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Hexavalent Vaccines in Preterm Infants: What Real-World and Clinical Data Reveal

Article For Year 1 Vaccination 7 min read

Authored by GSK Vaxipedia

In this article

Summary

Key points

Preterm birth affects ~13.4 million infants annually, making this population highly vulnerable to vaccine‑preventable infections¹
Preterm infants have immature immune systems and reduced maternal antibody transfer, increasing susceptibility to infectious diseases^2,3
Evidence from >1600 preterm infants across multiple studies and long-term surveillance supports the safety and immunogenicity of hexavalent vaccines²
High seroprotection rates are achieved post-primary series, including ≥98% for diphtheria (95% CI: 96.1-100) & tetanus (95% CI: 96.1-100) and 100% for poliovirus (95% CI: 94.5-100), with strong responses for Hib and pertussis²
Booster doses result in 100% seroprotection for key antigens (diphtheria, pertactin, tetanus, polio type 1,2,& 3 (95% CI: 95.7-100)), confirming effective immune priming and memory²
Hexavalent vaccines can be co-administered with routine pediatric vaccines without compromising immune response²
Reactogenicity profile is comparable to term infants, with mostly mild events such as fever, irritability, and injection-site reactions²
Cardiorespiratory events are generally transient and related to prematurity rather than vaccination²

Infection Risk and Vaccination Challenges in Preterm Infants

Preterm birth and low birth weight remain major contributors to infant morbidity and mortality worldwide. In 2020, an estimated 13.4 million infants — about one in ten live births — were born preterm (<37 weeks’ gestation), with nearly one million deaths attributed to complications of prematurity.¹Between 2010 and 2020, approximately 152 million infants were born preterm, with little change in global rates.¹ Prematurity is now the leading cause of death among children under five years, accounting for more than one in five deaths in this age group.¹

Infants born prematurely or with low birth weight (LBW, ˂2500 g) are particularly vulnerable to infection due to immaturity of innate immune responses.²This includes poor pathogen recognition, reduced secretion of pro-inflammatory cytokines, low complement levels, impaired migration and activity of cellular mediators, and reduced monocyte and neutrophil numbers and pathogen-killing capacity, which may limit T-cell activation and impair the ability to fight infections.² In addition, the transplacental transfer of maternal immunoglobulin G (IgG), a key source of early-life protection, occurs predominantly during the third trimester, resulting in lower levels of maternally derived antibodies in preterm infants.^2,3Maternal IgG is transported across the placenta via neonatal Fc-receptor (FcRn) mediated mechanisms, but because most transfer occurs late in gestation, preterm infants generally have lower antigen-specific IgG levels at birth.³

This immunological vulnerability increases susceptibility to vaccine-preventable infections like pertussis, invasive pneumococcal disease, and Haemophilus influenzae type b infection.²Although vaccination in preterm infants may sometimes be delayed due to clinical concerns, guidelines recommend routine immunization according to chronological age and scheduled doses to ensure timely protection.²Combination vaccines can facilitate adherence to immunization schedules by reducing the number of injections. Hexavalent vaccines combining diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b antigens are therefore an important component of infant immunization programs and have been evaluated for their immunogenicity and safety in preterm and LBW infants.²

Clinical Evidence on Hexavalent Vaccination in Preterm and Low Birth Weight Infants

Evidence base

A review evaluating the hexavalent diphtheria–tetanus–acellular pertussis–hepatitis B–inactivated poliovirus–Haemophilus influenzae type b vaccine (DTPa-HBV-IPV/Hib) summarized data from 10 clinical studies and 15 years of post-marketing safety surveillance in infants with a history of prematurity or LBW.²

>1600 preterm infants
Infants with gestational age as early as 24 weeks evaluated
Vaccine administered alone or co-administered with routine pediatric vaccines

