GVP Product- or Population-Specific Considerations III: Pregnancy and Breastfeeding

Introduction

Medicinal-product use during pregnancy and breastfeeding requires pharmacovigilance to consider more than the safety of the person receiving treatment. During pregnancy, exposure may have implications for the embryo or fetus as well as the pregnant woman. During breastfeeding, exposure may affect the breastfed child, while the medicine may also affect milk production or breastfeeding itself.

This creates a distinctive benefit-risk problem. The potential harm from treatment must be considered alongside the harm that may result from untreated maternal disease or from withholding an effective treatment. The assessment therefore cannot be reduced to asking whether an exposed pregnancy was followed by an adverse outcome.

The current EMA GVP Product- or Population-Specific Considerations III became legally effective on 9 February 2026. EMA identifies the guidance as covering pregnant and breastfeeding women and their children exposed in utero or via breastmilk. citeturn0search0

1. Why Pregnancy and Breastfeeding Require Specific Pharmacovigilance

Pregnancy changes the clinical and biological context in which a medicinal product is used. Exposure may occur before pregnancy is recognised, during different developmental stages, or after delivery. The consequences of exposure can therefore depend on timing as well as dose and duration.

Breastfeeding creates a different exposure pathway. The medicinal product may pass into breast milk, and the clinical relevance depends on the concentration, timing, properties of the product, amount of milk consumed and characteristics of the infant.

These differences mean that pregnancy and breastfeeding safety information requires structured collection and interpretation rather than simply adding a pregnancy flag to a routine adverse-event record.

2. The Benefit-Risk Question Is Broader Than Maternal Risk

For a medicinal product used during pregnancy, the assessment should consider benefits and risks for the woman and, where relevant, the embryo or fetus. The underlying disease also matters because failure to treat maternal disease can itself affect both the woman and the developing child.

For breastfeeding, the assessment additionally considers the benefits of breastfeeding, the potential exposure of the infant through breast milk and any effect of treatment on milk production or breastfeeding.

EMA's guidance explicitly frames these additional elements as part of the benefit-risk evaluation. citeturn0search12

The resulting question is therefore not simply whether exposure carries risk. It is whether treatment provides sufficient benefit in the particular clinical circumstances, given the available evidence and uncertainty.

3. Exposure May Occur Before Pregnancy Is Recognised

Pregnancy may be unplanned, and treatment may begin before a woman knows she is pregnant. Exposure can therefore occur during an early developmental period without deliberate treatment of a known pregnancy.

This has important implications for pharmacovigilance systems. The absence of a documented pregnancy at the time of treatment does not establish absence of pregnancy exposure.

The system should be capable of identifying relevant exposure when pregnancy subsequently becomes known and preserving the chronology needed for later assessment.

4. Timing of Exposure Matters

The potential consequences of exposure may depend on when exposure occurs during pregnancy.

The assessment may need to distinguish exposure before conception, during early embryonic development, during organogenesis, later pregnancy and around delivery. The relevant outcomes also differ across these periods.

A pregnancy outcome cannot therefore be interpreted adequately without understanding the timing and duration of exposure.

5. The Pregnant Woman and the Exposed Child Are Linked but Distinct Subjects of Assessment

A pregnancy exposure may generate information about the woman's health, the pregnancy, the fetus or later child outcomes. These observations should not automatically be collapsed into one clinical concept.

Maternal adverse reactions, pregnancy complications, fetal outcomes, congenital anomalies, fetal growth, neonatal outcomes and later developmental findings may represent different safety questions.

The pharmacovigilance record should preserve enough information to distinguish these outcomes and relate each to the relevant exposure.

6. Pregnancy Exposure Does Not Establish Harm

The occurrence of a pregnancy after medicinal-product exposure is not itself evidence of a drug-related adverse outcome.

Pregnancy outcomes occur at background rates, and the underlying maternal disease, concomitant medicines, age, lifestyle, genetic factors and other exposures can influence outcomes.

The scientific assessment must therefore distinguish exposure, outcome and causal attribution.

7. Background Risk Is Essential

Many adverse pregnancy outcomes occur in the general population without medicinal-product exposure.

Interpreting a series of exposed pregnancies therefore requires knowledge of the relevant background risk and, where possible, an appropriate comparator or reference population.

Without this context, an observed number of outcomes can easily be mistaken for evidence of an increased risk.

8. Confounding by Indication

The condition for which a medicinal product is prescribed may itself influence pregnancy outcomes.

For example, a severe maternal disease may be associated with an increased risk of an adverse pregnancy outcome. If treatment is preferentially given to women with more severe disease, an association between exposure and outcome may reflect the disease rather than the medicine.

