Gestational psittacosis: a systematic review of clinical manifestations and outcomes

Abstract

Background

Gestational psittacosis is a rare but severe zoonotic infection caused by Chlamydia psittaci. This systematic review aims to evaluate the clinical characteristics, diagnostic challenges, therapeutic interventions, and maternal–fetal outcomes of this condition.

Methods

A systematic search was conducted in PubMed, Embase, Web of Science, CNKI, and Wanfang Data from inception to October 31, 2025. Two investigators independently performed study selection and data extraction encompassing maternal demographics, clinical manifestations, laboratory findings, diagnostic modalities, antimicrobial regimens, and maternal–fetal outcomes.

Results

A total of 32 cases from 30 publications were included. The median maternal age was 29 years (IQR: 26–32), and the median gestational age at diagnosis was 26.5 weeks (IQR: 21–30). All patients presented with fever (32/32, 100%), and common symptoms included headache (17/32, 53%), cough (15/32, 47%), and dyspnea (15/32, 47%). Severe disease was frequent: 66% (21/32) required intensive care unit (ICU) admission, 34% (11/32) required endotracheal intubation, and maternal mortality was 13% (4/32). Thrombocytopenia (26/32, 81%), hepatic dysfunction (27/32, 84%), renal impairment (18/32, 56%), and disseminated intravascular coagulation (DIC) (15/32, 47%) were the most prominent laboratory abnormalities. Diagnostic approaches evolved from serology to molecular methods. Recent studies have demonstrated the potential value of metagenomic next-generation sequencing (mNGS) in diagnosis, but further research is needed to confirm its clinical utility. The overall fetal and neonatal mortality was 68% (21/31 with available data), primarily due to stillbirth, spontaneous abortion, or therapeutic induction. These estimates reflect outcomes among reported cases and may overestimate true population-level risk.

Conclusion

Gestational psittacosis is a rare but life-threatening infection associated with substantial maternal morbidity and a high risk of fetal loss, although these outcomes may be influenced by publication bias. mNGS has facilitated earlier diagnosis in recent case reports; however, comparative performance data for gestational psittacosis remain limited.

Trial registration

PROSPERO, CRD420251275911 (Registered 30 December 2025).

Clinical trial number

Not applicable.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12879-026-13575-1.

Background

Psittacosis is a zoonotic infectious disease caused by Gram-negative, obligate intracellular bacterium Chlamydia psittaci. The pathogen primarily circulates among wild birds, psittacine birds, and poultry [1], although livestock such as sheep, goats, cattle, and horses also serve as significant reservoirs [2]. Human infection typically occurs via the inhalation of contaminated aerosols or direct contact with infectious animal excreta [3], while human-to-human transmission is rare [4]. Psittacosis is an uncommon cause of community-acquired pneumonia (CAP). A meta-analysis found that C. psittaci is responsible for 1% of CAP cases annually [5]. However, the pathogen exhibits potent pathogenicity and rapid intracellular proliferation, which can provoke intense inflammatory responses and severe pulmonary involvement [6], and has been identified in approximately 8% of severe CAP cases in China [7]. Gestational psittacosis, defined as the occurrence of psittacosis during pregnancy, is rare but can result in increased maternal and fetal morbidity and mortality. One study reported fetal and maternal mortality of 94% and 6%, respectively [8]. Similarly, the analysis by Daisuke Katsura et al. [9] documented corresponding rates of 83% (19/23) and 9% (2/23). However, due to its non-specific clinical presentation and the paucity of pregnancy-specific data, gestational psittacosis remains frequently under-recognized, and consensus regarding its diagnosis and management remains limited. In this context, we conducted a retrospective analysis of published cases of gestational psittacosis to characterize its clinical features, diagnostic approaches, management, and maternal–fetal outcomes, with the goal of improving clinical recognition and pregnancy outcomes.

Methods

Registration and eligibility criteria

This systematic review was conducted in accordance with the PRISMA 2020 statement [10]. The protocol was registered in PROSPERO (CRD420251275911) on 30 December 2025. Registration occurred after the literature search but before completion of the final analysis.

Gestational psittacosis was defined as Chlamydia psittaci infection during pregnancy. We adopted the clinical definitions from the original studies, contingent upon meeting our laboratory criteria. In this review, a laboratory-supported diagnosis was established if at least one of the following criteria was met: (1) Serological evidence, requiring a four-fold or greater rise in specific antibody titers between paired acute and convalescent sera, or a single highly elevated titer deemed diagnostic; (2) Microbiological or histopathological evidence, including pathogen isolation from clinical specimens or characteristic histopathological identification, such as typical basophilic inclusions in the placental syncytiotrophoblast; or (3) Molecular evidence, requiring positive detection via specific polymerase chain reaction (PCR) or metagenomic next-generation sequencing (mNGS). For mNGS, given the obligate intracellular nature of Chlamydia psittaci and its absence in the normal human microbiome, the detection of at least one strictly mapped specific read (reads ≥ 1), combined with a compatible clinical syndrome, was considered diagnostic. Consequently, suspected cases relying solely on clinical symptoms and exposure history without any of the aforementioned laboratory or pathological confirmations were strictly excluded.

