Low birth weight is weight less than 2500 g or 5.5 lb. at birth. Globally, more than 20 million infants (15-20%) are born with a low birth weight each year. Birth weight is the primary indicator of the health status of neonates and is the primary factor that determines the infant’s physical, survival, and mental growth. Thus, the study aimed to investigate the determinants of low birth weight among newborn babies delivered at Tirunesh Beijing General Hospital, Addis Ababa, Ethiopia.p-value of ≤0.05 was used to declare statistical significance.We performed a facility-based unmatched case-control study among 453 (151 cases and 302 controls) deliveries conducted at Tirunesh Beijing General Hospital. Birth records and maternal antenatal care (ANC) files were reviewed from March 1 to April 30, 2019. Consecutive sampling was employed to select study participants. Data were entered into Epi-data version 4.2.1 and analyzed using SPSS version 25 statistical software. Descriptive statistics and logistic regression analysis were computed to identify independent determinants of low birth weight. A . Women who reside in rural area [AOR (CI) = 3.12 (1.63-5.98)], being merchant [(AOR (CI) = 2.90 (1.03-8.22)], danger sign during pregnancy [(AOR (CI) = 4.14 (1.68-10.2)], and maternal weight during pregnancy [(AOR (CI) = 4.94 (3.26-7.52)] were found to be a significant determinants of low birth weight.Four hundred fifty-three birth records of babies (151 cases and 302 controls) were reviewedResidence, occupation, danger signs, and maternal weight during pregnancy were significant determinants of low birth weight. Socioeconomic development, early detection and management of complications, and encouraging nutrition and weight during pregnancy are crucial for minimizing the risk of delivering low birth weight babies. The birth weight of a newborn baby is the first weight record, preferably taken within an hour of birth. Birth weight is a good summary of multifaceted public health problems, including long-term maternal malnutrition, chronic illness, and poor health care during pregnancy . World HEvery year more than 20 million babies are born weighing below 2500 g. Globally, this figure accounts for 17% of total birth in low-income countries, a rate more than twofold that of developed countries (7%) . In Sub-Low birth weight babies are highly vulnerable to death during their early childhood periods. Even those who escaped death in their early months and years are still prone to a high incidence of chronic diseases like type II diabetes mellitus, cardiovascular disease, hypertension, immunodeficiency, and impaired language development in their adulthood and old age. It also hurts their reproductive outcomes, i.e., preterm and low birth weight, and neurocognitive development such as intellectual disability, learning impairment, cerebral palsy, retinopathy, and mental retardation .A baby’s birth weight is substantially influenced by the mother’s early life, including fetal growth, childhood and adolescent nutrition, hereditary, and body composition during conception . Other pAccording to the Ethiopian Demographic Health Survey, the burden of low birth weight in Ethiopia was not decreased significantly, 11% in 2011 and 13% in 2016 . This miIn Ethiopia, LBW is still a significant public health concern. The attainment of a sustainable development goal is also intensely affected by the progress in newborn deaths. The government of Ethiopia has appreciated the depth of the problem, and nowadays, some changes are being employed by governmental, non-governmental organizations , WHO), and professional associations like Ethiopian pediatrics society. Evidence-based intervention is required to reduce the burden of the problem and improve newborns’ survival. Observational data on the incidence and determinants of low birth weight are essential for designing interventional activities, particularly in Sub-Saharan Africa . Thus, tA facility-based unmatched case-control study was conducted in Tirunesh Beijing General Hospital, Addis Ababa, from March 1 to April 30, 2019. The hospital is found South of Addis Ababa, the capital city of Ethiopia. The town contains ten sub-cities and 116 woredas. It has 12 governmental and nine non-governmental hospitals. Tirunesh Beijing General Hospital is one of the famous public general hospitals providing a range of medical, maternal, and child health services, including delivery services and various inpatient and outpatient healthcare services for more than four hundred thousand catchment populations surrounding the Oromia region.In the preceding year, all mothers delivered in Tirunesh Beijing General Hospital were the source population. There were 3798 deliveries in the past year. Cases were those newborns with low birth weight (LBW) (weight of < 2500 g) and controls  were those live births weighing ≥2500 g and those delivered on the same day as enrolled regardless of the mode of delivery. All singleton births delivered after 28 weeks of gestation or weight of at least 1000 g, and with available information on birth weight in the medical records were included. Newborns with twin or multiple births, visible congenital deformity, i.e., hydrocephalus, stillbirths, birth weight ≥ 4000 g, and incomplete data were excluded from the study.The sample size was determined using the Open Epi version 3.03 statistical software package. The following considerations were made: percent of controls exposed, odds ratio, confidence level 95%, power 80%, and the ratio of controls to cases 2 Table . By addiBirth weight was the outcome variable. Socio-demographic factors , maternal and obstetrics characteristics , and complications during pregnancy,  were the exposure variables.The weight of the newborns measured within the first 15 min of birth [Weight at birth between 2500 g and 4000 g.Any one or more early or late pregnancy bleeding, leakage of amniotic fluid, reduced fetal movement, severe headache, convulsion, blurred vision, fever, and severe abdominal pain .The number of times a woman has been pregnant, whether a term, live births, stillbirth, abortion, ectopic, or molar pregnancy.The number of times a woman gives birth to a fetus with a gestational age of 28 weeks or more, regardless of the outcome.For this study, mothers who supplemented and took iron and folic acid for at least 3 months were considered as “Yes.”Women trades in commodities produced by other people, i.e., vegetables , plastics , clothing  metals .The data were derived from four weight measurements in pregnancy from antenatal care registration books, and the average weight was considered for analysis.A structured and pre-tested checklist was used to extract the maternal antenatal care (ANC) files and birth records. The checklist was designed from the Demographic Health Survey questionnaire and other similar literature works , 14, 18.Four trained midwives and one supervisor participated in the data extraction. Consecutive sampling was employed to select cases and controls. For each case (low birth weight) record, two consecutive controls  records were set and reviewed starting from the data collection date.The questionnaire was first prepared in English and later translated to the local language, Amharic, and then back to English by an independent translator to keep the data collection instrument consistent. The tool was first pre-tested on 5% of the samples (8 cases and 15 controls) in Zewditu Memorial Hospital before the actual date of data collection. A necessary adjustment was considered following the result of the pre-test. A one-day training has been given concerning the objective, instrument, and data collection procedure for both data collectors and supervisors. The supervisor and the principal investigators checked and reviewed the collected data for clarity, completeness, and accuracy.p-value of ≤0.25 in the bivariable logistic regression were selected for the final model. Multivariable logistic regression models were run to identify independent determinants of LBW. The level of multi-collinearity was checked and fitted using variance inflation factor and tolerance. An adjusted odds ratio (AOR) with a 95% confidence interval (CI) was reported to describe the strength of association. The Omnibus test and Hosmer-Lemeshow goodness-of-fit were applied to check for model fitness. A statistically significant level was stated at a p-value of < 0.05.The data were coded, cleaned, and edited. Errors identified during the data cleaning were adjusted after reviewing the original data using the code numbers. Data were entered into Epi-Data version 4.2.1 and analyzed using SPSS version 25 statistical software. The descriptive statistics were summarized and presented using frequency tables, means, standard deviation, and percentages. When the frequencies became smaller, re-categorization/recoding of variables was done. Variables with a A total of 453 (151 cases and 302 controls) birth records and antenatal care files were reviewed. The mean (±SD) age of cases and controls were 29.17 ± 7.12 and 27.22 ± 5.59, respectively. Twenty-nine (6%) records were incomplete and excluded from the analysis. About 58.3% of cases and 77.5% of controls were within 20 – 35 years. Eighty-six (57%) cases reside in rural areas, while two hundred ten (69.5%) of controls were urban residents. Around 33.1% of cases and 27.5% of controls had attended primary school, and 40.6% of the case group and 21.2% of the control group mothers were within the weight range of 50 – 60 kg during their recent pregnancy. Further, nearly half of mothers in cases (49.7%) and controls (50.7%) were housewives (Table The mean (±SD) birth weight was 2133.5 ± 332.88 g for the low-birth-weight newborns and 3080 ± 360.93 g for the normal birth weight newborns. About 66.3% of cases and 55% of controls were multiparas, and 83.4% of cases and 89.4% of controls were supplemented with iron during pregnancy. The majority of the case group (86.1%) and control group mothers (91.4%) had antenatal care (ANC) follow-up. Female newborns accounted for the more significant proportion of cases (55.0%) and controls (51.7%). Regarding complications during pregnancy, 5.3, 19.9, and 31.8% of case group mothers had chronic hypertension, pregnancy-induced hypertension, and danger signs of pregnancy, respectively. Additionally, five (3.3%) of mothers with cases had a history of low birth weight, and twelve (7.9%) of mothers had a history of abortion  = 3.12 (1.63-5.98). The risk of low birth weight was also significantly higher among merchant mothers compared to those employed (AOR (CI) = 2.90 (1.03-8.22). Furthermore, mothers who had a danger sign during pregnancy were four times more likely to deliver low birth weight babies compared to those who have no danger signs (AOR (CI) = 4.14 (1.68-10.2). Mothers whose pregnancy weight ranges from 50 to 60 kg were approximately five times more likely to have low birth weight neonates, compared to those whose weight exceeds 81 kg (AOR (CI) = 4.94 (3.26-7.52).Low birth weight continues to be a significant cause of neonatal morbidity and mortality. In this study, residence, occupation, danger signs, and maternal weight during pregnancy were significant associates of low birth weight.The odds of low birth weight were higher among mothers from rural residents than their urban counterparts. This finding was consistent with past studies conducted in India , MalaysiHowever, this finding was in contrast with the report from Jimma Zone, Southwest Ethiopia, where the risk of low birth weight was significantly higher among urban residents . This maThis study revealed that the risk of low birth weight was significantly higher among merchant mothers. Our finding is concordant with Snijder et al.’s finding, which documented a significant association between being a merchant and low birth weight . This coDanger signs during pregnancy were also significantly increased the odds of low birth weight. According to this study, mothers who had a danger sign during pregnancy were four times more likely to deliver low birth weight babies. This finding was supported by previous studies done in India , Debre BMoreover, maternal weight during pregnancy was found to be another determinant factor for low birth weight. Mothers whose pregnancy weight ranges from 50 to 60 kg were more likely to deliver low birth weight babies than those whose weight exceeds 81 kg. This finding was consistent with a previous study in the context of five African countries: maternal underweight significantly increased the risk of low birth weight . A similOver 69% of women in the case group delivered before 37 completed weeks of gestation compared to only 3% in the control group. Similarly, in Brazil, prematurity increased the odds of LBW ten times . In addiSince secondary data were used, some potential risk factors such as income, height, mid-upper arm circumference, alcohol use, and smoking status could not be obtained.Residence, occupation, danger signs, and maternal weight during pregnancy were significant determinants of low birth weight. Socioeconomic development, early detection and management of complications, and encouraging nutrition and weight during pregnancy are crucial to minimizing the risk of delivering low birth weight babies. The health care providers would be better to emphasize antenatal counseling and health promotion regarding nutrition and danger signs with the appropriate actions to be taken.


