Intravitreal bevacizumab for retinopathy of prematurity as first line or rescue therapy with focal laser treatment. A case series

Objectives: Laser therapy is effective in the treatment of severe forms of retinopathy of prematurity (ROP), and aggressive posterior ROP (APROP), but always damages the retina. We report our preliminary findings in seven premature infants with complicated ROP or APROP who were treated with intravitreal bevacizumab (IVB) as first line monotherapy or rescue therapy combined with laser treatment. Methods: We studied retrospectively seven preterm infants, who were affected by APROP (n = 4) or pre-threshold ROP (n = 3). Infants were treated with IVB (0.625 mg; Avastin®, Roche, Basel, Switzerland) monotherapy (n = 2) when they were too sick to undergo lengthy laser treatment. Results: Monotherapy IVB (n = 3 eyes) and IVB combined with laser therapy (n = 3 eyes) of APROP cases were followed by regression of the ROP and complete peripheral vascularization. The combined therapy with IVB and laser therapy of pre-threshold ROP (5 eyes) produced a regression of neovascularization and good retinal anatomical outcome. Conclusions: In our series, IVB was successful in treating ROP in a small cohort of extremely preterm infants with APROP or pre-threshold ROP, both as monotherapy or rescue treatment after laser therapy, without the development of ocular and systemic short- and long-term adverse effects.     

Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: a randomized controlled study

Objectives: Lutein and its isomer zeaxanthin (L/Z) function in the eye as antioxidant agents and blue-light filters. Our aim was to evaluate whether their administration could help decrease the occurrence of retinopathy of prematurity (ROP) in preterm infants. Methods: Infants with gestational age ≤32 weeks were randomly assigned to receive a daily dose of L/Z (0.14?+?0.006?mg) or placebo until discharge. Results: ROP occurrence was similar in the L/Z (11/58; 19%) and placebo (15/56; 27%) groups, as the occurrence of ROP at each stage and the need of eye surgery. Conclusion: L/Z supplementation was ineffective in preventing ROP in preterm infants and did not affect the outcome at discharge of our patients.     

The lack of association between vascular endothelial growth factor and retinopathy of prematurity in an observational study

Purpose: The objective of this study was to investigate the association between prematurity, vascular endothelial growth factor A (VEGF-A), VEGFR-1 (soluble fms-like tyrosine kinase-1 (sFLT-1)) and retinopathy of prematurity (ROP).

Methods: A cohort of 53 neonates (gestation <28?weeks) was recruited into this study and peripheral venous samples for VEGF and sFLT-1 measurement were obtained between gestational ages 32⁰–32⁶?weeks.

Results: The mean birth weight for the preterm neonates was 850 (178)?g and the median gestational age was 26.4 [24.7–27.4] weeks. The median VEGF-A level was 1348 [608–2216] pg/mL and the median sFLT-1 level was 178 [103–244] pg/mL. Thirty-three neonates (33/53) developed various stages of ROP during their stay in the neonatal unit but only five neonates developed severe (stage 3) ROP needing treatment. The neonates with ROP were smaller (birth weight 801 (111) vs. 990 (175) g; p?p?p=?.012). There was no statistically significant difference in the VEGF-A level or sFLT-1 levels between those who developed ROP and those who did not. There was a positive correlation between VEGF and both birth weight and gestation, respectively. There was no correlation between sFLT1 and birth weight or gestation. VEGF-A/sFLT-1 ratio in babies treated for ROP was significantly lower compared to those not treated (2.8 [1.0–5.7] vs. 9.9 [5.6–13.7]; p?=?.04). A logistic regression model identified gestational age to be a statistically significant predictor of ROP (odds ratio 0.03 (0.001–0.550); p?=?.019).

Conclusions: There is no direct correlation between systemic VEGF-A or sFLT-1 plasma levels and severity of ROP in extremely preterm neonates. The link between VEGF and ROP remains to be fully understood.     

Effect of revised IOM weight gain guidelines on perinatal outcomes

Objective.?We sought to examine perinatal outcomes in women with a body mass index (BMI) of 25?kg/m² comparing those whose weight gain met 2009 IOM guidelines to women meeting 1990 IOM guidelines.

