Pregnancy with osteogenesis imperfecta: A scoping review

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Limited literature is available regarding pregnancy with OI. Objectives The objective is to capture the available literature on OI and pregnancy. Methods A scoping review methodology was used to record and summarize the existing research evidence. The review process was conducted following the PRISMA-ScR guidelines. Three databases (Pubmed, Embase, web of science) were searched systematically. Literature published between 1975-2024 was extracted. Original studies mentioning OI with a minimum of 25 pregnancies were included. Results 546 articles were identified for title and abstracts screening. 28 records were reviewed for full text; seven studies met the inclusion criteria and were included. Reference details, study characteristics, topics of interest, and main findings are presented. The review showed that cesarian delivery was more common. Prolonged breast feeding was a risk factor for the occurrence of maternal fractures after pregnancies. OI pregnancies are at risk of increased neonatal morbidities, and congenital anomalies consistently. Conclusion There are significant data gaps in the literature concerning the experience of OI and pregnancy outcomes. This study underscores the crucial need for further research and clarity about maternal and neonatal complications associated with OI pregnancies. 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Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] Krupa Shah https://orcid.org/0000-0001-8445-4170 1 , Kosha Sheth 2 , Dhairya Shah 3 , Hitesh Shah https://orcid.org/0000-0002-2940-3108 4 Krupa Shah https://orcid.org/0000-0001-8445-4170 1 , Kosha Sheth 2 , Dhairya Shah 3 , Hitesh Shah https://orcid.org/0000-0002-2940-3108 4 PUBLISHED 01 Aug 2025 Author details Author details 1 Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India 2 Consultant, Apple children Hospital, Ellis bridge, Ahmedabad, India 3 Department of medicine, Father Muller Medical, Mangalore, Karnataka, 575002, India 4 Department of Paediatric Orthopaedics, Kasturba Medical College, Manipal,, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Krupa Shah Roles: Data Curation, Formal Analysis, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kosha Sheth Roles: Data Curation, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dhairya Shah Roles: Data Curation, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Hitesh Shah Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. This article is included in the Rare diseases collection. Abstract Purpose Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by genotype and phenotypic heterogeneity. Limited literature is available regarding pregnancy with OI. Objectives The objective is to capture the available literature on OI and pregnancy. Methods A scoping review methodology was used to record and summarize the existing research evidence. The review process was conducted following the PRISMA-ScR guidelines. Three databases (Pubmed, Embase, web of science) were searched systematically. Literature published between 1975-2024 was extracted. Original studies mentioning OI with a minimum of 25 pregnancies were included. Results 546 articles were identified for title and abstracts screening. 28 records were reviewed for full text; seven studies met the inclusion criteria and were included. Reference details, study characteristics, topics of interest, and main findings are presented. The review showed that cesarian delivery was more common. Prolonged breast feeding was a risk factor for the occurrence of maternal fractures after pregnancies. OI pregnancies are at risk of increased neonatal morbidities, and congenital anomalies consistently. Conclusion There are significant data gaps in the literature concerning the experience of OI and pregnancy outcomes. This study underscores the crucial need for further research and clarity about maternal and neonatal complications associated with OI pregnancies. READ ALL READ LESS Keywords Osteogenesis imperfecta, pregnancy, pregnancy complications, fractures Corresponding Author(s) Hitesh Shah ( [email protected] ) Close Corresponding author: Hitesh Shah Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Shah K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Shah K, Sheth K, Shah D and Shah H. Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] . F1000Research 2025, 14 :753 ( https://doi.org/10.12688/f1000research.165960.1 ) First published: 01 Aug 2025, 14 :753 ( https://doi.org/10.12688/f1000research.165960.1 ) Latest published: 01 Aug 2025, 14 :753 ( https://doi.org/10.12688/f1000research.165960.1 ) Introduction Osteogenesis imperfecta (OI) is a rare connective tissue disorder characterized by bone fragility and recurrent fractures. 1 It is an inherited disease caused by mutations in collagen genes, leading to defective maturation of collagen. 2 , 3 Heterogeneity in genes and clinical heterogeneity are common. 4 It is rare, with a prevalence of approximately 1 in 20,000 individuals. 5 The common clinical features include bone fragility, short stature, recurrent fracture, deformities of the limbs and spine and skeleton, and extra-skeletal manifestations. 1 Pregnancy in OI women is not uncommon. 6 Owing to preexisting poor-quality bones, pregnancy can further add to osteoporosis. 7 , 8 Pregnancy with OI significantly impacts pregnancy and childbirth. 9 , 10 Pregnancies with OI encounter unique challenges during the antepartum, intrapartum, and postnatal periods. 11 Owing to the rarity of the combination of pregnancy and osteogenesis imperfecta, the available literature is limited. 