Association Between Maternal Body Mass Index and Fetal Acidosis in Term Twin Pregnancies: A Retrospective Cohort Study.

OBJECTIVES: Given the increased risk of fetal acidosis in singleton neonates born to pregnant people with an elevated BMI, our objective was to evaluate the association between pre-pregnancy/first-trimester BMI and fetal acidosis among term twin pregnancies. METHODS: Retrospective study of pregnant people with twin gestation and their term infants admitted to our centre between 2014 and 2019. Using a generalized estimating equation, the association between maternal BMI and fetal acidosis was determined using odds ratios (ORs) with 95% CIs. A two-sided P < 0.05 was considered significant. RESULTS: A total of 275 pregnant people and 550 infants were analyzed. The number (%) of pregnancies in each BMI class were 10 (4%) underweight, 155 (56%) normal weight, 66 (24%) overweight, 22 (8%) class I, 9 (3%) class II, and 13 (5%) class III. The prevalence of maternal diabetes and hypertension was highest in class III (31%) and class II (44%), respectively. Fetal acidosis was diagnosed in 35 (6%) infants. After adjusting for confounders (maternal age, diabetes, and hypertension), infants born to those with elevated BMI did not have increased odds of fetal acidosis compared to those born to underweight and normal weight group (OR 1.29; 95% CI 0.38-4.41 for class I, P = 0.67 and OR 2.80; 95% CI 0.62-12.62 for the combined classes II and III, P = 0.18). CONCLUSIONS: Maternal BMI was not associated with fetal acidosis in term twin pregnancies. Further research is required to corroborate study findings due to small sample size.

Association of Co-Exposure of Antenatal Steroid and Prophylactic Indomethacin with Spontaneous Intestinal Perforation.

OBJECTIVE: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at <26 weeks of gestation or <750 g birth weight. STUDY DESIGN: We conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (>7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. RESULTS: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. CONCLUSIONS: In preterm neonates of <26 weeks of gestation or birth weight <750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality.

Use of real-time ultrasound for locating tip position in neonates undergoing peripherally inserted central catheter insertion: A pilot study.

BACKGROUND & OBJECTIVES: Securing long-term venous access is an essential part of sick newborn care. The malposition of central line tip leads to several complications. There is a need for an easily available bedside investigating tool to diagnose these malpositions. This study was done to compare the effectiveness of real-time ultrasound (RTUS) with X-ray in identifying the peripherally inserted central catheter (PICC) line tip. METHODS: This pilot observational study was conducted in a level III Neonatal Intensive Care Unit of a tertiary care hospital in India, from June 2012 to June 2013. A total of 33 PICC lines in 31 infants were included in the study. After insertion of PICC line, X-ray and RTUS were done to locate the tip of the PICC line. RESULTS: In this study, PICC line tip could be identified by bedside RTUS in 94 per cent of line insertions. Standard X-ray identified the tip in all cases. RTUS has been shown to have good diagnostic utility in comparison with X-ray with sensitivity and specificity being 96.55 and 100 per cent, respectively. In our study, majority of malpositions were identified and manipulated by RTUS, thus second X-rays were avoided. INTERPRETATION & CONCLUSIONS: The result of this pilot study shows that RTUS may be a reliable and safe bedside tool for determining the tip of PICC lines. However, studies with large sample size need to be done to confirm these findings.

Intermittent versus continuous phototherapy for the treatment of neonatal non-hemolytic moderate hyperbilirubinemia in infants more than 34 weeks of gestational age: a randomized controlled trial.