A 41-year-old woman presented to the emergency department with pain in her abdomen during menstruation. On examination, we detected a cystic lump in the midline, just below the umbilicus. Ultrasonography of the whole abdomen was suggestive of uterine fibroids with a probable mesenteric cyst. Computed tomography of the abdomen confirmed an otherwise asymptomatic, silent, urachal cyst connected to the umbilicus and urinary bladder by obliterated bands. The cyst was explored and removed surgically under combined spinal-epidural anesthesia, following a single-staged approach. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was subsequently performed. Urachal cysts are rare congenital anomalies. Any unexpected finding on clinical examination should alert clinicians for further evaluation and treatment. Urachal cysts are rare congenital urachal anomalies that are typically detected in childhood and rarely in adults ,2. TheseA 41-year-old woman (parity two) presented to the emergency room with pain in her abdomen during menstruation for the past seven months. Abdominal pain was gradual in onset, colicky in nature, and appreciable mainly over the lower abdomen. It was moderate to severe in intensity and was relieved with sleep or medication. The pain was associated with heavy menstrual flow, with occasional clots. The patient more frequently experienced the pain during the initial days of menstruation, and it decreased progressively in intensity after that. However, the patient had noted a change in the nature of her pain over the past two months, in that it persisted even after cessation of menstrual flow, affecting her daily activities.The patient had attained menarche at the age of 13 years, and her periods were otherwise regular with average flow and duration. Her last childbirth via spontaneous vaginal delivery was eight years prior to the current presentation. On examination, the patient was anxious and afebrile. Her vitals  were stable. No significant findings were noted on inspection. There was no superficial tenderness, guarding, or rigidity. No organomegaly was felt on deep palpation. Mild tenderness was present over the lower part of the abdomen.A globular lump of ~5 cm in diameter was palpable in the midline below the umbilicus. The margins were well defined, the surface was smooth, and the consistency was smooth to firm. The lump was nontender, nonreducible, noncompressable, nonpulsatile, and did not move with respiration but did demonstrate some side-to-side mobility. The lump tended to be less prominent on the leg-rising test. Hernial sites were intact. On percussion, the typical tympanic note was present over the abdomen, except over the lump, where the note was dull. On auscultation, normal peristaltic sounds were heard over the abdomen, and there was no bruit over the lump. No abnormality was detected on digital rectal examination. The uterus was bulky on vaginal examination.Ultrasonography (USG) of the entire abdomen was advised and was suggestive of a mild bulky retroverted uterus with intramural fibroids and a well-defined anechoic cyst (40 × 33 × 30 mm) in the hypogastrium, with no solid component or calcification, and abutting the peritoneal surface of the anterior abdominal wall, which suggested a probable mesenteric cyst Figure .Further evaluation of the cyst via computed tomography (CT) of the abdomen showed a well-defined, thin-walled, hypodense, intraabdominal cystic lesion just below (approximately 2 cm) the level of the umbilicus and along the course of the urachus, measuring approximately 65 × 37 × 43 mm . No calcification or septation was noted. A thin, nonenhancing band was seen extending cranially from the upper pole of the cyst to the umbilicus and an obliterated urachal band from the lower pole of the cyst to the apex of the urinary bladder, suggestive of a urachal cyst  and her functional classification was American Society of Anesthesiologists II. She was of average build and height for her race, age, and sex with a normal spine and back. Consistent with the surgical intervention and to continue analgesia in the postoperative period, combined spinal-epidural anesthesia was planned. Antibiotic coverage and mild anxiolytic were started from the night prior to the proposed day of surgery.On the day of surgery, after setting up the epidural catheter at the level of L3-L4, a subarachnoid block was administered at L4-L5 using 16 mg bupivacaine heavy 0.5% and 25 μg fentanyl. We approached through a lower midline incision and entered the peritoneal cavity. A globular cystic swelling ~4 cm diameter was noted in the midline, just below the umbilicus , which itself is the vestigial remnant of the cloaca and the allantois . In earlThe urachal cyst ensues when the urachus is involuted at either endpoint but persists in between. Most commonly, it is found around the lower one-third of the urachus . UrachalRadiologic investigations play a pivotal role in differentiating a urachal cyst from other causes of acute abdomen. A simple cyst appears as a fluid-filled cavity on a CT scan or USG abdomen -18. WhenFor a urachal cyst, complete surgical excision of the cyst is the treatment of choice. Two methods have been described in the literature: a single-stage excision and a two-stage approach, whereby the initial incision and drainage of the cyst is followed by secondary excision. Many authors have reported that the two-stage approach is associated with reduced hospital stay and a decreased complication rate -25. In oUrachal cysts are rare congenital urachal anomalies that are typically asymptomatic and diagnosed when they produce symptoms secondary to infection or hemorrhage or during some other routine examination. As such, cysts may lie anywhere between the umbilicus and the urinary bladder apex, and they can have varied symptoms, at times mimicking acute abdomen. Rarely, the cyst may rupture, leading to localized or generalized peritonitis. Because timely intervention is the key for any healthy patient outcome, any unexplained mass on clinical examination should alert the clinician to make an alternative diagnosis with relevant clinical and radiologic evaluation.


