(P=0.023,OR=16. 65,95%CI:1. 47～188. 09)为NEC发病的独立危险因素。结论喂养不耐受、早期贫血、NEC发病前48小时内浓缩红细胞输注与NEC发病相关。     

新生儿重症监护室肺炎克雷伯菌败血症危险因素及临床特征

目的分析新生儿重症监护室（NICU）中肺炎克雷伯菌败血症的危险因素和临床特征，做到早期诊断和合理治疗。方法对我院NICU 2005年1月至2008年5月期间16例确诊为肺炎克雷伯菌败血症患儿的临床资料和药敏结果进行回顾性分析，并与同期32例非败血症患儿和33例其他病原体所致败血症患儿进行比较。结果低出生体质量、外周静脉中心静脉置管（PICC）、先期使用3代头孢菌素为肺炎克雷伯菌败血症的危险因素，所有病例均属于医院获得性感染，全部发生在早产儿，81．2％是极低出生体重儿；若同时合并其他致病菌感染预后差；肺炎克雷伯菌93％为产β内酰胺酶（ESBL）菌株，100％对亚胺培南类药物敏感，对常用头孢类药物不敏感。结论肺炎克雷伯菌已成为NICU中败血症的主要致病茵，而且多为医院感染。与早产低出生体质量、PICC、先期使用3代头孢菌素有关，耐药性强，碳青霉烯类是敏感药物。     

A role for metabolism in determining neonatal immune function

Immune responses of neonates differ markedly to those of adults, with skewed cytokine phenotypes, reduced inflammatory properties and drastically diminished memory function. Recent research efforts have started to unravel the role of cellular metabolism in determining immune cell fate and function. For studies in humans, much of the work on metabolic mechanisms underpinning innate and adaptive immune responses by different haematopoietic cell types is in adults. Studies investigating the contribution of metabolic adaptation in the unique setting of early life are just emerging, and much more work is needed to elucidate the contribution of metabolism to neonatal immune responses. Here, we discuss our current understanding of neonatal immune responses, examine some of the latest developments in neonatal immunometabolism and consider the possible role of altered metabolism to the distinctive immune phenotype of the neonate. Understanding the role of metabolism in regulating immune function at this critical stage in life has direct benefit for the child by affording opportunities to maximize immediate and long-term health. Additionally, gaining insight into the diversity of human immune function and naturally evolved immunometabolic strategies that modulate immune function could be harnessed for a wide range of opportunities including new therapeutic approaches.     

新生儿重症监护病房医院内感染高危因素及防治策略

随着新生儿重症监护病房(neonatal intensive care unit,NICU)诊治技术的不断发展,医院内感染逐渐增多.做好NICU院内感染的监控工作,对提高新生儿的存活率及NICU的管理水平至关重要.该文分析探讨医院内感染的原因,并讨论医院内感染的防治对策.     

Risk factors for nosocomial sepsis in newborn intensive and intermediate care units

Abstract A multicentre prospective study was performed to estimate the incidence of hospital infections and to identify the most relevant risk factors for sepsis in a large and unselected population of high-risk newborns. The study involved 49 neonatal intensive care units and 17 neonatal intermediate care units in Italy. Newborns were followed up from admittance to the units until discharge. Data on demographics and clinical characteristics, exposure to the principal invasive procedures, and onset of infectious complications were prospectively collected. Only infections developing after 48 h from admittance to the unit were recorded. A multiple logistic regression was performed to identify which factors were independently associated with sepsis. Among the 8263 newborns included in the analysis, the incidence of infected newborns was 14.4 per 100 newborns and 0.9/100 days of stay. The incidence of infections was 19.1/100 newborns and 1.2/100 days of stay. Sepsis represented 15.4% of all infections (incidence 2.9/100 newborns and 0.2/100 days of stay). The following factors were independently associated with sepsis: umbilical catheterization, both through the vein and the artery for more than 5 days; mechanical ventilation for more than 5 days; necrotizing enterocolitis; birth weight equal to or less than 2500 g; nasogastric tube; total parenteral nutrition; and transfer from other hospitals. Umbilical catheters accounted for the highest proportion of sepsis (62%), followed by arterial catheters (31%), nasopharyngeal cannulae (26%), tracheal cannulae (20%), and nasal cannulae (20%). The population attributable risk for the other procedures was less than 10%.Conclusion This study demonstrates that in a large and unselected newborn population, several host factors and invasive procedures are independently associated with an increased risk of sepsis. After adjustment for clinical severity, intravascular catheterization and assisted ventilation were found to be responsible for a considerable proportion of observed sepsis. They shoudl therefore be considered as priorities for interventions, aimed both at reducing unnecessary use and promoting more strict compliance with aseptic practices.     