Methods.?This is a retrospective cohort study utilizing birth records linked to hospital discharge data for all term, singleton infants born to overweight, Missouri residents (2000–2006) with a BMI of 25?kg/m². We excluded congenital anomalies, mothers with diabetes, hypertension, or previous cesarean delivery.

Results.?Fourteen thousand nine hundred fifty-five women gained 25–35?lbs (1990 guidelines); 1.6% delivered low birth weight (LBW) infants and 1.1% delivered macrosomic infants. Eight thousand three hundred fifty women gained 15–25?lbs (2009 guidelines); 3.4% delivered LBW infants and 0.6% delivered macrosomic infants. Women who gained 15–25 lbs were 1.99 (95% CI 1.67, 2.38) times more likely to have a LBW infant and 0.59 (95% CI 0.40, 0.76) times less likely to deliver a macrosomic infant.

Conclusion.?Limiting weight gain in women with a BMI of 25?kg/m², per the 2009 guidelines, increases the risk of LBW deliveries and decreases the risk of macrosomia but does not reduce associated adverse perinatal outcomes. Further studies should explore the optimal weight gain to reduce these outcomes.     

Prenatal and postnatal factors increase risk of severe ROP

Abstract

To determine that slower weight premature twins have more risk to develop severe retinopathy of prematurity (ROP) than the higher weight twins. We know that the lower weight twins had less optimal intra-uterine environments than their higher weight twins. We screened 94 consecutive premature twins for ROP. We compared the lower weight twins (n?=?47) against their higher weight twins (n?=?47). The risk of severe ROP (ROP stage 3 or greater) was significantly higher in the lower weight twin group (p?<?0.006). In the same way, in the lower weight twin group the non-perfused area of the temporal retinal artery was higher than that of the other group (an average of 1.2 diameters of the optic nerve head), in the 4–6 postnatal weeks (p?<?0.004). The lower weight twin group have an increased risk of severe ROP associated with bacteremia (p?=?0.045), or a weight gain less than 7?g per day in the 4–6 postnatal weeks (p?=?0.013) or a supplementary postnatal oxygen >4 days (p?=?0.007) compared to the higher weight twin group. We confirm Dr. Lee's work that less optimal prenatal factors, in preterm twins, increase the risk of severe ROP.     

Pregnancy disorders appear to modify the risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia

Abstract

Objective: To explore (1) whether extremely low gestational age newborns exposed to inflammation-associated pregnancy disorders differ in retinopathy of prematurity (ROP) risk from infants exposed to placenta dysfunction-associated disorders, and (2) whether ROP risk associated with postnatal hyperoxemia and bacteremia differs among infants exposed to these disorders.

Methods: Pregnancy disorders resulting in preterm birth include inflammation-associated: preterm labor, prelabor premature rupture of membranes (pPROM), cervical insufficiency, and abruption and placenta dysfunction-associated: preeclampsia and fetal indication. The risk of severe ROP associated with pregnancy disorders was evaluated by multivariable analyses in strata defined by potential effect modifiers, postnatal hyperoxemia and bacteremia.

Results: Compared to preterm labor, infants delivered after pPROM were at reduced risk of plus disease (Odds ratio?=?0.4, 95% confidence interval: 0.2–0.8) and prethreshold/threshold ROP (0.5, 0.3–0.8). Infants delivered after abruption had reduced risk of zone I ROP (0.2, 0.1–0.8) and prethreshold/threshold ROP (0.3, 0.1–0.7). In stratified analyses, infants born after placenta dysfunction had higher risks of severe ROP associated with subsequent postnatal hyperoxemia and bacteremia than infants born after inflammation-associated pregnancy disorders.

Conclusion: Infants exposed to placenta dysfunction have an increased risk of severe ROP following postnatal hyperoxemia and bacteremia compared to infants exposed to inflammation-associated pregnancy disorders.     

The association between maternal weight gain and spontaneous preterm birth in twin pregnancies

Abstract

Objective: To estimate the association between maternal weight gain and SPTB in twin pregnancies.