This is a central consideration in pregnancy pharmacovigilance and should be addressed explicitly when evidence permits.

9. Concomitant Exposures

Pregnant women may receive several medicines, vaccines or other exposures during the same period.

The assessment should therefore consider the complete exposure history where available rather than attributing an outcome automatically to the medicinal product under investigation.

The timing of concomitant exposures can be particularly important when different products have different biological mechanisms or developmental windows.

10. Pregnancy Exposure Data Are Often Limited Before Authorisation

Pre-authorisation clinical studies generally provide limited information on pregnancy exposure because pregnancy may be an exclusion criterion and because study populations, duration and follow-up may not be sufficient to characterise uncommon pregnancy outcomes.

Consequently, important pregnancy safety information may need to be generated after authorisation.

EMA's current guidance emphasises the importance of post-authorisation data collection even when no pregnancy safety concern was identified before authorisation. citeturn0search12

11. Post-Authorisation Data Collection

Post-authorisation pharmacovigilance can provide information about exposure that was not available during clinical development.

Potential sources include spontaneous reports, pregnancy registries, observational studies, databases, literature and other structured data-collection systems. Each source has different strengths and limitations.

The choice of source should follow the safety question. A registry may support systematic follow-up of exposed pregnancies, while a spontaneous report may provide an early indication of an unusual outcome.

12. Prospective and Retrospective Information

Prospectively identified pregnancy exposures can often support more structured follow-up because information is collected before the outcome is known.

Retrospective reports may still be valuable, particularly for identifying rare outcomes or signals, but they can be more vulnerable to incomplete exposure information and selective reporting.

The distinction should be preserved during assessment because it affects the reliability and interpretation of the evidence.

13. Pregnancy Registries

A pregnancy registry can provide structured information about exposure and outcomes in a defined population.

Its usefulness depends on design, enrolment, follow-up, completeness, appropriate comparator selection and the ability to characterise exposure accurately.

A registry should therefore not be judged solely by the number of pregnancies enrolled. The quality and relevance of the collected information determine its value for pharmacovigilance.

14. Prospective Follow-Up

Where a pregnancy exposure is identified prospectively, follow-up can be designed to collect information about the course and outcome of the pregnancy and, where relevant, the child.

The timing of follow-up should be appropriate to the outcomes being evaluated. Some outcomes are apparent at birth, while others may require later assessment.

The follow-up plan should therefore be aligned with the scientific question rather than limited to immediate pregnancy outcome.

15. Outcome Categories

Pregnancy pharmacovigilance may need to distinguish outcomes such as spontaneous abortion, stillbirth, preterm birth, congenital anomalies, fetal growth abnormalities, neonatal outcomes and other clinically relevant findings.

The exact outcome definition matters. Broad categories can obscure clinically meaningful differences, while excessively fragmented categories can reduce analytical power.

Outcome definitions should therefore be sufficiently precise to answer the question being investigated and sufficiently consistent to support meaningful comparison.

16. Congenital Anomalies

Congenital anomalies require particular care because their baseline occurrence is not negligible and because detection may depend on the timing and completeness of assessment.

A suspected association should be evaluated using the specific phenotype, timing of exposure, biological plausibility, alternative causes and appropriate background or comparative information.

A report of a congenital anomaly following exposure is therefore an important observation, but it is not by itself proof of teratogenicity.

17. Developmental Outcomes

Some potential effects may not be apparent at birth.

Where a medicinal product has a plausible relationship with later developmental, neurological or other child outcomes, the follow-up period and assessment methods should reflect that possibility.

The organisation should avoid implying that absence of an abnormality at birth excludes all later effects when the scientific question requires longer follow-up.

18. Maternal Outcomes

Pregnancy pharmacovigilance should not focus exclusively on fetal outcomes.

The medicinal product may affect the woman's health during pregnancy, labour or the postpartum period. Conversely, pregnancy itself may alter the pharmacokinetics, effectiveness or tolerability of treatment.

Maternal and child outcomes should therefore be considered together while retaining their distinct clinical meanings.

19. Outcomes Around Delivery

Exposure near delivery can raise different questions from exposure earlier in pregnancy.

Depending on the medicinal product, relevant considerations may include neonatal adaptation, withdrawal, sedation, respiratory effects, bleeding, infection risk or other clinically plausible outcomes.

The assessment should be product-specific and evidence-based rather than assuming that every medicine requires the same delivery-related precautions.

20. Pre-Conception Exposure

Exposure before conception may be relevant when a medicinal product has a long half-life, persistent biological effects or mechanisms that could plausibly affect reproductive outcomes.

