Widespread use of RhIG started with postpartum administration, as delivery is the main source of significant fetomaternal hemorrhage.
A D-negative mother who is not alloimmunized to D should also receive an appropriate dose of RhIG after delivery of a D-positive infant. (In older recommendations, the Rh status of the infant is only known at delivery from testing of  cord blood .) [ 9 ]  If the infant is D-positive, the mother should have a postpartum blood sample screened for fetomaternal hemorrhage in order to determine the appropriate dosage of RhIG to be administered.  (The presence of residual anti-D from antepartum RhIG administration does not indicate ongoing protection from alloimmunization – repeat administration of RhIG is necessary.) [ 13 ]


The  rosette test  is a sensitive method to detect fetomaternal hemorrhage of 10 cc or more.  This qualitative (not quantitative) test will be positive if fetal D-positive cells are present in the maternal sample, indicating a significantly large fetomaternal hemorrhage has occurred.  A rosette test may be falsely positive if the mother is positive for the  weak D  phenotype and falsely negative if the neonate is weak D.  If the mother is positive for the weak D phenotype, the rosette test should not be used; instead, a quantitative test such as the  Kleihauer–Betke test  or flow cytometry should be utilized. If the rosette test is negative, then a dose of 300 micrograms of RhIG is given (sufficient to prevent alloimmunization after delivery in 99% of cases). [ 11 ] [ 19 ]   The RhIG dose suppresses the immune response to up to 30 cc of whole fetal blood (15 cc of red blood cells). If a fetomaternal hemorrhage in excess of 30 cc has occurred, additional testing is mandatory in order to determine the appropriate dosage of RhIG to prevent alloimmunization.  A positive rosette test should be followed by a quantitative test such as the Kleihauer–Betke test or an alternative approach such as  flow cytometry .  See the article on Kleihauer–Betke test for details on how the volume of fetomaternal hemorrhage is calculated. The dosage of RhIG is calculated from the volume of fetal hemorrhage (in mL).  Ex: 50 mL fetal hemorrhage / 30 mL = 1.667 (round up to 2) then add 1 = 3 vials of RhIG. [ citation needed ]


Postpartum RhIG should be administered within 72 hours of delivery.  If prophylaxis is delayed, the likelihood that alloimmunization will be prevented is decreased.  However, ACOG still recommends that RhIG be administered because partial protection still occurs. [ 11 ] [ 12 ]   If the D-type of a newborn or stillborn is unknown or cannot be determined, RhIG should be administered.


Primary  immune thrombocytopenia  (ITP) is an acquired immune-mediated disorder characterized by isolated  thrombocytopenia , defined as a peripheral blood platelet count less than 100 x 10 9 /L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia.  Symptoms of ITP include abnormal bleeding and bruising due to the reduction in  platelet count . [ 20 ]   Rh o (D) Immune Globulin Intravenous [Human; Anti-D] is indicated for use in non-splenectomized, Rh o (D)-positive children with chronic or acute ITP, adults with chronic ITP, and children and adults with ITP secondary to HIV infection. Anti-D must be administered via the intravenous route when used in clinical situations requiring an increase in platelet count. The mechanism of action of anti-D is not fully understood; however, after administration the anti-D coated red blood cell complexes saturate  Fcγ receptors  sites on  macrophages , resulting in preferential destruction of  red blood cells  (RBCs), therefore sparing antibody-coated  platelets . [ 21 ]  Anti-D is recommended as a first-line therapy for ITP, along with corticosteroids and intravenous immune globulin (IVIG). [ 20 ] [ 22 ]   [WinRho SDF is an anti-D manufactured, distributed and marketed by  Cangene  in the US. There is a black box warning on WinRho SDF due to the risk of potentially fatal intravascular hemolysis when used in the treatment of ITP. [ 21 ]  Life-threatening  anemia ,  kidney  failure, and  disseminated intravascular coagulation  (DIC) have occurred in people treated with WinRho SDF for ITP. [ citation needed ]


The following females are not candidates for RhIG:


The first Rho(D) immune globulin treatment "skymed" was introduced by  Ortho Clinical Diagnostics , a subsidiary holding of  Jskymed , and was first administered on May 29, 1968, to Marianne Cummins in  Teaneck ,  New Jersey . [ 24 ]


In 1996, ZLB Bioplasma (part of  CSL Behring ) was given approval to sell Rhophylac in Europe. Effectiveness was demonstrated in a clinical trial in 2003 and in 2004 Rhophylac was approved in the United States. [ 25 ]


Conventional Rho(D) immune globulin is extracted from human  blood plasma . Excluding  autoimmunity , only people who are themselves Rho(D) negative can make the anti-D antibody. As a result, there is a limited pool of people from which to draw plasma that can contain the desired IgG. Special anti-D donation programs are set up to account for this rarity. [ 26 ]  Volunteers are given an injection containing the D antigen in order to make their immune system start producing the antibody (alloimmunization) or to boost the amounts. Only those who have no ability to become pregnant may apply. [ 27 ]


The most common way anti-D products are manufactured is by a form of the  Cohn cold ethanol fractionation process  developed in the 1950s.  Variations of the Cohn method developed in the 1950s may not completely clear aggregates of immunoglobulins, which can cause problems for patients if administered intravenously, and is a primary reason why most anti-Ds are for intramuscular use only.  A non-Cohn manufacturing variation is ChromaPlus process approved by the  U.S. Food and Drug Administration  (FDA) that is used to make Rhophylac. [ 28 ]   Rho(D) immune globulin may trigger an allergic reaction. Steps are taken in the plasma-donor screening process and the manufacturing process to eliminate bacterial and viral contamination, although a small, residual risk may remain for contamination with small viruses. There is also a theoretical possibility of transmission of the  prion  responsible for  Creutzfeldt–Jakob disease , or of other, unknown infectious agents. [ 29 ]


There has been continual attempts to produce a  monoclonal  anti-D IgG formulation suitable for replacing the current polyclonal formulation. [ 30 ]  A monoclonal antibody can be produced without requiring human donors (and associated supply and disease risks) and would be more consistent from batch to batch. [ 8 ]


India has approved a monoclonal formulation called  Rhoclone  (Bharat Serums and Vaccines Ltd.), [ 31 ]  made from  hybridoma cultures . The country has also tested and recently marketed a  recombinant  version of Rhoclone expressed in  CHO cells . [ 32 ]  This recombinant formulation, Trinbelimab, marketed as AntiD, is also being evaluated in a large Real-world Prospective Study that aims to enroll 20,000 Rh-negative mothers. [ 33 ]


Roledumab  and  Rozrolimupab  are two other formulations that have undergone some clinical trials. The former is a monoclonal IgG. The latter is a recombinant mixture of 25 IgGs. [ 8 ]


RhIG can be administered by either intramuscular (IM) or intravenous (IV) injection, depending on the preparation. [ 34 ]   The IM-only preparation should never be administered IV due to the risk of complement system activation.  Multiple IM doses should be given at different sites or at different times within the 72-hour window.  Or, multiple IV doses can be administered according to the instructions in the package insert. [ citation needed ]


Rh o (D) immune globulin is also spelled Rh 0 (D) immune globulin (letter  o  and digit  zero  are both widely attested; more at  Rh blood group system - Rh nomenclature ).


AntiD (Recombinant) and Rhoclone are the only Rh0(D) immune globulin marketed in the world. both manufactured by BSV Ltd. Rhophylac is manufactured by CSL Limited. RhoGAM and MICRhoGam are brand names of Kedrion Biopharma. Other brand names are BayRHo-D, Gamulin Rh, HypRho-D Mini-Dose, Mini-Gamulin Rh, Partobulin SDF ( Baxter ), Rhesonativ (Octapharma), and RhesuGam (NBI).  KamRho-D I.M. is a brand name of Kamada Ltd.


The United States  distribution  rights for WinRho SDF (another brand name) were transferred from Baxter to the manufacturer,  Cangene , in 2010; they had been held by Baxter since 2005. [ 35 ]   Sales of WinRho fell every year under the agreement with Baxter, the supposition being that Baxter was favoring the sale of its own product over WinRho; according to one analyst, "WinRho was always an afterthought for a big company like Baxter." [ 36 ]


Rooming-in  is the practice followed in hospitals and maternity ward where the baby's  crib  is kept by the side of the mother's bed. [ 1 ]  This arrangement gives an opportunity for the parents to know their baby. [ 2 ]  The  bond  between the parent and the child is well established in roomed-in babies. There is a better chance of success with  breast-feeding  in roomed-in babies. [ 3 ]  Parents do not have the fear of baby-switching while roomed-in. Rooming-in is one of the components of  baby-friendly hospitals , devised by  WHO . [ 4 ]


Ropivacaine  ( rINN )  / r oʊ ˈ p ɪ v ə k eɪ n /  is a  local anaesthetic  drug belonging to the  amino   amide  group. The name ropivacaine refers to both the  racemate  and the marketed  S - enantiomer . Ropivacaine hydrochloride is commonly marketed by  AstraZeneca  under the brand name  Naropin .


Ropivacaine was developed after  bupivacaine  was noted to be associated with  cardiac arrest , particularly in pregnant women. Ropivacaine was found to have less  cardiotoxicity  than bupivacaine in animal models.


Ropivacaine is contraindicated for  intravenous regional anaesthesia  (IVRA). However, new data suggested both ropivacaine (1.2-1.8 mg/kg in 40ml) and levobupivacaine (40 ml of 0.125% solution) can be used, because they have less cardiovascular and central nervous system toxicity than racemic bupivacaine. [ 1 ]


Adverse drug reactions  (ADRs) are rare when it is administered correctly. Most ADRs relate to administration technique (resulting in systemic exposure) or pharmacological effects of anesthesia, however  allergic  reactions can rarely occur.


Systemic exposure to excessive quantities of ropivacaine mainly result in  central nervous system  (CNS) and  cardiovascular  effects – CNS effects usually occur at lower  blood plasma  concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth,  tinnitus , tremor, dizziness, blurred vision,  seizures  followed by depression (drowsiness, loss of consciousness),  respiratory depression  and  apnea ). Cardiovascular effects include  hypotension ,  bradycardia ,  arrhythmias , and/or  cardiac arrest  – some of which may be due to  hypoxemia  secondary to respiratory depression. [ 2 ]


Ropivacaine is toxic to  cartilage  and their intra-articular infusions can lead to  Postarthroscopic glenohumeral chondrolysis . [ 3 ]


As for  bupivacaine ,  Celepid , a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose in animal experiments [ 4 ]  and in humans in a process called  lipid rescue . [ 5 ] [ 6 ] [ 7 ]


Roses Revolution  is an international movement against  obstetric violence , originally founded in  Spain  in 2011. It observes November 25, the  International Day for the Elimination of Violence against Women , additionally as "Roses Revolution Day". Women place roses in front of the delivery rooms or hospitals where they suffered varying forms of physical or psychological violence as a sign of protest.


The WHO maintains that "Every woman has the right to the highest attainable standard of health, which includes the right to dignified, respectful health care", but "many women experience disrespectful and abusive treatment during childbirth in facilities worldwide. Such treatment not only violates the rights of women to respectful care, but can also threaten their rights to life, health, bodily integrity, and freedom from discrimination." WHO therefore "calls for greater action, dialogue, research and advocacy on this important public health and human rights issue." [ 1 ]  Roses Revolution is one of several initiatives worldwide against this form of violence.


