This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Lamotrigine Pregnancy Registry (LAM05) (NCT01064297), a registered phase not stated study. The primary outcome is Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01064297 |
| Phase | Phase not stated |
| Condition | Epilepsy, Bipolar Disorder |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 3416 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
The primary outcome concerns prospectively enrolled pregnancies exposed to lamotrigine monotherapy. The broader registry record covers pregnancy exposures among women with epilepsy and other approved indications, including bipolar disorder. The record lists an enrollment of 3416, but that figure should not be read as the size of the primary-outcome population or as the count in any particular exposure group.
Intervention
The exposures listed are lamotrigine monotherapy, lamotrigine polytherapy including valproate, and lamotrigine polytherapy without valproate. The primary outcome is specifically organized around the earliest pregnancy trimester of exposure to lamotrigine monotherapy. The record describes exposure monitoring rather than assignment to a treatment.
Comparator
The registry lists different exposure groups, but it is not a randomized comparison, and allocation is not stated. These groups are not a like-for-like control comparison. In particular, differences between exposure groups could not be attributed to the exposure alone using these descriptive data.
Primary question
Among prospectively enrolled pregnancies exposed to lamotrigine monotherapy, how many live births, fetal deaths, induced abortions, and spontaneous pregnancy losses were recorded according to the earliest trimester of exposure? The registry description says that major congenital malformations are not assessed for spontaneous losses because their identification is inconsistent. Numerical results for these birth-outcome categories are not reported in the registry record.
3. Trial Design
This is a pregnancy registry record, not a randomized clinical trial. Its stated purpose is to monitor lamotrigine exposure during pregnancy. The background explains why such monitoring is used: pregnant women are routinely excluded from clinical trials, animal-model findings may not translate directly to humans, and pregnancy exposure may occur when women have epilepsy or another approved indication, including bipolar disorder.
The record lists GlaxoSmithKline as sponsor and gives a status of COMPLETED. Its listed start is 2001-11, and its primary completion is 2010-07. The background separately says that the International Lamotrigine Pregnancy Registry was established by GlaxoSmithKline in 1992. These dates refer to different statements in the record and should not be treated as interchangeable.
The listed exposure categories are lamotrigine monotherapy, lamotrigine polytherapy including valproate, and lamotrigine polytherapy without valproate. The primary-outcome population is described as prospectively enrolled pregnancies exposed to monotherapy. The registry record lists an enrollment of 3416, but does not give the number contributing to each primary-outcome category in the registry record for this summary.
Allocation is not stated, and the record explicitly indicates that this is not a randomized comparison. The exposure groups therefore should not be interpreted as randomized treatment arms or as equivalent groups differing only in medication exposure. Details of recruitment procedures, follow-up operations, or other design features are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Lamotrigine Monotherapy Pregnancy Exposures | Lamotrigine Polytherapy With Valproate Pregnancy Exposures | Lamotrigine Polytherapy Without Valproate Pregnancy Exposures |
|---|---|---|---|
| STARTED | 2567 | 219 | 630 |
| COMPLETED | 1776 | 171 | 497 |
| NOT COMPLETED | 791 | 48 | 133 |
Reasons for not completing this period:
| Reason | Lamotrigine Monotherapy Pregnancy Exposures | Lamotrigine Polytherapy With Valproate Pregnancy Exposures | Lamotrigine Polytherapy Without Valproate Pregnancy Exposures |
|---|---|---|---|
| Lost to Follow-up | 791 | 48 | 133 |
Analysis population for the primary outcome, as defined in the registry: Prospectively enrolled pregnancies exposed to lamotrigine monotherapy.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Lamotrigine Monotherapy Pregnancy Exposures | Lamotrigine Polytherapy With Valproate Pregnancy Exposures | Lamotrigine Polytherapy Without Valproate Pregnancy Exposures | Total |
|---|---|---|---|---|---|
| Participants analysed | 2567 | 219 | 630 | 3416 | |
| Age Continuous | years | 27.9 (SD 5.84) | 25.8 (SD 5.49) | 28.1 (SD 6.08) | 27.8 (SD 5.89) |
| Sex: Female, Male: Female | Participants | 2567 | 219 | 630 | 3416 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy, measured over Although reports and diagnoses of major congenital malformations are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | infants |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is a count of birth outcomes among prospectively enrolled pregnancies exposed to lamotrigine monotherapy, organized by the earliest trimester in which exposure occurred. The recorded outcome types are live births, fetal deaths, induced abortions, and spontaneous pregnancy losses. The unit is infants, and the outcome is described as a number rather than a rate or a modeled treatment effect.
