Inborn Errors of MetabolismNCT02322177
Maternal Inborn Errors of Metabolism in Pregnancy: A Pregnancy Registry Protocol
An observational study of Inborn Errors of Metabolism and Pregnancy, run by National Human Genome Research Institute (NHGRI) at 2 sites in United States.
Trial summary
Background: People with inborn errors of metabolism can t turn food into energy the right way. This can affect a person s growth and health. Researchers want to know how this condition affects a pregnant woman and her baby. Read more about this study
- Who is it for?
- Ages 14 to 50 years, women only
- Conditions the study is for
- Inborn Errors of Metabolism, Pregnancy, Acidemias
- How many people
- 2 participants
- Where
- 2 sitesUnited States
- Study dates
- 19 Dec 2014to 20 Aug 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 50 years
- Women only
- No healthy volunteers
- Child, Adult
Study population: Participants are women with inborn errors of metabolism who have been pregnant
Who may be able to join
- Patients clinically diagnosed with methylmalonic acidemia or another inborn error of metabolism are eligible to participate; mutational and enzymatic status is preferred but not required. Biochemical testing is required.
- Women with inborn errors of metabolism who have had a clinically documented prior pregnancy, currently are pregnant or planning a pregnancy.
Who cannot join
- Patients with phenylketonuria or hyperphenylalaninemia.
- Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
- Medical condition(s) or mental retardation are not in themselves reason for exclusion if in the judgment of the referring physician this would involve no more than minimal risk. We will make every effort to explain the study for the purpose of assent in a manner that the family feels is both age and developmentally appropriate for that child.
- We will review a clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to exclude cases that are not definitively diagnosed by metabolites and/or molecular genetics or related to our direct research interests. We expect this to be a rare minority.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Human Genome Research Institute (NHGRI)
Bethesda, Maryland, 20892
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Background:
- People with inborn errors of metabolism can t turn food into energy the right way. This can affect a person s growth and health. Researchers want to know how this condition affects a pregnant woman and her baby.
Read more
Objectives:
- To collect data from the medical records of women with an inborn error of metabolism. Also, to create a pregnancy registry of inborn errors of metabolism.
Eligibility:
- Women with an inborn error of metabolism who either:
- have been pregnant in the past,
- are currently pregnant, or
- have recently talked with their doctor about becoming pregnant.
Design:
- This study will collect data only. No extra tests will be done.
- Participants will be in the study for the length of their pregnancy and for 1 year after delivery.
- Participants will answer questions about their family s health.
- The participant s doctor will send their medical records to researchers. These may include data about:
- Last health care visit before pregnancy
- Blood, urine, ultrasound, or lab results during pregnancy
- Delivery and recovery after delivery
- Researchers will ask for the test(s) used to confirm pregnancy.
- After the participant has her baby, researchers will ask for data about how the baby is doing. This may include when the baby is sitting, walking, talking, etc.
- The data will be placed into a database. The database will not include the participant s name or identifying data.
Read the detailed description
Women with inherited metabolic disorders are reaching child bearing age more often due to advances in early diagnosis and improved pediatric care. For many of these disorders, there is very little information in the literature to guide the counseling and treatment of these patients and their pregnancies.
The most information for the effects of an underlying inborn error of metabolism in pregnancy derives from the study of phenylketonuria (PKU). From the knowledge gained through the collection of information from multiple cases of pregnancy affected by PKU, important management issues were identified. For example, children born to mothers with an unrestricted diet were substantially more likely to have intellectual disability, microcephaly, and low birth weights than women who maintained a phenylalanine restricted diet. The excess phenylalanine poses long-term health risks to the developing fetus and now a vigilant metabolic approach is recognized as mandatory in women with PKU desiring pregnancy.
Compared to PKU, most or all other intermediary metabolic disorders have been understudied. For example, there are nine published cases of methylmalonic acidemia (MMA) in pregnancy and one case of cobalamin C deficiency in pregnancy, and review articles have reported the same cases. For other inborn errors of metabolism there is even less published or known. The paucity of publication of pregnancy in IEMs other than PKU may be due to the lack of organized research to address pregnancy management in metabolic disorders.
