Etiology and Epidemiology of Twin Pregnancy
Twin pregnancy may result from the fertilization of two oocytes by two sperms, generating
dizygotic twins, or from the fertilization of a single oocyte that will subsequently
split into two similar structures, each capable of developing an individual, generating
monozygotic twins.[6]
[12]
Dizygotic pregnancies are the majority and occur spontaneously due to an increased
concentration of follicle-stimulating hormone (FSH) in the woman.[6] Therefore, the risk factors for its occurrence are: geography (it occurs more frequently
in countries with milder climate),[6] ethnicity (black ethnicity),[8] multiparity,[6]
[8] advanced maternal age (ovarian hyperstimulation due to increased gonadotrophins
between the ages of 35 and 39 years old),[5]
[6]
[8] low socioeconomic condition,[8] use of oral contraceptives,[8] family history (7–15% of the population have a dominant gene for twin pregnancy),[6]
[8] and use of assisted reproductive techniques.[5]
[6]
[8]
Monozygotic pregnancies occur in 30% of twin pregnancies and are widely determined
by genetic factors. In vitro fertilization is a risk factor for monozygotic pregnancies,
since the embryo procedures may generate an alteration in the zona pellucida.[8]
[12]
[13]
[14] Contrary to dizygotic pregnancies, which are always dichorionic, the chorionicity
in monozygotic pregnancies is determined by the time of the division of both cell
masses. Should the division occur in the first 72 hours after the fertilization, the
pregnancy is dichorionic and diamniotic. Should the division occur between days 4
and 8, the pregnancy is monochorionic and diamniotic. Should the division occur after
the eighth day, the pregnancy is monochorionic and monoamniotic.[6]
[12] About 75% of the monozygotic pregnancies are monochorionic and, among the monochorionic
pregnancies, ∼ 2% are monoamniotic.[13]
[15]
The chorionicity is evaluated by an ultrasonography performed early in the pregnancy,
within the first 13 weeks of gestation. The lambda sign, typical of dichorionic pregnancies,
is detected.[12]
[16] It is important to identify the chorionicity, owing to the occurrence of complications
that are most commonly associated with monochorionic pregnancies: abortion (3 times
more frequent); congenital malformations and chromosomal disorders, which occur in
2% of the twin pregnancies; minor malformations, which have an incidence of 4%; weight
discordance; preterm birth and LBW, consequently with increased perinatal mortality
and morbidity, which are 3 to 10 times higher in monochorionic pregnancies due to
the chorionicity.[13]
[14]
[15]
[16]
Monochorionic pregnancies are associated with specific conditions. The incidence of
twin-to-twin transfusion syndrome (TTTS) is 10 to 20% in monochorionic pregnancies.[17] In TTTS, a communicating unidirectional flow occurs between the fetuses, through
deep arteriovenous anastomoses and superficial venovenous and arterioarterial anastomoses,
with repercussions for both fetuses. It is clinically manifested by a donor twin with
severe growth restriction, anemia, and oligohydramnios, and a recipient twin affected
by circulatory overload with polycythemia, cardiac complications, hydrops, and polyhydramnios.
Selective FGR occurs in 10 to15% of all monochorionic pregnancies and is diagnosed
by a difference of weight higher than 25% between the fetuses and one fetus with weight
below the tenth percentile, associated with an increased perinatal morbidity and mortality.[18] When one twin dies, the risk of death or neurologic sequelae for the other fetus
is very high due to vascular anastomoses, requiring periodic ultrasonographic monitoring.
Umbilical cord accidents are a specific condition of monoamniotic pregnancies that
occur in 48 to 80% of the cases and are associated with high rates of perinatal mortality.[12]
[13]
[15]
Twin Pregnancy in Brazil
Few studies have adequately assessed twin pregnancies in Brazil. The existing studies
have investigated specific locations, and twin pregnancy was not characterized by
regions. The oldest prevalence data (1984–1996) was identified in a study with a small
population (116,699 deliveries) assessing perinatal mortality in comparison to singleton
pregnancies. In this study, a survey in the largest maternity hospital in Campinas,
Saõ Paulo state, Brazil, identified a prevalence of 0.9% twin births.[19] Another small study reported 7,997 deliveries in a private hospital in São Paulo,
São Paulo state, Brazil, from 1995–1998, identifying a prevalence of 24.02 twin deliveries
per 1,000 births, of which 19.51‰ were dizygotic pregnancies and 2.13‰ were triplet
pregnancies. In this study, there was an increase in the prevalence of dizygotic pregnancies
(13.51 in 1995–28.98‰ in 1998), possibly due to the advanced maternal age, multiparity
and in vitro fertilization.[20]
Using the Brazilian Information System on Live Births (SINASC, in the Portuguese acronym)
database, two studies were published including populations from different states.
