Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators.

BACKGROUND: Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. METHODS: We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. RESULTS: The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating. CONCLUSION: The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. IMPACT: Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators.

Short courses of dual-strain probiotics appear to be effective in reducing necrotising enterocolitis.

AIM: Prophylactic probiotics to reduce necrotising enterocolitis (NEC) are mostly given for at least 28 days or until discharge. We describe the effects of a shorter duration dosing strategy. METHODS: Retrospective cohort study of neonates (birthweight 400-1500 g) in three neonatal intensive care units in Switzerland and Germany that embarked on probiotic prophylaxis given for 10 or 14 days, employing a fixed combination (Lactobacillus acidophilus plus Bifidobacterium infantis, each 10(9) CFU/day) licensed as a drug in Switzerland. Probiotics were initiated upon discontinuation of antibiotics, or on day 1-3 in infants without antibiotics. Repeat probiotic courses were given whenever antibiotics had been instituted and were discontinued. RESULTS: Birthweight and gestational age were similar in the two 24-month pre- and postimplementation cohorts. NEC rates fell from 33 of 633 (5.2%) to 8 of 591 infants alive at three days (1.4%; risk ratio (RR) 0.26, 95% confidence interval (CI) 0.12-0.55). The drop in NEC was significant both for infants of 400-999 g (6.4% to 2.5%) and 1000-1500 g birthweight (4.4% to 0.6%). Mortality was 5.1% (32/633) without, as opposed to 3.5% (21/591) with probiotics, respectively (RR 0.69, 95% CI 0.41-1.19). CONCLUSION: Short courses of a dual-strain probiotics appear to be effective in reducing NEC.

Prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics and outcome in very low birth weight infants.

OBJECTIVE: To evaluate outcome data in an observational cohort of very low birth weight infants of the German Neonatal Network stratified to prophylactic use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics. STUDY DESIGN: Within the observational period (September 1, 2010, until December 31, 2012, n=5351 infants) study centers were categorized into 3 groups based on their choice of Lactobacillus acidophilus/Bifidobacterium infantis use: (1) no prophylactic use (12 centers); (2 a/b) change of strategy nonuser to user during observational period (13 centers); and (3) use before start of observation (21 centers). Primary outcome data of all eligible infants were determined according to center-specific strategy. RESULTS: The use of probiotics was associated with a reduced risk for necrotizing enterocolitis surgery (group 1 vs group 3: 4.2 vs 2.6%, P=.028; change of strategy: 6.2 vs 4.0%, P<.001), any abdominal surgery, and hospital mortality. Infants treated with probiotics had improved weight gain/day, and probiotics had no effect on the risk of blood-culture confirmed sepsis. In a multivariable logistic regression analysis, probiotics were protective for necrotizing enterocolitis surgery (OR 0.58, 95% CI 0.37-0.91; P=.017), any abdominal surgery (OR 0.7, 95% CI 0.51-0.95; P=.02), and the combined outcome abdominal surgery and/or death (OR 0.43; 95% CI 0.33-0.56; P<.001). CONCLUSIONS: Our observational data support the use of Lactobacillus acidophilus/Bifidobacterium infantis probiotics to reduce the risk for gastrointestinal morbidity but not sepsis in very low birth weight infants.

Developmental delay in hypoxia-induced HO-1 expression predisposes to gut injury.

AIMS: Necrotizing enterocolitis (NEC) is an often fatal disease that affects 5-8% of preterm newborn infants but does not occur in older infants and children. As carbon monoxide (CO) may exert protective effects against NEC, we assessed patterns of intestinal injury and investigated the expression of the CO-producing enzyme heme oxygenase-1 (HO-1) in mature and immature rat guts in response to hypercapnia and reoxygenation (H/R). METHODS: Gut barrier failure (increased permeability for dextran) was assessed in immature (newborn rats) and mature rats (weanling rats) subjected to H/R. Their guts were assayed for apoptosis (caspase-3 activity), expression of inducible NO synthase (iNOS) and HO-1 [quantitative polymerase chain reaction (PCR) and immunoblot]. The role of HO-1 was investigated in experiments involving HO-1 induction by hemin or HO-1 inhibition by tin protoporphyrin IX. RESULTS: In the mature gut, H/R induced the expression of intestinal HO-1 within 48 h, whereas in the immature gut HO-1 up-regulation was delayed by 48 h. Immature, but not mature, rats exhibited gut barrier failure, apoptosis and increased iNOS expression upon H/R. After the induction of HO-1 by hemin, gut barrier failure and apoptosis were abrogated in the immature gut, while the inhibition of HO-1 by tin protoporphyrin IX significantly aggravated gut injury. CONCLUSIONS: These experiments point to an immaturity-dependent lag in HO-1 expression upon H/R in the immature gut and link low HO-1 to gut barrier failure induced by H/R in a non-infectious dam-fed animal model of gut injury.

