Human metapneumovirus infection in pregnancy: A systematic review of cohort studies and case reports

Abstract

BACKGROUND

Human metapneumovirus (hMPV) is an important cause of acute respiratory tract infection worldwide, but its impact during pregnancy has not been systematically characterized.

AIM

To synthesize available evidence on maternal, obstetric and neonatal outcomes of hMPV infection in pregnancy.

METHODS

Following PRISMA 2020 guidelines, a comprehensive search of PubMed/MEDLINE, EMBASE, Scopus, Web of Science and Google Scholar from inception to November 2025 identified studies reporting laboratory-confirmed hMPV infection in pregnant women. Eligible designs included case reports, case series and observational studies; however, the available evidence consisted predominantly of case reports and small case series, with only two prospective cohort studies contributing population-level data. Given anticipated heterogeneity, findings were synthesized narratively.

RESULTS

Seven studies met inclusion criteria, comprising two prospective community-based cohorts and five case reports/series. Across studies, approximately 50-60 women had laboratory-confirmed antenatal hMPV infection after exclusion of postpartum-only cases and accounting for non-overlapping cohorts. In community cohorts from Nepal and Thailand, hMPV accounted for a modest but non-trivial proportion of symptomatic antenatal respiratory illnesses, most of which were mild to moderate, self-limited, and did not require hospitalization or intensive care. In contrast, case-based reports described severe pneumonia and acute respiratory distress syndrome (ARDS) in women—typically in the second or third trimester-with underlying comorbidities such as asthma, morbid obesity, diabetes, chronic kidney disease or hypertensive disorders; no maternal deaths were reported. Obstetric outcomes were generally reassuring, although one cohort demonstrated an increased risk of small-for-gestational-age infants after antenatal hMPV infection, while evidence for preterm birth and other major complications remained limited and inconsistent. Neonatal outcomes were mostly favorable, with live births, gestational age and birthweight distributions comparable to uninfected pregnancies, and no confirmed congenital hMPV infections.

CONCLUSION

hMPV is an under-recognized cause of respiratory illness in pregnancy, usually resulting in mild disease but occasionally associated with severe pneumonia and ARDS in women with comorbidities. A possible association with fetal growth restriction has been reported; however, given the predominance of case reports and small cohort data, causality cannot be inferred for obstetric outcomes. Evidence for other adverse maternal and neonatal outcomes remains limited and inconsistent.

Key Words: Obstetric outcomes; Viral infection; Pregnancy; Human metapneumovirus; Neonatal outcomes

Core Tip: Human metapneumovirus (hMPV) is an under-recognized cause of respiratory illness during pregnancy. This systematic review synthesizes all available evidence on laboratory-confirmed hMPV infection in pregnant women, integrating data from community-based cohorts and hospital-based case reports. Most antenatal hMPV infections are mild and self-limited; however, severe pneumonia and acute respiratory distress syndrome can occur, particularly in women with underlying comorbidities. Obstetric and neonatal outcomes are generally reassuring, although a possible association with fetal growth restriction warrants further investigation. These findings highlight the need for greater clinical awareness of hMPV in pregnancy and for prospective studies to better define maternal and perinatal risks.

INTRODUCTION

Human metapneumovirus (hMPV), a member of the Paramyxoviridae family first described in 2001, is now recognized as a leading cause of acute respiratory tract infections worldwide[1]. The virus circulates seasonally with peaks often overlapping those of respiratory syncytial virus (RSV), and nearly all children are infected by the age of five years[2]. In adults, hMPV can cause upper and lower respiratory tract illness, and severe disease is most often observed in older adults, immunocompromised patients, and those with underlying cardiopulmonary disease[3,4]. A recent global systematic analysis estimated that hMPV is responsible for millions of respiratory infections annually, with hospitalisation rates in older adults comparable to influenza[5]. Despite increasing recognition of its clinical impact, there are currently no licensed vaccines or specific antivirals available for hMPV, and management remains supportive[6].

Clinically, hMPV presents with a spectrum ranging from mild upper respiratory tract symptoms to severe lower respiratory tract disease including pneumonia and bronchiolitis. In adults, manifestations often resemble those of influenza and RSV, and coinfections with other respiratory viruses are not uncommon[4,7]. The virus is a significant cause of hospitalisation, with studies showing that the risk of severe outcomes such as oxygen requirement, mechanical ventilation, and prolonged hospital stay increases with age and comorbidities[3,8]. Globally, hMPV contributes substantially to acute respiratory infections across age groups[5,9], yet it remains under-recognized in routine clinical practice compared with RSV and influenza, partly due to limited diagnostic testing outside research settings[10].

Pregnancy represents a unique state of immunological and cardiopulmonary adaptation that increases vulnerability to certain respiratory viral infections, most clearly demonstrated for influenza and RSV, where increased risks of pneumonia, hospitalization and adverse perinatal outcomes have been documented[11,12]. Whether hMPV follows a similar risk pattern remains unclear. Although hMPV is phylogenetically related to RSV and shares overlapping seasonal circulation, differences in viral immunopathogenesis, inflammatory response profiles, and potential placental interactions-none of which have been systematically studied in pregnancy—raise the possibility that maternal and fetal risks may not be identical. Current evidence is limited to small surveillance cohorts and scattered case reports describing maternal pneumonia, ARDS and intensive care requirement[13-16], with inconsistent findings regarding obstetric outcomes such as preterm birth or small-for-gestational-age (SGA) infants[13]. The heterogeneity and scarcity of data preclude firm conclusions regarding pregnancy-specific risks.

Unlike RSV and influenza-both of which have been the subject of pregnancy-specific systematic reviews, hMPV infection in pregnancy has not been formally synthesized. Existing reviews of hMPV focus on pediatric or general adult populations and mention pregnancy only tangentially, without structured analysis of maternal or perinatal outcomes.

Consolidating the available data is important not only to inform clinical management but also to guide public health strategies and priorities for vaccine development. Given the rarity of published cases and the lack of consolidated data, a systematic review including case reports, case series, and original observational studies is warranted to better characterize the clinical spectrum and outcomes of hMPV infection in pregnancy. Such an appraisal will provide a foundation for clinicians, highlight current knowledge gaps, and inform priorities for surveillance and prevention strategies.

Importantly, the current evidence based on hMPV infection in pregnancy is limited in both size and methodological robustness. Published data are dominated by case reports and small case series, with only two prospective cohort studies providing population-based estimates[13]. As such, most available findings should be interpreted as descriptive and hypothesis-generating rather than confirmatory. In particular, suggested associations with fetal growth restriction or risk stratification based on maternal comorbidities are derived from small samples and heterogeneous designs. The aim of this review is therefore to synthesize existing data while carefully delineating the strength and limitations of the underlying evidence.

MATERIALS AND METHODS

This systematic review is being conducted in accordance with the PRISMA 2020 statement[17]. The review protocol was registered on the International Prospective Register of Systematic Reviews to enhance transparency and minimize the risk of duplication (ID number CRD420251155029).