Previously, we found that the presence of maternal serum metals before the 24th week of gestation prospectively increased fasting plasma glucose (FPG) at 24–28 weeks. We further explored the prospective association between levels of metals and neonatal outcomes and assessed the mediating effects of FPG on these relationships.A total of 7,644 pregnant women were included in a retrospective cohort study, and the relationships between metals  and birth outcomes were explored. Quantile and linear regressions were performed to detect the shifts and associations between metals and neonatal size distribution focused on the 10th, 50th, and 90th percentiles. Mediation analysis was performed to assess the mediating effect of FPG on metals and birth outcomes.After adjustment, a 50% increase in Mn and Zn levels was related to a 0.136-cm (95% CI: 0.067–0.205) and 0.120-cm (95% CI: 0.046–0.193) increase in head circumference, respectively. Based on head circumference distribution, the magnitude of the association with Mn was smaller at the upper tail, while the magnitude of correlation with Zn was greater at the upper tail. A 50% increase in Mn and Zn levels was related to a 0.135-cm (95% CI: 0.058–0.212) and 0.095-cm (95% CI: 0.013–0.178) increase in chest circumference, respectively. The magnitude of the association with Mn increased with increasing chest circumference, while the magnitude of correlation with Zn decreased with increasing chest circumference. FPG explained 10.00% and 17.65% of the associations of Mn with head and chest circumference. A positive indirect effect of Zn associated with head circumference  and chest circumference  through FPG was also observed, and the estimated proportion of the mediating effect was 13.79% and 26.32%, respectively.Maternal serum Mn and Zn levels before the 24th week of gestation may prospectively increase the circumference of the neonatal head and chest. FPG at 24–28 weeks had positive mediating effects on these relationships. Further research is needed to identify a balance between maternal blood glucose and birth size. Environmental exposure including metals in pregnant women has been associated with health effects in both the mother and her offspring , 2. SuchPregnant women are in a critically important state for susceptibility to metal effects because of hemodynamics, hormone changes, and immature immune systems , and metFasting plasma glucose (FPG) is predominantly produced following the decomposition of liver glycogen, while basal insulin secretion can inhibit the output of liver glycogen and prevent higher FPG. Therefore, the level of fasting blood glucose can objectively reflect the secretion level of basal insulin in patients. Elevated metal levels can accumulate in pancreatic tissue where they may contribute to insulin resistance or damage islet β cells and impair insulin secretion . Mn has Therefore, after combining our previous study with those of others, we hypothesized that earlier metal exposure in pregnant women was prospectively associated with final birth outcome, and later FPG mediated their relationship. Here, we tested this hypothesis in a retrospective and longitudinal population-based cohort study to explore i) whether maternal early metal exposure including Mn, Cu, Pb, Zn, and Mg before 24 weeks was related to birth outcomes and ii) whether a maternal FPG of 75 g oral glucose tolerance test (OGTT) at 24–28 weeks mediated the relationship between metal exposure and birth outcomes.The retrospective cohort study was conducted between January 2017 and December 2018 in Foshan, China. Pregnant women were recruited at the first obstetric clinic visit in the Southern Medical University Affiliated Foshan Women and Children Hospital. The study was approved by the Human Subjects Committee of our hospital. The inclusion criteria were as follows: 1) singleton pregnancy, 2) no diabetes prior to pregnancy, and 3) gestational age in the first trimester (<14 weeks). The exclusion criteria were as follows: 1) no available data on metal detection before 24 weeks of pregnancy (<24 weeks), 2) missing data of OGTT at 24–28 weeks of gestation, and 3) stillbirth or without delivery data in our hospital. Of 11,845 women who initially met the above inclusion criteria, 7,646 were ultimately included for the study  and hypertensive disorders of pregnancy (HDP); and weight gain during the whole pregnancy. The delivery records  were retrieved. All identifying patient information was anonymized to protect patient identity.2) was divided into categories according to Chinese BMI criteria for general adults: BMI < 18.5 kg/m2, 18.5 kg/m2 ≤ BMI < 24 kg/m2, 24 kg/m2 ≤ BMI < 28 kg/m2, and BMI ≥ 28 kg/m2 : pregnant women were given OGTT at 24–28 weeks. The results were classified based on one of the following cutoff points: fasting plasma glucose  ≥5.1 mmol/L or 1-h PG  ≥10.0 mmol/L or 2-h PG  ≥8.5 mmol/L  of detection was ≤1%, and the relative error (B) of detection was ≤1%.Metal detection was performed according to the methods described in our previous article . MaternaBaseline characteristics were described as mean ± SD or number (%). In the analysis of birth outcomes, maternal serum metal levels were categorized into three parts according to tertiles. Comparisons for birth outcomes among three groups of metals used ANOVA, and the pairwise comparisons were conducted using Dunnett with a control category of the 1st tertile. The analyses were conducted using SPSS 24.0 software.Quantile regression was performed to detect the distribution shifts of neonatal size  and to explore the associations with metal levels primarily occurring at the tails of neonatal size. In particular, the 10th, 50th, and 90th percentiles of neonatal size were focused on. The metal linear regression was established for each percentile and the mean of neonatal size. Metal level was log-transformed based on a 1.5 logarithm function, assuring that 1-unit change on the transformed scale was close to or within the IQR. One-unit difference on the natural log-transformed scale corresponded to a much wider range than the IQR on the original range . The modP-value <0.05 was considered to indicate statistical significance.In our previous study , we foun2, and the mean weight gain during the whole of pregnancy was 12.70 kg. The mean gestational age at delivery was 38.47 weeks. The mean birth weight, birth length, head circumference, and chest circumference of the newborns were 3,155.13 g, 49.12 cm, 32.89 cm, and 32.70 cm, respectively.P < 0.05) (P < 0.05). No significant difference of gestational age, birth weight, or birth length was observed among the three tertiles of all five metals.The mean gestational age of metal detection was 16.56 weeks Table 1.In the further analysis, we explored the associations between metals and the distribution shifts of head and chest circumference. As shown in The correlations of metals with chest circumference were similar to those of head circumference Figure 2P < 0.001) and 17.65%  for the associations of serum Mn concentration with head and chest circumference. A positive indirect effect of Zn association with head circumference  and chest circumference  through OGTT0 level was also observed, and the estimated proportions of the mediating effect were 13.79% and 26.32%, respectively. In conclusion, there were positive correlations between maternal serum Mn and Zn levels and neonatal head and chest circumference, and these positive correlations were mediated by OGTT0 glucose level.Because of the significant correlations of Mn/Zn and head/chest circumference, mediation analysis was performed to explore the mediating effects of OGTT0 Figure 3The current study showed that maternal serum Mn and Zn levels before 24 weeks of gestation could prospectively increase neonatal head and chest circumference. For the head circumference, the magnitude of the association with Mn was smaller at the upper tail, while the magnitude of correlation with Zn was greater at the upper tail. For the chest circumference, the magnitude of the association with Mn was greater at the upper tail, while the magnitude of correlation with Zn was smaller at the upper tail. In addition, FPG at 24–28 weeks mediated the positive effect of Mn or Zn exposure on head or chest circumference. No relationships between Mn and Zn and other birth outcomes including gestational age, birth weight, and birth length were found. No correlation between Pb, Cu, and Mg and birth outcomes was observed.To date, several studies have explored the association between Mn exposure and birth outcome. However, only a few articles report a prospective and positive relationship between early maternal Mn level and neonatal birth size and the mediating effect of FPG on them. Maternal blood Mn has previously been shown to be positively related to neonatal head circumference, but not to birth weight and birth length , which iThe results of the current study further showed that maternal Mn might affect the birth outcome by influencing FPG during pregnancy. Mn, both an essential element and a potential toxicant, is a component of several enzymes and an activator for enzymes. Deficiency of Mn might affect growth and development of the body and glucose metabolism, and excessive intake of Mn could cause poisoning . Mn is sLarger offspring size has been attributed mainly to higher pregnancy glucose levels. We made a cautious hypothesis that the long-term effects of fetal glucose exposure could affect fetal β-cell capacity, especially exposure to higher FPG, and thus, higher maternal FPG might indirectly affect neonatal birth outcomes. Therefore, FPG might mediate the effect of Mn level on birth outcome. However, there are currently no metal requirement guidelines for pregnant women. The Mn level of our study population was slightly higher than that found in other populations, and serum Mn levels in most pregnant women in our study were below the lower limit of the reference range (0.15–0.22 μmol/L) for healthy adults . Mn requZn is a component of zinc-containing metalloenzymes involved in the activity of more than 80 enzymes. Zn is also an important immunomodulator and growth cofactor and plays an important role in anti-oxidation, anti-apoptosis, and anti-inflammation. About 90% of Zn in the body is distributed in muscles and bone . Blood ZOur current study found no association between Pb and birth outcomes, which is consistent with a previous study . HoweverExcess Cu is harmful to human health, but it is rarely excessive in the general population , and theThe reference range for serum Mg in adults is 0.75 mmol/L  ; our stuThe current study was the first study to show that metal exposure in early pregnancy could affect FPG in the late second trimester and, thus, affect neonatal head and chest circumference. This information may promote new regimens for the personalized control and management of birth size during pregnancy. The study sample size was also relatively large, which increased the accuracy of the findings and made them more applicable to other populations. However, some limitations in the study should be noted. First, despite the large sample size, none of the pregnant women in our study had a smoking or drinking habit. This limits the value of the study. Smoking and drinking habits were investigated in each pregnant woman during prenatal visits as they are risk factors for adverse pregnancy and birth outcomes, not just for the birth size of the newborn. This could be a good habit of women in southern China, although it is impossible to rule out a few cases of concealment. Second, our research was a single-center study; multicenter studies are needed in the future to make the results more precise and reliable. Third, data related to trace element supplementation during pregnancy in this study were not available, which might be a confounding factor affecting the results. We are currently conducting a prospective birth cohort study, aiming to collect more detailed and accurate data. Fourth, the study only examined maternal metal exposure in early pregnancy before 24 weeks, not in the third trimester, placenta, or umbilical cord blood. Metal requirements for pregnant women might vary in different trimesters, and the placental barrier might support different metal effects between mother and offspring. Further epidemiological and molecular studies should be conducted.In conclusion, our study suggests that maternal serum Mn and Zn levels in early pregnancy may prospectively increase neonatal head and chest circumference. FPG in the late second trimester could positively mediate the association of Mn and Zn exposure with head or chest circumference. However, maternal Mn and Zn levels in early pregnancy were not associated with birth weight and birth length. Further studies should explore the relationship between neonatal birth size and metals by integrating maternal nutrition, living habits, the genes of both parents, and other factors throughout pregnancy. In addition, further research is needed to find a balance between maternal blood glucose and neonatal birth size; the corresponding epidemiological and molecular studies need to explore and reveal the molecular mechanisms.