Lipid profile analysis during pregnancy and its association with adverse pregnancy outcomes: a retrospective cohort study.

Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy. This was a prospective study of consecutive singleton pregnancies complicated by late-onset FGR. Late-onset FGR was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd centile, or EFW or AC < 10th centile and umbilical artery (UA) pulsatility index (PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile, diagnosed after 32 weeks. EFW, uterine artery PI, UA-PI, fetal middle cerebral artery (MCA) PI, CPR and umbilical vein blood flow normalized for fetal abdominal circumference (UVBF/AC) were recorded at the time of the diagnosis of FGR. Doppler variables were expressed as Z-scores for gestational age. Composite adverse perinatal outcome was defined as the occurrence of at least one of emergency Cesarean section for fetal distress, 5-min Apgar score < 7, umbilical artery pH < 7.10 and neonatal admission to the special care unit. Logistic regression analysis was used to elucidate the strength of association between different ultrasound parameters and composite adverse perinatal outcome, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive accuracy. In total, 243 consecutive singleton pregnancies complicated by late-onset FGR were included. Composite adverse perinatal outcome occurred in 32.5% (95% CI, 26.7-38.8%) of cases. In pregnancies with composite adverse perinatal outcome, compared with those without, mean uterine artery PI Z-score (2.23 ± 1.34 vs 1.88 ± 0.89, P = 0.02) was higher, while Z-scores of UVBF/AC (-1.93 ± 0.88 vs -0.89 ± 0.94, P ≤ 0.0001), MCA-PI (-1.56 ± 0.93 vs -1.22 ± 0.84, P = 0.004) and CPR (-1.89 ± 1.12 vs -1.44 ± 1.02, P = 0.002) were lower. On multivariable logistic regression analysis, Z-scores of mean uterine artery PI (P = 0.04), CPR (P = 0.002) and UVBF/AC (P = 0.001) were associated independently with composite adverse perinatal outcome. UVBF/AC Z-score had an area under the ROC curve (AUC) of 0.723 (95% CI, 0.64-0.80) for composite adverse perinatal outcome, demonstrating better accuracy than that of mean uterine artery PI Z-score (AUC, 0.593; 95% CI, 0.50-0.69) and CPR Z-score (AUC, 0.615; 95% CI, 0.52-0.71). A multiparametric prediction model including Z-scores of MCA-PI, uterine artery PI and UVBF/AC had an AUC of 0.745 (95% CI, 0.66-0.83) for the prediction of composite adverse perinatal outcome. While CPR and uterine artery PI assessed at the time of diagnosis are associated independently with composite adverse perinatal outcome in pregnancies complicated by late-onset FGR, their diagnostic performance for composite adverse perinatal outcome is low. UVBF/AC showed better accuracy for prediction of composite adverse perinatal outcome, although its usefulness in clinical practice as a standalone predictor of adverse pregnancy outcome requires further research. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Major trauma in pregnancy: prediction of maternal and perinatal adverse outcomes

Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of Assisted Reproductive Technology (ART)

Can hemoglobin A1c in early pregnancy predict adverse pregnancy outcomes in diabetic patients?