Because the available literature on hMPV infection in pregnancy is limited and consists predominantly of case reports, small case series and only a small number of prospective observational cohorts, this review was designed primarily as a descriptive synthesis of the existing evidence. The objective was to characterize the clinical spectrum of maternal disease and to summarize reported maternal, obstetric and neonatal outcomes rather than to estimate pooled risks or establish causal associations with adverse pregnancy outcomes. Consequently, the review should be interpreted as exploratory and hypothesis-generating. Observed associations reported in individual studies, such as potential links with fetal growth restriction or severe maternal illness in the presence of comorbidities, are presented descriptively and should not be interpreted as evidence of quantified risk compared with uninfected pregnancies.

Search strategy

A comprehensive literature search of PubMed/MEDLINE, EMBASE, Scopus, Web of Science and Google Scholar was performed from database inception to November 2025. Because Google Scholar searches are not fully reproducible, screening was limited to the first 200 results sorted by relevance. Titles and abstracts were assessed for explicit mention of hMPV and pregnancy, and only studies meeting predefined eligibility criteria were retained.

The search strategy combined controlled vocabulary terms (MeSH/Emtree) and free-text keywords related to “human metapneumovirus”, “hMPV” and “pregnancy”. The full PubMed search strategy was as follows: (“human metapneumovirus”[MeSH Terms] OR “human metapneumovirus”[All Fields] OR hMPV[All Fields]) AND (“pregnancy”[MeSH Terms] OR “pregnant”[All Fields] OR “maternal”[All Fields]). This strategy was adapted appropriately for each of the other databases. No language restrictions were applied. In addition, the reference lists of all included articles and relevant review papers were manually screened to identify any additional eligible studies.

Eligibility criteria

Studies were eligible if they involved pregnant women with laboratory-confirmed hMPV infection, documented by polymerase chain reaction (PCR), antigen detection methods or serological assays. Serological diagnosis was considered acceptable only when temporally linked to an acute compatible illness during pregnancy; however, in the final included studies, all antenatal cases were confirmed by PCR-based methods. No study relied solely on serology for case ascertainment.

Eligible designs comprised case reports, case series and retrospective or prospective observational studies, including cohort, case-control and cross-sectional designs. To be included, studies had to report data on at least one predefined primary or secondary outcome.

Primary maternal outcomes were: Pneumonia, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, need for mechanical ventilation and maternal death. Primary obstetric outcome was SGA birth. Secondary outcomes included preterm birth, hypertensive disorders of pregnancy, stillbirth, mode of delivery, and neonatal outcomes [live birth, neonatal ICU (NICU) admission, neonatal respiratory morbidity and neonatal death].

Studies were excluded if they were reviews, editorials, commentaries or conference abstracts without sufficient primary data. Articles in which it was not possible to extract pregnancy-specific data separately from other populations were also excluded. Experimental animal studies and in vitro investigations were not considered eligible.

Study selection

Two reviewers independently screened the titles and abstracts of all retrieved records to identify potentially relevant studies. Full-text articles were obtained for all citations deemed potentially eligible and were assessed in detail against the predefined inclusion and exclusion criteria. Any discrepancies between reviewers were resolved by discussion and, when necessary, by consultation with a third reviewer.

A total of 1236 records were identified through database searching, with an additional 18 records found through manual searches of reference lists and relevant conference proceedings, yielding 1254 records overall. After removal of 312 duplicates, 942 titles and abstracts were screened, of which 881 were excluded as clearly unrelated to the review question (e.g., wrong population, non-respiratory infection, non-pregnant cohorts, or non-human studies). The full texts of the remaining 61 articles were assessed for eligibility. Of these, 54 were excluded for the following reasons: Wrong study design (e.g., narrative review, editorials; n = 21), absence of laboratory confirmation of infection (n = 12), lack of extractable maternal or neonatal outcome data (n = 15), and overlapping populations with another included study (n = 6). Overlap was identified through comparison of study setting, recruitment period, author group and participant characteristics. When duplication was suspected, the dataset with the largest sample size and/or most complete outcome reporting was retained.

Ultimately, 7 studies met the inclusion criteria and were included in the qualitative synthesis. The overall study selection process is documented using a PRISMA flow diagram (Figure 1).

Figure 1 PRISMA 2020 flow diagram of study selection. Numbers reflect pregnancy-specific studies reporting laboratory-confirmed human metapneumovirus infection in pregnant women and exclude postpartum-only cases and studies without extractable pregnancy-specific data.

Data extraction

Data was extracted using a standardized data collection form. For each included study, information was recorded on first author and year of publication, country, study setting and design, study period, the number of pregnant women enrolled and the number with laboratory-confirmed hMPV infection, gestational age at the time of infection, the diagnostic method used, maternal clinical course, obstetric outcomes and neonatal outcomes.

Quality assessment

Given the anticipated predominance of case reports and case series, methodological quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for case reports and case series, as appropriate[18]. For observational studies, risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS)[19]. All quality assessments were performed independently by two reviewers, with any disagreements resolved through discussion. All included prospective cohort studies reported approval by relevant institutional or national ethics committees, as documented in their original publications. As this review synthesized previously published, anonymized data, additional ethical approval was not required. The results of the quality assessment are provided in Supplementary material.

Data synthesis

Because substantial heterogeneity in study design, populations, case definitions and outcome reporting was anticipated, a quantitative meta-analysis was not planned and findings were instead synthesized narratively. After data extraction, studies were first grouped by design (prospective cohort vs case reports/series) and setting, and key methodological features and risk-of-bias assessments were summarized in tabular form. Maternal outcomes (symptom profile, pneumonia, respiratory failure, ICU admission, need for mechanical ventilation and maternal death), obstetric outcomes (gestational age at delivery, preterm birth, hypertensive disorders of pregnancy, fetal growth restriction/SGA birth, stillbirth) and neonatal outcomes (live birth, gestational age and birthweight distributions, Apgar scores, neonatal respiratory morbidity, NICU admission and mortality) were then described qualitatively, with particular attention to consistency of effect direction across studies and to the clinical context in which hMPV infection occurred (trimester of infection, presence of maternal comorbidities, coinfections and obstetric complications). Where available, crude or adjusted effect estimates for perinatal outcomes from cohort studies were extracted and reported, but not statistically pooled, owing to the small number of hMPV cases, overlapping populations and differences in comparison groups. Severe and critical illness case reports were synthesised separately to characterise the clinical course and to explore potential risk factors for adverse maternal and fetal outcomes, while clearly distinguishing these highly selected cases from community-based cohorts.