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of the Southern Medical University Affiliated Foshan Women and Children Hospital (FSFYMEC-2019-024). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.ZZ, DS, FW and ZL conceived and designed the study. ZZ, DY, GC, PL, LW, JY, DL, JR, DF, XG, HW and XG carried out data collection. ZZ carried out the statistical analyses and drafted the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the Basic and Applied Basic Research Foundation of Guangdong Province (Nos. 2019A1515110163 and 2019A1515111011), the Medical Science and Technology Foundation of Guangdong Province (No. C2019090), the Medical Research Foundation of Guangdong Province (No. A2019214), and the Foundation of Science and Technology Agency of Foshan City .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


PPD symptoms partially mediated and aggravated the association between preterm birth and child mental disorders. Preterm birth, maternal PPD symptoms and child mental disorders are associated, calling for timely prevention interventions.Preterm birth has been linked with postpartum depressive (PPD) disorders and high symptom levels, but evidence remains conflicting and limited in quality. It remains unclear whether PPD symptoms of mothers with preterm babies were already elevated before childbirth, and whether PPD symptoms mediate/aggravate the effect of preterm birth on child mental disorders. We examined whether preterm birth associated with maternal PPD symptoms, depressive symptoms trajectories from antenatal to postpartum stage, and whether PPD symptoms mediated/aggravated associations between preterm birth and child mental disorders. Mothers of preterm (n = 125) and term-born (n = 3033) children of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study reported depressive symptoms four times within 8 weeks before and twice within 12 months after childbirth. Child mental and behavioral disorder diagnoses until age 8.4–12.8 years came from medical register. Preterm birth associated with higher PPD symptoms (mean difference = 0.19 SD, 95% CI 0.01, 0.37,  It poses a risk for neurosensory impairments, and for physical, mental and behavioural disorders later in life5. Preterm birth also induces substantial challenges and distress among the parents of the preterm infants6. Hence, preterm birth has been implicated as a risk factor for maternal postpartum depression (PPD)7.Preterm birth (< 37 completed weeks of gestation) is the leading cause of perinatal morbidity and mortality8, we systematically assessed the quality of evidence of previous studies testing the association between preterm birth and maternal PPD D Tables  and ST2.D Tables , ST2. Of15, which suggests that PPD may be on a pathway between preterm birth and mental and behavioral disorders in children. One previous study has reported that maternal major depressive disorder (MDD) diagnosis between childbirth and child’s assessment in early childhood mediated the association between lower gestational age and child’s risk for anxiety disorders16. Another study reported that maternal PPD symptoms 9 months postpartum did not mediate the association between preterm birth and child’s cognitive function in early childhood17. However, we are not aware of studies that have tested whether maternal PPD symptoms mediate the associations between preterm birth and child mental and behavioral disorders. It also remains unknown if maternal PPD aggravates the association of preterm birth with these child mental health outcomes.Apart from the implicated association with preterm birth, maternal PPD has been also linked with the child’s higher risk for mental and behavioral disorders18) from the childbirth until 12 months postpartum. Further, to unravel if the depressive symptoms levels of women with a preterm baby were high already in the antenatal stage, we studied if preterm birth was associated with depressive symptoms trajectories from the antenatal to the postpartum stage. We also examined if these associations were independent of maternal mood disorders diagnosed before childbirth, and examined if maternal PPD symptoms mediated the association between preterm birth and mental and behavioral disorders in the children followed-up from birth until mid-childhood. Finally, we examined if the effects of preterm birth and maternal PPD on mental and behavioral disorders in the children were additive. We took into account important covariates and assessed whether maternal obstetric complications associated with the risk of preterm delivery, namely preeclampsia, placenta previa, chorionamnionitis, premature rupture of membranes and mode of delivery19, modified the associations of preterm birth with maternal PPD, depressive symptoms trajectories and child mental and behavioral disorders.We examined in a large pregnancy cohort of Finnish women and their children if preterm birth was associated with maternal PPD symptoms and probable clinical PPD  and 12% (n = 15) were born very or extremely preterm . Preterm born compared with term born children were more often boys. Mothers of preterm born compared with term born children more often had a pregnancy complicated by preeclampsia and premature rupture of membranes, they more often delivered via Caesarean section, especially urgent/emergency Caesarean section, and reported higher levels of antenatal depressive symptoms 8 weeks before childbirth  of the mothers in our sample the first PPD symptoms assessment occurred within the first 10 days after childbirth, a period known as the baby blues period27. Hence, since the vast majority of the mothers in our sample provided their first PPD assessment outside of baby blues period, and all second PPD assessments were way beyond this period, the baby blues period is unlikely to bias the associations. Young age of the children included in this study pertains to another limitation and precludes studying mental and behavioral disorders with peak age at onset beyond childhood, such as substance use disorders or schizophrenia-spectrum disorders28. Finally, our study is also limited by lacking data on paternal depressive symptoms, which may influence the associations. It has been previously demonstrated that in comparison to the fathers of term born children, fathers of preterm born children had elevated depressive symptoms 9 months after childbirth. These elevated paternal PPD symptoms, in turn, predicted child’s lower cognitive function in early childhood17. However, the symptoms did not mediate the associations between preterm birth and child’s cognitive function17.However, our study does not unravel the mechanisms underlying the association between preterm birth and maternal PPD symptoms, and mechanisms underlying their association with increased risk of mental and behavioral disorders in children. While data attrition in the child follow-up was null, our study suffers from selective dropout, as the women who participated in the postpartum follow-up and reported PPD symptoms were older, used substances less, and less often had been diagnosed with mood disorders than the women who did not. However, even selective dropout has been found to only marginally alter predictive modelsIn conclusion, our findings suggest that preterm birth and maternal PPD symptoms are associated. The continuity of depressive symptomatology from antenatal to postpartum period and its associations with preterm birth suggests that addressing depressive symptoms already in pregnancy may have beneficial effects on the risk of preterm birth, PPD and subsequently on child mental and behavioral disorders. Mediation and additive effects of preterm birth and maternal PPD on child’s higher risk for mental and behavioral disorders call for prevention interventions aimed at reducing PPD symptoms in women who gave preterm birth.29. In brief, it comprises 4777 mothers who gave birth to a singleton live-born child in Finland between 2006 and 2010. Recruitment took place at ten study hospitals in Southern/Eastern Finland at the first fetal ultrasound screening in early pregnancy. Three women have since withdrawn from the study. We excluded 6 mother–child dyads with unknown gestational age, 29 with missing Finnish Medical Birth Register (MBR) data, 178 with post-term birth , and 4 whom we did not have data on child mental or behavioral disorders from the Finnish Care Register for Health Care (HILMO). Of the 4559 women, 3158 (69.3%) completed questionnaires on depressive symptoms twice up to 12 months postpartum, and of them 125 (4.0%) gave preterm birth.The Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study is described in detail elsewhereDiagnoses of any mental disorder from birth until 31st December 2018, when the children were 8.4–12.8  9.5–10.8) years of age, were available for all children of the 3158 women.Characteristics of the women who did provide the data on PPD and those who did not are shown in the Table +6 gestational weeks + days or less and term birth as birth between 37+0 and 41+6 gestational weeks + days.Gestational age was derived from hospital records and/or MBR. We defined preterm birth as birth at 3618 twice up to 12 months postpartum . The 20 CES-D questions were rated on a scale from none (0) to all of the time (3). Higher scores indicate more depressive symptoms during the past week. We defined PPD symptoms as the mean of the two postpartum CES-D scores and probable clinical PPD as mean CES-D ≥ 1618.The women completed the Center for Epidemiologic Studies Depression Scale (CES‐D)30, a timeframe which is captured by the four biweekly consecutive CES-D measurement points before childbirth.Using the CES-D, the women also rated prospectively biweekly their antenatal depressive symptoms up to 14 times starting from 12 to 14 gestational week until delivery for women who gave birth to a preterm baby and until 38–39 gestational weeks for women who gave birth to a full-term baby. Of these biweekly CES-D measurements we identified the four consecutive measurements before childbirth: we have previously shown in this sample that in women who gave birth to a preterm baby, depressive symptoms begin increasing approximately 8 weeks before childbirth31. We studied any mental and behavioral disorder (ICD-10: F00-F99) as the outcome.We identified diagnoses of mental and behavioral disorders from the HILMO from the birth of the child between 11/07/2006 and 07/24/2010 to 12/31/2018. The HILMO includes primary and subsidiary diagnoses of all inpatient hospital treatments and outpatient visits in specialized medical care coded using the International Statistical Classification of Diseases and Related Health Problems-10 (ICD-10). HILMO is a valid tool for researchThe following variables were included as covariates: maternal age