The first study investigated multiple births in Porto Alegre, Rio Grande do Sul state,
Brazil, from 1994 to 2005, in a population of 263,252 births, and the prevalence of
multiple pregnancies was 2.1%. In the periods studied, the rate increased 24.7% for
twin pregnancies and 150% for triplet pregnancies or pregnancies with more fetuses.
Twin pregnancies were more frequent in women with higher levels of school education,
advanced age and deliveries in private hospitals, possibly suggesting a higher use
of assisted reproductive techniques.[21] The second study investigated births in the city of São Paulo, São Paulo state,
Brazil, from 2003 to 2014, identifying 24,589 (11.96–7.5‰ dizygotic and 4.42‰ monozygotic)
twin births and 736 (0.36‰) triplet or more fetuses in a total of 2,056,016 births.
Older maternal age was a factor strongly associated with twin pregnancies, particularly
dizygotic pregnancies, as well as other factors such as body mass index (BMI) and
air pollution.[22]
In Brazil, there is an interesting fact about a place called “Twin City.” Cândido
Godói is a small city of ∼ 6,000 inhabitants in the Rio Grande do Sul state, with
a high rate of twin births (2% from 1994–2006). In Linha de São Pedro, a subdistrict
of the city, the twin birth rates reached 10% in 1994, generating widespread assumptions.
One was a folkloric belief that Nazi studies may have been conducted in this population
by Joseph Mengele. Two different studies evaluated this population to find the reasons
for the high prevalence of twinning. Twin pregnancies were strongly associated with
genetic conditions in that population. Most specifically, genetic polymorphisms in
the p53 pathway, responsible for blastocyst implantation and maintenance of the embryo
within the uterus, played a role.[23]
[24]
The Importance of Vital Records in Rare Conditions such as Twin Pregnancies
Twin pregnancy is a rare condition that should be considered in vital statistics assessments.
Vital statistics refer to continuous routine birth and death registries in a certain
population. These registries can be integrated into a national surveillance program,
in which rare conditions can be identified. Rare conditions are hardly identified
in sample analyses but are easily identified in national-scale analyses.
Health records allow the surveillance and investigation of mortality, contributing
to population-based indicators, such as fertility and mortality, by assessing the
participation of individuals in economic, social, political life, safety and sustainability.
From the birth registries, people are recognized and counted, broadening government
responsibility and maximizing the access to human rights for the most vulnerable and
marginalized population. Registries provide a basis for decision-making in public
health policies that also involve social issues and enable the development of interventions
with better financial management and universal health care coverage.[25]
[26]
[27]
Despite its importance, this type of registry remains neglected.[27] It is estimated that 1 in every 3 children aged ≤ 5 years worldwide does not have
a birth record, and two-thirds of deaths were not registered or counted in vital records.
