What to expect after birth in idiopathic polyhydramnios? An analysis of postnatal diagnoses and their relationship to the polyhydramnios degree

What to expect after birth in idiopathic polyhydramnios? 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An analysis of postnatal diagnoses and their relationship to the polyhydramnios degree Sumeyra Gurel, Isil Ayhan, Lutfiye Uygur, Berk Ozgit, Oya Demirci This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2524533/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Sep, 2023 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 5 You are reading this latest preprint version Abstract Purpose: To analyze postnatal abnormalities in idiopathic polyhydramnios and to estimate whether there was a significant association between the severity of polyhydramnios and postnatally diagnosed abnormalities. Methods: This was a retrospective cohort study of all idiopathic polyhydramnios cases that delivered at our center between 2017 and 2021. Cases were identified as idiopathic after excluding known fetal genetic and/or structural abnormalities (including soft markers for aneuploidies), Rh isoimmunization, fetal anemia, multifetal pregnancies, pregestational (preGDM) or gestational diabetes (GDM), and known infection with TORCH group agents. The primary outcome was the association between polyhydramnios degree and any abnormalities detected after birth. Additional outcomes were the odds of specific groups of abnormalities based on polyhydramnios degree. Results: Outcomes of 242 pregnancies with idiopathic polyhydramnios were analyzed. At least one neurodevelopmental, structural, or genetic abnormality was diagnosed in 16.1% of children born to women with idiopathic polyhydramnios. Moderate and severe polyhydramnios are significantly associated with at least one abnormality diagnosed after birth (45.9%, and 41.6%, respectively, p <0.05). Neurodevelopmental disorders were the most frequent abnormality (8.2%), followed by genetic abnormalities (2.4%), gastrointestinal abnormalities (2%) and nocturnal enuresis (2%). Odds of genetic abnormalities, neurodevelopmental disorders and nocturnal enuresis in moderate polyhydramnios were significantly higher (aOR=5.5, 95%CI 1.01-30.2; aOR: 8.9, 95% CI 2.7-23.7 and OR: 8.9, 95% CI 1.4-55.5, respectively). Gastrointestinal anomalies were significantly associated with severe polyhydramnios, as expected (OR: 15.4, 95% CI 2.4-97.5). Conclusion: Postnatally detected abnormalities are associated with moderate and severe idiopathic polyhydramnios. Particularly high risks include neurodevelopmental disorders, genetic abnormalities, gastrointestinal atresias and nocturnal enuresis. Polyhydramnios neurodevelopmental disorder nocturnal enuresis gastrointestinal atresia Figures Figure 1 Introduction Polyhydramnios is defined as an excess amount of amniotic fluid and affects 1–2% of pregnancies[1,2]. Amniotic fluid disorders occur when the balance between amniotic fluid production and excretion is disrupted, which is mostly caused by decreased fetal swallowing and increased fetal urine output, due to various fetal and maternal conditions[3]. Perinatal morbidity, such as preterm birth, cesarean delivery, premature rupture of membranes, malpresentation, and perinatal mortality, are more frequent in women with polyhydramnios[4]. While fetal anatomical abnormalities and maternal diabetes are the most common causes of polyhydramnios, the majority of cases remain unexplained in the prenatal period and are thus classified as idiopathic. However, according to the literature, roughly 10% of idiopathic polyhydramnios cases will have at least one anomaly diagnosed after birth[5]. Because some fetal anatomic abnormalities (such as esophageal and anal atresia, fetal akinesia deformation sequence) may be overlooked in ultrasound scans, even in expert hands; moreover, some genetic disorders and/or neuromuscular diseases will not have a unique characteristic that can be seen in ultrasound; prenatal counseling of patients with idiopathic polyhydramnios, is challenging. In the literature, there is a paucity of robust data on how and when to anticipate fetal abnormalities in cases of idiopathic polyhydramnios. Some argue that if prenatal ultrasound scans are normal, the likelihood of abnormalities increases as the severity of polyhydramnios increases[1], yet contradictory data is also present[6,5]. We analyzed idiopathic polyhydramnios cases in this study to estimate whether there was a significant association between the severity of polyhydramnios and postnatally diagnosed abnormalities. Materials & Methods This is a retrospective cohort study of idiopathic polyhydramnios cases who had delivered at Zeynep Kamil Women and Children’s Diseases Training and Research Hospital between January, 2017 and December, 2021. Cases were collected from electronic health records by their “International Classification of Diseases (ICD)” code (O40: Polyhydramnios). The study is approved by the institutional review board of Zeynep Kamil Women and Children’s Diseases Training and Research Hospital (Decision number: 188). Diagnosis of polyhydramnios was made when ultrasonographic deepest vertical pocket (DVP) measurement of amniotic fluid ≥ 8 cm or amniotic fluid index (AFI) ≥ 24 cm. Mild polyhydramnios was defined as AFI of 24 to 29 cm or DVP of 8 to 11 cm, moderate polyhydramnios as AFI of 30 to 34 cm or DVP of 12 to 15 cm, and severe polyhydramnios as AFI ≥ 35 cm or DVP ≥ 16 cm. Medical and obstetric history information, records of oral glucose tolerance test (OGTT), indirect Coombs test (IDC), serology for TORCH (Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes Simplex Virus, and Parvovirus B19) group infections, second-trimester anatomy scans and follow-up ultrasound scans, obstetric and neonatal outcomes were reviewed. Exclusion criteria were known fetal genetic and/or structural abnormalities (including soft markers for aneuploidies), Rh isoimmunization, fetal anemia, multifetal pregnancies, pregestational (preGDM) or gestational diabetes (GDM), and known infection with TORCH group agents. Cases were identified as idiopathic polyhydramnios after the exclusion criteria were applied. Data on neurodevelopmental outcomes, genetic and structural abnormalities diagnosed after birth were obtained by electronic health records when available, and telephone interviews with the families. The primary outcome was the association between polyhydramnios severity and any abnormalities detected after birth. As a result, the final cohort was stratified based on the presence of any postnatal abnormality. Neurodevelopmental abnormalities were grouped as neuromuscular disorders, speech and language disorders, autism spectrum disorder (ASD) and neurodevelopmental delay. Speech and language disorders were further subgrouped as specific language impairment (abnormal development of comprehension and/or production of language where difficulties cannot be accounted for by generally slow development, physical abnormality of the speech apparatus, autism spectrum disorder, apraxia, acquired brain damage or hearing loss), articulation disorder (difficulty in physically producing sounds) and stuttering. Failure to achieve developmental milestones affecting motor function, emotion, learning ability, self-control, or memory, was defined as neurodevelopmental delay. The secondary outcome was the odds of specific groups of abnormalities based on polyhydramnios severity. Odds of neurodevelopmental disorders, genetic abnormalities, structural abnormalities and nocturnal enuresis were calculated in each group of polyhydramnios. Descriptive statistics of continuous variables were analyzed with Mann-Whitney U test or t-test. Categorical variables were analyzed with Chi-square and Fisher exact test. Logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of binary outcomes. All analyses were performed using STATA software, version 17.0 Basic Edition (Copyright 1985–2021 StataCorp LLC). A p-value of < 0.05 was considered statistically significant. Results A total of 36005 women had delivered at our center during the study period. Of those, 1853 (5.1%) had been diagnosed with polyhydramnios. After exclusion, 273 cases fulfilled the inclusion criteria. However, 28 cases had insufficient data and could not be communicated, therefore excluded. 