PEDIATRICS Vol. 108 No. 2 August 2001, pp. 342-346

Smoking During Pregnancy and Infantile Colic

Charlotte Søndergaard, MD^*, , Tine Brink Henriksen, MD, PhD^§, , Carsten Obel, MD^{*, §}, and Kirsten Wisborg, MD^§

From the ^* Danish Epidemiologic Science Centre, Department of Epidemiology and Social Medicine, University of Aarhus;  Medical Research Unit, Ringkjøbing County; ^§ Perinatal Epidemiological Research Unit, Department of Obstetrics and Gynaecology, Aarhus University Hospital; and  Department of Pediatrics, Aarhus University Hospital, Denmark.

	ABSTRACT

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Objective.  To evaluate the association between maternal smoking during pregnancy and infantile colic (IC).

Methods.  A follow-up study of singleton infants delivered by Danish mothers at the Aarhus University Hospital from May 1991 to February 1992 and still living in the municipality of Aarhus at the age of 8 months was conducted. A total of 1820 mothers and their infants were included. Self-administered questionnaires were used to collect data on smoking, other lifestyle factors, and sociodemographic variables at 16 and 30 weeks of gestation and 8 months postpartum. IC was defined in the 8-month questionnaire and based on Wessel's criteria, except that we used only the crying criterion.

Results.  IC was seen in 10.8% of all infants. We observed a twofold increased risk of IC among infants whose mothers smoked 15 or more cigarettes per day during their pregnancy(relative risk: 2.1; 95% confidence interval: 1.4-3.2) or in the postpartum period (relative risk: 2.0; 95% confidence interval: 1.3-3.1). Women who smoked continuously during pregnancy and the postpartum period had a relative risk of 1.5 (95% confidence interval: 1.1-2.0) of having a infant with IC compared with women who did not smoke during this period. Adjustment for maternal age, parity, marital status, alcohol intake, birth weight, gestational age, breastfeeding, caffeine intake postpartum, and paternal smoking did not change the effect measures.

Conclusion.  The results indicate that maternal smoking during pregnancy may increase the risk of IC.  Key words:  infantile colic, smoking, pregnancy, follow-up.

Infantile colic (IC) is defined by Wessel et al¹ as paroxysms of irritability, crying, or fussing that last for >3 hours a day for >3 days a week and for >3 weeks. Although it seems to be a self-limiting condition that most often starts in the first month of life and ends when the child is 3 to 4 months old, the parents often find it difficult to cope with the child's excessive crying and fussing. IC has even been mentioned as a possible reason for violence toward the child.^2,3 The reported incidence of IC ranges widely from 8% to 40%,^4,5 a discrepancy that may be attributable to differences in study design and definitions of IC.

The cause of IC remains unknown, although many somatic, developmental, and psychosocial risk factors have been suggested.^6-12 Five studies showed an increased risk of IC when the mother smoked during the lactation period and when the child was exposed to environmental smoking.^513-16 However, another study found no association.¹⁷ None of these studies took prenatal smoking into consideration. Smoking during pregnancy has a negative bearing on the fetal environment and may influence the child's health later in life.¹⁸ The aim of this study was to evaluate the association between maternal smoking during pregnancy and IC in a follow-up study of 1820 mothers and their newborns.

	METHODS

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Participants who were eligible for inclusion all were singleton children who were delivered by Danish mothers at the Aarhus University Hospital from May 1991 to February 1992 and still living in the municipality of Aarhus at the age of 8 months (N = 2055). Children with an Apgar score below 7 after 5 minutes (N = 40) were excluded. Information on IC was missing for 56 infants, and prenatal maternal smoking habits were missing for 137 mothers. Thus, a total of 1820 mothers and children remained for analysis.