This organization is useful for describing what was recorded across different exposure timings. A count can show the number of events in a category, but interpretation also depends on the number of pregnancies or infants contributing to that category and on how outcomes were identified. Those numerical outcome results and corresponding denominators are not reported in the registry record available for this account.
The registry description specifically cautions that major congenital malformations are not characterized among spontaneous losses because identification is inconsistent. It therefore makes no comment about the presence or absence of malformations in those losses. The listed timeframe notes that reports and diagnoses of major congenital malformations are accepted up to six years after birth, while most are reported after delivery-room or shortly-after-birth assessments. That description is context for ascertainment, not a numerical result or an estimate of malformation risk.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a pregnancy-exposure registry whose primary outcome is a set of birth-outcome counts categorized by earliest trimester of exposure to lamotrigine monotherapy. It does not report those primary-outcome counts in the registry record for this interpretation. Consequently, the direction, size, and precision of any difference across exposure timing categories cannot be described from this record alone.
The adverse-event summary reports three exposure groups. For lamotrigine monotherapy pregnancy exposures, it gives 1776 at risk and 35 affected. For lamotrigine polytherapy with valproate pregnancy exposures, it gives 171 at risk and 16 affected. For lamotrigine polytherapy without valproate pregnancy exposures, it gives 497 at risk and 12 affected. These are group-level counts as recorded; they are not estimates of a causal effect. The registry record says the groups are not a like-for-like control comparison, and allocation is not stated.
The serious-event terms listed include orofacial clefts at 1.8%, cardiac septal defect/murmur at 1.2%, club foot at 1.2%, gastroschisis at 0.6%, hydrocephalus/spina bifida at 0.6%, and meningomyelocele at 0.6%. These percentages are reported as terms in the adverse-event summary. The registry entries available do not specify the denominator or group assignment for each percentage, so they should not be used to infer a group-specific risk or to compare groups.
Counts alone do not indicate how precisely an underlying event frequency is estimated. Precision would normally be assessed using an interval estimate, which describes a range of values compatible with the data under a stated statistical method. Such interval estimates for the outcomes in question are not reported in the registry record. Nor are adjusted estimates, hypothesis tests, or a statistical comparison among groups reported in the registry record.
The record's stated primary outcome is descriptive and concerns pregnancy outcomes by exposure timing; the adverse-event summary is a separate presentation of events across exposure groups. Neither should be treated as proof that lamotrigine caused an outcome, or as proof that it did not. The available information supports describing the registry's recorded categories and counts, while leaving comparative and causal conclusions unresolved.
9. Statistical Methods Explained
What kind of evidence does a pregnancy registry provide?
In general, a registry follows or records people with a specified condition, exposure, or experience and describes outcomes observed in that setting. It can help organize information that may be difficult to obtain from conventional clinical trials, particularly when a population is routinely excluded from such trials. A registry does not, by its existence alone, create randomized groups. Here, the record says allocation is not stated and that the exposure groups are not a like-for-like control comparison. The evidence should therefore be read as observational description rather than as a randomized estimate of treatment effect.
What does a count measure?
A count is the number of recorded events or outcomes in a defined category. The primary outcome is described as counts of live births, fetal deaths, induced abortions, and spontaneous pregnancy losses, categorized by earliest trimester of exposure to monotherapy. A count does not by itself give the probability of an outcome. To interpret a frequency, the relevant denominator and the rules used to include and classify observations also matter. Numerical primary-outcome counts and their category denominators are not reported in the registry record available for this account.
Why does outcome ascertainment matter?
Ascertainment is the process by which an outcome is identified and recorded. In general, differences in timing, assessment, and completeness can affect which events appear in a dataset. The registry description says reports and diagnoses of major congenital malformations are accepted up to six years after birth and that most are reported after assessments in the delivery room or shortly after birth. It also says identification of major congenital malformations among spontaneous losses is inconsistent, so no comment is made about their presence or absence in those losses. This is an explicit limitation on what the registry can say about that outcome in that category.