3 cases had intrauterine fetal demise. A final cohort of 242 pregnancies with idiopathic polyhydramnios was analyzed (Fig. 1 ). The prevalence of idiopathic polyhydramnios was 14.7%. Clinical characteristics of idiopathic polyhydramnios cases are presented in Table 1 . The mean gestational age at the time of diagnosis was 31.1 \(\pm\) 3.6 weeks, and was not statistically different between groups (30.6 \(\pm\) 3.4 in the abnormality group, 31.3 \(\pm\) 3.6 in the no-abnormality group, p=0.33). The mean gestational age at delivery and birthweight were significantly lower in the abnormality group (37.4 \(\pm\) 3 vs. 38.4 \(\pm\) 1.5, p<0.05 and 3047 \(\pm\) 801 vs. 3424 \(\pm\) 461, p<0.05, respectively). There were three preterm births before the 34th weeks of gestation, and all were found to have an abnormality after birth. Neonatal intensive care unit (NICU) admission rate was also significantly higher in the abnormality group (48% vs. 13.3%, p <0.05). In the postnatal period, at least one neurodevelopmental, structural, or genetic abnormality was diagnosed in 16.1% of children born to women with idiopathic polyhydramnios. When stratified based on the degree of polyhydramnios, 74.7% of women had mild, 15.2% had moderate and 9.9% had severe polyhydramnios. There were no significant differences in fetal sex based on the degree of polyhydramnios (p = 0.567). Moderate and severe polyhydramnios are significantly associated with at least one abnormality diagnosed after birth (45.9%, and 41.6%, respectively, p < 0.05) (Table 2 ). The most frequent abnormality was neurodevelopmental disorders (neuromuscular diseases, speech and language disorders, autism spectrum disorder, and any form of neurodevelopmental delay), followed by genetic abnormalities, accounting for 8.2% and 2.4% of all idiopathic polyhydramnios cases, respectively. A gastrointestinal system abnormality was discovered after birth in 2% of cases; another 2% had nocturnal enuresis. Gastrointestinal anomalies were significantly associated with severe polyhydramnios (12.5% in severe polyhydramnios vs 0.55% in mild polyhydramnios, p < 0.05). Nocturnal enuresis was found in 2% of cases, too, and significantly associated with moderate polyhydramnios (8.1% vs 1.1% in moderate and mild polyhydramnios, respectively, p < 0.05). Polyhydramnios was not severe in any of the nocturnal enuresis cases. Table 3 shows the distribution of postnatally diagnosed abnormalities Univariate logistic regression analysis has shown that odds of any neurodevelopmental, structural, or genetic abnormality is 7 times higher in moderate polyhydramnios, and 4.6 times in severe polyhydramnios (OR = 7. 95% CI 3.2–15.4 and OR = 4.6, 95% CI 1.8–11.4). As expected, OR of gastrointestinal system abnormalities in severe polyhydramnios was high, 15.4 (95% CI 2.4–97.5). In moderate polyhydramnios cases, the odds of any neurodevelopmental disorder, including speech and language disorders, neuromuscular diseases, autism spectrum disorder, or neurodevelopmental delay, were 9 times higher. (OR = 9, 95% CI 3.1–26.3). Genetic abnormalities and nocturnal enuresis were more common in moderate polyhydramnios, also (OR = 5.9, 95% CI 1.1–30.6 and OR = 8.9, 95% CI 1.4–55.5, respectively). These findings were still significant after the effect sizes were adjusted for preterm birth (Table 4 ). Discussion Processes that maintain amniotic fluid volume are still not objectively clarified. Animal and human studies conducted decades ago reported swallowing rates up to 300 ml/kg/day[7,8]. Anatomic abnormalities that affect fetal swallowing- such as, micro/retrognathia, macroglossia and esophageal atresia- therefore cause polyhydramnios. Neuromuscular diseases and fetal akinesia deformation sequence also lead to polyhydramnios by impairing fetal swallowing. Our study shows that in polyhydramnios cases with no obvious etiology diagnosed in the prenatal period, 16.1% had at least one abnormality discovered after birth, which is greater than the previously reported prevalences of 9.3–11%[5,1]. With rates of 45.9% and 41.6%, respectively, moderate and severe polyhydramnios were strongly associated with a postnatal diagnosis of neurodevelopmental, genetic, or structural abnormality. Neurodevelopmental disorders were the mostly encountered group of abnormalities with an overall rate of 8.2%. Our center is a tertiary hospital where high-risk pregnancies are typically referred and followed by maternal-fetal medicine specialists. As a result, maternal etiologic factors are thoroughly investigated and structural anomalies that result in polyhydramnios are seeked in fetal anatomy scans. This may account for our center's surprisingly low prevalence of idiopathic polyhydramnios (14.7%). The proposition of “the more amniotic fluid, the greater risk of anomaly” is not supported with consistent evidence. Whereas some studies demonstrated this relationship[1,9,10], several studies did not[5,11,6]. We found that moderate polyhydramnios carries significantly more risk regarding a diagnosis of any abnormality in the postnatal period, compared to severe polyhydramnios. Still, abnormality rates in both moderate and severe polyhydramnios groups are clearly higher than mild ones, therefore, it is safe to say a postnatal abnormality diagnosis is less likely if the patient has mild polyhydramnios (6.6%). Neurodevelopmental disorders have previously been researched in polyhydramnios. The underlying mechanism might be the impairment of fetal swallowing in neuromuscular disorders, however, pathophysiology of speech impairment, autism spectrum disorder or neurodevelopmental delay is yet to be clarified. Yefet et al. reported a 6% prevalence of neurodevelopmental delay and 3.7% of attention and learning disorders[11]. The overall rate of neurodevelopmental disorders was 3.5 times higher than controls, after adjusting for diabetes (aOR = 3.5 95%CI 1.4–8.7)[11]. In the large cohort of 672 polyhydramnios cases of Dashe et al., only two central nervous system abnormalities diagnosed after birth were reported[1]. Adamczyk et al. analyzed the results of 64 idiopathic polyhydramnios cases, and 11% of those who had any abnormality had neuromuscular diseases or speech impairment[9]. A novel finding of our study is the 8.9-fold increase of neurodevelopmental disorders in moderate polyhydramnios, a previously unestablished relationship. The neurodevelopmental disorders that were diagnosed included Duchenne muscular dystrophy, myotonic dystrophy, specific language impairment, articulation disorders, stuttering, autism spectrum disorder, and motor and cognitive developmental delay. We can discuss the option of prenatal diagnostic testing for those with the parent(s), but the result may not always be conclusive. Although molecular genetic testing is increasingly accessible, copy number variants' phenotypes are often reported in small series, making it difficult to obtain reliable data. A recent study reported a 4-fold increased risk of having clinically significant chromosomal microarray (CMA) results in idiopathic, moderate polyhydramnios (RR = 4.2, 95% CI 1.6–11.3)[12]. In addition to the increased odds of neurodevelopmental abnormalities in moderate polyhydramnios we reported, Sagi-Dain et al. discovered a significant risk of aberrant CMA results in moderate polyhydramnios. Because neurodevelopmental disorders frequently have an underlying genetic abnormality, the findings of the two studies support each other. This newly discovered link between idiopathic, moderate polyhydramnios and genetic and/or neurodevelopmental abnormalities prompts the following hypothesis: Is idiopathic, moderate polyhydramnios more frequently caused by genetic causes, while severe polyhydramnios is more frequently caused by structural abnormalities? Regardless, future widespread use of pre- and postnatal genetic testing may help to reduce the previously reported high rates of idiopathic polyhydramnios. Prenatal counseling today should cover the possibility of unanticipated abnormalities in cases of idiopathic polyhydramnios, even after diagnostic testing. Gastrointestinal system diseases, mainly atresias, are noteworthy causes of polyhydramnios[13]. We found that 2% of our cohort had gastrointestinal atresia, and the odds of postnatally discovered gastrointestinal atresia in severe polyhydramnios group was 15.4 times higher, which was not surprising given the high rate of missed prenatal diagnosis. Renal abnormalities are commonly associated with polyhydramnios- Abele et al. reported a 10% rate[5]. We did not find any renal abnormalities, which was odd; however 2% prevalence of nocturnal enuresis suggests the possibility that these children have a bladder dysfunction in utero. The voluntary control of the bladder is negatively impacted by mildly delayed central nervous system maturation. Additionally, behavioral problems and bladder dysfunction have been linked in studies[14]. Given these, one could argue that postnatal nocturnal