Multiple gestation from cloherty in detail

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Cloherty Stark Manual Neonatal Care multiple gestation neonatal management

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mkdir -p "/tmp/workspace/cloherty-multiple-gestation/src" "/tmp/workspace/cloherty-multiple-gestation/output" && python - <<'PY' from pypdf import PdfReader from pathlib import Path p=Path('/tmp/workspace/attachments/e5794a75-f68d-444b-bba1-9d68210ce2d3/Cloherty and Stark’s Manual of Neonatal Care 2023.pdf') r=PdfReader(str(p)) print('pages',len(r.pages)) terms=['multiple gestation','multiple birth','twins','twin-to-twin','twin anemia','multiples'] for i,page in enumerate(r.pages): t=page.extract_text() or '' tl=t.lower() hits=[x for x in terms if x in tl] if hits: print('\nPAGE',i+1,'HITS',hits) for term in hits: at=tl.find(term) print((t[max(0,at-500):at+2500]).replace('\n',' ')[:3000]) break PY

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python - <<'PY' from pypdf import PdfReader from pathlib import Path src=Path('/tmp/workspace/attachments/e5794a75-f68d-444b-bba1-9d68210ce2d3/Cloherty and Stark’s Manual of Neonatal Care 2023.pdf') out=Path('/tmp/workspace/cloherty-multiple-gestation/src/multiple_births_pages_137_146.txt') r=PdfReader(str(src)) with out.open('w',encoding='utf-8') as f: for pno in range(162,172): f.write(f'\n\n===== PDF PAGE {pno} =====\n') f.write(r.pages[pno-1].extract_text() or '') print(out, out.stat().st_size) PY

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twin-to-twin transfusion syndrome AND neonatal outcomes

Multiple gestation / multiple births

This is summarized from the chapter “Multiple Births” in Cloherty and Stark’s Manual of Neonatal Care, 9th ed., pp. 137-146, with emphasis on neonatal relevance.

Key points

Multiple birth includes twins, triplets, and higher-order multiples.
Prematurity and low birth weight are the commonest and most important complications.
Risks are substantially higher in monozygotic than dizygotic twin pregnancies, largely because monozygotic twins are often monochorionic and can share placental vascular connections.
In progressive twin-to-twin transfusion syndrome (TTTS), fetoscopic laser ablation of placental anastomoses is the preferred fetal treatment.
At delivery, a separate, fully equipped resuscitation station and team for each infant must be prepared.
Cloherty and Stark’s Manual of Neonatal Care, p. 137; pp. 39-41.

1. Classification

A. By zygosity

Type	Origin	Genetic relationship
Monozygotic (MZ), identical	Division of one fertilized ovum	Usually same sex and genetically identical
Dizygotic (DZ), fraternal	Fertilization of two separate ova	Genetically like ordinary siblings, sex may differ
Higher-order multiples	May be multizygotic, monozygotic, or a combination	Variable

Monozygotic twins occur following division of the inner cell mass of a single blastocyst. Dizygotic twins result from multiple ovulation and fertilization.
Cloherty and Stark’s Manual of Neonatal Care, p. 137.

B. By chorionicity and amnionicity

Chorionicity is clinically more important than zygosity because it determines the likelihood of shared circulation and therefore major fetal complications.

Configuration	Placenta / chorion	Amniotic sacs	Typical origin	Principal concern
Dichorionic diamniotic, DCDA	Two chorions, often two placentas that may fuse	2	All DZ twins; some early-splitting MZ twins	Lowest twin-specific vascular risk
Monochorionic diamniotic, MCDA	One chorion / shared placenta	2	MZ split at about days 4-7	TTTS, TAPS, selective fetal growth restriction
Monochorionic monoamniotic, MCMA	One chorion / shared placenta	1	MZ split at about days 8-13	Cord entanglement and compression, TTTS, prematurity
Conjoined twins	Usually MCMA	Usually shared	Incomplete division after day 14	Shared anatomy and major malformations

Important timing of monozygotic splitting:

Days 0-3: DCDA.
Days 4-7: MCDA.
Days 8-13: MCMA.
Day 14 or later: conjoined twins.

