Smoking during pregnancy and diabetes mellitus in a British longitudinal birth cohort

Exposures in utero may increase the risk of type 2 diabetes.¹,² We tested the hypothesis that maternal smoking during pregnancy increases both the risk of early onset type 2 diabetes³ and non-diabetic obesity in offspring.

Methods and results

We used data are from the British National Child Development Study (NCDS),⁴ based on the Perinatal Mortality Survey (PMS) of about 17 000 births from 3 to 9 March 1958. The first sweep of the study in 1965 had 15 396 responses. The cohort remained generally representative at age 33 years (n=11 359).⁵ Missing data reduced the proportion in social class V from 6.4% in sweep 1 to 5.3%. Ethics committee approval was obtained for research involving medical examinations, and cohort members signed consent forms at age 33 years allowing access to medical records.

Medical examinations and record reviews by local authority medical officers were conducted at ages 7 and 16 years. Children with incomplete or equivocal information on diabetes or with a recorded onset before the age of 16 were not included in the main analysis as they are unlikely to have type 2 diabetes. A personal interview at age 33 years asked about diabetes. Those with only gestational diabetes were also excluded: 15 men and 13 women with an onset of diabetes between 16 and 33 years were identified.

At birth midwives recorded information on the child's sex, birth weight, mother's age, her age on leaving full time education, family social class, and smoking during pregnancy (after the 4th month) divided into non-smokers, medium (1-9 cigarettes/day) heavy (>10), and variable (a balance of medium and heavy). Details of maternal smoking were again recorded in 1974, as non-smoking and <1, 1-5, 6-10, 11-20, 21-30, or >30 cigarettes/day.

Cohort members' own smoking behaviour was recorded during an interview at age 16 and they were classified as non-smokers or as smoking <1, 1-9, 10-19, 20-29, >29 cigarettes/week. Interviewers measured height in centimetres and weight in kilograms using stadiometers and electronic balances at age 33. Multiple logistic regression analysis was used for two outcomes: diabetes and body mass index (BMI) of over 30, independent of diabetes. Where obesity was the outcome, those with diabetes were excluded and we adjusted for sex, own smoking at age 16, and all the maternal factors at birth.

Some 10% (n=602) were obese (BMI>30) at age 33. After we excluded the diabetic cohort members the adjusted odds ratios (and 95% confidence intervals) for obesity associated with maternal smoking during pregnancy are 1.34 (1.07 to 1.69), 1.35 (0.95 to 1.92), and 1.38 (1.06 to 1.79), with a statistically significant trend (P=0.003) for medium, variable, and heavy smokers, respectively (table). Non-diabetic cohort members who smoked at age 16 did not have an increased risk of obesity.

Comment

The association of diabetes with maternal smoking during pregnancy (independent of finer-grain measures of mothers' smoking in 1974, own smoking at age 16, and other potential confounding factors) suggests that it is a true risk factor for early adult onset diabetes. Cigarette smoking as a young adult was also independently associated with an increased risk of subsequent diabetes.

In utero exposures due to smoking during pregnancy may increase the risk of both diabetes and obesity through programming, resulting in lifelong metabolic dysregulation, possibly due to fetal malnutrition or toxicity. The odds ratios for obesity without type 2 diabetes are more modest than those for diabetes and the scope for confounding may be greater. Smoking during pregnancy may represent another important determinant of metabolic dysregulation and type 2 diabetes in offspring. Smoking during pregnancy should always be strongly discouraged.

Table.

Maternal smoking in pregnancy, own smoking at age 16 years, and risk of diabetes among young adults. Odds ratio with 95% confidence intervals using logistic regression with a diagnosis of diabetes after age 16 as the dependent variable

	People without diabetes No (%)	People with diabetes No (%)	Unadjusted			Adjusted*			Adjusted†
			OR (95% CI)	P		OR (95% CI)	P		OR (95% CI)	P
Mother smoking while pregnant (after 4th month)
Non-smoker	3430 (69.8)	12 (42.9)	1.00			1.00			1.00
Medium smoker	689 (14.0)	3 (10.7)	1.24 (0.35 to 4.42)	0.735		1.11 (0.31 to 4.04)	0.872		1.01 (0.23 to 4.53)	0.990
Varies between medium and heavy	277 (5.6)	4 (14.3)	4.13 (1.32 to 12.88)	0.015		4.13 (1.27 to 13.40)	0.018		3.55 (0.88 to 14.38)	0.076
Heavy smoker	521 (10.6)	9 (32.1)	4.94 (2.07 to 11.77)	<0.001		4.55 (1.82 to 11.36)	0.001		4.02 (1.14 to 14.14)	0.030
Own smoking at age 16 years (cigarettes/week)
Non-smoker	3251 (66.1)	13 (46.4)	1.00			1.00			1.00
<1	147 (3.0)	1 (3.6)	1.70 (0.22 to 13.09)	0.610		2.09 (0.254 to 17.23)	0.492		2.07 (0.25 to 17.19)	0.502
1-9	510 (10.4)	3 (10.7)	1.47 (0.42 to 5.18)	0.548		1.76 (0.48 to 6.46)	0.394		1.92 (0.52 to 7.10)	0.332
10-19	176 (3.6)	2 (7.1)	2.84 (0.64 to 12.69)	0.171		2.41 (0.51 to 11.41)	0.268		2.48 (0.52 to 11.97)	0.257
20-29	189 (3.8)	1 (3.6)	1.32 (0.17 to 10.17)	0.788		1.42 (0.177 to 11.43)	0.741		1.61 (0.20 to 12.96)	0.653
30+	644 (13.1)	8 (28.6)	3.11 (1.28 to 7.52)	0.012		3.53 (1.40 to 8.91)	0.008		3.62 (1.42 to 9.24)	0.007
Total	4917	28

^*Adjusted for maternal smoking during pregnancy, sex, mother's age at birth of cohort member, age mother left school, family social class at birth, birth weight, own smoking at age 16 years, and BMI at age 33 years. 

^†Adjusted for all of the above and maternal smoking in 1974.