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Somatic classification of neonates based on birth weight, length, and head circumference: quantification of the effects of maternal BMI and smoking.

We defined neonates as small, appropriate, or large for gestational age (SGA, AGA, LGA) based on birth weight, length, and head circumference. We analyzed the effects on the somatic classification of maternal body mass index (BMI) (<18.5, 18.5-24.99, 25.0-29.99, ≥ 30) and smoking during pregnancy (0, 1-7, 8-14, ≥ 15 cigarettes daily). Data were from the German Perinatal Survey (1998-2000; 433,669 cases). The following refers to the classification by birth weight. In the normal maternal weight population SGA rates increased with cigarette consumption: 9.8%, 17.8%, 21.6%, and 25.4% for non-smokers, and smokers of 1-7, 8-14, and ≥ 15 cigarettes daily, respectively. In non-smoking underweight women the SGA rate was 17.4%. In underweight smokers of ≥ 15 cigarettes daily the SGA rate was 38.5% [odds ratio 5.77, 95% confidence interval 5.10-6.53, compared with normal weight non-smokers]. In the normal maternal weight population, LGA rates were 9.9%, 5.3%, 4.6%, and 3.5% for non-smokers, and smokers of 1-7, 8-14, and ≥ 15 cigarettes daily, respectively. In the obese, LGA rates were 20.9% (non-smokers) and 11.4% (≥ 15 cigarettes). Similar findings were obtained for the somatic classifications based on birth length and head circumference. Results for the various combinations of maternal BMI and smoking status in the three classification systems are described. Our findings may assist in individualized risk assessment for SGA and LGA births.

Interaction of maternal peroxisome proliferator-activated receptor gamma2 Pro12Ala polymorphism with fetal sex affects maternal glycemic control during pregnancy.

It was suggested that fetal sex may substantially affect maternal glycemic control during pregnancy in genetically susceptible mothers. The peroxisome proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is known to affect glycemic control and may act in a sex-specific manner. This polymorphism is thus an attractive candidate to test this hypothesis using a second independent functionally relevant polymorphism. We analyzed the impact of fetal sex on maternal glycemic control during pregnancy in relation to the maternal PPARgamma2 Pro12Ala polymorphism. Two-thousand fourteen Caucasian women without preexisting diabetes and preexisting hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycemic control was analyzed by measuring total glycated hemoglobin at birth. Correction for confounding factors and multiple testing was considered in the analysis. The maternal PPARgamma2 Pro12Ala polymorphism without consideration of fetal sex had no effect on blood pressure, new onset of proteinuria and total glycated hemoglobin at delivery. Mothers carrying both G alleles (GG genotype) delivering a girl had a higher (P = 0.015) total glycated hemoglobin (6.81 or - 0.50%) versus mothers carrying the same alleles but delivering boys (5.85 + or - 0.58%). Comparing mothers with the GG genotype delivering girls with mothers with CC or CG genotypes also delivering girls (6.32 + or - 0.72%) revealed a significantly higher maternal total glycated hemoglobin at delivery in the former group (P < 0.009). Fetal sex/sex chromosomes may substantially affect maternal glycemic control in mothers who are carriers of the GG alleles of the PPARgamma2 Pro12Ala polymorphism.

