Maternal Reasons for Early Termination of Exclusive Breastfeeding in Premature Infants: A Prospective Study.

PURPOSE: Maternal concerns for health and growth in prematurely born infants affect the breastfeeding duration. METHOD: This prospective observational study evaluated whether maternal concerns regarding insufficient milk supply were supported by inadequate nutrients in human milk or low infant growth. The study followed mothers of 211 premature born infants for 6 months after delivery. RESULTS: Of the 211 infants, 156 were not exclusively breastfed for the recommended 6 months after delivery. For 79 of these 156 infants, termination was due to maternal concerns regarding insufficient milk supply. There was no difference in human milk nutrients or infant growth when comparing infants who were exclusively breastfed with those who were not. CONCLUSION: Maternal concern regarding insufficient milk supply was the primary explanation for termination of exclusive breastfeeding after premature delivery. Concerns regarding insufficient milk supply were not found associated with inadequate nutrients in the human milk, nor with low infant growth. IMPLICATIONS: Breastfeeding support should remain in focus in this population.

No long-term effect of oral stimulation on the intra-oral vacuum in healthy premature infants.

AIM: Exclusive breastfeeding is recommended for the first 6 months of life, but the breastfeeding rate in premature infants is low. We examined the effect of oral stimulation on infant's strength of suction and the relation between this intra-oral vacuum and breastfeeding duration. METHOD: Between 2016 and 2018, 211 infants in a Danish neonatal unit were randomised 1:1 and of these 108 to oral stimulation intervention and 103 to control. Suction was measured as peak vacuum at enrolment and a corrected age of 6 weeks. Breastfeeding duration was registered. RESULTS: Vacuum increased from enrolment to a corrected age of 6 weeks in all infants, and no effect of oral stimulation intervention was demonstrated P = .08. Infants born ≤32 gestational weeks had lower vacuum compared with infants born after, 350 vs 398 mbar P < .001. For infants born after 32 gestational weeks, the odds ratio for exclusive breastfeeding at 6 months was 1.99 per 100 mbar increase in vacuum P = .01. CONCLUSION: In our study, infant's intra-oral vacuum increased with age and was not affected by the oral stimulation intervention. For infants born after 32 gestational weeks, the exclusive breastfeeding rate was positively associated with a strong vacuum.

Randomised oral stimulation and exclusive breastfeeding duration in healthy premature infants.

AIM: Although exclusive breastfeeding is recommended for all newborn in the first 6 months of life, only 13% of Danish premature infants complies with this. This trial aimed to examine whether oral stimulation prolonged exclusive breastfeeding in premature infants. METHOD: A randomised controlled trial was conducted at the Neonatal Intensive Care Unit, Hvidovre Hospital, Denmark between 2016 and 2018. Systematic oral stimulation was performed by the parents after training by occupational therapists. Primary outcome was exclusive breastfeeding duration with 6 months' follow-up, analysed by intention-to-treat. RESULTS: Included were 211 infants (53% boys) with a mean gestational age of 231 days, allocated in ratio 1:1 to oral stimulation or standard care. There was no difference in exclusive breastfeeding duration between infants orally stimulated and control infants. Thus, for orally stimulated infants, median duration was 122 days (interquartile range 40-183) in contrast to 154 days (interquartile range 61-183) for the controls, P value .16. At 6 months of age, 27% of orally stimulated infants were exclusively breastfed compared with 25% of controls. CONCLUSION: In healthy premature infants, oral stimulation performed by parents has no long-lasting effect on breastfeeding duration. Attention should be directed to parental education and involvement.

Bacillus Calmette-Guérin vaccination, thymic size, and thymic output in healthy newborns.

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size. METHODS: In infants randomized to BCG or no BCG, thymic index (TI), and thymic/weight index (TWI) were measured by ultrasound at birth and at the age of 3 mo. T cell subpopulations including CD4+ T cells, CD8+ T cells, and recent thymic emigrants (RTEs) were assessed by flow cytometry. Infections up to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity in the newborn.

The association between Bacillus Calmette-Guérin vaccination (1331 SSI) skin reaction and subsequent scar development in infants.

BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence or absence of a BCG scar and the size the scar was measured at 13 months of age. RESULTS: Of 492 infants included, 87% had a wheal after vaccination, 11% had a bulge, and 2% had no reaction. The mean wheal size was 3.8 mm (95% confidence interval 3.7-3.9). Overall, 95% (442/466, 26 lost to follow-up) of BCG-vaccinated infants had a scar at 13 months of age. In infants with a wheal, the probability of developing a scar was 96%, declining to 87% in the case of a bulge, and to 56% in the case of no reaction (p for same probability = 0.03). Wheal size was positively correlated with the probability of getting a scar and scar size. CONCLUSION: Scarring after BCG vaccination has been associated with lower infant mortality. In a high-income setting, we found that correct injection technique is highly important for the development of a BCG scar and that registration of the category of BCG skin reaction (as wheal, bulge, or no reaction) may be used to identify infants at risk of scar failure. Finally, the wheal size was positively associated with both the probability of getting a scar and scar size. TRIAL REGISTRATION: The study was registered at www.ClinicalTrials.gov with trial registration number NCT01694108 .

Nonspecific effect of BCG vaccination at birth on early childhood infections: a randomized, clinical multicenter trial.

BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitment period. Participating children were randomized to receive BCG within 7 d of birth or to a no intervention control group. Parent-reported infections (events) were collected using telephone interviews at 3 and 13 mo. Data collectors were blinded to allocation. RESULTS: The analyses included 4,224/4,262 (99%) and 4,192/4,262 (98%) children at 3 and 13 mo. From 0 to 3 mo, there were 291 events in the BCG group vs. 336 events in the control group, incidence rate ratio (IRR) = 0.87 (95% confidence interval (CI): 0.72 to 1.05). In this age group, the IRR was 0.62 (95% CI: 0.39 to 0.98) if the mother was BCG vaccinated. From 3 to 13 mo, there were 7,028 vs. 6,791 events, IRR = 1.02 (95% CI: 0.97 to 1.07). CONCLUSION: This study did not find a nonspecific public health benefit of BCG on parent-reported infections. BCG may have reduced the incidence of infections in children of BCG-vaccinated mothers during the first 3 mo.

Glucose tolerance in obese pregnant women determines newborn fat mass.

INTRODUCTION: Offspring of obese women have both short-term and long-term increased morbidities. We investigated the relationship between maternal 2-h plasma glucose level determined by an oral glucose tolerance test, degree of obesity, gestational weight gain and total fat, abdominal fat, and fat-free masses in the offspring of obese mothers. MATERIAL AND METHODS: Obese mother-newborn dyads were recruited and 2-h plasma glucose levels were assessed during gestational weeks 27-30; neonatal body composition was measured by dual-energy X-ray absorptiometry scanning (DXA) within 48 h of birth. RESULTS: Among 264 term, healthy, and singleton infants eligible for inclusion, 248 were included. Of these, 205 (83%) obese mother-newborn dyads had a DXA scan and 2-h plasma glucose measurements. Linear regression analysis showed that birthweight z-scores correlated with 2-h plasma glucose levels (p = 0.002) after adjusting for gestational weight gain, maternal age, education, smoking, prepregnancy degree of obesity, parity, and birth length. Total (p = 0.012) and abdominal (p = 0.039) fat masses correlated with 2-h plasma glucose levels after adjusting for gestational weight gain, maternal age, education, smoking, prepregnancy degree of obesity, parity, gestational age, and newborn sex. There was no association between total (p = 0.88) and abdominal (p = 0.61) fat-free masses and 2-h plasma glucose. CONCLUSION: At 27-30 weeks of gestation, 2-h plasma glucose levels are related to total and abdominal newborn fat masses, but not to fat-free mass. Interventions targeting maternal postprandial glucose levels may induce more appropriate birthweight, thereby reducing the risk of subsequent morbidity.

DXA performance in a pediatric population: precision of body composition measurements in healthy term-born infants using dual-energy X-ray absorptiometry.

Dual-energy X-ray absorptiometry (DXA) has been hailed as a golden standard for measuring body composition in adults but remains to be fully assessed for the infant population. A total of 64 newborn infants were allocated to 1 of 3 groups. All underwent 2 Hologic Discovery A DXA scans. Suboptimal scans were reconstructed, and an investigation into the success of adjustment was carried out. Depending on group, the factors of weight change and repositioning were investigated. Test-retest variation and coefficients of variation for DXA body composition estimates were calculated. Furthermore, the effects of flannel sheets and breast milk were investigated using a pediatric phantom. Reconstruction of suboptimal scans resulted in more accurate body weight estimates. Moderate weight change and repositioning had no significant effect on the variation between scans. No significant body composition changes occurred between scans. The test-retest variation varied between 6.3% and 11.8%. Flannel sheets and breast milk affected DXA results significantly. High precision of DXA measurements was obtained in our newborn population. Reconstructing scans is a viable way of correcting minor movement artifacts. Moderate weight changes and repositioning have no significant effect on DXA results, whereas flannel sheets and milk do.