Adverse live-born pregnancy outcomes among pregnant people with anorexia nervosa

Introduction Hepatitis B is the most common form of viral hepatitis. Much has been done for the prevention of Hepatitis B transmission from mother to child. However, there is still very limited evidence looking at maternal obstetrics and perinatal outcomes, such as gestational diabetes, antepartum haemorrhage and preterm labour, hypertensive disorders in pregnancy and small for gestational age, with Hepatitis B infected women. These adverse pregnancy outcomes, if significant, may affect future antenatal care and have a negative impact on public health. This study aims to determine the association between these adverse pregnancy and neonatal outcomes with maternal Hepatitis B carrier state. Methods This is a retrospective cohort study comparing adverse pregnancy and neonatal outcomes in primigravid women who delivered singleton babies after 24 completed weeks of gestation and are carrier for Hepatitis B virus with those who are non-carrier for Hepatitis B virus, between 1992 and 2013 in Aberdeen Maternity Hospital. The adverse pregnancy and neonatal outcomes studied include hypertensive disorders in pregnancy, antepartum haemorrhage, preterm birth &lt;37 weeks, induction of labour, caesarean delivery, low birth weight and admission to neonatal unit. Data was extracted from the Aberdeen Maternity and Neonatal Databank (AMND), which was established in 1950 to record all pregnancy-related events occurring in Aberdeen city and district in the northeast of Scotland. Statistical analysis was done with SPSS version 21 using independent samples t-test for normally distributed continuous variables and chi-squared test for categorical variables. Multivariate logistic regression analysis using a multilevel random effects regression model was also conducted to adjust for confounding factors. Results The data set contained a sample size of 35116 primigravid women with singleton pregnancies, with 59 being carrier for Hepatitis B virus (represented by positive HBsAg status). HBsAg-positive women had significantly lower mean Body Mass Index and were more likely to be from the manual social class (registrar general’s occupation-based social class). On unadjusted analysis, there were no significant differences in the prevalence of all maternal and perinatal outcomes in both groups. However, after adjusting for confounding factors, HBsAg-positive women were more likely to have smaller babies (aOR 4.28; 95% CI 1.57-11.66). Conclusion Our study suggested higher frequencies of low birth weight babies in women with hepatitis B infection. We found no statistically significant differences in other adverse pregnancy and perinatal outcomes. As current evidence still shows inconsistent results, further research evaluating the possible effects of Hepatitis B viraemia on pregnancy outcomes is justified.

Sickle cell disease in pregnancy is associated with high maternal and fetal mortality. However, studies reporting pregnancy, fetal, and neonatal outcomes in women with sickle cell disease are extremely limited. The objectives of the study are to determine whether women with sickle cell disease have a greater risk of adverse pregnancy, fetal, and neonatal outcomes than women without sickle cell disease and identify the predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. A retrospective pair-matched case-control study was conducted to compare 171 pregnant women with sickle cell disease to 171 pregnant women without sickle cell disease in Muscat, Sultanate of Oman. All pregnant Omani women with sickle cell disease who delivered between January 2015 and August 2021 at Sultan Qaboos University Hospital and Royal Hospital, who were either primipara or multipara and who had a gestational age of 24-42 weeks, were included as patients, whereas women who had no sickle cell disease or any comorbidity during pregnancy, who delivered within the same timeframe and at the same hospitals, were recruited as controls. The data were retrieved from electronic medical records and delivery registry books between January 2015 and August 2021. Women with sickle cell disease who had severe anemia had increased odds of (χ2 = 58.56, p < 0.001) having adverse pregnancy outcomes. Women with sickle cell disease had 21.97% higher odds of delivering a baby with intrauterine growth retardation (χ2 = 17.80, unadjusted odds ratio = 2.91-166.13, p < 0.001). Newborns born to women with sickle cell disease had 3.93% greater odds of being admitted to the neonatal intensive care unit (χ2 = 16.80, unadjusted odds ratio = 1.97-7.84, p < 0.001). In addition, the children born to women with sickle cell disease had 10.90% higher odds of being born with low birth weight (χ2 = 56.92, unadjusted odds ratio = 5.36-22.16, p < 0.001). Hemoglobin level (odds ratio = 0.17, p < 0.001, 95% confidence interval = 0.10-3.0), past medical history (odds ratio = 7.95, p < 0.001, 95% confidence interval = 2.39-26.43), past surgical history (odds ratio = 17.69, p < 0.001, 95% confidence interval = 3.41-91.76), and preterm delivery (odds ratio = 9.48, p = 0.005, 95% confidence interval = 1.95-46.23) were identified as predictors of adverse pregnancy, fetal, and neonatal outcomes in women with sickle cell disease. As pregnant women with sickle cell disease are at increased risk for pregnancy, fetal, and neonatal adverse outcomes; improved antenatal surveillance and management may improve the outcomes.