The assessment should therefore consider the pharmacological characteristics of the product and the interval between exposure and conception.

Pre-conception counselling and risk communication may also be relevant where the product's characteristics warrant them.

21. Fertility and Reproductive Health

Some safety questions concern fertility or reproductive function rather than pregnancy outcome itself.

Evidence may arise from clinical studies, non-clinical data, spontaneous reports or other sources. The assessment should distinguish effects on the ability to conceive from effects occurring after conception.

This distinction can influence both the safety assessment and the information needed by patients and healthcare professionals.

22. Pregnancy Termination and Other Complex Outcomes

Pregnancy outcomes can involve complex clinical circumstances, including elective or medically indicated termination, fetal diagnosis and maternal illness.

The pharmacovigilance record should avoid treating every termination as evidence of an adverse drug reaction. The clinical reason, timing and relevant exposure history are necessary for interpretation.

Complex outcomes require careful clinical characterisation rather than automatic classification.

23. Pregnancy Exposure Through Clinical Practice

Routine prescribing systems may not capture pregnancy exposure systematically.

The pharmacovigilance system may therefore depend on spontaneous identification, targeted follow-up, registries, electronic health records or other sources to identify exposed pregnancies.

The organisation should understand the strengths and limitations of each source and avoid assuming that absence of reports demonstrates absence of exposure or absence of risk.

24. Signal Management in Pregnancy

Pregnancy-related signals should enter the same general signal-management framework while accounting for the distinctive evidence base.

A signal may arise from an unusual outcome, a cluster, a change in reporting frequency or a finding from a pregnancy study or registry. The assessment should integrate clinical, epidemiological and exposure information.

The pregnancy-specific context changes the interpretation of evidence; it does not create a separate standard of scientific proof.

25. Risk Management

Where pregnancy or breastfeeding becomes an important safety concern, the findings may affect the product's risk-management system.

Possible consequences include additional pharmacovigilance activities, targeted data collection, changes to risk-minimisation measures or updates to product information, depending on the evidence and regulatory assessment.

The existence of pregnancy exposure does not automatically require a restriction. The response should follow the assessed benefit-risk balance and the available options for managing uncertainty.

26. Avoiding Unnecessary Treatment Withholding

The objective of pregnancy pharmacovigilance is not to eliminate medicine use during pregnancy.

Untreated maternal disease can itself cause harm, and avoiding an effective treatment without adequate evidence may worsen outcomes for both the woman and the child.

EMA's guidance therefore emphasises reducing adverse outcomes associated with medicine use while avoiding unnecessary withholding of useful treatment options. citeturn0search12

The scientific system should consequently provide information that allows proportionate therapeutic decisions rather than simply identifying potential hazards.

27. Breastfeeding Is a Separate Exposure Question

Breastfeeding should not be treated as simply another stage of pregnancy exposure. The infant is exposed through breast milk after birth, and the relevant determinants of risk differ from fetal exposure during pregnancy.

The assessment should consider the properties of the medicinal product, maternal dose, timing of administration, transfer into milk, infant exposure and the infant's ability to handle the exposure.

The clinical question is whether the benefits of treatment and breastfeeding outweigh the potential risks to the infant and any effect on breastfeeding itself.

28. Transfer Into Breast Milk

The presence of a medicinal product in breast milk does not automatically establish clinically relevant harm to the infant.

The amount transferred, the concentration in milk, the timing of exposure and the infant's actual intake determine exposure. Protein binding, molecular characteristics, half-life and other pharmacokinetic properties may influence transfer.

Assessment should therefore distinguish detection in milk from clinically meaningful infant exposure and from demonstrated adverse effects.

29. Infant Exposure Is Not the Same as Maternal Exposure

The dose received by the mother cannot simply be used as the infant's exposure estimate.

Where information permits, the assessment should consider the concentration in breast milk, estimated milk intake and the resulting infant dose. Infant age and feeding pattern can also influence exposure.

This distinction is particularly important for medicines with a narrow therapeutic index or pharmacological effects that may be clinically relevant at low concentrations.

30. The Infant's Capacity to Handle Exposure

The same exposure can have different consequences in a premature neonate, a newborn and an older infant.

Organ maturation, body weight, renal and hepatic function and the developing nervous or immune system can influence susceptibility and elimination.

The assessment should therefore consider the characteristics of the exposed child rather than applying an adult safety assumption to breastfeeding exposure.

31. Effects on Lactation

A medicine may affect breastfeeding without causing direct toxicity in the infant.