Treating umbilical granuloma with topical clobetasol propionate cream at home is as effective as treating it with topical silver nitrate in the clinic.

AIM: There is a lack of evidence on the best treatment option for umbilical granuloma. The primary aim of this study was to compare three treatments for umbilical granuloma: standard treatment with topical silver nitrate, clobetasol propionate cream (0.05%) and ethanol wipes. The secondary aim was to evaluate whether the treatment could be successfully administered by a parent at home, rather than in the outpatient clinic. METHODS: A total of 109 infants were randomised to one of three groups and 94 infants completed the assigned treatment: 30 infants received standard treatment with silver nitrate (99%) in the outpatient clinic, 30 infants had topical clobetasol propionate cream (0.05%) applied at home, and 34 infants received cleansing with ethanol wipes (82%) at home. RESULTS: Silver nitrate and clobetasol propionate cream (0.05%) were significantly superior to ethanol wipes, with shorter healing times and higher resolution rates (p = 0.0001). Healing time and resolution rates were identical for silver nitrate and clobetasol propionate cream (0.05%). Mild side effects were occasionally reported, all of which were self-limiting. CONCLUSION: Treating umbilical granuloma with topical clobetasol propionate cream (0.05%) at home is as effective as treating it with topical silver nitrate (99%) in the clinic.

Transient hyperoxia does not affect regional cerebral tissue oxygen saturation in moderately preterm or term newborns.

AIM: Even short periods of hyperoxia may induce prolonged cerebral vasoconstriction in newborn infants, and this could theoretically lead to cerebral ischaemia even once normoxia is re-established. This study aimed to investigate the effect of brief hyperoxic exposures on regional cerebral tissue oxygen saturation (rStO2 ) and to evaluate whether any observed prolonged cerebral vasoconstriction was related to maturity. METHODS: The study included 30 infants with a postmenstrual age of more than 32 weeks, who were treated with nasal continuous positive airway pressure and a fraction of inspired oxygen of ≤0.3. The INVOS 5100C oximeter was used to measure rStO2 before, during and after two hyperoxic exposures. If hyperoxia induced a prolonged cerebral vasoconstriction, posthyperoxic rStO2 would be expected to decrease. RESULTS: rStO2 increased slightly after the first hyperoxic exposure, with a mean difference of 1.37% (95% CI 0.15, 2.6). After the second oxygen exposure, rStO2 remained unchanged with a mean difference of -0.4% (95% CI -1.6, 0.78). Differences in rStO2 were not related to gestational age in either of the two hyperoxic episodes. CONCLUSION: We found no evidence to support the theory that transient hyperoxia induces prolonged cerebral vasoconstriction in infants with a postmenstrual age above 32 weeks.

The Treatment of Obese Pregnant Women (TOP) study: a randomized controlled trial of the effect of physical activity intervention assessed by pedometer with or without dietary intervention in obese pregnant women.

OBJECTIVE: The objective of the study was to assess physical activity intervention assessed by a pedometer with or without dietary intervention on gestational weight gain (GWG) in obese pregnant women by comparing with a control group. STUDY DESIGN: This study was a randomized controlled trial of 425 obese pregnant women comparing 3 groups: (1) PA plus D, physical activity and dietary intervention (n = 142); (2) PA, physical activity intervention (n = 142); and (3) C, a control group receiving standard care (n = 141). All participants routinely in gestational weeks 11-14 had an initial dietary counseling session and were advised to limit GWG to less than 5 kg. Physical activity intervention included encouragement to increase physical activity, aiming at a daily step count of 11,000, monitored by pedometer assessment on 7 consecutive days every 4 weeks. Dietary intervention included follow-up on a hypocaloric Mediterranean-style diet. Instruction was given by a dietician every 2 weeks. The primary outcome measure was GWG, and the secondary outcome measures were complications of pregnancy and delivery and neonatal outcome. RESULTS: The study was completed by 389 patients (92%). Median values of GWG (ranges) were lower in each of the intervention groups (PA plus D, 8.6 [-9.6 to 34.1] kg, and group PA, 9.4 [-3.4 to 28.2] kg) compared with the control group (10.9 [-4.4 to 28.7] kg [PA+D vs C]; P = .01; PA vs C; P = .042). No significant difference was found between the 2 intervention groups. In a multivariate analysis, physical activity intervention decreased GWG by a mean of 1.38 kg (P = .040). The Institute of Medicine's recommendations for GWG were more frequently followed in the intervention groups. CONCLUSION: Physical activity intervention assessed by pedometer with or without dietary follow-up reduced GWG compared with controls in obese pregnant women.