Exclusion criteria were: (1) review articles, non-original publications (abstracts or correspondence), or animal and in vitro studies; (2) reports with insufficient clinical details or lacking laboratory confirmation; and (3) duplicate publications.

Search strategy and study selection

A comprehensive search was conducted across PubMed, Embase, Web of Science, CNKI, and Wanfang Data databases from their respective inception dates up to October 31, 2025. The search strategy utilized a combination of Medical Subject Headings (MeSH) and free-text terms, detailed in Table 1. The search was restricted to English and Chinese publications. Although grey literature was not systematically searched, preprints and indexed conference abstracts were eligible for inclusion to ensure a comprehensive evidence synthesis for this rare condition, provided they contained sufficient clinical and laboratory data.

Table 1.

Full search strategies for each database

Database	Search Strategy (Last search date: October 31, 2025)
PubMed	((“Psittacosis“[Mesh] OR “Chlamydia psittaci“[Mesh] OR psittacosis[tiab] OR “parrot fever“[tiab] OR “Chlamydia psittaci“[tiab] OR “Chlamydophila psittaci“[tiab])) AND ((“Pregnancy“[Mesh] OR pregnant*[tiab] OR gestation[tiab] OR gravid*[tiab] OR maternal[tiab]))
Embase	(‘psittacosis’/exp OR ‘psittacosis’:ti, ab OR ‘Chlamydia psittaci’/exp OR ‘Chlamydia psittaci’:ti, ab OR ‘parrot fever’:ti, ab OR ‘chlamydophila psittaci’:ti, ab) AND (‘pregnancy’/exp OR ‘pregnancy’:ti, ab OR ‘pregnant’:ti, ab OR ‘gestation’:ti, ab OR ‘gravid’:ti, ab OR ‘maternal’:ti, ab)
Web of Science	TS=(psittacosis OR “parrot fever” OR “Chlamydia psittaci” OR “Chlamydophila psittaci”) AND TS=(pregnancy OR pregnant* OR gestation OR gravid* OR maternal)
CNKI	(Psittacosis OR Chlamydia psittaci) AND (Pregnancy OR Pregnant women OR Parturient)
Wanfang Data	(Psittacosis OR Chlamydia psittaci) AND (Pregnancy OR Pregnant women OR Parturient)

The study selection process followed systematic stages of identification, screening, and eligibility assessment. Titles, abstracts, and full texts were screened independently and in duplicate by two investigators (JF and YW) to determine final inclusion. Any discrepancies were resolved through detailed discussion to reach a consensus, with arbitration by a third senior investigator (XH) when necessary. The entire selection process is summarized in the PRISMA flow diagram (Fig. 1).

Fig. 1.

PRISMA flow diagram of the study selection process. The diagram illustrates the identification, screening, and inclusion of studies on gestational psittacosis, following the PRISMA 2020 guidelines

Data extraction and quality assessment

Data extraction was independently performed by two investigators using a standardized form. The primary outcomes extracted were maternal and fetal/neonatal survival, the incidence of severe complications (e.g., DIC and hemophagocytic lymphohistiocytosis [HLH]), and ICU admission. Secondary outcomes encompassed patient demographics, exposure history, clinical manifestations, laboratory findings, diagnostic modalities, and antimicrobial regimens.

Due to the inclusion of only case reports and small case series, a quantitative meta-analysis was not feasible. Data were synthesized narratively using descriptive statistics: continuous variables are presented as medians with interquartile ranges (IQR), and categorical variables as frequencies and percentages. Formal statistical assessment of publication bias (e.g., funnel plots) was not applicable; however, the potential reporting bias toward severe or fatal cases was qualitatively assessed and considered in the outcome interpretation.

To assess the methodological quality of the included case reports, the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports was used. Two investigators (JF and YW) independently evaluated each study across eight domains. Discrepancies were resolved by consensus, with arbitration by a third senior investigator (XH) when needed. Detailed quality assessment results for each study are provided in Supplementary Table S1. The limitations and potential biases of case-based evidence are further discussed in the limitations section.

Results

Patient characteristics and exposure history

A total of 30 studies involving 32 cases were ultimately included after a systematic screening of the initial records [8, 9, 11–38] (Fig. 1), including two reports [12, 13] that documented two cases each. The median maternal age was 29 years (IQR: 26–32; n = 31). Infection spanned all stages of pregnancy (range: 6–36 weeks), with a median gestational age of 26.5 weeks (IQR: 21–30) at diagnosis. Geographically, cases were predominantly reported from the United Kingdom (13/32, 41%) and China (8/32, 25%). Among the 31 cases with available exposure data, the most frequent suspected sources of infection were contact with sheep in 42% (13/31 with available data) [11–18, 23, 24, 37] and avian species (9/31, 29%) [9, 21, 22, 26, 29–31, 34, 38], followed by goats (3/31, 10%) [8, 19, 25], and occupational exposure to multiple animal species in a slaughterhouse (1/31, 3%) [20]. Five patients (5/31, 16%) [27, 28, 32, 35, 36] denied any known animal exposure. Comprehensive demographics and detailed exposure histories for all 32 cases are summarized in Table 2.

