Maternal Smoking Exposure and Newborn Outcomes: A Study Using Cord Blood Cotinine

NCT07201181 | Not Yet Recruiting

• 1 other identifier: 141-2025
• Study Type: observational
• Target: 126
• Locations: 0 countries
• Sites: N/A

Brief Summary

Prenatal exposure to tobacco smoke, whether from active maternal smoking or secondhand exposure, has been associated with adverse neonatal adaptation, metabolic stress, and impaired fetal oxygenation. This single-center prospective observational cohort study will quantify prenatal tobacco exposure using cord blood cotinine measured at delivery and examine its association with early neonatal biochemical, metabolic, and physiologic outcomes. Participants will consist of mother-newborn dyads recruited consecutively at a tertiary academic hospital. After informed consent, cord blood obtained at delivery will be used for cotinine measurement. Based on pre-specified cotinine thresholds and maternal smoking history, newborns will be classified into three exposure groups: active exposure, passive exposure, or no exposure. No experimental intervention will be administered, and neonatal assessments will be based on routine perinatal and postnatal care. Neonatal data collected will include umbilical cord blood gas parameters (pH, pCO2, pO2, base excess, bicarbonate, and lactate), fetal carboxyhemoglobin (FCOHb), birthweight and anthropometric measurements, Apgar scores, oxygen saturation, heart rate, blood pressure, and routine laboratory indices obtained during the first postnatal day. These laboratory measures may include complete blood count parameters, inflammatory and hematologic ratios such as NLR and PLR, metabolic markers including albumin and lactate-to-albumin ratio, lipid parameters such as HDL and LDL, thyroid-stimulating hormone from the standard newborn screening program, and hearing screening results. Early follow-up data, including postnatal weight loss and bilirubin measurements at routine visits, will also be recorded where available. Maternal and perinatal covariates, including maternal age, parity, gestational age, delivery mode, intrapartum factors, smoking history, and relevant maternal comorbidities, will be collected to support adjusted analyses. The primary objective is to determine whether higher cord blood cotinine-defined exposure is associated with greater metabolic stress and impaired fetal oxygenation at birth, particularly as reflected by cord lactate, related blood gas parameters, and FCOHb. Secondary objectives include evaluating associations with early neonatal hematologic, metabolic, endocrine, and clinical indices, including birthweight, blood pressure, bilirubin levels, thyroid screening results, and hearing screening outcomes. The study will recruit consecutive eligible dyads in a prospective manner. Statistical analyses will follow a pre-specified plan and will include multivariable regression models to adjust for potential confounding factors. Sensitivity and subgroup analyses, including analyses by delivery mode and other clinically relevant strata, will be performed when feasible. This study is designed to provide prospectively collected, biochemically verified evidence on how prenatal tobacco exposure, classified by cord blood cotinine, relates to immediate neonatal metabolic, hematologic, and physiologic outcomes using measurements that are feasible within routine clinical care.

Conditions

Maternal Exposure During Pregnancy; Tobacco Smoke Pollution; Infant, Newborn; Carbon Monoxide Poisoning

Keywords

Prenatal Tobacco Exposure; Maternal Smoking

Outcome Measures

Primary Outcomes (1)

• Umbilical Cord Blood Lactate

  Cord blood lactate (mmol/L) measured per standard laboratory protocol. Primary analysis compares lactate across cotinine-defined exposure groups (active vs passive vs none) with multivariable adjustment (e.g., gestational age, mode of delivery). No extra blood drawn beyond routine cord sampling. Unit of Measure: mmol/L

  At birth (sample obtained within 10 minutes of delivery; analyzed within routine lab turnaround)

Secondary Outcomes (3)

• Umbilical Cord Blood pH

  At birth (within 10 minutes)

• Umbilical Cord Blood Base Excess (BE)

  At birth (within 10 minutes)

• Fetal Carboxyhemoglobin (FCOHb)

  At birth (same cord sample, routine CO-oximetry if available)

Study Arms (3)

Active Prenatal Tobacco Exposure (Cord Blood Cotinine-Defined)

Newborns with cord blood cotinine levels consistent with active prenatal tobacco exposure, based on pre-specified study thresholds and maternal smoking history. Neonatal outcomes recorded include cord blood gas parameters (including pH, base excess, lactate, and FCOHb), birthweight and anthropometric measures, vital signs and blood pressure, routine laboratory indices obtained during the first postnatal day, newborn screening TSH, hearing screening results, and early follow-up data where available. No experimental intervention is administered.

Passive Prenatal Tobacco Exposure (Cord Blood Cotinine-Defined)

Newborns with detectable cord blood cotinine levels below the active-exposure threshold, consistent with passive prenatal tobacco exposure, based on pre-specified study thresholds and maternal exposure history. The same neonatal biochemical, physiologic, and clinical measurements are collected as in the other cohorts. No experimental intervention is administered.

No Prenatal Tobacco Exposure (Reference)

Newborns with cord blood cotinine levels below the predefined no-exposure threshold or undetectable levels, consistent with no prenatal tobacco exposure, together with no relevant maternal smoking or secondhand exposure history. The same neonatal measurements are collected within routine clinical care. No experimental intervention is administered.

