Prenatal Tobacco Exposure and Newborn Outcomes: A Maternal Urinary Cotinine Study

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, through either active maternal smoking or secondhand exposure, has been associated with impaired fetal oxygenation, metabolic stress, and adverse early neonatal outcomes. This prospective, single-center observational cohort study will objectively assess maternal tobacco exposure using cotinine measured in maternal urine and examine its association with early neonatal biochemical, metabolic, and clinical outcomes. Consecutive eligible mother-newborn dyads will be recruited at a tertiary academic hospital after written informed consent is obtained. A clean-catch midstream maternal urine sample will be collected within 24 hours before delivery, preferably at admission to the delivery unit and before intravenous fluid administration, for quantitative cotinine and creatinine measurement. Maternal tobacco exposure will be assessed using the urinary cotinine concentration, the cotinine-to-creatinine ratio, and maternal self-reported smoking and secondhand smoke exposure. Based on prespecified biomarker thresholds and exposure history, participants will be classified as having active exposure, passive exposure, or no exposure. No experimental intervention will be administered. Neonatal data will include umbilical cord blood gas parameters, including pH, pCO2, pO2, base excess, bicarbonate, lactate, and fetal carboxyhemoglobin (FCOHb). Birthweight, length, head circumference, Apgar scores, oxygen saturation, heart rate, and blood pressure will also be recorded. Routine laboratory measurements obtained during the early postnatal period will include complete blood count parameters, hematologic and inflammatory indices such as NLR and PLR, albumin, the albumin-to-lactate ratio, HDL, LDL, and other routinely available biochemical markers. Thyroid-stimulating hormone results from the national newborn screening program and newborn hearing screening results will be recorded. Postnatal weight loss and bilirubin measurements from routine follow-up visits will also be collected when available. The primary objective is to determine whether increasing maternal urinary cotinine exposure is associated with higher umbilical cord blood lactate and FCOHb levels, indicating greater metabolic stress and impaired fetal oxygenation. Secondary objectives include evaluating associations with cord blood gas parameters, birthweight, early hematologic and biochemical indices, albumin and the albumin-to-lactate ratio, blood pressure, bilirubin levels, thyroid screening results, and hearing screening outcomes. Maternal, obstetric, and perinatal variables, including maternal age, parity, gestational age, mode of delivery, smoking history, intrapartum factors, and relevant maternal comorbidities, will be recorded for adjusted analyses. Statistical analyses will include comparisons among the three exposure groups and multivariable regression models evaluating urinary cotinine both as a continuous measure and as a categorical exposure variable. This study is designed to provide prospectively collected, biomarker-verified evidence regarding the relationship between maternal tobacco exposure and 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

  Umbilical cord blood lactate concentration measured using routine blood gas analysis. Lactate levels will be compared across maternal urinary cotinine-defined exposure groups (active, passive, and no exposure) and evaluated in multivariable regression models with adjustment for relevant maternal and perinatal factors. 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 (Maternal Urinary Cotinine-Defined)

Mother-newborn dyads in whom the maternal urinary cotinine-to-creatinine ratio is consistent with active tobacco exposure according to the prespecified study threshold. Maternal self-reported smoking and secondhand smoke exposure will also be recorded as supportive exposure information. Neonatal outcomes will include umbilical cord blood gas parameters, including pH, pCO2, pO2, base excess, bicarbonate, lactate, and fetal carboxyhemoglobin (FCOHb); birthweight and other anthropometric measurements; Apgar scores; oxygen saturation; heart rate; blood pressure; and routine laboratory measurements obtained during the early postnatal period. Laboratory variables will include complete blood count parameters, NLR, PLR, albumin, the albumin-to-lactate ratio, HDL, LDL, and other routinely available biochemical markers. Newborn screening TSH, hearing screening results, postnatal weight loss, and bilirubin measurements will also be recorded where available.

