Multicentre approach to epidemiological aspects of craniosynostosis in Germany.

We know of no current published data on the prevalence of craniosynostosis in Germany, so our objective in this study was to contribute to the limited knowledge of its epidemiology by assessing time trends, the frequency of prenatal diagnosis, and the timing of diagnosis and treatment. Data were collected in Saxony-Anhalt during the period 2000-17, and we designed a retrospective multicentre cohort study. The prevalence was 4.8 cases of craniosynostosis/10 000 births, and did not increase during that time. We compared the data of 91 patients with those of 273 controls. There were 75 boys and 16 girls (ratio 4.7:1). Fifty-one children had isolated craniosynostosis, consisting of 46 with a single-suture, and five with a multisuture, synostosis. Twenty-nine were associated with other congenital malformations, and 11 were syndromic. Three cases had been diagnosed prenatally, and 34 had skull deformities diagnosed immediately after birth at a mean (SD) age of 3.4 (4.7) months. The mean (SD) age at the time of first admission to hospital in one of the three surgical centres of Saxony-Anhalt was 5.9 (5.5) months, and 65 patients were operated on at a mean age of 9.1 (6.3) months. In contrast to published reports we found a prevalence of 4.8 cases of craniosynostosis/10 000 births that did not increase during the period 2000-16. Although we found a low prenatal detection rate, the diagnosis and treatment in this cohort study seemed timely.

[The Meaning of Neurological and Psychiatric Disease and Addiction for Pregnancy Outcome: A Case-control Study of the Birth Cohort 2010-2012]. / Die Bedeutung neurologischer, psychiatrischer und Suchterkrankungen für den Schwangerschaftsausgang: Fall-Kontroll-Studie der Geburtsjahrgänge 2010-2012.

BACKGROUND AND AIMS: The worldwide prevalence of neurological and psychiatric illnesses is steadily increasing. Consequently women of childbearing age are concerned as well. This survey examines the question of what kind of effects these illnesses have prenatally on mother and child. METHODS: In a case-control study, differences in pregnancy, birth process, and birth outcome were associated with a neurological or psychiatric illness of the expectant mother. 325 pregnant women with 331 born children were identified as cases, which were compared to 5 103 non diseased pregnant women with 5 195 born children. RESULTS: The age of the mother for admission was significantly lower in the case group than in the control group. The number of previous gestations and the number of previous induced abortion were significantly higher in the case group. Also the BMI before pregnancy and the length of stationary stay showed significantly higher values in the case group. Children belonging to the case group were born significantly earlier, had a lower birth weight, height, and head circumference. Furthermore Apgar scores were significantly lower in the case group. The frequency of postpartum stationary stay in a children's clinic as well as the length of stationary stay were also significantly higher when the mother suffered from a neurological or a psychiatric illness. CONCLUSION: The present results point out the correlation between most of the tested parameters and a neuropsychiatric illness of the newborn's mother. The interdisciplinary collaboration between gynecologists and pediatricians, as well as neurologists and psychiatrists should be strengthened to guarantee the best possible medical care.

Vein of galen aneurysmal malformations: an ultrasonographic incidental finding-a case report.

Background. The Vein of Galen aneurysmal malformation (VGAM) is a rare congenital, cerebral, arteriovenous deformity. Good cross-discipline cooperation is in demand because of associated complications and high mortality. The recognition of the optimal therapeutic window is useful to allow proper management. Case Report. We report on the successful treatment of a 2-week-old, healthy girl with a VGAM, which came across in the context of the newborn ultrasonographic screening. After interdisciplinary discussion, 2 embolizations of the VGAM followed without complications-the first in the age of 6 months and the second at 12 months of life. Before and after the intervention, the patient had an age-appropriate development without neurological deficits. Conclusion. The endovascular transarterial embolization is described as the treatment of choice. Time and method of intervention depend on clinical signs of the patient. In our case the patient was asymptomatic. So the arteriovenous abnormality was an incidental finding by ultrasound. Because of the natural history of the disease, and the potential severe neurocognitive consequences at long-term followup if left untreated, it was decided to embolize the lesion. Thanks to embolization with glue, good therapeutical and clinical results could be obtained with normal neurological development.