Cerebral vascular effects of hypovolemia and dopamine infusions: a study in newborn piglets.

AIM: Despite widespread use, effects of volume boluses and dopamine in hypotensive newborn infants remain controversial. We aimed to elucidate if hypovolemia alone impairs cerebral autoregulation (CA) and if dopamine affects cerebral vasculature. METHODS: In 12 piglets, cerebral perfusion (laser-Doppler flux) and oxygenation [near-infrared spectroscopy (NIRS)] were examined during dopamine (20-50 µg/kg per minute) and nonpharmacologically induced blood pressure (ABP) changes. Effect on cerebral perfusion and oxygenation was quantified as frequency gain between ABP and laser-Doppler flux (gain-LDF) and NIRS [gain-oxygenation index (OI)], respectively. Gain quantifies change in perfusion or oxygenation per ABP-change. CA was estimated as gain-LDF during nonpharmacologically induced ABP changes, that is, as degree of impairment. Dopamine's cerebrovascular effect was estimated by contrasting gain during dopamine- and nonpharmacologically induced ABP changes. Measurements were conducted during both normovolemia- and haemorrhage-induced hypovolemia. RESULTS: Hypovolemia elicited hypotension (p = 0.02) as well as increasing impairment of CA (p = 0.01). However, hypovolemia without hypotension did not affect CA significantly. Dopamine increased perfusion significantly compared to nonpharmacological challenges (mean difference: 1.5%/mmHg, 95% CI: 0.5-2.6, p = 0.007). Oxygenation was, however, similar (mean difference: 0.01 µmol/L per mmHg, 95% CI: -0.03 to 0.05, p = 0.7). CONCLUSION: Our findings do not support that hypovolemia alone impairs CA. Furthermore, dopamine seems to increase cerebral perfusion but not oxygenation.

Evaluation of the diagnostic process in neonates with conjugated hyperbilirubinaemia.

INTRODUCTION: The Danish Health Authority (DHA) recommends diagnostic evaluation of infants who develop prolonged jaundice and a serum conjugated bilirubin (CB) concentration ≥ 17 µmol/l. This study aimed to assess the efficacy of the programme in identifying infants with biliary atresia (BA) or other liver disease. Infants born in the Central Denmark Region from 2016 to 2021 were investigated. METHODS: A total of 693 infants were identified in the Central Biochemical Database (Labka). From a review of all medical records, CB measurements, results from diagnostic procedures and the final diagnosis were documented. RESULTS: Four infants were identified with BA. They had a mean CB concentration of 105 µmol/l. A total of 33 infants were diagnosed with other cholestatic diseases; this group had a mean CB concentration of 58.9 µmol/l. The remaining 656 infants with a mean CB of 20.5 µmol/l recovered spontaneously without any sign of cholestatic disease. Approximately 75% of all HIDA scintigraphies (100/134) were conducted in 647 infants with a maximum CB concentration less-than 30 µmol/l. They all had bile drainage to the intestines. Among these infants, twelve were diagnosed as heterozygote for alfa-1-antitrypsin deficiency. CONCLUSION: The CB threshold limit recommended by the DHA detected all patients with BA, but its use leads to over-investigation and over-diagnosing. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Applicability of near-infrared spectroscopy to measure cerebral autoregulation noninvasively in neonates: a validation study in piglets.

Impaired cerebral autoregulation (CA) is common and is associated with brain damage in sick neonates. Frequency analysis using spontaneous changes in arterial blood pressure (ABP) and cerebral near-infrared spectroscopy (NIRS) has been used to measure CA in several clinical studies. Coherence of the NIRS and ABP signals (i.e. correlation in the frequency domain) detects impairment of CA, whereas gain (i.e. magnitude of ABP variability passing from systemic to cerebral circulation) estimates the degree of this impairment. So far, however, this method has not been validated. In 12 newborn piglets, we compared NIRS-derived measures of CA with a conventional measure of CA: cerebral blood flow was measured by laser Doppler flowmetry, and changes in ABP were induced by inflating a thoracic aorta balloon. CA capacity was calculated as %ΔCVR/%ΔABP (i.e. percentage of full autoregulatory capacity), where CVR (i.e. cerebral vascular resistance) was estimated as ABP/Doppler flux. Correlation between coherence and CA capacity (r = -0.34, n = 24, p > 0.05) and between gain and CA capacity (r = -0.11, n = 24, p > 0.05) was limited. As expected, however, gain was significantly associated with CA capacity in measurements with significant coherence (r = -0.55, n = 15, p = 0.03). In conclusion, our data validate frequency analysis for estimation of CA in clinical research. Low precision, however, hampers its clinical application.