enuresis in cases of idiopathic polyhydramnios may be associated with neurodevelopmental disorders and thus counted as a neurodevelopmental outcome, theoretically increasing the rate of neurodevelopmental outcomes in idiopathic polyhydramnios. Cardiac malformations were reported to be frequent in idiopathic polyhydramnios[1,11], a finding our cohort did not express- only two cardiac abnormalities were detected and both were atrial septal defects. Idiopathic polyhydramnios might be associated with genetic disorders in 9 to as high as 28% in different series[5,15]. Prenatal detection of structural defects causing polyhydramnios became easier as ultrasound technology advanced and image resolutions increased. Some of these anomalies, though, continue to have low detection rates. In order to increase the detection of fetal akinesia deformation sequence and GIS atresias during an ultrasound scan, the authors emphasize the importance of observing fetal movements and swallowing. We found that 2.4% of idiopathic polyhydramnios cases had genetic abnormalities (Down, Noonan, Klinefelter, Bartter syndromes and a case of biotinidase deficiency). Possible acidosis in biotinidase deficiency might explain fetal polyuria[16]. Bartter syndrome causing excessive fetal urination is a well-known cause of polyhydramnios[17]. The disparity between our findings and those in the literature could be attributed to a higher threshold for ordering genetic testing in our healthcare setting, as well as a lack of widespread availability of molecular genetic tests throughout the study period. Genetic abnormalities were significantly more common in moderate polyhydramnios, similar to neurodevelopmental abnormalities, further supporting the above-mentioned theory. A miscellaneous abnormality detected in our cohort was a case of isolated macroglossia. Macroglossia and polyhydramnios are both features of Beckwith-Wiedemann syndrome. The case with isolated macroglossia had undergone genetic evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis for Beckwith-Wiedemann syndrome was ordered, yet the result was negative. Although microarray analysis was recommended, the family decided against it because of insurance issues. Nevertheless, the genetics team believes Beckwith-Wiedemann syndrome is likely to be present based on the phenotype. The retrospective nature of our study and the absence of objective criteria for neurodevelopmental delay in circumstances where the outcome data was obtained via telephone interview are its main limitations. Despite adjusting for preterm birth, the results of the regression analysis have wide 95% CIs. Considering that the width of the confidence interval for binary outcomes is dependent upon the likelihood of the event, this was most likely caused by the low prevalence of neurodevelopmental and genetic disorders, and GIS atresias in general population[18,19]. In conclusion, we should discuss with expecting parent(s) that, even though we have not yet discovered anything abnormal, there still might be a 16.1% chance that their baby may suffer from various degrees of neurodevelopmental impairment, an undetected structural malformation or genetic syndrome in the long term. The neonatology team will assess GIS atresias initially after birth by standard, however neurodevelopmental disorders and nocturnal enuresis might take years to manifest, therefore a thorough follow-up of the child may lead to early diagnosis and consequently, early treatment. Declarations Author Contribution S Gurel: Project development, Data collection, Manuscript writing I Ayhan: Data analysis, Manuscript writing L Uygur: Manuscript writing B Ozgit: Data collection O Demirci: Project development, Supervision, Manuscript writing All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sumeyra Gurel, Isil Ayhan and Berk Ozgit. The first draft of the manuscript was written by Isil Ayhan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interest The authors declare that there is no conflict of interest. Ethics Approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zeynep Kamil Women and Children’s Diseases Training and Research Hospital ( Decision number: 188 ). References Dashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM (2002) Hydramnios: anomaly prevalence and sonographic detection. 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Any abnormality (n=39) No abnormality (n=203) Total (n=242) p Age (years) 30.96.1 29.46 29.76 0.13 Gravidity 2 (1-9) 2 (1-8) 2 (1-9) 0.75 Parity 1 (0-3) 1 (0-4) 1 (0-4) 0.85 Gestational age at the time of diagnosis (weeks) 30.63.4 31.33.6 31.13.6 0.33 Gestational age at the time of delivery (weeks) 37.43 38.41.5 38.31.9 <0.05 Preterm birth* 3 (7.5) 0 3 (1.2) <0.05 Birthweight (gram) 3047801 3424461 3363547 <0.05 LGA newborn 4 (10.2) 14 (6.9) 18 (7.4) 0.46 Fetal sex Female Male 14 (35.9) 25 (64.1) 73 (35.9) 130 (64) 87 (35.9) 155 (64) 0.99 Mode of delivery Vaginal Cesarean Operative vaginal 15 (38.4) 23 (58.9) 1 (2.5) 80 (39.4) 122 (60.1) 1 (0.49) 95 (39.2) 145 (59.9) 2 (0.8) 0.55 Malpresentation 3 (7.6) 22 (10.8) 25 (10.3) 0.55 PPROM 1 (2.5) 3 (1.4) 4 (1.6) 0.6 NICU admission 19 (48.0) 27 (13.3) 46 (19) <0.05 Abbreviations: LGA, large for gestational age; PPROM, preterm prelabor rupture of membranes; NICU, neonatal intensive care unit. Data are presented as meanstandard deviation, median (range), or n (percentage). *Before 34 weeks of gestation. Table 2. Association of postnatally diagnosed abnormality with polyhydramnios degree. Any abnormality (n=39) No abnormality (n=203) p Mild polyhydramnios 12 (6.6) 169 (93.3) <0.05 Moderate polyhydramnios 17 (45.9) 20 (54) <0.05 Severe polyhydramnios 10 (41.6) 14 (58.3) <0.05 Data presented as n (percentage). Table 3. Abnormalities diagnosed after birth in idiopathic polyhydramnios cases. Idiopathic polyhydramnios (n=242) Neurodevelopmental disorders Speech and language disorders Specific language impairment Stuttering Articulation disorder Neuromuscular diseases Myotonic dystrophy Duchenne muscular dystrophy Autism spectrum disorder Any form of neurodevelopmental delay Motor developmental delay Cognitive developmental delay 20 (8.2) 8 (3.3) 3 3 2 4 (1.6) 3 1 4 (1.6) 4 (1.6) 3 1 Genetic abnormality Down syndrome Noonan syndrome Klinefelter syndrome Bartter syndrome Biotinidase deficiency 6 (2.4) 2 1 1 1 1 Nocturnal enuresis 5 (2) Gastrointestinal system disorders Esophageal atresia Jejunoileal atresia Anal atresia Biliary atresia 5 (2) 2 1 1 1 Cardiac malformations Atrial septal defect 2 (0.8) 2 Other abnormalities Isolated macroglossia 1 1 Data presented as n (percentage). Table 4. Multivariate logistic regression analysis for prediction of postnatally detected abnormalities At least one abnormality OR aOR ND abnormality OR aOR Genetic abnormality OR aOR GIS abnormality OR aOR* Nocturnal enuresis OR aOR* Moderate polyhydramnios 7 (95% CI 3.2-15.4) 5.8 (95% CI 2.6-12.7) 9 (95% CI 3.1-26.3) 8.9 (95% CI 2.7-23.7) 5.9 (95% CI 1.1-30.6) 5.5 (95% CI 1.01-30.2) 1.3 (95% CI 0.1-12.8) 8.9 (95% CI 1.4-55.5) Severe polyhydramnios 4.6 (95% CI 1.8-11.4) 3.8 (95% CI 1.4-10.0) 2.2 (95% CI 0.5-8.5) 1.8 (95% CI 0.4-7.6) 1.8 (95% CI 0.2-16.5) 0.7 (95% CI 0.04-12.9) 15.4 (95% CI 2.4-97.5) NA** Abbreviations: ND, neurodevelopmental; GIS, gastrointestinal system; OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval); NA, not applicable. *Multivariate logistic regression analysis could not be performed for GIS abnormalities and nocturnal enuresis, because there was no preterm birth in these cases. **None of the nocturnal enuresis cases had severe polyhydramnios. Cite Share Download PDF Status: Published Journal Publication published 26 Sep, 2023 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 03 Feb, 2023 Reviewers invited by journal 03 Feb, 2023 Editor invited by journal 30 Jan, 2023 Editor assigned by journal 29 Jan, 2023 First submitted to journal 28 Jan, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2524533","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":173112378,"identity":"727f8dce-ea83-4299-886b-a6fd5b4a16a9","order_by":0,"name":"Sumeyra Gurel","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sumeyra","middleName":"","lastName":"Gurel","suffix":""},{"id":173112379,"identity":"193ab6bc-d77d-47c1-bf4a-2b263b721606","order_by":1,"name":"Isil Ayhan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACNgbGxgNAOoGBgfkYRISdsJYGqBa2NAjFTIRNUC08ZmCKgZAWPv7DQFtqDufxz+759uDjj23yfMwMjB8+5uBxmEQiUMuxw8USd85uN5yRcNuwjZmBWXLmNnxaQH5hO5zYcCN3mzRPwm1GoBY2Zl58WvgPArX8O5w4/0bOM5AWe8JaGIAOY2w7nLjhRg4bSEsiYS0gvyT2pSduvJFmJjkj7XZyGzNjM16/yPcff/jgwzfrxHk3kp9JfLC5bTu/vfngh494tIBBAkMzMpexgYB6MKgjRtEoGAWjYBSMVAAA0HRTRK1XHpcAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-8160-7853","institution":"Zeynep