Gene/environment interactions in craniosynostosis: A brief review.

It is suggested that craniosynostosis is caused by a heterogeneous set of effects including gene mutations, teratogenic exposure during critical periods of development and gene/environment interactions. Distinguishing between sufficient, additive and interactive effects is important to the study of gene/environment interactions and allows for segregation of environmental exposures effecting susceptible populations. Through the identification of sufficient and interactive effects, efforts in prevention of craniosynostosis may be successful. Here, we provide a brief review focusing on defining these categorized exposures and relevant literature that has interrogated gene/environment interactions for craniosynostosis.

Effects of nicotine exposure on murine mandibular development.

Nicotine is known to affect cell proliferation and differentiation, two processes vital to proper development of the mandible. The mandible, the lower jaw in mammals and fish, plays a crucial role in craniofacial development. Malformation of the jaw can precipitate a plethora of complications including disrupting development of the upper jaw, the palate, and or impeding airway function. The purpose of this study was to test the hypothesis that in utero nicotine exposure alters the development of the murine mandible in a dose dependent manner. To test this hypothesis, wild type C57BL6 mice were used to produce in utero nicotine exposed litters by adding nicotine to the drinking water of pregnant dams at concentrations of 0 µg/ml (control), 50 µg/ml (low), 100 µg/ml (medium), 200 µg/ml (high) throughout pregnancy to birth of litters mimicking clinically relevant nicotine exposures. Resultant pups revealed no significant differences in body weight however, cephalometric investigation revealed several dimensions affected by nicotine exposure including mandibular ramus height, mandibular body height, and molar length. Histological investigation of molars revealed an increase in proliferation and a decrease in apoptosis with nicotine exposure. These results demonstrate the direct effects of nicotine on the developing mandible outside the context of tobacco use, indicating that nicotine use including tobacco alternatives, cessation methods, and electronic nicotine delivering products may disrupt normal growth and development of the craniofacial complex.

Cognitive and psychosocial development of 4-year-old children whose mothers were treated antenatally with betamethasone.

The present study was part of a larger study investigating the long-term development of children of mothers included in a controlled trial of betamethasone therapy in preterm labor, the purpose was to determine whether there are any benefits or hazards of treatment detectable up to the seventh year of life. The first 318 children of mothers included in the trial because of spontaneous premature labor were selected for study. Of 305 survivors, 258 (84.6%) were included in this phase of the study. Detailed tests of psychological development, together with assessments of psychosocial background, were made during the fifth year. Of the 258 children 144 were in the betamethasone group and 114 were control patients. Despite a heavy weighting of the betamethasone group with more prematurely delivered infants and more boys (resulting from improved perinatal survival of these children associated with betamethasone therapy), no significant differences emerged between the groups in measures of outcome. It was concluded that betamethasone therapy, under the conditions of the original trial, was not hazardous to cognitive development as measured in this study.

School progress and cognitive development of 6-year-old children whose mothers were treated antenatally with betamethasone.

The cognitive development of children whose mothers had been included in the first Auckland trials of betamethasone therapy in premature labor were studied. An earlier study of these children used psychometric tests during the fifth year of life. In the present study tests were given during the seventh year of life (the second year of school) to 250 (82.2%) of 304 surviving children. Of the 250 children, 139 were in the group whose mothers had received betamethasone and 111 were in the control group. Further tests of cognitive development were made, together with assessment of the children's progress in school. Again, on the majority of measures there were no significant differences between children whose mothers had received betamethasone and the children in the control group. Calculations of statistical power showed that important differences were unlikely to have been missed.

First year mortality and hospital morbidity after newborn intensive care.

First year mortality and hospital morbidity were studied in 4678 surviving infants liveborn at National Women's Hospital during 1980, of whom 1113 had been admitted to the neonatal intensive care unit. Of children born there, but never admitted to the neonatal unit, 8.3% were hospitalised in their first year for a mean of 6.7 days per admission or 0.8 days per child. Hospitalisation rates were increased in neonatal unit survivors, ranging from 11.6% in normal birthweight to 15.5% in very low birthweight survivors. The hospital admissions were, on average, longer: 11 days per admission or 2.1 days per infant of low birthweight (LBW, under 2500g), and 21 days per admission or 4.8 days per infant of very low birthweight (VLBW, under 1500g). The longer averages reflected long hospital stays by only a few children. Admissions were largely for respiratory infections: no VLBW survivor was admitted for developmental delay, failure to thrive or non-accidental injury. Neonatal unit survivors had no increase in first year mortality compared with other Auckland children, and none died a cot death. Deaths in normal birthweight survivors were due to congenital abnormalities. No VLBW survivor died after discharge from National Women's Hospital. Children surviving neonatal unit care in Auckland in 1980 appeared to have less continuing first year morbidity and mortality than has been reported elsewhere.

PIP: Researchers followed 4678 infants including 1113 admitted to the neonatal intensive care unit (NICU) born at the National Women's Hospital in 1980 in Auckland, New Zealand to determine subsequent mortality and hospital morbidity during the 1st year, 8.3% of infants born at this hospital and 7.2% of infants born at this hospital and not admitted to the NICU had been hospitalized at least once compared to 9.6% for all infants born in Auckland in 1980 (p.05 and p.001 respectively). An increased risk of subsequent hospitalization existed for infants who went to the NICU (11.7%; p.001), especially those weighing =or- 1500 g [VLBW] (15.5%; p.05). 30% of NICU infants had 1 subsequent hospitalization compared to 21.4% of all infants (p.05). Children born at this hospital and who had subsequent hospitalization averaged a 6.7 day hospitalization compared to 11 days for infants weighed 1501-2500 g (LBW) and 21.7 days for VLBW infants (both, p.001). Infections were the major reason for admissions for all groups, particularly for--VLBW infants (89.8%). The number of admission days for respiratory infections was substantially higher for NICU survivors than those not admitted to the NICU (621.7 vs. 114.4%; p.01). In addition, admission days for spina bifida/hydrocephalus for NICU survivors were significantly greater than those not admitted to the NICU (89.9 vs. 1.4; p.001). Nevertheless the median days/admission was similar for all birth weight groups. Physicians recorded feeding problems and apnea in all groups, and failure to thrive in all but the VLBW group. No NICU survivor had development delay or abnormal tone. The overall 1st year mortality rate was 5. None of the VLBW infants discharged from the NICU died during the 1st year. The highest 1st year mortality rate was for LBWs (8.6). Sudden infant death syndrome (SIDS) was responsible for 48% of all deaths. None of the NICU survivors died of SIDS. Congenital abnormalities were responsible for all deaths of NICU survivors 2500 g and 67% of all NICU survivors.

Low-temperature pasteurisation of human milk.

Human milk was pasteurised at 62.5 degrees C for 30 minutes. This treatment resulted in a 99.99 percent drop in the bacterial count of the milk. Only non-pathogenic organisms remained, and both Escherichia coli and Staphylococcus aureus were destroyed. There was some reduction (less than 50 percent) of the activities of specific antibody to E. coli and lactoferrin, but lysozyme was stable and the pasteurised milk remained effective at inhibiting in vitro growth of E. coli.