Table 2.

Demographic characteristics and exposure history of the 32 identified cases of gestational psittacosis

Case No.	First Author (Year) [Ref]	Country	Age (years)	GA (weeks)	Primary Exposure History
1	Roberts (1967) [11]	UK	22	26	Sheep (Indirect contact)
2	Beer (1982) [12]	UK	34	34	Sheep (Close contact with flock)
3	Beer (1982) [12]	UK	34	36	Sheep (Lambing assistance)
4	McKinlay (1985) [13]	UK	29	28	Sheep (Handling aborted fetus)
5	McKinlay (1985) [13]	UK	31	25	Multiple species (Vet nurse/Sheep)
6	Wong (1985) [14]	UK	28	28	Sheep (Lambing contact)
7	Helm (1989) [15]	UK	29	27	Sheep (Wiping newborn lambs)
8	Johnson (1985) [16]	UK	28	28	Sheep (Manual placental removal)
9	Herring (1987) [17]	UK	24	14	Sheep (Farmer’s wife)
10	Crosse (1991) [18]	UK	32	6	Sheep (Indirect/Farm visit)
11	Villemonteix (1990) [19]	France	26	32	Goats (Delivery assistance)
12	Hadley (1992) [20]	UK	35	19	Sheep/Cattle (Slaughterhouse)
13	Khatib (1995) [21]	USA	31	31	Avian (Pet parrots/cleaning cages)
14	Gherman (1995) [22]	USA	19	32	Avian (Pet parakeets)
15	Hyde (1997) [23]	USA	25	22	Sheep (Contact with products)
16	Jorgensen (1997) [24]	USA	25	21	Sheep (Manual placental removal)
17	Pospischil (2002) [25]	Switzerland	NR	19	Goats (Contact during abortion)
18	Walder (2005) [8]	Austria	28	25	Goats (Aborted placenta/fetus)
19	Walter (2014) [26]	UK	30	31	Avian (Infected parrots)
20	Paul (2018) [27]	USA	32	13	Denied (No known exposure)
21	Katsura (2020) [9]	Japan	31	17	Avian (Distant parrot contact)
22	Li (2021) [28]	China	29	21	Denied (No known exposure)
23	Yang (2021) [29]	China	33	29	Avian (Pet parrots)
24	Sun (2021) [30]	China	27	26	Avian (Poultry contact)
25	Liu (2022) [31]	China	25	36	Avian (Poultry contact)
26	Yoshimura (2022) [32]	Japan	26	23	Denied (No known exposure)
27	Yue (2023) [33]	China	31	27	NR
28	Wang (2023) [34]	China	41	16	Avian (Infected bird contact)
29	Miyauchi (2024) [35]	Japan	28	28	Denied (No known exposure)
30	Ye (2025) [36]	China	38	28	Denied (No known exposure)
31	Guscoth (2022) [37]	UK	30	31	Sheep (Handling dead lambs)
32	Wu (2024) [38]	China	27	22	Avian (Play with parrots)
Summary	-	UK: 13/32 (41%) China: 8/32 (25%) USA: 5/32 (16%) Japan: 3/32 (9%) Others: 3/32 (9%)	Median 29 (IQR: 26–32) (n = 31)	Median 26.5 (IQR: 21–30) (n = 32)	Sheep: 13/31 (42%) Avian: 9/31 (29%) Goat: 3/31 (10%) Multiple: 1/31 (3%) Denied: 5/31 (16%) NR: 1

Abbreviations: GA, gestational age; NR, not reported; Ref, reference; IQR, interquartile range

Clinical manifestations

The incubation period following human exposure to C. psittaci is typically 5–14 days [4]. Among the nine cases with a documented incubation period [8, 13, 15, 18–20, 24, 34, 38], the interval from exposure to symptom onset ranged from 5 days to 1 month, most commonly 1–2 weeks.

Although C. psittaci infection may involve multiple organ systems, pulmonary involvement predominated in the present cohort. Among the 32 patients included, the majority initially presented with influenza-like systemic symptoms accompanied by respiratory manifestations. Fever was the most prominent clinical manifestation, present in all cases (100%). Among patients with documented temperature measurements, peak body temperatures frequently exceeded 39 °C, reaching up to 40.5 °C. Other common symptoms included headache (17/32, 53%), cough (15/32, 47%), dyspnea (15/32, 47%), myalgia (10/32, 31%), fatigue (9/32, 28%), chest pain (5/32, 16%), and pharyngalgia (4/32, 13%).

Gastrointestinal symptoms primarily presented as nausea and vomiting (10/32, 31%). Neurological involvement (7/32, 22%) included impaired consciousness (3/32, 9%), dizziness (2/32, 6%), and photophobia (2/32, 6%). Less frequent features (e.g., abdominal pain, rash, and hemoptysis), alongside a comprehensive summary of all clinical manifestations, are detailed in Table 3.

Table 3.

