In 1978, within nine years of the Washington discovery, animal studies, including non-human monkey studies carried out at the University of Washington Primate Center by  Sterling Clarren , had confirmed that alcohol was a  teratogen . By 1978, 245 cases of FAS had been reported by medical researchers, and the syndrome began to be described as the most frequent known cause of  intellectual disability . [ citation needed ]  In 1979, the Washington and Nantes findings were confirmed by a research group in  Gothenburg , Sweden. [ 140 ]  Researchers in France, Sweden, and the United States were struck by how similar these children looked, though they were not related, and how they behaved in the same unfocused and  hyperactive  manner. [ 140 ]


Over time, subsequent research and clinical experience suggested that a range of effects could arise from prenatal alcohol exposure. The term  fetal alcohol effects  (FAE) was used for alcohol-related neurodevelopmental disorder and alcohol-related birth defects. [ 1 ]  It was initially used in research studies to describe humans and animals in whom teratogenic effects were seen after confirmed prenatal alcohol exposure (or unknown exposure for humans), but without obvious physical anomalies. [ 141 ]  Smith (1981) described FAE as an "extremely important concept" to highlight the debilitating effects of brain damage, regardless of the growth or facial features. [ 142 ]  This term fell out of favor with clinicians in the 1990s because it was often regarded by the public as a less severe disability than FAS, when in fact its effects could be just as detrimental. [ 143 ]  In 1996 the replacement terms ARBD and ARND were introduced. In 2002, the US Congress mandated that the CDC develop diagnostic guidelines for FAS and in 2004 a definition of a term that already had been used by some in the nineties, the Fetal Alcohol Spectrum Disorder (FASD) was adopted, [ 38 ] > to include FAS as well as other conditions resulting from prenatal alcohol exposure. [ 139 ]
Currently, FAS [ 19 ] [ 141 ] [ 137 ]  is the only expression of prenatal alcohol exposure defined by the  International Statistical Classification of Diseases and Related Health Problems  and assigned  ICD-9  and diagnoses. [ citation needed ]


Alcohol-related birth defects (ARBD), formerly known as possible fetal alcohol effect (PFAE), [ 141 ]  was a term proposed as an alternative to FAE and PFAE. [ 144 ]  The IOM presents ARBD as a list of congenital anomalies that are linked to maternal alcohol use but have no key features of FASD. [ 19 ]  PFAE and ARBD have fallen out of favor because these anomalies are not necessarily specific to maternal alcohol consumption and are not criteria for diagnosis of FASD. [ 13 ]


In 2013, the  American Psychiatric Association  introduced neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). [ 77 ]


Criminalization of substance use during pregnancy because of harm to the fetus or child is fiercely debated. [ 145 ] [ 146 ]  Elizabeth Armstrong has questioned the zero-tolerance approach taken towards alcohol consumption during pregnancy, describing it as a  moral panic . [ 147 ] [ 148 ]  While heavy alcohol consumption during pregnancy is known to be damaging to the unborn child, the effects of low intakes remain debatable, particularly in the absence of randomized controlled trials (c.f.  § Causes ). [ 44 ] [ 42 ]  The UK's abstinence recommendation was not chosen based on scientific evidence, but rather because it was simple advice that would ensure no one underestimated the risk. [ 149 ]  Tennessee's 2014 fetal assault law (which expired in 2016) was criticized for not addressing alcohol use. [ 150 ] [ 151 ]  The law criminalized opioid use during pregnancy and resulted in women avoiding professional medical care for fear of prosecution. [ 152 ]  A wide variety of professional organizations oppose criminalization. [ 153 ] [ 154 ]  Minnesota, North Dakota, Oklahoma, South Dakota, and Wisconsin have statutory authorization for the involuntary civil commitment of women who abuse alcohol during pregnancy. [ 155 ]


In 2016, a  CDC  press release and infographic entitled "More than 3 million US women at risk for alcohol-exposed pregnancy" caused controversy. [ 156 ]  The CDC release contained the message "The risk is real. Why take the chance?". [ 157 ] [ 158 ]  Darlena Cunha of Times Magazine interpreted the infographic as telling all women of child-bearing age not to drink at all, in case they might accidentally fall pregnant, and called them "scare tactics" and "shaming recommendations". [ 159 ]  Julie Beck said that the infographic insinuated that "your womb is a Schrodinger's box and you shouldn't pour alcohol into it unless you've peeked in there to be 100 percent sure the coast is clear". [ 160 ]  The CDC later clarified that the infographic was not intended to make any new guidelines or recommendations for women who are pre-pregnant, but rather to encourage conversations about alcohol with health professionals. [ 161 ]  Nonetheless, half of the pregnancies in developed countries and over 80% in developing countries are unplanned. Many women do not realize they are pregnant during the early stages and continue drinking when pregnant. [ 39 ]


In  Aldous Huxley 's 1932 novel  Brave New World  (where all fetuses are gestated  in vitro  in a factory), lower  caste  fetuses are created by receiving alcohol transfusions (Bokanovsky Process) to reduce intelligence and height, thus conditioning them for simple, menial tasks. Connections between alcohol and incubating embryos are made multiple times in the novel. [ 162 ]


The main character of the 2009 film  Defendor  is implied to have the condition. [ citation needed ]


Tony Loneman, a character in  Tommy Orange 's 2018 novel  There There , was born with fetal alcohol syndrome, which he calls "the Drome".


Creutzfeldt–Jakob disease


The  fetal head , from an obstetrical viewpoint, and in particular its size, is important because an essential feature of labor is the adaptation between the fetal head and the maternal bony  pelvis . Only a comparatively small part of the head at term is represented by the face. The rest of the head is composed of the firm skull, which is made up of two frontal, two parietal, and two  temporal bones , along with the upper portion of the occipital bone and the wings of the  sphenoid .


These bones are separated by membranous spaces, or sutures. The most important sutures are the frontal, between the two frontal bones; the  sagittal , between the two parietal bones; the two coronal, between the frontal and parietal bones; and the two  lambdoid , between the posterior margins of the  parietal bones  and upper margin of the  occipital bone . Where several sutures meet, an irregular space forms, which is enclosed by a membrane and designated as a fontanel. The greater, or anterior fontanel, is a lozenge-shaped space that is situated at the junction of the  sagittal  and the coronal sutures. The lesser, or posterior fontanel, is represented by a small triangular area at the intersection of the  sagittal  and  lambdoid  sutures. The localization of these fontanels gives important information concerning the presentation and position of the fetus. The temporal, or casserian fontanels, have no diagnostic


It is customary to measure certain critical diameters and circumferences of the newborn head. The diameters most frequently used, and the average lengths thereof, are:


The greatest circumference of the head, which corresponds to the plane of the  occipitofrontal  diameter, averages 34.5 cm (13.6 in), a size too large to fit through the pelvis without flexion. The smallest circumference, corresponding to the plane of the suboccipitobregmatic diameter, is 32 cm (13 in). The bones of the cranium are normally connected only by a thin layer of fibrous
tissue that allows considerable shifting or sliding of each bone to accommodate the size and shape of the maternal pelvis. This intrapartum process is termed molding. The head position and degree of skull ossification result in a spectrum of cranial plasticity from minimal to great and in some cases, undoubtedly contribute to fetopelvic disproportion, a leading indication for cesarean delivery.


Cunningham, F. Gary; Leveno, Kenneth J.; Gilstrap, Larry C. III; Hauth, John C. (March 31, 2005).  Williams Obstetrics  (22nd ed.). McGraw-Hill Professional.  ISBN   978-0071413152 .


Induction of final maturation  of  oocytes  is a procedure that is usually performed as part of  controlled ovarian hyperstimulation  to render the oocytes fully developed and thereby resulting in optimal  pregnancy chances . It is basically a replacement for the  luteinizing hormone  (LH) surge whose effects include final maturation in natural  menstrual cycles .


The main medications used for induction of final maturation are  human chorionic gonadotropin  (hCG) and  GnRH agonist . In fresh (rather than  frozen )  autologous  cycles of  in vitro  fertilization , final oocyte maturation triggering with GnRH agonist instead of hCG decreases the risk of  ovarian hyperstimulation syndrome  but decreases  live birth rate . In cycles followed by  oocyte donation , use of GnRH agonists instead of hCG decreases the risk of ovarian hyperstimulation syndrome with no evidence of a difference in live birth rate. [ 1 ]


Induction of final maturation also initiates the mechanisms that eventually result in  ovulation , and thereby makes the oocytes destined to undergo ovulation unless artificial  oocyte retrieval  is performed first. Therefore, induction of final maturation is also called  triggering oocyte release  from the ovary, and the administration of  pharmaceutical drugs  to induce final maturation is colloquially called giving a "trigger shot", even if the plan is to perform artificial oocyte retrieval before ovulation. [ 2 ]


Administration of a drug to trigger oocyte release without oocyte retrieval results in a predictable time of ovulation, with the interval from drug administration to ovulation depending on the type of drug. This avails for  sexual intercourse  or  intrauterine insemination  (IUI) to conveniently be scheduled at ovulation, the most likely time to achieve pregnancy. [ 3 ]


In  ovulation induction , using  clomifene  for intended conception by sexual intercourse, however, triggering oocyte release has been shown to decrease pregnancy chances compared to frequent monitoring with  LH surge  tests. [ 4 ]  Therefore, in such cases, triggering oocyte release is best reserved for women who require IUI and in whom LH monitoring proves difficult or unreliable. [ 4 ]  It may also be used when LH monitoring hasn't shown an LH surge by cycle day 18 (where cycle day 1 is the first day of the preceding menstruation) and there is an  ovarian follicle  of over 20 mm in size. [ 5 ]


In  in vitro  fertilization  (IVF), induction of final maturation avails for  egg retrieval  when the eggs are fully mature. [ citation needed ]


In IVF, final maturation induction is preceded by  controlled ovarian hyperstimulation . It is suggested that there should be a size of  ovarian follicles  of at least 15 mm, and serum estradiol level of 0.49 nmol/L before commencing final maturation induction. There are better prospects at a follicle size of 18 mm and serum estradiol level of 0.91 nmol/L. [ 6 ]


Medications used for final maturation and/or release of oocytes include:


Final maturation induction using GnRH agonist results in a substantial decrease in the risk of  ovarian hyperstimulation syndrome  (OHSS). A  Cochrane review  estimated that using GnRH agonist instead of hCG in IVF decreases the risk of mild, moderate or severe OHSS with an  odds ratio  of approximately 0.15. The review estimated that, for a woman with a 5% risk of mild, moderate or severe OHSS with the use of HCG, the risk of OHSS with the use of a GnRH agonist would be between 0 and 2%. [ 1 ]