at childbirth (years), smoking at any time during pregnancy (no/any smoking during pregnancy), mode of delivery , child's sex  and age (years) at first mental and behavioral disorder diagnosis with data extracted from hospital records, MBR and/or HILMO; maternal education level  levels 0 to 5)/tertiary (ISCED levels 6 to 8) and alcohol use  were self‐reported in early pregnancy. Smoking and alcohol use were combined into one variable representing smoking and/or alcohol use at any time during pregnancy (yes/no). Maternal mood disorder diagnoses before the childbirth were identified from HILMO . Effect modifiers of preterm birth on maternal and child outcomes included mode of delivery (defined as above), maternal preeclampsia , which was extracted from the hospital records, MBR and /or HILMO and verified by an expert jury comprising two medical doctors and a research nurse with expertise in obstetrics and gynecology, placenta previa (ICD-10 code O44), chorioamnionitis (ICD-10 code O41.1) and premature rupture of membranes (ICD-10 code O42), which were extracted from medical records, MBR and/or HILMO.Associations between preterm birth and maternal PPD symptoms levels were tested using linear regression and with probable clinical PPD using logistic regression.32, the optimal solution was based on (1) goodness-of-fit criteria , (2) reasonable distribution of participants across subgroups (at least 10% of the sample), (3) high certainty of classification identified by posterior probabilities, and (4) clear clinical characteristics of the participants within each of the subgroups. Using the optimal LCA solution, we then tested whether the women who gave birth to a preterm and term baby differed in their odds of belonging to groups differing in their depressive symptoms trajectories identified by the LCA.To identify trajectories of maternal depressive symptoms between antenatal and postpartum stage, we conducted latent class analysis (LCA) based on their four antenatal and two postpartum CES-D scores. We compared solutions with two to six latent classes. Based on criteria for the optimal number of classes described by Kongsted and Nielsen33. Before testing mediation, we ensured that the criteria for mediation were met, namely that the predictor, mediator and outcome variables were associated. Therefore, before proceeding to mediation analyses we also examined if preterm birth and maternal PPD symptoms were associated with mental and behavioral disorders in children by using Cox proportional hazards models. The proportionality assumptions were met .To study whether maternal PPD symptoms mediated the association between preterm birth and mental and behavioral disorders in the children, we used SPSS PROCESS macro with 5000 bootstrapped samplesTo study if mode of delivery, maternal preeclampsia, placenta previa, chorioamnionitis and premature rupture of membranes modified the effects of preterm birth on maternal PPD, depressive symptoms trajectories, and child mental and behavioral disorders, we included interaction terms between these variables and preterm birth into statistical models, followed by main effects of these variables.We then examined if preterm birth and maternal PPD symptoms had additive effects on the hazard of mental and behavioral disorders in children by applying Cox proportional hazards models. For this analysis, we compared the hazards of mental and behavioral disorders in the children who were born at term and whose mothers reported no probable clinical PPD (referent) with (a) children born at term and whose mothers reported probable clinical PPD, (b) preterm children whose mothers reported no probable clinical PPD and (c) preterm children whose mothers reported probable clinical PPD.We report the associations as unadjusted and adjusted for all covariates. Additionally, in examining the associations between preterm birth and PPD, we conducted sensitivity analyses in which we excluded women with a previous history of mood disorders diagnosed before childbirth. Statistical analyses were conducted by using SAS 9.4 , Stata 15  and SPSS-IBM . All methods were carried out in accordance with relevant guidelines and regulations.The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.Supplementary Information 1.Supplementary Information 2.Supplementary Information 3.Supplementary Information 4.Supplementary Information 5.Supplementary Information 6.Supplementary Information 7.


The objective of this analysis was to observe whether maternal and perinatal/neonatal outcomes of birth vary by timing of repeat cesarean among women with a history of one prior cesarean birth in a Guatemalan cohort.This secondary analysis was conducted using data from a prospective study conducted in communities in Chimaltenango, Guatemala through the Global Network for Women’s and Children’s Health Research.Between January 2017 and April 2020, 26,465 women delivered; 3,143 (11.9%) of those women had a singleton gestation and a history of prior cesarean delivery. 2,210 (79.9%) women with a history of prior cesarean birth had data available on mode of delivery and gave birth by repeat cesarean; 1312 (59.4%) were pre-labor cesareans while 896 (40.5%) were intrapartum cesarean births. Risk factors associated with an increased risk of intrapartum cesarean birth included hospital delivery as compared to “other” location  and dysfunctional labor . Variables associated with a reduced risk of intrapartum cesarean birth were hypertensive disease , schooling , and increasing age, which was associated with a very slight reduction in the outcome . Maternal and neonatal outcomes did not vary by type of cesarean birth.Outcomes of cesarean birth do not seem to vary by timing of repeat cesarean birth, with hypertensive disease increasing the likelihood of pre-labor cesarean. This information might be useful in counseling women that outcomes after failed trial of labor do not appear worse than those after pre-labor cesarean birth. The World Health Organization (WHO) has recommended use of the Robson Classification for Cesarean Birth to observe subgroups contributing to cesarean birth rates within and across facilities and countries, over time . When thWomen with a history of prior cesarean birth can elect to undergo repeat cesarean birth or pursue a trial of labor after cesarean . Is it eData analyzed represent that of a prospectively conducted study in communities in Chimaltenango, Guatemala from January 2017 through April 2020, through the Global Network for Women’s and Children’s Health Research, Maternal and Newborn Health Registry (MNHR) . The MNHThere are 8 distinct clusters in the Guatemalan MNHR including those served by health posts (42), health centers (30), and a referral hospital . Each con = 12), experienced miscarriages (n = 566), died prior to labor and delivery (n = 7), were lost to follow-up prior to delivery (n = 7), or those with missing data for delivery mode (n = 1806). The study population included pregnant women who were eligible, consented, and delivered by repeat cesarean birth in the study period [Only women with a history of one prior cesarean delivery with data on mode of birth (timing of cesarean) of the index pregnancy were included. Data were excluded from women who were enrolled but medically terminated pregnancies  associated with timing of repeat cesarean birth (pre-labor versus intrapartum) among women with a history of prior cesarean.The secondary outcomes were maternal and perinatal/neonatal outcomes associated with the timing of the repeat cesarean birth.P-values were obtained from bivariate comparisons as a function of each individual risk factor using Kruskal–Wallis, Fisher’s Exact, or Chi-squared tests depending on variable type.We used descriptive statistics to produce counts and percentages on timing of repeat cesarean among women with a history of prior cesarean delivery. Then we observed independent variables associated with timing of cesarean, and performed bivariate comparisons of sociodemographic and antenatal covariates, intrapartum characteristics, and maternal and perinatal/neonatal outcomes that we hypothesized might be associated with mode of delivery. p < 0.05 from the individual risk factor bivariate comparisons). We then used individual logistic regressions with type of cesarean as the dependent variable with maternal and perinatal/neonatal outcomes that were significantly different in bivariate comparisons by type of cesarean . No methods were used to adjust for any potential bias. All data analyses were performed with STATA software v.15.1. .All risk factors that occurred before delivery and might be associated with type of cesarean were included in a logistic regression  and were more likely to deliver in the hospital (95.8% versus 91.1%) compared to “other” locations, p < 0.05.Table p < 0.05. With respect to neonatal outcomes, none were statistically different between the two types of cesarean.Table Table Table The main findings of this analysis were that women with a history of prior cesarean with hypertensive disease, more education, or older age were more likely to pursue pre-labor repeat cesarean birth, while women experiencing dysfunctional labor or those delivering in the hospital were more likely to undergo repeat cesarean birth during the course of labor. Notably, maternal and perinatal outcomes did not vary by timing of the repeat cesarean birth. This data is from a large Guatemalan cohort and may be generalizable to similar Latin American populations.Our findings regarding hypertensive disease, age, and higher education being associated with pre-labor repeat cesarean birth in this cohort of Guatemalan women are consistent with the literature regarding cesarean birth, generally . HyperteRegarding risk factors that reduced the likelihood of pre-labor repeat cesarean birth, these were delivery in the hospital and dysfunctional labor. Only women attempting labor are eligible to experience dysfunctional labor, so it is not unexpected that this obstetric characteristic was associated with intrapartum repeat cesarean birth. Additionally, this is a known risk factor for cesarean birth, generally . Our delAn unexpected finding was the rate of postpartum infection being higher with pre-labor cesarean than intrapartum. Usually, postpartum infection occurs more commonly after an intrapartum course than after an elective cesarean . It is aStrengths of the analysis are the large sample size, which contributes to external validity, the high quality of the data, and the breadth of antepartum, intrapartum, and postpartum variables that were included in the analysis. This analysis is limited in lacking data on the preferred mode of delivery of these women with a history of prior cesarean. For example, we do not know if the intrapartum cesarean births represent women who desired a trial of labor after cesarean or those who desired a pre-labor cesarean birth but presented to the facility in spontaneous labor. Additionally, we do not have data from observation or chart review or survey about indications for cesarean birth and potentially how contraindications or other patient or labor characteristics may have contributed to mode of birth. Details on indication for cesarean are being added to the dataset so this would allow for additional future secondary analyses on this and related topics.In conclusion, this analysis found that maternal and neonatal outcomes are no worse after intrapartum cesarean births compared to pre-labor cesarean births, supporting the null hypothesis. While this result is only one consideration in a highly complex decision-making process regarding mode of delivery after a prior cesarean, these results may help in the counseling of women regarding the risks and benefits of pre-labor cesarean birth versus attempting trial of labor after cesarean, which may result in an intrapartum cesarean birth. Studying outcomes by women’s preferred delivery mode would be an important area for future research.