In general, incomplete or inconsistent identification can lead to outcomes being missed or classified differently. The record does not report how missing outcome information was handled, whether follow-up completeness was evaluated, or whether outcome classification was independently reviewed. Those details are not reported in the registry record.
How should group comparisons be understood?
In general, a fair comparison requires groups to be sufficiently comparable with respect to factors that can affect both exposure and outcome. Random allocation is one way a study may seek comparability, but this record is not randomized. Differences in recorded counts among exposure groups could reflect differences in the groups, differences in outcome observation, or other factors, as well as any relationship with exposure. The registry entries do not identify adjustments for potential confounders or a prespecified method for comparing the groups. An unadjusted comparison would not resolve those concerns.
The adverse-event summary supplies counts at risk and counts affected for three exposure groups. Those figures describe the record as presented; they do not establish the risk attributable to an exposure. The listed serious-event terms have percentages, but the registry entries do not identify the denominators or exposure-group mapping for those percentages. Without that context, direct comparison of the listed percentages with the group counts is not justified.
What do significance levels and planning illustrations mean?
In general, a significance level is a threshold used in a specified hypothesis-testing procedure. The planning assumptions named in the registry material specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The planning illustration is described as based on the observed effect, with the effect to detect expressed as a stated fraction of that observed effect. These assumptions describe an illustrative calculation, not the registry's own design. The resulting sample-size values are not reported in the registry record available for this account.
In general, a sample-size calculation estimates how much information a future study might need under stated assumptions. It is not observed power, and it does not show that the registry was designed to detect a particular effect. The record does not report a sample-size justification for the registry. It also does not report the observed effect needed to assess the planning illustration in this summary.
For time-to-event settings, a common planning approach can be expressed in terms of a total number of events; other planning approaches may be expressed as participants per arm. Those are general conventions, not results for this registry. The registry entries do not establish a time-to-event primary analysis for this pregnancy-outcome measure.
What can an interval estimate add?
In general, a confidence interval conveys statistical uncertainty around an estimate. A narrower interval indicates greater precision under the model and assumptions used; a wider interval indicates less precision. An interval does not by itself remove bias from nonrandom allocation, incomplete ascertainment, or confounding. No confidence intervals for the primary outcome or the adverse-event counts are reported in the registry entries available for this account.
Over-dispersion is a general issue that can arise when count outcomes vary more than a model's assumptions allow. If present, it can make uncertainty estimates too optimistic unless the analysis accounts for it. The registry entries do not report an over-dispersion assessment or a count-model specification. It would not be appropriate to infer that such a method was or was not used.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 9 outcome measures and 7 analyses. The existence of multiple outcomes and analyses raises a general interpretive issue: when many statistical questions are examined, some apparently unusual findings can arise by chance. Statistical methods may address this through prespecified primary outcomes, adjusted testing, or cautious interpretation. The registry record does not report whether a multiplicity adjustment was used, which analyses were confirmatory, or how secondary analyses were prioritized. The primary outcome is identified by title, but that alone does not establish the full statistical hierarchy.
The primary population is described as prospectively enrolled pregnancies exposed to lamotrigine monotherapy. The registry entries do not report detailed analysis-population rules, including how incomplete records, pregnancies with uncertain exposure timing, or other exclusions were handled. It is also not reported in the registry record whether missing observations were imputed, excluded, or handled through another approach. The number and pattern of missing observations for the primary outcome are not reported in the registry record for this account.
In general, missingness matters because observations that are unavailable may differ systematically from those that are recorded. The consequences depend on why information is missing and on the analysis method. Without information about completeness and handling, the effect of missing data on the outcome counts cannot be assessed.