RESULTS

Overview of the evidence base

HMPV infection in pregnancy appears to span a wide clinical spectrum, from self-limited febrile upper respiratory illness to fulminant viral pneumonia with ARDS requiring extracorporeal support. The available evidence base is small and methodologically heterogeneous. It consists of two prospective community-based cohorts and several small case reports and case series from high-income settings, together reporting slightly more than fifty antenatal hMPV infections. Given the small numbers, postpartum cases in some reports, and the need to exclude overlapping datasets, this total represents an approximate aggregation rather than a precise pooled count[13-16,20-22]. Because several studies reported aggregated surveillance data without individual-level identifiers or detailed case descriptions, precise de-duplication of cases across studies was not possible. Potential overlap was assessed based on study setting, recruitment period, author group and cohort characteristics. Consequently, the estimate of approximately 50-60 antenatal infections should be interpreted as an approximate aggregation rather than an exact pooled count. The predominance of descriptive case-based data limits the ability to estimate incidence, quantify risk, or establish causal relationships between hMPV infection and obstetric outcomes. Baseline characteristics of the included studies are summarized in Table 1. The seven included studies comprised two prospective community-based cohorts (Lenahan et al[13] in Nepal; Kittikraisak et al[21] in Thailand) and five hospital-based case reports or small case series (Haas et al[20], Fuchs et al[14], Emont et al[15], Shivarame Gowda et al[22], and Manyam et al[16]). The cohort studies employed active surveillance with PCR-based respiratory pathogen testing and reported denominator-based maternal and perinatal outcomes. In contrast, the case reports described individual or small clusters of severe, referral-based presentations confirmed by multiplex PCR panels.

Table 1 Characteristics of the included studies.