Roses Revolution designates the protest against abuse during childbirth as an additional aspect in connection with the  International Day for the Elimination of Violence against Women  on November 25, introduced in 1981 and an official UN awareness day since 2000. On Roses Revolution Day, women place roses outside hospitals and delivery rooms to protest against the physical or psychological violence they have experienced during childbirth, often including messages to pertinent physicians and midwives. [ 2 ]


Roses Revolution comments on the depositions of roses on  social media  like  Facebook  and  Instagram . The aim is to raise awareness of traumatic experiences caused by the misconduct of medical staff during childbirth. [ 3 ]  Support also includes other measures. For example, in 2021 Roses Revolution  Luxembourg  published a video on women who had suffered violence in both  French  and  Luxembourgish . [ 4 ]  Roses Revolution Hungary ( Rózsák Forradalma ) takes part in the regional activities of the  16 Days of Activism against Gender-based Violence . [ 5 ]


Spanish birth activist Mara "Jesusa" Ricoy founded Roses Revolution  as "La Revolución de las rosas" in 2011. At the third "Human Rights in Childbirth" conference in  Blankenberge ,  Belgium  on 4 November 2013, the movement was presented to international participants. Within three weeks, this led to action in  Italy ,  France ,  Great Britain ,  Slovakia , the  Czech Republic ,  Mexico ,  Brazil  und  Colombia . Finally, Roses Revolution became active in 30 countries. [ 6 ] [ 7 ]


Roses Revolution is supported by the German National Committee of  UN Women . [ 8 ]  A 2019  United Nations  report by  Dubravka Šimonović , the  United Nations Special Rapporteur on Violence Against Women , titled "A human rights-based approach to mistreatment and violence against women in reproductive health services with a focus on childbirth and obstetric violence" lists Roses Revolution as one of several initiatives on national and international level. [ 9 ]  The Austrian Ministry of health and social affairs lists Roses Revolution as a point of call for affected women in their report on women's health of 2022. [ 10 ]  A  European Union  study on  Obstetric and gynaecological violence in the EU  requested by the  European Parliament Committee on Women's Rights and Gender Equality  mentions Roses Revolution multiple times as being active in the EU countries Spain, Germany, Luxemburg,  Lithuania ,  France , Czechia,  Italy ,  Austria  and Slovakia - among other aspects being "the mother of all campaigns" against obstetric violence in Germany. [ 11 ]


Rupture of membranes  ( ROM ) or  amniorrhexis  is a term used during  pregnancy  to describe a rupture of the  amniotic sac . [ 1 ]  Normally, it occurs spontaneously at  full term  either during or at the beginning of  labor .  Rupture of the membranes is known colloquially as " breaking (one's) water ," especially when induced rather than spontaneous, or as one's " water breaking ". [ 2 ]  A  premature rupture of membranes  (PROM) is a rupture of the  amnion  that occurs at full term and prior to the onset of labor. [ 3 ]  In cases of PROM, options include expectant management without intervention, or interventions such as oxytocin or other methods of labor induction, and both are usually accompanied by close monitoring of maternal and fetal health. [ 3 ]  Preterm premature rupture of membranes (PPROM) is when water breaks both before the onset of labor and before the pregnancy's 37 week  gestation . [ 3 ] [ 4 ]  In the United States, more than 120,000 pregnancies per year are affected by a premature rupture of membranes, which is the cause of about one third of  preterm deliveries . [ 5 ]


Sometimes, a child is born with no rupture of the amniotic sac (no rupture of membranes). In such cases, the child may still be entirely within the sac once born; such a birth is known as an  en-caul  birth.


When the amniotic sac ruptures, production of  prostaglandins  increases and the cushioning between the fetus and uterus is decreased, both of which are processes that increase the frequency and intensity of  uterine contractions . [ 6 ]


On occasion, with the rupture of membranes, particularly if the head is not engaged, the  umbilical cord  may  prolapse . A  cord prolapse  is an  obstetrical emergency , as the descending head may block fetal-placental circulation.


Once the membranes are ruptured, bacteria may ascend and could lead to  amnionitis  and fetal infection.


A premature rupture of membranes can have multiple effects on the fetus such as increasing their risk of prematurity and facing neonatal or perinatal complications.


Rupture of membranes can affect ongoing labor management. Certain methods of labor induction or augmentation such as balloon catheters are relatively contraindicated after ROM. [ 7 ]


Detection of rupture of membranes mainly include: [ 10 ]


For results to be roughly 90% accurate in infection detection, a combination of both an arborization test and nitrazine paper test may be used. [ 11 ]  An arborization test assesses the patient's vaginal secretions, while a nitrazone paper test uses the nitrazine paper to examines vaginal pH.


Sacrococcygeal teratoma  ( SCT ) is a type of tumor known as a  teratoma  that develops at the base of the  coccyx  (tailbone) and is thought to be primarily derived from remnants of the  primitive streak . [ 1 ]  Sacrococcygeal teratomas are  benign  75% of the time,  malignant  12% of the time, and the remainder are considered "immature teratomas" that share benign and malignant features. Benign sacrococcygeal teratomas are more likely to develop in younger children who are less than 5 months old, and older children are more likely to develop malignant sacrococcygeal teratomas.


The  Currarino syndrome , due to an  autosomal dominant  mutation in the  MNX1  gene, consists of a presacral mass (usually a mature teratoma or anterior meningocele), anorectal malformation and sacral dysgenesis.


Maternal complications of pregnancy may include  mirror syndrome . [ 2 ]   Maternal complications of delivery may include a  cesarean section  or, alternatively, a vaginal delivery with mechanical  dystocia . [ 3 ]


Complications of the mass effect of a teratoma in general are addressed on the  teratoma  page.  Complications of the mass effect of a large SCT may include  hip dysplasia ,  bowel obstruction ,  urinary obstruction ,  hydronephrosis  and  hydrops fetalis .  Even a small SCT can produce complications of mass effect, if it is presacral (Altman Type IV). [ 4 ]   In the fetus, severe hydronephrosis may contribute to inadequate lung development.  Also in the fetus and newborn, the  anus  may be  imperforate . [ citation needed ]


Later complications of the mass effect and/or surgery may include  neurogenic bladder , other forms of  urinary incontinence ,  fecal incontinence , and other chronic problems resulting from accidental damage to or sacrifice of nerves and muscles within the pelvis. [ 5 ]   Removal of the coccyx  may include additional complications. In one review of 25 patients, [ 6 ]  however, the most frequent complication was an unsatisfactory appearance of the surgical scar.


Late effects are of two kinds:  consequences of the tumor itself, and consequences of surgery and other treatments for the tumor. [ citation needed ]


Complications of not removing the coccyx may include both recurrence of the teratoma [ 7 ]  and  metastatic cancer . [ 7 ] [ 8 ]   Late malignancies usually involve incomplete excision of the coccyx and are  adenocarcinoma . [ citation needed ] Although functional disability in survivors is common, [ 9 ]  a small comparative study [ 10 ]  found a nonsignificant difference between SCT survivors and a matched control group.


In rare cases, pelvic scarring may necessitate that a  pregnant woman  who is a SCT survivor deliver her baby by  cesarean section . [ 11 ]


SCT is seen in 1 in every 35,000 live births, and is the most common tumor  presenting  in newborn humans.  Most SCTs are found in babies and children, but SCTs have been reported in adults [ 12 ]  and the increasingly routine use of prenatal ultrasound exams has dramatically increased the number of diagnosed SCTs presenting in fetuses.  Like other teratomas, an SCT can grow very large.  Unlike other teratomas, an SCT sometimes grows larger than the rest of the fetus. [ citation needed ]


Sacrococcygeal teratomas are the most common type of  germ cell tumors  (both  benign  and  malignant ) diagnosed in  neonates ,  infants , and  children  younger than 4 years. [ 13 ]   SCTs occur more often in girls than in boys; ratios of 3:1 to 4:1 have been reported. [ 14 ]


Historically, sacrococcygeal teratomas present in 2 clinical patterns related to the child's age, tumor location, and likelihood of tumor malignancy.  With the advent of routine prenatal ultrasound examinations, a third clinical pattern is emerging. [ citation needed ]


During  prenatal ultrasound , an SCT having an external component may appear as a fluid-filled cyst or a solid mass sticking out from the fetus' body.  Fetal SCTs that are entirely internal may be undetected if they are small;  detection (or at least suspicion) is possible when the fetal bladder is seen in an abnormal position, due to the SCT pushing other organs out of place. [ citation needed ]


At  birth , the usual presentation is a visible lump or mass under the skin at the top of the buttocks crease.  If not visible, it can sometimes be felt; gently prodded, it feels somewhat like a hardboiled egg.  A small SCT, if it is entirely inside the body, may not present for years, until it grows large enough to cause pain, constipation and other symptoms of a large mass inside the  pelvis , or until it begins to extend out of the pelvis.  Even a relatively large SCT may be missed, if it is internal, because the bony  pelvis  conceals and protects it.   Mediastinal tumors , including teratomas, are similarly concealed and protected by the  rib cage . [ citation needed ]


Some SCTs are discovered when a child begins to talk at about age 2 years and complains of their bottom hurting or feeling "poopy" when they ride in a car seat.


Other tumors can occur in the sacrococcygeal and/or presacral regions [ 16 ]  and hence must be ruled out to obtain a  differential diagnosis .  These include  extraspinal ependymoma , [ 17 ]   ependymoblastoma , [ 18 ]   neuroblastoma  and  rhabdomyosarcoma .


Smaller SCTs with an external component, seen in prenatal ultrasounds or at birth, often are mistaken for  spina bifida . [ citation needed ]   Cystic SCT and terminal myelocystocele are especially difficult to distinguish;  for more accurate diagnosis, MRI has been recommended. [ 19 ]


The preferred first treatment for SCT is complete surgical removal (i.e., complete resection). The preferred approach to a small SCT is through the  perineum ; a large SCT may require an additional approach through the  abdomen .  Resection should include the coccyx and may also include portions of the  sacrum . The surgery should include reattachment of the small muscles and ligaments formerly attached to the coccyx, in effect reconstructing the posterior perineum.  If not, there is an increased risk of  perineal hernia  later in life. [ citation needed ]


SCTs are classified morphologically according to their relative extent outside and inside the body: [ citation needed ]


The Altman type is significant in the contexts of management of labor and delivery, surgical approach, and complications of SCT.  Serial ultrasound and MRI monitoring of SCTs in fetuses  in utero  has demonstrated that the Altman type can change over time.  As the tumor grows, it can push between other organs and through the perineum to the body surface where the tumor appears as a bulge covered only by skin.  Sometimes, the tumor bulge later slips back inside the perineum. [ citation needed ]


Like all  teratomas , a sacrococcygeal teratoma has the potential to be  malignant , and the standard of care requires long-term followup by an  oncologist .


