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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-000269-35 | EudraCT Number |
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The aim of this study is to assess the pharmacokinetic profile of Roledumab 300μg IM / IV in RhD-negative pregnant women carrying an RhD-positive foetus.
To assess the safety of Roledumab in RhD-negative pregnant women and in RhD-positive fetus and newborns.
In addition the efficacy of Roledumab 300μg IM and IV to prevent RhD alloimmunisation in RhD-negative pregnant women carrying an RhD-positive fetus and the immunogenicity of Roledumab will be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Roledumab Open-label IM | Experimental | - Planned antenatal prophylaxis: A single dose of 300 µg IM of Roledumab at 28 or 29 weeks of gestation. - Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IM anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence. - Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant. The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). |
|
| Roledumab Open-label IV | Experimental | - Planned antenatal prophylaxis: A single dose of 300 µg IV of Roledumab at 28 or 29 weeks of gestation. - Antenatal prophylaxis following sensitizing events: One or more dose(s) of 300μg IV anti-RhD antibodies (Rhophylac or Roledumab) based on the Kleihauer-test as soon as possible and no later than 72 hours after event occurrence. - Postnatal prophylaxis: Roledumab should be administered to the mother as soon as possible within 72 hours of delivery of an RhD positive infant. The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage (FMH). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ROLEDUMAB | Drug | See Arm description |
|
| Measure | Description | Time Frame |
|---|---|---|
| CL/F : Apparent Clearance | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
| V2/F : Central Volume of Distribution | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
| t 1/2 : Terminal Half-life | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
| C Max | C max (maximum observed serum concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Norbert WINER, MD | Nantes University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jeanne de Flandre Hospital | Lille | 59037 | France | |||
| Croix-Rousse Maternity |
100 subjects were pre-screened in the pre-assigment period, only 62 subjects were included in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | IM Arm Roledumab | Roledumab Open-label IM
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage |
| FG001 | IV Arm Roledumab | Roledumab Open-label IV
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Screening Visit V1 |
| |||||||||||||
| First Injection Visit |
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| Second Injection Visit |
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| ID | Title | Description |
|---|---|---|
| BG000 | IM Arm Roledumab | Roledumab Open-label IM Dosage and frequency of administration:
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | CL/F : Apparent Clearance | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | Posted | Mean | Standard Error | L/h | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
|
The safety of roledumab was assessed by recording all AEs occurring during the study, i.e. after signature of the informed consent and until the end of the study. AEs in both mother and fetus/newborn were collected and recorded. The safety of roledumab was to be assessed during the third trimester of pregnancy and during the postnatal follow-up visits up to 12 months after delivery.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IM Arm Roledumab | Arm with RhD-negative pregnant women who were allocated to the IM route of administration of LFB-R593 Dosage and frequency of administration:
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IM postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal injury | Injury, poisoning and procedural complications | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| C reactive protein increased | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical trial Information desk | LFB Biotechnologies | 33169825656 | supportqcm@lfb.fr |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 27, 2017 | Jun 27, 2020 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 15, 2018 | Jun 27, 2020 | SAP_003.pdf |
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| ID | Term |
|---|---|
| C549676 | LFB-R593 |
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| for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
| T Max | T max (time of the maximum observed plasma concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
| T 1/2 | T 1/2 (apparent plasma terminal elimination half-life) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV: T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
| AUC 0-t | AUC 0-t (area under the concentration-time curve from time 0 to time Tlast) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
| Lyon |
| 69317 |
| France |
| University Hospital Center | Nantes | 44093 | France |
| Armand-Trousseau Hospital | Paris | 75012 | France |
| Port-Royal Maternity | Paris | 75014 | France |
| Poissy-Saint-Germain-en-Laye Hospital | Poissy | 78303 | France |
| Maison Blanche Hospital | Reims | 51092 | France |
| Paule de Viguier Hospital | Toulouse | 31059 | France |
| NOT COMPLETED |
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| NOT COMPLETED |
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|
| BG001 | IV Arm Roledumab | Roledumab Open-label IV Dosage and frequency of administration:
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Primary | V2/F : Central Volume of Distribution | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | Posted | Mean | Standard Error | L | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
|
|
|
| Primary | t 1/2 : Terminal Half-life | The parameter was estimated through a population pharmacokinetic model, during which concentration data (ante- and postnatal) obtained after single IM or IV route dose of roledumab. All samples (ante- and postnatal samples for IM and IV route) will be used for population PK modeling. | Posted | Mean | Standard Error | hour | IM: Antenatal PK time points at T0, 48h, 120h, 9d, 29d,59d and Posnatal PK time points at TO, 3d,9d, 6 weeks IV: antenal PK time points at T0, 1h, 24h, 48h, 96-120h, 29d, 59d and Postnatal PK time points at T0, 3d, 9d, 6 weeks. |
|
|
|
| Primary | C Max | C max (maximum observed serum concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | In the IV arm (PKS3), the overall number of participants analyzed was 25. Due to a sensitizing event at late stage of pregnancy in one woman and a premature delivery in another woman, the number of subjects in the analyzed population was 23. | Posted | Median | Full Range | ng/mL | for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