Ref.	Country	Setting and design	Study period	N pregnant women in cohort	N pregnant with hMPV	GA at infection (pregnancy cases)	hMPV diagnostic method	Maternal clinical course (pregnancy hMPV cases)	Obstetric outcomes (pregnancy hMPV cases)	Neonatal outcomes (pregnancy hMPV cases)
Haas et al[20], 2012	The Netherlands	ICU-based case series of three adult patients with RT-PCR-confirmed hMPV respiratory infection requiring intensive care; one of the three was a pregnant woman at 30 weeks’ gestation with severe respiratory illness and suspected pyelonephritis	Cases admitted between January 2010 and March 2011 (winter seasons)	Not applicable as a defined pregnancy cohort; report describes three adult ICU patients, including one pregnant woman	1 pregnant woman with hMPV infection (among three ICU patients)	30 weeks’ gestation at onset of illness (G1P0, otherwise uncomplicated pregnancy)	Nasopharyngeal swab processed in general respiratory virus culture and tested by RT-PCR; positive for hMPV (Ct 24 in throat, Ct 33 in nose). Other respiratory viruses (adenovirus, influenza A/B, parainfluenza 1-3, rhinovirus, RSV A/B) were negative	Presented with 3 days of fever and right flank pain. Urinalysis showed leukocyturia and bacteriuria, and she was treated empirically for pyelonephritis with amoxicillin-clavulanate, escalated to a third-generation cephalosporin and then meropenem due to clinical deterioration and suspected sepsis. Despite a normal initial chest X-ray, she developed respiratory insufficiency requiring 40% oxygen and ICU transfer. On admission, she was febrile (39 °C), tachycardic, hypotensive, and tachypnoeic, with mild hypoxaemia on arterial blood gases. CT pulmonary angiography excluded pulmonary embolism but showed bilateral alveolar consolidations. Urine culture grew Escherichia coli susceptible to amoxicillin, and RT-PCR was positive for hMPV. She was treated with high-flow oxygen and antibiotics, without need for mechanical ventilation, and improved within 3 days, returning to the obstetric ward	Serial fetal monitoring during ICU stay (cardiotocography) remained normal, with no signs of fetal distress. The pregnancy continued uneventfully after maternal recovery. Delivery occurred about 6 weeks later, around 36 weeks’ gestation	A healthy girl was born 6 weeks after ICU admission. No obstetric complications (e.g., preeclampsia, postpartum haemorrhage) or neonatal respiratory compromise or infection were reported
Lenahan et al[13], 2017	Nepal	Rural community-based cohort, nested in randomized trial of maternal influenza vaccination; prospective active weekly home surveillance for febrile respiratory illness from mid-pregnancy to 6 months postpartum	Enrolment 2011-2013; follow-up to 2014	3693 pregnant women (15-40 years, 17-34 weeks at enrolment)	25 during pregnancy (55 total including postpartum episodes)	Median 32.5 weeks (IQR 22-37) at hMPV illness	RT-PCR on mid-nasal swabs collected during influenza-like illness (subjective fever plus ≥ 1 of cough, myalgia, rhinorrhea, sore throat)	All had fever; most had cough (about ⅔), rhinorrhea and myalgia (about ½), and sore throat (about 40%); median total symptom duration 5 days (fever 3 days, cough 2 days); 48% of pregnant cases sought medical care; no hospitalizations or maternal deaths among pregnancy hMPV cases; about half had viral co-infection (mainly rhinovirus)	All 25 pregnancies ended in livebirth; preterm birth in 2/25 (8%); low birthweight (< 2500 g) in 5/25 (25%); small for gestational age in 12/25 (about 63%), with increased risk vs women without fever (RR: 1.7, 95%CI: 1.0-2.6); median gestational age at delivery 40 weeks (IQR 38-41) and median birthweight 2.8 kg, similar to non-hMPV women	All infants liveborn; no neonatal deaths attributed to maternal hMPV; no clear difference in median birthweight or gestational age vs non-hMPV, but higher proportion small for gestational age; neonatal hMPV described mainly in context of postpartum maternal infection, not antenatal
Fuchs et al[14], 2017	United States (Brooklyn, New York)	Single-center case report from a tertiary hospital (Maimonides Medical Center) describing an 18-year-old primigravid woman in late-preterm pregnancy who developed severe hMPV pneumonia with ARDS requiring intensive care, mechanical ventilation and venovenous ECMO	Case diagnosed in late March (published 2017); exact calendar year not specified	Not a defined pregnancy cohort; report focuses on one pregnant patient with severe hMPV infection and ARDS	1 pregnant woman with hMPV infection at 36 + 2 weeks’ gestation	36 2/7 weeks of gestation at presentation with premature contractions, fever, nausea and vomiting; late-preterm stage with underlying mild intermittent asthma and morbid obesity (BMI 50 kg/m²)	Respiratory viral panel (multiplex PCR) on respiratory specimens, positive for human metapneumovirus; influenza and other common respiratory viruses were negative. Diagnosis made on postoperative day 3	On admission she had fever (101.9 °F), tachycardia (130-140 bpm), tachypnoea (24/minutes), and hypoxia (SpO2 91%-93% on room air) after a sick contact, with a normal chest examination. She was treated empirically for community-acquired pneumonia, influenza, and asthma exacerbation (ceftriaxone, azithromycin, oseltamivir, methylprednisolone, ipratropium, oxygen); chest X-ray was negative and CT angiography showed only small-airway disease. Her respiratory status deteriorated, requiring ICU transfer and high-setting BiPAP. When intubation became unavoidable, she underwent delivery under general anaesthesia. Postoperatively, she developed pulmonary oedema and refractory hypoxaemia consistent with ARDS, and venovenous ECMO was initiated for 2 days. She was extubated on postoperative day 4, decannulated from ECMO on day 6, completed a 10-day course of broad-spectrum antibiotics, and was discharged home on postoperative day 10 on antihypertensives and oral antibiotics	Obstetric course at presentation was complicated by fetal growth restriction (< 10th percentile) and oligohydramnios on ultrasound, but with normal umbilical artery Dopplers and reassuring biophysical profile (8/10). Despite these findings, initial management was expectant because of the hope of maternal respiratory improvement and the need to avoid general anaesthesia. As respiratory failure progressed on hospital day 2, a decision was made to proceed with delivery if intubation was required. Immediately before caesarean delivery, the patient developed severe-range blood pressures and was diagnosed with preeclampsia with severe features; magnesium sulfate was started. She underwent primary caesarean delivery under general anaesthesia with immediate intubation. Intraoperative findings included lower uterine atony, which responded to uterotonic agents; estimated blood loss was 800 mL. No other obstetric complications were reported postoperatively	A female neonate weighing 2530 g (19th percentile) was delivered at 36+ weeks’ gestation. Apgar scores were 2 and 9 at 1 and 5 minutes, respectively. At birth, the neonate required stimulation, nasal continuous positive airway pressure, oral suctioning and brief face-mask ventilation; nasal CPAP was weaned off after 2 minutes. The neonate was admitted to the neonatal intensive care unit in stable condition. No neonatal infection or respiratory failure attributed to hMPV was reported and the neonatal course was described as stable
Emont et al[15], 2019	United States (Rhode Island)	Single-center case report from Women and Infants Hospital of Rhode Island describing two pregnant women in the third trimester with respiratory illness and positive multiplex RPP for hMPV; one with asthma developed progressive respiratory failure requiring ICU admission, and the other developed superimposed bacterial pneumonia due to beta-lactamase producing Haemophilus influenzae	Not precisely specified; both cases occurred in late March during winter–early spring respiratory virus season	Not a defined pregnancy cohort; report focuses on two pregnant women with hMPV infection	2 pregnant women with hMPV infection (case 1 at 29 + 5 weeks; case 2 at 31 + 0 weeks)	Case 1: 40-year-old G10P2072 at 29 weeks 5 days’ gestation with mild intermittent asthma. Case 2: 36-year-old G4P2102 at 31 weeks’ gestation with multiple comorbidities (tobacco use, seizure disorder, Charcot-Marie-tooth, history of opioid dependence, bipolar disorder)	Both patients were tested using the GenMark Dx ePlex multiplex RPP on respiratory specimens. Initial RPP in Case 1 was negative; repeat RPP during worsening illness was positive only for hMPV. In case 2, RPP on admission for hypoxia was positive only for hMPV. Rapid influenza testing was negative when performed	Case 1: At 29 + 5 weeks she presented with dyspnoea, fever, cough, and myalgias; initial evaluation (normal exam, clear lungs, negative CXR/RPP/flu) led to discharge on prednisone for presumed asthma exacerbation. She returned 2 days later with worsening respiratory distress (HR: 120 bpm, RR: 32 minutes); repeat CXR showed left basilar atelectasis and small effusions. She required high-flow nasal cannula (45 L/minute, 100%) and ICU transfer; RPP was positive for hMPV. BiPAP was started on ICU day 2. Fever and new right lower lobe infiltrate on day 3 prompted broad-spectrum antibiotics, later de-escalated after negative cultures. She was diuresed for suspected pulmonary oedema, improved gradually, transferred from ICU on day 9, and discharged on day 16 off oxygen. Mechanical ventilation was not required. Case 2: At 31 weeks she initially had streptococcal pharyngitis treated with amoxicillin. Four days later she returned with cough and dyspnoea; SpO2 was 93% on room air with wheezes, and CXR was normal. RPP was positive for hMPV. She required 1-2 L/minutes oxygen and bronchodilators. On day 3, productive cough and crackles developed; sputum grew beta-lactamase-producing Haemophilus influenzae, prompting a switch from amoxicillin to ceftriaxone and then oral cefdinir. She remained stable without ICU care or ventilation and was discharged after clinical improvement	Case 1: Pregnancy continued after ICU admission and recovery from hMPV-related respiratory failure and suspected superimposed pneumonia. She subsequently went into spontaneous labour at 38 weeks 6 days’ gestation and had an uncomplicated spontaneous vaginal delivery. No preterm labour or hypertensive disorder was reported. Case 2: Pregnancy also continued after hospitalization for hMPV infection and Haemophilus influenzae pneumonia. She later had an elective repeat caesarean delivery at 39 weeks’ gestation. No obstetric complications such as preterm labour, preeclampsia, or postpartum haemorrhage were described	Case 1: Delivered a female infant weighing 3600 g at 38 + 6 weeks by spontaneous vaginal delivery; neonatal status was reported as uncomplicated. No neonatal respiratory compromise or infection was described. Case 2: Delivered a female infant weighing 3230 g at 39 + 0 weeks by elective repeat caesarean; neonatal condition was reported as normal with no neonatal respiratory illness or sepsis mentioned. Both infants were term and appropriate for gestational age