Management of most fetal SCTs involves  watchful waiting  prior to any treatment.  An often used  decision tree  is as follows: [ citation needed ]


Emergent problems include maternal  mirror syndrome ,  polyhydramnios , and  preterm labor .  Poor management decisions, including interventions that are either premature or delayed, can have dire consequences. [ 20 ] [ 21 ]   A very small retrospective study of 9 babies with SCTs greater than 10 cm diameter reported slightly higher survivorship in babies remaining in utero slightly longer. [ 22 ]


In many cases, a fetus with a small SCT (under 5 or 10 cm) may be delivered vaginally. [ 23 ] [ 24 ] [ 25 ] [ 26 ]  Prior to the advent of prenatal detection and hence scheduled C-section, 90% of babies diagnosed with SCT were born full term. [ 27 ]


SCTs are very rare in adults, and as a rule these tumors are benign and have extremely low potential for malignancy.  This estimation of potential is based on the idea that because the tumor existed for decades prior to diagnosis, without becoming malignant, it has little or no potential to ever become malignant.  For this reason, and because  coccygectomy in adults has greater risks than in babies , some surgeons prefer not to remove the coccyx of adult survivors of SCT.  There are case reports of good outcomes. [ 28 ]


Screening culture  is a type a  medical test  that is done to find an  infection . Screening cultures are often performed to find infections that do not have  signs  and  symptoms .


Perinatal Group B Streptococcal Disease  comes from an intrauterine infection of the  fetus  from the spread of  Group B Streptococcus  from the  vagina  of a colonized woman who is typically asymptomatic.  Medical studies  show that  prenatal  screening cultures reduce the incidence of Perinatal Group B Streptococcal Disease. Studies of single institutions or  health maintenance organizations  show institutions with a culture-based screening policy have close to 90% of delivering women with documented GBS screening, and close to 90% of GBS-positive women received intrapartum  antibiotics . [1]   Cost-effectiveness analyses of the screening- and risk-based strategies have indicated that although the initial costs associated with specimen collection and processing make the screening strategy more expensive than the risk-based approach, the overall cost savings due to disease prevention do not differ importantly between strategies. [2]


Intensive care units of major hospitals routinely provide nasal, groin or axilla swabs for screening of Methicillin-resistant  Staphylococcus aureus  (MRSA)or Multi-resistant organisms (MRO).


This  medical  diagnostic article is a  stub . You can help Wikipedia by  expanding it .


Sheehan's syndrome , also known as  postpartum pituitary gland necrosis , occurs when the  pituitary gland  is damaged due to significant  blood loss  and  hypovolemic shock  (ischemic  necrosis ) or stroke, originally described during or after  childbirth  leading to decreased functioning of the pituitary gland ( hypopituitarism ). [ 1 ]  Classically, in the milder partial form, the mother is unable to breastfeed her baby, due to failure of the pituitary to secrete the hormone prolactin, and also has no more periods, because FSH (Follicle Stimulating Hormone) and LH (Luteinising Hormone) are not secreted. Although postmenopausal, the mother with this milder form of Sheehan's syndrome does not experience hot flushes, because the pituitary fails to secrete FSH (high levels of FSH, secreted by the pituitary in healthy postmenopausal women is an attempt to trigger ovulation, and these high levels of FSH cause hot the flushes). The failure to breastfeed and  amenorrhea  no more periods, were seen as the syndrome (a collection of symptoms), but we now view Sheehan's as the pituitary failing to secrete 1-5 of the 9 hormones that it normally produces (the anterior (front) lobe of the pituitary produces FSH, LH, prolactin, ACTH (Adreno-cortico-trophic hormone),TSH (Thyroid Stimulating Hormone) and GH (Growth Hormone); the posterior (the lobe at the back) pituitary produces ADH (Anti-Diuretic Hormone) and Oxytocin, i.e. the pituitary is involved in the regulation of many hormones. It is very important to recognise Sheehan' stroke as, the ACTH deficiency Sheehan's in the presence of the stress of a bacterial infection, such as a urine infection, will result in death of the mother from  Addisonian crisis .  [ 2 ] [ 3 ]  This gland is located on the under-surface of the brain, the shape of a cherry and the size of a chickpea and sits in a pit or depression of the sphenoid bone known as the  sella turcica  (the Turk's saddle). [ 4 ]  The pituitary gland works in conjunction with the  hypothalamus , and other endocrine organs to modulate numerous bodily functions including growth, metabolism,  menstruation ,  lactation , and even the " fight-or-flight " response. [ 3 ]  These endocrine organs, (like the thyroid gland in the neck, or adrenals on the upper pole of the kidneys), release hormones in very specific pathways, known as hormonal axes. For example, the release of a hormone in the hypothalamus will target the pituitary to trigger the release thyroid stimulating hormone (TSH), and the pituitary's released hormone (TSH) will target the next organ in the pathway i.e. the thyroid to release thyroxin.  [ 3 ]  Hence, damage to the pituitary gland can have downstream effects on any of the aforementioned bodily functions.


The various signs and symptoms in Sheehan's syndrome are caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Since the pituitary controls many glands in the  endocrine system , partial or complete loss of a variety of functions may result. [ 5 ]  Many of the signs and symptoms of Sheehan's are considered "nonspecific" in the medical community; in other words these signs and symptoms are seen in a number of different disease processes, and are not specific to a singular disease or syndrome. [ 6 ]


In some cases, a woman with Sheehan syndrome may be relatively asymptomatic initially; therefore, the diagnosis would not be made until years later when features of  hypopituitarism  become evident. [ 7 ]  In rare instances this syndrome can present acutely with unstable vital signs, dangerously low blood glucose levels, heart failure, or even psychosis. [ 8 ] [ 9 ]  Hypopituitarism can lead to an interruption in any of the following hormone pathways: thyroid disorder (secondary  hypothyroidism ), adrenal gland (adrenal insufficiency due to glucocorticoid deficiency), sex hormone (gonadotropin deficiency), prolactin (a hormone responsible for lactation), growth hormone, or rarely anti-diuretic hormone deficiency (central  diabetes insipidus ). [ 3 ]  Since damage to the pituitary can cause a deficiency in more than one of these hormone pathways simultaneously, it is possible to have a mix of any of the signs or symptoms listed below. [ 9 ]


Sheehan's syndrome's most common initial symptoms are difficulties with or total absence of lactation ( agalactorrhea ). [ 7 ]  Another common sign is infrequent menstrual cycles ( oligomenorrhea ) or absent menstrual cycles ( amenorrhea ) following delivery. [ 9 ]  In addition to menstrual irregularities other signs of sex hormone deficiency are hot flashes, decreased libido, and breast involution. [ 6 ]  Symptoms and signs of thyroid disorder are tiredness,  intolerance to cold ,  constipation ,  weight gain ,  hair loss , slowed thinking, as well as  a slowed heart rate  and  low blood pressure . [ 10 ]  Adrenal gland malfunction can present acutely or chronically. In a more chronic case, it is similar to  Addison's disease  with symptoms including  fatigue ,  weight loss ,  hypoglycemia  (low blood sugar levels),  low hemoglobin levels (anemia)  and  hyponatremia  (low sodium levels) that develop over several months or years. [ 11 ]  Acute adrenal insufficiency is referred to as an adrenal crisis, which can be life-threatening, and occurs very shortly after the inciting event i.e. significant blood loss post-partum in the context of Sheehan's syndrome. [ 12 ]  Adrenal crisis signs and symptoms include hypoglycemia, hypotension, weakness, fatigue, and seizures from severe hyponatremia. [ 12 ]


Growth hormone deficiency is one of the most common hormone deficiencies of hypopituitarism seen in Sheehan's syndrome. [ 10 ]  Low levels of growth hormone may present with low energy, body aches, or subtle wrinkling of the skin around the eyes or mouth. [ 6 ] [ 8 ]  The symptoms of anti-diuretic hormone deficiency are increased thirst, excessive urination, headache, and fatigue. [ 13 ]  Hematological changes might be seen as well such as anemia or low platelets (thrombocytopenia). [ 10 ]  Hyponatremia is seen in many cases of Sheehan's syndrome because it can result from multiple etiologies. Drops in thyroid hormones and glucocorticoid/adrenal hormones can indirectly lead to hyponatremia through water retention, while blood loss can trigger hyponatremia through ADH secretion. [ 8 ]  The development of Syndrome of Inappropriate Anti-Diuretic Hormone in patients with Sheehan's syndrome has been documented in the literature, although the mechanism is not well understood. [ 8 ]


As stated, Sheehan's syndrome is caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. Sheehan's syndrome typically occurs because of excessive blood loss after delivery (post-partum hemorrhage), although there are several risk factors that may contribute to its development. [ 9 ]  This syndrome does not appear to be exclusively linked to childbirth, as Sheehan's syndrome has been reported in pregnant patients that experienced massive hemorrhage from non-obstetrical causes. [ 9 ]  The pituitary gland grows and has a higher metabolic demand during pregnancy because the pituitary needs to rev up the production of certain hormones associated with pregnancy. [ 9 ] [ 5 ]  This higher metabolic demand, in turn, leads to higher demand for blood flow. [ 5 ]


Thus, if the body enters a state of shock from excessive blood loss in post-partum delivery, the pituitary gland is more susceptible to injury. [ 5 ]  Although the vast majority of cases of Sheehan's syndrome occur in the setting of massive blood loss, cases have been documented of acute Sheehan's syndrome occurring with blood loss volumes that are not considered "massive". [ 14 ] [ 5 ]  Some possible predisposing factors to Sheehan's syndrome may include:  disseminated blood coagulation  (DIC), hypotension, small  sella  turcica size, and blood clots from a pre-existing hypercoagulable disorder. [ 9 ]   Atony  of the uterus is a leading cause of post-partum hemorrhage, therefore uterine atony could induce Sheehan's syndrome. [ 15 ]


This syndrome seems to arise when certain factors compound each other to cause pituitary injury. The physiologic enlargement of the pituitary gland in conjunction with an interference in its blood supply, such as  episiotomy  progressing to anal tearing, ultimately result in pituitary ischemia and necrosis. [ 9 ]  One cause of pituitary growth associated with the risk of Sheehan's syndrome is the hyperplasia of lactotrophs which produce prolactin, the hormone responsible for milk production. [ 5 ]  Other hormone-secreting cells of the pituitary undergo rapid growth in pregnant women as well, which contribute to the gland's enlargement. [ 10 ]


The anterior pituitary is supplied by a low pressure  portal venous system . [ 15 ]  The anterior pituitary is more commonly affected in Sheehan's syndrome because of the structure of the portal venous system. Posterior pituitary involvement leading to central diabetes insipidus is much rarer, and typically reflects more extensive damage to the organ and more severe disease. [ 13 ]  It has been suggested that the arrangement of the pituitary's blood supply contribute to its susceptibility for injury. "The highly vascularized pituitary tissue involves one of the most rapid blood flow in the human body and probably, therefore, has a tendency to infarction because even small degrees of change in the pituitary intravascular pressure cause an arrest of blood flow". [ 9 ]   Ischemia  may occur as a result of  vasospasm  from shock, hypotension,  thrombosis , or direct vascular compression of the hypophyseal artery from the enlarged pituitary gland itself. [ 9 ] [ 5 ] [ 15 ]  The presence of  disseminated intravascular coagulation  (i.e., in  amniotic fluid embolism  or  HELLP syndrome ) also appears to be a factor in its development. [ 9 ]