Kamil Kadin ve Cocuk Hastaliklari Egitim ve Arastirma Hastanesi","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Isil","middleName":"","lastName":"Ayhan","suffix":""},{"id":173112380,"identity":"70d2334c-9244-4dad-ad2c-689e60d21256","order_by":2,"name":"Lutfiye Uygur","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lutfiye","middleName":"","lastName":"Uygur","suffix":""},{"id":173112381,"identity":"2ea39b2e-0d61-4b72-82b8-8450c763a7b5","order_by":3,"name":"Berk Ozgit","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Berk","middleName":"","lastName":"Ozgit","suffix":""},{"id":173112382,"identity":"2c746bc6-f854-48c5-8e95-67f0775888b3","order_by":4,"name":"Oya Demirci","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Oya","middleName":"","lastName":"Demirci","suffix":""}],"badges":[],"createdAt":"2023-01-28 18:56:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2524533/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2524533/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-023-07216-0","type":"published","date":"2023-09-26T15:01:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":32557623,"identity":"616ccb3b-f4a1-4217-9159-1298258fb46d","added_by":"auto","created_at":"2023-02-07 00:25:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":68771,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart diagram of the study group.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2524533/v1/5a148d3a403b6e77bff83f25.png"},{"id":43974748,"identity":"24360b75-5d91-46d1-ba08-e62c73fa0688","added_by":"auto","created_at":"2023-10-02 15:09:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":279434,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2524533/v1/d4644852-c96c-467c-95dc-8258ad0ab7f5.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003e\u003cstrong\u003eWhat to expect after birth in idiopathic polyhydramnios? An analysis of postnatal diagnoses and their relationship to the polyhydramnios degree\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePolyhydramnios is defined as an excess amount of amniotic fluid and affects 1\u0026ndash;2% of pregnancies[1,2]. Amniotic fluid disorders occur when the balance between amniotic fluid production and excretion is disrupted, which is mostly caused by decreased fetal swallowing and increased fetal urine output, due to various fetal and maternal conditions[3]. Perinatal morbidity, such as preterm birth, cesarean delivery, premature rupture of membranes, malpresentation, and perinatal mortality, are more frequent in women with polyhydramnios[4]. While fetal anatomical abnormalities and maternal diabetes are the most common causes of polyhydramnios, the majority of cases remain unexplained in the prenatal period and are thus classified as idiopathic. However, according to the literature, roughly 10% of idiopathic polyhydramnios cases will have at least one anomaly diagnosed after birth[5]. Because some fetal anatomic abnormalities (such as esophageal and anal atresia, fetal akinesia deformation sequence) may be overlooked in ultrasound scans, even in expert hands; moreover, some genetic disorders and/or neuromuscular diseases will not have a unique characteristic that can be seen in ultrasound; prenatal counseling of patients with idiopathic polyhydramnios, is challenging.\u003c/p\u003e \u003cp\u003eIn the literature, there is a paucity of robust data on how and when to anticipate fetal abnormalities in cases of idiopathic polyhydramnios. Some argue that if prenatal ultrasound scans are normal, the likelihood of abnormalities increases as the severity of polyhydramnios increases[1], yet contradictory data is also present[6,5]. We analyzed idiopathic polyhydramnios cases in this study to estimate whether there was a significant association between the severity of polyhydramnios and postnatally diagnosed abnormalities.\u003c/p\u003e"},{"header":"Materials \u0026 Methods","content":"\u003cp\u003eThis is a retrospective cohort study of idiopathic polyhydramnios cases who had delivered at Zeynep Kamil Women and Children\u0026rsquo;s Diseases Training and Research Hospital between January, 2017 and December, 2021. Cases were collected from electronic health records by their \u0026ldquo;International Classification of Diseases (ICD)\u0026rdquo; code (O40: Polyhydramnios). The study is approved by the institutional review board of Zeynep Kamil Women and Children\u0026rsquo;s Diseases Training and Research Hospital (Decision number: 188).\u003c/p\u003e \u003cp\u003eDiagnosis of polyhydramnios was made when ultrasonographic deepest vertical pocket (DVP) measurement of amniotic fluid\u0026thinsp;\u0026ge;\u0026thinsp;8 cm or amniotic fluid index (AFI)\u0026thinsp;\u0026ge;\u0026thinsp;24 cm. Mild polyhydramnios was defined as AFI of 24 to 29 cm or DVP of 8 to 11 cm, moderate polyhydramnios as AFI of 30 to 34 cm or DVP of 12 to 15 cm, and severe polyhydramnios as AFI\u0026thinsp;\u0026ge;\u0026thinsp;35 cm or DVP\u0026thinsp;\u0026ge;\u0026thinsp;16 cm. Medical and obstetric history information, records of oral glucose tolerance test (OGTT), indirect Coombs test (IDC), serology for TORCH (Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes Simplex Virus, and Parvovirus B19) group infections, second-trimester anatomy scans and follow-up ultrasound scans, obstetric and neonatal outcomes were reviewed. Exclusion criteria were known fetal genetic and/or structural abnormalities (including soft markers for aneuploidies), Rh isoimmunization, fetal anemia, multifetal pregnancies, pregestational (preGDM) or gestational diabetes (GDM), and known infection with TORCH group agents. Cases were identified as idiopathic polyhydramnios after the exclusion criteria were applied. Data on neurodevelopmental outcomes, genetic and structural abnormalities diagnosed after birth were obtained by electronic health records when available, and telephone interviews with the families.\u003c/p\u003e \u003cp\u003eThe primary outcome was the association between polyhydramnios severity and any abnormalities detected after birth. As a result, the final cohort was stratified based on the presence of any postnatal abnormality. Neurodevelopmental abnormalities were grouped as neuromuscular disorders, speech and language disorders, autism spectrum disorder (ASD) and neurodevelopmental delay. Speech and language disorders were further subgrouped as specific language impairment (abnormal development of comprehension and/or production of language where difficulties cannot be accounted for by generally slow development, physical abnormality of the speech apparatus, autism spectrum disorder, apraxia, acquired brain damage or hearing loss), articulation disorder (difficulty in physically producing sounds) and stuttering. Failure to achieve developmental milestones affecting motor function, emotion, learning ability, self-control, or memory, was defined as neurodevelopmental delay.\u003c/p\u003e \u003cp\u003eThe secondary outcome was the odds of specific groups of abnormalities based on polyhydramnios severity. Odds of neurodevelopmental disorders, genetic abnormalities, structural abnormalities and nocturnal enuresis were calculated in each group of polyhydramnios.\u003c/p\u003e \u003cp\u003eDescriptive statistics of continuous variables were analyzed with Mann-Whitney U test or t-test. Categorical variables were analyzed with Chi-square and Fisher exact test. Logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of binary outcomes. All analyses were performed using STATA software, version 17.0 Basic Edition (Copyright 1985\u0026ndash;2021 StataCorp LLC). A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 36005 women had delivered at our center during the study period. Of those, 1853 (5.1%) had been diagnosed with polyhydramnios. After exclusion, 273 cases fulfilled the inclusion criteria. However, 28 cases had insufficient data and could not be communicated, therefore excluded. 