12 – 14 OI is transmitted as either autosomal dominant or autosomal recessive entity 4 ; hence, the likelihood of having an OI fetus is high for OI parents. OI fetuses can be diagnosed antenatally via ultrasound or genetic testing. Pregnancy with OI is considered high risk, as it has the potential for multiple complications, such as increased rates of antepartum hemorrhage, placental abruption, intrauterine growth restriction, and preterm birth. 11 , 15 Many reports suggest delivery routes only by Cesarean for these population. 6 , 11 Owing to spinal and pelvic malformations, anesthesia can be challenging, necessitating careful planning and often the use of spinal anesthesia. High frequencies of low birth weight, neonatal intensive care requirements, high neonatal mortality and high frequencies of neonatal fracture have been reported. 16 , 17 Due to the rare combination of pregnancy and OI, the exact occurrence of antenatal, perinatal and post-natal, neonatal and musculoskeletal issues of these pregnancies are not clear. Hence, we decided to perform a scoping review of pregnancy and related complications in patients with OI. The aims of the study The objective of this study was to systematically review the available literature on feto-maternal outcomes in pregnancies with osteogenesis imperfecta, via a scoping review methodology. Materials and methods Study design The study was conducted according to the PRISMA-Scr guidelines, which include research questions; identifying appropriate studies; selecting, extracting, and charting data; and collating, summarizing, the results. 18 A study protocol was developed. Definition of research question: The formulation of search string followed the PCC system Population – Pregnancies with OI Concepts – Feto-maternal outcome and delivery Context – Studies in English language The protocol was not registered anywhere before. Search strategies A systematic literature search was carried out in PubMed, Embase, and web of science database from January 1975 to January 2025. The MeSH words used were “Osteogenesis imperfecta”, “Brittle bone disease” or “dwarfism” and “pregnancy” or “cesarean deliveries” or “obstetrics”. Osteogenesis imperfecta related to humans was used. Two consultants approved the search strategy. The content of interest was antepartum, intrapartum, and postpartum outcomes. The topics of interest were antenatal complications, including preeclampsia, diabetes, hemorrhage, pregnancy loss, maternal fractures, mode of delivery, congenital anomalies, and Intrauterine growth restriction/small for gestational age. Inclusion criteria All original studies, surveys or case series of with a minimum of 25 pregnancies were included. Only quantitative studies were included. Only studies in the English language were included. Exclusion criteria Review articles, conference proceedings, original articles without pregnancies with OI, case series with fewer than 25 pregnancies with OI, expert comments, book chapters, guidelines and qualitative studies were excluded. Studies concerning only genetics, diagnostics, and prenatal diagnosis, other than English languages, were excluded. Study selection, data extraction, and synthesis Two reviewers (* and **) independently screened the titles and abstracts to identify potentially eligible articles. The full-text articles were selected and assessed for eligibility by two reviewers to obtain the final study articles. One reviewer (*) studied the inclusion and exclusion criteria, and one reviewer (**) extracted the data from eligible studies. The first reviewer verified the results to ensure the accuracy of the synthesis. A priori data extraction form was used. Any disagreement in the process of study selection and data extraction was resolved by discussion with the other reviewer. An assessment of the methodology quality and bias of the included studies was not performed. The articles included were presented in texts and tables. The data extracted included antepartum complications, medical and obstetrical complications, types of delivery, maternal and fetal outcomes, NICU admission, low APGAR scores, and maternal and fetal fractures. Results Search results The flow chart in Figure 1 depicts the research results and selection of eligible studies. The initial search generated a total of 1434 articles. After removing duplications and non-relevant studies, a total of 546 articles were identified for title and abstracts screening. 28 full-text articles were included for further analysis. Seven of them who met the eligibility criteria were included in the study. The main results of the excluded studies were case reports, series with fewer than twenty-five pregnancies, and original articles that included only OI children without maternal OI. All review articles and conference proceedings were excluded. Figure 1. PRISMA flow diagram of the search strategy and selection process. Primary studies Table 1 presents the characteristics of the included studies. It depicts the characteristics of primary studies with information on the year of study, author, title of study, country of origin, study time, type of study, and sample size. The included studies were registry databases, original cohort studies, retrospective studies or case series. The diagnosis of osteogenesis imperfecta was made clinically and radiologically, as were the data from the registry of the OI group. All except one study comprised inclusion and exclusion criteria. Including studies stated the limitations of the study. Regarding the country of origin, most studies were from the USA or Europe. The included studies were published after 2000. Studies focused on the characteristics of fractures, musculoskeletal issues during pregnancy, and maternal and fetal outcomes. Table 1. The characteristics of included studies. Study year Journal name Author