Typically an important clue that leads to a diagnosis of Sheehan's syndrome is identifying a deficiency in one or more of the hormones produced directly, or indirectly, by the pituitary gland. The extent of hormone deficiency, and which hormones are affected depends on the extent of the damage to the pituitary. Hormonal assays measure the levels of these hormones which include but are not limited to  T4 ,  TSH ,  estrogen ,  gonadotropin ,  cortisol , and  ACTH . [ 8 ]  It might be difficult to detect damage to these hormone pathways if hormone levels are at the borderline of the abnormal range. In this case, stimulation tests will be done to determine if the pituitary is responsive to hypothalamic hormones. [ 15 ]


MRI  is useful in diagnosing Sheehan's syndrome since it examines the structure of the pituitary and may identify any anatomical damage. [ 5 ]  MRI findings will vary based on how early or late in the disease process the test is being conducted. If an MRI is conducted early enough in the disease process the pituitary may appear larger than normal, and show changes that are consistent with damage from lack of blood supply. [ 16 ]  Later in the disease process of this syndrome the damage imposed on the pituitary gland will cause it to shrink, and leave a partially empty or totally empty sella turcica on MRI. [ 8 ]


The mainstay of treatment is hormone replacement therapy for the hormones that are missing. [ 17 ]  Treatment plans and dosages should be individualized by an  endocrinologist . Glucocorticoids may be administered to address or prevent an adrenal crisis, a potential serious complication of Sheehan's syndrome. [ 5 ]  Hormone replacement is vital in reducing the morbidity and mortality of this syndrome. [ 5 ]


The exact prevalence of this syndrome is difficult to define because the incidence varies so much from country to country. Sheehan syndrome is more prevalent in developing countries than developed countries. [ 15 ]  In a study from the United Kingdom in 2001 only 1.4% of patients with hypopituitarism were diagnosed with Sheehan's syndrome. [ 6 ]  Just a few years earlier in 1996 the World Health Organization estimated that 3 million women were effected by Sheehan's syndrome. [ 9 ]  In a study of 1,034 symptomatic adults, Sheehan's syndrome was found to be the sixth-most frequent etiology of growth hormone deficiency, being responsible for 3.1% of cases (versus 53.9% due to a pituitary tumor). [ 8 ]  Additionally, it was found that the majority of women who experienced Sheehan syndrome gave birth at home rather than in a hospital. [ 15 ]


The specific association with postpartum shock or hemorrhage was described in 1937 by the British pathologist  Harold Leeming Sheehan  (1900–1988). [ 18 ]  The initial distinction was made in the research article "Post-Partum Necrosis of the Anterior Pituitary". [ 19 ]  In his research, Dr. Sheehan reviewed (through  autopsy ) the effects of pituitary necrosis on 12 cases of patients that experienced postpartum necrosis. [ 19 ]  He observed cases where lesions and death occurred during or after pregnancy, as well as cases where death occurred in the late stage of necrosis (years later). This started the initial distinction of Sheehan's syndrome from Simmonds' disease (also known as  hypopituitarism ). Sheehan noted that significant feature of these patients' cases was hemorrhaging, which in his experience was most commonly caused by either:  placenta Previa  (low placenta), uterine rupture, cervical or uterine tears, post-partum  atony , or retained placenta.  Simmonds' disease , however, occurs in either sex due to causes unrelated to pregnancy. [ 15 ]


However, in his 1939 publication, "Simmonds' Disease due to Post-partum Necrosis of the Anterior Pituitary", Sheehan displays post-partum necrosis as a cause of Simmonds' disease, thus establishing the relationship between the two conditions. [ 20 ]  According to Sheehan in 1939 approximately 41% of survivors of severe  postpartum hemorrhage  (PPH) and/or  hypovolemic shock  experienced severe or partial hypopituitarism. [ 15 ]


In the developed world Sheehan's Syndrome is a rare complication of  pregnancy ; although this syndrome is more prevalent in developing countries it continues to effect women around the world. [ 9 ]  A retrospective study in Turkey found that the prevalence of Sheehan's syndrome was directly proportional to the amount of at-home deliveries each decade. [ 8 ]  This may be due to previously limited obstetric techniques present in a home environment. Blood loss associated with episiotomy and forceps exacerbating blood loss when the placenta separates from the wall of the uterus, particularly in mothers with low blood pressure, even in obstetric setting, namely hospital, caused a more subtle Sheehan's syndrome of Growth Hormone, Anti-Duretic Hormone, ACTH deficiency, which may be life threatening if missed; PubMed.gov Sheehan's in modern times:a nationwide retrospective study Iceland 2011, where every mother gives birth in hospital, with full obstetric care available.


At present, the part that autoimmunity plays in the development of Sheehan's syndrome is uncertain. Several case reports have identified anti-pituitary antibodies in patients diagnosed with Sheehan's. [ 5 ]  Some patients also tested positive for anti-hypothalamus antibodies. [ 21 ]  Given that many patients that have developed Sheehan's syndrome do not have detectable levels of these antibodies, it is unclear whether these antibodies cause this syndrome or result from it. [ 9 ]


The  Sisterhood Method  is a household survey to estimate  maternal deaths  recommended by the  World Health Organization  (WHO). Although maternal deaths are a major problem in developing countries, high quality data are rare. Yet, numbers are needed for planning in order to reduce the problem of maternal death. Several methods have been used to estimate maternal deaths. According to the WHO, "The approach was designed to overcome the problem of large sample sizes and thus reduce cost." [ 1 ] [ 2 ]


The death of a woman during or shortly after a pregnancy is an important medical problem in developing countries. 99% of all maternal deaths occur in developing countries. [ 3 ]  In the poorest countries in the world, e.g. Sierra Leone, the lifetime risk for a woman dying because of a maternal death is approx 1 in 6, whereas in developed countries, e.g. Sweden, the same lifetime risk is approx 1 in 30,000. [ 4 ]  Half of all maternal deaths occur in six countries only: Afghanistan, Democratic Republic of Congo, Ethiopia, India, Nigeria, and Pakistan. Worldwide, maternal deaths decreased from approx 500,000 in 1980 to approx 350,000 in 2008. This decline in maternal deaths was associated mainly with better maternal education, maternal income, increased availability of trained birth attendants, and decreased pregnancy rates. [ 5 ]


Although maternal deaths are a major problem in developing countries, seen globally, the numbers are not very large, and there is an absence of high quality data. Yet, numbers are needed for planning in order to reduce maternal deaths. Several methods have been used to estimate maternal deaths. They include analysing census records and medical/death certificates, [ 6 ]  and  Reproductive Age Mortality Studies  (RAMOS). [ 7 ]  Also, household surveys are used. All of these methods are not totally precise, but they can provide some useful information to decrease maternal mortality.


In contrast, full surveillance programmes would be too costly and too unrealistic for many developing countries. [ 8 ]


The Sisterhood Method is the most common household survey for estimating maternal deaths. It is time- and cost-effective, and reduces sample size requirements; in countries or areas with high levels of maternal deaths, i.e. over 500 maternal deaths per 100,000 live births, a sample size of 4000 households or less is acceptable for this method. [ 9 ]  But the method still provides a useful means of assessing maternal mortality.


This method includes four questions about the sisters of the woman in question: [ 10 ]


Deaths occurring over a large interval of time are documented. The overall estimate of maternal mortality is determined for 10–12 years before the survey. The Sisterhood Method is useful because usually maternal mortality changes slowly. It provides some meaningful data in countries or areas where there are no alternative means of generating estimates.


The Sisterhood Method is not appropriate in countries or areas where the total fertility rate is less than four children per family, in areas of significant migration, as well as during civil war, civil unrest or other significant social disruption.


The original Sisterhood Method is an indirect method. The newer Direct Sisterhood Method targets a more limited reference period for sister deaths and uses more in depth questions (e.g., deaths among all siblings, all deaths that are pregnancy related, and when these deaths occurred). This variant relies on fewer assumptions than the original Sisterhood Method. However, it requires a larger sample size, data gathering and analysis are more complex, and has large confidence intervals. Despite these limitations, the Direct Sisterhood Method can result in greater specificity of information. A retrospective maternal mortality ratio (MMR) can be calculated. This variant is used by  Demographic and Health Surveys  (DHS). [ 11 ] [ 12 ]


Sonicaid  Ltd was a medical electronics company headquartered in  West Sussex  best known for its range of  Doppler fetal monitors . The company also developed early  ultrasound scanners .  The word "Sonicaid" is in generic use for Doppler fetal monitors. Sonicaid is now a registered trademark of Huntleigh Healthcare. [ 1 ]


Sonicaid developed a range of fetal monitors, notably the portable Doppler ultrasound products D102, D104 ("Pocket Sonicaid", winner of a Design Council Award for medical equipment in 1976 [ 2 ] ), D205 [ 3 ] [ 4 ]  and D206 which provided audible output of fetal heart sounds. The original design was due to Frederick (Doug) Fielder who was Sonicaid's medical research director. [ 5 ] [ 6 ] [ 7 ] [ 8 ]


The FM series products used both ultrasound and ECG to provide continuous monitoring (recorded on paper charts), enabling clinical interpretation of changes in fetal heart rate during contractions. [ 9 ]  The FM3R [ 10 ]  received U.S.  Food and Drug Administration  (FDA) approval in 1977 [ 11 ]  and one of these instruments is displayed at the  Science Museum, London [ 12 ]  (the "machine that goes ping" in  The Meaning of Life  is identifiable as this model).


Sonicaid Ltd was involved in an early venture in the development of a 3D multiplanar scanner in the mid-1970s, [ 13 ]  building on the pioneering  obstetric ultrasonography  work by Prof  Ian Donald  and colleagues. [ 14 ]  They also developed the Sonicaid RTS5200 Real Time Scanner which was used in hospitals for obstetric applications.


Sonicaid Ltd was based in  Bognor Regis  in the 1970s [ 15 ]  with a unit in  Livingston, Scotland , and in  Chichester  in the 1980s. The company was acquired in 1987 by Oxford Instruments and developed the product range further [ 16 ]  as "Oxford Sonicaid".


Sperm sorting  is a means of choosing what type of  sperm cell  is to  fertilize  the  egg cell . Several conventional techniques of   centrifugation  or  swim-up . Newly applied methods such as flow cytometry expand the possibilities of sperm sorting and new techniques of sperm sorting are being developed.


It can be used to sort out sperm that are most healthy, as well as for determination of more specific traits, such as  sex selection  in which spermatozoa are separated into  X-  (female) and  Y-  (male) chromosome bearing populations based on their difference in DNA content. The resultant 'sex-sorted' spermatozoa are then able to be used in conjunction with other assisted reproductive technologies such as  artificial insemination  or  in-vitro fertilization  (IVF) to produce offspring of the desired sex - in farming animals but also in human medical practice.