Inflammatory bowel diseases (IBD) are significantly associated with adverse pregnancy and neonatal outcomes, though the pathomechanism is yet unknown. To investigate the relationship between IBD and adverse pregnancy outcomes by comparing neonatal outcomes and placental histopathology in two matched groups of patients with and without IBD. In this retrospective study, data of all patients who gave birth between 2008-2021 and were diagnosed with IBD were reviewed and compared to a control group matching two control cases for every IBD case. Neonatal outcomes and placental pathology were compared between the groups. Compared to the control group (n=76), the placentas of patients with IBD (n=36) were characterized by significantly lower placental weight (p < 0.001), and higher rates of maternal vascular malperfusion lesions (MVM, p < 0.001) and maternal and fetal inflammatory response lesions (p < 0.001). Neonates of patients with IBD were more frequently small for gestational age (SGA) (p=0.01), with increased rates of need for phototherapy (p = 0.03), respiratory morbidity and NICU admission (p < 0.001 for both outcomes). Multivariate logistic regression analyses adjusting for possible confounders (including maternal age, gestational age, chronic hypertension, smoking, and thrombophilia) confirmed the independent association between IBD and composite MVM lesions (aOR 4.31, p < 0.001), maternal inflammatory responses (aOR 40.22, p < 0.001) and SGA infants (aOR 4.31, p = 0.013). IBD is associated with increased rates of placental histopathological lesions and adverse pregnancy outcomes, including SGA infants. These novel findings imply the role of placental malperfusion and inflammatory processes in pregnancy complications of IBD patients, which should be followed accordingly. Approval of local ethics committee # WOMC-0219-20.

Background: Gestation complications have a recurrence risk and could predispose to each other in the next pregnancy. We aimed to evaluate the relationship between a history of adverse pregnancy and maternal-fetal outcomes in subsequent pregnancy in patients with Immunoglobulin A nephropathy (IgAN). Methods: A retrospective cohort study from a Chinese single center was conducted. Pregnant women with biopsy-proven primary IgAN and aged ≥18 years were enrolled and divided into the 2 groups by a history of adverse pregnancy. The primary outcome was adverse pregnancy outcome, which included maternal-fetal outcomes. Logistical regression model was used to evaluate the association of a history of adverse pregnancy with subsequent adverse maternal and fetal outcomes. Results: Ninety-one women with 100 pregnancies were included, of which 54 (54%) pregnancies had a history of adverse pregnancy. IgAN patients with adverse pregnancy history had more composite maternal outcomes (70.4% vs. 45.7%, p = 0.012), while there was no difference in the composite adverse fetal outcomes between the 2 groups (55.6% vs. 45.7%). IgAN patients with a history of adverse pregnancy were associated with an increased risk of subsequent adverse maternal outcomes (adjusted odds ratio [OR], 2.64; 95% CI, 1.07–6.47). Similar results were shown in those with baseline serum albumin <3.5 g/dL, 24 h proteinuria ≥1 g/day, and a history of hypertension. There was no association between a history of adverse pregnancy and subsequent adverse fetal outcomes in IgAN patients (adjusted OR, 1.56; 95% CI, 0.63–3.87). Conclusion: A history of adverse pregnancy was associated with an increased risk of subsequent adverse maternal outcomes, but not for adverse fetal outcomes in IgAN patients.