Title Study place Study type Std instruments Inclusion and exclusion criteria Limitation of study Study population women (pregnancy) 2024 Bone Lykking EK Pregnancy complications and birth outcome in patients with osteogenesis imperfecta - A population-based register study Denmark Registry based cohort study Registry data base Y/Y Y 134 (301) 2022 Bone Lykking EK Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers Denmark Registry, self-controlled case series Registry data base Y/Y Y 111 (205) 2022 Orphanet J Rare Dis Koumakis E Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum France Retrospective multicentric cohort Chart review Y/Y Y 50 (83) 2021 Am J Ob Gy Rao R Pregnancy in women with osteogenesis imperfecta: pregnancy characteristics, maternal, and neonatal outcomes USA Cross sectional Electronic survey Y/Y Y 132 (168) 2016 J Perinatol Ruiter-Ligeti J Pregnancy outcomes in women with osteogenesis imperfecta: a retrospective cohort study Canada Retrospective cohort Registry data base Y/Y Y NA (295) 2015 J Matern Fetal Neonatal Med Yimgang DP Pregnancy outcomes in women with osteogenesis imperfecta USA Cross sectional Questionnaire based Y/Y Y 274 (539) 2002 J Obstet Gynaecol McAllion SJ Musculo-skeletal problems associated with pregnancy in women with osteogenesis imperfecta UK Cross sectional Telephonic interview - Y 100 (213) Pregnancy characteristics Table 2 displays the main information of the included studies. The study includes 1096 pregnant women with OI (1804 pregnancies). Table 3 displays the summary of all included studies. Table 2. Main findings of included studies. Title and references details Design and methods Material Main results and conclusion Lykking EK et al. Pregnancy complications and birth outcome in patients with osteogenesis imperfecta - A population-based register study. Danish Registry based cohort study Descriptive epidemiology Pregnancy complications and birth outcome were studied. N = 134 Study period: 1997-2018 General population (1,330,617) non-OI pregnancy as reference to 301 OI liveborn singletons Pregnancies. Mean age – 29 years (25-31) Five registries with unique personal identifiers were used as data source Mean, median and percentage were used as statistical tool. 31% were delivered by CD in OI cohort whereas 19% in non-OI reference cohort. Miscarriage, Pre-eclampsia, antenatal and perinatal haemorrhage, and livebirths were similar in both the groups. Stillborn and congenital malformations were 2% v/s 0.4% and 12% v/s 5% in OI and non-OI reference group. Conclusion : OI pregnancies carry a risk of very few complications from antenatal period to livebirth journey. Lykking EK et al. Fractures following pregnancy in Osteogenesis imperfecta - A self-controlled case series using Danish Health Registers. Danish National Patient Registry WHO International Classification of Diseases code for OI was used to obtain data on delivery and mode of fracture. Self-controlled case series. N = 205 pregnancies in 111 women with OI Study period: 1995-2018. Median Age at pregnancy: 28, 30, 32 for first, second and third pregnancy. Median BMI was 23.3 kg/m 2 Modified Poisson models were the statistics tool. 37% of OI cohort had caesarean delivery. Total 20 fractures were identified, 10 preconception and 10 post conception. Nine fractures were of lower limbs and rest were at other sites. Incidence rate ratio - 1 for fractures in 12 months observation period. Conclusion : No increased in risk of fractures during and 12 months post-partum when compared to 12 months prior to conception. Koumakis E et al. Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum. Retrospective multicentric OI cohort of France from 10 bone centres. Chart review of OI with pregnancy N = 50 Study period: 2006-2019 Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group BMI: 24.1kg/m 2 Mann–Whitney test, and chi-square test as statistical tools. 12 patients experienced fractures during pregnancy or in the 6 months following delivery. The frequent sites of fractures were proximal femur (25%) and spine (25%). Breast feeding and higher age, low bone mineral density was associated with fractures. Conclusion : Fracture during pregnancy or post-partum was not associated with the severity of OI and modifiable risk factor should be optimally managed including avoidance of breast feeding to prevent fractures in OI women. Rao R et al. Pregnancy in women with osteogenesis imperfecta: pregnancy characteristics, maternal, and neonatal outcomes. Cross sectional Brittle bone disorder Consortium Contact Registry as source of information. N = 132 Study period: 2017 May to January 2018 1600 members in registry, 170 eligible for survey, Survey through online questionnaire 132 responded (77.6% response rate) BMI-26.7 kg/m 2 ANNOVA and chi square test. Caesarean delivery was found to be 68.5% in OI cohort. Higher rates of diabetes in pregnancy, caesarean section, need for blood transfusion, and antepartum and postpartum fractures were observed. Neonates born to women with osteogenesis imperfecta had higher risk for low birth weights as compared to the general population. Higher rate of neonatal intensive care unit admissions and neonatal mortality at 28 days of life were reported. Conclusion: Pregnancies with OI are at an increased risk for complications including haemorrhage, fractures, diabetes, and neonatal morbidity. Ruiter-Ligeti J et al. Pregnancy outcomes in women with osteogenesis imperfecta: a retrospective cohort study. Retrospective cohort Registry based US inpatient database was the source. Study period: 2003-2011 Birth registry cohort of 7,287,994 had 295 OI pregnancies Unconditional logistic regression was used. The prevalence was 4/1 00 000 deliveries. 