Several methods have been used to sort sperm before the advent of flow cytometry.  Density gradient centrifugation  (in a continuous or discontinuous gradient) can concentrate semen samples with low concentration of sperm, using the density of sperm as a measure of their quality. [ 1 ] [ 2 ]  Similarly, so-called  swim-up  techniques apply a centrifugation step and then sperm is allowed to swim up into a medium, thus enriching a subpopulation of motile sperm. However, use of sperm centrifugation is detrimental to the sperm viability and elicits production of reactive oxygen species. [ 1 ]  Conventional techniques are routinely used in assisted reproductive technology. [ 3 ]


Flow cytometry  is another method used to sort sperm and adaptations of this technique opens new opportunities in sperm sorting. However, because flow cytometry-based sperm sorting often uses fluorescent dyes that often stain DNA, the safety of this technique in human reproductive medicine is a matter of scientific discussion. [ 4 ] [ 5 ]


However, flow cytometry is the only currently used technique able to determine the sex of future progeny by measuring DNA content of individual sperm cells. It evaluates if they contain the larger  X chromosome  (giving rise to a female offspring) or smaller  Y chromosome  (leading to male progeny). It then allows separation of X and Y sperm. [ 6 ]  The so-called  Beltsfield Sperm Sexing Technology  was developed by USDA in conjunction with Lawrence Livermore National Laboratories, relying on the DNA difference between the X- and Y- chromosomes. [ 7 ]  Prior to flow cytometric sorting, semen is labeled with a fluorescent dye called  Hoechst 33342  which binds to the DNA of each spermatozoon. As the X chromosome is larger (i.e. has more DNA) than the Y chromosome, the "female" (X-chromosome bearing) spermatozoa will absorb a greater amount of dye than its male (Y-chromosome bearing) counterpart.  As a consequence, when exposed to UV light during flow cytometry, X spermatozoa fluoresce brighter than Y- spermatozoa.  As the spermatozoa pass through the flow cytometer in single file, each spermatozoon is encased by a single droplet of fluid and assigned an electric charge corresponding to its chromosome status (e.g. X-positive charge, Y-negative charge).  The stream of X- and Y- droplets is then separated by means of electrostatic deflection and collected into separate collection tubes for subsequent processing. [ 8 ]


Another cytometric technique used in sperm sorting is  magnetic-activated cell sorting  (MACS) which is routinely applied in assisted reproduction hospitals to sort out sperm with fragmented DNA. This is achieved using  antibodies  to surface markers of programmed cell death ( apoptosis ) such as  annexin V , coupled with magnetic beads. Following the binding of these antibodies, spermatozoa which undergo apoptosis are sorted by applying  magnetic field  to the sperm suspension. [ 9 ]  MACS obviates the need for fluorescent DNA binding molecules.


DNA damage  in sperm cells may be detected by using  Raman spectroscopy . [ 10 ]  It is not specific enough to detect individual traits, however. [ 10 ]  The sperm cells having least DNA damage may subsequently be injected into the egg cell by  intracytoplasmic sperm injection  (ICSI). [ 10 ]  Many other methods for sperm sorting have been proposed or are currently tested. [ 1 ] [ 3 ]


To select spermatozoa with low  DNA damage  index the population of sperm could be enriched with spermatozoa with non-fragmented DNA, with techniques like  electrophoresis , [ 11 ]   Z method [ 12 ]  and MACS (Magnetic Activating Cell Sorting), which in combination with density gradient centrifugation in single sperm preparation protocols results in spermatozoa with superior quality. [ 13 ]


Hyaluronic acid  (HA) binding sites on the sperm plasma membrane are an indicator of sperm maturity (Huszar et al., 2003, Yudin et al.,1999). There are two methods based on this fact: physiological intracytoplasmic sperm injection (PICSI), and a sperm slow procedure; both methods require sperm preparation via sperm washing or centrifugation.


Sperm undergoes a process of  natural selection  when millions of sperm enter the vagina but only few reach the egg cell and then only one is usually allowed to  fertilize  it. The sperm is selected not only by its highest  motility  but also by other factors such as  DNA integrity , production of  reactive oxygen species  and  viability . This selection is largely circumvented in case of  in-vitro fertilization  which leads to higher incidence of  birth defects  associated with  assisted reproductive techniques . Egg cells are often fertilized by sperm which would have low chance of fertilizing it in natural conditions. [ 1 ]  Sperm sorting could thus be used to decrease risks associated with assisted reproduction. Additionally, there is ongoing debate about using sperm sorting for choosing the child's sex.


Conventional methods of sperm sorting have been widely used to assess quality of sperm before subsequent  artificial insemination  or  in-vitro fertilization . It has been verified that sperm sorted using these techniques is of superior quality than unsorted. [ 14 ] [ 15 ]  However, important characteristics of sperm such as DNA integrity remain untested by these conventional methods. New flow-cytometry based techniques such as  YO-PRO  staining can discriminate  apoptotic  and dead spermatozoa from the viable ones. [ 2 ]  For example,  annexin V  staining followed by  MACS  can significantly improve pregnancy rates in couples with previous assisted reproduction failure. [ 9 ]


Sperm sorting by flow cytometry is an established technique in veterinary practice, and in the dairy industry most female cows are artificially inseminated with sorted semen to increase the number of female  calves  (using sperm sorting is less common in other species of farm animals, however artificial insemination is common). [ 16 ]  Artificial insemination of farm animals with sorted sperm is recognized by the  Food and Agriculture Organization  (FAO) as a promising way of increasing efficiency of agriculture needed to produce enough food for the growing human population. Utilizing artificial insemination with sorted sperm is seen as a way to create an optimal ratio of male and female calves to increase dairy  milk production . [ 16 ]


Choosing the sex of children might help prevent  sex-associated heritable diseases  such as  Duchene muscular dystrophy  or  haemophilia  in families with a history of these diseases. On the other hand, sperm sorting in humans raises the ethical concerns implicit to the idea of  sex selection . If applied large-scale, it has a potential to elicit a  sex-ratio imbalance . It could also have implications on gender equality if parents consistently choose to have a boy as their first-born (first-borns were shown to be more likely to succeed in life). [ 17 ]


There is no country in the world which explicitly permits sex selection for non-medical purposes. There were 31 countries in 2009 which allowed sex selection in case of sex-linked disease risk or other medical purpose. [ 18 ]  In the US, for humans, the application of sperm sorting in sex selection is tightly regulated by the  FDA . After the establishment of the MicroSort technique, it was offered to parents as a part of a  clinical trial . The procedure was made available to a limited number of participants each month, in addition to fulfilling certain criteria, such as having a disease with  sex linkage  or having at least one child (for family balancing). [ 19 ]  There are currently MicroSort laboratories and collaborating physicians in several countries (some for general purposes, some only offering service in case of genetic disease risks associated with one sex). [ 20 ]


While highly accurate, sperm sorting by flow cytometry will not produce two completely separate populations. That is to say, there will always be some "male" sperm among the "female" sperm and vice versa. The exact percentage purity of each population is dependent on the species being sorted and the 'gates' which the operator places around the total population visible to the machine. In general, the larger the DNA difference between the X and Y chromosome of a species, the easier it is to produce a highly pure population. In sheep and cattle, purities for each sex will usually remain above 90% depending on 'gating', while for humans these may be reduced to 90% for "female" spermatozoa and 70% for "male" spermatozoa. [ 19 ]


A  strawberry cervix  is a finding upon physical examination where the  cervix  has an erythematous, punctate, and papilliform appearance. It is named because of the superficial similar appearance to a  strawberry .


As opposed to a more general inflammation of the cervix found in  cervicitis , the strawberry cervix appearance is considered to be selectively associated with  Trichomonas  infections. [ 1 ]  A clinician discovering this finding would have a high suspicion for Trichomonas infection.


Streptococcus agalactiae  (also known as  group B streptococcus  or  GBS ) is a  gram-positive   coccus  (round  bacterium ) with a tendency to form chains (as reflected by the  genus  name  Streptococcus ). It is a beta- hemolytic ,  catalase -negative, and  facultative anaerobe . [ 1 ] [ 2 ]


S. agalactiae  is the most common human pathogen of streptococci belonging to group B of the Rebecca  Lancefield classification  of streptococci. GBS are surrounded by a  bacterial capsule  composed of  polysaccharides  (exopolysacharide). The species is subclassified into ten  serotypes  (Ia, Ib, II–IX) depending on the immunologic reactivity of their polysaccharide capsule. [ 1 ] [ 3 ] [ 4 ]


The plural term  group B streptococci  (referring to the serotypes) and the singular term  group B streptococcus  (referring to the single species) are both commonly used synonymously with  S. agalactiae  even though  S. halichoeri  and  S. pseudoporcinus  are also group B Streptococci. These species test positive as group B, but are not frequently carried by humans, and only rarely cause disease. [ 5 ]


In general, GBS is a harmless commensal bacterium being part of the human  microbiota  colonizing the  gastrointestinal  and genitourinary tract of up to 30% of healthy human adults ( asymptomatic carriers ). Nevertheless, GBS  can cause severe invasive infections especially in newborns, the elderly, and people with compromised immune systems. [ 6 ]


S. agalactiae  is also a common veterinary pathogen, because it can cause bovine mastitis (inflammation of the udder) in dairy cows. The species name  agalactiae  meaning "of no milk", alludes to this. [ 7 ]


GBS grows readily on blood  agar plates  as colonies surrounded by a narrow zone of β- hemolysis . GBS is characterized by the presence in the  cell wall  of the antigen group B of Lancefield classification ( Lancefield grouping ) that can be detected directly in intact bacteria using latex agglutination tests. [ 8 ] [ 9 ]  The  CAMP test  is also another important test for identification of GBS. The CAMP factor produced by GBS acts synergistically with the staphylococcal β-hemolysin inducing enhanced hemolysis of sheep or bovine erythrocytes. [ 8 ]  GBS is also able to hydrolyze  hippurate  and this test can also be used to identify presumptively GBS. [ 8 ]
Hemolytic GBS strains produce an orange-brick-red non- isoprenoid   polyene  (ornithine rhamnolipid) pigment ( granadaene ) [ 10 ]  when cultivated on  granada medium  that allows its straightforward identification. [ 11 ]
GBS can also be identified using  MALDI-TOF  (Matrix Assisted Laser Desorption/Ionization-Time of Flight) instruments. [ 12 ]
GBS colonies can additionally be identified tentatively after their appearance in  chromogenic agar  media, nevertheless GBS-like colonies that develop in chromogenic media should be confirmed as GBS using additional reliable tests (e.g.latex agglutination or the CAMP test) to avoid potential mis-identification. [ 9 ] [ 13 ] [ 14 ]
A summary of the laboratory techniques for GBS identification is depicted in Ref 7.
 [ 9 ]


GBS is a normal component of the intestinal and vaginal  microbiota  in some people, GBS is an  asymptomatic  (presenting no symptoms) colonizer of the  gastrointestinal tract  and vagina in up to 30% of otherwise healthy adults, including pregnant women. [ 3 ] [ 15 ]  GBS colonization may be permanent, intermittent or temporary. In different studies, GBS vaginal colonization rate ranges from 0% to 36%, most studies reporting colonization rates in sexually active women over 20%. [ 16 ]  It has been estimated that maternal GBS colonization worldwide is 18%, with regional variation from 11% to 35%. [ 17 ]
These variations in the reported prevalence of asymptomatic GBS colonization could be related to the detection methods used, and differences in populations sampled. [ 15 ] [ 18 ]


As other  virulent  bacteria, GBS harbors an important number of  virulence factors  (virulence factors are molecules produced by bacteria that boosts their capacity to infect and damage human tissues), the most important being the capsular polysaccharide (rich in  sialic acid ) [ 3 ] [ 19 ]
and a pore-forming  toxin , β-hemolysin. [ 19 ] [ 20 ] [ 21 ]
Today it is considered that GBS pigment (granadaene) and hemolysin are identical or closely related molecules. [ 22 ] [ 23 ] [ 24 ] [ 25 ]