The following information was collected by self-administered questionnaires at 16 and 30 weeks of gestation: medical and obstetric history, smoking habits, alcohol and caffeine intake, and psychological distress during pregnancy measured by the 30-item version of the General Health Questionnaires,^19,20 which is a screening instrument designed for use in the general population and validated in a Danish population.²¹ Information on delivery and the newborn was provided by the tending midwife using a structured coding sheet. Approximately 8 months postpartum, data on IC were collected by 2 self-administered questionnaires completed by the mother and the health visitor, who visits homes at least twice before the routine health examination of the child 8 months postpartum; the mother often consults the health visitor if problems arises. Families that have a child with IC generally will have more visits during the period when the child has IC. We simplified the definition of IC in the maternal questionnaire as several hours of crying per day for several days and described the associated symptoms as legs drawn up toward the abdomen, distended abdomen, and excessive flatus, because we wanted to simplify the large number of questions on IC. To the health visitors, IC was defined as >3 hours of crying per day for >3 days a week for >3 weeks or >1.5 hours of crying per day in 6 of 7 days; the associated symptoms were described as legs drawn up toward the abdomen, distended abdomen, and excessive flatus. To increase the number of participants in this study and because there was missing information in both the parents' and the health visitors' questionnaires, we used information from the parents when it was available (85.5%) and from the health visitors when the parents' information was not available (14.5%).

The mothers were categorized according to the self-reported information on smoking as nonsmoking, smoking 1 to 14 cigarettes per day, and smoking 15 or more cigarettes per day. It was shown previously that maternal smoking habits remain essentially unchanged from the first trimester throughout pregnancy and during the first 8 months postpartum in this cohort.²² We used information on maternal smoking from the 16th gestational week. When this was missing, we used information from the 30th gestational week. Changing of smoking habits during the period from early pregnancy to the postpartum period were categorized as 1) no risk: nonsmokers both during pregnancy and postpartum; 2) low risk: nonsmokers during pregnancy but smoking postpartum; and 3) high risk: mothers who smoked both during pregnancy and in the postpartum period and mothers who smoked only during pregnancy. Information on IC and on smoking during the breastfeeding period was collected when the child was 8 months old.

Statistical Analyses

The effect on IC of smoking during pregnancy is expressed as a relative risk (RR) with 95% confidence intervals (CI). A 2-sided P value of <0.05 was considered statistically significant. Factors with a biologically plausible influence or factors that were known from previous studies to be possible risk factors of IC were considered potential confounders. These factors included maternal age, parity, cohabitation, educational level, alcohol intake during pregnancy, maternal psychological distress during pregnancy, gender of the infant, birth weight and gestational age, smoking and caffeine intake postpartum, and breastfeeding. The variables were categorized as shown in Table 1 and entered into the logistic regression as a number of dummy variables equal to the number of categories minus 1. According to the change-in-estimate principle, a variable was kept in the final logistic regression model if the estimated effect of smoking on IC changed by more than 10%.^23,24 None of the confounders remained in the final models, and the crude RRs, therefore, are presented.

	RESULTS

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Among 1820 infants, 197 (10.8%) had IC. A total of 567 (31.2%) women smoked during their pregnancy, 24.8% smoked fewer than 15 cigarettes per day, and 6.4% smoked 15 or more cigarettes per day. The association between a number of sociodemographic variables and lifestyle factors and IC is shown in Table 1. Maternal age of 35 years and above, low birth weight (<2500 g), and gestational age of <37 completed weeks were associated with an increased risk of IC in the bivariate analyses, but parity, cohabitation status, psychological distress during pregnancy measured according to the General Health Questionnaires,²¹ educational level, alcohol intake, gender of the infant, caffeine intake postpartum, and breastfeeding (yes/no) were not.