The combined effect of maternal body mass index and smoking status on perinatal outcomes - an analysis of the german perinatal survey.

BACKGROUND: Maternal body mass index (BMI) outside the normal range and smoking are both associated with adverse perinatal outcomes, but their interaction needs further investigation. AIM: The aim of this study was to analyse the combined effects of smoking and BMI on birth weight, preterm birth rate, the somatic development of neonates, and complications of pregnancy. MATERIAL AND METHODS: Data from 508 926 singleton pregnancies from the German Perinatal Survey of 1998-2000 were analysed according to maternal BMI and smoking. RESULTS: Preterm birth rates were higher for non-smoking underweight (8.3%) and obese women (6.7%) than for normal weight (6.0%) or overweight women (5.6%); rates were higher in smokers than in non-smokers for every BMI category. The mean birth weight increased with increasing BMI and was decreased by smoking; it was 2,964 g in underweight smokers and 3,556 g in obese non-smokers. Small for gestational age (SGA) rates were least in obese women and highest in underweight women; large for gestational age (LGA) rates varied in the opposite direction. In smokers SGA rates were higher than in non-smokers for every BMI category and LGA rates were always lower. Hypertension, proteinuria, oedema, and pre-eclampsia/eclampsia were more common as BMI increased but were always lower in smokers. Pre-eclampsia/eclampsia occurred in 0.7% of underweight smokers but in 9.6% of obese non-smokers. CONCLUSIONS: Smoking and low maternal BMI in combination can cause high rates of preterm birth and SGA neonates as well as low mean birth weight. Although smoking offers some apparent benefit regarding LGA rates and pre-eclampsia this should not distract from its overall adverse influence.

Nicotine and its metabolites in amniotic fluid at birth--assessment of prenatal tobacco smoke exposure.

Amniotic fluid was collected from 78 pregnant women at birth additionally with their urine prior to delivery as well as neonatal urine and meconium. The smoking markers, nicotine and its metabolites cotinine and trans-3'-hydroxycotinine (OH-cotinine), were determined using high-performance liquid chromatography (HPLC). The self-reported smoking status during pregnancy determined by means of a questionnaire was verified by measurement of maternal urine. In all smokers, nicotine metabolites were detected in amniotic fluid and in 80% of them nicotine as well. However, the sum of the nicotine metabolites (Sum(met)) was significantly lower (p < .001) in amniotic fluid (704 +/- 464 nmol/L) than in meconium (921 +/- 588 nmol/L), neonatal urine (1139 +/- 813 nmol/L) and maternal urine (4496 +/- 3535 nmol/L). Concentrations of nicotine metabolites in amniotic fluid correlated well (p < .001) with that in the other specimen types. After environmental tobacco smoke (ETS) exposure, no nicotine or nicotine metabolites were detectable in amniotic fluid but only in maternal and neonatal urine. Analysis of amniotic fluid at birth lends itself to verifying smoking habits during pregnancy and clearly discriminating from ETS exposure, but it is not a suitable approach to differentiating between ETS exposure and non-exposure.

The influence of smoking during pregnancy on fetal growth. Considering daily cigarette consumption and the SGA rate according to length of gestation.

BACKGROUND: Smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations and is associated with, amongst other adverse effects, a higher rate of small-for-gestational-age (SGA) neonates. The rate of SGA neonates born before 32 weeks and its association with smoking have so far not been the focus of attention. MATERIAL AND METHODS: Using data of 643,288 primiparous women from the German perinatal statistics of 1995-2000, we aimed to investigate this relationship. We also analyzed our data according to daily cigarette consumption. RESULTS: We found that smoking during pregnancy was strongly associated with lower birth weight and higher SGA rates. This effect was especially pronounced in women >or=31 years. There was clear dose dependence with regard to daily cigarette consumption. An increase in SGA rates in smokers versus non-smokers can already be seen for very early preterm deliveries (31 weeks of gestation or less). CONCLUSIONS: Our results allow the definition of groups of women who are at higher risk of SGA births. We show that especially older primiparous women (aged >or=31 years) who smoke >10 cigarettes a day are at increased risk of experiencing fetal growth restriction.