3 cases had intrauterine fetal demise. A final cohort of 242 pregnancies with idiopathic polyhydramnios was analyzed (Fig. \u003cspan\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eThe prevalence of idiopathic polyhydramnios was 14.7%. Clinical characteristics of idiopathic polyhydramnios cases are presented in Table \u003cspan\u003e1\u003c/span\u003e. The mean gestational age at the time of diagnosis was 31.1\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e 3.6 weeks, and was not statistically different between groups (30.6\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e3.4 in the abnormality group, 31.3\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e3.6 in the no-abnormality group, p=0.33). The mean gestational age at delivery and birthweight were significantly lower in the abnormality group (37.4\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e3 vs. 38.4\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e1.5, p\u0026lt;0.05 and 3047\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e801 vs. 3424\u003cspan\u003e\u003cspan\u003e\\(\\pm\\)\u003c/span\u003e\u003c/span\u003e461, p\u0026lt;0.05, respectively). There were three preterm births before the 34th weeks of gestation, and all were found to have an abnormality after birth. Neonatal intensive care unit (NICU) admission rate was also significantly higher in the abnormality group (48% vs. 13.3%, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003eIn the postnatal period, at least one neurodevelopmental, structural, or genetic abnormality was diagnosed in 16.1% of children born to women with idiopathic polyhydramnios. When stratified based on the degree of polyhydramnios, 74.7% of women had mild, 15.2% had moderate and 9.9% had severe polyhydramnios. There were no significant differences in fetal sex based on the degree of polyhydramnios (p\u0026thinsp;=\u0026thinsp;0.567). Moderate and severe polyhydramnios are significantly associated with at least one abnormality diagnosed after birth (45.9%, and 41.6%, respectively, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table \u003cspan\u003e2\u003c/span\u003e). The most frequent abnormality was neurodevelopmental disorders (neuromuscular diseases, speech and language disorders, autism spectrum disorder, and any form of neurodevelopmental delay), followed by genetic abnormalities, accounting for 8.2% and 2.4% of all idiopathic polyhydramnios cases, respectively. A gastrointestinal system abnormality was discovered after birth in 2% of cases; another 2% had nocturnal enuresis. Gastrointestinal anomalies were significantly associated with severe polyhydramnios (12.5% in severe polyhydramnios vs 0.55% in mild polyhydramnios, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Nocturnal enuresis was found in 2% of cases, too, and significantly associated with moderate polyhydramnios (8.1% vs 1.1% in moderate and mild polyhydramnios, respectively, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Polyhydramnios was not severe in any of the nocturnal enuresis cases. Table \u003cspan\u003e3\u003c/span\u003e shows the distribution of postnatally diagnosed abnormalities\u003c/p\u003e\n\u003cp\u003eUnivariate logistic regression analysis has shown that odds of any neurodevelopmental, structural, or genetic abnormality is 7 times higher in moderate polyhydramnios, and 4.6 times in severe polyhydramnios (OR\u0026thinsp;=\u0026thinsp;7. 95% CI 3.2\u0026ndash;15.4 and OR\u0026thinsp;=\u0026thinsp;4.6, 95% CI 1.8\u0026ndash;11.4). As expected, OR of gastrointestinal system abnormalities in severe polyhydramnios was high, 15.4 (95% CI 2.4\u0026ndash;97.5). In moderate polyhydramnios cases, the odds of any neurodevelopmental disorder, including speech and language disorders, neuromuscular diseases, autism spectrum disorder, or neurodevelopmental delay, were 9 times higher. (OR\u0026thinsp;=\u0026thinsp;9, 95% CI 3.1\u0026ndash;26.3). Genetic abnormalities and nocturnal enuresis were more common in moderate polyhydramnios, also (OR\u0026thinsp;=\u0026thinsp;5.9, 95% CI 1.1\u0026ndash;30.6 and OR\u0026thinsp;=\u0026thinsp;8.9, 95% CI 1.4\u0026ndash;55.5, respectively). These findings were still significant after the effect sizes were adjusted for preterm birth (Table \u003cspan\u003e4\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eProcesses that maintain amniotic fluid volume are still not objectively clarified. Animal and human studies conducted decades ago reported swallowing rates up to 300 ml/kg/day[7,8]. Anatomic abnormalities that affect fetal swallowing- such as, micro/retrognathia, macroglossia and esophageal atresia- therefore cause polyhydramnios. Neuromuscular diseases and fetal akinesia deformation sequence also lead to polyhydramnios by impairing fetal swallowing.\u003c/p\u003e \u003cp\u003eOur study shows that in polyhydramnios cases with no obvious etiology diagnosed in the prenatal period, 16.1% had at least one abnormality discovered after birth, which is greater than the previously reported prevalences of 9.3\u0026ndash;11%[5,1]. With rates of 45.9% and 41.6%, respectively, moderate and severe polyhydramnios were strongly associated with a postnatal diagnosis of neurodevelopmental, genetic, or structural abnormality. Neurodevelopmental disorders were the mostly encountered group of abnormalities with an overall rate of 8.2%.\u003c/p\u003e \u003cp\u003eOur center is a tertiary hospital where high-risk pregnancies are typically referred and followed by maternal-fetal medicine specialists. As a result, maternal etiologic factors are thoroughly investigated and structural anomalies that result in polyhydramnios are seeked in fetal anatomy scans. This may account for our center's surprisingly low prevalence of idiopathic polyhydramnios (14.7%).\u003c/p\u003e \u003cp\u003eThe proposition of \u0026ldquo;the more amniotic fluid, the greater risk of anomaly\u0026rdquo; is not supported with consistent evidence. Whereas some studies demonstrated this relationship[1,9,10], several studies did not[5,11,6]. We found that moderate polyhydramnios carries significantly more risk regarding a diagnosis of any abnormality in the postnatal period, compared to severe polyhydramnios. Still, abnormality rates in both moderate and severe polyhydramnios groups are clearly higher than mild ones, therefore, it is safe to say a postnatal abnormality diagnosis is less likely if the patient has mild polyhydramnios (6.6%).\u003c/p\u003e \u003cp\u003eNeurodevelopmental disorders have previously been researched in polyhydramnios. The underlying mechanism might be the impairment of fetal swallowing in neuromuscular disorders, however, pathophysiology of speech impairment, autism spectrum disorder or neurodevelopmental delay is yet to be clarified. Yefet et al. reported a 6% prevalence of neurodevelopmental delay and 3.7% of attention and learning disorders[11]. The overall rate of neurodevelopmental disorders was 3.5 times higher than controls, after adjusting for diabetes (aOR\u0026thinsp;=\u0026thinsp;3.5 95%CI 1.4\u0026ndash;8.7)[11]. In the large cohort of 672 polyhydramnios cases of Dashe et al., only two central nervous system abnormalities diagnosed after birth were reported[1]. Adamczyk et al. analyzed the results of 64 idiopathic polyhydramnios cases, and 11% of those who had any abnormality had neuromuscular diseases or speech impairment[9]. A novel finding of our study is the 8.9-fold increase of neurodevelopmental disorders in moderate polyhydramnios, a previously unestablished relationship. The neurodevelopmental disorders that were diagnosed included Duchenne muscular dystrophy, myotonic dystrophy, specific language impairment, articulation disorders, stuttering, autism spectrum disorder, and motor and cognitive developmental delay. We can discuss the option of prenatal diagnostic testing for those with the parent(s), but the result may not always be conclusive. Although molecular genetic testing is increasingly accessible, copy number variants' phenotypes are often reported in small series, making it difficult to obtain reliable data. A recent study reported a 4-fold increased risk of having clinically significant chromosomal microarray (CMA) results in idiopathic, moderate polyhydramnios (RR\u0026thinsp;=\u0026thinsp;4.2, 95% CI 1.6\u0026ndash;11.3)[12]. In addition to the increased odds of neurodevelopmental abnormalities in moderate polyhydramnios we reported, Sagi-Dain et al. discovered a significant risk of aberrant CMA results in moderate polyhydramnios. Because neurodevelopmental disorders frequently have an underlying genetic abnormality, the findings of the two studies support each other. This newly discovered link between idiopathic, moderate polyhydramnios and genetic and/or neurodevelopmental abnormalities prompts the following hypothesis: Is idiopathic, moderate polyhydramnios more frequently caused by genetic causes, while severe polyhydramnios is more frequently caused by structural abnormalities? Regardless, future widespread use of pre- and postnatal genetic testing may help to reduce the previously reported high rates of idiopathic polyhydramnios. Prenatal counseling today should cover the possibility of unanticipated abnormalities in cases of idiopathic polyhydramnios, even after diagnostic testing.