More than half of the World Health Organization (WHO) member states have no mortality
data or their data are of inferior quality, with little value for public health policies
or planning.[28] These countries use indirect techniques to identify these events or use a sampling
method in research. However, the sample is not always sufficient to determine rare
events, and the indicators may not be interpreted as population-based parameters because
there may be limitations in the sampling design.[26]
[29]
Data obtained in vital statistics and population-based databases enable the creation
of the so-called e-registries (electronic registries), information systems and storage technologies,
as well as the analysis and dissemination of health data. These systems have assumed
importance because the global health agencies are supporting more sustainable and
safer ways to obtain and disseminate health information The aim of the e-registries is to unify information from the preconception to the postpartum period
and newborn and child health data. This population-based collection has less information
bias and its data validity is higher. These registries are an emergent opportunity
for researchers in maternal health, although middle- and low-income countries still
have an insufficient data collection, analysis, and notification of health data, resulting
in incomplete and fragmented data.[30]
[31]
Many countries have databases containing birth records. Norway has the Medical Birth
Registry of Norway (MBRN). The United States has the National Center for Health Statistics
(NCHS), and Brazil has the Health Informatics Department of the Brazilian Ministry
of Health (DATASUS, in the Portuguese acronym), which stores the SINASC data. The
SINASC is a birth registry of the entire Brazilian population that has been gradually
implemented since 1994. Its aim is to gather epidemiological birth data that is informed
throughout the national territory and provide birth data for all levels of the health
care system.[32]
Perinatal Outcomes in Twin Pregnancy
There are several perinatal complications associated with a twin pregnancy, although
the worst outcome is perinatal death. Perinatal death is defined as the sum of fetal
deaths (intrauterine death of any product after 22 completed weeks or 500 g in weight)
and deaths of live births in the first 7 days after birth. Twin pregnancies, when
compared to singleton pregnancies, increase two to three times the risk of perinatal
death. Preterm delivery and LBW are the most important factors for determining these
perinatal outcomes.[7]
[9]
[33]
[34]
Preterm birth has a prevalence ranging from 5 to 18% in different countries. Brazil,
India, China, Nigeria and the United States are among the 10 countries with the highest
estimated number of preterm births.[35]
[36]
[37]
[38]
[39] Preterm births occurred in 51% of the twin pregnancies and early preterm births
(birth at < 32 weeks) occurred in 14% of the twin pregnancies.[4]
[10]
[40]
Preterm birth is directly associated with an increased risk of neonatal death and
morbidity. Major causes of preterm birth are preterm delivery, premature rupture of
membranes, maternal conditions (hypertension, diabetes, placental abruption) and fetal
conditions that lead to preterm delivery (FGR, fetal distress, the death of one twin).
Morbidity associated with preterm birth refers mainly to respiratory distress, intraventricular
hemorrhage and necrotizing enterocolitis.[34]
[41]
[42] Neonatal morbidity seems to be more important when there is weight discordance between
both fetuses, with a higher likelihood of intracranial hemorrhage and patent ductus
arteriosus.[12]
Low birth weight, defined as weight < 2,500 g at birth, occurs in half of the cases
of twin pregnancy, due to preterm delivery and FGR.[12] Among the causes of growth restriction and weight discordance are unequal placentation
and uterine overload, with different blood flow and nutrients for the fetuses, genetic
differences, relative placental insufficiency, cord insertion abnormalities, malformations,
and infection. Twin and singleton pregnancies appear to be similar in growth until
∼ 30 weeks, when the twins are smaller than fetuses from singleton pregnancies. Between
34 and 35 weeks, the difference in fetal weight is clear and the incidence of FGR
at 38 weeks quadruples, including virtually half of the twin births.[4]
[10]
[12]
[40] Nevertheless, growth evaluation is usually based on growth curves established by
singleton pregnancies. Several studies have recommended the creation of growth curves
specific to twins or the use of some already existent curves for twin infants.[43]
[44]
[45]
[46]
Among the unfavorable outcomes are fetal death and neonatal death. The fetal death
rate is higher among twin pregnancies than in singleton pregnancies. In 2009, it was
estimated that this complication occurred in 12.3 per 1,000 twin births, while in
single pregnancies it occurred in 5 per 1,000 births.[4]
Recently, the concept of neonatal near-miss (NNM) has also emerged. It is a new marker
of severity that is similar to maternal near-miss (MNM) that enables the identification
of a group of newborn infants at a higher risk of neonatal death. Neonatal near-miss
is defined as a severe complication that almost resulted in the death of a newborn
infant during the neonatal period (the first 28 days of life). As MNM, NNM has a higher
incidence than neonatal death.[47]
[48]