Clinical manifestations, laboratory findings, and complications of 32 identified cases

Case No.	First Author [Ref]	Fever	Headache	Cough	Dyspnea	Nausea/ Vomiting	Thrombocytopenia	Hepatic Dysf.	Renal Impair.	Coagulopathy/DIC	Other Clinical Features
1	Roberts (1967) [11]	+	+	-	-	+	+	+	+	-	Back pain, Impaired consciousness
2	Beer (1982) [12]	+	+	-	+	-	-	-	-	+	Abdominal pain
3	Beer (1982) [12]	+	+	-	-	+	+	-	-	+	-
4	McKinlay (1985) [13]	+	-	-	+	-	+	+	+	+	Myalgia, Chest pain, Pharyngalgia, Impaired consciousness, Diarrhea
5	McKinlay (1985) [13]	+	+	-	-	+	-	-	-	+	Photophobia, Rash, Petechiae
6	Wong (1985) [14]	+	+	-	-	-	+	+	+	+	Fatigue
7	Helm (1989) [15]	+	+	-	-	-	+	+	+	+	Myalgia, Pharyngalgia, Jaundice, Epistaxis
8	Johnson (1985) [16]	+	-	-	-	+	+	+	+	+	MOF
9	Herring (1987) [17]	+	+	+	+	-	+	+	-	+	Back pain, Abdominal pain, Rash, Epistaxis
10	Crosse (1991) [18]	+	-	+	-	-	-	-	-	-	Fatigue, Chest pain
11	Villemonteix (1990) [19]	+	-	+	-	-	+	+	+	+	-
12	Hadley (1992) [20]	+	-	+	+	+	+	+	+	+	Chest pain, Hemoptysis, MOF, Constipation
13	Khatib (1995) [21]	+	+	+	+	+	+	+	-	-	Myalgia, Chest pain
14	Gherman (1995) [22]	+	+	+	-	+	+	+	+	+	Chest pain, Pharyngalgia, Photophobia, Abdominal pain
15	Hyde (1997) [23]	+	+	+	-	-	+	+	+	-	Myalgia, Fatigue
16	Jorgensen (1997) [24]	+	+	+	-	-	+	+	-	-	Myalgia, Fatigue, Back pain
17	Pospischil (2002) [25]	+	-	-	-	+	-	-	-	-	Dizziness
18	Walder (2005) [8]	+	-	-	-	-	+	+	+	-	Myalgia
19	Walter (2014) [26]	+	-	-	-	+	+	+	-	-	-
20	Paul (2018) [27]	+	+	-	-	-	+	+	-	-	Fatigue
21	Katsura (2020) [9]	+	+	-	+	-	+	+	+	+	Myalgia, Fatigue, MOF
22	Li (2021) [28]	+	-	+	+	-	+	+	+	-	-
23	Yang (2021) [29]	+	-	+	-	-	+	+	-	-	Fatigue
24	Sun (2021) [30]	+	-	+	+	-	+	+	+	+	Diarrhea, Hemoptysis, HLH
25	Liu (2022) [31]	+	-	+	+	-	+	+	-	-	-
26	Yoshimura (2022) [32]	+	+	-	-	+	+	+	-	-	Myalgia, Fatigue, Rash, HLH
27	Yue (2023) [33]	+	+	+	+	-	+	+	-	-	Dizziness
28	Wang (2023) [34]	+	+	-	+	-	+	+	+	-	-
29	Miyauchi (2024) [35]	+	-	+	+	-	+	+	+	+	Impaired consciousness, MOF
30	Ye (2025) [36]	+	+	-	+	-	+	+	+	+	Myalgia, Fatigue, Pharyngalgia, Jaundice, Petechiae Conjunctival injection
31	Guscoth (2022) [37]	+	-	-	+	-	-	+	+	-	-
32	Wu (2024) [38]	+	-	+	+	-	-	+	+	-	Myalgia
Summary	n/N (%)	32/32 (100%)	17/32 (53%)	15/32 (47%)	15/32 (47%)	10/32 (31%)	26/32 (81%)	27/32 (84%)	18/32 (56%)	15/32 (47%)

Abbreviations: DIC, disseminated intravascular coagulation; Dysf., dysfunction; HLH, hemophagocytic lymphohistiocytosis; Impair., impairment; MOF, multiple organ failure

Notes: “+” indicates that the symptom or abnormality was explicitly reported as present; “–” indicates that it was either explicitly reported as absent or not described in the original report

Within the included cohort, gestational psittacosis frequently presented with a severe clinical course. ICU admission was required in 66% (21/32) of patients, and endotracheal intubation was performed in 34% (11/32), with a maternal mortality of 13% (4/32); these estimates may be inflated by publication bias. Table 4 presents observational data comparing maternal survivors (n = 28) and non-survivors (n = 4), as the small sample size precluded formal statistical analysis.

Table 4.