Table 2 shows that smoking 15 or more cigarettes per day during pregnancy or in the postpartum period (RR: 2.1; 95% CI: 1.4-3.2) doubled the child's risk of developing IC (RR: 2.0; 95% CI: 1.3-3.1). Mothers who smoked both during pregnancy and in the postpartum period had an increased risk of having an infant with IC (RR: 1.5; 95% CI: 1.1-2.0). The risk of IC also was increased if the father smoked 15 or more cigarettes per day 8 months postpartum (RR: 1.8; 95% CI: 1.3-2.5). The association between maternal smoking during pregnancy and IC decreased by <10% when adjusted for paternal smoking (results not shown). Constructing a variable including pre- and postnatal information on maternal smoking habits showed that children of women who smoked only postpartum had a very slight excess risk of IC (RR: 1.1; 95% CI: 0.6-2.0). Categorizing mothers into different risk groups showed that being a smoker in both periods was associated with the highest risk of IC (RR: 1.5; 95% CI: 1.1-2.0). However, we did not have sufficient data to analyze the risk for those who changed smoking habits from the prenatal to the postpartum period, and we therefore were unable to conclude which period of exposure was the most important. According to the change-in-estimate principle, adjustment for maternal age, parity, marital status, educational level, alcohol, birth weight, gestational age, caffeine intake postpartum, breastfeeding, and paternal smoking did not change the association between maternal smoking during pregnancy and IC.

	DISCUSSION

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The results indicate that maternal smoking during pregnancy increases the risk of IC. The major strengths of this study are its size and the prospective collection of information on smoking and potential confounders during pregnancy. It is widely known that smokers and nonsmokers differ also in respect to other lifestyle factors. It therefore is important to adjust for possible confounders. However, residual confounding or confounding by unknown confounders still may be present. We also performed the analyses on term children with a birth weight above 2500 g only, but the results remained essentially unchanged.

We strove to avoid misclassification by seeking information on IC through 2 different sourcesparents and health visitorsneither of whom knew the purpose of the study. Both the mothers and the health visitors answered the questionnaires retrospectively, which may have introduced a recall bias. The interobserver agreement between the mothers' and the health visitors' reporting of IC was good with a Kappa coefficient of 0.8,²⁵ and our results remained essentially the same whether the analyses were performed with the maternal information on IC or with the health visitors' recordings. We do not have information about the time at which the health visitor filled in the questionnaires; if they consulted the mother first, then this may explain the high Kappa coefficient. The occurrence of IC among the children whose IC information was from the health visitors' questionnaires did not differ from that of the children whose IC information was from the parents' questionnaires, indicating no major misclassification between the parents' and the health visitors' questionnaires.

There is a remote risk of a certain recall bias as information on IC was collected up to 5 months after the symptoms disappeared, but it seems unlikely that recall was related to the mother's reporting of smoking during pregnancy. A differential misclassification would be possible if, for example, smokers reported more IC than the true value of IC compared with nonsmokers. This would overestimate the association between smoking and IC. A bias toward the null hypothesis would be possible if the smokers recorded less IC than the true value of IC compared with nonsmokers. We were not able to conclude on a direction of this possible bias, but an IC occurrence of 10.8% is in accordance with another study that uses the same definition of IC.²⁶

The primary limitation of our study is our inability to adjust for postnatal smoking, because only few pregnant women changed their smoking habits from pregnancy to the postnatal period. The association between prenatal and postnatal smoking and IC could be attributable to an association between postnatal smoking in the home and IC rather than to a pregnancy exposure effect or be a matter of undetected confounding. Furthermore, the temperament of the child might have been a confounder for which we were not able to adjust. An association between maternal smoking and child temperament has been found in a few studies,^27,28 but conflicting results exit on IC and temperament.^29-31 Another limitation is the missing information on some of the participants on educational level, psychosocial status during pregnancy, and caffeine intake and smoking in the postpartum period. Excluding these mothers from the analyses reduced the bivariate estimate between maternal smoking during pregnancy and IC, indicating that this strategy led to selection bias or incomplete confounder control. Thus, these mothers were included in the final model as separate categories.

