Integrated breast massage versus traditional breast massage for treatment of plugged milk duct in lactating women: a randomized controlled trial.

BACKGROUND: Plugged milk duct during lactation is a common problem in breastfeeding. Traditional breast massage (TBM) has been performed in Thailand with reasonable outcomes, but several follow-up sessions are often required. A new massage technique, the integrated breast massage (IBM), was subsequently developed. This study aimed to compare resolution time, reduction in mass size, and pain score after breast massage between the IBM and TBM techniques. METHODS: This randomized controlled trial was conducted at the Lactation Clinic of the Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during February 2019-July 2020. Women presenting with acute plugged milk duct were enrolled and randomly allocated to the IBM or TBM/control groups. Mass size in square centimeters (cm2) was calculated by multiplying the perpendicular axes of the mass. Pain score was self-scored by participants using a numerical rating scale. Median time (95% confidence interval [CI]) to resolution of plugged milk duct was derived using Kaplan-Meier survival analysis. Intention-to-treat analysis was performed. RESULTS: Eighty-four women (42 per group) were included. All enrolled study participants completed the study and were included in the final analysis. Twenty-six (61.9%) and 25 (59.5%) participants from IBM and TBM, respectively, had mass diameter > 5 cm. The median (interquartile range [IQR]) mass size was 30 (20-48) and 20 (12-14) cm2 in IBM and TBM (p = 0.05), respectively. The median (95% CI) time to resolution of plugged duct was 0 (not available) and 1 (0.47-1.53) day in IBM and TBM, respectively (p < 0.01). After the first breast massage, the median (IQR) size of mass reduction was 30 (20-48) and 10 (10-26) cm2 in IBM and TBM, respectively (p = 0.01). The median (IQR) reduction in pain score was 8 (7-8) and 6 (4-7) in IBM and TBM, respectively (p = 0.01). No participants developed skin bruising or hematoma after breast massage. CONCLUSIONS: The IBM technique resolved plugged milk duct significantly faster, with significantly less pain, and with significantly greater reduction in mass size after the first massage compared to TBM. TRIAL REGISTRATION: Retrospectively registered in the Thai Clinical Trials Registry on 25 September 2019 ( TCTR20190925001 ).

Rare cause of neonatal apnea from congenital central hypoventilation syndrome.

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare condition caused by mutations in the Paired-Like Homeobox 2B (PHOX2B) gene. It causes alveolar hypoventilation and autonomic dysregulation. This report aimed to raise awareness of this rare cause of neonatal apnea and hypoventilation as well as described the diagnostic work up to confirm the diagnosis in resource-limited setting where polysomnography for neonate is unavailable. CASE PRESENTATION: A late preterm female newborn born from a non-consanguineous primigravida 31-year-old mother had desaturation soon after birth followed by apnea and bradycardia. After becoming clinically stable, she still had extubation failure from apnea without hypercapnic ventilatory response which worsened during non-rapid eye movement (NREM) sleep. After exclusion of other etiologies, we suspected congenital central hypoventilation syndrome and sent genetic testing. The result showed a PHOX2B gene mutation which confirmed the diagnosis of CCHS. We gave the patient's caregivers multidisciplinary home respiratory care training including tracheostomy care, basic life support, and simulation training for respiratory problem solving. Then, the patient was discharged and scheduled for follow-up surveillance for associated conditions. CONCLUSION: Diagnosis of CCHS in neonates includes the main clue of the absence of hypercapnic ventilatory response which worsens during non-rapid eye movement (NREM) sleep after exclusion of other causes. Molecular testing for PHOX2B gene mutation was used to confirm the diagnosis.

Association of Antenatal Terbutaline and Respiratory Support Requirements in Preterm Neonates.

BACKGROUND: Before the advent of antenatal steroids, early non-invasive respiratory support (NIV), and intratracheal surfactant, antenatal terbutaline was also used to improve lung compliance and reduce the incidence of respiratory distress syndrome (RDS). OBJECTIVES: The objective of this paper was to study the association between antenatal terbutaline and endotracheal intubation (ET) within the first 24 hours of life, RDS, bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH) in infants with the gestational age (GA) of <32 weeks, and to study the association between antenatal terbutaline, and ET or NIV within the first 24 hours of life, and RDS in infants with the GA of 32 to 36 weeks. METHOD: This was a retrospective medical record review of preterm infants delivered at a single tertiary care center from October 2016 to December 2020. Multivariable logistic regression was used to explore the association between antenatal terbutaline and neonatal respiratory support. RESULT: 1,794 infants were included, 234 (13.0%) had the GA of <32 weeks and 1,560 (86.9%) had the GA of 32 to 36 weeks. Antenatal terbutaline, corticosteroid, or both agents were administered in 561 (31.3%), 1,461 (81.4%), and 555 (30.9%), respectively. Antenatal terbutaline was significantly associated with a reduction in ET (adjusted odds ratio [aOR] = 0.40, 95% confident interval [CI] 0.19-0.82, p = 0.012) in infants with the GA of <32 weeks, but not in infants with the GA of 32-36 weeks. Antenatal terbutaline was not associated with RDS or BPD but was significantly associated with a reduction in grade III-IV IVH (aOR 0.11, CI 0.01-0.98; p = 0.048), in infants with the GA of <32 weeks. CONCLUSION: In a state-of-the-art neonatal care setting, antenatal terbutaline was associated with a reduction in ET during the first 24 hours in infants with the GA of <32 weeks. The use of antenatal terbutaline to improve acute neonatal respiratory outcomes merits reconsideration. KEY POINTS: · The neonatal respiratory benefits of antenatal terbutaline in the era of antenatal corticosteroids were uncertain.. · Terbutaline is associated with a reduction in endotracheal intubation in a modern care setting.. · The role of terbutaline, and potentially other betamimetics, to improve neonatal respiratory outcomes merits reconsideration..