Comparison of clinical features and complications between maternal survivors and non-survivors

Characteristics	Survivors (n = 28)	Non-survivors (n = 4)	Total (N = 32)
Clinical manifestations
Fever	28 (100%)	4 (100%)	32 (100%)
Headache	14 (50%)	3 (75%)	17 (53%)
Dyspnea	12 (43%)	3 (75%)	15 (47%)
Laboratory and complication profile
Thrombocytopenia	23 (82%)	3 (75%)	26 (81%)
Hepatic dysfunction	24 (86%)	3 (75%)	27 (84%)
Renal impairment	16 (57%)	2 (50%)	18 (56%)
Coagulopathy / DIC	12 (43%)	3 (75%)	15 (47%)
Multiple organ failure (MOF)	2 (7%)	2 (50%)	4 (13%)
Hemophagocytic lymphohistiocytosis (HLH)	1 (4%)	1 (25%)	2 (6%)
Fetal and neonatal outcomes
Fetal/neonatal mortality	17/27 (63%)*	4/4 (100%)	21/31 (68%)*

Abbreviations: DIC, disseminated intravascular coagulation; HLH, hemophagocytic lymphohistiocytosis; MOF, multiple organ failure

Notes: Data are presented as n (%) or n/N (%). Given the small sample size of maternal non-survivors (n = 4), these comparisons are purely descriptive and should be interpreted with caution. *One case among the survivors was excluded from the fetal outcome calculation due to an unspecified neonatal outcome (available n = 27 for survivors)

Fatal cases typically exhibited fulminant progression. One patient rapidly developed severe DIC and circulatory failure after a 48-hour prodrome, resulting in fetal demise within 12 h of admission and maternal death 14 h later [12]. Two additional cases reported rapid progression to acute respiratory distress syndrome (ARDS), severe DIC, and shock, ultimately causing irreversible multiple organ dysfunction syndrome (MODS) and death within hours to days [9, 35].

A subset of cases developed severe complications. Sun et al. [30] reported a patient with secondary HLH after pneumonia control, presenting with high-grade fever, pancytopenia, hypertriglyceridemia, hyperferritinemia, and bone marrow hemophagocytosis, who achieved remission with etoposide and dexamethasone. Yoshimura et al. [32] described fulminant HLH without respiratory symptoms, rapidly progressing to mortality within 48 h. Ye et al. [36] documented a TTP-like syndrome with fever, headache, acute kidney injury, thrombocytopenia, microangiopathic hemolytic anemia, and reduced ADAMTS-13 activity, successfully treated with plasma exchange, immunosuppressive therapy, and antimicrobial treatment.

Radiological characteristics

Among 21 patients with available chest imaging, predominant findings included consolidation and infiltrative opacities, mainly involving the lower lobes and basal segments [8, 11, 14, 16, 18, 20, 21, 24, 28–30, 33, 34], consistent with typical imaging features of C. psittaci pneumonia [39]. Rapid radiological progression was noted in some cases, with development of multifocal confluent consolidation and ground-glass opacities (GGO) [9, 20, 30, 37]. Pleural effusion was present in 43% (9/21 with available data), typically small-to-moderate and often bilateral [14, 16, 22, 28–30, 33, 34, 36]. Hilar or mediastinal lymphadenopathy occurred in a minority [11, 18], including one sarcoidosis-like presentation [18].

Laboratory findings

In this cohort, thrombocytopenia occurred in 81% (26/32), with 38% (12/32) < 50 × 10⁹/L, 22% (7/32) < 20 × 10⁹/L, and a nadir of 9 × 10⁹/L [17]. White blood cell (WBC) counts were normal in 59% (19/32). Leukocytosis occurred in 22% (7/32) with a peak of 46 × 10⁹/L [20], while leukopenia occurred in 19% (6/32) with a nadir of 2.0 × 10⁹/L [8]. Anemia affected 63% (20/32), with hemoglobin as low as 60 g/L [19]. Coagulation abnormalities occurred in 47% (15/32), often with DIC or severe coagulopathy and peak D-dimer > 20 mg/L [36].

Elevated transaminases (84%, 27/32) and hyperbilirubinemia (41%, 13/32) were prevalent, with hepatosplenomegaly noted in some cases. Lactate dehydrogenase (LDH) was elevated in all 15 patients with available data. Renal impairment occurred in 56% (18/32) of the cohort. Procalcitonin (PCT; 100%, 7/7 with available data) and C-reactive protein (CRP; 100%, 13/13 with available data) were elevated, including in cases without evidence of co-infection. Hyponatremia occurred in 63% (20/32) of the cohort. The primary laboratory findings are summarized in Table 3.

Fetal and neonatal outcome

In the present study, one case [36] did not specify the neonatal outcome. Fetal and neonatal mortality was 68% (21/31 with available data), likely overestimated due to publication bias. Fatal outcomes included spontaneous abortion (n = 7) [11, 17, 18, 20, 25, 27, 34], therapeutic induction (n = 3) [23, 24, 30], intrauterine death or stillbirth (n = 10) [9, 12–16, 19, 28, 32, 35], and early neonatal death (n = 1) [13].

Of the 10 surviving neonates, 5 cases [12, 21, 26, 31, 38] had stable outcomes and required no specialized medical intervention. The remaining five survivors [8, 22, 29, 33, 37] required respiratory support or intensive care due to complications. For instance, the neonate reported by Walder et al. [8] (31 weeks, 970 g) required mechanical ventilation for 9 weeks but demonstrated normal development at 6 months.