Methods: A case-control study of patients with twin pregnancies and a normal prepregnancy BMI (18.5–24.9?kg/m²) in one maternal-fetal medicine practice from 2005 to 2013. We reviewed maternal weight in six time periods: prepregnancy, 12–15 6/7 weeks, 16–19 6/7 weeks, 20–23 6/7 weeks, 24–27 6/7 weeks and 28–31 6/7 weeks. We compared maternal weight gain patterns across pregnancy between patients who did and did not have SPTB <32 weeks. Student’s t-test and chi-square were used for analysis.

Results: In total, 382 patients were included, 29 (7.6%) of whom had SPTB <32 weeks. The baseline height, weight and BMI did not differ between the groups, nor did maternal age, IVF status, race or chorionicity. Patients with SPTB <32 weeks had significantly less weight gain as early as 15 6/7 weeks (2.9?±?4.6 versus 7.3?±?6.6?lb, p?<?0.001), and this continued until 31 6/7 weeks (25.3?±?8.7 versus 30.8?±?10.9?lb, p?=?0.037).

Conclusions: In twin pregnancies with a normal prepregnancy BMI, there is a significant association between SPTB <32 weeks and lower maternal weight gain, particularly prior to 16 weeks. Future studies are needed to test if prepregnancy or early nutritional interventions in twin pregnancies can reduce the risk of preterm birth and improve neonatal outcomes in this high-risk population.     

早产儿视网膜病107例临床特点及预后分析

摘要：目的　评价早产儿视网膜病（ROP）临床特点及远期治疗效果。方法　回顾性分析2004-01-01—2009-07-31复旦大学附属儿科医院新生儿科收治的107例ROP患儿临床资料、ROP分期、治疗情况及远期预后。结果　1期和2期ROP共64例,6例2期病变达Ⅰ型阈值前病变而采用激光治疗,其他均未进行特殊治疗;除失访和死亡病例外,所有随访病例ROP病变均消退,远期视力不受影响。3期病变15例,其中14例达阈值病变者给予激光或冷凝治疗,1例未达阈值病变者不需要治疗。有完整随访资料的11例患儿中3例术后视力严重受损,仅存在光感,其余8例视力正常。4期和5期ROP共28例,随访的18例患儿中,仅1例手术后保存了正常视力（占5.6％）,失明者达12例（占66.7％）,其余5例虽保存视力,但视力极差,仅存光感（占27.7％）。结论　ROP防治关键在于预防ROP发生,当出现ROP早期病变时应严格筛查和及时干预,一旦疾病进入晚期,出现视网膜脱离时再治疗,则治疗效果不佳。     

Propofol and fentanyl sedation for laser treatment of retinopathy of prematurity to avoid intubation

Background: Despite the optimization of neonatal assistance, severe retinopathy of prematurity (ROP, stage III–IV) remains a common condition among preterm infants. Laser photocoagulation usually requires general anesthesia and intubation, but extubation can be difficult and these infants often affected by chronic lung disease. We retrospectively evaluated the clinical charts of 13 neonates that were sedated with propofol in association with fentanyl for the laser treatment of ROP. This protocol was introduced in our unit to avoid intubation and minimize side effects of anesthesia and ventilation.

Methods: Propofol 5% followed by a bolus of fentanyl was administered as sedation during laser therapy to 13 preterm infants, affected by ROP stage III–IV. Propofol was initially infused as a slow bolus of 2–4?mg/kg and then continuously during the entire procedure, at 4?mg/kg/hour, increasing the dosage to 6?mg/kg/hour if sedation was not achieved. A laryngeal mask was placed and patients were ventilated with a flow-inflating resuscitation bag.

Results: Thirteen neonates were treated allowing to perform surgery without intubation. Only 4/13 (30.8%) of infants required minimal respiratory support during and/or after surgery. Heart rate after the intervention was higher than that at the beginning while remaining in the range of normal values. Blood pressures before, during and after surgery were similar. No episodes of bradycardia nor hypotension were recorded. Laser treatment was always successful.