Among monozygotic twins, Cloherty reports approximately 30% DCDA, 70% MCDA, and less than 1% MCMA.
Cloherty and Stark’s Manual of Neonatal Care, pp. 137-138.

2. Epidemiology and causes

Epidemiology

The chapter reports a 2019 US twin birth rate of 32.1 per 1,000 live births. The rate of higher-order multiple births has declined, in part because fertility treatment now increasingly aims to reduce multifetal pregnancy.
Cloherty and Stark’s Manual of Neonatal Care, p. 138.

Factors associated with dizygotic twinning

Advanced maternal age, especially about 35-39 years
Maternal family tendency to twinning
Higher maternal FSH levels
Ovulation induction
Assisted reproductive technology, including IVF
Artificial insemination

The maternal genotype, rather than paternal genotype, influences familial predisposition to DZ twinning.
Cloherty and Stark’s Manual of Neonatal Care, p. 138.

3. Antenatal diagnosis and relevance to the neonatologist

Diagnosis

Multiple gestational sacs may be seen on ultrasound at approximately 5 weeks.
More than one fetal cardiac activity may be detected at about 6 weeks.
First-trimester or early second-trimester ultrasonography is best for determining chorionicity.
A lambda sign suggests dichorionic placentation.
A dichorionic intertwin membrane is thicker because it contains two amnions and two chorionic layers.
A monochorionic dividing membrane contains only two thin amnions.
Placental pathology at birth is important to establish or verify chorionicity.
Cloherty and Stark’s Manual of Neonatal Care, p. 139.

Prenatal information to obtain before delivery

For every multiple gestation, the neonatal team should establish:

Number of fetuses and liveborn infants expected.
Gestational age and estimated weight of each fetus.
Chorionicity and amnionicity.
Fetal growth pattern and intertwin weight discordance.
Presence of TTTS, TAPS, TRAP sequence, selective growth restriction, hydrops, or demise of a co-twin.
Antenatal steroid exposure, magnesium sulfate, maternal diabetes, hypertension, infection, bleeding, and rupture of membranes.
Fetal anomalies, echocardiography findings, Doppler abnormalities, and genetic investigations.
Mode of delivery, presentation, anticipated hemorrhage, and any intrapartum compromise.

4. Maternal and obstetric complications

Multiple pregnancy increases maternal complications, which often indirectly determine neonatal outcomes.

Gestational diabetes may be more frequent.
Spontaneous loss before 20 weeks may occur, including a vanishing twin.
Short cervix is more common.
Placental abruption risk rises with fetal number.
Preterm premature rupture of membranes occurs in approximately 7%-10% of twin pregnancies, compared with 2%-4% of singleton pregnancies.
Preterm labor/birth occurs in approximately 57% of twin pregnancies and in more than 90% of higher-order multiple gestations.
Pregnancy-induced hypertension and preeclampsia occur about 2.5 times more often than in singleton pregnancy.
Cesarean delivery is common, reported in roughly 66% of twin and 91% of triplet pregnancies in the chapter.
Cloherty and Stark’s Manual of Neonatal Care, p. 140.

5. Fetal and neonatal complications

A. Prematurity and low birth weight

This is the principal neonatal problem in multiple gestation.

Mean gestational ages at birth reported by Cloherty:

Pregnancy	Mean gestational age at birth
Singleton	39 weeks
Twin	35 weeks
Triplet	32 weeks
Quadruplet	30 weeks

The probability of birth weight below 1,500 g is approximately:

8 times greater in twins
31 times greater in triplets
More than 50 times greater in higher-order multiples

when compared with singleton pregnancies.
Cloherty and Stark’s Manual of Neonatal Care, p. 140.