Determinants of Bacille Calmette-Guérin scarification in Danish children.

BACKGROUND: Studies in low-income countries have shown that among Bacille Calmette-Guérin (BCG) vaccinated children, those who develop a BCG-scar have significantly better survival than those who do not develop a scar. In a Danish multicenter randomized clinical trial we assessed determinants for developing a BCG-scar and for BCG scar size following neonatal BCG vaccination. METHODS: At three Danish hospitals, newborns were randomized 1:1 to BCG vaccination or no BCG vaccination. The infants were invited for a clinical examination at the ages of 3 and 13 months. At 13 months, the scar site was inspected and scar size measured. We investigated three groups of determinants; external, parental, and individual-level determinants on relative scar prevalence and differences in median scar sizes. RESULTS: Among 2118 BCG vaccinated infants, 2039 (96 %) were examined at 13 months; 1857 of these (91 %) had developed a BCG-scar. Compared with Copenhagen University Hospital, Hvidovre (85 %), Copenhagen University Hospital, Rigshospitalet had a scar prevalence of 95 % (adjusted Prevalence ratio (aPR) = 1.24 [CI 95 %: 1.18 to 1.30]); it was 93 % at Kolding Hospital (aPR 1.27 [CI 95 %: 1.19 to 1.35]). Increasing vaccine experience was positively associated with developing a scar and with scar size. CONCLUSION: Across multiple potential determinants of BCG scaring and size, logistical factors dominated. The results support that injection technique is an important determinant of developing a scar. Given the strong link between having a BCG scar and subsequent health, improved BCG vaccination technique could play a major role for child health.

Newborn body composition after maternal bariatric surgery.

INTRODUCTION: In pregnancy after Roux-en-Y gastric bypass (RYGB), there is increased risk of low birthweight in the offspring. The present study examined how offspring body composition was affected by RYGB. MATERIAL AND METHODS: Mother-newborn dyads, where the mothers had undergone RYGB were included. Main outcome measure was neonatal body composition. Neonatal body composition was assessed by dual-energy X-ray absorptiometry scanning (DXA) within 48 hours after birth. In a statistical model offspring born after RYGB were compared with a reference material of offspring and analyses were made to estimate the effect of maternal pre-pregnancy body mass index (BMI), gestational weight gain, parity, gestational age at birth and newborn sex on newborn body composition. Analyses were made to estimate the impact of maternal weight loss before pregnancy and of other effects of bariatric surgery respectively. The study was performed at a university hospital between October 2012 and December 2013. RESULTS: We included 25 mother-newborn dyads where the mothers had undergone RYGB and compared them to a reference material of 311 mother-newborn dyads with comparable pre-pregnancy BMI. Offspring born by mothers after RYGB had lower birthweight (335g, p<0.001), fat-free mass (268g, p<0.001) and fat% (2.8%, p<0.001) compared with reference material. Only 2% of the average reduction in newborn fat free mass could be attributed to maternal pre-pregnancy weight loss whereas other effects of RYGB accounted for 98%. Regarding reduction in fat mass 52% was attributed to weight loss and 47% to other effects of surgery. CONCLUSION: Offspring born after maternal bariatric surgery, had lower birthweight, fat-free mass and fat percentage when compared with a reference material. RYGB itself and not the pre-pregnancy weight loss seems to have had the greatest impact on fetal growth.

[Neonatal survival and health in Denmark].

This review gives a summary of Danish preterm care, which has been defined by national adaptation of antenatal corticosteroids in the 1970ies and continuous positive airway pressure in the 1980ies. Today, preterm survival in Denmark is high, by international standards, but lower than in the neighbouring countries Sweden and Norway. The lack of a national neonatal quality database may offer an explanation to this. Starting in 2019, the Danish Newborn Quality Database reports complete population-based measures of newborn survival and health and may help improve standards of care in the future.