|
|
|
| Primary | T Max | T max (time of the maximum observed plasma concentration) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | In the IV arm (PKS3), the overall number of participants analyzed was 25. Due to a sensitizing event at late stage of pregnancy in one woman and a premature delivery in another woman, the number of subjects in the analyzed population was 23. | Posted | Median | Full Range | hour | for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
|
|
|
| Primary | T 1/2 | T 1/2 (apparent plasma terminal elimination half-life) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | In the IM arm, the number of participants analyzed was 34, but only 28 subjects with AUCextrap <30% were eligible. In the IV arm, the number of participants analyzed was 25. Due to a sensitizing event at late stage of pregnancy in one woman and a premature delivery in another woman, the number of subjects in the analyzed population was 23. | Posted | Median | Full Range | hour | for IM:T0, 48h, 120h, 9 days, 29 days, 59 days and for IV: T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
|
|
|
| Primary | AUC 0-t | AUC 0-t (area under the concentration-time curve from time 0 to time Tlast) of Roledumab in all ITT subjects enrolled in the IM arm or the IV arm, who had at least one valid PK assessment after the first IMP administration, providing at least one evaluable PK parameter. Only samples post-first administration (antenatal samples) will be analyzed by NCA PK analysis for each study arm. | In the IV arm, the number of participants analyzed was 25. Due to a sensitizing event at late stage of pregnancy in one woman and a premature delivery in another woman, the number of subjects in the analyzed population was 23. | Posted | Median | Full Range | h*ng/mL | for IM: T0, 48h, 120h, 9 days, 29 days, 59 days and for IV T0, 1h, 24h, 48h, 96-120h, 29 days, 59 days |
|
|
|
| 0 |
| 36 |
| 15 |
| 36 |
| 36 |
| 36 |
| EG001 | IV Arm Roledumab | Arm with RhD-negative pregnant women who were allocated to the IV route of administration of LFB-R593 Dosage and frequency of administration:
The postnatal dose must still be given even when antenatal prophylaxis has been administered. Before Roledumab 300μg IV postnatal administration, a Kleihauer-Betke test will be performed on maternal blood sample taken no earlier than 30 min after delivery in order to determine the volume of foetomaternal hemorrhage. | 0 | 26 | 9 | 26 | 26 | 26 |
| EG002 | All Patients | Arm with RhD-negative pregnant women who were allocated to the IV and the IM route of administration of LFB-R593 | 0 | 62 | 24 | 62 | 62 | 62 |
| Foetal heart rate disorder | Cardiac disorders | Systematic Assessment |
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| Poland's syndrome | Congenital, familial and genetic disorders | Systematic Assessment | Event diagnosed during pregnancy for the fetus and confirmed in the newborn |
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| Polydactyly | Congenital, familial and genetic disorders | Systematic Assessment |
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| Polycythaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Premature rupture of membranes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| preterm premature rupture of mebranes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Prolonged rupture of membranes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Retained placenta of membranes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Foetal hypokinesia | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| premature baby | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| HELLP sydrome | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Oligohydramnios | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Threatened labour | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Prolonged pregnancy | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Postpartum haemorrhage | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Jaundice neonatal | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| fever neonatal | General disorders | Systematic Assessment |
|
| Pyelocaliectasis | General disorders | Systematic Assessment | Event diagnosed during pregnacy for the fetus and confirmed in the newborn |
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| Urinary retention | Renal and urinary disorders | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Feeding disorder | Metabolism and nutrition disorders | Systematic Assessment |
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| Amniotic cavity infection | Infections and infestations | Systematic Assessment |
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| Neonatal infection | Infections and infestations | Systematic Assessment |
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| Bronchiolitis | Infections and infestations | Systematic Assessment |
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| Anaemia of pregnancy | Blood and lymphatic system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Afterbirth pain | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| prolonged labour | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| prolonged rupture of membranes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Uterine contractions abnormal | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| uterine contractions during pregnancy | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| caput succedaneum | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Jaundice neonatal | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Gestational diabetes | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | Systematic Assessment |
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| Injection site haematoma | General disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment | 6 mothers and 4 newborns |
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| Infantile colic | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Nipple disorder | Reproductive system and breast disorders | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| ligament pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | Systematic Assessment |
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| nasopharyngitis | Infections and infestations | Systematic Assessment |
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| Vulvovaginal mycotic infection | Infections and infestations | Systematic Assessment |
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| Neonatal candida infection | Infections and infestations | Systematic Assessment |
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