Epidemiological research of events related to labor and delivery frequently uses maternal interview or birth certificates as a primary method of data collection; however, the validity of these data are rarely confirmed. This study aimed to examine the validity of birth certificate data and maternal interview of maternal demographics and events related to labor and delivery with data abstracted from medical records in a US setting.Birth certificate and maternal recall data from the Iowa Health in Pregnancy Study (IHIPS), a population-based case-control study of risk factors for preterm and small-for-gestational age births, were linked to medical record data to assess the validity of events that occurred during labor and delivery along with reported maternal demographics. Sensitivity, specificity, positive and negative predictive values, and kappa scores were calculated.Postpartum maternal recall and birth certificate data were excellent for infant characteristics  and variables related to labor and delivery (mode of delivery) when compared with medical records. Birth certificate data for labor induction had low sensitivity (46.3%) and positive predictive value (18.3%) compared to medical records. Compared to maternal interview, birth certificate data also had poor agreement for smoking and alcohol use during pregnancy. Agreement between all three methods of data collection was very low for pregnancy weight gain (kappa = 0.07-0.08).Maternal interview and birth certificate data can be a valid source for collecting data on infant characteristics and events that occurred during labor and delivery. However, caution should be used if solely using birth certificate data to gather data on maternal demographic and/or lifestyle factors. Epidemiological research of events related to labor and delivery frequently uses maternal self-report from interviews and/or questionnaires as the primary method of data collection. Although medical records are often considered to be the most accurate source of information, collecting self-report data is typically faster and less expensive than other methods of data acquisition. Further, medical records often do not contain information outside of medical diagnoses, procedures, and test results that were obtained during the prenatal visits and/or labor and delivery, including maternal stress and experiences, lifestyle habits, and/or domestic abuse. Other existing data sources, such as birth certificates, can also be used as a means for data collection and are also used frequently to identify potential study participants. However, despite the widespread use of both birth certificate data and data from maternal interviews, the validity of the data collected is rarely examined within a study population.To ensure data accuracy across all three sources, further research is necessary in order to observe how one set of data compares to the others. Previous studies have shown that the validity of maternal recall data against data from the medical records varies by the type of information, ranging from very good for infant characteristics such as birth weight –6 and geThe purpose of this study was to examine the validity of birth certificate data and data from maternal interviews for events related to labor and delivery with data abstracted from medical records using data from the Iowa Health in Pregnancy Study (IHIPS). This will help us gain further insight on the level of agreement between labor and delivery data from maternal interviews and birth certificates compared to their corresponding medical records.n = 7202) followed by a phone call inviting them to be screened for eligibility (n = 4250 reached by telephone). Participants were excluded from the study if they met any of the following criteria: < 18 years of age at the time of delivery; non-English speaker; index pregnancy included twins or higher order birth; or if the woman had a prepregnancy diagnosis of type 1 or type 2 diabetes, systemic lupus, or chronic renal disease (n = 548 excluded). Those who were eligible provided verbal consent were asked to complete a 45-min computer-assisted telephone interview . Medical record review of the their prenatal and hospital delivery records to validate the preterm and SGA outcomes was completed for 72.9% of participants in this analysis. In total, data from at least two sources  and from all three sources  were available for 2709 and 1976 women, respectively. Of note, the IHIPS study was conducted before it was common practice to ask participants about their gender identification and pronoun preference. We refer to our participants as “women” throughout the manuscript, although we want to acknowledge that some of our participants may not identify themselves as such.The Iowa Health in Pregnancy Study (IHIPS) is a population-based case-control study designed to identify risk and protective factors associated with preterm (PTB) and small-for-gestational age (SGA) births , 17. ParWe defined low birth weight (LBW) as any infant born weighing < 2500 g (< 5 lbs. 8 oz). Infants were considered preterm if they were born at < 37 weeks gestation and post-term if born at ≥41 weeks gestation. Gestational weight gain was defined as an increase in the woman’s weight from prepregnancy to the end of pregnancy . Quantitative measures of gestational weight gain were not used due to the sparsity of available data.Birth certificate data were initially used to identify potential case and control study participants for IHIPS. Data from the birth certificates consisted of general information about the infant, demographic information about the mother and father , and information about the birth . Birth weight was reported in either grams or pounds and ounces, and gestational age was reported in weeks. Other data pertaining to the events of labor and delivery reported on the birth certificate include mode of delivery, Apgar score, and whether or not labor was induced.Women who consented to participate in IHIPS completed a 45-min CATI survey that included questions related to her demographics, health history, reproductive history, pregnancy experiences with the index pregnancy, and her partner(s). Women were also asked to recall specific details about the index pregnancy, including the baby’s birth weight (pounds and ounces), sex , the gestational age (weeks), and events related to labor and delivery.Among participants who consented to having their medical records reviewed, trained medical record abstractors reviewed prenatal and hospital delivery records. In addition to events from labor and delivery, available data pertaining to the woman’s reproductive history and prenatal care were also abstracted when available. Birth weight data was recorded in grams when possible. All gestational age values were abstracted in weeks; when the details were provided, we recorded the number of weeks + days.Validation statistics were calculated for the following comparisons: 1) birth certificate and maternal interview; 2) birth certificate and medical record; and 3) maternal interview and medical record. Validation of categorical variables was measured by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa scores. The validity of continuous variables was determined by calculating the proportion of gestational age and birth weight measures that fell within one week and 50 g increments. Analyses were performed using SAS Studio version 3.8.The prevalence (%) of each labor and delivery event in the maternal interview, birth certificate, and medical record data are shown in Table Tables Tables In this study comparing birth certificate, maternal interview data, and medical records from women who participated in IHIPS, we found excellent agreement between maternal interview and/or birth certificates compared to medical records for key labor and delivery outcomes: gestational age (in weeks), preterm birth, post-term birth, infant sex, Apgar scores, mode of delivery, birth weight (grams), and low birth weight. Birth certificate data was in moderate agreement with medical records regarding labor induction, but poor agreement with maternal interview regarding smoking and alcohol use during pregnancy. Further, all three data sources were in poor agreement as to whether or not the women gained weight during their pregnancy (kappa 0.07-0.26). Inaccurate reporting of either the exposure and/or outcome can result in misclassification of study participants, biasing study results. Understanding the most accurate, and feasible, data source for a given research question is imperative to minimization of bias.Birth weight and gestational age are important metrics for assessing pregnancy outcomes, but they are also key characteristics in studies of how early life events from the perinatal period impact future health and disease. We found excellent agreement between medical charts and maternal interview for both birth weight and gestational age, with 95.4% of birth weights recalled within ±100 g and 98.9% exact gestational age agreement compared to medical record data. Our results are similar to those of prior validation studies of birth weight and gestational age –5, 7, 8,Additional characteristics surrounding labor and delivery can also be identified from multiple data sources, however, the validity varies widely depending upon the variable(s) of interest. Similar to our findings, prior validation studies have found excellent agreement between medical records and maternal recall for mode of delivery –10, 18, n = 1168 and 1158); however, birth certificates from deliveries at a second hospital indicate nearly 20x the number of labor inductions compared to the medical records  [To our knowledge, only two studies have assessed the validity of labor induction between birth certificates and medical records. A study using birth certificate and medical record data from PRAMS participants in New York City and Vermont found similar rates of labor induction between the data sources in both states, although the birth certificates consistently showed a 1-2% lower prevalence of labor induction . A seconctively) , suggestWe observed very low agreement between maternal recall and birth certificates for smoking and alcohol use during pregnancy. Because the demographic information on birth certificates is usually completed by the mother soon after delivery, we would have expected the agreement to have been higher. However, the prevalence of smoking during pregnancy was reportedly higher on the birth certificates than the maternal interview (12.0 vs 11.3%) while alcohol use during pregnancy had a reportedly higher prevalence in the survey data than the birth certificates (5.5 vs 1.0%). One prior study that evaluated maternal recall of smoking and alcohol use 8-10 years postpartum also found low agreement with medical records for alcohol use during pregnancy (kappa = 0.08), but substantially