The record does not report interim analyses, a detailed statistical analysis plan, or the methods used to control for multiple comparisons. Those details are not reported in the registry record. This absence means that the posted counts and categories can be described, but the available information does not support conclusions about a prespecified testing strategy or the robustness of findings across analyses.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Lamotrigine Monotherapy Pregnancy Exposures | 35 | 1776 | 2.0% |
| Lamotrigine Polytherapy With Valproate Pregnancy Exposures | 16 | 171 | 9.4% |
| Lamotrigine Polytherapy Without Valproate Pregnancy Exposures | 12 | 497 | 2.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lamotrigine Monotherapy Pregnancy Exposures | 0 of 0 |
| Lamotrigine Polytherapy With Valproate Pregnancy Exposures | 0 of 0 |
| Lamotrigine Polytherapy Without Valproate Pregnancy Exposures | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Lamotrigine Monotherapy Pregnancy Exposures | Lamotrigine Polytherapy With Valproate Pregnancy Exposures | Lamotrigine Polytherapy Without Valproate Pregnancy Exposures |
|---|---|---|---|---|
| Club foot | Congenital, familial and genetic disorders | 3 of 1776 | 2 of 171 | 0 of 497 |
| Orofacial clefts | Congenital, familial and genetic disorders | 2 of 1776 | 3 of 171 | 0 of 497 |
| Cardiac septal defect/murmur | Congenital, familial and genetic disorders | 0 of 1776 | 2 of 171 | 2 of 497 |
| Polydactyly | Congenital, familial and genetic disorders | 2 of 1776 | 1 of 171 | 1 of 497 |
| Anencephaly | Congenital, familial and genetic disorders | 3 of 1776 | 0 of 171 | 0 of 497 |
| Hypospadias | Congenital, familial and genetic disorders | 2 of 1776 | 0 of 171 | 1 of 497 |
| Pyloric stenosis | Congenital, familial and genetic disorders | 2 of 1776 | 1 of 171 | 0 of 497 |
| Renal defect (absent, polysystic, fluid on kidney) | Congenital, familial and genetic disorders | 3 of 1776 | 0 of 171 | 0 of 497 |
| Transposition of great vessels | Congenital, familial and genetic disorders | 2 of 1776 | 1 of 171 | 0 of 497 |
| Ventricular septal defects | Congenital, familial and genetic disorders | 3 of 1776 | 0 of 171 | 0 of 497 |
Serious events with the highest arm-level rate: orofacial clefts (1.8%), cardiac septal defect/murmur (1.2%), club foot (1.2%), gastroschisis (0.6%), hydrocephalus/spina bifida (0.6%).
The serious-event summary reports 1776 at risk and 35 affected for lamotrigine monotherapy pregnancy exposures; 171 at risk and 16 affected for lamotrigine polytherapy with valproate pregnancy exposures; and 497 at risk and 12 affected for lamotrigine polytherapy without valproate pregnancy exposures. These are counts, not percentages. The record also lists serious-event terms with percentages: orofacial clefts, 1.8%; cardiac septal defect/murmur, 1.2%; club foot, 1.2%; gastroschisis, 0.6%; hydrocephalus/spina bifida, 0.6%; and meningomyelocele, 0.6%.
The registry entries do not state the denominator or exposure group for each listed percentage, so these terms should not be interpreted as group-specific rates. The groups are not randomized, and they are not described as like-for-like controls. Counts across groups therefore do not establish that an exposure caused or prevented an event. Death figures are not reported in the registry record. The serious-event summary and the primary birth-outcome description are distinct presentations and should not be conflated.
12. What the Result Does, and Does Not, Mean
The record provides a structured description of a registry established to monitor lamotrigine exposure during pregnancy. It identifies the exposure categories, defines a primary outcome based on birth-outcome counts by earliest trimester of monotherapy exposure, and gives adverse-event counts for three exposure groups. This is useful context for understanding what information the registry was intended to collect and what categories appear in its record.
The numerical primary-outcome results are not reported in the registry record available for this account. As a result, it is not possible to describe the observed numbers of live births, fetal deaths, induced abortions, or spontaneous pregnancy losses by exposure timing from these registry entries. The serious-event counts and listed terms can be quoted as recorded, but the registry entries do not establish a causal comparison or provide enough information to interpret each listed percentage as a group-specific risk.
The record does not make the exposure groups randomized, and it explicitly warns that they are not like-for-like controls. In general, observational comparisons may be affected by differences between groups and by how outcomes are ascertained. The registry entries do not describe adjustment for such differences, missing-data handling, or uncertainty intervals. Those limits restrict how far an interpretation can go beyond straightforward description.