Consequences of prematurity

The usual prematurity-related conditions should be anticipated individually in each infant:

Respiratory distress syndrome and need for CPAP, surfactant, or ventilation
Apnea of prematurity
Hypothermia
Hypoglycemia
Feeding difficulty and poor suck-swallow coordination
Necrotizing enterocolitis
Sepsis
Patent ductus arteriosus
Intraventricular hemorrhage and white-matter injury
Retinopathy of prematurity
Bronchopulmonary dysplasia
Anemia of prematurity
Long-term neurodevelopmental impairment

B. Intrauterine growth restriction and growth discordance

Fetal growth is generally similar to singleton growth until approximately 30 weeks, after which growth of multiples falls behind.

Growth discordance

Twin growth discordance is generally defined as a birth-weight difference greater than 20% of the larger twin’s weight.

[ \text{Growth discordance (%)} = \frac{\text{weight of larger twin} - \text{weight of smaller twin}} {\text{weight of larger twin}} \times 100 ]

It may be categorized as:

Mild: less than 15%
Moderate: 15%-30%
Severe: more than 30%

Risk factors include monochorionic placentation, velamentous cord insertion, placental dysfunction, preeclampsia, antepartum bleeding, TTTS, infection, and structural or chromosomal abnormalities.

The smaller twin is at higher risk of fetal demise, perinatal death, and complications of prematurity.
Cloherty and Stark’s Manual of Neonatal Care, pp. 140-141.

Neonatal implications of fetal growth restriction

Assess the smaller or growth-restricted infant for:

Hypoglycemia
Hypothermia
Polycythemia
Thrombocytopenia
Feeding intolerance
Perinatal depression and hypoxic-ischemic injury
Congenital infection, malformation, or chromosomal disorder if indicated by phenotype or prenatal findings

C. Death of one fetus in utero

The death of one twin is particularly dangerous in monochorionic twins because of shared vascular connections.

Monochorionic co-twin demise

The surviving twin may develop:

Acute hypotension due to blood loss into the dead co-twin’s circulation
Thromboembolic phenomena
Cerebral ischemia or hemorrhage
Multiorgan injury
Neurologic injury

Cloherty notes a 20%-40% risk of neurologic injury in the surviving monochorionic co-twin. The insult generally happens at the time of co-twin death, so early delivery does not necessarily prevent injury.
Cloherty and Stark’s Manual of Neonatal Care, p. 141.

Postnatal approach

For a surviving monochorionic twin after intrauterine co-twin demise:

Obtain a detailed antenatal timeline.
Perform careful neurologic examination.
Monitor perfusion, renal function, hemoglobin/hematocrit, coagulation status, and acid-base balance.
Maintain a low threshold for cranial ultrasound and brain MRI according to the infant’s condition and local protocol.
Counsel family early about uncertainty in neurologic prognosis.

D. Congenital anomalies and deformation

Congenital malformations are more common in multifetal pregnancies, especially MZ twins. The risk in MZ twins is approximately three- to fivefold higher than in singleton pregnancies according to the chapter.

Examples include:

Cardiac anomalies
Neural tube defects
Gastrointestinal atresias
Limb defects or limb disruption
Craniofacial abnormalities
Renal and genitourinary anomalies

Deformations due to uterine crowding include:

Clubfoot
Developmental dysplasia/dislocation of the hip
Cranial synostosis or molding abnormalities

Even identical twins may be discordant for congenital anomalies.
Cloherty and Stark’s Manual of Neonatal Care, pp. 141-142.

6. Disorders unique to monochorionic twins

A. Twin-to-twin transfusion syndrome, TTTS

TTTS occurs only in monochorionic gestations. It results from unbalanced placental vascular anastomoses, especially deep arteriovenous connections.

Pathophysiology

One twin is the donor, with chronic blood transfer to the recipient twin.

Donor twin	Recipient twin
Anemia	Polycythemia
Hypovolemia	Hypervolemia
Oliguria	Polyuria
Oligohydramnios	Polyhydramnios
“Stuck twin” appearance	Distended amniotic sac
Growth restriction	Volume-overload cardiomyopathy
Renal hypoperfusion/insufficiency	Hydrops
Brain ischemia	Thrombosis, cerebral emboli, DIC

TTTS is usually diagnosed at 16-26 weeks but may appear as early as 13 weeks. Untreated severe early TTTS has very high mortality.
Cloherty and Stark’s Manual of Neonatal Care, p. 143.