Potential effects on milk production, milk composition or the mother's ability to breastfeed may therefore form part of the safety assessment where clinically relevant.

Such effects should be distinguished from infant adverse reactions because they involve different mechanisms and may require different management.

32. Breastfeeding Benefits Matter

Breastfeeding can provide important nutritional and health benefits to the infant and may be important to the mother's wellbeing.

A safety assessment should therefore consider the potential benefits of continuing breastfeeding alongside the potential medicine-related risk.

The appropriate clinical decision may involve continuing treatment and breastfeeding, changing treatment, temporarily interrupting breastfeeding or another approach depending on the medicine and evidence.

33. Timing of Maternal Dosing and Feeding

For some medicines, the relationship between dosing and breastfeeding may influence infant exposure.

Where the pharmacokinetic profile makes timing relevant, this can be considered as part of risk management. However, timing strategies should not be recommended simply because they appear intuitive; they should be supported by an understanding of exposure and pharmacology.

The objective is to reduce meaningful exposure where feasible without creating impractical or unsafe treatment arrangements.

34. Pregnancy and Breastfeeding Data Should Be Linked Carefully

A woman may be exposed during pregnancy and continue treatment while breastfeeding. The resulting safety record may contain information about both prenatal and postnatal exposure.

The data should preserve the distinction between exposure in utero and exposure through breast milk because the biological pathways and outcomes differ.

This also allows later assessment to determine whether an infant outcome could plausibly relate to one or both exposure periods.

35. Collection of Pregnancy Exposure Information

A useful pregnancy exposure record should capture enough information to reconstruct the relevant clinical circumstances.

Important elements can include maternal characteristics, indication, medicinal product, dose, route, treatment dates, gestational timing, concomitant exposures, underlying disease and pregnancy outcome.

The precise data required depend on the safety question, but incomplete exposure chronology can substantially limit interpretation.

36. Collection of Breastfeeding Exposure Information

Breastfeeding records may need information about maternal treatment, timing, dose, infant age, breastfeeding pattern, relevant infant characteristics and observed outcomes.

Where breast-milk concentration data are available, they can help characterise exposure, but their interpretation still requires consideration of infant intake and pharmacological properties.

The record should distinguish information reported by the mother from information established through clinical or analytical evidence.

37. Follow-Up of Pregnancy Reports

Pregnancy reports often require follow-up because the initial report may identify exposure without a final outcome.

The follow-up process should be sufficiently structured to obtain meaningful information while avoiding unnecessary burden on the patient or healthcare professional.

Follow-up should focus on information capable of changing the assessment rather than collecting large amounts of data with no defined purpose.

38. Loss to Follow-Up

Loss to follow-up can create important uncertainty because exposed pregnancies with unknown outcomes cannot always be interpreted as unaffected outcomes.

The organisation should understand the extent and pattern of missing outcomes when evaluating pregnancy data. If loss to follow-up is substantial or differential, it may introduce bias.

The absence of an outcome record should therefore not automatically be classified as a normal outcome.

39. Data Quality

Pregnancy and breastfeeding safety assessments are particularly sensitive to missing or ambiguous dates.

Errors in gestational age, treatment dates, outcome dates or breastfeeding duration can change the interpretation of exposure windows.

Data-quality controls should therefore focus on the variables that materially affect the scientific question rather than treating every field as equally important.

40. Registries and Comparator Groups

When a registry or observational study is used to estimate risk, the choice of comparator is critical.

A comparison with the general population may be useful in some circumstances, while a disease-matched or exposure-matched comparator may be more informative in others.

The comparator should reflect the causal question. A poorly chosen comparator can create or obscure an apparent association.

41. Signal Detection From Pregnancy Data

Routine signal-detection methods may be less informative when exposure numbers are small or when outcomes are heterogeneous.

Qualitative clinical review, targeted surveillance and epidemiological analysis may therefore complement automated methods.

The detection strategy should reflect the nature of pregnancy outcomes and the limitations of the available data rather than relying on a single method.

42. Interpreting Clusters

A cluster of similar pregnancy outcomes can be important, particularly when the phenotype is unusual or exposure timing is consistent.

However, clustering can also occur by chance, through common background factors or because reports were stimulated by a shared external event.

The assessment should therefore examine whether the cases share a plausible exposure-related pattern and whether alternative explanations are credible.

43. Developmental Windows

A potential developmental effect may depend strongly on the period of exposure.

When evaluating a suspected association, the assessor should compare the timing of exposure with the biological window during which the relevant developmental process occurs.

An exposure outside a biologically plausible window may weaken one hypothesis while leaving other mechanisms possible. Timing should therefore inform, rather than mechanically determine, causality assessment.