UNLABELLED: Intermittent phototherapy with "12 h on and then 12 h off" schedule in comparison with continuous phototherapy for neonatal hyperbilirubinemia may save costs and decrease anxiety of parents. In this non-inferiority-randomized controlled trial, healthy late preterm (>34 weeks) and term neonates with neonatal hyperbilirubinemia under phototherapy for 8 h and total serum bilirubin (TSB) < 18 mg/dL were randomized either into intermittent (IPT) or continuous (CPT) group. Infants in IPT group received 12 h on and 12 h off cycles of phototherapy. In both arms, phototherapy was continued until TSB < 13 mg/dL. Primary outcome was rate of fall of bilirubin. Seventy-five infants (IPT n = 36 vs. CPT n = 39) were enrolled in the study. The rate of fall of bilirubin was significantly higher with "IPT" phototherapy (p = 0.002). CONCLUSION: In term and late preterm infants with non-hemolytic moderate hyperbilirubinemia, intermittent phototherapy with 12 h on and 12 h off cycles is as efficacious as continuous phototherapy.

Efficacy and safety of dexmedetomidine for analgesia and sedation in neonates: a systematic review.

Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.

Kangaroo Mother Care in Kangaroo ward for improving the growth and breastfeeding outcomes when reaching term gestational age in very low birth weight infants.

AIM: To study the effect of Kangaroo mother care in the Kangaroo ward in comparison with conventional care at neonatal unit on growth and breastfeeding in very low birth weight infants at 40 weeks' corrected gestational age. METHODS: One hundred and forty neonates with birth weight <1500 g were randomized. The primary outcome was the average weight gain (g/kg/day) from the time of randomization to term gestational age. RESULTS: Mean birth weight, age in days and weight at randomization were similar in both the groups. At term gestational age, average weight gain (g/kg/day) post randomization (23.3 ± 8.7 g vs. 22.64 ± 9.1 g, p = 0.67) and breastfeeding rate (85.9% vs. 87.0%) were comparable. There was no difference in weight gain (g/kg/day) from randomization to hospital discharge between the Kangaroo care group and conventional care group (18.01 g vs. 15.64 g, p = 0.12). Mortality, morbidities like sepsis, hypothermia, apnoea, hypoglycaemia and duration of hospitalization were equally distributed. On average, 11.5 days of intermediate care were saved in the kangaroo group. CONCLUSION: Kangaroo mother care in the Kangaroo ward is as effective as conventional care in the neonatal unit without any increase in morbidity or mortality in stable VLBW infants.

Timing of Systemic Steroids and Neurodevelopmental Outcomes in Infants < 29 Weeks Gestation

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks' gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week's delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Association of Empiric Antibiotic Regimen Discordance With 30-Day Mortality in Neonatal and Pediatric Bloodstream Infection-A Global Retrospective Cohort Study.

BACKGROUND: While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens. METHODS: Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression. RESULTS: Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics. CONCLUSIONS: Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation.

Predictors of CPAP Failure - 10 years' Data of Multiple Trials from a Single Center: A Retrospective Observational Study.

OBJECTIVES: To identify risk factors and outcomes associated with early failure of nasal continuous positive airway pressure (CPAP) in premature infants with respiratory distress (RD). METHODS: This is a retrospective observational study of all the preterm infants with RD primarily supported on nasal CPAP and included in CPAP trials conducted at the study site. Data was collected from the raw excel sheets of the previous trials but limited to eligible patients from study site. Early CPAP failure was defined as the need for mechanical ventilation in the first 72 h after birth. Predictor variables for CPAP failure included baseline maternal and infant characteristics, CPAP care practices, morbidities and adjuvant therapies. The morbidities and outcomes were compared among infants with CPAP failure and CPAP success. RESULTS: Six hundred and fifty-two infants were enrolled in the study. Early CPAP failure was seen in 96 infants (14.7%, 95% CI: 12%-17.5%). On logistic regression, adjusting for gestation and year of study, time of starting CPAP in hours (OR 1.01, 95% CI: 1.003-1.013), time of surfactant administration in hours (OR 1.12, 95% CI: 1.05-1.19), InSurE (Intubate Surfactant Extubate) (OR 2.7, 95% CI: 1.43-5.06) and higher starting FiO2 (OR 1.03, 95% CI: 1.01-1.05) predicted early CPAP failure. Neonatal morbidities and hospital duration were significantly higher in infants who failed CPAP. CONCLUSIONS: Early starting of CPAP, InSurE, early surfactant administration, lower CPAP pressures and lower FiO2 at starting of CPAP were the important determinants of success.