BackgroundA dolutegravir (DTG)-based antiretroviral regimen has been rolled out for pregnant women in low- and middle-income countries since 2020. However, available safety data are limited to a few clinical trials and observational studies. Hence, we present real-world pregnancy and birth outcome safety data from a large sample multicenter cohort study in Ethiopia.MethodsA retrospective cohort study was conducted in fourteen hospitals across Ethiopia from 2017 to 2022. HIV-infected pregnant women were followed from the date of prevention of mother-to-child transmission (PMTCT) care enrolment until the infant was 6–8 weeks old. The primary safety outcome was a composite of adverse pregnancy events comprising spontaneous abortion, intrauterine fetal death (IUFD) before onset of labor, preterm birth, and maternal death. Additionally, a composite adverse birth outcome was assessed, comprising intrapartum fetal demise, low birth weight, and neonatal death. Finally, a composite of adverse pregnancy or birth outcome was also investigated. The exposure of interest was the antiretroviral treatment (ART) regimen used during pregnancy for PMTCT of HIV.ResultsDuring the study period, 2643 women were enrolled in routine PMTCT care. However, 2490 (92.2%) participants were eligible for the study. A total of 136/1724 (7.9%, 95% CI: 6.7–9.3%) women experienced adverse pregnancy outcomes. Fewer women in the DTG-based group (5.4%, 95% CI: 3.7–7.5%) had adverse pregnancy outcomes than in the Efavirenz (EFV)-based group (8.3%, 95% CI: 6.6–10.3%), P = 0.004. After controlling for baseline differences, the DTG group had a 43% lower risk of adverse pregnancy outcomes (adjusted odd ratio (AOR), 0.57; 95% CI, 0.32–0.96%) and a 53% lower risk of preterm birth (AOR, 0.47; 95% CI, 0.22–0.98%) compared to the EFV group. A total of 103/1616 (6.4%, 95% CI: 5.2–7.7%) women had adverse birth outcomes. Although the difference was not statistically significant, fewer women in the DTG group (30/548; 5.5%, 95% CI: 3.7–7.7%) than in the EFV group (57/830; 6.9%, 95% CI: 5.2–8.8%) had adverse birth outcomes.ConclusionsIn this study, we observed that DTG-based regimens were associated with better pregnancy and birth outcome safety profiles, reaffirming the WHO recommendation. However, a prospective study is recommended to assess uncaptured maternal and perinatal adverse outcomes, such as congenital abnormalities, and infant growth and neurocognitive development.

Background: Adverse pregnancy outcomes (APO) pose long-term cardiovascular risks. Considering the potential impact of APO on maternal health, this study aims to investigate the characteristics and clinical outcomes of women who have experienced APO and subsequently undergo transcatheter mitral valve repair (TMVr). Methods: This is a retrospective cohort study that analyzed data from 15,220 women who underwent transcatheter mitral valve repair (TMVr) and it was divided into two groups: history of adverse pregnancy outcome (APO, n=3240) and without a history of APO (No APO, n=11,980). Comparative analyses between the APO and No APO groups were performed using t-tests for continuous variables and chi-square tests for categorical variables. Multivariate logistic regression models were employed to adjust for potential confounders and identify independent predictors of in-hospital mortality and other adverse outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for each variable. Results: Patients with a history of adverse pregnancy outcomes (APOs) were younger (mean age 73.3 vs. 79.0 years, p&lt;0.001) and more frequently identified as Black/African American (20.9% vs. 8.0%, p&lt;0.001). They had a higher mean Charlson Comorbidity Index (3.2 vs. 2.8, p&lt;0.001). After adjustment, these patients were more likely to require mechanical ventilation (OR 0.76, 95% CI 0.61-0.94, p=0.0112) and vasopressors (OR 1.37, 95% CI 1.05-1.79, p=0.0205), experience heart block (OR 2.29, 95% CI 2.00-2.63, p&lt;0.001), and develop acute kidney injury (OR 1.26, 95% CI 1.12-1.42, p=0.0001). However, the adjusted odds of in-hospital mortality did not differ significantly between the groups (OR 0.99, 95% CI 0.73-1.32, p=0.9355). Conclusions: Women with a history of adverse pregnancy outcomes (APOs) undergoing TMVr face higher risks of complications, such as heart block and acute kidney injury, highlighting the importance of incorporating pregnancy history into cardiovascular risk assessment and management for these patients.

