Article 1: Biophysical Effects, Safety, and Efficacy of Raspberry Leaf Use in Pregnancy: A Systematic Integrative Review

Abstract:

Background: Childbearing women have been using various herbs to assist with pregnancy, labor and birth for centuries. One of the most common is raspberry leaf. The evidence base for the use of raspberry leaf is however under-developed. It is incumbent on midwives and other maternity care providers to provide women with evidence-based information so they can make informed choices. The aim of this study was to review the research literature to identify the evidence base on the biophysical effects, safety and efficacy of raspberry leaf in pregnancy.

Methods: A systematic, integrative review was undertaken. Six databases were searched to identify empirical research papers published in peer reviewed journals including in vitro, in vivo, human and animal studies. The search included the databases CINAHL, MEDLINE, Cochrane Library, Scopus and Web of Science Core Collection and AMED. Identified studies were appraised independently by two reviewers using the MMAT appraisal instrument. An integrative approach was taken to analysis.

Results: Thirteen studies were included. Five were laboratory studies using animal and human tissue, two were experiments using animals, and six were human studies. Included studies were published between 1941 and 2016. Raspberry leaf has been shown to have biophysical effects on animal and human smooth muscle including the uterus. Toxicity was demonstrated when high doses were administered intravenously or intraperitoneally in animal studies. Human studies have not shown any harm or benefit though one study demonstrated a clinically meaningful (though non-statistically significant) reduction in length of second stage and augmentation of labor in women taking raspberry leaf.

Conclusions: Many women use raspberry leaf in pregnancy to facilitate labor and birth. The evidence base supporting the use of raspberry leaf in pregnancy is weak and further research is needed to address the question of raspberry leaf’s effectiveness.

Type of Study: Systematic Review

Summary:

                  This article focuses on the use of raspberry leaf in pregnancy as well as fetal outcomes. Raspberry leaf is associated with smooth muscle relaxation which, according to some studies, is particularly helpful during the active and latent phases of labor. One study conducted by Whitehouse demonstrated that raspberry leaves can relax the uterus without impacting blood pressure. While this is a significant finding, there are also unfavorable side effects associated with this product. For instance, in another study reported by Nguyen, women with gestational diabetes developed hypoglycemia after consuming 16 oz of raspberry tea leaf a day for 3 days. Care should be taken in women who are using insulin to manage their gestational diabetes as it may potentiate worsening hypoglycemia. Some women, however, may want to raspberry leaf to manage their gestational diabetes, though they must be monitored extremely closely.  Another study included in this article reported findings which demonstrated alterations of the CYP in offspring of mothers who used this herb during pregnancy. Other studies focused on the effect of raspberry leaf on pregnancy outcome. For one study, researchers documented increased incidence of c-section births in women using this herb. However, there were “no statistically significant differences” in between women who used raspberry leaf and women who didn’t where APGAR score, diastolic blood pressure, meconium-stained liquor, transfer to neonatal ICU, and postpartum hemorrhage were concerned. There were also no differences for other factors either such as labor augmentation, epidural, length of the stages of labor, etc. There is not enough evidence to indicate that use of this herb is beneficial in pregnancy and more research must be conducted before a definitive conclusion is established.

Chief Complaint: “I’ve been having heavy, painful menstrual bleeding every month for the past 4 years”

History of Present Illness: 46 y/o G10P4154 F presents today for heavy, painful menstrual bleeding x4 years. Patient states that symptoms began when she was diagnosed with fibroids four years ago. She states that her menses “have always been heavy”, lasting approximately five days. Her menses are now 26-28 days apart, lasting 7-8 days. She admits to using 12 medium sized sanitary napkins on the heaviest day of her menses. She endorses weakness during this time and admits to requiring two transfusions in the past as well as iron therapy due to her heavy menstrual bleeding. Patient states that she experiences severe, dull and achy, LT sided cramps which have been present for 6 years. As per patient, these cramps begin shortly before her menses and last throughout the entire cycle. She reports using heating packs and ibuprofen with minimal relief, and rates her pain a 10/10 in severity. LMP: current. Patient denies intermenstrual bleeding, postcoital bleeding, recent weight loss, dysuria, hematuria, urinary urgency, urinary frequency, abnormal vaginal discharge, excessively rough intercourse, or trauma.