75% of women with OI had Caesarean delivery. Complications like antepartum Haemorrhages (OR 2.01), placenta abruption (OR 2.50) intrauterine growth restriction and small-for-gestational-age infants (OR 2.42) congenital malformation (OR 7.32) and preterm birth (OR 2.24) were higher. Maternal mortality or stress fractures were not significantly different among groups. Venous thrombo- embolism was less but uterine rupture and hospital stay were significantly higher. Conclusion : Pregnancies with OI has more maternal and foetal complications. Yimgang DS et al. Pregnancy outcomes in women with osteogenesis imperfecta. A cross-sectional study. Self-reported international OI registry data either electronically or writing were used. Severity of OI type to mode of delivery, pregnancy outcome and medical complications were corelated. N = 274, Period of gathering data: 2010-2014 1043 women of 20 years and older were consented 435 reported having a child, 274 had self- reporting of OI type and completed questionnaire, 63% response rate. Chi-square was statistical tools. The caesarean section reported by 55% of the women. 29% (n = 80) women reported pregnancy complications. There was a significant relationship between the mode of delivery and OI type. Type 3, 4, 5 had C-section between 70-100%. The pregnancy complications were not associated with mode of delivery or number of children. Conclusions : OI type, pre-natal genetic counselling, and number of children were strong predictors for choosing the mode of delivery. However, they may not predict pregnancy complications. Hence, the complexity of each case would decide pregnancy management. McAllion SJ et al. Musculo-skeletal problems and pregnancy in women with osteogenesis imperfecta. A telephonic interview of 100 OI with 213 pregnancies. Database was used but selection of OI cohort from United Kingdom or the Republic of Ireland residents. Study period followed: 1957-1998 First 100 women of 18-50 years, who had child were contacted by telephone Age: 15 to 42 years. Mean age at delivery was 25.9 years, Semi-structured interview was obtained. Chi square test as statistical tool. OI type 1 had 26.9% caesarean rate. Moderate to severe back pain was more with caesarean delivery. 13.1% had severe backpain related to period of gestations (28 weeks or more). 7 women had height loss, which was not associated with severity of pain. 18 had fracture of one or more bones antenatally or post- natal in their pregnancies. One mortality, 13 spontaneous abortions, and 197 had live births. Conclusion : No identifiable relation of type of OI to mode of delivery or back pain was reported. Avoidance of long period of breast feeding was suggested to curtail musculoskeletal adverse effect particularly with those who had vertebral fractures. Table 3. Summary of key findings of included studies. 1 Preeclampsia, eclampsia and perinatal haemorrhage are similar between OI pregnancy and reference population. Caesarean delivery is higher among OI pregnancy (25-75%). Prevalence of low birth weight, low Apgar score, need for CPAP, birth related fracture is similar in OI pregnancy and reference population. Pregnancy with OI increase the risk of additional congenital anomalies in the offspring (12% vs 5%) and incidence of still birth (2% vs 0.4%) higher than reference population. 2 The fracture rate during pregnancy and 12 months/19 months post-partum in pregnant OI women is not higher than 12 months to 19 months prior to conception. This data was not supported with breast feeding information. Fracture during pregnancy or post-partum was not associated with the severity of OI. 3 Breastfeeding is risk factor among 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group. 4 Women with osteogenesis imperfecta have a 10–12% rate of fracture during pregnancy and the postpartum time period and an increased relative risk of fracture compared to the general population. Pregnancy with osteogenesis imperfecta is at an increased risk for complications including haemorrhage, fractures, diabetes, and increased neonatal morbidity. Neonates (Child of OI pregnancy) have an increased rate of NICU admission and higher mortality at 28 days of life, regardless of neonatal osteogenesis imperfecta status. 5 There is an increased risk of antepartum haemorrhage, placenta abruption, intrauterine growth restriction and small-for-gestational-age infants, congenital malformation and preterm birth with pregnancy with OI. No differences in rates of stress fracture and maternal death in OI pregnancy with general population. 6 29% of patients reported pregnancy complications. Severity of OI, parity and mode of delivery are not associated with increased pregnancy complications in women with OI. OI type, pre-natal genetic counselling, and number of children were strong predictors for choosing the mode of delivery in women with OI. 7 Severe back pain is common after 28 weeks of pregnancies (13%) (might be related to vertebral fracture). Avoiding prolonged breast feeding is recommended women with OI who have vertebral fractures. Age at pregnancy: Five studies mentioned the age of the women at pregnancy. The age range mentioned was between 15-42 years. BMI: BMI was mentioned in 4 studies. It was in the range of 23.4 kg/m 2 to 26.7 kg/m 2 . The mean height mentioned was 153-164 cm. Severity of OI: Four studies mentioned the severity of OI. A mild phenotype was frequently noted (75–86%), and a moderate and severe OI phenotype is observed in 14–25% of patients. 7 , 8 , 11 , 14 Maternal observations OI pregnancies carry a greater risk of complications from the antenatal period to delivery. Yimgang et al. reported that 29% of maternal complications were associated with the severity of OI and not with the mode of delivery or number of children. 