This is the largest study performed to date to examine the effect of prenatal exposure to cocaine on growth to age 6 years and the first to examine the independent effects of SGA and cocaine on growth to age 6 years. This study found detrimental effects of cocaine on growth to age 6 only in children who were AGA at birth, but not in those who were SGA at birth. In this multi-institutional, prospective longitudinal study we found that SGA status at birth had a greater negative impact on growth through 6 years of age than prenatal cocaine exposure. We have previously reported that consistent use of cocaine throughout each trimester was associated with detrimental effects on birth weight and head circumference when drug use was evaluated during each trimester of pregnancy [21
] and that deceleration of growth following prenatal cocaine exposure occurred after 32 weeks gestation in a full term pregnancy [2
]. We have also noted that prenatal cocaine exposure increased the likelihood of low birth weight with tobacco and cocaine having additive effects [3
]. Bandstra and colleagues found a symmetrical negative impact on growth parameters following cocaine exposure that is partially mediated by gestational age in a full term pregnancy [4
The effect of prenatal cocaine exposure on growth in childhood has been evaluated by many investigators. Chasnoff et al [8
] and Lumeng and co-workers [17
] found that catch up growth in the cocaine-exposed infants occurred early in childhood without any differences among exposure groups (heavy, light or no exposure). Neither of these 2 studies has noted the proportion of SGA children in their cohorts.
Richardson and co-authors recently reported slower growth at 10 years of age among cocaine exposed children (n=99) compared to those not exposed to cocaine (n=125) during the first trimester [20
]. The study did include 11% of children who were SGA; however the impact of SGA status is not reported. Covington and colleagues have noted that children born to women exposed prenatally to cocaine were shorter and likely to fall below the 10th
percentile in height as compared to control children; differential effects of cocaine and alcohol were noted with maternal age moderating the effects [11
]. In their study, the investigators do not state if any of the children were SGA. Minnes and associates evaluated 154 six year old children prenatally exposed to cocaine and 131 high risk children of similar race and social class [18
]. The authors noted greater prenatal cocaine exposure predicted lower weight for height z-scores. In their study 12.5% of the cohort was SGA, however, the impact of SGA status at birth on growth at 6 years is not reported.
In our study, we have examined, for the first time, the effects of SGA status at birth and prenatal cocaine exposure and suggest that SGA status at birth may account for some of the differences noted between our study and those of other investigators. SGA status at birth is associated with deficits in childhood growth in previous publications [22
] and was confirmed in our study. Hediger evaluated growth of young children from the Third National Health and Nutrition Examination Survey with 423 SGA infants, 3,570 AGA and 438 who were large for gestational age [13
]. At 47 months of age, children who were born SGA had a deficit of 0.75 standard deviation units for weight and 0.60 standard deviation units for height and head circumference compared to the children born AGA. In a nation-wide population-based study where a large cohort was followed longitudinally to adulthood, adults who were born SGA were shorter than their appropriate for gestational age peers at the age of 21 years [24
]. As noted by Barker et al [6
] and Bhargava and colleagues [7
] the growth of the fetus may be influenced by many factors including maternal weight and body mass index. An impaired growth rate in-utero is often accompanied by impaired growth during childhood; however, it has also been shown that growth restriction in-utero may be followed by rapid weight gain in childhood because of an increase in adiposity of the fetus [5
We can only speculate on the potential mechanism of the moderating effect of cocaine on SGA status at birth or SGA on cocaine exposure. Fetal growth is influenced by placental size, perfusion of fetal nutrition, and genes linked to growth factors [12
]. SGA status at birth may be due to early
fetal growth deceleration secondary to fetal under nutrition often starting with the first trimester as a result of maternal health problems (under nutrition/hypertension/overweight status). The placenta is often compromised when the infant is SGA at birth. The impact of cocaine on fetal weight may be due to decreasing transport of amino acids through the placenta [19
]. The impact of cocaine on fetal weight is noted late in gestation [2
]. It is therefore possible that the detrimental effects of cocaine are less on the fetus and placenta that are already compromised throughout pregnancy as noted in SGA infants.
Our study has limitations; details of prenatal causes of SGA status such as poor maternal nutrition or placental insufficiency could not be elucidated. We did not have information on the pre-pregnancy weight of the mothers at the time of the 6 year visit to the clinic [26
]. We did not include current maternal alcohol and drug use as covariates. It is possible that children who remained in this study differed from those who did not remain in the study on some factors that we did not measure.
In summary we have demonstrated in a large prospective longitudinal study that SGA status at birth has a greater negative impact on growth through 6 years of age than prenatal cocaine exposure. In future research it is very important to conduct these growth analyses either examining interactions with SGA status at birth, or stratifying analyses based on SGA status at birth. This study is important for clinical care and future research because understanding the causes of SGA status at birth and preventing these conditions as well as avoiding exposure to illicit drugs such as cocaine during pregnancy will optimize maternal and childhood outcomes. We plan to follow this high risk cohort and evaluate whether growth restriction continues to adulthood among those born SGA at birth and whether the other consequences of SGA status occur such as obesity, impaired glucose tolerance or risk for coronary heart disease [5