Shivarame Gowda et al[22], 2023	United Arab Emirates (Abu Dhabi)	Single-center case report from a district community hospital describing two pregnant women with acute respiratory illness and pneumonia, both found positive for hMPV on respiratory panel PCR, with respiratory distress and presumed superimposed bacterial pneumonia, requiring ICU-level care	Not clearly specified; cases described in a 2023 case report	Not applicable (case report); two pregnant women with hMPV are described	2 pregnant women with hMPV infection (case 1 at term gestation; case 2 at approximately 7 months’ gestation)	Case 1: 34-year-old G3P2 at term gestation. Case 2: 37-year-old at about 7 months’ gestation with ongoing pregnancy at discharge	Respiratory pneumonia panel PCR on respiratory samples, positive for hMPV in both cases; COVID-19 was excluded by rapid PCR in case 2	Case 1: She initially presented with cough, sore throat, fatigue and mild dyspnoea, with leukocytosis and mildly raised CRP. Six hours after caesarean delivery she developed acute respiratory distress with severe cough and frothy sputum. Examination and imaging showed bilateral wheeze, crepitations, pleural effusion and basal consolidation; labs revealed marked leukocytosis and elevated CRP, D-dimer and procalcitonin. She was transferred to ICU and treated with oxygen, bronchodilator nebulisations, anti-failure therapy and IV ceftriaxone plus vancomycin. Sputum culture grew normal flora. She improved clinically and radiologically and was discharged home on day 6 on oral antibiotics. Case 2: At seven months’ gestation she presented with fever, productive cough, severe dyspnoea and tachypnoea, with diffuse wheeze/crackles, leukocytosis and markedly elevated CRP. CT chest showed bilateral patchy ground-glass opacities. She was admitted to ICU and treated with oxygen, nebulisations, ceftriaxone, oseltamivir, azithromycin and supportive care. Respiratory PCR was positive for hMPV; sputum culture later showed normal flora. She improved by day 3, stepped down from ICU on day 4, CT on day 5 showed regressing opacities, and she was discharged on day 6 on oral antibiotics. Mechanical ventilation was not required in either case, and both women recovered	Case 1: Underwent caesarean section at term, delivering a healthy female infant weighing 3695 g. No obstetric complications such as preterm labour, pre-eclampsia or postpartum hemorrhage were reported. Case 2: Pregnancy continued throughout the hospitalization; fetal monitoring during maternal ICU stay showed reassuring fetal heart rate tracings, and no preterm labour or other obstetric complications were described during the admission	Case 1: Neonatal outcome explicitly reported as a healthy term infant (3695 g) following caesarean delivery, with no respiratory compromise or neonatal infection described. Case 2: No delivery occurred during hospitalization and neonatal outcomes are not reported; the fetus remained well by monitoring at the time of maternal discharge
Kittikraisak et al[21], 2025	Thailand	Prospective cohort of pregnant women (PRIME study) at two hospitals in Thailand; twice-weekly active surveillance for acute respiratory illness throughout pregnancy with self-collected midturbinate nasal swabs; primary analysis focused on RSV incidence and its association with perinatal outcomes, with descriptive data on hMPV	2017-2018 respiratory viral seasons	2764 fully enrolled pregnant women. Overall in the cohort (not virus-specific), about 8% had preterm delivery and about 7% had SGA infants	29 antenatal hMPV illness episodes among pregnant women (22 in 2017, 7 in 2018); overall incidence 23 per 10000 pregnant person-months (95%CI: 16-33)	Gestational age at individual hMPV illness episodes was not reported in detail. Trimester-specific hMPV incidences per 10000 person-months were: First trimester 24.3, second 20.9, third 25.0. Median gestational age at cohort enrollment was 10 weeks (IQR 7-14)	Real-time reverse transcription PCR on self-collected midturbinate nasal swabs from women with acute respiratory illness (new onset or worsening of ≥ 1 of myalgia, cough, runny nose/nasal congestion, sore throat, or difficulty breathing within 7 days)	Among hMPV illnesses, approximately 21% had measured fever > 100.4 °F, 34% reported inability to complete routine daily activities, 34% sought medical care, and none were hospitalized. Median hMPV illness duration was 10 days (IQR: 8-13). Overall, hMPV illnesses in pregnancy were generally mild to moderate, with functional limitation but no severe outcomes reported	The study did not conduct specific statistical analyses of pregnancy or delivery outcomes among women with hMPV illness. Reported figures for preterm birth (8%) and SGA (7%) apply to the entire cohort and are not stratified by hMPV status. Therefore, no relative risks or hazard ratios for preterm birth or SGA associated with hMPV can be extracted	Neonatal outcomes (e.g., SGA, preterm birth) were evaluated at the cohort level but not separately for infants of mothers with hMPV illness. No specific associations between antenatal hMPV and neonatal outcomes are presented, reflecting the small number of hMPV cases and the analytic focus on RSV
Manyam et al[16], 2025	United States (Georgia; referral from outside hospital)	Two-case case report from an academic tertiary care center (Medical College of Georgia, Augusta University) describing severe respiratory illness due to hMPV in the second trimester of pregnancy: One case managed on an obstetric service with inpatient observation and steroids, and one case of hMPV-associated ARDS requiring intubation, mechanical ventilation, prone positioning and intensive care	Not precisely specified; cases reported in a 2025 publication and occurred during winter-early spring respiratory virus season	Not a defined pregnancy cohort; report focuses on two individual pregnant patients	2 pregnant women with hMPV infection (case 1 at 19 + 1 weeks; case 2 at 24 + 5 to 25 + 0 weeks’ gestation)	Case 1: 49-year-old G9P2234 at 19 weeks 1 day gestation. Case 2: 22-year-old G2P0101 at 24 weeks 5 days at initial outside hospital presentation, transferred at 24 + 6 weeks and delivered at 25 + 0 weeks by emergent caesarean section	Both cases were diagnosed via multiplex respiratory PCR panels. Case 1: BioFire respiratory panel on a nasal swab performed after admission returned positive for hMPV following a benign initial work-up (normal chest X-ray, ECG and laboratory studies). Case 2: A respiratory panel at the outside hospital was positive for hMPV in the setting of radiographic right lower and middle lobe pneumonia; on transfer, additional testing for influenza and RSV was negative, and blood, urine and bronchoalveolar lavage cultures showed no growth	Case 1: At 19 + 1 weeks she presented with severe dyspnoea after a recent ED visit for similar symptoms. She was afebrile with normal oxygen saturation and unremarkable CXR, ECG, and labs. Treated with bronchodilators, IV methylprednisolone, and empiric ampicillin, she was later found to be hMPV-positive on BioFire panel. Management was supportive with 48 hours of IV steroids followed by an oral taper. She required neither oxygen nor ICU care and was discharged on hospital day 8 in stable condition. Case 2: At 24 + 5 weeks, with type 1 diabetes, CKD, and chronic hypertension, she developed progressive hypoxic respiratory failure due to hMPV pneumonia. Despite broad-spectrum antibiotics and diuretics, she deteriorated with ARDS requiring intubation, prone ventilation, and vasopressors, and was transferred at 24 + 6 weeks. With worsening maternal oxygenation and non-reassuring fetal status, emergent caesarean section was performed at 25 + 0 weeks. Postoperatively, she had reduced LVEF (36%-40%) and required dialysis for refractory acidosis. Gradual respiratory and renal recovery followed; she was extubated, weaned to low-flow oxygen, transitioned to oral heart failure therapy, and discharged on hospital day 12 on 2 L home oxygen with close follow-up	Case 1: No obstetric complications occurred during the index hospitalisation at 19 + 1 weeks. Following resolution of her respiratory symptoms, she was discharged with high-risk obstetric follow-up and ultimately delivered at term at an outside hospital; no details on mode of delivery, labour course or hypertensive or haemorrhagic complications were provided. Case 2: Maternal respiratory failure due to hMPV-associated ARDS prompted emergent caesarean delivery at 25 + 0 weeks’ gestation for non-reassuring fetal status in the setting of worsening maternal hypoxaemia. The postoperative course was complicated by transient systolic heart failure with reduced ejection fraction, dialysis-requiring metabolic acidosis and difficult-to-control hypertension, all of which improved with intensive care and medical management. No further obstetric events were reported after delivery	Case 1: The patient delivered at term at an outside hospital; the infant’s health status and detailed neonatal outcomes were not available to the authors. No perinatal loss was reported. Case 2: Delivery occurred at 25 + 0 weeks’ gestation; the article focuses on maternal course and does not provide detailed neonatal information (e.g., birthweight, Apgar scores, respiratory support, or survival to discharge). The neonate was extremely preterm, but specific short-term or long-term outcomes are not described