Maternal and fetal PROGINS progesterone receptor polymorphism reduces the risk for transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is the most common perinatal respiratory disorder. It was suggested that the pathogenesis of TTN might involve altered activity of female sex hormones. This study analyzed whether the PROGINS progesterone receptor polymorphism, which is less responsive to progesterone, is associated with TTN. METHODS: A cohort of 2352 infants born to Caucasian women at the Obstetrics Department of the Charite was investigated prospectively. The collected information included the occurrence of respiratory disorders, birth weight, gestational age at delivery, mode of delivery, and maternal morbidity. Mothers and newborns were genotyped for the PROGINS progesterone receptor polymorphism. Statistical analyses considered correction for confounding factors. RESULTS: The presence of the mutated T2-allele either in mothers or in infants was associated with a reduction of the incidence of TTN in a gene dose-dependent manner (mothers T1/T1: 6.6%, T1/T2: 4.3% T2/T2: 2.3%, p < 0.01; infants T1/T1: 6.5%, T1/T2: 4.7%, T2/T2: 0.0%, p = 0.02 in a multivariable regression model). The total number of mutated T2-alleles present in a mother/child pair was associated with a reduction of TTN (4 T2-alleles: 6.4%, n=95; 3: 5.9%, n=30; 2: 3.1%, n=9; 1: 1.4%, n=1; 0:0%, n=0; p < 0.01 in a multivariable regression model). CONCLUSIONS: Both the maternal and fetal mutated alleles of the PROGINS progesterone receptor polymorphism seem to protect from TTN. The same phenotype occurs regardless of whether the mutation is localized in the mother or in the infant. Fetal as well as maternal T2-alleles synergistically reduce the risk for TTN in a gene dose-dependent manner.

Early subcutaneous administration of etanercept (Enbrel) prevents from hyperoxia-induced lung injury.

Both hyperoxia-induced proapoptotic sensitization of alveolar type II cells (TII cells) and high-stretch mechanical ventilation induced pulmonary inflammation are tumor necrosis factor alpha (TNFalpha) mediated. Therefore, binding of free TNFalpha should protect from TNFalpha-mediated acute lung injury and ameliorate the subsequently developing chronic lung disease. Here, the authors show that a single subcutaneous pretreatment of rat with etanercept, a recombinant p75 TNF receptor 2 human immunoglobulin G1 (IgG1) construct, inhibits the hyperoxia-induced and TNFalpha-mediated increase in the expression of TNFalpha receptor, the activation of caspase 3 in TII cells, and, as an early indicator of lung injury, the capillary-alveolar leakage and granulocyte number in lung lavage. The authors assume that subcutaneous administration of etanercept might be suitable to prevent acute lung injury and its sequelae induced by hyperoxic ventilation of premature neonates and critically ill patients.

Trefoil factors in human milk.

We measured concentrations of the gastrointestinal protective peptides Trefoil factors in human milk. By the use of in-house ELISA we detected high amounts of TFF3, less TFF1 and virtually no TFF2 in human breast milk obtained from 46 mothers with infants born extremely preterm (24-27 wk gestation), preterm (28-37 wk gestation), and full term (38-42 wk gestation). Samples were collected during the first, second, third to fourth weeks and more than 4 wks postpartum. Median (range) TFF1 [TFF3] concentrations in human milk were 320 (30-34000) [1500 (150-27,000)] pmol/L in wk 1, 120 (30-720) [310 (50-7100)] pmol/L in wk 2, 70 (20-670) [120 (20-650)] pmol/L in wks 3 to 4, and 60 (30-2500) [80 (20-540)] pmol/L in >4 wks after delivery. The lowest concentrations of TFF1 and TFF3 were found later than 2 wks after birth. In conclusion, TFF was present in term and preterm human milk with rapidly declining concentrations during the first weeks post partum. The clinical significance of TFF present in human milk remains to be explored, both regarding development of the fetal gut and protection against necrotizing enterocolitis.

Impact of maternal angiotensinogen M235T polymorphism and angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure, protein excretion and fetal outcome in pregnancy.

OBJECTIVE: To test the hypothesis that genetically determined alterations of the renin-angiotensin system are associated with hypertensive disorders in pregnancy. METHODS: A genetic association study was conducted at the obstetrics department of the Charité university hospital, Berlin, Germany. A total of 1068 Caucasian women were consecutively included after delivery and genotyped for the angiotensinogen M235T polymorphism and the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism. RESULTS: Women homozygous for the angiotensinogen T allele have significantly elevated mean systolic and diastolic blood pressures in the third trimester (118.4 +/- 1.1/71.5 +/- 0.7 versus 116.9 +/- 0.3/70.4 +/- 0.2 mmHg, n = 128 versus 940; P < 0.05). This finding is especially pronounced in the subgroup of primigravid women. The ACE polymorphism is not associated with blood pressure during pregnancy. None of the polymorphisms is associated with urinary protein excretion or oedema during pregnancy. Maternal polymorphisms do not influence fetal growth and birth weight. There is, however, an interesting trend towards an increased incidence of circulatory system malformations in newborns carrying alleles that are known to be associated with decreased intrinsic renin-angiotensin system activity. CONCLUSION: We demonstrate for the first time in a large Caucasian population that a common maternal polymorphism of the angiotensinogen gene is related to a blood pressure increase during pregnancy. The angiotensinogen M235T polymorphism might contribute to the multifactorial pathogenesis of gestational hypertension and pre-eclampsia.