44. Maternal Disease as a Confounder

The underlying maternal condition may influence both medicine use and pregnancy outcome.

This is particularly important when treatment is concentrated in women with severe disease or when the disease itself affects fetal development, pregnancy duration or neonatal health.

Where comparative data are available, analyses should attempt to distinguish treatment effects from disease effects.

45. Multiple Medicines During Pregnancy

Polypharmacy can make attribution difficult.

The assessment should consider whether one medicine, several medicines, an interaction or the underlying disease provides the most plausible explanation for the observed outcome.

A signal associated with a combination may nevertheless be clinically important even if no individual component can be confidently identified as the sole cause.

46. Vaccines During Pregnancy

Vaccination during pregnancy may require specific assessment of both maternal and pregnancy outcomes.

The fact that an event follows vaccination does not establish causality, and background pregnancy outcomes remain relevant. At the same time, vaccination may be intended to protect the mother or indirectly protect the infant, so the benefit side of the assessment can be substantial.

Vaccine-specific pharmacovigilance principles should therefore be considered alongside the pregnancy-specific framework.

47. Biological Medicines During Pregnancy and Breastfeeding

Biological medicines may present additional considerations related to molecular size, placental transfer, persistence, immunogenicity and the timing of exposure.

The assessment should consider the specific product rather than assuming that all biological medicines behave similarly.

Where a biological product is used during pregnancy or breastfeeding, the biological-medicinal-product and pregnancy-specific frameworks may need to be applied together.

48. Exposure to Medicines With Long Persistence

Medicines with long half-lives or prolonged biological activity can create exposure that extends beyond the last administered dose.

This may be relevant to conception, pregnancy progression or breastfeeding. The exposure assessment should therefore consider pharmacokinetics and pharmacodynamics rather than relying solely on administration dates.

49. Unplanned Pregnancy During Treatment

An unplanned pregnancy during treatment can create immediate uncertainty for the patient and clinician.

The pharmacovigilance system should support appropriate collection of exposure information while clinical management follows the applicable product-specific and clinical guidance.

The existence of an unplanned exposure should not automatically be treated as evidence that treatment must be stopped. The relevant clinical decision depends on the medicine, indication, timing and evidence.

50. Pregnancy Prevention and Risk Minimisation

For medicines where pregnancy exposure presents an established or important potential risk, risk-minimisation measures may include pregnancy-prevention requirements, contraception advice, testing, prescribing restrictions or targeted communication.

Such measures should have a clear safety rationale and should be proportionate to the evidence and seriousness of the risk.

Where a measure is implemented, the organisation should also consider how its implementation and effectiveness will be evaluated.

51. Risk Communication to Patients

Pregnancy and breastfeeding information must communicate uncertainty without causing unnecessary fear.

Patients need to understand the known risks, the limitations of the evidence and the potential consequences of untreated disease. A communication that simply lists possible fetal or infant harms without explaining uncertainty and clinical context can lead to inappropriate treatment decisions.

The objective is informed decision-making, not avoidance of all exposure at any cost.

52. Communication to Healthcare Professionals

Healthcare professionals may need more detailed information about the evidence, exposure timing, identified risks and available management options.

The communication should distinguish established findings from suspected associations and should explain when evidence is insufficient.

Where a pregnancy-specific risk-management measure exists, the communication should make the required action clear.

53. Product Information

Pregnancy and breastfeeding information in product information should reflect the current regulatory assessment and available evidence.

The wording should not imply a stronger level of certainty than the evidence supports. Conversely, important established risks should not be obscured by overly cautious language.

Changes to product information should remain traceable to the underlying safety assessment and regulatory decision.

54. Relationship With the RMP

Pregnancy or breastfeeding may constitute an important safety concern or an area of missing information within the risk-management system.

The RMP should reflect the relevant safety knowledge and uncertainty, and additional pharmacovigilance or risk-minimisation measures should be considered where justified.

The need for an additional activity should follow from the identified evidence gap rather than from the mere fact that pregnancy exposure is possible.

55. Relationship With Signal Management

A pregnancy signal may originate from an individual case, cluster, registry, study or other source.

Once identified, it should be evaluated through the general signal-management framework, with pregnancy-specific clinical and epidemiological considerations incorporated into the assessment.

The outcome may be reassurance, continued monitoring, further evidence generation, risk-management action or regulatory assessment depending on the totality of evidence.

56. Relationship With Aggregate Reporting

Pregnancy and breastfeeding findings may need to contribute to aggregate safety evaluation, including the PSUR where relevant.