Sialic acid is a notable virulence factor in  S. agalactiae  despite being found normally in humans and many other animals. By expressing an unusually high amount of sialic acid on the bacterial cell surface,  S. agalactiae  can subvert the  innate immune system , convincing  leukocytes  that the bacteria are human cells. [ 26 ] [ 27 ]


GBS colonization of the vagina usually does not cause problems in healthy women, nevertheless during pregnancy it can sometimes cause serious illness for the mother and the newborn. GBS is the leading cause of bacterial  neonatal infection  in the baby during gestation and after delivery with significant mortality rates in premature infants. GBS infections in the mother can cause  chorioamnionitis  (a severe infection of the  placental  tissues) infrequently, postpartum infections (after birth) and it had been related with prematurity and fetal death. [ 28 ]  GBS  urinary tract infections  (UTI) may also induce labor and cause premature delivery. [ 3 ]
In the western world, GBS (in the absence of effective prevention measures) is the major cause of several bacterial infections of the newborn  neonatal infection   sepsis ,  pneumonia , and  meningitis , which can lead to death or long-term  sequelae . [ 3 ]


GBS neonatal infection typically originates in the lower reproductive tract of infected mothers.
GBS infections in newborns are separated into two clinical  syndromes , early-onset disease (EOD) and late-onset disease (LOD). [ 29 ]
EOD manifests from 0 to 7 living days in the newborn, most of the cases of EOD being apparent within 24h of birth. [ 3 ] [ 30 ] [ 31 ]  The most common clinical syndromes of EOD are  sepsis  without apparent focus,  pneumonia , and less frequently meningitis. EOD is acquired vertically ( vertical transmission ),  through exposure of the fetus or the baby to GBS from the vagina of a colonized woman, either intrautero or during birth after rupture of membranes. Infants can be infected during passage through the birth canal, nevertheless newborns that acquire GBS through this route can become only colonized, and these colonized infants habitually do not develop EOD. Roughly 50% of newborns to GBS colonized mothers are also GBS colonized and (without prevention measures) 1–2% of these newborns will develop EOD. [ 32 ]


In the past, the incidence of EOD ranged from 0.7 to 3.7 per thousand live births in the US [ 3 ]  and from 0.2 to 3.25 per thousand in Europe. [ 18 ]
In 2008, after widespread use of antenatal screening and intrapartum antibiotic prophylaxis (IAP), the CDC reported an incidence of 0.28 cases of EOD per thousand live births in the US. [ 33 ]
Multistate surveillance 2006-2015 shows a decline in EOD from 0.37 to 0.23 per 1000 live births in the US but LOD remains steady at 0.31 per 1000 live births. [ 34 ]
In 2021 had been estimated a total of 1970 deaths ((0.59/100,000 population) in the US caused by GBS neonatal infections. It was estimated that 226 infants (49 per 100,000) in the United States had a clinically significant GBS infection, and that approximately 11 (2.4%) of those cases resulted in death. [ 35 ]


It has been indicated that where there was a policy of providing IAP for GBS colonized mothers the overall risk of EOGBS is 0.3%. [ 36 ]


Though maternal GBS colonization is the key determinant for EOD, other factors also increase the risk. These factors include onset of labor before 37 weeks of gestation ( premature birth ),  prolonged rupture of membranes  (≥18h before delivery), intra-partum fever (>38 °C,  >100.4 °F), amniotic infections (chorioamnionitis), young maternal age, and low levels of GBS anticapsular polysaccharide antibodies in the mother. [ 3 ] [ 30 ] [ 31 ]  Nevertheless, most babies who develop EOD are born to GBS colonized mothers without any additional risk factor. [ 30 ] [ 31 ]  A previous sibling with EOD is also an important risk factor for development of the infection in subsequent deliveries, probably reflecting a lack of GBS polysaccharides protective antibodies in the mother.
Heavy GBS vaginal colonization is also associated with a higher risk for EOD. [ 30 ]
Overall, the case–fatality rates from EOD have declined, from 50% observed in studies from the 1970s to 2 to 10% in recent years, mainly as a consequence of improvements in therapy and management. Fatal neonatal infections by GBS are more frequent among premature infants. [ 3 ] [ 30 ] [ 31 ] [ 37 ]


GBS LOD affects infants from 7 days to 3 months of age and is more likely to cause  bacteremia  or meningitis. LOD can be acquired from the mother or from environmental sources. Hearing loss and mental impairment can be a long-term sequela of GBS meningitis. [ 3 ] [ 38 ] [ 39 ]  In contrast with EOD, the incidence of LOD has remained unchanged at 0.26 per 1000 live births in the US. [ 40 ]   S. agalactiae   neonatal meningitis  does not present with the hallmark sign of adult meningitis, a stiff neck; rather, it presents with  nonspecific symptoms , such as fever, vomiting and irritability, and can consequently lead to a late diagnosis. [ 2 ]


The only reliable way to prevent EOD currently is intrapartum  antibiotic prophylaxis  (IAP), that is to say administration of antibiotics during delivery.  It has been proved that intravenous  penicillin  or  ampicillin  administered for at least 4 hours before delivery to GBS colonized women is very effective at preventing vertical transmission of GBS from mother to baby and EOD. Intravenous penicillin remains the agent of choice for IAP, with intravenous ampicillin as an acceptable alternative. [ 3 ] [ 30 ] [ 31 ]  For penicillin allergic women, the laboratory requisitions for ordering antepartum GBS screening cultures should indicate clearly the presence of penicillin allergy. [ 31 ]
 Cefazolin ,  clindamycin , and  vancomycin  are used to prevent EOD in infants born to penicillin-allergic mothers. [ 30 ] [ 31 ]
Intravenous vancomycin is recommended for IAP in women colonized with a clindamycin-resistant Group B Streptococcus strain and a severe penicillin allergy. [ 29 ] [ 31 ]


There are two ways to identify female candidates to receive intrapartum antibiotic prophylaxis: a risk-based approach or a culture-based screening approach. The culture-based screening approach identifies candidates to receive IAP using lower vaginal and rectal cultures obtained between 36 and 37 weeks' gestation [ 30 ] [ 31 ]  (32–34 weeks of gestation for women with twins [ 41 ] ) and IAP is administered to all GBS colonized women. The risk-based strategy identifies candidates to receive IAP by the aforementioned risk factors known to increase the probability of EOD without considering if the mother is or is not a GBS carrier. [ 3 ] [ 42 ]


IAP is also recommended for women with intrapartum risk factors if their GBS carrier status is not known at the time of delivery, for women with GBS bacteriuria during their pregnancy, and for women who have had an infant with EOD previously. [ citation needed ]


The risk-based approach for IAP is in general less effective than the culture-based approach because in most of the cases EOD develops among newborns, which are born to mothers without risk factors. [ 18 ]


In 2010, the Centers for Disease Control and Prevention (CDC), in collaboration with several professional groups, issued its revised GBS prevention guidelines. [ 30 ]


In 2018, the task of revising and updating the GBS prophylaxis guidelines was transferred from the CDC   [ 43 ]  to ACOG ( American College of Obstetricians and Gynecologists ), the  American Academy of Pediatrics  and to the American Society for Microbiology. [ 14 ] [ 29 ] [ 31 ]


The ACOG committee issued an update document on Prevention of Group B Streptococcal Early-Onset Disease in Newborns in 2019. [ 31 ]  This document does not introduce important changes from the CDC guidelines. The key measures necessary for preventing neonatal GBS early onset disease continue to be universal prenatal screening by culture of GBS from swabs collected from the lower vagina and rectum, correct collection and microbiological processing of the samples, and proper implementation of intrapartum antibiotic prophylaxis. The ACOG now recommends performing universal GBS screening between 36 and 37 weeks of gestation.
This new recommendation provides a five-week window  [ 44 ]  for valid culture results that includes births that occur up to a gestational age of at least 41 weeks.


The culture-based screening approach is followed in most developed countries [ 45 ]  such as the United States, [ 29 ] [ 30 ] [ 31 ]   France, [ 46 ]  Spain, [ 47 ]  Belgium, [ 48 ]  Canada, Argentina, [ 49 ]  and Australia. The risk-based strategy is followed in the United Kingdom, [ 41 ] [ 50 ]  and the Netherlands. [ 18 ] [ 51 ]


Though the GBS colonization status of women can change during pregnancy, cultures to detect GBS carried out ≤5 weeks before delivery predict quite accurately the GBS carrier status at delivery. [ citation needed ]


In contrast, if the prenatal culture is performed more than five weeks before delivery it is unreliable for predicting accurately the GBS carrier status at delivery. [ 30 ] [ 31 ] [ 44 ] [ 52 ] [ 53 ]


The clinical specimens recommended for culture of GBS at 36–37 weeks' gestation, this recommendation provides a 5-week window for valid culture results that includes births that occur up to a gestational age of at least 41 weeks  [ 31 ]  (32–34 weeks of gestation for women with twins [ 41 ] ) are swabs collected the lower vagina (near the introitus) and then from the rectum (through the anal sphincter) without use of a speculum. [ 30 ] [ 31 ]  Vaginal-rectal samples should be collected using a flocked swab preferably, since flocked swabs releases samples and microorganisms more effectively than fiber swabs. [ 14 ]


Following the recommendations of the  Centers for Disease Control and Prevention  of United States  (CDC) these swabs should be placed into a non-nutritive transport medium and later inoculated into a selective enrichment broth, Todd Hewitt broth with selective antibiotics  ( enrichment culture ). [ 30 ]  After incubation the enrichment broth is subcultured to blood agar plates and GBS like colonies are identified by the CAMP test or using latex agglutination with GBS  antisera . After incubation the enrichment broth can also be subcultured to  granada medium  agar  [ 11 ]  where GBS grows as pink-red colonies or to chromogenic agars, where GBS grows as colored colonies. [ 9 ] [ 30 ]
GBS-like colonies that develop in chromogenic media should be confirmed as GBS using additional reliable tests to avoid mis-identification. [ 9 ]


Nucleic acid amplification tests  (NAAT) such as  polymerase chain reaction  (PCR) and DNA  hybridization probes  have been developed for identifying GBS directly from recto-vaginal samples, but they has a high false negative rate, and still cannot replace antenatal culture for the most accurate detection of GBS carriers. This technology to detect GBS must be improved and simplified to make the method cost-effective and useful as a  point-of-care  test.
Nevertheless These tests can also be used to detect GBS directly from broth media, after the enrichment step, avoiding the subculture of the incubated enrichment broth to an appropriate agar plate. [ 14 ]


Though IAP for EOD prevention is associated with a large decline in the incidence of the disease, there is, however, no effective strategy for preventing late-onset neonatal GBS disease. [ 54 ]


Vaccination  is considered an ideal solution to prevent not only EOD and LOD but also GBS infections in adults at risk. [ 55 ]
Nevertheless, though research and  clinical trials  for the development of an effective vaccine to prevent GBS infections are underway, no vaccine was available in 2023. [ 56 ] [ 57 ] [ 58 ] [ 59 ]
The capsular polysaccharide of GBS is not only an important GBS virulence factor but it is also an excellent candidate for the development of an effective vaccine. [ 18 ] [ 60 ] [ 61 ] [ 62 ]  Protein-based vaccines are also in development. [ 56 ] [ 63 ] [ 58 ] [ 64 ]