Towards understanding global patterns of antimicrobial use and resistance in neonatal sepsis: insights from the NeoAMR network.

OBJECTIVE: To gain an understanding of the variation in available resources and clinical practices between neonatal units (NNUs) in the low-income and middle-income country (LMIC) setting to inform the design of an observational study on the burden of unit-level antimicrobial resistance (AMR). DESIGN: A web-based survey using a REDCap database was circulated to NNUs participating in the Neonatal AMR research network. The survey included questions about NNU funding structure, size, admission rates, access to supportive therapies, empirical antimicrobial guidelines and period prevalence of neonatal blood culture isolates and their resistance patterns. SETTING: 39 NNUs from 12 countries. PATIENTS: Any neonate admitted to one of the participating NNUs. INTERVENTIONS: This was an observational cohort study. RESULTS: The number of live births per unit ranged from 513 to 27 700 over the 12-month study period, with the number of neonatal cots ranging from 12 to 110. The proportion of preterm admissions <32 weeks ranged from 0% to 19%, and the majority of units (26/39, 66%) use Essential Medicines List 'Access' antimicrobials as their first-line treatment in neonatal sepsis. Cephalosporin resistance rates in Gram-negative isolates ranged from 26% to 84%, and carbapenem resistance rates ranged from 0% to 81%. Glycopeptide resistance rates among Gram-positive isolates ranged from 0% to 45%. CONCLUSION: AMR is already a significant issue in NNUs worldwide. The apparent burden of AMR in a given NNU in the LMIC setting can be influenced by a range of factors which will vary substantially between NNUs. These variations must be considered when designing interventions to improve neonatal mortality globally.

Point prevalence surveys of antimicrobial use among eight neonatal intensive care units in India: 2016.

BACKGROUND: Information about antimicrobial use is scarce and poorly understood among neonatal intensive care units (NICUs) in India. In this study, we describe antimicrobial use in eight NICUs using four point prevalence surveys (PPSs). METHODS: As part of the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children (GARPEC) study, one-day, cross-sectional, hospital-based PPSs were conducted four times between 1 February 2016 and 28 February 2017 in eight NICUs. Using a standardized web-based electronic data entry form, detailed data were collected for babies on antimicrobials. RESULTS: A total of 403 babies were admitted to NICUs across all survey days, and 208 (51.6%) were prescribed one or more antimicrobials. Among 208 babies, 155 (74.5%) were prescribed antimicrobials for treatment of an active infection. Among 155 babies with an active infection, treatment was empiric in 109 (70.3%). Sepsis (108, 49.1%) was the most common reason for prescribing antimicrobials. Amikacin (17%) followed by meropenem (12%) were the two most commonly prescribed antimicrobials. For community-acquired sepsis, piperacillin-tazobactam (17.5%) was the most commonly prescribed drug. A combination of ampicillin and gentamicin was prescribed in only two babies (5%). CONCLUSIONS: The recommended first-line antimicrobial agents, ampicillin and gentamicin, were rarely prescribed in Indian NICUs for community acquired neonatal sepsis.

Comparison of Sucking Pattern in Premature Infants With Different Feeding Methods.

OBJECTIVE: To compare the sucking pattern of preterm infants on different feeding methods. METHODS: The sucking behavior on a gloved finger was evaluated for infants receiving breastfeeding, spoon-feeding and tube-feeding. RESULTS: The mean (SD) numbers of sucks in spoon-fed infants [49 (20) vs. 35 (23); P=0.04] were significantly higher, and the grade of suck was significantly better compared to the tube-fed group. The mean (SD) number of sucks was significantly higher [83 (30) vs. 49 (20), P<0.001] in breastfed infants compared to spoon-fed infants; all infants on breast feeds had grade 2 suction. CONCLUSION: The sucking behavior varies between tube-fed, spoon-fed, and breastfed preterm infant.