[Evaluation of maternal parameters as risk factors for premature birth (individual and combined effects)]. / Evaluierung von mütterlichen Merkmalen als Risikofaktoren für Frühgeburtlichkeit (Einzel- und Kombinationswirkung).

OBJECTIVE: We aimed to examine the individual and combined effects of nine maternal parameters (biological, medical, and social) on rates of prematurity. Our objective was to provide obstetricians with a way of screening women for likely premature deliveries. METHODS: We conducted a retrospective analysis on the data of about 2.3 million pregnancies taken from the German perinatal statistics of 1995-2000. Rates of prematurity were calculated with single and multi-dimensional analyses on the basis of nine maternal parameters (age, weight, height, number of previous live births, stillbirths, miscarriages and terminations of pregnancy, smoking status, previous premature delivery). The following combinations of parameters were investigated in particular: rates of prematurity according to the number of previous stillbirths, miscarriages, and terminations; rates of prematurity according to the number of previous live births and maternal age, height and weight. We also included daily cigarette consumption and previous premature deliveries in our analyses. RESULTS: The rate of prematurity (< or =36 weeks of gestation) in our population was 7.0%; the rate of moderately early premature deliveries (32-36 weeks) was 5.9%, and the rate of very early premature deliveries (< or =31 weeks) was 1.1%. Our multi-dimensional analyses revealed rates of prematurity (< or =36 weeks) between 5.1% and 27.5% depending on the combination of parameters. We found the highest rate of prematurity of 27.5% in women with the following combination of parameters: > or =1 stillbirth, > or =2 terminations of pregnancy and > or =2 miscarriages. A rather high risk of premature delivery (>11%) was also found for elderly (> or =40 years) grand multiparous women as well as small (< or =155 cm) and slim women (< or =45 kg). CONCLUSIONS: We have shown that certain combinations of maternal parameters are associated with a high risk of premature deliveries (>10%). The risk table that we present here may assist in predicting premature delivery.

Does breastfeeding reduce the risk of sudden infant death syndrome?

BACKGROUND: In the last 20 years, the prevention campaigns to reduce the risk of sudden infant death syndrome were very successful. In some countries the advice to breastfeed is included in the campaigns' messages, but in other countries it is not. OBJECTIVE: To examine the association between type of infant feeding and sudden infant death syndrome. METHODS: The German Study of Sudden Infant Death is a case-control study of 333 infants who died of sudden infant death syndrome and 998 age-matched controls. RESULTS: A total of 49.6% of cases and 82.9% of controls were breastfed at 2 weeks of age. Exclusive breastfeeding at 1 month of age halved the risk, partial breastfeeding at the age of 1 month also reduced the risk of sudden infant death syndrome, but after adjustment this risk was not significant. Being exclusively breastfed in the last month of life/before the interview reduced the risk, as did being partially breastfed. Breastfeeding survival curves showed that both partial breastfeeding and exclusive breastfeeding were associated with a reduced risk of sudden infant death syndrome. CONCLUSIONS: This study shows that breastfeeding reduced the risk of sudden infant death syndrome by approximately 50% at all ages throughout infancy. We recommend including the advice to breastfeed through 6 months of age in sudden infant death syndrome risk-reduction messages.

Prone sleeping position increases the risk of SIDS in the day more than at night.