[49] Since it is a very new concept, the majority of articles published still discusses
the diagnostic criteria for its identification. An article published in 2015 defined
two sets of criteria for identifying NNM cases: pragmatic criteria and management
criteria, shown in [Table 1]. Based on these criteria, a systematic review was conducted, identifying an NNM
rate that ranged from 21.4 to 72.5 per 1,000 live births. No other study has evaluated
the association between NNM and twin pregnancy until the present.[47]
[48]
[49]
Table 1
Diagnostic criteria for neonatal near miss
|
Neonatal near-miss: at least one of these criteria
|
|
Pragmatic diagnostic criteria
|
|
Birthweight < 1,750 g
|
|
Apgar score < 7 at the 5th minute
|
|
Gestational age < 33 weeks
|
|
Management criteria
|
|
Use of intravenous antibiotics
|
|
Nasal CPAP
|
|
Any intubation in the first 7 days
|
|
Use of phototherapy in the first 24 hours
|
|
Cardiopulmonary resuscitation
|
|
Use of any vasoactive drug
|
|
Use of anticonvulsants
|
|
Use of surfactant
|
|
Transfusion of blood derivatives
|
|
Use of corticosteroid for treatment of refractory hypoglycemia
|
|
Any surgical procedure
|
Abbreviations: CPAP, continuous positive airway pressure,
Source: Modified from Santos et al. (2015).[47]
[48]
Maternal Morbidity Associated with Twin Pregnancy
Maternal morbidity is associated with the maternal adaptation to physiological alterations
that occur during a twin pregnancy.[12]
[40] In the first trimester, due to the increased levels of gonadotrophic hormone (hCG),
nausea and vomiting occur more frequently, as well as hyperemesis gravidarum. A greater
expansion of blood volume also occurs (in 40–50% of the single pregnancies and in
50–60% of the twin pregnancies), with hemodilution anemia and cardiovascular alterations,
further exacerbated when related to preeclampsia and pulmonary edema.[4]
[9]
[12]
[40]
Twin pregnancies are associated with a 2-fold to 3.5-fold higher risk of hypertensive
alterations (preeclampsia, eclampsia, hemolysis, elevated liver enzymes, low platelet
count [HELLP] syndrome and fatty liver of pregnancy) than singleton pregnancies, which
present an incidence of 12.9 to 37%, mainly after the 20th week of gestation.[9]
[12]
[50]
[51] The higher production of Human Placental Lactogen (HPL) in twin pregnancies causes
insulin intolerance. In association with other factors such as weight gain, maternal
age, and BMI, this could lead to gestational diabetes.[9]
Regarding local alterations, uterine overdistension is observed, generating an organ
compression that may lead to urologic obstructive disorders and urinary tract infection,
in addition to preterm labor (PTL), placental abruption and premature rupture of membranes
(PROM). Furthermore, postpartum complications such as uterine atony and postpartum
hemorrhage may also occur.[12]
[40]
Despite all the recommendations of vaginal birth for twin pregnancies, even under
ideal conditions, when the first twin is in cephalic presentation and weighs more
than 1,500 g, 75 to 80% of these pregnancies still result in cesarean deliveries.
The literature shows evidence that cesarean deliveries do not reduce complications
such as neonatal sepsis, fetal distress for the second twin, or preterm delivery.
In contrast, they increase the risk of postpartum hemorrhage, hysterectomy, blood
transfusion, and complications due to placenta previa, placental accreta and placental
abruption.[2]
[3]
[9]
[52]
[53]
[54]
[55]
Maternal mortality (MM) is the most severe complication associated with a twin pregnancy.
The literature reports a 2.5 times higher incidence of MM is in twin pregnancies than
in single pregnancies.[4]
[34] Maternal morbidity is very important in twin pregnancy. However, even more important
is severe maternal morbidity (SMM), a marker of obstetric care that precedes and shares
many characteristics with maternal death (MD). It is defined as the sum of cases of
maternal near-miss and potentially life-threatening conditions (PLTCs).[56] Maternal near-miss is defined by the WHO as a woman who almost died but survived
complications during pregnancy, childbirth, or within 42 days of the termination of
the pregnancy.[56]
A chain of severe maternal events may culminate in the extreme event of MM. In this
chain of events, the pregnancy may be complicated or not. Complicated pregnancies
may threaten a woman's life and be a PLTC. In the latter, the woman may recover, have
temporary or permanent incapacity, or die.[56] Severe maternal morbidity represents the set of possible results for PLTCs ([Figure 1]).[57]
Figure 1 The continuum of maternal morbidity: from uncomplicated pregnancies to maternal death.
The diagnostic criteria for these conditions, shown in [Table 2], were defined in 2009 by the WHO, who elaborated a list of PLTCs and 3 sets of criteria
for MNM: clinical (capable of identifying severe cases essentially by using clinical
judgment, without the need of special techniques or of specific laboratory exams),
laboratory (specific laboratory alterations in diverse organs or system dysfunctions)
and management criteria. Prior to this, the cases were identified by the so-called
pragmatic criteria, which consisted of the presence of at least one of the following
conditions: admission in an intensive care unit (ICU), blood transfusion, hysterectomy,
and eclampsia.[57]
[58]
[59]
[60]
Table 2
Definition criteria for severe maternal morbidity according to the World Health Organization.