Humoral immune response

Antibody	Post primary vaccination (DTPa-HBV-IPV/Hib)		Post 18–20-month booster (DTPa-HBV-IPV/Hib)		Post 4-year booster (DTPa)
	N	% (95% CI)	N	% (95% CI)	N	% (95% CI)
Anti-HBs (≥10 mIU/ml)	91	93.4 (86.2–97.2)	83	91.6 (83.4–96.5)	–	–
Anti-PRP (≥0.15 µg/ml)	93	92.5 (85.1–96.9)	84	100 (95.7–100)	–	–
Anti-PRP (≥1.0 µg/ml)	93	76.3 (66.4–84.5)	84	100 (95.7–100)	–	–
Anti-diphtheria (≥0.1 IU/ml)	93	100 (96.1–100)	84	100 (95.7–100)	74	100 (95.1–100)
Anti-tetanus (≥0.1 IU/ml)	93	100 (96.1–100)	84	100 (95.7–100)	73	100 (95.1–100)
Anti-poliovirus type 1 (≥1:8)	69	100 (94.8–100)	80	100 (95.5–100)	–	–
Anti-poliovirus type 2 (≥1:8)	66	100 (94.6–100)	80	100 (95.5–100)	–	–
Anti-poliovirus type 3 (≥1:8)	65	100 (94.5–100)	73	100 (95.1–100)	–	–
Anti-PT VR	93	98.9 (94.2–100)	83	–	73	–
Anti-FHA VR	93	100 (96.1–100)	84	–	74	–
Anti-PRN VR	93	100 (96.1–100)	84	–	74	–

GSK created this table based on data presented in Omeñaca et al., 2018²

HBs = hepatitis B surface antibody; PRP = polyribosyl ribitol phosphate; PT = pertussis toxin; FHA = filamentous hemagglutinin;

PRN = pertactin; VR = vaccine response; CI = confidence interval.

Following primary vaccination, high seroprotection rates were observed across vaccine antigens in preterm and LBW infants.²Anti-PRP geometric mean titers correlated with gestational age and birth weight, while lower geometric mean titers were observed in infants with very low birth weight (<1500 g).²Booster vaccination elicited strong immune responses, with 100% seroprotection against diphtheria and tetanus after booster dosing.²

Cell-Mediated Immunity²

In one study, pertussis-specific cell-mediated immunity was demonstrated in preterm infants (<31 weeks’ gestation), with detectable T-cell responses to pertussis antigens, showing immune responses comparable to those in term infants and a T helper type-2 (Th2)–biased pattern typical of early life immunity.

Co-administration with other vaccines²

The hexavalent vaccine was safely co-administered with routine pediatric vaccines such as pneumococcal conjugate, rotavirus, and meningococcal vaccines, as well as respiratory syncytial virus immunoglobulin, without compromising immune responses to hexavalent vaccine antigens.

Safety and Reactogenicity

The clinical studies indicate that the DTPa-HBV-IPV/Hib vaccine is generally well tolerated in preterm and low birth weight infants. The occurrence and intensity of solicited local and general symptoms such as fever, drowsiness, and irritability after primary vaccination were similar in preterm and term infants and were not influenced by birth weight. Overall safety following primary and booster vaccination in preterm infants was comparable to that observed in term infants, with the exception of cardiorespiratory events.²

Cardiorespiratory Events After Vaccination

Cardiorespiratory events such as apnea, bradycardia, and oxygen desaturation have been reported in preterm infants following vaccination. In these clinical studies, 13–30% of medically stable preterm infants experienced apnea and/or bradycardia after receiving the vaccine, most commonly after the first dose.²Episodes were generally transient and resolved spontaneously or with minimal intervention (e.g., supplemental oxygen or tactile stimulation). The risk appears to be influenced primarily by underlying neonatal conditions, and 48–72-hour monitoring may be considered in very premature infants.²

Post-Marketing Safety Surveillance

Additional safety data from 15 years of post-marketing surveillance further support the vaccine’s safety profile in preterm infants. Since launch until 01 September 2015, 421 adverse event cases were reported in infants with a history of prematurity. The most frequently reported events included pyrexia, crying, apnea, cyanosis, and bradycardia.²

Conclusion

Evidence from clinical studies and long-term post-marketing surveillance indicates that the hexavalent DTPa-HBV-IPV/Hib vaccine demonstrates strong immunogenicity and an acceptable safety profile in preterm and low birth weight infants.²High seroprotection rates following primary and booster vaccination support effective immune protection in this vulnerable population.²Although transient cardiorespiratory events such as apnea and bradycardia may occur in very premature infants, these events are generally self-limited.²Overall, current evidence supports vaccination according to chronological age to ensure timely protection against multiple vaccine-preventable diseases in preterm infants.²

Key Safety Information⁴

Contraindications

Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.

