June 19, 2025

The Science of Twins: A Comprehensive Guide to Multiple Pregnancy

Twin pregnancies represent one of nature's most fascinating reproductive phenomena, occurring in approximately 1 in every 250 pregnancies worldwide. From the molecular mechanisms of twin formation to the complex physiological adaptations required to carry two babies, twin pregnancy involves intricate biological processes that have captivated scientists and families for generations. This comprehensive guide explores the science behind twin formation, the different types of twins, factors influencing twinning rates, and the remarkable journey of carrying and delivering twins.

Understanding Twin Formation: The Science Behind Multiple Pregnancy

The Fundamental Biology of Twinning

Twin formation occurs through two distinct biological mechanisms, each resulting in fundamentally different types of twins with unique genetic relationships and developmental patterns. The timing of embryonic splitting or the release of multiple eggs determines whether twins will be identical (monozygotic) or fraternal (dizygotic), with each process involving complex molecular and cellular events that occur within specific developmental windows.

Twin formation represents a fascinating intersection of genetics, reproductive biology, and developmental science, with each type of twinning involving distinct cellular and molecular mechanisms that occur at precisely timed stages of early human development.

Monozygotic (Identical) Twins: The Mystery of Embryonic Splitting

Identical twins result from the spontaneous division of a single fertilized embryo, a process that remains one of the most enigmatic phenomena in reproductive biology.

The Molecular Mechanisms of Embryonic Splitting

Current research suggests that monozygotic twinning results from mechanical forces during early embryonic development, possibly involving disruption of cell adhesion molecules or asymmetric distribution of developmental signals. The process typically occurs between days 1-14 after fertilization, with the timing determining the degree of separation between the twins.

Studies using advanced microscopy techniques have identified that embryonic splitting most commonly occurs during the blastocyst stage (days 4-8), accounting for approximately 75% of monozygotic twins. Earlier splitting (days 1-3) results in completely separate placentas and amniotic sacs, while later splitting can result in shared membranes.

Timing-Dependent Outcomes in Identical Twin Formation

The precise timing of embryonic splitting determines the placental and membrane arrangements, which significantly impact pregnancy management and outcomes.

Split Timing and Resulting Twin Types

Days 1-3 (30% of identical twins): Complete separation - two placentas, two amniotic sacs (dichorionic-diamniotic)
Days 4-8 (65% of identical twins): Shared placenta, separate amniotic sacs (monochorionic-diamniotic)
Days 8-13 (4% of identical twins): Shared placenta and amniotic sac (monochorionic-monoamniotic)
Days 13+ (1% of identical twins): Incomplete separation resulting in conjoined twins

Dizygotic (Fraternal) Twins: The Science of Multiple Ovulation

Fraternal twins result from the simultaneous fertilization of two separate eggs, a process called hyperovulation that involves complex hormonal and genetic factors.

Hormonal Mechanisms of Hyperovulation

Multiple ovulation occurs when elevated levels of follicle-stimulating hormone (FSH) cause multiple ovarian follicles to mature simultaneously during a single menstrual cycle. This process is influenced by genetic variants affecting FSH sensitivity, maternal age-related hormonal changes, and environmental factors including nutrition and body composition.

Research has identified specific genetic variants in the FSHB and SMAD3 genes that increase the likelihood of hyperovulation, explaining why fraternal twinning shows strong familial clustering through the maternal line. Women carrying these variants have 1.5-2.0 fold increased odds of conceiving fraternal twins.

Types of Twins: Beyond the Basic Categories

Standard Twin Classifications

While identical and fraternal twins represent the two primary categories, modern reproductive science recognizes several specialized subtypes with unique characteristics and formation mechanisms.

Monozygotic Twin Subtypes

Mirror Image Twins: Occurring in 25% of identical twins, these develop asymmetric features where one twin displays the mirror image of the other's characteristics, including handedness, hair whorls, and sometimes organ placement. This results from splitting that occurs after the establishment of the left-right body axis around day 9-12.

Polar Body Twins: A Theoretical Third Type

Some researchers propose the existence of "polar body twins" - formed when an egg and its polar body are both fertilized by separate sperm. These hypothetical twins would share maternal genes but have different paternal contributions, making them more similar than fraternal twins but not identical. However, this mechanism remains unproven in human reproduction.