BACKGROUND: SIDS mortality is higher during the night than in the day. AIM: (1) To examine risk factors for SIDS by time of day and (2) to see if the proportion of deaths at night has changed from prior to the 'Back to Sleep' campaign, which recommended infants sleep supine. METHODS: A large population-based SIDS matched case-control (GeSID) study conducted from 1998 to 2001 (when the prevalence of infants placed prone to sleep was 4.1%). The reference sleep of the controls was matched for the estimated time of death for the case. Risk factors for SIDS were examined for night-time and day-time deaths. The estimated time of death was compared with that from an earlier study in Germany (1990-1994 when prevalence of prone sleeping was 32.2%). RESULTS: There were 333 SIDS cases and 998 matched controls. The increased risk with placed prone to sleep was significantly different during the day [adjusted OR = 18.15 (95% CI = 5.91-55.69)] compared with during the night [adjusted OR = 3.49 (95% CI = 1.46-8.39; p-value for interaction = 0.011)]. There was no significant difference in the other risk factors examined by time of day in the multivariate analysis. The mean time found dead was 09:07. In the earlier study the mean time found dead was 08:54 and the difference was not significant (p = 0.57). CONCLUSIONS: This study confirms previous observations that prone sleeping position carries a greater risk during the day than at night. However, the reduction in infants sleeping prone has not been associated with a reduced number of deaths in the day in Germany.

Lung deposition after inhalation with various nebulisers in preterm infants.

AIM: To compare pulmonary deposition after inhalation with three different nebulisers in preterm infants under conditions relevant to practice. METHODS: The relative lung deposition (bioavailability) was estimated by inhalation of the marker substance, sodium cromoglycate (SCG), and measurement of urinary excretion of SCG. Seventeen spontaneously breathing preterm infants received 20 mg of SCG as nebuliser solution by means of (a) an LC Star jet nebuliser; (b) an LS 290 ultrasonic nebuliser; and (c) a Projet ultrasonic nebuliser in a randomised three-period, crossover design. Serial urine samples were collected until about 12 hours after inhalations, and the excreted SCG was determined by high-performance liquid chromatography. RESULTS: The mean (SD) total amounts of SCG excreted in urine measured after inhalation with the LC Star nebuliser (0.089 (0.036) mg) were significantly higher than those obtained with the LS 290 (0.055 (0.019) mg) or the Projet nebuliser (0.046 (0.025) mg). The average pulmonary deposition after inhalation using the LC Star, LS 290 and Projet devices was estimated as 0.89%, 0.55% and 0.46% of the nominal dose, respectively. CONCLUSION: Inhalation with the LC Star jet nebuliser producing the greatest proportion of droplets <2 mum yielded a higher lung deposition in preterm infants than the LS 290 and Projet ultrasonic nebulisers.

Assessment of prenatal tobacco smoke exposure by determining nicotine and its metabolites in meconium.

Meconium samples collected from 115 neonates were analysed for nicotine, cotinine and trans -3-hydroxycotinine (OH-cotinine) by means of high-performance liquid chromatography (HPLC) to identify prenatal smoke exposure. The self-reported maternal smoking status during pregnancy was determined by means of a questionnaire and verified by measurements in urine prior to childbirth. The total sum of nicotine and its metabolites (Sum(tot)) of the first passed meconium samples was 1560 +/- 1024 pmol/g in newborns of smoking mothers. Smoking of less than five cigarettes was clearly detected. Sum(tot) remained constant in all meconium samples passed by a neonate in succession. However, the proportion of nicotine decreased with the time of passage after birth and the OH-cotinine proportion increased, whereas cotinine hardly changed. Nicotine or its metabolites were not detectable in meconium (detection limit < 20 pmol/g), when the mothers were only exposed to environmental tobacco smoke (ETS) using the HPLC method. The hypothesis that the content of nicotine metabolites in meconium reflects long-term smoke exposure could not be confirmed in newborns whose mothers had quit smoking during the latter half of pregnancy. Determining Sum(tot) enables the intensity of continuous smoking during pregnancy to be estimated in all meconium samples passed by a newborn.

Sudden infant death syndrome: no increased risk after immunisation.