Nasal continuous positive airway pressure therapy in a non-tertiary neonatal unit: reduced need for up-transfers.

OBJECTIVE: To evaluate the need for up-transfer after starting of nasal continuous positive airway pressure (n-CPAP) services in a Level II special newborn care unit (SNCU). METHODS: Five hundred fifty infants admitted to Level II SNCU, 252 infants during one year prior to introduction of n-CPAP (retrospective data from case records and electronic data base) and 298 infants during one year after introduction of n-CPAP services (prospective data in predefined case reporting form) were evaluated in this before and after intervention trial. The primary outcome was proportion of infants needing up-transfers from Level II SNCU for any indication. RESULTS: Baseline demographic data like birth weight, gestation and other perinatal factors were similar between the two epochs. Among the infants admitted to Level II SNCU, up-transfer for any reason was significantly higher in the pre-CPAP epoch compared with CPAP epoch (n = 93, 36 % vs. n = 74, 24.8 %, p = 0.002, OR 0.56, 95 % CI 0.38 to 0.83). However parent desired up-transfers were similar between the two epochs (n = 9, 3 % vs. n = 16, 5 %, p = 0.40). Introduction of n-CPAP treatment modality reduced up-transfers in subgroups of very low birth weight infants (VLBW) (n = 20, 74 % vs. n = 15, 37 %, p = 0.003) and also in preterm infants (n = 50, 54 % vs. n = 34, 32 %, p = 0.002). CONCLUSIONS: Introduction of n-CPAP services in a non-tertiary care neonatal unit, significantly reduced the need for up-transfers, especially in VLBW and preterm infants.

A novel algorithm in the management of hypoglycemia in newborns.

Study Objective. To evaluate the safety of a new protocol in comparison to the standard protocol for managing hypoglycemia in neonates. Methods. Open label RCT-pilot study. Neonates admitted to NICU with hypoglycemia and requiring intravenous fluids were included. Fifty-seven eligible neonates were randomly allocated to either intervention group (starting fluids with 10% dextrose and increments of 1.5%) or standard protocol group (GIR of 6 mg/kg/min with increments of 2 mg/kg/min) till control of hypoglycemia. Primary outcome of the study was to know proportion of infants with subsequent hypoglycemia and hyperglycemia after enrolment. Results. The initial GIR (6 ± 0 mg/kg/min versus 4.8 ± 1.4 mg/kg/min, P < 0.001), the mean maximum GIR (6.7 ± 1.6 mg/kg/min versus 5.6 ± 2 mg/kg/min, P = 0.03), the maximum concentration of glucose infused (13.8 ± 2.9% versus 10.9 ± 1.9%, P < 0.001), and the total amount of glucose infused were significantly lower in the intervention group. The mean maximum blood sugar was significantly higher (129 ± 57 mg/dL versus 87 ± 30 mg/dL, P = 0.001) and there was a trend towards high proportion of infants with Hyperglycemia in the standard protocol group (n = 10, 39% versus n = 5, 16%, P = 0.07). The median difference between the highest and the lowest recorded sugar for any infant was significantly higher in the standard protocol group (median 93 mg/dL, IQR 52 to 147 mg/dL versus median 50 mg/dL, IQR 38 to 62.5 mg/dL, P = 0.03). Conclusion. A new and novel algorithm in the management of hypoglycemia in neonates is as safe as the standard protocol and requires further testing before routine implementation.

Early routine versus late selective surfactant in preterm neonates with respiratory distress syndrome on nasal continuous positive airway pressure: a randomized controlled trial.