Rare Twin Phenomena

Several extraordinarily rare twinning phenomena challenge our understanding of early human development and genetic inheritance.

Chimeric Twins

In extremely rare cases (fewer than 100 documented worldwide), fraternal twin embryos can fuse early in development, creating a single individual with two distinct cell lines - a human chimera. These individuals may have different blood types in different organs or even different colored eyes, representing one of the most remarkable examples of human genetic mosaicism.

Vanishing twin syndrome affects 20-30% of early twin pregnancies, where one embryo is reabsorbed during the first trimester. Advanced ultrasound technology has revealed that twin conception rates may be 3-5 times higher than twin birth rates, suggesting that single births often represent survivors of early twin pregnancies.

Semi-identical (Sesquizygotic) Twins

First documented in 2007, semi-identical twins represent an extremely rare phenomenon where a single egg is fertilized by two sperm, followed by embryonic splitting.

The Molecular Basis of Sesquizygotic Twinning

These twins share 100% of their maternal DNA but only 50% of their paternal DNA, making them genetically between identical and fraternal twins. The mechanism requires the rare event of dispermic fertilization followed by embryonic reorganization and splitting - a process that violates normal developmental rules and occurs in fewer than 1 in 10 million pregnancies.

Global Twin Statistics and Prevalence Patterns

Worldwide Twin Birth Rates

Twin birth rates vary dramatically across populations, with genetic, environmental, and cultural factors contributing to striking geographical differences.

Global twin birth rates range from 6 per 1,000 births in East Asia to over 40 per 1,000 births in some African populations. Nigeria has the highest documented twinning rate at 4.4%, while Japan has among the lowest at 0.6%, representing a more than 7-fold difference between populations.

Twin Rates by Region

Sub-Saharan Africa: 15-40 per 1,000 births (highest globally)
European Populations: 10-16 per 1,000 births
North America: 12-18 per 1,000 births
South America: 8-14 per 1,000 births
East Asia: 6-8 per 1,000 births (lowest globally)
India/South Asia: 8-12 per 1,000 births

The Modern Twin Boom: Assisted Reproduction's Impact

Twin birth rates have increased dramatically in developed countries since the 1980s, primarily due to the widespread use of assisted reproductive technologies.

ART's Contribution to Twinning

In vitro fertilization (IVF) and fertility drugs increase twin rates through multiple mechanisms: controlled ovarian hyperstimulation leading to multiple ovulation, transfer of multiple embryos, and possible increased spontaneous splitting rates in laboratory-manipulated embryos. In some countries, ART accounts for 30-40% of all twin births despite representing only 2-5% of total births.

Data from the Society for Assisted Reproductive Technology shows that IVF twin rates peaked at 35-40% in the early 2000s but have declined to 15-20% due to single embryo transfer policies. However, ART twin rates remain 5-10 times higher than natural conception rates.

Maternal Age and Twin Probability

Advanced maternal age significantly increases the likelihood of fraternal twinning through age-related hormonal changes affecting ovulation patterns.

Age-Related Hyperovulation

FSH levels naturally increase with age as ovarian responsiveness declines, leading to recruitment of multiple follicles in attempts to maintain normal ovulation. This mechanism explains why fraternal twin rates increase steadily with maternal age, peaking in the late 30s and early 40s before declining as fertility decreases.

Women aged 35-39 have 4-5 times higher odds of conceiving fraternal twins compared to women under 20, with the peak twinning age occurring around 37-38 years. Identical twin rates remain constant across all maternal ages, confirming their random, non-heritable nature.

Factors Influencing Twin Conception Without Heredity

Nutritional and Environmental Factors

Multiple environmental and lifestyle factors can influence twinning rates independent of genetic predisposition, offering insights into modifiable risk factors for multiple pregnancy.

Dietary Influences on Hyperovulation

Populations with high dairy consumption show increased fraternal twinning rates, attributed to insulin-like growth factor-1 (IGF-1) present in dairy products. IGF-1 increases ovarian sensitivity to FSH, promoting multiple follicle development. Studies comparing vegan women to dairy consumers show 5-fold higher twinning rates in dairy consumers.