Prenatal diagnostic findings

Monochorionic pregnancy
Oligohydramnios in donor sac
Polyhydramnios in recipient sac
Bladder visibility differences
Umbilical cord size discrepancy
Cardiac dysfunction in recipient
Abnormal umbilical artery or ductus venosus Doppler findings
Significant growth discordance

The Quintero system is commonly used for staging.
Cloherty and Stark’s Manual of Neonatal Care, p. 143.

Antenatal treatment

Some stage I pregnancies may be observed closely.
Fetoscopic laser photocoagulation/ablation of placental vascular anastomoses is standard treatment for stage II-IV TTTS before 26 weeks.
The chapter cites improved survival and lower cystic periventricular leukomalacia with laser therapy versus serial amnioreduction.
Cloherty and Stark’s Manual of Neonatal Care, pp. 143-144.

A more recent systematic review supports ongoing reassessment of perinatal outcomes after fetoscopic laser surgery for early TTTS, so local fetal-medicine protocols should guide management: 2024 systematic review.

Delivery room and neonatal management of TTTS

Prepare for potentially very different physiology in the two infants.

Donor twin

May be pale, hypotensive, hypovolemic, anemic, growth restricted, and acidotic.
May need respiratory support, early vascular access, cautious volume expansion, packed RBC transfusion, and assessment of renal function.

Recipient twin

May be plethoric, hypervolemic, polycythemic, hypertensive or in cardiac failure, and hydropic.
May require respiratory/cardiovascular support, evaluation for hyperviscosity and thrombosis, and partial exchange transfusion if significant symptomatic polycythemia is present.

For both twins:

Obtain cord blood or early neonatal CBC with hematocrit and platelet count.
Assess glucose and electrolytes.
Monitor blood pressure, perfusion, urine output, lactate, and renal function.
Obtain echocardiography if cardiac dysfunction is suspected.
Perform neuroimaging to look for CNS injury.
Cloherty and Stark’s Manual of Neonatal Care, p. 144.

B. Twin anemia-polycythemia sequence, TAPS

TAPS is a chronic, slow intertwin transfusion through tiny placental vascular connections. It may arise spontaneously or after incomplete laser treatment for TTTS.

Unlike typical TTTS, there is usually no oligohydramnios-polyhydramnios sequence.

TAPS donor	TAPS recipient
Severe anemia	Marked polycythemia
Pale	Plethoric
May have reticulocytosis and circulatory compromise	Hyperviscosity, thrombosis risk, jaundice risk

At birth, obtain CBC, hematocrit, reticulocyte count, bilirubin, and clinical assessment for hypoperfusion or hyperviscosity. The donor may need RBC transfusion; the recipient may need partial exchange transfusion depending on symptoms and hematocrit.
Cloherty and Stark’s Manual of Neonatal Care, pp. 144, 632, 646-647.

C. Twin reversed arterial perfusion, TRAP sequence

TRAP occurs in monochorionic twins, where an acardiac or severely malformed twin is perfused in reverse from the structurally normal pump twin.

The pump twin may develop:

High-output cardiac failure
Hydrops
Polyhydramnios
Prematurity

Fetal intervention to interrupt blood supply to the acardiac twin can improve pump-twin survival.
Cloherty and Stark’s Manual of Neonatal Care, p. 142.

D. Monoamniotic twins

Monochorionic monoamniotic twins have substantial fetal risk from:

Umbilical cord entanglement
Cord compression
Congenital anomalies
IUGR
Prematurity

Cloherty reports perinatal mortality as high as 40%, and these pregnancies are often delivered electively at 32-34 weeks.
Cloherty and Stark’s Manual of Neonatal Care, p. 144.

7. Delivery room preparation

Multiple gestation is a high-risk delivery. The delivery room team should anticipate premature birth, perinatal depression, malpresentation, hemorrhage, TTTS/TAPS, and congenital anomalies.