BACKGROUND: Preterm neonates with respiratory distress syndrome (RDS) benefit from early application of nasal continuous positive airway pressure (nCPAP). However, it is not clear whether surfactant should be administered early as a routine to all such infants or later in a selective manner. OBJECTIVE: It was the aim of this study to compare the efficacy of early routine versus late selective surfactant treatment in reducing the need for mechanical ventilation (MV) during the first week of life among moderate-sized preterm infants with RDS being supported by nCPAP. METHODS: Infants born at 28(0/7) to 33(6/7) weeks of gestation with RDS and on nCPAP were randomly assigned within the first 2 h of life to early routine surfactant administration by the InSurE technique (early surfactant group) or to late selective administration of surfactant (late surfactant group). The primary outcome was need for MV in the first 7 days of life. RESULTS: Among 153 infants randomized to early (n = 74) or late surfactant (n = 79) groups, the need for MV was significantly lower in the early surfactant group (16.2 vs. 31.6%; relative risk 0.41, 95% confidence interval 0.19-0.91). The incidence of pneumothorax (1.9 vs. 2.3%) and the need for supplemental O2 at 28 days (2.7 vs. 8.9%) were similar in the two groups. CONCLUSION: Early routine surfactant administration within 2 h of life as compared to late selective administration significantly reduced the need for MV in the first week of life among preterm infants with RDS on nCPAP.

Hemolytic disease of the newborn- anti c antibody induced hemolysis.

Hemolytic disease in the newborn, as a cause of early jaundice, is not uncommon. This is mostly due to Rh (D), ABO incompatibility and rarely due to other minor blood group incompatibility. The authors report two cases of Rh anti c isoimmunization presenting as significant early neonatal jaundice within the 20 h of life. Both the babies were treated with intensive phototherapy. One baby underwent exchange transfusion and the other required packed cell transfusion for anemia.

Endovascular stenting of the obstructed vertical vein in a neonate with supracardiac total anomalous pulmonary venous return.

A newborn baby presented with respiratory distress, cyanosis and shock within 2 hours of birth. The cardiac evaluation showed supracardiac total anomalous pulmonary venous return with critically obstructed vertical vein. The baby underwent successful stenting of the vertical vein at 12 hours of life.

Gestational age-specific centile charts for anthropometry at birth for South Indian infants.

OBJECTIVE: To construct centile charts for birth weight, length and head circumference for infants born from 24 to 42 weeks of gestation and to compare with the other national and international growth charts. STUDY DESIGN: Observational descriptive study. SUBJECTS: All consecutively live born singleton infants from 24 to 42 weeks of gestation. METHODS: Data were retrieved for the birth weight, length and head circumference of infants born from July 1999 to October 2009. Smoothened percentile curves were created separately for the male and female infants by Lambda Mu Sigma (LMS) method. The new curves were compared with the other Indian and international growth charts. RESULTS: Raw and smoothened curves for weight, length and head circumference centiles at birth were created from 31,391 (males: 16,054 and females: 15,337), 28,812, (males: 14,730 and females: 14,082), and 28,790 (males: 14,724 and females: 14,066) infants, respectively. Females infants were lighter than the male infants, especially from 35 weeks onwards. On comparing the study curves with the other Indian growth curves, for infants less than 35 weeks, the mean birth weight for the study infants were similar or lower and for infants greater than 35 weeks, they were higher. On comparison of our weight centiles with the international data, across all gestations and across all centiles, our birth weights are lower. CONCLUSION: The updated centile charts in this study may be used as reference charts for the birth weight, length and head circumference for the local population. Using earlier growth charts or the Western charts would misclassify the infants at birth into SGA or LGA.

Symptomatic aneurysm of ductus arteriosus in neonates.

Four neonates presented within 24 hours of birth with stridor, respiratory distress and a weak cry. Clinical examination of the cardiovascular system revealed no abnormality. The transthoracic echocardiogram showed large aneurysm of ductus arteriosus at the aortic isthmus, tapering to a small tortuous channel at the site of pulmonary artery insertion. Computerized tomography scan performed in two of the neonates demonstrated considerable compression of adjacent thoracic structures. One required surgical excision due to persistence of symptoms. Serial echocardiograms in the remaining three babies showed transition through various stages of resolution over a period of 6 weeks to 3 months, resulting in the obliteration of the aneurysm. All babies are doing well during the follow-up.