VCSIP Follow-up Study

The overall aims of this protocol are to determine whether prenatal supplementation with
vitamin C to pregnant smokers can improve pulmonary function and decrease wheeze at 5 years
of age in their offspring. This is a continuation of the VCSIP trial, to follow the offspring
through 5 years of age. The hypothesis for this protocol is an extension of the VCSIP trial
that supplemental vitamin C in pregnant smokers can significantly improve their children's
PFTs and decrease the incidence of wheeze. The reasons for this protocol are to follow the
children born to mothers randomized in the VCSIP to the age of 5 to differentiate the
patients with transient versus recurrent wheeze (and therefore more likely to develop
asthma); to determine if early protective effects of vitamin C are sustained to this older
age; and to continue to collect biologic samples from the children for future mechanistic
studies of vitamin C action.

The primary aim of this study is to demonstrate improved pulmonary function at 5 years of age
in the offspring of pregnant smokers randomized to vitamin C (500 mg/day) versus placebo. The
investigators hypothesize that vitamin C supplementation in pregnancy will block the adverse
effects of maternal smoking on offspring pulmonary function measured at 5 years of age by
spirometry. Impulse oscillometry (IOS) will also be used at 3-5 years of age to assess
pulmonary function.

Specific Aim 2 (Secondary Outcome): The secondary aim of this study is to demonstrate a
decreased incidence of wheeze at 5 years of age in offspring of pregnant smokers randomized
to vitamin C (500 mg/day) versus placebo. The investigators hypothesize that vitamin C
supplementation during pregnancy will decrease the incidence of wheeze at 5 years of age in
offspring of smokers. Respiratory health will be assessed by quarterly validated respiratory
questionnaires and clinician report.

Inclusion Criteria:

- Women and their offspring randomized to vitamin C versus placebo during pregnancy as
well as pregnant nonsmokers and their offspring enrolled as the reference group in the
current RCT.

Exclusion Criteria:

- Patients specifically withdrawing consent.