Previous studies focused on postnatal smoking, without taking prenatal smoking into consideration.^5,13,15,16 Prenatal exposure to smoking is associated with impaired fetal growth³² and to diseases and development in later childhood.^33-35 It therefore is important to examine the effect of smoking during pregnancy and to take it into consideration when studying exposure to smoking postpartum and IC.

A Norwegian follow-up study of 885 women and their newborns found a higher frequency of IC among children of breastfeeding smokers (40%) compared with children of breastfeeding nonsmokers (26%). Information on postnatal smoking was collected 18 weeks postpartum, and it was noticed that smoking habits mostly remained the same during pregnancy and did not change until the postnatal period. They reported a higher frequency of IC compared with our study, which might be explained by differences in the definition of IC, if maternal smoking is associated with the reporting of IC.⁵ A Dutch cross-sectional study of 3345 infants found a twofold increased risk of IC when the mothers were smoking postpartum and a higher risk among infants who were formula fed and exposed to maternal smoking compared with infants who were breastfed and exposed to maternal smoking.¹⁶ A Swedish study of 376 mothers and their newborns found no statistically significant association between smoking in the breastfeeding period or smoking indoors at home and IC.¹⁷ However, only 12% were smokers, and the statistical power of this study may be limited. These studies did not adjust for prenatal smoking, which therefore cannot be used to elucidate which exposure period is most important to the development of IC.^5,13,15,17 Only one study, which studied parental smoking and the risk of postprandial IC, controlled for socioeconomic status, breastfeeding (yes/no), and birth weight but did not control for smoking during pregnancy.¹⁵

Prenatal smoking is known to inhibit fetal growth, and a number of diseases have been associated with fetal growth retardation probably through an "organ programming effect."¹⁸ IC may arise as a result of a delay in the development of the central nervous system or the gastrointestinal tract, caused by smoking or environmental tobacco smoke exposure postpartum. We cannot, with the data available, distinguish between these 2 mechanisms.

If smoking during pregnancy is a risk factor in IC, then we may expect children of mothers who smoked during their pregnancy to have an earlier onset of IC than children of mothers who did not smoke during their pregnancy. This prediction was corroborated by our observation that IC started in the first week in 21% of the children whose mothers were nonsmokers during their pregnancy but in 30% of the children of mothers who smoked during their pregnancy, although insignificant (results not shown). If postnatal smoking has an effect on the child's crying, then mothers who smoke during the postpartum period should expect their children to have IC for a longer period than mothers who do not smoke during the postpartum period. This was not found in our study, in which IC lasted for more than 12 weeks in 25% of the infants of mothers who smoked postpartum and in 35% of the infants of mothers who did not smoke postpartum, but is an insignificant difference (results not shown).

	CONCLUSION

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Our study indicates that maternal smoking during pregnancy or in the postpartum period increases the risk of IC. Ante- and postnatal care that includes advice of smoking cessation is important and also might be important for preventing IC.

	ACKNOWLEDGMENTS

This study was supported by the Medical Research Unit Ringkjøbing County, and the activities of the Danish Epidemiology Science Centre are financed by a grant from the Danish National Research Foundation. This project was supported by Grant JN 12-1663-1 from the Danish Medical Research Council.

We thank Professor Niels Jørgen Secher; Morten Hedegaard, MD, PhD; and Elisabeth Skajaa for their key roles in initiation of the prenatal cohort and the health visitors of the municipality of Aarhus for data collection. We also thank Professor Jørn Olsen for fruitful discussions and comments during the analyses and preparation of this article.

	FOOTNOTES

Received for publication Sep 29, 2000; accepted Jan 12, 2001.

Reprint requests to (C.S.) Danish Epidemiologic Science Centre, Department of Epidemiology and Social Medicine, University of Aarhus, Vennelyst Boulevard 6, DK-8000 Aarhus, Denmark. E-mail: cos{at}dadlnet.dk

	ABBREVIATIONS

IC, infantile colic; RR, relative risk; CI, confidence interval.

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