Early pregnancy metabolic syndrome and risk for adverse pregnancy outcomes: findings from Rajarata Pregnancy Cohort (RaPCo) in Sri Lanka.

BACKGROUND: Despite the intergenerational effects of metabolic disorders, evidence is greatly lacking on early pregnancy metabolic syndrome (MetS) and its effects on pregnancy outcomes from low- and middle-income countries. Thus, this prospective cohort of South Asian pregnant women aimed to evaluate how early pregnancy MetS would affect pregnancy outcomes. METHODS: A prospective cohort study was conducted among first-trimester (T1) pregnant women of Anuradhapura district, Sri Lanka recruited to the Rajarata Pregnancy Cohort in 2019. MetS was diagnosed by the Joint Interim Statement criteria before 13 weeks of gestational age (GA). Participants were followed up until their delivery, and the major outcomes measured were large for gestational age (LGA), small for gestational age (SGA), preterm birth (PTB) and miscarriage (MC). Gestational weight gain, gestational age at delivery and neonatal birth weight were used as measurements to define the outcomes. Additionally, outcome measures were re-assessed with adjusting fasting plasma glucose (FPG) thresholds of MetS to be compatible with hyperglycemia in pregnancy (Revised MetS). RESULTS: 2326 T1 pregnant women with a mean age of 28.1 years (SD-5.4), and a median GA of 8.0 weeks (IQR-2) were included. Baseline MetS prevalence was 5.9% (n = 137, 95%CI-5.0-6.9). Only 2027 (87.1%) women from baseline, had a live singleton birth, while 221(9.5%) had MC and 14(0.6%) had other pregnancy losses. Additionally, 64(2.8%) were lost to follow-up. A higher cumulative incidence of LGA, PTB, and MC was noted among the T1-MetS women. T1-MetS carried significant risk (RR-2.59, 95%CI-1.65-3.93) for LGA, but reduced the risk for SGA (RR-0.41, 95%CI-0.29-0.78). Revised MetS moderately increased the risk for PTB (RR-1.54, 95%CI-1.04-2.21). T1-MetS was not associated (p = 0.48) with MC. Lowered FPG thresholds were significantly associated with risk for all major pregnancy outcomes. After adjusting for sociodemographic and anthropometric confounders, revised MetS remained the only significant risk predictor for LGA. CONCLUSION: Pregnant women with T1 MetS in this population are at an increased risk for LGA and PTB and a reduced risk for SGA. We observed that a revised MetS definition with lower threshold for FPG compatible with GDM would provide a better estimation of MetS in pregnancy in relation to predicting LGA.

Serum creatinine and estimated glomerular filtration rate (eGFR) in early pregnancy and changes during the pregnancy.

Renal functions in pregnancy undergo rapid changes, and the thresholds for normal values are a major research gap and are still debatable. The lack of prospective population-based studies with early pregnancy recruitment hampered the decision-making process on the best thresholds to be used in clinical practice. We present the serum creatinine (sCr) and sCr-based estimated glomerular filtration rates (eGFR) in early pregnancy with changes over the gestational period in a large prospective, community-based cohort, the Rajarata Pregnancy Cohort (RaPCo). We carried out a community-based prospective cohort study with 2,259 healthy pregnant women with a gestation period of less than 13 weeks and without pre-existing medical conditions. Gestational period-specific sCr and sCr-based eGFR were calculated for different age strata, and the participants were followed up until the second trimester. Renal functions of pregnant women were compared with 2.012 nonpregnant women from the same geographical area. The mean (SD) sCr of the 2,012 nonpregnant women was 62.8(12.4) µmol/L, with the 97.5th percentile of 89.0 µmol/L. Among the pregnant women, mean (SD) sCr was 55.1(8.3), 52.7(8.1), 51.1(9.1), 47.1(7.2), and 49.3 (9.9), while the 97.5th percentile for sCr was 72.4, 69.1, 70.0, 63.6, and 66.0 µmol/L respectively during the 4-7, 8-9, 10-12, 24-27 and 28-30 weeks of gestation. The average sCr value was 84.7% and 76.4% of the nonpregnant group, respectively, in the first and second trimesters. The mean eGFR was 123.4 (10.7) mL/min/1.73 m2 in the first trimester and increased up to 129.5 mL/min/1.73 m2 in the 24th week of gestation. The analysis of cohort data confirmed a significant reduction in sCr with advancing pregnancy (p<0 .001). This study provides thresholds for renal functions in pregnancy to be used in clinical practice. Clinical validation of the proposed thresholds needs to be evaluated with pregnancy and newborn outcomes.