BACKGROUND: Although previous studies have shown either no association between immunisation and SIDS or even a decreased risk of SIDS, adverse effects, including death, from immunisations continue to cause concern, especially when a new vaccine is introduced. METHODS: A large case control study with immunisation data on 307 SIDS cases and 971 controls. RESULTS: SIDS cases were immunised less frequently and later than controls. Furthermore there was no increased risk of SIDS in the 14 days following immunisation. There was no evidence to suggest the recently introduced hexavalent vaccines were associated with an increased risk of SIDS. CONCLUSIONS: This study provides further support that immunisations may reduce the risk of SIDS.

Do risk factors differ between explained sudden unexpected death in infancy and sudden infant death syndrome?

BACKGROUND: In Germany, 2910 infants died in 2004; for many infants the reason was clear, especially prematurity or congenital abnormalities. However, 394 babies die every year suddenly and unexpectedly. The cause may be immediately clear, but is often not obvious. AIMS: (1) To describe the causes of explained sudden unexpected death in infancy (SUDI) and (2) to compare risk factors for sudden infant death syndrome (SIDS) and explained SUDI. METHODS: A 3-year population-based case-control study in Germany, 1998-2001. RESULTS: 455 deaths, of which 51 (11.2%) were explained. Most of these deaths were due to respiratory or generalised infections. The risk factors for SIDS and explained SUDI were remarkably similar except for sleep position and breast feeding. Prone sleeping position is a major risk factor for SIDS (adjusted odds ratio (OR) 7.16, 95% confidence interval (CI) 3.85 to 13.31) but not for explained SUDI (adjusted OR 1.71, 95% CI 0.25 to 11.57). Not being breast fed in the first 2 weeks of life is a risk factor for SIDS (adjusted OR 2.37, 95% CI 1.46 to 3.84) but not for explained SUDI (adjusted OR 0.39, 95% CI 0.08 to 1.83). CONCLUSIONS: Prone sleeping position is a unique risk factor for SIDS. Socioeconomic disadvantage and maternal smoking are risk factors for both SIDS and explained SUDI, and provide an opportunity for targeted intervention.

Prevention of sudden infant death syndrome (SIDS) due to an active health monitoring system 20 years prior to the public "Back to Sleep" campaigns.

BACKGROUND: Before reunification, the post-neonatal mortality rate was lower in East Germany than in West Germany. Moreover, the incidence of SIDS (sudden infant death syndrome) was much lower in the East. METHODS: Mortality data on sudden infant death syndrome (SIDS) from West and East Germany since 1980 as well as post-neonatal mortality data for both states since 1970 were examined. 95% Confidence intervals were calculated for the rates. Witnesses from the former East Germany who were involved at the time were also interviewed and archives were searched. RESULTS: We found that as early as 1972 active monitoring of infant and child mortality rates in East Germany had shown that the prone sleeping position was dangerous for infants: the post-neonatal mortality rate was approximately 1 per 1000 live births lower in East than in West Germany during the 20 years before reunification. In contrast, in the West, prone sleeping was only discovered to be a risk factor for SIDS in the early 1990s. CONCLUSIONS: Active monitoring is an effective tool in the early detection of risk factors and serves to prevent unnecessary deaths.

Infection, health problems, and health care utilisation, and the risk of sudden infant death syndrome.

AIM: To examine whether symptoms suggestive of infection, health problems, and health care utilisation are risk factors for SIDS. METHODS: Matched case-control study with 333 SIDS infants and 998 control infants matched for region, age, gender, and reference sleep. Information was obtained by parental interview, paediatrician completed questionnaire, and hospital admission data. RESULTS: No symptoms were associated with SIDS after adjustment for potential confounders. Illness in the last four weeks as reported by the paediatrician did not differ between cases and controls. Developmental problems and special investigations at any stage of life significantly increased the risk of SIDS (adjusted OR = 2.14 and 2.07). Admission to hospital after the first week of life was associated with an increased risk of SIDS (adjusted OR = 1.88). CONCLUSION: Symptoms of infection and illness are no longer risk factors for SIDS in communities such as Germany where few infants sleep prone. The increased risk of SIDS with developmental problems may indicate that infants which subsequently die of SIDS are abnormal or in some way vulnerable.