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.

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.

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.

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.

Bacille Calmette-Guérin vaccination at birth and differential white blood cell count in infancy. A randomised clinical trial.

BACKGROUND: The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) may have beneficial non-specific effects (NSEs) beyond the protection against TB. This may be related to modifications of the innate immune system. We investigated the effect of BCG at birth on differential white blood cell (WBC) count in healthy, Danish infants. METHOD: The Danish Calmette Study randomised newborns to BCG at birth (Danish strain 1331, Statens Serum Institut) or no intervention. A sub-group of infants had blood samples collected 4 days after randomisation (n = 161), and at age 3 months (n = 152) and 13 months (n = 300). We evaluated the effect of BCG on WBC differential count (total leucocytes, lymphocytes, monocytes, eosinophil, neutrophil and basophil granulocytes (109 cells/L)) measured in peripheral blood. RESULTS: Overall, we found no effect of BCG on differential WBC counts at any time point. CONCLUSION: BCG at birth did not affect WBC count in our cohort of healthy, Danish infants.

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.

BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children: A Randomized Clinical Multicenter Trial.

BACKGROUND: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. METHODS: A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85-1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86-1.16).Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45-0.94); the HR for children who had a non-BCG-vaccinated mother was 1.10 (95% CI, 0.93-1.29) (P = .01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54-0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92-1.30] in other children; P = .02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95-3.43), whereas the HR was 0.94 (95% CI, 0.82-1.08) for children born at term (P = .05). CONCLUSION: BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration.

LED virtual windows are valuable in windowless consultation rooms.

INTRODUCTION: Due to the design of Hvidovre Hospital, the outpatient clinic of the Department of Paediatrics has windowless consultation rooms. Work environment surveys revealed that nurses and doctors working in these windowless rooms considered the lack of natural light a considerable health problem. This study evaluated the effects of installing light-emitting diode (LED) virtual windows in these rooms. METHODS: Four similar windowless consultations rooms located next to each other were used in the study. All had older T-5 fluorescent luminaires installed. In two of these rooms, Servodan LED virtual windows depicting various natural scenes were installed. The illuminance and correlated colour temperature (CCT) of each room's lighting was measured, and a work environment questionnaire was filled out by nurses and doctors working in each room. RESULTS: A total of 113 questionnaires were collected and evaluated. LED virtual windows produced an improved perception of lighting conditions, both at the desk (p < 0.001) and in the rooms in general (p < 0.001) and improved the overall positive experience of the rooms (p = 0.02). A tendency towards concentration difficulties was reported less often in the rooms with LED virtual windows, (p = 0.11). Retinal illuminance (p = 0.02) as well as CCT at the desk (p < 0.005) and at the retina (p < 0.01) alike were increased in rooms with LED virtual windows. CONCLUSIONS: LED virtual windows improved the lighting experience, the impression of the space, the retinal illuminance and the CCT at the desk and at the retina in the windowless rooms. FUNDING: none. TRIAL REGISTRATION: not relevant.

Effects of Bacillus Calmette-Guérin (BCG) vaccination at birth on T and B lymphocyte subsets: Results from a clinical randomized trial.

The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial non-specific effects (NSEs) on infant health. Within a randomized trial on the effect of neonatal BCG on overall health, we investigated the possible immunological impact of neonatal BCG vaccination on lymphocyte subsets, determined by flow cytometry. In 118 infants blood samples were obtained 4 (±2) days post randomization to BCG vaccination or no intervention, and at 3 and 13 months of age. No effects of BCG were found at 4 days. However, BCG increased proportions of effector memory cells at 3 months (Geometric mean ratio (GMR) 1.62, 95% confidence interval (CI) (1.20-2.21), p = 0.002 for CD4+ T cells and GMR 1.69, 95% CI (1.06-2.70), p = 0.03 for CD8+ T cells), and reduced proportions of late differentiated CD4+ T cells (GMR = 0.62, 95% CI (0.38-1.00), p = 0.05) and apoptotic CD4+ T cells at 13 months (GMR = 0.55, 95% CI (0.32-0.92), p = 0.03). In conclusion, limited overall impact of neonatal BCG vaccination on lymphocyte subsets was found in healthy Danish infants within the first 13 months of life. This is in line with the limited clinical effects of BCG observed in our setting.

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 .

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort.

Importance: Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective: To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance: Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.

Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.

INTRODUCTION: BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. RESULTS: Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. CONCLUSIONS AND RELEVANCE: Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed.

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.

BCG vaccination at birth and early childhood hospitalisation: a randomised clinical multicentre trial.

BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age. Randomisation was stratified by prematurity. The primary study outcome was number of all-cause hospitalisations analysed as repeated events. Hospitalisations were identified using The Danish National Patient Register. Data were analysed by Cox proportional hazards models in intention-to-treat and per-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child compared with 1003 hospitalisations among 2133 control children (mean 0.47), resulting in a HR comparing BCG versus no BCG of 1.05 (95% CI 0.93 to 1.18) (intention-to-treat analysis). The effect of BCG was the same in children born at term (1.05 (0.92 to 1.18)) and prematurely (1.07 (0.63 to 1.81), p=0.94). The effect was also similar in the two sexes and across study sites. The results were essentially identical in the per-protocol analysis and after adjustment for baseline characteristics. CONCLUSIONS: BCG vaccination at birth did not reduce the risk of hospitalisation for somatic acquired disease until 15 months of age in this Danish study population. TRIAL REGISTRATION NUMBER: NCT01694108, results.

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.

A new model of paired clinical teaching of international and Danish medical students.

INTRODUCTION: Since 2006, one hospital has offered two clinical courses in obstetrics/gynaecology and paediatrics to international (I) students. However, as I-student enrolment increased, the hospital faced cut-backs. As from 2010, I-team course evaluations therefore dropped to unacceptable levels and more I- than Danish (DK) students failed exams. Therefore, in 2012 we started a three-year internationalisation project (I-project) at two hospitals. The primary intervention was to pair training for I- and DK-students at clinical contact, and to offer an exclusive daily lecturer for I-teams. METHODS: We compared the course evaluations and exam grades of I-teams and DK-teams for two years prior to (107 from I-teams - 211 participants from DK-teams) and during the I-project (245 participants from I-teams - 575 from DK-teams). RESULTS: During the I-project, the I-teams' course evaluations increased to acceptable values and to levels comparable to the evaluation scores of DK-teams. Furthermore, I-students now considered that their communication with the patients was acceptable. Before the I-project, I-students had lower exam grades (median = 10 (range: 0-12)) than DK-students (10 (4-12)) (p = 0.03), but during the I-project, exam grades increased to the levels achieved by DK-students (10 (2-12) - 10 (0-12) (p = 0.22), and no more I- than DK-students failed exams (p = 0.51). CONCLUSIONS: Pairing students for clinical training and allocating an exclusive lecturer for I-teams produced improved courses for internationalisation. Allocating an exclusive lecturer was associated with a cost of about 615 EUR per student per course when the team consisted of ten students. FUNDING: The Capital Region of Denmark and the University of Copenhagen. TRIAL REGISTRATION: not relevant.