\u003c/p\u003e \u003cp\u003eGastrointestinal system diseases, mainly atresias, are noteworthy causes of polyhydramnios[13]. We found that 2% of our cohort had gastrointestinal atresia, and the odds of postnatally discovered gastrointestinal atresia in severe polyhydramnios group was 15.4 times higher, which was not surprising given the high rate of missed prenatal diagnosis. Renal abnormalities are commonly associated with polyhydramnios- Abele et al. reported a 10% rate[5]. We did not find any renal abnormalities, which was odd; however 2% prevalence of nocturnal enuresis suggests the possibility that these children have a bladder dysfunction in utero. The voluntary control of the bladder is negatively impacted by mildly delayed central nervous system maturation. Additionally, behavioral problems and bladder dysfunction have been linked in studies[14]. Given these, one could argue that postnatal nocturnal enuresis in cases of idiopathic polyhydramnios may be associated with neurodevelopmental disorders and thus counted as a neurodevelopmental outcome, theoretically increasing the rate of neurodevelopmental outcomes in idiopathic polyhydramnios. Cardiac malformations were reported to be frequent in idiopathic polyhydramnios[1,11], a finding our cohort did not express- only two cardiac abnormalities were detected and both were atrial septal defects. Idiopathic polyhydramnios might be associated with genetic disorders in 9 to as high as 28% in different series[5,15]. Prenatal detection of structural defects causing polyhydramnios became easier as ultrasound technology advanced and image resolutions increased. Some of these anomalies, though, continue to have low detection rates. In order to increase the detection of fetal akinesia deformation sequence and GIS atresias during an ultrasound scan, the authors emphasize the importance of observing fetal movements and swallowing.\u003c/p\u003e \u003cp\u003eWe found that 2.4% of idiopathic polyhydramnios cases had genetic abnormalities (Down, Noonan, Klinefelter, Bartter syndromes and a case of biotinidase deficiency). Possible acidosis in biotinidase deficiency might explain fetal polyuria[16]. Bartter syndrome causing excessive fetal urination is a well-known cause of polyhydramnios[17]. The disparity between our findings and those in the literature could be attributed to a higher threshold for ordering genetic testing in our healthcare setting, as well as a lack of widespread availability of molecular genetic tests throughout the study period. Genetic abnormalities were significantly more common in moderate polyhydramnios, similar to neurodevelopmental abnormalities, further supporting the above-mentioned theory.\u003c/p\u003e \u003cp\u003eA miscellaneous abnormality detected in our cohort was a case of isolated macroglossia. Macroglossia and polyhydramnios are both features of Beckwith-Wiedemann syndrome. The case with isolated macroglossia had undergone genetic evaluation, multiplex ligation-dependent probe amplification (MLPA) analysis for Beckwith-Wiedemann syndrome was ordered, yet the result was negative. Although microarray analysis was recommended, the family decided against it because of insurance issues. Nevertheless, the genetics team believes Beckwith-Wiedemann syndrome is likely to be present based on the phenotype.\u003c/p\u003e \u003cp\u003eThe retrospective nature of our study and the absence of objective criteria for neurodevelopmental delay in circumstances where the outcome data was obtained via telephone interview are its main limitations. Despite adjusting for preterm birth, the results of the regression analysis have wide 95% CIs. Considering that the width of the confidence interval for binary outcomes is dependent upon the likelihood of the event, this was most likely caused by the low prevalence of neurodevelopmental and genetic disorders, and GIS atresias in general population[18,19].\u003c/p\u003e \u003cp\u003eIn conclusion, we should discuss with expecting parent(s) that, even though we have not yet discovered anything abnormal, there still might be a 16.1% chance that their baby may suffer from various degrees of neurodevelopmental impairment, an undetected structural malformation or genetic syndrome in the long term. The neonatology team will assess GIS atresias initially after birth by standard, however neurodevelopmental disorders and nocturnal enuresis might take years to manifest, therefore a thorough follow-up of the child may lead to early diagnosis and consequently, early treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS Gurel: Project development, Data collection, Manuscript writing\u003c/p\u003e\n\u003cp\u003eI Ayhan: Data analysis, Manuscript writing\u003c/p\u003e\n\u003cp\u003eL Uygur: Manuscript writing\u003c/p\u003e\n\u003cp\u003eB Ozgit: Data collection\u003c/p\u003e\n\u003cp\u003eO Demirci: Project development, Supervision, Manuscript writing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Sumeyra Gurel, Isil Ayhan and Berk Ozgit. The first draft of the manuscript was written by Isil Ayhan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zeynep Kamil Women and Children\u0026rsquo;s Diseases Training and Research Hospital (\u003c/em\u003eDecision number: 188\u003cem\u003e).\u003c/em\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eDashe JS, McIntire DD, Ramus RM, Santos-Ramos R, Twickler DM (2002) Hydramnios: anomaly prevalence and sonographic detection. Obstet Gynecol 100 (1):134-139. doi:10.1016/s0029-7844(02)02013-6\u003c/li\u003e\n\u003cli\u003eBauserman M, Nathan R, Lokangaka A, McClure EM, Moore J, Ishoso D, Tshefu A, Figueroa L, Garces A, Harrison MS, Wallace D, Saleem S, Mirza W, Krebs N, Hambidge M, Carlo W, Chomba E, Miodovnik M, Koso-Thomas M, Liechty EA, Esamai F, Swanson J, Swanson D, Goldenberg RL, Bose C (2019) Polyhydramnios among women in a cluster-randomized trial of ultrasound during prenatal care within five low and low-middle income countries: a secondary analysis of the first look study. BMC Pregnancy Childbirth 19 (1):258. doi:10.1186/s12884-019-2412-6\u003c/li\u003e\n\u003cli\u003eDashe JS, Pressman EK, Hibbard JU (2018) SMFM Consult Series #46: Evaluation and management of polyhydramnios. Am J Obstet Gynecol 219 (4):B2-b8. doi:10.1016/j.ajog.2018.07.016\u003c/li\u003e\n\u003cli\u003eOtt WJ (2005) Reevaluation of the relationship between amniotic fluid volume and perinatal outcome. Am J Obstet Gynecol 192 (6):1803-1809; discussion 1809. doi:10.1016/j.ajog.2004.12.062\u003c/li\u003e\n\u003cli\u003eAbele H, Starz S, Hoopmann M, Yazdi B, Rall K, Kagan KO (2012) Idiopathic polyhydramnios and postnatal abnormalities. Fetal Diagn Ther 32 (4):251-255. doi:10.1159/000338659\u003c/li\u003e\n\u003cli\u003eKyriacou C, Roper L, Mappouridou S, Lees C, Prior T (2021) Contemporary experience of polyhydramnios: A single-centre experience. Australas J Ultrasound Med 24 (3):137-142. doi:10.1002/ajum.12247\u003c/li\u003e\n\u003cli\u003ePritchard JA (1966) Fetal swallowing and amniotic fluid volume. Obstet Gynecol 28 (5):606-610\u003c/li\u003e\n\u003cli\u003eSherman DJ, Ross MG, Day L, Humme J, Ervin MG (1991) Fetal swallowing: response to graded maternal hypoxemia. J Appl Physiol (1985) 71 (5):1856-1861. doi:10.1152/jappl.1991.71.5.1856\u003c/li\u003e\n\u003cli\u003eAdamczyk M, Kornacki J, Wirstlein P, Szczepanska M, Wender-Ozegowska E (2019) Follow-up of children with antenatally diagnosed idiopathic polyhydramnios. Ginekol Pol 90 (2):93-99. doi:10.5603/gp.2019.0016\u003c/li\u003e\n\u003cli\u003eKornacki J, Adamczyk M, Wirstlein P, Osiński M, Wender-Ożegowska E (2017) Polyhydramnios - frequency of congenital anomalies in relation to the value of the amniotic fluid index. Ginekol Pol 88 (8):442-445. doi:10.5603/GP.a2017.0081\u003c/li\u003e\n\u003cli\u003eYefet E, Daniel-Spiegel E (2016) Outcomes From Polyhydramnios With Normal Ultrasound. Pediatrics 137 (2):e20151948. doi:10.1542/peds.2015-1948\u003c/li\u003e\n\u003cli\u003eSagi-Dain L, Singer A, Falik-Zaccai T, Peleg A, Bar-Shira A, Feingold-Zadok M, Ben Shachar S, Maya I (2021) The effect of polyhydramnios degree on chromosomal microarray results: a retrospective cohort analysis of 742 singleton pregnancies. Arch Gynecol Obstet 304 (3):649-656. doi:10.1007/s00404-021-05995-y\u003c/li\u003e\n\u003cli\u003eBen-Chetrit A, Hochner-Celnikier D, Ron M, Yagel S (1990) Hydramnios in the third trimester of pregnancy: a change in the distribution of accompanying fetal anomalies as a result of early ultrasonographic prenatal diagnosis. Am J Obstet Gynecol 162 (5):1344-1345. doi:10.1016/0002-9378(90)90058-f\u003c/li\u003e\n\u003cli\u003eDuel BP, Steinberg-Epstein R, Hill M, Lerner M (2003) A survey of voiding