Predictive factors for intensive birth resuscitation in a developing-country: a 5-year, single-center study.

Objective: To identify risk factors outlined in the International Liaison Committee on Resuscitation (ILCOR) 2010 guideline and requirement for high-intensity resuscitation.Study design: A retrospective cross-sectional study of infants born to high-risk mothers from 2011 to 2015.Results: Totally 11,446 infants were analyzed; 37% were preterm, 36% were low-birth weight infants or less. 1506 infants required respiratory support; 82 (0.7%) and 61 (0.5%) infants needed chest compression and/or epinephrine. Very-preterm infants received more intensive resuscitation than moderate preterm or term infants. Breech presentation, maternal infection and maternal diabetes were significantly associated with need for respiratory support. Fetal anomalies, breech presentation, oligohydramnios, and multiple gestation were significantly associated with need for hemodynamic support.Conclusion: Most infants defined in the ILCOR 2010 guideline required nonintensive ventilation. Very-preterm infants, fetal anomalies, and breech presentation necessitate neonatal attendance at delivery. In developing countries, maternal infection and diabetes remain high-risk criteria despite deletion from the ILCOR 2016 guideline.

Effect of fortifiers on the osmolality of preterm human milk.

Background: The nutritional content of preterm human milk (HM) can be increased by adding human milk fortifier (HMF). Premature formula (PF) has been used as an alternative to HMF due to the high cost of HMF in some countries. However, the osmolality of HM after fortification remains a matter of concern. Aim: To evaluate the osmolality of fortified preterm HM. Methods: This was a cross-sectional study. HM was collected from 28 mothers of infants with a gestational age of <32 weeks or birthweight <1500 g. Expressed HM was divided into (i) pure HM; (ii) HM+PF to 24 kcal/oz; (iii) HM+PF to 28 kcal/oz; and (iv) HM+HMF to 24 kcal/oz + protein powder 0.5 g/100 ml. Results: Twenty-eight samples of preterm HM were analysed. The mean (SD) osmolality of baseline HM was 297.6 (9.7) mOsm/kg. Mean osmolality of preterm HM after fortification with PF to 24 and 28 kcal/oz was 357.2 (11.1) and 419.9 (18.8) mOsm/kg, respectively. The mean osmolality after fortification with HMF plus protein powder was 464.1 (18.8) mOsm/kg. Repeated-measures ANOVA was used to compare osmolality between pure HM and HM fortified with different fortifiers. All pairwise comparisons by the Bonferroni method were statistically significant (p < 0.001). Conclusions: The osmolality of preterm HM fortified with PF up to 28 kcal/oz does not exceed the American Academy of Paediatrics recommendation of 450 mOsm/kg. The addition of extra protein to preterm HM fortified with commercial HMF must be cautiously considered due to the risk of excessively high osmolality.

Positive end-expiratory pressure during resuscitation at birth in very-low birth weight infants: A randomized-controlled pilot trial.

BACKGROUND: There is limited evidence of the effect of positive end-expiratory pressure (PEEP) during resuscitation soon after birth. Premature neonates may experience respiratory distress from surfactant insufficiency and providing PEEP after the very first breath, may improve outcomes following appropriate resuscitation. The objective of this study was to evaluate the short term respiratory outcomes after positive pressure ventilation (PPV) with PEEP in preterm infants at birth. METHODS: A prospective randomized-controlled, pilot trial was conducted. Premature neonates ≤ 32 weeks gestational age or birth weight < 1500 g were recruited. Subjects were allocated to either PEEP of 5 cm H2O (PEEP-5) or no PEEP (PEEP-0) if PPV was administered. Pre-ductal, peripheral capillary oxygen saturation (SpO2) and fraction of inspired oxygen concentration (FiO2) were monitored at 1, 3, 5, 10, 15, and 20 min after birth. FiO2 was adjusted to achieve targeted SpO2 using the 2010 neonatal resuscitation protocol guidelines. RESULTS: 56% (14/25; PEEP-0) and 50% (13/26; PEEP-5) infants received PPV. Mean gestational age was 30 (PEEP-0) vs 31 (PEEP-5) weeks. The mean [SD] birthweight (g) of PEEP-0 was significantly lower than PEEP-5 (1050.4 [262.7] vs 1218.8 [236.8], p = 0.02). Pre-ductal SpO2, FiO2 delivered at each time point, and rates of pneumothorax, surfactant administration and oxygen dependency at 36 weeks postmenstrual age or death was similar. CONCLUSION: Due to the small sample size and potential bias accrued through random allocation of higher birthweight infants to the PEEP-5 group, the results did not confirm differences in outcomes between the groups, despite evidence favoring postnatal ventilation with PEEP. A further randomized, controlled clinical trial with a larger sample size is warranted to determine the utility and safety of PEEP during the resuscitation of premature infants immediately after birth.