Essential preparation

One resuscitation station per infant
- Radiant warmer
- Blended oxygen
- T-piece or other PPV device
- Masks, suction, pulse oximeter, ECG monitoring
- Intubation and medication equipment
Adequate skilled staff
- At least one appropriately trained neonatal provider per infant.
- Additional personnel for likely extremely preterm infants or TTTS.
Thermal care
- Prewarm delivery room when very preterm birth is expected.
- Plastic wrap/bag and hat for very preterm infants where appropriate.
- Prevent both hypothermia and hyperthermia.
Anticipate hemodynamic instability
- Obtain blood products if TTTS, TAPS, abruption, vasa previa, or fetal anemia is suspected.
- Be prepared for emergency vascular access and volume or RBC administration.
Individual identification
- Correctly identify each infant immediately.
- Link each infant to the proper cord blood, placenta, prenatal findings, and maternal chart.

Cloherty specifically directs that in multiple gestations, clinicians should prepare a fully equipped resuscitation station for each newborn.
Cloherty and Stark’s Manual of Neonatal Care, p. 41.

8. Immediate neonatal assessment

For each infant, document:

Birth order and sex
Gestational age and birth weight
Apgar scores and resuscitation details
Placental/cord assignment
Chorionicity and prenatal complications
Cord gases if clinically indicated
Temperature, glucose, oxygen saturation, respiratory effort, and perfusion
Full physical examination for congenital anomaly or deformation
Accurate measurement of weight, length, and head circumference
Growth discordance calculation
CBC/hematocrit when TTTS, TAPS, anemia, polycythemia, fetal growth restriction, or bleeding is suspected

Targeted investigations

Clinical context	Useful tests
Prematurity	Glucose, blood gas if ill, CBC as indicated, sepsis evaluation when risk factors exist
Growth restriction	Glucose, hematocrit, platelets, bilirubin, temperature monitoring
TTTS/TAPS	CBC, hematocrit, reticulocytes, bilirubin, blood gas, glucose, renal profile, coagulation tests if ill
Recipient TTTS twin	Echocardiography, assessment for cardiac dysfunction, thrombosis, hyperviscosity
Donor TTTS twin	Hemodynamic monitoring, renal function, anemia evaluation
Co-twin demise	Cranial ultrasound and consideration of MRI, renal function, hematocrit, coagulation studies
Monochorionic twin	Low threshold for neuroimaging when antenatal compromise or abnormal examination is present

9. Outcomes and prognosis

Twin birth carries higher neonatal mortality than singleton birth at all gestational ages. The main determinants are:

Gestational age
Birth weight
Chorionicity
Growth restriction or discordance
TTTS/TAPS/TRAP
Congenital anomalies
Intrauterine demise of a co-twin
Perinatal depression and need for resuscitation

Cloherty emphasizes that prematurity and low birth weight are the predominant drivers of morbidity and mortality in multiple births.
Cloherty and Stark’s Manual of Neonatal Care, p. 144.

10. Exam-oriented summary

Most important facts to remember

Chorionicity determines risk. Monochorionic twins have shared placental vascular connections and risk TTTS, TAPS, TRAP, acute co-twin injury after fetal demise, and selective growth restriction.
Prematurity is the main neonatal problem.
DCDA twins have the lowest twin-specific vascular risk.
TTTS = donor oligohydramnios/anemia/hypovolemia and recipient polyhydramnios/polycythemia/hypervolemia/cardiomyopathy.
TTTS treatment of choice for significant progressive disease is fetoscopic laser ablation of placental anastomoses.
TAPS has anemia-polycythemia discordance without the typical oligo-polyhydramnios sequence.
Co-twin death in monochorionic pregnancy can cause immediate hypotensive or thromboembolic brain injury to the survivor.
Prepare one complete neonatal resuscitation setup and team per infant.
Examine the placenta and assign samples accurately to each newborn.
Think of different needs for each twin, especially in TTTS: donor may need RBC transfusion and recipient may need partial exchange transfusion.

Primary source: Cloherty and Stark’s Manual of Neonatal Care, 9th ed., Chapter 11, “Multiple Births,” pp. 137-146.

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