Differential Diagnosis:

1. Heavy menstrual bleeding secondary to uterine fibroids
2. Adenomyoma
3. Endometrial hyperplasia/malignancy
4. Von Willebrand disease

Medications

Genvoya 150 mg daily with food

Aspirin 81 mg chewable tablet

Denies OTC or herbal supplement use

Past Medical History:

Asthma, not controlled

HIV positive, viral load undetectable

HPV positive on anal pap

Hx of CVA at age 30

Immunization History:  

Immunizations are up to date

Gardasil incomplete; last dose was due March 2023

Preventative Medicine Screening:

Mammography (contrast enhanced)  – (11/20/2023)  low suspicion for malignancy. LT breast densely enhanced, mass measuring 25×16 mm. RT breast mass measuring 13×10 mm, probably benign. Patient underwent LT breast lumpectomy on 11/22/2023. Patient was due for mammography early August 2024.

Pap Smear – (10/27/2023) negative for intraepithelial lesion or malignancy. No HPV cotesting performed at this time.

Bone Density/DEXA Scan – not due for screening

Colonoscopy – not due for screening

Dental – N/A

Ophthalmologic – N/A

Past Surgical History:

C-section x1 performed at Mount Sinai

Cholecystectomy performed at Mount Sinai

Hysteroscopy D&C performed at Woodhull Medical Center

Umbilical Hernia repair performed at Mount Sinai

Right inguinal hernia repair performed at Mount Sinai

LT eardrum surgery performed at Mount Sinai

RT foot surgery  performed at Woodhull Medical Center

Allergies:

Latex, reaction: hives

Peanuts, reaction: shortness of breath   

Pitocin, reaction: unknown

Family History:

Maternal cousin with breast cancer at 56, alive and in chemotherapy

Maternal uncle with colon/prostate cancer at unknown age, unknown if alive

Sister with ovarian cancer at unknown age, alive, unknown if in chemotherapy

Other family members with lymphoid cancers, unknown

Social History:

N.D. is a 46 y/o F living in Flushing Queens

Habits – denies smoking or alcohol use. Admits to marijuana use.

Travel – no recent travel

Diet – patient reports eating frequent meals during the day with limited vegetable intake

Exercise – patient reports minimal daily exercise

Sleep – reports some nights of interrupted sleep, some nights are uninterrupted

Safety measures – patient practices seatbelt safety

OB History:

• G10P4154
  • Four children carried to term
  • One child born preterm
  • 5 abortions; 4 living children

GYN/Sexual History:

Menarche: age 12

Menstrual Cycle: regular and heavy; 26-28 days apart, lasting 7-8 days

LMP: current (09/04/2024)

Sexually active with 1 male partner

Contraception: none

STD History: HIV positive, no history of other STDs

Review of Systems:

General: Reports weakness during menses. Denies fever, chills, night sweats, fatigue, loss of appetite, recent weight gain or loss

Skin, hair, nails: Denies changes in texture, excessive dryness or sweating, discolorations, pigmentations, moles/rashes, pruritus, changes in hair distribution

HEENT: Denies headache, vertigo, head trauma, unconsciousness, coma, use of contacts, glasses, visual disturbances, fatigue, lacrimation, photophobia, deafness, pain, discharge, tinnitus, use of hearing aids, nasal discharge, epistaxis, bleeding gums, sore tongue, sore throat, mouth ulcers, voice changes, dentures

Neck: Denies localized swelling/lumps, stiffness/decreased range of motion

Breast: Denies lumps, nipple discharge, pain

Pulmonary system: Denies dyspnea, SOB, cough, wheezing, hemoptysis, cyanosis, orthopnea, PND

Cardiovascular system: Denies chest pain, HTN, palpitations, irregular heartbeat, edema/swelling of ankles or feet, syncope, known heart murmur

Genitourinary: Denies frequency, urgency, incontinence, dysuria, nocturia, oliguria, polyuria

Sexual history: as per GYN/Sexual History

Menstrual and Obstetrical: date of last normal period: 4 years ago, menarche: age 12, interval between periods 26-28 days, duration and amount of flow 7-8 days,  12 medium sized pads/24 hours. Admits dysmenorrhea, menorrhagia, premenstrual symptoms: abdominal pain. Denies postcoital bleeding, vaginal discharge, dyspareunia, menopause.