Body Composition and Twinning

Taller, heavier women have increased fraternal twin rates, possibly due to higher IGF-1 levels and improved nutritional status supporting multiple ovulation. Women with BMI >30 kg/m² have 1.5-2.0 fold increased odds of fraternal twins, while underweight women (BMI <20) have reduced twinning rates.

A large cohort study of 126,000 pregnancies found that women who consumed >5 servings of dairy per day had twin rates of 1.8%, compared to 0.8% in women consuming <1 serving daily, representing a more than 2-fold difference independent of genetic factors.

Seasonal and Geographic Variations

Environmental factors including sunlight exposure, seasonal nutrition variations, and altitude may influence twinning rates through effects on reproductive hormones.

Latitude and Light Exposure Effects

Populations living at higher latitudes show seasonal variations in twinning rates, with peaks occurring 9 months after periods of maximum daylight. This pattern suggests that increased light exposure may stimulate FSH production or improve general reproductive function, supporting multiple ovulation.

Medical Interventions and Twin-Inducing Treatments

Fertility Medications: Controlled Hyperovulation

Various fertility treatments intentionally or unintentionally increase multiple pregnancy rates through controlled ovarian stimulation.

Clomiphene Citrate (Clomid)

This selective estrogen receptor modulator blocks estrogen feedback at the hypothalamus, leading to increased FSH and LH secretion. Clomiphene induces ovulation in 80% of anovulatory women and increases twin rates to 5-10% compared to 0.4% in natural cycles. The mechanism involves recruitment of multiple ovarian follicles during the stimulated cycle.

Gonadotropin Therapy

Direct injection of FSH (follitropin) or hMG (human menopausal gonadotropin) can produce multiple follicle development with twin rates of 15-25% and higher-order multiple rates of 3-5%. These medications require careful monitoring with ultrasound and hormone levels to prevent dangerous ovarian hyperstimulation syndrome.

Modern fertility treatment protocols aim to balance effectiveness with safety by using the minimum effective doses and employing single embryo transfer policies in IVF. However, even controlled ovulation induction carries significantly higher multiple pregnancy rates than natural conception.

In Vitro Fertilization and Embryo Transfer

IVF procedures influence twinning through multiple mechanisms beyond simple embryo transfer numbers.

Laboratory-Induced Splitting

Single embryo transfers in IVF still result in 1-3% identical twin rates, compared to 0.3-0.4% in natural conception. Laboratory manipulation, including assisted hatching, extended culture to blastocyst stage, and freezing/thawing cycles may increase the likelihood of embryonic splitting through zona pellucida weakening or cellular stress responses.

Analysis of 1.2 million IVF cycles shows that even single blastocyst transfers result in monozygotic twin rates of 1.36%, representing a 3-4 fold increase over natural conception rates. This elevation suggests that IVF laboratory conditions may predispose to embryonic splitting through unknown mechanisms.

The Physiology of Carrying Twins

Maternal Adaptations to Multiple Pregnancy

Carrying twins requires extraordinary physiological adaptations that push maternal systems to their limits, involving dramatic changes in cardiovascular, respiratory, and metabolic function.

Cardiovascular System Changes

Twin pregnancies require 40-50% increases in cardiac output compared to 30-40% in singleton pregnancies. Blood volume expands by 50-60% (versus 40-45% for singletons), placing enormous demands on maternal cardiac function. Heart rate increases by 15-20 beats per minute, and blood pressure changes may be more pronounced due to increased circulatory demands.

Metabolic Demands

Twin pregnancies require an additional 300-500 calories daily beyond singleton pregnancy needs, with protein requirements increasing to 75-100g daily. Iron demands nearly double due to increased red blood cell production and fetal requirements, making anemia much more common in multiple pregnancies.

The physiological stress of twin pregnancy is equivalent to that experienced by elite athletes during training, with oxygen consumption increasing by 20-25% and resting heart rate elevated throughout pregnancy. These adaptations help explain why twin pregnancies carry higher risks for maternal complications.

Uterine Growth and Space Constraints

The uterus must accommodate remarkable expansion to house two growing fetuses, leading to unique mechanical and physiological challenges.

Uterine Overdistension

Twin pregnancies reach the uterine size of 40-week singleton pregnancies by 32-34 weeks gestation. This overdistension contributes to increased preterm labor risk through mechanical stretch activation of myometrial contractions and potential compromise of uterine blood flow to the developing fetuses.