A/B: Influenza A or B; ARDS: Acute respiratory distress syndrome; BAL: Bronchoalveolar lavage; BiPAP: Bilevel positive airway pressure; BMI: Body mass index; CPAP: Continuous positive airway pressure; CRP: C-reactive protein; CT: Computed tomography; CXR: Chest X-ray; ECG: Electrocardiogram; ECMO: Extracorporeal membrane oxygenation; GA: Gestational age; hMPV: Human Metapneumovirus; HR: Heart rate; ICU: Intensive care unit; IQR: Interquartile range; IV: Intravenous; MRSA: Methicillin-resistant Staphylococcus aureus; PCR: Polymerase chain reaction; PRIME: Name of the parent cohort study (PRIME study on pregnancy and influenza); RPP: Respiratory pathogen panel; RR: Relative risk; RSV: Respiratory syncytial virus; RT-PCR: Reverse transcription polymerase chain reaction; SGA: Small for gestational age; SpO₂: Peripheral capillary oxygen saturation; LVEF: Left ventricular ejection fraction; CKD: Chronic kidney disease; ED: Emergency department; COVID-19: Coronavirus disease 2019.

Results of the quality assessment

Methodological appraisal supports cautious interpretation of the findings. Case reports and case series generally demonstrated high reporting quality using JBI criteria, with clear diagnostic confirmation by PCR and detailed clinical course descriptions. However, consecutive inclusion and complete case ascertainment were frequently unclear, introducing potential selection and publication bias typical of descriptive case literature. The single cohort providing virus-specific perinatal analyses achieved 7/9 stars on the NOS, reflecting strong selection and outcome ascertainment domains but limited comparability due to absence of multivariable adjustment for key confounders. Collectively, while reporting quality was generally good, the small sample size, descriptive designs and limited control of confounding substantially constrain causal inference.

Incidence and epidemiology of hMPV in pregnancy

In the two cohort studies from Nepal and Thailand, hMPV accounted for a modest but non-negligible proportion of symptomatic respiratory infections in pregnancy. In rural Nepal, Lenahan et al[13] identified 25 antenatal hMPV infections among 3693 women under active weekly home surveillance, corresponding to an incidence of 16.7 per 1000 person-years during pregnancy. In Thailand, Kittikraisak et al[21] observed 29 antenatal hMPV illness episodes in 2764 women, with an incidence of 23 per 10000 pregnant person-months and broadly similar rates across trimesters. Because testing was symptom-triggered and conducted within research-intensive surveillance frameworks, these figures should not be interpreted as population-wide prevalence estimates. They instead reflect incidence of clinically apparent illness within actively monitored cohorts and may not be generalizable to routine obstetric populations.

Community-based prospective cohort evidence

In the two community-based prospective cohorts from Nepal and Thailand, antenatal hMPV infections were identified through systematic surveillance of symptomatic pregnant women[13,21]. These studies provide the only population-denominated estimates within this review. In both settings, maternal illness was predominantly mild to moderate and self-limited. In Nepal, no pregnant women with hMPV required hospitalization or intensive care[13]. Similarly, in Thailand, no hospital admissions or severe respiratory failure occurred among women with hMPV illness episodes[21].

These findings suggest that, in unselected populations undergoing active surveillance, most antenatal hMPV infections do not result in severe maternal respiratory compromise.

Referral-based and hospital case reports/series

In contrast, the case-based literature derives primarily from tertiary referral centers and hospital settings, where testing was performed in women presenting with significant respiratory compromise. These reports are enriched for severe presentations and do not provide population denominators.

Across these referral-based cases, several pregnant women developed hMPV-associated pneumonia requiring ICU admission, and some progressed to ARDS necessitating mechanical ventilation or extracorporeal support[14-16,20,22]. These cases illustrate the upper spectrum of clinical severity but arise from referral-based settings enriched for complicated presentations. They should not be extrapolated to the broader pregnant population, as community-based cohorts did not demonstrate comparable rates of severe disease. Several severe cases described suspected or documented bacterial superinfection, radiologic consolidation or secondary pneumonia[15,22], making it difficult to attribute the full severity of respiratory compromise to hMPV alone.

Obstetric outcomes

Importantly, interpretation of obstetric outcomes must distinguish between community-based cohort findings and referral-based case reports. Cohort studies provide denominator-based estimates, whereas case reports describe outcomes in selected severe presentations without comparison groups.

Obstetric outcomes in the cohort studies are largely limited, with a single-study signal for fetal growth restriction. In Nepal, antenatal hMPV infection was associated with a higher proportion of SGA births compared with women without febrile illness during pregnancy (relative risk: 1.7, 95%CI: 1.0-2.6)[13]. Because approximately half of the maternal hMPV illness episodes involved viral co-infections and analyses were not adjusted for these factors, this finding should be interpreted cautiously. However, this estimate is based on only 25 exposed pregnancies, confidence intervals approach the null, and analyses were not adjusted for key confounders such as maternal nutrition, socioeconomic status or other causes of febrile illness. The Thai cohort did not report virus-specific obstetric outcomes[21]. This finding should therefore be viewed as a preliminary, potentially confounded signal rather than evidence of a causal relationship.

Within the case reports and series, most pregnancies with hMPV infection resulted in liveborn infants, frequently at term. Late-third-trimester infections described by Shivarame Gowda et al[22], Emont et al[15] and Fuchs et al[14] predominantly culminated in deliveries at or near term, either spontaneously or by planned or urgent caesarean section. In Fuchs et al[14] case, delivery at 36 weeks was precipitated by worsening maternal respiratory failure and the onset of pre-eclampsia with severe features. Emont et al[15] two women delivered at 38 + 6 and 39 weeks, respectively, with uncomplicated obstetric courses. Haas et al[20] patient delivered a healthy infant at approximately 36 weeks after recovering from ICU admission.

Preterm birth associated with hMPV in the case literature appears to be primarily iatrogenic and driven by maternal respiratory compromise or non-reassuring fetal status rather than spontaneous preterm labor. The most striking example is Manyam et al[16] second case, in which a woman with ARDS at 24-25 weeks underwent emergent caesarean delivery at 25 weeks for worsening fetal heart-rate abnormalities in the context of severe maternal hypoxemia.

Neonatal outcomes

Neonatal outcomes were generally favorable. In the Lenahan et al[13] cohort, all antenatally exposed infants were liveborn, with no neonatal deaths attributed to maternal hMPV, and birthweight and gestational age distributions were broadly comparable to uninfected pregnancies apart from a higher frequency of SGA. In case reports, most neonates were delivered at term or late preterm and had uncomplicated early courses; brief respiratory support was described in one late-preterm infant[14], while detailed outcomes were limited for the extremely preterm infant delivered at 25 weeks[16]. No reports confirmed congenital hMPV infection; however, systematic neonatal virological testing was not routinely performed, and standardized neonatal sampling protocols were rarely described. As a result, the absence of documented congenital transmission may reflect under-ascertainment rather than a true absence of vertical transmission. Early infant infection was documented only in postpartum cases[13], suggesting horizontal transmission; however, conclusions regarding vertical transmission are limited by the lack of systematic neonatal testing protocols.