GBS is also an important infectious agent able to cause invasive infections in adults. Serious life-threatening invasive GBS infections are increasingly recognized in the elderly and individuals compromised by underlying diseases such as diabetes,  cirrhosis  and cancer. [ 65 ]  GBS infections in adults include urinary tract infection, skin and soft-tissue infection ( skin and skin structure infection ) bacteremia,  osteomyelitis , meningitis and  endocarditis . [ 6 ]  GBS infection in adults can be serious and related with high mortality. In general penicillin is the antibiotic of choice for treatment of GBS infection. [ 66 ] [ 67 ]  Gentamicin (for synergy with penicillin G or ampicillin) can also be used in patients with life-threatening invasive GBS. [ 66 ]


Streptococcus agalactiae  was historically studied as a disease of  cattle  that harmed milk production, leading to its name "agalactiae" which means "absence of milk". Strains of bovine and human bacteria are generally interchangeable, with evidence of transmission from animals to humans and vice versa. [ 68 ]


GBS is a major cause of  mastitis  (an infection of the  udder ) in dairy cattle and an important source of economic loss for the industry.  GBS in cows can either produce an acute febrile disease or a subacute more  chronic condition . Both lead to diminishing milk production (hence its name: agalactiae meaning "of no milk"). [ 69 ]  Outbreaks in herds are common, so this is of major importance for the  dairy industry , and programs to reduce the impact of  S. agalactiae  disease have been enforced in many countries over the last 40 years. [ 7 ] [ 68 ]


GBS also causes severe epidemics in farmed fish, causing sepsis and external and internal hemorrhages, having been reported from wild and captive fish involved in  epizootics  in many countries. [ 70 ] [ 71 ]  Vaccination is an effective method to prevent pathogenic
diseases in aquaculture and different kinds vaccines to prevent GBS infections have been developed recently. [ 72 ]


GBS has also been found in many other animals, such as camels, dogs, cats, crocodiles, seals, elephants and dolphins. [ 73 ] [ 74 ]


Stretch marks , also known as  striae  ( / ˈ s t r aɪ iː / ) [ citation needed ]  or  striae distensae , [ 1 ]  are a form of  scarring  on the  skin  with an off-color hue. Over time, they may diminish, but will not disappear completely. Striae are caused by tearing of the  dermis  during periods of rapid growth of the body, such as during  puberty  or  pregnancy , in which they usually form during the  last trimester . Usually on the belly, these striae also commonly occur on the breasts, thighs, hips, lower back, and buttocks. Pregnancy-related striae are known as  striae gravidarum . [ 2 ]  Striae may also be influenced by the  hormonal  changes associated with puberty, pregnancy,  bodybuilding , or  hormone replacement therapy . There is no evidence that creams used during pregnancy prevent stretch marks. [ 3 ]  Once they have formed, there is no clearly effective treatment, though various methods have been attempted and studied. [ 4 ]


Striae, or "stretch marks", begin as reddish or purple  lesions  which can appear anywhere on the body, but are most likely to appear in places where larger amounts of fat are stored. The most common places are the  abdomen  (especially near the  navel ), breasts, upper arms, underarms, back, thighs (both inner and outer), hips, and buttocks. Over time, they tend to  atrophy  and lose  pigmentation . The affected areas appear empty, and are soft to the touch. [ 5 ]


Stretch marks occur in the  dermis , the resilient middle tissue layer that helps the  skin  retain its shape. No stretch marks will form as long as there is support within the dermis; stretching plays a role in where the marks occur and in what direction they run.


They can (but do not always) cause a burning and itching sensation, as well as emotional distress. They pose no inherent health risk on their own, and do not compromise the body's ability to function normally and repair itself. However, some people dislike the way stretch marks look. [ 6 ]  Young women are generally affected the most and often seek treatment for them from a  dermatologist [ 7 ]  and following  pregnancy . [ 8 ]


Stretch marks appear to be caused by stretching of the skin. This is especially true when there is an increase in  cortisone [ 9 ]  –  an increase in cortisone levels can increase the probability or severity of stretch marks by reducing the skin's pliability. More specifically, it affects the  dermis  by preventing the  fibroblasts  from forming  collagen  and  elastin  fibers necessary to keep rapidly growing skin taut; this can create a lack of supportive material as the skin is stretched, and lead to dermal and  epidermal  tearing, which in turn can produce scarring in the form of stretch marks. This is particularly the case when there is new tissue growth, which can interfere with the underlying physical support of the dermis or epidermis by displacing the supportive tissue. [ citation needed ]


Examples of cases where stretch marks are common include weight gain (in the form of  fat  and/or  muscle ),  pregnancy , and adolescent  growth spurts , though it is also noted that some medications, as well as other medical conditions and diseases, may increase the likelihood of stretch marks appearing. Common medications that can contribute to stretch marks include " corticosteroid  creams, lotions and pills and chronic use of oral or systemic  steroids ". [ 9 ]  Medical conditions that can contribute to stretch marks include  Ehlers–Danlos syndrome ,  Cushing's syndrome ,  Marfan syndrome , and  adrenal gland diseases . [ 10 ] [ 11 ] [ 12 ]


Pregnancy stretch marks, also known as  striae gravidarum , are a specific form of  scarring  of the skin of the abdominal area due to rapid expansion of the  uterus  as well as sudden weight gain during pregnancy. About 90% of pregnant women are affected. [ 13 ]


A number of additional factors appear to promote the appearance of stretch marks: one study of 324 women, done just after they had given birth, demonstrated that low maternal age, high  body mass index , weight gain over 15 kg (33 pounds) and higher neonatal birth weight were independently correlated with the occurrence of striae. Teenagers were found to be at the highest risk of developing severe striae. [ 14 ]


These skin marks are  symptoms of pregnancy  caused by the tearing of the  dermis , resulting in  atrophy  and loss of  rete ridges . [ 15 ]  These scars often appear as reddish or bluish streaks on the abdomen, and can also appear on the breasts and thighs. Some of these striae disappear with time, while others remain as permanent discolorations of the body. [ citation needed ]


Mechanical distension and rapidly developing areas of the body during pregnancy (such as the abdomen, breasts, and thighs) are most commonly associated with striae formation. Some have suggested that  relaxin  and  estrogen  combined with higher levels of  cortisol  during pregnancy can cause an accumulation of  mucopolysaccharides , which increases water absorption of  connective tissue , making it prime for tearing under mechanical  stress . [ 7 ] [ 14 ]  There also seems to be an association between higher body mass indices and in women with bigger babies and the incidence and severity of striae. Also, younger women seem to be at higher risk of developing striae during pregnancy. [ 7 ] [ 16 ]


The prevalence and severity of striae gravidarum varies among populations. The current literature suggest that in the general population of the United States, there is a 50% to 90% prevalence of striae associated with pregnancy, [ 16 ]  partly as a result of the normal hormonal changes associated with pregnancy and partly due to stretching of skin fibers. [ 3 ] [ 17 ]  Many women experience striae gravidarum during their first pregnancy. Nearly 45% percent of women develop striae gravidarum before 24 weeks of gestation. [ citation needed ]  Many women who develop lesions during the first pregnancy do not develop them during later pregnancies. Genetic factors such as  genealogy  and race also seem to be predictive in the appearance of striae. [ 17 ]


Collagen and elastin are proteins in the skin that contribute to the skin's strength, resilience, flexibility, and help skin that has been stretched to recover its original state. Boosting the production of collagen and elastin helps prevent stretch marks from occurring. [ 18 ]  Stretch marks can also derive from  nutritional deficiencies . Consuming foods that contribute to the skin's health, such as  zinc -rich foods, protein-rich foods, and foods high in vitamin A, C, and D, can help suppress stretch marks. [ 19 ]  A systematic review has not found evidence that creams and oils are useful for preventing or reducing stretch marks in pregnancy. [ 3 ]  The safety in pregnancy of one ingredient,  Centella asiatica , has been questioned. [ 17 ]  Evidence on treatments for reducing the appearance of the scars after pregnancy is limited. [ 17 ]


There are no clearly useful treatments for stretch marks, although there are many different suggestions on how to remove them or lessen their appearance. [ 4 ]


Various efforts that have been tried including  laser treatments ,  glycolic acid , and  microdermabrasion . [ 20 ]   Tretinoin  (0.1% w/w), which is a  retinoid , has found to be effective on early stretch marks in several studies.  Hyaluronic acid  also improves the appearance of stretch marks. [ 21 ] [ 22 ]  Topical tretinoin is categorized by the  United States Food and Drug Administration  (FDA) as a known  teratogen  (causing malformations in fetuses) in animals, without adequate human studies on safety in pregnancy. [ 23 ]


Carboxytherapy  is a known procedure; however, there is a lack of evidence to support how effective it is. [ 24 ]


Research into a new  skin grafting  technique called "microcolumn grafting / micrografting", which uses needles to take autologous full-thickness  skin biopsies , is also being investigated as a potential treatment for stretch marks. [ 25 ] [ 26 ] [ 27 ]


Since ancient times, people have sought remedies to prevent stretch marks during pregnancy. Both ancient  Greeks  and  Romans  used  olive oil , while  Ethiopians  and  Somalis  used  frankincense . [ 28 ]


Striae were first recognized by  Roederer  in 1773, and were later histologically described by  Troisier  and  Ménétrier  in 1889. [ 29 ]  In 1936, Nardelli made the first morphologically correct descriptions. [ 30 ]


Medical terminology  for these kinds of markings includes: striae atrophicae, vergetures, stria distensae, striae cutis distensae, lineae atrophicae, linea albicante, or simply striae. [ citation needed ]


Subinvolution  is a medical condition in which after  childbirth , the  uterus  does not return to its normal size.


The condition may be asymptomatic. The predominant symptoms are:


When the  involution  is impaired or retarded it is called subinvolution. The uterus is the most common organ affected by subinvolution. As it is the most accessible organ to be measured per abdomen, the uterine involution is considered clinically as an index to assess subinvolution.


In  pregnancy , there is an  increased susceptibility and/or severity of several  infectious diseases .