However, using GnRH agonist has a lower  live birth rate  than when using hCG in  autologous  oocyte transfers (rather than ones using  oocyte donation ). A Cochrane review of autologous oocyte transfers estimated that GnRH agonist, compared to hCG, gives an  odds ratio  of pregnancy of approximately 0.47. It estimated that, for a woman with a 31% chance of achieving live birth with the use of hCG, the chance of a live birth with the use of an GnRH agonist would be between 12% and 24%. [ 1 ]  Likewise, using GnRH agonist instead of hCG was associated with a lower ongoing pregnancy rate (pregnancy beyond 12 weeks) than was seen with HCG (odds ratio 0.70) and a higher rate of early (less than 12 weeks)  miscarriage  (odds ratio 1.74). However, a higher pregnancy rate when using hCG is only found in those receiving  luteal support  without  luteinizing hormone  activity (such as  progesterone  or  progestin ). [ 1 ]


Final maturation induction using a GnRH agonist is recommended in women with cancer undergoing  fertility preservation , because ovarian hyperstimulation syndrome is associated with an increased risk of arterial thrombotic events such as  stroke ,  myocardial infarction  and peripheral  arterial embolism , and this risk can add to an already increased risk caused by the cancer. [ 11 ]


Using hCG versus GnRH agonist has no effect on the risk of  multiple pregnancy . [ 1 ]  Also, no difference has been found between the regimens regarding  live birth rate  or ongoing  pregnancy rate  when the controlled ovarian hyperstimulation was followed by  oocyte donation . [ 1 ]


In  obstetrics , the term  flexion point  refers to a spot on the fetal head on which the cup of a  ventouse  should to be placed for extraction of the child to be most effective.


When the cup of the ventouse is applied on the flexion point, the fetal head will remain flexed under traction, hence the name  flexion point .


The flexion point is located on the  sagittal suture , 3 cm (about 1 inch) forward of the  posterior fontanelle . [ 1 ]


Foetal cerebral redistribution  or 'brain-sparing' is a diagnosis in  foetal medicine .  It is characterised by preferential flow of blood towards the brain at the expense of the other vital organs, and it occurs as a  haemodynamic  adaptation in foetuses which have  placental insufficiency .  [ 1 ]  The underlying mechanism is thought to be  vasodilation  of the  cerebral arteries . [ 2 ]  Cerebral redistribution is defined by the presence of a low  middle cerebral artery   pulsatility index  (MCA-PI).  Ultrasound  of the middle cerebral artery to examine the  Doppler  waveform is used to establish this. [ 3 ]  Although cerebral redistribution represents an effort to  preserve  brain development in the face of  hypoxic  stress, it is nonetheless associated with adverse  neurodevelopmental  outcome. [ 1 ]  The presence of cerebral redistribution will be one factor taken into consideration when deciding whether to artificially deliver a baby with placental insufficiency via  induction of labour  or  caesarian section .


In the fetal  heart , the  foramen ovale  ( / f ə ˈ r eɪ m ən   oʊ ˈ v æ l i ,   - m ɛ n -,   - ˈ v ɑː -,   - ˈ v eɪ -/ [ 1 ] [ 2 ] [ 3 ] ), also  foramen Botalli  or the  ostium secundum of Born , allows blood to enter the left  atrium  from the right atrium. It is one of two fetal  cardiac shunts , the other being the  ductus arteriosus  (which allows blood that still escapes to the right ventricle to bypass the  pulmonary circulation ). Another similar adaptation in the fetus is the  ductus venosus . In most individuals, the foramen ovale closes at birth. It later forms the  fossa ovalis .


The foramen ovale (from  Latin  'oval hole') forms in the late fourth week of  gestation , as a small passageway between the septum secundum and the ostium secundum. Initially the atria are separated from one another by the  septum primum  except for a small opening below the septum, the  ostium primum . As the septum primum grows, the ostium primum narrows and eventually closes. Before it does so, bloodflow from the  inferior vena cava  wears down a portion of the septum primum, forming the  ostium secundum . Some embryologists postulate that the ostium secundum may be formed through  programmed cell death . [ 4 ]


The ostium secundum provides communication between the atria after the ostium primum closes completely. Subsequently, a second wall of tissue, the  septum secundum , grows over the ostium secundum in the right atrium. Blood then passes from the right to left atrium only by way of a small passageway in the septum secundum and then through the ostium secundum. This passageway is called the foramen ovale . [ citation needed ]


The foramen ovale often closes at birth. At birth, when the lungs become functional, the pulmonary vascular pressure decreases and the left atrial pressure exceeds that of the right. This forces the  septum primum  against the  septum secundum , functionally closing the foramen ovale. In time the septa eventually fuse, leaving a remnant of the foramen ovale, the  fossa ovalis .


A  fetus  receives oxygen not from its lungs, but from the mother's oxygen-rich blood via the  placenta . Oxygenated blood from the placenta travels through the umbilical cord to the right atrium of the fetal heart. As the fetal lungs are non-functional at this time, the blood bypasses them through two cardiac shunts. The first is the foramen ovale (the valve present between them called eustachian valve)  which shunts blood from the right atrium to the left atrium. The second is the  ductus arteriosus  which shunts blood from the pulmonary artery (which, after birth, carries blood from the right side of the heart to the lungs) to the descending aorta. [ citation needed ]


In about 25% of adults the foramen ovale does not close completely, but remains as a small  patent foramen ovale ("PFO") . [ 5 ]  In most of these individuals, the PFO causes no problems and remains undetected throughout life.


PFO has long been studied because of its role in  paradoxical embolism  (an  embolism  that travels from the venous side to the arterial side). This may lead to a  stroke  or  transient ischemic attack .  Transesophageal echocardiography  is considered the most accurate investigation to demonstrate a patent foramen ovale. A patent foramen ovale may also be an incidental finding.


Fundal height , or  McDonald's rule , is a measure of the size of the  uterus  used to assess  fetal growth  and development during  pregnancy . It is measured from the top of the mother's uterus to the top of the mother's pubic symphysis. Fundal height, when expressed in centimeters, roughly corresponds to gestational age in weeks between 16 and 36 weeks for a vertex fetus. When a tape measure is unavailable, finger widths are used to estimate centimeter (week) distances from a corresponding anatomical landmark. However, landmark distances from the pubic symphysis are highly variable depending on body type. In clinical practice, recording the actual fundal height measurement from the palpable top of the uterus to the superior edge of the pubic symphysis is standard practice beginning around 20 weeks gestation.


Most caregivers will record their patient's fundal height on every prenatal visit. Measuring the fundal height can be an indicator of proper fetal growth [ 1 ]  and amniotic fluid development.


Knowledge of gestational age may impact how the height is measured. [ 2 ]


A shorter measure can happen for one of the following reasons:


On the other side, a longer measure can be caused by:


As a  pregnancy  approaches its end, the fundal height will become less accurate.
Symphysiofundal height is more accurate at 14–32 weeks.


In  obstetrics ,  gestational age  is a measure of the age of a  pregnancy  taken from the beginning of the woman's  last menstrual period  (LMP), [ 1 ]  or the corresponding age of the gestation as estimated by a more accurate method, if available. Such methods include adding 14 days to a known duration since  fertilization  (as is possible in  in vitro fertilization ), or by  obstetric ultrasonography . The popularity of using this measure of pregnancy is largely due to convenience:  menstruation is usually noticed, while there is generally no convenient way to discern when fertilization or  implantation  occurred.


Gestational age is contrasted with  fertilization age , which takes the date of fertilization as the start date of  gestation . There are  different approaches to defining the start of a pregnancy . This definition is unusual in that it describes women as becoming "pregnant" about two weeks before they even had sex. The definition of pregnancy and the calculation of gestational age are also relevant  in the context of the abortion debate  and the philosophical debate over the  beginning of human personhood .


According to  American College of Obstetricians and Gynecologists , the main methods to calculate gestational age are: [ 2 ]


Gestational age can also be estimated by calculating days from  ovulation  if it was estimated from related signs or  ovulation tests , and adding 14 days by convention. [ 4 ]


A more complete listing of methods is given in following table: [ 5 ]


As a general rule, the official gestational age should be based on the actual beginning of the last menstrual period, unless any of the above methods gives an estimated date that differs more than the variability for the method, in which case the difference cannot probably be explained by that variability alone. [ 5 ]  For example, if there is a gestational age based on the beginning of the last menstrual period of 9.0 weeks, and a first-trimester obstetric ultrasonography gives an estimated gestational age of 10.0 weeks (with a 2  SD  variability of ±8% of the estimate, thereby giving a variability of ±0.8 weeks), the difference of 1.0 weeks between the tests is larger than the 2 SD variability of the ultrasonography estimate, indicating that the gestational age estimated by ultrasonography should be used as the official gestational age. [ 5 ]


Once the estimated due date (EDD) is established, it should rarely be changed, as the determination of gestational age is most accurate earlier in the pregnancy. [ 6 ]


Assessment of gestational age can be made based on selected head and trunk parameters. [ 7 ]  Following are diagrams for estimating gestational age from  obstetric ultrasound , by various target parameters:


The  fertilization or conceptional age  (also called  embryonic age  and later  fetal age ) is the time from the  fertilization . It usually occurs within a day of  ovulation , which, in turn, occurs on average 14.6 days after the beginning of the preceding menstruation (LMP). [ 8 ]  There is also considerable variability in this interval, with a 95%  prediction interval  of the ovulation of 9 to 20 days after menstruation even for an average woman who has a mean LMP-to-ovulation time of 14.6. [ 9 ]  In a reference group representing all women, the 95% prediction interval of the LMP-to-ovulation is 8.2 to 20.5 days. [ 8 ]  The actual variability between gestational age as estimated from the beginning of the last menstrual period (without the use of any additional method mentioned in previous section) is substantially larger because of uncertainty which menstrual cycle gave rise to the pregnancy. For example, the menstruation may be scarce enough to give the false appearance that an earlier menstruation gave rise to the pregnancy, potentially giving an estimated gestational age that is approximately one month too large. Also, vaginal bleeding occurs during 15–25% of first trimester  pregnancies , [ 10 ]  and may be mistaken as menstruation, potentially giving an estimated gestational age that is too low.