The objective of this study is to establish a pregnancy registry of women with inborn errors of metabolism other than PKU. We will collect management plans, baseline laboratory values, prenatal and postpartum course including metabolic and obstetrical issues, and fetal/neonatal outcomes. This study will also investigate reproductive issues including infertility and use of artificial reproductive technologies. A registry of this type will allow physicians and patients to report varying management and outcomes, both positive and negative, with the broader goal of delineating optimal maternal and fetal outcomes for these unique patient populations. Our registry data would also serve as a vehicle to disseminate management experience for all providers, recognizing that individual centers may not have sufficient experience to make accurate management decisions on their own.
- Conditions
- Inborn Errors of Metabolism, Pregnancy, Acidemias
- Keywords
- Inborn Error of Metabolism, Pregnancy, Amino acid disorder, Fatty acid oxidation disorder, Organic Acidemia, Natural History
- Medical subject headings
- Metabolism, Inborn Errors, Amino Acid Metabolism, Inborn Errors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Participants are women with inborn errors of metabolism who have been pregnant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maternal inborn errors of metabolism
Measured: Yearly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2014 (estimated)
- Study start19 Dec 2014
- Primary completion20 Aug 2018
- Study completion20 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Inborn Errors of MetabolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charles P Venditti, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322177
- Sponsor's protocol ID
- 150049
- Other IDs
- 15-HG-0049
- Status last verified
- 23 Jun 2026
- First submitted
- 19 Dec 2014
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kuseyri O, Weissbach A, Bruggemann N, Klein C, Gizewska M, Karall D, Scholl-Burgi S, Romanowska H, Krzywinska-Zdeb E, Monavari AA, Knerr I, Yapici Z, Leuzzi V, Opladen T. Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders. J Inherit Metab Dis. 2018 Sep;41(5):849-863. doi: 10.1007/s10545-018-0169-0. Epub 2018 Mar 28.
PubMed 29594647Raval DB, Merideth M, Sloan JL, Braverman NE, Conway RL, Manoli I, Venditti CP. Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review. J Inherit Metab Dis. 2015 Sep;38(5):839-46. doi: 10.1007/s10545-014-9802-8. Epub 2015 Jan 8.
PubMed 25567501
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maternal Inborn Errors of Metabolism in Pregnancy: A Pregnancy Registry Protocol
- ClinicalTrials.gov ID
- NCT02322177
- Acronym / sponsor ID
- 150049
- Conditions
- Inborn Errors of Metabolism, Pregnancy, Acidemias
- Keywords
- Inborn Error of Metabolism, Pregnancy, Amino acid disorder, Fatty acid oxidation disorder, Organic Acidemia, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 19 Dec 2014
- Primary completion
- 20 Aug 2018 (actual)
- Study completion
- 20 Aug 2018 (actual)
- First posted
- 23 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- People with inborn errors of metabolism can t turn food into energy the right way. This can affect a person s growth and health. Researchers want to know how this condition affects a pregnant woman and her baby.
Objectives:
- To collect data from the medical records of women with an inborn error of metabolism. Also, to create a pregnancy registry of inborn errors of metabolism.
Eligibility:
- Women with an inborn error of metabolism who either:
- have been pregnant in the past,
- are currently pregnant, or
- have recently talked with their doctor about becoming pregnant.
Design:
- This study will collect data only. No extra tests will be done.
- Participants will be in the study for the length of their pregnancy and for 1 year after delivery.
- Participants will answer questions about their family s health.
- The participant s doctor will send their medical records to researchers. These may include data about:
- Last health care visit before pregnancy
- Blood, urine, ultrasound, or lab results during pregnancy
- Delivery and recovery after delivery
- Researchers will ask for the test(s) used to confirm pregnancy.
- After the participant has her baby, researchers will ask for data about how the baby is doing. This may include when the baby is sitting, walking, talking, etc.