14 However, observations vary across studies. Rao noted greater rates of diabetes during pregnancy, hemorrhage, cesarean section, and antepartum and postpartum fractures. 11 Similar observations were made by Ruiter-Ligeti et al., 6 who reported increased chances of antepartum hemorrhage, placental abruption, uterine rupture and hospital stay. Lykking revealed similar complications of miscarriage, preeclampsia, and antenatal and perinatal hemorrhage in both the case and control groups. 12 Ruiter-Ligeti et al. reported no changes in maternal mortality or stress fractures compared with those in the control group. 6 Preeclampsia, premature rupture of membrane (PROM), excessive bleeding, breech presentation, other musculoskeletal issues, bone fractures, bone deformities, and joint dislocation are common complications. 14 The Mentioned incidence of various observations is as below: Antenatal observations Pregnancy loss was studied in two studies. Termination of pregnancy in the OI cohort was reported to be approximately 18% before 12 weeks, which was similar to the non-OI cohort. 30% of pregnancies were aborted before 22 weeks of gestation, which was 5% greater than that of the reference population. 12 Elective abortions were less common in the OI group in comparison to the non-OI group (4% vs. 21%). 11 Antepartum hemorrhage was studied in Four studies. 6 , 11 , 12 , 14 In 5% of the OI population had early hemorrhage, and 3% had late hemorrhage, which was like the findings in the reference cohort. 12 The abruption of placenta was significantly associated with OI, with an odds ratio (OR) of 2 and an antepartum hemorrhage of 1.5 OR. 6 Gestational diabetes was not widely studied however, two studies have evaluated GDM incidence. A greater proportion of OI had GDM but was not significantly associated with OI 6 ; a higher GDM (13.3 vs. 7%) was noted in another study. 11 Four studies evaluated hypertension during pregnancy. Study by Ruiter-Ligeti et al. and Lykking EK et al. suggested no difference in the incidence of preeclampsia 6 , 12 ; However, another study reported a higher incidence 18%, 14 while another reported 12.8%. 11 Intrapartum and post-partum observations Period of gestation at delivery was studied by four studies. The prevalence of preterm delivery varies between 6-15%. 11 , 12 , 14 One study reported significant higher prevalence. 6 Term delivery/past dates were observed in 84-92% of the patients in the OI group, whereas it was 94% among the reference population. 6 , 11 , 12 Postpartum hemorrhage (PPH) was reported in three studies. Mild PPH was observed which was not different than reference population. 6 , 12 However, the increase in the risk of hemorrhage and need of blood transfusion was 8.3% in OI population vs 1.5% in non-OI population. 11 The mode of delivery was well studied (six studies). Cesarian delivery was common, accounting for 25% to 75% of deliveries. A study revealed that the frequency of cesarians was comparable to that of the general population (26%), 8 whereas the frequency of cesarians was high (55%) in another study. 14 The rate of cesarean delivery was almost 2-fold greater than that of the reference population. 12 Elective LSCS was 3-fold greater, and emergency pre-labor and labor LSCSs were like those in the reference population. 12 Seventy-five percent of LSCS patients with a history of maternal pelvic fractures or pelvic deformity due to OI need delivery via LSCS. 6 Other complications and observations: Blood transfusion and venous thromboembolism were significantly more common. 6 Genetic counseling was provided in 45% of the patients. 14 Sixteen to 21% of the population used bisphosphonate before pregnancy. 7 Mal-presentation and preterm PROM were found to be more common in two studies. 6 , 11 No difference in the incidence of placenta previa or polyhydramnios was found. 6 Two cases of uterine rupture were reported after a trial of labor for previous LSCS. 6 The length of hospital stay of mothers was significantly greater than that of the reference population. 6 One case of maternal mortality was reported in one study. 8 Fetal complications Rao reported a higher frequency of low birth weights (LBW) in neonates born to OI mothers than in the general population (LBW-26% vs. 6.8%) (very LBW-13% vs. 1.5%). A higher rate of neonatal intensive care unit admission of OI neonates (19% vs. 5.6%) and neonatal mortality at 28 days of life, regardless of neonatal OI status (4.8% vs. 0.4%), were noted. 11 Ruiter-Ligeti et al. reported a higher frequency of intrauterine growth restriction/small-for-gestational-age infants (2.44-fold increase) and congenital malformation. 6 However, Lykking noted that the frequencies of low birth weight, low Apgar score, need for CPAP, and birth-related fracture are similar between OI pregnancies and the control population. 12 The true incidence of OI in offspring could not be evaluated. Congenital abnormalities (excluding OI) were more common (12% vs. 6%) in the OI cohort. 12 However, a 7-fold increase in the incidence of congenital malformation was noted. 6 Forty-eight percent of cases involve OI children, and 5% of cases involve other anomalies. 11 Rao evaluated the BF rate at 6 months, which was lower than that reported in the general population (34.8% vs. 54%), but the BF rates at 1 month were not similar. 11 Fractures during pregnancy Five studies evaluated fractures during pregnancy. The frequency of fractures among pregnant OI patients was 10%-25%. The frequency of fracture among pregnant OIs significantly differed from that in the control population. Lykking et al. reported that the frequency of fractures was similar without an increase in the risk of fractures during and 12 months postpartum compared with 12 months prior to conception. 