Histopathological examinations of placental tissue across multiple studies [14, 16, 23, 25, 32] have consistently revealed characteristic acute placentitis, featuring diffuse intervillositis with dense neutrophilic infiltration, perivillous fibrinoid necrosis and deposition, extensive trophoblast necrosis, and the presence of distinctive basophilic inclusions within the cytoplasm of syncytiotrophoblasts. Maternal and fetal outcomes for all identified cases are presented in Table 5.

Table 5.

Diagnostic methods, antibiotic treatments, and maternal–fetal outcomes of 32 identified cases

Case No.	First Author [Ref]	Diagnostic Method	Antibiotic Treatment (Antenatal/Postpartum)	ICU Admission	Maternal Outcome	Fetal/Neonatal Outcome
1	Roberts (1967) [11]	Serology	Tetracycline	No	Survived	Spontaneous abortion
2	Beer (1982) [12]	Serology	Cephalothin, Gentamicin, Erythromycin	Yes	Died	IUD / Stillbirth
3	Beer (1982) [12]	Serology	Ampicillin, Gentamicin	No	Survived	Alive (Good condition)
4	McKinlay (1985) [13]	Serology	Penicillin, Gentamicin, Doxycycline	Yes	Survived	IUD / Stillbirth
5	McKinlay (1985) [13]	Serology	Mezlocillin, Erythromycin, Doxycycline	Yes	Survived	Early neonatal death
6	Wong (1985) [14]	Pathogen isolation	Penicillin, Cloxacillin, Cefoxitin	Yes	Survived	IUD / Stillbirth
7	Helm (1989) [15]	Pathogen isolation	Ceftazidime, Erythromycin, Tetracycline	No	Survived	IUD / Stillbirth
8	Johnson (1985) [16]	Pathogen isolation	Ampicillin, Penicillin, Cefoxitin	Yes	Survived	IUD / Stillbirth
9	Herring (1987) [17]	Pathology	Erythromycin, Rifampicin	Yes	Survived	Spontaneous abortion
10	Crosse (1991) [18]	Serology	Erythromycin, Oxytetracycline	No	Survived	Spontaneous abortion
11	Villemonteix (1990) [19]	Serology/Pathology	Amoxicillin, Gentamicin, Spiramycin	Yes	Survived	IUD / Stillbirth
12	Hadley (1992) [20]	Pathology	Cefuroxime, Amoxicillin, Doxycycline	Yes	Survived	Spontaneous abortion
13	Khatib (1995) [21]	Serology	Erythromycin, Doxycycline	Yes	Survived	Alive (Good condition)
14	Gherman (1995) [22]	Serology	Erythromycin, Doxycycline	No	Survived	Alive (IMV, NICU)
15	Hyde (1997) [23]	Pathology/Serology	None (Pregnancy termination)	Yes	Survived	Therapeutic induction
16	Jorgensen (1997) [24]	Pathology/Serology	Cefazolin	No	Survived	Therapeutic induction
17	Pospischil (2002) [25]	PCR/Pathology	Tetracycline	No	Survived	Spontaneous abortion
18	Walder (2005) [8]	Serology	Doxycycline	Yes	Survived	Alive (IMV, NICU)
19	Walter (2014) [26]	Serology	Macrolide	No	Survived	Alive (Good condition)
20	Paul (2018) [27]	mNGS (Postmortem)	Cefuroxime, Prednisone	No	Survived	Spontaneous abortion
21	Katsura (2020) [9]	PCR	Meropenem	Yes	Died	IUD / Stillbirth
22	Li (2021) [28]	mNGS	Azithromycin, Meropenem, Moxifloxacin	Yes	Survived	IUD / Stillbirth
23	Yang (2021) [29]	mNGS	Meropenem, Doxycycline, Moxifloxacin	No	Survived	Alive (NIV, NICU)
24	Sun (2021) [30]	mNGS	Doxycycline, Moxifloxacin, Vancomycin	Yes	Survived	Therapeutic induction
25	Liu (2022) [31]	mNGS	Ceftriaxone, Doxycycline	Yes	Survived	Alive (Good condition)
26	Yoshimura (2022) [32]	Pathology/PCR	None (Rapid clinical course)	No	Died	IUD / Stillbirth
27	Yue (2023) [33]	mNGS	Doxycycline, Azithromycin, Meropenem	Yes	Survived	Alive (NIV, NICU)
28	Wang (2023) [34]	mNGS	Meropenem, Moxifloxacin, Azithromycin	Yes	Survived	Spontaneous abortion
29	Miyauchi (2024) [35]	Pathology/PCR	Meropenem	Yes	Died	IUD / Stillbirth
30	Ye (2025) [36]	mNGS	Omadacycline, Azithromycin	Yes	Survived	Unspecified
31	Guscoth (2022) [37]	Serology	Doxycycline, Clarithromycin, Ceftriaxone	Yes	Survived	Alive (NICU)
32	Wu (2024) [38]	mNGS/PCR	Azithromycin, Tigecycline	Yes	Survived	Alive (Good condition)
Summary n/N (%)	-	Serology: 14/32 (44%) mNGS: 9/32 (28%) Pathology/Isolation: 5/32 (16%) PCR: 4/32 (13%)	-	21/32 (66%)	Survived: 28/32 (88%) Died: 4/32 (13%)	Survival:10/31 (32%) Death:21/31 (68%) Unspecified: 1