There are several potential risk factors or causes to this increased risk:


Pregnant women are more severely affected by  influenza ,  hepatitis E ,  herpes simplex  and  malaria . [ 1 ]  The evidence is more limited for  coccidioidomycosis ,  measles ,  smallpox , and  varicella . [ 1 ]  Pregnancy may also increase susceptibility for  toxoplasmosis . [ 2 ]


During the  2009 H1N1 pandemic , as well as during interpandemic periods, women in the  third trimester  of pregnancy were at increased risk for severe
disease, such as disease requiring admission to an  intensive care unit  or resulting in death, as compared with women in an earlier stage of pregnancy. [ 1 ]


For  hepatitis E , the case fatality rate among pregnant women has been estimated to be between 15% and 25%, as compared with a range of 0.5 to 4% in the population overall, with the highest susceptibility in the third trimester. [ 1 ]


Primary  herpes simplex  infection, when occurring in pregnant women, has an increased risk of dissemination and hepatitis, an otherwise rare complication in immunocompetent adults, particularly during the third trimester. [ 1 ]  Also, recurrences of  herpes genitalis  increase in
frequency during pregnancy. [ 1 ]


The risk of severe  malaria  by  Plasmodium falciparum  is three times as high in pregnant women, with a median maternal mortality of 40% reported in studies in the Asia–Pacific region. [ 1 ]  In women where the pregnancy is not the first, malaria infection is more often asymptomatic, even at high parasite loads, compared to women having their first pregnancy. [ 1 ]  There is a decreasing susceptibility to malaria with increasing parity, probably due to immunity to pregnancy-specific  antigens . [ 1 ]  Young maternal age and increases the risk. [ 1 ]  Studies differ whether the risk is different in different  trimesters . [ 1 ]  Limited data suggest that malaria caused by  Plasmodium vivax  is also more severe during pregnancy. [ 1 ]


Severe and disseminated  coccidioidomycosis  has been reported to occur in increased frequency in pregnant women in several reports and case series, but subsequent large surveys, with the overall risk being rather low. [ 1 ]


Varicella  occurs at an increased rate during pregnancy, but mortality is not higher than that among men and non-pregnant women. [ 1 ]


Listeriosis  mostly occurs during the third trimester, with  Hispanic  women appearing to be at particular risk. [ 1 ]  Listeriosis is a  vertically transmitted infection  that may cause  miscarriage ,  stillbirth ,  preterm birth , or serious  neonatal disease . [ 1 ]


Some infections are  vertically transmissible , meaning that they can affect the embryo, fetus, or baby. [ citation needed ]


A  teratoma  is a  tumor  made up of several types of  tissue , such as  hair ,  muscle ,  teeth , or  bone . [ 4 ]  Teratomata typically form in the  tailbone  (where it is known as a  sacrococcygeal teratoma ),  ovary , or  testicle . [ 4 ]


Symptoms may be minimal if the tumor is small. [ 2 ]  A testicular teratoma may present as a painless lump. [ 1 ]  Complications may include  ovarian torsion ,  testicular torsion , or  hydrops fetalis . [ 1 ] [ 2 ] [ 3 ]


They are a type of  germ cell tumor  (a tumor that begins in the cells that give rise to  sperm  or  eggs ). [ 4 ] [ 8 ]  They are divided into two types: mature and immature. [ 4 ]  Mature teratomas include  dermoid cysts  and are generally  benign . [ 8 ]  Immature teratomas may be  cancerous . [ 4 ] [ 9 ]  Most ovarian teratomas are mature. [ 10 ]  In adults, testicular teratomas are generally cancerous. [ 11 ]  Definitive diagnosis is based on a  tissue biopsy . [ 2 ]


Treatment of coccyx, testicular, and ovarian teratomas is generally by surgery. [ 5 ] [ 6 ] [ 12 ]  Testicular and immature ovarian teratomas are also frequently treated with  chemotherapy . [ 6 ] [ 10 ]


Teratomas occur in the coccyx in about one in 30,000 newborns, making them one of the most common tumors in this age group. [ 5 ] [ 7 ]  Females are affected more often than males. [ 5 ]  Ovarian teratomas represent about a quarter of  ovarian tumors  and are typically noticed during middle age. [ 10 ]  Testicular teratomas represent almost half of  testicular cancers . [ 13 ]  They can occur in both children and adults. [ 14 ]  The term comes from the Greek word for "monster" [ 15 ]  plus the "-oma" suffix used for tumors.


Teratomas can cause an autoimmune illness called  Anti-NMDA receptor encephalitis . In this condition, the teratomas may contain B cells with NMDA-receptor specificities. [ 16 ]


After teratoma removal surgery,  a risk exists of regrowth in place, or in nearby organs. [ 17 ]


A mature teratoma is a grade 0 teratoma.  They are highly variable in form and histology, and may be solid, cystic, or a combination of the two.  A mature teratoma often contains several different types of tissue such as  skin ,  muscle , and  bone .  Skin may surround a cyst and grow abundant  hair   (see:  § Dermoid cyst ) .  Mature teratomas generally are benign, with 0.17–2% of mature cystic teratomas becoming malignant. [ 18 ]


Immature teratoma is the malignant counterpart of the mature teratoma and contains immature tissues which typically show  primitive or embryonal   neuroectodermal  histopathology. Immature teratoma has one of the lowest rates of  somatic mutation  of any tumor type and results from one of five mechanisms of  meiotic failure . [ 19 ]


Gliomatosis peritoneii, which presents as a deposition of mature glial cells in the peritoneum, is almost exclusively seen in conjunction with cases of ovarian teratoma. Through genetic studies of exome sequence, it was found that gliomatosis is genetically identical to the parent ovarian tumor and developed from cells that disseminate from the ovarian teratoma. [ 19 ]


A  dermoid cyst  is a mature cystic teratoma containing hair (sometimes very abundant) and other structures characteristic of normal skin and other tissues derived from the  ectoderm . The term is most often applied to teratoma on the skull sutures and in the ovaries of females. [ citation needed ]


Fetus  in fetu  and fetiform teratoma are rare forms of mature teratomas that include one or more components resembling a malformed fetus.  Both forms may contain or appear to contain complete organ systems, even major body parts, such as a torso or limbs.  Fetus  in fetu  differs from fetiform teratoma in having an apparent  spine  and  bilateral symmetry . [ 20 ]


Most authorities agree that fetiform teratomas are highly developed mature teratomas;  the natural history of fetus  in fetu  is controversial. [ 20 ]  It has been noted that fetiform teratoma is reported more often (by gynecologists) in ovarian teratomas, and fetus  in fetu  is reported more often (by general surgeons) in retroperitoneal teratomas.  Fetus  in fetu  has often been interpreted as a  fetus  growing within its  twin .  As such, this interpretation assumes a special complication of  twinning , one of several grouped under the term  parasitic twin .  In many cases, the fetus  in fetu  is reported to occupy a fluid-filled cyst within a mature teratoma. [ 21 ] [ 22 ] [ 23 ] [ 24 ]   Cysts within mature teratomas may have partially-developed organ systems: reports include cases of partial  cranial bones ,  long bones  and a rudimentary, beating heart. [ 25 ] [ 26 ]


Regardless of whether fetus  in fetu  and fetiform teratoma are one entity or two, they are distinct from and not to be confused with  ectopic pregnancy .


A struma ovarii (also known as  goitre  of the ovary or ovarian goiter) is a rare form of mature teratoma that contains mostly  thyroid  tissue. [ 27 ]


Epignathus is a rare teratoma originating in the oropharyngeal area that occurs  in utero . It presents with a mass protruding from the mouth at birth. Untreated, breathing is impossible. An  EXIT procedure  is the recommended initial treatment.


Teratomas may be found in babies, children, and adults. Teratomas of embryonal origin are most often found in babies at birth, in young children, and, since the advent of  ultrasound imaging , in fetuses.


The most diagnosed fetal teratomas are  sacrococcygeal teratoma  (Altman types I, II, and III) and cervical (neck) teratoma.  Because these teratomas project from the fetal body into the surrounding  amniotic fluid , they can be seen during routine prenatal ultrasound exams.  Teratomas within the fetal body are less easily seen with ultrasound;  for these, MRI of the pregnant uterus is more informative. [ 28 ] [ 29 ]


Teratomas are not dangerous for the fetus unless either a  mass effect  occurs or a large amount of blood flows through the tumor (known as vascular steal). The mass effect frequently consists of obstruction of normal passage of fluids from surrounding organs.  The vascular steal can place a strain on the growing heart of the fetus, even resulting in heart failure, thus must be monitored by fetal  echocardiography .


Teratomas belong to a class of tumors known as  nonseminomatous   germ cell tumor .  All tumors of this class are the result of abnormal development of  pluripotent  cells:  germ cells  and  embryonal cells . Teratomas of embryonic origin are  congenital ; teratomas of germ cell origin may or may not be congenital. The kind of pluripotent cell appears to be unimportant, apart from constraining the location of the teratoma in the body.


Teratomas derived from germ cells occur in the  testicle  and  ovaries . Teratomas derived from embryonic cells usually occur on the subject's midline: in the brain, elsewhere in the  skull , in the nose, in the tongue, under the tongue, and in the  neck  (cervical teratoma),  mediastinum ,  retroperitoneum , and attached to the  coccyx .  Teratomas may also occur elsewhere: very rarely in solid organs (most notably the heart and liver) and hollow organs (such as the stomach and bladder), and more commonly on the  skull sutures .


Teratoma rarely include more complicated body parts such as  teeth ,  brain matter , [ 30 ]   eyes , [ 31 ] [ 32 ]  or  torso . [ 33 ]


Concerning the origin of teratomas,  numerous hypotheses exist. [ 20 ]   These hypotheses are not to be confused with the unrelated hypothesis that fetus  in fetu  (see below) is not a teratoma at all, but rather a  parasitic twin .


Teratomas are thought to originate  in utero , so can be considered  congenital  tumors. Many teratomas are not diagnosed until much later in childhood or in adulthood. Large tumors are more likely to be diagnosed early on. Sacrococcygeal and cervical teratomas are often detected by prenatal  ultrasound . Additional diagnostic methods may include prenatal  magnetic resonance imaging . In rare circumstances, the tumor is so large that the fetus may be damaged or die. In the case of large sacrococcygeal teratomas, a significant portion of the fetus'  blood flow  is redirected toward the teratoma (a phenomenon called  steal syndrome ), causing  heart failure , or  hydrops , of the fetus. In certain cases,  fetal surgery  may be indicated.


Beyond the newborn period, symptoms of a teratoma depend on its location and organ of origin. Ovarian teratomas often present with abdominal or  pelvic pain , caused by  torsion  of the ovary or irritation of its ligaments. A recently discovered condition where ovarian teratomas cause encephalitis associated with antibodies against the  N-methyl-D-aspartate  receptor antibody (NMDAR) - often referred to as " anti-NMDA receptor encephalitis ", was identified as a serious complication. Patients develop a multistage illness that progresses from psychosis, memory deficits, seizures, and language disintegration into a state of unresponsiveness with catatonic features often associated with abnormal movements, and autonomic and breathing instability. [ 34 ]  Testicular teratomas present as a palpable mass in the testis;  mediastinal  teratomas often cause compression of the lungs or the airways and may present with  chest pain  and/or respiratory symptoms.


Some teratomas contain  yolk sac  elements, which secrete  alpha-fetoprotein . Its detection may help to confirm the diagnosis and is often used as a marker for recurrence or treatment efficacy, but is rarely the method of initial diagnosis. (Maternal serum  alpha-fetoprotein  is a useful  screening test  for other fetal conditions, including  Down syndrome ,  spina bifida , and  abdominal wall  defects such as  gastroschisis .)


Regardless of location in the body, a teratoma is classified according to a  cancer staging  system.  This indicates whether  chemotherapy  or  radiation therapy  may be needed in addition to surgery.  Teratomas commonly are classified using the  Gonzalez-Crussi [ 20 ]  grading system: 0 or mature ( benign ); 1 or immature, probably benign; 2 or immature, possibly  malignant  (cancerous); and 3 or frankly malignant. If frankly malignant, the tumor is a cancer for which additional cancer staging applies. [ citation needed ]