To investigate the association between cervical elastographic parameters and adverse pregnancy outcome in pregnancy with placenta previa. This retrospective cohort study included 64 pregnant women with placenta previa who had examined cervical elastography using E-cervixTM (WS80A, Samsung Medison, Seoul, Republic of Korea) at 20–34 weeks of gestation from 2019 to 2020 at Severance Hospital. Clinical characteristics and commercially available elastography parameters (IOS, EOS, ECI and HR) were compared with or without adverse outcome. Adverse pregnancy outcome included spontaneous preterm delivery (sPTD) < 37 weeks or admission due to excessive vaginal bleeding. Cervical elastographic and pregnancy outcomes were analysed using the Chi-square test, Mann-Whitney U test, and logistic regression analysis adjusted by cervical length and gestational age at examination. 64 pregnant women enrolled in this study and 124 cases of cervical elastography were acquired. Of them, 19 (29.6%) had sPTD < 37 weeks and 23 (35.9%) had admitted to hospital with excessive vaginal bleeding. Adverse pregnancy outcome group had higher IOS and ECI than those of the control group (p = 0.006 and 0.047, respectively). The odds of adverse pregnancy outcome increased by 1.11-fold for each 0.1 increase in IOS (adjusted for cervical length and gestational age at examination; p = 0.003). In combination with elastographic parameters, IOS*ECI and IOS*HR were associated with adverse pregnancy outcome. On logistic regression analysis, IOS*ECI (odds ratio [OR], 5.32; p = 0.009) and IOS*HR (OR, 1.23; p = 0.003) were independent predictors of adverse pregnancy outcomes. Cervical elastography may be useful for the prediction of women with placenta previa for adverse pregnancy outcomes.

Adverse pregnancy outcomes, which can be caused by multiple factors, present a significant threat to the health of mothers and their babies. Cell-free fetal DNA (cffDNA) from placental trophoblast cells might be able to reflect placental and fetal status. Previous studies have yielded controversial results regarding the association of FF or cffDNA with various adverse pregnancy outcomes. A previous study has attempted to systematically assess the association between low fetal fraction (FF) and adverse pregnancy outcomes, but it failed to perform quantitative analyses due to the few studies included. In the present study, we attempted to quantitatively assess the association of FF (or cffDNA) with adverse pregnancy outcomes and further analyze the causes of heterogeneity. To investigate the association of high/low FF or cffDNA with adverse pregnancy outcomes. We searched the databases of PubMed, Embase, Cochrane, and Web of Science from January 1, 1990, to June 15, 2022 in this meta-analysis. Studies on the relationships of adverse pregnancy outcomes in women with FF or cell free DNA were included. Non-English literature was excluded. Data about pregnancy outcomes and cell free DNA were extracted and meta-analyzed. Subgroup analysis was performed by different outcomes. There were 11 studies included involving 8280 participants. No significant heterogeneity was observed among the studies (I2 = 27%, 25%), and a fixed-effect model was used for weighted quantitative analysis. The results revealed that the FF or cffDNA during pregnancy was significantly associated with adverse pregnancy outcomes in pregnant women (OR = 1.57, 95% CI [1.24, 1.99], P = 0.233). The overall incidence of the maternal adverse outcomes was 8% (95% CI: 5-13). Subgroup analysis of different outcomes showed an evident association between low FF or cffDNA and hypertensive disorders of pregnancy (HDP) (OR = 1.76, 95% CI [1.36, 2.27], P = 0.581). There was no evidence that the occurrence of spontaneous preterm birth (sPTB) and placental abnormality was associated with FF or cffDNA. No association was observed between low FF or cffDNA during pregnancy and adverse outcomes in fetuses (OR = 1.39, 95% CI [0.99, 1.94], P = 0.242). The overall incidence of adverse outcomes in fetuses was 8% (95% CI: 6-11). There were controversies over the association between high FF or cffDNA and HDP, and sPTB and small for gestational age infant, among different studies. Pregnant women with low FF or cffDNA during the first or second trimester of pregnancy have an overall increased risk of adverse pregnancy outcomes, especially HDP. However, the association between FF and various pregnancy outcomes needs to be further explored by more prospective studies.