|
Potentially life-threatening conditions
|
|
Hemorrhagic disorders
|
Hypertensive disorders
|
Other systemic disorders
|
Severe management indicators
|
|
Abruptio placentae
Placenta accreta/increta/percreta
Ectopic pregnancy
Postpartum hemorrhage
Ruptured uterus
|
Severe preeclampsia
Eclampsia
Severe Hypertension
Hypertensive encephalopathy
HELLP syndrome
|
Endometritis
Pulmonary edema
Respiratory failure
Seizures
Sepsis
Shock
Thrombocytopenia < 100,000
Thyroid crisis
|
Blood transfusion
Central venous access
Hysterectomy
ICU admission
Prolonged hospital stay (7 days)
No anesthetic intubation
Return to operating room
Surgical intervention
|
|
Maternal near-miss: women who almost die, but survive a complication during pregnancy
or childbirth within 42 days after birth
|
|
Clinical criteria
|
Laboratory-based criteria
|
Management based criteria
|
|
Acute cyanosis
Gasping
Respiratory rate > 40 or < 6/min
Shock
Oliguria non-responsive to fluids or diuretics
Clotting failure
Loss of consciousness lasting ≥12 hours
Loss of consciousness and absence of pulse/heart beat
Stroke
Uncontrollable fit/total paralysis
Jaundice in the presence of preeclampsia
|
Oxygen saturation < 90% for ≥60 minutes
PaO2/FiO2 < 200 mm Hg
Creatinine ≥ 300 µmol/l or ≥ 3.5 mg/dl
Bilirubin > 100µmol/l or 6.0 mg/dl
pH < 7.1
Lactate > 5
Acute thrombocytopenia (< 50,000 platelets)
Loss of consciousness and the presence of glucose and ketoacidosis in urine
|
Use of continuous vasoactive drugs
Hysterectomy following infection or hemorrhage
Transfusion of ≥5 red cell units
Intubation and ventilation for ≥60 minutes not related to anesthesia
Dialysis for acute renal failure
Cardio-pulmonary resuscitation
|
|
Severe maternal outcome: refer to all cases of maternal near miss and maternal death
|
|
Maternal death: death of a woman while pregnant or within 42 days of the termination of the pregnancy
|
Abbreviation: HELLP, hemolysis, elevated liver enzymes, low platelet count.
Source: Modified from Say et al. (2009).[56]
The WHO, in addition to determining the criteria for the identification of SMO cases,
also proposed indicators to monitor the quality of obstetric care in MNM and MM cases.
These indicators may be used to monitor the performance of care offered in health
care units to women with complications.[56]
[61]
[62]
There has been an increasing interest in the subject, although until 2011 the prevalence
of SMO was widely variable in the literature, mainly due to the use of non-standardized
criteria for the identification of cases, with a rate of MNM ranging from 0.01 to
14.98%, depending on the clinical criterion used to identify SMO cases. The use of
unique diagnostic criteria enables the identification and monitoring of MNM cases
with the proposal of interventions required for its prevention.[57]
[60]
[61]
[62]
[63]
[64]
[65] Thus, many recent studies that used the WHO criteria were capable of identifying
the prevalence of MNM cases in a more uniform manner.[66]
[67]
[68]
Few studies have investigated the association between SMM and twin pregnancy, possibly
because it still is a relatively new concept. However, the WHO Global Survey on Maternal
and Perinatal Health (WHOGS), a cross-sectional multicenter study that evaluated more
than 6,000 twin pregnancies and identified MNM by using pragmatic diagnostic criteria,
concluded that twin pregnancy is a significant risk factor for maternal and perinatal
morbidity when compared to single pregnancy in middle- or low-income countries.[34] Until recently, the WHOGS was the largest and most complete assessment available
of the relationship between twin pregnancy and SMO.
It is well known that twin pregnancy is associated with several maternal and fetal
complications. Its incidence has increased in the last decades, making the condition
an important object of study in the clinical practice. Nevertheless, it is difficult
to obtain a database with a significant number of twin pregnancies. The use of large
databases may provide surprising results regarding SMM, perinatal outcomes and NNM.
As previously mentioned, few studies have evaluated SMM associated with twin pregnancy.
Knowledge of this association may help us understand the severity of twin pregnancy
for the woman, identify risk factors and enable the diagnosis of early signs of potentially
life-threatening conditions. The investigation of NNM in twin pregnancies may be unprecedented,
but the characterization of perinatal outcomes may modify the care approach in twin
pregnancies.
