Influenza in pregnancy and postpartum: immune response and maternal antibodies

Seasonal influenza is an acute respiratory viral infection, primarily caused by influenza type A and B viruses, which affects mostly during the cold months (autumn-winter) and is easily transmitted via respiratory droplets (cough, sneezing) or contact with contaminated surfaces.

Clinical management of influenza in pregnancy and postpartum

The management of influenza and fever in pregnant women and new mothers represents a clinical challenge that requires a deep understanding of the biological and pharmacological processes involved. Drug biodynamics is central in this context, as it allows for the evaluation of the interaction of an active ingredient with the organism at a level molecular, cellular and systemic, determining not only the therapeutic efficacy but also the risk of exposure to the fetus and newborn.

During drug intake, their absorption, distribution, metabolism and excretion affect the maternal plasma concentration and, consequently, the amount transferred to the fetus through the placenta and to the newborn through breast milk. Drugs administered orally undergo first-pass hepatic metabolism, while those administered intravenously quickly enter the circulation, resulting in higher peak concentrations. Distribution depends on lipophilicity and plasma protein binding; lipophilic and low protein-bound drugs tend to pass into the milk more easily. Hepatic metabolism can generate active or inactive metabolites, some of which may affect the newborn if present in milk. Excretion into milk depends on the half-life of the drug, the milk pH, the volume produced and the frequency of feedings. Premature infants or those with hepatic or renal impairment metabolize drugs more slowly, increasing the risk of adverse effects. The Relative Infant Dose (RID) parameter allows for the evaluation of drug safety, with values below 10% of the infant therapeutic dose generally considered safe according to LactMed and WHO guidelines.

 

Immune response in pregnancy and fetal protection

Pregnancy induces immunological and physiological changes that modify the response to influenza syndrome. A shift toward the humoral Th2 response occurs at the expense of the cellular Th1 response, reducing inflammatory reactivity to protect the fetus but increasing susceptibility to severe forms of viral infection. Cardiovascular and respiratory changes, such as the physiological increase in cardiac output and reduction in functional residual capacity of the lungs, make pregnant women more vulnerable to complications from fever and infection.

Despite this, pregnant women are able to produce specific IgG antibodies against influenza, which cross the placenta via receptorsFcRn  and provide the fetus with passive protection in the first months of life. These antibodies neutralize viral proteins, preventing the entry of the virus into respiratory epithelial cells and reducing the severity of the infection and its complications.

 

Maternal fever, vaccination and pharmacological treatment

The maternal fever, while not significantly altering the composition of the milk, can temporarily reduce milk production if the mother is dehydrated or debilitated. It is therefore essential to ensure hydration and rest. Influenza vaccination in pregnancy increases the concentration of IgG antibodies in maternal blood and milk, protecting both the mother and the newborn.

Pharmacological treatment of fever and influenza symptoms must consider the biodynamics and safety of drugs during breastfeeding. Paracetamol represents the drug of choice, with a minimal concentration in milk and RID below 1%, making it safe. Ibuprofen, with a short half-life and low transfer into milk, is also compatible with breastfeeding. Drugs such as oral decongestants or opioids require caution due to the possible effect on milk production or the risk of sedation in the newborn, particularly in metabolizersultrarapid CYP2D6. Influenza-specific antivirals, such as oseltamivir, are considered safe during breastfeeding according to CDC and AAP guidelines, and their use reduces the duration of maternal symptoms and the viral load exposed to the newborn.

 

Clinical recommendations and international guidelines

Current clinical recommendations, supported by the latest guidelines, indicate not to interrupt breastfeeding in case of fever or influenza, to prefer drugs with low transfer into milk and to monitor fragile or preterm infants in case of maternal intake of drugs with sedative potential or active metabolites. Breastfeeding, even during maternal infection, remains safe and provides the newborn with protective antibodies that reduce the risk of illness. Understanding drug biodynamics, maternal immune response and the transfer of IgG and IgA antibodies allows for the safe management of fever and influenza in pregnant women and new mothers, while simultaneously protecting the fetus and the newborn.

The main scientific sources and guidelines supporting these recommendations include the Centers for Disease Control and Prevention (CDC, 2025), which provides guidance on the management of influenza in breastfeeding women and the use of safe antivirals, the American Academy of Pediatrics (AAP, 2025) which recommends the continuation of breastfeeding and the use of drugs compatible with breast milk, the World Health Organization (WHO, 2024) for clinical guidelines on seasonal influenza, and the LactMed database of the National Institutes of Health (NIH), which documents drug transfer into milk and safe exposure levels for the infant.

 

Drug biodynamics and transfer into breast milk

Drug biodynamics is the study of the processes by which an active ingredient exerts its action in the body, including cellular, tissue and systemic effects. In clinical practice, biodynamics is integrated with pharmacokinetics and pharmacodynamics to evaluate efficacy, safety and the risk of transfer into infants during breastfeeding.