Abbreviations: IUD, intrauterine death; mNGS, metagenomic next-generation sequencing; PCR, polymerase chain reaction; NICU, neonatal intensive care unit; IMV, invasive mechanical ventilation; NIV, non-invasive ventilation

Notes: Percentages may not sum to 100% due to rounding

Diagnostic methods

Diagnostic confirmation across the 32 cases relied on serology (14/32, 44%), mNGS (9/32, 28%), pathogen isolation or histopathology (5/32, 16%), and targeted polymerase chain reaction (PCR) (4/32, 13%) (Table 5). Exact daily intervals from symptom onset to diagnosis could not be consistently determined due to variable reporting details.

Serological testing, primarily complement fixation tests (CFT) and micro-immunofluorescence (MIF), was historically the mainstay of diagnosis. Confirmation based on a fourfold or greater increase in C. psittaci–specific antibody titers resulted in retrospective diagnosis after clinical recovery or pregnancy termination. In the cases confirmed via histopathology or isolation, specimens primarily included placental tissue, fetal heart blood, and fetal lung. These cases were identified through pathogen isolation from clinical samples or the histopathological observation of characteristic basophilic inclusions within the syncytiotrophoblast cytoplasm.

Molecular diagnostics, including PCR and mNGS, were utilized in the remaining cases. PCR-based detection was first recorded by Pospischil et al. [25] using placental tissue. mNGS was subsequently applied to identify C. psittaci nucleic acids in clinical specimens including blood, bronchoalveolar lavage fluid (BALF), sputum, and archived lung tissue obtained at autopsy [27, 28, 34].

Treatment

Initial empirical antimicrobial therapy varied, with β-lactams most commonly used before definitive diagnosis [9, 12–16, 24, 35]. Upon suspicion or confirmation of C. psittaci infection, therapy was guided by gestational status: macrolides predominated antenatally [21, 22, 26], whereas tetracyclines, mainly doxycycline, were preferred postpartum [8, 13, 21]. Severe cases often received multidrug regimens [28, 29, 34].

Among maternal survivors, most received targeted intracellular agents, though some received only β-lactams, aminoglycosides, or no specific antibiotics, often in association with pregnancy termination [12, 14, 16, 23, 24, 27]. In four maternal deaths, treatments included meropenem [9, 35], cephalothin/gentamicin/erythromycin [12], or no antibiotics due to rapid deterioration [32]. One report described maternal recovery and a healthy neonate after a 24-day azithromycin-tigecycline course [38]. Treatment duration and neonatal follow-up were frequently underreported.

Discussion

Pregnant women are more susceptible to intracellular pathogens, likely due to altered cell-mediated immunity [35]. Our analysis of 32 cases shows gestational psittacosis as a severe disease with rapid deterioration and multisystem involvement, with 66% requiring ICU care, maternal mortality of 13%, and fetal/neonatal mortality of 68%. For comparison, Katsura et al. [9] reported maternal and fetal mortality of 9% and 83%, respectively. These figures may overestimate population-level risk due to reporting bias.

High fetal loss is driven by multiple factors. Maternal complications such as septic shock, DIC, and ARDS exacerbate fetal hypoxia and hypotension. Histopathology in several cases [14, 16, 23, 25, 32] shows active pathogen replication in the placenta causing acute placentitis and trophoblast necrosis, resulting in utero-placental malperfusion and fetal death without direct fetal infection. Iatrogenic termination or early delivery due to maternal deterioration also contributes to fetal and neonatal loss.

Gestational psittacosis is a rare zoonotic infection, with 81% (26/32) of patients in our cohort reporting animal exposure. Clinical presentations vary, reflecting differences in exposure intensity and host immunity. Common laboratory abnormalities include hepatic (84%) and renal impairment (56%), alongside thrombocytopenia (81%). Platelets play a key role in vascular immunity [40], and their progressive decline signals increasing disease severity. In our cohort, severe thrombocytopenia was linked to fulminant complications such as DIC and secondary hemophagocytic syndrome [30, 34]. Due to its nonspecific clinical and laboratory features, gestational psittacosis can be easily confused with pregnancy-related conditions such as HELLP syndrome or acute fatty liver of pregnancy (AFLP). Consequently, when encountering pregnant women presenting with unexplained persistent fever (> 48 h) and thrombocytopenia, clinicians should be alert to the possibility of psittacosis, especially if an epidemiological link to avian or ruminant sources exists. To facilitate early recognition and clinical management of suspected cases, we propose a diagnostic and therapeutic algorithm for gestational psittacosis based on the findings of this review (Fig. 2).

Fig. 2.