Gestational age is used for example for: [ citation needed ]


The mean pregnancy length has been estimated to be 283.4 days of gestational age as timed from the first day of the  last menstrual period  and 280.6 days when retrospectively estimated by  obstetric ultrasound  measurement of the  fetal biparietal diameter  (BPD) in the second trimester. [ 12 ]  Other algorithms take into account other variables, such as whether this is the first or subsequent child, the mother's race, age, length of menstrual cycle, and menstrual regularity.  In order to have a standard reference point, the normal pregnancy duration is assumed by medical professionals to be 280 days (or 40 weeks) of gestational age. Furthermore, actual childbirth has only a certain probability of occurring within the limits of the estimated due date. A study of singleton live births determined that childbirth has a  standard deviation  of 14 days when gestational age is estimated by first-trimester  ultrasound  and 16 days when estimated directly by last menstrual period. [ 11 ]


The most common system used among healthcare professionals is  Naegele's rule , which estimates the expected date of delivery (EDD) by adding a year, subtracting three months, and adding seven days to the first day of a woman's last menstrual period (LMP) or corresponding date as estimated from other means.


There is no sharp limit of development, gestational age, or weight at which a human fetus automatically becomes viable. [ 13 ]  According to studies between 2003 and 2005, 20 to 35 percent of babies born at 23  weeks of gestation  survive, while 50 to 70 percent of babies born at 24 to 25 weeks, and more than 90 percent born at 26 to 27 weeks, survive. [ 14 ]  It is rare for a baby weighing less than 500 g (17.6 ounces) to survive. [ 13 ]  A baby's chances for survival increases 3–4% per day between 23 and 24 weeks of gestation and about 2–3% per day between 24 and 26 weeks of gestation. After 26 weeks the rate of survival increases at a much slower rate because survival is high already. [ 15 ]  Prognosis depends also on medical protocols on whether to resuscitate and aggressively treat a very premature newborn, or whether to provide only  palliative care , in view of the high risk of severe disability of very preterm babies. [ 16 ]


Using gestational age, births can be classified into broad categories:


Using the LMP (last menstrual period) method, a full-term human pregnancy is considered to be 40 weeks (280 days), though pregnancy lengths between 38 and 42 weeks are considered normal. A fetus born prior to the 37th week of gestation is considered to be  preterm .  A preterm baby is likely to be  premature  and consequently faces increased risk of  morbidity  and  mortality . An estimated due date is given by  Naegele's rule .


According to the WHO, a preterm birth is defined as "babies born alive before 37 weeks of pregnancy are completed." [ 20 ]  According to this classification, there are three sub-categories of preterm birth, based on gestational age: extremely preterm (fewer than 28 weeks), very preterm (28 to 32 weeks), moderate to  late preterm  (32 to 37 weeks). [ 20 ]  Various jurisdictions may use different classifications.


For most of the 20th century, official definitions of a  live birth  and  infant death  in the  Soviet Union  and  Russia  differed from common international standards, such as those established by the  World Health Organization  in the latter part of the century. [ 21 ] [ 22 ]  Babies who were fewer than 28 weeks of gestational age, or weighed fewer than 1000 grams, or fewer than 35 cm in length – even if they showed some sign of life (breathing, heartbeat, voluntary muscle movement) – were classified as "live fetuses" rather than "live births." Only if such newborns survived seven days (168 hours) were they then classified as live births. If, however, they died within that interval, they were classified as stillbirths.  If they survived that interval but died within the first 365 days they were classified as infant deaths.


More recently, thresholds for " fetal death " continue to vary widely internationally, sometimes incorporating weight as well as gestational age. The gestational age for statistical recording of fetal deaths ranges from 16 weeks in Norway, to 20 weeks in the US and Australia, 24 weeks in the UK, and 26 weeks in Italy and Spain. [ 23 ] [ 24 ] [ 25 ]


The WHO defines the  perinatal period  as "The perinatal period commences at 22 completed weeks (154 days) of gestation and ends seven completed days after birth." [ 26 ]  Perinatal mortality is the death of fetuses or neonates during the perinatal period. A 2013 study found that "While only a small proportion of births occur before 24 completed weeks of gestation (about 1 per 1000), survival is rare and most of them are either fetal deaths or live births followed by a neonatal death." [ 23 ]


Gestational age (as well as  fertilization age ) is sometimes used postnatally (after birth) to estimate various risk factors. For example, it is a better predictor than postnatal age for risk of  intraventricular hemorrhage  in  premature babies  treated with  extracorporeal membrane oxygenation . [ 27 ]


Child's gestational age at birth (pregnancy length) is associated with various likely causal maternal non-genetic factors: stress during pregnancy, [ 28 ]  age, parity, smoking, infection and inflammation,  BMI . Also, preexisting maternal medical conditions with genetic component, e.g.,  diabetes mellitus type 1 ,  systemic lupus erythematosus ,  anaemia . Parental ancestral background (race) also plays a role in pregnancy duration. Gestational age at birth is on average shortened by various pregnancy aspects: twin pregnancy,  prelabor rupture of (fetal) membranes ,  pre-eclampsia ,  eclampsia ,  intrauterine growth restriction . [ 29 ]  The ratio between fetal growth rate and uterine size (reflecting uterine distension) is suspected to partially determine the pregnancy length. [ 30 ]


Family-based studies showed that gestational age at birth is partially (25–40%) determined by genetic factors. [ 31 ]


Hegar's sign  is a non-sensitive indication of  pregnancy  in women—its absence does not exclude pregnancy. It pertains to the features of the  cervix  and the  uterine isthmus . It is demonstrated as a softening in the consistency of the uterus, and the uterus and  cervix  seem to be two separate regions. [ 1 ]


The sign is usually present from 4–6 weeks [ 2 ]  until the 12th week of pregnancy. Hegar's sign is more difficult to recognize in  multiparous  women.


Interpretation: On bimanual examination (two fingers in the anterior fornix and two fingers below the uterus per abdomen), the abdominal and vaginal fingers seem to oppose below the body of uterus (examination must be gentle to avoid abortion). [ 3 ]


This sign was repeatedly demonstrated and described by  Ernst Ludwig Alfred Hegar , a  German   gynecologist , in 1895. Hegar credited Reinl, one of his assistants, who originally described this sign in 1884. [ 4 ]


Immunization during pregnancy  is the administration of a  vaccine  to a  pregnant  individual. [ 1 ]  This may be done either to protect the individual from disease or to induce an  antibody  response, such that the antibodies cross the  placenta  and provide  passive immunity  to the infant after birth. In many countries, including the US, [ 2 ]  Canada, [ 3 ]  UK, [ 4 ]  Australia [ 5 ] [ 6 ]  and New Zealand, [ 7 ]  vaccination against  influenza ,  COVID-19  and  whooping cough  is routinely offered during pregnancy.


Other vaccines may be offered during pregnancy where travel-related or occupational exposure to disease-causing organisms warrant this. However, certain vaccines are contra-indicated in pregnancy. These include vaccines that include  live attenuated  organisms, such as the  MMR  and  BCG  vaccines, since there is a potential risk that these could infect the fetus.


Newborns are at increased risk of infection, particularly before they receive their first infant vaccinations. For this reason, certain vaccinations are offered during pregnancy in order to induce an antibody response, resulting in the passage of  antibody  across the  placenta  and into the  fetus : this confers  passive immunity  on the newborn. As early as 1879, it was noted that infants born following smallpox vaccination in pregnancy were themselves protected against smallpox. [ 8 ]  However, the original smallpox vaccination was never widely used during pregnancy because, as a live vaccine, its use is contraindicated. [ citation needed ]


Tetanus  is a bacterial infection caused by  Clostridium tetani .  Newborns can be infected  via their unhealed umbilical stump, particularly when the umbilical cord is cut with a non-sterile instrument, and suffer a generalised infection. The  tetanus toxoid vaccine  was first licensed for use in 1938 and, during the 1960s, it was noted that tetanus vaccination in pregnancy could prevent neonatal tetanus. [ 9 ]  Subsequent trials showed that vaccination of pregnant women reduces infant deaths from tetanus by 94%. [ 10 ] [ 11 ]  In 1988, the World Health Assembly passed a resolution to use maternal vaccination to eliminate neonatal tetanus by the year 2000. Although neonatal tetanus has not yet been eliminated, by 2017 there were an estimated 31,000 annual infant deaths from tetanus, down from 787,000 in 1987. [ 12 ]


Whooping cough , or pertussis, is a contagious respiratory disease caused by the bacteria  Bordetella pertussis . It is fatal in an estimated 0.5% of infants in the USA. [ 13 ]  The first vaccine against whooping cough was developed in the 1930s, and in the 1940s a study found that vaccination in pregnancy protected infants against developing whooping cough. [ 14 ]


The tetanus and whooping cough vaccinations are generally administered in combination during pregnancy, for example as the  DTaP  vaccine (which also protects against diphtheria) or the 4-in-1 vaccine (which also protects against diphtheria and polio). [ citation needed ]


Influenza  is a respiratory infection caused by  influenza viruses . Pregnant women are disproportionately affected by influenza: in the 1918 pandemic, mortality rates as high as 27% were reported in this population and in the 1957 pandemic, nearly 20% of deaths in pregnancy were attributed to influenza. In the 2009 pandemic, even with medical advances, pregnant women accounted for a disproportionately high percentage of deaths. [ 15 ]


The influenza vaccine was first used in the US military from 1938, and then in the civilian population from the 1940s. Given the increased risk of influenza during pregnancy, public health bodies in the USA recommended that pregnant women should be prioritised for influenza vaccination from the 1960s, [ 16 ]  with the CDC endorsing the recommendation from 1997. [ 17 ]  However, it was not until 2005 that a randomised clinical trial formally demonstrated the efficacy of influenza vaccination in pregnancy. [ 18 ]


Following the 2009 pandemic, both Australia and the UK added influenza vaccination to the recommended schedule for pregnant women. [ 19 ]


COVID-19  is a respiratory infection caused by the  SARS-CoV2  virus. Before COVID-19 vaccines were available, pregnant women who caught the disease were at increased risk of needing intensive care, invasive ventilation or ECMO, but not at increased risk of death. [ 20 ]  Infection significantly increased the risk of preterm birth, stillbirth and pre-eclampsia. [ 21 ]


COVID-19 vaccination during pregnancy is safe and associated with improved levels of risk for  stillbirth ,  premature birth  and admission of the newborn to  intensive care . Vaccination can prevent COVID-19 infection during pregnancy although these immunity benefits are not passed on to the child. [ 22 ]


mRNA COVID-19 vaccines were first rolled out in December 2020. At this time, in recognition of the risks posed by COVID-19 disease in pregnancy, the US and Israel offered the vaccines to all pregnant women shortly afterwards, and the first safety and effectiveness data therefore came from these vaccines and these nations. [ 23 ]


Rubella , or German measles, is an infection caused by the  rubella virus . In childhood, it usually causes a mild disease but infection in pregnancy can result in fetal infection, or  congenital rubella syndrome , which causes neonatal deaths, deafness, blindness and intellectual disabilities. The first rubella vaccine was licensed for use in 1969, with its development largely spurred by the heavy burden of congenital rubella experienced in the 1960s. [ 24 ]


Because the rubella vaccine is a live attenuated vaccine, there is a theoretical risk that it could cause fetal infection, although this has never been seen to occur. Therefore, rubella vaccination is usually avoided during pregnancy. Rather, vaccination is offered to children to reduce the prevalence of rubella virus in circulation and/or to adolescent girls, to boost their immunity before they are likely to conceive. [ 25 ] [ 26 ]


Implantation , also known as  nidation , [ 1 ]  is the stage in the  mammalian   embryonic development  in which the  blastocyst  hatches, attaches, adheres, and invades into the  endometrium  of the female's  uterus . [ 2 ]  Implantation is the first stage of  gestation , and, when successful, the female is considered to be  pregnant . [ 3 ]  An implanted  embryo  is detected by the presence of increased levels of  human chorionic gonadotropin  (hCG) in a  pregnancy test . [ 3 ]  The implanted embryo will receive oxygen and nutrients in order to grow.