Conclusion: The good level of anesthesia and analgesia achieved sustains the efficacy of sedation with propofol during laser photocoagulation to avoid intubation and mechanical ventilation during and after the procedure.     

早产儿视网膜病变的冷凝治疗

目的 评价早产儿视网膜病（retinopathy of prematurity，ROP）冷凝治疗效果，探讨围手术期管理模式。方法 对370例符合筛查指征的早产儿进行眼底筛查，对25例阈值或Ⅰ型阈值前期病变ROP患儿进行冷凝治疗，术前术后在新生儿病房管理，新生儿科医师负责处理围手术期全身并发症，眼科医师术后定期随访检查眼底。结果 ROP的发生率为22％，阈值和Ⅰ型阈值前期病变发生率为6．8％。56例1期、2期病变未治疗，定期随访眼底恢复正常。25例50只眼阈值、Ⅰ型阈值前病变冷凝治疗成功率为92％，2例4只眼冷凝治疗后发生部分视网膜脱离，经玻璃体视网膜手术病变控制。随访9个月病变控制眼底正常的有44只眼（88％），出现视网膜脱离或后极部视网膜皱褶的有6只眼（12％）。6例术后12h内发生呼吸暂停，3例术后第1天出现窦性心动过速。结论 冷凝治疗可以作为治疗ROP阈值病变的选择，近期疗效较好。ROP围手术期处理的重点是呼吸管理。ROP患儿围手术期处理需要眼科医师和新生儿科医师密切合作共同管理。     

Personality type influence the gestational weight gain

Pregnancy is frequently followed by the development of obesity. Aside from psychological factors, hormonal changes influence weight gain in pregnant women. We attempted to assess the potential association between personality type and the extent of gestational weight gain. The study group involved 773 women after term delivery (age 26.3?±?3.9 years, body mass before pregnancy 61.2?±?11.1?kg). Weight gain during pregnancy was calculated by using self-reported body mass prior to and during the 38th week of pregnancy. Personality type was assessed using the Polish version of the Framingham Type A Behavior Patterns Questionnaire (adapted by Juczynski). Two hundred forty-six (31.8%) study subjects represented type A personalities, 272 (35.2%) type B and 255 (33.0%) an indirect type. Gestational weight gain was related to the behavior patterns questionnaire score and age. In women?<30?years with type A personality, the weight gain was higher than in women with type B behavior of the same age. In women >30, the gestational weight gain was larger for type B personalities. Type A personality and increased urgency in younger pregnant women increases the risk of developing obesity during pregnancy in women below 30?years old. A higher level of competitiveness demonstrates a risk factor of excessive weight gain during pregnancy regardless of age.     

Gestational weight gain and the risk of infant mortality amongst women with normal prepregnancy BMI: the Friedmann-Balayla model

Objective: The study of the association between gestational weight gain (GWG) and infant mortality is riddled with methodological concerns, particularly with limitations in accounting for gestational age-specific weight gain. In our study, we developed a new model, which accounts for gestational age, to determine whether insufficient or excessive GWG is associated with an increased risk of infant death amongst women with normal prepregnancy BMI (18.5–24.9?kg/m²).

Methods: We developed and implemented the Friedmann-Balayla model to mitigate gestational age-related biases in our assessment, and conducted a population-based cohort study using the CDC’s 2013 Period-Linked Birth-Infant Death data. The impact of GWG according to the 2009 IOM guidelines on the risk of infant mortality was estimated using logistic regression analysis, adjusting for relevant confounders.

Results: Our cohort consisted of 1,517,525 singleton deliveries and 6138 infant deaths. Overall, relative to women achieving adequate GWG, neither women gaining insufficient nor excessive weight had greater odds of infant death during the first year of life (OR [95%CI]): 1.06 [0.97–1.17] (p?=?0.174), and 0.98 [0.91–1.04] (p?=?0.523), respectively. This relationship did not change when restricting our analysis to term or preterm deliveries or when conducting sensitivity analyses accounting for maternal morbidities (p?>?0.05).

Conclusion: Using this novel analytic approach, there does not appear to be an increased risk of infant mortality if GWG falls outside of the IOM guidelines in women with normal prepregnancy BMI. Future studies should apply this methodology to other BMI categories.     