Accuracy of transcutaneous bilirubin measured by the BiliCare device in late preterm and term neonates.

OBJECTIVE: The objective of this study is to explore the accuracy and performance of a new transcutaneous bilirubinometer (TCB) for the screening of jaundice in late preterm and term infants. METHODS: A cross-sectional study was conducted. TCB measurements were performed using the BiliCare(TM) bilirubinometer. Paired TCB and serum bilirubin (SB) measurements were analysed. RESULTS: One hundred and fourteen paired samples were collected from 93 healthy late preterm and term infants. Bilirubin measurements were done at median (interquartile range) of 50.5 (34, 72) hours. The mean (SD) difference between the TCB and SB was 1.87 (1.98) mg/dL. A TCB cut-off level at 8.0 mg/dL provides a sensitivity of 97.3% with a negative predictive value (NPV) of 87.5% to detect a SB level of at least 8.0 mg/dL. For SB levels of at least 10.0 mg/dL, a TCB cut-off at 9.0 mg/dL shows a sensitivity of 97.5%; NPV 95.4%. For a SB level of at least 13.0 mg/dL, a TCB cut-off at 12 or 13 mg/dL had a sensitivity of 92.9% and NPV of 98.7%. CONCLUSION: The BiliCare(TM) demonstrated good performance with positive bias for the screening of jaundice in healthy late preterm or term infants. However, if adopted, proper cut-off levels should be chosen because of sub-optimal device precision.

Thiophenecarboxylate suppressor of cyclic nucleotides discovered in a small-molecule screen blocks toxin-induced intestinal fluid secretion.

We carried out a "pathway" screen of 50,000 small molecules to identify novel modulators of cAMP signaling. One class of compounds, the 2-(acylamino)-3-thiophenecarboxylates, strongly suppressed cAMP and cGMP in multiple cell lines in response to different agonists acting on G-protein-coupled receptors, adenylyl cyclase, and guanylyl cyclase. The best compounds from structure-activity analysis of 124 analogs, including several synthesized chiral analogs, had and IC(50) of <5 microM for suppression of agonist-induced cAMP and cGMP elevation. Measurements of cAMP, cGMP, and downstream signaling in response to various activators/inhibitors suggested that the 2-(acylamino)-3-thiophenecarboxylates function as nonselective phosphodiesterase activators, although it was not determined whether their action on phosphodiesterases is direct or indirect. The 2-(acylamino)-3-thiophenecarboxylates suppressed CFTR-mediated Cl(-) current in T84 colonic cells in response to cholera and Escherichia coli (STa) toxins, and prevented intestinal fluid accumulation in a closed-loop mouse model of secretory diarrhea. They also prevented cyst growth in an in vitro renal epithelial cell model of polycystic kidney disease. The 2-(acylamino)-3-thiophenecarboxylates represent the first small-molecule cyclic nucleotide suppressors, whose potential therapeutic indications include secretory diarrheas, polycystic kidney disease, and growth inhibition of cAMP-dependent tumors.

Small-molecule vasopressin-2 receptor antagonist identified by a g-protein coupled receptor "pathway" screen.

G-protein-coupled receptors (GPCRs) such as the vasopressin-2 receptor (V(2)R) are an important class of drug targets. We developed an efficient screen for GPCR-induced cAMP elevation using as read-out cAMP activation of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. Fischer rat thyroid cells expressing CFTR and a halide-sensing yellow fluorescent protein (H148Q/I152L) were transfected with V(2)R. Increased cell Cl(-) conductance after agonist-induced cAMP elevation was assayed using a plate reader from cell fluorescence after solution I(-) addition. The Z' factor for the assay was approximately 0.7 with the V(2)R agonist [deamino-Cys1, Val4, d-Arg8]-vasopressin (1 nM) as positive control. Primary screening of 50,000 small molecules yielded a novel, 5-aryl-4-benzoyl-3-hydroxy-1-(2-arylethyl)-2H-pyrrol-2-one class of V(2)R antagonists that are unrelated structurally to known V(2)R antagonists. The most potent compound, V(2)R(inh)-02, which was identified by screening 35 structural analogs, competitively inhibited V(2)R-induced cAMP elevation with K(i) value of approximately 70 nM and fully displaced radiolabeled vasopressin in binding experiments. V(2)R(inh)-02 did not inhibit forskolin or beta(2)-adrenergic receptor-induced cAMP production and was more than 50 times more potent for V(2)R than for V(1a)R. The favorable in vitro properties of the pyrrol-2-one antagonists suggests their potential usefulness in aquaretic applications. The CFTR-linked cAMP assay developed here is applicable for efficient, high-throughput identification of modulators of cAMP-coupled GPCRs.