For implantation to take place the uterus must become receptive. Uterine receptivity involves much  cross-talk  between the embryo and the uterus, initiating changes to the endometrium. This stage gives a synchrony that opens a window of implantation that  enables successful implantation of a viable embryo. [ 4 ]  The  endocannabinoid system  plays a vital role in this synchrony in the uterus, influencing uterine receptivity, and embryo implantation. [ 5 ]  The embryo expresses  cannabinoid receptors  early in its development that are responsive to  anandamide   (AEA) secreted in the uterus. AEA is produced at higher levels before implantation and is then down-regulated at the time of implantation. This signaling is of importance in the embryo-uterus crosstalk in regulating the timing of embryonic implantation and uterine receptivity. Adequate concentrations of AEA  that are neither too high or too low, are needed for successful implantation. [ 5 ] [ 6 ] [ 7 ]


There is an extensive variation in the type of  trophoblast cells , and structures of the  placenta  across the different species of mammals. [ 8 ]  Of the five recognised stages of implantation including two pre-implantation stages that precede  placentation , the first four are similar across the species. The five stages are migration and hatching, pre-contact, attachment, adhesion, and invasion. [ 8 ]  The two pre-implantation stages are associated with the  pre-implantation embryo . [ 9 ] [ 10 ]


In humans, following the stage of hatching that takes place around four to five days after  fertilization , the process of implantation begins. By the end of the first week, the blastocyst is  superficially attached  to the uterine endometrium. By the end of the second week, implantation has completed. [ 11 ]


There are five recognized stages of implantation in mammals, including two pre-implantation stages that precede the  formation of the placenta . They are: migration and hatching, pre-contact, attachment, adhesion, and invasion. The first four stages are similar across the species with the process of invasion being variable. [ 8 ] [ 12 ]  These three stages of  apposition ,  attachment , and  invasion  are also alternatively termed  contact  (apposition),  adhesion  (attachment), and  penetration  (invasion), [ 10 ] [ 9 ]  and can only take place during a limited timeframe known as the  window of implantation  when the uterus is at its most receptive.


There are two stages of migration involved in implantation, the first is the migration of the  zygote , and the second is the migration of the  trophoblast . [ 13 ]  Fertilization of the oocyte, takes place in the  ampulla  of the  fallopian tube .  Cilia  on the lining of the tube move the zygote in its migration towards the uterus. [ 13 ]


During this migration the zygote undergoes  a number of cell divisions  that creates a ball of 16  compacted   blastomeres  called a  morula . [ 14 ]  The morula enters the uterus after three or four days, and as it does a cavity called the  blastocoel  is formed in the morula to produce the  blastocyst . The blastocyst contains the  inner cell mass  that will go on to develop into the  embryo  proper, and an outer cell layer of trophoblasts that will develop into the extraembryonic membranes ( fetal membranes ). [ 15 ]


The blastocyst is still enclosed in the egg-coat known as the  zona pellucida , and for it to be able to implant into the uterine wall it must rid itself of this covering. This stage is known as  zona hatching , and when there is sufficient dissolution the blastocyst is able to initiate the apposition stage of implantation.  Lytic factors  in the uterine cavity, as well as factors from the blastocyst itself are essential for the breakdown of the egg-coat. Mechanisms in the latter are indicated by the fact that the zona pellucida remains intact if an unfertilized egg is placed in the uterus under the same conditions. [ 16 ]


Among the known molecular regulators that promote hatching are predominantly  proteases  that are stimulated by various  growth factors . [ 17 ]  The blastocyst also produces  cytokines , both pro-inflammatory and anti-inflammatory, that have crucial roles during implantation and other stages of pregnancy. Both types of cytokines modulate the activity of proteases, including  MMPs ,  plasminogen  activators, and  cathepsins . [ 17 ]  It is unknown whether the cytokines involved in hatching are pro-inflammatory or anti-inflammatory, or which proteases are involved. However, it is well accepted that the pro-inflammatory cytokines are dominant during implantation. Cytokines are also present in the  uterine milk  which might regulate the development and function of the blastocyst but there is no evidence to support their involvement in hatching.  Leukemia inhibitory factor  (LIF) is a pro-inflammatory cytokine expressed in the endometrium during the  luteal phase  of the  menstrual cycle , with the highest expression seen during the window of implantation. LIF plays a role in adhesion and invasion. [ 17 ]


Assisted zona hatching  may take place in assisted reproduction, where the zona pellucida may be artificially pierced to facilitate hatching. [ 18 ]


Following zona hatching, the very first loose connection or contact between the blastocyst and the endometrium is called apposition. Apposition is usually made where there is a small crypt in the endometrium, and also where there has been enough breakdown of the zona pellucida to allow the blastocyst  trophoblast  to directly contact the underlying endometrium. Ultimately, the  inner cell mass  (also embryoblast), inside the  trophoblast  layer, is aligned closest to the  decidua . If the inner cell mass is not aligned with the decidua at apposition, it has the ability to freely rotate within the trophoblast and achieve this alignment. Apposition is only a weak interaction of the trophectoderm with the uterine epithelium that is unstable to  shear stress . Apposition is also reversible allowing repositioning of the blastocyst in the uterus. [ 14 ]


Adhesion is a much stronger attachment to the endometrium than the loose apposition. [ citation needed ]


The trophoblasts adhere by penetrating the endometrium, with protrusions of trophoblast cells. [ citation needed ]


This adhering activity is by microvilli that are on the trophoblast. The trophoblast have binding fiber connections, laminin, collagen type IV, and integrins that assist in this adhesion process. [ 19 ]


Mucin-16  is a transmembrane mucin expressed at the apical surface of uterine epithelia. This mucin prevents the blastocyst from implanting in an undesired located on the epithelium. Thus, MUC-16 inhibits cell-cell adhesion. Its removal during  pinopode  formation has been shown to facilitate trophoblast invasion  in vitro . [ 20 ]


The identity of the molecules on the trophoblast and the endometrial epithelia that mediate the initial interaction between the two remain unidentified. However, a number of research groups have proposed that  MUC1 , a member of the  mucin  family of glycosylated proteins, is involved. [ 21 ]  MUC1 is a transmembrane  glycoprotein  expressed at the apical surface of endometrial epithelial cells during the window of implantation in humans and has been shown to be differentially expressed between fertile and infertile subjects during this time. [ 21 ]  MUC1 displays carbohydrate moieties on its extracellular domain that are ligands of  L-selectin , a  cell adhesion molecule  on the surface of trophoblast cells. [ 22 ] [ 23 ]  An in vitro model of implantation gave evidence to support the hypothesis that L-selectin mediates apposition of the blastocyst to the  uterine epithelium  by interacting with its ligands. [ 24 ]


Invasion is the further establishment of the blastocyst into the endometrium. The protrusions of trophoblast cells that adhere into the endometrium continue to proliferate and penetrate into the endometrium using  gelatinases   A ( MMP-2 ), and B ( MMP-9 ). [ 25 ]  Trophoblasts invade the uterus attempting to reach maternal blood supply, for setting up the foundation for fetal blood flow. [ 26 ]  They also secrete  preimplantation factor , a peptide that helps their invasion and placenta formation. [ 27 ]  As these trophoblasts penetrate, they fuse with their neighbours, terminally differentiating into a  multinucleated  tissue, a  syncytium  known as the  syncytiotrophoblast . Between this layer and the blastocyst lies the  cytotrophoblast . [ 28 ] [ 29 ]


When the syncytiotrophoblast reaches the basal membrane beneath the  decidual cells , it dislodges them to further invade into the uterine stroma. Dislodging is accomplished by degrading the  cell adhesion molecules  (CAMs) that link the decidual cells, and the associated  extracellular matrix . Degradation is achieved by the secretion of  tumor necrosis factor-alpha  from the syncytiotrophoblast, which inhibits the expression of CAMs and  beta-catenin . The extracellular matrix is degraded by  metalloproteinases  such as  collagenases ,  gelatinases  and  matrix metalloproteinases , and by   serine proteases . [ 30 ]  The collagenases digest  types I ,  II ,  III ,  VII  and  X collagen . [ 30 ]  The gelatinases exist in two forms; one digesting  Type-IV collagen  and one digesting  gelatin . [ 30 ]  The extracellular matrix is degraded by  serine endopeptidases  and  metalloproteinases . The syncytiotrophoblast can then invade into the endometrium taking the embryo with it where it becomes embedded. [ 30 ]  Eventually, the syncytiotrophoblast comes into contact with maternal blood and forms  chorionic villi  – the beginning of  placentation . Following invasion, the breach in the uterine epithelium made by the blastocyst's entry is sealed by a  fibrin plug . The fibrin plug is a coagulation of a blood clot and cellular debris. [ 11 ]


Extravillous trophoblasts  are cells from the invading villi that migrate into the myometrium of the mother's uterus. These cells remodel the  spiral arteries  to improve and secure maternal blood flow to the growing embryo. There is also evidence that this process occurs with the uterine veins, stabilizing them to improve drainage of fetal blood and metabolic wastes. [ 31 ]  Trophoblasts have also been documented to migrate into various tissues in the mother. Due to this, trophoblasts have been implicated in a phenomenon known as  fetomaternal microchimerism  where fetal cells establish cell lines in maternal tissues. [ 32 ]


Pre-implantation blastocysts have been shown to be capable of secreting growth factors, hormones and trypsin-like proteases to participate in the hatching process. [ 33 ]