Other: Maternal Urinary Cotinine Assessment

Passive Prenatal Tobacco Exposure (Maternal Urinary Cotinine-Defined)

Mother-newborn dyads in whom the maternal urinary cotinine-to-creatinine ratio is detectable but below the active-exposure threshold and is consistent with passive prenatal tobacco exposure according to the prespecified study thresholds. Maternal self-reported smoking and secondhand smoke exposure will also be recorded as supportive exposure information. The same neonatal biochemical, metabolic, physiologic, and clinical measurements will be collected as in the active-exposure and reference cohorts. No experimental intervention will be administered.

Other: Maternal Urinary Cotinine Assessment

No Prenatal Tobacco Exposure (Maternal Urinary Cotinine-Defined Reference Cohort)

Mother-newborn dyads in whom the maternal urinary cotinine-to-creatinine ratio is below the prespecified no-exposure threshold or below the analytical detection limit. Maternal smoking and secondhand smoke exposure history will also be recorded to assess agreement between biomarker-based and self-reported exposure classifications. The same neonatal biochemical, metabolic, physiologic, and clinical measurements will be collected as in the exposed cohorts. No experimental intervention will be administered.

Other: Maternal Urinary Cotinine Assessment

Interventions

Maternal Urinary Cotinine Assessment OTHER

A clean-catch midstream maternal urine sample will be collected within 24 hours before delivery, preferably at admission to the delivery unit and before intravenous fluid administration. Urinary cotinine and creatinine concentrations will be measured, and the cotinine-to-creatinine ratio will be used to objectively classify prenatal tobacco exposure. No treatment or behavioral intervention will be assigned.

Active Prenatal Tobacco Exposure (Maternal Urinary Cotinine-Defined); No Prenatal Tobacco Exposure (Maternal Urinary Cotinine-Defined Reference Cohort); Passive Prenatal Tobacco Exposure (Maternal Urinary Cotinine-Defined)

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. Consecutive eligible mother-newborn dyads are recruited during the delivery hospitalization. Maternal clean-catch urine is collected within 24 hours before delivery for cotinine and creatinine measurement. Dyads are classified as active exposure, passive exposure, or no exposure according to prespecified urinary cotinine-to-creatinine thresholds and maternal exposure history. Outcomes are obtained mainly from routine care and include cord blood lactate, pH, base excess, FCOHb, birthweight, anthropometric measurements, Apgar scores, vital signs, early laboratory results, newborn screening TSH, hearing screening, and follow-up weight loss and bilirubin where available. No experimental intervention or additional neonatal blood sampling is planned.

You may qualify if:

• Pregnant individual expected to deliver a liveborn infant at the study hospital and providing written informed consent before delivery.
• Singleton pregnancy with an anticipated gestational age of ≥35 completed weeks at delivery.
• Maternal clean-catch urine sample obtainable within 24 hours before delivery, preferably at admission and before intravenous fluid administration, for urinary cotinine and creatinine measurement.
• Availability of routine umbilical cord blood gas analysis at birth, including at minimum lactate, pH, and base excess, with fetal carboxyhemoglobin recorded when available.
• Availability of routine neonatal clinical data, including birthweight, anthropometric measurements, Apgar scores, vital signs, and early postnatal assessments according to unit practice.

You may not qualify if:

• Multiple gestation.
• Major congenital anomaly, known chromosomal or genetic disorder, or major metabolic disease likely to affect neonatal adaptation or the study outcomes.
• Emergency clinical circumstances in which obtaining informed consent or the maternal urine sample could delay or interfere with urgent maternal or neonatal care.
• Inability to obtain an adequate maternal urine sample before delivery for cotinine and creatinine measurement.
• Severe perinatal condition preventing acquisition or reliable interpretation of the primary outcome data, including major birth trauma or prolonged intensive care requirement.
• Missing umbilical cord blood lactate measurement or other critical primary outcome data.
• Previous enrollment of the same mother-newborn dyad.

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: August 1, 2026
• Primary Completion (Estimated): November 8, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 21, 2026

Record last verified: 2026-07