12 Koumakis et al. reported that one-quarter of patients experienced fractures during pregnancy (femur, pelvic, rib, ankle, or spine). 7 One quarter experienced a fracture within 6 months of delivery (mainly in the proximal femur and spine). A total of 10% of fractures during pregnancy and 12% of fractures after delivery have been reported. 11 The spine and other bones are common sites after delivery. The rate of fracture was significantly greater than that in the general population. 11 McAllion reported fractures of the limb and spine during pregnancy (vertebral crush fracture-9, tibia-4, radius-1, ankle-2, finger-1, and rib-1). One post-natal maternal fracture was noted. 8 Only one stress fracture has been reported in a large cohort studied by Ruiter-Ligeti et al. 6 Breastfeeding, increased age, and low bone mineral density were associated with the frequency of fractures. Breastfeeding was a risk factor for 85.7% of patients in the fractured group and 47.1% in the non-fractured group. 7 Other musculoskeletal issues during pregnancy Back pain during delivery was noted to be similar to that in the normal population. 11 Worsening pain during pregnancy and the need for limited activities were noted in 44% of the patients. 11 Fifty-eight percent of the OI population had back pain. 8 Moderate to severe backache was noted in 13–35% of the patients. Backache was common with high gestational age and with cesarean delivery. Recurrent sprain of the ankle, hyper extensible knee joint, frozen shoulder and symphysis pubis separation were other musculoskeletal problems. 8 A height loss of 1 cm to 11 cm was noted. Spondylolisthesis with severe backache during subsequent pregnancy was observed. 8 Discussion Pregnancy care is challenging for OI. The literature concerning pregnancies with OI and other skeletal dysplasia is limited 19 ; hence, normal obstetricians may lack knowledge and experience in dealing with pregnant women with OI. Women with disability may face many barriers to obstetrics and gynecology care. 20 Although exceptional best practice guidelines exist for the prenatal and perinatal evaluation of pregnant women with skeletal dysplasia, 21 there are no specific guidelines for referral of skeletal dysplasia pregnancies and on osteogenesis imperfecta pregnancies. Hence, a scoping review addressing pregnant women with OI is performed. Publication trends All but one included study was published in the last decade. Very few original articles addressing rare combinations of pregnancy with OI were published earlier. This might be due to the increased number of registries and databases of rare diseases such as OI in recent times. In all included studies, Pre-pregnancy BMI was similar to BMI in the general population. The height of a woman is considered a pseudo marker of severity. The height indirectly predicts the severity of the disease; a milder form has a near-normal height, and severe OI results in more shortness. Most of the included studies mentioned milder cases of OI. Antenatal issues There are no uniform observations of increased antenatal and perinatal complications in OI pregnant women. This might be due to differences in demographic characteristics. A few studies compared OI groups with non-OI groups, and a few studies evaluated only the OI registry and databases. Many complications were not clearly studied or mentioned in the included cohort. For example, spontaneous miscarriage was not clearly mentioned in a study of late pregnancy registrations. 6 Few etiological factors for abortions, such as the rates of exposure to teratogenic drugs, smoking and bisphosphonate, were similar between the OI group and the reference non-OI group. Hence, the rate of abortion might be related to OI pathogenicity. Similarly, higher frequency of preterm labor was also noted. The possible causes of higher frequencies of preterm labor are the abruption of the placenta, antepartum hemorrhage, growth restrictions and preterm prolabor rupture of membranes. A higher marginal incidence of pre-eclampsia and gestational diabetes was associated with OI. The causes of these observations were unknown. OI-related cardio-respiratory problems were not mentioned in any of the studies. Collagen is an important component of the extracellular matrix; hence, it plays a key role in the structural integrity and function of the uterus and cervix. Defective collagen can lead to improper wound healing following cesarean deliveries leading to higher chances of uterine rupture in subsequent deliveries. Collagen defects in OI can impair vascular integrity and intrinsic platelet defects resulting in greater incidence of antepartum hemorrhage and PPH. Fetal growth restriction is also common. It is related to the severity of maternal and fetal OI. 17 Multifactorial intrauterine fractures have also been shown to play a role in etiogenesis. 6 None of the included studies evaluated the exact frequency of prenatal diagnosis. Perinatal issues, including type of delivery A greater rate of cesarean delivery in the OI population is a consistent finding in most studies. Pelvic deformities leading to CPD, abnormal fetal presentation, fear of maternal pelvic fracture during delivery, and fetal OI detection are contributing variables for higher LSCS in the OI population. 16 , 17 Most of the time, the decision of an obstetrician is to choose LSCS in fear of fetal trauma when an intrauterine diagnosis of OI is made. Anesthetic management (general and spinal) of these deliveries is challenging due to spine and pelvic deformities and intubation difficulties due to the short neck, prominent mandible and occipital projection. 