Eligibility Criteria

• Age: 0 Minutes - 72 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

This is a single-center prospective cohort study conducted at a tertiary hospital. Eligible participants are consecutively recruited mother-newborn dyads during birth hospitalization. Newborns are stratified into three prenatal tobacco exposure groups according to cord blood cotinine levels and maternal exposure history: active exposure, passive exposure, and no exposure. Study outcomes are derived from routine clinical care and early scheduled follow-up. Collected data include umbilical cord blood gas parameters (including pH, base excess, lactate, and FCOHb where available), birthweight and anthropometric measurements, Apgar scores, oxygen saturation, heart rate, blood pressure, first postnatal day laboratory parameters, newborn screening TSH, hearing screening results, and follow-up weight loss and bilirubin measurements where available. No experimental intervention is administered, and no extra phlebotomy beyond routine care is planned.

You may qualify if:

• Liveborn neonate delivered at the study hospital, aged 0-72 hours at assessment.
• Routine umbilical cord blood gas available at birth (pH, base excess, lactate).
• Cord blood cotinine available or obtainable at delivery for exposure classification.
• Singleton live birth at ≥35 weeks of gestation.
• Availability of routine umbilical cord blood gas parameters at birth, including at minimum pH, base excess, and lactate, with FCOHb recorded where available.
• Availability of routine first postnatal day clinical and laboratory data according to unit practice.
• Parent/guardian provides informed consent for use of neonatal data obtained from routine care.
• Standard newborn assessments obtainable within 72 hours (e.g., birthweight, \~6-hour vitals/BP, TSH at 24-48 h, hearing screen ≤72 h per unit practice).

You may not qualify if:

• Emergent clinical scenarios where any research step could delay urgent care.
• Major congenital anomaly, known chromosomal/genetic disorder, or major metabolic disease likely to affect neonatal adaptation or study outcomes.
• Severe perinatal condition preventing acquisition of core study data or making outcome interpretation unreliable, including major birth trauma or prolonged intensive care requirement.
• Missing cord blood cotinine measurement or missing core primary outcome data.
• Multiple gestation.
• Prior enrollment of the same neonate (no re-enrollment).

Sponsors & Collaborators

• Haseki Training and Research Hospital: lead

Related Publications (6)

• Abraham M, Alramadhan S, Iniguez C, Duijts L, Jaddoe VW, Den Dekker HT, Crozier S, Godfrey KM, Hindmarsh P, Vik T, Jacobsen GW, Hanke W, Sobala W, Devereux G, Turner S. A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis. PLoS One. 2017 Feb 23;12(2):e0170946. doi: 10.1371/journal.pone.0170946. eCollection 2017.

  PMID: 28231292 BACKGROUND

• Filis P, Hombach-Klonisch S, Ayotte P, Nagrath N, Soffientini U, Klonisch T, O'Shaughnessy P, Fowler PA. Maternal smoking and high BMI disrupt thyroid gland development. BMC Med. 2018 Oct 23;16(1):194. doi: 10.1186/s12916-018-1183-7.

  PMID: 30348172 BACKGROUND

• Di HK, Gan Y, Lu K, Wang C, Zhu Y, Meng X, Xia WQ, Xu MZ, Feng J, Tian QF, He Y, Nie ZQ, Liu JA, Song FJ, Lu ZX. Maternal smoking status during pregnancy and low birth weight in offspring: systematic review and meta-analysis of 55 cohort studies published from 1986 to 2020. World J Pediatr. 2022 Mar;18(3):176-185. doi: 10.1007/s12519-021-00501-5. Epub 2022 Jan 28.

  PMID: 35089538 BACKGROUND

• Berlin I, Heilbronner C, Georgieu S, Meier C, Spreux-Varoquaux O. Newborns' cord blood plasma cotinine concentrations are similar to that of their delivering smoking mothers. Drug Alcohol Depend. 2010 Mar 1;107(2-3):250-2. doi: 10.1016/j.drugalcdep.2009.10.008. Epub 2009 Nov 24.

  PMID: 19939584 BACKGROUND

• Hayde M, Bernaschek G, Stevenson DK, Knight GJ, Haddow JE, Widness JA. Antepartum fetal and maternal carboxyhemoglobin and cotinine levels among cigarette smokers. Acta Paediatr. 1999 Mar;88(3):327-31. doi: 10.1080/08035259950170123.

  PMID: 10229047 BACKGROUND

• Wang X, Tager IB, Van Vunakis H, Speizer FE, Hanrahan JP. Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study. Int J Epidemiol. 1997 Oct;26(5):978-88. doi: 10.1093/ije/26.5.978.

  PMID: 9363518 BACKGROUND

MeSH Terms

Conditions

Carbon Monoxide Poisoning

Condition Hierarchy (Ancestors)

Gas Poisoning; Poisoning; Chemically-Induced Disorders

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD - Pediatrician (Principal Investigator)

Study Record Dates

• First Submitted: September 23, 2025
• First Posted: October 1, 2025
• Study Start: May 4, 2026
• Primary Completion (Estimated): August 4, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04