Aggregate review can identify patterns across multiple individual reports and studies, while pregnancy-specific analyses can add context that may not be apparent in general safety surveillance.

The interfaces should allow important findings to move in both directions between pregnancy surveillance and broader pharmacovigilance activities.

57. Special Situations Require Explicit Clinical Context

Some pregnancy and breastfeeding reports contain circumstances that make interpretation particularly difficult. Exposure may occur before pregnancy recognition, multiple medicines may be involved, the pregnancy may have an important underlying medical condition, or the outcome may have several plausible causes.

These situations should not be resolved by assigning a default causal explanation. The assessment should make the competing explanations visible and identify which additional information would most reduce uncertainty.

58. Reports With Incomplete Pregnancy Information

A report may contain only partial information about gestational age, dose, treatment dates or outcome.

Incomplete information does not necessarily make the report unusable. It determines what conclusions can reasonably be drawn from it. Follow-up should focus on the missing information most likely to affect the assessment.

For example, an approximate exposure period may be sufficient for one question but inadequate for assessing a suspected developmental-window effect.

59. Reports of Congenital Anomalies

A congenital anomaly following exposure should be clinically characterised as precisely as possible.

The assessment may consider the specific phenotype, maternal disease, concomitant exposure, family history, timing of exposure and relevant background incidence. A broad description such as "birth defect" may be insufficient for meaningful scientific evaluation.

The aim is to determine whether the observed phenotype provides evidence for a reproducible association rather than simply counting exposed pregnancies with anomalies.

60. Reports of Pregnancy Loss

Pregnancy loss has many possible causes and occurs at a measurable background rate.

The assessment should therefore consider gestational age at loss, maternal characteristics, underlying disease, concomitant exposure and medicinal-product exposure timing.

A cluster of losses may warrant investigation, but the cluster should be evaluated against appropriate background expectations and alternative explanations.

61. Neonatal Findings After In Utero Exposure

Some effects may become apparent only after delivery.

The neonatal assessment should consider the timing of the final maternal exposure, the pharmacological properties of the medicine and the clinical condition of the newborn.

Where the suspected effect could be transient, the course and resolution of the finding may provide useful evidence. Persistent or delayed effects may require longer follow-up.

62. Long-Term Child Follow-Up

Long-term follow-up may be relevant when the scientific question concerns development or another outcome that cannot be assessed reliably at birth.

The need for extended follow-up should be based on the characteristics of the medicine, the exposure and the potential outcome rather than automatically applied to every pregnancy exposure.

Where long-term follow-up is undertaken, the purpose, outcome measures and duration should be scientifically justified.

63. Breastfeeding Reports With Infant Adverse Events

When an infant develops an adverse event while breastfeeding during maternal treatment, the assessment should establish the exposure pathway and consider other possible causes.

Relevant information may include maternal dose and timing, infant age, feeding pattern, infant illness, concomitant infant medicines and the clinical course of the event.

The temporal relationship can support a hypothesis but does not by itself establish that exposure through milk caused the event.

64. Infant Laboratory Findings

Laboratory abnormalities in breastfed infants may provide evidence of exposure or pharmacological effect, but interpretation depends on age-appropriate reference ranges and clinical context.

A laboratory finding should therefore not automatically be classified as abnormal drug exposure without considering the infant's developmental stage and other possible causes.

65. When the Mother Requires Treatment

Pregnancy and breastfeeding pharmacovigilance must remain connected to the clinical need for maternal treatment.

For some diseases, withholding treatment may create substantial risks for the woman and child. For others, alternative therapies may provide similar benefit with less uncertainty.

The pharmacovigilance system should provide evidence that supports this clinical decision rather than assuming that medicine exposure is inherently the dominant risk.

66. Evidence From Other Populations

Evidence from non-pregnant adults may provide information about maternal adverse reactions but cannot automatically answer questions about fetal or infant safety.

Likewise, non-clinical reproductive-toxicity findings can inform biological plausibility but do not automatically establish a clinical risk in humans.

The assessment should integrate evidence from different populations while preserving the limits of each source.

67. Non-Clinical Reproductive Toxicology

Non-clinical reproductive and developmental toxicity findings can provide mechanistic context for human pharmacovigilance.

Such findings may influence the hypotheses being evaluated, particularly when the affected developmental process has a plausible relationship to the medicinal product's pharmacology.

They should nevertheless be interpreted together with human exposure and outcome data rather than treated as direct evidence of a clinical effect.

68. Pregnancy Exposure and Pharmacokinetics

Pregnancy can alter pharmacokinetic parameters through physiological changes affecting distribution, metabolism and elimination.