22 Neonatal complications Neonatal OI and other congenital anomalies are more common among OI pregnant women. The increased incidence of neonatal OI might be related to autosomal dominant and autosomal recessive inheritance. The reason for the higher risk of congenital anomalies other than those in reference populations is unknown. 12 Neonates requiring NICU admission and CPAP therapy were more common in the OI cohort, which may be due to the greater number of affected children with OI. In children with OI, the birth fracture rate is similar irrespective of the type of delivery (vaginal/cesarean delivery). 16 , 17 Hence, it was recommended that cesareans be performed only for other fetal or maternal indications but not for the objectives of fracture prevention in OI neonates. 16 , 17 The milder form of OI might not affect neonatal outcomes; however, severe and lethal varieties of OI could increase the frequency of neonatal complications, including high neonatal mortality. Higher associated cardiac anomalies might affect hospital stay and neonatal complications. Higher rates of cesarean delivery in the OI group may increase the number of respiratory complications requiring a longer hospital stay. Vertebra collapse and pneumonia in the neonatal period might also compromise respiratory function, leading to prolonged NICU admission. Musculoskeletal issues Low BMD is found in most patients with OI. 7 The effect of low BMD increases the risk of fracture at any age. During pregnancy, due to calcium transfer to the fetus (mainly in third trimester), further depletion of BMD occurs. Preconception bisphosphonate is recommended to reduce the fracture rate among this population. 6 However, there is no consensus regarding the use of bisphosphonate in reproductive-aged women due to possible adverse effects on the baby. 23 Bisphosphonate should be stopped soon after pregnancy is detected to avoid adverse effects on the fetus. 24 The third trimester of pregnancy and the 2-month postpartum period are the most crucial factors for the occurrence of fracture in this population. 7 Breastfeeding reduces maternal calcium even more, leading to bone loss of nearly 10%. Hence, women with OI or osteoporosis during pregnancy are often advised to refrain from breastfeeding. Breastfeeding, increased age, and low bone mineral density are constant risk factors associated with a high frequency of fractures. 7 However, the exact causal effect of these variables has not been studied until now. Many reported high prevalence of backaches during pregnancy, whereas others reported no change in backache. 11 McAllion reported height loss during pregnancy (1–11 cm) indirectly. 8 Strengths This is the first scoping review of a unique combination of pregnancy and OI. This is the only study that combined a description of antenatal, perinatal, and postnatal musculoskeletal complications in pregnant women with OI. An attempt was made to extract all available data on pregnancy and related complications. This study could be useful for formulating obstetric and orthopedics specific recommendations to pregnant women with OI. Limitations Due to the rare combination of pregnancy and OI, very few articles are included in the scoping review. Only English language articles were included. All included studies were either from North America or Europe; hence, the global perspective might be missing from this scoping review. The frequency of complications and the conclusions of various studies contradict those of other studies. The characteristics of the complications are different. Hence, we cannot recommend any guidelines on the basis of this scoping review. Critical appraisal of the included articles was not done. This review includes articles published over 50 years, and the practice of obstetrics as well as advances in technology might affect the final maternal and fetal outcomes. Further research, including large-scale, prospective studies, is needed to provide a greater level of evidence. Implications and future directions This study provides baseline information on the types and occurrence of maternal, fetal and musculoskeletal complications among women with OI. Multicenter studies including registries of every woman with OI should be started to estimate the exact frequency of maternal and fetal complications. Data specific to obstacles and complications related to obstetrics should be collected to form formal guidelines specific to OI pregnancies. Conclusion The frequency of pregnancy and fracture-related complications varies among women with osteogenesis imperfecta. Significant data gaps describe the limited experience of OI in pregnancy and its different outcomes. This study underscores the crucial need for further research and clarity about maternal and neonatal complications associated with OI pregnancies. Data availability Underlying data No data is associated with this article. Extended data The data generated for the article is depicted as PRISMA-Scr guidelines checklist and uploaded to data repository. All authors agreed to make all data freely available. The dataset can be accessed. Data file 1 Repository name: PRISMA-SCr guidelines checklist, word format. https://doi.org/10.6084/m9.figshare.29259962.v1 18 DOI: 10.6084/m9.figshare.29259962 Data file 2 Repository name: Pregnancy with osteogenesis imperfecta: A scoping review- protocol and proforma, word format. https://doi.org/10.6084/m9.figshare.29291780 25 DOI: 10.6084/m9.figshare.29291780 Reporting guidelines Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). References 1. Van Dijk FS, Sillence DO: Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am. J. Med. Genet. A. 2014; 164a (6): 1470–1481. PubMed Abstract | Publisher Full Text 2. Rauch F, Glorieux FH: Osteogenesis imperfecta. 