Temperature, metabolic adaptation and crying in healthy full-term newborns cared for skin-to-skin or in a cot

The aim of the present study was to compare temperatures, metabolic adaptation and crying behavior in 50 healthy, full-term, newborn infants who were randomized to be kept either skin-to-skin with the mother or next to the mother in a cot "separated". The babies were studied during the first 90 min after birth. Axillary and skin temperatures were significantly higher in the skin-to-skin group; at 90 min after birth blood glucose was also significantly higher and the return towards zero of the negative base-excess was more rapid as compared to the "separated" group. Babies kept in cots cried significantly more than those kept skin-to-skin with the mother. Keeping the baby skin-to-skin with the mother preserves energy and accelerates metabolic adaptation and may increase the well-being of the newborn.     

Risk factors for invasive fungal infection in neonates

Invasive fungal infection is an uncommon, but increasing cause of morbidity and mortality in neonates. There are few controlled studies defining risk factors for the development of fungal infection in a contemporary neonatal population. This retrospective case-control study was undertaken to investigate antenatal, demographic and postnatal variables that may be potentially important in the development of fungal infection. Two gestation-matched controls were identified for each index case. Information about perinatal and demographic variables, as well as important neonatal outcomes, was obtained from case notes. Microbiological data collected included the presence of fungal colonization, and organisms responsible for invasive fungal infection. Over a 5-y period, 24 infants with invasive fungal infection and 48 controls were identified. Candida albicans was the organism identified in 75% of cases of fungal septicaemia, and in all cases complicated by fungal meningitis. Preceding fungal colonization, pulmonary haemorrhage and intrauterine growth restriction were factors significantly and independently associated with invasive fungal infection. Fifty-four percent of infants with invasive fungal infection died, and 82% of survivors developed chronic lung disease.

Conclusion : Some new and potentially important risk factors for the development of invasive fungal infection in a contemporary population of infants admitted to a neonatal intensive care were identified.     

Risk factors associated with gut and nasopharyngeal colonization by common Gram-negative species and yeasts in neonatal intensive care units patients

Aim

To characterize dynamics of mucosal colonization of neonates by common aerobic Gram negative species and Candida spp. and to identify independent perinatal, neonatal, and environmental factors influencing the colonization process.

Study design

The nasopharyngeal (n = 1145) and rectal (n = 1242) swabs were collected on admission and thereafter twice a week in neonates with risk factors of early onset sepsis (n = 276) admitted within the first 72 h of life. The association between colonization by different microbes and a total of 22 predefined risk factors was assessed using univariate and multiple logistic regression analyses.

Results

Throughout the study about half of the patients had rectal (55.8%) or nasopharyngeal colonization (42.8%) with common Gram-negative microorganisms. Colonization dynamics and risk factors were in general similar for a given bacterial species in both mucosal sites; nonfermentative microbes more often found in nasopharyngeal swabs and Enterobacteriaceae in rectal swabs. All organisms except Escherichia coli were influenced by the duration of intensive care unit stay but other risk factors were species specific, perhaps reflecting their mode of acquisition. While colonization by E. coli and Candida albicans was associated with perinatal factors like term birth, vaginal delivery, and breast milk feeding; colonization by Klebsiella pneumoniae, Enteribacter cloacae, Acinetobacter spp. and non-albicans Candida spp. were mostly determined by hospital environment (treatment unit and period, artificial interventions and their duration) and gestation age ≤ 28 weeks.

Conclusions

The knowledge of risk factor profiles may permit the development of strategies to prevent heavy colonization and subsequent invasive disease in high risk infants.