Association between maternal passive smoking and increased risk of delivering small-for-gestational-age infants at full-term using plasma cotinine levels from The Hokkaido Study: a prospective birth cohort

Abstract

Objectives: To investigate the association between plasma cotinine level measured at the 8th gestational month and the delivery of small-for-gestational-age (SGA) infants, using a highly sensitive ELISA method.

Design: Prospective birth cohort study from The Hokkaido Study on Environment and Children's Health.

Setting: Hokkaido, Japan.

Participants: Our sample included 15 198 mother-infant pairs enrolled in 2003-2012.

Main outcome measures: SGA, defined as a gestational age-specific weight Z-score below -2.

Results: The number of SGA infants was 192 (1.3%). The cotinine cut-off level that differentiated SGA infants from other infants was 3.03 ng/mL for both the total population and the full-term births subgroup (sensitivity 0.307; positive predictive value 2.3%). Compared with infants of mothers with a plasma cotinine level of <3.03 ng/mL, infants of mothers with a plasma cotinine level of ≥3.03 ng/mL showed an increased OR for SGA in the total population and the full-term infant group (2.02(95% CI 1.45 to 2.83) and 2.44(95% CI 1.73 to 3.44), respectively).

Conclusion: A plasma cotinine level of ≥3.03 ng/mL, which included both passive and active smokers, was associated with an increased risk of SGA. This finding is of important relevance when educating pregnant women about avoiding prenatal passive and active smoking due to the adverse effects on their infants, even those born at full-term.

Keywords: epidemiology; preventive medicine; public health; reproductive medicine.

Figure 1

Flowchart of the participants.

Figure 2

(A) Frequency distribution of plasma cotinine level during the third trimester, (B) line graph of rate of SGA according to plasma cotinine level during the third trimester and ROC curve analysis of plasma cotinine levels for differentiating SGA infants from non-SGA infants among (C) the total population, (D) the full-term subgroup and (E) the preterm subgroup Plasma cotinine levels during the third trimester: rate of detection=73.6%, mean=18.5 ng/mL, minimum=0.12 ng/mL, 10 percentiles=0.12 ng/mL, 25 percentiles=0.12 ng/mL, median =0.32 ng/mL, 75 percentiles=1.25 ng/mL, 90 percentiles=74.1 ng/mL, maximum=1088.3 ng/mL. Cut-off: 0.21 ng/mL (value differentiating non-passive smokers from passive smokers among non-active smokers), 11.48 ng/mL (value differentiating non-active smokers from active smokers). The parity, infant sex and gestational age-specific birth weight Z (SD) score, which was based on definition from the Japan Pediatric Society, was calculated using software prepared by Japanese Society for Pediatric Endocrinology. Accordingly, we defined SGA as weight Z-score below −2 SD and non-SGA as weight Z-score equal or above −2 SD. AUC, area under the curve; ROC, receiver operating characteristics; SGA, small-for-gestational-age.

Figure 3

OR of full-term SGA infants of passive and active smokers compared with (A and B) mothers with plasma cotinine levels of <3.03 ng/mL (both non-passive and passive smokers) and (C) mothers with plasma cotinine levels of ≤0.21 ng/mL (non-passive smokers). Cut-off: 0.21 ng/mL (value differentiating non-passive smokers from passive smokers among non-active smokers), 11.48 ng/mL (value differentiating non-active smokers from active smokers). The parity-specific, infant sex-specific and gestational age-specific birth weight Z (SD) score, which was based on definition from the Japan Pediatric Society, was calculated using software prepared by Japanese Society for Pediatric Endocrinology. Accordingly, we defined SGA as weight Z-score below −2 SD and non-SGA as weight Z-score equal or above −2 SD. Logistic regression models are adjusted for maternal age, height, weight before pregnancy, alcohol drinking during the first trimester, education level, annual household income, pregnancy-induced hypertension and gestational diabetes mellitus. Bar represents OR (±95% CI) for SGA compared with infants of reference group. *P<0.05; **P<0.01; ***P<0.001. SGA, small-for-gestational-age.