Musculoskeletal System: Denies muscle/joint pain, deformity or swelling, redness, arthritis

Peripheral Vascular System: Denies intermittent claudication, coldness of trophic changes, varicose veins, or peripheral edema, color change

Hematologic System: Denies easy bruising or lymph node enlargement

Endocrine System: Denies polyuria, polydipsia, polyphagia, heat or cold intolerance, goiter, hirsutism

Nervous System: Reports hx CVA at 30. Denies loss of consciousness, ataxia, loss of strength, change in cognition/mental status/memory, weakness (asymmetric)

Psychiatric: depression/sadness/anxiety

Vital Signs:       

Temperature: 97.8 degrees Fahrenheit

O2 Sat: 100% on room air

Height: 65 inches

Weight: 62.6 kg

BMI:  22.96 kg/m2

Respiratory Rate: 18

Heart Rate: 60 bears per minutes

Blood Pressure: 100/72 RT arm, seated

Physical:

General: Patient appears clean & well groomed, alert & oriented to time, place, and person. Has good posture and appears to be a reliable source of information. Appears stated age and appears to be mildly uncomfortable.

Skin/Hair/Nails: skin is warm and moist, and non-icteric, no lesions noted. Cannot visualize hair because patient is wearing a wig.

HEENT: Head is normocephalic, atraumatic, and non-tender to palpation. Face is symmetrical with no signs of drooping, swelling, or trauma. Eyes are symmetrical OU, conjunctiva is white. Bilateral ears are symmetrical and appropriate in size without lesions, masses, or trauma on external ears. The nose symmetrical without masses, deformities, trauma, or discharge. Good dentition, no obvious dental caries noted. No gingival hyperplasia or erythema noted. Pharynx is non-erythematous, uvula is midline.

Neck, Thyroid, and Lymph Nodes:

The trachea is midline without masses or scars. The thyroid is consistent in size and shape and non-tender to palpation. Evaluation of lymph nodes deferred.

Abdomen:

Abdomen is soft and non-tender to palpation. No guarding or rebounding noted. Pfannenstiel incision scar well-approximated and well-healed without any evidence of appreciable masses around or underneath it.

Breast Exam:

Deferred

Genitalia:

External genitalia without erythema or lesions. There is active, brisk vaginal bleeding noted. No clots or tissue are visible. Cervix appears closed and without lesions or trauma. No cervical motion tenderness noted. Uterus anterior, midline, smooth, non-tender and not enlarged. No adnexal tenderness or masses noted. No inguinal adenopathy.

Rectal:

Deferred

Peripheral Neurologic Exam

No atrophy, tics, tremors, or fasciculation. Gait steady with no ataxia. Strength and sensation intact.

Mental Status Exam

Patient is well appearing, good hygiene and neatly groomed. Patient is alert and oriented to name, date, time, and location. Speech and language ability intact, with normal quantity, fluency, and articulation. Patient denies changes to mood. Conversation progresses logically. Insight, judgement, cognition, memory, and attention intact.

Peripheral Vascular Exam

The extremities are normal in color, size and temperature. No clubbing, cyanosis or edema noted bilaterally. No stasis changes or ulcerations noted.

MSK Upper and Lower Extremity

No soft tissue swelling/erythema/ecchymosis/atrophy/or deformities in bilateral upper and lower extremities. FROM of all upper and lower extremities bilaterally.

Imaging:

Image not available  Pelvic U/S performed at Mt. Sinai on 07/08/2024

Indication: LLQ pain, concern for torsion

Technique: transabdominal and pelvic ultrasound

Comparison: pelvic ultrasound on 08/30/2016

Findings:

• Uterus: 9.9 x 5.5 x 7.4 cm, anteverted in configuration. Numerous fibroids present. sample fibroids measuring 2.4×2.3×1.9 cm, second measuring 1.5×1.6×1.9 cm, and smaller fibroid measuring 0.7×0.8×0.8 cm.
• Endometrium: 0.2 cm in double layer thickness 
• Right Ovary: 3.0 x 1.5 x 1.4 cm. 3.2 mL. Normal. Adnexal cys measuring 1.2×1.0x0.5 cm. Doppler color flow and spectral analysis demonstrates normal arterial and venous waveforms.
• Left Ovary: 2.7×1.6×1.7 cm. 4.0 mL. Normal. Doppler floor flow and spectral analysis demonstrates normal arterial and venous waveforms. 
• Free Fluid: none

Assessment:

46 y/o G10P4154 F presents today for heavy, painful menstrual bleeding x4 years. Transabdominal and pelvic ultrasounds reveal the presence of multiple small fibroids. Patient has extensive family history cancers, including GYN cancers. Endometrial biopsy required before determining best course of management.

Plan:

Return after menses have ceased for endometrial biopsy

Follow up in clinic to discuss results & definitive management (patient would like to undergo hysterectomy but unsure if partial or total)  

BRCA testing

Tranexamic acid to temporarily improve heavy menstrual bleeding; patient says she has adverse effects associated with OCPs