The registry description also limits interpretation of malformations among spontaneous losses because identification is inconsistent. It therefore makes no comment on their presence or absence in that category. This is not evidence that malformations were either present or absent; it is a stated limit on what the registry reports for those losses.
Overall, the registry record documents the scope and categories of pregnancy-exposure monitoring, but the registry entries available do not support a conclusion about comparative safety or a causal effect. The distinctions between recorded counts, outcome ascertainment, and causal inference are essential when reading the results.
13. Why This Trial Matters Statistically
Pregnancy exposure is a setting where evidence can be difficult to collect through conventional clinical trials. The registry background explains that pregnant women are routinely excluded from clinical trials and that animal-model data may not translate directly to humans. A registry can therefore provide a way to organize observations about exposures and pregnancy outcomes, while retaining the limitations of nonrandomized evidence.
This record is statistically important because it makes the outcome structure explicit. The primary outcome counts live births, fetal deaths, induced abortions, and spontaneous pregnancy losses by the earliest trimester of exposure to lamotrigine monotherapy. It also documents an ascertainment constraint: major congenital malformations are not characterized among spontaneous losses because identification is inconsistent. Such definitions matter because they determine what a count represents and which questions the data can address.
The record also illustrates why exposure-group counts should not automatically be read as comparative effects. Allocation is not stated, and the groups are explicitly not a like-for-like control comparison. A descriptive registry can document observed events, but group differences may reflect factors other than exposure. Statistical interpretation should therefore separate the value of systematic monitoring from the stronger claim that a particular exposure caused an outcome.
Finally, the record shows why completeness, denominators, and uncertainty estimates are central to interpretation. The registry entries available give serious-event counts and terms, but do not report primary-outcome numbers, group-specific denominators for the listed percentages, or confidence intervals. These omissions limit precision and comparative assessment. Recognizing those limits is part of sound statistical reading, not a reason to disregard the registry's descriptive role.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The record is observational rather than randomized. Allocation is not stated, and the record cautions that the exposure groups are not a like-for-like control comparison. Consequently, differences in recorded outcomes cannot be attributed to lamotrigine exposure alone using the information available. Potential confounders and any adjustment methods are not reported in the registry record.
The primary outcome is defined, but its numerical results are not reported in the registry record for this account. The group denominators for those outcomes are likewise not given. The serious-event summary provides at-risk and affected counts, while the listed event-term percentages lack denominators and group assignments in the registry entries. This limits direct comparison and interpretation of those percentages.
Outcome ascertainment is a specific concern identified by the registry itself. It states that major congenital malformations are not characterized among spontaneous losses because identification is inconsistent. Although the timeframe allows reports and diagnoses up to six years after birth, the registry entries do not describe how complete follow-up was, how late reports were incorporated, or how missing outcome information was handled.
The record lists 9 outcome measures and 7 analyses, but does not describe multiplicity procedures, a detailed analysis plan, interim analyses, or sample-size justification. Confidence intervals and adjusted comparisons are also not reported in the registry record for this account. These gaps prevent assessment of statistical precision and of how analyses were selected or interpreted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Lamotrigine Pregnancy Registry (LAM05) — NCT01064297.
- Registry record last updated 2013-02-25; status last verified 2013-02.
- Results first posted 2010-10-11.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry record is titled Lamotrigine Pregnancy Registry (LAM05), with NCT identifier NCT01064297. It lists epilepsy and bipolar disorder as conditions, GlaxoSmithKline as sponsor, an enrollment of 3416, and a COMPLETED status. The listed start is 2001-11 and primary completion is 2010-07. The background states that the International Lamotrigine Pregnancy Registry was established in 1992 to monitor pregnancy safety.
Listed exposures are lamotrigine monotherapy, lamotrigine polytherapy including valproate, and lamotrigine polytherapy without valproate. The primary outcome concerns counts of birth outcomes by earliest trimester of lamotrigine monotherapy exposure in prospectively enrolled pregnancies. Numerical results for that outcome are not reported in the registry record available for this account. The record also reports serious-event counts by exposure group and lists serious-event terms with percentages, but does not support a randomized or like-for-like comparison.