Clinical algorithm for the evaluation and management of suspected gestational psittacosis. CAP, community-acquired pneumonia; HELLP, hemolysis, elevated liver enzymes, low platelets; PCR, polymerase chain reaction; BALF, bronchoalveolar lavage fluid; mNGS, metagenomic next-generation sequencing; DIC, disseminated intravascular coagulation; MOF, multiple organ failure; HLH, hemophagocytic lymphohistiocytosis

Traditional serology is limited by its retrospective nature, cross-reactivity with other Chlamydia species, and blunted antibody responses from early antibiotic therapy [21, 41], reducing specificity and delaying acute diagnosis. mNGS shows promise for diagnosing severe or atypical psittacosis [39, 42–44], though its clinical utility requires further validation. Regarding management, macrolides are the mainstay of treatment during pregnancy, with tetracyclines typically reserved postpartum [45]. Early delivery or termination was often necessary to prevent maternal deterioration [23, 24, 30]. Although a recent case reported successful use of azithromycin-tigecycline [38], its safety and efficacy in pregnancy remain unestablished.

Given the zoonotic nature of gestational psittacosis, public health strategies should emphasize exposure counseling for pregnant women regarding the risks associated with livestock, particularly birds and ruminants. Furthermore, high-risk occupational groups warrant heightened vigilance, and adherence to standard biosafety measures is recommended.

This review synthesizes evidence exclusively from retrospective case reports and small case series, which constitutes its primary limitation. Despite the rigorous literature search and structured quality assessment, the overall quality of evidence remains of low certainty due to the absence of controlled observational studies or randomized trials for this rare condition. These study designs are inherently susceptible to significant publication and selection bias. The overrepresentation of severe, fatal, or diagnostically challenging cases likely leads to an overestimation of morbidity and mortality rates. Consequently, these estimates reflect outcomes among reported cases rather than true population-level risks, as milder infections remain underrepresented. Furthermore, the heterogeneity in diagnostic methods, clinical practices, and reporting completeness across several decades affects data consistency. Together, these constraints necessitate a cautious interpretation of the synthesized clinical patterns and highlight the critical need for systematic, prospective data collection.

Conclusions

Gestational psittacosis is a rare zoonotic infection predominantly characterized by severe atypical pneumonia and multi-organ dysfunction. Our synthesis of 32 cases demonstrates substantial risks of maternal mortality (13%) and adverse fetal outcomes (68%). These estimates should be interpreted cautiously, as publication bias may overestimate true population-level risks. The adoption of molecular diagnostics, particularly mNGS, has facilitated earlier diagnosis in recent reports and can aid in initiating targeted antimicrobial therapy, pending further comparative data. Heightened clinical awareness is necessary to differentiate this condition from pregnancy-specific syndromes and optimize maternal–fetal outcomes.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

ADAMTS-13

A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13

ARDS

Acute respiratory distress syndrome

BALF

Bronchoalveolar lavage fluid

CAP

Community-acquired pneumonia

CFT

Complement fixation tests

CNKI

China National Knowledge Infrastructure

CRP

C-reactive protein

DIC

Disseminated intravascular coagulation

GGO

Ground-glass opacities

HELLP

Hemolysis, elevated liver enzymes, low platelet count syndrome

HLH

Hemophagocytic lymphohistiocytosis

ICU

Intensive care unit

IMV

Invasive mechanical ventilation

IQR

Interquartile range

IUD

Intrauterine death

JBI

Joanna Briggs Institute

LDH

Lactate dehydrogenase

MeSH

Medical Subject Headings

MIF

Micro-immunofluorescence

mNGS

Metagenomic next-generation sequencing

MODS

Multiple organ dysfunction syndrome

MOF

Multiple organ failure

NICU

Neonatal intensive care unit

NIV

Non-invasive ventilation

PCR

Polymerase chain reaction

PCT

Procalcitonin

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO

International Prospective Register of Systematic Reviews

TTP

Thrombotic thrombocytopenic purpura

WBC

White blood cell

Author contributions

JF and YW contributed equally to this work and are considered co-first authors. XH conceived and designed the study. JF and YW performed the literature search, study selection, data extraction, and quality assessment. JH, JL, and WX participated in data verification, literature organization, and preparation of tables and figures. JF drafted the manuscript, and XH and YW revised it for important intellectual content. All authors have read and approved the final manuscript.

Funding

This work was supported by the following grants: Scientific Research Project of Chengdu Municipal Health Commission (Grant No. 2025359). Key Research and Development Support Program of Chengdu Science and Technology Bureau (Grant No. 2024-YF09-00021-SN). Primary Health Care Research Project of Ganzi County People’s Hospital (Grant No. 2025GZX002). 2025 Scientific Research Project of Sichuan Rehabilitation Medical Association (Grant No. SCKFKY20250217).

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Declarations

Ethics approval and consent to participate

Not applicable. This study is a systematic review of previously published literature and does not involve the primary collection of human data or tissue. As this research is a secondary analysis of publicly available data, ethical approval and informed consent were not required according to institutional and national guidelines.

Consent for publication

Not applicable. This manuscript does not contain any identifiable individual person’s data in any form (including individual details, images, or videos) collected directly by the authors. All clinical information presented was extracted from previously published case reports and series.

Competing interests

The authors declare no competing interests.