To explore the application value of serum Gal-13, GLP-1 and VEGF in the prevention and guidance of adverse pregnancy outcomes in gestational diabetes (GDM). A retrospective study with case-control method was used to select 1 012 GDM patients from Haikou Maternal and Child Health Hospital from January 2019 to December 2022 as the study objects, and they were divided into poor pregnancy outcome group (n=342) and good pregnancy outcome group (n=670) according to whether they had adverse pregnancy outcomes. The medical records of 521 healthy women with normal glucose metabolism were selected as the control group. Serum Gal-13 and GLP-1 were detected by enzyme-linked immunosorbent assay and VEGF was determined by IAMMGE specific protein analyzer. After comparing the differences of the above factors among the three groups, multivariate logistic regression model was used to analyze the influencing factors of adverse pregnancy outcomes in GDM patients, and ROC curve was drawn to analyze the predictive value of serum Gal-13, GLP-1 and VEGF levels on adverse pregnancy outcomes in GDM patients. The results showed that Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) in the adverse pregnancy outcome group were 5.92(4.98, 6.41) mmol/L, 5.32(4.96, 5.47)%, 62.56(49.21,99.50) pmol/L, VEGF was 495.47(389.14, 567.13) ng/L, TSH was 1.48(1.34, 1.58) mIU/L, right ventricular myocardial work index (Tei index) was 0.59(0.45, 0.67), 89 cases of elderly parturients; FPG was 4.45(4.16, 5.03) mmol/L, HbA1c was 5.04(4.86, 5.29)%, FINS was 57.41(46.90, 74.08) pmol/L, VEGF was 405.84(348.02, 462.68) ng/L, TSH was 1.42(1.25, 1.50) mIU/L, Tei index was 0.50(0.47, 0.64), there were 142 cases of old women. In the control group, FPG was 4.33(4.05, 4.75) mmol/L, HbA1c was 5.01(4.13, 5.18)%, FINS was 38.48(36.76, 41.72) pmol/L and VEGF was 302.45(283.14, 336.56) ng/L, TSH was 1.32(1.24, 1.47)mIU/L, Tei index was 0.48(0.39, 0.59), and there were 106 elderly parturiencies. The levels of FPG, HbA1c, FINS, VEGF, TSH and Tei index in the adverse pregnancy outcome group and the good pregnancy outcome group were higher than those in the control group, and the proportion of elderly parturients was higher than that in the control group, and the adverse pregnancy outcome group was higher than that in the good pregnancy outcome group. The differences were statistically significant (H=8.620, P<0.001, H=2.616, P=0.014, H=6.156, P<0.001, H=3.051, P<0.001, H=4.892, P=0.044, χ2=2.548, P=0.045). In the adverse pregnancy outcome group, Gal-13 was 15.27(8.35, 24.45)pg/ml, GLP-1 was 9.27(8.26, 12.35) pmol/L and FT4 was 11.59(9.67, 13.48) pmol/L. In the group with good pregnancy outcome, Gal-13 was 25.34(20.14, 29.73) pg/ml, GLP-1 was 12.38(10.25, 15.63) pmol/L and FT4 was 13.86(10.67, 15.10) pmol/L. In the control group, Gal-13 was 31.21(27.48, 34.45) pg/ml, GLP-1 was 11.34(10.40, 14.37) pmol/L and FT4 was 14.15(10.75, 15.43)pmol/L. The levels of Gal-13, GLP-1 and FT4 in the adverse pregnancy outcome group and the good pregnancy outcome group were significantly lower than those in the control group, and the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group. The differences were statistically significant (H=6.458, P=0.011, H=8.445, P<0.001, H=5.694, P<0.001). The levels of Gal-13 and GLP-1 in normal blood glucose recovery group were higher than those in non-normal blood glucose recovery group, and the levels of VEGF were lower than those in non-normal blood glucose recovery group (P<0.05).In multivariate logistic regression analysis, Gal-13, GLP-1, VEGF, TSH, FT4 and Tei indexes were independent influencing factors for adverse pregnancy outcomes with GDM (P<0.05). ROC curve analysis showed that the AUC of Gal-13, GLP-1 and VEGF alone in predicting adverse pregnancy were 0.779, 0.761 and 0.615, respectively. The value of the combined diagnosis was the highest (AUC=0.912), the sensitivity was 90.1%, and the specificity was 80.0%. In conclusion, Gal-13, GLP-1 and VEGF may be independent influencing factors for adverse pregnancy outcomes in GDM patients, and the combined detection of the three may help to improve the auxiliary diagnostic efficacy for predicting adverse pregnancy outcomes.