During invasion the blastocyst secretes factors for a multitude of purposes. [ 33 ]  It secretes several  autocrine  factors, targeting itself and stimulating it to further invade the endometrium.  Human chorionic gonadotropin  (hCG) is an autocrine growth factor for the blastocyst, while  insulin-like growth factor 2 , stimulates its invasiveness. [ 30 ]
Human chorionic gonadotropin not only acts as an immunosuppressive, but also  signals to the mother that she is pregnant , preventing  luteolysis  of the  corpus luteum  and menstruation by sustaining the function of the corpus luteum. [ 30 ]  Secretions loosen decidual cells from each other, prevent the embryo from being rejected by the mother, trigger the final decidualization and prevent menstruation.  Preimplantation factor  is secreted by trophoblast cells ahead of placenta formation. [ 27 ]


The embryo differs from the cells of the mother, and would be rejected as a parasite by the  immune system  of the mother if it did not secrete,  immunosuppressive  agents. Such agents include  platelet-activating factor ,  human chorionic gonadotropin ,  early pregnancy factor ,  prostaglandin E2 ,  interleukin-1 alpha ,  interleukin 6 ,  interferon -alpha,  leukemia inhibitory factor  and  colony-stimulating factor . [ citation needed ]


Other factors secreted by the blastocyst are; [ citation needed ]


To enable implantation, the  uterus  goes through changes in order to be able to receive the conceptus. Receptivity includes changes to endometrial cells in the formation of  pinopodes  that help to absorb uterine fluid; changes in the thickness of the  endometrium  and its blood supply development, and the formation of the  decidua . Collectively these changes are known as  plasma membrane transformation , and bring the  blastocyst  nearer to the endometrium and immobilize it. During this stage the blastocyst can still be eliminated by being flushed out of the uterus. [ 34 ] [ 35 ]


Successful implantation is co-dependent on the viability of the embryo, and the receptivity of the uterus. [ 4 ]  A critical involved factor is the developmental  synchrony  between the embryo and the uterus. [ 36 ]  The synchrony gives a short period of receptivity known as the window of implantation, and involves much  crosstalk  between the blastocyst and the endometrium at this stage. [ 37 ] [ 38 ] [ 39 ]


The  endocannabinoid system  plays a vital role in this synchrony in the uterus, influencing uterine receptivity, and embryo implantation. [ 5 ]  The embryo expresses  cannabinoid receptors  early in its development that are responsive to  anandamide   (AEA) secreted in the uterus. This signaling is of importance in the embryo-uterus crosstalk in regulating the timing of embryonic implantation and uterine receptivity. Adequate concentrations of AEA  that are neither too high or too low, are needed for successful implantation. [ 5 ] [ 40 ]  IL-6 and FAAH are both crucial for uterine receptivity and together with  AEA there is seen to be a link with adequate endometrial thickness that sustains pregnancy. [ 5 ]


During adhesion the cross-talk is conveyed by  receptor - ligand -interactions, both integrin-matrix and proteoglycan ones. Proteoglycan receptors are found on the surface of the decidua, and their counterparts, the proteoglycans, are found around the trophoblast cells of the blastocyst. This ligand-receptor system is also present just at the implantation window. [ 30 ]  The blastocyst signals to the endometrium to adapt further to its presence, for example by changes in the  cytoskeleton  of  decidual cells . This, in turn, dislodges the decidual cells from their connection to the underlying  basal lamina , which enables the blastocyst to perform the succeeding invasion. [ 30 ]


The  window of implantation  is a limited timeframe for the successful attachment of the blastocyst. [ 41 ]  In humans uterine receptivity is optimum on days 20-24 of the  secretory phase  of the  menstrual cycle  when  luteinizing hormone  levels are at their peak. [ 9 ] [ 42 ]  The crosstalk between the embryo and the endometrium takes place during this time. [ 9 ]  The endothelial epithelial cells lining the uterus are the first cells to detect signals from the blastocyst, and they are transduced into downstream signalling pathways. [ 33 ]  In humans the window of implantation is only available for 24–36 hours. [ 43 ]


The  endometrial microbiome  has been indicated as having an important role in successful implantation in controlling endometrial cell function, and the function of the local immunity system that prevents pathogen growth. This is associated with the secretion of protective substances. [ 44 ] [ 45 ]


Pinopodes  are formed at the beginning of the window of implantation, and are found in many species. [ 46 ] [ 41 ]  They are mushroom-like protrusions from the apical cell membrane of uterine epithelial cells. [ 41 ]  Pinopodes are formed by the swelling of these epithelial cells, and the fusing together of a number of microvilli, to reach a maximum size. [ 46 ]
They appear between day 19 and day 21 of  gestational age , and are fully formed at day 20. [ 41 ]  This corresponds to a  fertilization age  of approximately five to seven days, which corresponds well with the time of implantation. Pinopodes only persist for a maximum of two days, and are seen as the ultrastructural markers of receptivity. [ 46 ]


Their development is enhanced by  progesterone , and inhibited by  estrogens . During the window of implantation, cell to cell adhesion is inhibited by  MUC1  a cell surface glycoprotein, belonging to the  glycocalyx . The pinopodes are taller than the microvilli and protrude through the glycocalyx enabling direct contact with the adhering trophoblast. The most important attribute of pinopodes is this removal of glycoproteins from the cell surfaces of the uterine epithelial cells. [ 9 ]   MUC16  has also been shown to disappear from the cell surfaces with the development of the pinopodes.
Some studies have reported that pinopodes entrap cilia, which prevents embryo movement, and during implantation allows close contact and adherence of the embryo. [ 41 ]


Pinopodes bring uterine fluid and its macromolecules into the cells by the process of  endocytosis . This decreases the volume of the uterus, taking the walls closer to the blastocyst floating in it. Thus, the period of active pinopodes might limit the implantation window. [ 30 ]  Pinopodes continue to absorb fluid, removing most of it during the early stages of implantation. [ 47 ]


The endometrium increases thickness, becomes  vascularized  and its  glands  grow to be tortuous and boosted in their secretions. These changes reach their maximum about seven days after  ovulation . [ citation needed ]


Furthermore, the surface of the endometrium produces a kind of rounded cells, which cover the whole area toward the uterine cavity. This happens about 9 to 10 days after ovulation. [ 30 ]  These cells are called  decidual cells , which emphasises that the whole layer of them is shed off in every  menstruation  if no pregnancy occurs, just as leaves of  deciduous trees . The uterine glands, on the other hand, decrease in activity and degenerate around 8 to 9 days [ 30 ]  after ovulation in absence of pregnancy.


The decidual cells originate from the stromal cells that are always present in the endometrium, and make up a new layer, the  decidua . The rest of the endometrium, in addition, expresses differences between the luminal and the basal sides. The luminal cells form the  stratum compactum  of the endometrium, in contrast to the basalolateral  stratum spongiosum , which consists of the rather spongy stromal cells. [ 30 ]


Decidualization  expands if pregnancy occurs, further developing the uterine glands, the zona compacta and the epithelium of decidual cells lining it. The decidual cells become filled with lipids and glycogen and take the polyhedral shape characteristic of decidual cells. Factors from the blastocyst also trigger the final formation of decidual cells into their proper form. In contrast, some decidual cells in the proximity of the blastocyst degenerate, providing nutrients for it. [ 30 ]  An indication of embryonic influence is that decidualization occurs at a higher degree in conception cycles than in nonconception cycles. [ 30 ]  Furthermore, similar changes are observed when giving stimuli mimicking the natural invasion of the embryo. [ 30 ]


The embryo releases serine proteases which causes the epithelial cell membrane to  depolarize  and activates the epithelial  sodium channel . This triggers an influx of  calcium ions  (Ca 2+ ) and phosphorylation of CREB. Phosphorylation of CREB upregulates the expression of  COX2 , which leads to the release of prostaglandin E2 (PGE2) from epithelial cells. PGE2 acts on the stroma cells activating cAMP-related pathways in stromal cell leading to decidualization. [ 48 ]


The decidua can be organized into separate sections, although they have the same composition.


After implantation the decidua remains, at least through the first trimester. [ 30 ]  However, its most prominent time is during the early stages of pregnancy, during implantation. Its function as a surrounding tissue is replaced by the definitive  placenta . However, some elements of the decidualization remain throughout pregnancy. [ 30 ]


The compacta and spongiosa layers are still observable beneath the decidua in pregnancy. The glands of the spongiosa layer continue to secrete during the first trimester, when they degenerate. However, before that disappearance, some glands secrete unequally much. This phenomenon of hypersecretion is called the  Arias-Stella phenomenon , [ 30 ]  after the pathologist  Javier Arias-Stella .


secreted by the  uterine glands [ 30 ]


Not only the lining of the uterus transforms, but the secretion from its  glands  changes. This change is induced by increased levels of  progesterone  from the  corpus luteum . The target of the secretions is the embryoblast, and has several functions on it.


The embryo spends approximately 72 hours in the uterine cavity before implanting. In that time, it cannot receive nourishment directly from the blood of the mother, and must rely on secreted nutrients into the uterine cavity, e.g. iron and fat-soluble vitamins. [ 30 ]


In addition to nourishment, the endometrium secretes several  steroid -dependent proteins, important for growth and implantation.  Cholesterol , and steroids are also secreted. [ 30 ]   Implantation is further facilitated by synthesis of  matrix  substances,  adhesion molecules  and surface  receptors  for the matrix substances.


Reproduction in humans is not very efficient. Only around 30% of natural conceptions result in successful pregnancies. Of the failed pregnancies around 85% are due to implantation failure. [ 49 ]  Implantation failure is considered to be caused by inadequate uterine receptivity in two-thirds of cases, and by problems with the embryo itself in the other third. [ 50 ]  Most  IVF  procedures fail because of implantation failure accounting for almost half of all pregnancy failures. [ 49 ]


Inadequate uterine receptivity may be caused by abnormal  cytokine  and hormonal signaling as well as  epigenetic alterations . [ 51 ]  Recurrent implantation failure is a cause of  female infertility . Therefore,  pregnancy rates  can be improved by optimizing endometrial receptivity for implantation. [ 51 ]  Evaluation of implantation markers may help to predict pregnancy outcome and detect occult implantation deficiency. [ 51 ]  As part of the  organ-on-a-chip  program, an  endometrium-on-a-chip  has been developed to model the functioning of the endometrium that could more clearly identify causes of implantation failure. [ 52 ]   Organoids  have also been developed to model the endometrium and its role in implantation. [ 53 ]


In women with more than  three implantation failures  in  assisted reproduction , a review of several small  randomized controlled studies  estimated that the use of adjunct  low molecular weight heparin  improves  live birth rate  by approximately 80%. [ 54 ]   Luteal phase support  can include the use of  progesterone  and  human chorionic gonadotropin  (hCG) to improve the chances of a successful implantation. [ 55 ]


Zinc  is crucial in pre-conception, (and successful pregnancy), and its  deficiency  can lead to incompetent blastocyst development. Once an egg is fertilized zinc is released in a  zinc spark  which promotes changes that include the hardening of the zona pellucida preventing  polyspermy . [ 56 ]


Bleeding and spotting are common during the luteal phase of the menstrual cycle, and early stages of pregnancy, but are unrelated to implantation. Implantation bleeding occurs between 7 and 14 days after fertilization, [ 57 ]  and is a small amount of light  vaginal bleeding  or spotting that can occur in early pregnancy due to the blastocyst penetrating the lining of the uterus during implantation. [ 58 ] [ 59 ] [ 60 ]  By day 13 the penetration site in the endometrium has usually been closed by a  fibrin plug  but increased blood flow into the syncytiotrophoblast spaces can sometimes cause bleeding at that site. [ 58 ]  Implantation bleeding may be accompanied by symptoms such as cramping, nausea, breast tenderness, and headaches. [ 61 ]  Implantation bleeding can be distinguished from  period bleeding  by color, clotting, strength and duration of flow. [ 62 ] [ 63 ]


In  human reproduction , a  live birth  occurs when a  fetus  exits the mother showing any definite sign of life such as  voluntary movement ,  heartbeat , or pulsation of the  umbilical cord , for however brief a time and regardless of whether the umbilical cord or  placenta  are intact. [ 1 ]  After the fetus is expelled from the maternal body it is called a  neonate . Whether the  birth  is  vaginal  or by  caesarean section , and whether the neonate is ultimately viable, is irrelevant.


