Objectives

The authors examined the associations of maternal smoking in pregnancy with various fetal growth characteristics among 7,098 pregnant women participating in the Generation R Study (2002-2006), a population-based prospective cohort study of pregnant women and their children in Rotterdam, the Netherlands. Maternal smoking was assessed by questionnaires administered in early, mid-, and late pregnancy. Fetal growth characteristics evaluated included head circumference, abdominal circumference, and femur length measured repeatedly in mid- and late pregnancy. Maternal smoking during pregnancy was associated with reduced growth in head circumference (-0.56 mm/week; 95% confidence interval (CI): -0.73, -0.40), abdominal circumference (-0.58 mm/week; 95% CI: -0.81, -0.34), and femur length (-0.19 mm/week; 95% CI: -0.23, -0.14). This reduced growth resulted in a smaller femur length from midpregnancy (gestational age 18-24 weeks) onwards and smaller head and abdominal circumferences from late pregnancy (gestational age > or =25 weeks) onwards. Analyses using standard deviation scores for the growth characteristics demonstrated the largest effect estimates for femur length. The authors concluded that maternal smoking during pregnancy is associated with reduced growth in fetal head circumference, abdominal circumference, and femur length. The larger effect on femur length suggests that smoking during pregnancy affects primarily peripheral tissues.

Background-It has been suggested that an adverse fetal environment increases susceptibility to hypertension and cardiovascular disease in adult life. This increased risk may result from suboptimal development of the heart and main arteries in utero and from adaptive cardiovascular changes in conditions of reduced fetal growth. The aim of the present study was to evaluate whether reduced fetal growth is associated with fetal circulatory changes and cardiac dysfunction. Methods and Results-This study was embedded in a population-based, prospective cohort study starting in early fetal life.Fetal growth characteristics and fetal circulation variables were assessed with ultrasound and Doppler examinations in 1215 healthy women. The fetal circulation was examined in relation to estimated fetal weight. Higher placental resistance indices were strongly associated with decreased fetal growth. Cerebral resistance showed a gradual decline with reduced fetal growth. Cardiac output, peak systolic velocity of the outflow tracts, and cardiac compliance showed a gradual reduction with diminished fetal growth, whereas intraventricular pressure gradually increased. Conclusions-Decreased

Nicotine, as has been shown in animal studies, is a neuroteratogen, even in concentrations that do not cause growth retardation. In humans, there is only indirect evidence for negative influences of nicotine on brain development from studies on the association between maternal smoking in pregnancy and behavioural and cognitive development in the offspring. We investigated the associations of maternal smoking in pregnancy with foetal head growth characteristics in 7042 pregnant women. This study was embedded in the Generation R Study, a population-based prospective cohort study from foetal life until adulthood. Maternal smoking was assessed by questionnaires in early, mid- and late pregnancy. Head circumference, biparietal diameter, transcerebellar diameter and atrial width of lateral ventricles were repeatedly measured by ultrasound. When mothers continued to smoke during pregnancy, foetal head circumference showed a growth reduction of 0.13 mm [95% confidence interval (CI): -0.18, -0.09] per week compared to foetuses of mothers who never smoked during pregnancy. Biparietal diameter of foetuses with smoking mothers grew 0.04 mm (95% CI: -0.05, -0.02) less per week than that of foetuses of nonsmoking mothers. Atrial width of lateral ventricle was 0.12 mm (95% CI: -0.22, -0.02) smaller and transcerebellar diameter was 0.08 mm (95% CI: -0.15, -0.00) smaller if mothers smoked, but growth per week of these characteristics was not affected by maternal smoking in pregnancy. In conclusion, continuing to smoke during pregnancy leads to reduced growth of the foetal head. Further research should focus on the causal pathway from prenatal cigarette exposure via brain development to behavioural and cognitive functions.

Intrauterine growth restriction has been linked to infant behavioral problems. While typically only birth weight is examined, here the authors assessed fetal circulatory redistribution, also called the "brain-sparing effect," which is a fetal adaptive reaction to placental insufficiency. They aimed to investigate whether fetal circulatory redistribution protects against behavioral problems. Within the Generation R Study (Rotterdam, the Netherlands, 2003-2007), fetal circulation variables for the umbilical artery and the middle and anterior cerebral arteries were assessed with Doppler ultrasound in late pregnancy. Ratios between placental resistance and cerebral resistance were related to behavioral problems, as measured by the Child Behavior Checklist, in 935 toddlers aged 18 months. The umbilical/anterior cerebral ratio was associated with the Total Problems summary score from the Child Behavior Checklist (per standard-deviation increase, odds ratio = 1.2, 95% confidence interval: 1.0, 1.5). Children with higher umbilical/anterior cerebral ratios had higher risks of internalizing problems, emotional reactivity, somatic complaints, and attention problems. A high umbilical/middle cerebral ratio was related to higher scores on the Internalizing and Somatic Complaints scales. The authors conclude that infants with circulatory redistribution in gestation are more likely to have behavioral problems. This suggests that "brain-sparing" does not completely spare the brain and indicates underlying pathology with consequences for later behavior.