Risk factors for severe disease

Across the severe and critical illness case reports, hMPV infection in pregnancy appears to interact with underlying maternal comorbidities and pregnancy-related physiological changes. Asthma and other chronic respiratory conditions are frequent backgrounds in women who developed pneumonia, respiratory failure or required ICU admission, including the morbidly obese adolescent with mild intermittent asthma who progressed to ARDS and required ECMO in the report by Fuchs et al[14], as well as the third-trimester asthma case with ICU admission described by Emont et al[15], and the pneumonic ICU cases reported by Shivarame Gowda et al[22]. Morbid obesity, pre-existing type 1 diabetes, chronic kidney disease and chronic hypertension recur in these severe presentations, most strikingly in the ECMO-treated case of Fuchs et al[14] and the ARDS case with diabetes, chronic kidney disease and chronic hypertension reported by Manyam et al[16]. In addition, several reports describe overlap between severe maternal hMPV infection and obstetric complications such as fetal growth restriction, oligohydramnios and superimposed pre-eclampsia in the Fuchs et al[14], or severe hypertensive and cardiac complications in the postpartum course of the Manyam et al[16] ARDS case, although a direct causal relationship with hMPV cannot be established. Some women with hMPV pneumonia requiring intensive care had fewer baseline comorbidities, as in the ICU-managed pregnancy case in the series by Haas et al[20], underscoring the heterogeneity of host susceptibility. The very small numbers, descriptive design and absence of control groups in these case reports preclude formal quantification of risk; moreover, community-based and hospital-based cohorts from Nepal and Thailand, in which antenatal hMPV illnesses were generally mild and not associated with hospitalization, do not show a clear signal for excess severe outcomes[13,21]. While severe maternal presentations appear to cluster in women with asthma, obesity or cardiometabolic disease, these observations derive primarily from case reports without control groups. The absence of comparative denominators precludes estimation of relative risk. Consequently, these patterns should be viewed as suggestive but unproven risk signals.

DISCUSSION

This systematic review synthesizes, for the first time, the available evidence on hMPV infection in pregnancy, drawing together two prospective community-based cohorts and a small but growing number of hospital-based case reports and case series. Overall, the data suggest that hMPV is a recognized cause of symptomatic respiratory illness in pregnant women worldwide, with most infections being mild and self-limited, but with a clinically important tail of severe disease including ARDS in women with underlying comorbidities. This systematic review synthesizes a limited and predominantly descriptive evidence base. The data comprise two prospective cohorts-only one of which provided virus-specific perinatal analyses-and a series of case reports and small case series enriched for severe hospital-based presentations. Consequently, while the review provides the first structured overview of hMPV in pregnancy, the strength of inference is modest. Most observations should be regarded as exploratory and hypothesis-generating rather than confirmatory.

Referral-based severe disease phenotype

Severe disease almost always occurs in women with comorbidities such as asthma, morbid obesity, diabetes, chronic kidney disease or hypertensive disorders[14-16,22], mirroring broader adult hMPV data in which high viral load, co-infection, older age and immunocompromise predict worse outcomes[23,24]. Pregnancy-related physiological changes and immune modulation may further increase vulnerability in women with underlying cardiometabolic or pulmonary disease, although direct mechanistic data are lacking. Comparisons with RSV and influenza should be interpreted cautiously. Unlike these viruses-where substantially larger pregnancy-specific datasets exist[11,12,25-29]-the evidence base for hMPV in pregnancy is small and predominantly case-based. Observed similarities in clinical presentation are therefore contextual rather than evidence of equivalent risk magnitude.

Community-based epidemiology and predominantly mild disease

The most frequently discussed obstetric signal in the available literature is a possible association with fetal growth restriction. In the community-based cohort from rural Nepal, antenatal hMPV infection was associated with a higher proportion of SGA births compared with women without febrile illness during pregnancy[13]. However, interpretation of this finding requires caution. The comparison group in that analysis consisted of women without febrile respiratory illness rather than women specifically without hMPV infection, which limits the ability to attribute the observed association to hMPV itself. In addition, approximately half of the maternal hMPV illness episodes in that cohort involved viral co-infections, and the analyses were not adjusted for co-infecting pathogens or for other potential confounders such as maternal nutritional status, socioeconomic factors or other causes of febrile illness. The definition of SGA was based on cohort-level birthweight assessment within the study population rather than standardized international growth references, which may further influence comparability with other populations. Taken together, these methodological considerations indicate that the observed association should be interpreted as a preliminary signal rather than evidence of a causal relationship between antenatal hMPV infection and impaired fetal growth.

Although direct mechanistic data linking hMPV infection to adverse pregnancy outcomes are currently lacking, several biologically plausible pathways may explain how maternal respiratory viral infection could influence placental function and fetal growth. Systemic maternal inflammation during acute viral infection can lead to increased circulating cytokines and inflammatory mediators, which may disrupt placental vascular regulation and nutrient exchange. In cases of moderate or severe respiratory disease, maternal hypoxaemia and impaired pulmonary gas exchange could also contribute to transient placental hypoperfusion, potentially affecting fetal growth trajectories. In addition, respiratory viral infections have been associated in other contexts with endothelial dysfunction and alterations in coagulation pathways, processes that may influence placental perfusion and microvascular integrity. These potential mechanisms are extrapolated primarily from studies of other respiratory viruses, including influenza and severe acute respiratory syndrome coronavirus 2, and should therefore be viewed as conceptual frameworks rather than evidence of a confirmed pathogenic pathway for hMPV in pregnancy.

Although influenza infection has been associated with adverse perinatal outcomes in larger studies[26-28], the evidence base for hMPV is substantially smaller and does not allow direct risk comparison.

In contrast, robust evidence linking hMPV to preterm birth, stillbirth or other major obstetric complications is lacking: HMPV was not significantly associated with preterm delivery or low birthweight in Nepal, and the Thai cohort was underpowered for virus-specific obstetric outcomes[13,21]. In case reports, preterm birth is usually iatrogenic and temporally related to maternal respiratory deterioration or non-reassuring fetal status, as illustrated by emergency caesarean delivery for worsening ARDS and fetal compromise at 25 weeks in Manyam et al[16].

From a clinical perspective, the available evidence suggests that hMPV should be considered among the potential viral causes of moderate to severe respiratory illness in pregnancy, particularly when testing for more commonly recognized pathogens such as influenza or RSV is negative. Contemporary multiplex PCR respiratory panels frequently include hMPV; however, these tests may not always be routinely requested in obstetric populations, potentially contributing to under-recognition. In most reported cases, particularly those identified through community-based surveillance, maternal illness was mild and self-limited and management was supportive, similar to approaches used in non-pregnant adults. Given the limited and predominantly descriptive nature of the available data, any clinical considerations should be interpreted cautiously and viewed as expert-informed interpretation rather than evidence-based management recommendations. In women with underlying respiratory or cardiometabolic comorbidities-such as asthma, obesity or diabetes-greater clinical awareness and careful maternal–fetal monitoring during significant respiratory illness may be prudent, although pregnancy-specific management strategies for hMPV infection have not been systematically studied.