Consequently, the maternal exposure achieved by a standard dose may differ during pregnancy, and changes in exposure may affect both effectiveness and tolerability.

This is a clinical and pharmacological consideration that can become relevant to pharmacovigilance when interpreting changes in maternal adverse events or treatment failure.

69. Postpartum Changes

The transition after delivery can rapidly alter physiology and medication exposure.

The pharmacovigilance assessment may therefore need to distinguish events occurring during pregnancy from those occurring postpartum and consider whether breastfeeding creates an additional exposure pathway.

This distinction can be important when an event appears to change around delivery.

70. Data From Electronic Health Records

Electronic health records and other routinely collected healthcare data can provide valuable information about pregnancy exposure and outcomes.

Their usefulness depends on the quality of exposure recording, gestational dating, outcome coding, linkage and follow-up. Misclassification can materially affect the estimated association.

Routine healthcare data should therefore be assessed for fitness for purpose rather than treated as automatically complete.

71. Data Linkage

Linking maternal treatment information with pregnancy and child outcomes can substantially improve the ability to study safety.

However, linkage methods can introduce errors if records are incorrectly matched or if relevant outcomes occur outside the linked healthcare system.

The validity of the linkage should therefore form part of the evidence assessment.

72. Comparative Epidemiology

When sufficient data exist, epidemiological studies can help distinguish an exposure-related risk from background risk and confounding.

The choice of study design, comparator, outcome definition and analytical approach should follow the causal question.

A well-designed comparative study can provide evidence that individual case reports cannot, but it remains subject to limitations such as residual confounding, exposure misclassification and outcome ascertainment.

73. Communicating Evidence That Remains Limited

Pregnancy and breastfeeding information often remains incomplete even after years of post-authorisation experience.

Communication should therefore explain what is known, what is not known and what evidence is being generated. The absence of definitive evidence should not be converted into either an assurance of safety or an assumption of harm.

Clear uncertainty can support more appropriate clinical decisions than false precision.

74. Governance of Pregnancy and Breastfeeding Safety

The MAH should have appropriate processes for identifying pregnancy and breastfeeding exposures, obtaining relevant follow-up, evaluating emerging evidence and escalating important findings.

The QPPV should have appropriate visibility of significant pregnancy or breastfeeding safety concerns and of the effectiveness of the processes used to manage them.

As with other pharmacovigilance activities, specialist clinical and epidemiological work can be distributed across qualified functions while overall system responsibility remains with the MAH.

75. Vendor and Registry Oversight

Where pregnancy registries, follow-up services or other external organisations collect data, the MAH should maintain appropriate oversight of the quality and timeliness of the information returned.

The important question is not merely whether the service provider has completed the contracted activity. The organisation should be able to determine whether the resulting data are fit for the pharmacovigilance purpose for which they were collected.

76. Illustrative Inspection Scenario: Pregnancy Reports Are Collected but Not Followed Up

An organisation records pregnancy exposure reports but has no effective process for obtaining outcomes. As a result, many records remain without final pregnancy information.

The potential weakness is not the existence of incomplete reports. It is the failure of the system to obtain information that was reasonably necessary for the defined safety question.

The appropriate corrective approach would examine follow-up strategy, workload, contact methods, data requirements and escalation of important missing information.

77. Illustrative Inspection Scenario: Exposure Is Known but Timing Is Not

The organisation can identify that a patient used the medicinal product during pregnancy but cannot determine when exposure occurred relative to gestational development.

The potential weakness is a data structure that captures exposure status without preserving the chronology needed for scientific interpretation.

78. Illustrative Inspection Scenario: Breastfeeding Exposure Is Assumed to Be Clinically Significant

A report documents that a medicinal product is detectable in breast milk, and the assessment concludes that the infant is therefore at risk.

The potential weakness is failure to distinguish presence in milk from clinically meaningful infant exposure and adverse effect.

A scientifically defensible assessment would consider the amount transferred, infant exposure, pharmacology, infant characteristics and observed clinical outcome.

79. Illustrative Inspection Scenario: Background Risk Is Ignored

An assessment identifies several congenital anomalies among exposed pregnancies but does not compare the observed pattern with an appropriate background expectation.

The potential weakness is interpreting exposed outcomes without considering that congenital anomalies occur independently of medicinal-product exposure.

80. Illustrative Inspection Scenario: Untreated Disease Is Not Considered

A risk assessment recommends avoiding a medicine during pregnancy without considering the consequences of discontinuing treatment for a serious maternal disease.

The potential weakness is an incomplete benefit-risk assessment. Pregnancy pharmacovigilance must consider both medicine-related risk and the risks of untreated disease.