higher agreement for smoking during pregnancy (kappa = 0.73) [This study is unable to distinguish between reasons for imperfect recall and/or database inaccuracies. Factors that can affect the accuracy of maternal recall include: maternal knowledge of an event, the perceived importance of an event, how an event is defined, the way a question is asked on the survey or interview, time between delivery and completion of the interview, or simple memory lapses. While we assume that the information contained in the medical chart was made known to the mother, this assumption is probably not correct. Additionally, because birth certificates are completed by hospital staff using information from the medical charts, we would also assume a high agreement. However, data entry error, lack of reporting standards , and missing/incomplete data could explain the observed disagreements. Because few validation studies have been performed between birth certificate and medical record data, it is unclear how generalizable our overall validation findings between birth certificates and medical chart data may be to other populations.Despite the large study population and multiple sources of data for validity comparisons, this study is not without limitations. One limitation of the study is the heterogeneity between labor and delivery hospitals. While we do not have data as to which hospital a woman delivered her infant, the study population arose from a four-county catchment area that included several university-affiliated and private hospitals. While the birth certificate forms are standardized across the state of Iowa, medical records are not standardized. Each provider and health care system may have systematic differences in how events of labor and delivery are recorded in the patient’s chart, particularly negative findings or non-events . AdditioAlthough medical record data are believed to be among the most accurate sources of health outcome information, their use can be impractical due to limited financial and human resources. Conversely, acquiring birth certificates is considerably less expensive and much faster. Surveying or interviewing participants is also typically less expensive than medical record abstraction and can yield information not available through medical records. Our study indicates strong overall agreement between all three data sources for most of the interrogated labor and delivery events, signifying it is plausible for medical records, birth certificates, and maternal interviews to be valid sources for data collection. Future research should focus on identifying factors that may be associated with poorer agreement between data sources and validation of other labor and delivery events not included in our study.


Can electronic health care records be used to monitor and project changes in pregnancy and birth rates after the COVID-19 pandemic societal shutdown?In this cohort study of pregnancies within a large US university health care system, a model using electronic medical records (used retrospectively from 2017 and modeled prospectively to 2021) projected an initial decline in births associated with the COVID-19 pandemic societal shutdown, predominantly related to fewer conceptions following the societal changes instituted to control COVID-19 spread. This decline was followed by a projected birth volume surge anticipated to occur in summer 2021.These findings suggest that electronic medical records can be used to model and project birth volume changes and demonstrate that the COVID-19 pandemic societal changes are associated with reproductive choices. This cohort study of all pregnancies in a large US university health care system examines changes in birth volumes associated with the COVID-19 societal shutdown and models prospective trends for birth volume post–societal shutdown. The influence of the COVID-19 pandemic on fertility rates has been suggested in the lay press and anticipated based on documented decreases in fertility and pregnancy rates during previous major societal and economic shifts. Anticipatory planning for birth rates is important for health care systems and government agencies to accurately estimate size of economy and model working and/or aging populations.To use projection modeling based on electronic health care records in a large US university medical center to estimate changes in pregnancy and birth rates prior to and after the COVID-19 pandemic societal lockdowns.This cohort study included all pregnancy episodes within a single US academic health care system retrospectively from 2017 and modeled prospectively to 2021. Data were analyzed September 2021.Pre– and post–COVID-19 pandemic societal shutdown measures.The primary outcome was number of new pregnancy episodes initiated within the health care system and use of those episodes to project birth volumes. Interrupted time series analysis was used to assess the degree to which COVID-19 societal changes may have factored into pregnancy episode volume. Potential reasons for the changes in volumes were compared with historical pregnancy volumes, including delays in starting prenatal care, interruptions in reproductive endocrinology and infertility services, and preterm birth rates.P < .001). This decrease appeared to be due to a decrease in conceptions that followed the March 15 mandated COVID-19 pandemic societal shutdown. Prospective modeling of pregnancies currently suggests that a birth volume surge can be anticipated in summer 2021.This cohort study documented a steadily increasing number of pregnancy episodes over the study period, from 4100 pregnancies in 2017 to 4620 in 2020 . A 14% reduction in pregnancy episode initiation was observed after the societal shutdown of the COVID-19 pandemic (risk ratio, 0.86; 95% CI, 0.79-0.92; This cohort study using electronic medical record surveillance found an initial decline in births associated with the COVID-19 pandemic societal changes and an anticipated increase in birth volume. Future studies can further explore how pregnancy episode volume changes can be monitored and birth rates projected in real-time during major societal events. In the US, a multitude of factors could variably influence pregnancy rates. For example, economic concerns may lead people to postpone conception, whereas decreased access to contraceptive services could lead to increased unintended pregnancy rates. A 2020 Guttmacher Institute study4 demonstrated that 40% of women reported changes in plans for childbearing due to the COVID-19 pandemic, 41% of women with children reported worry about being able to take care of their children, and 33% of women had to delay or cancel an appointment for reproductive health or contraception care. Additionally, the COVID-19 pandemic has highlighted longstanding economic and health disparities in the US,6 yet how such disparities will influence fertility rates and obstetric complications are unknown at this time.The COVID-19 pandemic and associated societal measures to control the spread of the virus have brought about significant changes in almost every aspect of life in the US and globally. The economic and societal effects of the pandemic are vast, with consequences not only for large systems such as health care and education, but also for individuals and families. Previous large societal disruptions in the US, such as the 1918 H1N1 Influenza pandemic,Anticipatory planning for birth rates is important for health care systems to appropriately anticipate increasing or decreasing staffing needs and patient volumes. Population size and population dynamics are of interest to economists to document size of economy and model working and/or aging populations. Often, the consequences of major societal events such as economic and natural disasters or infection pandemics are documented only after the fact or as decreasing birth rates are noted. At the University of Michigan Hospital, we use projection modeling and active management of estimated date of deliveries (EDD) to control obstetric birth volumes in our system and anticipate staffing needs for our birth center. In this analysis, we applied our EDD management modeling techniques to project anticipated delivery volumes after the COVID-19 pandemic and describe the projected decrease in birth rates from our center.STROBE) reporting guideline for cohort studies.This observational cohort study including all pregnancy episodes within the health care system of the University of Michigan Hospital, a large US academic hospital, examined birth rates retrospectively from 2017 through current pregnancy episodes and modeled them prospectively to October 2021. The primary exposure was the COVID-19 pandemic societal shutdown. The stay-at-home order in Michigan was placed on March 15, 2020. Our primary outcome of interest was the start of pregnancy episodes within our health care system, trends in the volume of pregnancies, and evaluation of potential explanations for these volume changes. This analysis was approved by the University of Michigan institutional review board, which exempted the study because it used deidentified data kept by the system for institutional quality improvement, and deemed that no direct informed consent from individual patients was required. Data reporting and analyses followed the Strengthening the Reporting of Observational Studies in Epidemiology  and ultrasound and is associated with the pregnancy episode in the medical record. We excluded any deleted episode that had been entered in error as noted by a comment entered in the electronic medical record (EMR).Pregnancy episodes begin with a patient-initiated contact with our health care system to request pregnancy-related care, such as initial prenatal visit or ultrasound for pregnancy dating. Pregnancy episodes remain open until 1 of the following events occurs: (1) delivery, (2) documented pregnancy loss , or (3) no contact with the patient for 90 days after the EDD. The final EDD was determined by best obstetric estimate2 tests for categorical variables.We conducted descriptive data analyses using the pregnancy episode data from our health care institution’s internal EMR system. The data included patient-specific demographic characteristics , clinical characteristics , and socioeconomic indicators . Race/ethnicity is patient-reported and documented in the EMR. Because this analysis consists of pregnancy episodes, no sex-specific analyses were performed. Baseline demographic characteristics in our obstetric population were analyzed in 2 ways: an annual comparison of pregnancy episodes between 2019 and 2020 and a comparison of new pregnancy episodes started before and after the COVID-19 mandated societal shutdown measures in March 2020. For the before and after comparisons, we defined time periods as January 1 through March 31, 2020, as the pre–societal shutdown period, and