The definition of the term "live birth" was created by the  World Health Organization  in 1950, and is chiefly used for public health and statistical purposes. However, the term "live birth" was in common use long before 1950. [ 2 ]


In the United States, the term "born alive" is defined by federal law [ 3 ]  known as the  born alive rule . Live births are recorded on a U.S. Standard Certificate of Live Birth, also known as a  birth certificate . [ 4 ]  The United States recorded 3,605,201 live births in 2020 which is a 4% decrease from 2019 and the 6th consecutive year of decline in births. [ 5 ]


Not all pregnancies result in live births. A woman may choose to end her pregnancy by  abortion .  Miscarriage , also known as spontaneous abortion and pregnancy loss, is the natural death of an  embryo  or fetus before it is  able to survive independently . [ 6 ] [ 7 ]  Some use the cutoff of 20 weeks of  gestation , after which fetal death is known as a  stillbirth . [ 8 ]  The death of the fetus or neonate at the end of the pregnancy, during labour and delivery, or just after birth is counted as  perinatal mortality .


Measured in weeks, gestational age is a term used to describe how far along a pregnancy is starting from the first day of the woman's last menstrual cycle to the current date. [ 9 ]  A baby born "at term" is between the gestational age of 37 weeks to 41 weeks. A  preterm  baby is born before the gestational age of 37 weeks. A pregnancy that lasts 41 weeks up to 42 weeks is called  late-term  and a pregnancy longer than 42 weeks is called  post-term . [ 10 ]  The general consensus is that a fetus is viable at 24 weeks, however, a live birth may occur earlier in gestation with the assistance from  neonatal intensive care unit  (NICU) resources. Gestational age is the main determinant of whether a baby will be able to live and survive outside of the  uterus .


While gestational age is the most significant predictor of fetal viability, the condition of the neonate at birth also significantly indicates how well it tolerates life outside of the mother. Factors measured at birth include birth weight, head circumference, and body length. An  Apgar score  is given at the time of birth to report the status of the newborn infant and the response to resuscitation if needed. [ 11 ]


The maternal recovery period directly following the events of human  childbirth , regardless of whether it is a live birth, is called the  postpartum period .


There is one case report of a woman having a live birth derived from a frozen embryo obtained before she began cancer treatment. [ 12 ]


In the field of  obstetrics ,  lochia  is the  vaginal discharge  after giving birth, containing  blood ,  mucus , and  uterine  tissue. [ 1 ]  Lochia discharge typically continues for four to eight weeks after  childbirth , [ 2 ]  a time known as the  postpartum period  or puerperium. A 2016 review ties this "lochial period" to worldwide customs of  postpartum confinement , a time for the new mother and baby to bond. [ 3 ]


Lochia is sterile for the first two days, but not so by the third or fourth day, as the uterus begins to be colonized by vaginal commensals such as non-hemolytic  streptococci  and  E. coli . [ 4 ]  The  Cleveland Clinic  recommends that pads be used instead of tampons to absorb the fluid as materials should not be inserted in the vagina soon after childbirth. [ 5 ]


It progresses through three stages: [ 6 ]


In general, lochia has an odor similar to that of normal menstrual fluid. Any offensive odor or change to a greenish color indicates contamination by organisms such as chlamydia or  staph saprophyticus . [ 8 ]


Lochia that is retained within the uterus is known as  lochiostasis [ 9 ]  or lochioschesis, and can result in  lochiometra [ 10 ]  (distention of the uterus - pushing it out of shape).  Lochiorrhea  describes an excessive flow of lochia and can indicate infection. [ 11 ]


The  low birth-weight paradox  is an apparently  paradoxical  observation relating to the  birth weights  and  mortality rate  of children born to  tobacco smoking  mothers.  Low birth-weight  children born to  smoking mothers  have a  lower   infant mortality  rate than the low birth weight children of non-smokers. It is an example of  Simpson's paradox .


Traditionally, babies weighing less than a certain amount (which varies between countries) have been classified as having  low birth weight . In a given population, low birth weight babies have a significantly higher  mortality  rate than others; thus, populations with a higher rate of low birth weights typically also have higher rates of child mortality than other populations.


Based on prior research, the children of smoking mothers are more likely to be of low birth weight than children of non-smoking mothers.  Thus, by extension the child mortality rate should be higher among children of smoking mothers.  So it is a surprising real-world observation that low birth weight babies of smoking mothers have a lower child mortality than low birth weight babies of non-smokers.


At first sight these findings seemed to suggest that, at least for some babies, having a smoking mother might be beneficial to one's health. However the paradox can be explained  statistically  by uncovering a  lurking variable  between smoking and the two key variables: birth weight and risk of mortality. Both variables are acted on independently by smoking and other adverse conditions—birth weight is lowered and the risk of mortality increases. However, each condition does not necessarily affect both variables to the same extent.


The birth weight  distribution  for children of smoking mothers is shifted to lower weights by their mothers' actions. Therefore, otherwise healthy babies (who would weigh more if it were not for the fact their mother smoked) are born underweight. However, they still have a lower mortality rate than children who have other, more severe, medical reasons why they are born underweight.


In short, smoking is harmful in that it contributes to low birth weight which has higher mortality than normal birth weight, but other causes of low birth weight are generally  more  harmful than smoking.


If one corrects and adjusts for the confounding by smoking, via stratification or multivariable regression modelling to statistically control for smoking, one finds that the association between birth weight and mortality may be attenuated towards the null. Nevertheless, most epidemiological studies of birth weight and mortality have controlled for maternal smoking, and the adjusted results, although attenuated after adjusting for smoking, still indicated a significant association.


Additional support for the hypothesis that birth weight and mortality can be acted on independently came from the analysis of birth data from  Colorado : compared with the birth weight distribution in the US as a whole, the distribution curve in Colorado is also shifted to lower weights. The overall child mortality of Colorado children is the same as that for US children however, and if one corrects for the lower weights as above, one finds that babies of a given (corrected) weight are just as likely to die, whether they are from Colorado or not. The likely explanation here is that the higher altitude of Colorado affects birth weight, but not mortality.


The  Malinas score  is an  evaluation  that allows to determine whether a  pregnant woman  is about to  give birth . [ 1 ]  It was invented by  Yves Malinas  ( French   physician , died 20 January 1997).


It is mainly used in case of unexpected prehospital cases: the score indicates if it is possible to transport the pregnant woman or if it is best to let her give birth onsite. It is based on five criteria: how many times she has been pregnant, the duration of the labour so far, the duration of each contraction, the interval between two contractions, and whether or not her waters have broken. Each criterion is evaluated by a number between zero and two:


The score is the sum of these five criteria. When the score is less than five, it is possible to transport the pregnant woman to a  maternity hospital  or a medical structure. When the score is six or more, an imminent  parturition  (i.e. childbirth) is likely, especially if the woman feels a need to push.


In a study published in 2001, it was suggested that the Malinas Score alone was not a reliable indicator of imminent birth as approximately 25% of unplanned homebirths in the study had a Malinas Score of less than five. [ 2 ]  An amended scoring system has been proposed which would add additional scores for hemorrhaging, whether the expectant mother was panicking and how long transport to the hospital would take. This amended system would result in the pregnant woman being transported on a score less than seven. [ 1 ]


Maternal health  is the health of people during  pregnancy ,  childbirth , and the  postpartum period . In most cases, maternal health encompasses the  health care  dimensions of  family planning ,  preconception ,  prenatal , and  postnatal  care in order to ensure a positive and fulfilling experience. In other cases, maternal health can reduce maternal morbidity and  mortality . [ 1 ]  Maternal health revolves around the health and wellness of pregnant individuals, particularly when they are pregnant, at the time they give birth, and during child-raising.  WHO  has indicated that even though motherhood has been considered as a fulfilling natural experience that is emotional to the mother, a high percentage of women develop health problems, sometimes resulting in death. [ 2 ]  Because of this, there is a need to invest in the health of women. The investment can be achieved in different ways, among the main ones being subsidizing the healthcare cost, education on maternal health, encouraging effective family planning, and checking up on the health of individuals who have given birth. [ 3 ]  Maternal morbidity and mortality particularly affects women of color and women living in low and lower-middle income countries. [ 4 ] [ 5 ]


WHO estimates that about 295,000 maternal deaths occurred in 2017. [ 6 ]  The causes of these maternal deaths range from severe bleeding to obstructed labour, all of which have highly effective interventions. Further, indirect causes of maternal mortality include anemia and malaria. [ 6 ]  As women have gained access to family planning and skilled birth attendance with backup emergency obstetric care, the global maternal mortality has fallen by about 44 percent, which represented a decline of about 2.3 percent annually over the period from 1990 to 2015. While there has been a decline in worldwide mortality rates after much efforts, high rates still exist particularly in low and middle income countries (99%).  Sub-saharan Africa  accounts for approximately two thirds of these deaths and South Asia accounts for about one-fifth of them. [ 7 ]  One third of the maternal deaths occur in India and Nigeria. [ 8 ]   The effect of a mother's death results in vulnerable families, and their  infants , if they survive childbirth, are more likely to die before reaching their second birthday. [ 9 ]


Both  maternal mortality  (death) and severe maternal morbidity (illness) are "associated with a high rate of preventability." [ 10 ]