During breastfeeding, infant exposure depends not only on the maternal dose, but also on physiological and pharmacological parameters:

1. Absorption

• • The drug must reach the maternal circulation to be potentially transferred into the milk.
  • The route of administration is fundamental: orally administered drugs pass through first-pass hepatic metabolism, sometimes reducing bioavailability, while intravenous drugs enter the blood directly, rapidly increasing plasma concentration.
  • Some topical or inhaled drugs have minimal systemic absorption, reducing the amount transferred into the milk.

2. Distribution

• • After absorption, the drug is distributed between plasma, tissues and hydrophilic or lipophilic compartments.
  • The percentage of plasma protein binding is crucial: highly protein-bound drugs (e.g., warfarin) are less likely to diffuse into the milk, while free or lipophilic drugs pass more easily.
  • The lipophilicity of the drug favors passage into the mammary cells and into the milk, which contains lipids.

3. Metabolism

• • Most drugs are metabolized in the liver via enzymes such as CYP450 or UDP-glucuronyl transferase.
  • Genetic variations in liver enzymes (genetic polymorphisms, maternal age or liver status) can modify the drug concentration and active metabolites.
  • Some metabolites can be more active or more toxic than the original drug, influencing the risk for the infant.

4. Excretion

• • Lipophilic and non-ionized drugs pass more easily into the milk.
  • The plasma half-life determines how long the drug remains available for transfer into the milk: drugs with a short half-life have less cumulative exposure.
  • The frequency of feedings affects the total drug ingested by the infant; a drug administered immediately after a feeding reduces exposure.

5. Other factors affecting transfer into milk

• • Slightly acidic milk pH (≈7.0) can favor so-called “ion trapping” of basic drugs, increasing the concentration in milk compared to plasma.
  • Volume of milk produced and frequency of feedings determine the total dose of drug ingested by the infant.
  • Gestational age and metabolic maturity of the infant: preterm infants or those with renal/hepatic impairment metabolize drugs more slowly, increasing the risk of accumulation and adverse effects.

6. Safety indicators: Relative Infant Dose (RID)

• • The RID represents the percentage of the infant therapeutic dose taken through milk.
  • RID <10% is generally considered safe; higher values require clinical evaluation and monitoring.
  • For example, paracetamol and ibuprofen have RID <1%, while codeine in ultrarapid metabolizers can have RID >10% with significant risks.

 

Influenza and fever during breastfeeding

Influenza in the mother can cause fever, muscle pain, cough, fatigue and respiratory congestion. Clinical management must balance the treatment of maternal symptoms with the safety of the infant.

Effects of fever on milk and the infant

• The fever does not significantly alter the composition of the milk. Breast milk maintains proteins, antibodies and essential nutrients.
• High fever can temporarily reduce milk production if the mother is dehydrated or fatigued; therefore, it is advisable to maintain hydration and rest.
• The infant benefits from specific anti-influenza antibodies present in breast milk, which can reduce the severity of the infection if the infant were to contract it.

 

Farmaci antipiretici e analgesici  

Drug	Mechanism of action	Biodynamics	Transfer into milk	Clinical safety/Effects on the newborn
Paracetamol	Analgesic and antipyretic, acts centrally on the nervous system and on the thermal regulation of the hypothalamus	Rapidly absorbed orally, metabolized in the liver and excreted mainly as glucuronide and sulfate	Very low concentration in milk (RID <1%).	Indicated as the first-choice drug for fever and pain during breastfeeding.
Ibuprofen	Reversible inhibitor of COX-1 and COX-2, reduces the synthesis of inflammatory prostaglandins.	Rapid oral absorption, metabolized in the liver, short half-life (~2 hours).	RID <1%; compatible with breastfeeding.	Not significant under normal clinical conditions

 

 

Influenza-specific antivirals

Oseltamivir

• Mechanism of action: viral neuraminidase inhibitor, blocks the release of the influenza virus from infected cells.
• Biodynamics: prodrug transformed into active metabolite (oseltamivir carboxylate), excreted in minimal amounts in breast milk.
• Safety: clinical studies and CDC/AAP guidelines indicate that use does not require discontinuation of breastfeeding.
• Efficacy: reduces the duration of maternal symptoms and may reduce the viral load the infant is exposed to.

Other antivirals

• Insufficient data for baloxavir or zanamivir; use reserved for selected cases or clinical trials.
• Clinical choice based on the risk-benefit ratio and pediatric monitoring.

 

Conclusion 

In-depth knowledge of drug biodynamics allows for an understanding of the transfer of pharmacological substances into milk and an assessment of safety for the infant.

• Common antipyretics such as paracetamol and ibuprofen are first-choice drugs and safe.
• Antivirals such as oseltamivir can be used without interrupting breastfeeding.
• Stimulant or opioid drugs require attention and monitoring.

Breastfeeding remains safe and recommended during maternal fever and influenza if guidelines are followed, with attention to drug choice and clinical biodynamics.