dysfunction in children with attention deficit-hyperactivity disorder. J Urol 170 (4 Pt 2):1521-1523; discussion 1523-1524. doi:10.1097/01.ju.0000091219.46560.7b\u003c/li\u003e\n\u003cli\u003eDorleijn DMJ, Cohen-Overbeek TE, Groenendaal F, Bruinse HW, Stoutenbeek P (2009) Idiopathic polyhydramnios and postnatal findings. The Journal of Maternal-Fetal \u0026amp; Neonatal Medicine 22 (4):315-320. doi:10.1080/14767050802531870\u003c/li\u003e\n\u003cli\u003eSaleem H, Simpson B (2022) Biotinidase Deficiency. In: StatPearls. StatPearls Publishing Copyright \u0026copy; 2022, StatPearls Publishing LLC., Treasure Island (FL), \u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez-Soriano J (1998) Bartter and related syndromes: the puzzle is almost solved. Pediatr Nephrol 12 (4):315-327. doi:10.1007/s004670050461\u003c/li\u003e\n\u003cli\u003eCassina M, Ruol M, Pertile R, Midrio P, Piffer S, Vicenzi V, Saugo M, Stocco CF, Gamba P, Clementi M (2016) Prevalence, characteristics, and survival of children with esophageal atresia: A 32-year population-based study including 1,417,724 consecutive newborns. Birth Defects Res A Clin Mol Teratol 106 (7):542-548. doi:10.1002/bdra.23493\u003c/li\u003e\n\u003cli\u003eShevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, Majnemer A, Noetzel M, Sheth RD (2003) Practice parameter: evaluation of the child with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology 60 (3):367-380. doi:10.1212/01.wnl.0000031431.81555.16\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Clinical features of idiopathic polyhydramnios cases based on the presence of any postnatal abnormality.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.041322314049587%\"\u003e\n \u003cp\u003eAny abnormality (n=39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eNo abnormality (n=203)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(n=242)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e30.96.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e29.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e29.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eGravidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e2 (1-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2 (1-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e2 (1-9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eParity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e1 (0-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1 (0-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e1 (0-4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eGestational age at the time of diagnosis (weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.041322314049587%\"\u003e\n \u003cp\u003e30.63.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e31.33.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e31.13.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eGestational age at the time of delivery (weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.041322314049587%\"\u003e\n \u003cp\u003e37.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e38.41.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e38.31.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003ePreterm birth*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.041322314049587%\"\u003e\n \u003cp\u003e3 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e3 (1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eBirthweight (gram)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e3047801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3424461\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3363547\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eLGA newborn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e4 (10.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e14 (6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e18 (7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eFetal sex\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Female\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (35.9)\u003c/p\u003e\n \u003cp\u003e25 (64.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e73 (35.9)\u003c/p\u003e\n \u003cp\u003e130 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e87 (35.9)\u003c/p\u003e\n \u003cp\u003e155 (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eMode of delivery\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Vaginal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Cesarean\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Operative vaginal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (38.4)\u003c/p\u003e\n \u003cp\u003e23 (58.9)\u003c/p\u003e\n \u003cp\u003e1 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e80 (39.4)\u003c/p\u003e\n \u003cp\u003e122 (60.1)\u003c/p\u003e\n \u003cp\u003e1 (0.49)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e95 (39.2)\u003c/p\u003e\n \u003cp\u003e145 (59.9)\u003c/p\u003e\n \u003cp\u003e2 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eMalpresentation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e3 (7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e22 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e25 (10.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003ePPROM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e1 (2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e3 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e4 (1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003eNICU admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.041322314049587%\"\u003e\n \u003cp\u003e19 (48.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e27 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e46 (19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003eAbbreviations: \u0026nbsp; LGA, large for gestational age; PPROM, preterm prelabor rupture of membranes; NICU, neonatal intensive care unit. Data are presented as meanstandard deviation, median (range), or n (percentage).\u003c/p\u003e\n\u003cp\u003e*Before 34 weeks of gestation.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2. Association of postnatally diagnosed abnormality with polyhydramnios degree.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.635761589403973%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.364238410596027%\"\u003e\n \u003cp\u003eAny abnormality (n=39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003eNo abnormality (n=203)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.635761589403973%\"\u003e\n \u003cp\u003eMild polyhydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.364238410596027%\"\u003e\n \u003cp\u003e12 (6.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e169 (93.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.635761589403973%\"\u003e\n \u003cp\u003eModerate polyhydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.364238410596027%\"\u003e\n \u003cp\u003e17 (45.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e20 (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.635761589403973%\"\u003e\n \u003cp\u003eSevere polyhydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.364238410596027%\"\u003e\n \u003cp\u003e10 (41.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e14 (58.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25%\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Data presented as n (percentage).\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 3. Abnormalities diagnosed after birth in idiopathic polyhydramnios cases.