阈值期早产儿视网膜病变的临床特征及治疗效果分析

目的 分析阈值期早产儿视网膜病变(ROP)的临床特征,并评价眼底激光凝固术的治疗效果.方法 对549例符合筛查指征的早产儿进行眼底筛查,共发现ROP患儿108例,1、2期及3期非阈值病变ROP患儿74例,阈值病变ROP患儿34例;对阈值病变ROP患儿进行眼底激光凝固术治疗,术后眼科医师定期检查眼底.结果 ROP总发生率为8.6%(108/1255),占筛查数的19.7%(108/549),阈值病变ROP占早产儿的2.7%(34/1255),占筛查数的6.2%(34/549).1、2期及3期非阈值病变ROP患儿的胎龄、出生体重均较阈值病变ROP患儿大,而吸氧时间较短,差异均有统计学意义(P<0.05);74例1、2期及3期非阈值病变患儿未治疗,定期随访至眼底恢复正常.34例阈值病变ROP患儿的68只眼接受眼底激光凝固术治疗,成功率为94.1%,2例(4只眼)治疗后发生部分视网膜脱离,经玻璃体视网膜手术后病变控制.结论 早产儿胎龄越小、出生体重越低、吸氧时间越长,ROP阈值病变的发生率越高;预防的关键是早期筛查;眼底激光凝固术治疗是阻止阈值期ROP发展的有效方法;术后处理重点是呼吸管理.     

间接检眼镜眼底成像技术支持下的早产儿视网膜病变筛查研究

目的 研究间接检眼镜眼底成像技术支持下的早产儿视网膜病变(ROP)筛查模式和特点.方法 采用双目间接检眼镜成像系统对250例早产儿进行ROP筛查.结果 250例早产儿检出ROP 23例,其中1期10例,2期5例,3期4例,急性后极部ROP 1例,5期3例.通过间接检眼镜成像技术,ROP 1期、2期、3期病变,附加病变等典型病变的特征图像均被捕获,并总结出正常早产儿和ROP患儿的眼底特征.结论 间接检眼镜成像技术支持下的ROP筛查模式能够清晰获取早产儿眼底图像,并准确记录ROP筛查结果.操作简单,可望成为ROP筛查项目开展的基础.     

早产儿视网膜病激光治疗及相关危险因素研究

目的探讨早产儿视网膜病(retinopathy of prematurity,ROP)激光治疗效果及该病发生的相关危险因素。方法以35例因各种疾病住院治疗的早产儿为观察对象。对性别、胎龄、出生体重、Apgar评分、出生时及出生后缺氧、贫血、黄疸、感染、母亲年龄及孕期情况进行观察并进行头颅B超检查。用χ2检验、Fisher确切概率法、t检验以及Logistic回归做统计分析,评价激光治疗的疗效,分析早产儿视网膜病发生的危险因素。结果35例患病早产儿中有27例发生早产儿视网膜病,发生率77.1%。25例患儿接受激光治疗,并分别于术后7～14d及3个月进行随访,治愈率分别为74.1%和92.6%。ROP组出生体重(1144.81±284.83)g,明显小于未发病组(8例)出生体重(1743.75±423.79)g,P<0.01;ROP组胎龄(29.04±2.70)周,明显小于未发病组胎龄(32.50±1.85)周,P<0.01。且出生体重越低,胎龄越小,ROP发生率越高,P<0.01。经Fisher确切概率法检验显示出生后缺氧、贫血等因素在ROP发病组与未发病组差异有统计学意义(P<0.05)。结论早产儿视网膜病在伴随各种疾病的早产儿中发生率较常见患病率高,其发病与缺氧、贫血、胎龄和出生体重有关。对患病早产儿进行激光治疗可获得较好的疗效,采取早监测、早发现、早治疗,则可获得较好的预后。     