Ultrasound studies show that uterine volume in twin pregnancies increases to 4,500-5,000 mL by 32 weeks compared to 3,500-4,000 mL in singleton pregnancies at term. This represents a 25-30% greater expansion that significantly impacts maternal comfort and physiological function.

Placental Function in Multiple Pregnancy

Twin pregnancies involve complex placental arrangements that significantly impact fetal development and pregnancy management.

Monochorionic vs. Dichorionic Placentas

Twins sharing a single placenta (monochorionic) face unique risks due to vascular connections that can lead to unequal blood distribution. Twin-to-twin transfusion syndrome affects 10-15% of monochorionic pregnancies, while dichorionic twins with separate placentas have pregnancy outcomes similar to two singleton pregnancies.

Twin-to-Twin Interactions: The Science of Fetal Relationships

Intrauterine Behavioral Studies

Advanced ultrasound technology has revealed sophisticated behavioral interactions between twins in utero, providing insights into early human social development and neurological function.

Twin Contact and Communication

4D ultrasound studies document that twins begin interacting as early as 14 weeks gestation, with deliberate reaching, touching, and even apparent "play" behaviors. By 18-20 weeks, twins spend 20-30% of their time in physical contact, showing preferential reaching toward their co-twin rather than toward the uterine wall or placenta.

Research using advanced fetal monitoring has demonstrated that twins show synchronized sleep-wake cycles and coordinated movements by the third trimester, suggesting early development of social bonding and communication skills that may persist after birth.

Fetal Competition and Growth Dynamics

Twin fetuses face unique challenges related to resource competition and space constraints that can significantly impact their development.

Growth Discordance Patterns

Significant growth differences (>20% weight difference) occur in 15-25% of twin pregnancies, resulting from unequal placental blood flow, genetic factors, or twin-to-twin transfusion. These discordances can lead to long-term developmental differences and require careful monitoring throughout pregnancy.

Studies using Doppler ultrasound show that even dichorionic twins can experience growth discordance due to unequal placental implantation sites, with the twin whose placenta implants on the fundus typically showing 5-10% greater growth velocity compared to the twin with lower uterine implantation.

Neurological Development in Twins

The unique intrauterine environment of twin pregnancy may influence brain development and long-term neurological outcomes.

Space Constraint Effects on Brain Development

Limited uterine space may affect fetal head growth and brain development, particularly in the third trimester. However, studies suggest that twins demonstrate remarkable neuroplasticity, with brain development patterns that may differ from singletons but generally result in normal long-term neurological function.

Twin-to-Twin Transfusion Syndrome: A Unique Twin Complication

Pathophysiology of TTTS

Twin-to-twin transfusion syndrome represents one of the most serious complications unique to monochorionic twin pregnancies, involving complex vascular imbalances.

Vascular Connection Mechanisms

TTTS results from unequal blood flow through placental vascular connections (anastomoses) between the two fetal circulations. Arterio-venous connections cause one twin (donor) to pump blood to the other (recipient), leading to volume depletion in the donor and volume overload in the recipient.

Severe TTTS affects 10-15% of monochorionic twins and carries 80-90% mortality rates without treatment. Modern laser therapy to seal the vascular connections has improved survival rates to 65-85%, making early diagnosis and specialized care crucial for affected pregnancies.

Diagnostic Criteria and Staging

TTTS diagnosis relies on specific ultrasound findings that reflect the severity of vascular imbalance between the twins.

TTTS Staging System (Quintero)

Stage I: Oligohydramnios (donor) and polyhydramnios (recipient)
Stage II: Non-visualization of donor bladder
Stage III: Abnormal Doppler studies in either twin
Stage IV: Hydrops fetalis in either twin
Stage V: Fetal death of one or both twins

Historical Perspectives on Twin Studies

Twins in Ancient Cultures and Mythology

Throughout history, twins have held special significance in human cultures, often viewed as either blessed or cursed depending on societal beliefs.

Historical Twin Beliefs

Ancient Egyptian, Greek, and Roman cultures often considered twins divine gifts, with many twin deities including Castor and Pollux, Isis and Nephthys. Conversely, some African and Native American cultures viewed twinning with suspicion, believing it indicated infidelity or supernatural intervention. These varying cultural responses highlight humanity's long fascination with this biological phenomenon.