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" width=\"100%\"\u003e\n \u003cp\u003eIdiopathic polyhydramnios (n=242)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eNeurodevelopmental disorders\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Speech and language disorders\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Specific language impairment\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Stuttering\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Articulation disorder \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Neuromuscular diseases\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Myotonic dystrophy \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Duchenne muscular dystrophy\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Autism spectrum disorder\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Any form of neurodevelopmental delay\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Motor developmental delay\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Cognitive developmental delay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e20 (8.2)\u003c/p\u003e\n \u003cp\u003e8 (3.3)\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e4 (1.6)\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e4 (1.6)\u003c/p\u003e\n \u003cp\u003e4 (1.6)\u003c/p\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eGenetic abnormality\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Down syndrome\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Noonan syndrome\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Klinefelter syndrome\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Bartter syndrome\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Biotinidase deficiency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e6 (2.4)\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eNocturnal enuresis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e5 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eGastrointestinal system disorders\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Esophageal atresia\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Jejunoileal atresia\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Anal atresia\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Biliary atresia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e5 (2)\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eCardiac malformations\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Atrial septal defect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e2 (0.8)\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eOther abnormalities\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Isolated macroglossia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Data presented as n (percentage).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4. Multivariate logistic regression analysis for prediction of postnatally detected abnormalities\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"573\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.767888307155324%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.75392670157068%\"\u003e\n \u003cp\u003eAt least one abnormality\u003c/p\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.57940663176265%\"\u003e\n \u003cp\u003eND abnormality\u003c/p\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003cp\u003eaOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003eGenetic abnormality\u003c/p\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;aOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003eGIS abnormality\u003c/p\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; aOR*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.787085514834207%\"\u003e\n \u003cp\u003eNocturnal enuresis\u003c/p\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; aOR*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.767888307155324%\"\u003e\n \u003cp\u003eModerate polyhydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.75392670157068%\"\u003e\n \u003cp\u003e7 (95% CI 3.2-15.4)\u003c/p\u003e\n \u003cp\u003e5.8 (95% CI 2.6-12.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.57940663176265%\"\u003e\n \u003cp\u003e9 (95% CI 3.1-26.3)\u003c/p\u003e\n \u003cp\u003e8.9 (95% CI 2.7-23.7)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003e\u0026nbsp;5.9 (95% CI 1.1-30.6)\u003c/p\u003e\n \u003cp\u003e5.5 (95% CI 1.01-30.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003e1.3 (95% CI 0.1-12.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.787085514834207%\"\u003e\n \u003cp\u003e8.9 (95% CI 1.4-55.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"20.767888307155324%\"\u003e\n \u003cp\u003eSevere polyhydramnios\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.75392670157068%\"\u003e\n \u003cp\u003e4.6 (95% CI 1.8-11.4)\u003c/p\u003e\n \u003cp\u003e3.8 (95% CI 1.4-10.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.57940663176265%\"\u003e\n \u003cp\u003e2.2 (95% CI 0.5-8.5)\u003c/p\u003e\n \u003cp\u003e1.8 (95% CI 0.4-7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003e\u0026nbsp;1.8 (95% CI 0.2-16.5)\u003c/p\u003e\n \u003cp\u003e0.7 (95% CI 0.04-12.9)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.05584642233857%\"\u003e\n \u003cp\u003e15.4 (95% CI 2.4-97.5)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.787085514834207%\"\u003e\n \u003cp\u003eNA**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Abbreviations: ND, neurodevelopmental; GIS, gastrointestinal system; OR, odds ratio; aOR, adjusted odds ratio; CI, confidence interval); NA, not applicable.\u003c/p\u003e\n\u003cp\u003e*Multivariate logistic regression analysis could not be performed for GIS abnormalities and nocturnal enuresis, because there was no preterm birth in these cases.\u003c/p\u003e\n\u003cp\u003e**None of the nocturnal enuresis cases had severe polyhydramnios.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Polyhydramnios, neurodevelopmental disorder, nocturnal enuresis, gastrointestinal atresia","lastPublishedDoi":"10.21203/rs.3.rs-2524533/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2524533/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo analyze postnatal abnormalities in idiopathic polyhydramnios and to estimate whether there was a significant association between the severity of polyhydramnios and postnatally diagnosed abnormalities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e This was a retrospective cohort study of all idiopathic polyhydramnios cases that delivered at our center between 2017 and 2021. Cases were identified as idiopathic after excluding known fetal genetic and/or structural abnormalities (including soft markers for aneuploidies), Rh isoimmunization, fetal anemia, multifetal pregnancies, pregestational (preGDM) or gestational diabetes (GDM), and known infection with TORCH group agents. The primary outcome was the association between polyhydramnios degree and any abnormalities detected after birth. Additional outcomes were the odds of specific groups of abnormalities based on polyhydramnios degree.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOutcomes of\u003cstrong\u003e \u003c/strong\u003e242 pregnancies with idiopathic polyhydramnios were analyzed. At least one neurodevelopmental, structural, or genetic abnormality was diagnosed in 16.1% of children born to women with idiopathic polyhydramnios. Moderate and severe polyhydramnios are significantly associated with at least one abnormality diagnosed after birth (45.9%, and 41.6%, respectively, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05). Neurodevelopmental disorders were the most frequent abnormality (8.2%), followed by genetic abnormalities (2.4%), gastrointestinal abnormalities (2%) and nocturnal enuresis (2%). Odds of genetic abnormalities, neurodevelopmental disorders and nocturnal enuresis in moderate polyhydramnios were significantly higher (aOR=5.5, 95%CI 1.01-30.2; aOR: 8.9, 95% CI 2.7-23.7 and OR: 8.9, 95% CI 1.4-55.5, respectively). Gastrointestinal anomalies were significantly associated with severe polyhydramnios, as expected (OR: 15.4, 95% CI 2.4-97.5).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Postnatally detected abnormalities are associated with moderate and severe idiopathic polyhydramnios. Particularly high risks include neurodevelopmental disorders, genetic abnormalities, gastrointestinal atresias and nocturnal enuresis.\u003c/p\u003e","manuscriptTitle":"What to expect after birth in idiopathic polyhydramnios? An analysis of postnatal diagnoses and their relationship to the polyhydramnios degree","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-02-07 00:24:57","doi":"10.21203/rs.3.rs-2524533/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2023-02-03T14:11:08+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-02-03T12:47:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2023-01-30T13:14:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-01-30T03:36:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-01-28T13:56:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"34e8f60c-10cc-4e75-9bf2-1a9f9db305a7","owner":[],"postedDate":"February 7th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-02T15:07:48+00:00","versionOfRecord":{"articleIdentity":"rs-2524533","link":"https://doi.org/10.1007/s00404-023-07216-0","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2023-09-26 15:01:01","publishedOnDateReadable":"September 26th, 2023"},"versionCreatedAt":"2023-02-07 00:24:57","video":"","vorDoi":"10.1007/s00404-023-07216-0","vorDoiUrl":"https://doi.org/10.1007/s00404-023-07216-0","workflowStages":[]},"version":"v1","identity":"rs-2524533","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2524533","identity":"rs-2524533","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}