In 2010 the U.S.  Joint Commission on Accreditation of Healthcare Organizations  described maternal mortality as a " sentinel event ", and uses it to assess the quality of a health care system. [ 11 ]


Subsidizing the cost of healthcare will help improve the health status of women. However, the health status of women should not be generalized with that of the other category of people. Countries such as the U.S, U.K, and others have laws where government and non-governmental bodies work to reduce and even eliminate any fee that is directed to pregnant women or women who have health issues that are related to pregnancy. When women deliver their babies in certified healthcare facilities without paying or paying a very small amount of money, they are motivated to use their own money on the diet of the baby, clothing, and other needs. [ 12 ]  Also, when women attend clinics without being charged and are issued with free supplements, their health is maintained, and this reduces the cost that the monetary resources that the government invests in healthcare. In turn, the maternal morbidity rate, together with mortality rates, is lowered. [ 13 ]


Education on various issues related to maternal health is essential to control and improve the healthcare of women. Women who have the resources have a  low chance of their health status deteriorating because of the knowledge they have. These women are informed to make decisions regarding family planning, the best time to give birth as far as their financial capabilities are concerned, and their nutrition, before, during, and after giving birth. Additionally, many approaches involving women, families, and local communities as active stakeholders in interventions and strategies to improve maternal health. [ 14 ]  Gannon (n.p) reports that the maternal rate of mortality reduced by 70% between 1946 and 1953, when women started getting maternal education. The study has recommended that the study should focus on communities that are marginalized and girls who are below the age of 18. When the government manages to reduce unwanted and unplanned pregnancies among these two groups of people, it will become easier to reduce the maternal health issue and the cost associated with it. [ citation needed ]


According to a  UNFPA  report, social and economic status, culture norms and values, and geographic remoteness all increase maternal mortality, and the risk for maternal death (during pregnancy or childbirth) in sub-Saharan Africa is 175 times higher than in developed countries, and risk for pregnancy-related illnesses and negative consequences after birth is even higher. [ 15 ]   Poverty , maternal health, and outcomes for the child are all interconnected. [ 16 ]


Women living in poverty-stricken areas are more likely to be  obese  and engage in unhealthy behaviors such as  cigarette smoking  and substance use, are less likely to engage in or even have access to legitimate prenatal care, and are at a significantly higher risk for adverse outcomes for both the mother and child. [ 17 ]  A study conducted in Kenya observed that common maternal health problems in poverty-stricken areas include hemorrhaging,  anemia ,  hypertension , malaria, placenta retention,  premature labor , prolonged/complicated labor, and  pre-eclampsia . [ 18 ]


Generally, adequate prenatal care encompasses medical care and educational, social, and nutritional services during pregnancy. [ 19 ]  For example, prenatal care could include serum integrated screening tests for potential chromosomal abnormalities as well as blood pressure measurements, or uterus measurements to assess fetal growth. Although there are a variety of reasons women choose not to engage in proper prenatal care, 71% of low-income women in a US national study had difficulties getting access to prenatal care when they sought it out. [ 19 ]  Additionally, immigrants and Hispanic women are at higher risk than white or black women for receiving little to no prenatal care, where level of education is also an indicator (since education and race are correlated). Adolescents are least likely to receive any prenatal care at all. Throughout several studies, women and adolescents ranked inadequate finances and lack of transportation as the most common barriers to receiving proper prenatal care. [ 20 ]


Income is strongly correlated with quality of prenatal care. [ 20 ]   Sometimes, proximity to healthcare facilities and access to transportation have significant effects on whether or not women have access to prenatal care.  An analysis conducted on maternal healthcare services in Mali found that women who lived in rural areas, far away from healthcare facilities were less likely to receive prenatal care than those who lived in urban areas.  Furthermore, researchers found an even stronger relationship between lack of transportation and prenatal and delivery care. [ 21 ]  In addition to proximity being a predictor of prenatal care access, Materia and colleagues found similar results for proximity and antenatal care in rural Ethiopia. [ 22 ]  Also, inadequate and poor quality services contributes in increasing maternal morbidity and mortality. [ 23 ]


Pre-existing (pregestational) maternal Type 1 or Type 2 diabetes is a known factor that increases the risk of adverse outcomes, including pre-term birth, preeclampsia, and congenital birth defects. [ 24 ]  Studies from the United States and Australia indicate that the prevalence of pregestational diabetes is around 1% of pregnancies. [ 24 ] [ 25 ]  Even healthy pregnancy causes a state of hyperglycemia. As a result, mothers with pregestational diabetes are at an increased risk for hyperglycemia. [ 26 ] [ 27 ]


Maternal HIV rates vary around the world, ranging from 1% to 40%, with African and Asian countries having the highest rates. [ 28 ]   Whilst maternal HIV infection largely has health implications for the child, [ 29 ]  especially in countries where poverty is high and education levels are low, [ 30 ]  having HIV/AIDS while pregnant can also cause heightened health risks for the mother. [ 31 ]  A large concern for HIV-positive pregnant women is the risk of contracting tuberculosis (TB) and/or malaria, in developing countries. [ 28 ]  28% of maternal deaths are from  obstructed labour  and indirect causes, meaning diseases that complicate pregnancy or that are complicated by pregnancy (malaria, anemia, HIV/AIDS, and cardiovascular diseases). [ 8 ]


During pregnancy, women of an average pre-pregnancy weight ( BMI  18.5-24.9) should expect to gain between 25–35 pounds (11–16 kg) over the course of the pregnancy. [ 32 ]  Increased rates of hypertension, diabetes, respiratory complications, and infections are prevalent in cases of maternal obesity and can have detrimental effects on pregnancy outcomes. [ 33 ]  Obesity is an extremely strong risk factor for  gestational diabetes . [ 34 ]  Research has found that obese mothers who lose weight (at least 10 pounds or 4.5 kg) between pregnancies reduce the risk of gestational diabetes during their next pregnancy, whereas mothers who gain weight actually increase their risk. [ 35 ]  Women who are pregnant should aim to exercise for at least 150 minutes per week, including muscle strengthening exercises. [ 36 ]  However, it is recommended that pregnant women discuss what exercise they can do safely with their OB/GYN in the early prenatal period. [ 37 ]


Vigorous Exercise


The current guidelines for moderate intensity activity during pregnancy have been outlined by organizations such as the WHO and ACOG to be the same 150 minutes per week as regular physical activity guidelines. [ 38 ]  Certain modifications such as avoiding supine position after 20 weeks are also recommended.  [ 38 ]  Vigorous activity guidelines during pregnancy have not been outlined as clearly or studied as much, so consulting a healthcare professional to get a safe, tailored,  fitness plan is recommended. Current research supports that vigorous activity for most non-complicated singleton pregnancies is beneficial and has little negative impact on fetal wellbeing. [ 39 ] [ 40 ]  It has also been shown to have similar benefits to those who perform the same level of activity outside of pregnancy.  [ 40 ]  The concerns related to high intensity exercise during pregnancy are usually around fetal wellbeing measures such as heart rate and blood flow. No abnormal measures of fetal distress, such as heart rate or maternal/fetal blood flow [ 39 ] were found during high intensity/vigorous exercise, if the mother stayed under 90% of her heart rate maximum. [ 40 ]   [ 39 ]  Risks of exceeding this heart rate included decreased uterine artery blood flow and fetal bradycardia. [ 40 ] [ 41 ]  If using vigorous exercise as a means of lowering maternal weight gain during pregnancy, it's important to note there is little evidence to suggest that higher intensity has more of an effect than moderate intensity activity on normal pregnancies; [ 41 ] [ 40 ]  It was shown in one study that the obese/overweight population during pregnancy had improved maternal weight gain with more vigorous exercise compared to moderate although more studies are needed. [ 41 ]  When related to birth outcome measures such as mode of delivery, pain control, and duration all were unaffected when compared to moderate intensity. [ 40 ] [ 41 ] High intensity exercises such as stationary biking, uphill running, cross country skiing, and resistance circuit training, all showed similar benefits.  [ 41 ] [ 40 ]


It is important to further study the effects and limitations of vigorous exercise during pregnancy as it becomes more prevalent for female athletes, and in the average population. Overall if one is already performing vigorous activity before pregnancy, no negative effects were found with the continuation of similar activity levels during pregnancy, if staying under 90% of the mothers heart rate maximum. [ 39 ] [ 41 ] [ 40 ]  Always consult a physician to ensure any physical activity performed is safe during pregnancy, as the recommended amount of physical activity can depend on other factors during pregnancy as well.


During and after pregnancy, mothers should receive continuous care from a physician, in-person or via telehealth depending on the need, [ 42 ]  to monitor the growth and status of the fetus. Maternal health organizations suggest that at a minimum pregnant women should receive one ultrasound at week 24 to help predict any possible growth anomalies and prevent future gestational concerns. [ 43 ]  It is also stated that pregnant women should also fulfill any missing vaccinations as soon as possible including the tetanus vaccine and influenza vaccine. [ 44 ] [ 45 ]  For pregnant women who are at an increased risk for  Pre-eclampsia , one could take a dietary supplement of low dose aspirin as prophylaxis before 20 weeks gestation. [ 43 ]  Pregnant women should also monitor their blood sugars as they are able to monitor the potential development of gestational diabetes. Other prenatal screening tests include serum integrated protein tests, cell free DNA blood tests to check for chromosomal abnormalities, and nuchal translucency ultrasounds. If their medical system is able to provide them, mothers can also undergo more invasive diagnostic tests such as an amniocentesis, or chorionic villous sampling to detect abnormalities with greater accuracy. [ 46 ] [ 47 ]


Analysis of the Pregnancy Mortality Surveillance System, conducted by the Center for Disease Control and Prevention (CDC), indicates significant racial and ethnic disparities in pregnancy related deaths. [ 48 ]  The pregnancy related mortality ratio (PRMR) represents the number of deaths per 100,000 live births resulting from pregnancy or pregnancy related causes. A 2019 report from the CDC shows that the PRMRs of Black women and Indigenous women in the United States are 3-4 times higher than that of White women. White women had a PRMR of approximately 13 maternal deaths per 100,000 live births. While Black and Indigenous women had PRMRs of 41 and 30 maternal deaths per 100,000 live births respectively. The majority of these deaths were due to preventable diseases associated with pregnancy  such as hypertension. While the fatality rate of these diseases was higher among Black and Indigenous women, the initial prevalence was generally the same across all races. [ 49 ]  Although lower than that of Black and Indigenous women, the PRMR for Asian and Pacific Islander women was still slightly higher than that of the white women at 13.5. [ 49 ]  The PRMR for Hispanic women has shown a decline in recent years. However, state specific reports show that Hispanic women still face high rates of maternal morbidity, or health problems that arise from pregnancy and birth. [ 50 ]