The Birth of Modern Twin Research

Scientific study of twins began in the 19th century and revolutionized our understanding of genetics, psychology, and human development.

Francis Galton's Pioneering Work

In 1875, Francis Galton published the first systematic study of twins, proposing that identical twins could help distinguish between nature (genetics) and nurture (environment) in human traits. His work established the foundation for modern twin studies that continue to provide crucial insights into heritability of complex traits.

The modern twin registry movement began in Scandinavia in the 1960s, with the Danish Twin Registry now containing data on over 85,000 twin pairs. These comprehensive databases have enabled groundbreaking research on the heritability of diseases, behavioral traits, and longevity patterns.

Nazi Twin Experiments and Medical Ethics

The dark history of twin research during World War II led to fundamental changes in medical research ethics and human subject protections.

The Legacy of Mengele's Experiments

Josef Mengele's horrific experiments on twins at Auschwitz violated every principle of medical ethics and humanity. While producing no scientific value, these atrocities led to the development of the Nuremberg Code and modern informed consent practices that govern all human research today.

Modern Twin Research Applications

Genetic and Environmental Studies

Contemporary twin studies continue to provide unique insights into the relative contributions of genetics and environment to human health and behavior.

Twin studies have revealed that most human traits show moderate heritability (30-70%), with genetics playing important but not deterministic roles in everything from intelligence to disease susceptibility. These findings have revolutionized our understanding of human development and personalized medicine approaches.

Disease Research Through Twin Studies

Identical twins provide natural experiments for studying disease mechanisms and treatment responses.

Cancer Research Applications

Studies of identical twin pairs where only one develops cancer have identified crucial environmental triggers and protective factors. These "discordant twin" studies are particularly valuable for understanding diseases with both genetic and environmental components, including breast cancer, diabetes, and autoimmune conditions.

The Swedish Twin Registry's 50-year follow-up of 44,788 twin pairs found that inherited factors account for 42% of cancer risk overall, with significant variation by cancer type: 58% for prostate cancer, 27% for breast cancer, and 35% for colorectal cancer, highlighting the complex interplay of genes and environment.

Pregnancy Management and Medical Care

Specialized Monitoring Requirements

Twin pregnancies require intensive surveillance and specialized care protocols to optimize outcomes for both mothers and babies.

Ultrasound Surveillance Protocols

Monochorionic twins require ultrasound examinations every 2 weeks starting at 16 weeks to screen for TTTS and growth discordance. Dichorionic twins need monitoring every 3-4 weeks after 20 weeks. These intensive protocols allow early detection of complications and appropriate intervention timing.

Nutritional Management

Twin pregnancies require specialized nutrition counseling with recommendations for 35-45 pound weight gain (compared to 25-35 pounds for singletons), increased protein intake, and supplementation of iron, folic acid, and calcium. Proper nutrition significantly impacts fetal growth and reduces complications.

Delivery Planning and Timing

Twin delivery requires careful planning regarding timing, mode of delivery, and hospital resources to ensure optimal outcomes.

Current evidence supports delivery of uncomplicated dichorionic twins at 37-38 weeks and monochorionic twins at 36-37 weeks to balance the risks of prematurity against the increasing risks of intrauterine complications with advancing gestational age.
Large cohort studies show that planned vaginal delivery is appropriate for twins when the presenting twin is vertex, with success rates of 70-80%. However, emergency cesarean rates are higher (25-30%) compared to singleton deliveries (15-20%) due to complications with the second twin's delivery.

Neonatal Outcomes and Long-term Development

Immediate Neonatal Challenges

Twin babies face unique challenges related to prematurity, growth restriction, and intrauterine competition effects.

Prematurity Rates and Consequences

Approximately 60% of twins are born before 37 weeks gestation compared to 10% of singletons. This increased prematurity rate contributes to higher rates of respiratory distress syndrome, feeding difficulties, and neurological complications. However, twins of the same gestational age generally have better outcomes than singleton premature infants, possibly due to accelerated lung maturation from intrauterine stress.

Growth and Development Patterns

Twin infants and children show unique growth and developmental patterns that differ from singleton norms.