Delivery in Twin Pregnancy
In the past, there was much discussion about the best route of delivery in twin pregnancies,
primarily for the second twin, who appeared to have the worst outcomes when the delivery
route was vaginal.[53]
[69] However, multicenter studies currently provide strong evidence that vaginal delivery
is safe when the first twin is in cephalic presentation.[70]
[71] Despite the evidence, cesarean section (CS) is the main delivery route in twin pregnancies,
and the literature reports a prevalence ranging between 34 and 82%.[34]
[53]
[55]
[72]
[73] As occurs in vaginal delivery, labor induction has also been shown to be safe, but
its prevalence is still very low.[74] It was observed that the prevalence of cesarean delivery in twin pregnancies is
elevated, irrespective of the population-based sample evaluated, particularly in Brazil.
The WHO recommends that the CS rates do not exceed 10 to 15% of the total number of
deliveries, since higher rates of cesarean deliveries are not associated with a reduction
in maternal or neonatal mortality. In contrast, high CS rates may be associated with
worse maternal results. These results raise doubts as to the safety of twin deliveries,
diagnostic delays, and treatment of complications. Nevertheless, we should think about
the possibility of inadequate care, considering scientific evidence-based management.
Further studies are important to better understand the profile of twin pregnancy and
its management. Twin pregnancy is a high-risk condition that requires adequate prenatal
care to obtain the best possible maternal and perinatal outcomes.[4]
[35]
Particularities in Statistical Analysis of Twin Pregnancies
Little has been discussed about the statistical approach to twin pregnancy, and analyses
are performed in a heterogeneous manner. Studies that use a mixed population of single
and twin pregnancies often face difficulties in determining the sample. Efforts should
be made to obtain a standardized analytical approach to be used in studies focusing
on twin pregnancy.
Data collection instruments are often inadequate. The twin pregnancy is identified,
but the data may be deficient or incomplete, especially for the second twin, whose
data are frequently entered descriptively in an open field in the research clinical
form. Chorionicity is easy to evaluate clinically. However, differently from assisted
reproductive techniques, it may not be questioned in studies that interview women.
Therefore, this information is not frequently assessed and would be of great importance,
especially for perinatal outcomes.
The first difficulty in twin pregnancy lies in the rarity of the condition. Therefore,
many studies generate results without statistical significance. The use of large databases
and multicenter studies should be encouraged to assess rare conditions such as twin
pregnancies. Databases such as the Brazilian SINASC exist and are often in the public
domain. Data are available, but the information is being underused.
On a more specific statistical analysis, the identification of the study population
may hinder the assessment of twin pregnancy. In a study where the woman/pregnancy
is the focus, the number of live births from twin pregnancies is not always clear.
In a study where the newborn infant is the focus, the number of women/pregnancies
is rarely explicit. The number of live twin births is not always clear and does not
simply correspond to twice the number of pregnancies, since triple births or those
of a higher order may obviously occur. Furthermore, there may also occur fetal deaths.
An estimate of the number of live births can be made, which is fundamental to calculate
health indicators, and may specifically guide the estimation of twin pregnancies.
This situation is yet to be better discussed in the literature.
Fetal weight is also evaluated in a customized manner on the analysis of similar studies,
as previously mentioned. The use of specific curves for twin fetuses and newborn infants
would be ideal. However, it is also possible to use curves that represent characteristics
of the study population. Small-for-gestational-age (SGA) fetuses can be identified.
Small-for-gestational-age is a condition that corresponds to the concept of fetal
growth restriction. In addition, other curves may be used and should be considered,
in an attempt to encompass the conditions associated with a twin pregnancy.
Another difficulty in the analysis of twin pregnancies concerns the assessment of
newborn vitality, commonly expressed by a 5-minute appearance, pulse, grimace, activity,
respiration (Apgar) score < 7. In multiple pregnancies, specifically, a reasonable
proposal would be to consider the whole set of possible arrangements of perinatal
conditions with compromised vitality. For instance, 3 groups could be created: both
newborn infants with Apgar score < 7; only the first with Apgar score < 7; and only
the second with Apgar score < 7. All these analytical approaches may contribute to
the resolution of some situations that emerge in the special condition termed twin
pregnancy, which remains a challenge for researchers.