Phenotype of palmitic acid transport and of signalling in alveolar type II cells from E/H-FABP double-knockout mice: contribution of caveolin-1 and PPARgamma.

Based on the assumption that fatty-acid-binding proteins (FABPs) of the epidermal-type (E-FABP) and heart-type (H-FABP) in murine alveolar type II (TII) cells mediate the synthesis of dipalmitoyl phosphatidylcholine (DPPC), the main surfactant phospholipid, we analysed TII cells isolated from wild-type (wt) and E/H-FABP double-knockout (double-ko) mice. Application of labelled palmitic acid to these cells revealed a drop in uptake, beta-oxidation, and incorporation into neutral lipids and total phosphatidylcholine (PC) of TII cells from double-ko mice. Whereas incorporation of labelled palmitic acid into DPPC remained unchanged, degradation studies demonstrated a substantial shift in DPPC synthesis from de novo to reacylation. In addition, increased expression of mRNAs and proteins of caveolin-1 and PPARgamma, and an increase of the mRNA encoding fatty acid translocase (FAT) was observed in the double-ko phenotype. As caveolin-1 interacted with PPARgamma, we assumed that FAT, caveolin-1, and PPARgamma form a signalling chain for fatty acid or drug. Consequently, PPARgamma-selective pioglitazone was added to the diet of double-ko mice. We found that further activation of PPARgamma could 'heal' the E/H-FABP double-ko effect in these TII cells as transport and utilisation of labelled palmitic acid restored a wt phenocopy. This indicated that E-FABP and/or H-FABP are involved in the mediation of DPPC synthesis in wt TII cells.

Vitamin E differentially regulates the expression of peroxiredoxin-1 and -6 in alveolar type II cells.

Vitamin E is the primary lipophilic antioxidant in mammals. Lack of vitamin E may lead to an increase of cytotoxic phospholipid-peroxidation products (PL-Ox). However, we could previously show that alimentary vitamin E-depletion in rats did not change the concentrations of dienes, hydroperoxides, and platelet-activating factor-related oxidation products in alveolar type II cells (TII cells). We hypothesized that vitamin E deficiency increases the activity of enzymes involved in the degradation of PL-Ox. Degradation of PL-Ox may be catalyzed by phospholipase A2, PAF-acetylhydrolase, or peroxiredoxins (Prx's). Alimentary vitamin E deficiency in rats increased the expression of Prx-1 at the mRNA and protein levels and the formation of Prx-SO3, but it did not change the expression of Prx-6 or the activity of phospholipase A2 and PAF-acetylhydrolase in TII cells. H2O2-induced oxidative stress in isolated TII cells activated protein kinase Calpha (PKCalpha) and increased the expression of Prx-1 and Prx-6. Inhibition of PKCalpha in isolated TII cells by long-time incubation with PMA inhibited PKCalpha and Prx-1 but not Prx-6. We concluded that the expression of Prx-1 and -6 is selectively regulated in TII cells; PKCalpha regulates the expression of Prx-1 but not Prx-6. Prx-6 expression may be closely linked to lipid peroxidation.

Inhibition of TNFalpha in vivo prevents hyperoxia-mediated activation of caspase 3 in type II cells.