Catch-up Growth Potential

Most twins show rapid catch-up growth during the first 2-3 years of life, with 85-90% achieving normal growth parameters by school age. This catch-up is most pronounced in dichorionic twins and those without significant intrauterine growth restriction.

Long-term studies show that twins have slightly increased risks of learning disabilities and developmental delays, primarily related to prematurity and lower birth weights rather than being a twin per se. With appropriate early intervention, most twins achieve normal developmental milestones.

Psychological and Social Aspects of Twinship

Twin Bond Development

The unique relationship between twins begins in utero and continues to influence their development throughout life.

Language Development in Twins

Twins often show delayed language development compared to singletons, attributed to reduced individual attention from parents and the development of "private languages" or cryptophasia between twins. However, most twins catch up to singleton language skills by school age, and their early communication patterns may enhance social cognition skills.

Studies of 1,200 twin pairs found that 40% develop some form of private communication system by age 2-3 years, with 15% maintaining these patterns until age 5-6. While initially concerning to parents, these communications generally transition to normal language without intervention.

Identity Development and Individual Differences

Despite genetic similarity, identical twins develop distinct personalities and identities through complex interactions of genetics, environment, and choice.

The Importance of Individual Recognition

Research emphasizes the importance of treating twins as individuals rather than as a unit. Parents and caregivers who encourage individual interests, relationships, and achievements help twins develop healthy separate identities while maintaining their special bond.

Ethical Considerations in Twin Research and Treatment

Modern Research Ethics

Contemporary twin research operates under strict ethical guidelines that protect participants while advancing scientific knowledge.

Modern twin registries operate with comprehensive consent processes, privacy protections, and participant control over data use. These ethical frameworks ensure that twin research contributes positively to human knowledge while respecting individual rights and dignity.

Genetic Privacy and Twin Rights

The genetic similarity of identical twins raises unique questions about privacy, consent, and individual autonomy in genetic testing and research.

Implications of Genetic Testing

When one identical twin undergoes genetic testing, the results have direct implications for the co-twin's genetic status. This creates complex ethical situations regarding consent, disclosure, and the right not to know genetic information that affects both individuals.

Future Directions in Twin Science

Emerging Technologies

Advanced technologies are opening new frontiers in twin research and clinical care.

Epigenetic Studies

Research on identical twins is revealing how environmental factors can modify gene expression through epigenetic mechanisms. These studies are providing crucial insights into how lifestyle, stress, and environmental exposures can influence health outcomes even among genetically identical individuals.

Large-scale epigenetic studies of identical twins have identified environmentally-induced DNA methylation differences that correlate with disease risks, suggesting that genetic identity doesn't guarantee identical health outcomes. These findings are revolutionizing personalized medicine approaches.

Improved Prenatal Interventions

Advancing technology is improving outcomes for complicated twin pregnancies through better diagnostic tools and treatment options.

Fetal Surgery Advances

Minimally invasive fetal surgeries for TTTS and other twin complications are showing improved outcomes with reduced risks. Laser photocoagulation techniques continue to be refined, and new approaches including selective fetal growth restriction treatments are under development.

Conclusion: The Continuing Marvel of Twins

Twin pregnancy represents one of nature's most remarkable phenomena, involving complex biological processes that continue to advance our understanding of human development, genetics, and reproductive biology. From the mysterious mechanisms of embryonic splitting to the sophisticated interactions between twins in utero, multiple pregnancy offers unique insights into the fundamentals of human life.

The science of twins encompasses far more than simple categorization into identical and fraternal types. Modern research reveals intricate molecular mechanisms of twin formation, sophisticated maternal adaptations to multiple pregnancy, and complex fetal interactions that begin in the earliest stages of development.

For families expecting twins, understanding the science behind twin pregnancy can provide valuable insights into the remarkable journey ahead. While twin pregnancies carry additional risks and challenges, advances in prenatal care, delivery management, and neonatal intensive care have dramatically improved outcomes for both mothers and babies.

Looking toward the future, twin research continues to unlock secrets of human genetics, development, and disease. From personalized medicine applications to improved treatments for pregnancy complications, the unique biology of twins promises to advance human health and our understanding of what makes each individual unique, even among those who share identical DNA.