Asthma in a prospective cohort of rural pregnant women from Sri Lanka: Need for better care during the pre-conceptional and antenatal period.

OBJECTIVES: To describe the epidemiology and the effect of asthma on pregnancy outcomes in pregnant women from a rural geography. METHODS: We conducted a prospective cohort study in Anuradhapura district, Sri Lanka enrolling all eligible pregnant women registered in the maternal care program. An interviewer-administered questionnaire-based symptom analysis and clinical assessment was conducted in the first and second trimesters. RESULTS: We recruited 3374 pregnant women aged 15-48 years at conception. Self-reported physician-diagnosed asthma prevalence was 6.6% (n = 223) with only 41.7% (n = 93) on regular medical follow-up for asthma. The prevalence of wheeze reduced from pre-pregnancy (67.0%) to the first (46.4%) and second trimesters (47.7%; p<0.01). Of the 73 asthmatic women who did not have wheeze in the last 3 months preceding pregnancy, new-onset wheeze was reported by 6(8.2%) and 12(16.4%) in the first and second trimester, respectively. Pregnant women who sought medical care for asthma in the private sector had a lower likelihood of developing new-onset wheeze in the first trimester (p = 0.03; unadjusted OR = 0.94;95%CI 0.89-0.99). Thirty-four (33.3%) pregnant women had at least one hospital admission due to exacerbation of wheeze during the first and second trimester. The prevalence of low birth weight (16.0%) was higher among pregnant asthmatic women. CONCLUSION: This study reports the high prevalence of asthma and asthma-associated pregnancy outcomes in women from a rural geography signifying the importance of targeted management.

Comparison of global definitions of metabolic syndrome in early pregnancy among the Rajarata Pregnancy Cohort participants in Sri Lanka.

Metabolic syndrome (MetS) in pregnancy shows epigenetic associations with intergenerational inheritance of metabolic diseases. The presence of different diagnostic criteria influences MetS prevalence estimates. We evaluated MetS and metabolic derangements to determine the utility of its assessment in early pregnancy. A cross-sectional analysis of metabolic derangements in pregnant women with period of gestation (POG) ≤ 12 weeks was done among Rajarata Pregnancy Cohort participants in Sri Lanka. 2682 women with mean age 27.9 year (SD-5.5) and median POG 8.0wk (IQR-3) were analyzed. Mean levels of triglycerides (TG), total cholesterol (TC), high-density-lipoprotein (HDL), low-density-lipoprotein (LDL), fasting plasma glucose, and 2 h oral glucose tolerance test were 87.71 (SD 38.7), 172.2 (SD 34.7), 49.6 (SD 11.5), 122.6 (SD 32.3), 82.2 (SD 12.8) and 120.3 (SD 11.5) respectively. All serum lipids except LDL increase significantly from 6 to 12 weeks, with TG by 23 and TC by 8 units. High MetS prevalence was observed with AHA/NHLBI (n = 150, 5.6%, 95% CI 4.8-6.5) followed by IDF (n = 144, 5.4%, 95% CI 4.6-6.3), NCEP-ATP III (n = 112, 4.2%, 95% CI 3.4-5.0) and WHO (n = 81, 3.0%, 95% CI 2.4-3.7) definitions respectively. Significant difference in prevalence was noted among different sociodemographic characteristics (p < 0.001). Regardless of the criterion used, the change of metabolic parameters in early pregnancy leads to significant differences in prevalence estimates of MetS. The best MetS definition concerning pregnancy outcomes needs to be determined with prospective studies.