April 1 through June 30, 2020, as the post–societal shutdown period. Comparisons in demographic characteristics were compared with parametric or nonparametric tests as appropriate for continuous variables and with χ8 Because there is a delay between conception and the start of a pregnancy care episode of at least 2 weeks, we assigned the intervention binary variable of pre– and post–societal lockdown to begin March 29, 2020, 2 weeks after the start of the spring stay-at-home order, and last until June 14, 2020, 2 weeks after the end of the order. To examine whether prenatal care was being delayed during the COVID-19 pandemic, we examined the time between LMP and contact with the health care system in the time frame before the COVID-19 shutdown to the time period after the shutdown using both the Kolmogorov-Smirnov test and the Fleming-Harrington test for right-censored, 2-sampled time data. We projected future delivery volumes each month from October 2020 through February 2021 using EDDs of active pregnancy episodes with a growth rate applied, which represented the volume of patients who would deliver in an upcoming month who did not yet have a record in the EMR. This growth rate was based on data from 2019. We tested the accuracy of our birth volume projection models compared with actual birth volumes for December 2020 through February 2021.We analyzed the volume of initiation of new pregnancy episodes in our system compared with prior years and explored the association between the COVID-19 lockdown measures on volume of pregnancy episodes and projected future births. We identified the number of pregnancy episodes that began each week between January 2017 and March 2021 and used an interrupted time series study to characterize the differences in pregnancy starts both before and after the initiation of the spring lockdown. A Poisson regression model was used, and Fourier terms were used to adjust for annual seasonal patterns in conception, as described by Bernal et al.P < .05 were considered significant. Statistical analyses were performed with the R statistical programming language version 3.6.0  and Microsoft Excel (Microsoft Corp). Missing data were handled in the following manner: missing race data were included in the other category, unknown Hispanic ethnicity was categorized as non-Hispanic, unknown insurance was categorized as non-Medicaid/Medicare, unknown zip codes were categorized as greater than 30 miles away, and unknown age was excluded from age analysis but included in pregnancy episode and birth projection analysis.We explored factors contributing to observed pregnancy volume changes including COVID-19 shutdown of in vitro fertilization (IVF) cycles and preterm birth rates. Rates of preterm births  per week were explored and quantified using changepoint analysis to determine whether an abrupt change occurred during time-series data. Preterm birth rates before and after the identified changepoint were statistically compared using the Kolmogorov-Smirnov test. Two-sided P = .002) and within 2020 before and after the COVID-19 pandemic shutdown .P < .001).This finding of decreased pregnancy episodes could either be because of an actual decrease in initiation of prenatal care or a delay in initiation of prenatal care. To examine the possibility of delay in initiation of prenatal care, we examined the duration from LMP to first contact with our center to open the pregnancy episode. We found no change in the duration from LMP to contact with our health care center , suggesting that the observed decrease in pregnancy episodes was not associated with a delay in initiation of prenatal care.We used our institutional EDD capacity modeling to project future delivery volumes based on pregnancy episodes in our system . In thisBased on our model, decreased delivery volume was expected from October 2020 through February 2021 . The nadP = .001).We explored factors that may have contributed to the observed and anticipated decreased delivery volumes occurring after the COVID-19 shutdown. We examined the association of closure of assisted reproduction cycles occurring March 16, as was required by state and institutional mandates, with decreased delivery volumes. We documented that there were no IVF patients who began a pregnancy episode between early April and the end of June 2020  birth rates after major societal events. We documented an anticipated decline in births after the COVID-19 pandemic, starting in November of 2020 and persisting until spring of 2021, after which is projected a rebound in anticipated births that may exceed anticipated birth volume based on annual trajectories derived from the prior 5 years of institutional data. In our institution, we modeled pregnancy episode volume to surveil for capacity constraints and projected periods of high and low delivery volume for internal planning reasons. These same modeling techniques can be applied to estimate impacts on anticipated birth rates within a hospital or health care system, or for local/state epidemiologic surveillance. Our data suggest that the anticipated decrease in the birth rate may be best explained by lower conception rates in the weeks and months immediately following the March 2020 COVID-19 pandemic major societal shutdown. Additionally, we found that preterm birth rates may have decreased after the COVID-19 pandemic shutdown.11 Changing birth rates in other societal crises have been linked retrospectively to changes in economic conditions, morbidity and mortality rates among reproductive age populations, and other destabilizing societal conditions . Often, changes in birth rates are recorded as birth rates change, not modeled prospectively to anticipate these changes and plan accordingly.1 How the COVID-19 pandemic may affect birth rates has been speculated in the lay press17 but has not been fully documented, even as the societal impacts of the pandemic have persisted for longer than a year.Pandemics and other major societal events alter population dynamics by both changing fertility rates and changing aging and death rates.19 In fact, encouragement of childbearing is the focus of recent government and societal policies, such as 12-month paid parental leave and other financial bonuses for childbearing in countries concerned with declining fertility rates.18 From a hospital perspective, planning of birth rates is important for appropriate anticipation of maternal and obstetric care needs, as well as anticipation of neonatal intensive care and pediatric subspecialty volumes.Population dynamics are of interest for governments, businesses, and economists because fluctuations in young and aging, workforce, and school-aged populations are critical variables in the ability to plan appropriately for social well-being, to make investments, and to anticipate economic patterns.4 There were notable racial and ethnic disparities, with Black and Hispanic women significantly more likely than White women to state that they were delaying childbearing or wanted fewer children. Our study documented decreased birth volume from November 2020 through February 2021 and an anticipated birth volume surge anticipated in the summer of 2021. In our institution, we do not yet see any clinically meaningful evidence of changing racial or insurance demographic distributions within the pregnant population, although our data are from a single center and do not fully capture the social consequences of the COVID-19 pandemic to its end. Similar to our findings, other centers in the US have also reported decreased preterm birth rates after the COVID-19 pandemic.20 A study from Smith et al21 estimated a potentially permanent impact on birth rates attributable just to closures of assisted reproductive technologies such as IVF, because the closures of these procedures combined with maternal aging may result in loss of fertility that will not be regained after reopening. Our study documented that decreased access to infertility treatment contributes to decreasing pregnancy rates but does not fully explain it. At this time, continued infections of and death from COVID-19, vaccine rollout initiatives, and varied societal reopening may require continued surveillance to determine the full impact of the COVID-19 pandemic on birth rates.Given the recency and evolving situation in the COVID-19 pandemic, there are few objective calculations of how it may influence birth rates globally or in the US. In June 2020, the Guttmacher Institute published survey data on how the COVID-19 pandemic is affecting female sexual and reproductive health, which found that more than 40% of women reported changing their plans about when to have children and how many children to have, with 34% wanting fewer children or to delay having children.Strengths of our study include the ability to use novel modeling techniques to project birth rate volumes with relative certainty prospectively instead of waiting until decreased birth rates are observed. Additionally, by layering on demographic characteristics, such as maternal age and race/ethnicity, assisted reproduction, and preterm birth rates, we can estimate the effects of the COVID-19 pandemic on birth demographic characteristics prospectively. We could apply changing demographic patterns within our models to anticipate fertility rates in specific patient populations, plan for high- and low-risk obstetric volumes, and plan for neonatal intensive care unit and pediatric subspecialty needs.This study had several limitations that should be considered. First, our data are based on a single tertiary care academic center that serves both a local population as well as transported referral populations from throughout the state of Michigan. Thus, our findings may or may not be generalizable to other centers or other regions of the country. Second, we found no significant maternal demographic differences from pre– to post–COVID-19 pandemic time frames. This may be because it is too early to detect those nuanced changes or because of the specific demographic composition of our obstetric population. Third, our projections require that the pregnancy be known to the health care system. Thus, we fail to capture early pregnancy losses, terminations, or pregnancies that might be ongoing but not presenting for prenatal care.In this cohort study, we documented decreased birth rates following the COVID-19 pandemic societal changes, followed by a projected birth volume surge, suggesting that major societal changes may factor into reproductive choices. We demonstrated the use of EMR modeling to project birth rates and investigate in real-time the underlying reasons for changes in observed birth rates. These projection modeling techniques can be used in partnerships between hospitals and governmental or societal organizations to minimize the detrimental effects of the COVID-19 pandemic on society.