Special warnings and precautions

Carefully consider decision to give further doses if: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Administer with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13.

Special populations

HIV infection not a contraindication. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity.

Pregnancy and Lactation

INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Undesirable effects

Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

References

United Nations Children’s Fund (UNICEF). 150 million babies born preterm in the last decade. Published May 10, 2023. Accessed May 5, 2026. https://www.unicef.org/press-releases/150-million-babies-born-preterm-last-decade
Omeñaca F, Vázquez L, Garcia-Corbeira P, et al. Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity. Vaccine. 2018;36(7):986-996. doi: 10.1016/j.vaccine.2018.01.005
Fouda GG, Martinez DR, Swamy GK, Permar SR. The Impact of IgG transplacental transfer on early life immunity. Immunohorizons. 2018;2(1):14-25. doi:10.4049/immunohorizons.1700057
Infanrix Hexa Prescribing information, Version: IFX-H/PI/IN/2025/01 Dated: 09-Dec-2025. https://india-pharma.gsk.com/media/a3hbdio3/infanrixhexa.pdf

GSK is not responsible for the third-party website content

Disclaimer

For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website http://india-pharma.gsk.com/en-in/products/prescribing-information/ for full Product Information. Please report adverse events with any GSK product to the company at [email protected] © 2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).

CL Code: PM-IN-INH-WCNT-260017 | DOP: June 2026

For more information, please refer the following link

https://india-pharma.gsk.com/media/a3hbdio3/infanrixhexa.pdf

For Indian Healthcare Professionals Only

Key Safety Information

Contraindications

Special warnings and precautions

Special populations

Pregnancy and Lactation

INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Undesirable effects

Very Common- Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory

Abbreviated Prescribing information of INFANRIX HEXA [Diphtheria, tetanus, pertussis (acellular component), hepatitis B (rDNA), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed) Ph. Eur.]

ACTIVE INGREDIENT: Each 0.5 ml dose of reconstituted vaccine contains (i) Diphtheria toxoid ≥ 30 IU, (ii) Tetanus toxoid ≥ 40 IU, (iii) Bordetella pertussis antigens (Pertussis toxoid 25mcg, Filamentous Haemagglutinin 25 mcg, Pertactin 8 mcg), (iv) Hepatitis B surface antigen 10 mcg, (v) Inactivated Poliovirus [type 1 (Mahoney strain) 40 D-antigen unit, type 2 (MEF-1 strain) 8 D-antigen unit, type 3 (Saukett strain) 32 D-antigen unit), (vi) Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate, PRP) 10 mcg conjugated to tetanus toxoid as carrier protein (approximately 25 mcg).

INDICATION: Primary and booster vaccination of infants against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b.

DOSAGE AND ADMINISTRATION: Posology: The primary vaccination schedule should be administered according to official recommendations. Full-term infants or Preterm infants (≥24 weeks gestational age): 3-dose primary vaccination: interval of ≥1 month between primary doses. Booster dose ≥6 months after last priming dose; preferably ≤18 months of age. 2-dose primary vaccination: interval of ≥2 month between primary doses. Booster dose ≥6 months after last priming dose; preferably between 11-13 months of age. Administered according to official recommendations. The Expanded Program on Immunisation schedule (at 6, 10, 14 weeks of age) may only be used if hepatitis B vaccine given at birth. Safety and efficacy not been established in children > 36 months of age. Method of Administration: Deep intramuscular injection, preferably at alternating sites for subsequent injections.

CONTRA-INDICATIONS: Hypersensitivity to any active substance or excipient or formaldehyde, neomycin and polymyxin. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib vaccines. Encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Postpone administration in acute severe febrile illness.