不同胎龄新生儿血清雌二醇水平变化及其与早产儿视网膜病的关系

目的 测定不同胎龄新生儿和早产儿视网膜病(retinopathy of prematurity,ROP)患儿血清雌二醇水平变化,探讨其与ROP发生发展的关系.方法 新人院新生儿184例.根据出生胎龄分为＜32周早产儿组、32～37周早产儿组和足月儿组,再根据是否吸氧分为未吸氧和吸氧两个亚 组.出生体重＜2000 g的早产儿均定期眼科筛查,确诊为ROP的患儿作为ROP组.各组分别在生 后第1、3、5、7周用放射免疫法检测血清雌二醇水平.组间结果比较采用非配对t检验和单因素方差 分析.结果 新生儿血清雌二醇水平随着日龄增加迅速下降.在未吸氧新生儿中,32～37周早产 儿组血清雌二醇水平在第1周和第3周分别为(3506±1376)pmol/L和(1431±92)pmol/L,显著高 于足月儿组[分别为(1717±179)pmol/L和(996±102)pmol/L](P均＜0.05);＜32周早产儿组仅第l周[(3173±1369) pmol/L]显著高于足月儿组(P＜0.05).＜32周早产儿血清雌二醇水平在生 后第5周为(560±355)pmol/L,明显低于32～37周早产儿[(1124±128)pmol/L](P＜0.05).在同一胎龄组中,吸氧与未吸氧患儿雌二醇水平差异均无统计学意义.ROP组与＜32周早产儿组血清雌 二醇水平差异无统计学意义.ROP组血清雌二醇水平在纠正胎龄29周和32～36周时低于非ROP 早产儿组,但差异无统计学意义.结论 早产儿低血清雌二醇水平可能与ROP发生有关.     

Optimization of gestational weight gain in the obese gravida: a review

Because of the consistent association between gestational weight gain and birth weight (along with other maternal and child outcomes such as postpartum weight retention and child obesity), helping women avoid excessive weight gain during pregnancy should be an important objective of prenatal and preconceptional care. This article focuses on the updated Institute of Medicine gestational weight gain recommendations and measures directed at maintaining those guidelines and improving pregnancy outcome.     

Evaluation of serum ischemia-modified albumin levels in anemia of prematurity

Purpose: Ischemia-modified albumin (IMA) is used to determine tissue hypoxia. We aimed to evaluate the serum IMA levels in preterm infants requiring transfusion due to anemia of prematurity, a clinical condition to cause tissue hypoxia.

Materials and methods: This prospective study was performed in Etlik Zubeyde Hanim Hospital, Turkey. Preterm infants with birth weight less than 1500?g and born between 25 and 32 weeks were included during assessment for anemia of prematurity. The transfused infants with anemia of prematurity formed the “transfusion group”, the control group consisted of gender, gestational and postnatal age-matched infants without transfusion requirement. Serum samples of control group and pre-transfusion and post-transfusion samples of transfusion group were analyzed for IMA (ABS unit). Serum IMA levels were compared between control group and pre-transfusion samples of transfusion group and were also evaluated for the significance of change after transfusion.

Results: Sixty-two infants were included (transfusion group: 31, control group: 31). The pretransfusion serum IMA levels were higher than that of infants in the control group [ABS unit; transfusion group; pre-transfusion: 1.00 (0.76–1.09) and control group: 0.81 (0.52?1.04); p?=?.03]. Serum IMA levels decreased significantly to 0.79 (0.59–0.95) after transfusion; p?=?.007. Infants with hematocrit higher than 30% had lower IMA levels [0.69 (0.54?0.96)] than infants with lower hematocrit [0.96 (0.75?1.05)]; p?=?.002.

Conclusions: Clinicians may bear in mind that serum IMA levels could be utilized as a marker in deciding on erythrocyte transfusion in premature anemia.     

Nursing update on retinopathy of prematurity

One of the problems that plagues premature infants is retinopathy of prematurity, a potentially blinding disease that occurs because the retina is immature before 34 weeks gestation and must develop in a suboptimal environment when a baby is born early. Prevention by minimizing oxygen exposure has been somewhat effective, but survival of the tiniest babies has led to a recent resurgence in cases. Oxygen targeting and early surgery show promise to reduce the risk of blindness in the smallest premature infants. Nurses play an important role in oxygen management and parental support.