The CDC cites multiple causes for the racial gap in maternal mortality. They say that most pregnancy related deaths are the combined result of 3-4 contributing factors. Some of these factors include higher rates of chronic conditions in minor communities, [ 51 ]  lower rates of prenatal care, [ 52 ]  and lower rates of insurance coverage. [ 52 ]  Furthermore, teen pregnancy rates are higher in minority communities, which is a risk factor for pregnancy or birth complications. [ 52 ]  Black and Indigenous women can also encounter racial bias held by healthcare providers, which affects the quality of care given to treat or prevent a fatal disease. For example, an NIH report states that Black women are two to three times more likely to die of hemorrhage or embolisms during pregnancy or the postpartum period. [ 53 ]  Outside of provider-patient interactions, structural factors can contribute to the racial gap in maternal mortality. This includes the gap in access to primary and preventative care as well as other social determinants of health such as education and community support. [ 52 ]   Chronic conditions such as high blood pressure and hypertension can cause pregnancy complications and maternal morbidity, and these conditions arise from the effects of the  weathering hypothesis . [ 54 ]   The weathering hypothesis also states a higher rate of preterm birth among Black pregnant people in the United States, which is not only dangerous for the baby but also has effects on the birth parent. A Black birth parent of a preterm baby is more likely to experience high blood pressure following a preterm birth and subsequent higher rates of coronary artery calcification. [ 55 ]


There are many factors that influence maternal health and the access of resources. One of these factors that recent studies have highlighted is religion. For example, one such study stated that, due to the insensitivity and lack of knowledge that physicians showed immigrant Muslim women in Canada, their health information and treatment suffered. [ 56 ]  The health care that they received from physicians did not provide information in respect to their religious or cultural practices and did little to provide cultural adjustments and emotional support. [ 56 ]  In order to provide a safer and more comfortable environment for Muslim women, it was proven that they needed more support that would connect with the immigrant community and health-related information. [ 56 ]  Discrimination based on religion is a factor that effects the maternal health care of women from different backgrounds. There is not a lot of discussion on the studies that reflect the hardships that women go through in terms of their religion and maternal care. Stigmatizing certain maternal and reproductive practices is common within the context of religion. For example, in a study that focused on interviewing women who have had abortions, one participant used the word "guilt" 16 times in her one-hour interview. [ 57 ]  She cited that the cause of her guilt was because of her Catholic upbringing. [ 57 ]  The overall data showed that there was a strong relationship between religion and self-stigma. [ 57 ]  Among the women who identified as a practicing Christian, 65% made statements that proved self-stigma effects. [ 57 ]  There is a lot of stigma and norms regarding religion that, in turn, place women at risk when receiving health-care. [ 58 ]  Other religious practices and traditions have shown to influence maternal health in a negative way. Practitioners of apostolicism in Zimbabwe have been associated with higher maternal mortality. [ 59 ]  Results of a study showed the dangerous associations that religion may have on maternal health. [ 59 ]  The general trend shows that Apostolicism promotes high fertility, early marriage, non-use of contraceptives and low or non-use of hospital care. [ 59 ]  There are delays in recognizing danger signs, deciding to seek care and receiving appropriate health care. [ 59 ]  Future studies can look at how societal traditions or expectations such as gender roles may combine with religion to result in poorer maternal health care. [ citation needed ]


Although factors of religion can negatively influence maternal health care, other studies show the necessity of understanding different religious beliefs and practices. In Ghana, interviews of women showed the benefits of transparent religious beliefs and practices while pregnant and in labor. [ 60 ]  Spiritual interventions done by pastors in pregnancy included prayer, revelations, reversing negative dreams, laying of hands and anointing women. [ 60 ]  Religious artifacts used among the women during pregnancy and labor were anointing oil, blessed water, stickers, blessed white handkerchief, blessed sand, Bible and Rosary. [ 60 ]  The women made many connections to these practices and to their religion such as God having the capability to reduce labor pain and to provide a safe and successful delivery. [ 60 ]  The results concluded that spirituality is an integral part of the care of pregnant women in Ghana. [ 60 ]  In order to ensure the safety of these women, their religious practices should not be in secrecy. [ 60 ]  The presence of artifacts implies that women do not have the freedom to practice their religion at home. [ 60 ]  It was concluded that pastors should be sensitive to their role in the labor process and that revelations and spiritual interventions should not lead to pregnancy or labor complications. [ 60 ]  Future studies in religion and maternal health care will focus on the role of pastors, familiar support, and the views of midwives or health care professionals in different societies around the world.


Prenatal care  is an important part of basic maternal health care. [ 61 ]  It is recommended expectant mothers receive at least four antenatal healthcare visits, in which a health worker can check for signs of illness – such as underweight, anaemia or infection – and monitor the health and status of the fetus. [ 62 ]  During these visits, women are counselled on nutrition and hygiene to optimize their health prior to, and following, delivery. These visits can also include health maintenance of any pre-existing health conditions the woman may have had prior to becoming pregnant - such as diabetes, hypertension, or renal disease. In collaboration with her healthcare provider, the patient can develop a birth plan which outlines how to reach care and what to do in the event of an emergency. [ citation needed ]


The model CenteringPregnancy (group prenatal care) is a relatively new addition to prenatal healthcare, and has shown to improve both birth outcomes and patient & provider satisfaction. [ 63 ]  Specifically, a randomized controlled trial indicated a 33 percent reduction in preterm birth (n=995), and the decrease was even more pronounced for Black/African American participants. [ 64 ]  CenteringPregnancy provides physical exams, education, and peer support to a group of pregnant women who all have a similar due date. [ 63 ]  Research in race concordant group prenatal care (like the EMBRACE group at UCSF) has not yet been researched enough to indicate improved outcomes. [ 65 ]  Nonetheless, race concordant care has been proven to improve patient experience [ 66 ]  and patient & provider communication. [ 67 ]  Moreover, newborn-physician racial concordance was significantly associated with mortality improvements for Black infants. [ 68 ]


Poverty, malnutrition, and substance use may contribute to impaired cognitive, motor, and behavioral problems across childhood. [ 69 ]  In other words, if a mother is not in optimal health during the prenatal period (the time while she is pregnant) and/or the fetus is exposed to teratogen(s), the child is more likely to experience health or developmental difficulties, or death. The environment in which the mother provides for the embryo/fetus is critical to its wellbeing well after gestation and birth.


A  teratogen  is "any agent that can potentially cause a birth defect or negatively alter cognitive and behavioral outcomes." [ 70 ]  Dose, genetic susceptibility, and time of exposure are all factors for the extent of the effect of a teratogen on an embryo or fetus. [ 71 ]


Prescription drugs taken during pregnancy such as streptomycin, tetracycline, some antidepressants, progestin, synthetic estrogen, and Accutane, [ 72 ] [ 73 ]  as well as over-the-counter drugs such as diet pills, can result in teratogenic outcomes for the developing embryo/fetus.  Additionally, high dosages of aspirin are known to lead to maternal and fetal bleeding, although low-dose aspirin is usually not harmful. [ 74 ] [ 75 ]


Newborns whose mothers use heroin during the gestational period often exhibit withdrawal symptoms at birth and are more likely to have attention problems and health issues as they grow up. [ 76 ]  Use of stimulants like methamphetamine and cocaine during pregnancy are linked to a number of problems for the child such as  low birth weight  and small head circumference, motor and cognitive developmental delays, as well as behavioral problems across childhood. [ 77 ] [ 78 ] [ 79 ] [ 80 ]  The  American Academy of Child and Adolescent Psychiatry  found that six-year-olds whose mothers had smoked during pregnancy scored lower on an intelligence test than children whose mothers had not. [ 81 ]


Cigarette smoking during pregnancy can have a multitude of detrimental effects on the health and development of the offspring.  Common results of smoking during pregnancy include pre-term births, low birth weights, fetal and neonatal deaths, respiratory problems, and  sudden infant death syndrome  (SIDS), [ 71 ]  as well as increased risk for cognitive impairment, attention deficit hyperactivity disorder (ADHD) and other behavioral problems. [ 82 ]  Also, in a study published in the International Journal of Cancer, children whose mothers smoked during pregnancy experienced a 22% risk increase for non-Hodgkin lymphoma. [ 83 ]


Although alcohol use in careful moderation (one to two servings a few days a week) during pregnancy are not generally known to cause  fetal alcohol spectrum disorder  (FASD), the US Surgeon General advises against the consumption of alcohol at all during pregnancy. [ 84 ]  Excessive alcohol use during pregnancy can cause FASD, which commonly consist of physical and cognitive abnormalities in the child such as facial deformities, defective limbs, face, and heart, learning problems, below average intelligence, and intellectual disability (ID). [ 85 ] [ 86 ]


Although HIV/AIDS can be transmitted to offspring at different times, the most common time that mothers pass on the virus is during pregnancy. During the perinatal period, the embryo/fetus can contract the virus through the placenta. [ 71 ]


Gestational diabetes  is directly linked with obesity in offspring through adolescence. [ 87 ]  Additionally, children whose mothers had diabetes are more likely to develop  Type II diabetes . [ 88 ]  Mothers who have gestational diabetes have a high chance of giving birth to very large infants (10 pounds (4.5 kg) or more). [ 71 ]  This is a cause of macrosomia. Neonates with macrosomia have significantly increased rates of hypoglycemia compared to infants of mothers without diabetes. This is because macrosomic neonates are used to high levels of circulating blood sugars in utero, which results in naturally high levels of insulin. At birth, when the gestational source of blood sugar is abruptly removed, this causes the neonates to experience severe drops in blood sugar. [ 89 ]


Because the embryo or fetus's nutrition is based on maternal protein, vitamin, mineral, and total caloric intake, infants born to malnourished mothers are more likely to exhibit malformations. Additionally, maternal stress can affect the fetus both directly and indirectly.   When a mother is under stress, physiological changes occur in the body that could harm the developing fetus. Additionally, the mother is more likely to engage in behaviors that could negatively affect the fetus, such as  tobacco smoking , substance use, and alcohol use. [ 71 ]


Genital herpes , rubella, cytomegalovirus, varicella, parvovirus B19, and enteroviruses can be passed to the baby through the birth canal during delivery. [ 90 ] [ 91 ] [ 92 ]  In pregnancies where the mother is infected with the virus, 25% of babies delivered through an infected birth canal become brain damaged, and 1/3 die. [ 71 ]  HIV/AIDS can also be transmitted during childbirth through contact with the mother's body fluids or transmission to the fetus via the placenta. [ 71 ]  Mothers in developed countries may often elect to undergo a caesarean section to reduce the risk of transmitting the virus through the birth canal, but this option is not always available in developing countries. [ 93 ]