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Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 01 Aug 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India 2 Consultant, Apple children Hospital, Ellis bridge, Ahmedabad, India 3 Department of medicine, Father Muller Medical, Mangalore, Karnataka, 575002, India 4 Department of Paediatric Orthopaedics, Kasturba Medical College, Manipal,, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India Krupa Shah Roles: Data Curation, Formal Analysis, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Kosha Sheth Roles: Data Curation, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Dhairya Shah Roles: Data Curation, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Hitesh Shah Roles: Conceptualization, Data Curation, Formal Analysis, Methodology, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 01 Aug 2025, 14:753 https://doi.org/10.12688/f1000research.165960.1 Copyright © 2025 Shah K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Shah K, Sheth K, Shah D and Shah H. Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] . F1000Research 2025, 14 :753 ( https://doi.org/10.12688/f1000research.165960.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 01 Aug 2025 Views 0 Cite How to cite this report: Fratzl-Zelman N. Reviewer Report For: Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] . F1000Research 2025, 14 :753 ( https://doi.org/10.5256/f1000research.182783.r415784 ) The direct URL for this report is: https://f1000research.com/articles/14-753/v1#referee-response-415784 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 11 Oct 2025 Nadja Fratzl-Zelman , Ludwig Boltzmann Institute of Osteology, Vienna Bone and Growth Center, , Austria., Vienna, Austria Approved VIEWS 0 https://doi.org/10.5256/f1000research.182783.r415784 Krupa Shah and coworkers present a systematic review on feto-maternal outcome and delivery in pregnancies of patients with osteogenesis imperfecta. They reviewed 28 articles that were published between January 1975 and January 2025 and reported on pregnancy characteristics, maternal, antenatal, ... Continue reading READ ALL Krupa Shah and coworkers present a systematic review on feto-maternal outcome and delivery in pregnancies of patients with osteogenesis imperfecta. They reviewed 28 articles that were published between January 1975 and January 2025 and reported on pregnancy characteristics, maternal, antenatal, intrapartum and post-partum observations. This is an important study because due to the scarcity of the disorder there is only limited information available on pregnancies-related complications. The objectives, search strategies, inclusion and exclusion criteria are presented in a detailed manner. In particular, the summary presented in Table 3 is very clear and address properly all points discussed in the study. The authors concluded that there is a crucial need for further research about maternal and neonatal complications associated with OI pregnancies and in fact there are further cohort studies on pregnancy-related complications in patients with osteogenesis imperfecta published since the end of the recorded period of the present review. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Rare bone diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Fratzl-Zelman N. Reviewer Report For: Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] . F1000Research 2025, 14 :753 ( https://doi.org/10.5256/f1000research.182783.r415784 ) The direct URL for this report is: https://f1000research.com/articles/14-753/v1#referee-response-415784 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 01 Aug 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 1 01 Aug 25 read Nadja Fratzl-Zelman , Vienna Bone and Growth Center, , Austria., Vienna, Austria Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Fratzl-Zelman N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 11 Oct 2025 | for Version 1 Nadja Fratzl-Zelman , Ludwig Boltzmann Institute of Osteology, Vienna Bone and Growth Center, , Austria., Vienna, Austria 0 Views copyright © 2025 Fratzl-Zelman N. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Krupa Shah and coworkers present a systematic review on feto-maternal outcome and delivery in pregnancies of patients with osteogenesis imperfecta. They reviewed 28 articles that were published between January 1975 and January 2025 and reported on pregnancy characteristics, maternal, antenatal, intrapartum and post-partum observations. This is an important study because due to the scarcity of the disorder there is only limited information available on pregnancies-related complications. The objectives, search strategies, inclusion and exclusion criteria are presented in a detailed manner. In particular, the summary presented in Table 3 is very clear and address properly all points discussed in the study. The authors concluded that there is a crucial need for further research about maternal and neonatal complications associated with OI pregnancies and in fact there are further cohort studies on pregnancy-related complications in patients with osteogenesis imperfecta published since the end of the recorded period of the present review. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Yes Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests No competing interests were disclosed. Reviewer Expertise Rare bone diseases I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Fratzl-Zelman N. Peer Review Report For: Pregnancy with osteogenesis imperfecta: A scoping review [version 1; peer review: 1 approved] . F1000Research 2025, 14 :753 ( https://doi.org/10.5256/f1000research.182783.r415784) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-753/v1#referee-response-415784 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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