- The data will be placed into a database. The database will not include the participant s name or identifying data.
Detailed description
Women with inherited metabolic disorders are reaching child bearing age more often due to advances in early diagnosis and improved pediatric care. For many of these disorders, there is very little information in the literature to guide the counseling and treatment of these patients and their pregnancies.
The most information for the effects of an underlying inborn error of metabolism in pregnancy derives from the study of phenylketonuria (PKU). From the knowledge gained through the collection of information from multiple cases of pregnancy affected by PKU, important management issues were identified. For example, children born to mothers with an unrestricted diet were substantially more likely to have intellectual disability, microcephaly, and low birth weights than women who maintained a phenylalanine restricted diet. The excess phenylalanine poses long-term health risks to the developing fetus and now a vigilant metabolic approach is recognized as mandatory in women with PKU desiring pregnancy.
Compared to PKU, most or all other intermediary metabolic disorders have been understudied. For example, there are nine published cases of methylmalonic acidemia (MMA) in pregnancy and one case of cobalamin C deficiency in pregnancy, and review articles have reported the same cases. For other inborn errors of metabolism there is even less published or known. The paucity of publication of pregnancy in IEMs other than PKU may be due to the lack of organized research to address pregnancy management in metabolic disorders.
The objective of this study is to establish a pregnancy registry of women with inborn errors of metabolism other than PKU. We will collect management plans, baseline laboratory values, prenatal and postpartum course including metabolic and obstetrical issues, and fetal/neonatal outcomes. This study will also investigate reproductive issues including infertility and use of artificial reproductive technologies. A registry of this type will allow physicians and patients to report varying management and outcomes, both positive and negative, with the broader goal of delineating optimal maternal and fetal outcomes for these unique patient populations. Our registry data would also serve as a vehicle to disseminate management experience for all providers, recognizing that individual centers may not have sufficient experience to make accurate management decisions on their own.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Participants are women with inborn errors of metabolism who have been pregnant |
Who may qualify
- Ages
- 14 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Participants are women with inborn errors of metabolism who have been pregnant
Key inclusion criteria (2 listed)
- Patients clinically diagnosed with methylmalonic acidemia or another inborn error of metabolism are eligible to participate; mutational and enzymatic status is preferred but not required. Biochemical testing is required.
- Women with inborn errors of metabolism who have had a clinically documented prior pregnancy, currently are pregnant or planning a pregnancy.
Key exclusion criteria (4 listed)
- Patients with phenylketonuria or hyperphenylalaninemia.
- Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent.
- Medical condition(s) or mental retardation are not in themselves reason for exclusion if in the judgment of the referring physician this would involve no more than minimal risk. We will make every effort to explain the study for the purpose of assent in a manner that the family feels is both age and developmentally appropriate for that child.
- We will review a clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to exclude cases that are not definitively diagnosed by metabolites and/or molecular genetics or related to our direct research interests. We expect this to be a rare minority.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Maternal inborn errors of metabolism
Time frame: Yearly
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 29594647Kuseyri O, Weissbach A, Bruggemann N, Klein C, Gizewska M, Karall D, Scholl-Burgi S, Romanowska H, Krzywinska-Zdeb E, Monavari AA, Knerr I, Yapici Z, Leuzzi V, Opladen T. Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders. J Inherit Metab Dis. 2018 Sep;41(5):849-863. doi: 10.1007/s10545-018-0169-0. Epub 2018 Mar 28.
- Background: PubMed 25567501Raval DB, Merideth M, Sloan JL, Braverman NE, Conway RL, Manoli I, Venditti CP. Methylmalonic acidemia (MMA) in pregnancy: a case series and literature review. J Inherit Metab Dis. 2015 Sep;38(5):839-46. doi: 10.1007/s10545-014-9802-8. Epub 2015 Jan 8.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles P Venditti, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inborn Errors of Metabolism and Pregnancy, run by National Human Genome Research Institute (NHGRI) at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maternal inborn errors of metabolism (time frame: Yearly). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02322177, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.