BackgroundIn addition to hyperglycemia, women with hypoglycemia identified during pregnancy have a higher risk of adverse pregnancy outcomes. However, there is limited evidence of the association between prepregnant hypoglycemia and adverse pregnancy outcomes in women without pre-existing diabetes. This study aims to explore the association between maternal preconception hypoglycemia and adverse pregnancy outcomes among childbearing-aged women in China.Methods and findingsThis was a retrospective cohort study of the National Free Preconception Checkup Project (NFPCP), including women who were aged 20–49, successfully conceived within one year without multiple gestations, and had complete information on pregnancy outcomes. Maternal fasting plasma glucose (FPG) concentrations were analyzed in the preconception examination stage, and women were divided into normal (FPG 3.9 to <5.6 mmol/L) and hypoglycemia (FPG < 3.9 mmol/L) groups. Adverse pregnancy outcomes included medical abortion, miscarriage or early stillbirth, preterm birth (PTB), macrosomia, low birth weight (LBW), large for gestational age (LGA), small for gestational age (SGA), birth defects, and perinatal death. Baseline characteristics of the two groups were balanced using inverse probability treatment weighting (IPTW) based on propensity scores. Both multivariable-adjusted and IPTW odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between preconception hypoglycemia and adverse pregnancy outcomes. Models adjusted for maternal age, ethnicity, educational level, occupation, region of gross domestic product, smoking, passive smoking, alcohol consumption, maternal preconception body mass index (BMI), parity, history of adverse pregnancy outcome, preconception medicine use, folic acid intake, diabetes, hypertension, anemia, thyroid disorder, liver disorder, and infection. ORs of adverse pregnancy outcomes with preconception hypoglycemia stratified by BMI were also reported. Among 4,866,919 women who participated in NFPCP during 2013–2016, 239,128 (4.91%) had preconception hypoglycemia. Compared to the normal group, women with preconception hypoglycemia had increased IPTW-multivariate adjusted ORs of PTB by 10% (95% CI [1.08, 1.12], P < 0.001), LBW by 8% (95% CI [1.03, 1.12], P = 0.001), SGA by 7% (95% CI [1.05, 1.08], P < 0.001), and birth defects by 21% (95% CI [1.06, 1.37], P = 0.004), while the ORs of medical abortion decreased by 6% (95% CI [0.91, 0.98], P = 0.002), miscarriage or early stillbirth by 5% (95% CI [0.92, 0.97], P < 0.001), macrosomia by 12% (95% CI [0.86, 0.90], P < 0.001), and LGA by 12% (95% CI [0.86, 0.89], P < 0.001) if mothers had a preconception hypoglycemia. The associations of maternal preconception hypoglycemia and adverse pregnancy outcomes varied among BMI groups. Among underweight women, preconception hypoglycemia was associated with a lower risk of medical abortion, miscarriage or early stillbirth, LGA, and PID, while overweight women had a lower risk of macrosomia and LGA. Moreover, a higher risk of miscarriage or early stillbirth and PTB was observed in obesity and underweight, respectively, in association with preconception hypoglycemia. Main limitations in the current study included the limited generalizability in other countries with varying disparities in healthcare and the lack of information on certain potential confounders (such as gestational complications and whether they received any related intervention after preconception examination).ConclusionPreconception hypoglycemia was significantly associated with adverse pregnancy outcomes, and maternal preconception BMI could modify the association. In addition to paying attention to women with preconception hyperglycemia, our findings call for increased concern for women with hypoglycemia in preconception glycemic screening, with consideration of modified effects by preconception BMI, which might be worth exploring as a means to reduce adverse pregnancy outcomes.