BACKGROUND: The mechanisms during the initial phase of oxygen toxicity leading to pulmonary tissue damage are incompletely known. Increase of tumour necrosis factor alpha (TNFalpha) represents one of the first pulmonary responses to hyperoxia. We hypothesised that, in the initial phase of hyperoxia, TNFalpha activates the caspase cascade in type II pneumocytes (TIIcells). METHODS: Lung sections or freshly isolated TIIcells of control and hyperoxic treated rats (48 hrs) were used for the determination of TNFalpha (ELISA), TNF-receptor 1 (Western blot) and activity of caspases 8, 3, and 9 (colorimetrically). NF-kappaB activation was determined by EMSA, by increase of the p65 subunit in the nuclear fraction, and by immunocytochemistry using a monoclonal anti-NF-kappaB-antibody which selectively stained the activated, nuclear form of NF-kappa B. Apoptotic markers in lung tissue sections (TUNEL) and in TIIcells (cell death detection ELISA, Bax, Bcl-2, mitochondrial membrane potential, and late and early apoptotic cells) were measured using commercially available kits. RESULTS: In vivo, hyperoxia activated NF-kappaB and increased the expression of TNFalpha, TNF-receptor 1 and the activity of caspase 8 and 3 in freshly isolated TIIcells. Intratracheal application of anti-TNFalpha antibodies prevented the increase of TNFRI and of caspase 3 activity. Under hyperoxia, there was neither a significant change of cytosolic cytochrome C or of caspase 9 activity, nor an increase in apoptosis of TIIcells. Hyperoxia-induced activation of caspase 3 gradually decreased over two days of normoxia without increasing apoptosis. Therefore, activation of caspase 3 is a temporary effect in sublethal hyperoxia and did not mark the "point of no return" in TIIcells. CONCLUSION: In the initiation phase of pulmonary oxygen toxicity, an increase of TNFalpha and its receptor TNFR1 leads to the activation of caspase 8 and 3 in TIIcells. Together with the hyperoxic induced increase of Bax and the decrease of the mitochondrial membrane potential, activation of caspase 3 can be seen as sensitisation for apoptosis. Eliminating the TNFalpha effect in vivo by anti-TNFalpha antibodies prevents the pro-apoptotic sensitisation of TIIcells.

Vitamin E deficiency reduces surfactant lipid biosynthesis in alveolar type II cells.

Reactive oxygen species play an important role in development of lung injury. Neonates exhibit a high risk of developing acute and/or chronic lung disorder, often associated with surfactant deficiency, and in parallel they show low vitamin E concentration. We investigated whether the vitamin E status of adult rats affects the content of phospholipids (PL) in bronchoalveolar lavage and alveolar type II cells. Phosphatidylcholine (PtdCho) is the dominant and functional most important PL in lung surfactant. Therefore, we determined its formation via de novo synthesis and reacylation of lyso-PtdCho in type II cells. Vitamin E depletion caused a decrease of PL content in bronchoalveolar lavage and type II cells and decreased glycerol-3-phosphate O-acyltransferase (G3P-AT) activity, de novo synthesis of PtdCho, and reacylation of lyso-PtdCho in type II cells. Preincubation of type II cell homogenates with dithiothreitol restored the activity of G3P-AT and de novo synthesis but inhibited reacylation. Reacylation was strongly reduced by chelerythrine-mediated inhibition of protein kinase C. We conclude that antioxidant and PKC-modulating properties of vitamin E regulate de novo synthesis of PtdCho and reacylation of lyso-PtdCho in alveolar type II cells. Vitamin E depletion reduced the two pathways of PL synthesis and caused a decrease of PL content in alveolar surfactant of rats.

[Integrating problem-based learning into traditional medical courses: the PBL approach to Pediatrics in Berlin]. / Einbindung von Problemorientiertem Lernen in den konventionellen Studiengang: Das Berliner "Pädiatrie POL-Praktikum".

Integrating a problem-based learning (PBL) approach into the classical curriculum for medical students is often considered difficult because of fundamental differences in the two teaching methods. At the Charité, the medical school of Berlin's Humboldt University, students with a regular medical curriculum are offered to choose between a regular and a PBL class for their course in Paediatrics. During the three-week course in PBL Paediatrics medical students spend the morning in different clinics of the "Otto Heubner Centre for Paediatrics". They are strongly involved in the medical care of 3-4 patients with typical paediatric diseases. Each afternoon, one of the students presents a patient. Patient problems are discussed according to the seven steps of PBL. Subsequently, students use different tools and sources through self-studies to obtain information on the specific disease. By integrating the principles of "Evidence-based medicine" students are trained to critically appraise the medical literature. At the end of the course students are asked to evaluate the quality of the medical teacher, thus allowing for continuous improvement of the teaching methods. We conclude that the principles of PBL can be integrated into a conventional curriculum in medical school.

Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy.

UNLABELLED: HYPOTHESIS/ INTRODUCTION: : We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism. MATERIAL AND METHODS: : One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charité obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done. RESULTS: : Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 ± 0.70% vs. 6.21 ± 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 ± 0.80%) compared to II mothers delivering boys (6.21 ± 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension. CONCLUSIONS: : Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.