Early pregnancy hyperglycaemia as a significant predictor of large for gestational age neonates.

AIMS: We aimed to determine the effect of early pregnancy hyperglycaemia on having a large for gestational age (LGA) neonate. METHODS: A prospective cohort study was conducted among pregnant women in their first trimester. One-step plasma glucose (PG) evaluation procedure was performed to assess gestational diabetes mellitus (GDM) and diabetes mellitus (DM) in pregnancy as defined by the World Health Organization (WHO) criteria with International Association of Diabetes in Pregnancy Study Group (IADPSG) thresholds. The main outcome studied was large for gestational age neonates (LGA). RESULTS: A total of 2,709 participants were recruited with a mean age of 28 years (SD = 5.4) and a median gestational age (GA) of eight weeks (interquartile range [IQR] = 2). The prevalence of GDM in first trimester (T1) was 15.0% (95% confidence interval [CI] = 13.7-16.4). Previously undiagnosed DM was detected among 2.5% of the participants. Out of 2,285 live births with a median delivery GA of 38 weeks (IQR = 3), 7.0% were LGA neonates. The cumulative incidence of LGA neonates in women with GDM and DM was 11.1 and 15.5 per 100 women, respectively. The relative risk of having an LGA neonate among women with DM and GDM was 2.30 (95% CI = 1.23-4.28) and 1.80 (95% CI = 1.27-2.53), respectively. The attributable risk percentage of a LGA neonate for hyperglycaemia was 15.01%. T1 fasting PG was significantly correlated with both neonatal birth weight and birth weight centile. CONCLUSIONS: The proposed WHO criteria for hyperglycaemia in pregnancy are valid, even in T1, for predicting LGA neonates. The use of IADPSG threshold for Fasting PG, for risk assessment in early pregnancy in high-risk populations is recommended.

The hidden burden of adolescent pregnancies in rural Sri Lanka; findings of the Rajarata Pregnancy Cohort.

BACKGROUND: Adolescent fertility is a main indicator of the Sustainable Developmental Goal (SGD) three. Although Sri Lanka is exemplary in maternal health, the utilization of Sexual and Reproductive Health services (SRH) by adolescents is less documented. We describe the hidden burden, associated biological and psychosocial factors and utilization patterns of pre-conceptional services among pregnant adolescents in rural Sri Lanka. METHODS: The study is based on the baseline assessment of the Rajarata Pregnancy Cohort (RaPCo) in Anuradhapura. Pregnant women newly registered from July to September 2019 were recruited to the study. The period of gestation was confirmed during the second follow-up visit (around 25-28 weeks of gestation) using ultra sound scan data. A history, clinical examination, anthropometric measurements, blood investigations were conducted. Mental health status was assessed using the Edinburgh Postpartum Depression Scale (EPDS). RESULTS: Baseline data on gestation was completed by 3,367 pregnant women. Of them, 254 (7.5%) were adolescent pregnancies. Among the primigravida mothers (n = 1037), 22.4% (n = 233) were adolescent pregnancies. Maternal and paternal low education level, being unmarried, and less time since marriage were statistically significant factors associated with adolescent pregnancies (p < 0.05). Contraceptive usage before pregnancy, utilization of pre-conceptional health care services, planning pregnancy and consuming folic acid was significantly low among adolescents (p < 0.001). They also had low body mass index (p < 0.001) and low hemoglobin levels (p = 0.03). Adolescent mothers were less happy of being pregnant (p = 0.006) and had significantly higher levels of anxiety (p = 0.009). CONCLUSION: One fifth of women in their first pregnancy in this study population are adolescents. Nulli-parous adolescents exert poor social stability and compromised physical and mental health effects. The underutilization and/or unavailability of SRH services is clearly associated with adolescent pregnancies.