SPECIAL WARNINGS and SPECIAL PRECAUTIONS: Precede vaccination by review of medical history and clinical examination. Protective immune response may not be elicited in all vaccinees. Will not prevent disease caused by pathogens other than Corynebacterium diphtheriae, Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. However, Hepatitis D can be expected to be prevent. If any following events have occurred in temporal relation to receipt of pertussis-containing vaccine, carefully considered decision to give further doses of pertussis-containing vaccines: temperature of ≥40.0°C (<48 hours of vaccination), not due to another identifiable cause; collapse or shock-like state (<48 hours of vaccination); persistent, inconsolable crying lasting ≥3 hours (<48 hours of vaccination); convulsions with or without fever, (<3 days of vaccination). Appropriate medical treatment and supervision be available in case of rare anaphylactic event. Carefully weigh risk-benefit of immunising or deferring vaccination in infant or child suffering from new onset or progression of severe neurological disorder. Administered with caution in thrombocytopenia or a bleeding disorder. Do not administer intravascularly or intradermally. History of febrile convulsions, family history of convulsions or Sudden Infant Death Syndrome (SIDS) not a contraindication for use. Vaccinees with history of febrile convulsions should be closely followed up. Rate of febrile reactions higher when co-administered with pneumococcal conjugate vaccine, or with measles-mumps-rubella-varicella vaccine; reactions mostly moderate (less than or equal to 39°C) and transient. Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of INFANRIX HEXA and Prevenar 13. Antipyretic treatment should be initiated according to local treatment guidelines. Special populations: HIV infection not a contraindication. Expected immunological response may not be obtained in immunosuppressed patients. Can be given to preterm infants; however lower immune response been observed for some antigens. Consider potential risk of apnoea and need for respiratory monitoring for 48-72h when administering primary immunisation series to very preterm infants (born ≤28 weeks of gestation) and particularly if history of respiratory immaturity. Benefit of vaccination is high; vaccination should not be withheld or delayed. Interference with laboratory testing: Hib capsular polysaccharide antigen excreted in urine, positive urine test observed within 1-2 weeks. Interaction with other medicinal products and other forms of interaction: INFANRIX HEXA can be given concomitantly with pneumococcal conjugate vaccine (PCV7, PCV10 and PCV13), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), oral rotavirus vaccine and measles-mumps-rubella-varicella (MMRV) vaccine. Pregnancy and Lactation: INFANRIX HEXA is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

ADVERSE EFFECTS: The following drug-related adverse reactions were reported in clinical studies (data from more than 16,000 subjects) and during post-marketing surveillance.

Very common (≥1/10): Appetite lost, crying abnormal, irritability, restlessness, somnolence, fever ≥38°C, local swelling at the injection site (≤50 mm), pain, redness.

Common (≥1/100 to <1/10): Nervousness, diarrhoea, vomiting, fever >39.5°C, injection site reactions, including induration, local swelling at the injection site (>50 mm).

Uncommon (≥1/1,000 to <1/100): Upper respiratory tract infection, cough, diffuse swelling of the injected limb, sometimes involving the adjacent joint, fatigue.

Rare (≥1/10,000 to <1/1,000): Lymphadenopathy, thrombocytopenia, anaphylactic reactions, anaphylactoid reactions (including urticaria), allergic reactions (including pruritus), collapse or shock-like state (hypotonic-hyporesponsive episode), bronchitis, apnoea, rash, angioedema, swelling of the entire injected limb, extensive swelling reactions, injection site mass, injection site vesicles.

Very rare (<1/10,000): Appetite lost, Convulsions (with or without fever), dermatitis.

OVERDOSE: No cases of overdose reported.

Version: IFX-H/API/IN updated on 10 May 2023.

Registered medical practitioners can refer company website www.gsk-india.com/product-prescribing-information.aspx for full Product Information.

Please report adverse events with any GSK product to the company at [email protected]

For the use only of a registered medical practitioner or a hospital or a laboratory. Trademarks are owned by or licensed to the GSK group of companies. Refer to full prescribing information before use. Registered medical practitioners can refer company website: india-pharma.gsk.com/en-in/products/prescribing-information/ for Full Product Information. Please report adverse events with any GSK product to the company at [email protected]. ©2026 GSK group of companies or its licensor. For more information, please contact: GlaxoSmithKline Pharmaceuticals Limited, Dr. Annie Besant Road, Worli, Mumbai – 400030 (India).