At the population level, hMPV currently lacks specific prophylactic or therapeutic options. This contrasts with RSV, for which maternal vaccination and long-acting monoclonal antibodies (such as nirsevimab) are now being implemented to protect young infants from severe lower respiratory tract disease[30,31]. Several experimental vaccine candidates and antiviral approaches targeting hMPV are under investigation, but none have yet reached clinical use[32,33]. Should safe and effective immunization strategies become available in the future, pregnant women and their infants-particularly those with underlying maternal comorbidities-may represent an important population for consideration in prevention strategies. Until such interventions exist, prevention remains focused on general respiratory infection control measures, recommended maternal vaccinations such as influenza and pertussis immunization, and early recognition and supportive management of severe viral respiratory illness regardless of specific etiology.

This review has several strengths. It systematically collates the scattered pregnancy-specific hMPV literature across multiple regions and care settings, integrates cohort and case-based data, and situates hMPV within the broader context of respiratory virus infections in pregnancy.

However, several limitations of the underlying evidence warrant emphasis. The total number of reported antenatal hMPV infections remains small, limiting statistical precision and stability of effect estimates. Much of the literature consists of case reports and small case series originating from tertiary care settings, which introduces publication and referral bias and likely over-represents severe presentations while under-representing mild community-managed infections. In addition, most severe maternal cases lack comparator groups, precluding reliable estimation of relative risk or causal inference. Population-based cohort data are limited to a small number of hMPV-positive pregnancies, and obstetric outcome analyses rely largely on a single cohort study with limited adjustment for potential confounders such as maternal comorbidities, co-infections and socioeconomic factors. Diagnostic ascertainment in these cohorts was symptom-triggered, meaning asymptomatic or minimally symptomatic infections were likely missed, potentially leading to underestimation of incidence and exposure misclassification in outcome analyses. Finally, systematic placental evaluation, standardized neonatal virological testing and long-term infant follow-up are largely absent from the available literature, further constraining.

Implications of risk of bias for interpretation of outcomes

The methodological limitations of the available studies also influence the degree of confidence that can be placed in specific outcome domains. For maternal disease severity, most evidence derives from hospital-based case reports and small case series, which are inherently subject to referral and publication bias. Severe presentations such as pneumonia, respiratory failure or ARDS are therefore likely to be overrepresented relative to the broader spectrum of community-managed infections. Conversely, the prospective community-based cohorts included systematic surveillance and PCR confirmation but involved relatively small numbers of hMPV-positive pregnancies, limiting the precision of estimates for severe maternal outcomes.

Evidence regarding obstetric outcomes, particularly fetal growth restriction or SGA birth, is primarily derived from a single cohort study. Although that study provided denominator-based comparisons, the exposed sample size was small and analyses were not fully adjusted for potential confounders such as maternal nutritional status, socioeconomic factors or other febrile illnesses. As a result, the observed association should be interpreted cautiously and cannot be considered evidence of a causal relationship.

Similarly, evidence for preterm birth remains limited and heterogeneous. In case reports, preterm delivery was frequently iatrogenic and related to maternal clinical deterioration rather than spontaneous preterm labour. However, the absence of standardized obstetric outcome definitions and the lack of consistent comparison groups across studies limit the ability to assess whether antenatal hMPV infection independently increases the risk of prematurity.

Neonatal outcome data are also constrained by incomplete reporting and lack of systematic neonatal virological testing. Most reports describe favourable neonatal outcomes, but small sample sizes, absence of standardized follow-up and incomplete documentation of neonatal infection status reduce confidence in conclusions regarding neonatal risk and the possibility of vertical transmission.

Another important methodological consideration relates to diagnostic ascertainment. In both prospective cohort studies included in this review, respiratory virus testing was performed only when pregnant participants reported symptoms consistent with an acute respiratory illness. Consequently, asymptomatic or minimally symptomatic hMPV infections were likely not captured. This symptom-triggered testing strategy may therefore underestimate the true incidence of antenatal hMPV infection in the population. In addition, it introduces the possibility of exposure misclassification in analyses of pregnancy outcomes, as some women classified as uninfected may in fact have experienced undetected infections. Such non-differential misclassification would tend to bias associations toward the null and further complicates interpretation of the limited available data on obstetric and neonatal outcomes.

An additional limitation concerns the assessment of potential vertical transmission. Although no included reports confirmed congenital hMPV infection, systematic neonatal diagnostic evaluation was rarely performed. Most studies did not include standardized sampling protocols such as cord blood testing, placental tissue analysis, or early neonatal respiratory swabs obtained immediately after birth. In the absence of such standardized virological assessment, vertical transmission cannot be definitively excluded. The currently available data therefore reflect limited ascertainment rather than evidence that congenital infection does not occur.

Future research should prioritize large, well-designed prospective pregnancy cohorts with systematic virological testing of respiratory illnesses across all trimesters and adequate statistical power for virus-specific analyses. Particular emphasis should be placed on standardized fetal growth assessment, including serial ultrasound-based biometry and placental evaluation where feasible, to clarify whether the reported association with SGA birth reflects true growth restriction or residual confounding. In addition, systematic neonatal testing at birth and structured long-term infant follow-up are needed to evaluate potential vertical transmission and longer-term developmental outcomes. Finally, prospective studies should carefully characterize maternal comorbidities—such as asthma, obesity and cardiometabolic disease—and assess their independent contribution to severe maternal and perinatal outcomes in order to distinguish virus-specific risk from host-related vulnerability.

Pregnancy registries and multicenter ICU collaborations could improve ascertainment of severe hMPV disease and clarify the contribution of individual comorbidities. Finally, as hMPV vaccine candidates and antivirals progress through development, inclusion of pregnant women in appropriately designed trials will be crucial to ensure that this population, which is already prioritized for other respiratory virus vaccines, is not left behind.

CONCLUSION

hMPV may represent an under-recognized cause of respiratory illness in pregnancy; however, the available evidence remains limited in size and methodological robustness. Community-based cohort data suggest that most antenatal infections are mild and self-limited, whereas referral-based case reports describe a small number of severe presentations-including pneumonia and ARDS-often in women with significant comorbidities. These observations suggest a possible spectrum of disease severity, but they do not permit reliable estimation of population-level risk.

A potential association with fetal growth restriction has been reported in a single cohort study, yet current data are insufficient to establish causality. The predominance of case reports, small sample sizes and limited virus-specific analyses substantially constrain inference regarding maternal, obstetric and neonatal outcomes.

Important uncertainties remain. It is not known whether hMPV directly affects placental function, whether vertical transmission occurs under specific conditions, or whether antenatal exposure has long-term developmental implications for infants. Larger, prospectively designed pregnancy cohorts with systematic virological testing, placental evaluation and structured infant follow-up are required to clarify causality and define true maternal and perinatal risk before evidence-based clinical recommendations can be made.