The enduring fascination with twins reflects their role as natural experiments in human biology, providing insights that benefit not only twin families but all of humanity in our quest to understand the miracle of human development and the complex interplay between genetics and environment that shapes each unique individual.

Scientific References

1. Hall JG. Twinning. *The Lancet*. 2003;362(9385):735-743.

2. Hoekstra C, Zhao ZZ, Lambalk CB, et al. Dizygotic twinning. *Human Reproduction Update*. 2008;14(1):37-47.

3. Steinman G. Mechanisms of twinning. VII. Effect of diet and heredity on the human twinning rate. *Journal of Reproductive Medicine*. 2006;51(5):405-410.

4. Blickstein I, Keith LG. Multiple pregnancy: epidemiology, gestation, and perinatal outcome. 2nd ed. London: Informa Healthcare; 2005.

5. Machin G. Non-identical monozygotic twins, intermediate twin types, zygosity testing, and the non-random nature of monozygotic twinning: a review. *American Journal of Medical Genetics Part C*. 2009;151C(2):110-127.

6. Gabbett MT, Laporte J, Sekar R, et al. Molecular support for heterogonesis resulting in sesquizygotic twinning. *New England Journal of Medicine*. 2019;380(9):842-849.

7. Monden C, Pison G, Smits J. Twin Peaks: more twinning in humans than ever before. *Human Reproduction*. 2021;36(6):1666-1673.

8. Chauhan SP, Scardo JA, Hayes E, Abuhamad AZ, Berghella V. Twins: prevalence, problems, and preterm births. *American Journal of Obstetrics & Gynecology*. 2010;203(4):305-315.

9. Quintero RA, Morales WJ, Allen MH, Bornick PW, Johnson PK, Kruger M. Staging of twin-twin transfusion syndrome. *Journal of Perinatology*. 1999;19(8):550-555.

10. Lewi L, Jani J, Blickstein I, et al. The outcome of monochorionic diamniotic twin gestations in the era of invasive fetal therapy: a prospective cohort study. *American Journal of Obstetrics & Gynecology*. 2008;199(5):514.e1-8.

11. Caspi A, Moffitt TE, Morgan J, et al. Maternal expressed emotion predicts children's antisocial behavior problems: using monozygotic-twin differences to identify environmental effects on behavioral development. *Developmental Psychology*. 2004;40(2):149-161.

12. Lichtenstein P, De Faire U, Floderus B, Svartengren M, Svedberg P, Pedersen NL. The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies. *Journal of Internal Medicine*. 2002;252(3):184-205.

13. Piontelli A. Development of normal fetal movements: the first 25 weeks of gestation. Milan: Springer-Verlag; 2010.

14. D'Antonio F, Khalil A, Dias T, Thilaganathan B, Southwest Thames Obstetric Research Collaborative (STORK). Weight discordance and perinatal mortality in twins: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort. *Ultrasound in Obstetrics & Gynecology*. 2013;41(6):643-648.

15. Hack KE, Derks JB, Elias SG, et al. Increased perinatal mortality and morbidity in monochorionic versus dichorionic twin pregnancies: clinical implications of a large Dutch cohort study. *BJOG*. 2008;115(1):58-67.

16. Fox NS, Rebarber A, Roman AS, Klauser CK, Peress D, Saltzman DH. Weight gain in twin pregnancies and adverse outcomes: examining the 2009 Institute of Medicine guidelines. *Obstetrics & Gynecology*. 2010;116(1):100-106.

17. Ananth CV, Chauhan SP. Epidemiology of twinning in developed countries. *Seminars in Perinatology*. 2012;36(3):156-161.

18. Roque H, Gillen-Goldstein J, Funai E, Young BK, Lockwood CJ. Perinatal outcomes in monoamniotic gestations. *Journal of Maternal-Fetal & Neonatal Medicine*. 2003;13(6):414-421.

19. Wadhawan R, Oh W, Hintz SR, et al. Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous closure of patent ductus arteriosus: a comparison with pharmacological closure. *Journal of Pediatrics*. 2009;154(4):555-561.

20. Rutter M, Thorpe K, Greenwood R, Northstone K, Golding J. Twins as a natural experiment to study the causes of mild language delay: I: Design; twin-singleton differences in language, and obstetric risks. *Journal of Child Psychology and Psychiatry*. 2003;44(3):326-341.

Comments