81. A Mature Pregnancy and Breastfeeding Pharmacovigilance Model

The overall system can be represented as:

Exposure identified
        ↓
Characterise maternal / infant exposure
        ↓
Establish timing and clinical context
        ↓
Characterise outcome
        ↓
Consider background risk and alternatives
        ↓
Integrate clinical + epidemiological evidence
        ↓
Assess causality / association
        ↓
Define uncertainty
        ↓
Benefit-risk / RMP / regulatory assessment
        ↓
Communication and clinical implementation
        ↓
Further evidence and reassessment

The model applies equally to pregnancy and breastfeeding, but the exposure pathway and outcome questions differ. The system should therefore share common governance while preserving the biological distinctions between fetal and infant exposure.

82. Practical Review Questions

For an important pregnancy or breastfeeding safety issue, the organisation should be able to answer:

1. What was the maternal indication?
2. What product, dose and formulation were used?
3. When did exposure occur?
4. Was exposure in utero, through breast milk or both?
5. What concomitant exposures were present?
6. What was the relevant maternal and child clinical context?
7. What outcome occurred and how was it characterised?
8. What is the appropriate background risk?
9. What alternative explanations exist?
10. What evidence supports or weakens the association?
11. What uncertainty remains?
12. What further information could reduce that uncertainty?
13. What RMP or product-information implications were considered?
14. What communication is appropriate?
15. When will the assessment be revisited?

83. Final Principle

Pregnancy and breastfeeding pharmacovigilance exists to improve the quality of therapeutic decisions in situations where evidence is often incomplete and the consequences of both treatment and non-treatment can be important.

The scientific task is to characterise exposure, outcomes and competing explanations accurately enough to distinguish background events from potential medicine-related risks. The clinical task is then to place that evidence within the benefit-risk context of the woman and, where relevant, the exposed child.

A mature system therefore does not treat pregnancy exposure as synonymous with harm, and it does not treat limited evidence as proof of safety. It preserves uncertainty, generates useful evidence and communicates what is known in a form that supports proportionate decisions.

Key Takeaways

Pregnancy and breastfeeding require specific pharmacovigilance because exposure can affect the treated woman and, depending on the circumstances, the embryo, fetus, neonate, infant or child. The exposure pathway, developmental timing and clinical context determine which safety questions need to be answered.

The assessment must distinguish exposure from outcome and outcome from causality. Background risk, underlying disease, concomitant exposures and incomplete follow-up are central to interpretation.

For breastfeeding, detection of a medicinal product in milk does not by itself establish clinically meaningful infant exposure or harm. Maternal benefit, breastfeeding benefit, infant susceptibility and the properties of the medicine all contribute to the benefit-risk assessment.

The purpose of the system is not to eliminate medicine use during pregnancy or breastfeeding. It is to generate and communicate evidence that allows treatment decisions to balance maternal and child risks and benefits appropriately.

References

1. European Medicines Agency. Good Pharmacovigilance Practices (GVP): Product- or population-specific considerations III — Pregnant and breastfeeding women and their children exposed in utero or via breastmilk. EMA/653036/2019 Corr.
2. European Medicines Agency. Good Pharmacovigilance Practices (GVP): Product- or population-specific considerations I — Vaccines for prophylaxis against infectious diseases.
3. European Medicines Agency. Good Pharmacovigilance Practices (GVP): Product- or population-specific considerations II — Biological medicinal products.
4. European Medicines Agency. Good Pharmacovigilance Practices (GVP), Module V — Risk management systems.
5. European Medicines Agency. Good Pharmacovigilance Practices (GVP), Module VI — Collection, management and submission of reports of suspected adverse reactions to medicinal products.
6. European Medicines Agency. Good Pharmacovigilance Practices (GVP), Module IX — Signal Management.
7. European Medicines Agency. Good Pharmacovigilance Practices (GVP), Module XV — Safety communication.
8. Regulation (EC) No 726/2004, as amended.
9. Directive 2001/83/EC, as amended.
10. Commission Implementing Regulation (EU) No 520/2012, as amended.

Regulatory Note

This article explains the scientific and pharmacovigilance framework for medicinal-product exposure during pregnancy and breastfeeding. It distinguishes regulatory requirements, GVP guidance, scientific interpretation and operational practice. The current GVP Product- or Population-Specific Considerations III became legally effective on 9 February 2026. Current legislation, GVP guidance and applicable EMA or national competent-authority procedures should be verified when applying the framework to a specific medicinal product or clinical situation.

Inspection scenarios are illustrative and are not presented as documented regulatory findings.